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BackgroundIn pregnancy, epidemiological data have consistently shown strong associations between sleep quality and duration and maternal glycemia. However, other sleep disturbances such as difficulty falling asleep and staying asleep are common in pregnancy. They may contribute to impaired maternal glycemia through sympathetic nervous system activity, systemic inflammation, and hormonal pathways. However, there is little research examining associations between these specific sleep disturbances and maternal glycemia.ObjectiveThis study aimed to investigate the associations of sleep disturbances during mid-pregnancy and mid-pregnancy maternal glycemia and gestational diabetes subtypes.Study DesignThis is a secondary data analysis of the Comparison of Two Screening Strategies for Gestational Diabetes trial. Participants (n = 828) self-reported the frequency of sleep disturbances (i.e., trouble falling asleep, trouble staying asleep, waking several times per night, and waking feeling tired or worn out) in mid-pregnancy. Gestational diabetes was diagnosed using either the International Associations of Diabetes and Pregnancy Study Groups or Carpenter-Coustan approach. We defined gestational diabetes subtypes based on the degree of insulin resistance and beta-cell dysfunction. We used multinomial logistic regression to examine associations of sleep disturbances with gestational diabetes status (i.e., normal, mild glycemic dysfunction, and gestational diabetes) and gestational diabetes subtypes (i.e., neither insulin resistance or beta-cell dysfunction, insulin resistance only, beta-cell dysfunction only, and insulin resistance and beta- cell dysfunction).ResultsA total of 665 participants (80%) had normal glycemia, 81 (10%) mild hyperglycemia, and 80 (10%) had gestational diabetes. Among participants with gestational diabetes, 62 (78%) had both insulin resistance and beta-cell dysfunction, 15 (19 %) had insulin resistance only, and 3 had beta-cell dysfunction only or neither insulin resistance nor beta-cell dysfunction. Sleep disturbance frequency was not associated with maternal glycemia or gestational diabetes subtypes.ConclusionsSleep disturbances in mid-pregnancy were not associated with maternal glycemia during mid-pregnancy. Future research should collect data on sleep disturbances at multiple time points in pregnancy and in combination with other sleep disturbances to determine whether sleep plays any role in maternal glycemic control.

Per- and polyfluoroalkyl substances (PFAS) have been found to be associated with gestational diabetes mellitus (GDM) development, a maternal health disorder in pregnancy with negative effects that can extend beyond pregnancy. Studies that report on this association are difficult to summarize due to weak associations and wide confidence intervals. One way to advance this field is to sharpen the biologic theory on a causal pathway behind this association, and to measure it directly by way of molecular biomarkers. The aim of this review is to summarize the literature that supports a novel pathway between PFAS exposure and GDM development. Epidemiological studies demonstrate a clear association of biomarkers of thyroid hormones and glucose metabolism with GDM development. We report biologic plausibility and epidemiologic evidence that PFAS dysregulation of maternal thyroid hormones and thyrotropin (TSH) may disrupt glucose homeostasis, increasing the risk of GDM. Overall, epidemiological studies demonstrate that PFAS were positively associated with TSH and negatively with triiodothyronine (T3) and thyroxine (T4). PFAS were generally positively associated with glucose and insulin levels in pregnancy. We propose dysregulation of thyroid function and glucose metabolism may be a critical and missing component in the accurate estimation of PFAS on the risk of GDM. Supplementary Information The online version contains supplementary material available at 10.1186/s12940-021-00740-z.

Background Gestational diabetes mellitus (GDM) is associated with fetal overgrowth, and certain treatments are associated with an increased risk of macrosomia. However, there are limited data about the long-term effect of GDM treatment on childhood growth. Methods Cohort study of 816 women with GDM and their offspring delivered between 2009 and 2012. Childhood height and weight through age 3 were collected from the medical record and z-scores and body mass index (BMI) were calculated. We assessed the association between GDM treatment and childhood growth using linear mixed modeling. Results Treatment was divided into medical nutritional therapy (MNT) (n = 293), glyburide (n = 421), and insulin (n = 102). At delivery, birthweight, z-score, and BMI were higher in the offspring of women treated with either glyburide or insulin compared to MNT. However, weight, z-score, and BMI were similar among all offspring at 6 months and 1, 2, and 3 years of age. After controlling for covariates, there were differences in the weight z-score (P = 0.01) over the 3-year period by treatment group, but no differences in weight (P = 0.06) or change in BMI (P = 0.28). Pairwise comparisons indicated that insulin was associated with more weight gain compared with MNT (0.69 kg; 95% CI, 0.10-1.28; P = 0.02) and glyburide was associated with a trend toward lower weight z-score compared with MNT (−0.24; 95% CI, −0.47 to 0.003; P = 0.05). Conclusion Despite growth differences detected at birth, we observed no meaningful differences in childhood growth from 6 months to 3 years among treatment groups, including in the offspring of women with GDM treated with glyburide.

Diabetes is a common complication of pregnancy associated with both short- and long-term adverse maternal and offspring effects. All types of diabetes in pregnancy are increasing in prevalence. Treatment of diabetes in pregnancy, targeting glycemic control, improves both maternal and offspring outcomes, albeit imperfectly for many women. Pharmacologic treatment recommendations differ between pre-gestational and gestational diabetes; in each case, effectiveness appears limited by co-morbid obesity due to overlapping maternal and offspring risks associated with obesity and diabetes in pregnancy. Despite changes in patient characteristics and increasing evidence of heterogeneous pathophysiology contributing to diabetes in pregnancy, current practice still presupposes a single common treatment strategy, including pharmacologic agents and glycemic targets, with little distinction by diabetes type or pathophysiologic mechanism. Furthermore, while diabetes in pregnancy is associated with long-term offspring risks, few studies have assessed long-term outcomes following exposure to different diabetes treatments in utero. Improved treatment of diabetes in pregnancy will need to consider maternal disease heterogeneity and comorbidities as well as long-term offspring outcomes. In this review, we will summarize recent clinical studies to highlight established pharmacologic treatments for diabetes in pregnancy and provide suggestions for further research.

To evaluate whether inadequate or excessive gestational weight gain before the third trimester is associated with adverse pregnancy outcomes, and to evaluate the association of weight gain in the third trimester with fetal growth.This was a retrospective cohort study of all eligible overweight and obese women with singleton pregnancies delivered at an academic institution between 2012 and 2014. Our primary exposure was inadequate or excess gestational weight gain during the first and second trimesters. Outcomes included small- (SGA) or large- (LGA) for-gestational-age birth weight as well adverse maternal outcomes and composite neonatal morbidity. Multivariable logistic regression was used to assess the relationship between weight gain and perinatal outcomes, and stratified analyses evaluated the relationship between third trimester weight gain and birth weight category.Of the 5,814 women, 1,280 (22%) had adequate, 1,428 (24.6%) had inadequate, and 3,106 (53.4%) had excessive weight gain in the first and second trimesters. Women with inadequate early gestational weight gain were more likely to deliver an SGA neonate (adjusted odds ratio [aOR] 1.59, 95% CI 1.23-2.06) and less likely to deliver an LGA neonate (aOR 0.73, 95% CI 0.54-0.98), whereas those with excessive early gestational weight gain were less likely to deliver an SGA neonate (aOR 0.66, 95% CI 0.52-0.85) and more likely to deliver an LGA neonate (aOR 1.66, 95% CI 1.32-2.1). Higher weight gain in the third trimester was associated with increased risk for LGA birth weight, but third trimester weight gain was not related to SGA birth weight.Early gestational weight gain is associated with birth weight category. Modifying weight gain in the third trimester may limit the risk for LGA birth weight, but higher weight gain in late gestation does not alter the association between inadequate early weight gain and the risk for SGA.

Diabetes screening in early pregnancy is recommended by professional organizations, and some of these recommendations are based on the presence of clinical risk factors. We sought to assess the relationship between the number of diabetes risk factors and the prevalence of both GDM and other adverse pregnancy outcomes among a retrospective cohort of overweight and obese women. We collected information on diabetes-associated risk factors including maternal age, race, hypertension, prior GDM, and a first-degree relative with diabetes. Out of 1212 pregnant overweight and obese women, 313 (26%) had zero, 546 (45%) had one, and 353 (29%) had 2 or more risk factors. Women with 2 or more risk factors were more like to be older (p Disclosure M. N. Feghali: None. C. M. Scifres: None. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (K23HD092893)

Background: Spontaneous abortion (SAB) is a common early pregnancy complication globally, impacting 15% of clinically recognized pregnancies. The biological pathways leading to SAB are not clearly understood, although early SAB is often attributed to chromosomal abnormalities. Elevated blood pressure (BP) in women of reproductive age predicts cardiovascular disease later in life, but less clear is whether elevated BP during preconception and/or early pregnancy BP elevations can affect prenatal outcomes. Hypothesis: Elevated BP during preconception and the first trimester will be positively associated with SAB. Methods: We conducted a secondary analysis of data collected from 577 primiparous women (15-35 years) who participated in the Longitudinal Indian Family hEalth (LIFE) prospective pregnancy cohort study in Telangana State, India. Resting blood pressure was measured by trained technicians using a standardized study protocol at a preconception registration visit and in the first trimester. Odds ratio (OR) and 95% confidence intervals (CI) of any SAB ( Results: Preconception measurements were assessed at the first study visit, conducted at registration and within a mean±SD of 11±12 months prior to pregnancy. Higher than optimal preconception BP (120/80 mmHg) was not associated with SAB (OR adj 0.82 (95% CI 0.51, 1.32)). In contrast, first trimester elevated BP was associated with a two-fold increased likelihood of SAB, although results were of borderline significance (OR adj 2.12 (95%CI 0.87, 5.14). In addition, we observed an association between elevated first trimester BP and late SAB (OR adj 2.32 (95%CI 0.95, 5.68)); there were no associations between elevated preconception or first trimester BP and early SAB. Conclusions: We found that elevated first trimester but not preconception BP was associated with an increased risk of pregnancy loss, suggesting that dysregulated adaption to pregnancy may impact pregnancy loss more than preconception BP status, especially SABs that occur after 8 weeks gestation. Our findings support the notion that clinical and environmental factors may have a greater impact on later SABs as opposed to earlier losses. The null relationship with early pregnancy loss in our study may be due to an expected genetic mutation etiology for those losses. Studies exploring the trajectory of preconception and prenatal blood pressure changes and impact on pregnancy outcomes are warranted.

Objective This study aimed to evaluate the prevalence of severe insulin resistance (insulin requirements ≥2 units/kg) at delivery and the relationship between severe insulin resistance, glycemic control, and adverse perinatal outcomes in pregnant women with type-2 diabetes mellitus. Study Design This is a retrospective cohort study of women with type-2 diabetes mellitus who delivered between January 2015 and December 2017 at a tertiary academic medical center. Maternal demographic information, self-monitored blood sugars, and insulin doses were abstracted from the medical record. Multivariable logistic regression was used to identify maternal baseline characteristics associated with severe insulin resistance at delivery. Results Overall 72/160 (45%) of women had severe insulin resistance. Women in the severe insulin resistance group demonstrated evidence of suboptimal glycemic control as evidenced by higher mean hemoglobin A1c (HbA1c) values (7.2 [ ± 1.1] vs. 6.6 [ ± 1.3%], p = 0.003), higher mean fasting (104.0 [ ± 17.4] vs. 95.2 [ ± 11.7 mg/dL], p Conclusion Severe insulin resistance is common among pregnant women with type-2 diabetes, and it is associated with suboptimal glycemic control. Future studies are necessary to develop strategies to identify women with severe insulin resistance early in pregnancy and facilitate adequate insulin dosing. Key Points

Objective We assessed if the initial response to medical nutritional therapy (MNT) can help predict the need for pharmacological therapy in women with gestational diabetes mellitus (GDM). Study Design We identified 1,174 women with GDM who underwent standardized dietary counseling and reported glucose values from the first week of MNT. We compared women who required pharmacological therapy with those who did not use bivariate statistics, and used multivariable logistic regression modeling to assess for factors predicting the need for pharmacological therapy. Results We identified 819 women (69.8%) who needed pharmacological therapy. They had higher prepregnancy body mass index, higher rates of GDM diagnosis before 24 weeks, and higher oral glucose tolerance test values. After adjustment for covariates, age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.01–1.08), obesity (OR: 2.49; 95% CI: 1.70–3.66), and ≥33% of abnormal glucose values from the first week of MNT (OR: 13.84; 95% CI: 9.4–20.20) were associated with the need for pharmacological therapy. Area under the curve of the regression model was 0.83, with a sensitivity of 72.2%, a specificity of 86.8%, and a positive predictive value of 92.5%. Conclusion Glucose values from the first week of MNT were the strongest predictor of needing pharmacological therapy. Further studies are needed to define metabolic predictors of response to MNT in women with GDM.

Objective Antibiotics are commonly used in pregnancy. Prior studies have indicated that antibiotic use in pregnancy may affect birth weight, whereas data in nonpregnant individuals suggest that antibiotic exposure may increase diabetes risk. We evaluated the impact of antibiotic prescriptions during pregnancy on the prevalence of small for gestational age (SGA) and large for gestational age (LGA) birth weight and gestational diabetes mellitus (GDM). Study Design This retrospective cohort study of 12,551 women who delivered at a large academic medical center between 2012 and 2014 assessed the number and type of antibiotic prescriptions prior to GDM testing using the electronic medical record. SGA and LGA birth weight and GDM rates were compared among women who were or were not prescribed antibiotics. Results Overall, 3,991 (31.8%) of 12,551 patients received at least one antibiotic prescription. After covariate adjustment, no differences existed in risk of SGA (adjusted odds ratio [aOR]: 1; 95% confidence interval [CI]: 0.88–1.15; p = 0.94), LGA (aOR: 1; 95% CI: 0.86–1.17; p = 0.97), or GDM (aOR: 0.90; 95% CI: 0.72–1.13; p = 0.36) between women who were or were not prescribed antibiotics. Conclusion Antibiotic use does not affect the risk of SGA or LGA birth weight or GDM in pregnant women. These results provide reassurance regarding the use of antibiotics when clinically indicated in pregnancy.

To evaluate the prevalence of early diabetes screening in pregnancy, rates of abnormal diabetes test results before 24 weeks of gestation, and factors associated with early diabetes screening.This was a retrospective cohort study of all singleton deliveries from 2012 to 2014 among diverse clinical practices at a large academic medical center. We assessed rates of early (less than 24 weeks of gestation) and routine (at or beyond 24 weeks of gestation) diabetes screening, with abnormal test results defined using the Carpenter-Coustan criteria, a 50-g glucose challenge test result greater than 200 mg/dL, or a hemoglobin A1C level greater than 6.5%. Univariate and multivariate analyses were used to evaluate clinical and demographic determinants of screening and diagnosis.Overall, 1,420 of 11,331 (12.5%) women underwent early screening. Increasing body mass index (BMI) category, race, public insurance, history of gestational diabetes mellitus, a family history of diabetes, and chronic hypertension were associated with early screening. Early screening rates rose with increasing BMI category, but only 268 of 551 (48.6%) of women with class III obesity underwent early screening. Among those screened early, 2.0% of normal-weight women, 4.0% of overweight women, 4.2% of class I obese women, 3.8% of class II obese women, and 9.0% of class III obese women had abnormal early test results (P.001).Early diabetes screening is used inconsistently, and many women with risk factors do not undergo early screening. A significant proportion of women with class III obesity will test positive for gestational diabetes mellitus before 24 weeks of gestation, and studies are urgently needed to assess the effect of early diabetes screening and diagnosis on perinatal outcomes in high-risk women.

Overweight and obese women with gestational diabetes mellitus are at increased risk for adverse perinatal outcomes, and they are also more likely to have suboptimal glycemic control. However, there is a paucity of data evaluating whether lower glycemic targets could improve outcomes.To evaluate the feasibility of intensive glycemic control in overweight and obese women with gestational diabetes mellitus.We randomized 60 overweight or obese women with gestational diabetes mellitus, diagnosed between 12 and 32 weeks' gestation to either intensive (fasting90 mg/dL, 1 hour postprandial120 mg/dL) or standard (fasting95 mg/dL, 1 ho postprandial140 mg/dL) glycemic targets. Maternal glucose was assessed in 2 ways: blinded continuous glucose monitors, worn for 5 days at 2 time points (at 12-32 weeks and again at 32-36 weeks), and self-monitored glucose measurement 4 times per day. All women underwent standardized dietary counseling, and medical therapy was prescribed as needed to achieve glycemic control.Between December 2015 and December 2017, we randomized 60 women to either intensive (n = 30) or standard (n = 30) glycemic control. Baseline characteristics including maternal age, body mass index, and gestational age at diagnosis were similar between the intensive and standard groups. Medical therapy was more common in women in the intensive group than those in the standard group (83 vs 57%, P = .02). Women in the intensive glycemic control group had lower glucose values as assessed by continuous glucose monitors at including 24-hour mean (-8.1; 95% confidence interval, -12.0 to -4.3 mg/dL; P .0001) and 1-h postprandial (-11.8; 95% confidence interval, -19.7 to -3.9 mg/dL, P = .004) values. Hypoglycemia60 mg/dL was uncommon and did not differ between groups.Intensive glycemic targets can be used in overweight and obese women with minimal hypoglycemia, and this approach results in improved glycemic control when compared to standard glycemic targets. Further studies are needed to determine whether intensive glycemic targets can improve maternal and neonatal outcomes in high-risk women with gestational diabetes mellitus.NCT02530866; clinicaltrials.gov.

Maternal diabetes mellitus (DM) affects fetal growth and we sought to examine the impact of birth weight category on growth in the first 3 years of life. We conducted a retrospective cohort study of 787 women with gestational (n=629) or pre-gestational DM (n=158). Maternal characteristics and perinatal outcomes, as well as childhood height and weight through age 3, were collected. Bivariate and multivariable linear regression analyses were used to assess factors associated with early childhood growth. We compared weight z-scores and BMI at 6 months, 1, 2, and 3 years of age among those born small for gestational status (SGA) (n=71), adequate for gestational age (AGA) (n=619) and large for gestational age (LGA) (n=97). Weight z-scores and BMI at all time points were higher in infants born LGA and lower among those with SGA birth weight. BMI >85th percentile at age 3 was more common in offspring born LGA compared to those born AGA or SGA (44.57 vs. 21.09 vs. 12.9%, p Our findings suggest that birth weight category is a significant predictor of early childhood growth, and interventions that reduce the prevalence of LGA birth weight or optimize early childhood nutrition may impact long-term obesity risks. Disclosure M.N. Feghali: None. S. Caritis: None. C.M. Scifres: None. Funding National Institutes of Health (K23HD092893)

Type 2 diabetes mellitus (DM) is associated with adverse perinatal outcomes, but insulin requirements and the prevalence of inadequate glycemic control across gestation are not well characterized. We therefore conducted a retrospective cohort study of women with type 2 DM who delivered from 2015 to 2017. Self-monitored blood glucose and insulin doses across gestation were abstracted, and inadequate glycemic control was defined as a mean blood glucose >95 mg/dL fasting or >140 mg/dL 1 hour post-prandial. We compared insulin dosing in early gestation and at delivery by maternal glycemic control. Multivariable logistic regression was used to identify predictors of high insulin requirements at delivery. Inadequate glycemic control occurred in 96/155 (62%) of women. Maternal BMI, gestational age at first prenatal visit, and duration of diabetes were similar between women with inadequate and adequate control. Baseline HbA1c (8.1 ±2.0 vs. 7.5 ±1.9%, p=0.10) and percent of women receiving medical therapy before initiation of prenatal care (71.3% vs. 69.5%, p=0.81) were also similar between groups. Women with inadequate and adequate control had similar insulin doses in early pregnancy (0.7 ±0.5 vs. 0.7 ±0.5 units/kg, p=0.86), but by delivery women with inadequate control required significantly higher doses (2.3 ±1.2 vs. 1.8 ±1.0 units/kg, p=0.004). The highest quartile of insulin dose at delivery was >2.7 units/kg. Multivariable logistic regression modeling demonstrated that maternal BMI at the first prenatal visit (aOR 1.0, 95% CI 0.99-1.01), non-white race (aOR 0.35, 95% CI 0.16-0.78), and baseline HbA1c (aOR 1.22, 95% CI 1.02-1.46) had poor ability to predict high insulin requirements at delivery (AUC 0.67). Although high insulin requirements may be related to suboptimal glycemic control in women with type 2 DM, it is difficult to identify these women using baseline characteristics. Further studies are urgently needed to optimize insulin dosing in women with Type 2 DM. Disclosure H.C. Nadeau: None. M.E. Maxted: None. D. Madhavan: None. S. Pierce: None. M.N. Feghali: None. C.M. Scifres: None.

Maternal vascular malperfusion (MVM) lesions represent hypoxic-ischemic damage to the placenta, and they are associated with adverse pregnancy outcomes. Women with gestational diabetes (GDM) are at increased risk for pregnancy complications, so we set out to characterize the prevalence and clinical correlates of MVM lesions in this cohort.This was a retrospective cohort study of 1187/1374 (86.4%) women with GDM delivered between 2009 and 2012 who had placental pathology available. Placental lesions of all types were tabulated and grouped into constructs of related entities. MVM lesions specifically included villous infarcts, decidual vasculopathy, increased syncytial knots, perivillous fibrin, and fibrin deposition. We compared maternal characteristics between women with and without MVM lesions, and we also assessed the impact of these lesions on birth weight, preterm birth, and pre-eclampsia using multivariable logistic regression analysis.MVM lesions were the most common placental lesion type in women with GDM (n = 362, 30.5%). Excess gestational weight gain was independently associated with MVM lesions (aOR 1.42, 95% CI 1.06-1.91, p = 0.02) after adjusting for maternal characteristics. MVM lesions were associated with lower birth weight (-90.3 g, 95% CI -148.0 to -32.7, p = 0.002), as well as a 2-fold increased risk for delivery of a small for gestational age infant (10.8 vs 5.9%, p = 0.01) in overweight and obese women. MVM lesions were also associated with increased risk for preterm birth34 weeks (adjusted OR 2.36, 95% CI 1.31-4.23, p = 0.004) and hypertensive disorders of pregnancy (HDP; adjusted OR 1.58, 95% CI 1.13-2.22, p = 0.02).Placental maternal vascular malperfusion lesions may be one pathway linking excess gestational weight gain to adverse pregnancy outcomes in women with GDM, and future studies are needed to identify metabolic factors that may explain this association.

Gestational diabetes mellitus (GDM) is associated with childhood obesity and there is concern that glyburide is associated with macrosomia and perhaps childhood overgrowth. We sought to examine if GDM treatment type is associated with differences in early childhood growth using a retrospective cohort of 952 women with GDM and their offspring. We collected pregnancy and breastfeeding data as well as height and weight through age 3. We used bivariate and multivariable regression analyses to compare early childhood growth among maternal GDM treatment. Treatment was divided into medical nutritional therapy (MNT), glyburide, and insulin. LGA at birth was more common in offspring exposed to insulin and glyburide compared to those treated with MNT (11.7 vs. 9.2 vs. 5.7%, p=0.03). Weight or BMI at 6 months, 1, 2 and 3 years of age did not differ among children born to women with different GDM treatments. GDM treatment type was not predictive of weight or associated with a higher risk for BMI >85th percentile at age 2 or 3 years after adjusting for covariates including gender, age at recorded weight, birth weight category, pre-pregnancy BMI, gestational weight gain, and breastfeeding. Our findings suggest that maternal pre-pregnancy BMI but not GDM treatment is associated with variations in early childhood growth. Further studies are needed to determine if these findings persist beyond 3 years of age and to explore differences in body composition. Factors associated with offspring weight at 2 yearsFactors associated with offspring weight at 3 yearsBeta Coefficient (95% CI)PBeta Coefficient (95% CI)PMNT (n=344) Glyburide (n=490) Insulin (n=117)Ref -0.16 (-0.48-0.15) -0.27 (-0.74-0.21)n/a 0.30 0.27Ref -0.13 (-0.53-0.26) 0.35 (-0.22-0.93)n/a 0.50 0.23Female gender-0.48 (-0.75- -0.20)0.001-0.59 (-0.94- -0.25)0.001Prepregnancy BMI0.16 (0.06-0.27)0.0030.17 (0.02-0.31)0.026Pregnancy weight gain (lbs)0.0(-0.003-0.02)0.150.036 (0.011-0.061)0.004Any breastfeeding-0.30 (-0.06- -0.02)0.04-0.41 (-0.77- -0.04)0.03Birth weight category AGA SGA LGARef -1.16 (-1.6- -0.7) 0.88 (0.32-1.44)n/a Disclosure M.N. Feghali: None. J. Atlass: None. S. Caritis: None. J.M. Catov: None. C.M. Scifres: None.

Background: In high-income countries, maternal obesity is one of the most important modifiable causes of stillbirth, yet the pathways underpinning this association remain unclear. Objective: We estimated the association between maternal prepregnancy body mass index (BMI) and the risk of stillbirth defined by pathophysiologic contributors or causes. Design: Using a case-cohort design, we randomly sampled 1829 singleton deliveries from a cohort of 68,437 eligible deliveries at Magee-Womens Hospital in Pittsburgh, Pennsylvania (2003–2010), and augmented it with all remaining cases of stillbirth for a total of 658 cases. Stillbirths were classified based on probable cause(s) of death (maternal medical conditions, obstetric complications, fetal abnormalities, placental diseases, and infection). A panel of clinical experts reviewed medical records, placental tissue slides and pathology reports, and fetal postmortem reports of all stillbirths. Causes of fetal death were assigned by using the Stillbirth Collaborative Research Network Initial Causes of Fetal Death protocol from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Proportional hazards models were used to estimate the BMI-stillbirth association after adjustment for confounders. Results: The rate of stillbirth among lean, overweight, obese, and severely obese women was 7.7, 10.6, 13.9, and 17.3 per 1000 live-born and stillborn infants, respectively. Adjusted stillbirth HRs (95% CIs) were 1.4 (1.1, 1.8) for overweight, 1.8 (1.3, 2.4) for obese, and 2.0 (1.5, 2.8) for severely obese women, respectively, compared with lean women; associations strengthened when limited to antepartum stillbirths. Obesity and severe obesity were associated with stillbirth resulting from placental diseases, hypertension, fetal anomalies, and umbilical cord abnormalities. BMI was not related to stillbirth caused by placental abruption, obstetric conditions, or infection. Conclusions: Multiple mechanisms appear to link obesity to stillbirth. Interventions to reduce stillbirth among obese mothers should consider targeting stillbirth due to hypertension and placental diseases—the most common causes of fetal death in this at-risk group.

Objective Fetal congenital lung masses generate concern for compromised postnatal respiratory function. Congenital pulmonary adenomatoid malformation volume ratio (CVR) has been used to predict the risk of hydrops fetalis and need for antenatal intervention. This study investigates whether CVR could be used to predict neonatal respiratory outcomes. Methods The ultrasounds of fetuses diagnosed with a lung mass between 2005 and 2013 were reviewed. CVR was calculated at each ultrasound using the formula for a prolate ellipse divided by head circumference. The pregnancy outcome and information about NICU admission for respiratory insufficiency were collected. Results Forty-two fetuses were diagnosed with a lung mass during the study period. CVR prior to 24 weeks and between 24 and 32 weeks were associated with NICU admission (p

OBJECTIVE To evaluate the association of obesity with pregnancy outcomes in women with gestational diabetes mellitus (GDM) and identify potentially modifiable risk factors for adverse outcomes in obese women with GDM. METHODS This was a retrospective cohort study of 1,344 women with GDM who delivered between 2009 and 2012. Demographic data, blood sugar values, gestational weight gain, and maternal and neonatal outcome data were abstracted from the medical record and compared among normal-weight, overweight, and obese women. RESULTS Overweight and obese women had higher mean fasting and postprandial blood sugars despite higher doses of and more frequent use of medication. Obesity was independently associated with macrosomia (adjusted odds ratio [OR] 2.03, 95% confidence interval [CI] 1.07-3.89, P=.03), indicated preterm birth (adjusted OR 2.21, 95% CI 1.02-4.78, P=.04), and hypertensive disorders of pregnancy (adjusted OR 2.19, 95% CI 1.38-3.49, P=.001). In our stratified analyses, obese women with fasting blood sugars greater than 88.7 mg/dL and postprandial blood sugars greater than 123.8 mg/dL had higher rates of macrosomia (13.1% compared with 5.7%, P=.004 for fasting, 13.0% compared with 6.5%, P=.01 for postprandial blood sugars) and indicated preterm birth (11.4% compared with 6.1%, P=.04 for fasting, 11.9% compared with 5.8%, P=.01 for postprandial blood sugars) when compared with obese women with lower values. Hypertensive disorders of pregnancy were significantly increased in obese women with postdiagnosis weight gain greater than 0.6 lb per week (29.4% compared with 15.2%, P

AIM: To examine pregnancy outcomes in women with gestational diabetes mellitus (GDM) based on the timing of diagnosis. METHOD: We compared demographics, blood sugars and outcomes between women diagnosed before (n=167) or after 24 weeks’ gestation (n=1202) in a single hospital between 2009 and 2012. Because early screening is risk-based we used propensity score modelling and conditional logistic regression to account for systematic differences. RESULTS: Women diagnosed with GDM before 24 weeks were more likely to be obese and they were less likely to have excess gestational weight gain (35 vs. 45%, p=0.04). Early diagnosis was associated with more frequent therapy including glyburide (65 vs. 56%, p

To evaluate the prevalence and clinical effects of excess gestational weight gain on birth weight and other pregnancy outcomes in women with type 1 diabetes.We performed a retrospective cohort study of women with type 1 diabetes delivered between 2009 and 2012. Patients with excess weight gain were identified using the 2009 Institute of Medicine weight gain recommendations adjusted for gestational age at delivery and prepregnancy body mass index (BMI) category. Demographic and outcome data were abstracted from the medical record, and pregnancy outcomes were compared between women with and without excess gestational weight gain.Excess gestational weight gain occurred in 114 of 175 women (65.1%). Large-for-gestational-age (LGA) birth weight occurred in 48 of 114 (42.1%) of women with excess gestational weight gain and 5 of 61 (8.2%) of women with recommended weight gain (P.001). The association between excess maternal weight gain and LGA birth weight remained significant after adjustment for prepregnancy BMI, gestational age at delivery, nulliparity, vascular complications, and hemoglobin A1c measurements (adjusted odds ratio 8.9, 95% confidence interval 3.1-26.2, P.001). Stratified analyses demonstrated that excess maternal weight gain is associated with LGA neonates in both normal-weight and overweight or obese women.Excess maternal weight gain is common and leads to higher rates of LGA neonates in both normal-weight and overweight or obese women with type 1 diabetes. Interventions designed to limit excess gestational weight gain may reduce the risk for fetal overgrowth in women with type 1 diabetes.II.

To examine the influence of maternal pre-pregnancy body mass index (BMI) on the rates of recurrent spontaneous preterm birth (SPTB) in women receiving 17α-hydroxyprogesterone caproate (17P).Retrospective analysis of a cohort of 6253 women with a singleton gestation and prior SPTB enrolled in 17P home administration program between 16.0 and 26.9 weeks. Data were grouped by pre-pregnancy BMI (lean18.5 kg/m(2), normal 18.5-24.9 kg/m(2), overweight 25-29.9 kg/m(2) and obese ≥30.0 kg/m(2)). Delivery outcomes were compared using χ(2) and Kruskal-Wallis tests with statistical significance set at p 0.05.SPTB28 weeks was significantly lower in normal weight women. Rates of recurrent SPTB37 weeks were highest in the group with BMI18.5 kg/m(2). Lean gravidas were younger, more likely to smoke, and less likely to be African-American than those with normal or increased BMI. In logistic regression, after controlling for race and prior preterm birth28 weeks, the risk of SPTB37 weeks decreased 2% for every additional 1 kg/m(2) increase in BMI.Recurrent spontaneous preterm delivery37 weeks in patients on 17P is more common in lean women (BMI18.5 kg/m(2)), and less common in obese women (BMI ≥30 kg/m(2)) suggesting that the current recommended dosing of 17 P is adequate for women with higher BMI.

Objective There is limited data regarding the use of oral hypoglycemic agents (OHAs) in pregnant women with type 2 diabetes mellitus (T2DM). Study Design This was a retrospective cohort study of women with T2DM who were treated with OHA or insulin from the first trimester onward. Bivariate and multivariate logistic regression analyses were used to compare pregnancy outcomes in women treated with OHA to those treated with insulin. Results One-third (67/198) of women were treated with OHA. Women treated with OHA had a shorter disease duration (4.4 vs. 6.8 years; p = 0.001), were more likely to have a normal prepregnancy body mass index, and had less gestational weight gain (GWG; 22.4 vs. 30.4 lbs; p = 0.005). A lower GWG was noted in obese women treated with OHA (19.9 ± 18.6 vs. 28.3 ± 17.7 pounds; p = 0.008). First-trimester hemoglobin A1c values were lower with OHAs, but second- and third-trimester values were similar. Among women who started pregnancy using OHA, 37/67 (55.2%) remained on OHA at delivery. Pregnancy outcomes did not differ between women who received OHA and those treated with insulin. Conclusion OHA treatment is more likely in women with T2DM who begin pregnancy with less severe disease, and use of OHA may be associated with decreased GWG.

Despite major advances in neonatal care, the burden of preterm birth remains high. This is not unexpected since strategies to identify and treat risk factors in early pregnancy have not been very effective in reducing the preterm birth rate. Initial studies suggested a potential benefit for 17-alpha-hydroxyprogesterone caproate (17-OHPC) in decreasing the risk of recurrent preterm birth women with a singleton gestation. However, the use of 17-OHPC has not conferred benefit for other categories of women at high risk for preterm delivery (twins, triplets, and short cervical length). The increasing body of evidence suggests that preterm birth is a complex condition with variable mechanisms of disease and significant individual heterogeneity. This review will examine the plausibility of 17-OHPC in preventing preterm birth and the investigation of its clinical efficacy. We will also highlight factors to explain variations in clinical trial outcomes and outline the trajectory needed for future investigations.

Women with gestational diabetes mellitus (GDM) commonly undergo induction of labor (IOL) at term, but the risks and benefits of IOL are incompletely understood.We examined the relationship among gestational age, IOL, and the rate of cesarean delivery (CD) in women with GDM.We identified 863 women with GDM who underwent either IOL or spontaneous labor ≥37 0/7 weeks. Demographic, cervical favorability, and outcome data were abstracted from the medical record. We compared the CD rate in women undergoing IOL at each week of gestation with expectant management to a later gestational age.When compared to women who were expectantly managed, IOL at 37 weeks (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 0.76-3.06; P = .23), 38 weeks (aOR, 2.07; 95% CI, 0.89-4.80; P = .09), and 39 weeks (aOR, 0.79; 95% CI, 0.44-1.42; P = .43)) was associated with similar risk for CD as expectant management after adjustment for nulliparity, body mass index, baseline simplified Bishop score, and maternal age. CD rates were higher in nulliparous women, but did not differ significantly in those undergoing IOL or expectant management. In multiparous women, IOL was significantly associated with an increased risk for CD at 38 weeks (aOR, 7.47; 95% CI, 1.6-34.8; P = .01) and rates of CD (17.39% vs 2.2%, P = .001) were significantly higher in multiparous women with an unfavorable Bishop score induced39 weeks. Neonatal morbidity was similar across gestational ages after adjustment for maternal body mass index and maternal glycemic control.IOL results in similar risk for CD as expectant management between 37-40 weeks of gestation. Rates of CD differed based on cervical exam and parity. These findings suggest that gestational age alone does not significantly impact maternal and neonatal outcomes, but that decisions regarding delivery in women with GDM should take into account cervical exam and parity.

Background Women with gestational diabetes mellitus (GDM) commonly undergo induction of labor (IOL) at term, but the risks and benefits of IOL are incompletely understood. Objective We examined the relationship among gestational age, IOL, and the rate of cesarean delivery (CD) in women with GDM. Study Design We identified 863 women with GDM who underwent either IOL or spontaneous labor ≥37 0/7 weeks. Demographic, cervical favorability, and outcome data were abstracted from the medical record. We compared the CD rate in women undergoing IOL at each week of gestation with expectant management to a later gestational age. Results When compared to women who were expectantly managed, IOL at 37 weeks (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 0.76–3.06; P = .23), 38 weeks (aOR, 2.07; 95% CI, 0.89–4.80; P = .09), and 39 weeks (aOR, 0.79; 95% CI, 0.44–1.42; P = .43)) was associated with similar risk for CD as expectant management after adjustment for nulliparity, body mass index, baseline simplified Bishop score, and maternal age. CD rates were higher in nulliparous women, but did not differ significantly in those undergoing IOL or expectant management. In multiparous women, IOL was significantly associated with an increased risk for CD at 38 weeks (aOR, 7.47; 95% CI, 1.6–34.8; P = .01) and rates of CD (17.39% vs 2.2%, P = .001) were significantly higher in multiparous women with an unfavorable Bishop score induced Conclusion IOL results in similar risk for CD as expectant management between 37-40 weeks of gestation. Rates of CD differed based on cervical exam and parity. These findings suggest that gestational age alone does not significantly impact maternal and neonatal outcomes, but that decisions regarding delivery in women with GDM should take into account cervical exam and parity.

To determine whether the second stage of labor affects the progression of retinopathy in women with type I diabetes mellitus (DM). RESEARCH AND DESIGN: The study is a secondary analysis of 192 pregnant women with type I DM who participated in an interdisciplinary diabetes in pregnancy intervention program between 1978 and 1993. Evaluation for diabetic retinopathy (DR) was performed each trimester and 6-12 weeks postpartum by the same two ophthalmologists. Women were divided into three groups: (i) elective cesarean delivery (n = 60), (ii) cesarean delivery prior to the second stage of labor (n = 69) and (iii) vaginal or cesarean delivery in the second stage (n = 63). Progression of DR during pregnancy and between pregnancy and postpartum was compared among the groups.Maternal demographics, glycemic control and pregnancy complications were similar among groups. Progression of retinopathy from early and late pregnancy to postpartum did not differ between the three groups.With close follow-up and good glycemic control, expulsive efforts in the second stage of labor do not affect the progression of retinopathy in women with type I DM. Our data support the premise that pregnant women with type I DM and stable retinopathy should not be denied vaginal delivery, if otherwise not contraindicated.

To test the hypothesis that fetal exposure to a hyperglycemic intrauterine environment in women with type 1 diabetes is associated with asymmetrically distributed excessive fetal growth and imprinting consistent with adverse health issues later in life.We report findings from a feasibility study on 19 young adults, born to mothers with type 1 diabetes. Long-term follow-up of the offspring in young adulthood included: oral glucose tolerance test, body mass index (BMI), dual X-ray absorptiometry, and blood pressure (BP). We report z-BMI and z-BP to account for varying gender and age.The young adults born to women with diabetes averaged 19.9 years at follow-up; 37% were female, and 21% African American. Maternal glycohemoglobin A(1) concentration in the 2nd trimester was 9.2% for offspring born with asymmetric LGA and 7.5% for those born with symmetric LGA or AGA. There was significant correlation between maternal glucose control during pregnancy and fasting glucose, z-BMI and z-systolic BP in the young adults.The hyperglycemic intrauterine environment is associated with short-term morbidity, manifested as asymmetric LGA (the "fat" baby). In addition, increasing level of maternal hyperglycemia during pregnancy is associated with increased adiposity and elevated fasting glucose in the young adult offspring.

We sought to examine neonatal morbidity in four groups of offspring (asymmetric large for gestational age [LGA], symmetric LGA, asymmetric non-LGA, symmetric non-LGA) exposed in utero to maternal type 1 diabetes, and the association between rate of fetal abdominal circumference growth and asymmetric LGA. We performed a secondary analysis of 302 singleton pregnancies. Neonatal morbidity (respiratory distress syndrome, polycythemia, hypoglycemia, hyperbilirubinemia, acidosis, and composite morbidity [any of the five]) was assessed. Serial ultrasound examinations after 20 weeks' gestation were available for 35 fetuses. Logistic regression and general linear mixed modeling were used for analysis. Asymmetric LGA infants had 3.5-, 2.2-, and 3.2-fold greater odds of hypoglycemia, hyperbilirubinemia, and composite morbidity, respectively, compared with symmetric non-LGA infants. The rate of growth of the abdominal circumference in asymmetric LGA infants (1.11 cm/wk) was greater than for both the symmetric LGA infants (0.87 cm/wk, P = 0.09) and the symmetric non-LGA infants (0.87 cm/wk, P = 0.03). Asymmetric LGA infants are at higher risk for morbidity than symmetric LGA and non-LGA infants. Intrauterine growth rate of the abdominal circumference may potentially be used as a marker to identify the asymmetric LGA and thereby aid in the identification of newborns at greatest risk for perinatal complications.

Pregnancy is a complex state where changes in maternal physiology have evolved to favor the development and growth of the placenta and the fetus. These adaptations may affect preexisting disease or result in pregnancy-specific disorders. Similarly, variations in physiology may alter the pharmacokinetics or pharmacodynamics that determines drug dosing and effect. It follows that detailed pharmacologic information is required to adjust therapeutic treatment strategies during pregnancy. Understanding both pregnancy physiology and the gestation-specific pharmacology of different agents is necessary to achieve effective treatment and limit maternal and fetal risk. Unfortunately, most drug studies have excluded pregnant women based on often-mistaken concerns regarding fetal risk. Furthermore, over two-thirds of women receive prescription drugs while pregnant, with treatment and dosing strategies based on data from healthy male volunteers and non-pregnant women, and with little adjustment for the complex physiology of pregnancy and its unique disease states. This review will describe basic concepts in pharmacokinetics and their clinical relevance and highlight the variations in pregnancy that may impact the pharmacokinetic properties of medications.

OBJECTIVE To assess the accuracy of a large-for-gestational-age (LGA) ultrasound diagnosis and the subsequent risk for cesarean delivery associated with ultrasound diagnosis of LGA among women with gestational diabetes mellitus. METHODS This was a retrospective cohort study of 903 women with GDM who delivered after 36 weeks of gestation with an ultrasound-estimated fetal weight within 31 days of delivery. Delivery outcomes were compared between women with an ultrasound diagnosis of LGA and a non-LGA ultrasound diagnosis. RESULTS Based on ultrasound assessments, we identified 248 women with an LGA fetus and 655 women with a non-LGA fetus. Among women with an LGA ultrasound diagnosis, 56 of 248 (22.6%) delivered an LGA neonate, whereas, of women with a non-LGA ultrasound diagnosis, 18 of 655 (2.8%) delivered an LGA neonate. Ultrasound diagnosis of LGA was associated with increased risk for cesarean delivery (adjusted odds ratio [OR] 3.13, 95% confidence interval [CI] 2.10-4.67, P

Despite advances in neonatal care, the burden of preterm birth remains high. Preterm birth is a multifactorial problem, and strategies to identify and treat medical risk factors in early pregnancy have not been effective in reducing preterm birth rates. In a sentinel clinical trial, prophylactic therapy with 17-hydoxyprogesterone caproate (17-OHPC) reduced the risk of recurrent, spontaneous preterm birth in 34% of women. As a result, clinical practice changed and extensive research on 17-OHPC followed. The increasing body of evidence demonstrated a variable efficacy of the drug. This review will examine the plausibility, pharmacology, clinical efficacy, and safety of 17-OHPC when used in the setting of preterm birth prevention. We will also discuss pharmacokinetic and pharmacodynamics data to highlight drug metabolism and mechanism of action, which will help clarify the variability in clinical outcomes and efficacy.

The purpose of this study was to evaluate the labor curves of patients who undergo preterm induction of labor (IOL) and to assess possible predictors of vaginal delivery (VD).Data from the National Institute of Child Health and Human Development Consortium on Safe Labor were analyzed. A total of 6555 women who underwent medically indicated IOL at37 weeks of gestation were included in this analysis. Patients were divided into 4 groups based on gestational age (GA): group A, 24-27+6 weeks; B, 28-30+6 weeks; C, 31-33+6 weeks; and D, 34-36+6 weeks. Pregnant women with a contraindication to VD, IOL ≥37 weeks of gestation, and without data from cervical examination on admission were excluded. Analysis of variance was used to assess differences between GA groups. Multiple logistic regression was used to assess predictors of VD. A repeated measures analysis was used to determine average labor curves.Rates of vaginal live births increased with GA, from 35% (group A) to 76% (group D). Parous women (odds ratio, 6.78; 95% confidence interval, 6.38-7.21) and those with a favorable cervix at the start of IOL (odds ratio, 2.35; 95% confidence interval, 2.23-2.48) were more likely to deliver vaginally. Analysis of labor curves in nulliparous women showed shorter duration of labor with increasing GA; the active phase of labor was, however, similar across all GAs.Most women who undergo medically indicated preterm IOL between 24 and 36+6 weeks of gestation deliver vaginally. The strongest predictor of VD was parity. Preterm IOL had a limited influence on estimated labor curves across GAs.

The placebo effect has not been characterised in pregnant women suffering from nausea and vomiting of pregnancy (NVP). Our aim was to characterise determinants of the placebo effect in women treated with placebo for NVP. We analysed data from a multicentre, double blind randomised controlled trial of Diclectin (delayed release doxylamine and pyridoxine) vs placebo for the treatment of NVP. A total of 127 women in the placebo arm and 130 in the active arm provided evaluable data for this analysis. Women who chose to continue placebo on a compassionate basis (n = 41) had significantly better improvement in symptoms of NVP and higher Wellbeing scores than those who did not ask to continue compassionate use. Results were similar in the active drug arm. The request to continue compassionate use of either placebo or active drug could be predicted by greater improvement in symptoms of NVP during the trial period.