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. While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.
The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”
NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.
“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.
Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.
According to Dr. Stika, many pregnant women are reluctant to take drugs at all or participate in drug studies, “so the combination of nonpharmaceutical/pharmaceutical treatment might be a bit more appealing.” She noted that some women have such severe nausea they are literally starving and so weak they are bedridden or even hospitalized.
Both treatments have been recommended for some time, and the American College of Obstetricians and Gynecologists’ 2018 practice bulletin recommends acupuncture for mild nausea.
Design
The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.
Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
Suited to milder symptoms?
Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.
“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”
And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”
Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”
Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.
Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.
"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.
Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."
This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.
Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.
Dr. Stika and Dr. Carroll had no competing interests to disclose.
. While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.
The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”
NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.
“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.
Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.
According to Dr. Stika, many pregnant women are reluctant to take drugs at all or participate in drug studies, “so the combination of nonpharmaceutical/pharmaceutical treatment might be a bit more appealing.” She noted that some women have such severe nausea they are literally starving and so weak they are bedridden or even hospitalized.
Both treatments have been recommended for some time, and the American College of Obstetricians and Gynecologists’ 2018 practice bulletin recommends acupuncture for mild nausea.
Design
The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.
Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
Suited to milder symptoms?
Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.
“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”
And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”
Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”
Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.
Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.
"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.
Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."
This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.
Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.
Dr. Stika and Dr. Carroll had no competing interests to disclose.
. While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.
The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”
NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.
“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.
Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.
According to Dr. Stika, many pregnant women are reluctant to take drugs at all or participate in drug studies, “so the combination of nonpharmaceutical/pharmaceutical treatment might be a bit more appealing.” She noted that some women have such severe nausea they are literally starving and so weak they are bedridden or even hospitalized.
Both treatments have been recommended for some time, and the American College of Obstetricians and Gynecologists’ 2018 practice bulletin recommends acupuncture for mild nausea.
Design
The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.
Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
Suited to milder symptoms?
Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.
“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”
And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”
Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”
Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.
Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.
"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.
Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."
This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.
Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.
Dr. Stika and Dr. Carroll had no competing interests to disclose.
FROM ANNALS OF INTERNAL MEDICINE