Objective:In utero exposure to maternal prepregnancy diabetes is associated with an increased risk for abnormal glycemic outcomes in children, including impaired glucose tolerance, insulin resistance, and type 2 diabetes. Our objective was to evaluate the timing of exposure to maternal dysglycemia and whether the effects persist into adulthood. Study Design:The Transgenerational Effects on Adult Morbidity (TEAM) Study followed offspring of mothers with prepregnancy insulin-dependent diabetes mellitus (IDDM), who participated in a Program Project Grant (PPG) between 1978 and 1995. These women had a detailed characterization of glycemic measures across pregnancy and comprehensive obstetric and delivery data. Offspring participated in a complete clinical exam, which included an oral glucose tolerance test (OGTT). Multiple regression methods were used to identify associations between trimester-specific maternal hemoglobin A1 (HbA1) standard deviation (HbA1SD) and maternal glucose profiles with offspring glycemic outcomes, adjusting for covariates. Results:Among 161 offspring up to 42 years of age (mean age, 32.3 years), first trimester HbA1SD was associated with increased offspring fasting plasma glucose and HbA1c ≥6.5% after adjusting for maternal age, family history of diabetes, presence of microvascular disease, and body mass index (BMI) at the last menstrual period. Both second- and third-trimester maternal HbA1SD were positively associated with offspring HbA1c and inversely associated with the acute insulin response to glucose (AIRg), defined as the rapid, first-phase release of insulin from pancreatic beta-cells within 10 minutes of the OGTT. Conclusion:Our findings add to the current literature showing that the association between trimester-specific gestational maternal glycemic status and offspring adverse glycemic outcome persists into adulthood in the offspring. Key Points:· Exposure to maternal IDDM is associated with offspring glycemic outcomes.. · Maternal glycohemoglobin, particularly in the first trimester, is associated with HbA1c and fasting glucose.. · Mid-late pregnancy hyperglycemia was associated with reduced offspring acute insulin response..

CONTEXT:Little data exist on early and late gestational diabetes (GDM) in sub-Saharan Africa. OBJECTIVE:We assessed the prevalence of GDM in South Africa, including early and late GDM, and investigated insulin sensitivity, 1st phase insulin secretion, and beta cell function to understand the underlying pathophysiology of glucose metabolism in early and late pregnancy. METHODS:We enrolled women with HIV (WWH) and HIV-seronegative women at ≤18 weeks' gestation. A 75 g oral glucose tolerance test was administered at enrollment (early) and 32-36 weeks' gestation (late) to diagnose GDM using WHO criteria. Matsuda, Stumvoll, oral disposition index, and glucose sensitivity from Mari models were calculated. Logistic regression models were used to assess the association of HIV with GDM. RESULTS:Among 1573 (n = 668 WWH) participants, median age was 28 years, gestation 13 weeks. Overall, 7.9% had GDM (6.7% WWH, 9.1% HIV-seronegative); of these, 65% had early GDM. Women with early GDM had the lowest Matsuda, Stumvoll, oral disposition index, and glucose sensitivity at enrollment compared to those with late GDM and those without GDM. In adjusted analyses, WWH had lower odds of GDM than HIV-seronegative women (adjusted odds ratio: 0.57, 95% Confidence Interval: 0.38-0.85). CONCLUSION:GDM prevalence in South Africa is similar to North America/Europe. Early GDM was diagnosed in a large majority of women who also exhibited features of poorer insulin sensitivity and beta cell function than those diagnosed late in pregnancy or without GDM. WWH had lower GDM risk than HIV-seronegative women. Future studies to understand the implications of early GDM in African populations are warranted.

Abstract Aim Examine cross-sectional associations between mid-pregnancy food intake indicators and prenatal depressive symptomatology. Methods This secondary analysis of the Comparison of Two Screening Strategies for Gestational Diabetes trial (N = 718) examined domains of mid-pregnancy food intake (direct timing, energy timing, meal/snack structure, meal energy distribution, diet quality) derived from 24-hour dietary recalls. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS). Generalized linear models examined associations between food intake indicators, total, and high (EPDS ≥13) depressive symptoms. Results Mean (SD) EPDS score was [6.3 (4.9)]; 12.4% (n = 89) had high depressive symptoms. Eating frequency (B = 0.08 [0.02, 0.14], p = 0.009), snack frequency (B = 0.06 [0.00, 0.12], p = 0.040), nighttime snacking frequency (B = 0.06 [0.00, 0.11], p = 0.041), and total daily energy intake (B = 0.06 [0.01, 0.12], p = 0.031) were positively associated with total depressive symptoms. Energy intake from breakfast (PR = 1.2 [1.0, 1.3], p = 0.017) was associated with a higher prevalence of high depressive symptoms. Energy intake from dinner (PR = 0.81 [0.69, 0.94], p = 0.007), later timing of the first eating episode (PR = 0.83 [0.70, 0.99], p = 0.034) and first energy quartile (PR = 0.84 [0.70, 1.0], p = 0.048), were associated with a lower prevalence of high depressive symptoms. Conclusion These findings extend prior chrononutrition-depression literature to the prenatal period, implicating eating frequency, energy intake, and meal energy timing and distribution in depressive symptomatology during pregnancy, warranting further longitudinal investigation. Key Messages Eating frequency, snacking, nighttime snacking, and longer eating windows were positively associated with increased prevalence of depressive symptomatology within the prenatal period. Each of these results align with previous literature in general adult or postpartum populations and extend to prenatal populations specifically. These results suggest the role of circadian misalignment (potentially via mechanisms including nocturnal cortisol response, serotonin and dopamine dysregulation, systemic inflammation, and delayed melatonin production) in prenatal psychopathology. Importantly, the potential bidirectional nature of food intake and depression cannot be overlooked. Total energy consumed per day, percentage of energy from breakfast and dinner, as well as later timing of initial energy intake and first caloric quartile were positively associated with prenatal depression. Additionally, particular indicators of dietary quality and macronutrient percentages (e.g., percentage of energy obtained from fat), were not significantly associated with prenatal depression. These findings call for future research to explore nuance regarding macronutrient consumption, energy intake percentages, meal timing regularity, and the possible implications of emotionally responsive eating in the relationship between food intake and prenatal depression The current study is exploratory in nature, being the first to explore a robust range of food intake indicators and their relationship to depressive symptomatology in the prenatal period. As prenatal depression is a strong predictor of worsening mental health during postpartum, it is important that future research test a priori hypotheses regarding food intake indicators and prenatal depression longitudinally in order to determine both temporal precedence and validate the associations found within our study. If validated, multiple domains of food intake may potentially provide modifiable behaviors that can protect against depression during the prenatal period.

Objectives:We and others have shown that maternal hyperglycemia during pregnancy in women with insulin-dependent diabetes mellitus (IDDM) influences fetal growth. Less is understood regarding how trimester-specific glycemic patterns, particularly glucose variability, shape offspring obesity risk across the life course and whether this is mediated by birthweight. Leveraging data from the Diabetes in Pregnancy Program Grant (PPG; 1978-1995) and the Transgenerational Effects on Adult Morbidity (TEAM Study; 2017-2023) cohort, we aimed to evaluate whether the association between maternal glycemic control and adult offspring obesity status was mediated in part through infant birthweight. Study Design:Maternal glycohemoglobinA1 levels were collected monthly during pregnancy and harmonized across laboratories using standard deviation units (HbA1SD). Functional principal component analysis characterized patterns in blood glucose level and variability. TEAM Study participants, adult offspring of PPG women, completed in-person or online assessments (via Zoom) of body anthropometrics. Linear mixed-effects models and generalized estimating equations estimated associations between maternal glycemia and adult offspring outcomes. Classical mediation methods tested whether birthweight mediated observed relationships. Results:Consistent with prior findings, third-trimester HbA1SD demonstrated the most consistent positive associations with adult offspring body mass index (BMI) outcomes, after adjustment for maternal BMI at last menstrual period, maternal education, gestational weight gain, and sex of offspring (for offspring weight only). There was no evidence that birthweight mediated the relationship between maternal glycemic patterns and adult offspring overweight and obesity; however, birthweight exhibited an independent direct effect on adult offspring BMI in fully adjusted models. Conclusion:Infant birthweight was not shown to be a mediator in the association of maternal gestational glycemic control and overweight/obesity in adult offspring of women with IDDM. Although birthweight does not appear to mediate these long-term associations, the findings underscore the importance of trimester-specific evaluation of blood glucose level and variability, motivating further investigation into transgenerational metabolic risk pathways. Key Points:· It is unlikely that birthweight mediates the association between gestational blood glucose levels and offspring adult obesity.. · Higher birthweight is an important risk factor for overweight and obesity in the adult offspring.. · Early gestation hyperglycemia may program obesity in adult offspring of IDDM women..

CONTEXT:Gestational diabetes mellitus (GDM) is associated with long-term risk for type 2 diabetes. OBJECTIVE:We evaluated metabolic characteristics and β-cell function during pregnancy and at 12 months postpartum among individuals with varying levels of gestational glucose intolerance. METHODS:This was a planned 12-month postpartum follow-up to the Gestational Diabetes Diagnostic Methods (GDM2) trial, which randomized pregnant individuals to GDM testing using either the International Association of Diabetes and Pregnancy Study Group (IADPSG) or Carpenter-Coustan (CC) criteria. All GDM2 participants with treated GDM (diagnosed by either CC or IADPSG), those with untreated glucose intolerance in the CC arm, and half of the participants with normal glucose tolerance were invited for 12-month follow-up. Glucose values, Stumvoll and Matsuda Indices to evaluate insulin sensitivity and resistance, the disposition index (DI), lipids, leptin, and adiponectin were assessed at 12 months postpartum.  . RESULTS:Of the 407 individuals seen at 12 months, 49 (12%) had untreated glucose intolerance and 53 (13%) had treated GDM (CC and IADPSG). Both during pregnancy and at 12 months postpartum, there were significant differences in insulin sensitivity, β-cell function, dyslipidemia, and alterations in leptin and adiponectin among individuals with both untreated glucose tolerance and treated GDM when compared with those with normal glucose testing. CONCLUSION:Individuals with untreated glucose intolerance in pregnancy by the CC criteria have impaired β-cell function and significant metabolic abnormalities at 12 months postpartum similar to individuals with treated GDM, highlighting the need for ongoing preventive attention in this population to prevent type 2 diabetes later in life.

Fetal fat accumulation is an important indicator of the nutritional environment in pregnancy and placental function. Excessive fat accretion leading to high adiposity at birth, however, can increase a child's long-term risk for obesity and metabolic disease. While maternal body mass index is associated with neonatal adiposity, there is a wide variation in body composition among babies born to women with and without obesity. The placenta orchestrates a complex exchange of nutrients and signals between the mother and baby. To better understand the molecular mechanisms that govern fetal fat accumulation, we profiled the transcriptomics of 79 placentas collected from mothers with and without obesity. We identified a set of 18 neonatal adiposity-associated genes, common to pregnancies with and without obesity. A coexpressed cluster of these genes is involved in innate immune responses, particularly neutrophil activation. We also identified neonatal adiposity-associated genes unique to mothers with or without obesity, suggesting different biological pathways support high newborn adiposity, and/or are responsive to a common initial immune signal. These findings suggest that placental inflammation may influence fetal fat accumulation. Understanding these pathways may help identify novel ways to support healthy fetal growth and reduce the risk of long-term disease.

Introduction and Objective: Data are limited as to whether continuous glucose monitoring (CGM) can be used to accurately diagnose gestational diabetes mellitus (GDM). We aimed to develop GDM diagnostic criteria based on CGM metrics at 24-28 weeks’ gestation. Methods: Planned analysis of a longitudinal, multi-site prospective cohort of gravidas without pregestational diabetes who wore a blinded CGM for 10 days at 24-28 week’s gestation and had an OGTT on the day of CGM placement. The primary outcome was GDM diagnosed using Carpenter-Coustan criteria. A2GDM (treated with medication) was a secondary outcome. In a training dataset, a range of 24-hr CGM metrics were considered as candidate diagnostic variables, including time above glycemic thresholds, measures of glycemic variability (e.g. mean amplitude of glycemic excursions [MAGE]) and central tendency. Continuous metrics maximizing area under the ROC curve (AUC) were selected for further analysis. For these top metrics, optimal binary diagnostic cutoffs were then identified via grid search to maximize specificity while maintaining sensitivity ≥75%. These final criteria to most accurately diagnose GDM were validated by estimating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in a separate dataset. Results: Of 2178 participants, 81.3% had valid CGM data; 93.3% completed OGTTs; 15.4% were diagnosed with GDM (7.1% A2GDM). The best continuous metrics (AUC, 95% CI) for GDM diagnosis included MAGE (0.73, 0.68-0.78), time above 150 mg/dL (0.71, 0.66-0.76), and time above 140 mg/dL (0.7, 0.65-0.75). The optimal MAGE threshold was ≥43 mg/dL (specificity 59.7%, sensitivity 75.4%, PPV 14.5%, NPV 96.4%). Time ≥140 and 150 mg/dL also performed poorly, with thresholds ≥2% and ≥1%, respectively. Findings held true in the validation dataset and were similar for A2GDM. Conclusion: Detection of GDM at 24-28 weeks with CGM data was limited by modest performance, including low specificity. CGM metrics do not predict GDM well enough to replace OGTT for diagnosis. Disclosure A. Merriam: None. M. Banker: None. P. Catalano: None. F.L. Facco: None. M. Feghali: None. W. Grobman: None. E. LeBlanc: None. W. Lowe: None. M. Mourad: None. C. Oshiro: None. C. Powe: Research Support; Current; Dexcom, Inc. Other - Associate Editor of Diabetes Care, Honoraria for Educational Materials; Current; American Diabetes Association. Other - Royalties for Up To Date chapters; Current; Wolters Kluwer (Up To Date). Other - Speaker; Ended; Medscape. U. Reddy: None. D. Rouse: None. D. Scholtens: None. J. Sherr: Other - research support, consultant, advisory board member; Current; Abbott Diabetes. Other - advisory board member, consultant; Current; Vertex Pharmaceuticals Incorporated. Consultant; Current; Ypsomed AG. Research Support; Current; Dexcom, Inc., JDRF, Provention Bio, Inc., National Institutes of Health. Other - research support, consultant, advisory board member; Current; Insulet Corporation, Medtronic. Research Support; Current; Sanofi. Advisory Panel; Current; sequel med tech. A.C. Spadola: None. K. Vesco: None. E. Werner: None. N. Zork: None. L.M. Yee: None. Funding The GO MOMs study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. U01DK123795 to Massachusetts General Hospital; U01DK123791 to Kaiser Permanente; U01DK123759 and U01DK123745 to Northwestern University; U01DK123799 to Yale University; U01DK123783 to Women & Infants Hospital of Rhode Island. Dexcom provided the CGM systems used in the study free of charge.

Abstract Introduction Perinatal depression is a leading contributor to maternal morbidity, affecting 20% of pregnancies. While food intake timing has been associated with depression in adults, its role during pregnancy is underexplored. Our aim is to examine the cross-sectional association between mid-pregnancy (24-28 weeks’ gestation) food timing profiles and depressive symptomatology. Methods This is a secondary data analysis of the Comparison of Two Screening Strategies for Gestational Diabetes (GDM2) trial (N = 719). Latent profile analysis was used to identify food timing profiles based on four food timing indicators: timing of first/last eating episode, total eating window, and caloric midpoint time obtained from 24-hour dietary recalls. Prenatal depression was defined as an Edinburgh Postnatal Depression score >10. Log-binomial regression was used to examine the association between mid-pregnancy food timing profiles and prenatal depressive symptomatology, adjusting for known covariates (e.g., insomnia symptoms, maternal age, stress, education, etc.). Results We identified four unique food timing profiles. The “early eating” profile (n = 210) began/ended eating at 7:45 AM-7:30 PM with caloric midpoint at 1:30 PM and an eating window of 11.6 hours. The “daytime eating” (n = 222) profile had the latest caloric midpoint (3:30 PM) and a typical eating window (M = 11.8-hour). The “extended window” profile (n = 151) had the earliest first intake and the longest eating window (M = 14.5 hours). The “restricted eating” profile (n = 136) had the latest first intake and shortest eating window (M = 8.8 hours). Participants with an extended window eating profile (vs. early eating profile) had a 63% higher risk of depression (95% CI 1.11-2.42). There were no statistically significant differences between the early eating and the daytime eating (RR = 1.41, 95% CI 0.95-2.08), and restricted window (RR = 1.16, 95% CI 0.74-1.80) profiles. Conclusion Results support previous literature reporting associations between later eating times and depression. The timing of food intake is an important factor in assessing depressive symptoms during the prenatal period. Support (if any) Eunice Kennedy Shriver National Institute of Child Health & Human Development [R01HD079647 (PI: Davis)], the University of Pittsburgh Clinical & Translational Science Institute (CTSI) [UL1TR001857]

Objective To determine relationships between measurements of total body, visceral, and ectopic (liver, skeletal muscle) fat with insulin sensitivity in pregnancy. Research Design and Methods Pregnant women of varying pre-pregnancy weights were prospectively studied in early (n=59) and late (n=47) gestation. At each visit participants underwent body composition measurements including fat mass (FM), fat-free mass (FFM), abdominal subcutaneous (SAT), visceral (VAT) fat, ectopic lipid amounts in liver (IHL) and calf skeletal muscle (IMCL, EMCL) and hyperinsulinemia-euglycemic clamp to determine insulin sensitivity (Rd), endogenous glucose production (EGP), hepatic insulin sensitivity index (HISI), and free fatty acid (FFA) levels. Results In early pregnancy, Rd ((mg/kg FFM/min)/IU/mL) inversely correlated (P-values < .05) with body mass index (BMI), FM, SAT, VAT, IHL, IMCL, and FFA. HISI inversely correlated (P-values < .05) with BMI, FM, SAT, VAT, IMCL, and FFA, but not IHL. In late pregnancy, however, neither EGP ((mg/kg FFM/min)/IU/mL) nor Rd correlated with regional or ectopic fat measures, but HISI remained inversely correlated with BMI, FM, SAT, VAT, and IMCL. Early pregnancy IHL levels did not predict late pregnancy insulin sensitivity. Pregnant women with pre-pregnancy obesity were more insulin resistant but gained less gestational weight, VAT, and SAT, and experienced less decline in insulin sensitivity, than normal pre-pregnancy weight women. Conclusions Insulin resistance in early pregnancy is strongly associated with total, regional, and ectopic adiposity. However, in late pregnancy, factors other than regional and ectopic adiposity predominately influence insulin sensitivity. Pre-pregnancy weight categories proportionately alter gestational weight gain, adiposity distribution, and glucometabolic responses.

BACKGROUND:Mitochondrial dysfunction in adipose tissue is associated with diabetes pathophysiology. We examined this relationship in pregnant women with HIV (WWH) receiving tenofovir/lamivudine/dolutegravir (TLD). METHODS:South African WWH (n = 67) and HIV-seronegative women (n = 31) underwent a gluteal subcutaneous adipose tissue biopsy at ≤ 14 weeks' gestational age (GA) (trimester 1, T1) and 28-37 weeks' GA (T3). High-resolution respirometry was employed to measure mitochondrial respiration. Insulin sensitivity was calculated using the Matsuda index. Linear regression models were fit to examine effect modification by HIV status and TLD duration of the association between mitochondrial respiration and log-Matsuda. RESULTS:At enrolment, WWH and HIV-seronegative women were similar in median age (28 years), GA (12 weeks), and body mass index (28 kg/m 2 ). At T3, HIV infection was associated with higher complex I-linked mitochondrial respiration (β = 0.13, P = 0.02). This association was more pronounced among WWH on TLD for ≤ 6 months (β = 0.16, P = 0.02) who also had higher complex I+II-linked respiration (β = 0.13, P = 0.04) compared with HIV-seronegative women. At T1, WWH with > 6 months' TLD duration had a stronger association between electron transport system capacity and log-Matsuda (β = 0.55, P = 0.04) compared with HIV-seronegative women. Similar results were observed at T3 for electron transport system (β = 1.05, P = 0.03) and for a change score for leak (β = 87.80, P = 0.03) for > 6 months' TLD duration compared with ≤ 6 months' TLD duration. CONCLUSIONS:HIV infection and longer TLD duration appear to be associated with stronger associations between mitochondrial respiration and insulin sensitivity, warranting further investigation into how HIV/TLD may influence glucose metabolism in adipose tissue.

Objective:Limited data are available to describe the long-term implications of pre-pregnancy diabetes on offspring body composition in adulthood. The objective of this study was to examine the association between maternal glucose control and variation throughout pregnancy and long-term obesity in offspring. A second objective was to identify the critical windows of gestational exposure most related to the development of long-term obesity. Research Design and Methods:This cohort study included offspring of women with insulin-dependent diabetes (IDDM) who participated in the Diabetes in Pregnancy Program Project Grant (PPG) between 1978 and 1995 to evaluate the long-term implications of in utero glucose exposure. Offspring completed a comprehensive study visit which included measures of height and weight, and measures from dual-energy X-ray absorptiometry. The exposure was maternal glucose control as measured by glycohemoglobin A1 concentration (where HbA1 was represented as standard deviation units from the mean for the laboratory HBA1SD), and blood glucose level and variation across pregnancy, and by trimester, characterized using functional principal components (fPC). Outcomes were adult offspring BMI (kg/m2), as well as visceral and whole-body fat. Results:A total of 161 offspring completed a study visit. Mean offspring age at follow-up was 32.3 years (± 4.6), 50.3% were female and 17.4% identified as Black. After adjustment for covariates (maternal age, education, family history of diabetes, diabetes severity, and BMI at last menstrual period), third-trimester maternal HbA1SD was significantly associated with offspring adiposity measures including BMI, BMI ≥ 30 kg/m2, and visceral and whole-body fat mass and percentage. The third-trimester fPC representing variability of glucose demonstrated a consistent positive association with obesity outcomes but did not reach statistical significance in adjusted models. Conclusions:Our findings corroborate that the third trimester is a critical window of exposure associated with offspring adiposity. Specifically, higher levels of third-trimester maternal glycohemoglobin A1 is a risk factor for obesity in the adult offspring of IDDM mothers. Additionally, results suggest that glucose variability may increase the risk for obesity in the adult offspring.

OBJECTIVE:To determine whether pregnancy dysglycemia in the early third trimester was associated with a higher estimated risk of postpartum metabolic dysfunction-associated steatotic liver disease (MASLD) assessed 10-14 years after delivery. METHODS:This was a secondary analysis from the prospective international cohort study HAPO FUS (Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study). The exposure was pregnancy dysglycemia in the third trimester, identified by the glucose summary z-score of a 75-g oral glucose tolerance test (OGTT) at 24-32 weeks of gestation, and, secondarily, a diagnosis of gestational diabetes mellitus (GDM). The outcome was the estimated 6-year risk of MASLD determined by the Framingham Fatty Liver Disease Risk Function. Multivariable linear and multinomial regression models were used and adjusted for baseline covariates at the time of the OGTT, including study field center, age, parity, gestational age, and duration from enrollment to follow-up. RESULTS:Of 4,697 assessed pregnant individuals, the median age was 30.5 years (interquartile range 26.0, 34.1 years) and the median body mass index was 26.6 (interquartile range 24.1, 29.9); 14.3% (n=672) were diagnosed with GDM. At 10-14 years after delivery (median 11.6 years, interquartile range 10.8, 12.4 years), the median estimated 6-year risk of MASLD was 6.0% (interquartile 3.0%, 13.0%). Individuals with a higher third trimester glucose summary z-score were at higher estimated risk of postpartum MASLD (adjusted beta coefficient 3.2 per 1 SD; 95% CI, 2.7-3.6), as were those who were diagnosed with GDM (adjusted beta coefficient 4.2%; 95% CI, 3.1-5.2). When MASLD risk was assessed in tertiles, an increase of 1 SD in the summary z-score was associated with greater adjusted odds of being in the highest-risk MASLD tertile (adjusted odds ratio 1.1; 95% CI, 1.0-1.3); however, a diagnosis of GDM was not associated with greater adjusted odds of being in the highest-risk MASLD tertile. CONCLUSION:Increasing pregnancy dysglycemia in the third trimester was associated with a higher estimated risk of postpartum MASLD using cardiometabolic risk factors measured 10-14 years after delivery. Whether postpartum interventions to improve cardiometabolic health for individuals with prior pregnancy dysglycemia decreases the risk of MASLD requires further investigation.

Background: This article aims to characterize midpregnancy food timing profiles and examine their association with gestational weight gain (GWG). Materials and Methods: This secondary data analysis of a randomized controlled trial of two gestational diabetes screening approaches included 641 individuals with primary exposures and outcomes data. Food timing indicators (i.e., first and last eating episode time, caloric midpoint time, and the total eating window) were assessed using two 24-hour dietary recalls conducted in midpregnancy. Latent profile analysis was used to identify distinct food timing profiles based on these indicators. Regression analyses explored the associations between individual food intake timing indicators, food timing profiles, and GWG. Results: We identified four food timing profiles: extended window eating (n = 133; earliest first eating episode and the longest eating window), restricted window eating (n = 120; latest first eating episode and shortest eating window), early eating (n = 188; earliest caloric midpoint), and typical eating (n = 200; food intake aligning with the sample median). Participants with a restricted window eating profile (vs. typical eating profile) had an increased risk of insufficient GWG (unadjusted relative risk [RR] = 1.85, 95% confidence interval [CI] 1.12, 3.05). Each hour increase in the timing of the last eating episode was associated with 0.39 kg (0.03, 0.75) higher GWG. Both associations were attenuated in adjusted models and no longer statistically significant in adjusted models. Conclusions: We identified four distinct midpregnancy food timing profiles, but these profiles were not independently associated with GWG. These findings suggest that midpregnancy food timing may not play a major role in GWG.

HYPOTHESIS:Declines in insulin sensitivity during pregnancy important for fetal growth are associated with impairments in skeletal muscle post-receptor insulin signaling. The primary initiator of these changes is unknown but believed to originate in the placenta. We hypothesize that placental miRNAs are associated with maternal sensitivity changes and impact insulin-sensitive mechanisms in target tissues in vitro. METHODS:Using qPCR, miRNA expression was measured in plasma in early (12-16 wk) and late (34-36 wk) gestation (N = 39) and placental tissue at term (37-41 weeks) (N = 142) collected from independent cohorts. Insulin-sensitive glucose uptake was measured in human skeletal muscle myoblasts exposed to miRNA mimics in vitro. Multi-linear and binomial regression models were generated to test for associations between miRNAs, insulin sensitivity and fetal growth outcomes, adjusting for relevant clinical variables. P < 0.05 was considered significant. RESULTS:Placental expression of chromosome 19 miRNA cluster (C19MC) members was higher in patients with obesity and positively correlated with maternal HOMA-IR (Homeostatic Model Assessment for Insulin Resistance; miR-516b-5p, miR-517a-3p, miR-1283). Placental expression of miR-517a-3p was higher in offspring with high adiposity and birthweight. Plasma miR-517a-3p in early and late pregnancy was related to decreases in insulin sensitivity during pregnancy. Mimics for miR-517a-3p and miR-524-3p both impaired insulin-sensitive glucose uptake in human skeletal myocytes in vitro. DISCUSSION:Our findings based on data from two independent pregnancy cohorts and in vitro studies support a role for members of the C19 cluster of miRNAs - particularly miR-517a-3p - in physiological changes in insulin sensitivity over pregnancy, which may impact fetal growth.

AIMS:Studies evaluating the relationship between adverse pregnancy outcomes (APOs), namely hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), with the estimated risk of atherosclerotic cardiovascular disease (ASCVD) remains limited and could inform patient-centred decision-making in the postpartum period. We examined whether HDP or GDM were associated with a higher 10- and 30-year predicted risk of ASCVD measured 10-14 years after delivery. METHODS:A secondary analysis from the international prospective Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (2013-2016) cohort. The exposures were HDP or GDM (untreated according to the International Association of the Diabetes and Pregnancy Study Groups criteria). Outcomes were 10- and 30-year predicted risk of ASCVD (composite of fatal and non-fatal coronary heart disease and stroke) as quantified by the validated Framingham Risk Score as a continuous measure, and secondarily, at thresholds used for clinical decision-making of ≥7.5% for 10-year predicted risk and ≥20% for 30-year predicted risk. RESULTS:Of 4432 individuals at a median age of 30.5 years and a median gestational age of 27.9 weeks at pregnancy enrollment, 10.7% developed HDP and 13.7% developed GDM. At 10-14 years after delivery, individuals with HDP had a higher 10-year predicted risk of ASCVD (least squares mean: 2.9% vs. 2.2%; adj. β: 0.59; 95% CI: 0.41-0.77) and a higher 30-year predicted risk of ASCVD (7.7% vs. 6.1%; adj. β: 1.27; 95% CI: 0.81-1.72) compared with those without HDP. Similarly, individuals with GDM had a higher predicted risk of ASCVD (10-year: 3.2% vs. 2.1%; adj. β: 0.51; 95% CI: 0.34-0.67 and 30-year: 8.8% vs. 5.8%; adj. β: 1.56; 95% CI: 1.11-2.01) compared with those without GDM. These results were similar when predicted ASCVD risk was assessed at thresholds of ≥7.5% at 10 years and ≥20% at 30 years. CONCLUSION:Individuals who experienced HDP or GDM had a higher predicted 10- and 30-year risk of ASCVD measured 10-14 years after delivery compared with individuals who did not experience these APOs.

Maternal diabetes, a common pregnancy complication, has long-term implications for both mother and offspring. While the developmental origins of metabolic health from prenatal diabetes exposure are well known, cognitive consequences in offspring are still being explored. The timing of hyperglycemia during pregnancy that most affects cognitive development and whether these effects persist into adulthood remains unclear. This study aimed to determine the association between trimester-specific hyperglycemia exposure and adult cognition in the offspring of women with pregestational diabetes. The Transgenerational Effect on Adult Morbidity (TEAM) Study evaluated health outcomes in young adult offspring of mothers with pregestational diabetes who participated in a Diabetes in Pregnancy Program Project Grant (PPG) at the University of Cincinnati (1978-1995). The TEAM Study visit (March 2018 - August 2022) included a comprehensive clinical examination and cognitive assessment (Wechsler Abbreviated Scale of Intelligence - II). Linear regression estimated the association between prenatal hyperglycemia and offspring's perceptual reasoning and verbal comprehension. The mean age at follow-up was 32.1 years. Hyperglycemia during pregnancy was inversely associated with cognitive measures, controlling for confounders including maternal education and pre-pregnancy obesity. Higher glycohemoglobin in the second and third trimesters was significantly linked to lower IQ scores, matrix reasoning, and vocabulary subtest scores. Third-trimester hyperglycemia was also associated with lower block design subtest scores. In summary, hyperglycemia, particularly in the latter half of pregnancy, was associated with lower cognitive ability in adult offspring of women with pre-pregnancy pregestational diabetes.

AIMS:Metabolic characteristics and outcomes were compared among pregnant individuals with varying levels of glucose intolerance. METHODS:827 participants from a randomized clinical trial comparing the IADPSG and Carpenter Coustan Criteria were grouped as follows: normal glucose tolerance, mild glucose intolerance (100 g OGTT with one abnormal value) and treated GDM (diagnosed by Carpenter Coustan or IADPSG criteria). Differences in metabolic characteristics and perinatal outcomes were assessed using inverse probability of treatment weighting. RESULTS:Mild glucose intolerance had lower insulin sensitivity and beta cell response than normal glucose tolerance, and similar findings to treated GDM. Small for gestational age (SGA) (OR 0.13, 95% CI 0.08-0.24) and neonatal composite morbidity were lower (OR 0.53, 95% CI 0.38-0.74), and maternal composite morbidity higher (OR 2.03, 95% CI 1.57-2.62) when comparing mild intolerance to normal glucose tolerance. Large for gestational age (OR 3.42 95% CI 1.39-8.41) was higher while SGA (OR 0.21, 95% CI 0.05-0.81) and neonatal composite morbidity (OR 0.31, 95% CI 0.17-0.57) were lower with mild glucose intolerance compared to treated GDM. CONCLUSIONS:Mild glucose intolerance has a similar metabolic profile to treated GDM, and outcome differences are likely related to knowledge of diagnosis and treatment. CLINICAL TRIALS REGISTRY:NCT02309138.