The importance of nutrition in pregnancy and lactation: lifelong consequences.

Most women in the United States do not meet the recommendations for healthful nutrition and weight before and during pregnancy. Women and providers often ask what a healthy diet for a pregnant woman should look like. The message should be "eat better, not more." This can be achieved by basing diet on a variety of nutrient-dense, whole foods, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report "prudent" or "health-conscious" eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed. Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants.

Single Cell RNA Sequencing of Human Milk-Derived Cells Reveals Sub-Populations of Mammary Epithelial Cells with Molecular Signatures of Progenitor and Mature States: a Novel, Non-invasive Framework for Investigating Human Lactation Physiology.

Cells in human milk are an untapped source, as potential "liquid breast biopsies", of material for investigating lactation physiology in a non-invasive manner. We used single cell RNA sequencing (scRNA-seq) to identify milk-derived mammary epithelial cells (MECs) and their transcriptional signatures in women with diet-controlled gestational diabetes (GDM) with normal lactation. Methodology is described for coordinating milk collections with single cell capture and library preparation via cryopreservation, in addition to scRNA-seq data processing and analyses of MEC transcriptional signatures. We comprehensively characterized 3740 cells from milk samples from two mothers at two weeks postpartum. Most cells (>90%) were luminal MECs (luMECs) expressing lactalbumin alpha and casein beta and positive for keratin 8 and keratin 18. Few cells were keratin 14+ basal MECs and a small immune cell population was present (<10%). Analysis of differential gene expression among clusters identified six potentially distinct luMEC subpopulation signatures, suggesting the potential for subtle functional differences among luMECs, and included one cluster that was positive for both progenitor markers and mature milk transcripts. No expression of pluripotency markers POU class 5 homeobox 1 (POU5F1, encoding OCT4) SRY-box transcription factor 2 (SOX2) or nanog homeobox (NANOG), was observed. These observations were supported by flow cytometric analysis of MECs from mature milk samples from three women with diet-controlled GDM (2-8 mo postpartum), indicating a negligible basal/stem cell population (epithelial cell adhesion molecule (EPCAM)-/integrin subunit alpha 6 (CD49f)+, 0.07%) and a small progenitor population (EPCAM+/CD49f+, 1.1%). We provide a computational framework for others and future studies, as well as report the first milk-derived cells to be analyzed by scRNA-seq. We discuss the clinical potential and current limitations of using milk-derived cells as material for characterizing human mammary physiology.

Maternal Non-glycemic Contributors to Fetal Growth in Obesity and Gestational Diabetes: Spotlight on Lipids.

PURPOSE OF REVIEW: Excess fetal growth is increasingly recognized as a risk factor for childhood obesity, and mounting evidence supports that maternal glucose is not the only driver. This review focuses on the role of clinically applicable maternal non-glycemic contributors to excess fetal growth, particularly lipids, in addition to amino acids (AA), insulin resistance, inflammation, maternal nutrition, and gestational weight gain (GWG) in obesity and gestational diabetes mellitus (GDM). RECENT FINDINGS: Lipids, specifically triglycerides and free fatty acids, appear to be strong contributors to excess fetal fat accretion and adiposity at birth, particularly in obese pregnancies, which account for the largest number of large-for-gestational-age infants. Maternal pre-pregnancy body mass index (BMI), GWG, insulin resistance, inflammation, and glucose, lipid, and AA concentrations have both independent and interacting effects on fetal growth, operating both early and late in pregnancy. All are sensitive to maternal nutrition. Early vs. later gestational exposure to excess maternal fuels in fasting and postprandial conditions may differentially impact fetoplacental outcomes. Compelling evidence suggests that targeting interventions early in pregnancy beyond glucose may be critical to improve fetal growth patterns.

A cautionary response to SMFM statement: pharmacological treatment of gestational diabetes.

Use of oral agents to treat gestational diabetes mellitus remains controversial. Recent recommendations from the Society for Maternal-Fetal Medicine assert that metformin may be a safe first-line alternative to insulin for gestational diabetes mellitus treatment and preferable to glyburide. However, several issues should give pause to the widespread adoption of metformin use during pregnancy. Fetal concentrations of metformin are equal to maternal, and metformin can inhibit growth, suppress mitochondrial respiration, have epigenetic modifications on gene expression, mimic fetal nutrient restriction, and alter postnatal gluconeogenic responses. Because both the placenta and fetus express metformin transporters and exhibit high mitochondrial activity, these properties raise important questions about developmental programming of metabolic disease in offspring. Animal studies have demonstrated that prenatal metformin exposure results in adverse long-term outcomes on body weight and metabolism. Two recent clinical randomized controlled trials in women with gestational diabetes mellitus or polycystic ovary syndrome provide evidence that metformin exposure in utero may produce a metabolic phenotype that increases childhood weight or obesity. These developmental programming effects challenge the conclusion that metformin is equivalent to insulin. Although the Society for Maternal-Fetal Medicine statement endorsed metformin over glyburide if oral agents are used, there are few studies directly comparing the 2 agents and it is not clear that metformin alone is superior to glyburide. Moreover, it should be noted that prior clinical studies have dosed glyburide in a manner inconsistent with its pharmacokinetic properties, resulting in poor glycemic control and high rates of maternal hypoglycemia. We concur with the American Diabetes Association and American Congress of Obstetricians and Gynecologists, which recommend insulin as the preferred agent, but we believe that it is premature to embrace metformin as equivalent to insulin or superior to glyburide. Due to the uncertainty of the long-term metabolic risks of either metformin or glyburide, we call for carefully controlled studies that optimize oral medication dosing according to their pharmacodynamic and pharmacokinetic properties in pregnancy, appropriately target medications based on individual patterns of hyperglycemia, and follow the offspring long-term for metabolic risk.

Infant Adiposity is Independently Associated with a Maternal High Fat Diet but not Related to Niacin Intake: The Healthy Start Study.

Objectives Over-nutrition during pregnancy resulting from maternal obesity or an unhealthy diet can lead to excess infant adiposity at birth. Specific dietary macro- and micronutrients have been shown to increase fat cell development in both in-vitro and in-vivo models and may therefore link maternal diet to increased infant adiposity. We hypothesized that high maternal dietary niacin intake during pregnancy, especially in combination with a high-fat diet (HFD) would increase infant adiposity. Methods We included 1040 participants from a pre-birth cohort of mother-infant pairs. Maternal diet was assessed using multiple 24-hour dietary recalls. HFD was defined as ≥30% of calories from fat and ≥12% of fat calories from saturated fat. Neonatal body composition (% fat mass [%FM], fat mass [FM], fat-free mass [FFM]) was measured by PEAPOD. We used multivariate regression to assess the joint effect of maternal dietary niacin and maternal HFD on neonatal body composition. Results Dietary niacin was not associated with neonatal body composition, and maternal HFD did not modify this finding. However, maternal HFD was independently associated with %FM (ß = 0.8 [0.1, 1.4]%, p < 0.01] and FM (ß = 32.4 [6.7, 58.0] g, p < 0.01). Conclusions for Practice Our results suggest that a HFD during pregnancy may increase infant adiposity, therefore supporting the need for improved diet counseling of pregnant women at both the clinical and community levels.

Microbial transmission from mothers with obesity or diabetes to infants: an innovative opportunity to interrupt a vicious cycle.

Maternal obesity and diabetes dramatically increase the long-term risk for obesity in the next generation, and pregnancy and lactation may be critical periods at which to aim primary prevention to break the obesity cycle. It is becoming increasingly clear that the gut microbiome in newborns and infants plays a significant role in gut health and therefore child development. Alteration of the early infant gut microbiome has been correlated with the development of childhood obesity and autoimmune conditions, including asthma, allergies and, more recently, type 1 diabetes. This is likely to be due to complex interactions between mode of delivery, antibiotic use, maternal diet, components of breastfeeding and a network of regulatory events involving both the innate and adaptive immune systems within the infant host. Each of these factors are critical for informing microbiome development and can affect immune signalling, toxin release and metabolic signals, including short-chain fatty acids and bile acids, that regulate appetite, metabolism and inflammation. In several randomised controlled trials, probiotics have been administered with the aim of targeting the microbiome during pregnancy to improve maternal and infant health but the findings have often been confounded by mode of delivery, antibiotic use, ethnicity, infant sex, maternal health and length of exposure. Understanding how nutritional exposure, including breast milk, affects the assembly and development of both maternal and infant microbial communities may help to identify targeted interventions during pregnancy and in infants born to mothers with obesity or diabetes to slow the transmission of obesity risk to the next generation. The aim of this review is to discuss influences on infant microbiota colonisation and the mechanism(s) underlying how alterations due to maternal obesity and diabetes may lead to increased risk of childhood obesity.

Can Fetal Limb Soft Tissue Measurements in the Third Trimester Predict Neonatal Adiposity?

OBJECTIVES: Neonatal adiposity is associated with chronic metabolic sequelae such as diabetes and obesity. Identifying fetuses at risk for excess neonatal body fat may lead to research aimed at limiting nutritional excess in the prenatal period. We sought to determine whether fetal arm and leg soft tissue measurements at 28 weeks' gestation were predictive of neonatal percent body fat METHODS : In this prospective observational cohort study of singleton term pregnancies, we performed sonography at 28 and 36 weeks' gestation, including soft tissue measurements of the fetal arm and thigh (fractional limb volume and cross-sectional area). We estimated the neonatal body composition (percent body fat) using anthropometric measurements and air displacement plethysmography. We estimated Spearman correlations between sonographic findings and percent body fat and performed modeling to predict neonatal percent body fat using maternal characteristics and sonographic findings. RESULTS: Our analysis of 44 women yielded a mean maternal age of 30 years, body mass index of 26 kg/m(2), and birth weight of 3382 g. Mean neonatal percent body fat was 8.1% by skin folds at birth and 12.2% by air displacement plethysmography 2 weeks after birth. Fractional thigh volume measurements at 28 weeks yielded the most accurate model for predicting neonatal percent body fat (R(2) = 0.697; P = .001), outperforming models that used abdominal circumference (R(2)= 0.516) and estimated fetal weight (R(2)= 0.489). CONCLUSIONS: Soft tissue measurements of the fetal thigh at 28 weeks correlated better with neonatal percent body fat than currently used sonographic measurements. After validation in a larger cohort, our models may be useful for prenatal intervention strategies aimed at the prevention of excess fetal fat accretion and, potentially, optimization of long-term metabolic health.

Insulin Management for Gestational and Type 2 Diabetes in Pregnancy.

Insulin is preferred as the first-line agent for glucose management of gestational diabetes mellitus and type 2 diabetes in pregnancy when nutritional and lifestyle modifications are unable to achieve pregnancy-specific glucose targets. Individual heterogeneity in defects of insulin secretion or sensitivity in liver and muscle, unique genetic influences on pregnancy glycemic regulation, and variable cultural and lifestyle behaviors that affect meal, activity, sleep, and occupational schedules necessitate a personalized approach to insulin regimens. Newer insulin preparations have been developed to mimic the physiologic release of endogenous insulin, maintaining appropriate basal levels to cover hepatic gluconeogenesis and simulate the rapid, meal-related, bolus rise of insulin. Such physiologic basal-bolus dosing of insulin can be administered safely, achieving tighter glycemic control while reducing episodes of hypoglycemia. Insulin initiation and titration require understanding the pharmacodynamics of different insulin preparations in addition to a patient's glycemic profiles, effect of variable nutritional intake and mealtimes, physical activity, stress, timing of sleep cycles, and cultural habits. Educating and empowering patients to learn how their glucose responds to insulin, portion and content of meals, and physical activity can increase personal engagement in therapy, flexibility in eating patterns, and improved glycemic control. This Clinical Expert Series article is focused on optimizing insulin management (initiation, dosing, and titration) of gestational and type 2 diabetes in pregnancy.

The Fit After Baby randomized controlled trial: An mHealth postpartum lifestyle intervention for women with elevated cardiometabolic risk.

BACKGROUND: Postpartum women with overweight/obesity and a history of adverse pregnancy outcomes are at elevated risk for cardiometabolic disease. Postpartum weight loss and lifestyle changes can decrease these risks, yet traditional face-to-face interventions often fail. We adapted the Diabetes Prevention Program into a theory-based mobile health (mHealth) program called Fit After Baby (FAB) and tested FAB in a randomized controlled trial. METHODS: The FAB program provided 12 weeks of daily evidence-based content, facilitated tracking of weight, diet, and activity, and included weekly coaching and gamification with points and rewards. We randomized women at 6 weeks postpartum 2:1 to FAB or to the publicly available Text4baby (T4B) app (active control). We measured weight and administered behavioral questionnaires at 6 weeks, and 6 and 12 months postpartum, and collected app user data. RESULTS: 81 eligible women participated (77% White, 2% Asian, 15% Black, with 23% Hispanic), mean baseline BMI 32±5 kg/m2 and age 31±5 years. FAB participants logged into the app a median of 51/84 (IQR 25,71) days, wore activity trackers 66/84 (IQR 43,84) days, logged weight 17 times (IQR 11,24), and did coach check-ins 5.5/12 (IQR 4,9) weeks. The COVID-19 pandemic interrupted data collection for the primary 12-month endpoint, and impacted diet, physical activity, and body weight for many participants. At 12 months postpartum women in the FAB group lost 2.8 kg [95% CI -4.2,-1.4] from baseline compared to a loss of 1.8 kg [95% CI -3.8,+0.3] in the T4B group (p = 0.42 for the difference between groups). In 60 women who reached 12 months postpartum before the onset of the COVID-19 pandemic, women randomized to FAB lost 4.3 kg [95% CI -6.0,-2.6] compared to loss in the control group of 1.3 kg [95% CI -3.7,+1.1] (p = 0.0451 for the difference between groups). CONCLUSIONS: There were no significant differences between groups for postpartum weight loss for the entire study population. Among those unaffected by the COVID pandemic, women randomized to the FAB program lost significantly more weight than those randomized to the T4B program. The mHealth FAB program demonstrated a substantial level of engagement. Given the scalability and potential public health impact of the FAB program, the efficacy for decreasing cardiometabolic risk by increasing postpartum weight loss should be tested in a larger trial.

Barriers to implementing good nutrition in pregnancy and early childhood: Creating equitable national solutions.

Exposure to deleterious stressors in early life, such as poor nutrition, underlies most adult-onset chronic diseases. As rates of chronic disease continue to climb in the United States, a focus on good nutrition before and during pregnancy, lactation, and early childhood provides a potential opportunity to reverse this trend. This report provides an overview of nutrition investigations in pregnancy and early childhood and addresses racial disparities and health outcomes, current national guidelines, and barriers to achieving adequate nutrition in pregnant individuals and children. Current national policies and community interventions to improve nutrition, as well as the current state of nutrition education among healthcare professionals and students, are discussed. Major gaps in knowledge and implementation of nutrition practices during pregnancy and early childhood were identified and action goals were constructed. The action goals are intended to guide the development and implementation of critical nutritional strategies that bridge these gaps. Such goals create a national blueprint for improving the health of mothers and children by promoting long-term developmental outcomes that improve the overall health of the US population.

Intrahepatic fat is increased in the neonatal offspring of obese women with gestational diabetes.

OBJECTIVES: To assess precision magnetic resonance imaging in the neonate and determine whether there is an early maternal influence on the pattern of neonatal fat deposition in the offspring of mothers with gestational diabetes mellitus (GDM) and obesity compared with the offspring of normal-weight women. STUDY DESIGN: A total of 25 neonates born to normal weight mothers (n = 13) and to obese mothers with GDM (n = 12) underwent magnetic resonance imaging for the measurement of subcutaneous and intra-abdominal fat and magnetic resonance spectroscopy for the measurement of intrahepatocellular lipid (IHCL) fat at 1-3 weeks of age. RESULTS: Infants born to obese/GDM mothers had a mean 68% increase in IHCL compared with infants born to normal-weight mothers. For all infants, IHCL correlated with maternal prepregnancy body mass index but not with subcutaneous adiposity. CONCLUSION: Deposition of liver fat in the neonate correlates highly with maternal body mass index. This finding may have implications for understanding the developmental origins of childhood nonalcoholic fatty liver disease.

Strategies in the nutritional management of gestational diabetes.

Elucidating the optimal macronutrient composition for dietary management of gestational diabetes mellitus has enormous potential to improve perinatal outcomes. Diet therapy may result in significant cost savings if effective in deterring the need for expensive medical management within this growing population. In only 6 randomized controlled trials in 250 women, data suggest that a diet higher in complex carbohydrate and fiber, low in simple sugar, and lower in saturated fat may be effective in blunting postprandial hyperglycemia, preventing worsened insulin resistance and excess fetal growth. The use of diet in gestational diabetes mellitus remains an area in grave need for high-quality randomized controlled trials.

Randomization to a Provided Higher-Complex-Carbohydrate Versus Conventional Diet in Gestational Diabetes Mellitus Results in Similar Newborn Adiposity.

OBJECTIVE: Nutrition therapy for gestational diabetes mellitus (GDM) has conventionally focused on carbohydrate restriction. In a randomized controlled trial (RCT), we tested the hypothesis that a diet (all meals provided) with liberalized complex carbohydrate (60%) and lower fat (25%) (CHOICE diet) could improve maternal insulin resistance and 24-h glycemia, resulting in reduced newborn adiposity (NB%fat; powered outcome) versus a conventional lower-carbohydrate (40%) and higher-fat (45%) (LC/CONV) diet. RESEARCH DESIGN AND METHODS: After diagnosis (at ∼28-30 weeks' gestation), 59 women with diet-controlled GDM (mean ± SEM; BMI 32 ± 1 kg/m2) were randomized to a provided LC/CONV or CHOICE diet (BMI-matched calories) through delivery. At 30-31 and 36-37 weeks of gestation, a 2-h, 75-g oral glucose tolerance test (OGTT) was performed and a continuous glucose monitor (CGM) was worn for 72 h. Cord blood samples were collected at delivery. NB%fat was measured by air displacement plethysmography (13.4 ± 0.4 days). RESULTS: There were 23 women per group (LC/CONV [214 g/day carbohydrate] and CHOICE [316 g/day carbohydrate]). For LC/CONV and CHOICE, respectively (mean ± SEM), NB%fat (10.1 ± 1 vs. 10.5 ± 1), birth weight (3,303 ± 98 vs. 3,293 ± 81 g), and cord C-peptide levels were not different. Weight gain, physical activity, and gestational age at delivery were similar. At 36-37 weeks of gestation, CGM fasting (86 ± 3 vs. 90 ± 3 mg/dL), 1-h postprandial (119 ± 3 vs. 117 ± 3 mg/dL), 2-h postprandial (106 ± 3 vs. 108 ± 3 mg/dL), percent time in range (%TIR; 92 ± 1 vs. 91 ± 1), and 24-h glucose area under the curve values were similar between diets. The %time >120 mg/dL was statistically higher (8%) in CHOICE, as was the nocturnal glucose AUC; however, nocturnal %TIR (63-100 mg/dL) was not different. There were no between-group differences in OGTT glucose and insulin levels at 36-37 weeks of gestation. CONCLUSIONS: A ∼100 g/day difference in carbohydrate intake did not result in between-group differences in NB%fat, cord C-peptide level, maternal 24-h glycemia, %TIR, or insulin resistance indices in diet-controlled GDM.

Endocrine Emergencies During Pregnancy: Diabetic Ketoacidosis and Thyroid Storm.

The physiologic changes and common signs and symptoms of pregnancy can make the early recognition of endocrine emergencies more challenging. Diabetic ketoacidosis (DKA) can occur at only modestly elevated glucose levels (euglycemic DKA), often accompanied by starvation ketosis due to substantial fetal-placental glucose demands and is associated with a high stillbirth rate. Thyroid storm is life threatening with a higher rate of heart failure and both require prompt and aggressive treatment to avoid maternal and fetal morbidity and mortality. Treatment of these disorders and the special considerations for recognition and management in the context of pregnancy are reviewed.

A maternal higher-complex carbohydrate diet increases bifidobacteria and alters early life acquisition of the infant microbiome in women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is associated with considerable imbalances in intestinal microbiota that may underlie pathological conditions in both mothers and infants. To more definitively identify these alterations, we evaluated the maternal and infant gut microbiota through the shotgun metagenomic analysis of a subset of stool specimens collected from a randomized, controlled trial in diet-controlled women with GDM. The women were fed either a CHOICE diet (60% complex carbohydrate/25% fat/15% protein, n=18) or a conventional diet (CONV, 40% complex carbohydrate/45% fat/15% protein, n=16) from 30 weeks' gestation through delivery. In contrast to other published studies, we designed the study to minimize the influence of other dietary sources by providing all meals, which were eucaloric and similar in fiber content. At 30 and 37 weeks' gestation, we collected maternal stool samples; performed the fasting measurements of glucose, glycerol, insulin, free fatty acids, and triglycerides; and administered an oral glucose tolerance test (OGTT) to measure glucose clearance and insulin response. Infant stool samples were collected at 2 weeks, 2 months, and 4-5 months of age. Maternal glucose was controlled to conventional targets in both diets, with no differences in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). No differences in maternal alpha or beta diversity between the two diets from baseline to 37 weeks' gestation were observed. However, women on CHOICE diet had higher levels of Bifidobacteriaceae, specifically Bifidobacterium adolescentis, compared with women on CONV. Species-level taxa varied significantly with fasting glycerol, fasting glucose, and glucose AUC after the OGTT challenge. Maternal diet significantly impacted the patterns of infant colonization over the first 4 months of life, with CHOICE infants showing increased microbiome alpha diversity (richness), greater Clostridiaceae, and decreased Enterococcaceae over time. Overall, these results suggest that an isocaloric GDM diet containing greater complex carbohydrates with reduced fat leads to an ostensibly beneficial effect on the maternal microbiome, improved infant gut microbiome diversity, and reduced opportunistic pathogens capable of playing a role in obesity and immune system development. These results highlight the critical role a maternal diet has in shaping the maternal and infant microbiome in women with GDM.

Human milk imparts higher insulin concentration in infants born to women with type 2 diabetes mellitus.

OBJECTIVE: Human milk (HM) insulin plays many roles for the infant, especially for the newborn. We hypothesized HM insulin in women with type 2 diabetes (T2DM) would be higher than BMI-matched women with either gestational diabetes (GDM) or normal glucose tolerance (NGT). In T2DM, we also assessed macronutrient composition and relationships between maternal glycemic control and HM insulin. STUDY DESIGN: HM was characterized at 2-weeks postpartum among three BMI-matched groups: T2DM (n= 12), diet-controlled GDM (n= 12), and NGT (n= 12). In T2DM, additional fasting and postprandial HM samples were collected while wearing a continuous glucose monitor (CGM), as well as fasting and 90-minute postprandial samples after a standardized meal at 1-2 weeks postpartum. RESULTS: Fasting HM insulin was two times higher in T2DM compared to GDM and NGT (p < .001), which were not different from each other. Among T2DM, fasting (p < .001) and postprandial (p = .01) HM insulin levels were between 2 and 5× higher than plasma. Postprandial HM insulin (p = .03) and glucose (p < .001) were increased compared to fasting. Mean nocturnal glucose (p < .01) and maternal hemoglobin A1c (p < .01) positively associated with fasting HM insulin. CONCLUSIONS: These data are the first to show HM insulin concentrations are doubled in T2DM compared to BMI-matched GDM and NGT. In HM of T2DM, insulin increases postprandially, may be concentrated relative to plasma, and is influenced by maternal glycemic control, with potential clinical implications that merit further study.

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.

Sleep-disordered breathing in pregnancy: a developmental origin of offspring obesity?

Sleep-disordered breathing (SDB) worsens over pregnancy, and obstructive sleep apnea is associated with serious maternal complications. Intrauterine exposures that provoke insulin resistance (IR), inflammation, or oxidative stress may have long-term offspring health consequences. In obesity, worsening maternal SDB appears to be an exposure that increases the risk for both small- or large-for-gestational-age (SGA, LGA, respectively), suggesting distinct outcomes linked to a common maternal phenotype. The aim of this paper is to systematically review and link data from both mechanistic rodent models and descriptive human studies to characterize the impact of maternal SDB on fetal development. A systematic review of the literature was conducted using PubMed, Embase, and CINAHL (01/2000-09/2019). Data from rodent (9 studies) and human models (48 studies, 5 meta-analyses) were included and reviewed using PRISMA guidelines. Evidence from rodent models suggests that intermittent maternal hypoxia results in mixed changes in birth weight (BW) followed by accelerated postnatal growth, while maternal sleep fragmentation results in normal BW followed by later metabolic derangement. Human studies support that maternal SDB is associated with both SGA and LGA, both of which may predispose offspring to later obesity. Evidence also suggests a link between SDB, inflammation, and oxidative stress that may impact maternal metabolism and/or placental function. SDB is common in pregnancy and affects fetal growth and development. Given that SDB has significant potential to adversely influence the intrauterine metabolic environment, larger, prospective studies in humans are urgently needed to fully elucidate the effects of this exposure on offspring metabolic risk.

Effect of type 2 diabetes mellitus on placental expression and activity of nutrient transporters and their association with birth weight and neonatal adiposity.

AIMS: Infants born to women with Type 2 Diabetes Mellitus (T2DM) are at risk of being born large for gestational age due to excess fetal fat accretion. Placental nutrient transport determines fetal nutrient availability, impacting fetal growth. The aims of the study were to evaluate the effect of T2DM on placental insulin signaling, placental nutrient transporters and neonatal adiposity. METHODS: Placentas were collected from BMI-matched normoglycemic controls (NGT, n = 9) and T2DM (n = 9) women. Syncytiotrophoblast microvillous (MVM) and basal (BM) plasma membranes were isolated. Expression of glucose (GLUT1, -4), fatty acid (FATP2, -4, -6, FAT/CD36), amino acid (SNAT1, -2, -4, LAT1, -2) transporters, insulin signaling, and System A transporter activity was determined. Neonatal fat mass (%) was measured in a subset of neonates born to T2DM women. RESULTS: GLUT1 protein expression was increased (p = 0.001) and GLUT4 decreased (p = 0.006) in BM from T2DM. MVM FATP6 expression was increased (p = 0.02) and correlated with birth weight in both T2DM and NGT groups (r = 0.65, p = 0.02). BM FATP6 expression was increased (p = 0.01) in T2DM. In MVM of T2DM placentas, SNAT1 expression was increased (p = 0.05) and correlated with birth weight (r = 0.84, p = 0.004); SNAT2 was increased (p = 0.01), however System A transporter activity was not different between groups. MVM LAT1 expression was increased (p = 0.01) in T2DM and correlated with birth weight (r = 0.59, p = 0.04) and neonatal fat mass (r = 0.76, p = 0.06). CONCLUSION: In pregnancies complicated by T2DM placental protein expression of transporters for glucose, amino acids and fatty acids is increased, which may contribute to increased fetal growth and neonatal adiposity.