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Abstract Background Pre-diagnostic disturbances in the microbiome-derived metabolome have been associated with an increased risk of diabetes in non-pregnant populations. However, the roles of microbiome-derived metabolites, the end-products of microbial metabolism, in gestational diabetes (GDM) remain understudied. We examined the prospective association of microbiome-derived metabolites in early to mid-pregnancy with GDM risk in a diverse population. Methods We conducted a prospective discovery and validation study, including a case–control sample of 91 GDM and 180 non-GDM individuals within the multi-racial/ethnic The Pregnancy Environment and Lifestyle Study (PETALS) as the discovery set, a random sample from the PETALS (42 GDM, 372 non-GDM) as validation set 1, and a case–control sample (35 GDM, 70 non-GDM) from the Gestational Weight Gain and Optimal Wellness randomized controlled trial as validation set 2. We measured untargeted fasting serum metabolomics at gestational weeks (GW) 10–13 and 16–19 by gas chromatography/time-of-flight mass spectrometry (TOF–MS), liquid chromatography (LC)/quadrupole TOF–MS, and hydrophilic interaction LC/quadrupole TOF–MS. GDM was diagnosed using the 3-h, 100-g oral glucose tolerance test according to the Carpenter-Coustan criteria around GW 24–28. Results Among 1362 annotated compounds, we identified 140 of gut microbiome metabolism origin. Multivariate enrichment analysis illustrated that carbocyclic acids and branched-chain amino acid clusters at GW 10–13 and the unsaturated fatty acids cluster at GW 16–19 were positively associated with GDM risk (FDR

Abstract Background Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. Methods Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA). Results A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. Conclusions Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.

Abstract Background Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals and are commonly found in everyday items. PFAS have been linked to disrupting glucose homeostasis, however, whether they are associated with gestational diabetes mellitus (GDM) risk remains inconclusive. We examined prospective associations of PFAS concentrations measured twice in pregnancy with GDM risk. Methods In the PETALS pregnancy cohort, a nested case–control study which included 41 GDM cases and 87 controls was conducted. PFAS analytes were measured in blood serum collected in both early and mid-pregnancy (mean [SD]: 13.9 [2.2] and 20.2 [2.2] gestational weeks, respectively), with cumulative exposure calculated by the area-under-the-curve (AUC) to integrate both the PFAS concentration and the timing of the exposure. Individual adjusted weighted unconditional logistic regression models examined seven PFAS in association with GDM risk. P-values were corrected using the false-discovery-rate (FDR). Mixture models were analyzed with Bayesian kernel machine regression (BKMR). Results PFDA, PFNA and PFOA were individually associated with higher GDM risk per interquartile range (IQR) in early pregnancy (OR [95% CI]: 1.23 [1.09, 1.38]), 1.40 [1.24, 1.58]), and 1.15 [1.04, 1.27], respectively), mid-pregnancy (1.28 [1.15, 1.43], 1.16 [1.05, 1.28], and 1.20 [1.09, 1.33], respectively), and with cumulative exposure (1.23 [1.09, 1.38], 1.21 [1.07, 1.37], and 1.19 [1.09, 1.31], respectively). PFOS in mid-pregnancy and with cumulative exposure was associated with increased GDM risk (1.41 [1.17, 1.71] and 1.33 [1.06, 1.58], respectively). PFUnDA in early pregnancy was associated with lower GDM risk (0.79 [0.64, 0.98]), whereas mid-pregnancy levels were associated with higher risk (1.49 [1.18, 1.89]). PFHxS was associated with decreased GDM risk in early and mid-pregnancy (0.48 [0.38, 0.60] and 0.48 [0.37, 0.63], respectively) and with cumulative exposure (0.49 [0.38,0.63]). PFPeA was not associated with GDM. Similar conclusions were observed in BKMR models; however, overall associations in these models were not statistically significant. Conclusions Higher risk of GDM was consistently observed in association with PFDA, PFNA, and PFOA exposure in both early and mid-pregnancy. Results should be corroborated in larger population-based cohorts and individuals of reproductive age should potentially avoid known sources of PFAS.

Healthy lifestyle behaviors influence maternal cardiovascular health, but motivation for them in pregnancy is poorly understood. We examined whether intrinsic motivation (assessed on 5-point scales for each behavior) is associated with three lifestyle behaviors in early pregnancy: physical activity, by intensity level; healthy eating, quantified with the Alternate Healthy Eating Index for Pregnancy (AHEI-P); and weight self-monitoring, a standard weight management technique. Participants in the Northern California Pregnancy, Lifestyle and Environment Study (PETALS) population-based cohort completed validated surveys in early pregnancy (2017–18; N = 472; 22 % Asian, 6 % Black, 30 % Hispanic, 13 % multiracial, 30 % White). Cross-sectional data were analyzed in 2021–22. Overall, 40.7 % (n = 192) met United States national physical activity guidelines; the average AHEI-P score was 62.3 out of 130 (SD 11.4); and 36.9 % reported regular self-weighing (≥once/week; n = 174). In models adjusted for participant characteristics, 1-unit increases in intrinsic motivation were associated with increased likelihood of meeting physical activity guidelines (risk ratio [95 % CI]: 1.66 [1.48, 1.86], p

Abstract Background Prior research has demonstrated bidirectional associations between gestational diabetes mellitus (GDM) and perinatal maternal depression. However, the association between GDM, prenatal depression, and postpartum depression (PPD) has not been examined in a prospective cohort longitudinally. Methods Participants in the current analysis included 5,822 women from the National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) Research Program: N = 4,606 with Neither GDM nor Prenatal Maternal Depression (Reference Category); N = 416 with GDM only; N = 689 with Prenatal Maternal Depression only; and N = 111 with Comorbid GDM and Prenatal Maternal Depression. The PROMIS-D scale was used to measure prenatal and postnatal maternal depressive symptoms. Primary analyses consisted of linear regression models to estimate the independent and joint effects of GDM and prenatal maternal depression on maternal postpartum depressive symptoms. Results A higher proportion of women with GDM were classified as having prenatal depression (N = 111; 21%) compared to the proportion of women without GDM who were classified as having prenatal depression (N = 689; 13%), however this finding was not significant after adjustment for covariates. Women with Comorbid GDM and Prenatal Maternal Depression had significantly increased postpartum depressive symptoms measured by PROMIS-D T-scores compared to women with Neither GDM nor Prenatal Maternal Depression (mean difference 7.02, 95% CI 5.00, 9.05). Comorbid GDM and Prenatal Maternal Depression was associated with an increased likelihood of PPD (OR 7.38, 95% CI 4.05, 12.94). However, women with GDM only did not have increased postpartum PROMIS-D T-scores or increased rates of PPD. Conclusions Our findings underscore the importance of universal depression screening during pregnancy and in the first postpartum year. Due to the joint association of GDM and prenatal maternal depression on risk of PPD, future studies should examine potential mechanisms underlying this relation.

Abstract Background Gestational diabetes (GDM) is prevalent and benefits from timely and effective treatment, given the short window to impact glycemic control. Clinicians face major barriers to choosing effectively among treatment modalities [medical nutrition therapy (MNT) with or without pharmacologic treatment (antidiabetic oral agents and/or insulin)]. We investigated whether clinical data at varied stages of pregnancy can predict GDM treatment modality. Methods Among a population-based cohort of 30,474 pregnancies with GDM delivered at Kaiser Permanente Northern California in 2007–2017, we selected those in 2007–2016 as the discovery set and 2017 as the temporal/future validation set. Potential predictors were extracted from electronic health records at different timepoints (levels 1–4): (1) 1-year preconception to the last menstrual period, (2) the last menstrual period to GDM diagnosis, (3) at GDM diagnosis, and (4) 1 week after GDM diagnosis. We compared transparent and ensemble machine learning prediction methods, including least absolute shrinkage and selection operator (LASSO) regression and super learner, containing classification and regression tree, LASSO regression, random forest, and extreme gradient boosting algorithms, to predict risks for pharmacologic treatment beyond MNT. Results The super learner using levels 1–4 predictors had higher predictability [tenfold cross-validated C-statistic in discovery/validation set: 0.934 (95% CI: 0.931–0.936)/0.815 (0.800–0.829)], compared to levels 1, 1–2, and 1–3 (discovery/validation set C-statistic: 0.683–0.869/0.634–0.754). A simpler, more interpretable model, including timing of GDM diagnosis, diagnostic fasting glucose value, and the status and frequency of glycemic control at fasting during one-week post diagnosis, was developed using tenfold cross-validated logistic regression based on super learner-selected predictors. This model compared to the super learner had only a modest reduction in predictability [discovery/validation set C-statistic: 0.825 (0.820–0.830)/0.798 (95% CI: 0.783–0.813)]. Conclusions Clinical data demonstrated reasonably high predictability for GDM treatment modality at the time of GDM diagnosis and high predictability at 1-week post GDM diagnosis. These population-based, clinically oriented models may support algorithm-based risk-stratification for treatment modality, inform timely treatment, and catalyze more effective management of GDM.

BackgroundPhysical activity (PA) during pregnancy influences women and offspring’s health via fatty acids metabolism. However, studies on associations of PA with plasma monounsaturated fatty acids (MUFAs) across pregnancy are sparse. Thus, our study aimed to examine associations of PA with individual plasma phospholipid MUFAs throughout pregnancy in a prospective and longitudinal study in the United States (US).Materials and methodsThe study included 318 pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons cohort. PA was measured four times: PA reported at 10–14 gestational weeks (GWs) representing PA in the past year, and at 15–26 GWs, 23–31 GWs, and 33–39 GWs representing PA since the last visit. Plasma phospholipid MUFAs were measured at the same four visits as the measurement of PA. Associations between moderate-to-vigorous PA (MVPA) and the total MUFAs and seven individual plasma phospholipid MUFAs (i.e., palmitoleic acid, 18:1n6-9 trans, 18:1n6c, cis-vaccenic acid, oleic acid, eicosenoic acid, and nervonic acid) were assessed at each visit using multivariable linear regression models adjusting for confounders.ResultsMVPA (hours/week) reported at 15–26 GWs representing MVPA since the last visit was positively associated with total MUFAs (% of total fatty acids) [adjusted β*102 (standard error (SE)*102) = 10.41 (3.19), P = 0.001] at 15–26 GWs. For individual MUFAs, MVPA reported at 15–26 GWs representing MVPA since the last visit was positively associated with oleic acid [adjusted β*102 (SE*102) = 8.56 (2.65), P = 0.001] and eicosenoic acid [adjusted β*102 (SE*102) = 0.55 (0.20), P = 0.01] at 15–26 GWs. MVPA reported at 23–31 GWs representing MVPA since the last visit was positively associated with palmitoleic acid [adjusted β*102 (SE*102) = 2.24 (0.64), P = 0.001] at 23–31 GWs. MVPA reported at 10–14 GWs and 33–39 GWs was not associated with total or individual MUFAs.ConclusionWe found novel positive associations of MVPA with individual MUFAs, such as oleic acid, eicosenoic acid, and palmitoleic acid, during middle-to-late pregnancy. These findings suggest that MVPA represents a potentially modifiable factor for plasma individual MUFA levels during pregnancy.

Carrie Breton and colleagues review the literature supporting evidence for transgenerational health effects of environmental exposures by epigenetic mechanisms. This Review summarizes current knowledge based on animal and human cohort studies, and discusses the ethical, legal, and social implications of epigenetic research in humans

Objective: This study evaluated whether COVID-19 pandemic-related health, healthcare and economic factors during pregnancy are associated with prenatal depression and anxiety.Methods: We conducted a cross-sectional study of 6,628 pregnant members of Kaiser Permanente Northern California who responded to a survey between 22 June and 30 September 2020. The survey included questions about depression (Patient Health Questionnaire) and anxiety (Generalized Anxiety Disorder) symptoms and COVID-19-related health and healthcare (e.g., had COVID-19) and economic (e.g., food insecurity) factors.Results: Over one third of individuals reported depression (25% mild, 8% moderate, 3% severe) or anxiety (22% mild, 8% moderate, 5% severe) symptoms. In multivariable analyses, COVID-19 during pregnancy, employment with greater risk of COVID-19, distress over changes in prenatal care, job loss, changes in childcare and food insecurity were associated with greater odds of prenatal depression or anxiety.Conclusion: Findings suggest the COVID-19 pandemic may have severe mental health repercussions for pregnant individuals. Support services for pregnant individuals experiencing these COVID-19-related factors and monitoring of those who had moderate/severe prenatal depression and anxiety symptoms during the COVID-19 pandemic is warranted.

BackgroundThis study aimed to identify racial and ethnic disparities in prenatal mental health and identify COVID-19 pandemic-related health/healthcare and economic contributors to these disparities, using an established framework for disparity investigation.MethodsThis cross-sectional study includes 10,930 pregnant people at Kaiser Permanente Northern California who completed an online survey between June 22, 2020 and April 28, 2021 on COVID-19 pandemic-related health/healthcare and economic stressors, depression, and anxiety. Self-reported race and ethnicity were extracted from electronic health records. Weighted analyses were used to evaluate the association between racial and ethnic category and prenatal depression and anxiety; the prevalence of each stressor by race and ethnicity; and the relationship between each stressor and prenatal depression and anxiety in each racial and ethnic category.ResultsThe sample was 22% Asian, 3% Black, 20% Hispanic, 5% Other/Multiracial/Unknown, and 49% White. Compared to White people, Black and Hispanic people had a higher prevalence of prenatal depression (aPR: 1.85, 95% CI: 1.45, 2.35 and aPR: 1.17, 95% CI: 1.00, 1.37, respectively) and anxiety (aPR: 1.71, 95% CI: 1.34, 2.18 and aPR: 1.10, 95% CI: 0.94, 1.29, respectively). Compared to White people, Black and Hispanic people had a higher prevalence of moderate/severe distress due to changes in prenatal care (24 vs. 34 and 31%), and food insecurity (9 vs. 31 and 24%). Among Black and Hispanic people, distress due to changes in prenatal care was associated with a greater prevalence of prenatal depression (aPR: 2.27, 95% CI: 1.41, 3.64 and aPR: 2.76, 95% CI: 2.12, 3.58, respectively) and prenatal anxiety (aPR: 3.00, 95% CI: 1.85, 4.84 and aPR: 2.82, 95% CI: 2.15, 3.71, respectively). Additionally, among Hispanic people, high-risk employment and food insecurity were associated with a greater prevalence of prenatal depression and anxiety.ConclusionsThis study identified racial and ethnic disparities in mental health for pregnant Black and Hispanic people. Distress due to prenatal care changes contributed to the observed disparities in prenatal depression and anxiety for Black and Hispanic people and food insecurity additionally contributed to the observed disparities for Hispanic people. Addressing distress due to changes to prenatal care and food insecurity specifically in Black and Hispanic people may help reduce the high burden of poor mental health and reduce observed disparities in these communities.

Meeting the Institute of Medicine (IOM) gestational weight gain (GWG) guidelines is associated with a reduced risk of adverse perinatal outcomes. Overall diet quality comprehensively assesses dietary components and accounts for interactions between them. While GWG is influenced by maternal diet, its association with overall diet quality—measured by various dietary quality indices—is not well-defined. We prospectively estimated the relationship between four established dietary quality indices and the risk of GWG rate above (excessive) or below (inadequate) IOM guidelines in a multi-racial and ethnic cohort of 2914 pregnant people from the Pregnancy Environment and Lifestyle Study (2014–2019). We assessed diet quality using the Healthy Eating Index 2010 (HEI-2010), alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH), and Empirical Dietary Inflammatory Index (EDIP). Following the first trimester, 56% of the cohort had excessive GWG, and 14% had inadequate GWG. Poor diet quality (below the 75th percentile), measured by HEI-2010, was associated with a higher risk of excessive GWG in the second and third trimesters [RR = 1.03 (1.00, 1.06)]. Effect modification of this relationship by race and ethnicity and pre-pregnancy BMI was assessed. We found poor diet quality to be associated with elevated risk of excessive GWG among Black participants [RR = 1.14 (1.02, 1.28)] and White participants [RR 1.07 (1.01, 1.12)]. This was also the case for participants with pre-pregnancy BMI < 25.0 [RR 1.05 (1.00, 1.10)]. These results suggest that diet quality measured by the HEI-2010 is associated with excessive GWG, and the associations appear to be stronger among pregnant people without overweight or obesity and pregnant people who identify as Black or White race and ethnicity.

Objective Household food insufficiency (HFIS) is a major public health threat to children. Children may be particularly vulnerable to HFIS as a psychological stressor due to their rapid growth and accelerated behavioural and cognitive states, whereas data focusing on HFIS and childhood mental disorders are as-yet sparse. We aimed to examine the associations of HFIS with depression and anxiety in US children.Design Cross-sectional study.Setting The 2016–2018 National Survey of Children’s Health, a nationally-representative study.Participants Primary caregivers of 102 341 children in the USA.Primary and secondary outcome measures Physician diagnosed depression and anxiety were assessed by questionnaires administered to primary caregivers of 102 341 children. Multivariable logistic regression models estimated adjusted OR (aOR) for current depression or anxiety associated with HFIS measured through a validated single-item instrument.Results Among children aged 3–17 years, 3.2% and 7.4% had parent-reported physician-diagnosed current depression and anxiety, respectively. Compared with children without HFIS, children with HFIS had approximately twofold higher weighted prevalence of anxiety or depression. After adjusting for covariates, children with versus without HFIS had a 1.53-fold (95% CI 1.15 to 2.03) and 1.48-fold (95% CI 1.20 to 1.82) increased odds of current depression and anxiety, respectively. Associations were slightly more pronounced among girls (aOR (95% CI): depression 1.69 (1.16 to 2.48); anxiety 1.78 (1.33 to 2.38)) than boys (1.42 (0.98 to 2.08); 1.32 (1.00 to 1.73); both P-for-interaction

This study examined the relationship between maternal food source and preparation during pregnancy and the duration of breastfeeding among 751 mother–child dyads in the United States. The data collected from the Environmental influences on Child Health Outcomes (ECHO) Program included twelve cohorts of mothers (age ≥ 18) who delivered infant(s). Three categories of maternal food source and preparation including, High, Moderate, or Low Food Source Quality were derived from the mother report. The mean duration of breastfeeding differed strongly across the three categories. The High Food Source Quality group breastfed an average of 41 weeks, while shorter durations were observed for the Moderate (26 weeks) and Low (16 weeks) Food Source Quality groups. Cox proportional hazards models were used to estimate the relative hazard of time to breastfeeding cessation for each participant characteristic. The full model adjusted for clustering/cohort effect for all participant characteristics, while the final model adjusted for the subset of characteristics identified from variable reduction modeling. The hazard of breastfeeding cessation for those in the High Food Source Quality group was 24% less than the Moderate group (RH = 0.76; 95% CI, 0.63–0.92). Pregnant women in the High Food Source Quality group breastfed longer than the Moderate and Low groups. We encourage more detailed studies in the future to examine this relationship longitudinally.

BackgroundResearch on COVID-19 during pregnancy has mainly focused on women hospitalized for COVID-19 or other reasons during their pregnancy. Little is known about COVID-19 in the general population of pregnant women.ObjectiveTo describe the prevalence of COVID-19, symptoms, consequent healthcare use, and possible sources of COVID-19 exposure among a population-based sample of pregnant women residing in Northern California.MethodsWe analyzed data from 19,458 members of Kaiser Permanente Northern California who were pregnant between January 2020 and April 2021 and responded to an online survey about COVID-19 testing, diagnosis, symptoms, and their experiences during the COVID-19 pandemic. Medical diagnosis of COVID-19 during pregnancy was defined separately by self-report and by documentation in electronic health records (EHR). We examined relationships of COVID-19 with sociodemographic factors, underlying comorbidities, and survey measures of COVID-19-like symptoms, consequent healthcare utilization, and possible COVID-19 exposures.ResultsAmong 19,458 respondents, the crude prevalence of COVID-19 was 2.5% (n = 494) according to self-report and 1.4% (n = 276) according to EHR. After adjustment, the prevalence of self-reported COVID-19 was higher among women aged ConclusionsObserved COVID-19 prevalence differences by sociodemographic and socioeconomic factors underscore social and health inequities among reproductive-aged women. Women with COVID-19 reported unique symptoms and low frequency of hospitalization. Many were not aware of an exposure to someone with COVID-19.

Objective: Prolactin and progesterone are implicated in glucose homeostasis in and outside of pregnancy. However, their associations with gestational diabetes (GDM) risk were not well-understood. This study investigates this question in a prospective and longitudinal cohort.Methods: This is a nested case-control study of 107 incident GDM cases and 214 matched non-GDM controls within the NICHD Fetal Growth Studies-Singleton Cohort. Blood samples were collected at gestational weeks 10–14, 15–26, 23–31, and 33–39. The odds ratios (OR) of GDM were estimated using conditional logistic regression. The longitudinal changes in prolactin and progesterone were estimated using linear mixed-effects models.Results: Compared to controls, cases have significantly higher prolactin levels at weeks 10–14 (median: 50.4 vs. 42.1 ng/mL), and significantly lower progesterone levels at weeks 10–14 (median: 109.4 vs. 126.5 nmol/L). Prolactin levels at weeks 10–14 were significantly and positively associated with GDM risk; the adjusted ORs across increasing quartiles were 1.00, 1.13, 1.80, 2.33 (p-trend = 0.02). A similar but slightly attenuated association was observed at weeks 15–26 (p-trend = 0.05). Progesterone was not associated with GDM risk at either time points. Longitudinal changes in prolactin and progesterone between the first two visits were not associated with GDM risk. In addition, prolactin was significantly and positively associated with insulin and C-peptide levels at weeks 10–14, and significantly and inversely associated with C-peptide levels at weeks 15–26; progesterone was significantly and inversely associated with glucose and insulin levels.Conclusions: This study provided the first prospective evidence of a positive association between prolactin levels in early pregnancy and GDM risk.

Lactation is associated with a lower risk of subsequent cardiometabolic disease among parous women; however, the underlying mechanisms are unknown. Further, the potential protective effects of lactation on cardiometabolic risk markers at mid-life among high-risk women with past gestational diabetes (GDM) are not established. Using data from the Diabetes & Women’s Health Study (2012–2014; n = 577), a longitudinal cohort of women with past GDM from the Danish National Birth Cohort (1996–2002), we assessed associations of cumulative lactation duration (none, 2 (IQR 24.6, 33.0); 28.6% of participants had T2D, 39.7% had prediabetes, and 41.2% had obesity. Relative risks (95% CI) of T2D for 0–6, 6–12, 12–24, and ≥24 months of cumulative lactation duration compared to none were 0.94 (0.62,1.44), 0.88 (0.59,1.32), 0.73 (0.46,1.17), and 0.71 (0.40,1.27), respectively. Cumulative lactation duration was not significantly associated with any other clinical outcome or continuous biomarker. In this high-risk cohort of middle-aged women with past GDM, T2D, prediabetes, and obesity were common at follow-up, but not associated with history of cumulative lactation duration 9–16 years after the index pregnancy. Further studies in diverse populations among women at mid-age are needed to understand associations of breastfeeding with T2D.

Despite increasing interest in the health effects of polyunsaturated FAs (PUFAs), their roles in fetal and neonatal growth remain understudied. Within the NICHD Fetal Growth Studies—Singleton Cohort, we prospectively investigated the associations of individual and subclasses of plasma phospholipid PUFAs at gestational weeks (GW) 10–14, 15–26, 23–31, and 33–39 with neonatal anthropometric measures as surrogates for fetal growth among 107 women with gestational diabetes mellitus (GDM) and 214 non-GDM controls. Multivariable weighted linear regression models estimated the associations between plasma phospholipid PUFAs and neonatal anthropometric measures. Adjusted beta coefficients for phospholipid docosahexaenoic acid (DHA) per standard deviation (SD) increase at GW 23–31 in association with birthweight z-score, neonatal length, and neonatal fat mass were 0.25 (95% CI: 0.08–0.41), 0.57 (0.11–1.03) cm, and 54.99 (23.57–86.42) g, respectively; all false discovery rates (FDRs) < 0.05. Estimated Δ5-desaturase activity per SD increase at GW 33–39 but not at other time points was positively associated with birthweight z-score: 0.29 (95% CI: 0.08–0.33); neonatal length: 0.61 (0.29–0.94) cm; and neonatal fat mass: 32.59 (8.21–56.96) g; all FDRs < 0.05. Longitudinal analysis showed consistent results. Our findings suggest that mid-to-late pregnancy presented as critical windows for primarily diet-derived DHA and Δ5-desaturase activity in relation to neonatal anthropometric measures.

As surrogate readouts reflecting mitochondrial dysfunction, elevated levels of plasma acylcarnitines have been associated with cardiometabolic disorders, such as obesity, gestational diabetes, and type 2 diabetes. This study aimed to examine prospective associations of acylcarnitine profiles across gestation with neonatal anthropometry, including birthweight, birthweight z score, body length, sum of skinfolds, and sum of body circumferences. We quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in plasma collected at gestational weeks 10–14, 15–26, 23–31, and 33–39 among 321 pregnant women from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons. A latent-class trajectory approach was applied to identify trajectories of acylcarnitines across gestation. We examined the associations of individual acylcarnitines and distinct trajectory groups with neonatal anthropometry using weighted generalized linear models adjusting for maternal age, race/ethnicity, education, parity, gestational age at blood collection, and pre-pregnancy body mass index (BMI). We identified three distinct trajectory groups in C2, C3, and C4 and two trajectory groups in C5, C10, C5–DC, C8:1, C10:1, and C12, respectively. Women with nonlinear decreasing C12 levels across gestation (5.7%) had offspring with significantly lower birthweight (−475 g; 95% CI, −942, −6.79), birthweight z score (−0.39, −0.71, −0.06), and birth length (−1.38 cm, −2.49, −0.27) than those with persistently stable C12 levels (94.3%) (all nominal p value < 0.05). Women with consistently higher levels of C10 (6.1%) had offspring with thicker sum of skinfolds (4.91 mm, 0.85, 8.98) than did women with lower levels (93.9%) during pregnancy, whereas women with lower C10:1 levels (12.6%) had offspring with thicker sum of skinfolds (3.23 mm, 0.19, 6.27) than did women with abruptly increasing levels (87.4%) (p < 0.05). In conclusion, this study suggests that distinctive trajectories of C10, C10:1, and C12 acylcarnitine levels throughout pregnancy were significantly associated with neonatal anthropometry.

Amino acids, fatty acids, and acylcarnitine metabolites play a pivotal role in maternal and fetal health, but profiles of these metabolites over pregnancy are not completely established. We described longitudinal trajectories of targeted amino acids, fatty acids, and acylcarnitines in pregnancy. We quantified 102 metabolites and combinations (37 fatty acids, 37 amino acids, and 28 acylcarnitines) in plasma samples from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies—Singletons cohort (n = 214 women at 10–14 and 15–26 weeks, 107 at 26–31 weeks, and 103 at 33–39 weeks). We used linear mixed models to estimate metabolite trajectories and examined variation by body mass index (BMI), race/ethnicity, and fetal sex. After excluding largely undetected metabolites, we analyzed 77 metabolites and combinations. Levels of 13 of 15 acylcarnitines, 7 of 25 amino acids, and 18 of 37 fatty acids significantly declined over gestation, while 8 of 25 amino acids and 10 of 37 fatty acids significantly increased. Several trajectories appeared to differ by BMI, race/ethnicity, and fetal sex although no tests for interactions remained significant after multiple testing correction. Future studies merit longitudinal measurements to capture metabolite changes in pregnancy, and larger samples to examine modifying effects of maternal and fetal characteristics.

Abstract Background Increasing recognition has been received regarding the proven and suggested links between multi-level environmental exposures on a broad scale (e.g., chemical, clinical, behavioral, physical and social) and health deficits originated from the critical window of development. However, such prospective human data are limited. In 2016, the National Institutes of Health funded 35 centers comprising 84 extant cohorts for the Environmental Influences on Child Health Outcomes (ECHO) pediatric cohorts program. The Pregnancy Environment and Lifestyle Study (PETALS) is one of the cohorts at the participating centers of Kaiser Permanente Northern California (KPNC). Methods PETALS was originally funded by the National Institute of Environmental Health Sciences to establish a longitudinal birth cohort of 3,350 mother-infant pairs and conduct a nested case–control study of 300 women with gestational diabetes (GDM) and 600 matched controls to investigate the associations between phenol exposures in first and second trimesters and GDM risk and the related outcome of infant macrosomia. This paper describes the prospective cohort design of PETALS, current research activities, and cohort profile of enrolled women who delivered as of February 2016. Women are enrolled from the KPNC membership. Fasting blood draw, urine collection, anthropometric measurements, and questionnaires on health history and lifestyle are completed at baseline and follow-up clinic visits with targeted windows of 10–13 and 16–19 weeks of gestation, respectively. Further, women’s clinical and health assessments before and after the index pregnancy in addition to their children’s birth outcomes and health information can be abstracted from electronic health records, allowing future follow-up. Study data could also be linked and extended to a myriad of additional observational data including environmental and area-level databases and census data. Discussion In this racially- and ethnically-diverse pregnancy cohort, the generated biospecimen and data repository will establish a comprehensive framework which may provide unique opportunities to address a multitude of research questions on the intrauterine environment and adverse pregnancy and birth outcomes in a representative multi-racial/ethnic population with generalizable findings.

BackgroundDespite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM).Methods and findingsWithin the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15-26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42-0.96; P = 0.042) and 33% (0.67; 95% CI 0.45-0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10-14 and DGLA at GWs 10-14 and 15-26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15-26 was associated with a 45% (0.55; 95% CI 0.37-0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (ConclusionsOur findings may suggest a potential role of primarily endogenously metabolized plasma phospholipid n-6 PUFAs including GLA, DGLA, and DTA in early to midpregnancy in the development of GDM. Null findings on primarily diet-derived n-3 EPA and DHA and n-6 LA do not provide strong evidence to suggest a beneficial role in prevention of GDM, although not excluding the potential benefit of EPA and DHA on glucose-insulin homeostasis given the inverse associations with insulin-resistance markers. Our findings highlight the importance of assessing individual circulating PUFAs to investigate their distinct pathophysiologic roles in glucose homeostasis in pregnancy.

Maternal plasma phospholipid polyunsaturated fatty acids (PUFAs) play critical roles in maternal health and fetal development. Beyond dietary factors, maternal moderate-to-vigorous physical activity (MVPA) has been linked to multiple health benefits for both the mother and offspring, but studies investigating the influence of maternal MVPA on maternal PUFA profile are scarce. The objective of present study was to examine the time-specific and prospective associations of MVPA with plasma PUFA profile among pregnant women. This study included 321 participants from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies–Singletons cohort. Maternal plasma phospholipid PUFAs and MPVA were measured at four visits during pregnancy (10–14, 15–26, 23–31, and 33–39 gestational weeks (GW)). Associations of maternal MVPA with individual plasma PUFAs and desaturase activity were examined using generalized linear models. Maternal MVPA was associated inversely with plasma phospholipid linoleic acid, gamma-linolenic acid, and Δ6-desaturase in late pregnancy (23–31 or 33–39 GW), independent of maternal age, race, education, parity, pre-pregnancy body mass index, and dietary factors. Findings from this longitudinal study indicate that maternal habitual MVPA may play a role on PUFAs metabolism, particular by alerting plasma n-6 subclass and desaturase activity in late pregnancy. These associations are novel and merit confirmation in future studies.

Background: Liver enzymes may be implicated in glucose homeostasis; liver enzymes progressively change during pregnancy but longitudinal data during pregnancy in relation to insulin resistance and gestational diabetes (GDM) risk are lacking. We investigated longitudinal associations of γ-glutamyl transferase (GGT) and alanine aminotransferase (ALT) with insulin secretion and resistance markers across early to mid-pregnancy and subsequent GDM risk.Methods: Within the prospective Pregnancy Environment and Lifestyle Study cohort, 117 GDM cases were ascertained and matched to 232 non-GDM controls in a nested case-control study. Fasting blood samples were collected at two clinic visits (CV1, gestational weeks 10–13; CV2, gestational weeks 16–19). Linear mixed model and conditional logistic regression were used, adjusting for major risk factors for GDM.Results: In repeated measure analysis, after adjusting for confounders including body mass index and waist-to-hip ratio, GGT per standard deviation increment was associated with elevated fasting glucose and HOMA-IR (% change = 1.51%, 95% CI 0.56–2.46% and 7.43%, 95% CI 1.76–13.11%, respectively) and decreased adiponectin (% change = −2.86%, 95% CI−5.53 to −0.20%) from CV1 to CV2. At CV1 and CV2, GGT levels comparing the highest versus lowest quartile were associated with 3.01-fold (95% CI 1.32–6.85) and 3.51-fold (95% CI 1.37–8.97) increased risk of GDM, respectively. Progressively increased (

Findings on maternal 25-hydroxyvitamin D (25[OH]D) and neonatal anthropometry are inconsistent, and may at least be partly due to variations in gestational week (GW) of 25(OH)D measurement and the lack of longitudinal 25(OH)D measurements across gestation. The aim of the current study was to examine the associations of longitudinal measures of maternal 25(OH)D and neonatal anthropometry at birth. This study included 321 mother⁻offspring pairs enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies⁻Singletons. This study was a prospective cohort design without supplementation and without data on dietary supplementation. Nevertheless, measurement of plasma 25(OH)D reflects vitamin D from different sources, including supplementation. Maternal concentrations of total 25(OH)D were measured at 10⁻14, 15⁻26, 23⁻31, and 33⁻39 GW and categorized as 75 nmol/L. Generalized linear models were used to examine associations of 25(OH)D at each time-point with neonate birthweight z-score, length, and sum of skinfolds at birth. At 10⁻14 GW, 16.8% and 49.2% of women had 25(OH)D 2), overweight/obese (25.0⁻44.9 kg/m2)). All analyses were stratified by prepregnancy BMI status. Among women with an overweight/obese BMI, 25(OH)D

BACKGROUND: Gestational per- and polyfluoroalkyl substances (PFAS) exposure may be associated with adiposity and increased risk of obesity among children and adolescents. However, results from epidemiological studies evaluating these associations are inconsistent. OBJECTIVES: We estimated the associations of pregnancy PFAS concentrations with child body mass index (BMI) z-scores and risk of overweight/ obesity in eight U.S. cohorts. METHODS: We used data from 1,391 mother–child pairs who enrolled in eight Environmental influences on Child Health Outcomes (ECHO) cohorts (enrolled: 1999–2019). We quantified concentrations of seven PFAS in maternal plasma or serum in pregnancy. We measured child weight and height between the ages of 2 and 5 y and calculated age- and sex-specific BMI 풵-scores; 19.6% children had more than one BMI measurement. We estimated covariate-adjusted associations of individual PFAS and their mixture with child BMI 풵-scores and risk of overweight/obesity using linear mixed models, modified Poisson regression models, and Bayesian approaches for mixtures. We explored whether child sex modified these associations. RESULTS: We observed a pattern of subtle positive associations of PFAS concentrations in pregnancy with BMI 풵-scores and risk of overweight/obesity. For instance, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI 풵-scores (β=0.07; 95% CI: 0.01, 0.12). Each doubling in perfluroundecanoic acid [relative risk (RR)=1.10; 95% CI: 1.04, 1.16] and 푁-methyl perfluorooctane sulfonamido acetic acid (RR=1.06; 95% CI: 1.00, 1.12) was associated with increased risk of overweight/obesity, with some evidence of a monotonic dose–response relation. We observed weaker and more imprecise associations of the PFAS mixture with BMI or risk of overweight/obesity. Associations did not differ by child sex. DISCUSSION: In eight U.S.-based prospective cohorts, gestational exposure to higher levels of PFAS were associated with slightly higher childhood BMI 풵-score and risk of overweight or obesity. Future studies should examine associations of gestational exposure to PFAS with adiposity and related cardiometabolic consequences in older children. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine racial/ethnic disparities in the prevalence of diabetes and prediabetes by BMI category. RESEARCH DESIGN AND METHODS: In a consortium of three U.S. integrated health care systems, 4,906,238 individuals aged ‡20 years during 2012–2013 were included. Diabetes and prediabetes were ascertained by diagnosis and laboratory results; antihyperglycemic medications were also included for diabetes ascertainment. RESULTS: The age-standardized diabetes and prediabetes prevalence estimates were 15.9% and 33.4%, respectively. Diabetes but not prediabetes prevalence increased across BMI categories among all racial/ethnic groups (P for trend < 0.001). Racial/ethnic minorities reached a given diabetes prevalence at lower BMIs than whites; Hawaiians/Pacific Islanders and Asians had a diabetes prevalence of 24.6% (95% CI 24.1–25.2%) in overweight and 26.5% (26.3–26.8%) in obese class 1, whereas whites had a prevalence of 23.7% (23.5–23.8%) in obese class 2. The age-standardized prediabetes prevalence estimates in overweight among Hispanics (35.6% [35.4–35.7%]), Asians (38.1% [38.0–38.3%]), and Hawaiians/Pacific Islanders (37.5% [36.9–38.2%]) were similar to those in obese class 4 among whites (35.3% [34.5–36.0%]), blacks (36.8% [35.5–38.2%]), and American Indians/Alaskan Natives (34.2% [29.6–38.8%]). In adjusted models, the strength of association between BMI and diabetes was highest among whites (relative risk comparing obese class 4 with normal weight 7.64 [95% CI 7.50–7.79]) and lowest among blacks (3.16 [3.05–3.27]). The association between BMI and prediabetes was less pronounced. CONCLUSIONS: Racial/ethnic minorities had a higher burden of diabetes and prediabetes at lower BMIs than whites, suggesting the role of factors other than obesity in racial/ethnic disparities in diabetes and prediabetes risk and highlighting the need for tailored screening and prevention strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND: The National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns. OBJECTIVES: Our aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research. METHODS: We searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring. RESULTS: For the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring. DISCUSSION: The 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals. [ABSTRACT FROM AUTHOR]

Objective Food insecurity is positively associated with asthma, the most common chronic childhood disease, yet directionality is unclear. The objective was to determine the association between exposure to food insecurity in early childhood and the odds of asthma later in childhood. Design Data from four waves of the Early Childhood Longitudinal Study-Kindergarten (ECLS-K) cohort, a prospective, dual-frame, multistage probability cluster sampling study of school-aged US children were entered in multivariate logistic regression models, adjusted for covariates. Exposures to food insecurity were based on parental responses to the validated USDA 18-item module at each wave. Setting Public and private primary and secondary schools between 1998 and 2007. Participants At its inception (1999), the ECLS-K had 20 578 kindergarteners; by the spring of eighth grade (2007), the cohort dropped to 9725 due to attrition. Children missing an exposure, outcome or confounding variable were excluded, final n=6731. Primary outcome measure Child's diagnosis of asthma by a healthcare professional as reported by the parent. Results Household food insecurity (vs food security) in the year before kindergarten and in second grade had a higher odds of asthma by 18% (95% CI 1.17 to 1.20) and 55% (95% CI 1.51 to 1.55). After removing asthmatics before third grade from the model, food insecurity in second grade was associated with higher odds of asthma at fifth or eighth grades (OR 1.55; 95% CI 1.53 to 1.58), whereas food insecurity in the year before kindergarten had a lower odds at fifth or eighth grades. Conclusions Food insecurity in the year before kindergarten and in second grade were associated with a higher odds of asthma in third grade. Food insecurity in second grade retained the signal for increased odds of asthma after third and through eighth grades. Additional research is needed to explore childhood windows of vulnerability to asthma. [ABSTRACT FROM AUTHOR]

Objective: Evaluate whether a tailored letter improved gestational weight gain (GWG) and whether GWG mediated a multicomponent intervention's effect on postpartum weight retention among women with gestational diabetes mellitus (GDM).Research Design and Methods: A cluster-randomized controlled trial of 44 medical facilities (n = 2,014 women) randomized to usual care or a multicomponent lifestyle intervention delivered during pregnancy (tailored letter) and postpartum (13 telephone sessions) to reduce postpartum weight retention. The tailored letter, using electronic health record (EHR) data, recommended an end-of-pregnancy weight goal tailored to prepregnancy BMI and GWG trajectory at GDM diagnosis: total GWG at the lower limit of the IOM range if BMI ≥18.5 kg/m2 or the midpoint if <18.5 kg/m2 and weight maintenance if women had exceeded this. The outcomes for this study were the proportion of women meeting the Institute of Medicine (IOM) guidelines for weekly rate of GWG from GDM diagnosis to delivery and meeting the end-of-pregnancy weight goal.Results: The tailored letter significantly increased the proportion of women meeting the IOM guidelines (72.6% vs. 67.1%; relative risk 1.08 [95% CI 1.01-1.17]); results were similar among women with BMI <25.0 kg/m2 (1.07 [1.00-1.15]) and ≥25.0 kg/m2 (1.08 [0.98-1.18]). Thirty-six percent in the intervention vs. 33.0% in usual care met the end-of-pregnancy weight goal (1.08 [0.99-1.18]); the difference was statistically significant among women with BMI <25.0 kg/m2 (1.28 [1.05-1.57]) but not ≥25.0 kg/m2 (0.99 [0.87-1.13]). Meeting the IOM guidelines mediated the effect of the multicomponent intervention in reducing postpartum weight retention by 24.6% (11.3-37.8%).Conclusions: A tailored EHR-based letter improved GWG, which mediated the effect of a multicomponent intervention in reducing postpartum weight retention. [ABSTRACT FROM AUTHOR]

Objective: To examine whether gestational diabetes mellitus (GDM), independent of subsequent diabetes, is an early risk factor for renal impairment long term after the index pregnancy.Research Design and Methods: In the Diabetes & Women's Health (DWH) study (2012-2016), we examined the independent and joint associations of GDM and subsequent diabetes with long-term renal function among 607 women with and 619 women without GDM in the Danish National Birth Cohort (DNBC) index pregnancy (1996-2002). At median follow-up of 13 years after the index pregnancy, serum creatinine (mg/dL) and urinary albumin (mg/L) and creatinine (mg/dL) were measured, from which estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) and urinary albumin-to-creatinine ratio (UACR) (mg/g) were derived.Results: Compared with women without GDM or subsequent diabetes, women with a GDM history had significantly higher eGFR even if they had not subsequently developed diabetes (adjusted β-coefficient [95% CI] = 3.3 [1.7, 5.0]). Women who had a GDM history and later developed diabetes (n = 183) also had significantly higher UACR [exponent β = 1.3 [95% CI 1.1, 1.6]) and an increased risk of elevated UACR (≥20 mg/g) [adjusted relative risk [95% CI] = 2.3 [1.1, 5.9]) compared with women with neither. After adjusting for potential confounders including prepregnancy BMI and hypertension, GDM without subsequent diabetes was not related to UACR.Conclusions: Women who develop GDM in pregnancy were more likely to show increased eGFR levels 9-16 years postpartum, which could indicate early stages of glomerular hyperfiltration and renal damage. However, only those who subsequently developed diabetes showed overt renal damage as evidenced by elevated UACR. [ABSTRACT FROM AUTHOR]

Background: Extreme ambient temperatures have been linked to preterm birth. Preterm premature rupture of membranes is a common precursor to preterm birth but is rarely studied in relation to temperature.Methods: We linked 15,381 singleton pregnancies with premature rupture of membranes from a nationwide US obstetrics cohort (2002-2008) to local temperature. Case-crossover analyses compared daily temperature during the week preceding delivery and the day of delivery to 2 control periods, before and after the case period. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence intervals (CIs) of preterm and term premature rupture of membranes for a 1°C increase in temperature during the warm (May-September) and cold (October-April) season separately after adjusting for humidity, barometric pressure, ozone, and particulate matter.Results: During the warm season, 1°C increase during the week before delivery was associated with a 5% (95% CI, 3%, 6%) increased preterm premature rupture of membranes risk, and a 4% (95% CI, 3%, 5%) increased term premature rupture of membranes risk. During the cold season, 1°C increase was associated with a 2% decreased risk for both preterm (95% CI, 1%, 3%) and term premature rupture of membranes (95% CI, 1%, 3%). The day-specific associations for the week before delivery were similar, but somewhat stronger for days closer to delivery.Conclusions: Relatively small ambient temperature changes were associated with the risk of both preterm and term premature of membranes. Given the adverse consequences of premature rupture of membranes and concerns over global climate change, these findings merit further investigation. See video abstract at, http://links.lww.com/EDE/B312. [ABSTRACT FROM AUTHOR]

Background: Animal data suggest sexually dimorphic programming of obesity in response to altered intrauterine environment, but the longitudinal impact of gestational diabetes mellitus (GDM) on sex-specific risk of offspring obesity in humans is unclear.Methods: We conducted a prospective analysis of 15 009 US individuals (7946 female and 7063 male) from the Growing-Up Today Study, who were followed from 1996 (ages 9-14 years) through 2010. Height and weight from validated questionnaires were used to derive body mass index (BMI) at different ages. Obesity during childhood (< 18 years) and adulthood (≥ 18 years) were defined using the International Obesity Task Force and the World Health Organization criteria. GDM exposure was identified through self-reported questionnaires from mothers. Relative risks were estimated using multivariable log-binomial regression models with generalized estimating equations accounting for clustering within the same family.Results: Male offspring born from pregnancies complicated by GDM had higher BMI compared with non-GDM offspring and had increased risk of obesity; the adjusted relative risk [RR, 95% confidence interval (CI)] was 1.47 (1.11-1.95) for all age groups, 1.59 (1.05-2.41) for late childhood, 1.48 (1.06-2.06) for adolescence and 1.39 (1.00-1.94) for early adulthood. No significant association between obesity and maternal GDM was observed among female participants (RR = 0.97, 95% CI: 0.71-1.33).Conclusions: The association of GDM with offspring obesity from late childhood through early adulthood may differ by sex; a significant association was observed among male but not female offspring. [ABSTRACT FROM AUTHOR]

Background: Artificial sweeteners are widely replacing caloric sweeteners. Data on long-term impact of artificially sweetened beverage (ASB) consumption during pregnancy on offspring obesity risk are lacking. We prospectively investigated intake of ASBs and sugar-sweetened beverages (SSBs) during pregnancy in relation to offspring growth through age 7 years among high-risk children born to women with gestational diabetes.Methods: In a prospective study of 918 mother-singleton child dyads from the Danish National Birth Cohort, maternal dietary intake was assessed by a food frequency questionnaire during pregnancy. Offspring body mass index z-scores (BMIZ) and overweight/obesity status were derived using weight and length/height at birth, 5 and 12 months and 7 years. Linear regression and Poisson regression with robust standard errors were used, adjusting for major risk factors.Results: Approximately half of women reported consuming ASBs during pregnancy and 9% consumed daily. Compared to never consumption, daily ASB intake during pregnancy was positively associated with offspring large-for-gestational age [adjusted relative risk (aRR) 1.57; 95% CI: 1.05, 2.35 at birth], BMIZ (adjusted β 0.59; 95% CI: 0.23, 0.96) and overweight/obesity (aRR 1.93; 95% CI; 1.24, 3.01) at 7 years. Per-serving-per-day substitution of ASBs with water during pregnancy was related to a lower overweight/obesity risk at 7 years (aRR 0.83; 95% CI: 0.76, 0.91), whereas SSB substitution with ASBs was not related to a lower risk (aRR 1.14; 95% CI: 1.00, 1.31).Conclusions: Our findings illustrated positive associations between intrauterine exposure to ASBs and birth size and risk of overweight/obesity at 7 years. Data with longer follow-up are warranted. [ABSTRACT FROM AUTHOR]

Background: Self-report is often used in identifying gestational diabetes events in epidemiologic studies; however, validity data are limited, with little to no data on self-reported severity or treatment.Methods: We aimed to assess the validity of self-reported gestational diabetes diagnosis and evaluate the accuracy of glucose diagnosis results and gestational diabetes treatment self-reported at 6-week postpartum. Data were from 82 and 83 women with and without gestational diabetes, respectively, within the prospective National Institute Child Health and Human Development Fetal Growth Studies-Singletons (2009-2013). Medical record data were considered the gold standard.Results: Sensitivity was 95% (95% confidence interval [CI] = 88, 98), and specificity was 100% (95% CI = 96, 100); four women with gestational diabetes incorrectly reported not having the disease, and none of the women without gestational diabetes reported having gestational diabetes. Sensitivity did not vary substantially across maternal characteristics including race/ethnicity. For women who attempted to recall their values (84/159 women), self-reported glucose challenge test results did not differ from the medical records (median difference: 0; interquartile range: 0-0 mg/dl). Medical records indicated that 42 (54%) of 78 women with confirmed gestational diabetes were treated by diet only and 33 (42%) were treated by medication. All 42 women with diet-treated gestational diabetes correctly reported having had diet and lifestyle modification, and 28 (85%) of 33 women with medication-treated gestational diabetes indicated postpartum that they had medication treatment.Conclusions: At 6-week postpartum, regardless of race/ethnicity or socioeconomic status, women accurately recalled whether they had gestational diabetes and, as applicable, their treatment method. [ABSTRACT FROM AUTHOR]

Air pollution has been linked to hypertension in the general population, but data on gestational hypertension (GH) are limited. We investigated criteria air pollutants and air toxics during the period before conception and in early gestation in relation to GH risk in the Consortium on Safe Labor/Air Quality and Reproductive Health Study (United States, 2002-2008). Modified Community Multi-scale Air Quality models estimated air pollution exposures for 6,074 singleton pregnancies in which GH was present and 199,980 normotensive pregnancies. Generalized estimating equations estimated relative risks per interquartile-range increment for pollutants and high exposure (≥75th percentile) for air toxics after adjustment for major risk factors. For an interquartile-range increment, GH risk was significantly increased by 18% for sulfur dioxide during the 3 months before conception and, during gestational weeks 1-20, 17% for nitrogen oxides, 10% for particulate matter with an aerodynamic diameter <2.5 µm, 7% for particulate matter with an aerodynamic diameter <10 µm, and 22% for sulfur dioxide. High exposures to several polycyclic aromatic hydrocarbons before conception and during the first trimester were significantly associated with 8%-20% higher risk of GH. Further, preconceptional exposures to several volatile organic compounds were significantly associated with 11%-19% higher risk. Our findings suggest that early exposures to criteria air pollutants, particularly from transport emissions, and high exposure to several air toxics before conception may increase GH risk. [ABSTRACT FROM AUTHOR]

Background: Refined grains, a major source of dietary carbohydrates, have been related to impaired glucose homeostasis and obesity. Emerging animal data suggest that in utero exposure to dietary refined carbohydrates may predispose offspring to an obese phenotype, indicating a potential role for nutritional programming in the early origins of obesity, but intergenerational human data are lacking. Objective: We prospectively investigated refined-grain intake during pregnancy in association with offspring growth through age 7 y among high-risk children born to women with gestational diabetes mellitus (GDM). Design: The analysis included 918 mother-singleton child dyads from the Danish National Birth Cohort. Offspring body mass index z scores (BMIZs) were calculated by using weight and length or height measured at birth, 5 and 12 mo, and 7 y. Overweight or obesity was defined by WHO cutoffs. Linear and Poisson regressions were used, with adjustment for maternal demographic, lifestyle, and dietary factors. Results: Refined-grain intake during pregnancy was positively associated with offspring BMIZ (adjusted β per serving increase per day: 0.09; 95% CI: 0.02, 0.15) and risk of overweight or obesity at age 7 y [adjusted RR (aRR) comparing the highest with the lowest quartile: 1.80; 95% CI: 1.09, 2.98; P-trend = 0.032]. The association appeared to be more pronounced among children who were breastfed <6 mo. The substitution of 1 serving refined grains/d with an equal serving of whole grains during pregnancy was related to a 10% reduced risk of offspring overweight or obesity at 7 y of age (aRR: 0.90; 95% CI: 0.82, 0.98). No associations were observed between refined-grain intake and infant growth. Conclusions: Higher maternal refined-grain intake during pregnancy was significantly related to a greater BMIZ and a higher risk of overweight or obesity at age 7 y among children born after pregnancies complicated by GDM. The findings highlight pregnancy as a potential window of susceptibility associated with off-spring growth and obesity risk among this high-risk population. Data with longer follow-up are warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Climate change is expected to have adverse health effects, but the association between extreme ambient temperatures and stillbirth is unclear. OBJECTIVES: We investigated acute and chronic associations between extreme ambient temperatures and stillbirth risk, and estimated the attributable risk associated with local temperature extremes in the United States. METHODS: We linked 223,375 singleton births ≥23 weeks of gestation (2002-2008) from 12 U.S. sites to local temperature. Chronic exposure to hot (>90th percentile), cold (<10th percentile), or mild (10th-90th percentile) temperatures was defined using window- and site-specific temperature distributions for three-months preconception, first and second trimester, and whole-pregnancy averages. For acute exposure, average temperature for the week preceding delivery was compared to two alternative control weeks in a case-crossover analysis. RESULTS: In comparison with mild, whole-pregnancy exposure to cold [adjusted odds ratio (aOR) = 4.75; 95% confidence interval (CI): 3.95, 5.71] and hot (aOR = 3.71; 95% CI: 3.07, 4.47) were associated with stillbirth risk, and preconception and first and second trimester exposures were not. Approximately 17-19% of stillbirth cases were potentially attributable to chronic whole-pregnancy exposures to local temperature extremes. This is equivalent to ∼1,116 cold-related and ∼1,019 hot-related excess cases in the United States annually. In the case-crossover analysis, a 1°C increase during the week preceding delivery was associated with a 6% (3-9%) increase in stillbirth risk during the warm season (May-September). This incidence translates to ∼4 (2-6) additional stillbirths per 10,000 births for each 1°C increase. CONCLUSIONS: Extremes of local ambient temperature may have chronic and acute effects on stillbirth risk, even in temperate zones. Temperature-related effects on pregnancy outcomes merit additional investigation. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether prepregnancy obesity is associated with adverse pregnancy outcomes among women without chronic disease.Methods: Singleton deliveries (N=112,309) among mothers without chronic diseases in the Consortium on Safe Labor, a retrospective U.S. cohort, were analyzed using Poisson regression with robust variance estimation. Relative risks and 95% confidence intervals (CIs) estimated perinatal risks in relation to prepregnancy obesity status adjusted for age, race-ethnicity, parity, insurance, smoking and alcohol use during pregnancy, and study site.Results: Obstetric risks were variably (and mostly marginally) increased as body mass index (BMI) category and obesity class increased. In particular, the risk of gestational hypertensive disorders, gestational diabetes, cesarean delivery, and induction increased in a dose-response fashion. For example, the percentage of gestational diabetes among obese class III women was 14.6% in contrast to 2.8% among women with normal BMIs (corresponding relative risks [95% CI] 1.99 [1.86-2.13], 2.94 [2.73-3.18], 3.97 [3.61-4.36], and 5.47 [4.96-6.04] for overweight, obese class I, obese class II, and obese class III women, respectively) compared with women with normal BMIs. Similarly, neonatal risks increased in a dose-response fashion with maternal BMI status including preterm birth at less than 32 weeks of gestation, large for gestational age (LGA), transient tachypnea, sepsis, and intensive care unit admission. The percentage of LGA neonates increased from 7.9% among women with normal BMIs to 17.3% among obese class III women and relative risks increased to 1.52 (1.45-1.58), 1.74 (1.65-1.83), 1.93 (1.79-2.07), and 2.32 (2.14-2.52) as BMI category increased.Conclusion: Prepregnancy obesity is associated with increased risks of a wide range of adverse pregnancy and neonatal outcomes among women without chronic diseases. [ABSTRACT FROM AUTHOR]

Premature rupture of membranes (PROM) is a major factor that predisposes women to preterm delivery. Results from previous studies have suggested that there are associations between exposure to air pollution and preterm birth, but evidence of a relationship with PROM is sparse. Modified Community Multiscale Air Quality models were used to estimate mean exposures to particulate matter less than 10 um or less than 2.5 um in aerodynamic diameter, nitrogen oxides, carbon monoxide, sulfur dioxide, and ozone among 223,375 singleton deliveries in the Air Quality and Reproductive Health Study (2002-2008). We used log-linear models with generalized estimating equations to estimate adjusted relative risks and 95% confidence intervals for PROM per each interquartile-range increase in pollutants across the whole pregnancy, on the day of delivery, and 5 hours before delivery. Whole-pregnancy exposures to carbon monoxide and sulfur dioxide were associated with an increased risk of PROM (for carbon monoxide, relative risk (RR) = 1.09, 95% confidence interval (CI): 1.04, 1.14; for sulfur dioxide, RR= 1.15, 95% CI: 1.06,1.25) but not preterm PROM. Ozone exposure increased the risk of PROM on the day of delivery (RR = 1.06, 95% CI: 1.02, 1.09) and 1 day prior (RR = 1.04, 95% CI: 1.01, 1.07). In the 5 hours preceding delivery, there were 3%-7% increases in risk associated with exposure to ozone and particulate matter less than 2.5 um in aerodynamic diameter and inverse associations with exposure to carbon monoxide and nitrogen oxides. Acute and long-term air pollutant exposures merit further study in relation to PROM. [ABSTRACT FROM AUTHOR]

Women who developed gestational diabetes mellitus represent a high-risk population for hypertension later in life. The role of diet in the progression of hypertension among this susceptible population is unknown. We conducted a prospective cohort study of 3818 women with a history of gestational diabetes mellitus in the Nurses' Health Study II as part of the ongoing Diabetes & Women's Health Study. These women were followed-up from 1989 to 2011. Incident hypertension was identified through self-administered questionnaires that were validated previously by medical record review. Adherence scores for the alternative Healthy Eating Index 2010, the alternative Mediterranean diet, and the Dietary Approaches to Stop Hypertension were computed for each participant. Cox proportional hazard models were used to evaluate the associations between dietary scores and hypertension while adjusting for major risk factors for hypertension. We documented 1069 incident hypertension cases during a median of 18.5 years of follow-up. After adjustment for major risk factors for hypertension, including body mass index, alternative Healthy Eating Index 2010, alternative Mediterranean diet, and Dietary Approaches to Stop Hypertension scores were significantly inversely associated with the risk of hypertension; hazard ratio and 95% confidence interval comparing the extreme quartiles (highest versus lowest) were 0.76 (0.61-0.94; P for linear trend =0.03) for AHEI score, 0.72 (0.58-0.90; P for trend =0.01) for Dietary Approach to Stop Hypertension score, and 0.70 (0.56-0.88; P for trend =0.002) for alternative Mediterranean diet score. Adherence to a healthful dietary pattern was related to a lower subsequent risk of developing hypertension among women with a history of gestational diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Given the long-term adverse sequelae of childhood obesity, identification of early life factors related to fetal growth and childhood obesity is warranted. Investigation on growth and obesity in early life in association with intrauterine exposure to maternal hyperglycemia, a common metabolic pregnancy complication, is of public health significance and clinical implications. Objective: We investigated the association of fasting plasma glucose (FPG) concentrations during pregnancy with offspring growth and risk of overweight/obesity through age 7 y, after adjustment for confounders, including maternal prepregnancy obesity status. Design: FPG concentrations at 28 gestational weeks (IQR: 22-32 wk) were extracted from medical records for 661 pregnancies complicated by gestational diabetes mellitus in the Danish National Birth Cohort (1996-2002). Offspring's ponderal index was derived from birth weight and length; age- and sex-specific body mass index (BMI) z scores at 5 mo, 12 mo, and 7 y were calculated based on WHO reference data. Relations between FPG and offspring growth and obesity were assessed by linear and Poisson regression with robust standard errors, adjusting for maternal prepregnancy BMI and sociodemographic and perinatal factors. Results: At birth, maternal FPG during pregnancy was significantly associated with offspring ponderal index (β = 0.46; 95% CI: 0.14, 0.78 per 1-mmol/L increase) and risk of macrosomia (birth weight >4000 g) (RR = 1.21; 95% CI: 1.07, 1.38 per 1-mmol/L increase). At 7 y, higher maternal FPG concentrations were significantly associated with increased BMI z scores (β = 0.20; 95% CI: 0.04, 0.36) and elevated risk of overweight/obesity (RR = 1.21; 95% CI: 1.01, 1.50). Additional adjustment for birth weight and childhood lifestyle factors did not appreciably alter results. No associations were observed at 5 or 12 mo. Conclusion: Among women with gestational diabetes mellitus, maternal FPG concentrations during pregnancy were significantly and positively associated with offspring birth size and overweight/obesity risk at 7 y, adjusting for maternal prepregnancy BMI. [ABSTRACT FROM AUTHOR]

Objective: Low-carbohydrate diets (LCDs) may improve short-term glycemic control in patients with gestational diabetes mellitus (GDM), but the long-term effect on progression from GDM to type 2 diabetes mellitus (T2DM) is unknown. We aimed to examine the long-term risk of T2DM in association with a low-carbohydrate dietary pattern among women with a history of GDM.Research Design and Methods: Overall, 4,502 women with a history of GDM from the Nurses' Health Study II (NHSII) cohort, as part of the Diabetes & Women's Health (DWH) study, were followed up from 1991 to 2011. Overall, animal, or vegetable LCD scores, which represent adherence to different low-carbohydrate dietary patterns, were calculated using diet intake information assessed every 4 years since 1991 by validated food-frequency questionnaires. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs.Results: We documented 722 incident cases of T2DM during 68,897 person-years of observation. The multivariable-adjusted HRs (95% CIs) of T2DM, comparing the highest with lowest quintiles, were 1.36 (1.04-1.78) for overall LCD score (P = 0.003 for trend), 1.40 (1.06-1.84) for animal LCD score (P = 0.004 for trend), and 1.19 (0.91-1.55) for vegetable LCD score (P = 0.50 for trend).Conclusions: Among women with a history of GDM, a low-carbohydrate dietary pattern, particularly with high protein and fat intake mainly from animal-source foods, is associated with higher T2DM risk, whereas a low-carbohydrate dietary pattern with high protein and fat intake from plant-source foods is not significantly associated with risk of T2DM. [ABSTRACT FROM AUTHOR]

Background The relationship between gestational weight gain (GWG) and childhood growth remains controversial. An examination on whether infant feeding practices mediate this relationship may improve our understanding of it. Methods We investigated whether the relationships among GWG, birth weight and childhood anthropometrics were mediated through infant feeding practices (breastfeeding duration and age at introduction of solid foods) in a cross-sectional multiethnic study of 1387 mothers and their children aged 0-5.9 years in the USA (2011-2012). Child anthropometrics included age-specific and sex-specific z-scores for weight-for-age (WAZ), height/length-for-age (HAZ), weight-for-height/length (WHZ) and body mass index-for-age (BMIZ); and ulnar length, a marker for limb growth. We used structural equation modelling to calculate standardised path coefficients and total, direct and indirect associations of GWG, birth weight and infant feeding practices with child anthropometrics. Results Maternal GWG had a positive indirect association with all anthropometrics mediated via birth weight, whereas longer breastfeeding duration reduced the positive associations of GWG and birth weight with WAZ, WHZ and BMIZ in non-Hispanics (β=-0.077, -0.064 and -0.106, respectively). Longer breastfeeding duration and introducing solid foods at a later age were positively associated with ulnar length (β=0.023 and 0.030, respectively) but not HAZ, suggesting a distinct association, for the first time, with limb growth. Conclusions Findings suggest that promoting longer breastfeeding duration among women with excessive GWG who had high birthweight newborns may mitigate the potential for their offspring to develop obesity. In addition, findings reinforce the importance of promoting appropriate GWG and preventing high birth weight, which are positively associated with childhood anthropometrics. [ABSTRACT FROM AUTHOR]

Surrogate measures are needed when recumbent length or height is unobtainable or unreliable. Arm span has been used as a surrogate but is not feasible in children with shoulder or arm contractures. Ulnar length is not usually impaired by joint deformities, yet its utility as a surrogate has not been adequately studied. In this cross-sectional study, we aimed to examine the accuracy and reliability of ulnar length measured by different tools as a surrogate measure of recumbent length and height. Anthropometrics [recumbent length, height, arm span, and ulnar length by caliper (ULC), ruler (ULR), and grid (ULG)] were measured in 1479 healthy infants and children aged <6 y across 8 study centers in the United States. Multivariate mixed-effects linear regression models for recumbent length and height were developed by using ulnar length and arm span as surrogate measures. The agreement between the measured length or height and the predicted values by ULC, ULR, ULG, and arm span were examined by Bland-Altman plots. All 3 measures of ulnar length and arm span were highly correlated with length and height. The degree of precision of prediction equations for length by ULC, ULR, and ULG (R² = 0.95, 0.95, and 0.92, respectively) was comparable with that by arm span (R² = 0.97) using age, sex, and ethnicity as covariates; however, height prediction by ULC (R² = 0.87), ULR (R² = 0.85), and ULG (R² = 0.88) was less comparable with arm span (R² = 0.94). Our study demonstrates that arm span and ULC, ULR, or ULG can serve as accurate and reliable surrogate measures of recumbent length and height in healthy children; however, ULC, ULR, and ULG tend to slightly overestimate length and height in young infants and children. Further testing of ulnar length as a surrogate is warranted in physically impaired or nonambulatory children. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between age at menarche and risk of gestational diabetes mellitus (GDM).Research Design and Methods: A prospective cohort study of 42,109 eligible pregnancies from 27,482 women in the Nurses' Health Study II.Results: The adjusted risk ratios for GDM across the age at menarche categories (≤11, 12, 13, and ≥14 years) were 1.34 (95% CI 1.14-1.58), 1.13 (0.97-1.31), 1.11 (0.95-1.29), and 1.00 (referent; P for trend = 0.0005), respectively. Analysis of the mediating effect indicated that 42.1% (P = 0.0007) of the association was mediated through prepregnancy BMI.Conclusions: These findings suggested that earlier menarche was significantly associated with an increased risk of GDM. This association was largely mediated through prepregnancy excessive body adiposity. [ABSTRACT FROM AUTHOR]