Monique M. Hedderson

Gestational diabetes mellitus (GDM) has long been viewed as a metabolic condition first recognized during pregnancy. However, research now demonstrates that underlying metabolic abnormalities are detectable during the preconception period in individuals who subsequently develop GDM and that GDM carries long-term implications for both mothers and offspring. In this article, I provide an overview of the work that my colleagues and I have conducted over the past 25 years, aimed at understanding when GDM risk emerges, how risk can be modified, and how intrauterine exposure to hyperglycemia and its treatment influences health across the life course. This work spans population-based epidemiology, preconception biomarker studies, efficacy prevention trials, and pragmatic interventions embedded within an integrated health care system. Together, these findings affirm Norbert Freinkel’s concept of fuel-mediated teratogenesis and underscore the need for precision prevention and treatment strategies that address biological, behavioral, and social determinants of health risk factors.

Comprehensive assessment of 24-hour movement profiles can reveal patterns of physical activity, sedentary behavior, and sleep across pregnancy. To fully ca

Importance: Excessive gestational weight gain (GWG) occurs in 50% of pregnant patients with overweight or obesity and is associated with several perinatal complications. Scalable, evidence-based lifestyle interventions are needed. Objective: To test whether an adaptive mobile health lifestyle intervention plus standard care reduces excessive GWG compared with standard care alone. Design, Setting, and Participants: This cluster-randomized clinical trial, with randomization at the clinician level, enrolled pregnant patients with a singleton pregnancy, prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) 25.0 to less than 40.0, and receiving care within an integrated health system. Data were analyzed from May 1, 2024, to February 12, 2026. Interventions: Clinicians randomized to the intervention received motivational interviewing guidance for discussing GWG, and their patients received personalized, automated feedback on GWG and physical activity via a smartphone application; a wireless scale and activity tracker; 13 weekly education topics delivered via app; and step-wise chats and/or phone support from a lifestyle coach, for those experiencing accelerated GWG. Main Outcomes and Measures: The co–primary outcomes were weekly rate of GWG and total GWG (both continuous and categorized per IOM guidelines). Results: From a total of 58 clinicians who consented to participate, 1265 patients (mean [SD] age, 33.4 (4.6) years; mean [SD] prepregnancy BMI, 29.8 [3.8]) consented to participate and were enrolled in the trial, including 677 patients in the intervention group and 588 patients in the standard care condition. The weekly rate of GWG was significantly lower in the intervention group vs standard care group (mean [SD] rate, 0.25 [0.20] vs 0.28 [0.20] kg/week; mean between-group difference, −0.03 [95% CI, −0.05 to −0.01] kg/week). Fewer patients in the intervention group exceeded IOM guidelines for weekly rate of GWG than in the standard care group (351 patients [51.9%] vs 354 patients [60.2%]; RR, 0.86 [95% CI, 0.78-0.95]), while more patients gained below the guidelines (148 patients [21.8%] vs 101 patients [17.2%]; relative risk [RR], 1.27 [95% CI, 1.01-1.61]). Total GWG was significantly lower in the intervention group than the standard care group (mean [SD], 9.7 [6.2] vs 10.6 [6.2] kg; mean between-group difference, −0.87 [95% CI, −1.40 to −0.34] kg). Fewer patients in the intervention exceeded IOM guidelines for total GWG than in standard care (299 patients [44.1%] vs 301 patients [51.2%]; RR, 0.87 [95% CI, 0.77-0.98]) while more patients gained below the total GWG guidelines [182 patients [26.8%] vs 126 patients [21.5%]; RR, 1.23 [95% CI, 1.04-1.45]). Conclusions and Relevance: This cluster-randomized trial found that an adaptive intervention leveraging technology effectively reduced the rate of GWG and total GWG among pregnant patients with overweight or obesity. Trial Registration: ClinicalTrials.gov Identifier: NCT03880461

Objective: This study aimed to evaluate associations of maternal prepregnancy BMI with offspring BMI and blood pressure in childhood, specifically for infants born preterm. Methods: In this observational cohort study of children in the Environmental Influences on Child Health Outcomes (ECHO) Cohort, we utilized four levels of maternal prepregnancy BMI and child BMI. Children were categorized as being born extremely, very, or moderately preterm; late preterm; or term. Results: In total, 13,810 children from 44 ECHO cohorts were included in these analyses. After adjusting for maternal education, maternal age at delivery, and singleton birth, a monotonic dose relationship was noted between child BMI z ‐scores and maternal prepregnancy BMI level. For child blood pressure outcomes, only extremely preterm children born to mothers with healthy weight and obesity and very/moderately preterm children born to mothers with healthy weight had higher odds of elevated blood pressure/hypertension compared with their term counterparts. Conclusions: High maternal prepregnancy BMI was associated with a stepwise increase in offspring BMI in childhood. Preterm children had a higher probability of elevated blood pressure/hypertension than term children. These findings highlight a possible window of opportunity to modify lifestyles and behavior of at‐risk children prior to adolescence to positively impact adolescent cardiometabolic health.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Physical activity (PA) and sleep during pregnancy may mitigate the increased risk for adverse pregnancy outcomes posed by gestational diabetes and high gestational weight gain in pregnant individuals with pre-pregnancy overweight and obesity. Recent studies have conceptualized PA, sedentary behavior, and sleep as part of a 24-hour movement framework; however, there is a gap in knowledge about the relationship between 24-hour movement and pregnancy outcomes. Objective: This paper describes the study protocol for the 24MOVE study, a prospective cohort study that examines associations between 24-hour movement profiles across pregnancy and maternal glucose tolerance, gestational weight gain, and infant birthweight. Methods: Participants (n=306) were recruited from a large, integrated health care delivery system at 10 weeks gestation. In early (10-12 weeks), mid (20-22 weeks), and late (33-35 weeks) pregnancy, all eligible individuals with a pre-pregnancy BMI of ≥25 kg/m2 completed online surveys collecting information on sociodemographic characteristics and pregnancy symptoms and behaviors, including sleep quality. Participants concurrently wore a research-grade accelerometer for 24 hours per day for 7 consecutive days to capture movement, sedentary behavior, and sleep data. Data from accelerometry will be processed to create 24-hour movement profiles. Pregnancy outcomes will be ascertained from the electronic health record. We will use compositional data analysis methods, modeling associations of reallocations of time from one component behavior to another at various timepoints with outcomes. Results: Over an 18-month recruitment period, 2,035 individuals were invited to participate and of those, 306 eligible participants enrolled in this study. The enrolled cohort had a median age of 33 years and BMI of 28.8 kg/m². Most participants had private insurance (87%) and were multiparous (76%). Follow-up data collection is ongoing. Conclusions: The 24MOVE Study is designed to address gaps in our knowledge of the impact of 24-hour movement during pregnancy on maternal glucose metabolism, gestational weight gain, and other risk factors for childhood obesity, such as high birthweight. Data from this study will also serve as a rich resource for future investigations of 24-hour movement profiles and behavior substitutions and other perinatal mental and physical health outcomes.

We examined relationships between prenatal dietary patterns and child autism-related outcomes, including parent-reported clinician diagnoses of autism spectrum disorder (ASD) and Social Responsiveness Scale (SRS-2) scores, in up to 6084 participants (with analytic samples ranging from 1671 to 4128 participants) from 14 cohorts in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Associations between quartiles of the Healthy Eating Index (HEI-2015), the Alternative Healthy Eating Index modified for Pregnancy (AHEI-P), and the Empirical Dietary Inflammatory Pattern (EDIP), calculated based on reported prenatal diet, and outcomes were examined using crude and multivariable regression (quantile for SRS scores and logistic for diagnosis). In adjusted models, the higher quartile of prenatal HEI score was associated with lower SRS scores (Q4 vs. Q1 β for median quantile = −3.41 95% CI = −5.15, −1.26). A similar association was observed for the AHEI-P score when adjusting for total calories (Q4 vs. Q1 β = −2.52 95% −4.59, −0.45). There were no significant associations of prenatal diet with ASD diagnosis. Findings from this large U.S.-based study do not suggest strong associations between prenatal dietary patterns and ASD-related outcomes, although subtle associations with broader traits suggest the need to further consider how prenatal diet may relate to ASD-related phenotypes.

Importance: Being born either small for gestational age (SGA) or large for gestational age (LGA) and experiencing rapid or slow growth after birth are associated with later-life obesity. Understanding the associations of dietary quality during pregnancy with infant growth may inform obesity prevention strategies.Objective: To evaluate the associations of prenatal dietary quality according to the Healthy Eating Index (HEI) and the Empirical Dietary Inflammatory Pattern (EDIP) with infant size at birth and infant growth from birth to age 24 months.Design, Setting, and Participants: This cohort study used data from birthing parent–child dyads in 8 cohorts participating in the Environmental influences on Child Health Outcomes program between 2007 and 2021. Data were analyzed from March 2021 to August 2024.Exposures: The HEI and the EDIP dietary patterns.Main Outcomes and Measures: Outcomes of interest were infant birth weight, categorized as SGA, reference range, or LGA, and infant growth from birth to ages 6, 12, and 24 months, categorized as slow growth (weight-for-length z score [WLZ] score difference <−0.67), within reference range (WLZ score difference −0.67 to 0.67), or rapid (WLZ score difference, >0.67).Results: The study included 2854 birthing parent–child dyads (median [IQR] maternal age, 30 [25-34] years; 1464 [51.3%] male infants). The cohort was racially and ethnically diverse, including 225 Asian or Pacific Islander infants (7.9%), 640 Black infants (22.4%), 1022 Hispanic infants (35.8%), 664 White infants (23.3%), and 224 infants (7.8%) with other race or multiple races. A high HEI score (>80), indicative of a healthier diet, was associated with lower odds of LGA (adjusted odds ratio [aOR], 0.88 [95% CI, 0.79-0.98]), rapid growth from birth to age 6 months (aOR, 0.80 [95% CI, 0.37-0.94]) and age 24 months (aOR 0.82 [95% CI, 0.70- 0.96]), and slow growth from birth to age 6 months (aOR, 0.65 [95% CI, 0.50-0.84]), 12 months (aOR, 0.74 [95% CI, 0.65-0.83]), and 24 months (OR, 0.65 [95% CI, 0.56-0.76]) compared with an HEI score 80 or lower. There was no association between high HEI and SGA (aOR, 1.14 [95% CI, 0.95-1.35]). A low EDIP score (ie, ≤63.6), indicative of a less inflammatory diet, was associated with higher odds of LGA (aOR, 1.24 [95% CI, 1.13-1.36]) and rapid infant growth from birth to age 12 months (aOR, 1.50 [95% CI, 1.18-1.91]) and lower odds of rapid growth to age 6 months (aOR, 0.77 [95% CI, 0.71-0.83]), but there was no association with SGA (aOR, 0.80 [95% CI, 0.51-1.25]) compared with an EDIP score of 63.6 or greater.Conclusions and Relevance: In this cohort study, a prenatal diet that aligned with the US Dietary Guidelines was associated with reduced patterns of rapid and slow infant growth, known risk factors associated with obesity. Future research should examine whether interventions to improve prenatal diet are also beneficial in improving growth trajectory in children.

Vasomotor symptoms (VMS; night sweats and hot flashes) are the hallmark signs of menopause. Growing evidence suggests an association between VMS and the increased cardiometabolic risk experienced in women during and after the menopausal transition (MT).¹ While most women experience VMS,² the frequency and the temporal patterns vary dramatically across subgroups of women.³ Past studies examined the association of VMS at 1 time point with diabetes; thus, it remains unknown whether VMS trajectories across the MT are associated with risk of type 2 diabetes (T2D). We examined the associations of frequency and trajectories of VMS with incident T2D over the MT in the Study of Women’s Health Across the Nation (SWAN).

OBJECTIVE: Prediabetes, which is a condition characterized by higher-than-normal blood glucose levels that are under the threshold for diabetes, impacts over one-third of U.S. adults. Excise taxes on sugar-sweetened beverages (SSBs) are a proposed policy intervention to lower population consumption of SSBs and generate revenue to support health-related programs, thus potentially delaying or preventing the development of diabetes in individuals with prediabetes. We leveraged data from Kaiser Permanente in California to examine the impact of SSB taxes in California on individual-level mean HbA1c levels and rates of incident diabetes. RESEARCH DESIGN AND METHODS: We compared two outcomes, mean HbA1c levels and rates of incident diabetes, among a matched cohort of adults with prediabetes who lived and did not live in SSB excise tax cities, using outcomes collected in the 6 years prior and 4 years following SSB tax implementation. We used multivariable linear mixed effects models to analyze longitudinal mean HbA1c and discrete-time survival models for incident diabetes. RESULTS: We included 68,658 adults in the analysis. In adjusted models, longitudinal mean HbA1c was 0.007% (95% CI 0.002, 0.011) higher in the tax cities compared with control individuals; while the estimated difference was statistically significant, it was not clinically significant (HbA1c <0.5%). There was no significant difference in the risk of incident diabetes between individuals living in tax and control cities. CONCLUSIONS: We found no clinically significant association between SSB taxes and either longitudinal mean HbA1c or incident diabetes among adults with prediabetes in the 4 years following SSB tax implementation.

OBJECTIVE: To investigate the associations of longitudinal changes in sex hormone binding globulin (SHBG) and testosterone (T) over the menopause transition with the risk of diabetes. RESEARCH DESIGN AND METHODS: We followed 2,952 participants in the Study of Women’s Health Across the Nation (SWAN) who were premenopausal or early perimenopausal and diabetes-free at baseline. SHBG,T, and estradiol (E2) levels were measured at up to 13 follow-up visits (over up to 17 years). We used complementary log-log–based discrete-time survival models anchored at baseline. RESULTS: Diabetes developed in 376 women. A 5-unit increase in time-varying SHBG was associated with a 10% reduced risk of diabetes (hazard ratio [HR] 0.91, 95% CI 0.87–0.95), adjusting for covariates, and baseline SHBG,T, and E2 levels. Time-varying T was not associated with diabetes risk. Compared with the lowest quartile for annual rate of change of SHBG since baseline (quartile 1 [Q1] −92.3 to −1.5 nmol/L), all other quartiles were associated with a decreased risk of diabetes adjusting for covariates and baseline SHBG; associations persisted after adjusting for rate of change of T and E2 (Q2 [> −1.5 to −0.2 nmol/L] HR 0.33, 95% CI 0.23–0.48; Q3 [> −0.2 to 1.3 nmol/L] HR 0.37, 95% CI 0.25–0.55; Q4 [>1.3 to 82.0 nmol/L] HR 0.43, 95% CI 0.30–0.63). CONCLUSIONS: Increasing levels of SHBG over the menopause transition were associated with a decreased risk of incident diabetes. Stable to increasing rates of change in SHBG were also independently associated with a decreased risk of diabetes compared with decreasing rates of change, suggesting SHBG may affect glucose through a mechanism beyond androgenicity.