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Background Plasma phospholipid fatty acids (FAs) in early and mid-pregnancy have been prospectively related to gestational diabetes mellitus (GDM) risk. Yet, changes of FAs following GDM diagnosis and treatment and their implications for glucose metabolism and control remain understudied. Methods From the Eunice Kennedy Shriver National Institute Child Health and Human Development Fetal Growth Studies–Singleton Cohort of 2802 pregnant women, we ascertained 85 GDM cases using the Carpenter and Coustan criteria and 85 non-GDM controls after exclusion. Using plasma collected before (23–31 weeks) and after GDM diagnosis (33–39 weeks), we quantified 25 saturated, poly- and monounsaturated FAs levels. We estimated the fold change of FAs before and after GDM diagnosis, using multiple linear mixed models adjusting for confounders. Results Eight FAs showed significant fold changes from the baseline values (23–31 weeks) among GDM cases as compared to women without GDM. Five FAs showed reduced fold changes [myristic acid (14:0): β: −0.22 (95% CI: −0.30, −0.14), palmitic acid (16:0): β: −0.02 (95% CI: −0.04, −0.01), cis-palmitoleic acid (16:1n7): β: −0.15 (95% CI: −0.24, −0.05), alpha-linolenic acid (18:3n3): β: −0.19 (95% CI: −0.31, −0.07], and dihomo-gamma-linoleic acid (20:3n6): β:−0.16; 95% CI: −0.21, −0.11)], whereas 3 showed increases [heptadecanoic acid (17:0): β: 0.17 (95% CI: 0.11, 0.22), cis-vaccenic acid (18:1n7): β: 0.06 (95% CI: 0.03, 0.10), and arachidonic acid (20:4n6): β: 0.10 (95% CI: 0.06, 0.13)]. Conclusions Our study identified 8 FAs with unique patterns of change before and after GDM diagnosis that differed significantly between women with and without GDM. Our findings may shed light on the role of FA metabolism in the pathophysiology and disease management and progression of GDM. Clinical Trial Registry NCT00912132

RATIONALE Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset. OBJECTIVES To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association. METHODS We studied 8,716 children between ages 6 and 18.5 years who were nonobese at study entry participating in 18 US cohorts of the Environmental influences on Child Health Outcomes program (among 7,299 children with complete covariate data mean [SD] study entry age = 7.2 [1.6] years and follow up = 5.3 [3.1] years). MEASUREMENTS AND MAIN RESULTS We defined asthma based on caregiver report of provider diagnosis. Incident obesity was defined as the first documented body mass index ≥95th percentile for age and sex following asthma status ascertainment. Over the study period, 26% of children had an asthma diagnosis and 11% developed obesity. Cox proportional hazards models with sex-specific baseline hazards were fitted to assess the association of asthma diagnosis with obesity incidence. Children with asthma had a 23% (95% confidence intervals [CI] = 4, 44) higher risk for subsequently developing obesity compared with those without asthma. A novel mediation analysis was also conducted to decompose the total asthma effect on obesity into pathways mediated and not mediated by asthma medication use. Use of asthma medication attenuated the total estimated effect of asthma on obesity by 64% (excess hazard ratios = 0.64; 95% CI = -1.05, -0.23). CONCLUSIONS This nationwide study supports the hypothesis that childhood asthma is associated with later risk of obesity. Asthma medication may reduce this association and merits further investigation as a potential strategy for obesity prevention among children with asthma.

Summary Background & aims Prospective and longitudinal data on the association between acylcarnitines and gestational diabetes (GDM) are lacking. This study aims to prospectively investigate 28 acylcarnitines in relation to subsequent GDM risk. Methods Within the NICHD Fetal Growth Studies-Singleton Cohort, plasma levels of acylcarnitines and cardiometabolic biomarkers were measured at gestational week (GW) 10–14, 15–26, 23–31, and 33–39 among 107 GDM cases and 214 controls. Results At GW 10–14, per standard deviation (SD) increased level of C14:1-OH was associated with a 55% increased risk of GDM after adjusting for major risk factors for GDM [OR (95% CI): 1.55 (1.05–2.29)]. At GW 15–26, C4, C8:1 and C16:1-OH were associated with an increased risk of GDM [OR (95% CI) for per SD increase: 1.42 (1.01–2.00), 1.41 (1.02–1.96), and 1.77 (1.10–2.84), respectively]. Whereas increased C10 and C18 were related to lower risk of GDM [OR (95% CI) for per SD increase: 0.74 (0.55–1.00), and 0.69 (0.49–0.97), respectively]. Moreover, we observed correlations of individual acylcarnitine with multiple clinical markers implicated in glucose homeostasis and cardiometabolic function among non-GDM women. Conclusions Our results demonstrate that several plasma acylcarnitine species are differentially associated with GDM risk by chain length. Future studies are warranted to investigate the distinct roles of individual acylcarnitine in glucose homeostasis in pregnancy.

BACKGROUND: Maternal nutrition during pregnancy has a significant effect on the health of the offspring and mother, highlighting the need for identifying factors that may impact diet during pregnancy. Research in non-pregnant and pregnant populations suggest depression may play a role. OBJECTIVE: Investigate the relationship between prenatal depression and diet quality during pregnancy overall and by race/ethnicity and explore the relationships between prenatal depression and the 12 Healthy Eating Index (HEI-2010) dietary components. DESIGN: A cross-sectional secondary analysis of a cohort study of Kaiser Permanente Northern California women entering prenatal care between October 2011 and April 2013. PARTICIPANTS/SETTING: Participants included 1,160 adult pregnant women. MAIN OUTCOME MEASURES: Poor diet quality was defined as a HEI-2010 score in the lowest quartile. STATISTICAL ANALYSES PERFORMED: Logistic regression was used to assess the relationship between prenatal depression (defined as a depression diagnosis, PHQ-9 score of 10 or greater or antidepressant medication dispensing between the last menstrual period and completion of the FFQ) and poor diet quality overall and by race/ethnicity. T-tests and linear regression analyses were used to assess the relationships between prenatal depression and each of the 12 HEI-2010 dietary components. RESULTS: 159 (14%) of the participants had prenatal depression. Women with prenatal depression had nearly two times the odds of poor diet quality (OR:1.80;95%CI:1.23,2.60) compared to women without prenatal depression, after adjusting for potential confounders. Differences emerged by race/ethnicity; after adjusting for potential confounders the adjusted odds of poor diet quality were significant only among Hispanic women. Hispanic women with prenatal depression had an increased odds of poor diet quality compared to Hispanic women without prenatal depression (OR:2.66, 95%CI:1.15,6.06). Women with prenatal depression had a higher consumption of empty calories (from solid fats, alcohol, and added sugars; threshold for counting alcohol is greater than 13g/1,000 kcal ) (p=0.01) and lower consumption of greens and beans (p

This cohort study uses data from the Nurses’ Health Study II to assess the association between habitual alcohol consumption and subsequent risk for type 2 diabetes among women with a history of gestational diabetes., Key Points Question Among women with a history of gestational diabetes, is there an association of habitual alcohol intake with subsequent risk for type 2 diabetes? Findings In this cohort study of 4740 women with a history of gestational diabetes, after adjustment for major dietary and lifestyle factors and body mass index, women who consumed 5.0-14.9 g/d had a 41% lower risk for developing incident type 2 diabetes compared with those who did not consume any alcohol. Meaning These findings should be interpreted in the context of other known risks and benefits of alcohol consumption when considering clinical recommendations for individual women with a history of gestational diabetes., Importance Women with gestational diabetes are at high risk for type 2 diabetes. Identifying modifiable dietary and lifestyle factors, such as alcohol intake, that can be useful in delaying or preventing progression to overt type 2 diabetes is of particular interest. Objective To evaluate the association between alcohol consumption and risk for type 2 diabetes among women with a history of gestational diabetes. Design, Setting, and Participants This cohort study included women from the Nurses’ Health Study II cohort who reported a history of gestational diabetes and were followed up from January 1, 1991, to December 31, 2017, as part of the Diabetes & Women’s Health Study. Data analysis was performed from 2020 to 2021. Exposures Dietary intakes, including alcohol, were assessed every 4 years using validated food-frequency questionnaires. Main Outcomes and Measures Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for the association of alcohol intake with risk for incident type 2 diabetes after a pregnancy during which gestational diabetes was diagnosed. Results A total of 4740 women were included in the study; the mean (SD) age at baseline was 38.2 (5.0) years, and the median follow-up time was 24 years (interquartile range, 18-28 years), resulting in 78 328 person-years of follow-up. During this period, 897 incident cases of type 2 diabetes were reported. After adjustment for major dietary and lifestyle factors, compared with women who did not consume any alcohol, only alcohol consumption of 5.0 to 14.9 g/d was associated with decreased risk for incident type 2 diabetes (HR, 0.45; 95% CI, 0.33-0.61); there was no association of alcohol consumption of 0.1 to 4.9 g/d or 15.0 g/d or more (maximum, 74.2 g/d) with risk of type 2 diabetes (0.1 to 4.9 g/d: HR, 0.87 [95% CI, 0.73-1.03]; ≥15.0 g/d: HR, 0.62 [95% CI, 0.37-1.04]). After additional adjustment for body mass index, women who reported alcohol consumption of 5.0 to 14.9 g/d had a 41% lower risk for developing incident type 2 diabetes (HR, 0.59; 95% CI, 0.42-0.81); consumption of 0.1 to 4.9 g/d and consumption of 15.0 g/d or more were still not associated with risk of type 2 diabetes, but the results were attenuated (0.1-4.9 g/d: HR, 1.02 [95% CI, 0.85-1.23]; ≥15.0 g/d: HR, 0.75 [95% CI, 0.42-1.33]). Conclusions and Relevance In this cohort study, among women with a history of gestational diabetes, usual alcohol intake of 5.0 to 14.9 g/d (approximately 0.5-1 drinks per day) was associated with a lower risk for type 2 diabetes. These findings should be interpreted in the context of other known risks and benefits of alcohol consumption when considering clinical recommendations for individual women with a history of gestational diabetes.

OBJECTIVES: Both inadequate and excessive intake of micronutrients in pregnancy have the potential to negatively impact child health outcomes. We examined micronutrient intake in a large, diverse sample of women with singleton pregnancies across the United States, including intake by maternal age, race/ethnicity, education, and pre-pregnancy body mass index (BMI). METHODS: Fifteen observational cohorts in the Environmental influences on Child Health Outcomes (ECHO) consortium assessed prenatal food intake and dietary supplement use with 24-hour dietary recalls (5 cohorts; 1859 women) or food frequency questionnaires (10 cohorts; 8064 women) from 1999–2019. We compared mean daily intake of 19 micronutrients to the age-specific estimated average requirement (EAR), adequate intake (AI), and tolerable upper intake level (UL) for pregnancy, overall and within sociodemographic and anthropometric subgroups. For recall data, we used a measurement error method to estimate distributions of usual intake, proportion below the EAR/AI, and above the UL. For FFQ data, we calculated the proportion below the EAR/AI and above the UL. RESULTS: Risk of inadequate intake from foods alone ranged from 0–93%, depending on the micronutrient or assessment method. With dietary supplements, more than 1 in 5 women remained at risk for inadequate intake of choline, magnesium, and vitamins D, E, and K; or excessive intake of folic acid, iron, and zinc. Higher risks for inadequate intakes were observed among women with obesity (magnesium, vitamin K), who were

Background: Previous studies have shown that phospholipids fatty acid (FA) levels in early and mid-pregnancy were associated with incident gestational diabetes mellitus (GDM). However, the subsequent changes of such FAs profile following GDM diagnosis/treatment are understudied. Methods: Within the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort of 2,802 pregnant women, we ascertained 85 GDM cases according to Carpenter and Coustan criteria, and 85 non-GDM controls matched on maternal age, race/ethnicity, and gestational week at voluntary blood collection. We quantified participants’ plasma FAs concentrations via gas chromatography prior to GDM diagnosis (23-31 weeks) and after GDM treatment initiation (33-39 weeks), respectively. We estimated the GDM-specific FAs changes before and after GDM diagnosis, in reference to the controls using multiple linear mixed models adjusting for major confounders including pre-pregnancy BMI. Results: Eleven FAs exhibited distinctive pre- and post-GDM diagnosis changes among GDM cases. Compared with controls, GDM cases tended to have greater reduction in GDM risk-related FAs such as 14:0 (β -0.22; 95% CI: -0.30, -0.14), 16:0 (-0.02; -0.04, -0.01) and palmitoleic acid (16:1n7) (-0.02; -0.04, -0.01), while greater increment in GDM protective FAs such as heptadecanoic acid (17:0) (0.17; 0.11, 0.22), vaccenic acid (18:1n7) (0.06; 0.03, 0.10) and DHA (22:6n3) (0.08; 0.02, 0.15). Conclusion: Our data identified distinctive FAs changes between pre- and post GDM diagnosis among GDM subjects. These novel findings, along with prior evidence between antenatal FAs and incident GDM, shed lights on further understanding the FAs metabolism in the GDM etiological relevance. Disclosure L. Li: None. Y. Zhu: None. J. Wu: None. D. K. Tobias: None. S. Hinkle: None. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. M. Y. Tsai: None. C. Zhang: None. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development(HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C, HHSN275201000001Z)

Gestational diabetes (GDM) predisposes 7-10% of pregnant women in the U.S. to a myriad of adverse health sequelae. Early prediction is critical. By leveraging metabolomics and clinical data, we aimed to develop and validate predictive metabolic signatures in early to mid-pregnancy for GDM. In a nested matched case-controls study of 91 women with GDM and 180 non-GDM controls in the Pregnancy Environment and Lifestyle Study (PETALS) cohort (discovery set), 157 annotated primary metabolites were measured by gas chromatography/time-of-flight mass spectrometry using fasting serum at gestational weeks (GW) 10-13 and 16-19. Machine learning algorithm using 10-fold cross validated Lasso regression identified predictive metabolomics signatures for GDM risk in the discovery set. We validated the signature at GW 10-13 in a random PETALS subsample (42 GDM, 372 non-GDM; validation set 1) and a matched case-control study within the GLOW trial of overweight/obese women (35 GDM, 70 non-GDM; validation set 2) and the signature at GW 16-19 in validation set 1. Upregulated aromatic and acidic amino acids and purinones at both GW 10-13 and 16-19 and additionally hexoses at GW 16-19 were significantly associated with GDM risk (FDR-adjusted P Disclosure Y. Zhu: None. A. Ngo: None. S. Fan: None. D. Barupal: None. C. Quesenberry: None. O. Fiehn: None. A. Ferrara: None. Funding National Institutes of Health (K12HD052163); National Institute of Diabetes and Digestive and Kidney Diseases (K01DK120807)

Background Weight extremes and food insecurity (FIS) represent public-health challenges, yet their associations in childhood remain unclear. We aimed to investigate the longitudinal time-specific relationship between FIS and risk of overweight/obesity and underweight in kindergarten through 8th grade. Methods In the prospective Early Childhood Longitudinal Study–Kindergarten Cohort (1998–2007) of 6368 children, household FIS was assessed by the validated US Household Food Security Survey Module in kindergarten, 3rd, 5th and 8th grades. Multivariable linear-regression and Poisson-regression models were computed. Results Compared with children experiencing food security (FS), children exposed to FIS in 5th grade had 0.19 [95% confidence interval (CI): 0.07–0.30] and 0.17 (0.06–0.27) higher body mass index z-score (BMIZ) in the 5th and 8th grades, respectively, whereas FIS in the 8th grade was associated with a 0.29 (0.19–0.40) higher BMIZ at the same wave, after adjusting for covariates and FIS at earlier waves. Children with FIS vs FS had 27% (relative risk: 1.27, 95% CI: 1.07–1.51), 21% (1.21, 1.08–1.35) and 28% (1.28, 1.07–1.53) higher risk of overweight/obesity in the 3rd, 5th and 8th grades, respectively, adjusting for covariates and FIS at prior wave(s). Children with FIS vs FS in kindergarten had a 2.76-fold (1.22–6.25) higher risk of underweight in the 8th grade. Conclusions Proximal exposure to household FIS was associated with a higher risk of overweight/obesity in the 3rd, 5th and 8th grades. FIS in kindergarten was associated with a risk of underweight in the 8th grade. Thus, FIS coexists in weight extremes during vulnerable early-life windows in the USA, similarly to the global burden of FIS.

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.

Author(s): Hinkle, Stefanie N; Rawal, Shristi; Bjerregaard, Anne Ahrendt; Halldorsson, Thor I; Li, Mengying; Ley, Sylvia H; Wu, Jing; Zhu, Yeyi; Chen, Liwei; Liu, Aiyi; Grunnet, Louise Groth; Rahman, Mohammad L; Kampmann, Freja Bach; Mills, James L; Olsen, Sjurdur F; Zhang, Cuilin | Abstract: BackgroundArtificially sweetened beverages (ASBs) are commonly consumed and recommended for individuals at high risk for cardiometabolic diseases; however, the health effects of ASBs remain contradictory. Given that cross-sectional analyses are subject to reverse causation, prospective studies with long-term follow-up are needed to evaluate associations between ASBs and cardiometabolic health, especially among high-risk individuals.ObjectiveThe aim of this study was to examine associations of ASB intake and cardiometabolic health among high-risk women with prior gestational diabetes mellitus (GDM).MethodsWe included 607 women with GDM from the Danish National Birth Cohort (DNBC; 1996-2002) who completed a clinical exam 9-16 y after the DNBC pregnancy for the Diabetes a Women's Health (DWH) Study (2012-2014). We assessed ASB intake using FFQs completed during the DNBC pregnancy and at the DWH Study clinical exam. We examined cardiometabolic outcomes at the DWH clinical exam. We estimated percentage differences in continuous cardiometabolic markers and RRs for clinical endpoints in association with ASB intake both during pregnancy and at follow-up adjusted for prepregnancy BMI, diet, and lifestyle factors. Sensitivity analyses to account for reverse causation were performed.ResultsIn pregnancy and at follow-up, 30.4% and 36.4% of women regularly (≥2 servings/wk) consumed ASB, respectively. Consumption of ASBs, both during pregnancy and at follow-up, was associated with higher glycated hemoglobin (HbA1c), insulin, HOMA-IR, triglycerides, liver fat, and adiposity and with lower HDL at follow-up. After adjustment for covariates, particularly prepregnancy BMI, the majority of associations between ASB intake in pregnancy and outcomes at follow-up became null with the exception of HbA1c. ASB intake at follow-up (≥1 serving/d compared with l1 serving/mo) was associated with higher HbA1c (6.5%; 95% CI: 1.9, 11.3; P-trend = 0.007); however, associations were not upheld in sensitivity analyses for reverse causation.ConclusionsAmong Danish women with a history of GDM, ASB intake was not significantly associated with cardiometabolic profiles.

BACKGROUND Despite increasing regulation, exposure to persistent organic pollutants (POPs) remains a serious public health concern due to their accumulation in the environment and ability to biomagnify up the food chain. POPs are associated with endocrine-disrupting effects including adverse reproductive outcomes that could affect fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP). OBJECTIVE AND RATIONALE Results of epidemiologic studies that examine the impact of various chemical classes of POPs on TTP have not been synthesised. We undertook a systematic review to summarise the strength of evidence for associations of four common groups of POPs with couple fecundability and to identify gaps and limitations in the literature in order to inform policy decisions and future research. SEARCH METHODS We performed an electronic search of literature published between 1 January 2007 and 6 August 2019 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE and POPLINE. We included empirical research papers that examined human exposure to organochlorine (OC) pesticides, brominated flame retardants, polychlorinated organic compounds and/or per- and polyfluoroalkyl substances (PFAS) and considered TTP or fecundability as an outcome. Standardised forms for screening, data extraction and study quality were developed using DistillerSR software, and all reviews were completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies. OUTCOMES The search returned 4573 articles, and 28 papers from 19 different studies met inclusion criteria. Among them, four studies measured TTP prospectively, three had data on participants’ prenatal exposure, three examined associations in both male and female partners and one focused exclusively on males. Analyses varied widely in terms of exposure characterisation, precluding a meta-analytic approach. Evidence was strongest for adverse associations of female exposure to polychlorinated biphenyls with TTP, with some additional support for associations of female exposure to polybrominated diphenyl ethers and PFAS with longer TTP. Our review provided little or no support for associations between female exposure to OC pesticides or male exposure to any of the POP groups and TTP. WIDER IMPLICATIONS Evidence suggests that female exposure to at least some POPs may reduce fecundability. Although many of these chemicals are no longer in production, they are still detectable in human biosamples because of their persistence in the environment. Replacement chemicals that are being introduced as older ones are restricted may have similar reproductive consequences. Future studies should examine these newer POPs, assess interactions between POPs and other chemical and non-chemical exposures, investigate how POPs are distributed in and metabolised by the human body and focus on populations that may be disproportionately exposed.

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&ndash, Singletons cohort. Maternal plasma phospholipid PUFAs and MPVA were measured at four visits during pregnancy (10&ndash, 14, 15&ndash, 26, 23&ndash, 31, and 33&ndash, 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 &Delta, 6-desaturase in late pregnancy (23&ndash, 31 or 33&ndash, 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.

Preterm birth (PTB) remains a leading cause of neonatal mortality and long-term morbidity. Individual factors have been linked to PTB risk. The impact of a healthy lifestyle, with multiple modifiable prenatal factors, remains unknown.We aimed to examine the associations of preconceptional and early-pregnancy low-risk modifiable factors (individually and in combination) with PTB risk.This prospective cohort study included 2449 women with singleton pregnancies in the Pregnancy Environment and Lifestyle Study. PTB was defined as ultrasound-confirmed obstetric estimate-based gestational age at delivery37 wk. A set of low-risk modifiable factors were identified: healthy weight (prepregnancy BMI: 18.5-24.9 kg/m2) based on clinical measurements and high-quality diet (Alternate Healthy Eating Index-Pregnancy score ≥75th percentile) and low-to-moderate stress during early pregnancy (Perceived Stress Scale score75th percentile) assessed at gestational weeks 10-13. Poisson regression estimated adjusted relative risk (aRR) of PTB in association with individual and combined low-risk modifiable prenatal factors, adjusting for sociodemographic, clinical, and other prenatal factors.One hundred and sixty women (6.5%) delivered preterm. Risk of PTB was lower among women who had a healthy weight (aRR: 0.58; 95% CI: 0.39, 0.86), high-quality diet (aRR: 0.68; 95% CI: 0.39, 0.99), and low-to-moderate stress (aRR: 0.60; 95% CI: 0.41, 0.88). Women with 1, 2, or 3 low-risk modifiable prenatal factors compared with none had a 38% (aRR: 0.72; 95% CI: 0.45, 1.16), 51% (aRR: 0.49; 95% CI: 0.29, 0.84), or 70% (aRR: 0.30; 95% CI: 0.13, 0.70) lower PTB risk, respectively. Associations of having ≥1 low-risk factor with PTB risk were more pronounced for medically indicated than for spontaneous PTB and for late than for early or moderate PTB. Associations also varied by race or ethnicity, although with overlapping 95% CIs.A healthy prenatal lifestyle with multiple low-risk modifiable factors was associated with lower risk of PTB. Our findings may inform multicomponent preconceptional or early-pregnancy prevention strategies to mitigate PTB risk.

OBJECTIVES: To investigate the associations of household mold and pesticide use with risk of childhood asthma and examine the potential effect modification by child’s sex at a national level in the U.S. METHODS: Nationally representative data were drawn from the cross-sectional 2017 and 2018 National Surveys of Children’s Health. Household mold and pesticide exposures during the past 12 months and physician-diagnosed childhood asthma were assessed by standard questionnaires administered to primary caregivers. Multivariable logistic regression models were used to calculate adjusted odds ratios (aOR) for current asthma, adjusting for child, caregiver, and household covariates. We also examined potential effect modification by child’s sex. Sampling weights accounted for the complex survey design. RESULTS: Among 41,423 U.S. children in 2017–2018, the weighted prevalence of current asthma was 10.8% in household mold-exposed children, compared with 7.2% in non-exposed children (P

ObjectiveNut intake has been associated with reduced cardiometabolic risk, but few studies have examined its association with renal function. We examined associations between nut intake and renal function among women with previous gestational diabetes mellitus (GDM), a population with an increased risk for renal dysfunction.Design and methodsThis study included 607 women with a history of GDM who participated in the Diabetes & Women's Health Study (2012-2014) follow-up clinical examination in Denmark. At the clinic, biospecimens were collected, and habitual intake of nuts (9 types) in the past year was assessed using a food frequency questionnaire. A total of 330 women free of major chronic diseases were included in the analysis. Total nut intake was classified as none (≤1 serving/month), monthly (2-3 servings/month), weekly (1-6 servings/week), and daily (≥1 serving/day). One serving was defined as 28 g. Renal function markers included estimated glomerular rate (eGFR) and urinary albumin-to-creatinine ratio (UACR), calculated based on plasma creatinine (mg/dL), and urinary albumin (mg/L), and creatinine (mg/dL) measurements, respectively. We estimated percent differences with 95% confidence intervals for each outcome by nut intake, adjusted for current body mass index, age, physical activity, energy intake, alcohol consumption, and vegetables intake.ResultsWe observed a nonlinear association between total nut intake and UACR with lowest UACR values among women with weekly intake. Compared to women with weekly intake (n=222), the adjusted UACR values were higher by 86% [95% confidence interval: 15%, 202%], 24% [-1%, 54%], and 117% [22%, 288%] among women with no (n=13), monthly (n=86), and daily (n=9) intake, respectively. Compared to weekly consumers, daily nut consumers also had 9% [0%, 19%] significantly higher eGFR values, but eGFR values were similar among women with no and monthly intake.ConclusionModerate nut consumption may be beneficial to kidney health among women with prior GDM.

Hypertensive disorders in pregnancy and GDM are among the leading causes of maternal and perinatal morbidity. In 2017, the American College of Cardiology/American Heart Association released a new guideline for hypertension: systolic/diastolic blood pressure (SBP/DBP) ≥130/80 vs. previous 140/90 mmHg. However, these new cut-points have not been applied to pregnant women due to the lack of evidence on its impact on perinatal outcomes. We examined in women with and without GDM whether the risk of perinatal complications increased across SBP/DBP levels: normal ( Disclosure Y. Zhu: None. J. Feng: None. A. Ngo: None. C. Quesenberry: None. A. Ferrara: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K01DK120807)

IntroductionDisruption of lipid metabolism is implicated in gestational diabetes (GDM). However, prospective studies on lipidomics and GDM risk in race/ethnically diverse populations are sparse. Here, we aimed to (1) identify lipid networks in early pregnancy to mid-pregnancy that are associated with subsequent GDM risk and (2) examine the associations of lipid networks with glycemic biomarkers to understand the underlying mechanisms.Research design and methodsThis study included 107 GDM cases confirmed using the Carpenter and Coustan criteria and 214 non-GDM matched controls from the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort, untargeted lipidomics data of 420 metabolites (328 annotated and 92 unannotated), and information on glycemic biomarkers in maternal plasma at visit 0 (10–14 weeks) and visit 1 (15–26 weeks). We constructed lipid networks using weighted correlation network analysis technique. We examined prospective associations of lipid networks and individual lipids with GDM risk using linear mixed effect models. Furthermore, we calculated Pearson’s partial correlation for GDM-related lipid networks and individual lipids with plasma glucose, insulin, C-peptide and glycated hemoglobin at both study visits.ResultsLipid networks primarily characterized by elevated plasma diglycerides and short, saturated/low unsaturated triglycerides and lower plasma cholesteryl esters, sphingomyelins and phosphatidylcholines were associated with higher risk of developing GDM (false discovery rate (FDR) ConclusionsPlasma lipid metabolites in early pregnancy both individually and interactively in distinct networks were associated with subsequent GDM risk in race/ethnically diverse US women. Future research is warranted to assess lipid metabolites as etiologic markers of GDM.

IntroductionSeveral adipokines are implicated in the pathophysiology of gestational diabetes mellitus (GDM), however, longitudinal data in early pregnancy on many adipokines are lacking. We prospectively investigated the association of a panel of adipokines in early and mid-pregnancy with GDM risk.Research design and methodsWithin the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (n=2802), a panel of 10 adipokines (plasma fatty acid binding protein-4 (FABP4), chemerin, interleukin-6 (IL-6), leptin, soluble leptin receptor (sOB-R), adiponectin, omentin-1, vaspin, and retinol binding protein-4) 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 to estimate ORs of each adipokine and GDM, controlling for known GDM risk factors including pre-pregnancy body mass index.ResultsThroughout pregnancy changes in chemerin, sOB-R, adiponectin, and high-molecular-weight adiponectin (HMW-adiponectin) concentrations from 10–14 to 15–26 GWs were significantly different among GDM cases compared with non-GDM controls. In early and mid-pregnancy, FABP4, chemerin, IL-6 and leptin were positively associated with increased GDM risk. For instance, at 10–14 GWs, the OR comparing the highest versus lowest quartile (ORQ4–Q1) of FABP4 was 3.79 (95% CI 1.63 to 8.85). In contrast, in both early and mid-pregnancy adiponectin (eg, ORQ4–Q1 0.14 (0.05, 0.34) during 10–14 GWs) and sOB-R (ORQ4–Q1 0.23 (0.11, 0.50) during 10–14 GWs) were inversely related to GDM risk. At 10–14 GWs a model that included conventional GDM risk factors and FABP4, chemerin, sOB-R, and HMW-adiponectin improved the estimated prediction (area under the curve) from 0.71 (95% CI 0.66 to 0.77) to 0.77 (95% CI 0.72 to 0.82).ConclusionsA panel of understudied adipokines including FABP4, chemerin, and sOB-R may be implicated in the pathogenesis of GDM with significant associations detected approximately 10–18 weeks before typical GDM screening.

Background: Physical activity (PA) is a key components of energy expenditure and can alter fat metabolism. Maternal polyunsaturated fatty acids (PUFA), particularly endogenous PUFA, plays critical roles on maternal health and fetal development. However, studies investigating the longitudinal association of PA with PUFA during pregnancy are scarce. Objective: To examine the prospective associations of PA with PUFA among pregnant women. Methods: This study used longitudinal data from a nested gestational diabetes mellitus case-control study (n=321) within the NICHD Fetal Growth Studies-Singletons. Plasma phospholipid PUFA and PA were measured at 4 time-points during pregnancy (10-14, 15-26, 23-31, and 33-39 GW). Total PA was calculated as energy expenditure in metabolic equivalent (METs-hour) and physically active was defined as spending ≥150 min on moderate-to-vigorous exercise per week. Associations of PA with total n-3, n-6, and individual PUFAs were examined using generalized linear models where the sample was weighted to represent the entire cohort. Results: Total PA was positively associated with EDA, but inversely associated with ALA and GLA, independent of maternal age, race, parity, pre-pregnancy BMI, and dietary intake of FA. Being physically active was inversely associated with total n-3 PUFA but positively associated with total n-6 PUFA. However, the direction of the associations of individual PUFA varied: an inverse association for ALA (n-3) and LA (n-6); a positive association for DHA (n-3), AA (n-6) and DPA (n-6). Conclusions: Findings from this study indicate that PA may alter PUFA metabolism in pregnant women. The inverse association between total PA and GLA (an endogenous PUFA) is novel and merits confirmation in future studies.

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. https://doi.org/10.1289/EHP5133

OBJECTIVE This study examined the associations of central obesity measures, waist to hip ratio (WHR) and waist circumference (WC), in early pregnancy with subsequent risk of gestational diabetes mellitus (GDM) and evaluated the potential mediating role of insulin resistance markers. METHODS Within the prospective Pregnancy Environment and Lifestyle Study cohort of 1,750 women, WC and hip circumference were measured at gestational weeks 10 to 13. In a nested case-control study within the cohort, 115 GDM cases and 230 controls had fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and adiponectin measurements at gestational weeks 16 to 19. Poisson and conditional logistic regression models were used, adjusting for established risk factors for GDM, including prepregnancy overweight or obesity. RESULTS For women with WHR

ObjectiveIn resource-constrained facilities or during resuscitation, immediate paediatric weight estimation remains a fundamental challenge. We aimed to develop and validate weight estimation models based on ulna length and forearm width and circumference measured by simple and portable tools; and to compare them against previous methods (advanced paediatric life support (APLS), Theron and Traub–Johnson formulas).DesignCross-sectional analysis of anthropometric measurements. Four ulna- and forearm-based weight estimation models were developed in the training set (n 1016). Assessment of bias, precision and accuracy was examined in the validation set (n 457).SettingNational Children’s Study-Formative Research in Anthropometry (2011–2012).SubjectsMulti-racial/ethnic infants and children aged n 1473).ResultsDeveloped Models 1–4 had high predictive precision (R2=0·91–0·97). Mean percentage errors between predicted and measured weight were significantly smaller across the developed models (0·1–0·7 %) v. the APLS, Theron and Traub–Johnson formulas (−1·7, 9·2 and −4·9 %, respectively). Root-mean-squared percentage error was overall smaller among Models 1–4 v. the three existing methods (range=7·5–8·7 v. 9·8–13·3 %). Further, Models 1–4 were within 10 and 20 % of actual weight in 72–87 and 95–99 % of the weight estimations, respectively, which outperformed any of the three existing methods.ConclusionsUlna length, forearm width and forearm circumference by simple and portable tools could serve as valid and reliable surrogate measures of weight among infants and children aged

Context Previous studies have not examined the ability of multiple preconception biomarkers, considered together, to improve prediction of gestational diabetes mellitus (GDM). Objective To develop a preconception biomarker risk score and assess its association with subsequent GDM. Design A nested case-control study among a cohort of women with serum collected as part of a health examination (1984 to 1996) and subsequent pregnancy (1984 to 2009). Biomarkers associated with GDM were dichotomized into high/low risk. Setting Integrated health care system. Participants Two controls were matched to each GDM case (n = 256 cases) on year and age at examination, age at pregnancy, and number of pregnancies between examination and index pregnancy. Main Outcome Measure GDM. Results High-risk levels of sex hormone-binding globulin (SHBG; 90 mg/dL), total adiponectin (3.9) were independently associated with 2.34 [95% confidence interval (CI): 1.50, 3.63], 2.03 (95% CI: 1.29, 3.19), 1.83 (95% CI: 1.16, 2.90), and 1.67 (95% CI: 1.07, 2.62) times the odds of GDM and included in the biomarker risk score. For each unit increase in the biomarker risk score, odds of GDM were 1.94 times greater (95% CI: 1.59, 2.36). A biomarker risk score including only SHBG and glucose was sufficient to improve prediction beyond established risk factors (age, race/ethnicity, body mass index, family history of diabetes, previous GDM; area under the curve = 0.73 vs 0.67, P = 0.002). Conclusions The improved, predictive ability of the biomarker risk score beyond established risk factors suggests clinical use of the biomarker risk score in identifying women at risk for GDM before conception for targeted prevention strategies.

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. More...

ContextT3 is the biologically active thyroid hormone involved in glucose metabolism. The free T3 (fT3)/free T4 (fT4) ratio, a marker indicating conversion of fT4 to fT3, is also implicated in glucose homeostasis.ObjectiveTo examine associations of fT3 and the fT3/fT4 ratio with gestational diabetes mellitus (GDM).DesignIn a case-control study, thyroid markers (fT3, fT4, TSH) were measured and the fT3/fT4 ratio was derived across four visits in pregnancy, including first (gestational weeks 10 to 14) and second (weeks 15 to 26) trimester. Conditional logistic regression adjusting for thyroid autoimmunity status and major GDM risk factors estimated trimester-specific associations of thyroid markers with subsequent GDM risk.SettingTwelve US clinical centers.ParticipantsOne hundred seven GDM cases and 214 non-GDM controls from a multiracial pregnancy cohort of 2802 women.Main Outcome MeasuresGDM diagnosis ascertained from medical records.ResultsBoth fT3 and the fT3/fT4 ratio were positively associated with GDM: adjusted OR (95% CI) comparing the highest vs lowest fT3 quartile was 4.25 (1.67, 10.80) at the first trimester and 3.89 (1.50, 10.10) at the second trimester. Similarly, the corresponding risk estimates for the fT3/fT4 ratio were 8.63 (2.87, 26.00) and 13.60 (3.97, 46.30) at the first and second trimester, respectively. Neither TSH nor fT4 was significantly associated with GDM.ConclusionsHigher fT3 levels, potentially resulting from de novo synthesis or increased fT4 to fT3 conversion, may be an indicator of GDM risk starting early in pregnancy.

BACKGROUND: Increased maternal adiposity and inflammation have impacts on fetal growth. OBJECTIVES: The purpose of this prospective study was to investigate the associations of 3 proinflammatory adipokines in pregnancy with neonatal anthropometry. METHODS: In a sample of 321 US pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (NCT00912132), plasma IL-6, fatty acid binding protein-4 (FABP4), and chemerin were measured in plasma samples collected at 10–14, 15–26, 23–31, and 33–39 weeks of gestation. Generalized linear models were used to estimate associations of adipokines with neonatal weight, thigh, and crown-heel length, and skinfolds at birth. Models adjusted for age, race/ethnicity, education, nulliparity, prepregnancy BMI, and weeks of gestation at blood collection. RESULTS: At each time point, higher IL-6 was associated with lower neonatal birthweight and thigh length. At 15–26 weeks of gestation, a 1 SD pg/mL increase in IL-6 was associated with –84.46 g lower neonatal birthweight (95% CI: –150.70, –18.22), –0.17 cm shorter thigh length (95% CI: –0.27, –0.07), –0.43 cm shorter crown-heel length (95% CI: –0.75, –0.10), and –0.75 mm smaller sum of skinfolds (95% CI: –1.19, –0.31), with similar associations at 23–31 and 33–39 weeks of gestation. There were no associations of FABP4 and chemerin with neonatal anthropometry. CONCLUSIONS: Starting as early as 15 weeks of gestation, higher maternal IL-6 concentrations in pregnancy were associated with lower neonatal birthweight, thigh and crown-heel length, and skinfolds. These data provide insight into the relevance of maternal inflammatory markers 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.

OBJECTIVES: Plasma profile of acylcarnitines has been suggested to associate with adverse maternal outcomes such as gestational diabetes. However, data on their associations with neonatal outcomes are sparse. Therefore, this study aimed to examine the prospective profile of acylcarnitines across gestation and its association with neonatal anthropometry, including birthweight (BW), BW z-score, the sum of skinfolds (SSF), length, and circumferences. METHODS: Among 321 pregnant women from the NICHD Fetal Growth Studies-Singletons cohort, we quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in the plasma at gestational weeks 10–14, 15–26, 23–31 and 33–39, accordingly. We firstly applied a latent-class trajectory approach to identify trajectories of acylcarnitines across gestation, and secondly examined associations of individual acylcarnitine and distinct trajectory groups with neonatal anthropometry using weighted linear models with robust standard errors, adjusting for maternal age, race/ethnicity, education, parity, gestational week of blood collection, and pre-pregnancy body mass index. RESULTS: We identified three distinct trajectory groups of C2, C3 and C4, and two trajectory groups of C5, C10, C5-DC, C8:1, C10:1 and C12, respectively. Newborns of women with nonlinear decline of C12 levels across gestation (5.7%) had significantly smaller BW (−475 g; 95% CI: −942, −6.79 g), BW z-score (−0.39; −0.71, −0.06), and length (−1.38 cm; −2.49, −0.27 cm) than those with persistently stable C12 levels (94.3%). Newborns of women with consistently higher levels of C10 (6.1%) had greater sum of skinfolds (4.91 mm; 0.85, 8.98 mm) than those with lower levels (93.9%) across pregnancy, whereas newborns of women with declining C10:1 levels (12.6%) had larger sum of skinfolds (3.23 mm; 0.19, 6.27 mm) than those with abruptly increasing levels (87.4%). CONCLUSIONS: In conclusion, gestational trajectories of C10, C10:1, and C12 acylcarnitine levels were significantly associated with neonatal anthropometry. Further studies are needed to verify and further explore the potential clinical utility of these findings. FUNDING SOURCES: Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding; American Recovery and Reinvestment Act funding.

OBJECTIVES: Maternal physical activity (PA) may influence pregnant women and offspring health via its impact on fatty acids metabolism. This study aimed to examine associations of PA with plasma phospholipid monounsaturated fatty acids (MUFAs) during pregnancy. METHODS: The study included 321 pregnant women from the NICHD Fetal Growth Studies (N = 2802) with plasma phospholipid MUFAs and PA measured four times at 10–14, 15–26, 23–31, and 33–39 gestational weeks (GWs). Leisure time moderate-to-vigorous PA (MVPA) was analyzed as both continuous (hour/week) and binary variables (i.e., high MVPA: ≥150 min/week vs. low MVPA

OBJECTIVES: Using an untargeted approach to identify plasma metabolomics signature of the Mediterranean diet, a healthful dietary pattern related to both maternal and fetal outcomes, in pregnancy. METHODS: This study included 193 pregnant women from the NICHD Fetal Growth Studies-Singletons (FGS) cohort who had habitual dietary intake in the past three months measured at 8–13 gestational weeks (GW) by the semi-quantified food frequency questionnaire. Fasting plasma metabolomics profiles at 15–26 GW were measured by the high-throughput liquid chromatography quadrupole time of-flight mass spectrometry (LC-QTOF MS/MS). Metabolites were re-scaled to a median of 1 for each batch and log transformed. Alternate Mediterranean Diet (aMED) score was calculated by eight food and nutrient components (i.e., fruits, vegetables, whole grains, nuts, fish, legumes, red and processed meats, and monounsaturated-to-saturated fat ratio), with a higher score indicating a better adherence. Prospective associations of aMED score in peri-conception and early pregnancy with individual metabolites at 15–26 GW were estimated using the linear regression adjusting for potential confounders and multiple testing. LASSO (Least Absolute Shrinkage and Selection Operator) regression with 10-fold cross-validation was performed to select metabolites that were jointly associated with high aMED score (defined as the top tertile). All statistical analyses were weighted to represent the entire FGS cohort. RESULTS: A total of 460 known metabolites were profiled and annotated. Six metabolites were selected as the biomarkers of high aMED score by the LASSO regression (i.e., with no-zero coefficients). Among them, glutamic acid and 3-hydroxybutyric acid were negatively whereas PC (40:7), CE (20:5), TG (49:1), and TG (58:4) were positively associated with aMED score. The six biomarkers were also confirmed by the linear regression with false discovery rates

Background Abnormal lipid profiles have been associated with gestational diabetes mellitus (GDM), but studies with longitudinal measures of lipids throughout pregnancy are sparse. We aimed to characterize the longitudinal changes in lipid profiles throughout pregnancy and prospectively examine the associations of plasma lipid levels with risk of GDM. Methods This is a nested case-control study including 107 GDM cases and 214 matched non-GDM controls from participants in the NICHD Fetal Growth Studies-Singleton Cohort. Blood samples were longitudinally collected at gestational weeks 10-14, 15-26 (fasting sample), 23-31 and 33-39. Plasma concentrations of triglycerides, total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured by enzymatic assays. Low-density lipoprotein cholesterol (LDL-C) was calculated by the Friedewald's formula. Results Plasma levels of triglycerides, total cholesterol, and LDL-C increased as pregnancy progressed. At gestational weeks 10-14, the adjusted odds ratios (ORs) of GDM comparing the highest versus lowest quartile were 3.15 (95% confidence interval [CI] 1.38-7.15; P for trend = 0.002) for triglycerides and 0.44 (95% CI 0.18-1.09; P for trend = 0.045) for HDL-C. At gestational weeks 15-26, the corresponding ORs were 6.57 (95% CI 2.25-19.17; P for trend = 0.001) for triglycerides and 0.23 (95% CI 0.08-0.63; P for trend = 0.005) for HDL-C. We observed no significant associations for total cholesterol and LDL-C levels with risk of GDM. Conclusions Higher plasma triglyceride and lower HDL-C concentrations in early and mid-pregnancy were significantly associated with greater risk of GDM. Total cholesterol and LDL-C levels during pregnancy were not significantly associated with GDM risk.

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.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.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).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.

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

Exposures to extreme ambient temperature and air pollution are linked to adverse birth outcomes, but the associations with small for gestational age (SGA) and term low birthweight (tLBW) are unclear. We aimed to investigate exposures to site-specific temperature extremes and selected criteria air pollutants in relation to SGA and tLBW.We linked medical records of 220,572 singleton births (2002-2008) from 12 US sites to local temperature estimated by the Weather Research and Forecasting model, and air pollution estimated by modified Community Multiscale Air Quality models. Exposures to hot (95th percentile) and cold (5th percentile) were defined using site-specific distributions of daily temperature over three-month preconception, each trimester, and whole-pregnancy. Average concentrations of five criteria air pollutants and six fine particulate matter constituents were also calculated for these pregnancy windows. Poisson regression with generalized estimating equations calculated the relative risks (RR) and 95% confidence intervals for SGA (weight10th percentile conditional on gestational age and sex) and tLBW (≥37 weeks and2500g) associated with an interquartile range increment of air pollutants, and cold or hot compared to mild (5-95th percentile) temperature. Models were adjusted for maternal demographics, lifestyle, and clinical factors, season, and site.Compared to mild temperature, cold exposure during trimester 2 [RR: 1.21 (1.05-1.38)], trimester 3 [RR: 1.18 (1.03-1.36)], and whole-pregnancy [RR: 2.57 (2.27-2.91)]; and hot exposure during trimester 3 [RR: 1.31 (1.15-1.50)] and whole-pregnancy [RR: 2.49 (2.20-2.83)] increased tLBW risk. No consistent association was observed between temperature and SGA. Air pollutant analyses were generally null but preconception elemental carbon was associated with a 4% increase in SGA while dust particles increased tLBW by 10%. Particulate matter ≤10µm in the second trimester and whole pregnancy also appeared related to tLBW.Our findings suggest prenatal exposures to extreme ambient temperature relative to usual environment may increase tLBW risk. Given concerns related to climate change, these findings merit further investigation.

Background: Extreme temperature is associated with adverse birth outcomes but it is unclear whether it increases early delivery risk. Objectives: We aimed to determine the association between ambient temperature and early delivery. Methods: Medical records from 223,375 singleton deliveries from 12 U.S. sites were linked to local ambient temperature. Exposure to hot (> 90th percentile) or cold (< 10th percentile) using site-specific and window-specific temperature distributions were defined for 3-months preconception, 7-week periods during the first two trimesters, 1 week preceding delivery, and whole pregnancy. Poisson regression with generalized estimating equations calculated the relative risk (RR) and 95% confidence interval for early deliveries associated with hot/cold exposures, adjusting for conception month, humidity, site, sex, maternal demographics, parity, insurance, prepregnancy body mass index, pregnancy complications, and smoking or drinking during pregnancy. Acute temperature associations were estimated separately for warm (May–September) and cold season (October–April) in a case-crossover analysis using conditional logistic regression. Results: Compared with mild temperature (10–90th percentile), exposure to hot or cold during weeks 1–7 increased risk for early preterm (< 34 weeks) [RRhot: 1.11 (95% CI: 1.01, 1.21); RRcold: 1.20 (95% CI: 1.11, 1.30)], late preterm (34–36 weeks) [RRcold: 1.09 (95% CI: 1.04, 1.15)], and early term (37–38 weeks) [RRhot: 1.04 (95% CI: 1.02, 1.07); RRcold: 1.03 (95% CI: 1.00, 1.05)] delivery. Findings were similar for hot exposures during weeks 15–21. Examining deliveries at each week from 23 through 38, whole-pregnancy hot exposures increased delivery risk by 6–21% at weeks 34 and 36–38. In the case-crossover analysis, a 5°F increase during the week preceding delivery was associated with 12–16% higher and 4–5% lower early delivery risk during warm and cold season, respectively. Conclusions: Both acute and chronic ambient temperature extremes may affect early delivery risk. Citation: Ha S, Liu D, Zhu Y, Kim SS, Sherman S, Mendola P. 2017. Ambient temperature and early delivery of singleton pregnancies. Environ Health Perspect 125:453–459; http://dx.doi.org/10.1289/EHP97Citation: Ha S, Liu D, Zhu Y, Kim SS, Sherman S, Mendola P. 2017. Ambient temperature and early delivery of singleton pregnancies. Environ Health Perspect 125:453–459; http://dx.doi.org/10.1289/EHP97

We aimed to study the potential impact of proximity to major roadways on time-to-pregnancy and infertility in couples attempting pregnancy in the Longitudinal Investigation of Fertility and Environment (LIFE) study (2005-2009), a population-based, prospective cohort study. Couples attempting pregnancy (n=500) were enrolled and followed prospectively until pregnancy or 12 months of trying and 393 couples (78%) had complete data and full follow-up. Time-to-pregnancy was based on a standard protocol using fertility monitors, tracking estrone-3-glucuonide and luteinizing hormone, and pregnancy test kits to detect human chorionic gonadotropin (hCG). The fecundability odds ratio (FOR) and 95% confidence interval (CI) were estimated using proportional odds models. Infertility was defined as 12 months of trying to conceive without an hCG pregnancy and the relative risk (RR) and 95% CI were estimated with log-binomial regression. Final models were adjusted for age, parity, study site, and salivary alpha-amylase, a stress marker. Infertile couples (53/393; 14%) tended to live closer to major roadways on average than fertile couples (689 m vs. 843 m, respectively) but the difference was not statistically significant. The likelihood of pregnancy was increased 3% for every 200 meters further away the couples residence was from a major roadway (FOR=1.03; CI=1.01-1.06). Infertility also appeared elevated at moderate distances compared to 1000 meters or greater, but estimates lacked precision. Our findings suggest that proximity to major roadways may be related to reductions in fecundity. Prospective data from larger populations is warranted to corroborate these findings.

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.

BACKGROUND: Short telomere length, an indicator of cellular aging and oxidative stress, has been implicated in glucose homeostasis. Additionally, studies have illustrated that the association of telomere length with health outcomes may vary by age. Yet, data on the association between telomere length and gestational diabetes (GDM) are sparse and the potential effect modification by age remains unknown. METHODS: We prospectively investigated telomere length in early pregnancy in relation to subsequent GDM risk in a case-control study of 93 women with GDM and 186 randomly selected controls matched on age, race/ethnicity, and gestational weeks at blood collection. Telomere length was measured using blood samples collected at 10-14 gestational weeks and reported as the T/S ratio, a ratio of telomere repeat length T to copy number of a single copy gene S. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression adjusted for major risk factors. RESULTS: Overall, telomere length was not significantly associated with GDM risk. The telomere length-GDM association was significantly modified by age (P(interaction)=0.02). Shorter telomere length in early pregnancy was associated with an increased GDM risk among women aged

Background Despite 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 findings Within 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 (, Cuilin Zhang and colleagues reveal a potential association between polyunsaturated fatty acids in early to midpregnancy with the development of gestational diabetes., Author summary Why was this study done? Dietary guidelines promote intakes of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, whereas evidence on PUFAs for pregnant women is scarce. Experimental and observational studies have linked both dietary and circulating fatty acids to the risk of developing type 2 diabetes, insulin resistance, and β-cell dysfunction, but only a few studies did for the risk of developing gestational diabetes mellitus (GDM). In particular, evidence is missing for the associations of individual plasma phospholipid PUFAs, rather than total PUFAs conventionally via dietary assessment, with the risk of subsequent GDM. What did the researchers do and find? In this longitudinal study of 107 women with GDM and 214 matched non-GDM women within the prospective National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies–Singleton Cohort in the United States, we evaluated the associations of individual plasma phospholipid PUFAs in early to midpregnancy with a panel of glucose metabolism and cardiometabolic markers and subsequent risk of GDM. Total and individual plasma phospholipid n-3 PUFAs—specifically, diet-derived eicosapentaenoic acid and docosahexaenoic acid—were inversely correlated with insulin-resistance markers but not associated with the risk of GDM. Associations of individual plasma phospholipid n-6 PUFAs with GDM risk were differential, with no associations for the major diet-derived n-6 PUFAs (linolenic acid and arachidonic acid) comprising over 80% of total n-6 PUFAs and with null, positive, or negative associations for minor n-6 PUFAs recognized to be primarily produced from endogenous metabolism of linolenic acid. What do these findings mean? No significant associations of major diet-derived n-6 PUFAs and significant findings for the other minor n-6 PUFAs known to reflect endogenous metabolism suggest a potential role of circulating levels of plasma phospholipid n-6 PUFAs in pathophysiology of GDM. Furthermore, our findings do not provide strong evidence to suggest beneficial roles of primarily diet-derived n-3 PUFAs in prevention of GDM, although also not excluding the possibility of benefit on glucose–insulin homeostasis given their inverse correlations with insulin-resistance markers. Similarly, our findings suggest neither a harmful nor a beneficial role of diet-derived n-6 PUFA linolenic acid in GDM pathophysiology. Our findings among pregnant women highlight the need to recognize the heterogeneous associations of individual circulating PUFAs with subsequent GDM risk and to investigate the underlying metabolism.