Intrinsic motivation for physical activity, healthy eating, and self-weighing in association with corresponding behaviors in early pregnancy.

Healthy lifestyle behaviors influence maternal cardiovascular health, but motivation for them in pregnancy is poorly understood. We examined whether intrinsic motivation (assessed on 5-point scales for each behavior) is associated with three lifestyle behaviors in early pregnancy: physical activity, by intensity level; healthy eating, quantified with the Alternate Healthy Eating Index for Pregnancy (AHEI-P); and weight self-monitoring, a standard weight management technique. Participants in the Northern California Pregnancy, Lifestyle and Environment Study (PETALS) population-based cohort completed validated surveys in early pregnancy (2017-18; N = 472; 22 % Asian, 6 % Black, 30 % Hispanic, 13 % multiracial, 30 % White). Cross-sectional data were analyzed in 2021-22. Overall, 40.7 % (n = 192) met United States national physical activity guidelines; the average AHEI-P score was 62.3 out of 130 (SD 11.4); and 36.9 % reported regular self-weighing (≥once/week; n = 174). In models adjusted for participant characteristics, 1-unit increases in intrinsic motivation were associated with increased likelihood of meeting physical activity guidelines (risk ratio [95 % CI]: 1.66 [1.48, 1.86], p < 0.0001); meeting sample-specific 75th percentiles for vigorous physical activity (1.70 [1.44, 1.99], p < 0.0001) and AHEI-P (1.75 [1.33, 2.31], p < 0.0001); and regular self-weighing (2.13 [1.92, 2.37], p < 0.0001). A 1-unit increase in intrinsic motivation lowered the risk of meeting the 75th percentile for sedentary behavior (0.79 [0.67, 0.92], p < 0.003). Intrinsic motivation was not associated with reaching 75th percentiles for total, light, or moderate activity. Intrinsic motivation is associated with physical activity, healthy eating, and self-weighing among diverse individuals in early pregnancy. Results can inform intervention design to promote maternal health via increased enjoyment of lifestyle behaviors.

PFAS concentrations in early and mid-pregnancy and risk of gestational diabetes mellitus in a nested case-control study within the ethnically and racially diverse PETALS cohort.

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

Urinary Phenols in Early to Midpregnancy and Risk of Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort.

Environmental phenols are ubiquitous endocrine disruptors and putatively diabetogenic. However, data during pregnancy are scant. We investigated the prospective associations between pregnancy phenol concentrations and gestational diabetes mellitus (GDM) risk. In a nested matched case-control study of 111 individuals with GDM and 222 individuals without GDM within the prospective PETALS cohort, urinary bisphenol A (BPA), BPA substitutes (bisphenol F and bisphenol S [BPS]), benzophenone-3, and triclosan were quantified during the first and second trimesters. Cumulative concentrations across the two times were calculated using the area under the curve (AUC). Multivariable conditional logistic regression examined the association of individual phenols with GDM risk. We conducted mixture analysis using Bayesian kernel machine regression. We a priori examined effect modification by Asian/Pacific Islander (A/PI) race/ethnicity resulting from the case-control matching and highest GDM prevalence among A/PIs. Overall, first-trimester urinary BPS was positively associated with increased risk of GDM (adjusted odds ratio comparing highest vs. lowest tertile [aORT3 vs. T1] 2.12 [95% CI 1.00-4.50]). We identified associations among non-A/Ps, who had higher phenol concentrations than A/PIs. Among non-A/PIs, first-trimester BPA, BPS, and triclosan were positively associated with GDM risk (aORT3 vs. T1 2.91 [95% CI 1.05-8.02], 4.60 [1.55-13.70], and 2.88 [1.11-7.45], respectively). Triclosan in the second trimester and AUC were positively associated with GDM risk among non-A/PIs (P < 0.05). In mixture analysis, triclosan was significantly associated with GDM risk. Urinary BPS among all and BPA, BPS, and triclosan among non-A/PIs were associated with GDM risk. Pregnant individuals should be aware of these phenols' potential adverse health effects.

Development and validation of prediction models for gestational diabetes treatment modality using supervised machine learning: a population-based cohort study.

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

Glycemic Control Trajectories and Risk of Perinatal Complications Among Individuals With Gestational Diabetes.

Importance: Glycemic control is the cornerstone of gestational diabetes management. Glycemic control trajectories account for differences in longitudinal patterns throughout pregnancy; however, studies on glycemic control trajectories are scarce. Objective: To examine whether glycemic control trajectories from gestational diabetes diagnosis to delivery were associated with differential risk of perinatal complications. Design, Setting, and Participants: This population-based cohort study included individuals with gestational diabetes with longitudinal electronic health record data from preconception to delivery who received prenatal care at Kaiser Permanente Northern California (KPNC) and were enrolled in KPNC's telemedicine-based gestational diabetes care program between January 2007 and December 2017. Data analysis was conducted from September 2021 to January 2022. Exposures: Glycemic control trajectories were derived using latent class modeling based on the American Diabetes Association's recommended self-monitoring of blood glucose measurements. Optimal glycemic control was defined as at least 80% of all measurements meeting the targets at KPNC clinical settings. Main Outcomes and Measures: Multivariable Poisson regression models were used to estimate the associations of glycemic control trajectories with cesarean delivery, preterm birth, shoulder dystocia, large- and small-for-gestational-age, and neonatal intensive care unit admission and stay of 7 days or longer. Results: Among a total of 26 774 individuals (mean [SD] age, 32.9 [5.0] years; 11 196 Asian or Pacific Islander individuals [41.8%], 1083 Black individuals [4.0%], 7500 Hispanic individuals [28.0%], and 6049 White individuals [22.6%]), 4 glycemic control trajectories were identified: stably optimal (10 528 individuals [39.3%]), rapidly improving to optimal (9151 individuals [34.2%]), slowly improving to near-optimal (4161 individuals [15.5%]), and slowly improving to suboptimal (2934 individuals [11.0%]). In multivariable models with the rapidly improving to optimal trajectory group as the reference group, glycemic control trajectories were associated with perinatal complications with a gradient across stably optimal to slowly improving to suboptimal. For individuals in the stably optimal trajectory group, there were lower risks of cesarean delivery (adjusted relative risk [aRR], 0.93 [95% CI, 0.89-0.96]), shoulder dystocia (aRR, 0.75 [95% CI, 0.61-0.92]), large-for-gestational age (aRR, 0.74 [95% CI, 0.69-0.80]), and neonatal intensive care unit admission (aRR, 0.90 [95% CI, 0.83-0.97]), while for patients in the slowly improving to suboptimal glycemic control trajectory group, risks were higher for cesarean delivery (aRR, 1.18 [95% CI, 1.12-1.24]; (P for trend < .001), shoulder dystocia (aRR, 1.41 [95% CI, 1.12-1.78]; P for trend < .001), large-for-gestational-age (aRR, 1.42 [95% CI, 1.31-1.53]; P for trend < .001), and neonatal intensive care unit admission (aRR, 1.33 [95% CI, 1.20-1.47]; P for trend < .001). The risk of small-for-gestational-age was higher in patients in the stably optimal group (aRR, 1.10 [95% CI, 1.02-1.20]) and lower in the slowly improving to suboptimal group (aRR, 0.63 [95% CI, 0.53-0.75]). Conclusions and Relevance: These findings suggest that slowly improving to near-optimal and slowly improving to suboptimal glycemic control trajectories were associated with increased risk of perinatal complications. Future interventions should help individuals achieve glycemic control early after gestational diabetes diagnosis and throughout pregnancy to decrease the risk of perinatal complications.

Uptake of guideline-recommended postpartum diabetes screening among diverse women with gestational diabetes: associations with patient factors in an integrated health system in USA.

INTRODUCTION: Clinical guidelines urge timely postpartum screening for diabetes among women with gestational diabetes mellitus (GDM), yet patient factors associated with screening uptake remain unclear. We aimed to identify patient factors associated with completed postpartum diabetes screening (2-hour oral glucose tolerance test within 4-12 weeks postpartum), as recommended by the American Diabetes Association (ADA). RESEARCH DESIGN AND METHODS: Within the context of Gestational Diabetes' Effects on Moms (GEM), a pragmatic cluster randomized trial (2011-2012), we examined survey and electronic health record data to assess clinical and sociodemographic factors associated with uptake of ADA-recommended postpartum screening. Participants included 1642 women (76% racial/ethnic minorities) identified with GDM according to the Carpenter and Coustan criteria in a health system that deploys population-level strategies to promote screening. To contextualize these analyses, screening rates derived from the GEM trial were compared with those in the health system overall using registry data from a concurrent 10-year period (2007-2016, n=21 974). RESULTS: Overall 52% (n=857) completed recommended postpartum screening in the analytic sample, comparable to 45.7% (n=10 040) in the registry. Screening in the analytic sample was less likely among women at elevated risk for type 2 diabetes, assessed using items from an ADA risk test (vs non-elevated; adjusted rate ratio (aRR)=0.86 (95% CI 0.75 to 0.98)); perinatal depression (0.88 (0.79 to 0.98)); preterm delivery (0.84 (0.72 to 0.98)); parity ≥2 children (vs 0; 0.80 (0.69 to 0.93)); or less than college education (0.79 (0.72 to 0.86)). Screening was more likely among Chinese Americans (vs White; 1.31 (1.15 to 1.49)); women who attended a routine postpartum visit (5.28 (2.99 to 9.32)); or women who recalled receiving healthcare provider advice about screening (1.31 (1.03 to 1.67)). CONCLUSIONS: Guideline-recommended postpartum diabetes screening varied by patient clinical and sociodemographic factors. Findings have implications for developing future strategies to improve postpartum care.

Predictive Metabolomic Markers in Early to Mid-pregnancy for Gestational Diabetes Mellitus: A Prospective Test and Validation Study.

Gestational diabetes mellitus (GDM) predisposes pregnant individuals to perinatal complications and long-term diabetes and cardiovascular diseases. We developed and validated metabolomic markers for GDM in a prospective test-validation study. In a case-control sample within the PETALS cohort (GDM n = 91 and non-GDM n = 180; discovery set), a random PETALS subsample (GDM n = 42 and non-GDM n = 372; validation set 1), and a case-control sample within the GLOW trial (GDM n = 35 and non-GDM n = 70; validation set 2), fasting serum untargeted metabolomics were measured by gas chromatography/time-of-flight mass spectrometry. Multivariate enrichment analysis examined associations between metabolites and GDM. Ten-fold cross-validated LASSO regression identified predictive metabolomic markers at gestational weeks (GW) 10-13 and 16-19 for GDM. Purinone metabolites at GW 10-13 and 16-19 and amino acids, amino alcohols, hexoses, indoles, and pyrimidine metabolites at GW 16-19 were positively associated with GDM risk (false discovery rate <0.05). A 17-metabolite panel at GW 10-13 outperformed the model using conventional risk factors, including fasting glycemia (area under the curve: discovery 0.871 vs. 0.742, validation 1 0.869 vs. 0.731, and validation 2 0.972 vs. 0.742; P < 0.01). Similar results were observed with a 13-metabolite panel at GW 17-19. Dysmetabolism is present early in pregnancy among individuals progressing to GDM. Multimetabolite panels in early pregnancy can predict GDM risk beyond conventional risk factors.

Healthy preconception and early-pregnancy lifestyle and risk of preterm birth: a prospective cohort study.

BACKGROUND: 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. OBJECTIVES: We aimed to examine the associations of preconceptional and early-pregnancy low-risk modifiable factors (individually and in combination) with PTB risk. METHODS: 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 delivery <37 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 score <75th 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. RESULTS: 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. CONCLUSIONS: 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.

Exercise During the First Trimester of Pregnancy and the Risks of Abnormal Screening and Gestational Diabetes Mellitus.

OBJECTIVE: To estimate the effects of exercise during the first trimester on the risks of abnormal screening and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Data come from PETALS, a prospectively followed pregnancy cohort (n = 2,246, 79% minorities) receiving care at Kaiser Permanente Northern California. A Pregnancy Physical Activity Questionnaire was used to assess exercise. Glucose testing results for screening and diagnostic tests were obtained from electronic health records. Inverse probability of treatment weighting and targeted maximum likelihood with data-adaptive estimation (machine learning) of propensity scores and outcome regressions were used to obtain causal risk differences adjusted for potential confounders, including prepregnancy BMI, exercise before pregnancy, and gestational weight gain. Exercise was dichotomized at 1) the cohort's 75th percentile for moderate- to vigorous-intensity exercise (≥13.2 MET-h per week or ≥264 min per week of moderate exercise), 2) current recommendations (≥7.5 MET-h per week or ≥150 min per week of moderate exercise), and 3) any vigorous exercise. RESULTS: Overall, 24.3% and 6.5% had abnormal screening and GDM, respectively. Exercise meeting or exceeding the 75th percentile decreased the risks of abnormal screening and GDM by 4.8 (95% CI 1.1, 8.5) and 2.1 (0.2, 4.1) fewer cases per 100, respectively, in adjusted analyses. CONCLUSIONS: Exercise reduces the risks of abnormal screening and GDM, but the amount needed to achieve these risk reductions is likely higher than current recommendations. Future interventions may consider promoting ≥38 min per day of moderate-intensity exercise to prevent GDM.

A telehealth lifestyle intervention to reduce excess gestational weight gain in pregnant women with overweight or obesity (GLOW): a randomised, parallel-group, controlled trial.

BACKGROUND: Excess gestational weight gain (GWG) among women with overweight or obesity synergistically increases their already elevated risk of having gestational diabetes, a caesarean delivery, a large for gestational age infant, and post-partum weight retention, and increases their child's risk of obesity. We investigated whether a primarily telehealth lifestyle intervention reduced excess GWG among women with overweight or obesity. METHODS: We did a randomised controlled trial in five antenatal clinics of Kaiser Permanente; Oakland, San Leandro, Walnut Creek, Fremont, and Santa Clara, CA, USA. Women at 8-15 weeks' gestation with singletons, pre-pregnancy BMI 25·0-40·0 kg/m2, and aged 18 years or older were randomly assigned (1:1) to receive the telehealth lifestyle intervention or usual antenatal care. Randomisation was adaptively balanced for age, BMI, and race and ethnicity. Data collectors and investigators were masked to group assignments. The core lifestyle intervention consisted of two in-person and 11 telephone sessions on behavioural strategies to improve weight, diet, and physical activity, and stress management to help women meet a trial goal of gaining at the lower limit of the Institute of Medicine (IOM) guidelines range for total GWG: 7 kg for women with overweight and 5 kg for women with obesity. Usual antenatal care included an antenatal visit at 7-10 weeks' gestation, an additional seven antenatal visits, on average, and periodic health education newsletters, including the IOM GWG guidelines and information on healthy eating and physical activity in pregnancy. The primary outcome was weekly rate of GWG expressed as excess GWG, per Institute of Medicine guidelines and mean assessed in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT02130232. FINDINGS: Between March 24, 2014, and Sept 26, 2017, 5329 women were assessed for eligibility and 200 were randomly assigned to the lifestyle intervention group and 198 to the usual care group. Analyses included 199 women in the lifestyle intervention group (one lost to follow-up) and 195 in the usual care group (three lost to follow-up). 96 (48%) women in the lifestyle intervention group and 134 (69%) women in the usual care group exceeded Institute of Medicine guidelines for rate of GWG per week (relative risk 0·70, 95% CI 0·59 to 0·83). Compared with usual care, women in the lifestyle intervention had reduced weekly rate of GWG (mean 0·26 kg per week [SD 0·15] vs 0·32 kg per week [0·13]; mean between-group difference -0·07 kg per week, 95% CI -0·09 to -0·04). No between-group differences in perinatal complications were observed. INTERPRETATION: Our evidence-based programme showed that health-care delivery systems could further adapt to meet the needs of their clinical settings to prevent excess GWG and improve healthy behaviours and markers of insulin resistance among women with overweight or obesity by using telehealth lifestyle interventions. FUNDING: US National Institutes of Health.

Exercise During the First Trimester and Infant Size at Birth: Targeted Maximum Likelihood Estimation of the Causal Risk Difference.

This cohort study sought to estimate the differences in risk of delivering infants who were small or large for gestational age (SGA or LGA, respectively) according to exercise during the first trimester of pregnancy (vs. no exercise) among 2,286 women receiving care at Kaiser Permanente Northern California in 2013-2017. Exercise was assessed by questionnaire. SGA and LGA were determined by the sex- and gestational-age-specific birthweight distributions of the 2017 US Natality file. Risk differences were estimated by targeted maximum likelihood estimation, with and without data-adaptive prediction (machine learning). Analyses were also stratified by prepregnancy weight status. Overall, exercise at the cohort-specific 75th percentile was associated with an increased risk of SGA of 4.5 (95% CI: 2.1, 6.8) per 100 births, and decreased risk of LGA of 2.8 (95% CI: 0.5, 5.1) per 100 births; similar findings were observed among the underweight and normal-weight women, but no associations were found among those with overweight or obesity. Meeting Physical Activity Guidelines was associated with increased risk of SGA and decreased risk of LGA but only among underweight and normal-weight women. Any vigorous exercise reduced the risk of LGA in underweight and normal-weight women only and was not associated with SGA risk.

Central Obesity Increases the Risk of Gestational Diabetes Partially Through Increasing Insulin Resistance.

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 < 0.85, one or more established risk factors increased GDM risk 1.99-fold (95% CI: 0.99-4.02). For women with WHR ≥ 0.85 but no established risk factors, GDM risk increased 2.41-fold (95% CI: 1.14-5.06), and in those with established risk factors it increased 6.22-fold (95% CI: 3.49-11.10). Similar but attenuated results were observed for WC ≥ 88 cm. Insulin, HOMA-IR, and adiponectin levels mediated the WHR-GDM association by 9% to 11%; corresponding mediation proportions for the WC-GDM association were 35% to 41% (all P < 0.04). CONCLUSIONS: Central obesity in early pregnancy represented a high-risk phenotype for GDM independent of other risk factors, including overweight or obesity, and may inform early screening and prevention strategies.

Poor diet quality in pregnancy is associated with increased risk of excess fetal growth: a prospective multi-racial/ethnic cohort study.

BACKGROUND: Nutritional perturbations during pregnancy may impact fetal and long-term childhood growth, although there are limited data on overall diet quality. We investigated whether diet quality, measured by the Healthy Eating Index-2010 (HEI-2010), during pregnancy was related to birthweight z-score (BWZ) and the clinically relevant birth outcomes of large- and small-for-gestational age (LGA and SGA). METHODS: In a prospective cohort of 2269 multi-racial/ethnic women from the Pregnancy Environment and Lifestyle Study (2014-2017), dietary intake was assessed by a food frequency questionnaire during early pregnancy. Offspring BWZ and LGA or SGA were derived based on gestational age-, sex-, and racial/ethnic-specific birthweight distributions. Multivariable linear and Poisson regression with robust standard errors were used. RESULTS: About 80% of women did not achieve good diet quality (HEI-2010 < 80). After adjusting for covariates, infants born to women in the lowest vs highest quartile of HEI-2010 (37.5-64.4 vs 78.7-94.2) had a 0.12 standard-deviation [95% confidence interval (CI) 0.01-0.23, P-for-trend = 0.023] greater BWZ and 1.76-fold (1.08-2.87, P-for-trend = 0.037) increased risk of LGA. No association was observed between HEI-2010 and SGA. Per-5-point substitution of the reversely coded empty calories component score with the whole grains component score in the HEI-2010 was related to a 25% (95% CI 0.66-0.86) lower risk of LGA. CONCLUSIONS: Poor diet quality in pregnancy was associated with higher birthweight and increased risk of LGA independent of maternal obesity and other covariates. Substitution of empty calories with whole grains may mitigate the risk of excess fetal growth. Our findings may inform potential prevention strategies and dietary guidelines for pregnant women.

Liver Enzymes in Early to Mid-pregnancy, Insulin Resistance, and Gestational Diabetes Risk: A Longitudinal Analysis.

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

The Pregnancy Environment and Lifestyle Study (PETALS): a population-based longitudinal multi-racial birth cohort.

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

Outreach to diversify clinical trial participation: A randomized recruitment study.

BACKGROUND/AIMS: Racial and ethnic minorities remain underrepresented in clinical research, yet few recruitment strategies have been rigorously evaluated. METHODS: We experimentally tested whether targeted recruitment letters acknowledging diabetes health disparities and health risks specific to recipients' racial/ethnic group improved two metrics of trial participation: willingness to be screened and enrollment. This experiment was efficiently nested within a randomized clinical trial examining a preventive lifestyle intervention among women at high risk for diabetes. Pregnant women with gestational diabetes or impaired glucose tolerance (N = 445) were randomized to receive a targeted recruitment letter with health risk information specific to their racial/ethnic group (n = 216), or a standard letter with risk information for the general population (n = 229). All letters were bilingual in English and Spanish. RESULTS: The targeted as compared to the standard letter did not improve screening or enrollment rates overall or within separate racial/ethnic groups. Among Latina women who preferred Spanish, the targeted letter showed trends for improved screening (66.7% vs 33.3%, p = .06) and enrollment rates (38.9% vs 13.3%, p = .13). In contrast, among Latina women who preferred English, the targeted letter significantly lowered screening (29.6% vs 57.1%, p = .04) and showed trends for lowered enrollment rates (25.9% vs 50.0%, p = .07). CONCLUSION: Results from this randomized study appear to suggest that recruitment letters with diabetes health risk information targeted to recipients' race/ethnicity may improve one metric of clinical trial participation among Latina women who prefer Spanish, but not English. Larger experimental studies, incorporating input from diverse participant stakeholders, are needed to develop evidence-based minority recruitment strategies.

Change in body mass index between pregnancies and the risk of gestational diabetes in a second pregnancy.

OBJECTIVE: To estimate the association between interpregnancy change in body mass index (BMI) and the risk of gestational diabetes mellitus (GDM) in a second pregnancy. METHODS: In a retrospective cohort analysis of 22,351 women, logistic regression models provided adjusted estimates of the risk of GDM in women gaining 3.0 or more 2.0-2.9, and 1.0-1.9 BMI units, or losing 1.0-2.0 and more than 2.0 units between pregnancies (one BMI unit corresponds to 5.9 pounds for the average height [5 feet 4 inches] of the study population). Women with stable BMIs (±1.0 BMI unit) comprised the reference. RESULTS: For those with GDM in the first pregnancy, the age-adjusted risk of GDM in the second pregnancy was 38.19% (95% confidence interval [CI] 34.96-41.42); for those whose first pregnancy was not complicated by GDM, the risk was 3.52% (95% CI 3.27-3.76). Compared with women who remained stable, interpregnancy BMI gains were associated with an increased risk of GDM in the second pregnancy (odds ratio [OR] 1.71 [95% CI 1.42-2.07] for gaining 1.0-1.9 BMI units; OR 2.46 [95% CI 2.00-3.02] for 2.0-2.9 BMI units; and OR 3.40 [95% CI 2.81-4.12] for 3.0 or more BMI units). The loss of BMI units was associated with a lower risk of GDM only among women who were overweight or obese in the first pregnancy (OR 0.26 [95% CI 0.14-0.47] for the loss of at least 2.0 BMI units). In overweight and obese women, those with GDM in the first pregnancy that did not develop the condition again gained fewer BMI units than those experiencing recurrent GDM (mean change 0.66 [95% CI 0.25-1.07] compared with 2.00 [95% CI 1.56-2.43] BMI units, respectively). CONCLUSION: Interpregnancy increases in BMI between the first and second pregnancy increases a woman's risk of GDM pregnancy.

A pregnancy and postpartum lifestyle intervention in women with gestational diabetes mellitus reduces diabetes risk factors: a feasibility randomized control trial.

OBJECTIVE: To pilot, among women with gestational diabetes mellitus (GDM), the feasibility of a prenatal/postpartum intervention to modify diet and physical activity similar to the Diabetes Prevention Program. The intervention was delivered by telephone, and support for breastfeeding was addressed. RESEARCH DESIGN AND METHODS: The goal was to help women return to their prepregnancy weight, if it was normal, or achieve a 5% reduction from prepregnancy weight if overweight. Eligible participants were identified shortly after a GDM diagnosis; 83.8% consented to be randomly assigned to intervention or usual medical care (96 and 101 women, respectively). The retention was 85.2% at 12 months postpartum. RESULTS: The proportion of women who reached the postpartum weight goal was higher, although not statistically significant, in the intervention condition than among usual care (37.5 vs. 21.4%, absolute difference 16.1%, P=0.07). The intervention was more effective among women who did not exceed the recommended gestational weight gain (difference in the proportion of women meeting the weight goals: 22.5%, P=0.04). The intervention condition decreased dietary fat intake more than the usual care (condition difference in the mean change in percent of calories from fat: -3.6%, P=0.002) and increased breastfeeding, although not significantly (condition difference in proportion: 15.0%, P=0.09). No differences in postpartum physical activity were observed between conditions. CONCLUSIONS: This study suggests that a lifestyle intervention that starts during pregnancy and continues postpartum is feasible and may prevent pregnancy weight retention and help overweight women lose weight. Strategies to help postpartum women overcome barriers to increasing physical activity are needed.

Longitudinal study of prepregnancy cardiometabolic risk factors and subsequent risk of gestational diabetes mellitus: The CARDIA study.

This study examined prepregnancy cardiometabolic risk factors and gestational diabetes mellitus (GDM) in subsequent pregnancies. The authors selected 1,164 women without diabetes before pregnancy who delivered 1,809 livebirths between 5 consecutive examinations from 1985 to 2006 in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The authors measured prepregnancy cardiometabolic risk factors and performed multivariate repeated-measures logistic regression to compute the odds of GDM adjusted for race, age, parity, birth order, and other covariates. Impaired fasting glucose (100-125 vs. <90 mg/dL), elevated fasting insulin (>15-20 and >20 vs. <10 µU/mL), and low levels of high-density lipoprotein cholesterol (<40 vs. >50 mg/dL) before pregnancy were directly associated with GDM: The odds ratios = 4.74 (95% confidence interval (CI): 2.14, 10.51) for fasting glucose, 2.19 (95% CI: 1.15, 4.17) for middle insulin levels and 2.36 (95% CI: 1.20, 4.63) for highest insulin levels, and 3.07 (95% CI: 1.62, 5.84) for low levels of high-density lipoprotein cholesterol among women with a negative family history of diabetes; all P < 0.01. Among overweight women, 26.7% with 1 or more cardiometabolic risk factors developed GDM versus 7.4% with none. Metabolic impairment exists before GDM pregnancy in nondiabetic women. Interconceptual metabolic screening could be included in routine health assessments to identify high-risk women for GDM in a subsequent pregnancy and to potentially minimize fetal exposure to metabolic abnormalities that program future disease.

Duration of lactation and incidence of the metabolic syndrome in women of reproductive age according to gestational diabetes mellitus status: a 20-Year prospective study in CARDIA (Coronary Artery Risk Development in Young Adults).

OBJECTIVE: The objective of the study was to prospectively assess the association between lactation duration and incidence of the metabolic syndrome among women of reproductive age. RESEARCH DESIGN AND METHODS: Participants were 1,399 women (39% black, aged 18-30 years) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, an ongoing multicenter, population-based, prospective observational cohort study conducted in the U.S. Women were nulliparous and free of the metabolic syndrome at baseline (1985-1986) and before subsequent pregnancies, and reexamined 7, 10, 15, and/or 20 years after baseline. Incident metabolic syndrome case participants were identified according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Complementary log-log models estimated relative hazards of incident metabolic syndrome among time-dependent lactation duration categories by gestational diabetes mellitus (GDM) adjusted for age, race, study center, baseline covariates (BMI, metabolic syndrome components, education, smoking, physical activity), and time-dependent parity. RESULTS: Among 704 parous women (620 non-GDM, 84 GDM), there were 120 incident metabolic syndrome case participants in 9,993 person-years (overall incidence rate 12.0 per 1,000 person-years; 10.8 for non-GDM, 22.1 for GDM). Increased lactation duration was associated with lower crude metabolic syndrome incidence rates from 0-1 month through >9 months (P < 0.001). Fully adjusted relative hazards showed that risk reductions associated with longer lactation were stronger among GDM (relative hazard range 0.14-0.56; P = 0.03) than non-GDM groups (relative hazard range 0.44-0.61; P = 0.03). CONCLUSIONS: Longer duration of lactation was associated with lower incidence of the metabolic syndrome years after weaning among women with a history of GDM and without GDM, controlling for preconception measurements, BMI, and sociodemographic and lifestyle traits. Lactation may have persistent favorable effects on women's cardiometabolic health.