Call to action for a life course approach.

Gestational diabetes remains the most common medical disorder in pregnancy, with short-term and long-term consequences for mothers and offspring. New insights into pathophysiology and management suggest that the current gestational diabetes treatment approach should expand from a focus on late gestational diabetes to a personalised, integrated life course approach from preconception to postpartum and beyond. Early pregnancy lifestyle intervention could prevent late gestational diabetes. Early gestational diabetes diagnosis and treatment has been shown to be beneficial, especially when identified before 14 weeks of gestation. Early gestational diabetes screening now requires strategies for integration into routine antenatal care, alongside efforts to reduce variation in gestational diabetes care, across settings that differ between, and within, countries. Following gestational diabetes, an oral glucose tolerance test should be performed 6-12 weeks postpartum to assess the glycaemic state. Subsequent regular screening for both dysglycaemia and cardiometabolic disease is recommended, which can be incorporated alongside other family health activities. Diabetes prevention programmes for women with previous gestational diabetes might be enhanced using shared decision making and precision medicine. At all stages in this life course approach, across both high-resource and low-resource settings, a more systematic process for identifying and overcoming barriers to preventative care and treatment is needed to reduce the current global burden of gestational diabetes.

Epidemiology and management of gestational diabetes.

Gestational diabetes is defined as hyperglycaemia first detected during pregnancy at glucose concentrations that are less than those of overt diabetes. Around 14% of pregnancies globally are affected by gestational diabetes; its prevalence varies with differences in risk factors and approaches to screening and diagnosis; and it is increasing in parallel with obesity and type 2 diabetes. Gestational diabetes direct costs are US$1·6 billion in the USA alone, largely due to complications including hypertensive disorders, preterm delivery, and neonatal metabolic and respiratory consequences. Between 30% and 70% of gestational diabetes is diagnosed in early pregnancy (ie, early gestational diabetes defined by hyperglycaemia before 20 weeks of gestation). Early gestational diabetes is associated with worse pregnancy outcomes compared with women diagnosed with late gestational diabetes (hyperglycaemia from 24 weeks to 28 weeks of gestation). Randomised controlled trials show benefits of treating gestational diabetes from 24 weeks to 28 weeks of gestation. The WHO 2013 recommendations for diagnosing gestational diabetes (one-step 75 gm 2-h oral glucose tolerance test at 24-28 weeks of gestation) are largely based on the Hyperglycemia and Adverse Pregnancy Outcomes Study, which confirmed the linear association between pregnancy complications and late-pregnancy maternal glycaemia: a phenomenon that has now also been shown in early pregnancy. Recently, the Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) trial showed benefit in diagnosis and treatment of early gestational diabetes for women with risk factors. Given the diabesity epidemic, evidence for gestational diabetes heterogeneity by timing and subtype, and advances in technology, a life course precision medicine approach is urgently needed, using evidence-based prevention, diagnostic, and treatment strategies.

Study Design and Protocol of the Multisite Pregnancy 24/7 Cohort Study.

Hypertensive disorders of pregnancy and other adverse pregnancy outcomes (APOs) are associated with an increased risk of future maternal cardiovascular disease. Physical activity during pregnancy reduces the risk of these APOs, yet few meet physical activity guidelines during pregnancy. Little is known about the role of sedentary behavior or sleep in APOs, a critical gap in knowledge given these behaviors comprise the majority of a 24-hour day. To address this knowledge gap, the Pregnancy 24/7 cohort study (2020-2025) uses 2 devices for 24-hour activity assessment in each trimester of pregnancy to examine associations of sedentary behavior, sleep, and the 24-hour activity cycle (composition of sedentary behavior, physical activity, and sleep) with hypertensive disorders and other APOs. Participants (n = 500) are recruited from the University of Iowa, University of Pittsburgh, and West Virginia University in early pregnancy and followed through delivery. The activPAL3 micro and Actiwatch Spectrum Plus are worn in each trimester for 7 days of 24-hour wear to assess the 24-hour activity cycle. APOs are abstracted from medical charts. This study will provide critical data to fuel future research examining how modifying the 24-hour activity cycle in pregnancy can improve maternal health.

From Standard of Care to Emerging Innovations: Navigating the Evolution of Pharmacological Treatment of Gestational Diabetes.

The incidence of gestational diabetes mellitus (GDM) continues to increase in the United States and globally. While the first-line treatment of GDM remains diet and exercise, 30% of patients with GDM will require pharmacotherapy. However, many controversies remain over the specific glycemic threshold values at which pharmacotherapy should be started, how intensified the therapy should be, and whether oral agents are effective in GDM and remain safe for long-term offspring health. This review will summarize recently completed and ongoing trials focused on GDM pharmacotherapy, including those examining different glycemic thresholds to initiate therapy and treatment intensity. KEY POINTS: · The incidence of GDM continues to increase in the United States and globally.. · While the first-line treatment of GDM remains diet, 30% of patients require pharmacotherapy.. · Controversies remain over the specific glycemic threshold values at which pharmacotherapy is needed.. · Another controversy is how tightly to control GDM.. · Additional controversies are the safety of metformin and incretins in terms of offspring's long-term health..

A pathway level analysis of PFAS exposure and risk of gestational diabetes mellitus.

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.

Insulin Dosing, Glycemic Control, and Perinatal Outcomes in Pregnancies Complicated by Type-2 Diabetes.

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 < 0.001) and postprandial glucose values (132.4 [ ± 17.2] vs. 121.9 [ ± 16.9 mg/dL]), p < 0.001), and a higher percentage of total glucose values that were elevated above targets (37.7 [95% confidence interval (CI): 26.8-50] vs. 25.6 [95% CI: 13.3-41.3%], p < 0.001). Maternal HbA1c ≥6.5% and insulin use prior to pregnancy were associated with a higher prevalence of severe insulin resistance, while Hispanic ethnicity and non-White race were associated with a lower prevalence of severe insulin resistance. The rates of adverse perinatal outcomes including large for gestational age (LGA) birth weight, cesarean delivery, and hypertensive disorders of pregnancy did not differ between groups. 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: · Severe insulin resistance is common.. · BMI does not predict severe insulin resistance.. · Suboptimal glycemic control is common..

Perinatal Outcomes Associated with Early Diabetes Testing in Pregnancies Complicated by Obesity.

OBJECTIVE: This study aimed to determine whether early diabetes testing is associated with differences in perinatal outcomes among pregnant women with obesity (body mass index ≥30 kg/m2). STUDY DESIGN: We conducted a retrospective cohort study of singleton pregnancies from 2012 to 2014 at a large academic medical center which examined the association of diabetes testing (HBA1c, 50 g glucose challenge test, or 100 g oral glucose tolerance test) before 24 weeks with perinatal outcomes using propensity score modeling and logistic regression. RESULTS: Among women with obesity, 790 out of 2,698 (29.3%) underwent early diabetes testing. Propensity score modeling demonstrated that early testing was associated with higher rates of diabetes diagnosis (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.10-2.37, p = 0.01) and a trend toward small for gestational age birth weight (OR: 1.38, 95% CI: 1.00-1.90, p = 0.05) and neonatal composite morbidity (OR: 1.25, 95% CI: 1.00-1.57, p = 0.05) compared with routine testing. Women with inadequate weight gain were more likely a small for gestational age (SGA) infant if they underwent early testing compared with those with routine testing alone (19.8 vs. 11.6%, p = 0.01). CONCLUSION: Early testing targets higher risk women and yields a higher diabetes diagnosis rate, but inadequate weight gain in these women may increase risk SGA birth weight and neonatal morbidity. Randomized clinical trials are urgently needed to assess whether early diabetes testing improves outcomes in women with obesity.

Antibiotic Use in Pregnancy, Abnormal Fetal Growth, and Development of Gestational Diabetes Mellitus.

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.

Response to Medical Nutritional Therapy and Need for Pharmacological Therapy in Women with Gestational Diabetes.

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.

Glycemic Control and Pregnancy Outcomes in Women with Type 2 Diabetes Treated with Oral Hypoglycemic Agents.

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.

Timing of delivery and pregnancy outcomes in women with gestational diabetes.

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 <39 weeks. Neonatal morbidity was similar across gestational ages after adjustment for maternal body mass index and maternal glycemic control. 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.

Preterm induction of labor: predictors of vaginal delivery and labor curves.

OBJECTIVE: 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). STUDY DESIGN: 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 at <37 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. RESULTS: 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. CONCLUSION: 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.

Ultrasound assessment of congenital fetal lung masses and neonatal respiratory outcomes.

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 < 0.0001 and <0.008, respectively). CVR increased up to 32 weeks and decreased thereafter for most subjects. The decrease in CVR beyond 32 weeks was larger for cases that required NICU admission (p = 0.002). For a CVR cut-off of <0.5, the sensitivity was 100%, the specificity 85.7%, and negative predictive value was 100% for regular nursery care. CONCLUSION: In pregnancies diagnosed with fetal lung masses, CVR predicted normal respiratory outcomes and need for NICU admission. This information may be helpful for delivery planning. © 2015 John Wiley & Sons, Ltd.

Intensive glycaemic targets in overweight and obese individuals with gestational diabetes mellitus: clinical trial protocol for the iGDM study.

INTRODUCTION: The prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and caesarean delivery. Women with GDM who are also overweight or obese have higher rates of pregnancy complications when compared with normal-weight women with GDM, which may occur in part due to suboptimal glycaemic control. The current recommendations for glycaemic targets in pregnant women with diabetes are based on limited evidence and exceed the mean fasting (70.9±7.8 mg/dL) and 1-hour postprandial (108.9±12.9 mg/dL) glucose values in pregnant individuals without diabetes. Our prior work demonstrated that the use of intensive (fasting <90 mg/dL and 1-hour postprandial <120 mg/dL) compared with standard (fasting <95 mg/dL and 1-hour postprandial <140 mg/dL) glycaemic targets resulted in improved glycaemic control without increasing the risk for hypoglycaemia in pregnant individuals with GDM, but the impact of intensive glycaemic targets on perinatal outcomes is unknown. METHODS AND ANALYSIS: The Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus: A Multicenter Randomized Trial (iGDM Trial) is a large, pragmatic randomised clinical trial designed to investigate the impact of intensive versus standard glycaemic targets on perinatal outcomes in women with GDM who are overweight and obese. During the 5-year project period, a multidisciplinary team of investigators from five medical centres representing regions of the USA with high rates of obesity will randomise 828 overweight and obese women with GDM to either intensive or standard glycaemic targets. We will test the central hypothesis that intensive glycaemic targets will result in lower rates of neonatal composite morbidity including large for gestational age birth weight, neonatal hypoglycaemia, respiratory distress syndrome and need for phototherapy when compared with standard glycaemic targets using the intention-to-treat approach to analysis. ETHICS AND DISSEMINATION: The Institutional Review Board (IRB) at Indiana University School of Medicine approved this study (IRB# 11435; initial approval date 25 August 2021). We will submit the results of the trial for publication in peer-reviewed journals and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT05124808.

Comparative effectiveness trial of metformin versus insulin for the treatment of gestational diabetes in the USA: clinical trial protocol for the multicentre DECIDE study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycaemic control decreases the risk of adverse pregnancy outcomes for the affected pregnant individual and the infant exposed in utero. One in four individuals with GDM will require pharmacotherapy to achieve glycaemic control. Injectable insulin has been the mainstay of pharmacotherapy. Oral metformin is an alternative option increasingly used in clinical practice. Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterised, adequately powered study of a diverse US population remain lacking. Because metformin crosses the placenta, long-term safety data, in particular, the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remain to be characterised, including barriers to and facilitators of metformin versus insulin use. METHODS AND ANALYSIS: In a two-arm open-label, pragmatic comparative effectiveness randomised controlled trial, we will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. We plan to recruit 1572 pregnant individuals with GDM who need pharmacotherapy at 20 US sites using consistent diagnostic and treatment criteria for oral metformin versus injectable insulin and follow them and their children through delivery to 2 years post partum. More information is available at www.decidestudy.org. ETHICS AND DISSEMINATION: The Institutional Review Board at The Ohio State University approved this study (IRB: 2024H0193; date: 7 December 2024). We plan to submit manuscripts describing the results of each study aim, including the pregnancy outcomes, the 2-year follow-up outcomes, and mixed-methods assessment of patient experiences for publication in peer-reviewed journals and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT06445946.

Mid-pregnancy sleep disturbances are not associated with mid-pregnancy maternal glycemia.

Background: In 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. Objective: This study aimed to investigate the associations of sleep disturbances during mid-pregnancy and mid-pregnancy maternal glycemia and gestational diabetes subtypes. Study Design: This 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). Results: A 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. Conclusions: Sleep 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.

Clinical therapeutics in pregnancy.

Most drugs are not tested for use during pregnancy, consequently, labeling, which may include information about fetal safety, includes nothing about dosing, efficacy, or maternal safety. Yet these are concerns of health care providers considering treatment of disease during pregnancy. Therefore, the practitioner treats the pregnant woman with the same dose recommended for use in adults (typically men) or may decide not to treat the disease at all. However, is the choice of not treating a woman during pregnancy better than dealing with the challenges which accompany treatment? This paper, which summarizes metabolic and physiologic changes induced by pregnancy, illustrates that standard adult dosing is likely to be incorrect during pregnancy.

Treatment of Gestational Diabetes Mellitus and Offspring Early Childhood Growth.

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.

Asymmetric large-for-gestational-age infants of type 1 diabetic women: morbidity and abdominal growth.

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.

Drugs to Control Diabetes During Pregnancy.

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 pregestational and gestational diabetes. 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, the authors summarize recent clinical studies to highlight established pharmacologic treatments for diabetes in pregnancy and provide suggestions for further research.