Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.

BACKGROUND: Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. OBJECTIVE: To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. METHODS: A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. RESULTS: The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. CONCLUSION: The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

Performance of the Dexcom G7 Continuous Glucose Monitoring System in Pregnant Women with Diabetes.

Background: We evaluated accuracy and safety of a seventh-generation real-time continuous glucose monitoring (CGM) system during pregnancy. Materials and Methods: Evaluable data for accuracy analysis were obtained from 96 G7 sensors (Dexcom, Inc.) worn by 96 of 105 enrolled pregnant women with type 1 (n = 59), type 2 (n = 21), or gestational diabetes (n = 25). CGM values were compared with arterialized venous glucose values from the YSI comparator instrument during 6-h clinic sessions at different time points throughout the sensors' 10-day wear period. The primary endpoint was the proportion of CGM values in the 70-180 mg/dL range within 15% of comparator glucose values. Secondary endpoints included the proportion of CGM values within 20% or 20 mg/dL of comparator values ≥ or <100 mg/dL, respectively (the %20/20 agreement rate). Results: Of the 1739 pairs with CGM in the 70-180 mg/dL range, 83.2% were within 15% of comparator values. The lower bound of the 95% confidence interval was 79.8%. Of the 2102 pairs with CGM values in the 40-400 mg/dL range, the %20/20 agreement rate was 92.5%. Of the 1659 pairs with comparator values in the 63-140 mg/dL range, the %20/20 agreement rate was 92.3%. The %20/20 agreement rates on days 1, 4 and 7, and 10 were 78.6%, 96.3%, and 97.3%, respectively. Consensus error grid analysis showed 99.8% of pairs in the clinically acceptable A and B zones. There were no serious adverse events. The sensors' 10-day survival rate was 90.3%. Conclusion: The G7 system is accurate and safe during pregnancies complicated by diabetes and does not require confirmatory fingerstick testing. Clinical Trial Registration: clinicaltrials.gov NCT04905628.

High-throughput methylome analysis reveals differential methylation for early and late onset preeclampsia for mothers and their children.

Preeclampsia is a hypertensive disorder of pregnancy that affects ∼2%-5% of all pregnancies, contributes to 4 of the top 10 causes of pregnancy-related deaths, and remains a long-term risk factor for cardiometabolic diseases. Yet, little is still known about the molecular mechanisms that lead to this disease. There is evidence that some cases have a genetic cause. However, it is well appreciated that harmful factors in the environment, such as poor nutrition, stress, and toxins, may lead to epigenetics changes that can contribute to this disease. DNA methylation is one of the epigenetic modifications known to be fairly stable and impact gene expression. Using DNA from buccal swabs, we analyzed global DNA methylation among three groups of individuals: mothers who experienced 1) early-stage preeclampsia (<32 wk), 2) late-stage preeclampsia (>37 wk), or 3) no complications during their pregnancies, as well as the children from these three groups. We found significant differentially methylated regions (DMRs) between mothers who experienced preeclampsia compared with those with no complications adjacent or within genes that are important for placentation, embryonic development, cell adhesion, and inflammation (e.g., the cadherin pathway). A significant portion of DMR genes showed expression in tissues relevant to preeclampsia (i.e., the brain, heart, kidney, uterus, ovaries, and placenta). As this study was performed on DNA extracted from cheek swabs, this opens the way to future studies in different tissues, aimed at identifying possible biomarkers of risk and early detection, developing targeted interventions, and reducing the progression of this life-threatening disease.NEW & NOTEWORTHY Preeclampsia is a life-threatening hypertensive disorder, affecting 2%-5% of pregnancies, that remains poorly understood. This study analyzed DNA methylation from buccal swabs from mothers who experienced early and late-stage preeclampsia and those with uncomplicated pregnancies, along with their children. Differentially methylated regions were found near and within genes crucial for placental function, embryonic development, and inflammation. Many of these genes are expressed in preeclampsia-related tissues, offering hope for future biomarker development for this condition.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

Perinatal Stressors and Consequences for Neonates with Critical Congenital Heart Disease.

INTRODUCTION: The prenatal diagnosis of congenital heart disease (CHD) is a traumatic event that can cause expectant parents to experience anxiety, depression, and toxic stress. Prenatal exposure to stress may impact neonatal postoperative outcomes. In addition, expectant parents may have other psychosocial stressors that may compound maternal stress. We investigated the relationship between stress in pregnancies complicated by prenatally diagnosed CHD and their neonatal outcomes. METHODS: A pilot retrospective cohort study of pregnancies with prenatally diagnosed critical CHD (2019-2021) was performed. The collected data included pregnancy characteristics and neonatal and postoperative outcomes (including the need for exogenous corticosteroid treatment (ECT)). In order to quantify prenatal stressors, a composite prenatal stress score (PSS) was established and utilized. RESULTS: In total, 41 maternal-fetal dyads were evaluated. Thirteen (32%) neonates had single-ventricle anatomy. The need for ECT after CHD surgery was associated with higher pregnant patient PSS (p = 0.01). PSS did not correlate with birthweight, infection, or hypoglycemia in the neonatal period. CONCLUSIONS: Prenatal stress is multifactorial; higher PSS is correlates with post-bypass ECT, suggesting that a stressful intrauterine environment may be associated with worse neonatal postoperative outcomes.

Adverse Perinatal and Neonatal Outcomes among Adolescent Pregnancies in the United States.

OBJECTIVE: Despite a downward trend in recent years, adolescent pregnancies in the United States remain higher than any other western country. Adolescent pregnancies have been inconsistently associated with adverse perinatal outcomes. The objective of this study is to investigate the association between adolescent pregnancies and adverse perinatal and neonatal outcomes in the United States. STUDY DESIGN: This is a retrospective cohort study of singleton births in the United States from 2014 to 2020 using national vital statistics data. Perinatal outcomes included gestational diabetes, gestational hypertension, preterm delivery <37 weeks (preterm birth [PTB]), cesarean delivery (CD), chorioamnionitis, small for gestational age (SGA), large for gestational age (LGA), and neonatal composite outcome. Chi-square tests were used to compare outcomes among adolescent (13-19 years) versus adult (20-29 years) pregnancies. Multivariable logistic regression models were used to examine association of adolescent pregnancies with perinatal outcomes. For each outcome, we utilized three models: unadjusted logistic regression, adjusted for demographics, and adjusted for demographics and medical comorbidities. Similar analyses were used to compare younger (13-17 years) and older (18-19 years) adolescent pregnancies to adults. RESULTS: In a cohort of 14,014,078 pregnancies, we found that adolescents were at an increased risk of PTB (adjusted odds ratio [aOR]: 1.12, 99% confidence interval (CI): 1.12-1.13) and SGA (aOR: 1.02, 99% CI: 1.01-1.03) compared with adult pregnancies. We also found that multiparous adolescents with a prior history of CD were at an increased risk of CD, compared with adults. For all other outcomes, adult pregnancies were at higher risk for adverse outcomes in the adjusted models. When comparing birth outcomes among adolescents, we found that older adolescents are at an increased risk of PTB, whereas younger adolescents are at an increased risk of both PTB and SGA. CONCLUSION: After adjusting for confounders, our study demonstrates adolescents have an increased risk of PTB and SGA, compared with adults. KEY POINTS: · Adolescents as a whole subgroup have an increased risk of PTB and SGA compared with adults.. · Younger adolescents have a risk of PTB and SGA, whereas older adolescents have a risk of PTB only.. · Adverse birth outcomes in adults are gestational diabetes, chorioamnionitis, LGA, and worse neonatal composite score..

Influence of Neighborhood Socioeconomic Status on Adverse Outcomes in Pregnancy.

PURPOSE: To evaluate whether ZIP-code level neighborhood socioeconomic status (SES) is associated with adverse pregnancy outcomes. METHODS: A retrospective study of 2009-2014 Oregon Health and Science University (OHSU) births with maternal ZIP codes in one of 89 Portland metropolitan area ZIP codes. Deliveries with ZIP codes outside of the Portland metro area were excluded. Deliveries were stratified by SES based on ZIP code median household income: low (below 10th percentile), medium (11th-89th percentile), and high (above 90th percentile). Univariate analysis and multivariable logistic regression with medium SES as the reference group evaluated perinatal outcomes and strength of association between SES and adverse events. RESULTS: This study included 8118 deliveries with 1654 (20%) classified as low SES, 5856 (72%) medium SES, and 608 (8%) high SES. The low SES group was more likely to be younger, have a higher maternal BMI, have increased tobacco use, identify as Hispanic or Black, and less likely to have private insurance. Low SES was associated with a significantly increased risk of preeclampsia (RR 1.23 95% CI 1.01-1.49), but this was no longer significant after adjusting for confounders (aRR 1.23 95% CI .971-1.55). High SES was negatively associated with gestational diabetes mellitus (GDM), even after adjusting for confounders (aRR 0.710, 95% CI 0.507-0.995). CONCLUSION: In the Portland metropolitan area, high SES was associated with a lower risk of GDM. Low SES was associated with a higher risk of preeclampsia before accounting for covariates. ZIP code-based risk assessment may be a useful indicator in detecting healthcare disparities.

Comprehensive Management of Type 2 Diabetes During Pregnancy.

This JAMA Insights Clinical Update discusses a comprehensive approach to treating pregnant patients with type 2 diabetes to reduce adverse perinatal and neonatal outcomes.

Medications for Managing Preexisting and Gestational Diabetes in Pregnancy.

Persons with gestational and pregestational diabetes during pregnancy may require pharmacologic agents to achieve pregnancy glycemic targets, and the available medications for use in pregnancy are limited. Insulin is the only FDA-approved medication for use in pregnancy and has the greatest evidence for safety and efficacy. Metformin and glyburide are the most commonly used oral agents in pregnancy. Understanding each medication's unique pharmacokinetics, potential side effects, fetal or childhood risks, gestational age of medication initiation and patient's diabetes care barriers are important aspects of shared decision-making and choosing a regimen that will achieve glycemic and pregnancy goals.

Association of perinatal outcomes among pregnant patients with gestational diabetes receiving benefits from the Special Supplemental Nutrition Program for Women, Infants, and Children.

BACKGROUND: Treatment of gestational diabetes mellitus has been demonstrated to improve perinatal outcomes. However, the role of the Special Supplemental Nutrition Program for Women, Infants, and Children in maternal and neonatal outcomes for qualifying patients with gestational diabetes mellitus is less understood. OBJECTIVE: The objective of this study is to observe the relationship of enrollment in the Special Supplemental Nutrition Program for Women, Infants, and Children with pregnancy outcomes in patients with gestational diabetes. STUDY DESIGN: This was a retrospective cohort study using National Vital Statistics Birth Data of pregnant persons diagnosed with gestational diabetes mellitus between 2014 and 2018. The study population was composed of patients who had Medicaid coverage for maternity care; patients with Medicaid are automatically qualified for the Special Supplemental Nutrition Program for Women, Infants, and Children. The study groups were defined as those who enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children vs those who did not enroll. In addition, maternal and neonatal outcomes for these groups were analyzed. Univariate and multivariable logistic regression analyses adjusted for significant covariates were performed. RESULTS: Of 460,377 pregnant persons with pregnancies complicated by gestational diabetes mellitus, 73% were enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children, and 27% were not. Pregnant persons with gestational diabetes mellitus enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children had decreased odds of preterm delivery before 34 and 37 weeks of gestation. Although the Special Supplemental Nutrition Program for Women, Infants, and Children group had higher odds of large-for-gestational-age neonates and cesarean delivery, the overall rates of these outcomes in both cohorts were high. CONCLUSION: The Special Supplemental Nutrition Program for Women, Infants, and Children provides a resource for perinatal support, supplemental food, and nutritional education. The decrease in the rates of preterm deliveries in pregnant persons with gestational diabetes mellitus that enroll in the Special Supplemental Nutrition Program for Women, Infants, and Children, Infants, and Children relative to those that qualified for the program but did not enroll suggested that having access to available education and food sources may influence perinatal outcomes.

Association of interpregnancy interval and gestational diabetes mellitus.

OBJECTIVE: To evaluate the association between interpregnancy interval (IPI) and risk for gestational diabetes mellitus (GDM). METHODS: We conducted a retrospective cohort study among singleton, non-anomalous, live birth pregnancies of 5,705,812 pregnant individuals in the United States from 2016 to 2018. We examined IPI of 4-<6 months, 6-11 months, 12-17 months, 24-35 months, 36-47 months, 48-59 months, 60-71 months, and ≥72 months in comparison to the reference interval of 18-23 months in relation to risk for GDM. We used logistic regression to evaluate the association between IPI and risk for GDM. RESULTS: There is a significantly increased risk for GDM associated with IPIs of 6-11 months and 12-17 months compared to the reference of 18-23 months (adjusted Odds Ratio [aOR] 1.05, 95% CI: 1.03-1.07; aOR 1.02, 95% CI: 1.01-1.03). The risk for GDM is greater for longer IPIs (36-47 months aOR 1.10, 95% CI: 1.05-1.08; 48-59 months aOR 1.11, 95% CI: 1.09-1.13; 60-71 months aOR 1.14, 95% CI: 1.12-1.16; ≥72 months aOR 1.31, 95% CI: 1.30-1.33). CONCLUSION: Our findings support the growing evidence that shorter and longer IPI increase the risk of GDM in pregnant individuals. Screening guidelines for detection of GDM may need to be re-evaluated and updated to include longer IPIs (≥36 months) as a risk factor for earlier screening prior to current recommendation of 24 weeks gestational age.

Association of Prenatal Care Expansion With Use of Antidiabetic Agents During Pregnancies Among Latina Emergency Medicaid Recipients With Gestational Diabetes.

Importance: Access to necessary prenatal care is not guaranteed through Medicaid for some people with low income based on their immigration status. Although states have the option to extend emergency Medicaid coverage for prenatal care, many states have not expanded coverage. Objective: To evaluate whether the receipt of prenatal care services through the extension of emergency Medicaid coverage is associated with an increase in antidiabetic medication use among Latina patients with gestational diabetes. Design, Setting, and Participants: This cohort study used linked Medicaid claims and birth certificate data on live births to 4869 Latina patients from October 1, 2010, to December 31, 2019, with a difference-in-differences design to compare the rollout of prenatal care and services in Oregon in 2013 with a comparison state, South Carolina, that did not cover prenatal or postpartum care. Exposure: Medicaid coverage of prenatal care. Main Outcomes and Measures: The main outcome was the receipt of antidiabetic agents. Secondary outcomes included hypertensive disorders, cesarean delivery, postpartum contraception, and a newborn morbidity composite outcome (large size for gestational age, neonatal intensive care unit admission, and preterm birth). Results: The study sample included live births to 4869 Latina patients (mean [SD] age, 32.7 [5.5] years [range, 12-44 years]) enrolled in emergency Medicaid who were mainly aged 25 to 34 years (1499 of 2907 [51.6%]), multiparous (2626 of 2907 [90.3%]), and living in urban areas (2299 of 2907 [79.1%]). After Oregon's policy change to offer prenatal coverage to individuals receiving emergency Medicaid, there was a large and significant increase in the receipt of antidiabetic agents among all people with diabetes during pregnancy (gestational diabetes). Prior to the policy, only 0.3% of all Latina emergency Medicaid recipients with gestational diabetes (2 of 617) received any medication (oral agents or insulin) to manage their blood glucose level. After the policy change, 28.8% of all patients with gestational diabetes (295 of 1023) received medication to manage their blood glucose level, translating to a 27.9-percentage-point increase (95% CI, 24.5-31.2 percentage points) in the receipt of antidiabetic agents in the adjusted model. The policy was also associated with a 10.4-percentage-point (95% CI, 5.3-15.5 percentage points) increase in insulin use during pregnancy among all patients with gestational diabetes. We observed an increase in postpartum contraceptive use (21.2 percentage points; 95% CI, 14.9-27.5 percentage points), the majority of which was due to postpartum sterilization (increase of 16.1 percentage points; 95% CI, 10.4-21.8 percentage points). We did not observe a significant association with gestational hypertension, cesarean births, or newborn health. Conclusions and Relevance: This retrospective cohort study suggests that expanded emergency Medicaid benefits that included prenatal care were associated with an increased use of antidiabetic medications and postpartum contraception during pregnancy.

Strategies for Prevention or Treatment of Tobacco and Cannabis Use Disorder.

Tobacco and cannabis use in pregnancy are associated with increased adverse perinatal and long-term offspring outcomes. Products for both have evolved with various forms available on the market, challenging accurate counseling of risks and quantification of tobacco and cannabis usage during the perinatal period. Health care providers are recommended to screen for any type of use, provide consistent messaging of harms of tobacco and cannabis use in pregnancy, and offer individualized interventions. The journey to cessation can be complicated by barriers and triggers, lack of social supports, and mental health challenges that should be addressed to prevent relapse and withdrawals.

The Risk of Perinatal Mortality in Nulliparous Women Compared to Primiparous Women at Term.

OBJECTIVE: The aim of this study was to determine the rate of perinatal mortality among nulliparous women compared with primiparous women at term and further characterize the risk of stillbirth by each week of gestation. STUDY DESIGN: This is a retrospective cohort study of all term, singleton, nonanomalous births comparing perinatal mortality (stillbirth and neonatal death [NND]) between primiparous (parity = 1, with no history of abortion) and nulliparous (parity = 0) women who delivered in California between 2007 and 2011. Chi-squared tests and multivariable logistic regression analyses were performed to determine the frequencies and strength of association of perinatal mortality with parity, adjusting for maternal age, race, body mass index, pregestational diabetes, chronic hypertension, fetal sex, smoking status, and socioeconomic status. The risk of stillbirth at each gestational age at term was calculated using a pregnancies-at-risk life table method. A p-value less than 0.05 was used to indicate statistical significance. RESULTS: Of 1,317,761 total deliveries, 765,995 (58.1%) were to nulliparous women and 551,766 (41.9%) were to primiparous women with one prior birth. Nulliparous women had increased odds of stillbirth (adjusted odds ratio [aOR], 3.30; 95% confidence interval [CI], 2.93-3.72) and NND (aOR, 1.54; 95% CI, 1.19-1.98) compared with primiparous women. The risk of stillbirth in nulliparous women was greater at every gestational age between 370/7 and 410/7 weeks compared with primiparous women. Nulliparous women also had increased odds of small for gestational age infants at less than 10% birth weight (aOR, 1.76; 95% CI, 1.72-1.79), less than 5% birth weight (aOR, 1.91; 95% CI, 1.86-1.98), and less than 3% birth weight (aOR, 2.02; 95% CI, 1.93-2.11). CONCLUSION: Perinatal mortality is significantly greater in nulliparous women compared with primiparous women with term deliveries. These findings suggest that low-risk nulliparous women may require increased surveillance. There may be a role in improving maternal health by maximizing physiologic adaptation in nulliparous women. KEY POINTS: · Parity is associated with perinatal mortality.. · Perinatal mortality is significantly greater in nulliparous women compared with primiparous women.. · The risk of stillbirth in nulliparous women is greater at every gestational age compared with primiparous women..

Hyperglycemia and gestational diabetes suppress placental glycolysis and mitochondrial function and alter lipid processing.

The degree that maternal glycemia affects placental metabolism of trophoblast cell types [cytotrophoblast (CTB) and syncytiotrophoblast (SCT)] in pregnant persons with gestational diabetes mellitus (GDM) is unknown. We tested the hypotheses that (a) hyperglycemia suppresses the metabolic rates of CTB and SCT; and (b) low placental metabolic activity from GDM placentas is due to decreased oxygen consumption of CTB. Trophoblast cells isolated from GDM and non-GDM term placentas were cultured for 8-hour (CTB) and following syncytialization at 72-hour (SCT) in 5 mM of glucose or 25 mM of glucose. Oxygen consumption rates, glycolysis, ATP levels, and lipid droplet morphometries were determined in CTB and SCT. In CTB from GDM placentas compared to control CTB: (a) oxidative phosphorylation was decreased by 44% (41.8 vs 74.2 pmol O2 /min/100 ng DNA, P = .002); (b) ATP content was 39% lower (1.1 × 10-7 vs 1.8 × 10-7  nM/ng DNA, P = .046); and (c) lipid droplets were two times larger (31.0 vs 14.4 µm2 /cell, P < .001) and 1.7 times more numerous (13.5 vs 7.9 lipid droplets/cell, P < .001). Hyperglycemia suppressed CTB glycolysis by 55%-60% (mean difference 20.4 [GDM, P = .008] and 15.4 [non-GDM, P = .029] mpH/min/100 ng DNA). GDM SCT was not metabolically different from non-GDM SCT. However, GDM SCT had significantly decreased expression of genes associated with differentiation including hCG, GCM1, and syncytin-1. We conclude that suppressed metabolic activity by the GDM placenta is attributable to metabolic dysfunction of CTB, not SCT. Critical placental hormone expression and secretion are decreased in GDM trophoblasts.

Management of Women with Polycystic Ovary Syndrome During Pregnancy.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women and is associated with subfertility and adverse perinatal outcomes, which may include early pregnancy loss, gestational diabetes mellitus, hypertensive spectrum disorder, preterm birth, fetal growth disorders, and cesarean deliveries. The phenotypic heterogeneity, different diagnostic criteria, and PCOS-related conditions that women enter pregnancy with have limited evidenced-based studies and guidelines to reduce pregnancy complications among this high-risk population. This review summarizes the available evidence on the approach and management of women with PCOS preconception, prenatal, and postpartum.

Increased rates of adverse perinatal outcomes in women with gestational diabetes and depression.

OBJECTIVE: We sought to examine the impact of depression on adverse perinatal outcomes in women with Gestational Diabetes Mellitus (GDM). METHODS: We performed a retrospective cohort study comparing the rates of perinatal complications among singleton, nonanomalous births to women with GDM and the diagnosis of depression compared to GDM women without depression between 2007 and 2011 in California. Perinatal outcomes were analyzed using chi-square and multivariable logistic regression to compare frequencies of characteristics and outcomes and to determine the strength of association of depression and adverse perinatal outcomes among women with GDM. Statistical comparisons with a p-value of less than .05 and 95% CI that did not cross the null were considered statistically significant. RESULTS: Among the cohort of 170,572 women with GDM, 2090 (1.22%) were diagnosed with antenatal depression. Women with GDM and depression had significantly higher rates of preeclampsia (adjusted Odds Ratio [aOR] 1.28, 95% CI 1.11-1.49) and gestational hypertension (aOR 1.23, 95% CI 1.05-1.44). Women with GDM and depression also had higher rates of preterm delivery at <37, and <34 weeks gestational age (aOR 1.33, 95% CI 1.18-1.50 and 1.36, 95% CI 1.15-1.61, respectively). CONCLUSION: Women with GDM and a diagnosis of depression have higher rates of adverse perinatal outcomes than women with GDM alone. Identifying and managing depression among women with GDM has the potential to improve the care and health of this high-risk population.