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BackgroundAmong people with gestational diabetes mellitus (GDM), there is inter-individual variability in clinical outcomes that appears to be related to factors beyond glycemia. However, the precise factors (information on the unique pathophysiology within a person, environment, and/or context) that may help refine the diagnosis of GDM remain unclear. To determine if a precision medicine approach could refine the diagnosis of GDM, we conducted a systematic review of a variety of potential precision markers analyzed in studies among individuals with GDM.MethodsSystematic literature searches were performed in PubMed (https://pubmed.ncbi.nlm.nih.gov/) and EMBASE (https://www.embase.com) databases from inception to March 2022 for observational studies and controlled trials. Studies were included if they reported data on, and compared outcomes between, individuals with GDM. The following categories of precision markers were included in the current search: non-glycemic biochemical markers (cholesterol, insulin profiles); genetics/genomics or other -omics (proteomics, lipidomics, metabolomics, metagenomics); maternal/fetal anthropometric (eg., maternal BMI, gestational weight gain, fetal biometry ultra-sound measures); clinical risk factors (medical/familial history, prior delivery complicated by macrosomia or a large for gestational age [LGA] neonate); sociocultural or environmental modifiers (diet, smoking, race/ethnicity, socioeconomic status).ResultsWe focused on synthesizing the literature on genetics, -omics, non-glycemic biomarkers, maternal anthropometry/fetal biometry, and clinical/sociocultural risk factors. A total of 5,905 titles and abstracts were screened, 775 underwent full-text review, and 137 studies that included a total of 432,156 GDM cases were synthesized. Of the studies on non-glycemic biomarkers (n=33), lipids and insulin sensitivity/secretion indices were the two most common precision markers, with elevated maternal triglycerides and insulin resistance generally associated with greater risk of LGA and macrosomia. Studies of genetics or other -omics were scarce (n=5); however, differences in genetic variants in adiponectin or adiponutrient genes and non-coding RNAs accounted for variability in perinatal outcomes. The majority of studies (n=77) evaluated maternal anthropometry or fetal biometry as a precision marker, and these studies demonstrate that individuals with adiposity who develop GDM are at a substantially higher risk of LGA or macrosomia than those with GDM and lower adiposity. There were 49 studies evaluating GDM risk factors or sociocultural markers, with only six studies examining multiple risk factors as a composite marker. There were inconsistent findings that GDM risk factors, such as older maternal age, accounted for variation in adverse outcomes.ConclusionsOur review demonstrates that a major gap exists in studies examining non-glycemic biochemical, genetic, or other ‘omic precision markers among individuals with GDM. Given that people meeting current diagnostic criteria for GDM may have different risk profiles, our review identifies several factors (including obesity, insulin resistance, hypertriglyceridemia) that may be useful in risk stratification of GDM, setting the stage for a precision approach to its diagnosis.

AIMS/HYPOTHESIS: Limited data exist on the association between maternal diet quality during pregnancy and metabolic traits in offspring during early childhood, which is a sensitive period for risk of obesity-related disorders later in life. We aimed to examine the association of maternal diet quality, as indicated by the Healthy Eating Index-2010 (HEI), in pregnancy with offspring metabolic biomarkers and body composition at age 4–7 years. METHODS: We used data from 761 mother–offspring pairs from the Healthy Start study to examine sex-specific associations of HEI >57 vs ≤57 with offspring fasting glucose, leptin, cholesterol, HDL, LDL, percentage fat mass, BMI z score and log-transformed insulin, 1/insulin, HOMA-IR, adiponectin, triacylglycerols, triacylglycerols:HDL, fat mass, and sum of skinfolds. Multivariable linear regression models accounted for maternal race/ethnicity, age, education, smoking habits during pregnancy and physical activity, and child’s age. RESULTS: During pregnancy, mean (SD) HEI score was 55.0 (13.3), and 43.0% had an HEI score >57. Among boys, there was an inverse association of maternal HEI with offspring glucose, insulin, HOMA-IR and adiponectin. For instance, maternal HEI >57 was associated with lower fasting glucose (−0.11; 95% CI −0.20, −0.02 mmol/l), and lower concentrations of: insulin by 15.3% (95% CI −24.6, −5.0), HOMA-IR by 16.3% (95% CI −25.7, −5.6) and adiponectin by 9.3% (95% CI −16.1, −2.0). Among girls, there was an inverse association of maternal HEI with insulin and a positive association with LDL. However, following covariate adjustment, all estimates among girls were attenuated to the null. CONCLUSIONS/INTERPRETATION: Greater compliance with the USA Dietary Guidelines via the HEI may improve the maternal–fetal milieu and decrease susceptibility for poor metabolic health among offspring, particularly boys. Future studies are warranted to confirm these associations and determine the underlying mechanisms.

OBJECTIVES: To characterize prevalence of ideal cardiovascular health (ICVH) during early childhood (4–7 years), and to identify pre- and perinatal biological, sociodemographic, metabolic, and behavioral correlates of ICVH. STUDY DESIGN: Among 350 mother-child pairs in the Healthy Start Study, we defined ICVH as no exposure to second hand smoke (SHS), ≥1 h/day of moderate-to-vigorous physical activity, BMI≤85(th) percentile; systolic and diastolic blood pressure85%) children met criteria for SHS, BMI, blood pressure, cholesterol, and glucose, and only 1/3 met criteria for physical activity (31.4%) and diet (35.1%). In multivariable analyses, key correlates of ICVH were maternal weight status (OR(overweight/obese vs. non-overweight/obese)=0.41 [0.23, 0.73]) and offspring sex (OR(male vs. female)=2.14 [1.22, 3.65]). CONCLUSIONS: At age 4–7 years, ICVH prevalence is already low, with diet and adequate physical activity being the limiting factors. Healthy maternal weight prior to pregnancy and male sex are potential determinants of childhood ICVH. Additional work is required to explore associations of early-life ICVH with future health outcomes.

ImportanceThe in utero metabolic milieu is associated with offspring adiposity. Standard definitions of maternal obesity (according to prepregnancy body mass index [BMI]) and gestational diabetes (GDM) may not be adequate to capture subtle yet important differences in the intrauterine environment that could be involved in programming.ObjectivesTo identify maternal metabolic subgroups during pregnancy and to examine associations of subgroup classification with adiposity traits in their children.Design, Setting, and ParticipantsThis cohort study included mother-offspring pairs in the Healthy Start prebirth cohort (enrollment: 2010-2014) recruited from University of Colorado Hospital obstetrics clinics in Aurora, Colorado. Follow-up of women and children is ongoing. Data were analyzed from March to December 2022.ExposuresMetabolic subtypes of pregnant women ascertained by applying k-means clustering on 7 biomarkers and 2 biomarker indices measured at approximately 17 gestational weeks: glucose, insulin, Homeostatic Model Assessment for Insulin Resistance, total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, free fatty acids (FFA), HDL-C:triglycerides ratio, and tumor necrosis factor α.Main Outcomes and MeasuresOffspring birthweight z score and neonatal fat mass percentage (FM%). In childhood at approximately 5 years of age, offspring BMI percentile, FM%, BMI in the 95th percentile or higher, and FM% in the 95th percentile or higher.ResultsA total of 1325 pregnant women (mean [SD] age, 27.8 [6.2 years]; 322 [24.3%] Hispanic, 207 non-Hispanic Black [15.6%], and 713 [53.8%] non-Hispanic White), and 727 offspring with anthropometric data measured in childhood (mean [SD] age 4.81 [0.72] years, 48% female) were included. We identified the following 5 maternal metabolic subgroups: reference (438 participants), high HDL-C (355 participants), dyslipidemic–high triglycerides (182 participants), dyslipidemic–high FFA (234 participants), and insulin resistant (IR)–hyperglycemic (116 participants). Compared with the reference subgroup, women in the IR-hyperglycemic and dyslipidemic–high FFA subgroups had offspring with 4.27% (95% CI, 1.94-6.59) and 1.96% (95% CI, 0.45-3.47) greater FM% during childhood, respectively. There was a higher risk of high FM% among offspring of the IR-hyperglycemic (relative risk, 8.7; 95% CI, 2.7-27.8) and dyslipidemic–high FFA (relative risk, 3.4; 95% CI, 1.0-11.3) subgroups; this risk was of greater magnitude compared with prepregnancy obesity alone, GDM alone, or both conditions.Conclusions and RelevanceIn this cohort study, an unsupervised clustering approach revealed distinct metabolic subgroups of pregnant women. These subgroups exhibited differences in risk of offspring adiposity in early childhood. Such approaches have the potential to refine understanding of the in utero metabolic milieu, with utility for capturing variation in sociocultural, anthropometric, and biochemical risk factors for offspring adiposity.

Osteoarthritis (OA) is one of the most common diseases that cause disability among older adults. The objective of this study was to assess the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) and OA in American adults. This study included adults (≥ aged 20 years) who participated in the National Health and Examination Survey (NHANES) 2007-2016 in the United States. Adherence to the DASH score was calculated from 8 food groups. Higher scores indicate better adherence to the DASH dietary pattern. Among the 21,901 participants included in this study, 10.26% reported having OA. Results of our multivariable logistic regression indicated a statistically significant inverse association between DASH score tertiles and OA. The adjusted ORs (95% CI) were 1.00 (ref), 0.89 (0.72; 1.10), and 0.78 (0.60; 1.00) across increasing DASH score tertiles (P for trend = 0.045). In this representative sample of American adults, greater adherence to the DASH dietary pattern was associated with lower likelihood of having OA.

BACKGROUND: Intrauterine overnutrition has been associated with pediatric nonalcoholic fatty liver disease (NAFLD), but the exact mechanisms involved remain unclear. OBJECTIVE: To examine whether maternal fuels and metabolic markers during pregnancy are associated with offspring hepatic fat in childhood. METHODS: This analysis included 286 mother-child pairs from the Healthy Start Study, a longitudinal pre-birth cohort in Colorado. Fasting blood draws were collected in early pregnancy (~17 weeks) and mid pregnancy (~27 weeks). Offspring hepatic fat was assessed by magnetic resonance imaging (MRI) at ~5 years. RESULTS: In early pregnancy, maternal triglycerides (TGs) and free fatty acids (FFAs) were positively associated with offspring hepatic fat [Back-transformed β (95% CI): 1.15 (1.05,1.27) per 1 standard deviation (SD) TGs; 1.14 (1.05,1.23) per 1 SD FFAs]. Maternal total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were also associated with offspring hepatic fat, but only among boys [1.22 (1.08,1.37) per 1 SD TC; 1.21 (1.07,1.37) per 1 SD LDL-C]. In mid pregnancy, only maternal TGs remained associated with offspring hepatic fat. Adjusting for potential confounders or mediators did not affect associations. CONCLUSIONS: Maternal lipid concentrations, especially in early pregnancy, are associated with higher offspring hepatic fat, and may, therefore, be targeted in future interventions among pregnant women.

Background Maternal nutritional status affects placental function, which may underlie the intrauterine origins of obesity and diabetes. The extent to which diet quality is associated with placental signaling, and which specific pathways are impacted is unknown. Objective To examine sex-specific associations of maternal diet quality according to the Healthy Eating Index (HEI) - developed to align with recommendations from the Dietary Guidelines for Americans - with placental proteins involved in metabolism and mediators of environmental stress/inflammation/growth factor. Design Among 108 women from the Healthy Start cohort with a mean (SD) age of 29.0 (6.1) and pre-pregnancy BMI of 24.8 (5.3) we conducted multivariable linear regression analysis stratified by offspring sex. We adjusted for maternal race or ethnicity, age, education, prenatal smoking habits, and physical activity and tested for an association of maternal HEI>57 vs. ≤57 and the abundance and phosphorylation of key proteins involved in insulin/growth factor signaling, mediators of environmental stress/inflammation/growth factors, mechanistic target of rapamycin signaling proteins, and energy sensing in placental villus samples. HEI> 57 was chosen given its prior relevance among Healthy Start mother-child dyads. Results In adjusted models, HEI >57 was associated with greater abundance of insulin receptor-β (0.80; 95% CI: 0.11, 1.49) in placentas of female. In males, maternal HEI >57 was associated with greater activation and abundance of select placental nutrient sensing proteins and environmental stress/inflammation/growth factor proteins (S6K1 Thr389 /S6K1 [0.81; 95% CI: 0.21, 1.41], and JNK1 Thr183/Tyr185/ JNK1 [0.82; 95% CI: 0.27, 1.37], JNK2 Thr183/Tyr185/ JNK2 [0.57; 95% CI: 0.02, 1.11]). Conclusion Higher quality diet had sex-specific associations with placental protein abundance/phosphorylation. Given that these proteins have been correlated with neonatal anthropometry, our findings provide insight into modifiable factors and placental pathways that should be examined in future studies as a potential links between maternal diet and offspring metabolic health.Study registration ID: NCT02273297Study registration URL: https://clinicaltrials.gov/ct2/show/NCT02273297?term = NCT02273297&draw = 2&rank = 1.

Purpose: Strong evidence supports the relationship between health coverage and improved health status. Little is known about the lasting impact of prior health insurance on the prior insured's use of health services. We aimed to examine the association between prior insurance status and health service utilization (HSU) among the long-term uninsured (LTU) in South Carolina. Methods: The current study used data from in-person interviews of the LTU collected in a 2014 cross-sectional South Carolina survey. Men and women between 18–64 years of age who reported not having health insurance for at least 24 months at the time of data collection were included. Propensity score analysis was used to examine the associations between prior insurance status and three outcome variables: (1) having a usual source of care, (2) HSU, and (3) delaying health care needs. Results: Prior health insurance significantly predicted a greater likelihood of having a usual source of care (effect size: 9.2%, p=0.004) and having had at least one preventive visit during the past 2 years (effect size: 6.4%, p=0.035). Prior insurance coverage was positively associated with delayed health care utilization, but the result was not statistically significant (p=0.703). Conclusions: Among the LTU, ever having insurance coverage was positively associated with having a usual source of care and HSU. The lasting impact of insurance coverage on HSU behavior extends beyond the period of insurance coverage, which provides a more comprehensive and deeper understanding of the long-term implications of national and local efforts in expanding insurance coverage.

ObjectivesGroup prenatal care (GPC), an alternative to individual prenatal care (IPC), is becoming more prevalent. This study aimed to describe the attendance and reasons of low attendance among pregnant women who were randomly assigned to receive GPC or IPC and explore the maternal characteristics associated with low-attendance.MethodsThis study was a descriptive study among Medically low risk pregnant women (N = 992) who were enrolled in an ongoing prospective study. Women were randomly assigned to receive CenteringPregnany GPC (N = 498) or IPC (N = 994) in a single clinical site The attendance frequency and reason for low-attendance (i.e. ≤ 5/10 sessions in GPC or ≤ 5 visits in IPC) were described separately in GPC and IPC. Multivariable logistic regressions were performed to explore the associations between maternal characteristics and low-attendance.ResultsOn average, women in GPC attended 5.32 (3.50) sessions, with only 6.67% attending all 10 sessions. Low-attendance rate was 34.25% in GPC and 10.09% in IPC. The primary reasons for low-attendance were scheduling barriers (23.19%) and not liking GPC (16.43%) in GPC but leaving the practice (34.04%) in IPC. In multivariable analysis, lower perceived family support (P = 0.01) was positively associated with low-attendance in GPC, while smoking in early pregnancy was negatively associated low-attendance (P = 0.02) in IPC.Conclusions for practiceScheduling challenges and preference for non-group settings were the top reasons for low-attendance in GPC. Changes may need to be made to the current GPC model in order to add flexibility to accommodate women's schedules and ensure adequate participation.Trial registrationNCT02640638 Date Registered: 12/20/2015.

AIMS/HYPOTHESIS: The aim of this work was to investigate the association of maternal HbA(1c) during mid-pregnancy with biomarkers of glucose–insulin homeostasis during early childhood (4–7 years of age) and to assess whether and how offspring adiposity at birth and at age 4–7 years mediates this relationship among 345 mother–child pairs in the Healthy Start Study. METHODS: The exposure was maternal HbA(1c) (mmol/mol) measured at 20–34 gestational weeks and categorised into tertiles. The outcomes were offspring fasting glucose, 1/insulin, HOMA2-IR, and HOMA2-B at age 4–7 years. The mediators were per cent fat mass (%FM) at birth, %FM at age 4–7 years, and the sum of the two as a metric of cumulative adiposity. Mediation analyses were conducted via a counterfactual-based approach. All models accounted for maternal race/ethnicity, offspring age and sex. RESULTS: There was a significant total effect of maternal HbA(1c) on offspring glucose and 1/insulin. Specifically, we observed a positive trend across tertiles of HbA(1c) and offspring glucose (p trend

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.

Maternal diabetes during pregnancy impacts offspring body composition and has been associated with greater offspring adiposity across the life course. However, the extent to which the relationship between maternal glycemia and offspring adiposity during later life is independent of neonatal adiposity is unclear. In a prospective study of 544 mother-child pairs in the Healthy Start Study, we estimated the total effect of maternal HbA1c on childhood fat mass (FM) %, and the direct effect independent of neonatal FM %. We measured maternal fasting HbA1c at a gestational age of 20-34 weeks, and offspring FM % using air displacement plethysmography at birth and during childhood (age 4-7 y). We used multivariable linear regression with HbA1c tertiles (T1 [reference], T2, T3) as the exposure, neonatal FM % as the mediator, and childhood FM % as the outcome. A counterfactual-based approach was used to estimate total and direct effects, while also accounting for exposure-mediator interaction. Covariates were maternal race, education, gestational weight gain and smoking, and offspring sex and age. The medians (interquartile ranges) of the HbA1c tertiles were T1: 4.80 (3.70, 4.90), T2: 5.05 (5.00, 5.10), and T3: 5.30 (5.20, 6.30). The estimated total effect on child FM % was 1.27 (95% CI: 0.00, 2.54) units higher for T2 vs. T1, and 1.53 (0.23, 2.82) units higher for T3 vs. T1 (P-trend=0.02). After adjusting for pre-pregnancy BMI, the total effect was 1.18 (-0.09, 2.44) and 1.31 (0.00, 2.62) units higher for T2 vs. T1 and T3 vs. T1, respectively (P-trend=0.04). The direct effect after accounting for neonatal FM % was slightly attenuated (T2 vs. T1: 1.14 [-0.11, 2.39], T3 vs. T1: 1.20 [-0.11, 2.51]; P-trend=0.07). Excluding women with gestational diabetes mellitus (n=27) did not substantially impact the results. Our data suggest that maternal glycemia during pregnancy, even within normal levels, may influence childhood adiposity through pathways that are in part mediated by programming of neonatal adiposity. Disclosure E.C. Francis: None. B. Ringham: None. D.H. Glueck: None. W. Perng: None. D. Dabelea: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK076648-10)

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 Gestational diabetes mellitus (GDM) reflects an increased risk of developing type 2 diabetes (T2D) after pregnancy in women. Offspring born to mothers with GDM are at an elevated risk of obesity and T2D at a young age. Currently, there are lack of ways for identifying women in early pregnancy who are at risk of developing GDM. As a result, both mothers and fetus are not treated until late in the second trimester when GDM is diagnosed. The recent advance in metabolomics, a new approach of systematic investigation of the metabolites, provides an opportunity for early detection of GDM, and classifying the risk of subsequent chronic diseases among women and their offspring. Methods We reviewed the literatures published in the past 20 years on studies using high-throughput metabolomics technologies to investigate women with GDM and their offspring. Conclusions Despite the inconsistent results, previous studies have identified biomarkers that involved in specific metabolite groups and several pathways, including amino acid metabolism, steroid hormone biosynthesis, glycerophospholipid metabolism, and fatty acid metabolism. However, most studies have small sample sizes. Further research is warranted to determine if metabolomics will result in new indicators for the diagnosis, management, and prognosis of GDM and related complications.

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.

Healthy dietary patterns may promote kidney health and prevent adverse renal outcomes. Although reviews have summarized the findings from studies on dietary patterns for chronic kidney disease (CKD) management, less is known about dietary patterns for maintaining kidney health prior to CKD development. The current review summarized the results from observational studies from March 2009 to March 2019 investigating associations between dietary patterns and renal outcomes in the general population. The main renal outcome assessed was CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2). A total of twenty-six research articles met the inclusion criteria. Adherence to the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets were significantly associated with a decreased risk of CKD in the majority of the studies. Furthermore, a posteriori “unhealthy” dietary patterns were associated with an increased risk of CKD. In conclusion, the findings from this review suggest that adherence to DASH and Mediterranean dietary patterns may be useful in promoting kidney health and preventing CKD in the general population. More studies, in particular among minorities, are warranted to investigate the role of diet, a potentially modifiable factor, in promoting kidney health.

OBJECTIVES: Women with gestational diabetes (GDM) are at increased risk for renal complications later in life. Nut intake has been associated with reduced cardiometabolic risk, but few studies have examined its association with renal function. We examined associations of nut intake and renal function among women with prior GDM. METHODS: We studied 330 women from the Danish National Birth Cohort (1996–2002) with a GDM pregnancy who participated in a clinical exam 9 to 16 years after the index pregnancy as part of the Diabetes & Women's Health Study (2012–2014) and were free of major chronic diseases at follow-up. Habitual past year intake of nine types of nuts was ascertained at follow-up using a food frequency questionnaire. Total nut intake was classified as none (1 serving/d). Estimated glomerular filtration rate (eGFR) via CKD-EPI equation and urine albumin-to-creatinine ratio (UACR) were calculated based on serum creatinine (mg/dL) and urine albumin (mg/L), and creatinine (mg/dL) measurements respectively. We estimated % differences with 95% confidence intervals (CI) in these outcomes by nut intake adjusted for current body mass index, age, physical activity, energy intake, and dietary variables. We explored possible non-linear relations using restricted cubic splines. RESULTS: A significant non-linear U-shaped association was detected between total nut consumption and UACR (P = 0.001) with lowest UACR levels among women with weekly consumption. Compared to women with weekly intake (n = 222), adjusted UACR levels were 86% [95% CI: 15%, 200%] and 23% [−1%, 54%] higher among women with no or monthly nut intake, respectively, while UACR levels were 118% [22%, 286%] higher among women with daily intake. Compared to weekly consumers, adjusted eGFR levels were 9% [0%, 19%] higher among daily consumers. CONCLUSIONS: Moderate nut consumption may be beneficial to kidney health among women with prior GDM. FUNDING SOURCES: Intramural Research Program of the NICHD, March of Dimes Birth Defects Foundation, Innovation Fund Denmark, Health Foundation, Heart Foundation, EU, Danish Diabetes Academy supported by Novo Nordisk Foundation, and NIH Building Interdisciplinary Research Careers in Women's Health Program.

OBJECTIVES: Women diagnosed with gestational diabetes (GDM) are usually advised to reduce carbohydrate intake and increase physical activity (PA). There is limited longitudinal population-based evidence on whether these women change their diet and PA after diagnosis. Our aim was to examine if women with GDM do in fact alter their diet and PA post diagnosis and identify characteristics of women with favorable changes. METHODS: This study included 1735 women from the NICHD Fetal Growth Studies-Singletons (2009–2013) who completed an Automated Self-Administered 24-Hour dietary recall and a Pregnancy PA Questionnaire at 16–22, 24–29, 30–33, 34–37, and 38–41 (PA only) gestational weeks (GW). GDM was ascertained by medical records (n = 85; 4.9%), diagnosed at a mean of 27.7 GW (S.D. 4.7). We used adjusted linear mixed models with random effects to estimate changes in diet/PA post-GDM screening (non-GDM)/diagnosis (GDM) and tested for differences by GDM status. For factors that changed among women with GDM, we tested for differences by covariates. RESULTS: Women with GDM significantly reduced total sugar intake after diagnosis by 27.9 g/d (95% confidence interval −41.5, −14.3), while it increased in women without GDM by 3.7 g/d (0.7, 6.7) after screening (Figure). Specifically, women with GDM reduced added sugars [−12.0 g/d (−22.0, −2.0)] and fruit juice [−0.4 serving/d (−0.6, −0.2)], and increased artificially sweetened beverage intake [0.2 servings/d (0.1, 0.3)]. The significant reduction in total sugar persisted in all women except Hispanics [−9.0 g/d (−27.2, 9.3); P-interaction = 0.08] and non-nulliparous women [−10.7 g/d (−25.5, 4.2); P-interaction = 0.001]. Women with GDM performed less moderate intensity PA [−30.6 MET-hr/wk (−43.2, −18.0)] after diagnosis than before, which was less than women without GDM [−17.1 (−19.9, −14.3)]. CONCLUSIONS: Majority of women with GDM undergoing usual care substantially decreased their overall sugar intake after diagnosis primarily by reducing added sugars and fruit juice, and increasing artificially sweetened beverages. Greater dietary counseling efforts may be needed among Hispanic and multiparous women, and for PA in all women with GDM. FUNDING SOURCES: This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

OBJECTIVES: Prospective studies with measurement of a comprehensive panel of adipokines in early pregnancy and gestational diabetes (GDM) risk are sparse, and studies of adipokines for prediction of GDM are limited. We aimed to prospectively investigate a comprehensive panel of adipokines in relation to GDM risk. METHODS: We investigated a panel of adipokines in relation to GDM risk. In a nested case-control study within the NICHD Fetal Growth Studies-Singleton cohort (2009–2013), we identified 107 GDM cases and selected 214 controls matched on age, race/ethnicity, and gestational week (GW) at blood draw. Plasma Leptin, Soluble Leptin Receptor (sOB-R), Free Leptin, Chemerin, Fatty Acid Binding Protein 4 (FABP4), Retinol Binding Protein 4, Adiponectin, Omentin1, and Vaspin were measured prior to GDM at GWs 10–14, 15–26. Adjusting for maternal age, GW of blood collection, nulliparity, and family history of diabetes, conditional logistic analysis was performed to estimate adjusted odds ratios (aOR) for associations of adipokines with GDM. Receiver-operating-characteristic (ROC) curves assessed the predictive value of adipokines for GDM diagnosis. RESULTS: Before GDM diagnosis, Leptin, Free Leptin, Chemerin, and FABP4 concentrations were significantly higher, and Adiponectin, and sOB-R were lower among cases than controls. At GW 10–14, Adiponectin, and sOB-R were significantly and inversely related to GDM risk. For example, across increasing quartiles of sOB-R the aOR were 1.00 (ref), 0.37 (0.19, 0.74), 0.28 (0.13, 0.59), and 0.24 (0.11, 0.52) (P(trend )≤ .0001). In contrast, Leptin, Free Leptin, Chemerin, and FABP4 were significantly and positively associated with GDM risk; P(trend) ≤ .0001, ≤.0001, 0.005, 0.004, respectively. In general, associations of adipokines with GDM were stronger at GW 15–26. In addition, at GW 15–26, sOB-R significantly improved GDM prediction over conventional risk factors (age, GW, race, nulliparity, family history of diabetes, prepregnancy BMI) and glucose (P = 0.02). CONCLUSIONS: A panel of adipokines may be implicated in the pathogenesis of GDM with significant associations and incremental predictive value detected in early pregnancy before GDM is usually screened for. FUNDING SOURCES: Ellen Francis was supported by the Graduate Partnership Program in the Office of Intramural Training & Education, a component of the National Institutes of Health. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

Prospective studies with measurement of a comprehensive panel of adipokines in early pregnancy and gestational diabetes (GDM) risk are sparse, and studies of adipokines for prediction of GDM are limited. We investigated a panel of adipokines in relation to GDM risk. In a nested case-control study within the NICHD Fetal Growth Studies-Singleton cohort (2009-2013), we identified 107 GDM cases and selected 214 controls matched on age, race/ethnicity, and gestational week (GW) at blood draw. Plasma Leptin, Soluble Leptin Receptor (sOB-R), Free Leptin, Chemerin, Fatty Acid Binding Protein 4 (FABP4), Retinol Binding Protein 4, Adiponectin, Omentin1, and Vaspin were measured prior to GDM at GWs 10-14, 15-26. Adjusting for maternal age, GW of blood collection, nulliparity, and family history of diabetes, conditional logistic analysis was performed to estimate adjusted odds ratios (aOR) for associations of adipokines with GDM. Receiver-operating-characteristic (ROC) curves assessed the predictive value of adipokines for GDM diagnosis. Leptin, Free Leptin, Chemerin, and FABP4 concentrations were significantly higher. Adiponectin, and sOB-R were significantly lower among cases than controls. At GW 10-14, Adiponectin, and sOB-R were significantly and inversely related to GDM risk. For example, across increasing quartiles of sOB-R the aOR were 1.00 (ref), 0.37 (0.19, 0.74), 0.28 (0.13, 0.59), and 0.24 (0.11, 0.52) (Ptrend≤.0001). In contrast, Leptin, Free Leptin, Chemerin, and FABP4 were significantly and positively associated with GDM risk. In general, associations of adipokines with GDM were stronger at GW 15-26. In addition, at GW 15-26, sOB-R significantly improved GDM prediction over conventional risk factors (age, GW, race, nulliparity, family history of diabetes, prepregnancy BMI) and glucose (P = 0.02). A panel of adipokines may be implicated in the pathogenesis of GDM with significant associations and incremental predictive value detected in early pregnancy before GDM is usually screened for. Disclosure E.C. Francis: None. M. Li: None. S. Hinkle: None. J. Chen: None. L. Chen: None. C. Zhang: None. Funding National Institutes of Health

The authors examined patient and hospitalization characteristics associated with receiving a mental health assessment and disposition to an inpatient psychiatric facility among patients hospitalized for deliberate drug overdose.This retrospective analysis of 2012-2013 South Carolina all-payer data included adults ages 18-64 with at least one inpatient admission for a primary diagnosis of deliberate illicit or pharmaceutical drug overdose (N=2,686). Outcomes were receipt of a mental health assessment and disposition to an inpatient psychiatric facility. Multivariable logistic regression models were used to estimate the effects of patient and hospitalization characteristics on study outcomes.Non-Hispanic blacks and people of other races-ethnicities were less likely than non-Hispanic whites to receive a mental health assessment (non-Hispanic blacks, adjusted odds ratio [AOR]=0.52, 95% CI=0.34-0.81; other races-ethnicities, AOR=0.24, 95% CI=0.12-0.49). Non-Hispanic blacks were also less likely than non-Hispanic whites to be discharged to an inpatient psychiatric facility than to home (AOR=0.60, 95% CI=0.47-0.77). Compared with persons without insurance, those with insurance, except those with Medicaid, were more likely to be discharged to an inpatient psychiatric facility than to home (Medicare, AOR=3.06, 95% CI=2.36-3.96; private, AOR=2.78, 95% CI=2.23-3.47; other, AOR=7.58, 95% CI=4.21-13.6).Non-Hispanic white race-ethnicity and having insurance were predictive of receipt of a mental health assessment and disposition to an inpatient psychiatric facility among patients hospitalized for deliberate drug overdose. Study findings can inform clinical strategies and interventions aimed at reducing mental health care disparities among populations who are vulnerable to overdose or suicide.

Women with gestational diabetes mellitus (GDM) may be at an increased risk of liver complications because chronic hyperglycemia is a risk factor for liver fat accumulation and potential liver dysfunction. Large prospective studies examining liver fat accumulation following a GDM pregnancy are lacking.The DiabetesWomen's Health Study (2012-2014) examined the association between GDM and subsequent fatty liver scores among 607 women with and 619 women without GDM in the Danish National Birth Cohort. Nine to 16 years postpartum, a clinical examination was performed, with measurement of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase, from which fatty liver scoring indices were calculated to assess liver fat score, fatty liver index, hepatic steatosis index, and liver fat percentage. Relative risks (RR) with 95% confidence intervals (CI) for elevated liver scoring indices by GDM status were assessed adjusting for major risk factors, including prepregnancy body mass index.Women with prior GDM had higher adjusted ALT and AST levels than women without GDM (by 6.7% [95% CI 1.7-12.0] and 4.8% [95% CI 0.6-9.1], respectively). Women with GDM also had adjusted increased risks for elevated liver fat score (RR 2.34; 95% CI 1.68-3.27), fatty liver index (RR 1.59; 95% CI 1.27-1.99), and hepatic steatosis index (RR 1.44; 95% CI 1.21-1.71).Women with GDM during pregnancy were at an increased risk for fatty liver 9 to 16 years postpartum. Gestational diabetes mellitus may serve as another risk indicator for the early identification and prevention of liver fat accumulation.背景: 妊娠期糖尿病(gestational diabetes mellitus，GDM)女性发生肝脏并发症的风险可能增加，因为慢性高血糖是肝脏脂肪蓄积及潜在肝功能异常的危险因素。目前评估GDM患者产后肝脏脂肪蓄积的大型前瞻性研究不足。 方法: 糖尿病与女性健康研究(The DiabetesWomen's Health Study, 2012-2014)使用丹麦国家出生队列，在607例合并GDM的女性和619例无GDM的女性中调查了GDM与后续脂肪肝评分之间的相关性。在产后9-16年进行临床检查，测定丙氨酸氨基转移酶(alanine aminotransferase，ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase，AST)和γ-谷氨酰转移酶，由此计算脂肪肝评分指标，评估肝脏脂肪评分、脂肪肝指数、肝脏脂肪变性指数以及肝脏脂肪百分比。校正主要风险因素(包括妊娠前体重指数)后，根据GDM状态评估导致肝脏评分指标升高的相对风险(relative risk，RR)及其95%可信区间(confidence interval，CI)。 结果: 既往患GDM的女性校正的ALT及AST水平均高于无GDM的女性(分别高出6.7%[95% CI: 1.7-12.0]与4.8%[95% CI: 0.6-9.1])。GDM女性的校正后肝脏脂肪评分(RR 2.34；95% CI: 1.68-3.27)、脂肪肝指数(RR 1.59；95% CI: 1.27-1.99)及肝脏脂肪变性指数(RR 1.44；95% CI: 1.21-1.71)升高的风险也增加。 结论: 妊娠期合并GDM的女性在产后9-16年发生脂肪肝的风险增加。GDM可作为早期发现和预防肝脏脂肪蓄积的另一个风险指标。.

Chronic hyperglycemia is a risk factor for liver dysfunction. Women with gestational diabetes mellitus (GDM), glucose intolerance first recognized in pregnancy, may identify a population of individuals at an increased risk for liver complications. However, large prospective studies examining liver function following a GDM pregnancy are lacking. The Diabetes & Women’s Health (DWH) Study (2012-2014) followed women with and without GDM in the Danish National Birth Cohort (DNBC). DNBC was a population-based cohort study of pregnant Danish women (1996-2002). At 9-16 years postpartum, the DWH Study conducted a clinical exam and collected bio-specimens on 607 of 1,274 women with GDM and 619 of a random sample of 1,457 women without GDM during the index DNBC pregnancy. Markers of liver function measured at follow-up included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT). Liver function scoring indices were used to assess liver capacity including: nonalcoholic fatty liver disease liver fat score (NAFLD-LFS), fatty liver index (FLI), hepatic steatosis index (HSI), and liver fat percentage. The mean (standard deviation) age (years) at follow-up for women without and with prior GDM was 43.4 (4.5) and 43.8 (4.6), respectively. Women with prior GDM had an increased risk at follow-up of elevated NAFLD-LFS (Adjusted Relative risk [RR], 2.34; 95% CI, 1.68-3.27), FLI (RR, 1.59; 95% CI, 1.27-1.99), and HSI (RR, 1.44; 95% CI, 1.21-1.71) adjusted for pre-pregnancy BMI and other relevant risk factors compared to women without prior GDM. Women with prior GDM also had a significantly higher fatty liver percentage (Adjusted difference (%), 1.93; 95% CI, 1.10-2.77). Women with GDM during pregnancy were at an increased risk for subsequent abnormal liver function 9-16 years postpartum. GDM may serve as another risk indicator for the early identification and prevention of liver dysfunction. Disclosure S. Donnelly: None. S. Hinkle: None. S. Rawal: None. L. Grunnet: None. J.E. Chavarro: None. A.A. Vaag: Employee; Self; AstraZeneca. J. Wu: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. M. Li: None. A.A. Bjerregaard: None. A. Thuesen: None. R.E. Gore-Langton: None. E.C. Francis: None. F. Hu: None. M.Y. Tsai: None. S.F. Olsen: None. C. Zhang: None.

Preconception and prenatal nutrition is critical for fetal brain development. However, its associations with offspring neurodevelopmental disorders are not well understood. This study aims to systematically review the associations of preconception and prenatal nutrition with offspring risk of neurodevelopmental disorders. We searched the PubMed and Embase for articles published through March 2019. Nutritional exposures included nutrient intake or status, food intake, or dietary patterns. Neurodevelopmental outcomes included autism spectrum disorders (ASD), attention deficit disorder-hyperactivity (ADHD) and intellectual disabilities. A total of 2169 articles were screened, and 20 articles on ASD and 17 on ADHD were eventually reviewed. We found an overall inverse association between maternal folic acid or multivitamin supplementation and children’s risk of ASD; a meta-analysis including six prospective cohort studies estimated an RR of ASD of 0.64 (95% CI: 0.46, 0.90). Data on associations of other dietary factors and ASD, ADHD and related outcomes were inconclusive and warrant future investigation. Future studies should integrate comprehensive and more objective methods to quantify the nutritional exposures and explore alternative study design such as Mendelian randomization to evaluate potential causal effects.

OBJECTIVES: Osteoarthritis (OA) is a common disease which significantly contributes to disability among older adults. Dietary factors are suggested to play a role in preventing OA, however, studies in this area spare. The objective of this study was to assess the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) and OA in American adults. METHODS: This study included United States (US) adults (≥aged 20 years) who participated NHANES cycles 2007–2016. The Dietary Approaches to Stop Hypertension (DASH) score was calculated from nine food items with a higher DASH score indicating better adherence to the DASH dietary pattern. Multivariable logistic regression models adjusted for age, education, race/ethnicity, household income, smoking, alcohol consumption, and total energy intake were used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI) of DASH with OA. All analyses accounted for the complex survey design. RESULTS: Among the 17,349 participants included in this study, 9.05% reported OA. The DASH score was inversely associated with OA. The aOR (95% CI) were 1.00 (ref), 0.09 (0.70, 1.16), and 0.74 (0.58, 0.94) (P(trend) = 0.01) across the DASH score tertiles. When analyses were stratified by BMI categories (normal, overweight, obese) the magnitude of the association was stronger and remained significant only among obese participants (i.e., BMI ≥ 30 kg/m(2)). Among participants with an obese BMI, participants with a DASH score in the highest tertile compared to participants with a DASH score in the lowest tertile had a 17% lower likelihood of having OA (P = 0.009). CONCLUSIONS: In a representative sample of American adults, higher adherence to the DASH dietary pattern was associated with lower likelihood of having OA and this association was particularly evident among obese individuals. FUNDING SOURCES: N/A. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

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&ndash, offspring pairs enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies&ndash, 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&ndash, 14, 15&ndash, 26, 23&ndash, 31, and 33&ndash, 39 GW and categorized as &lt, 50 nmol/L, 50&ndash, 75 nmol/L, and &gt, 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&ndash, 14 GW, 16.8% and 49.2% of women had 25(OH)D &lt, 50 nmol/L and between 50&ndash, 75 nmol/L, respectively. The association of maternal 25(OH)D with neonatal anthropometry differed by GW and women&rsquo, s prepregnancy BMI (normal (&lt, 25.0 kg/m2), overweight/obese (25.0&ndash, 44.9 kg/m2)). All analyses were stratified by prepregnancy BMI status. Among women with an overweight/obese BMI, 25(OH)D &lt, 50 nmol/L at 10&ndash, 14 GW was associated with lower birthweight z-score (0.56, 95% CI: &minus, 0.99, &minus, 0.13) and length (&minus, 1.56 cm, 3.07, &minus, 0.06), and at 23&ndash, 31 GW was associated with shorter length (&minus, 2.77 cm, 13.38, &minus, 4.98) and lower sum of skinfolds (&minus, 9.18 mm, 4.98). Among women with a normal BMI, 25(OH)D &lt, 14 GW was associated with lower sum of skinfolds (&minus, 2.64 mm, 5.03, &minus, 0.24), at 23&ndash, 31 GW was associated with larger birthweight z-scores (0.64, 95% CI: 0.03, 1.25), and at 33-39 GW with both higher birthweight z-score (1.22, 95% CI: 0.71, 1.73) and longer length (1.94 cm, 95% CI: 0.37, 3.52). Maternal 25(OH)D status during pregnancy was associated with neonatal anthropometric measures, and the associations were specific to GW of 25(OH)D measurement and prepregnancy BMI.

A large, nonprofit, decentralized behavioral health agency with a multitude of services explored levels of resiliency of youth receiving residential treatment and non-clinical, community-based services. Significant differences in resiliency were found between different community-based programs and youth groups with different levels of need, using the Resiliency Scales for Children and Adolescents (Resiliency Scales for Children and Adolescents: A Profile of Personal Strengths Manual. San Antonio, TX). Consistent with expectations, higher reactivity and greater vulnerability characterized the residential youth. However, individual youth in residential treatment and across all community-based programs showed scores in similar typical and atypical ranges, indicating that youth in every setting could benefit from therapy or attention to elements of what constitutes resiliency.