Could tackling maternal obesity prevent later CVD in offspring?

 

Offspring of obese mothers should be regarded as a high-risk population for endothelial cell dysfunction and, therefore, for cardiovascular events later in life, authors of a thematic literature review concluded.

Maternal obesity has been tied to the development of cardiovascular disease (CVD) and premature death in epidemiologic studies, the authors noted in the review.

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One hypothesis, referred to as fetal programming, posits that in utero environmental factors may have adverse metabolic consequences in the offspring. Thus far, however, most evidence supporting this hypothesis has come from animal studies, they cautioned.

Nevertheless, endothelial cell dysfunction is a reversible process, offering a “window of opportunity” for intervention, according to authors Karolien Van De Maele and Inge Gies, MD, of the division of pediatric endocrinology at the University Hospital of Brussels and Roland Devlieger, MD, PhD, head of fetal maternal medicine at the University Hospitals Leuven (Belgium).

“The fundamental solution to break the vicious cycle seems [to be] an intervention before or in early pregnancy,” authors said in the journal Atherosclerosis.

Mary Norine Walsh, MD, immediate past president of the American College of Cardiology, agreed with the review article’s conclusion that more evidence would be needed to show that fetal programming is implicated in the associations between maternal obesity and long-term cardiovascular effects.

“As of right now, we cannot say the offspring of pregnant women have an increased risk of cardiovascular risk in later life due to ‘X’ because those studies haven’t been done yet,” Dr. Walsh said in an interview. “So I think it’s a really good framework to think about based on the animal work that’s been done, but we have yet to identify obesity in pregnant women as an independent risk factor for vascular disease in the offspring – we just have an association.”

On the other hand, it is known that obesity increases the risk of hypertension and diabetes in both pregnant and nonpregnant women, said Dr. Walsh, and that hypertensive disorders are a leading cause of maternal morbidity and mortality.

“I think it’s really important to recognize that maternal obesity puts a woman at significant risk, and we certainly can’t forget that in the process of thinking about the offspring,” said Dr. Walsh, medical director of the heart failure and cardiac transplantation program at St. Vincent Heart Center, Indianapolis.

In the recent review article in Atherosclerosis, Ms. Van De Maele and coauthors cited evidence linking maternal obesity to adverse outcomes in offspring from a 2013 report in the BMJ that included 28,540 women in Scotland and their 37,709 offspring.

In that study, after adjustment for maternal age, socioeconomic status, and other factors, offspring of mothers who had a body mass index greater than 30 kg/m² had higher all-cause mortality (hazard ratio, 1.35; 95% confidence interval, 1.17-1.55) and increased risk of hospital admission for a cardiovascular event (HR, 1.29; 95% CI, 1.06-1.57), compared with those whose mothers had a healthy BMI.

“Evidence from animal models and emerging data from humans suggest that maternal obesity also creates an adverse in utero environment, with long-term ‘programmed’ detrimental effects for the offspring,” the authors of that BMJ report wrote at the time.

Ms. Van De Maele and her colleagues also cited animal studies, including several looking at offspring of animals fed with a maternal high-fat diet during pregnancy. In those studies, they said, investigators observed impaired endothelial cell relaxation, along with raised thickness of the intimal wall and increased vascular inflammatory marker expression.

 

“Raised leptin levels, secreted by the adipose tissue, inhibit the in vitro proliferation of smooth muscle cells and could impede the angiogenesis process in vivo, but this assumption needs scientific validation in humans,” they said in their review.

However, human studies are lacking, aside from the epidemiologic reports that “cannot be used to confirm or contradict” the fetal programming hypothesis, they said.

Meanwhile, an increasing body of evidence has suggested that stressors in critical periods of fetal development may lead to epigenetic alterations that could play a role in either up-regulating atherogenic genes or down-regulating enzymatic activities that guard against oxidative stress.

For example, cohort studies have shown differences in DNA methylation among offspring born before and after bariatric surgery in the mother, which has lent credence to the hypothesis that maternal obesity in pregnancy alters methylation patterns for those offspring, Ms. Van De Maele and her colleagues wrote.

Lifestyle changes in obese pregnant women may have an effect on adverse metabolic or cardiovascular outcomes in offspring, although results to date are inconclusive, they added.

Diet, exercise, or both during pregnancy may lower the risk of macrosomia, respiratory distress syndrome, or other neonatal outcomes, particularly in high-risk women, according to the conclusions of a 2015 Cochrane review that Ms. Van De Maele and her coauthors cited.

However, follow-up studies on offspring are scarce and have shown no clear effects on long-term metabolic profiles in offspring, likely because of insufficient follow-up time, they said in their review.

Ms. Van De Maele and her coauthors said they had no conflict of interest disclosures related to their manuscript.

SOURCE: Van De Maele K et al. Atherosclerosis. 2018 Jun. doi: 10.1016/j.atherosclerosis.2018.06.016.

 

Offspring of obese mothers should be regarded as a high-risk population for endothelial cell dysfunction and, therefore, for cardiovascular events later in life, authors of a thematic literature review concluded.

Maternal obesity has been tied to the development of cardiovascular disease (CVD) and premature death in epidemiologic studies, the authors noted in the review.

anopdesignstock/Thinkstock

One hypothesis, referred to as fetal programming, posits that in utero environmental factors may have adverse metabolic consequences in the offspring. Thus far, however, most evidence supporting this hypothesis has come from animal studies, they cautioned.

Nevertheless, endothelial cell dysfunction is a reversible process, offering a “window of opportunity” for intervention, according to authors Karolien Van De Maele and Inge Gies, MD, of the division of pediatric endocrinology at the University Hospital of Brussels and Roland Devlieger, MD, PhD, head of fetal maternal medicine at the University Hospitals Leuven (Belgium).

“The fundamental solution to break the vicious cycle seems [to be] an intervention before or in early pregnancy,” authors said in the journal Atherosclerosis.

Mary Norine Walsh, MD, immediate past president of the American College of Cardiology, agreed with the review article’s conclusion that more evidence would be needed to show that fetal programming is implicated in the associations between maternal obesity and long-term cardiovascular effects.

“As of right now, we cannot say the offspring of pregnant women have an increased risk of cardiovascular risk in later life due to ‘X’ because those studies haven’t been done yet,” Dr. Walsh said in an interview. “So I think it’s a really good framework to think about based on the animal work that’s been done, but we have yet to identify obesity in pregnant women as an independent risk factor for vascular disease in the offspring – we just have an association.”

On the other hand, it is known that obesity increases the risk of hypertension and diabetes in both pregnant and nonpregnant women, said Dr. Walsh, and that hypertensive disorders are a leading cause of maternal morbidity and mortality.

“I think it’s really important to recognize that maternal obesity puts a woman at significant risk, and we certainly can’t forget that in the process of thinking about the offspring,” said Dr. Walsh, medical director of the heart failure and cardiac transplantation program at St. Vincent Heart Center, Indianapolis.

In the recent review article in Atherosclerosis, Ms. Van De Maele and coauthors cited evidence linking maternal obesity to adverse outcomes in offspring from a 2013 report in the BMJ that included 28,540 women in Scotland and their 37,709 offspring.

In that study, after adjustment for maternal age, socioeconomic status, and other factors, offspring of mothers who had a body mass index greater than 30 kg/m² had higher all-cause mortality (hazard ratio, 1.35; 95% confidence interval, 1.17-1.55) and increased risk of hospital admission for a cardiovascular event (HR, 1.29; 95% CI, 1.06-1.57), compared with those whose mothers had a healthy BMI.

“Evidence from animal models and emerging data from humans suggest that maternal obesity also creates an adverse in utero environment, with long-term ‘programmed’ detrimental effects for the offspring,” the authors of that BMJ report wrote at the time.

Ms. Van De Maele and her colleagues also cited animal studies, including several looking at offspring of animals fed with a maternal high-fat diet during pregnancy. In those studies, they said, investigators observed impaired endothelial cell relaxation, along with raised thickness of the intimal wall and increased vascular inflammatory marker expression.

 

“Raised leptin levels, secreted by the adipose tissue, inhibit the in vitro proliferation of smooth muscle cells and could impede the angiogenesis process in vivo, but this assumption needs scientific validation in humans,” they said in their review.

However, human studies are lacking, aside from the epidemiologic reports that “cannot be used to confirm or contradict” the fetal programming hypothesis, they said.

Meanwhile, an increasing body of evidence has suggested that stressors in critical periods of fetal development may lead to epigenetic alterations that could play a role in either up-regulating atherogenic genes or down-regulating enzymatic activities that guard against oxidative stress.

For example, cohort studies have shown differences in DNA methylation among offspring born before and after bariatric surgery in the mother, which has lent credence to the hypothesis that maternal obesity in pregnancy alters methylation patterns for those offspring, Ms. Van De Maele and her colleagues wrote.

Lifestyle changes in obese pregnant women may have an effect on adverse metabolic or cardiovascular outcomes in offspring, although results to date are inconclusive, they added.

Diet, exercise, or both during pregnancy may lower the risk of macrosomia, respiratory distress syndrome, or other neonatal outcomes, particularly in high-risk women, according to the conclusions of a 2015 Cochrane review that Ms. Van De Maele and her coauthors cited.

However, follow-up studies on offspring are scarce and have shown no clear effects on long-term metabolic profiles in offspring, likely because of insufficient follow-up time, they said in their review.

Ms. Van De Maele and her coauthors said they had no conflict of interest disclosures related to their manuscript.

SOURCE: Van De Maele K et al. Atherosclerosis. 2018 Jun. doi: 10.1016/j.atherosclerosis.2018.06.016.

 

Offspring of obese mothers should be regarded as a high-risk population for endothelial cell dysfunction and, therefore, for cardiovascular events later in life, authors of a thematic literature review concluded.

Maternal obesity has been tied to the development of cardiovascular disease (CVD) and premature death in epidemiologic studies, the authors noted in the review.

anopdesignstock/Thinkstock

One hypothesis, referred to as fetal programming, posits that in utero environmental factors may have adverse metabolic consequences in the offspring. Thus far, however, most evidence supporting this hypothesis has come from animal studies, they cautioned.

Nevertheless, endothelial cell dysfunction is a reversible process, offering a “window of opportunity” for intervention, according to authors Karolien Van De Maele and Inge Gies, MD, of the division of pediatric endocrinology at the University Hospital of Brussels and Roland Devlieger, MD, PhD, head of fetal maternal medicine at the University Hospitals Leuven (Belgium).

“The fundamental solution to break the vicious cycle seems [to be] an intervention before or in early pregnancy,” authors said in the journal Atherosclerosis.

Mary Norine Walsh, MD, immediate past president of the American College of Cardiology, agreed with the review article’s conclusion that more evidence would be needed to show that fetal programming is implicated in the associations between maternal obesity and long-term cardiovascular effects.

“As of right now, we cannot say the offspring of pregnant women have an increased risk of cardiovascular risk in later life due to ‘X’ because those studies haven’t been done yet,” Dr. Walsh said in an interview. “So I think it’s a really good framework to think about based on the animal work that’s been done, but we have yet to identify obesity in pregnant women as an independent risk factor for vascular disease in the offspring – we just have an association.”

On the other hand, it is known that obesity increases the risk of hypertension and diabetes in both pregnant and nonpregnant women, said Dr. Walsh, and that hypertensive disorders are a leading cause of maternal morbidity and mortality.

“I think it’s really important to recognize that maternal obesity puts a woman at significant risk, and we certainly can’t forget that in the process of thinking about the offspring,” said Dr. Walsh, medical director of the heart failure and cardiac transplantation program at St. Vincent Heart Center, Indianapolis.

In the recent review article in Atherosclerosis, Ms. Van De Maele and coauthors cited evidence linking maternal obesity to adverse outcomes in offspring from a 2013 report in the BMJ that included 28,540 women in Scotland and their 37,709 offspring.

In that study, after adjustment for maternal age, socioeconomic status, and other factors, offspring of mothers who had a body mass index greater than 30 kg/m² had higher all-cause mortality (hazard ratio, 1.35; 95% confidence interval, 1.17-1.55) and increased risk of hospital admission for a cardiovascular event (HR, 1.29; 95% CI, 1.06-1.57), compared with those whose mothers had a healthy BMI.

“Evidence from animal models and emerging data from humans suggest that maternal obesity also creates an adverse in utero environment, with long-term ‘programmed’ detrimental effects for the offspring,” the authors of that BMJ report wrote at the time.

Ms. Van De Maele and her colleagues also cited animal studies, including several looking at offspring of animals fed with a maternal high-fat diet during pregnancy. In those studies, they said, investigators observed impaired endothelial cell relaxation, along with raised thickness of the intimal wall and increased vascular inflammatory marker expression.

 

“Raised leptin levels, secreted by the adipose tissue, inhibit the in vitro proliferation of smooth muscle cells and could impede the angiogenesis process in vivo, but this assumption needs scientific validation in humans,” they said in their review.

However, human studies are lacking, aside from the epidemiologic reports that “cannot be used to confirm or contradict” the fetal programming hypothesis, they said.

Meanwhile, an increasing body of evidence has suggested that stressors in critical periods of fetal development may lead to epigenetic alterations that could play a role in either up-regulating atherogenic genes or down-regulating enzymatic activities that guard against oxidative stress.

For example, cohort studies have shown differences in DNA methylation among offspring born before and after bariatric surgery in the mother, which has lent credence to the hypothesis that maternal obesity in pregnancy alters methylation patterns for those offspring, Ms. Van De Maele and her colleagues wrote.

Lifestyle changes in obese pregnant women may have an effect on adverse metabolic or cardiovascular outcomes in offspring, although results to date are inconclusive, they added.

Diet, exercise, or both during pregnancy may lower the risk of macrosomia, respiratory distress syndrome, or other neonatal outcomes, particularly in high-risk women, according to the conclusions of a 2015 Cochrane review that Ms. Van De Maele and her coauthors cited.

However, follow-up studies on offspring are scarce and have shown no clear effects on long-term metabolic profiles in offspring, likely because of insufficient follow-up time, they said in their review.

Ms. Van De Maele and her coauthors said they had no conflict of interest disclosures related to their manuscript.

SOURCE: Van De Maele K et al. Atherosclerosis. 2018 Jun. doi: 10.1016/j.atherosclerosis.2018.06.016.