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BMI and reproduction – weighing the evidence
Arguably, no topic during an infertility consultation generates more of an emotional reaction than discussing body mass index (BMI), particularly when it is high. Patients have become increasingly sensitive to weight discussions with their physicians because of concerns about body shaming. Among patients with an elevated BMI, criticism on social media of health care professionals’ counseling and a preemptive presentation of “Don’t Weigh Me” cards have become popular responses. Despite the medical evidence on impaired reproduction with an abnormal BMI, patients are choosing to forgo the topic. Research has demonstrated “extensive evidence [of] strong weight bias” in a wide range of health staff.1 A “viral” TikTok study revealed that medical “gaslighting” founded in weight stigma and bias is harmful, as reported on KevinMD.com.2 This month, we review the effect of abnormal BMI, both high and low, on reproduction and pregnancy.
A method to assess relative weight was first described in 1832 as its ratio in kilograms divided by the square of the height in meters, or the Quetelet Index. The search for a functional assessment of relative body weight began after World War II when reports by actuaries noted the increased mortality of overweight policyholders. The relationship between weight and cardiovascular disease was further revealed in epidemiologic studies. The Quetelet Index became the BMI in 1972.3
Weight measurement is a mainstay in the assessment of a patient’s vital signs along with blood pressure, pulse rate, respiration rate, and temperature. Weight is vital to the calculation of medication dosage – for instance, administration of conscious sedative drugs, methotrexate, and gonadotropins. Some state boards of medicine, such as Florida, have a limitation on patient BMI at office-based surgery centers (40 kg/m2).
Obesity is a disease
As reported by the World Health Organization in 2022, the disease of obesity is an epidemic afflicting more than 1 billion people worldwide, or 1 in 8 individuals globally.4 The health implications of an elevated BMI include increased mortality, diabetes, heart disease, and stroke, physical limitations to activities of daily living, and complications affecting reproduction.
Female obesity is related to poorer outcomes in natural and assisted conception, including an increased risk of miscarriage. Compared with normal-weight women, those with obesity are three times more likely to have ovulatory dysfunction,5 infertility,6 a lower chance for conception,7 higher rate of miscarriage, and low birth weight.8,9During pregnancy, women with obesity have three to four times higher rates of gestational diabetes and preeclampsia,10 as well as likelihood of delivering preterm,11 having a fetus with macrosomia and birth defects, and a 1.3- to 2.1-times higher risk of stillbirth.12
Obesity is present in 40%-80% of women with polycystic ovary syndrome,13 the most common cause of ovulatory dysfunction from dysregulation of the hypothalamic-pituitary-ovarian axis. While PCOS is associated with reproductive and metabolic consequences, even in regularly ovulating women, increasing obesity appears to be associated with decreasing spontaneous pregnancy rates and increased time to pregnancy.14
Obesity and IVF
Women with obesity have reduced success with assisted reproductive technology, an increased number of canceled cycles, and poorer quality oocytes retrieved. A prospective cohort study of nearly 2,000 women reported that every 5 kg of body weight increase (from the patient’s baseline weight at age 18) was associated with a 5% increase in the mean duration of time required for conception (95% confidence interval, 3%-7%).15 Given that approximately 90% of these women had regular menstrual cycles, ovulatory dysfunction was not the suspected pathophysiology.
A meta-analysis of 21 cohort studies reported a lower likelihood of live birth following in vitro fertilization for women with obesity, compared with normal-weight women (risk ratio, 0.85; 95% CI, 0.82-0.87).16 A further subgroup analysis that evaluated only women with PCOS showed a reduction in the live birth rate following IVF for individuals with obesity, compared with normal-weight individuals (RR, 0.78; 95% CI, 0.74-0.82).
In a retrospective study of almost 500,000 fresh autologous IVF cycles, women with obesity had a 6% reduction in pregnancy rates and a 13% reduction in live birth rates, compared with normal-weight women. Both high and low BMI were associated with an increased risk of low birth weight and preterm delivery.17 The live birth rates per transfer for normal-weight and higher-weight women were 38% and 33%, respectively.
Contrarily, a randomized controlled trial showed that an intensive weight-reduction program resulted in a large weight loss but did not substantially affect live birth rates in women with obesity scheduled for IVF.18
Low BMI
A noteworthy cause of low BMI is functional hypothalamic amenorrhea (FHA), a disorder with low energy availability either from decreased caloric intake and/or excessive energy expenditure associated with eating disorders, excessive exercise, and stress. Consequently, a reduced GnRH drive results in a decreased pulse frequency and amplitude leading to low levels of follicle-stimulating hormone and luteinizing hormone, resulting in anovulation. Correction of lifestyle behaviors related to FHA can restore menstrual cycles. After normal weight is achieved, it appears unlikely that fertility is affected.19 In 47% of adolescent patients with anorexia, menses spontaneously returned within the first 12 months after admission, with an improved prognosis in secondary over primary amenorrhea.20,21 Interestingly, mildly and significantly underweight infertile women have pregnancy and live birth rates similar to normal-weight patients after IVF treatment.22
Pregnancy is complicated in underweight women, resulting in an increased risk of anemia, fetal growth retardation, and low birth weight, as well as preterm birth.21
Take-home message
The extremes of BMI both impair natural reproduction. Elevated BMI reduces success with IVF but rapid weight loss prior to IVF does not improve outcomes. A normal BMI is the goal for optimal reproductive and pregnancy health.
Dr. Trolice is director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
References
1. Talumaa B et al. Obesity Rev. 2022;23:e13494.
2. https://bit.ly/3rHCivE.
3. Eknoyan G. Nephrol Dial Transplant. 2008;23:47-51.
4. Wells JCK. Dis Models Mech. 2012;5:595-607.
5. Brewer CJ and Balen AH. Reproduction. 2010;140:347-64.
6. Silvestris E et al. Reprod Biol Endocrinol. 2018;16:22.
7. Wise LA et al. Hum Reprod. 2010;25:253-64.
8. Bellver J. Curr Opin Obstet Gynecol. 2022;34:114-21.
9. Dickey RP et al. Am J Obstet Gynecol. 2013;209:349.e1.
10. Alwash SM et al. Obes Res Clin Pract. 2021;15:425-30.
11. Cnattingius S et al. JAMA. 2013;309:2362-70.
12. Aune D et al. JAMA. 2014;311:1536-46.
13. Sam S. Obes Manag. 2007;3:69-73.
14. van der Steeg JW et al. Hum Reprod. 2008;23:324-8.
15. Gaskins AJ et al. Obstet Gynecol. 2015;126:850-8.
16. Sermondade N et al. Hum Reprod Update. 2019;25:439-519.
17. Kawwass JF et al. Fertil Steril. 2016;106[7]:1742-50.
18. Einarsson S et al. Hum Reprod. 2017;32:1621-30.
19. Chaer R et al. Diseases. 2020;8:46.
20. Dempfle A et al. Psychiatry. 2013;13:308.
21. Verma A and Shrimali L. J Clin Diagn Res. 2012;6:1531-3.
22. Romanski PA et al. Reprod Biomed Online. 2020;42:366-74.
Arguably, no topic during an infertility consultation generates more of an emotional reaction than discussing body mass index (BMI), particularly when it is high. Patients have become increasingly sensitive to weight discussions with their physicians because of concerns about body shaming. Among patients with an elevated BMI, criticism on social media of health care professionals’ counseling and a preemptive presentation of “Don’t Weigh Me” cards have become popular responses. Despite the medical evidence on impaired reproduction with an abnormal BMI, patients are choosing to forgo the topic. Research has demonstrated “extensive evidence [of] strong weight bias” in a wide range of health staff.1 A “viral” TikTok study revealed that medical “gaslighting” founded in weight stigma and bias is harmful, as reported on KevinMD.com.2 This month, we review the effect of abnormal BMI, both high and low, on reproduction and pregnancy.
A method to assess relative weight was first described in 1832 as its ratio in kilograms divided by the square of the height in meters, or the Quetelet Index. The search for a functional assessment of relative body weight began after World War II when reports by actuaries noted the increased mortality of overweight policyholders. The relationship between weight and cardiovascular disease was further revealed in epidemiologic studies. The Quetelet Index became the BMI in 1972.3
Weight measurement is a mainstay in the assessment of a patient’s vital signs along with blood pressure, pulse rate, respiration rate, and temperature. Weight is vital to the calculation of medication dosage – for instance, administration of conscious sedative drugs, methotrexate, and gonadotropins. Some state boards of medicine, such as Florida, have a limitation on patient BMI at office-based surgery centers (40 kg/m2).
Obesity is a disease
As reported by the World Health Organization in 2022, the disease of obesity is an epidemic afflicting more than 1 billion people worldwide, or 1 in 8 individuals globally.4 The health implications of an elevated BMI include increased mortality, diabetes, heart disease, and stroke, physical limitations to activities of daily living, and complications affecting reproduction.
Female obesity is related to poorer outcomes in natural and assisted conception, including an increased risk of miscarriage. Compared with normal-weight women, those with obesity are three times more likely to have ovulatory dysfunction,5 infertility,6 a lower chance for conception,7 higher rate of miscarriage, and low birth weight.8,9During pregnancy, women with obesity have three to four times higher rates of gestational diabetes and preeclampsia,10 as well as likelihood of delivering preterm,11 having a fetus with macrosomia and birth defects, and a 1.3- to 2.1-times higher risk of stillbirth.12
Obesity is present in 40%-80% of women with polycystic ovary syndrome,13 the most common cause of ovulatory dysfunction from dysregulation of the hypothalamic-pituitary-ovarian axis. While PCOS is associated with reproductive and metabolic consequences, even in regularly ovulating women, increasing obesity appears to be associated with decreasing spontaneous pregnancy rates and increased time to pregnancy.14
Obesity and IVF
Women with obesity have reduced success with assisted reproductive technology, an increased number of canceled cycles, and poorer quality oocytes retrieved. A prospective cohort study of nearly 2,000 women reported that every 5 kg of body weight increase (from the patient’s baseline weight at age 18) was associated with a 5% increase in the mean duration of time required for conception (95% confidence interval, 3%-7%).15 Given that approximately 90% of these women had regular menstrual cycles, ovulatory dysfunction was not the suspected pathophysiology.
A meta-analysis of 21 cohort studies reported a lower likelihood of live birth following in vitro fertilization for women with obesity, compared with normal-weight women (risk ratio, 0.85; 95% CI, 0.82-0.87).16 A further subgroup analysis that evaluated only women with PCOS showed a reduction in the live birth rate following IVF for individuals with obesity, compared with normal-weight individuals (RR, 0.78; 95% CI, 0.74-0.82).
In a retrospective study of almost 500,000 fresh autologous IVF cycles, women with obesity had a 6% reduction in pregnancy rates and a 13% reduction in live birth rates, compared with normal-weight women. Both high and low BMI were associated with an increased risk of low birth weight and preterm delivery.17 The live birth rates per transfer for normal-weight and higher-weight women were 38% and 33%, respectively.
Contrarily, a randomized controlled trial showed that an intensive weight-reduction program resulted in a large weight loss but did not substantially affect live birth rates in women with obesity scheduled for IVF.18
Low BMI
A noteworthy cause of low BMI is functional hypothalamic amenorrhea (FHA), a disorder with low energy availability either from decreased caloric intake and/or excessive energy expenditure associated with eating disorders, excessive exercise, and stress. Consequently, a reduced GnRH drive results in a decreased pulse frequency and amplitude leading to low levels of follicle-stimulating hormone and luteinizing hormone, resulting in anovulation. Correction of lifestyle behaviors related to FHA can restore menstrual cycles. After normal weight is achieved, it appears unlikely that fertility is affected.19 In 47% of adolescent patients with anorexia, menses spontaneously returned within the first 12 months after admission, with an improved prognosis in secondary over primary amenorrhea.20,21 Interestingly, mildly and significantly underweight infertile women have pregnancy and live birth rates similar to normal-weight patients after IVF treatment.22
Pregnancy is complicated in underweight women, resulting in an increased risk of anemia, fetal growth retardation, and low birth weight, as well as preterm birth.21
Take-home message
The extremes of BMI both impair natural reproduction. Elevated BMI reduces success with IVF but rapid weight loss prior to IVF does not improve outcomes. A normal BMI is the goal for optimal reproductive and pregnancy health.
Dr. Trolice is director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
References
1. Talumaa B et al. Obesity Rev. 2022;23:e13494.
2. https://bit.ly/3rHCivE.
3. Eknoyan G. Nephrol Dial Transplant. 2008;23:47-51.
4. Wells JCK. Dis Models Mech. 2012;5:595-607.
5. Brewer CJ and Balen AH. Reproduction. 2010;140:347-64.
6. Silvestris E et al. Reprod Biol Endocrinol. 2018;16:22.
7. Wise LA et al. Hum Reprod. 2010;25:253-64.
8. Bellver J. Curr Opin Obstet Gynecol. 2022;34:114-21.
9. Dickey RP et al. Am J Obstet Gynecol. 2013;209:349.e1.
10. Alwash SM et al. Obes Res Clin Pract. 2021;15:425-30.
11. Cnattingius S et al. JAMA. 2013;309:2362-70.
12. Aune D et al. JAMA. 2014;311:1536-46.
13. Sam S. Obes Manag. 2007;3:69-73.
14. van der Steeg JW et al. Hum Reprod. 2008;23:324-8.
15. Gaskins AJ et al. Obstet Gynecol. 2015;126:850-8.
16. Sermondade N et al. Hum Reprod Update. 2019;25:439-519.
17. Kawwass JF et al. Fertil Steril. 2016;106[7]:1742-50.
18. Einarsson S et al. Hum Reprod. 2017;32:1621-30.
19. Chaer R et al. Diseases. 2020;8:46.
20. Dempfle A et al. Psychiatry. 2013;13:308.
21. Verma A and Shrimali L. J Clin Diagn Res. 2012;6:1531-3.
22. Romanski PA et al. Reprod Biomed Online. 2020;42:366-74.
Arguably, no topic during an infertility consultation generates more of an emotional reaction than discussing body mass index (BMI), particularly when it is high. Patients have become increasingly sensitive to weight discussions with their physicians because of concerns about body shaming. Among patients with an elevated BMI, criticism on social media of health care professionals’ counseling and a preemptive presentation of “Don’t Weigh Me” cards have become popular responses. Despite the medical evidence on impaired reproduction with an abnormal BMI, patients are choosing to forgo the topic. Research has demonstrated “extensive evidence [of] strong weight bias” in a wide range of health staff.1 A “viral” TikTok study revealed that medical “gaslighting” founded in weight stigma and bias is harmful, as reported on KevinMD.com.2 This month, we review the effect of abnormal BMI, both high and low, on reproduction and pregnancy.
A method to assess relative weight was first described in 1832 as its ratio in kilograms divided by the square of the height in meters, or the Quetelet Index. The search for a functional assessment of relative body weight began after World War II when reports by actuaries noted the increased mortality of overweight policyholders. The relationship between weight and cardiovascular disease was further revealed in epidemiologic studies. The Quetelet Index became the BMI in 1972.3
Weight measurement is a mainstay in the assessment of a patient’s vital signs along with blood pressure, pulse rate, respiration rate, and temperature. Weight is vital to the calculation of medication dosage – for instance, administration of conscious sedative drugs, methotrexate, and gonadotropins. Some state boards of medicine, such as Florida, have a limitation on patient BMI at office-based surgery centers (40 kg/m2).
Obesity is a disease
As reported by the World Health Organization in 2022, the disease of obesity is an epidemic afflicting more than 1 billion people worldwide, or 1 in 8 individuals globally.4 The health implications of an elevated BMI include increased mortality, diabetes, heart disease, and stroke, physical limitations to activities of daily living, and complications affecting reproduction.
Female obesity is related to poorer outcomes in natural and assisted conception, including an increased risk of miscarriage. Compared with normal-weight women, those with obesity are three times more likely to have ovulatory dysfunction,5 infertility,6 a lower chance for conception,7 higher rate of miscarriage, and low birth weight.8,9During pregnancy, women with obesity have three to four times higher rates of gestational diabetes and preeclampsia,10 as well as likelihood of delivering preterm,11 having a fetus with macrosomia and birth defects, and a 1.3- to 2.1-times higher risk of stillbirth.12
Obesity is present in 40%-80% of women with polycystic ovary syndrome,13 the most common cause of ovulatory dysfunction from dysregulation of the hypothalamic-pituitary-ovarian axis. While PCOS is associated with reproductive and metabolic consequences, even in regularly ovulating women, increasing obesity appears to be associated with decreasing spontaneous pregnancy rates and increased time to pregnancy.14
Obesity and IVF
Women with obesity have reduced success with assisted reproductive technology, an increased number of canceled cycles, and poorer quality oocytes retrieved. A prospective cohort study of nearly 2,000 women reported that every 5 kg of body weight increase (from the patient’s baseline weight at age 18) was associated with a 5% increase in the mean duration of time required for conception (95% confidence interval, 3%-7%).15 Given that approximately 90% of these women had regular menstrual cycles, ovulatory dysfunction was not the suspected pathophysiology.
A meta-analysis of 21 cohort studies reported a lower likelihood of live birth following in vitro fertilization for women with obesity, compared with normal-weight women (risk ratio, 0.85; 95% CI, 0.82-0.87).16 A further subgroup analysis that evaluated only women with PCOS showed a reduction in the live birth rate following IVF for individuals with obesity, compared with normal-weight individuals (RR, 0.78; 95% CI, 0.74-0.82).
In a retrospective study of almost 500,000 fresh autologous IVF cycles, women with obesity had a 6% reduction in pregnancy rates and a 13% reduction in live birth rates, compared with normal-weight women. Both high and low BMI were associated with an increased risk of low birth weight and preterm delivery.17 The live birth rates per transfer for normal-weight and higher-weight women were 38% and 33%, respectively.
Contrarily, a randomized controlled trial showed that an intensive weight-reduction program resulted in a large weight loss but did not substantially affect live birth rates in women with obesity scheduled for IVF.18
Low BMI
A noteworthy cause of low BMI is functional hypothalamic amenorrhea (FHA), a disorder with low energy availability either from decreased caloric intake and/or excessive energy expenditure associated with eating disorders, excessive exercise, and stress. Consequently, a reduced GnRH drive results in a decreased pulse frequency and amplitude leading to low levels of follicle-stimulating hormone and luteinizing hormone, resulting in anovulation. Correction of lifestyle behaviors related to FHA can restore menstrual cycles. After normal weight is achieved, it appears unlikely that fertility is affected.19 In 47% of adolescent patients with anorexia, menses spontaneously returned within the first 12 months after admission, with an improved prognosis in secondary over primary amenorrhea.20,21 Interestingly, mildly and significantly underweight infertile women have pregnancy and live birth rates similar to normal-weight patients after IVF treatment.22
Pregnancy is complicated in underweight women, resulting in an increased risk of anemia, fetal growth retardation, and low birth weight, as well as preterm birth.21
Take-home message
The extremes of BMI both impair natural reproduction. Elevated BMI reduces success with IVF but rapid weight loss prior to IVF does not improve outcomes. A normal BMI is the goal for optimal reproductive and pregnancy health.
Dr. Trolice is director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
References
1. Talumaa B et al. Obesity Rev. 2022;23:e13494.
2. https://bit.ly/3rHCivE.
3. Eknoyan G. Nephrol Dial Transplant. 2008;23:47-51.
4. Wells JCK. Dis Models Mech. 2012;5:595-607.
5. Brewer CJ and Balen AH. Reproduction. 2010;140:347-64.
6. Silvestris E et al. Reprod Biol Endocrinol. 2018;16:22.
7. Wise LA et al. Hum Reprod. 2010;25:253-64.
8. Bellver J. Curr Opin Obstet Gynecol. 2022;34:114-21.
9. Dickey RP et al. Am J Obstet Gynecol. 2013;209:349.e1.
10. Alwash SM et al. Obes Res Clin Pract. 2021;15:425-30.
11. Cnattingius S et al. JAMA. 2013;309:2362-70.
12. Aune D et al. JAMA. 2014;311:1536-46.
13. Sam S. Obes Manag. 2007;3:69-73.
14. van der Steeg JW et al. Hum Reprod. 2008;23:324-8.
15. Gaskins AJ et al. Obstet Gynecol. 2015;126:850-8.
16. Sermondade N et al. Hum Reprod Update. 2019;25:439-519.
17. Kawwass JF et al. Fertil Steril. 2016;106[7]:1742-50.
18. Einarsson S et al. Hum Reprod. 2017;32:1621-30.
19. Chaer R et al. Diseases. 2020;8:46.
20. Dempfle A et al. Psychiatry. 2013;13:308.
21. Verma A and Shrimali L. J Clin Diagn Res. 2012;6:1531-3.
22. Romanski PA et al. Reprod Biomed Online. 2020;42:366-74.
Plant-based diet cut hot flashes 78%: WAVS study
Women eating a reduced-fat vegan diet combined with a daily serving of soybeans experienced a 78% reduction in frequency of menopausal hot flashes over 12 weeks, in a small, nonblinded, randomized-controlled trial.
“We do not fully understand yet why this combination works, but it seems that these three elements are key: avoiding animal products, reducing fat, and adding a serving of soybeans,” lead researcher Neal Barnard, MD, explained in a press release. “These new results suggest that a diet change should be considered as a first-line treatment for troublesome vasomotor symptoms, including night sweats and hot flashes,” added Dr. Barnard, who is president of the Physicians Committee for Responsible Medicine, and adjunct professor at George Washington University, Washington. 
But, while “the findings from this very small study complement everything we know about the benefits of an excellent diet and the health benefits of soy,” they should be interpreted with some caution, commented Susan Reed, MD, president of the North American Menopause Society, and associate program director of the women’s reproductive research program at the University of Washington, Seattle.
For the trial, called WAVS (Women’s Study for the Alleviation of Vasomotor Symptoms), the researchers randomized 84 postmenopausal women with at least two moderate to severe hot flashes daily to either the intervention or usual diet, with a total of 71 subjects completing the 12-week study, published in Menopause. Criteria for exclusion included any cause of vasomotor symptoms other than natural menopause, current use of a low-fat, vegan diet that includes daily soy products, soy allergy, and body mass index < 18.5 kg/m2.
Participants in the intervention group were asked to avoid animal-derived foods, minimize their use of oils and fatty foods such as nuts and avocados, and include half a cup (86 g) of cooked soybeans daily in their diets. They were also offered 1-hour virtual group meetings each week, in which a registered dietitian or research staff provided information on food preparation and managing common dietary challenges.
Control group participants were asked to continue their usual diets and attend four 1-hour group sessions.
At baseline and then after the 12-week study period, dietary intake was self-recorded for 2 weekdays and 1 weekend day, hot flash frequency and severity was recorded for 1 week using a mobile app, and the effect of menopausal symptoms on quality of life was measured using the vasomotor, psychosocial, physical, and sexual domains of the Menopause-Specific Quality of Life (MENQOL) questionnaire.
Equol production was also assessed in a subset of 15 intervention and 12 control participants who had urinary isoflavone concentrations measured after eating half a cup (86 g) of soybeans twice daily for 3 days. This was based on the theory that diets such as the intervention in this study “seem to foster the growth of gut bacteria capable of converting daidzein to equol,” noted the authors. The ability to produce equol is detected more frequently in individuals following vegetarian diets than in omnivores and … has been proposed as a factor in soy’s apparent health benefits.”
The study found that total hot flash frequency decreased by 78% in the intervention group (P < .001) and 39% (P < .001) in the control group (between-group P = .003), and moderate to severe hot flashes decreased by 88% versus 34%, respectively (from 5.0 to 0.6 per day, P < .001 vs. from 4.4 to 2.9 per day, P < .001; between-group P < .001). Among participants with at least seven moderate to severe hot flashes per day at baseline, moderate to severe hot flashes decreased by 93% (from 10.6 to 0.7 per day) in the intervention group (P < .001) and 36% (from 9.0 to 5.8 per day) in the control group (P = .01, between-group P < .001). The changes in hot flashes were paralleled by changes in the MENQOL findings, with significant between-group differences in the vasomotor (P = 0.004), physical (P = 0.01), and sexual (P = 0.03) domains.
Changes in frequency of severe hot flashes correlated directly with changes in fat intake, and inversely with changes in carbohydrate and fiber intake, such that “the greater the reduction in fat intake and the greater the increases in carbohydrate and fiber consumption, the greater the reduction in severe hot flashes,” noted the researchers. Mean body weight also decreased by 3.6 kg in the intervention group and 0.2 kg in the control group (P < .001). “Equol-production status had no apparent effect on hot flashes,” they added.
The study is the second phase of WAVS, which comprises two parts, the first of which showed similar results, but was conducted in the fall, raising questions about whether cooler temperatures were partly responsible for the results. Phase 2 of WAVS enrolled participants in the spring “ruling out the effect of outside temperature,” noted the authors.
“Eating a healthy diet at midlife is so important for long-term health and a sense of well-being for peri- and postmenopausal women,” said Dr Reed, but she urged caution in interpreting the findings. “This was an unblinded study,” she told this news organization. “Women were recruited to this study anticipating that they would be in a study on a soy diet. Individuals who sign up for a study are hoping for benefit from the intervention. The controls who don’t get the soy diet are often disappointed, so there is no benefit from a nonblinded control arm for their hot flashes. And that is exactly what we saw here. Blinded studies can hide what you are getting, so everyone in the study (intervention and controls) has the same anticipated benefit. But you cannot blind a soy diet.”
Dr. Reed also noted that, while the biologic mechanism of benefit should be equol production, this was not shown – given that both equol producers and nonproducers in the soy intervention reported marked symptom reduction.
“Only prior studies with estrogen interventions have observed reductions of hot flashes of the amount reported here,” she concluded. “Hopefully future large studies will clarify the role of soy diet for decreasing hot flashes.”
Dr. Barnard writes books and articles and gives lectures related to nutrition and health and has received royalties and honoraria from these sources. Dr. Reed has no relevant disclosures.
Women eating a reduced-fat vegan diet combined with a daily serving of soybeans experienced a 78% reduction in frequency of menopausal hot flashes over 12 weeks, in a small, nonblinded, randomized-controlled trial.
“We do not fully understand yet why this combination works, but it seems that these three elements are key: avoiding animal products, reducing fat, and adding a serving of soybeans,” lead researcher Neal Barnard, MD, explained in a press release. “These new results suggest that a diet change should be considered as a first-line treatment for troublesome vasomotor symptoms, including night sweats and hot flashes,” added Dr. Barnard, who is president of the Physicians Committee for Responsible Medicine, and adjunct professor at George Washington University, Washington.
But, while “the findings from this very small study complement everything we know about the benefits of an excellent diet and the health benefits of soy,” they should be interpreted with some caution, commented Susan Reed, MD, president of the North American Menopause Society, and associate program director of the women’s reproductive research program at the University of Washington, Seattle.
For the trial, called WAVS (Women’s Study for the Alleviation of Vasomotor Symptoms), the researchers randomized 84 postmenopausal women with at least two moderate to severe hot flashes daily to either the intervention or usual diet, with a total of 71 subjects completing the 12-week study, published in Menopause. Criteria for exclusion included any cause of vasomotor symptoms other than natural menopause, current use of a low-fat, vegan diet that includes daily soy products, soy allergy, and body mass index < 18.5 kg/m2.
Participants in the intervention group were asked to avoid animal-derived foods, minimize their use of oils and fatty foods such as nuts and avocados, and include half a cup (86 g) of cooked soybeans daily in their diets. They were also offered 1-hour virtual group meetings each week, in which a registered dietitian or research staff provided information on food preparation and managing common dietary challenges.
Control group participants were asked to continue their usual diets and attend four 1-hour group sessions.
At baseline and then after the 12-week study period, dietary intake was self-recorded for 2 weekdays and 1 weekend day, hot flash frequency and severity was recorded for 1 week using a mobile app, and the effect of menopausal symptoms on quality of life was measured using the vasomotor, psychosocial, physical, and sexual domains of the Menopause-Specific Quality of Life (MENQOL) questionnaire.
Equol production was also assessed in a subset of 15 intervention and 12 control participants who had urinary isoflavone concentrations measured after eating half a cup (86 g) of soybeans twice daily for 3 days. This was based on the theory that diets such as the intervention in this study “seem to foster the growth of gut bacteria capable of converting daidzein to equol,” noted the authors. The ability to produce equol is detected more frequently in individuals following vegetarian diets than in omnivores and … has been proposed as a factor in soy’s apparent health benefits.”
The study found that total hot flash frequency decreased by 78% in the intervention group (P < .001) and 39% (P < .001) in the control group (between-group P = .003), and moderate to severe hot flashes decreased by 88% versus 34%, respectively (from 5.0 to 0.6 per day, P < .001 vs. from 4.4 to 2.9 per day, P < .001; between-group P < .001). Among participants with at least seven moderate to severe hot flashes per day at baseline, moderate to severe hot flashes decreased by 93% (from 10.6 to 0.7 per day) in the intervention group (P < .001) and 36% (from 9.0 to 5.8 per day) in the control group (P = .01, between-group P < .001). The changes in hot flashes were paralleled by changes in the MENQOL findings, with significant between-group differences in the vasomotor (P = 0.004), physical (P = 0.01), and sexual (P = 0.03) domains.
Changes in frequency of severe hot flashes correlated directly with changes in fat intake, and inversely with changes in carbohydrate and fiber intake, such that “the greater the reduction in fat intake and the greater the increases in carbohydrate and fiber consumption, the greater the reduction in severe hot flashes,” noted the researchers. Mean body weight also decreased by 3.6 kg in the intervention group and 0.2 kg in the control group (P < .001). “Equol-production status had no apparent effect on hot flashes,” they added.
The study is the second phase of WAVS, which comprises two parts, the first of which showed similar results, but was conducted in the fall, raising questions about whether cooler temperatures were partly responsible for the results. Phase 2 of WAVS enrolled participants in the spring “ruling out the effect of outside temperature,” noted the authors.
“Eating a healthy diet at midlife is so important for long-term health and a sense of well-being for peri- and postmenopausal women,” said Dr Reed, but she urged caution in interpreting the findings. “This was an unblinded study,” she told this news organization. “Women were recruited to this study anticipating that they would be in a study on a soy diet. Individuals who sign up for a study are hoping for benefit from the intervention. The controls who don’t get the soy diet are often disappointed, so there is no benefit from a nonblinded control arm for their hot flashes. And that is exactly what we saw here. Blinded studies can hide what you are getting, so everyone in the study (intervention and controls) has the same anticipated benefit. But you cannot blind a soy diet.”
Dr. Reed also noted that, while the biologic mechanism of benefit should be equol production, this was not shown – given that both equol producers and nonproducers in the soy intervention reported marked symptom reduction.
“Only prior studies with estrogen interventions have observed reductions of hot flashes of the amount reported here,” she concluded. “Hopefully future large studies will clarify the role of soy diet for decreasing hot flashes.”
Dr. Barnard writes books and articles and gives lectures related to nutrition and health and has received royalties and honoraria from these sources. Dr. Reed has no relevant disclosures.
Women eating a reduced-fat vegan diet combined with a daily serving of soybeans experienced a 78% reduction in frequency of menopausal hot flashes over 12 weeks, in a small, nonblinded, randomized-controlled trial.
“We do not fully understand yet why this combination works, but it seems that these three elements are key: avoiding animal products, reducing fat, and adding a serving of soybeans,” lead researcher Neal Barnard, MD, explained in a press release. “These new results suggest that a diet change should be considered as a first-line treatment for troublesome vasomotor symptoms, including night sweats and hot flashes,” added Dr. Barnard, who is president of the Physicians Committee for Responsible Medicine, and adjunct professor at George Washington University, Washington.
But, while “the findings from this very small study complement everything we know about the benefits of an excellent diet and the health benefits of soy,” they should be interpreted with some caution, commented Susan Reed, MD, president of the North American Menopause Society, and associate program director of the women’s reproductive research program at the University of Washington, Seattle.
For the trial, called WAVS (Women’s Study for the Alleviation of Vasomotor Symptoms), the researchers randomized 84 postmenopausal women with at least two moderate to severe hot flashes daily to either the intervention or usual diet, with a total of 71 subjects completing the 12-week study, published in Menopause. Criteria for exclusion included any cause of vasomotor symptoms other than natural menopause, current use of a low-fat, vegan diet that includes daily soy products, soy allergy, and body mass index < 18.5 kg/m2.
Participants in the intervention group were asked to avoid animal-derived foods, minimize their use of oils and fatty foods such as nuts and avocados, and include half a cup (86 g) of cooked soybeans daily in their diets. They were also offered 1-hour virtual group meetings each week, in which a registered dietitian or research staff provided information on food preparation and managing common dietary challenges.
Control group participants were asked to continue their usual diets and attend four 1-hour group sessions.
At baseline and then after the 12-week study period, dietary intake was self-recorded for 2 weekdays and 1 weekend day, hot flash frequency and severity was recorded for 1 week using a mobile app, and the effect of menopausal symptoms on quality of life was measured using the vasomotor, psychosocial, physical, and sexual domains of the Menopause-Specific Quality of Life (MENQOL) questionnaire.
Equol production was also assessed in a subset of 15 intervention and 12 control participants who had urinary isoflavone concentrations measured after eating half a cup (86 g) of soybeans twice daily for 3 days. This was based on the theory that diets such as the intervention in this study “seem to foster the growth of gut bacteria capable of converting daidzein to equol,” noted the authors. The ability to produce equol is detected more frequently in individuals following vegetarian diets than in omnivores and … has been proposed as a factor in soy’s apparent health benefits.”
The study found that total hot flash frequency decreased by 78% in the intervention group (P < .001) and 39% (P < .001) in the control group (between-group P = .003), and moderate to severe hot flashes decreased by 88% versus 34%, respectively (from 5.0 to 0.6 per day, P < .001 vs. from 4.4 to 2.9 per day, P < .001; between-group P < .001). Among participants with at least seven moderate to severe hot flashes per day at baseline, moderate to severe hot flashes decreased by 93% (from 10.6 to 0.7 per day) in the intervention group (P < .001) and 36% (from 9.0 to 5.8 per day) in the control group (P = .01, between-group P < .001). The changes in hot flashes were paralleled by changes in the MENQOL findings, with significant between-group differences in the vasomotor (P = 0.004), physical (P = 0.01), and sexual (P = 0.03) domains.
Changes in frequency of severe hot flashes correlated directly with changes in fat intake, and inversely with changes in carbohydrate and fiber intake, such that “the greater the reduction in fat intake and the greater the increases in carbohydrate and fiber consumption, the greater the reduction in severe hot flashes,” noted the researchers. Mean body weight also decreased by 3.6 kg in the intervention group and 0.2 kg in the control group (P < .001). “Equol-production status had no apparent effect on hot flashes,” they added.
The study is the second phase of WAVS, which comprises two parts, the first of which showed similar results, but was conducted in the fall, raising questions about whether cooler temperatures were partly responsible for the results. Phase 2 of WAVS enrolled participants in the spring “ruling out the effect of outside temperature,” noted the authors.
“Eating a healthy diet at midlife is so important for long-term health and a sense of well-being for peri- and postmenopausal women,” said Dr Reed, but she urged caution in interpreting the findings. “This was an unblinded study,” she told this news organization. “Women were recruited to this study anticipating that they would be in a study on a soy diet. Individuals who sign up for a study are hoping for benefit from the intervention. The controls who don’t get the soy diet are often disappointed, so there is no benefit from a nonblinded control arm for their hot flashes. And that is exactly what we saw here. Blinded studies can hide what you are getting, so everyone in the study (intervention and controls) has the same anticipated benefit. But you cannot blind a soy diet.”
Dr. Reed also noted that, while the biologic mechanism of benefit should be equol production, this was not shown – given that both equol producers and nonproducers in the soy intervention reported marked symptom reduction.
“Only prior studies with estrogen interventions have observed reductions of hot flashes of the amount reported here,” she concluded. “Hopefully future large studies will clarify the role of soy diet for decreasing hot flashes.”
Dr. Barnard writes books and articles and gives lectures related to nutrition and health and has received royalties and honoraria from these sources. Dr. Reed has no relevant disclosures.
HPV-positive women who undergo IVF don’t have worse outcomes
A new study provides more evidence that HPV infection doesn’t raise the risk of poor outcomes in women who undergo fertility treatment via in vitro fertilization with fresh embryos. In fact, HPV-positive women were somewhat more likely than HPV-negative women to become pregnant (relative risk, 1.20; 95% confidence interval, 1.03-1.39) and have live births (RR, 1.39; 95% CI, 1.13-1.70), researchers reported Oct. 24 at the American Society for Reproductive Medicine’s 2022 meeting .
“This evidence should reassure women that being HPV positive will not affect live birth rates after a fresh embryo transfer cycle,” said study coauthor and ob.gyn. Nina Vyas, MD, a clinical fellow at Weill Cornell Medicine, New York, in an interview.
According to Dr. Vyas, previous studies have offered conflicting results about whether HPV affects pregnancy outcomes. In 2006, for example, her group performed a pilot study (Fertil Steril. Jun 16. doi: 10.1016/j.fertnstert.2006.01.051) that linked lower pregnancy rates to HPV-positive tests on the day of egg retrieval.
“We sought to reevaluate this finding in a retrospective manner,” Dr. Vyas said. “You’re taking eggs out of their home, injecting with sperm, and putting them back. There’s so much that we don’t know, and we want to make sure there’s no extra risk.”
Also, she added, “prior studies had a relatively low sample size. We sought to use our patient volume to address this question on a larger scale. Our current study benefits from a large sample size and using the clinically meaningful endpoint of live birth as our primary outcome.”
For the new study, researchers retrospectively analyzed 1,333 patients (of 2,209 screened) who received first fresh embryo transfers from 2017 to 2019. All had cytology or HPV status documented per cervical cancer screening guidelines within 6 months before embryos were transferred.
The researchers looked at only fresh embryo transfers “so we could account for pregnancy outcomes closest to the documented HPV status at the time of egg retrieval,” Dr. Vyas said.
Ten percent (133) of patients were HPV positive. Of those, 60.1% became pregnant, and 43.6% of them had live births. Of the HPV-negative women (90% of subjects, n = 1,200), 52.2% became pregnant and 33.5% had live births. The researchers didn’t calculate P values, but Dr. Vyas said an analysis determined that the differences between HPV-positive and HPV-negative women were statistically significant.
The study size doesn’t allow researchers to determine whether HPV actually has a protective effect on pregnancy/live birth rates in IVF, Dr. Vyas said. Even if it did, the virus is dangerous.
What else could explain the discrepancy? “Some elements driving this could the smaller sample size of the HPV-positive group, differences in HPV prevalence between the general population and our population,” she said, “or other confounding factors we were not able to appreciate due to the limitations of the retrospective study.”
Researchers also reported that they found “no significant difference in biochemical or spontaneous abortion rates” between HPV-positive and HPV-negative women.
What is the message of the study? “Women with HPV can rest assured that they won’t have worse outcomes than their non-HPV [infected] counterparts after a fresh embryo transfer cycle,” Dr. Vyas said.
In an interview, McGill University, Montreal, epidemiologist Helen Trottier, PhD, MSc, noted that she recently coauthored a study that linked persistent HPV infection in pregnancy to premature births. The findings appear convincing, she said: “I think we can say that HPV is associated with preterm birth.”
She praised the new study but noted “the relative risks that are reported need to be adjusted for race and possibly other factors.”
Dr. Vyas said that kind of adjustment will occur in a future study that’s in progress. “We are now prospectively enrolling patients and collecting cytology data to understand whether there might be a difference for women with higher malignancy potential/different types of HPV genotypes.”
The study authors have no disclosures. Disclosure information for Dr. Trottier was unavailable.
A new study provides more evidence that HPV infection doesn’t raise the risk of poor outcomes in women who undergo fertility treatment via in vitro fertilization with fresh embryos. In fact, HPV-positive women were somewhat more likely than HPV-negative women to become pregnant (relative risk, 1.20; 95% confidence interval, 1.03-1.39) and have live births (RR, 1.39; 95% CI, 1.13-1.70), researchers reported Oct. 24 at the American Society for Reproductive Medicine’s 2022 meeting .
“This evidence should reassure women that being HPV positive will not affect live birth rates after a fresh embryo transfer cycle,” said study coauthor and ob.gyn. Nina Vyas, MD, a clinical fellow at Weill Cornell Medicine, New York, in an interview.
According to Dr. Vyas, previous studies have offered conflicting results about whether HPV affects pregnancy outcomes. In 2006, for example, her group performed a pilot study (Fertil Steril. Jun 16. doi: 10.1016/j.fertnstert.2006.01.051) that linked lower pregnancy rates to HPV-positive tests on the day of egg retrieval.
“We sought to reevaluate this finding in a retrospective manner,” Dr. Vyas said. “You’re taking eggs out of their home, injecting with sperm, and putting them back. There’s so much that we don’t know, and we want to make sure there’s no extra risk.”
Also, she added, “prior studies had a relatively low sample size. We sought to use our patient volume to address this question on a larger scale. Our current study benefits from a large sample size and using the clinically meaningful endpoint of live birth as our primary outcome.”
For the new study, researchers retrospectively analyzed 1,333 patients (of 2,209 screened) who received first fresh embryo transfers from 2017 to 2019. All had cytology or HPV status documented per cervical cancer screening guidelines within 6 months before embryos were transferred.
The researchers looked at only fresh embryo transfers “so we could account for pregnancy outcomes closest to the documented HPV status at the time of egg retrieval,” Dr. Vyas said.
Ten percent (133) of patients were HPV positive. Of those, 60.1% became pregnant, and 43.6% of them had live births. Of the HPV-negative women (90% of subjects, n = 1,200), 52.2% became pregnant and 33.5% had live births. The researchers didn’t calculate P values, but Dr. Vyas said an analysis determined that the differences between HPV-positive and HPV-negative women were statistically significant.
The study size doesn’t allow researchers to determine whether HPV actually has a protective effect on pregnancy/live birth rates in IVF, Dr. Vyas said. Even if it did, the virus is dangerous.
What else could explain the discrepancy? “Some elements driving this could the smaller sample size of the HPV-positive group, differences in HPV prevalence between the general population and our population,” she said, “or other confounding factors we were not able to appreciate due to the limitations of the retrospective study.”
Researchers also reported that they found “no significant difference in biochemical or spontaneous abortion rates” between HPV-positive and HPV-negative women.
What is the message of the study? “Women with HPV can rest assured that they won’t have worse outcomes than their non-HPV [infected] counterparts after a fresh embryo transfer cycle,” Dr. Vyas said.
In an interview, McGill University, Montreal, epidemiologist Helen Trottier, PhD, MSc, noted that she recently coauthored a study that linked persistent HPV infection in pregnancy to premature births. The findings appear convincing, she said: “I think we can say that HPV is associated with preterm birth.”
She praised the new study but noted “the relative risks that are reported need to be adjusted for race and possibly other factors.”
Dr. Vyas said that kind of adjustment will occur in a future study that’s in progress. “We are now prospectively enrolling patients and collecting cytology data to understand whether there might be a difference for women with higher malignancy potential/different types of HPV genotypes.”
The study authors have no disclosures. Disclosure information for Dr. Trottier was unavailable.
A new study provides more evidence that HPV infection doesn’t raise the risk of poor outcomes in women who undergo fertility treatment via in vitro fertilization with fresh embryos. In fact, HPV-positive women were somewhat more likely than HPV-negative women to become pregnant (relative risk, 1.20; 95% confidence interval, 1.03-1.39) and have live births (RR, 1.39; 95% CI, 1.13-1.70), researchers reported Oct. 24 at the American Society for Reproductive Medicine’s 2022 meeting .
“This evidence should reassure women that being HPV positive will not affect live birth rates after a fresh embryo transfer cycle,” said study coauthor and ob.gyn. Nina Vyas, MD, a clinical fellow at Weill Cornell Medicine, New York, in an interview.
According to Dr. Vyas, previous studies have offered conflicting results about whether HPV affects pregnancy outcomes. In 2006, for example, her group performed a pilot study (Fertil Steril. Jun 16. doi: 10.1016/j.fertnstert.2006.01.051) that linked lower pregnancy rates to HPV-positive tests on the day of egg retrieval.
“We sought to reevaluate this finding in a retrospective manner,” Dr. Vyas said. “You’re taking eggs out of their home, injecting with sperm, and putting them back. There’s so much that we don’t know, and we want to make sure there’s no extra risk.”
Also, she added, “prior studies had a relatively low sample size. We sought to use our patient volume to address this question on a larger scale. Our current study benefits from a large sample size and using the clinically meaningful endpoint of live birth as our primary outcome.”
For the new study, researchers retrospectively analyzed 1,333 patients (of 2,209 screened) who received first fresh embryo transfers from 2017 to 2019. All had cytology or HPV status documented per cervical cancer screening guidelines within 6 months before embryos were transferred.
The researchers looked at only fresh embryo transfers “so we could account for pregnancy outcomes closest to the documented HPV status at the time of egg retrieval,” Dr. Vyas said.
Ten percent (133) of patients were HPV positive. Of those, 60.1% became pregnant, and 43.6% of them had live births. Of the HPV-negative women (90% of subjects, n = 1,200), 52.2% became pregnant and 33.5% had live births. The researchers didn’t calculate P values, but Dr. Vyas said an analysis determined that the differences between HPV-positive and HPV-negative women were statistically significant.
The study size doesn’t allow researchers to determine whether HPV actually has a protective effect on pregnancy/live birth rates in IVF, Dr. Vyas said. Even if it did, the virus is dangerous.
What else could explain the discrepancy? “Some elements driving this could the smaller sample size of the HPV-positive group, differences in HPV prevalence between the general population and our population,” she said, “or other confounding factors we were not able to appreciate due to the limitations of the retrospective study.”
Researchers also reported that they found “no significant difference in biochemical or spontaneous abortion rates” between HPV-positive and HPV-negative women.
What is the message of the study? “Women with HPV can rest assured that they won’t have worse outcomes than their non-HPV [infected] counterparts after a fresh embryo transfer cycle,” Dr. Vyas said.
In an interview, McGill University, Montreal, epidemiologist Helen Trottier, PhD, MSc, noted that she recently coauthored a study that linked persistent HPV infection in pregnancy to premature births. The findings appear convincing, she said: “I think we can say that HPV is associated with preterm birth.”
She praised the new study but noted “the relative risks that are reported need to be adjusted for race and possibly other factors.”
Dr. Vyas said that kind of adjustment will occur in a future study that’s in progress. “We are now prospectively enrolling patients and collecting cytology data to understand whether there might be a difference for women with higher malignancy potential/different types of HPV genotypes.”
The study authors have no disclosures. Disclosure information for Dr. Trottier was unavailable.
FROM ASRM 2022
Bugs, drugs, and the placenta
How exquisitely designed is the human body? Despite our efforts to occasionally derail our health and well-being, our bodies come with helpful built-in protective functional barriers. The blood-brain barrier and the placenta are two examples. In basic terms, both restrict the free flow of substances from the systemic circulation and help prevent harmful substances from reaching the brain and the fetus, respectively. The placenta is unique in that it develops along with the fetus and, at delivery, is expelled after having done its work. But what happens when a disease or treatment alters the ability of the placenta to operate as a control gate for the fetus?
In keeping with this column’s title, let’s start with bugs. Based on the 2021 World Malaria Report, malaria continues to strike hardest against pregnant women and children in Africa.1 In 2020 in 33 moderate- and high-transmission African countries, 34% of pregnancies (11.6 million of 33.8 million) were exposed to malaria infection. Malaria infection during pregnancy is associated with adverse birth outcomes, including small for gestational age and preterm birth, which in turn increase the risk for neonatal and childhood mortality.
Malaria is caused by the parasite of the genus Plasmodium and is transmitted by infective female Anopheles mosquitoes. The predominant parasite in sub-Saharan Africa is Plasmodium falciparum. Pregnant women are particularly vulnerable. Once a subject is bitten, the P. falciparum parasite is injected into the human blood stream where it is taken up initially by the liver and subsequently by the erythrocytes of the host which adhere to placental receptors, triggering placental inflammation and subsequent damage. This leads to impaired placental development and function, placental insufficiency, and the adverse birth outcomes identified above.2 In targeting the placenta, this parasite can cause structural and functional placental alterations through infection and inflammation. A recent review by McColl et al. has shown that placental inflammation with or without infection affects the normal function of placental amino acid transporters, leading to similar adverse pregnancy outcomes.3
Moving on to drugs and drug safety in pregnancy, concern generally focuses on exposure during pregnancy that might directly affect the fetus at critical time windows during growth and development. There is a need to understand not only the size of the drug molecules and the degree to which they cross the placenta, but also how those medications may affect the development and function of the placenta itself. New research methods such as the “placenta-on-a-chip” that models the transport of nutrients and drugs allow direct evaluation of placental function.4 Assessing placental function using such tools during drug development will contribute to a better understanding of the safety and efficacy of new medications for use in pregnancy, providing important information at the preclinical phases.5
The placenta is a dynamic organ with metabolic, endocrine, immunologic, and transport functions. Most importantly, it protects a healthy pregnancy. It also provides the advantage of immunologic protection to the fetus when maternal antibodies cross the placenta and provide initial protection until the newborn’s own immune system matures. Using our knowledge of placental alteration models and new research methods such as “placenta-on-a-chip” can help expand our understanding of the role of the placenta in medication safety in pregnancy.
Dr. Hardy is executive director, head of pharmacoepidemiology, at Biohaven Pharmaceuticals. She serves as a member of Council for the Society for Birth Defects Research and Prevention, represents the BDRP on the Coalition to Advance Maternal Therapeutics, and is a member of the North American Board for Amandla Development, South Africa. Dr. Tassinari is a consultant and was formerly employed by Pfizer and the Food and Drug Administration. Dr. Tassinari is a past president of BDRP (formerly the Teratology Society) and currently serves as a member of the External Science Advisory Committee for The Medicines for Malaria Venture and is a member of the Science Advisory Committee for the COVID-19 Vaccines International Pregnancy Exposure Registry.
References
1. World malaria report 2021. Geneva: World Health Organization; 2021.
2. Chua CLL et al. Front Immunol. 2021;12:621382.
3. McColl ER et al. Drug Metab Dispos. May 2022.
4. Blundeli C et al. Adv Healthc Mater. 2018. January;7(2).
5. David AL et al. Ther Innov Regul Sci. 2022.
How exquisitely designed is the human body? Despite our efforts to occasionally derail our health and well-being, our bodies come with helpful built-in protective functional barriers. The blood-brain barrier and the placenta are two examples. In basic terms, both restrict the free flow of substances from the systemic circulation and help prevent harmful substances from reaching the brain and the fetus, respectively. The placenta is unique in that it develops along with the fetus and, at delivery, is expelled after having done its work. But what happens when a disease or treatment alters the ability of the placenta to operate as a control gate for the fetus?
In keeping with this column’s title, let’s start with bugs. Based on the 2021 World Malaria Report, malaria continues to strike hardest against pregnant women and children in Africa.1 In 2020 in 33 moderate- and high-transmission African countries, 34% of pregnancies (11.6 million of 33.8 million) were exposed to malaria infection. Malaria infection during pregnancy is associated with adverse birth outcomes, including small for gestational age and preterm birth, which in turn increase the risk for neonatal and childhood mortality.
Malaria is caused by the parasite of the genus Plasmodium and is transmitted by infective female Anopheles mosquitoes. The predominant parasite in sub-Saharan Africa is Plasmodium falciparum. Pregnant women are particularly vulnerable. Once a subject is bitten, the P. falciparum parasite is injected into the human blood stream where it is taken up initially by the liver and subsequently by the erythrocytes of the host which adhere to placental receptors, triggering placental inflammation and subsequent damage. This leads to impaired placental development and function, placental insufficiency, and the adverse birth outcomes identified above.2 In targeting the placenta, this parasite can cause structural and functional placental alterations through infection and inflammation. A recent review by McColl et al. has shown that placental inflammation with or without infection affects the normal function of placental amino acid transporters, leading to similar adverse pregnancy outcomes.3
Moving on to drugs and drug safety in pregnancy, concern generally focuses on exposure during pregnancy that might directly affect the fetus at critical time windows during growth and development. There is a need to understand not only the size of the drug molecules and the degree to which they cross the placenta, but also how those medications may affect the development and function of the placenta itself. New research methods such as the “placenta-on-a-chip” that models the transport of nutrients and drugs allow direct evaluation of placental function.4 Assessing placental function using such tools during drug development will contribute to a better understanding of the safety and efficacy of new medications for use in pregnancy, providing important information at the preclinical phases.5
The placenta is a dynamic organ with metabolic, endocrine, immunologic, and transport functions. Most importantly, it protects a healthy pregnancy. It also provides the advantage of immunologic protection to the fetus when maternal antibodies cross the placenta and provide initial protection until the newborn’s own immune system matures. Using our knowledge of placental alteration models and new research methods such as “placenta-on-a-chip” can help expand our understanding of the role of the placenta in medication safety in pregnancy.
Dr. Hardy is executive director, head of pharmacoepidemiology, at Biohaven Pharmaceuticals. She serves as a member of Council for the Society for Birth Defects Research and Prevention, represents the BDRP on the Coalition to Advance Maternal Therapeutics, and is a member of the North American Board for Amandla Development, South Africa. Dr. Tassinari is a consultant and was formerly employed by Pfizer and the Food and Drug Administration. Dr. Tassinari is a past president of BDRP (formerly the Teratology Society) and currently serves as a member of the External Science Advisory Committee for The Medicines for Malaria Venture and is a member of the Science Advisory Committee for the COVID-19 Vaccines International Pregnancy Exposure Registry.
References
1. World malaria report 2021. Geneva: World Health Organization; 2021.
2. Chua CLL et al. Front Immunol. 2021;12:621382.
3. McColl ER et al. Drug Metab Dispos. May 2022.
4. Blundeli C et al. Adv Healthc Mater. 2018. January;7(2).
5. David AL et al. Ther Innov Regul Sci. 2022.
How exquisitely designed is the human body? Despite our efforts to occasionally derail our health and well-being, our bodies come with helpful built-in protective functional barriers. The blood-brain barrier and the placenta are two examples. In basic terms, both restrict the free flow of substances from the systemic circulation and help prevent harmful substances from reaching the brain and the fetus, respectively. The placenta is unique in that it develops along with the fetus and, at delivery, is expelled after having done its work. But what happens when a disease or treatment alters the ability of the placenta to operate as a control gate for the fetus?
In keeping with this column’s title, let’s start with bugs. Based on the 2021 World Malaria Report, malaria continues to strike hardest against pregnant women and children in Africa.1 In 2020 in 33 moderate- and high-transmission African countries, 34% of pregnancies (11.6 million of 33.8 million) were exposed to malaria infection. Malaria infection during pregnancy is associated with adverse birth outcomes, including small for gestational age and preterm birth, which in turn increase the risk for neonatal and childhood mortality.
Malaria is caused by the parasite of the genus Plasmodium and is transmitted by infective female Anopheles mosquitoes. The predominant parasite in sub-Saharan Africa is Plasmodium falciparum. Pregnant women are particularly vulnerable. Once a subject is bitten, the P. falciparum parasite is injected into the human blood stream where it is taken up initially by the liver and subsequently by the erythrocytes of the host which adhere to placental receptors, triggering placental inflammation and subsequent damage. This leads to impaired placental development and function, placental insufficiency, and the adverse birth outcomes identified above.2 In targeting the placenta, this parasite can cause structural and functional placental alterations through infection and inflammation. A recent review by McColl et al. has shown that placental inflammation with or without infection affects the normal function of placental amino acid transporters, leading to similar adverse pregnancy outcomes.3
Moving on to drugs and drug safety in pregnancy, concern generally focuses on exposure during pregnancy that might directly affect the fetus at critical time windows during growth and development. There is a need to understand not only the size of the drug molecules and the degree to which they cross the placenta, but also how those medications may affect the development and function of the placenta itself. New research methods such as the “placenta-on-a-chip” that models the transport of nutrients and drugs allow direct evaluation of placental function.4 Assessing placental function using such tools during drug development will contribute to a better understanding of the safety and efficacy of new medications for use in pregnancy, providing important information at the preclinical phases.5
The placenta is a dynamic organ with metabolic, endocrine, immunologic, and transport functions. Most importantly, it protects a healthy pregnancy. It also provides the advantage of immunologic protection to the fetus when maternal antibodies cross the placenta and provide initial protection until the newborn’s own immune system matures. Using our knowledge of placental alteration models and new research methods such as “placenta-on-a-chip” can help expand our understanding of the role of the placenta in medication safety in pregnancy.
Dr. Hardy is executive director, head of pharmacoepidemiology, at Biohaven Pharmaceuticals. She serves as a member of Council for the Society for Birth Defects Research and Prevention, represents the BDRP on the Coalition to Advance Maternal Therapeutics, and is a member of the North American Board for Amandla Development, South Africa. Dr. Tassinari is a consultant and was formerly employed by Pfizer and the Food and Drug Administration. Dr. Tassinari is a past president of BDRP (formerly the Teratology Society) and currently serves as a member of the External Science Advisory Committee for The Medicines for Malaria Venture and is a member of the Science Advisory Committee for the COVID-19 Vaccines International Pregnancy Exposure Registry.
References
1. World malaria report 2021. Geneva: World Health Organization; 2021.
2. Chua CLL et al. Front Immunol. 2021;12:621382.
3. McColl ER et al. Drug Metab Dispos. May 2022.
4. Blundeli C et al. Adv Healthc Mater. 2018. January;7(2).
5. David AL et al. Ther Innov Regul Sci. 2022.
Early estrogen loss increases cardiovascular risk in women
The relationship between estrogen levels and heart health makes it particularly important for clinicians to be aware of those patients who might be at risk for cardiovascular disease despite not having other traditional risk factors, according to a presentation Oct. 12 at the North American Menopause Society annual meeting in Atlanta.
”Endogenous estrogens are protective for cardiovascular disease in premenopausal women,” Chrisandra L. Shufelt, MD, chair of the division of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Fla., told attendees. Yet, “a substantial population of young women are dying prematurely from cardiovascular disease,” with rates of cardiovascular death increasing in women aged 35-44 even as rates have decreased in postmenopausal women and in men. One potential reason may be premature estrogen loss.
Dr. Shufelt reminded attendees of four major causes of premature estrogen loss: Natural premature menopause, surgical menopause, chemotherapy-induced menopause, and premature ovarian insufficiency. But she would go on to discuss a less widely recognized condition, functional hypothalamic amenorrhea, that also may be contributing to increased cardiovascular risk.
First, Dr. Shufelt reviewed the evidence supporting the relationship between estrogen and cardiovascular health, starting with the Framingham study’s findings that cardiovascular disease is approximately two to four times more common in postmenopausal women than in premenopausal women, depending on the age range.
“Menopause at an early age, particularly under the age of 40, matters,” Dr. Shufelt said. “So we should be discussing this with our patients.”
Surgical menopause makes a difference to cardiovascular health as well, she said. In women under age 35, for example, the risk of a nonfatal heart attack in those with a bilateral oophorectomy was 7.7 times greater than in women who retained both ovaries and their uterus, and 1.5 times greater in women who had a hysterectomy without bilateral oophorectomy.
In a 2019 study, surgical premature menopause was associated with an 87% increased risk of heart disease even after researchers accounted for age, cardiovascular risk factors, and some forms of hormone therapy. The increased risk from natural premature menopause, on the other hand, was lower – a 36% increased risk of heart disease – compared with those producing endogenous hormones. Although randomized controlled trials are unavailable and unlikely to be done, the Nurses’ Health Study and the Danish Nurses Cohort Study, both observational studies, found that heart disease risk was diminished in those taking hormone therapy after surgical premature menopause.
Recommendations for premature or early menopause, from a wide range of different medical societies including NAMS, are that women without contraindications be given estrogen-based hormone therapy until the average age of natural menopause. Though not included in the same guidance, research has also shown that estrogen after oophorectomy does not increase the risk of breast cancer in women with a BRCA1 mutation, Dr. Shufelt said. Hormone therapy for premature or early menopause should adequately replace the levels women have lost and that means younger menopausal women often need higher doses than what older women receive, such as 2 mg/day of oral estradiol rather than the standard doses of 0.5 or 1 mg/day.
Functional hypothalamic amenorrhea and cardiovascular risk
Dr. Shufelt then discussed functional hypothalamic amenorrhea (hypogonadotropic hypogonadism), a common type of secondary amenorrhea that affects at least 1.4 million U.S. women. Diagnosis includes lack of a period for at least 3 months in someone who previously menstruated plus lab values below 50 pg/mL for estradiol, below 10 mIU/L for follicle stimulating hormone, and below 10 mIU/L for luteinizing hormone. Causes of this reversible form of infertility can include stress, overexercising, undereating, or some combination of these, plus an underlying genetic predisposition.
“After ruling out polycystic ovary syndrome, prolactinoma, and thyroid dysfunction, clinicians need to consider the diagnosis of hypothalamic amenorrhea,” Dr. Shufelt said. This condition goes beyond low estrogen levels: Women have elevated cortisol, low thyroid levels, low leptin levels, and increased ghrelin.
”This is not going away,” Dr. Shufelt said, sharing data on stress levels among U.S. adults, particularly Gen Z and millennial adults, noting that the ongoing “national mental health crisis” may be contributing to functional hypothalamic amenorrhea.
A 2020 substudy from the Nurses’ Health Study II found an increased risk of premature death in those who didn’t have a period or always had irregular periods starting as early as 14-17 years old. The increased risk of premature death rose with age in those with irregular or absent cycles – a 37% higher risk in 18- to 22-year-olds and a 39% increased risk in 29- to 46-year-olds.
But clinicians aren’t adequately identifying the “phenotype of the hypothalamic women,” Dr. Shufelt said, despite research showing overlap between hypothalamic amenorrhea and a higher risk of cardiovascular disease. Hypothalamic amenorrhea is so understudied that the last original research on the topic was in 2008, Dr. Shufelt said in an interview. ”No research except mine has been done to evaluate heart health in these young women,” she said.
Dr. Shufelt described a study she led involving 30 women with functional hypothalamic amenorrhea, 29 women with normal menstrual cycles, and 30 women who were recently menopausal and not on hormone therapy. The women with hypothalamic amenorrhea had average stress levels but their depression scores were higher than those of the other two groups.
The results showed that women with hypothalamic amenorrhea had lower estradiol and leptin levels and higher testosterone levels compared with the control group, and they had higher cortisol levels than those of both groups. Despite having similar body mass indexes as the control and menopausal groups, women with hypothalamic amenorrhea had lower blood pressure than that of the other two groups, yet they had higher cholesterol levels than those of the control group. EndoPAT© (Itamar Medical) testing showed that they had poor vascular function.
“In fact, one-third of the women [with hypothalamic amenorrhea] entered the trial with a diagnosis of what would be considered endothelial dysfunction,” Dr. Shufelt said. “Our results demonstrated significantly higher circulating levels of serum proinflammatory cytokines in the women with hypothalamic amenorrhea compared to eumenorrheic controls.”
Dr. Shufelt’s team then tested whether giving estradiol to the women with hypothalamic amenorrhea for 12 weeks would improve their vascular health, but they saw no significant differences between the women who received estrogen and those who received placebo.
“Endothelial function is partly mediated by estrogen, and it was expected that giving back estrogen would ‘fix’ the endothelium, but that is not what happened,” Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado at Denver, Aurora, said in interview. “The mechanisms that maintain vascular function in women are not limited to hormones,” said Dr. Santoro, who was not involved in Dr. Shufelt’s study but attended her lecture. “We need to think beyond the simple model of estrogen-good, no-estrogen-bad.”
Dr. Santoro noted how easy it is to overlook the women who may have cardiovascular risk because of hypothalamic amenorrhea.
“Because many women with functional hypothalamic amenorrhea are super athletic and do not have the typical features of people with cardiometabolic disease – such as glucose intolerance, obesity, abnormal cholesterol or triglycerides, or high blood pressure – clinicians tend to think of them as healthy and to think that simply giving back hormones will fix the problems with bone density and vascular function, but that is not enough,” Dr. Santoro said. “The cognitive-behavioral therapy model for treatment of women with functional hypothalamic amenorrhea addresses the stress-related factors that drive the disorder, and this needs to be considered the standard of care for treatment.”
Stephanie S. Faubion, MD, professor of medicine and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Fla., who was not involved in Dr. Shufelt’s presentation, also emphasized the importance of recognizing functional hypothalamic amenorrhea.
“This is an underrecognized entity to begin with, and the fact that these women appear to be at increased risk for vascular dysfunction and potentially increased risk for cardiovascular disease down the road makes it even more important for clinicians to identify them and provide interventions early on,” Dr. Faubion said in an interview. “These women need to be identified and the etiology of the amenorrhea addressed, whether it relates to overexercising, being underweight, or experiencing significant stressors that have led to the loss of menstrual cycles.”
Dr. Shufelt’s research was funded by the National Institutes of Health. She had no disclosures. Dr. Santoro is a member of the scientific advisory board for Astellas, Menogenix, Amazon Ember, and Que Oncology, and she consults for Ansh Labs. Dr. Faubion had no disclosures.
The relationship between estrogen levels and heart health makes it particularly important for clinicians to be aware of those patients who might be at risk for cardiovascular disease despite not having other traditional risk factors, according to a presentation Oct. 12 at the North American Menopause Society annual meeting in Atlanta.
”Endogenous estrogens are protective for cardiovascular disease in premenopausal women,” Chrisandra L. Shufelt, MD, chair of the division of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Fla., told attendees. Yet, “a substantial population of young women are dying prematurely from cardiovascular disease,” with rates of cardiovascular death increasing in women aged 35-44 even as rates have decreased in postmenopausal women and in men. One potential reason may be premature estrogen loss.
Dr. Shufelt reminded attendees of four major causes of premature estrogen loss: Natural premature menopause, surgical menopause, chemotherapy-induced menopause, and premature ovarian insufficiency. But she would go on to discuss a less widely recognized condition, functional hypothalamic amenorrhea, that also may be contributing to increased cardiovascular risk.
First, Dr. Shufelt reviewed the evidence supporting the relationship between estrogen and cardiovascular health, starting with the Framingham study’s findings that cardiovascular disease is approximately two to four times more common in postmenopausal women than in premenopausal women, depending on the age range.
“Menopause at an early age, particularly under the age of 40, matters,” Dr. Shufelt said. “So we should be discussing this with our patients.”
Surgical menopause makes a difference to cardiovascular health as well, she said. In women under age 35, for example, the risk of a nonfatal heart attack in those with a bilateral oophorectomy was 7.7 times greater than in women who retained both ovaries and their uterus, and 1.5 times greater in women who had a hysterectomy without bilateral oophorectomy.
In a 2019 study, surgical premature menopause was associated with an 87% increased risk of heart disease even after researchers accounted for age, cardiovascular risk factors, and some forms of hormone therapy. The increased risk from natural premature menopause, on the other hand, was lower – a 36% increased risk of heart disease – compared with those producing endogenous hormones. Although randomized controlled trials are unavailable and unlikely to be done, the Nurses’ Health Study and the Danish Nurses Cohort Study, both observational studies, found that heart disease risk was diminished in those taking hormone therapy after surgical premature menopause.
Recommendations for premature or early menopause, from a wide range of different medical societies including NAMS, are that women without contraindications be given estrogen-based hormone therapy until the average age of natural menopause. Though not included in the same guidance, research has also shown that estrogen after oophorectomy does not increase the risk of breast cancer in women with a BRCA1 mutation, Dr. Shufelt said. Hormone therapy for premature or early menopause should adequately replace the levels women have lost and that means younger menopausal women often need higher doses than what older women receive, such as 2 mg/day of oral estradiol rather than the standard doses of 0.5 or 1 mg/day.
Functional hypothalamic amenorrhea and cardiovascular risk
Dr. Shufelt then discussed functional hypothalamic amenorrhea (hypogonadotropic hypogonadism), a common type of secondary amenorrhea that affects at least 1.4 million U.S. women. Diagnosis includes lack of a period for at least 3 months in someone who previously menstruated plus lab values below 50 pg/mL for estradiol, below 10 mIU/L for follicle stimulating hormone, and below 10 mIU/L for luteinizing hormone. Causes of this reversible form of infertility can include stress, overexercising, undereating, or some combination of these, plus an underlying genetic predisposition.
“After ruling out polycystic ovary syndrome, prolactinoma, and thyroid dysfunction, clinicians need to consider the diagnosis of hypothalamic amenorrhea,” Dr. Shufelt said. This condition goes beyond low estrogen levels: Women have elevated cortisol, low thyroid levels, low leptin levels, and increased ghrelin.
”This is not going away,” Dr. Shufelt said, sharing data on stress levels among U.S. adults, particularly Gen Z and millennial adults, noting that the ongoing “national mental health crisis” may be contributing to functional hypothalamic amenorrhea.
A 2020 substudy from the Nurses’ Health Study II found an increased risk of premature death in those who didn’t have a period or always had irregular periods starting as early as 14-17 years old. The increased risk of premature death rose with age in those with irregular or absent cycles – a 37% higher risk in 18- to 22-year-olds and a 39% increased risk in 29- to 46-year-olds.
But clinicians aren’t adequately identifying the “phenotype of the hypothalamic women,” Dr. Shufelt said, despite research showing overlap between hypothalamic amenorrhea and a higher risk of cardiovascular disease. Hypothalamic amenorrhea is so understudied that the last original research on the topic was in 2008, Dr. Shufelt said in an interview. ”No research except mine has been done to evaluate heart health in these young women,” she said.
Dr. Shufelt described a study she led involving 30 women with functional hypothalamic amenorrhea, 29 women with normal menstrual cycles, and 30 women who were recently menopausal and not on hormone therapy. The women with hypothalamic amenorrhea had average stress levels but their depression scores were higher than those of the other two groups.
The results showed that women with hypothalamic amenorrhea had lower estradiol and leptin levels and higher testosterone levels compared with the control group, and they had higher cortisol levels than those of both groups. Despite having similar body mass indexes as the control and menopausal groups, women with hypothalamic amenorrhea had lower blood pressure than that of the other two groups, yet they had higher cholesterol levels than those of the control group. EndoPAT© (Itamar Medical) testing showed that they had poor vascular function.
“In fact, one-third of the women [with hypothalamic amenorrhea] entered the trial with a diagnosis of what would be considered endothelial dysfunction,” Dr. Shufelt said. “Our results demonstrated significantly higher circulating levels of serum proinflammatory cytokines in the women with hypothalamic amenorrhea compared to eumenorrheic controls.”
Dr. Shufelt’s team then tested whether giving estradiol to the women with hypothalamic amenorrhea for 12 weeks would improve their vascular health, but they saw no significant differences between the women who received estrogen and those who received placebo.
“Endothelial function is partly mediated by estrogen, and it was expected that giving back estrogen would ‘fix’ the endothelium, but that is not what happened,” Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado at Denver, Aurora, said in interview. “The mechanisms that maintain vascular function in women are not limited to hormones,” said Dr. Santoro, who was not involved in Dr. Shufelt’s study but attended her lecture. “We need to think beyond the simple model of estrogen-good, no-estrogen-bad.”
Dr. Santoro noted how easy it is to overlook the women who may have cardiovascular risk because of hypothalamic amenorrhea.
“Because many women with functional hypothalamic amenorrhea are super athletic and do not have the typical features of people with cardiometabolic disease – such as glucose intolerance, obesity, abnormal cholesterol or triglycerides, or high blood pressure – clinicians tend to think of them as healthy and to think that simply giving back hormones will fix the problems with bone density and vascular function, but that is not enough,” Dr. Santoro said. “The cognitive-behavioral therapy model for treatment of women with functional hypothalamic amenorrhea addresses the stress-related factors that drive the disorder, and this needs to be considered the standard of care for treatment.”
Stephanie S. Faubion, MD, professor of medicine and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Fla., who was not involved in Dr. Shufelt’s presentation, also emphasized the importance of recognizing functional hypothalamic amenorrhea.
“This is an underrecognized entity to begin with, and the fact that these women appear to be at increased risk for vascular dysfunction and potentially increased risk for cardiovascular disease down the road makes it even more important for clinicians to identify them and provide interventions early on,” Dr. Faubion said in an interview. “These women need to be identified and the etiology of the amenorrhea addressed, whether it relates to overexercising, being underweight, or experiencing significant stressors that have led to the loss of menstrual cycles.”
Dr. Shufelt’s research was funded by the National Institutes of Health. She had no disclosures. Dr. Santoro is a member of the scientific advisory board for Astellas, Menogenix, Amazon Ember, and Que Oncology, and she consults for Ansh Labs. Dr. Faubion had no disclosures.
The relationship between estrogen levels and heart health makes it particularly important for clinicians to be aware of those patients who might be at risk for cardiovascular disease despite not having other traditional risk factors, according to a presentation Oct. 12 at the North American Menopause Society annual meeting in Atlanta.
”Endogenous estrogens are protective for cardiovascular disease in premenopausal women,” Chrisandra L. Shufelt, MD, chair of the division of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Fla., told attendees. Yet, “a substantial population of young women are dying prematurely from cardiovascular disease,” with rates of cardiovascular death increasing in women aged 35-44 even as rates have decreased in postmenopausal women and in men. One potential reason may be premature estrogen loss.
Dr. Shufelt reminded attendees of four major causes of premature estrogen loss: Natural premature menopause, surgical menopause, chemotherapy-induced menopause, and premature ovarian insufficiency. But she would go on to discuss a less widely recognized condition, functional hypothalamic amenorrhea, that also may be contributing to increased cardiovascular risk.
First, Dr. Shufelt reviewed the evidence supporting the relationship between estrogen and cardiovascular health, starting with the Framingham study’s findings that cardiovascular disease is approximately two to four times more common in postmenopausal women than in premenopausal women, depending on the age range.
“Menopause at an early age, particularly under the age of 40, matters,” Dr. Shufelt said. “So we should be discussing this with our patients.”
Surgical menopause makes a difference to cardiovascular health as well, she said. In women under age 35, for example, the risk of a nonfatal heart attack in those with a bilateral oophorectomy was 7.7 times greater than in women who retained both ovaries and their uterus, and 1.5 times greater in women who had a hysterectomy without bilateral oophorectomy.
In a 2019 study, surgical premature menopause was associated with an 87% increased risk of heart disease even after researchers accounted for age, cardiovascular risk factors, and some forms of hormone therapy. The increased risk from natural premature menopause, on the other hand, was lower – a 36% increased risk of heart disease – compared with those producing endogenous hormones. Although randomized controlled trials are unavailable and unlikely to be done, the Nurses’ Health Study and the Danish Nurses Cohort Study, both observational studies, found that heart disease risk was diminished in those taking hormone therapy after surgical premature menopause.
Recommendations for premature or early menopause, from a wide range of different medical societies including NAMS, are that women without contraindications be given estrogen-based hormone therapy until the average age of natural menopause. Though not included in the same guidance, research has also shown that estrogen after oophorectomy does not increase the risk of breast cancer in women with a BRCA1 mutation, Dr. Shufelt said. Hormone therapy for premature or early menopause should adequately replace the levels women have lost and that means younger menopausal women often need higher doses than what older women receive, such as 2 mg/day of oral estradiol rather than the standard doses of 0.5 or 1 mg/day.
Functional hypothalamic amenorrhea and cardiovascular risk
Dr. Shufelt then discussed functional hypothalamic amenorrhea (hypogonadotropic hypogonadism), a common type of secondary amenorrhea that affects at least 1.4 million U.S. women. Diagnosis includes lack of a period for at least 3 months in someone who previously menstruated plus lab values below 50 pg/mL for estradiol, below 10 mIU/L for follicle stimulating hormone, and below 10 mIU/L for luteinizing hormone. Causes of this reversible form of infertility can include stress, overexercising, undereating, or some combination of these, plus an underlying genetic predisposition.
“After ruling out polycystic ovary syndrome, prolactinoma, and thyroid dysfunction, clinicians need to consider the diagnosis of hypothalamic amenorrhea,” Dr. Shufelt said. This condition goes beyond low estrogen levels: Women have elevated cortisol, low thyroid levels, low leptin levels, and increased ghrelin.
”This is not going away,” Dr. Shufelt said, sharing data on stress levels among U.S. adults, particularly Gen Z and millennial adults, noting that the ongoing “national mental health crisis” may be contributing to functional hypothalamic amenorrhea.
A 2020 substudy from the Nurses’ Health Study II found an increased risk of premature death in those who didn’t have a period or always had irregular periods starting as early as 14-17 years old. The increased risk of premature death rose with age in those with irregular or absent cycles – a 37% higher risk in 18- to 22-year-olds and a 39% increased risk in 29- to 46-year-olds.
But clinicians aren’t adequately identifying the “phenotype of the hypothalamic women,” Dr. Shufelt said, despite research showing overlap between hypothalamic amenorrhea and a higher risk of cardiovascular disease. Hypothalamic amenorrhea is so understudied that the last original research on the topic was in 2008, Dr. Shufelt said in an interview. ”No research except mine has been done to evaluate heart health in these young women,” she said.
Dr. Shufelt described a study she led involving 30 women with functional hypothalamic amenorrhea, 29 women with normal menstrual cycles, and 30 women who were recently menopausal and not on hormone therapy. The women with hypothalamic amenorrhea had average stress levels but their depression scores were higher than those of the other two groups.
The results showed that women with hypothalamic amenorrhea had lower estradiol and leptin levels and higher testosterone levels compared with the control group, and they had higher cortisol levels than those of both groups. Despite having similar body mass indexes as the control and menopausal groups, women with hypothalamic amenorrhea had lower blood pressure than that of the other two groups, yet they had higher cholesterol levels than those of the control group. EndoPAT© (Itamar Medical) testing showed that they had poor vascular function.
“In fact, one-third of the women [with hypothalamic amenorrhea] entered the trial with a diagnosis of what would be considered endothelial dysfunction,” Dr. Shufelt said. “Our results demonstrated significantly higher circulating levels of serum proinflammatory cytokines in the women with hypothalamic amenorrhea compared to eumenorrheic controls.”
Dr. Shufelt’s team then tested whether giving estradiol to the women with hypothalamic amenorrhea for 12 weeks would improve their vascular health, but they saw no significant differences between the women who received estrogen and those who received placebo.
“Endothelial function is partly mediated by estrogen, and it was expected that giving back estrogen would ‘fix’ the endothelium, but that is not what happened,” Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado at Denver, Aurora, said in interview. “The mechanisms that maintain vascular function in women are not limited to hormones,” said Dr. Santoro, who was not involved in Dr. Shufelt’s study but attended her lecture. “We need to think beyond the simple model of estrogen-good, no-estrogen-bad.”
Dr. Santoro noted how easy it is to overlook the women who may have cardiovascular risk because of hypothalamic amenorrhea.
“Because many women with functional hypothalamic amenorrhea are super athletic and do not have the typical features of people with cardiometabolic disease – such as glucose intolerance, obesity, abnormal cholesterol or triglycerides, or high blood pressure – clinicians tend to think of them as healthy and to think that simply giving back hormones will fix the problems with bone density and vascular function, but that is not enough,” Dr. Santoro said. “The cognitive-behavioral therapy model for treatment of women with functional hypothalamic amenorrhea addresses the stress-related factors that drive the disorder, and this needs to be considered the standard of care for treatment.”
Stephanie S. Faubion, MD, professor of medicine and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Fla., who was not involved in Dr. Shufelt’s presentation, also emphasized the importance of recognizing functional hypothalamic amenorrhea.
“This is an underrecognized entity to begin with, and the fact that these women appear to be at increased risk for vascular dysfunction and potentially increased risk for cardiovascular disease down the road makes it even more important for clinicians to identify them and provide interventions early on,” Dr. Faubion said in an interview. “These women need to be identified and the etiology of the amenorrhea addressed, whether it relates to overexercising, being underweight, or experiencing significant stressors that have led to the loss of menstrual cycles.”
Dr. Shufelt’s research was funded by the National Institutes of Health. She had no disclosures. Dr. Santoro is a member of the scientific advisory board for Astellas, Menogenix, Amazon Ember, and Que Oncology, and she consults for Ansh Labs. Dr. Faubion had no disclosures.
FROM NAMS 2022
Maternal deaths show that ‘racism does exist among physicians’
Black mothers giving birth in hospitals are 53% more likely to die during childbirth than are Hispanic and White women, according to researchers who attributed the gap at least in part to bias among physicians and the health care system.
The United States is in the midst of a maternal healthcare crisis, said Robert White, MD, assistant professor of anesthesiology at Weill Cornell Medicine, New York, and lead author of the study. The maternal death rate among U.S. women in 2018, for instance, was 17.4 per 100,000 births, more than twice the figure in Canada (8.6 per 100,000 live births) and the United Kingdom (6.5 per 100,000 live births in 2016), according to the Commonwealth Fund.
“At baseline, our maternal mortality rates are higher than other comparable Western nations, and at the same time, there’s a huge spread in the maternal mortality ratio between White mothers and Black mothers, where Black mothers are experiencing maternal mortality about two or three times higher,” Dr. White told this news organization.
Previous research has shown racial disparities in rates of maternal mortality. But Dr. White said that his study controlled for income level, type of insurance, and other social factors that may have affected the health of the women.
“The research that I conducted is one of the largest of its kind, and the logistic regression model that we were able to run was able to control for a lot of these factors,” he said.
For the new study, presented at the 2022 annual meeting of the American Society of Anesthesiologists, Dr. White and his team analyzed data from 9.5 million deliveries across six states (California, Florida, Kentucky, Maryland, New York, and Washington) between 2007 and 2018. They found that 49,472 mothers (0.5%) either died in the hospital or experienced an injury during childbirth, which included damages to the brain, heart, eyes, or kidneys.
Overall, 0.8% of Black women experienced either a death or an injury, compared with 0.5% of Hispanic women and 0.4% of White women. The researchers concluded that Black women had a 53% increased chance of dying during childbirth in a hospital, even after adjusting for factors such as insurance type, hospital type, and income.
If income, insurance type, and other social factors aren’t driving this disparity in maternal mortality, what is? Dr. White said that the study didn’t uncover the underlying cause, but in his opinion, racial bias and systemic racism are likely contributing to the gap in deaths.
“I think the takeaway for physicians should be that we should humbly accept that prejudice, bias, and racism does exist among physicians,” Dr. White said.
Adi Davidov, MD, associate chair of obstetrics and gynecology at Staten Island (N.Y.) University Hospital, said that both anesthesiologists and ob.gyns. have been aware of these disparate health outcomes for years but have historically attributed the higher odds of injuries and death amongst Black women to health issues rather than racism.
“It is now quite evident that there is more to the story and that there is a degree of unconscious bias as well as systemic racism in health care that contributes to the disparities in outcomes,” said Dr. Davidov, who was not involved in the study.
Meanwhile, new data show that maternal mortality worsened during the COVID-19 pandemic, particularly for Black women. The rate of maternal death for Black women was 44 per 100,000 live births in 2019, 55.3 in 2020, and 68.9 in 2021, according to the U.S. Government Accountability Office. In contrast, White women had death rates of 17.9, 19.1, and 26.1, respectively.
“Bias or discrimination within the health care system can create communication challenges between providers and their patients, which may increase the risk of adverse outcomes,” the report stated.
What can be done
The most important thing physicians can do is to understand and acknowledge unconscious bias, Dr. Davidov told this news organization. “It is important to learn how to identify biases and make sure that it does not affect your medical decision making,” he said.
Dr. White suggested that physicians receive training in implicit bias and cultural competency and stay up to date on research regarding race and medicine as well as learning and using inclusive language.
He also urged physicians closely follow protocols for standard care for their discipline.
“Standardized care protocols have been shown to reduce variance between care of patients of different social structures and shown to decrease this disparity gap,” he said.
The study was supported by a Foundation for Anesthesia Education and Research Mentored Research Training Grant. Dr. White and Dr. Davidov report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Black mothers giving birth in hospitals are 53% more likely to die during childbirth than are Hispanic and White women, according to researchers who attributed the gap at least in part to bias among physicians and the health care system.
The United States is in the midst of a maternal healthcare crisis, said Robert White, MD, assistant professor of anesthesiology at Weill Cornell Medicine, New York, and lead author of the study. The maternal death rate among U.S. women in 2018, for instance, was 17.4 per 100,000 births, more than twice the figure in Canada (8.6 per 100,000 live births) and the United Kingdom (6.5 per 100,000 live births in 2016), according to the Commonwealth Fund.
“At baseline, our maternal mortality rates are higher than other comparable Western nations, and at the same time, there’s a huge spread in the maternal mortality ratio between White mothers and Black mothers, where Black mothers are experiencing maternal mortality about two or three times higher,” Dr. White told this news organization.
Previous research has shown racial disparities in rates of maternal mortality. But Dr. White said that his study controlled for income level, type of insurance, and other social factors that may have affected the health of the women.
“The research that I conducted is one of the largest of its kind, and the logistic regression model that we were able to run was able to control for a lot of these factors,” he said.
For the new study, presented at the 2022 annual meeting of the American Society of Anesthesiologists, Dr. White and his team analyzed data from 9.5 million deliveries across six states (California, Florida, Kentucky, Maryland, New York, and Washington) between 2007 and 2018. They found that 49,472 mothers (0.5%) either died in the hospital or experienced an injury during childbirth, which included damages to the brain, heart, eyes, or kidneys.
Overall, 0.8% of Black women experienced either a death or an injury, compared with 0.5% of Hispanic women and 0.4% of White women. The researchers concluded that Black women had a 53% increased chance of dying during childbirth in a hospital, even after adjusting for factors such as insurance type, hospital type, and income.
If income, insurance type, and other social factors aren’t driving this disparity in maternal mortality, what is? Dr. White said that the study didn’t uncover the underlying cause, but in his opinion, racial bias and systemic racism are likely contributing to the gap in deaths.
“I think the takeaway for physicians should be that we should humbly accept that prejudice, bias, and racism does exist among physicians,” Dr. White said.
Adi Davidov, MD, associate chair of obstetrics and gynecology at Staten Island (N.Y.) University Hospital, said that both anesthesiologists and ob.gyns. have been aware of these disparate health outcomes for years but have historically attributed the higher odds of injuries and death amongst Black women to health issues rather than racism.
“It is now quite evident that there is more to the story and that there is a degree of unconscious bias as well as systemic racism in health care that contributes to the disparities in outcomes,” said Dr. Davidov, who was not involved in the study.
Meanwhile, new data show that maternal mortality worsened during the COVID-19 pandemic, particularly for Black women. The rate of maternal death for Black women was 44 per 100,000 live births in 2019, 55.3 in 2020, and 68.9 in 2021, according to the U.S. Government Accountability Office. In contrast, White women had death rates of 17.9, 19.1, and 26.1, respectively.
“Bias or discrimination within the health care system can create communication challenges between providers and their patients, which may increase the risk of adverse outcomes,” the report stated.
What can be done
The most important thing physicians can do is to understand and acknowledge unconscious bias, Dr. Davidov told this news organization. “It is important to learn how to identify biases and make sure that it does not affect your medical decision making,” he said.
Dr. White suggested that physicians receive training in implicit bias and cultural competency and stay up to date on research regarding race and medicine as well as learning and using inclusive language.
He also urged physicians closely follow protocols for standard care for their discipline.
“Standardized care protocols have been shown to reduce variance between care of patients of different social structures and shown to decrease this disparity gap,” he said.
The study was supported by a Foundation for Anesthesia Education and Research Mentored Research Training Grant. Dr. White and Dr. Davidov report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Black mothers giving birth in hospitals are 53% more likely to die during childbirth than are Hispanic and White women, according to researchers who attributed the gap at least in part to bias among physicians and the health care system.
The United States is in the midst of a maternal healthcare crisis, said Robert White, MD, assistant professor of anesthesiology at Weill Cornell Medicine, New York, and lead author of the study. The maternal death rate among U.S. women in 2018, for instance, was 17.4 per 100,000 births, more than twice the figure in Canada (8.6 per 100,000 live births) and the United Kingdom (6.5 per 100,000 live births in 2016), according to the Commonwealth Fund.
“At baseline, our maternal mortality rates are higher than other comparable Western nations, and at the same time, there’s a huge spread in the maternal mortality ratio between White mothers and Black mothers, where Black mothers are experiencing maternal mortality about two or three times higher,” Dr. White told this news organization.
Previous research has shown racial disparities in rates of maternal mortality. But Dr. White said that his study controlled for income level, type of insurance, and other social factors that may have affected the health of the women.
“The research that I conducted is one of the largest of its kind, and the logistic regression model that we were able to run was able to control for a lot of these factors,” he said.
For the new study, presented at the 2022 annual meeting of the American Society of Anesthesiologists, Dr. White and his team analyzed data from 9.5 million deliveries across six states (California, Florida, Kentucky, Maryland, New York, and Washington) between 2007 and 2018. They found that 49,472 mothers (0.5%) either died in the hospital or experienced an injury during childbirth, which included damages to the brain, heart, eyes, or kidneys.
Overall, 0.8% of Black women experienced either a death or an injury, compared with 0.5% of Hispanic women and 0.4% of White women. The researchers concluded that Black women had a 53% increased chance of dying during childbirth in a hospital, even after adjusting for factors such as insurance type, hospital type, and income.
If income, insurance type, and other social factors aren’t driving this disparity in maternal mortality, what is? Dr. White said that the study didn’t uncover the underlying cause, but in his opinion, racial bias and systemic racism are likely contributing to the gap in deaths.
“I think the takeaway for physicians should be that we should humbly accept that prejudice, bias, and racism does exist among physicians,” Dr. White said.
Adi Davidov, MD, associate chair of obstetrics and gynecology at Staten Island (N.Y.) University Hospital, said that both anesthesiologists and ob.gyns. have been aware of these disparate health outcomes for years but have historically attributed the higher odds of injuries and death amongst Black women to health issues rather than racism.
“It is now quite evident that there is more to the story and that there is a degree of unconscious bias as well as systemic racism in health care that contributes to the disparities in outcomes,” said Dr. Davidov, who was not involved in the study.
Meanwhile, new data show that maternal mortality worsened during the COVID-19 pandemic, particularly for Black women. The rate of maternal death for Black women was 44 per 100,000 live births in 2019, 55.3 in 2020, and 68.9 in 2021, according to the U.S. Government Accountability Office. In contrast, White women had death rates of 17.9, 19.1, and 26.1, respectively.
“Bias or discrimination within the health care system can create communication challenges between providers and their patients, which may increase the risk of adverse outcomes,” the report stated.
What can be done
The most important thing physicians can do is to understand and acknowledge unconscious bias, Dr. Davidov told this news organization. “It is important to learn how to identify biases and make sure that it does not affect your medical decision making,” he said.
Dr. White suggested that physicians receive training in implicit bias and cultural competency and stay up to date on research regarding race and medicine as well as learning and using inclusive language.
He also urged physicians closely follow protocols for standard care for their discipline.
“Standardized care protocols have been shown to reduce variance between care of patients of different social structures and shown to decrease this disparity gap,” he said.
The study was supported by a Foundation for Anesthesia Education and Research Mentored Research Training Grant. Dr. White and Dr. Davidov report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Immediate skin-to-skin contact after cesarean section improves outcomes for parent, newborn
Birth parents are typically separated from their newborns following a cesarean section. However, a recent study published in the journal Nursing Open suggests immediate skin-to-skin contact may accelerate uterine contractions, reduce maternal blood loss, reduce newborn crying, improve patient satisfaction and comfort, and increase the rate of breastfeeding.
“[O]ur study contributes to scientific knowledge with key information to reduce maternal morbidity and mortality rates in mothers who have undergone scheduled cesarean sections,” José Miguel Pérez-Jiménez, MD, of the faculty of nursing, physiotherapy, and podiatry at Hospital Universitario Virgen Macarena, University of Sevilla, Spain, and colleagues wrote in their study. It promotes greater stability in the mothers by reducing the risk of postpartum hemorrhage, making it better to not separate mother and child in the first hours after this surgery, he said.
Dr. Pérez-Jiménez and colleagues evaluated 83 women who underwent a scheduled cesarean section in an unblinded, randomized controlled trial. The women were randomized to receive skin-to-skin contact in the operating room that continued in the postpartum unit, or the normal protocol after cesarean section that consisted of having the mother transferred to the postanesthesia recovery room while the newborn was sent to a maternity room with a parent or companion. Researchers assessed variables such as plasma hemoglobin, uterine contractions, breastfeeding, and postoperative pain, as well as subjective measures such as maternal satisfaction, comfort, previous cesarean section experience, and newborn crying.
Women who received usual care following cesarean section were more likely to have uterine contractions at the umbilical level compared with the skin-to-skin contact group (70% vs. 3%; P ≤ .0001), while the skin-to-skin group was more likely to have uterine contractions at the infraumbilical level (92.5% vs. 22.5%; P ≤ .0001). There was a statistically significant decrease in predischarge hemoglobin in the control group compared with the skin-to-skin group (10.522 vs. 11.075 g/dL; P ≤ .017); the level of hemoglobin reduction favored the skin-to-skin group (1.01 vs. 2.265 g/dL; P ≤ .0001). Women in the skin-to-skin group were more likely to report mild pain on a 10-point visual analog scale (VAS) after being transferred to the recovery room (1.48 vs. 6.23 points; P ≤ .0001) and being transferred to a maternity room or room in the postpartum unit (0.60 vs. 5.23 points; P ≤ .0001). Breastfeeding at birth was significantly higher among patients with immediate skin-to-skin contact compared with the control group (92.5% vs. 32.5%; P ≤ .0001), and continued at 1 month after birth (92.5% vs. 12.5%; P ≤ .0001). Newborns of mothers in the skin-to-skin group were significantly less likely to cry compared with newborns in the control group (90% vs. 55%; P ≤ .001).
When asked to rate their satisfaction on a 10-point Likert scale, women in the skin-to-skin contact group rated their experience significantly higher than did the control group (9.98 vs. 6.5; P ≤ .0001), and all women who had previously had a cesarean section in the skin-to-skin group (30%) rated their experience at 10 points compared with their previous cesarean section without skin-to-skin contact.
Implementing skin-to-skin contact after cesarean section
Betsy M. Collins, MD, MPH, assistant professor of obstetrics and gynecology at Emory University, Atlanta, said in an interview that while some of the findings were largely unsurprising and “confirmed a lot of the things that we already know about skin-to-skin [contact],” one major finding was the “stark difference” in the percentage of new birth parents who started breastfeeding after skin-to-skin contact and were still breastfeeding at 1 month postpartum compared with birth parents in the control group. She was not involved with the study and noted that the results complement recommendations from the World Health Organization on starting breastfeeding within the first hour after birth and continuing breastfeeding through the first 6 months of life.
“That was likely one of the greatest take-home points from the study ... that early skin-to-skin really promoted initiation of breastfeeding,” Dr. Collins said.
Two reasons why skin-to-skin contact after cesarean section isn’t regularly provided is that it can be difficult for personnel and safety reasons to have an extra nurse to continue monitoring the health of the newborn in the operating room, and there is a lack of culture supporting of skin-to-skin contact in the OR, Dr. Collins explained.
“Just like anything else, if it’s built into your standard operating procedure, then you have everything set up in place to do that initial assessment of the infant and then get the baby skin-to-skin as quickly as possible,” she said. If it’s your standard operating procedure to not provide skin-to-skin contact, she said, then there is a little bit more inertia to overcome to start providing it as a standard procedure.
At her center, Dr. Collins said skin-to-skin contact is initiated as soon as possible after birth, even in the operating room. The steps to implementing that policy involved getting the anesthesiology department on board with supporting the policy in the OR and training the circulating nursing staff to ensure a that nurse is available to monitor the newborn.
“I think the most important thing to know is that it’s absolutely doable and that you just have to have a champion just like any other quality initiative,” she said. One of the best ways to do that is to have the patients themselves request it, she noted, compared with its being requested by a physician or nurse.
“I think some patients are disappointed when they have to undergo cesarean delivery or feel like they’re missing out if they can’t have a vaginal delivery,” Dr. Collins said. Immediate skin-to-skin contact is “very good for not only physiology, as we read about in this paper – all the things they said about the benefits of skin-to-skin [contact] are true – but it’s really good for mental health. That bonding begins right away.”
As a birth parent, being separated from your newborn for several hours after a cesarean section, on the other hand, can be “pretty devastating,” Dr. Collins said.
“I think this is something that, once it becomes a standard of care, it will be expected that most hospitals should be doing this,” she said.
The authors and Dr. Collins report no relevant conflicts of interest.
Birth parents are typically separated from their newborns following a cesarean section. However, a recent study published in the journal Nursing Open suggests immediate skin-to-skin contact may accelerate uterine contractions, reduce maternal blood loss, reduce newborn crying, improve patient satisfaction and comfort, and increase the rate of breastfeeding.
“[O]ur study contributes to scientific knowledge with key information to reduce maternal morbidity and mortality rates in mothers who have undergone scheduled cesarean sections,” José Miguel Pérez-Jiménez, MD, of the faculty of nursing, physiotherapy, and podiatry at Hospital Universitario Virgen Macarena, University of Sevilla, Spain, and colleagues wrote in their study. It promotes greater stability in the mothers by reducing the risk of postpartum hemorrhage, making it better to not separate mother and child in the first hours after this surgery, he said.
Dr. Pérez-Jiménez and colleagues evaluated 83 women who underwent a scheduled cesarean section in an unblinded, randomized controlled trial. The women were randomized to receive skin-to-skin contact in the operating room that continued in the postpartum unit, or the normal protocol after cesarean section that consisted of having the mother transferred to the postanesthesia recovery room while the newborn was sent to a maternity room with a parent or companion. Researchers assessed variables such as plasma hemoglobin, uterine contractions, breastfeeding, and postoperative pain, as well as subjective measures such as maternal satisfaction, comfort, previous cesarean section experience, and newborn crying.
Women who received usual care following cesarean section were more likely to have uterine contractions at the umbilical level compared with the skin-to-skin contact group (70% vs. 3%; P ≤ .0001), while the skin-to-skin group was more likely to have uterine contractions at the infraumbilical level (92.5% vs. 22.5%; P ≤ .0001). There was a statistically significant decrease in predischarge hemoglobin in the control group compared with the skin-to-skin group (10.522 vs. 11.075 g/dL; P ≤ .017); the level of hemoglobin reduction favored the skin-to-skin group (1.01 vs. 2.265 g/dL; P ≤ .0001). Women in the skin-to-skin group were more likely to report mild pain on a 10-point visual analog scale (VAS) after being transferred to the recovery room (1.48 vs. 6.23 points; P ≤ .0001) and being transferred to a maternity room or room in the postpartum unit (0.60 vs. 5.23 points; P ≤ .0001). Breastfeeding at birth was significantly higher among patients with immediate skin-to-skin contact compared with the control group (92.5% vs. 32.5%; P ≤ .0001), and continued at 1 month after birth (92.5% vs. 12.5%; P ≤ .0001). Newborns of mothers in the skin-to-skin group were significantly less likely to cry compared with newborns in the control group (90% vs. 55%; P ≤ .001).
When asked to rate their satisfaction on a 10-point Likert scale, women in the skin-to-skin contact group rated their experience significantly higher than did the control group (9.98 vs. 6.5; P ≤ .0001), and all women who had previously had a cesarean section in the skin-to-skin group (30%) rated their experience at 10 points compared with their previous cesarean section without skin-to-skin contact.
Implementing skin-to-skin contact after cesarean section
Betsy M. Collins, MD, MPH, assistant professor of obstetrics and gynecology at Emory University, Atlanta, said in an interview that while some of the findings were largely unsurprising and “confirmed a lot of the things that we already know about skin-to-skin [contact],” one major finding was the “stark difference” in the percentage of new birth parents who started breastfeeding after skin-to-skin contact and were still breastfeeding at 1 month postpartum compared with birth parents in the control group. She was not involved with the study and noted that the results complement recommendations from the World Health Organization on starting breastfeeding within the first hour after birth and continuing breastfeeding through the first 6 months of life.
“That was likely one of the greatest take-home points from the study ... that early skin-to-skin really promoted initiation of breastfeeding,” Dr. Collins said.
Two reasons why skin-to-skin contact after cesarean section isn’t regularly provided is that it can be difficult for personnel and safety reasons to have an extra nurse to continue monitoring the health of the newborn in the operating room, and there is a lack of culture supporting of skin-to-skin contact in the OR, Dr. Collins explained.
“Just like anything else, if it’s built into your standard operating procedure, then you have everything set up in place to do that initial assessment of the infant and then get the baby skin-to-skin as quickly as possible,” she said. If it’s your standard operating procedure to not provide skin-to-skin contact, she said, then there is a little bit more inertia to overcome to start providing it as a standard procedure.
At her center, Dr. Collins said skin-to-skin contact is initiated as soon as possible after birth, even in the operating room. The steps to implementing that policy involved getting the anesthesiology department on board with supporting the policy in the OR and training the circulating nursing staff to ensure a that nurse is available to monitor the newborn.
“I think the most important thing to know is that it’s absolutely doable and that you just have to have a champion just like any other quality initiative,” she said. One of the best ways to do that is to have the patients themselves request it, she noted, compared with its being requested by a physician or nurse.
“I think some patients are disappointed when they have to undergo cesarean delivery or feel like they’re missing out if they can’t have a vaginal delivery,” Dr. Collins said. Immediate skin-to-skin contact is “very good for not only physiology, as we read about in this paper – all the things they said about the benefits of skin-to-skin [contact] are true – but it’s really good for mental health. That bonding begins right away.”
As a birth parent, being separated from your newborn for several hours after a cesarean section, on the other hand, can be “pretty devastating,” Dr. Collins said.
“I think this is something that, once it becomes a standard of care, it will be expected that most hospitals should be doing this,” she said.
The authors and Dr. Collins report no relevant conflicts of interest.
Birth parents are typically separated from their newborns following a cesarean section. However, a recent study published in the journal Nursing Open suggests immediate skin-to-skin contact may accelerate uterine contractions, reduce maternal blood loss, reduce newborn crying, improve patient satisfaction and comfort, and increase the rate of breastfeeding.
“[O]ur study contributes to scientific knowledge with key information to reduce maternal morbidity and mortality rates in mothers who have undergone scheduled cesarean sections,” José Miguel Pérez-Jiménez, MD, of the faculty of nursing, physiotherapy, and podiatry at Hospital Universitario Virgen Macarena, University of Sevilla, Spain, and colleagues wrote in their study. It promotes greater stability in the mothers by reducing the risk of postpartum hemorrhage, making it better to not separate mother and child in the first hours after this surgery, he said.
Dr. Pérez-Jiménez and colleagues evaluated 83 women who underwent a scheduled cesarean section in an unblinded, randomized controlled trial. The women were randomized to receive skin-to-skin contact in the operating room that continued in the postpartum unit, or the normal protocol after cesarean section that consisted of having the mother transferred to the postanesthesia recovery room while the newborn was sent to a maternity room with a parent or companion. Researchers assessed variables such as plasma hemoglobin, uterine contractions, breastfeeding, and postoperative pain, as well as subjective measures such as maternal satisfaction, comfort, previous cesarean section experience, and newborn crying.
Women who received usual care following cesarean section were more likely to have uterine contractions at the umbilical level compared with the skin-to-skin contact group (70% vs. 3%; P ≤ .0001), while the skin-to-skin group was more likely to have uterine contractions at the infraumbilical level (92.5% vs. 22.5%; P ≤ .0001). There was a statistically significant decrease in predischarge hemoglobin in the control group compared with the skin-to-skin group (10.522 vs. 11.075 g/dL; P ≤ .017); the level of hemoglobin reduction favored the skin-to-skin group (1.01 vs. 2.265 g/dL; P ≤ .0001). Women in the skin-to-skin group were more likely to report mild pain on a 10-point visual analog scale (VAS) after being transferred to the recovery room (1.48 vs. 6.23 points; P ≤ .0001) and being transferred to a maternity room or room in the postpartum unit (0.60 vs. 5.23 points; P ≤ .0001). Breastfeeding at birth was significantly higher among patients with immediate skin-to-skin contact compared with the control group (92.5% vs. 32.5%; P ≤ .0001), and continued at 1 month after birth (92.5% vs. 12.5%; P ≤ .0001). Newborns of mothers in the skin-to-skin group were significantly less likely to cry compared with newborns in the control group (90% vs. 55%; P ≤ .001).
When asked to rate their satisfaction on a 10-point Likert scale, women in the skin-to-skin contact group rated their experience significantly higher than did the control group (9.98 vs. 6.5; P ≤ .0001), and all women who had previously had a cesarean section in the skin-to-skin group (30%) rated their experience at 10 points compared with their previous cesarean section without skin-to-skin contact.
Implementing skin-to-skin contact after cesarean section
Betsy M. Collins, MD, MPH, assistant professor of obstetrics and gynecology at Emory University, Atlanta, said in an interview that while some of the findings were largely unsurprising and “confirmed a lot of the things that we already know about skin-to-skin [contact],” one major finding was the “stark difference” in the percentage of new birth parents who started breastfeeding after skin-to-skin contact and were still breastfeeding at 1 month postpartum compared with birth parents in the control group. She was not involved with the study and noted that the results complement recommendations from the World Health Organization on starting breastfeeding within the first hour after birth and continuing breastfeeding through the first 6 months of life.
“That was likely one of the greatest take-home points from the study ... that early skin-to-skin really promoted initiation of breastfeeding,” Dr. Collins said.
Two reasons why skin-to-skin contact after cesarean section isn’t regularly provided is that it can be difficult for personnel and safety reasons to have an extra nurse to continue monitoring the health of the newborn in the operating room, and there is a lack of culture supporting of skin-to-skin contact in the OR, Dr. Collins explained.
“Just like anything else, if it’s built into your standard operating procedure, then you have everything set up in place to do that initial assessment of the infant and then get the baby skin-to-skin as quickly as possible,” she said. If it’s your standard operating procedure to not provide skin-to-skin contact, she said, then there is a little bit more inertia to overcome to start providing it as a standard procedure.
At her center, Dr. Collins said skin-to-skin contact is initiated as soon as possible after birth, even in the operating room. The steps to implementing that policy involved getting the anesthesiology department on board with supporting the policy in the OR and training the circulating nursing staff to ensure a that nurse is available to monitor the newborn.
“I think the most important thing to know is that it’s absolutely doable and that you just have to have a champion just like any other quality initiative,” she said. One of the best ways to do that is to have the patients themselves request it, she noted, compared with its being requested by a physician or nurse.
“I think some patients are disappointed when they have to undergo cesarean delivery or feel like they’re missing out if they can’t have a vaginal delivery,” Dr. Collins said. Immediate skin-to-skin contact is “very good for not only physiology, as we read about in this paper – all the things they said about the benefits of skin-to-skin [contact] are true – but it’s really good for mental health. That bonding begins right away.”
As a birth parent, being separated from your newborn for several hours after a cesarean section, on the other hand, can be “pretty devastating,” Dr. Collins said.
“I think this is something that, once it becomes a standard of care, it will be expected that most hospitals should be doing this,” she said.
The authors and Dr. Collins report no relevant conflicts of interest.
FROM NURSING OPEN
Vaginal estrogen not recommended with aromatase inhibitors
Women with breast cancer who are taking adjuvant endocrine therapy to reduce the risk for recurrence often report that the side effects of dampening down estrogen, such as hot flashes and vaginal dryness, spoil their quality of life, and these side effects can lead to discontinuation of therapy.
But medical measures to address these side effects carry risks, as shown in the results of a new study from Denmark.
The use of vaginal estrogen therapy (VET) increased the risk for breast cancer recurrence by 39% in women with early estrogen receptor–positive breast cancer who were taking aromatase inhibitors (AIs).
There was no increase in the risk for recurrence in women who were using VET and taking tamoxifen or in women who were using VET and not taking any adjuvant endocrine therapy.
The finding was published in the Journal of the National Cancer Institute.
“Patients who are taking aromatase inhibitors should try alternative strategies for management of genitourinary symptoms because (VET) will likely increase their risk for breast cancer recurrence,” warn the authors of an accompanying editorial, Elizabeth J. Cathcart-Rake, MD, and Kathryn J. Ruddy, MD, oncologists at the Mayo Clinic, Rochester, Minn.
The use of oral estrogen treatment, known as menopausal hormone therapy (MHT), is also not recommended in breast cancer survivors being treated with AIs, the editorialists added.
The study did not find an increase in the risk for recurrence with MHT added onto AIs, but that finding comes from a very small subgroup of only 37 women.
“The absence of an obvious detrimental impact of MHT on breast cancer recurrence or mortality” in this study “is not particularly reassuring,” especially given higher systemic estrogen levels seen with MHT, Dr. Cathcart-Rake and Dr. Ruddy commented.
Differences between endocrine therapies
“Our study is, to our knowledge, the first to report a potential increased risk of recurrence in patients receiving AIs treated with VET,” say the investigators, led by Søren Cold, MD, an oncology researcher at Odense University Hospital, Denmark.
They suggest that women who are taking VET and AIs should be switched to tamoxifen after 2-3 years.
Speculating as to the apparent safety differences between the two endocrine therapies, Dr. Cold and colleagues explained that “AIs lower or nearly eliminate estrogen. As such, even a modest increase in circulating estrogens may” increase recurrence risk.
Tamoxifen, on the other hand, competes for estrogen receptor binding, so “a modest elevation of the very low serum estrogen levels” with hormone therapy “is not assumed to counteract the receptor blockade,” they said.
Study details
Study participants, obtained from a nationwide registry in Denmark, were diagnosed with early-stage, invasive, estrogen receptor–positive breast cancer from 1997 to 2004. Upfront treatment included surgery plus, in the majority of women, radiation.
The review identified 8,461 such women. After initial treatment for breast cancer, 2,410 went on to adjuvant endocrine therapy, including 2,007 with tamoxifen and 403 with an AI.
Across the entire study population, nearly 2,000 women took VET and 133 women took MHT, as assessed by having redeemed at least two prescriptions. The hormone therapies were used in women who were both on and those who were not on endocrine therapy.
Overall, breast cancer recurred in 1,333 women (16%) over a median follow-up of 9.8 years.
The investigators then analyzed the risk for recurrence in various subgroups.
The 39% higher risk for recurrence was found among the 822 women who used VET while taking an AI, compared with 2,520 women who received AIs alone.
Findings in the study were adjusted for numerous potential confounders, including age, tumor biology, and comorbidities.
Women were a median of 61 years of age (range, 35-91 years). Seventy-seven percent had invasive ductal carcinoma, and 43% were node-positive. Women on hormone therapy tended to be younger, have smaller tumors, and be less likely to have lymph node metastases.
The investigators excluded women who had taken hormone replacement before their breast cancer diagnosis.
The work was funded by the Danish Cancer Society. Dr. Cold reports no disclosures, but some co-authors reported relationships with Samsung, Novartis, Pfizer, and other companies. Dr. Cathcart-Rake and Dr. Ruddy report no disclosures.
A version of this article first appeared on Medscape.com.
Women with breast cancer who are taking adjuvant endocrine therapy to reduce the risk for recurrence often report that the side effects of dampening down estrogen, such as hot flashes and vaginal dryness, spoil their quality of life, and these side effects can lead to discontinuation of therapy.
But medical measures to address these side effects carry risks, as shown in the results of a new study from Denmark.
The use of vaginal estrogen therapy (VET) increased the risk for breast cancer recurrence by 39% in women with early estrogen receptor–positive breast cancer who were taking aromatase inhibitors (AIs).
There was no increase in the risk for recurrence in women who were using VET and taking tamoxifen or in women who were using VET and not taking any adjuvant endocrine therapy.
The finding was published in the Journal of the National Cancer Institute.
“Patients who are taking aromatase inhibitors should try alternative strategies for management of genitourinary symptoms because (VET) will likely increase their risk for breast cancer recurrence,” warn the authors of an accompanying editorial, Elizabeth J. Cathcart-Rake, MD, and Kathryn J. Ruddy, MD, oncologists at the Mayo Clinic, Rochester, Minn.
The use of oral estrogen treatment, known as menopausal hormone therapy (MHT), is also not recommended in breast cancer survivors being treated with AIs, the editorialists added.
The study did not find an increase in the risk for recurrence with MHT added onto AIs, but that finding comes from a very small subgroup of only 37 women.
“The absence of an obvious detrimental impact of MHT on breast cancer recurrence or mortality” in this study “is not particularly reassuring,” especially given higher systemic estrogen levels seen with MHT, Dr. Cathcart-Rake and Dr. Ruddy commented.
Differences between endocrine therapies
“Our study is, to our knowledge, the first to report a potential increased risk of recurrence in patients receiving AIs treated with VET,” say the investigators, led by Søren Cold, MD, an oncology researcher at Odense University Hospital, Denmark.
They suggest that women who are taking VET and AIs should be switched to tamoxifen after 2-3 years.
Speculating as to the apparent safety differences between the two endocrine therapies, Dr. Cold and colleagues explained that “AIs lower or nearly eliminate estrogen. As such, even a modest increase in circulating estrogens may” increase recurrence risk.
Tamoxifen, on the other hand, competes for estrogen receptor binding, so “a modest elevation of the very low serum estrogen levels” with hormone therapy “is not assumed to counteract the receptor blockade,” they said.
Study details
Study participants, obtained from a nationwide registry in Denmark, were diagnosed with early-stage, invasive, estrogen receptor–positive breast cancer from 1997 to 2004. Upfront treatment included surgery plus, in the majority of women, radiation.
The review identified 8,461 such women. After initial treatment for breast cancer, 2,410 went on to adjuvant endocrine therapy, including 2,007 with tamoxifen and 403 with an AI.
Across the entire study population, nearly 2,000 women took VET and 133 women took MHT, as assessed by having redeemed at least two prescriptions. The hormone therapies were used in women who were both on and those who were not on endocrine therapy.
Overall, breast cancer recurred in 1,333 women (16%) over a median follow-up of 9.8 years.
The investigators then analyzed the risk for recurrence in various subgroups.
The 39% higher risk for recurrence was found among the 822 women who used VET while taking an AI, compared with 2,520 women who received AIs alone.
Findings in the study were adjusted for numerous potential confounders, including age, tumor biology, and comorbidities.
Women were a median of 61 years of age (range, 35-91 years). Seventy-seven percent had invasive ductal carcinoma, and 43% were node-positive. Women on hormone therapy tended to be younger, have smaller tumors, and be less likely to have lymph node metastases.
The investigators excluded women who had taken hormone replacement before their breast cancer diagnosis.
The work was funded by the Danish Cancer Society. Dr. Cold reports no disclosures, but some co-authors reported relationships with Samsung, Novartis, Pfizer, and other companies. Dr. Cathcart-Rake and Dr. Ruddy report no disclosures.
A version of this article first appeared on Medscape.com.
Women with breast cancer who are taking adjuvant endocrine therapy to reduce the risk for recurrence often report that the side effects of dampening down estrogen, such as hot flashes and vaginal dryness, spoil their quality of life, and these side effects can lead to discontinuation of therapy.
But medical measures to address these side effects carry risks, as shown in the results of a new study from Denmark.
The use of vaginal estrogen therapy (VET) increased the risk for breast cancer recurrence by 39% in women with early estrogen receptor–positive breast cancer who were taking aromatase inhibitors (AIs).
There was no increase in the risk for recurrence in women who were using VET and taking tamoxifen or in women who were using VET and not taking any adjuvant endocrine therapy.
The finding was published in the Journal of the National Cancer Institute.
“Patients who are taking aromatase inhibitors should try alternative strategies for management of genitourinary symptoms because (VET) will likely increase their risk for breast cancer recurrence,” warn the authors of an accompanying editorial, Elizabeth J. Cathcart-Rake, MD, and Kathryn J. Ruddy, MD, oncologists at the Mayo Clinic, Rochester, Minn.
The use of oral estrogen treatment, known as menopausal hormone therapy (MHT), is also not recommended in breast cancer survivors being treated with AIs, the editorialists added.
The study did not find an increase in the risk for recurrence with MHT added onto AIs, but that finding comes from a very small subgroup of only 37 women.
“The absence of an obvious detrimental impact of MHT on breast cancer recurrence or mortality” in this study “is not particularly reassuring,” especially given higher systemic estrogen levels seen with MHT, Dr. Cathcart-Rake and Dr. Ruddy commented.
Differences between endocrine therapies
“Our study is, to our knowledge, the first to report a potential increased risk of recurrence in patients receiving AIs treated with VET,” say the investigators, led by Søren Cold, MD, an oncology researcher at Odense University Hospital, Denmark.
They suggest that women who are taking VET and AIs should be switched to tamoxifen after 2-3 years.
Speculating as to the apparent safety differences between the two endocrine therapies, Dr. Cold and colleagues explained that “AIs lower or nearly eliminate estrogen. As such, even a modest increase in circulating estrogens may” increase recurrence risk.
Tamoxifen, on the other hand, competes for estrogen receptor binding, so “a modest elevation of the very low serum estrogen levels” with hormone therapy “is not assumed to counteract the receptor blockade,” they said.
Study details
Study participants, obtained from a nationwide registry in Denmark, were diagnosed with early-stage, invasive, estrogen receptor–positive breast cancer from 1997 to 2004. Upfront treatment included surgery plus, in the majority of women, radiation.
The review identified 8,461 such women. After initial treatment for breast cancer, 2,410 went on to adjuvant endocrine therapy, including 2,007 with tamoxifen and 403 with an AI.
Across the entire study population, nearly 2,000 women took VET and 133 women took MHT, as assessed by having redeemed at least two prescriptions. The hormone therapies were used in women who were both on and those who were not on endocrine therapy.
Overall, breast cancer recurred in 1,333 women (16%) over a median follow-up of 9.8 years.
The investigators then analyzed the risk for recurrence in various subgroups.
The 39% higher risk for recurrence was found among the 822 women who used VET while taking an AI, compared with 2,520 women who received AIs alone.
Findings in the study were adjusted for numerous potential confounders, including age, tumor biology, and comorbidities.
Women were a median of 61 years of age (range, 35-91 years). Seventy-seven percent had invasive ductal carcinoma, and 43% were node-positive. Women on hormone therapy tended to be younger, have smaller tumors, and be less likely to have lymph node metastases.
The investigators excluded women who had taken hormone replacement before their breast cancer diagnosis.
The work was funded by the Danish Cancer Society. Dr. Cold reports no disclosures, but some co-authors reported relationships with Samsung, Novartis, Pfizer, and other companies. Dr. Cathcart-Rake and Dr. Ruddy report no disclosures.
A version of this article first appeared on Medscape.com.
New electrodes made of sugar more effectively monitor mom’s health
A new type of electrode made from sugar could help doctors and researchers more effectively monitor contractions during preterm labor, a condition that precedes almost half of preterm births and is the leading cause of U.S. neonatal deaths.
The sensors, developed by engineers at the McKelvey School of Engineering at Washington University, St. Louis, could help us understand why some patients experience preterm labor, improve medical interventions, and save lives. In the experiment, the researchers built an array of the new electrodes and successfully tested it on a pregnant person in a lab.
The goal is a home-monitoring belt that is comfortable enough for patients to wear and accurate enough to be clinically useful. Built off a framework of sugar and conductive polymers, the thin electrodes have a sponge-like quality that allows them to hold more gel than standard electrodes, measure for 3 hours instead of 1, and resist artifacts created by patient movement. When tested on a pregnant woman, the new electrodes picked up clean signals even when the patient moved, said electrical engineer and article co-author Chuan Wang, PhD.
There is current technology that exists to monitor and map contractions during early labor, but the tests require hundreds of wire electrodes. Patients must sit still for half an hour while the electrodes are applied, then remain immobile for the test itself, which has a high sensitivity to movement.
“It’s very uncomfortable. In the clinical setting, the recording typically lasts for 15 minutes to half an hour. During that time, doctors want the patient to be still,” said Dr. Wang. “If the patient has to move, it’s going to introduce some artifacts, which is going to ruin the imaging process.”
Dr. Wang and colleagues wanted to develop an inexpensive new electrode that would be more comfortable for patients to wear for longer periods of time, yet sensitive enough to detect electrical signals in the body during preterm labor.
To do this, they used sugar structures to create a pliable electrode with a spongy structure. The new electrodes have micropores that hold conductive gel, increasing the amount of electrified surface area touching the skin.
“With the porous structure, we are effectively increasing the area by many, many times,” Dr. Wang said. “Because all those voids also contact the skin, increasing the contact area can boost the strength of the signal.”
With conventional electrodes, the gel dries quickly on the flat surface, causing signal quality to plummet. But the new electrodes can be used for “many hours” before drying out, according to Dr. Wang.
Additionally, the soft material of the new electrode acts “like a buffer” that absorbs motion and prevents the electrode from sliding around, according to Dr. Wang. That means patients can move while wearing the spongy electrodes without disturbing the recording of electrical signals in the body.
From sugar cube to spongy electrode
To create the new electrode, the researchers began by molding sugar into an electrode-shaped template. The template was then dipped into a liquid polymer, which oozed in between the grains of sugar. Next, the template underwent oven curing, emerging as a solid yet spongy structure. Hot water was then applied to dissolve the sugar.
The sugar structure is useful here because of the negative space around the grains, which is filled by the polymer – and then because of the negative space left when the sugar dissolves.
“When the sugar grains are removed, that’s where the pores are located,” Dr. Wang explained.
The sponge surface was then converted from hydrophobic to hydrophilic, thanks to an oxygen plasma treatment. Next, the sponge was blanketed in a layer of conductive polymer – a liquid that Dr. Wang likens to black ink – transforming it into an electrode. (Without the oxygen plasma step, the sponge wouldn’t have absorbed the conductive material.) After another oven-curing session, the device was affixed with wires and ready to be used.
The researchers are continuing to refine the concept and hope to develop a wireless wearable device with many spongy electrodes that record signals simultaneously – and that patients can use at home.
In addition to monitoring maternal and fetal health during labor, the researchers say the belt-like device could be used for other types of imaging and diagnosis.
“Depending on the scenario, different signals can be recorded,” Dr. Wang said. “It could be an EMG for a pregnant woman, or an ECG for an athlete or a patient with chronic cardiovascular disease that needs monitoring.”
This work was funded by the Bill & Melinda Gates Foundation (INV-005417, INV-035476). The authors acknowledge the Washington University in St. Louis Institute of Materials Science and Engineering for the use of instruments and staff assistance.
A version of this article first appeared on Medscape.com.
A new type of electrode made from sugar could help doctors and researchers more effectively monitor contractions during preterm labor, a condition that precedes almost half of preterm births and is the leading cause of U.S. neonatal deaths.
The sensors, developed by engineers at the McKelvey School of Engineering at Washington University, St. Louis, could help us understand why some patients experience preterm labor, improve medical interventions, and save lives. In the experiment, the researchers built an array of the new electrodes and successfully tested it on a pregnant person in a lab.
The goal is a home-monitoring belt that is comfortable enough for patients to wear and accurate enough to be clinically useful. Built off a framework of sugar and conductive polymers, the thin electrodes have a sponge-like quality that allows them to hold more gel than standard electrodes, measure for 3 hours instead of 1, and resist artifacts created by patient movement. When tested on a pregnant woman, the new electrodes picked up clean signals even when the patient moved, said electrical engineer and article co-author Chuan Wang, PhD.
There is current technology that exists to monitor and map contractions during early labor, but the tests require hundreds of wire electrodes. Patients must sit still for half an hour while the electrodes are applied, then remain immobile for the test itself, which has a high sensitivity to movement.
“It’s very uncomfortable. In the clinical setting, the recording typically lasts for 15 minutes to half an hour. During that time, doctors want the patient to be still,” said Dr. Wang. “If the patient has to move, it’s going to introduce some artifacts, which is going to ruin the imaging process.”
Dr. Wang and colleagues wanted to develop an inexpensive new electrode that would be more comfortable for patients to wear for longer periods of time, yet sensitive enough to detect electrical signals in the body during preterm labor.
To do this, they used sugar structures to create a pliable electrode with a spongy structure. The new electrodes have micropores that hold conductive gel, increasing the amount of electrified surface area touching the skin.
“With the porous structure, we are effectively increasing the area by many, many times,” Dr. Wang said. “Because all those voids also contact the skin, increasing the contact area can boost the strength of the signal.”
With conventional electrodes, the gel dries quickly on the flat surface, causing signal quality to plummet. But the new electrodes can be used for “many hours” before drying out, according to Dr. Wang.
Additionally, the soft material of the new electrode acts “like a buffer” that absorbs motion and prevents the electrode from sliding around, according to Dr. Wang. That means patients can move while wearing the spongy electrodes without disturbing the recording of electrical signals in the body.
From sugar cube to spongy electrode
To create the new electrode, the researchers began by molding sugar into an electrode-shaped template. The template was then dipped into a liquid polymer, which oozed in between the grains of sugar. Next, the template underwent oven curing, emerging as a solid yet spongy structure. Hot water was then applied to dissolve the sugar.
The sugar structure is useful here because of the negative space around the grains, which is filled by the polymer – and then because of the negative space left when the sugar dissolves.
“When the sugar grains are removed, that’s where the pores are located,” Dr. Wang explained.
The sponge surface was then converted from hydrophobic to hydrophilic, thanks to an oxygen plasma treatment. Next, the sponge was blanketed in a layer of conductive polymer – a liquid that Dr. Wang likens to black ink – transforming it into an electrode. (Without the oxygen plasma step, the sponge wouldn’t have absorbed the conductive material.) After another oven-curing session, the device was affixed with wires and ready to be used.
The researchers are continuing to refine the concept and hope to develop a wireless wearable device with many spongy electrodes that record signals simultaneously – and that patients can use at home.
In addition to monitoring maternal and fetal health during labor, the researchers say the belt-like device could be used for other types of imaging and diagnosis.
“Depending on the scenario, different signals can be recorded,” Dr. Wang said. “It could be an EMG for a pregnant woman, or an ECG for an athlete or a patient with chronic cardiovascular disease that needs monitoring.”
This work was funded by the Bill & Melinda Gates Foundation (INV-005417, INV-035476). The authors acknowledge the Washington University in St. Louis Institute of Materials Science and Engineering for the use of instruments and staff assistance.
A version of this article first appeared on Medscape.com.
A new type of electrode made from sugar could help doctors and researchers more effectively monitor contractions during preterm labor, a condition that precedes almost half of preterm births and is the leading cause of U.S. neonatal deaths.
The sensors, developed by engineers at the McKelvey School of Engineering at Washington University, St. Louis, could help us understand why some patients experience preterm labor, improve medical interventions, and save lives. In the experiment, the researchers built an array of the new electrodes and successfully tested it on a pregnant person in a lab.
The goal is a home-monitoring belt that is comfortable enough for patients to wear and accurate enough to be clinically useful. Built off a framework of sugar and conductive polymers, the thin electrodes have a sponge-like quality that allows them to hold more gel than standard electrodes, measure for 3 hours instead of 1, and resist artifacts created by patient movement. When tested on a pregnant woman, the new electrodes picked up clean signals even when the patient moved, said electrical engineer and article co-author Chuan Wang, PhD.
There is current technology that exists to monitor and map contractions during early labor, but the tests require hundreds of wire electrodes. Patients must sit still for half an hour while the electrodes are applied, then remain immobile for the test itself, which has a high sensitivity to movement.
“It’s very uncomfortable. In the clinical setting, the recording typically lasts for 15 minutes to half an hour. During that time, doctors want the patient to be still,” said Dr. Wang. “If the patient has to move, it’s going to introduce some artifacts, which is going to ruin the imaging process.”
Dr. Wang and colleagues wanted to develop an inexpensive new electrode that would be more comfortable for patients to wear for longer periods of time, yet sensitive enough to detect electrical signals in the body during preterm labor.
To do this, they used sugar structures to create a pliable electrode with a spongy structure. The new electrodes have micropores that hold conductive gel, increasing the amount of electrified surface area touching the skin.
“With the porous structure, we are effectively increasing the area by many, many times,” Dr. Wang said. “Because all those voids also contact the skin, increasing the contact area can boost the strength of the signal.”
With conventional electrodes, the gel dries quickly on the flat surface, causing signal quality to plummet. But the new electrodes can be used for “many hours” before drying out, according to Dr. Wang.
Additionally, the soft material of the new electrode acts “like a buffer” that absorbs motion and prevents the electrode from sliding around, according to Dr. Wang. That means patients can move while wearing the spongy electrodes without disturbing the recording of electrical signals in the body.
From sugar cube to spongy electrode
To create the new electrode, the researchers began by molding sugar into an electrode-shaped template. The template was then dipped into a liquid polymer, which oozed in between the grains of sugar. Next, the template underwent oven curing, emerging as a solid yet spongy structure. Hot water was then applied to dissolve the sugar.
The sugar structure is useful here because of the negative space around the grains, which is filled by the polymer – and then because of the negative space left when the sugar dissolves.
“When the sugar grains are removed, that’s where the pores are located,” Dr. Wang explained.
The sponge surface was then converted from hydrophobic to hydrophilic, thanks to an oxygen plasma treatment. Next, the sponge was blanketed in a layer of conductive polymer – a liquid that Dr. Wang likens to black ink – transforming it into an electrode. (Without the oxygen plasma step, the sponge wouldn’t have absorbed the conductive material.) After another oven-curing session, the device was affixed with wires and ready to be used.
The researchers are continuing to refine the concept and hope to develop a wireless wearable device with many spongy electrodes that record signals simultaneously – and that patients can use at home.
In addition to monitoring maternal and fetal health during labor, the researchers say the belt-like device could be used for other types of imaging and diagnosis.
“Depending on the scenario, different signals can be recorded,” Dr. Wang said. “It could be an EMG for a pregnant woman, or an ECG for an athlete or a patient with chronic cardiovascular disease that needs monitoring.”
This work was funded by the Bill & Melinda Gates Foundation (INV-005417, INV-035476). The authors acknowledge the Washington University in St. Louis Institute of Materials Science and Engineering for the use of instruments and staff assistance.
A version of this article first appeared on Medscape.com.
Hair straighteners’ risk too small for docs to advise against their use
Clarissa Ghazi gets lye relaxers, which contain the chemical sodium hydroxide, applied to her hair two to three times a year.
A recent study that made headlines over a potential link between hair straighteners and uterine cancer is not going to make her stop.
“This study is not enough to cause me to say I’ll stay away from this because [the researchers] don’t prove that using relaxers causes cancer,” Ms. Ghazi said.
Indeed, primary care doctors are unlikely to address the increased risk of uterine cancer in women who frequently use hair straighteners that the study reported.
In the recently published paper on this research, the authors said that they found an 80% higher adjusted risk of uterine cancer among women who had ever “straightened,” “relaxed,” or used “hair pressing products” in the 12 months before enrolling in their study.
This finding is “real, but small,” says internist Douglas S. Paauw, MD, professor of medicine at the University of Washington in Seattle.
Dr. Paauw is among several primary care doctors interviewed for this story who expressed little concern about the implications of this research for their patients.
“Since we have hundreds of things we are supposed to discuss at our 20-minute clinic visits, this would not make the cut,” Dr. Paauw said.
While it’s good to be able to answer questions a patient might ask about this new research, the study does not prove anything, he said.
Alan Nelson, MD, an internist-endocrinologist and former special adviser to the CEO of the American College of Physicians, said while the study is well done, the number of actual cases of uterine cancer found was small.
One of the reasons he would not recommend discussing the study with patients is that the brands of hair products used to straighten hair in the study were not identified.
Alexandra White, PhD, lead author of the study, said participants were simply asked, “In the past 12 months, how frequently have you or someone else straightened or relaxed your hair, or used hair pressing products?”
The terms “straightened,” “relaxed,” and “hair pressing products” were not defined, and “some women may have interpreted the term ‘pressing products’ to mean nonchemical products” such as flat irons, Dr. White, head of the National Institute of Environmental Health Sciences’ Environment and Cancer Epidemiology group, said in an email.
Dermatologist Crystal Aguh, MD, associate professor of dermatology at Johns Hopkins University, Baltimore, tweeted the following advice in light of the new findings: “The overall risk of uterine cancer is quite low so it’s important to remember that. For now, if you want to change your routine, there’s no downside to decreasing your frequency of hair straightening to every 12 weeks or more, as that may lessen your risk.”
She also noted that “styles like relaxer, silk pressing, and keratin treatments should only be done by a professional, as this will decrease the likelihood of hair damage and scalp irritation.
“I also encourage women to look for hair products free of parabens and phthalates (which are generically listed as “fragrance”) on products to minimize exposure to hormone disrupting chemicals.”
Not ready to go curly
Ms. Ghazi said she decided to stop using keratin straighteners years ago after she learned they are made with several added ingredients. That includes the chemical formaldehyde, a known carcinogen, according to the American Cancer Society.
“People have been relaxing their hair for a very long time, and I feel more comfortable using [a relaxer] to straighten my hair than any of the others out there,” Ms. Ghazi said.
Janaki Ram, who has had her hair chemically straightened several times, said the findings have not made her worried that straightening will cause her to get uterine cancer specifically, but that they are a reminder that the chemicals in these products could harm her in some other way.
She said the new study findings, her knowledge of the damage straightening causes to hair, and the lengthy amount of time receiving a keratin treatment takes will lead her to reduce the frequency with which she gets her hair straightened.
“Going forward, I will have this done once a year instead of twice a year,” she said.
Dr. White, the author of the paper, said in an interview that the takeaway for consumers is that women who reported frequent use of hair straighteners/relaxers and pressing products were more than twice as likely to go on to develop uterine cancer compared to women who reported no use of these products in the previous year.
“However, uterine cancer is relatively rare, so these increases in risks are small,” she said. “Less frequent use of these products was not as strongly associated with risk, suggesting that decreasing use may be an option to reduce harmful exposure. Black women were the most frequent users of these products and therefore these findings are more relevant for Black women.”
In a statement, Dr. White noted, “We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%.”
The findings were based on the Sister Study, which enrolled women living in the United States, including Puerto Rico, between 2003 and 2009. Participants needed to have at least one sister who had been diagnosed with breast cancer, been breast cancer-free themselves, and aged 35-74 years. Women who reported a diagnosis of uterine cancer before enrollment, had an uncertain uterine cancer history, or had a hysterectomy were excluded from the study.
The researchers examined hair product usage and uterine cancer incidence during an 11-year period among 33 ,947 women. The analysis controlled for variables such as age, race, and risk factors. At baseline, participants were asked to complete a questionnaire on hair products use in the previous 12 months.
“One of the original aims of the study was to better understand the environmental and genetic causes of breast cancer, but we are also interested in studying ovarian cancer, uterine cancer, and many other cancers and chronic diseases,” Dr. White said.
A version of this article first appeared on WebMD.com.
Clarissa Ghazi gets lye relaxers, which contain the chemical sodium hydroxide, applied to her hair two to three times a year.
A recent study that made headlines over a potential link between hair straighteners and uterine cancer is not going to make her stop.
“This study is not enough to cause me to say I’ll stay away from this because [the researchers] don’t prove that using relaxers causes cancer,” Ms. Ghazi said.
Indeed, primary care doctors are unlikely to address the increased risk of uterine cancer in women who frequently use hair straighteners that the study reported.
In the recently published paper on this research, the authors said that they found an 80% higher adjusted risk of uterine cancer among women who had ever “straightened,” “relaxed,” or used “hair pressing products” in the 12 months before enrolling in their study.
This finding is “real, but small,” says internist Douglas S. Paauw, MD, professor of medicine at the University of Washington in Seattle.
Dr. Paauw is among several primary care doctors interviewed for this story who expressed little concern about the implications of this research for their patients.
“Since we have hundreds of things we are supposed to discuss at our 20-minute clinic visits, this would not make the cut,” Dr. Paauw said.
While it’s good to be able to answer questions a patient might ask about this new research, the study does not prove anything, he said.
Alan Nelson, MD, an internist-endocrinologist and former special adviser to the CEO of the American College of Physicians, said while the study is well done, the number of actual cases of uterine cancer found was small.
One of the reasons he would not recommend discussing the study with patients is that the brands of hair products used to straighten hair in the study were not identified.
Alexandra White, PhD, lead author of the study, said participants were simply asked, “In the past 12 months, how frequently have you or someone else straightened or relaxed your hair, or used hair pressing products?”
The terms “straightened,” “relaxed,” and “hair pressing products” were not defined, and “some women may have interpreted the term ‘pressing products’ to mean nonchemical products” such as flat irons, Dr. White, head of the National Institute of Environmental Health Sciences’ Environment and Cancer Epidemiology group, said in an email.
Dermatologist Crystal Aguh, MD, associate professor of dermatology at Johns Hopkins University, Baltimore, tweeted the following advice in light of the new findings: “The overall risk of uterine cancer is quite low so it’s important to remember that. For now, if you want to change your routine, there’s no downside to decreasing your frequency of hair straightening to every 12 weeks or more, as that may lessen your risk.”
She also noted that “styles like relaxer, silk pressing, and keratin treatments should only be done by a professional, as this will decrease the likelihood of hair damage and scalp irritation.
“I also encourage women to look for hair products free of parabens and phthalates (which are generically listed as “fragrance”) on products to minimize exposure to hormone disrupting chemicals.”
Not ready to go curly
Ms. Ghazi said she decided to stop using keratin straighteners years ago after she learned they are made with several added ingredients. That includes the chemical formaldehyde, a known carcinogen, according to the American Cancer Society.
“People have been relaxing their hair for a very long time, and I feel more comfortable using [a relaxer] to straighten my hair than any of the others out there,” Ms. Ghazi said.
Janaki Ram, who has had her hair chemically straightened several times, said the findings have not made her worried that straightening will cause her to get uterine cancer specifically, but that they are a reminder that the chemicals in these products could harm her in some other way.
She said the new study findings, her knowledge of the damage straightening causes to hair, and the lengthy amount of time receiving a keratin treatment takes will lead her to reduce the frequency with which she gets her hair straightened.
“Going forward, I will have this done once a year instead of twice a year,” she said.
Dr. White, the author of the paper, said in an interview that the takeaway for consumers is that women who reported frequent use of hair straighteners/relaxers and pressing products were more than twice as likely to go on to develop uterine cancer compared to women who reported no use of these products in the previous year.
“However, uterine cancer is relatively rare, so these increases in risks are small,” she said. “Less frequent use of these products was not as strongly associated with risk, suggesting that decreasing use may be an option to reduce harmful exposure. Black women were the most frequent users of these products and therefore these findings are more relevant for Black women.”
In a statement, Dr. White noted, “We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%.”
The findings were based on the Sister Study, which enrolled women living in the United States, including Puerto Rico, between 2003 and 2009. Participants needed to have at least one sister who had been diagnosed with breast cancer, been breast cancer-free themselves, and aged 35-74 years. Women who reported a diagnosis of uterine cancer before enrollment, had an uncertain uterine cancer history, or had a hysterectomy were excluded from the study.
The researchers examined hair product usage and uterine cancer incidence during an 11-year period among 33 ,947 women. The analysis controlled for variables such as age, race, and risk factors. At baseline, participants were asked to complete a questionnaire on hair products use in the previous 12 months.
“One of the original aims of the study was to better understand the environmental and genetic causes of breast cancer, but we are also interested in studying ovarian cancer, uterine cancer, and many other cancers and chronic diseases,” Dr. White said.
A version of this article first appeared on WebMD.com.
Clarissa Ghazi gets lye relaxers, which contain the chemical sodium hydroxide, applied to her hair two to three times a year.
A recent study that made headlines over a potential link between hair straighteners and uterine cancer is not going to make her stop.
“This study is not enough to cause me to say I’ll stay away from this because [the researchers] don’t prove that using relaxers causes cancer,” Ms. Ghazi said.
Indeed, primary care doctors are unlikely to address the increased risk of uterine cancer in women who frequently use hair straighteners that the study reported.
In the recently published paper on this research, the authors said that they found an 80% higher adjusted risk of uterine cancer among women who had ever “straightened,” “relaxed,” or used “hair pressing products” in the 12 months before enrolling in their study.
This finding is “real, but small,” says internist Douglas S. Paauw, MD, professor of medicine at the University of Washington in Seattle.
Dr. Paauw is among several primary care doctors interviewed for this story who expressed little concern about the implications of this research for their patients.
“Since we have hundreds of things we are supposed to discuss at our 20-minute clinic visits, this would not make the cut,” Dr. Paauw said.
While it’s good to be able to answer questions a patient might ask about this new research, the study does not prove anything, he said.
Alan Nelson, MD, an internist-endocrinologist and former special adviser to the CEO of the American College of Physicians, said while the study is well done, the number of actual cases of uterine cancer found was small.
One of the reasons he would not recommend discussing the study with patients is that the brands of hair products used to straighten hair in the study were not identified.
Alexandra White, PhD, lead author of the study, said participants were simply asked, “In the past 12 months, how frequently have you or someone else straightened or relaxed your hair, or used hair pressing products?”
The terms “straightened,” “relaxed,” and “hair pressing products” were not defined, and “some women may have interpreted the term ‘pressing products’ to mean nonchemical products” such as flat irons, Dr. White, head of the National Institute of Environmental Health Sciences’ Environment and Cancer Epidemiology group, said in an email.
Dermatologist Crystal Aguh, MD, associate professor of dermatology at Johns Hopkins University, Baltimore, tweeted the following advice in light of the new findings: “The overall risk of uterine cancer is quite low so it’s important to remember that. For now, if you want to change your routine, there’s no downside to decreasing your frequency of hair straightening to every 12 weeks or more, as that may lessen your risk.”
She also noted that “styles like relaxer, silk pressing, and keratin treatments should only be done by a professional, as this will decrease the likelihood of hair damage and scalp irritation.
“I also encourage women to look for hair products free of parabens and phthalates (which are generically listed as “fragrance”) on products to minimize exposure to hormone disrupting chemicals.”
Not ready to go curly
Ms. Ghazi said she decided to stop using keratin straighteners years ago after she learned they are made with several added ingredients. That includes the chemical formaldehyde, a known carcinogen, according to the American Cancer Society.
“People have been relaxing their hair for a very long time, and I feel more comfortable using [a relaxer] to straighten my hair than any of the others out there,” Ms. Ghazi said.
Janaki Ram, who has had her hair chemically straightened several times, said the findings have not made her worried that straightening will cause her to get uterine cancer specifically, but that they are a reminder that the chemicals in these products could harm her in some other way.
She said the new study findings, her knowledge of the damage straightening causes to hair, and the lengthy amount of time receiving a keratin treatment takes will lead her to reduce the frequency with which she gets her hair straightened.
“Going forward, I will have this done once a year instead of twice a year,” she said.
Dr. White, the author of the paper, said in an interview that the takeaway for consumers is that women who reported frequent use of hair straighteners/relaxers and pressing products were more than twice as likely to go on to develop uterine cancer compared to women who reported no use of these products in the previous year.
“However, uterine cancer is relatively rare, so these increases in risks are small,” she said. “Less frequent use of these products was not as strongly associated with risk, suggesting that decreasing use may be an option to reduce harmful exposure. Black women were the most frequent users of these products and therefore these findings are more relevant for Black women.”
In a statement, Dr. White noted, “We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%.”
The findings were based on the Sister Study, which enrolled women living in the United States, including Puerto Rico, between 2003 and 2009. Participants needed to have at least one sister who had been diagnosed with breast cancer, been breast cancer-free themselves, and aged 35-74 years. Women who reported a diagnosis of uterine cancer before enrollment, had an uncertain uterine cancer history, or had a hysterectomy were excluded from the study.
The researchers examined hair product usage and uterine cancer incidence during an 11-year period among 33 ,947 women. The analysis controlled for variables such as age, race, and risk factors. At baseline, participants were asked to complete a questionnaire on hair products use in the previous 12 months.
“One of the original aims of the study was to better understand the environmental and genetic causes of breast cancer, but we are also interested in studying ovarian cancer, uterine cancer, and many other cancers and chronic diseases,” Dr. White said.
A version of this article first appeared on WebMD.com.