Maternal GDM Research Articles

Maternal pre-gestational and gestational diabetes and risk of offspring epilepsy: A cohort study

Abstract Background Despite growing evidence linking maternal diabetes to impaired brain physiology and neurodevelopment in offspring, evidence on its effect on epilepsy remains scarce. This study aims to determine if intrauterine exposure to maternal pre-existing and gestational diabetes mellitus is associated with risk of offspring epilepsy. Methods We studied >2.3 million singletons live-born in Sweden between 1998 and 2021, with final follow up until October 31, 2023. The Swedish Medical Birth Register was linked to the National Patient Register to identify gestational diabetes (GDM), maternal pre-gestational type 1 (T1DM) and type 2 diabetes (T2DM), and offspring epilepsy. The incidence of epilepsy, comparing offspring of mothers with versus without diabetes, was calculated as hazard ratios (HR), adjusting for maternal education, smoking, body mass index, hypertension, epilepsy and other important confounders. Paternal T1DM and T2DM were additionally analysed as negative control exposures to assess genetic confounding. Results Of the 2,335,245 offspring analysed (48.9% female), 13,883 (0.6%) were exposed to maternal T1DM, 4477 (0.2%) to T2DM, and 37,253 (1.6%) to GDM. During a median follow up of 13 years (range 0-26 years), 18,732 offspring were diagnosed with epilepsy. Maternal T1DM (HR 1.27, 95% confidence intervals [CI] 1.08-1.49) and T2DM (HR 1.34, 95% CI 1.00-1.49) were associated with higher hazards of epilepsy in offspring, compared with no exposure to maternal diabetes. Preterm birth and birth-asphyxia jointly mediated 63% and 39% of these associations, respectively. No association was found between maternal GDM and epilepsy. Paternal T1DM and T2DM did not show association with epilepsy. Conclusions In this nationwide population-based cohort study, children of mothers with T1DM or T2DM showed an elevated risk of epilepsy. The results from paternal comparison and mediation analyses suggest a key role of the intrauterine environment in the aetiology of epilepsy. Key messages • Maternal pre-existing T1DM and T2DM might be risk factors for epilepsy in offspring and are likely to influence the risk through the intrauterine environment independent of genetic mechanisms. • In the context of a globally rising prevalence of diabetes in women who get pregnant, it is crucial that the diabetes is well-regulated and birth complications associated with diabetes are prevented.

Atopy and asthma in children born to mothers at risk of gestational diabetes mellitus: a follow-up study

BackgroundGestational diabetes mellitus (GDM) is the most prevalent metabolic disturbance during pregnancy and is associated with adverse outcomes in offspring, including an elevated risk for developing atopic diseases in early childhood. Research is limited regarding only women at risk of GDM among whom some develop GDM while others do not. Information about adverse health outcomes in the offspring of these women is also lacking. The main aim was to assess whether maternal GDM increases the offspring’s risk of atopic dermatitis (AD), asthma and allergic rhinitis at 1, 2 and 5 years of age. The second aim was to analyze the association of other maternal health characteristics on the development of these disorders in offspring.MethodsThe follow-up study group of the Gestational Diabetes Study (GDS), conducted at Tartu University Hospital, Estonia, between 2014 and 2020, comprised 223 mother–child dyads. All women had at least one risk factor for GDM, of whom only some developed GDM. Information about the diagnoses of interest was obtained from Electronic Health Records. Allergen-specific IgE from children’s serum was measured using ImmunoCAP™ Phadiatop™ Infant, with results ≥ 0.35 kU/l considered positive. Statistical analysis was performed using the RStudio software (version 4.3.0).ResultsAccording to our results, only the cases of GDM requiring the use of antidiabetic medications were associated with the development of asthma and/or allergic rhinitis at 2 years of age (aOR 4.68, 95%CI 1.08–20.21, p = 0.039). Maternal obesity (BMI > 30) was associated with offspring´s asthma and/or allergic rhinitis diagnosis at 2 years of age (aOR 3.15, 95%CI 1.03–9.63, p = 0.045).Maternal abnormal weight gain during pregnancy was associated with asthma and/or allergic rhinitis at 5 years of age (aOR 2.76, 95%CI 1.04–7.31, p = 0.041).ConclusionAmong pregnant women at risk for GDM, maternal weight-related factors significantly influence the development of atopic diseases in their children between 1 and 5 years of age, regardless of the GDM diagnosis. This suggests that, besides women with GDM greater attention should also be paid to women at risk but who do not develop GDM, as their children seem to be at higher risk of atopic diseases.

Placental ceramide content is decreased in maternal obesity and GDM, independent of fetal sex.

Placental ceramide content is decreased in maternal obesity and GDM, independent of fetal sex.

Kisspeptin signalling and its correlation with placental ultrastructure and clinical outcomes in pregnant South African women with obesity and gestational diabetes

IntroductionGestational diabetes mellitus (GDM) is a major pregnancy metabolic disorder and is strongly linked with obesity. Kisspeptin is a hormone that increases several thousand-fold in the maternal circulation during human pregnancy, with placenta as its main source. Studies have suggested that kisspeptin regulates trophoblast invasion and promotes pancreatic insulin secretion and peripheral insulin sensitivity. MethodsIn a well-characterized cohort of pregnant South African women and molecular and histological techniques, this study explored the impact and interaction of maternal obesity and GDM on kisspeptin (KISS1) signalling in relation to placental morphology and maternal and neonatal parameters. ResultsWe found that GDM had no effect on placental KISS1 and KISS1R (KISS1 receptor) mRNA and/or protein expression. However, obesity reduced placental KISS1R mRNA expression even though overall KISS1 protein abundance or localization was not different from the non-obese group. Maternal and cord circulating KISS1 concentrations did not vary with obesity or GDM, but maternal circulating KISS1 was positively correlated with placenta weight in non-GDM obese women, and negatively correlated with placental intervillous space volume in non-GDM non-obese women. Cord serum KISS1 was positively correlated with infant weight in GDM obese women, but negatively correlated with maternal BMI in the non-obese GDM group. Placental syncytiotrophoblast extracellular vesicles exhibited detectable KISS1 and its abundance was ∼50 % lower in those from obese GDM compared to non-GDM women. DiscussionThis study shows maternal obesity and GDM can modulate placental kisspeptin signalling and placental morphological development with potential pathophysiological implications for clinically-relevant pregnancy and perinatal outcomes.

Placental programming mediates the vicious cycle between maternal gestational diabetes and offspring type 2 diabetes in a novel mouse model

Accumulating evidence from human epidemiological studies indicates that there is a vicious cycle between maternal gestational diabetes (GDM) and offspring type 2 diabetes (T2D). However, the underlying mechanisms remain unclear. A handful of studies found that mitochondrial defects occur in the GDM placenta, including excess accumulation of destroyed mitochondria, reduced ATP and enhanced ROS production, which indicates that mitophagy, a specific process to remove destroyed mitochondria, may be impaired in the GDM placenta. Our recent study suggested that BNIP3 plays a critical role in maintaining mitochondria homeostasis in human trophoblast cells. Therefore, in this study, we hypothesized that conditional knockout of BNIP3 specifically in mouse trophoblast cells will recapitulate the typical symptoms of GDM in maternal pregnancy and T2D in offspring. First, we made male mice with double homozygous Cre and LoxP by breeding Cyp19-Cre and Bnip3-LoxP mice, which was used to mate females with homozygous LoxP, forming a cKO group. On the other hand, wild-type female mice were bred by males with homozygous Cre, forming a control group (CT). Second, offspring from cKO and CT mothers were allowed to grow up. On Day 18 of pregnancy, glucose tolerance test was conducted in pregnant cKO or CT mice. The placental tissues were collected and mRNA and protein levels of BNIP3 were measured by qPCR and Western blotting, respectively. In male offspring at the age of eight months, glucose tolerance test was conducted, and metabolic rate was measured by CaloBox Indirect Calorimetry. All numerical parameters between the cKO and CT pregnant mice, and between their male offspring were analyzed by ANOVA (n=5). The main findings include: 1) On Day 18 of pregnancy, BNIP3 mRNA and protein levels in the placental tissue were reduced by 47% and by 40% in cKO compared to CT mice (p<0.05), respectively (p<0.05); 2) Pregnant cKO mice demonstrated enhanced glucose intolerance compared to those control mice; 3) At the age of 8 months, the body weight of male offspring from cKO mothers was increased by 1.16-fold (p<0.05) compared to those from CT mothers; 4) Male offspring from cKO mothers demonstrated enhanced glucose intolerance compared to those from CT mothers; 5) The metabolic rates was lower in male offspring from cKO mothers compared to those from CT mothers, with decreased oxygen consumption and carbon dioxide production by 1.18- and 1.19-fold, respectively (p<0.05). These results suggest that placental programming possibly via the disrupted functions of BNIP3 in trophoblast cells mediates the occurrence of maternal GDM and offspring T2D, therefore, placental BNIP3 may play a critical role in the vicious cycle of maternal GDM and offspring T2D and thus, being a potential target in treatment of GDM and prevention of T2D. NIH research grants R03HD095417, U54MD007597. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract MP47: Fetal Life Exposure to GDM and Postnatal Breastfeeding and Beverage Intake in the First Year Are Associated With Severe Child Obesity at 6 to 11 Years: The SWIFT Study in Youth

Objective: To evaluate associations between fetal exposure to GDM and postnatal breastfeeding (BF) and sugary beverages in the first year with risk of child overweight and obesity severity at 6-11 y. Methods: The sample included 850 children exposed to maternal GDM with BF and infant diet assessed by monthly surveys from birth to 1 y and weight and length/height measurements up to ages 6-11 y from electronic health records. Maternal GDM severity was classified by diagnosis time (Early <24 wks or Standard ≥24 wks) and treatment type (Diet or Medication). Child BMI percentiles at 6-11 y were categorized as normal <85 th (referent), overweight 85 th to <95 th , moderate obesity 100 to <120% of 95 th and severe obesity ≥120% of 95 th . Multinomial logistic regression estimated adjusted odds ratios (aOR) and 95%CI of child BMI categories associated with fetal GDM exposure (diagnosis time & treatment) and postnatal diet; BF inadequate <6 months or adequate >6 months and sugary beverages (fruit juice or sugar added) adjusted for race/ethnicity, WIC recipient, pre-pregnancy BMI and gestational weight gain. Results: There were 480 (56.5%) children with normal weight, 150 (17.6%) with overweight, 155 (18.2%) with moderate obesity and 65 (7.6%) with severe obesity. Child average age (SD) at follow-up was 9.6 (1.4) y. Early GDM diagnosis was associated with aORs [95%CI] of severe obesity = 3.06 (1.33-7.04) with medication, and 2.61 (1.08-6.35) with diet and of moderate obesity = 1.93 (1.05-3.55) with diet vs. Standard diagnosis with diet. Inadequate BF with sugary beverage or fruit juice was associated with aOR [95%CI] of severe obesity = 3.06 (1.07-8.72) vs. adequate BF and no beverage. Conclusions: Earlier fetal exposure to maternal GDM and shorter BF combined with sugary beverages in the first postnatal year shows persistent higher risk of severe child obesity about 10 y later. These findings highlight pre-pregnancy screening to avert GDM and the importance of adequate BF and avoidance of sugary beverages and fruit juice among offspring exposed to GDM.

Multigenerational diabetes mellitus.

Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing the risk of short- and long-term adverse outcomes for both mother and child. Children of mothers who have GDM during their pregnancy are more likely to develop Type 2 Diabetes (T2D), early-onset cardiovascular disease and GDM when they themselves become pregnant, perpetuating a multigenerational increased risk of metabolic disease. The negative effect of GDM is exacerbated by maternal obesity, which induces a greater derangement of fetal adipogenesis and growth. Multiple factors, including genetic, epigenetic and metabolic, which interact with lifestyle factors and the environment, are likely to contribute to the development of GDM. Genetic factors are particularly important, with 30% of women with GDM having at least one parent with T2D. Fetal epigenetic modifications occur in response to maternal GDM, and may mediate both multi- and transgenerational risk. Changes to the maternal metabolome in GDM are primarily related to fatty acid oxidation, inflammation and insulin resistance. These might be effective early biomarkers allowing the identification of women at risk of GDM prior to the development of hyperglycaemia. The impact of the intra-uterine environment on the developing fetus, "developmental programming", has a multisystem effect, but its influence on adipogenesis is particularly important as it will determine baseline insulin sensitivity, and the response to future metabolic challenges. Identifying the critical window of metabolic development and developing effective interventions are key to our ability to improve population metabolic health.

The dietary supplements effect on metabolic markers in non-pharmacologically managed gestational diabetes mellitus patients: a systematic review and meta-analysis and meta-regression of randomized controlled trials.

Although several randomized clinical trials have tested the effect of prenatal dietary supplements on plasma glucose and lipid levels in non-pharmacologically managed gestational diabetes mellitus patients (GDM), a rigorous meta-analytic compendium lacks in the context. Therefore, this study aims to address this evidence gap. Eligible trials retrieved from searches in the PubMed, Embase, and Scopus databases were appraised using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The weighted mean differences (WMD) between dietary supplements and placebo were estimated using random-effect meta-analysis models for plasma glycemic and lipid markers. Meta-regression analysis ensued for effect modifier identification. The statistical significance estimation happened at p < 0.05 (95% confidence interval). This review included 19 trials (mostly Iranian and of low risk of bias primarily) of > 8000 GDM patients. Meta-analysis showed favorable effects of dietary supplementation on fasting plasma glucose (WMD: -5.42 mg/dL, p < 0.001), homeostasis model assessment indexes- insulin resistance (HOMA-IR; WMD: -1.02, p < 0.001), quantitative insulin sensitivity check index (WMD: 0.01, p < 0.001), total cholesterol (TC; WMD: -7.70 mg/dL, p = 0.006), triglycerides (WMD: -10.23 mg/dL, p = 0.0083), TC/high-density lipoprotein (WMD: -0.31 mg/dL, p < 0.001), low-density lipoprotein (WMD: -5.79 mg/dL; p < 0.001) and very-low-density lipoprotein (WMD: -5.67 mg/dL, p < 0.001) levels. However, the HOMA- ß-cell function didn't increase (WMD: -17.91, p < 0.001). Baseline maternal age (ß = 0.28, p = 0.014) and GDM diagnostic criteria (ß = 0.90, p = 0.012) were effect moderators of HOMA-IR and body mass index (BMI) (ß = 6.07, p = 0.022) and supplement type (solo versus combined) (ß = 14.99, p = 0.006) were effect moderators of triglyceride levels. Altogether, antenatal dietary supplements achieved control over plasma glycemic and lipid profiles in non-pharmacologically treated GDM patients. Maternal age and GDM diagnostic criteria moderated HOMA-IR levels. BMI and supplement-type moderated triglyceride levels. The online version contains supplementary material available at 10.1007/s40200-023-01369-0.

Neonatal adiposity is associated with microRNAs in adipocyte-derived extracellular vesicles in maternal and cord blood, a discovery analysis.

Maternal body size, nutrition, and hyperglycemia contribute to neonatal body size and composition. There is little information on maternal-fetal transmission of messages which influence fetal growth. We analyzed adipocyte-derived small extracellular vesicular (ADsEV) microRNAs in maternal and cord blood to explore their adipogenic potential. There were 279 mother-neonate pairs with all phenotypic data (normal glucose tolerant NGT = 148, gestational diabetes mellitus GDM = 131). Neonates with adiposity were those in the highest tertile (T3) of sex-specific sum of skinfolds and those without adiposity (lean) in the lowest tertile T1 of NGT pregnancies. We studied ADsEV miRNAs in 76 and 51 neonates with and without adiposity respectively and their mothers based on power calculations (68 NGT and 59 GDM pregnancies). ADsEV miRNAs from maternal and cord blood plasma samples were profiled on Agilent 8*60 K microarray. Differential expression (DE) of ADsEV miRNAs in adipose vs. lean groups was studied before and after adjustment for maternal GDM, adiposity, and vitamin B12-folate status. Multiple miRNAs were common in maternal and cord blood and positively correlated. We identified 24 maternal and 5 cord blood miRNAs differentially expressed (discovery p ≤ 0.1) in the adipose group in unadjusted, and 19 and 26, respectively, in the adjusted analyses. Even though DE miRNAs were different in maternal and cord blood, they targeted similar adipogenic pathways (e.g., the forkhead box O (FOXO) family of transcription factors, mitogen‑activated protein kinase (MAPK) pathway, transforming growth factor beta (TGF-β) pathway). Maternal GDM and adiposity were associated with many DE ADsEV miRNAs. Our results suggest that the ADsEV miRNAs in mothers are potential regulators of fetal adiposity. The expression and functionality of miRNAs appear to be influenced by maternal adiposity, hyperglycemia, and micronutrient status during pregnancy.

Gestational diabetes is associated with the risk of offspring’s congenital anomalies: a register-based cohort study

BackgroundGestational diabetes mellitus (GDM) is a common pregnancy-related disorder and a well-known risk factor for adverse pregnancy outcomes. There are conflicting findings on the association of GDM with the risk of congenital anomalies (CAs) in offspring. In this study, we aimed to determine study whether maternal GDM is associated with an increased risk of major CAs in offspring.MethodsThis Finnish Gestational Diabetes (FinnGeDi) register-based study included 6,597 women with singleton pregnancies and a diagnosis of GDM and 51,981 singleton controls with no diabetes identified from the Finnish Medical Birth Register (MBR) in 2009. Data from MBR were combined in this study with the Register of Congenital Malformations, which includes the data of CAs. We used logistic regression to calculate odds ratios (OR) for CAs, together with their 95% confidence intervals (CIs), adjusting for maternal age, parity, pre-pregnancy body mass index (BMI), and maternal smoking status.ResultsThe risk of major CAs was higher in the GDM-exposed (n = 336, 5.09%) than in the non-exposed group (n = 2,255, 4.33%) (OR: 1.18, 95% CI: 1.05–1.33, p = 0.005). The adjusted OR (aOR) was 1.14 (95% CI: 1.00-1.30, p = 0.047). There was a higher overall prevalence of CAs, particularly chromosomal abnormalities (0.52% vs. 0.21%), in the GDM-exposed group (OR: 2.49, 95% Cl: 1.69–3.66, p < 0.001). The aOR was 1.93 (95% Cl: 1.25–2.99, p = 0.003).ConclusionsOffspring exposed to GDM have a higher prevalence of major CAs. Of note, risk factors other than GDM, such as older maternal age and a higher pre-pregnancy BMI, diminished the between group differences in the prevalence of major CAs. Nevertheless, our findings suggest that offspring exposed to maternal GDM are more likely to be diagnosed with a chromosomal abnormality, independent of maternal age, parity, pre-pregnancy BMI, and smoking.

Cohort profile update: the Norwegian STORK Groruddalen (STORK G) pregnancy and birth cohort—the role of ethnicity and causal pathways for obesity, type 2 diabetes, cardiovascular disease and other health issues

PurposeThe STORK Groruddalen cohort was set up in 2008 to explore ethnic differences in: (1) maternal health, primarily gestational diabetes (GDM) and related health issues during pregnancy and post partum,...

Development and validation of a nomogram to predict spontaneous preterm birth in singleton gestation with short cervix and no history of spontaneous preterm birth

BackgroundSpontaneous preterm birth (sPTB) stands as a leading cause of neonatal mortality. Consequently, preventing sPTB has emerged as a paramount concern in healthcare. Therefore, our study aimed to develop a nomogram, encompassing patient characteristics and cervical elastography, to predict sPTB in singleton pregnancies. Specifically, we targeted those with a short cervix length (CL), no history of sPTB, and who were receiving vaginal progesterone therapy. MethodsA total of 568 patients were included in this study. Data from 392 patients, collected between January 2016 and October 2019, constituted the training cohort. Meanwhile, records from 176 patients, spanning November 2019 to January 2022, formed the validation cohort. Following the univariate logistic regression analysis, variables exhibiting a P-value less than 0.05 were integrated into a multivariable logistic regression analysis. The primary objective of this subsequent analysis was to identify the independent predictors linked to sPTB in the training cohort. Next, we formulated a nomogram utilizing the identified independent predictors. This tool was designed to estimate the likelihood of sPTB in singleton pregnancies, particularly those with a short CL, devoid of any sPTB history, and undergoing vaginal progesterone therapy. The C-index, Hosmer-Lemeshow (HL) test, calibration curves, decision curve analysis (DCA), and receiver operating characteristic (ROC) were used to validate the performance of the nomogram. ResultsUpon finalizing the univariate analysis, we progressed to a multivariable analysis, integrating 8 variables with P < 0.05 from the univariate analysis. The multivariable analysis identified 7 independent risk factors: maternal age (OR = 1.072; P < 0.001), cervical length (OR = 0.854; P < 0.001), uterine curettage (OR = 7.208; P < 0.001), GDM (OR = 3.570; P = 0.006), HDP (OR = 4.661; P = 0.003), C-reactive protein (OR = 1.138; P < 0.001), and strain of AI (OR = 7.985; P < 0.001). The nomogram, tailored for sPTB prediction, was grounded on these 7 independent predictors. In predicting sPTB, the C-indices manifested as 0.873 (95% CI, 0.827–0.918) for the training cohort and 0.916 (95%CI, 0.870–0.962) for the validation cohorts, underscoring a good discrimination of the model. Additionally, the ROC curves served to evaluate the discrimination of nomogram model across both cohorts. Calibration curves were delineated, revealing no statistically significant differences in both the training (χ2 = 5.355; P = 0.719) and validation (χ2 = 2.708; P = 0.951) cohorts as evidenced by the HL tests. Furthermore, the DCA underscored the model's excellence as a predictive tool for sPTB. ConclusionsBy amalgamating patient characteristics and cervical elastography data from the second trimester, the nomogram emerged as a visually intuitive and dependable tool for predicting sPTB. Its relevance was particularly pronounced for singleton pregnancies characterized by a short CL, an absence of prior sPTB incidents, and those receiving vaginal progesterone therapy.

Maternal obesity and GDM affect regulation of placental protein metabolism in a fetal sex-dependent manner.

Maternal obesity and GDM affect regulation of placental protein metabolism in a fetal sex-dependent manner.

An observational study on the prevalence of congenital hypothyroidism and factors affecting TSH levels in premature babies at tertiary care rural centre

Background: Premature babies, particularly those with very low birth weight (VLBW), are at a higher risk of developing congenital hypothyroidism. The inadequate development of the hypothalamic-pituitary axis in preterm infants contributes to the higher prevalence of this condition in this population. However, the optimal screening and treatment protocols for congenital hypothyroidism in preterm newborns remain unclear. Methods: This was a hospital-based observational study conducted over a period of 18 months. The study included 150 preterm babies born at the Sri Adichunchanagiri hospital and research centre. Non-probability sampling was used to select the study subjects. Data on demographic and clinical factors were collected from mothers and newborns. Blood samples were collected at day 3 of life to estimate thyroid-stimulating hormone levels. Correlations between TSH levels and various parameters were analyzed using statistical methods. Results: The study found that the prevalence of congenital hypothyroidism in preterm newborns was 2%. The mean TSH level at day 3 was 7.56 mIU/L, and 9.3% of cases had TSH levels above 20 mIU/l. Significant associations were found between high TSH levels and primiparity, vaginal delivery, and maternal gestational diabetes mellitus. There was an inverse correlation between TSH levels and gestational age, birth weight, and Apgar scores at 1 and 5 minutes. Conclusions: The study revealed a prevalence of congenital hypothyroidism of 2% in preterm newborns. Risk factors such as primiparity, vaginal delivery, and maternal GDM were associated with high TSH levels. These findings highlight the importance of screening and early detection of congenital hypothyroidism in premature babies to improve outcomes.

Smoking during pregnancy and gestational diabetes mellitus: a systematic review and meta-analysis

PurposeTo investigate whether maternal cigarette smoking during pregnancy is a risk factor for developing GDM.MethodsMEDLINE, Scopus, CENTRAL and Google Scholar databases were searched from inception to December 2022 to identify eligible original articles. A systematic review and meta-analysis (weighted data, random-effects model) were performed. The primary outcome was the development of GDM in pregnant women. The results were expressed as odds ratios (OR) with 95% confidence interval (CI) (inverse variance method). Subgroup analysis was planned according to the maternal smoking status and GDM diagnostic criteria. Statistical heterogeneity was checked with the Chi-squared (Chi2) test and the I2 index was used to quantify it. The studies were evaluated for publication bias.ResultsThirty-five studies, including 23,849,696 pregnant women, met the inclusion criteria. The pooled OR of smoking during pregnancy compared with non-smoking (never smokers and former smokers) was 1.06 (95% CI 0.95–1.19), p = 0.30; I2 = 90%; Chi2 = 344; df=34; p < 0.001. Subgroup analysis was performed according to the two-step Carpenter-Coustan diagnostic criteria, due to the high heterogeneity among the other applied methods. The pooled OR for the Carpenter-Coustan subgroup was 1.19 (95% CI 0.95–1.49), p = 0.12; I2 = 63%; Chi2 = 27; df=10; p < 0.002. Further subgroup analysis according to maternal smoking status was not performed due to missing data.ConclusionThere is no evidence to support an association between maternal cigarette smoking during pregnancy and the risk for GDM. Universally accepted diagnostic criteria for GDM must be adopted to reduce heterogeneity and clarify the association between smoking and GDM.

1258-P: Gestational Diabetes by IADPSG Criteria and Risk of Adverse Birth Outcomes

This study assessed risk of adverse birth outcomes (ABO) associated with GDM by Carpenter-Coustan (C&amp;C) and International Association of the Diabetes and Pregnancy Study Groups (IADPSG) with and without abnormal fasting at OGTT screening. Data included 355,506 singletons born in a single healthcare system. Data on demographics, maternal GDM status with or without abnormal fasting, and six ABOs [caesarean section (CS), shoulder dystocia (SD), fetal distress (FD), neonatal hypoglycemia (NH), preterm birth (PTB), and large-for gestational age (LGA)] were extracted from electronic medical records. Logistic regression was used to assess associations adjusting for covariates. In this cohort, 27,990 (7.9%) were diagnosed by C&amp;C and 21,464 (6.0%) by IADPSG. In the C&amp;C group, 37.3% had abnormal fasting (C&amp;C_AF); among IADPSG, 23.3% met OGTT fasting thresholds (IADPSG_AF). Table 1 shows odds ratios (OR) of ABOs associated with GDM diagnostic types relative to no GDM. GDM by C&amp;C or IADPSG with or without abnormal fasting was associated with higher odds of CS, PTB (except IADPSG_AF), and LGA (except C&amp;C without abnormal fasting). IADPSG without abnormal fasting was associated with higher odds of SD and NH, and C&amp;C_AF was associated with higher odds of SD but lower odds FD and NH. These data suggest GDM by IADPSG was associated with risk of some ABOs; this group may benefit from diabetes care in pregnancy to reduce risk of ABOs. Disclosure S.A.Carter: None. J.C.Lin: None. T.Chow: None. M.P.Martinez: None. R.Feldman: None. K.A.Page: None. A.Xiang: None.

1195-P: Is Gestational Diabetes by IADPSG Criteria Associated with Risk of Autism in Offspring?

We assessed whether only one abnormal value from the OGTT screening during pregnancy, which qualify as GDM by the IADPSG criteria (GDM_IADPSG), was associated with risk of offspring autism spectrum disorders (ASD). The cohort included 590,001 singletons from a large integrated healthcare system with electronic medical records. GDM was largely screened by two-steps and Carpenter-Coustan criteria (GDM_CC). We excluded those exposed to pre-existing diabetes or 1-hr 50g glucose challenge test ≥ 200mg/dl. OGTT glucose levels were used to define GDM_IADPSG. Cox models with hazard ratio (HR) were used to assess associations. Among the cohort, 7.6% were exposed to maternal GDM_CC, an additional 5.9% to GDM_IADPSG with only one abnormal OGTT value. Within GDM_CC, 41.3% had abnormal fasting, 30.5% were diagnosed at ≤ 26 wks and 30.7% prescribed medications. Within GDM_IADPSG, 28.4% had abnormal fasting alone, 27.0% at ≤ 26 wks and none received medications. Table 1 shows the HRs (95% CI). GDM_IADPSG was associated with increased risk of ASD, with risk slightly lower compared to GDM_CC. However, the risk appeared greater if abnormal fasting presented at diagnosis. The risk of ASD associated with GDM_IADPSG by abnormal fasting alone was comparable to GDM_CC treated with medications. Studies are needed to assess whether diabetes management for pregnancies with only elevated fasting will reduce adverse effect on offspring. Disclosure A.Xiang: None. S.A.Carter: None. J.C.Lin: None. T.Chow: None. M.P.Martinez: None. K.A.Page: None. R.Feldman: None.

Association between maternal gestational diabetes and allergic diseases in offspring: a birth cohort study.

Previous studies have linked gestational diabetes (GDM) with allergies in offspring. However, the effect of specific glucose metabolism metrics was not well characterized, and the role of polyunsaturated fatty acids (PUFAs), a modifier of metabolism and the immune system, was understudied. We aimed to investigate the association between maternal GDM and allergic diseases in children and the interaction between glucose metabolism and PUFAs on allergic outcomes. This prospective cohort study included 706 mother-child dyads from Guangzhou, China. Maternal GDM was diagnosed via a 75-g oral glucose tolerance test (OGTT), and dietary PUFAs were assessed using a validated food frequency questionnaire. Allergic disease diagnoses and the age of onset were obtained from medical records of children within threeyears old. Approximately 19.4% of women had GDM, and 51.3% of children had any allergic diseases. GDM was positively associated with any allergic diseases (hazard ratio [HR] 1.40; 95% confidence interval (CI) 1.05-1.88) and eczema (HR 1.44; 95% CI 1.02-1.97). A unit increase in OGTT after two hours (OGTT-2h) glucose was associated with an 11% (95% CI 2%-21%) higher risk of any allergic diseases and a 17% (95% CI 1-36%) higher risk of food allergy. The positive associations between OGTT-2h glucose and any allergic diseases were strengthened with decreased dietary a-linolenic acid (ALA) and increasedn-6 PUFAs, linoleic acid (LA), LA/ALA ratio, andn-6/n-3 PUFA ratio. Maternal GDM was adversely associated with early-life allergic diseases, especially eczema. We were the first to identify OGTT-2h glucose to be more sensitive in inducing allergy risk and that dietary PUFAs might modify the associations.

Impact of gestational diabetes and other maternal factors on neonatal body composition in the first week of life: a case-control study.

Newborns of diabetic mothers are at increased risk of abnormal nutritional status at birth, thus developing metabolic disorders. The aim of this study was to evaluate the anthropometric measurements and body composition of newborns born to mothers with gestational diabetes in comparison to newborns born to mothers with normal glucose tolerance in pregnancy, in the first week of their life. Maternal factors affecting the gestational period were also evaluated. The study included 70 participants: neonates born to mothers with gestational diabetes (GDM) and neonates born to healthy mothers (non-GDM). A set of statistical methods (e.g., ANOVA, Kruskal-Wallis test, Chi-square test, regression, cluster analysis) was used to compare data between the study groups and to find their association with maternal factors. Our approach resulted in statistically significant classification (p < 0.05) by maternal history of hypothyroidism, weight gain during pregnancy and diagnosis of GDM. Newborns of mothers diagnosed with both GDM and hypothyroidism had lower birth weight and fat mass than newborns of mothers without GDM nor hypothyroidism (p < 0.05), however this finding might be associated with high incidence of excessive gestational weight gain among healthy mothers. No differences in body composition were found between the study groups on account of maternal GDM only (p > 0.05). Thus, well-controlled gestational diabetes mellitus as an individual factor does not significantly affect neonatal anthropometric measurements and body composition.

Severe gestational diabetes mellitus in lean dams is associated with low IL-1α levels and affects the growth of the juvenile mouse offspring

We investigated how maternal gestational diabetes (GDM) impacts the metabolic status of offspring. GDM was induced in CD1 mice consuming a fast-food diet (FFD) by repeated low-dose streptozotocin injections before mating. Offspring of normoglycemic standard chow or the FFD consuming dams served as controls. In 4-week-old offspring weaned to standard chow, plasma concentrations of extracellular DNA, inflammatory markers, and parameters of the cardiometabolic status (glycemia, liver lipid content; body, organ, and fat weight) were determined. Two-factor analysis of variance indicated that the male offspring of GDM dams manifest postnatal growth retardation and lower relative kidney weight. Regardless of sex, GDM offspring manifest the lowest IL-1α levels, and other inflammatory markers showed mild and inconsistent alterations. Offspring of dams consuming the FFD displayed higher liver triacylglycerols content. The three groups of offspring showed no significant differences in glycemia and extracellular DNA. Partial least squares-discriminant analysis indicated that male GDM offspring present lower kidney, body, and brown adipose tissue weights; lower IL-1α levels, and higher concentrations of GM-CSF and IL-10 compared with their FFD counterparts. The model failed to select discriminative variables in females. In conclusion, in mice, maternal GDM in the absence of obesity adversely affects the early growth of juvenile male offspring.