Neonatal Medicine

Several maternal chronic conditions increase the risk of giving birth to a child with cerebral palsy, based on data from more than 1.3 million Norwegian children.

Mothers with autoimmune disorders, such as diabetes and lupus, had the greatest risks, reported lead author Marianne S. Strøm, MD, of the University of Bergen (Norway) and colleagues.

“The etiologies of cerebral palsy are complex, and only a few prenatal risk factors have been identified,” the investigators wrote in Pediatrics. “Among these possible risk factors are maternal chronic conditions, although studies are typically underpowered and limited to one or two conditions.”

According to Dr. Strøm and colleagues, several components of maternal chronic conditions have been linked with cerebral palsy, including placental abnormalities, altered thrombotic state, and inflammation. Furthermore, mothers with chronic conditions are more likely to give birth prematurely and have children with congenital malformations, both of which have also been associated with cerebral palsy.

To date, however, “there has been no systematic description of maternal chronic conditions and risk of cerebral palsy in offspring,” the investigators noted.

The present, prospective cohort study aimed to meet this need with a population of 1,360,149 children born in Norway from 1990 to 2012, among whom 3,575 had cerebral palsy. Case data were extracted from the Norwegian Patient Registry and the National Insurance Scheme. Information about maternal chronic conditions was extracted from the Medical Birth Registry of Norway and the Norwegian Patient Registry, with the latter also providing information about paternal chronic conditions.

Using log binomial regression models, the investigators determined relative risks of having children with cerebral palsy among parents with chronic conditions versus parents from the general population. This revealed that chronic conditions in fathers had no correlation with cerebral palsy. In contrast, mothers with chronic conditions had a 30% increased risk (relative risk, 1.3; 95% confidence interval, 1.2-1.5), which could be further stratified by number of chronic conditions; mothers with one chronic condition, for instance, had a 20% increased risk (RR, 1.2; 95% CI, 1.1-1.4), while those with two chronic conditions had a 60% increased risk (RR, 1.6; 95% CI, 1.1-2.2), and those with more than two chronic conditions had triple the risk (RR, 3.1; 95% CI, 1.4-6.8)

“The lack of associations between the father’s chronic illness and cerebral palsy risk supports the interpretation that cerebral palsy risk in offspring is the direct result of the mother’s condition and not genetic predisposition or unmeasured situational factors,” the investigators wrote.

Maternal autoimmune conditions were particularly relevant, as they were associated with a 40% increased risk of cerebral palsy (RR, 1.4; 95% CI, 1.1-1.7), a rate that climbed dramatically, to 270%, among mothers with more than one autoimmune condition (RR, 2.7; 95% CI, 1.1-6.6).

“The role of autoimmune diseases in cerebral palsy risk (and maternal inflammation specifically) deserves closer attention,” the investigators wrote. “Using studies with larger sample sizes and a more clinical focus, including measures of placental structure and perinatal blood assays, researchers may be able to explore these possible connections between maternal autoimmune diseases and fetal neurodevelopment.”

Specifically, cerebral palsy in offspring was most strongly associated with maternal Crohn’s disease (RR, 2.1; 95% CI, 1.0-4.1), type 1 diabetes (RR, 2.2; 95% CI, 1.4-3.4), lupus erythematosus (RR, 2.7; 95% CI, 0.9-8.3), and type 2 diabetes (RR, 3.2; 95% CI, 1.8-5.4). Associations were also found for migraine (RR, 1.6; 95% CI, 1.2-2.2), multiple sclerosis (RR, 1.8; 95% CI, 0.8-4.4), and rheumatoid arthritis (RR, 2.0; 95% CI, 1.3-2.9). Several “weaker and less convincing associations” were detected for ulcerative colitis, thyroid disorder, epilepsy, asthma, anemia, and hypertension. Adjusting for parental education level, age, smoking status, and single-mother status did not significantly alter findings. Poisson and logistic regression models generated similar results.

In an accompanying editorial, Sandra Julsen Hollung, PhD, of the Cerebral Palsy Registry of Norway, Vestfold Hospital Trust, Tønsberg, and colleagues, advised that clinicians maintain perspective when discussing these findings with the general public.

“As the authors state, the absolute risk of cerebral palsy associated with at least one chronic maternal condition is low,” wrote Dr. Hollung and colleagues. “Among 1,000 pregnant women with any chronic and/or autoimmune disorder, more than 990 will deliver an infant who will not be diagnosed with cerebral palsy.”

They went on to emphasize that the study findings should not be viewed as firm evidence of causal relationships.

“Thus, the study cannot give clues to any specific preventive treatment,” wrote Dr. Hollung and colleagues. “However, if these disorders are part of a causal pathway, optimal treatment might reduce the risk of cerebral palsy.”

Although Dr. Hollung and colleagues advised that such efforts “would hardly affect the birth prevalence of cerebral palsy,” they also cited the Royal College of Obstetricians and Gynaecologists in the United Kingdom, noting that “each baby counts.”

Emeritus Professor Alastair MacLennan, AO, MB ChB, FRCOG, FRANZCOG, head of the Australian Collaborative Cerebral Palsy Research Group at the University of Adelaide (Australia) suggested that the findings may guide future research.

“An increasing proportion of cerebral palsy cases are being diagnosed by genome sequencing and other genetic techniques to have causative genetic variations,” Dr. MacLennan said. “The possibility of epigenetic interactions are also likely and are still to be investigated. Maternal disorders such as diabetes, lupus, or Crohn’s disease are possible epigenetic factors and this study helps to target these in future genetic and environmental studies of cerebral palsy causation. The days of attributing cerebral palsy to ‘birth asphyxia’ are over.”

The study was supported by the National Institutes of Health and the Western Norwegian Regional Health Authorities. The investigators reported no conflicts of interest.

Several maternal chronic conditions increase the risk of giving birth to a child with cerebral palsy, based on data from more than 1.3 million Norwegian children.

Mothers with autoimmune disorders, such as diabetes and lupus, had the greatest risks, reported lead author Marianne S. Strøm, MD, of the University of Bergen (Norway) and colleagues.

“The etiologies of cerebral palsy are complex, and only a few prenatal risk factors have been identified,” the investigators wrote in Pediatrics. “Among these possible risk factors are maternal chronic conditions, although studies are typically underpowered and limited to one or two conditions.”

According to Dr. Strøm and colleagues, several components of maternal chronic conditions have been linked with cerebral palsy, including placental abnormalities, altered thrombotic state, and inflammation. Furthermore, mothers with chronic conditions are more likely to give birth prematurely and have children with congenital malformations, both of which have also been associated with cerebral palsy.

To date, however, “there has been no systematic description of maternal chronic conditions and risk of cerebral palsy in offspring,” the investigators noted.

The present, prospective cohort study aimed to meet this need with a population of 1,360,149 children born in Norway from 1990 to 2012, among whom 3,575 had cerebral palsy. Case data were extracted from the Norwegian Patient Registry and the National Insurance Scheme. Information about maternal chronic conditions was extracted from the Medical Birth Registry of Norway and the Norwegian Patient Registry, with the latter also providing information about paternal chronic conditions.

Using log binomial regression models, the investigators determined relative risks of having children with cerebral palsy among parents with chronic conditions versus parents from the general population. This revealed that chronic conditions in fathers had no correlation with cerebral palsy. In contrast, mothers with chronic conditions had a 30% increased risk (relative risk, 1.3; 95% confidence interval, 1.2-1.5), which could be further stratified by number of chronic conditions; mothers with one chronic condition, for instance, had a 20% increased risk (RR, 1.2; 95% CI, 1.1-1.4), while those with two chronic conditions had a 60% increased risk (RR, 1.6; 95% CI, 1.1-2.2), and those with more than two chronic conditions had triple the risk (RR, 3.1; 95% CI, 1.4-6.8)

“The lack of associations between the father’s chronic illness and cerebral palsy risk supports the interpretation that cerebral palsy risk in offspring is the direct result of the mother’s condition and not genetic predisposition or unmeasured situational factors,” the investigators wrote.

Maternal autoimmune conditions were particularly relevant, as they were associated with a 40% increased risk of cerebral palsy (RR, 1.4; 95% CI, 1.1-1.7), a rate that climbed dramatically, to 270%, among mothers with more than one autoimmune condition (RR, 2.7; 95% CI, 1.1-6.6).

“The role of autoimmune diseases in cerebral palsy risk (and maternal inflammation specifically) deserves closer attention,” the investigators wrote. “Using studies with larger sample sizes and a more clinical focus, including measures of placental structure and perinatal blood assays, researchers may be able to explore these possible connections between maternal autoimmune diseases and fetal neurodevelopment.”

Specifically, cerebral palsy in offspring was most strongly associated with maternal Crohn’s disease (RR, 2.1; 95% CI, 1.0-4.1), type 1 diabetes (RR, 2.2; 95% CI, 1.4-3.4), lupus erythematosus (RR, 2.7; 95% CI, 0.9-8.3), and type 2 diabetes (RR, 3.2; 95% CI, 1.8-5.4). Associations were also found for migraine (RR, 1.6; 95% CI, 1.2-2.2), multiple sclerosis (RR, 1.8; 95% CI, 0.8-4.4), and rheumatoid arthritis (RR, 2.0; 95% CI, 1.3-2.9). Several “weaker and less convincing associations” were detected for ulcerative colitis, thyroid disorder, epilepsy, asthma, anemia, and hypertension. Adjusting for parental education level, age, smoking status, and single-mother status did not significantly alter findings. Poisson and logistic regression models generated similar results.

In an accompanying editorial, Sandra Julsen Hollung, PhD, of the Cerebral Palsy Registry of Norway, Vestfold Hospital Trust, Tønsberg, and colleagues, advised that clinicians maintain perspective when discussing these findings with the general public.

“As the authors state, the absolute risk of cerebral palsy associated with at least one chronic maternal condition is low,” wrote Dr. Hollung and colleagues. “Among 1,000 pregnant women with any chronic and/or autoimmune disorder, more than 990 will deliver an infant who will not be diagnosed with cerebral palsy.”

They went on to emphasize that the study findings should not be viewed as firm evidence of causal relationships.

“Thus, the study cannot give clues to any specific preventive treatment,” wrote Dr. Hollung and colleagues. “However, if these disorders are part of a causal pathway, optimal treatment might reduce the risk of cerebral palsy.”

Although Dr. Hollung and colleagues advised that such efforts “would hardly affect the birth prevalence of cerebral palsy,” they also cited the Royal College of Obstetricians and Gynaecologists in the United Kingdom, noting that “each baby counts.”

Emeritus Professor Alastair MacLennan, AO, MB ChB, FRCOG, FRANZCOG, head of the Australian Collaborative Cerebral Palsy Research Group at the University of Adelaide (Australia) suggested that the findings may guide future research.

“An increasing proportion of cerebral palsy cases are being diagnosed by genome sequencing and other genetic techniques to have causative genetic variations,” Dr. MacLennan said. “The possibility of epigenetic interactions are also likely and are still to be investigated. Maternal disorders such as diabetes, lupus, or Crohn’s disease are possible epigenetic factors and this study helps to target these in future genetic and environmental studies of cerebral palsy causation. The days of attributing cerebral palsy to ‘birth asphyxia’ are over.”

The study was supported by the National Institutes of Health and the Western Norwegian Regional Health Authorities. The investigators reported no conflicts of interest.

Several maternal chronic conditions increase the risk of giving birth to a child with cerebral palsy, based on data from more than 1.3 million Norwegian children.

Mothers with autoimmune disorders, such as diabetes and lupus, had the greatest risks, reported lead author Marianne S. Strøm, MD, of the University of Bergen (Norway) and colleagues.

“The etiologies of cerebral palsy are complex, and only a few prenatal risk factors have been identified,” the investigators wrote in Pediatrics. “Among these possible risk factors are maternal chronic conditions, although studies are typically underpowered and limited to one or two conditions.”

According to Dr. Strøm and colleagues, several components of maternal chronic conditions have been linked with cerebral palsy, including placental abnormalities, altered thrombotic state, and inflammation. Furthermore, mothers with chronic conditions are more likely to give birth prematurely and have children with congenital malformations, both of which have also been associated with cerebral palsy.

To date, however, “there has been no systematic description of maternal chronic conditions and risk of cerebral palsy in offspring,” the investigators noted.

The present, prospective cohort study aimed to meet this need with a population of 1,360,149 children born in Norway from 1990 to 2012, among whom 3,575 had cerebral palsy. Case data were extracted from the Norwegian Patient Registry and the National Insurance Scheme. Information about maternal chronic conditions was extracted from the Medical Birth Registry of Norway and the Norwegian Patient Registry, with the latter also providing information about paternal chronic conditions.

Using log binomial regression models, the investigators determined relative risks of having children with cerebral palsy among parents with chronic conditions versus parents from the general population. This revealed that chronic conditions in fathers had no correlation with cerebral palsy. In contrast, mothers with chronic conditions had a 30% increased risk (relative risk, 1.3; 95% confidence interval, 1.2-1.5), which could be further stratified by number of chronic conditions; mothers with one chronic condition, for instance, had a 20% increased risk (RR, 1.2; 95% CI, 1.1-1.4), while those with two chronic conditions had a 60% increased risk (RR, 1.6; 95% CI, 1.1-2.2), and those with more than two chronic conditions had triple the risk (RR, 3.1; 95% CI, 1.4-6.8)

“The lack of associations between the father’s chronic illness and cerebral palsy risk supports the interpretation that cerebral palsy risk in offspring is the direct result of the mother’s condition and not genetic predisposition or unmeasured situational factors,” the investigators wrote.

Maternal autoimmune conditions were particularly relevant, as they were associated with a 40% increased risk of cerebral palsy (RR, 1.4; 95% CI, 1.1-1.7), a rate that climbed dramatically, to 270%, among mothers with more than one autoimmune condition (RR, 2.7; 95% CI, 1.1-6.6).

“The role of autoimmune diseases in cerebral palsy risk (and maternal inflammation specifically) deserves closer attention,” the investigators wrote. “Using studies with larger sample sizes and a more clinical focus, including measures of placental structure and perinatal blood assays, researchers may be able to explore these possible connections between maternal autoimmune diseases and fetal neurodevelopment.”

Specifically, cerebral palsy in offspring was most strongly associated with maternal Crohn’s disease (RR, 2.1; 95% CI, 1.0-4.1), type 1 diabetes (RR, 2.2; 95% CI, 1.4-3.4), lupus erythematosus (RR, 2.7; 95% CI, 0.9-8.3), and type 2 diabetes (RR, 3.2; 95% CI, 1.8-5.4). Associations were also found for migraine (RR, 1.6; 95% CI, 1.2-2.2), multiple sclerosis (RR, 1.8; 95% CI, 0.8-4.4), and rheumatoid arthritis (RR, 2.0; 95% CI, 1.3-2.9). Several “weaker and less convincing associations” were detected for ulcerative colitis, thyroid disorder, epilepsy, asthma, anemia, and hypertension. Adjusting for parental education level, age, smoking status, and single-mother status did not significantly alter findings. Poisson and logistic regression models generated similar results.

In an accompanying editorial, Sandra Julsen Hollung, PhD, of the Cerebral Palsy Registry of Norway, Vestfold Hospital Trust, Tønsberg, and colleagues, advised that clinicians maintain perspective when discussing these findings with the general public.

“As the authors state, the absolute risk of cerebral palsy associated with at least one chronic maternal condition is low,” wrote Dr. Hollung and colleagues. “Among 1,000 pregnant women with any chronic and/or autoimmune disorder, more than 990 will deliver an infant who will not be diagnosed with cerebral palsy.”

They went on to emphasize that the study findings should not be viewed as firm evidence of causal relationships.

“Thus, the study cannot give clues to any specific preventive treatment,” wrote Dr. Hollung and colleagues. “However, if these disorders are part of a causal pathway, optimal treatment might reduce the risk of cerebral palsy.”

Although Dr. Hollung and colleagues advised that such efforts “would hardly affect the birth prevalence of cerebral palsy,” they also cited the Royal College of Obstetricians and Gynaecologists in the United Kingdom, noting that “each baby counts.”

Emeritus Professor Alastair MacLennan, AO, MB ChB, FRCOG, FRANZCOG, head of the Australian Collaborative Cerebral Palsy Research Group at the University of Adelaide (Australia) suggested that the findings may guide future research.

“An increasing proportion of cerebral palsy cases are being diagnosed by genome sequencing and other genetic techniques to have causative genetic variations,” Dr. MacLennan said. “The possibility of epigenetic interactions are also likely and are still to be investigated. Maternal disorders such as diabetes, lupus, or Crohn’s disease are possible epigenetic factors and this study helps to target these in future genetic and environmental studies of cerebral palsy causation. The days of attributing cerebral palsy to ‘birth asphyxia’ are over.”

The study was supported by the National Institutes of Health and the Western Norwegian Regional Health Authorities. The investigators reported no conflicts of interest.

Dried blood spot testing showed sensitivity comparable to saliva as a screening method for congenital cytomegalovirus infection in newborns, based on data from more than 12,000 newborns.

Congenital cytomegalovirus (cCMV) is a common congenital virus in the United States, but remains underrecognized, wrote Sheila C. Dollard, PhD, of the Centers for Disease Control and Prevention in Atlanta, and colleagues.

“Given the burden associated with cCMV and the proven benefits of treatment and early intervention for some affected infants, there has been growing interest in universal newborn screening,” but an ideal screening strategy has yet to be determined, they said.

In a population-based cohort study published in JAMA Pediatrics, the researchers screened 12,554 newborns in Minnesota, including 56 with confirmed CMV infection. The newborns were screened for cCMV via dried blood spots (DBS) and saliva collected 1-2 days after birth. The DBS were tested for CMV DNA via polymerase chain reaction (PCR) at the University of Minnesota (UMN) and the CDC.

The overall sensitivity rate was 85.7% for a combination of laboratory results from the UMN and the CDC, which had separate sensitivities of 73.2% and 76.8%, respectively.

The specificity of the combined results was 100.0% (100% from both UMN and CDC), the combined positive predictive value was 98.0% (100.0% from UMN, 97.7% from CDC), and the combined negative predictive value was 99.9% (99.9% from both UMN and CDC).

By comparison, saliva swab test results showed sensitivity of 92.9%, specificity of 99.9%, positive predictive value of 86.7%, and negative predictive value of 100.0%.

The study findings were limited by several factors including the false-positive and false-negative results from saliva screening. Overall, the false-positive rate was 0.06%, which is comparable to rates from other screening techniques, the researchers said. “The recent Food and Drug Administration approval of a point-of-care neonatal saliva CMV test (Meridian Bioscience), underscores the importance of further clarifying the role of false-positive saliva CMV test results and underscores the requirement for urine confirmation for diagnosis of cCMV,” they added.

However, the study findings support the acceptability and feasibility of cCMV screening, as parents reported generally positive attitudes about the process, the researchers said.

The study is ongoing, and designed to follow infants with confirmed cCMV for up to age 4 years to assess clinical outcomes, they added. “Diagnostic methods are always improving, and therefore, our results show the potential of DBS to provide low-cost CMV screening with smooth integration of sample collection, laboratory testing, and follow-up,” they concluded.
 

Findings lay foundation for widespread use

“By using enhanced PCR methods, Dollard et al. have rekindled the hope that NBDBS [newborn dried blood spots] testing may be a viable method for large-scale, universal newborn screening for congenital CMV,” Gail J. Demmler-Harrison, MD, of Texas Children’s Hospital, Houston, wrote in an accompanying editorial. Congenital CMV is a common infection, but accurate prevalence remains uncertain because not all newborns are tested, she noted. Detection of CMV currently may involve urine, saliva, and blood, but challenges to the use of these methods include “a variety of constantly evolving DNA detection methods,” she said.

Although urine and saliva samples have been proposed for universal screening, they would require the creation of new sample collection and testing programs. “The routine of collecting the NBDBS samples on all newborns and the logistics of routing them to central laboratories and then reporting results to caregivers is already in place and are strengths of NBDBS samples for universal newborn screening,” but had been limited by a less sensitive platform than urine or saliva, said Dr. Demmler-Harrison.

“The results in the study by Dollard et al. may be a total game changer for the NBDBS proponents,” she emphasized. “Furthermore, scientists who have adapted even more sensitive DNA detection assays, such as the loop-mediated isothermal assay for detection of DNA in clinical samples from newborns, may be able to adapt loop-mediated isothermal assay methodology to detect CMV DNA in NBDBS,” she added.

“By adapting the collection methods, by using optimal filter paper to enhance DNA adherence, by improving DNA elution procedures, and by developing novel amplification and detection methods, NBDBS may soon meet the challenge and reach the sensitivity and specificity necessary for universal screening for congenital CMV,” she concluded.

The study was supported by the CDC, the Minnesota Department of Health, the National Vaccine Program Office (U.S. federal government), and the University of South Carolina Disability Research and Dissemination Center.

Dr. Dollard and Dr. Demmler-Harrison had no financial conflicts to disclose.

Dried blood spot testing showed sensitivity comparable to saliva as a screening method for congenital cytomegalovirus infection in newborns, based on data from more than 12,000 newborns.

Congenital cytomegalovirus (cCMV) is a common congenital virus in the United States, but remains underrecognized, wrote Sheila C. Dollard, PhD, of the Centers for Disease Control and Prevention in Atlanta, and colleagues.

“Given the burden associated with cCMV and the proven benefits of treatment and early intervention for some affected infants, there has been growing interest in universal newborn screening,” but an ideal screening strategy has yet to be determined, they said.

In a population-based cohort study published in JAMA Pediatrics, the researchers screened 12,554 newborns in Minnesota, including 56 with confirmed CMV infection. The newborns were screened for cCMV via dried blood spots (DBS) and saliva collected 1-2 days after birth. The DBS were tested for CMV DNA via polymerase chain reaction (PCR) at the University of Minnesota (UMN) and the CDC.

The overall sensitivity rate was 85.7% for a combination of laboratory results from the UMN and the CDC, which had separate sensitivities of 73.2% and 76.8%, respectively.

The specificity of the combined results was 100.0% (100% from both UMN and CDC), the combined positive predictive value was 98.0% (100.0% from UMN, 97.7% from CDC), and the combined negative predictive value was 99.9% (99.9% from both UMN and CDC).

By comparison, saliva swab test results showed sensitivity of 92.9%, specificity of 99.9%, positive predictive value of 86.7%, and negative predictive value of 100.0%.

The study findings were limited by several factors including the false-positive and false-negative results from saliva screening. Overall, the false-positive rate was 0.06%, which is comparable to rates from other screening techniques, the researchers said. “The recent Food and Drug Administration approval of a point-of-care neonatal saliva CMV test (Meridian Bioscience), underscores the importance of further clarifying the role of false-positive saliva CMV test results and underscores the requirement for urine confirmation for diagnosis of cCMV,” they added.

However, the study findings support the acceptability and feasibility of cCMV screening, as parents reported generally positive attitudes about the process, the researchers said.

The study is ongoing, and designed to follow infants with confirmed cCMV for up to age 4 years to assess clinical outcomes, they added. “Diagnostic methods are always improving, and therefore, our results show the potential of DBS to provide low-cost CMV screening with smooth integration of sample collection, laboratory testing, and follow-up,” they concluded.
 

Findings lay foundation for widespread use

“By using enhanced PCR methods, Dollard et al. have rekindled the hope that NBDBS [newborn dried blood spots] testing may be a viable method for large-scale, universal newborn screening for congenital CMV,” Gail J. Demmler-Harrison, MD, of Texas Children’s Hospital, Houston, wrote in an accompanying editorial. Congenital CMV is a common infection, but accurate prevalence remains uncertain because not all newborns are tested, she noted. Detection of CMV currently may involve urine, saliva, and blood, but challenges to the use of these methods include “a variety of constantly evolving DNA detection methods,” she said.

Although urine and saliva samples have been proposed for universal screening, they would require the creation of new sample collection and testing programs. “The routine of collecting the NBDBS samples on all newborns and the logistics of routing them to central laboratories and then reporting results to caregivers is already in place and are strengths of NBDBS samples for universal newborn screening,” but had been limited by a less sensitive platform than urine or saliva, said Dr. Demmler-Harrison.

“The results in the study by Dollard et al. may be a total game changer for the NBDBS proponents,” she emphasized. “Furthermore, scientists who have adapted even more sensitive DNA detection assays, such as the loop-mediated isothermal assay for detection of DNA in clinical samples from newborns, may be able to adapt loop-mediated isothermal assay methodology to detect CMV DNA in NBDBS,” she added.

“By adapting the collection methods, by using optimal filter paper to enhance DNA adherence, by improving DNA elution procedures, and by developing novel amplification and detection methods, NBDBS may soon meet the challenge and reach the sensitivity and specificity necessary for universal screening for congenital CMV,” she concluded.

The study was supported by the CDC, the Minnesota Department of Health, the National Vaccine Program Office (U.S. federal government), and the University of South Carolina Disability Research and Dissemination Center.

Dr. Dollard and Dr. Demmler-Harrison had no financial conflicts to disclose.

Dried blood spot testing showed sensitivity comparable to saliva as a screening method for congenital cytomegalovirus infection in newborns, based on data from more than 12,000 newborns.

Congenital cytomegalovirus (cCMV) is a common congenital virus in the United States, but remains underrecognized, wrote Sheila C. Dollard, PhD, of the Centers for Disease Control and Prevention in Atlanta, and colleagues.

“Given the burden associated with cCMV and the proven benefits of treatment and early intervention for some affected infants, there has been growing interest in universal newborn screening,” but an ideal screening strategy has yet to be determined, they said.

In a population-based cohort study published in JAMA Pediatrics, the researchers screened 12,554 newborns in Minnesota, including 56 with confirmed CMV infection. The newborns were screened for cCMV via dried blood spots (DBS) and saliva collected 1-2 days after birth. The DBS were tested for CMV DNA via polymerase chain reaction (PCR) at the University of Minnesota (UMN) and the CDC.

The overall sensitivity rate was 85.7% for a combination of laboratory results from the UMN and the CDC, which had separate sensitivities of 73.2% and 76.8%, respectively.

The specificity of the combined results was 100.0% (100% from both UMN and CDC), the combined positive predictive value was 98.0% (100.0% from UMN, 97.7% from CDC), and the combined negative predictive value was 99.9% (99.9% from both UMN and CDC).

By comparison, saliva swab test results showed sensitivity of 92.9%, specificity of 99.9%, positive predictive value of 86.7%, and negative predictive value of 100.0%.

The study findings were limited by several factors including the false-positive and false-negative results from saliva screening. Overall, the false-positive rate was 0.06%, which is comparable to rates from other screening techniques, the researchers said. “The recent Food and Drug Administration approval of a point-of-care neonatal saliva CMV test (Meridian Bioscience), underscores the importance of further clarifying the role of false-positive saliva CMV test results and underscores the requirement for urine confirmation for diagnosis of cCMV,” they added.

However, the study findings support the acceptability and feasibility of cCMV screening, as parents reported generally positive attitudes about the process, the researchers said.

The study is ongoing, and designed to follow infants with confirmed cCMV for up to age 4 years to assess clinical outcomes, they added. “Diagnostic methods are always improving, and therefore, our results show the potential of DBS to provide low-cost CMV screening with smooth integration of sample collection, laboratory testing, and follow-up,” they concluded.
 

Findings lay foundation for widespread use

“By using enhanced PCR methods, Dollard et al. have rekindled the hope that NBDBS [newborn dried blood spots] testing may be a viable method for large-scale, universal newborn screening for congenital CMV,” Gail J. Demmler-Harrison, MD, of Texas Children’s Hospital, Houston, wrote in an accompanying editorial. Congenital CMV is a common infection, but accurate prevalence remains uncertain because not all newborns are tested, she noted. Detection of CMV currently may involve urine, saliva, and blood, but challenges to the use of these methods include “a variety of constantly evolving DNA detection methods,” she said.

Although urine and saliva samples have been proposed for universal screening, they would require the creation of new sample collection and testing programs. “The routine of collecting the NBDBS samples on all newborns and the logistics of routing them to central laboratories and then reporting results to caregivers is already in place and are strengths of NBDBS samples for universal newborn screening,” but had been limited by a less sensitive platform than urine or saliva, said Dr. Demmler-Harrison.

“The results in the study by Dollard et al. may be a total game changer for the NBDBS proponents,” she emphasized. “Furthermore, scientists who have adapted even more sensitive DNA detection assays, such as the loop-mediated isothermal assay for detection of DNA in clinical samples from newborns, may be able to adapt loop-mediated isothermal assay methodology to detect CMV DNA in NBDBS,” she added.

“By adapting the collection methods, by using optimal filter paper to enhance DNA adherence, by improving DNA elution procedures, and by developing novel amplification and detection methods, NBDBS may soon meet the challenge and reach the sensitivity and specificity necessary for universal screening for congenital CMV,” she concluded.

The study was supported by the CDC, the Minnesota Department of Health, the National Vaccine Program Office (U.S. federal government), and the University of South Carolina Disability Research and Dissemination Center.

Dr. Dollard and Dr. Demmler-Harrison had no financial conflicts to disclose.

A Zika virus vaccine candidate prompted antibody responses in 80% of individuals who received two doses in a phase 1 study.

©Aunt_Spray/Thinkstock

Although Zika cases have declined in recent years, “geographic expansion of the Aedes aegypti mosquito to areas where population-level immunity is low poses a substantial risk for future epidemics,” wrote Nadine C. Salisch, PhD, of Janssen Vaccines and Prevention, Leiden, the Netherlands, and colleagues in a paper published in Annals of Internal Medicine.

No vaccine against Zika is yet available, although more than 10 candidates have been studied in preclinical trials to date, they said.

The researchers randomized 100 healthy adult volunteers to an experimental Zika vaccine candidate known as Ad26.ZIKV.001 in either one-dose or two-dose regimens of 5x10¹⁰ viral particles (low dose) or 1x10¹¹ viral particles (high dose) or placebo. Approximately half (55%) of the participants were women, and 72% were White.

Approximately 80% of patients in both two-dose groups showed antibody responses for a year after vaccination. Geometric mean titers (GMTs) reached peak of 823.4 in the low-dose/low-dose group and 961.5 in the high-dose/high-dose group. At day 365, the GMTs for these groups were 68.7 and 87.0, respectively.

A single high-dose vaccine achieved a similar level of neutralizing antibody titers, but lower peak neutralizing responses than the two-dose strategies, the researchers noted.

Most of the reported adverse events were mild to moderate, and short lived; the most common were injection site pain or tenderness, headache, and fatigue, the researchers said. After the first vaccination, 75% of participants in the low-dose groups, 88% of participants in high-dose groups, and 45% of participants receiving placebo reported local adverse events. In addition, 73%, 83%, and 40% of the participants in the low-dose, high-dose, and placebo groups, respectively, reported systemic adverse events. Reports were similar after the second vaccination. Two serious adverse events not related to vaccination were reported; one case of right lower lobe pneumonia and one case of incomplete spontaneous abortion.

The researchers also explored protective efficacy through a nonlethal mouse challenge model. “Transfer of 6 mg of IgG from Ad26.ZIKV.001 vaccines conferred complete protection from viremia in most recipient animals, with statistically significantly decreased breakthrough rates and cumulative viral loads per group compared with placebo,” they said.

The study findings were limited by the inability to assess safety and immunogenicity in an endemic area, the researchers noted. However, “Ad26.ZIKV.001 induces potent ZIKV-specific neutralizing responses with durability of at least 1 year, which supports further clinical development if an unmet medical need reemerges,” they said. “In addition, these data underscore the performance of the Ad26 vaccine platform, which Janssen is using for different infectious diseases, including COVID-19,” they noted.
 

Ad26 vector platform shows consistency

“Development of the investigational Janssen Zika vaccine candidate was initiated in 2015, and while the incidence of Zika virus has declined since the 2015-2016 outbreak, spread of the ‘carrier’ Aedes aegypti mosquito to areas where population-level immunity is low poses a substantial risk for future epidemics,” lead author Dr. Salisch said in an interview. For this reason, researchers say the vaccine warrants further development should the need reemerge, she said.

“Our research has found that while a single higher-dose regimen had lower peak neutralizing responses than a two-dose regimen, it achieved a similar level of neutralizing antibody responses at 1 year, an encouraging finding that shows our vaccine may be a useful tool to curb Zika epidemics,” Dr. Salisch noted. “Previous experience with the Ad26 vector platform across our investigational vaccine programs have yielded similarly promising results, most recently with our investigational Janssen COVID-19 vaccine program, for which phase 3 data show a single-dose vaccine met all primary and key secondary endpoints,” she said.

“The biggest barrier [to further development of the candidate vaccine] is one that we actually consider ourselves fortunate to have: The very low incidence of reported Zika cases currently reported worldwide,” Dr. Salisch said. “However, the current Zika case rate can change at any time, and in the event the situation demands it, we are open to alternative regulatory pathways to help us glean the necessary insights on vaccine safety and efficacy to further advance the development of this candidate,” she emphasized.

As for additional research, “there are still questions surrounding Zika transmission and the pathomechanism of congenital Zika syndrome,” said Dr. Salisch. “Our hope is that a correlate of protection against Zika disease, and in particular against congenital Zika syndrome, can be identified,” she said.  

Consider pregnant women in next phase of research

“A major hurdle in ZIKV vaccine development is the inability to conduct large efficacy studies in the absence of a current outbreak,” Ann Chahroudi, MD, of Emory University, Atlanta, and Sallie Permar, MD, of Weill Cornell Medicine, New York, wrote in an accompanying editorial.

The current study provided some efficacy data using a mouse model, but “these data are obviously not conclusive for human protection,” they said.

“A further challenge for ZIKV vaccine efficacy trials will be to demonstrate fetal protection from [congenital Zika syndrome] after adult immunization. There should be a clear plan to readily deploy phase 3 trials for the most promising vaccines to emerge from phase 1 and 2 in the event of an outbreak, as was implemented for Ebola, including infant follow-up,” they emphasized.

The editorialists noted that the study did not include pregnant women, who represent a major target for immunization, but they said that vaccination of pregnant women against other neonatal pathogens such as influenza and tetanus has been effective. “Candidate ZIKV vaccines proven safe in phase 1 trials should immediately be assessed for safety and efficacy in pregnant women,” they said. Although Zika infections are not at epidemic levels currently, resurgence remains a possibility and the coronavirus pandemic “has taught us that preparedness for emerging infections is crucial,” they said.
 

Zika vaccine research is a challenge worth pursuing

“It is important to continue Zika vaccine research because of the unpredictable nature of that infection,” Kevin Ault, MD, of the University of Kansas, Kansas City, said in an interview. “Several times Zika has gained a foothold in unexposed and vulnerable populations,” Dr. Ault said.  “Additionally, there are some data about using this vector during pregnancy, and eventually this vaccine may prevent the birth defects associated with Zika infections during pregnancy, he noted.

Dr. Ault said he was not surprised by the study findings. “This is a promising early phase vaccine candidate, and this adenovirus vector has been used in other similar trials,” he said. Potential barriers to vaccine development include the challenge of conducting late phase clinical trials in pregnant women, he noted. “The relevant endpoint is going to be clinical disease, and one of the most critical populations is pregnant women,” he said. In addition, “later phase 3 trials would be conducted in a population where there is an ongoing Zika outbreak,” Dr. Ault emphasized.   

The study was supported by Janssen Vaccines and Infectious Diseases.

Dr. Chahroudi had no financial conflicts to disclose. Dr. Permar disclosed grants from Merck and Moderna unrelated to the current study. Dr. Ault had no relevant financial conflicts to disclose; he has served as an adviser to the Centers for Disease Control and Prevention, the World Medical Association, the National Vaccine Program Office, and the National Institute for Allergy and Infectious Diseases. He is a fellow of the Infectious Disease Society of American and a fellow of ACOG. 

A Zika virus vaccine candidate prompted antibody responses in 80% of individuals who received two doses in a phase 1 study.

©Aunt_Spray/Thinkstock

Although Zika cases have declined in recent years, “geographic expansion of the Aedes aegypti mosquito to areas where population-level immunity is low poses a substantial risk for future epidemics,” wrote Nadine C. Salisch, PhD, of Janssen Vaccines and Prevention, Leiden, the Netherlands, and colleagues in a paper published in Annals of Internal Medicine.

No vaccine against Zika is yet available, although more than 10 candidates have been studied in preclinical trials to date, they said.

The researchers randomized 100 healthy adult volunteers to an experimental Zika vaccine candidate known as Ad26.ZIKV.001 in either one-dose or two-dose regimens of 5x10¹⁰ viral particles (low dose) or 1x10¹¹ viral particles (high dose) or placebo. Approximately half (55%) of the participants were women, and 72% were White.

Approximately 80% of patients in both two-dose groups showed antibody responses for a year after vaccination. Geometric mean titers (GMTs) reached peak of 823.4 in the low-dose/low-dose group and 961.5 in the high-dose/high-dose group. At day 365, the GMTs for these groups were 68.7 and 87.0, respectively.

A single high-dose vaccine achieved a similar level of neutralizing antibody titers, but lower peak neutralizing responses than the two-dose strategies, the researchers noted.

Most of the reported adverse events were mild to moderate, and short lived; the most common were injection site pain or tenderness, headache, and fatigue, the researchers said. After the first vaccination, 75% of participants in the low-dose groups, 88% of participants in high-dose groups, and 45% of participants receiving placebo reported local adverse events. In addition, 73%, 83%, and 40% of the participants in the low-dose, high-dose, and placebo groups, respectively, reported systemic adverse events. Reports were similar after the second vaccination. Two serious adverse events not related to vaccination were reported; one case of right lower lobe pneumonia and one case of incomplete spontaneous abortion.

The researchers also explored protective efficacy through a nonlethal mouse challenge model. “Transfer of 6 mg of IgG from Ad26.ZIKV.001 vaccines conferred complete protection from viremia in most recipient animals, with statistically significantly decreased breakthrough rates and cumulative viral loads per group compared with placebo,” they said.

The study findings were limited by the inability to assess safety and immunogenicity in an endemic area, the researchers noted. However, “Ad26.ZIKV.001 induces potent ZIKV-specific neutralizing responses with durability of at least 1 year, which supports further clinical development if an unmet medical need reemerges,” they said. “In addition, these data underscore the performance of the Ad26 vaccine platform, which Janssen is using for different infectious diseases, including COVID-19,” they noted.
 

Ad26 vector platform shows consistency

“Development of the investigational Janssen Zika vaccine candidate was initiated in 2015, and while the incidence of Zika virus has declined since the 2015-2016 outbreak, spread of the ‘carrier’ Aedes aegypti mosquito to areas where population-level immunity is low poses a substantial risk for future epidemics,” lead author Dr. Salisch said in an interview. For this reason, researchers say the vaccine warrants further development should the need reemerge, she said.

“Our research has found that while a single higher-dose regimen had lower peak neutralizing responses than a two-dose regimen, it achieved a similar level of neutralizing antibody responses at 1 year, an encouraging finding that shows our vaccine may be a useful tool to curb Zika epidemics,” Dr. Salisch noted. “Previous experience with the Ad26 vector platform across our investigational vaccine programs have yielded similarly promising results, most recently with our investigational Janssen COVID-19 vaccine program, for which phase 3 data show a single-dose vaccine met all primary and key secondary endpoints,” she said.

“The biggest barrier [to further development of the candidate vaccine] is one that we actually consider ourselves fortunate to have: The very low incidence of reported Zika cases currently reported worldwide,” Dr. Salisch said. “However, the current Zika case rate can change at any time, and in the event the situation demands it, we are open to alternative regulatory pathways to help us glean the necessary insights on vaccine safety and efficacy to further advance the development of this candidate,” she emphasized.

As for additional research, “there are still questions surrounding Zika transmission and the pathomechanism of congenital Zika syndrome,” said Dr. Salisch. “Our hope is that a correlate of protection against Zika disease, and in particular against congenital Zika syndrome, can be identified,” she said.  

Consider pregnant women in next phase of research

“A major hurdle in ZIKV vaccine development is the inability to conduct large efficacy studies in the absence of a current outbreak,” Ann Chahroudi, MD, of Emory University, Atlanta, and Sallie Permar, MD, of Weill Cornell Medicine, New York, wrote in an accompanying editorial.

The current study provided some efficacy data using a mouse model, but “these data are obviously not conclusive for human protection,” they said.

“A further challenge for ZIKV vaccine efficacy trials will be to demonstrate fetal protection from [congenital Zika syndrome] after adult immunization. There should be a clear plan to readily deploy phase 3 trials for the most promising vaccines to emerge from phase 1 and 2 in the event of an outbreak, as was implemented for Ebola, including infant follow-up,” they emphasized.

The editorialists noted that the study did not include pregnant women, who represent a major target for immunization, but they said that vaccination of pregnant women against other neonatal pathogens such as influenza and tetanus has been effective. “Candidate ZIKV vaccines proven safe in phase 1 trials should immediately be assessed for safety and efficacy in pregnant women,” they said. Although Zika infections are not at epidemic levels currently, resurgence remains a possibility and the coronavirus pandemic “has taught us that preparedness for emerging infections is crucial,” they said.
 

Zika vaccine research is a challenge worth pursuing

“It is important to continue Zika vaccine research because of the unpredictable nature of that infection,” Kevin Ault, MD, of the University of Kansas, Kansas City, said in an interview. “Several times Zika has gained a foothold in unexposed and vulnerable populations,” Dr. Ault said.  “Additionally, there are some data about using this vector during pregnancy, and eventually this vaccine may prevent the birth defects associated with Zika infections during pregnancy, he noted.

Dr. Ault said he was not surprised by the study findings. “This is a promising early phase vaccine candidate, and this adenovirus vector has been used in other similar trials,” he said. Potential barriers to vaccine development include the challenge of conducting late phase clinical trials in pregnant women, he noted. “The relevant endpoint is going to be clinical disease, and one of the most critical populations is pregnant women,” he said. In addition, “later phase 3 trials would be conducted in a population where there is an ongoing Zika outbreak,” Dr. Ault emphasized.   

The study was supported by Janssen Vaccines and Infectious Diseases.

Dr. Chahroudi had no financial conflicts to disclose. Dr. Permar disclosed grants from Merck and Moderna unrelated to the current study. Dr. Ault had no relevant financial conflicts to disclose; he has served as an adviser to the Centers for Disease Control and Prevention, the World Medical Association, the National Vaccine Program Office, and the National Institute for Allergy and Infectious Diseases. He is a fellow of the Infectious Disease Society of American and a fellow of ACOG. 

A Zika virus vaccine candidate prompted antibody responses in 80% of individuals who received two doses in a phase 1 study.

©Aunt_Spray/Thinkstock

Although Zika cases have declined in recent years, “geographic expansion of the Aedes aegypti mosquito to areas where population-level immunity is low poses a substantial risk for future epidemics,” wrote Nadine C. Salisch, PhD, of Janssen Vaccines and Prevention, Leiden, the Netherlands, and colleagues in a paper published in Annals of Internal Medicine.

No vaccine against Zika is yet available, although more than 10 candidates have been studied in preclinical trials to date, they said.

The researchers randomized 100 healthy adult volunteers to an experimental Zika vaccine candidate known as Ad26.ZIKV.001 in either one-dose or two-dose regimens of 5x10¹⁰ viral particles (low dose) or 1x10¹¹ viral particles (high dose) or placebo. Approximately half (55%) of the participants were women, and 72% were White.

Approximately 80% of patients in both two-dose groups showed antibody responses for a year after vaccination. Geometric mean titers (GMTs) reached peak of 823.4 in the low-dose/low-dose group and 961.5 in the high-dose/high-dose group. At day 365, the GMTs for these groups were 68.7 and 87.0, respectively.

A single high-dose vaccine achieved a similar level of neutralizing antibody titers, but lower peak neutralizing responses than the two-dose strategies, the researchers noted.

Most of the reported adverse events were mild to moderate, and short lived; the most common were injection site pain or tenderness, headache, and fatigue, the researchers said. After the first vaccination, 75% of participants in the low-dose groups, 88% of participants in high-dose groups, and 45% of participants receiving placebo reported local adverse events. In addition, 73%, 83%, and 40% of the participants in the low-dose, high-dose, and placebo groups, respectively, reported systemic adverse events. Reports were similar after the second vaccination. Two serious adverse events not related to vaccination were reported; one case of right lower lobe pneumonia and one case of incomplete spontaneous abortion.

The researchers also explored protective efficacy through a nonlethal mouse challenge model. “Transfer of 6 mg of IgG from Ad26.ZIKV.001 vaccines conferred complete protection from viremia in most recipient animals, with statistically significantly decreased breakthrough rates and cumulative viral loads per group compared with placebo,” they said.

The study findings were limited by the inability to assess safety and immunogenicity in an endemic area, the researchers noted. However, “Ad26.ZIKV.001 induces potent ZIKV-specific neutralizing responses with durability of at least 1 year, which supports further clinical development if an unmet medical need reemerges,” they said. “In addition, these data underscore the performance of the Ad26 vaccine platform, which Janssen is using for different infectious diseases, including COVID-19,” they noted.
 

Ad26 vector platform shows consistency

“Development of the investigational Janssen Zika vaccine candidate was initiated in 2015, and while the incidence of Zika virus has declined since the 2015-2016 outbreak, spread of the ‘carrier’ Aedes aegypti mosquito to areas where population-level immunity is low poses a substantial risk for future epidemics,” lead author Dr. Salisch said in an interview. For this reason, researchers say the vaccine warrants further development should the need reemerge, she said.

“Our research has found that while a single higher-dose regimen had lower peak neutralizing responses than a two-dose regimen, it achieved a similar level of neutralizing antibody responses at 1 year, an encouraging finding that shows our vaccine may be a useful tool to curb Zika epidemics,” Dr. Salisch noted. “Previous experience with the Ad26 vector platform across our investigational vaccine programs have yielded similarly promising results, most recently with our investigational Janssen COVID-19 vaccine program, for which phase 3 data show a single-dose vaccine met all primary and key secondary endpoints,” she said.

“The biggest barrier [to further development of the candidate vaccine] is one that we actually consider ourselves fortunate to have: The very low incidence of reported Zika cases currently reported worldwide,” Dr. Salisch said. “However, the current Zika case rate can change at any time, and in the event the situation demands it, we are open to alternative regulatory pathways to help us glean the necessary insights on vaccine safety and efficacy to further advance the development of this candidate,” she emphasized.

As for additional research, “there are still questions surrounding Zika transmission and the pathomechanism of congenital Zika syndrome,” said Dr. Salisch. “Our hope is that a correlate of protection against Zika disease, and in particular against congenital Zika syndrome, can be identified,” she said.  

Consider pregnant women in next phase of research

“A major hurdle in ZIKV vaccine development is the inability to conduct large efficacy studies in the absence of a current outbreak,” Ann Chahroudi, MD, of Emory University, Atlanta, and Sallie Permar, MD, of Weill Cornell Medicine, New York, wrote in an accompanying editorial.

The current study provided some efficacy data using a mouse model, but “these data are obviously not conclusive for human protection,” they said.

“A further challenge for ZIKV vaccine efficacy trials will be to demonstrate fetal protection from [congenital Zika syndrome] after adult immunization. There should be a clear plan to readily deploy phase 3 trials for the most promising vaccines to emerge from phase 1 and 2 in the event of an outbreak, as was implemented for Ebola, including infant follow-up,” they emphasized.

The editorialists noted that the study did not include pregnant women, who represent a major target for immunization, but they said that vaccination of pregnant women against other neonatal pathogens such as influenza and tetanus has been effective. “Candidate ZIKV vaccines proven safe in phase 1 trials should immediately be assessed for safety and efficacy in pregnant women,” they said. Although Zika infections are not at epidemic levels currently, resurgence remains a possibility and the coronavirus pandemic “has taught us that preparedness for emerging infections is crucial,” they said.
 

Zika vaccine research is a challenge worth pursuing

“It is important to continue Zika vaccine research because of the unpredictable nature of that infection,” Kevin Ault, MD, of the University of Kansas, Kansas City, said in an interview. “Several times Zika has gained a foothold in unexposed and vulnerable populations,” Dr. Ault said.  “Additionally, there are some data about using this vector during pregnancy, and eventually this vaccine may prevent the birth defects associated with Zika infections during pregnancy, he noted.

Dr. Ault said he was not surprised by the study findings. “This is a promising early phase vaccine candidate, and this adenovirus vector has been used in other similar trials,” he said. Potential barriers to vaccine development include the challenge of conducting late phase clinical trials in pregnant women, he noted. “The relevant endpoint is going to be clinical disease, and one of the most critical populations is pregnant women,” he said. In addition, “later phase 3 trials would be conducted in a population where there is an ongoing Zika outbreak,” Dr. Ault emphasized.   

The study was supported by Janssen Vaccines and Infectious Diseases.

Dr. Chahroudi had no financial conflicts to disclose. Dr. Permar disclosed grants from Merck and Moderna unrelated to the current study. Dr. Ault had no relevant financial conflicts to disclose; he has served as an adviser to the Centers for Disease Control and Prevention, the World Medical Association, the National Vaccine Program Office, and the National Institute for Allergy and Infectious Diseases. He is a fellow of the Infectious Disease Society of American and a fellow of ACOG. 

Exposure to antibiotics in mid- to late pregnancy was associated with childhood asthma in vaginally born children, in a Danish birth cohort study.

The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.

Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
 

Antibiotic use in pregnancy likely to continue

Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.

The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.

“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”

Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.

To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
 

Children of mothers who took and did not take antibiotics compared

In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.

During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.

In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).

Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.

The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
 

Mode of delivery may matter

The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.

Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.

“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.

“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.

How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.

“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”

The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.

The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.

jremaly@mdedge.com

Exposure to antibiotics in mid- to late pregnancy was associated with childhood asthma in vaginally born children, in a Danish birth cohort study.

The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.

Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
 

Antibiotic use in pregnancy likely to continue

Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.

The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.

“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”

Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.

To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
 

Children of mothers who took and did not take antibiotics compared

In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.

During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.

In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).

Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.

The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
 

Mode of delivery may matter

The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.

Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.

“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.

“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.

How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.

“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”

The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.

The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.

jremaly@mdedge.com

Exposure to antibiotics in mid- to late pregnancy was associated with childhood asthma in vaginally born children, in a Danish birth cohort study.

The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.

Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
 

Antibiotic use in pregnancy likely to continue

Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.

The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.

“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”

Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.

To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
 

Children of mothers who took and did not take antibiotics compared

In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.

During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.

In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).

Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.

The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
 

Mode of delivery may matter

The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.

Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.

“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.

“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.

How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.

“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”

The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.

The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.

jremaly@mdedge.com

Gestational age and weight at discharge for infants aged 24-29 weeks increased steadily between 2005 and 2018, reported Erika M. Edwards, PhD, MPH, of the Vermont Oxford Network, Burlington, and associates.

Metin Kiyak/Thinkstock

Although they discussed several possible influencing factors, the authors were unable to explain the associated benefits, costs, and harms associated with increased age and weight at discharge, which remain undetermined. Infants are separated a week longer than they were at the beginning of the study period, the prolonged effects of which cannot be underestimated, Dr. Edwards and colleagues observed in a large cohort study in Pediatrics.

A total of 314,811 infants 24-29 weeks’ gestational age who were admitted to 824 neonatal ICUs (NICUs) throughout the United States survived to initial discharge. The median postmenstrual age at hospital discharge was 38.3 weeks. Over the 14-year period from 2005 to 2018, unadjusted postmenstrual age at discharge increased a median 9 days, compared with a median adjusted age of 8 days.

Of the 273,109 infants initially discharged from the hospital to home, median weight at discharge was 2,600 g. Over the 14 years from 2005 to 2018, median unadjusted discharge weight increased 360 g, compared with median adjusted weight, which was estimated to have increased 316 g.

Median unadjusted z scores for weight increased 0.22 standard units over the 14-year period, compared with median adjusted z scores for weight at discharge, which increased an estimated 0.19 standard units.

The proportion of infants who were consuming human milk at discharge increased over the study period from 40% in 2005 to 48% in 2018. The use of cardiorespiratory monitors and oxygen decreased from 49% to 26%, and 27% to 22% respectively. The number of infants who were never transferred to specialized care before discharge to home also improved, from 71% to 76%.
 

Despite the unknowns, good news for managing pediatricians?

In a separate interview, study author Dr. Edwards noted that “infants born very preterm, who are discharged home from the NICU today, are larger and more physiologically mature than they were in 2005. Pediatricians will likely find this news to be positive as it may be easier to manage care for a more physiologically mature [infant],” and it may reduce risk of readmission.

“Infants stayed, on average, 8 days longer in 2018 than they did in 2005. That is 8 days when they were not at home with their families. Despite efforts by NICU teams to increase family-centered care, the NICU is not the same as being at home. ... That extra time in the NICU cost [some families] an estimated $28,000. ... As health care costs continue to rise, we need to understand the true cost [behind] this increase,” added Dr. Edwards, noting that more research is needed to understand what may be driving the increase in NICU length of stay and the possible implications. More research to investigate whether babies did better after discharge also is needed.

Going forward, Dr. Edwards indicated that she and her colleagues are exploring ways to measure apnea of prematurity (AOP) and use of continuous pulse oximetry (CPO) as the subject of future studies. In our study, we showed that the number of infants discharged home on a cardiorespiratory monitor decreased, but we do not know if that is explained by differences in management of AOP and CPO. “Understanding the influence of AOP and CPO management on discharge age would be an important contribution [to future research].”
 

AOP may drive increase in postmenstrual age

In an accompanying editorial, Cody Arnold, MD, and Alexis S. Davis, MD, said: “We have focused on apnea of prematurity and discharge countdowns in this commentary because we believe that changes in related practices are likely the most important drivers of the increases in postmenstrual age” reported by the authors in this study. “Other factors, such as increasing availability of NICU beds or decreasing availability of home support services, may have contributed to longer length of stay. But these questions should be answered by research, not by speculation,” said Dr. Arnold, neonatologist, University of Texas Health Sciences Center, Houston, and Dr. Davis, clinical associate professor, Stanford (Calif.) University.

“Prospective research comparing alternative countdown strategies on the basis of readmission rates and other outpatient outcomes is overdue.” Additional research is needed operationally to clearly outline parameters for countdown events, countdown duration, indications for CPO, outpatient caffeine use, and parental shared decision-making.”

The study was funded by the Vermont Oxford Network. Dr. Edwards received a grant from the Vermont Oxford Network; several others also had ties to the Network. Dr. Arnold and Dr. Davis had no conflicts of interest and reported no disclosures.

Gestational age and weight at discharge for infants aged 24-29 weeks increased steadily between 2005 and 2018, reported Erika M. Edwards, PhD, MPH, of the Vermont Oxford Network, Burlington, and associates.

Metin Kiyak/Thinkstock

Although they discussed several possible influencing factors, the authors were unable to explain the associated benefits, costs, and harms associated with increased age and weight at discharge, which remain undetermined. Infants are separated a week longer than they were at the beginning of the study period, the prolonged effects of which cannot be underestimated, Dr. Edwards and colleagues observed in a large cohort study in Pediatrics.

A total of 314,811 infants 24-29 weeks’ gestational age who were admitted to 824 neonatal ICUs (NICUs) throughout the United States survived to initial discharge. The median postmenstrual age at hospital discharge was 38.3 weeks. Over the 14-year period from 2005 to 2018, unadjusted postmenstrual age at discharge increased a median 9 days, compared with a median adjusted age of 8 days.

Of the 273,109 infants initially discharged from the hospital to home, median weight at discharge was 2,600 g. Over the 14 years from 2005 to 2018, median unadjusted discharge weight increased 360 g, compared with median adjusted weight, which was estimated to have increased 316 g.

Median unadjusted z scores for weight increased 0.22 standard units over the 14-year period, compared with median adjusted z scores for weight at discharge, which increased an estimated 0.19 standard units.

The proportion of infants who were consuming human milk at discharge increased over the study period from 40% in 2005 to 48% in 2018. The use of cardiorespiratory monitors and oxygen decreased from 49% to 26%, and 27% to 22% respectively. The number of infants who were never transferred to specialized care before discharge to home also improved, from 71% to 76%.
 

Despite the unknowns, good news for managing pediatricians?

In a separate interview, study author Dr. Edwards noted that “infants born very preterm, who are discharged home from the NICU today, are larger and more physiologically mature than they were in 2005. Pediatricians will likely find this news to be positive as it may be easier to manage care for a more physiologically mature [infant],” and it may reduce risk of readmission.

“Infants stayed, on average, 8 days longer in 2018 than they did in 2005. That is 8 days when they were not at home with their families. Despite efforts by NICU teams to increase family-centered care, the NICU is not the same as being at home. ... That extra time in the NICU cost [some families] an estimated $28,000. ... As health care costs continue to rise, we need to understand the true cost [behind] this increase,” added Dr. Edwards, noting that more research is needed to understand what may be driving the increase in NICU length of stay and the possible implications. More research to investigate whether babies did better after discharge also is needed.

Going forward, Dr. Edwards indicated that she and her colleagues are exploring ways to measure apnea of prematurity (AOP) and use of continuous pulse oximetry (CPO) as the subject of future studies. In our study, we showed that the number of infants discharged home on a cardiorespiratory monitor decreased, but we do not know if that is explained by differences in management of AOP and CPO. “Understanding the influence of AOP and CPO management on discharge age would be an important contribution [to future research].”
 

AOP may drive increase in postmenstrual age

In an accompanying editorial, Cody Arnold, MD, and Alexis S. Davis, MD, said: “We have focused on apnea of prematurity and discharge countdowns in this commentary because we believe that changes in related practices are likely the most important drivers of the increases in postmenstrual age” reported by the authors in this study. “Other factors, such as increasing availability of NICU beds or decreasing availability of home support services, may have contributed to longer length of stay. But these questions should be answered by research, not by speculation,” said Dr. Arnold, neonatologist, University of Texas Health Sciences Center, Houston, and Dr. Davis, clinical associate professor, Stanford (Calif.) University.

“Prospective research comparing alternative countdown strategies on the basis of readmission rates and other outpatient outcomes is overdue.” Additional research is needed operationally to clearly outline parameters for countdown events, countdown duration, indications for CPO, outpatient caffeine use, and parental shared decision-making.”

The study was funded by the Vermont Oxford Network. Dr. Edwards received a grant from the Vermont Oxford Network; several others also had ties to the Network. Dr. Arnold and Dr. Davis had no conflicts of interest and reported no disclosures.

Gestational age and weight at discharge for infants aged 24-29 weeks increased steadily between 2005 and 2018, reported Erika M. Edwards, PhD, MPH, of the Vermont Oxford Network, Burlington, and associates.

Metin Kiyak/Thinkstock

Although they discussed several possible influencing factors, the authors were unable to explain the associated benefits, costs, and harms associated with increased age and weight at discharge, which remain undetermined. Infants are separated a week longer than they were at the beginning of the study period, the prolonged effects of which cannot be underestimated, Dr. Edwards and colleagues observed in a large cohort study in Pediatrics.

A total of 314,811 infants 24-29 weeks’ gestational age who were admitted to 824 neonatal ICUs (NICUs) throughout the United States survived to initial discharge. The median postmenstrual age at hospital discharge was 38.3 weeks. Over the 14-year period from 2005 to 2018, unadjusted postmenstrual age at discharge increased a median 9 days, compared with a median adjusted age of 8 days.

Of the 273,109 infants initially discharged from the hospital to home, median weight at discharge was 2,600 g. Over the 14 years from 2005 to 2018, median unadjusted discharge weight increased 360 g, compared with median adjusted weight, which was estimated to have increased 316 g.

Median unadjusted z scores for weight increased 0.22 standard units over the 14-year period, compared with median adjusted z scores for weight at discharge, which increased an estimated 0.19 standard units.

The proportion of infants who were consuming human milk at discharge increased over the study period from 40% in 2005 to 48% in 2018. The use of cardiorespiratory monitors and oxygen decreased from 49% to 26%, and 27% to 22% respectively. The number of infants who were never transferred to specialized care before discharge to home also improved, from 71% to 76%.
 

Despite the unknowns, good news for managing pediatricians?

In a separate interview, study author Dr. Edwards noted that “infants born very preterm, who are discharged home from the NICU today, are larger and more physiologically mature than they were in 2005. Pediatricians will likely find this news to be positive as it may be easier to manage care for a more physiologically mature [infant],” and it may reduce risk of readmission.

“Infants stayed, on average, 8 days longer in 2018 than they did in 2005. That is 8 days when they were not at home with their families. Despite efforts by NICU teams to increase family-centered care, the NICU is not the same as being at home. ... That extra time in the NICU cost [some families] an estimated $28,000. ... As health care costs continue to rise, we need to understand the true cost [behind] this increase,” added Dr. Edwards, noting that more research is needed to understand what may be driving the increase in NICU length of stay and the possible implications. More research to investigate whether babies did better after discharge also is needed.

Going forward, Dr. Edwards indicated that she and her colleagues are exploring ways to measure apnea of prematurity (AOP) and use of continuous pulse oximetry (CPO) as the subject of future studies. In our study, we showed that the number of infants discharged home on a cardiorespiratory monitor decreased, but we do not know if that is explained by differences in management of AOP and CPO. “Understanding the influence of AOP and CPO management on discharge age would be an important contribution [to future research].”
 

AOP may drive increase in postmenstrual age

In an accompanying editorial, Cody Arnold, MD, and Alexis S. Davis, MD, said: “We have focused on apnea of prematurity and discharge countdowns in this commentary because we believe that changes in related practices are likely the most important drivers of the increases in postmenstrual age” reported by the authors in this study. “Other factors, such as increasing availability of NICU beds or decreasing availability of home support services, may have contributed to longer length of stay. But these questions should be answered by research, not by speculation,” said Dr. Arnold, neonatologist, University of Texas Health Sciences Center, Houston, and Dr. Davis, clinical associate professor, Stanford (Calif.) University.

“Prospective research comparing alternative countdown strategies on the basis of readmission rates and other outpatient outcomes is overdue.” Additional research is needed operationally to clearly outline parameters for countdown events, countdown duration, indications for CPO, outpatient caffeine use, and parental shared decision-making.”

The study was funded by the Vermont Oxford Network. Dr. Edwards received a grant from the Vermont Oxford Network; several others also had ties to the Network. Dr. Arnold and Dr. Davis had no conflicts of interest and reported no disclosures.

Developmental outcomes in the first 2 years of life improved in children whose mothers received the revised Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) while pregnant, based on data from approximately 1,200 women.

Maternal nutrition is essential to healthy fetal development, and the WIC was revised in 2009 to align with current dietary guidelines and to support the health of women and children in low-income households, wrote Alice Guan, MPH, of the University of California, San Francisco, and colleagues.

“However, no researchers, to our knowledge, have evaluated effects of this revision on downstream child health or development,” they said.

In a study published in Pediatrics, the researchers reviewed data from mothers and their children who participated in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) longitudinal cohort study conducted in Tennessee between 2006 and 2011. Their quasi-experimental analysis included 700 women who received WIC during pregnancy and 525 women who did not.

The researchers considered core developmental outcomes of child growth, cognitive development, and socioemotional development at age 12 months and 24 months, and age 4-6 years.

Overall, infants of women who received the WIC food package showed significant increases in length-for-age z scores at 12 months of age (.33, representing approximately one-fifth of a standard deviation), compared to infants of women who did not receive the revised WIC package.

In addition, the Bayley Scales of Infant Development cognitive composite score showed a 4.3-point increase at 24 months of age (approximately one-third of a standard deviation) compared to infants of women who did not receive the revised WIC package.

No effects on growth at age 24 months or on cognitive development at age 4-6 years were noted, which suggests that the impact of the WIC program during pregnancy may fade over time, the researchers said.

“The magnitude of the findings in this study represents clinically relevant effect sizes and provides evidence that one of the largest U.S. safety net policies improves developmental outcomes among low-income and marginalized children,” they noted.

The study findings were limited by several factors including the statistical, quasi-experimental design; the reliance on self-reports for information on income, receipt of WIC, and other variables; and a potential lack of generalizability to other states, the researchers noted. However, the results support findings from previous studies and were strengthened by the review of multiple outcomes and use of a longitudinal database, they said.

“These findings provide timely and critical evidence for the role that WIC plays in improving the health of the nation’s most vulnerable populations, suggesting meaningful impacts of the revised WIC food package on child development,” the researchers said. In addition, “considering the relatively modest scope of the 2009 revision, more substantial updates to the program based on up-to-date nutritional guidance may have substantial effects on improving the health of WIC recipients,” they concluded.
 

Findings support program’s value

“Pediatrics has always had a commitment to reducing disparities in health care, and we are the main clinicians to see many Medicaid patients on a regular basis,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.

“We all know that pregnant women eating nutritiously ought to help child outcomes, but the current study provides an evidence base for something that seems like common sense,” he noted.

Having such an evidence base is helpful to reinforce the value of the WIC program for its intended recipients, especially in the wake of the COVID-19 pandemic when many funding sources are stretched thin, Dr. Lessin said.

The WIC is intended to try to reduce racial and socioeconomic disparities in the most basic form possible, by helping people who are disadvantaged get enough high-quality food to eat, but results of the program’s impact have not been well studied, he said.

“Outcomes are fiendishly difficult to measure,” and the study is subject to the limitations of its statistical nature, he said. But the large sample size adds support to the findings, which are encouraging, Dr. Lessin noted.

Other potential areas for research include comparing the quality of WIC programs in different states, but such research is very difficult, Dr. Lessin noted. However, the findings might encourage states with less robust WIC programs to consider increasing support, he said.

The study was funded by the National Institutes of Health (National Heart, Lung, and Blood Institute); the National Institute on Aging; the University of California, San Francisco, National Center of Excellence in Women’s Health; and the Urban Child Institute. The researchers had no financial conflicts to disclose. Dr. Lessin serves on the editorial advisory board of Pediatric News and had no relevant financial conflicts to disclose.

pdnews@mdedge.com

Developmental outcomes in the first 2 years of life improved in children whose mothers received the revised Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) while pregnant, based on data from approximately 1,200 women.

Maternal nutrition is essential to healthy fetal development, and the WIC was revised in 2009 to align with current dietary guidelines and to support the health of women and children in low-income households, wrote Alice Guan, MPH, of the University of California, San Francisco, and colleagues.

“However, no researchers, to our knowledge, have evaluated effects of this revision on downstream child health or development,” they said.

In a study published in Pediatrics, the researchers reviewed data from mothers and their children who participated in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) longitudinal cohort study conducted in Tennessee between 2006 and 2011. Their quasi-experimental analysis included 700 women who received WIC during pregnancy and 525 women who did not.

The researchers considered core developmental outcomes of child growth, cognitive development, and socioemotional development at age 12 months and 24 months, and age 4-6 years.

Overall, infants of women who received the WIC food package showed significant increases in length-for-age z scores at 12 months of age (.33, representing approximately one-fifth of a standard deviation), compared to infants of women who did not receive the revised WIC package.

In addition, the Bayley Scales of Infant Development cognitive composite score showed a 4.3-point increase at 24 months of age (approximately one-third of a standard deviation) compared to infants of women who did not receive the revised WIC package.

No effects on growth at age 24 months or on cognitive development at age 4-6 years were noted, which suggests that the impact of the WIC program during pregnancy may fade over time, the researchers said.

“The magnitude of the findings in this study represents clinically relevant effect sizes and provides evidence that one of the largest U.S. safety net policies improves developmental outcomes among low-income and marginalized children,” they noted.

The study findings were limited by several factors including the statistical, quasi-experimental design; the reliance on self-reports for information on income, receipt of WIC, and other variables; and a potential lack of generalizability to other states, the researchers noted. However, the results support findings from previous studies and were strengthened by the review of multiple outcomes and use of a longitudinal database, they said.

“These findings provide timely and critical evidence for the role that WIC plays in improving the health of the nation’s most vulnerable populations, suggesting meaningful impacts of the revised WIC food package on child development,” the researchers said. In addition, “considering the relatively modest scope of the 2009 revision, more substantial updates to the program based on up-to-date nutritional guidance may have substantial effects on improving the health of WIC recipients,” they concluded.
 

Findings support program’s value

“Pediatrics has always had a commitment to reducing disparities in health care, and we are the main clinicians to see many Medicaid patients on a regular basis,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.

“We all know that pregnant women eating nutritiously ought to help child outcomes, but the current study provides an evidence base for something that seems like common sense,” he noted.

Having such an evidence base is helpful to reinforce the value of the WIC program for its intended recipients, especially in the wake of the COVID-19 pandemic when many funding sources are stretched thin, Dr. Lessin said.

The WIC is intended to try to reduce racial and socioeconomic disparities in the most basic form possible, by helping people who are disadvantaged get enough high-quality food to eat, but results of the program’s impact have not been well studied, he said.

“Outcomes are fiendishly difficult to measure,” and the study is subject to the limitations of its statistical nature, he said. But the large sample size adds support to the findings, which are encouraging, Dr. Lessin noted.

Other potential areas for research include comparing the quality of WIC programs in different states, but such research is very difficult, Dr. Lessin noted. However, the findings might encourage states with less robust WIC programs to consider increasing support, he said.

The study was funded by the National Institutes of Health (National Heart, Lung, and Blood Institute); the National Institute on Aging; the University of California, San Francisco, National Center of Excellence in Women’s Health; and the Urban Child Institute. The researchers had no financial conflicts to disclose. Dr. Lessin serves on the editorial advisory board of Pediatric News and had no relevant financial conflicts to disclose.

pdnews@mdedge.com

Developmental outcomes in the first 2 years of life improved in children whose mothers received the revised Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) while pregnant, based on data from approximately 1,200 women.

Maternal nutrition is essential to healthy fetal development, and the WIC was revised in 2009 to align with current dietary guidelines and to support the health of women and children in low-income households, wrote Alice Guan, MPH, of the University of California, San Francisco, and colleagues.

“However, no researchers, to our knowledge, have evaluated effects of this revision on downstream child health or development,” they said.

In a study published in Pediatrics, the researchers reviewed data from mothers and their children who participated in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) longitudinal cohort study conducted in Tennessee between 2006 and 2011. Their quasi-experimental analysis included 700 women who received WIC during pregnancy and 525 women who did not.

The researchers considered core developmental outcomes of child growth, cognitive development, and socioemotional development at age 12 months and 24 months, and age 4-6 years.

Overall, infants of women who received the WIC food package showed significant increases in length-for-age z scores at 12 months of age (.33, representing approximately one-fifth of a standard deviation), compared to infants of women who did not receive the revised WIC package.

In addition, the Bayley Scales of Infant Development cognitive composite score showed a 4.3-point increase at 24 months of age (approximately one-third of a standard deviation) compared to infants of women who did not receive the revised WIC package.

No effects on growth at age 24 months or on cognitive development at age 4-6 years were noted, which suggests that the impact of the WIC program during pregnancy may fade over time, the researchers said.

“The magnitude of the findings in this study represents clinically relevant effect sizes and provides evidence that one of the largest U.S. safety net policies improves developmental outcomes among low-income and marginalized children,” they noted.

The study findings were limited by several factors including the statistical, quasi-experimental design; the reliance on self-reports for information on income, receipt of WIC, and other variables; and a potential lack of generalizability to other states, the researchers noted. However, the results support findings from previous studies and were strengthened by the review of multiple outcomes and use of a longitudinal database, they said.

“These findings provide timely and critical evidence for the role that WIC plays in improving the health of the nation’s most vulnerable populations, suggesting meaningful impacts of the revised WIC food package on child development,” the researchers said. In addition, “considering the relatively modest scope of the 2009 revision, more substantial updates to the program based on up-to-date nutritional guidance may have substantial effects on improving the health of WIC recipients,” they concluded.
 

Findings support program’s value

“Pediatrics has always had a commitment to reducing disparities in health care, and we are the main clinicians to see many Medicaid patients on a regular basis,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.

“We all know that pregnant women eating nutritiously ought to help child outcomes, but the current study provides an evidence base for something that seems like common sense,” he noted.

Having such an evidence base is helpful to reinforce the value of the WIC program for its intended recipients, especially in the wake of the COVID-19 pandemic when many funding sources are stretched thin, Dr. Lessin said.

The WIC is intended to try to reduce racial and socioeconomic disparities in the most basic form possible, by helping people who are disadvantaged get enough high-quality food to eat, but results of the program’s impact have not been well studied, he said.

“Outcomes are fiendishly difficult to measure,” and the study is subject to the limitations of its statistical nature, he said. But the large sample size adds support to the findings, which are encouraging, Dr. Lessin noted.

Other potential areas for research include comparing the quality of WIC programs in different states, but such research is very difficult, Dr. Lessin noted. However, the findings might encourage states with less robust WIC programs to consider increasing support, he said.

The study was funded by the National Institutes of Health (National Heart, Lung, and Blood Institute); the National Institute on Aging; the University of California, San Francisco, National Center of Excellence in Women’s Health; and the Urban Child Institute. The researchers had no financial conflicts to disclose. Dr. Lessin serves on the editorial advisory board of Pediatric News and had no relevant financial conflicts to disclose.

pdnews@mdedge.com

Does the name Bruce Lipton sound familiar to you? Until a few years ago the only bell that it rang with me was that I had a high school classmate named Bruce Lipton. I recall that his father owned the local grocery store and he was one of the most prolific pranksters in a class with a long history of prank playing. If the name dredges up any associations for you it may because you have heard of a PhD biologist who has written and lectured extensively on epigenetics. You may have even read his most widely published book, “The Biology of Belief.” It turns out the Epigenetics Guy and my high school prankster classmate are one and the same.

After decades of separation – he is in California and I’m here in Maine – we have reconnected via Zoom mini reunions that our class has organized to combat the isolation that has descended on us with the pandemic. While I haven’t read his books, I have watched and listened to some of his podcasts and lectures. The devilish twinkle in his eye in the 1950s and 1960s has provided the scaffolding on which he has built a charismatic and persuasive presentation style.

Bruce was no dummy in school but his early career as a cell biologist doing research in stem-cell function was a surprise to all of us. But then high school reunions are often full of surprises and should serve as good reminders of the danger of profiling and pigeon-holing adolescents.

Professor Lipton’s take on epigenetics boils down to the notion that our genome should merely be considered a blueprint and not the final determinant of who we are and what illnesses befall us. His research and observations suggest to him that there are an uncountable number extragenomic factors, including environmental conditions and our belief systems, that can influence how that blueprint is read and the resulting expression of the genes we have inherited.

At face value, Bruce’s basic premise falls very close to some of the conclusions I have toyed with in an attempt to explain what I have observed doing primary care pediatrics. For example, I have trouble blaming the meteoric rise of the ADHD phenomenon on a genetic mutation. I suspect there are likely to be extragenomic forces coming into play, such as sleep deprivation and changing child-rearing practices. In my Oct. 9, 2020, Letters from Maine column I referred to a Swedish twins study that suggested children from a family with a strong history of depression were more likely to develop depression when raised in an adopted family that experienced domestic turmoil. His philosophy also fits with my sense that I have more control over my own health outcomes than many other people.

However, Professor Lipton and I part company (just philosophically that is) when he slips into hyperbole and applies what he terms as the New Biology too broadly. He may be correct that the revolutionary changes which came in the wake of Watson and Crick’s double helix discovery have resulted in a view of pathophysiology that is overly focused on what we are learning about our genome. On the other hand it is refreshing to hear someone with his charismatic and persuasive skills question the status quo.

If you haven’t listened to what he has to say I urge you to browse the Internet and sample some of his talks. I am sure you will find what he has to say stimulating. I doubt you will buy his whole package but I suspect you may find some bits you can agree with.

It still boils down to the old nature versus nurture argument. He’s all in for nurture. I’m still more comfortable straddling the fence.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Does the name Bruce Lipton sound familiar to you? Until a few years ago the only bell that it rang with me was that I had a high school classmate named Bruce Lipton. I recall that his father owned the local grocery store and he was one of the most prolific pranksters in a class with a long history of prank playing. If the name dredges up any associations for you it may because you have heard of a PhD biologist who has written and lectured extensively on epigenetics. You may have even read his most widely published book, “The Biology of Belief.” It turns out the Epigenetics Guy and my high school prankster classmate are one and the same.

After decades of separation – he is in California and I’m here in Maine – we have reconnected via Zoom mini reunions that our class has organized to combat the isolation that has descended on us with the pandemic. While I haven’t read his books, I have watched and listened to some of his podcasts and lectures. The devilish twinkle in his eye in the 1950s and 1960s has provided the scaffolding on which he has built a charismatic and persuasive presentation style.

Bruce was no dummy in school but his early career as a cell biologist doing research in stem-cell function was a surprise to all of us. But then high school reunions are often full of surprises and should serve as good reminders of the danger of profiling and pigeon-holing adolescents.

Professor Lipton’s take on epigenetics boils down to the notion that our genome should merely be considered a blueprint and not the final determinant of who we are and what illnesses befall us. His research and observations suggest to him that there are an uncountable number extragenomic factors, including environmental conditions and our belief systems, that can influence how that blueprint is read and the resulting expression of the genes we have inherited.

At face value, Bruce’s basic premise falls very close to some of the conclusions I have toyed with in an attempt to explain what I have observed doing primary care pediatrics. For example, I have trouble blaming the meteoric rise of the ADHD phenomenon on a genetic mutation. I suspect there are likely to be extragenomic forces coming into play, such as sleep deprivation and changing child-rearing practices. In my Oct. 9, 2020, Letters from Maine column I referred to a Swedish twins study that suggested children from a family with a strong history of depression were more likely to develop depression when raised in an adopted family that experienced domestic turmoil. His philosophy also fits with my sense that I have more control over my own health outcomes than many other people.

However, Professor Lipton and I part company (just philosophically that is) when he slips into hyperbole and applies what he terms as the New Biology too broadly. He may be correct that the revolutionary changes which came in the wake of Watson and Crick’s double helix discovery have resulted in a view of pathophysiology that is overly focused on what we are learning about our genome. On the other hand it is refreshing to hear someone with his charismatic and persuasive skills question the status quo.

If you haven’t listened to what he has to say I urge you to browse the Internet and sample some of his talks. I am sure you will find what he has to say stimulating. I doubt you will buy his whole package but I suspect you may find some bits you can agree with.

It still boils down to the old nature versus nurture argument. He’s all in for nurture. I’m still more comfortable straddling the fence.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Does the name Bruce Lipton sound familiar to you? Until a few years ago the only bell that it rang with me was that I had a high school classmate named Bruce Lipton. I recall that his father owned the local grocery store and he was one of the most prolific pranksters in a class with a long history of prank playing. If the name dredges up any associations for you it may because you have heard of a PhD biologist who has written and lectured extensively on epigenetics. You may have even read his most widely published book, “The Biology of Belief.” It turns out the Epigenetics Guy and my high school prankster classmate are one and the same.

After decades of separation – he is in California and I’m here in Maine – we have reconnected via Zoom mini reunions that our class has organized to combat the isolation that has descended on us with the pandemic. While I haven’t read his books, I have watched and listened to some of his podcasts and lectures. The devilish twinkle in his eye in the 1950s and 1960s has provided the scaffolding on which he has built a charismatic and persuasive presentation style.

Bruce was no dummy in school but his early career as a cell biologist doing research in stem-cell function was a surprise to all of us. But then high school reunions are often full of surprises and should serve as good reminders of the danger of profiling and pigeon-holing adolescents.

Professor Lipton’s take on epigenetics boils down to the notion that our genome should merely be considered a blueprint and not the final determinant of who we are and what illnesses befall us. His research and observations suggest to him that there are an uncountable number extragenomic factors, including environmental conditions and our belief systems, that can influence how that blueprint is read and the resulting expression of the genes we have inherited.

At face value, Bruce’s basic premise falls very close to some of the conclusions I have toyed with in an attempt to explain what I have observed doing primary care pediatrics. For example, I have trouble blaming the meteoric rise of the ADHD phenomenon on a genetic mutation. I suspect there are likely to be extragenomic forces coming into play, such as sleep deprivation and changing child-rearing practices. In my Oct. 9, 2020, Letters from Maine column I referred to a Swedish twins study that suggested children from a family with a strong history of depression were more likely to develop depression when raised in an adopted family that experienced domestic turmoil. His philosophy also fits with my sense that I have more control over my own health outcomes than many other people.

However, Professor Lipton and I part company (just philosophically that is) when he slips into hyperbole and applies what he terms as the New Biology too broadly. He may be correct that the revolutionary changes which came in the wake of Watson and Crick’s double helix discovery have resulted in a view of pathophysiology that is overly focused on what we are learning about our genome. On the other hand it is refreshing to hear someone with his charismatic and persuasive skills question the status quo.

If you haven’t listened to what he has to say I urge you to browse the Internet and sample some of his talks. I am sure you will find what he has to say stimulating. I doubt you will buy his whole package but I suspect you may find some bits you can agree with.

It still boils down to the old nature versus nurture argument. He’s all in for nurture. I’m still more comfortable straddling the fence.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Antibodies against SARS-CoV-2 cross the placenta during pregnancy and are detectable in most newborns born to mothers who had COVID-19 during pregnancy, according to findings from a study presented Jan. 28 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“I think the most striking finding is that we noticed a high degree of neutralizing response to natural infection even among asymptomatic infection, but of course a higher degree was seen in those with symptomatic infection,” Naima Joseph, MD, MPH, of Emory University, Atlanta, said in an interview.

“Our data demonstrate maternal capacity to mount an appropriate and robust immune response,” and maternal protective immunity lasted at least 28 days after infection, Dr. Joseph said. “Also, we noted higher neonatal cord blood titers in moms with higher titers, which suggests a relationship, but we need to better understand how transplacental transfer occurs as well as establish neonatal correlates of protection in order to see if and how maternal immunity may also benefit neonates.”

The researchers analyzed the amount of IgG and IgM antibodies in maternal and cord blood samples prospectively collected at delivery from women who tested positive for COVID-19 at any time while pregnant. They used enzyme-linked immunosorbent assay to assess for antibodies for the receptor binding domain of the SARS-CoV-2 spike protein.

The 32 pairs of mothers and infants in the study were predominantly non-Hispanic Black (72%) and Hispanic (25%), and 84% used Medicaid as their payer. Most of the mothers (72%) had at least one comorbidity, most commonly obesity, hypertension, and asthma or pulmonary disease. Just over half the women (53%) were symptomatic while they were infected, and 88% were ill with COVID-19 during the third trimester. The average time from infection to delivery was 28 days.

All the mothers had IgG antibodies, 94% had IgM antibodies, and 94% had neutralizing antibodies against SARS-CoV-2. Among the cord blood samples, 91% had IgG antibodies, 9% had IgM antibodies, and 25% had neutralizing antibodies.

“It’s reassuring that, so far, the physiological response is exactly what we expected it to be,” Judette Louis, MD, MPH, an associate professor of ob.gyn. and the ob.gyn. department chair at the University of South Florida, Tampa, said in an interview. “It’s what we would expect, but it’s always helpful to have more data to support that. Otherwise, you’re extrapolating from what you know from other conditions,” said Dr. Louis, who moderated the oral abstracts session.

Symptomatic infection was associated with significantly higher IgG titers than asymptomatic infection (P = .03), but no correlation was seen for IgM or neutralizing antibodies. In addition, although mothers who delivered more than 28 days after their infection had higher IgG titers (P = .05), no differences existed in IgM or neutralizing response.

Infants’ cord blood titers were significantly lower than their corresponding maternal samples, independently of symptoms or latency from infection to delivery (P < .001), Dr. Joseph reported.

“Transplacental efficiency in other pathogens has been shown to be correlated with neonatal immunity when the ratio of cord to maternal blood is greater than 1,” Dr. Joseph said in her presentation. Their data showed “suboptimal efficiency” at a ratio of 0.81.

The study’s small sample size and lack of a control group were weaknesses, but a major strength was having a population at disproportionately higher risk for infection and severe morbidity than the general population.
 

Implications for maternal COVID-19 vaccination

Although the data are not yet available, Dr. Joseph said they have expanded their protocol to include vaccinated pregnant women.

“The key to developing an effective vaccine [for pregnant people] is in really characterizing adaptive immunity in pregnancy,” Dr. Joseph told SMFM attendees. “I think that these findings inform further vaccine development in demonstrating that maternal immunity is robust.”

The World Health Organization recently recommended withholding COVID-19 vaccines from pregnant people, but the SMFM and American College of Obstetricians and Gynecologists subsequently issued a joint statement reaffirming that the COVID-19 vaccines authorized by the FDA “should not be withheld from pregnant individuals who choose to receive the vaccine.”

“One of the questions people ask is whether in pregnancy you’re going to mount a good response to the vaccine the way you would outside of pregnancy,” Dr. Louis said. “If we can demonstrate that you do, that may provide the information that some mothers need to make their decisions.” Data such as those from Dr. Joseph’s study can also inform recommendations on timing of maternal vaccination.

“For instance, Dr. Joseph demonstrated that, 28 days out from the infection, you had more antibodies, so there may be a scenario where we say this vaccine may be more beneficial in the middle of the pregnancy for the purpose of forming those antibodies,” Dr. Louis said.
 

Consensus emerging from maternal antibodies data

The findings from Dr. Joseph’s study mirror those reported in a study published online Jan. 29 in JAMA Pediatrics. That study, led by Dustin D. Flannery, DO, MSCE, of Children’s Hospital of Philadelphia, also examined maternal and neonatal levels of IgG and IgM antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. They also found a positive correlation between cord blood and maternal IgG concentrations (P < .001), but notably, the ratio of cord to maternal blood titers was greater than 1, unlike in Dr. Joseph’s study.

For their study, Dr. Flannery and colleagues obtained maternal and cord blood sera at the time of delivery from 1471 pairs of mothers and infants, independently of COVID status during pregnancy. The average maternal age was 32 years, and just over a quarter of the population (26%) were Black, non-Hispanic women. About half (51%) were White, 12% were Hispanic, and 7% were Asian.

About 6% of the women had either IgG or IgM antibodies at delivery, and 87% of infants born to those mothers had measurable IgG in their cord blood. No infants had IgM antibodies. As with the study presented at SMFM, the mothers’ infections included asymptomatic, mild, moderate, and severe cases, and the degree of severity of cases had no apparent effect on infant antibody concentrations. Most of the women who tested positive for COVID-19 (60%) were asymptomatic.

Among the 11 mothers who had antibodies but whose infants’ cord blood did not, 5 had only IgM antibodies, and 6 had significantly lower IgG concentrations than those seen in the other mothers.

In a commentary about the JAMA Pediatrics study, Flor Munoz, MD, of the Baylor College of Medicine, Houston, suggested that the findings are grounds for optimism about a maternal vaccination strategy to protect infants from COVID-19.

“However, the timing of maternal vaccination to protect the infant, as opposed to the mother alone, would necessitate an adequate interval from vaccination to delivery (of at least 4 weeks), while vaccination early in gestation and even late in the third trimester could still be protective for the mother,” Dr. Munoz wrote.

Given the interval between two-dose vaccination regimens and the fact that transplacental transfer begins at about the 17th week of gestation, “maternal vaccination starting in the early second trimester of gestation might be optimal to achieve the highest levels of antibodies in the newborn,” Dr. Munoz wrote. But questions remain, such as how effective the neonatal antibodies would be in protecting against COVID-19 and how long they last after birth.

No external funding was used in Dr. Joseph’s study. Dr. Joseph and Dr. Louis have disclosed no relevant financial relationships. The JAMA Pediatrics study was funded by the Children’s Hospital of Philadelphia. One coauthor received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck unrelated to the study. Dr. Munoz served on the data and safety monitoring boards of Moderna, Pfizer, Virometix, and Meissa Vaccines and has received grants from Novavax Research and Gilead Research.

A version of this article first appeared on Medscape.com.

Antibodies against SARS-CoV-2 cross the placenta during pregnancy and are detectable in most newborns born to mothers who had COVID-19 during pregnancy, according to findings from a study presented Jan. 28 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“I think the most striking finding is that we noticed a high degree of neutralizing response to natural infection even among asymptomatic infection, but of course a higher degree was seen in those with symptomatic infection,” Naima Joseph, MD, MPH, of Emory University, Atlanta, said in an interview.

“Our data demonstrate maternal capacity to mount an appropriate and robust immune response,” and maternal protective immunity lasted at least 28 days after infection, Dr. Joseph said. “Also, we noted higher neonatal cord blood titers in moms with higher titers, which suggests a relationship, but we need to better understand how transplacental transfer occurs as well as establish neonatal correlates of protection in order to see if and how maternal immunity may also benefit neonates.”

The researchers analyzed the amount of IgG and IgM antibodies in maternal and cord blood samples prospectively collected at delivery from women who tested positive for COVID-19 at any time while pregnant. They used enzyme-linked immunosorbent assay to assess for antibodies for the receptor binding domain of the SARS-CoV-2 spike protein.

The 32 pairs of mothers and infants in the study were predominantly non-Hispanic Black (72%) and Hispanic (25%), and 84% used Medicaid as their payer. Most of the mothers (72%) had at least one comorbidity, most commonly obesity, hypertension, and asthma or pulmonary disease. Just over half the women (53%) were symptomatic while they were infected, and 88% were ill with COVID-19 during the third trimester. The average time from infection to delivery was 28 days.

All the mothers had IgG antibodies, 94% had IgM antibodies, and 94% had neutralizing antibodies against SARS-CoV-2. Among the cord blood samples, 91% had IgG antibodies, 9% had IgM antibodies, and 25% had neutralizing antibodies.

“It’s reassuring that, so far, the physiological response is exactly what we expected it to be,” Judette Louis, MD, MPH, an associate professor of ob.gyn. and the ob.gyn. department chair at the University of South Florida, Tampa, said in an interview. “It’s what we would expect, but it’s always helpful to have more data to support that. Otherwise, you’re extrapolating from what you know from other conditions,” said Dr. Louis, who moderated the oral abstracts session.

Symptomatic infection was associated with significantly higher IgG titers than asymptomatic infection (P = .03), but no correlation was seen for IgM or neutralizing antibodies. In addition, although mothers who delivered more than 28 days after their infection had higher IgG titers (P = .05), no differences existed in IgM or neutralizing response.

Infants’ cord blood titers were significantly lower than their corresponding maternal samples, independently of symptoms or latency from infection to delivery (P < .001), Dr. Joseph reported.

“Transplacental efficiency in other pathogens has been shown to be correlated with neonatal immunity when the ratio of cord to maternal blood is greater than 1,” Dr. Joseph said in her presentation. Their data showed “suboptimal efficiency” at a ratio of 0.81.

The study’s small sample size and lack of a control group were weaknesses, but a major strength was having a population at disproportionately higher risk for infection and severe morbidity than the general population.
 

Implications for maternal COVID-19 vaccination

Although the data are not yet available, Dr. Joseph said they have expanded their protocol to include vaccinated pregnant women.

“The key to developing an effective vaccine [for pregnant people] is in really characterizing adaptive immunity in pregnancy,” Dr. Joseph told SMFM attendees. “I think that these findings inform further vaccine development in demonstrating that maternal immunity is robust.”

The World Health Organization recently recommended withholding COVID-19 vaccines from pregnant people, but the SMFM and American College of Obstetricians and Gynecologists subsequently issued a joint statement reaffirming that the COVID-19 vaccines authorized by the FDA “should not be withheld from pregnant individuals who choose to receive the vaccine.”

“One of the questions people ask is whether in pregnancy you’re going to mount a good response to the vaccine the way you would outside of pregnancy,” Dr. Louis said. “If we can demonstrate that you do, that may provide the information that some mothers need to make their decisions.” Data such as those from Dr. Joseph’s study can also inform recommendations on timing of maternal vaccination.

“For instance, Dr. Joseph demonstrated that, 28 days out from the infection, you had more antibodies, so there may be a scenario where we say this vaccine may be more beneficial in the middle of the pregnancy for the purpose of forming those antibodies,” Dr. Louis said.
 

Consensus emerging from maternal antibodies data

The findings from Dr. Joseph’s study mirror those reported in a study published online Jan. 29 in JAMA Pediatrics. That study, led by Dustin D. Flannery, DO, MSCE, of Children’s Hospital of Philadelphia, also examined maternal and neonatal levels of IgG and IgM antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. They also found a positive correlation between cord blood and maternal IgG concentrations (P < .001), but notably, the ratio of cord to maternal blood titers was greater than 1, unlike in Dr. Joseph’s study.

For their study, Dr. Flannery and colleagues obtained maternal and cord blood sera at the time of delivery from 1471 pairs of mothers and infants, independently of COVID status during pregnancy. The average maternal age was 32 years, and just over a quarter of the population (26%) were Black, non-Hispanic women. About half (51%) were White, 12% were Hispanic, and 7% were Asian.

About 6% of the women had either IgG or IgM antibodies at delivery, and 87% of infants born to those mothers had measurable IgG in their cord blood. No infants had IgM antibodies. As with the study presented at SMFM, the mothers’ infections included asymptomatic, mild, moderate, and severe cases, and the degree of severity of cases had no apparent effect on infant antibody concentrations. Most of the women who tested positive for COVID-19 (60%) were asymptomatic.

Among the 11 mothers who had antibodies but whose infants’ cord blood did not, 5 had only IgM antibodies, and 6 had significantly lower IgG concentrations than those seen in the other mothers.

In a commentary about the JAMA Pediatrics study, Flor Munoz, MD, of the Baylor College of Medicine, Houston, suggested that the findings are grounds for optimism about a maternal vaccination strategy to protect infants from COVID-19.

“However, the timing of maternal vaccination to protect the infant, as opposed to the mother alone, would necessitate an adequate interval from vaccination to delivery (of at least 4 weeks), while vaccination early in gestation and even late in the third trimester could still be protective for the mother,” Dr. Munoz wrote.

Given the interval between two-dose vaccination regimens and the fact that transplacental transfer begins at about the 17th week of gestation, “maternal vaccination starting in the early second trimester of gestation might be optimal to achieve the highest levels of antibodies in the newborn,” Dr. Munoz wrote. But questions remain, such as how effective the neonatal antibodies would be in protecting against COVID-19 and how long they last after birth.

No external funding was used in Dr. Joseph’s study. Dr. Joseph and Dr. Louis have disclosed no relevant financial relationships. The JAMA Pediatrics study was funded by the Children’s Hospital of Philadelphia. One coauthor received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck unrelated to the study. Dr. Munoz served on the data and safety monitoring boards of Moderna, Pfizer, Virometix, and Meissa Vaccines and has received grants from Novavax Research and Gilead Research.

A version of this article first appeared on Medscape.com.

Antibodies against SARS-CoV-2 cross the placenta during pregnancy and are detectable in most newborns born to mothers who had COVID-19 during pregnancy, according to findings from a study presented Jan. 28 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“I think the most striking finding is that we noticed a high degree of neutralizing response to natural infection even among asymptomatic infection, but of course a higher degree was seen in those with symptomatic infection,” Naima Joseph, MD, MPH, of Emory University, Atlanta, said in an interview.

“Our data demonstrate maternal capacity to mount an appropriate and robust immune response,” and maternal protective immunity lasted at least 28 days after infection, Dr. Joseph said. “Also, we noted higher neonatal cord blood titers in moms with higher titers, which suggests a relationship, but we need to better understand how transplacental transfer occurs as well as establish neonatal correlates of protection in order to see if and how maternal immunity may also benefit neonates.”

The researchers analyzed the amount of IgG and IgM antibodies in maternal and cord blood samples prospectively collected at delivery from women who tested positive for COVID-19 at any time while pregnant. They used enzyme-linked immunosorbent assay to assess for antibodies for the receptor binding domain of the SARS-CoV-2 spike protein.

The 32 pairs of mothers and infants in the study were predominantly non-Hispanic Black (72%) and Hispanic (25%), and 84% used Medicaid as their payer. Most of the mothers (72%) had at least one comorbidity, most commonly obesity, hypertension, and asthma or pulmonary disease. Just over half the women (53%) were symptomatic while they were infected, and 88% were ill with COVID-19 during the third trimester. The average time from infection to delivery was 28 days.

All the mothers had IgG antibodies, 94% had IgM antibodies, and 94% had neutralizing antibodies against SARS-CoV-2. Among the cord blood samples, 91% had IgG antibodies, 9% had IgM antibodies, and 25% had neutralizing antibodies.

“It’s reassuring that, so far, the physiological response is exactly what we expected it to be,” Judette Louis, MD, MPH, an associate professor of ob.gyn. and the ob.gyn. department chair at the University of South Florida, Tampa, said in an interview. “It’s what we would expect, but it’s always helpful to have more data to support that. Otherwise, you’re extrapolating from what you know from other conditions,” said Dr. Louis, who moderated the oral abstracts session.

Symptomatic infection was associated with significantly higher IgG titers than asymptomatic infection (P = .03), but no correlation was seen for IgM or neutralizing antibodies. In addition, although mothers who delivered more than 28 days after their infection had higher IgG titers (P = .05), no differences existed in IgM or neutralizing response.

Infants’ cord blood titers were significantly lower than their corresponding maternal samples, independently of symptoms or latency from infection to delivery (P < .001), Dr. Joseph reported.

“Transplacental efficiency in other pathogens has been shown to be correlated with neonatal immunity when the ratio of cord to maternal blood is greater than 1,” Dr. Joseph said in her presentation. Their data showed “suboptimal efficiency” at a ratio of 0.81.

The study’s small sample size and lack of a control group were weaknesses, but a major strength was having a population at disproportionately higher risk for infection and severe morbidity than the general population.
 

Implications for maternal COVID-19 vaccination

Although the data are not yet available, Dr. Joseph said they have expanded their protocol to include vaccinated pregnant women.

“The key to developing an effective vaccine [for pregnant people] is in really characterizing adaptive immunity in pregnancy,” Dr. Joseph told SMFM attendees. “I think that these findings inform further vaccine development in demonstrating that maternal immunity is robust.”

The World Health Organization recently recommended withholding COVID-19 vaccines from pregnant people, but the SMFM and American College of Obstetricians and Gynecologists subsequently issued a joint statement reaffirming that the COVID-19 vaccines authorized by the FDA “should not be withheld from pregnant individuals who choose to receive the vaccine.”

“One of the questions people ask is whether in pregnancy you’re going to mount a good response to the vaccine the way you would outside of pregnancy,” Dr. Louis said. “If we can demonstrate that you do, that may provide the information that some mothers need to make their decisions.” Data such as those from Dr. Joseph’s study can also inform recommendations on timing of maternal vaccination.

“For instance, Dr. Joseph demonstrated that, 28 days out from the infection, you had more antibodies, so there may be a scenario where we say this vaccine may be more beneficial in the middle of the pregnancy for the purpose of forming those antibodies,” Dr. Louis said.
 

Consensus emerging from maternal antibodies data

The findings from Dr. Joseph’s study mirror those reported in a study published online Jan. 29 in JAMA Pediatrics. That study, led by Dustin D. Flannery, DO, MSCE, of Children’s Hospital of Philadelphia, also examined maternal and neonatal levels of IgG and IgM antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. They also found a positive correlation between cord blood and maternal IgG concentrations (P < .001), but notably, the ratio of cord to maternal blood titers was greater than 1, unlike in Dr. Joseph’s study.

For their study, Dr. Flannery and colleagues obtained maternal and cord blood sera at the time of delivery from 1471 pairs of mothers and infants, independently of COVID status during pregnancy. The average maternal age was 32 years, and just over a quarter of the population (26%) were Black, non-Hispanic women. About half (51%) were White, 12% were Hispanic, and 7% were Asian.

About 6% of the women had either IgG or IgM antibodies at delivery, and 87% of infants born to those mothers had measurable IgG in their cord blood. No infants had IgM antibodies. As with the study presented at SMFM, the mothers’ infections included asymptomatic, mild, moderate, and severe cases, and the degree of severity of cases had no apparent effect on infant antibody concentrations. Most of the women who tested positive for COVID-19 (60%) were asymptomatic.

Among the 11 mothers who had antibodies but whose infants’ cord blood did not, 5 had only IgM antibodies, and 6 had significantly lower IgG concentrations than those seen in the other mothers.

In a commentary about the JAMA Pediatrics study, Flor Munoz, MD, of the Baylor College of Medicine, Houston, suggested that the findings are grounds for optimism about a maternal vaccination strategy to protect infants from COVID-19.

“However, the timing of maternal vaccination to protect the infant, as opposed to the mother alone, would necessitate an adequate interval from vaccination to delivery (of at least 4 weeks), while vaccination early in gestation and even late in the third trimester could still be protective for the mother,” Dr. Munoz wrote.

Given the interval between two-dose vaccination regimens and the fact that transplacental transfer begins at about the 17th week of gestation, “maternal vaccination starting in the early second trimester of gestation might be optimal to achieve the highest levels of antibodies in the newborn,” Dr. Munoz wrote. But questions remain, such as how effective the neonatal antibodies would be in protecting against COVID-19 and how long they last after birth.

No external funding was used in Dr. Joseph’s study. Dr. Joseph and Dr. Louis have disclosed no relevant financial relationships. The JAMA Pediatrics study was funded by the Children’s Hospital of Philadelphia. One coauthor received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck unrelated to the study. Dr. Munoz served on the data and safety monitoring boards of Moderna, Pfizer, Virometix, and Meissa Vaccines and has received grants from Novavax Research and Gilead Research.

A version of this article first appeared on Medscape.com.

Peripartum maternal oxygen supplementation does not yield a clinically relevant improvement in umbilical artery gas pH or other neonatal outcomes, reported Nandini Raghuraman, MD, MS, of the Washington University School of Medicine, St. Louis, MO, and her associates.

In a meta-analysis of 16 studies identified between Feb. 18 and April 3, 2020, the investigators sought to determine whether maternal oxygen supplementation during delivery leads to improved measures in umbilical artery (UA) gas and neonatal outcomes. Using data from randomized clinical trials, they compared peripartum oxygen supplementation with room air and examined the link between oxygen delivery during regular labor or planned cesarean delivery (CD) with UA gas measures and other neonatal outcomes.

Altogether, 1,078 patients were randomized to the oxygen group or the room air group. UA pH remained similar between the two groups even after the researchers factored in risk of bias, use of low-flow devices, or FIO₂ below 60%, noted the authors. Oxygen supplementation also appeared to reduce rates of UA pH that were less than 7.2 and increase UA PaO₂ relative to room air during scheduled cesarean deliveries, they added.
 

Considerable interstudy heterogeneity was found

Although marginally lower one-minute Apgar scores were observed in infants whose mothers received oxygen during cesarean delivery, the mean difference between oxygen and room air was less than a point and there were no other statistically significant differences in any secondary outcomes, the authors said. Considerable interstudy heterogeneity was noted across most of the study outcomes.

It is important to note that results pooled from all the studies reviewed indicated an increase in UA PaO₂ but no notable differences in UA pH when oxygen was used. Citing multiple studies included in the review, the authors observed that UA PaO₂ is a “poor estimator of neonatal morbidity” because, when evaluated in cord blood gas, it represents dissolved oxygen and is not an accurate indication of how much oxygen is bound to hemoglobin. For this reason, dissolved oxygen content by itself is not an indication of hypoxia or subpar tissue oxygenation.

“Prolonged tissue hypoxia leads to anaerobic metabolism, resulting in decreased pH, which is why UA pH ultimately serves as a better marker for prediction of neonatal morbidity. An intervention that increases the PaO₂ without concomitantly increasing the pH has limited clinical benefit, particularly because hyperoxemia is associated with production of free radicals and oxidative cell damage in adults and neonates,” they explained.
 

With unproven benefits and potential for risk of harm, prolonged oxygen use should be limited

“A large, adequately powered trial is needed to investigate the effect of maternal oxygen supplementation in response to fetal heart rate tracings on short- and long-term neonatal morbidity,” the authors suggested. For the time being, they cautioned limiting prolonged oxygen use since the benefits are unproven and there is a potential risk of harm.

In a separate interview, Iris Krishna, MD, MPH, FACOG, Emory University, Atlanta, noted, “The use of maternal supplemental oxygen with the intent of improving fetal oxygenation is a common clinical practice. Previous studies on maternal oxygen supplementation during labor have yielded conflicting results; however, there is growing literature suggesting that maternal intrapartum supplemental oxygenation may not provide clinically significant benefit and there may even be potential harm to mother and baby.

“Unique to this meta-analysis is evaluation of maternal oxygen supplementation in the presence or absence of labor, hypothesizing that placental oxygen transfer may be affected by regular uterine contractions. The pooled results suggest that the use of maternal supplemental oxygenation does not result in clinically relevant fetal oxygenation in the presence or absence of labor when compared to room air. A limitation of this meta-analysis is that the use of oxygen in response to nonreassuring fetal tracing was not assessed, the most common clinical indication for maternal oxygen supplementation.

“This study further challenges the practice of maternal intrapartum supplemental oxygen and highlights that we have much to learn about the impact of this practice. More research is needed to assess optimal duration of oxygen supplementation, safety and efficacy of oxygen supplementation, appropriate clinical indications for oxygen supplementation, as well as the long-term neonatal outcomes of in utero hyperoxygenation.“

Dr. Raghuraman reported receiving multiple grants and acknowledged multiple funding sources. Her colleagues and Dr. Krishna had no conflicts of interest to report.

Peripartum maternal oxygen supplementation does not yield a clinically relevant improvement in umbilical artery gas pH or other neonatal outcomes, reported Nandini Raghuraman, MD, MS, of the Washington University School of Medicine, St. Louis, MO, and her associates.

In a meta-analysis of 16 studies identified between Feb. 18 and April 3, 2020, the investigators sought to determine whether maternal oxygen supplementation during delivery leads to improved measures in umbilical artery (UA) gas and neonatal outcomes. Using data from randomized clinical trials, they compared peripartum oxygen supplementation with room air and examined the link between oxygen delivery during regular labor or planned cesarean delivery (CD) with UA gas measures and other neonatal outcomes.

Altogether, 1,078 patients were randomized to the oxygen group or the room air group. UA pH remained similar between the two groups even after the researchers factored in risk of bias, use of low-flow devices, or FIO₂ below 60%, noted the authors. Oxygen supplementation also appeared to reduce rates of UA pH that were less than 7.2 and increase UA PaO₂ relative to room air during scheduled cesarean deliveries, they added.
 

Considerable interstudy heterogeneity was found

Although marginally lower one-minute Apgar scores were observed in infants whose mothers received oxygen during cesarean delivery, the mean difference between oxygen and room air was less than a point and there were no other statistically significant differences in any secondary outcomes, the authors said. Considerable interstudy heterogeneity was noted across most of the study outcomes.

It is important to note that results pooled from all the studies reviewed indicated an increase in UA PaO₂ but no notable differences in UA pH when oxygen was used. Citing multiple studies included in the review, the authors observed that UA PaO₂ is a “poor estimator of neonatal morbidity” because, when evaluated in cord blood gas, it represents dissolved oxygen and is not an accurate indication of how much oxygen is bound to hemoglobin. For this reason, dissolved oxygen content by itself is not an indication of hypoxia or subpar tissue oxygenation.

“Prolonged tissue hypoxia leads to anaerobic metabolism, resulting in decreased pH, which is why UA pH ultimately serves as a better marker for prediction of neonatal morbidity. An intervention that increases the PaO₂ without concomitantly increasing the pH has limited clinical benefit, particularly because hyperoxemia is associated with production of free radicals and oxidative cell damage in adults and neonates,” they explained.
 

With unproven benefits and potential for risk of harm, prolonged oxygen use should be limited

“A large, adequately powered trial is needed to investigate the effect of maternal oxygen supplementation in response to fetal heart rate tracings on short- and long-term neonatal morbidity,” the authors suggested. For the time being, they cautioned limiting prolonged oxygen use since the benefits are unproven and there is a potential risk of harm.

In a separate interview, Iris Krishna, MD, MPH, FACOG, Emory University, Atlanta, noted, “The use of maternal supplemental oxygen with the intent of improving fetal oxygenation is a common clinical practice. Previous studies on maternal oxygen supplementation during labor have yielded conflicting results; however, there is growing literature suggesting that maternal intrapartum supplemental oxygenation may not provide clinically significant benefit and there may even be potential harm to mother and baby.

“Unique to this meta-analysis is evaluation of maternal oxygen supplementation in the presence or absence of labor, hypothesizing that placental oxygen transfer may be affected by regular uterine contractions. The pooled results suggest that the use of maternal supplemental oxygenation does not result in clinically relevant fetal oxygenation in the presence or absence of labor when compared to room air. A limitation of this meta-analysis is that the use of oxygen in response to nonreassuring fetal tracing was not assessed, the most common clinical indication for maternal oxygen supplementation.

“This study further challenges the practice of maternal intrapartum supplemental oxygen and highlights that we have much to learn about the impact of this practice. More research is needed to assess optimal duration of oxygen supplementation, safety and efficacy of oxygen supplementation, appropriate clinical indications for oxygen supplementation, as well as the long-term neonatal outcomes of in utero hyperoxygenation.“

Dr. Raghuraman reported receiving multiple grants and acknowledged multiple funding sources. Her colleagues and Dr. Krishna had no conflicts of interest to report.

Peripartum maternal oxygen supplementation does not yield a clinically relevant improvement in umbilical artery gas pH or other neonatal outcomes, reported Nandini Raghuraman, MD, MS, of the Washington University School of Medicine, St. Louis, MO, and her associates.

In a meta-analysis of 16 studies identified between Feb. 18 and April 3, 2020, the investigators sought to determine whether maternal oxygen supplementation during delivery leads to improved measures in umbilical artery (UA) gas and neonatal outcomes. Using data from randomized clinical trials, they compared peripartum oxygen supplementation with room air and examined the link between oxygen delivery during regular labor or planned cesarean delivery (CD) with UA gas measures and other neonatal outcomes.

Altogether, 1,078 patients were randomized to the oxygen group or the room air group. UA pH remained similar between the two groups even after the researchers factored in risk of bias, use of low-flow devices, or FIO₂ below 60%, noted the authors. Oxygen supplementation also appeared to reduce rates of UA pH that were less than 7.2 and increase UA PaO₂ relative to room air during scheduled cesarean deliveries, they added.
 

Considerable interstudy heterogeneity was found

Although marginally lower one-minute Apgar scores were observed in infants whose mothers received oxygen during cesarean delivery, the mean difference between oxygen and room air was less than a point and there were no other statistically significant differences in any secondary outcomes, the authors said. Considerable interstudy heterogeneity was noted across most of the study outcomes.

It is important to note that results pooled from all the studies reviewed indicated an increase in UA PaO₂ but no notable differences in UA pH when oxygen was used. Citing multiple studies included in the review, the authors observed that UA PaO₂ is a “poor estimator of neonatal morbidity” because, when evaluated in cord blood gas, it represents dissolved oxygen and is not an accurate indication of how much oxygen is bound to hemoglobin. For this reason, dissolved oxygen content by itself is not an indication of hypoxia or subpar tissue oxygenation.

“Prolonged tissue hypoxia leads to anaerobic metabolism, resulting in decreased pH, which is why UA pH ultimately serves as a better marker for prediction of neonatal morbidity. An intervention that increases the PaO₂ without concomitantly increasing the pH has limited clinical benefit, particularly because hyperoxemia is associated with production of free radicals and oxidative cell damage in adults and neonates,” they explained.
 

With unproven benefits and potential for risk of harm, prolonged oxygen use should be limited

“A large, adequately powered trial is needed to investigate the effect of maternal oxygen supplementation in response to fetal heart rate tracings on short- and long-term neonatal morbidity,” the authors suggested. For the time being, they cautioned limiting prolonged oxygen use since the benefits are unproven and there is a potential risk of harm.

In a separate interview, Iris Krishna, MD, MPH, FACOG, Emory University, Atlanta, noted, “The use of maternal supplemental oxygen with the intent of improving fetal oxygenation is a common clinical practice. Previous studies on maternal oxygen supplementation during labor have yielded conflicting results; however, there is growing literature suggesting that maternal intrapartum supplemental oxygenation may not provide clinically significant benefit and there may even be potential harm to mother and baby.

“Unique to this meta-analysis is evaluation of maternal oxygen supplementation in the presence or absence of labor, hypothesizing that placental oxygen transfer may be affected by regular uterine contractions. The pooled results suggest that the use of maternal supplemental oxygenation does not result in clinically relevant fetal oxygenation in the presence or absence of labor when compared to room air. A limitation of this meta-analysis is that the use of oxygen in response to nonreassuring fetal tracing was not assessed, the most common clinical indication for maternal oxygen supplementation.

“This study further challenges the practice of maternal intrapartum supplemental oxygen and highlights that we have much to learn about the impact of this practice. More research is needed to assess optimal duration of oxygen supplementation, safety and efficacy of oxygen supplementation, appropriate clinical indications for oxygen supplementation, as well as the long-term neonatal outcomes of in utero hyperoxygenation.“

Dr. Raghuraman reported receiving multiple grants and acknowledged multiple funding sources. Her colleagues and Dr. Krishna had no conflicts of interest to report.

Three genes that could predict susceptibility to congenital Zika virus (ZIKV) infection have been identified, Dr. Irene Rivero-Calle, MD, shared at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

ZIKV, an emerging flavivirus, is responsible for one the most critical pandemic emergencies of the last decade and has been associated with severe neonatal brain disabilities, declared Dr. Rivero-Calle, of the Hospital Clínico Universitario de Santiago de Compostela in Santiago de Compostela, Spain. “We think that understanding the genomic background could explain some of the most relevant symptoms of congenital Zika syndrome (CZS) and could be essential to better comprehend this disease.”

To achieve this understanding, Dr. Rivero-Calle and her colleagues conducted a study aiming to analyze any genetic factors that could explain the variation in phenotypes in newborns from mothers who had a Zika infection during their pregnancy. Additionally, they strove to “elucidate if the possible genetic association is specific to mothers or their newborns, and to check if this genomic background or any genomic ancestry pattern could be related with the phenotype,” she explained.

In their study, Dr. Rivero-Calle and her team analyzed 80 samples, comprising 40 samples from mothers who had been infected by ZIKV during their pregnancy and 40 from their newborns. Of those descendants, 20 were asymptomatic and 20 were symptomatic (13 had CZS, 3 had microcephaly, 2 had a pathologic MRI, 1 had hearing loss, and 1 was born preterm).

Population stratification, which Dr. Rivero-Calle explained “lets us know if the population is African, European, or Native American looking at the genes,” did not show any relation with the phenotype. We had a mixture of population genomics among all samples.”

Dr. Rivero-Calle and her team then performed three analyses: genotype analysis, an allelic test, and gene analysis. The allelic test and gene-collapsing method highlighted three genes (PANO1, PIDD1, and SLC25A22) as potential determinants of the varying phenotypes in the newborns from ZIKV-infected mothers. Overrepresentation analysis of gene ontology terms shows that PIDD1 and PANO1 are related to apoptosis and cell death, which is closely related to early infantile epilepsy. This could explain the most severe complications of CZS: seizures, brain damage, microcephaly, and detrimental neurodevelopmental growth. Regarding reactome and KEGG analysis, gene PIID1 is related with p53 pathway, which correlates with cell’s death and apoptosis, and with microcephaly, a typical phenotypic feature of CZS.

“So, in conclusion, we found three genes which could predict susceptibility to congenital Zika infection; we saw that the functionality of these genes seems to be deeply related with mechanisms which could explain the different phenotypes; and we saw that these three genes only appear in the children’s cohort, so there is no candidate gene in the mother’s genomic background which can help predict the phenotype of the newborn,” Dr. Rivero-Calle declared. “Finally, there is no ancestry pattern associated with disabilities caused by Zika infection.”

Dr. Rivero-Calle reported that this project (ZikAction) has received funding from the European Union’s Horizon 2020 research and innovation program, under grant agreement 734857.

Three genes that could predict susceptibility to congenital Zika virus (ZIKV) infection have been identified, Dr. Irene Rivero-Calle, MD, shared at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

ZIKV, an emerging flavivirus, is responsible for one the most critical pandemic emergencies of the last decade and has been associated with severe neonatal brain disabilities, declared Dr. Rivero-Calle, of the Hospital Clínico Universitario de Santiago de Compostela in Santiago de Compostela, Spain. “We think that understanding the genomic background could explain some of the most relevant symptoms of congenital Zika syndrome (CZS) and could be essential to better comprehend this disease.”

To achieve this understanding, Dr. Rivero-Calle and her colleagues conducted a study aiming to analyze any genetic factors that could explain the variation in phenotypes in newborns from mothers who had a Zika infection during their pregnancy. Additionally, they strove to “elucidate if the possible genetic association is specific to mothers or their newborns, and to check if this genomic background or any genomic ancestry pattern could be related with the phenotype,” she explained.

In their study, Dr. Rivero-Calle and her team analyzed 80 samples, comprising 40 samples from mothers who had been infected by ZIKV during their pregnancy and 40 from their newborns. Of those descendants, 20 were asymptomatic and 20 were symptomatic (13 had CZS, 3 had microcephaly, 2 had a pathologic MRI, 1 had hearing loss, and 1 was born preterm).

Population stratification, which Dr. Rivero-Calle explained “lets us know if the population is African, European, or Native American looking at the genes,” did not show any relation with the phenotype. We had a mixture of population genomics among all samples.”

Dr. Rivero-Calle and her team then performed three analyses: genotype analysis, an allelic test, and gene analysis. The allelic test and gene-collapsing method highlighted three genes (PANO1, PIDD1, and SLC25A22) as potential determinants of the varying phenotypes in the newborns from ZIKV-infected mothers. Overrepresentation analysis of gene ontology terms shows that PIDD1 and PANO1 are related to apoptosis and cell death, which is closely related to early infantile epilepsy. This could explain the most severe complications of CZS: seizures, brain damage, microcephaly, and detrimental neurodevelopmental growth. Regarding reactome and KEGG analysis, gene PIID1 is related with p53 pathway, which correlates with cell’s death and apoptosis, and with microcephaly, a typical phenotypic feature of CZS.

“So, in conclusion, we found three genes which could predict susceptibility to congenital Zika infection; we saw that the functionality of these genes seems to be deeply related with mechanisms which could explain the different phenotypes; and we saw that these three genes only appear in the children’s cohort, so there is no candidate gene in the mother’s genomic background which can help predict the phenotype of the newborn,” Dr. Rivero-Calle declared. “Finally, there is no ancestry pattern associated with disabilities caused by Zika infection.”

Dr. Rivero-Calle reported that this project (ZikAction) has received funding from the European Union’s Horizon 2020 research and innovation program, under grant agreement 734857.

Three genes that could predict susceptibility to congenital Zika virus (ZIKV) infection have been identified, Dr. Irene Rivero-Calle, MD, shared at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

ZIKV, an emerging flavivirus, is responsible for one the most critical pandemic emergencies of the last decade and has been associated with severe neonatal brain disabilities, declared Dr. Rivero-Calle, of the Hospital Clínico Universitario de Santiago de Compostela in Santiago de Compostela, Spain. “We think that understanding the genomic background could explain some of the most relevant symptoms of congenital Zika syndrome (CZS) and could be essential to better comprehend this disease.”

To achieve this understanding, Dr. Rivero-Calle and her colleagues conducted a study aiming to analyze any genetic factors that could explain the variation in phenotypes in newborns from mothers who had a Zika infection during their pregnancy. Additionally, they strove to “elucidate if the possible genetic association is specific to mothers or their newborns, and to check if this genomic background or any genomic ancestry pattern could be related with the phenotype,” she explained.

In their study, Dr. Rivero-Calle and her team analyzed 80 samples, comprising 40 samples from mothers who had been infected by ZIKV during their pregnancy and 40 from their newborns. Of those descendants, 20 were asymptomatic and 20 were symptomatic (13 had CZS, 3 had microcephaly, 2 had a pathologic MRI, 1 had hearing loss, and 1 was born preterm).

Population stratification, which Dr. Rivero-Calle explained “lets us know if the population is African, European, or Native American looking at the genes,” did not show any relation with the phenotype. We had a mixture of population genomics among all samples.”

Dr. Rivero-Calle and her team then performed three analyses: genotype analysis, an allelic test, and gene analysis. The allelic test and gene-collapsing method highlighted three genes (PANO1, PIDD1, and SLC25A22) as potential determinants of the varying phenotypes in the newborns from ZIKV-infected mothers. Overrepresentation analysis of gene ontology terms shows that PIDD1 and PANO1 are related to apoptosis and cell death, which is closely related to early infantile epilepsy. This could explain the most severe complications of CZS: seizures, brain damage, microcephaly, and detrimental neurodevelopmental growth. Regarding reactome and KEGG analysis, gene PIID1 is related with p53 pathway, which correlates with cell’s death and apoptosis, and with microcephaly, a typical phenotypic feature of CZS.

“So, in conclusion, we found three genes which could predict susceptibility to congenital Zika infection; we saw that the functionality of these genes seems to be deeply related with mechanisms which could explain the different phenotypes; and we saw that these three genes only appear in the children’s cohort, so there is no candidate gene in the mother’s genomic background which can help predict the phenotype of the newborn,” Dr. Rivero-Calle declared. “Finally, there is no ancestry pattern associated with disabilities caused by Zika infection.”

Dr. Rivero-Calle reported that this project (ZikAction) has received funding from the European Union’s Horizon 2020 research and innovation program, under grant agreement 734857.