Sociodemographic inequities in food allergy: Insights on food allergy from birth cohorts.

A large and growing corpus of epidemiologic studies suggests that the population-level burden of pediatric FA is not equitably distributed across major sociodemographic groups, including race, ethnicity, household income, parental educational attainment, and sex. As is the case for more extensively studied allergic disease states such as asthma and atopic dermatitis epidemiologic data suggest that FA may be more prevalent among certain populations experiencing lower socioeconomic status (SES), particularly those with specific racial and ethnic minority backgrounds living in highly urbanized regions. Emerging data also indicate that these patients may also experience more severe FA-related physical health, psychosocial, and economic outcomes relating to chronic disease management. However, many studies that have identified sociodemographic inequities in FA burden are limited by cross-sectional designs that are subject to numerous biases. Compared with cross-sectional study designs or cohorts established later in life, birth cohorts offer advantages relative to other study designs when investigators seek to understand causal relationships between exposures occurring during the prenatal or postnatal period and the atopic disease status of individuals later in life. Numerous birth cohorts have been established across recent decades, which include evaluation of food allergy-related outcomes, and a subset of these also have measured sociodemographic variables that, together, have the potential to shed light on the existence and possible etiology of sociodemographic inequities in food allergy. This manuscript reports the findings of a comprehensive survey of the current state of this birth cohort literature and draws insights into what is currently known, and what further information can potentially be gleaned from thoughtful examination and further follow-up of ongoing birth cohorts across the globe.

Racial and ethnic differences in physical activity among mothers of young children: 2011-2018 NHANES.

BACKGROUND: American women tend to reduce physical activity (PA) during the transition to motherhood. Their main barrier to participation in PA is lack of time due to new/increased parenting and housework responsibilities. Because there are known racial/ethnic variations in time spent on housework among American women, their PA changes during the transition to motherhood might also differ by racial/ ethnic background. This study aimed to compare PA between American mothers of young child(ren) under age 5 years (YC) and American women without children by their racial/ethnic background. METHODS: Secondary data analyses were conducted using 2011-2018 US National Health and Nutrition Survey data. The study sample included 4,892 women aged 20-45 years (Asian n = 760; Black n = 1,162; Hispanic n = 1,324; White n = 1,646). Participants completed a Physical Activity Questionnaire that asked about participation in transportation and leisure-time moderate- and vigorous-intensity PA (MVPA; minutes/week). Multivariable regression analyses were conducted to compare MVPA among women living without children and with YC (no older children) in each of the racial/ethnic groups. RESULTS: Overall, the prevalence of physical inactivity, defined as zero minutes of MVPA in a typical week, was 43% (95% CI = 38-49%) vs. 32% (95% CI = 29-35%) among women living with YC vs. without children. The adjusted odds of physical inactivity for women living with YC, compared to women living without children, was significantly higher among Asian (OR = 2.08 [95% CI = 1.37-3.17]) and White women (OR = 1.63 [95% CI = 1.11-2.38]), while it was statistically insignificant among Hispanic and Black women. Among women who reported participating in MVPA, Asian women living with YC had 35 fewer minutes/week of MVPA than their counterparts living without children (p = 0.06), while other racial and ethnic groups showed no significant differences. CONCLUSIONS: American mothers of YC were less likely to engage in transportation or leisure-time MVPA, compared to those living without children. This association was particularly strong among Asian women. The study results suggest that a PA reduction in the transition to motherhood may be particularly large among Asian American women, calling for targeted efforts for PA promotion among Asian American mothers of YC; e.g., culturally-tailored community-based physical activity programs for Asian American mothers.

Gestational Diabetes Mellitus, Postpartum Lipidomic Signatures, and Subsequent Risk of Type 2 Diabetes: A Lipidome-Wide Association Study.

OBJECTIVE: To identify a postpartum lipidomic signature associated with gestational diabetes mellitus (GDM) and investigate the role of the identified lipids in the progression to type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This prospective cohort study enrolled 1,409 women at 24-72 h after delivery of a singleton baby and followed them prospectively at the Boston Medical Center. The lipidome was profiled by liquid chromatography-tandem mass spectrometry. Diagnoses of GDM and incident T2D were extracted from medical records and verified using plasma glucose levels. RESULTS: Mean (SD) age of study women at baseline was 28.5 (6.6) years. A total of 219 (16.4%) women developed incident diabetes over a median follow-up of 11.8 (interquartile range 8.2-14.8) years. We identified 33 postpartum lipid species associated with GDM, including 16 inverse associations (primarily cholesterol esters and phosphatidylcholine plasmalogens), and 17 positive associations (primarily diacyglycerols and triacyglycerols). Of these, four were associated with risk of incident T2D and mediated ∼12% of the progression from GDM to T2D. The identified lipid species modestly improved the predictive performance for incident T2D above classical risk factors when the entire follow-up period was considered. CONCLUSIONS: GDM was associated with a wide range of lipid metabolic alterations at early postpartum, among which some lipid species were also associated with incident T2D and mediated the progression from GDM to T2D. The improvements attained by including lipid species in the prediction of T2D provides new insights regarding the early detection and prevention of progression to T2D.

Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator.

BACKGROUND: In utero exposure to diabetes has been shown to contribute to preterm birth, though the underlying biological mechanisms are yet to be fully elucidated. Fetal epigenetic variations established in utero may be a possible pathway. This study aimed to investigate whether in utero exposure to diabetes was associated with a change in newborn DNA methylation, and whether the identified CpG sites mediate the association between diabetes and preterm birth in a racially diverse birth cohort population. METHODS: This study included 954 mother-newborn pairs. Methylation levels in the cord blood were determined using the Illumina Infinium MethylationEPIC BeadChip 850 K array platform. In utero exposure to diabetes was defined by the presence of maternal pregestational or gestational diabetes. Preterm birth was defined as gestational age at birth less than 37 weeks. Linear regression analysis was employed to identify differentially methylated CpG sites. Differentially methylated regions were identified using the DMRcate Package. RESULTS: 126 (13%) newborns were born to mothers with diabetes in pregnancy and 173 (18%) newborns were born preterm, while 41 newborns were born both preterm and to mothers with diabetes in pregnancy. Genomic-wide CpG analysis found that eighteen CpG sites in cord blood were differentially methylated by maternal diabetes status at an FDR threshold of 5%. These significant CpG sites were mapped to 12 known genes, one of which was annotated to gene Major Histocompatibility Complex, Class II, DM Beta (HLA-DMB). Consistently, one of the two identified significant methylated regions overlapped with HLA-DMB. The identified differentially methylated CpG sites mediated the association between diabetes in pregnancy and preterm birth by 61%. CONCLUSIONS: In this US birth cohort, we found that maternal diabetes was associated with altered fetal DNA methylation patterns, which substantially explained the link between diabetes and preterm birth.

Cord Blood Insulin Concentration and Hypertension Among Children and Adolescents Enrolled in a US Racially Diverse Birth Cohort.

BACKGROUND: Although insulin resistance is closely related to hypertension, the debate continues as to whether insulin resistance is a cause or a consequence of hypertension. This study investigated the associations of cord blood insulin concentration with blood pressure (BP) and hypertension in childhood and adolescence. METHODS: This study included 951 children enrolled from 1998 to 2012 and followed from birth onwards at the Boston Medical Center, Boston, MA. Cord blood insulin concentration was measured using a sandwich immunoassay. Hypertension in childhood and adolescence was defined based on the 2017 American Academy of Pediatrics Clinical Practice Guidelines. RESULTS: The median (interquartile range) for cord blood insulin concentration was 12.1 (7.2-19.0) µIU/mL. The age range of BP measurements was 3 to 18 years (median, 10.6 years). Cord blood insulin concentration was positively associated with systolic and diastolic BP as well as the risk of hypertension at age 3 to 18 years. Compared with the lowest tertile of cord blood insulin concentration, the top tertile insulin concentration was associated with a 5.18 (95% CI, 1.97-8.39) percentile increase in systolic BP, 4.29 (95% CI, 1.74-6.84) percentile increase in diastolic BP, and 1.62-fold (95% CI, 1.27-2.08) higher risk of hypertension. The association between insulin and hypertension was stronger among children born preterm (P for interaction=0.048). Furthermore, preterm birth and childhood overweight or obesity enhanced the associations. CONCLUSIONS: Our results suggest that elevated insulin concentration at birth plays a critical role in the early life origins of hypertension and support the hypothesis implicating insulin resistance in the etiology of hypertension.

Where in the world: Mapping medical student learning using the Social and Structural Determinants of Health Curriculum Assessment Tool (SSDH CAT).

INTRODUCTION: Addressing the Social and Structural Determinants of Health (SSDH) is a primary strategy for attaining health equity. Teaching and learning about SSDH has increased across medical schools throughout the world; however, the published literature describing these efforts continues to be limited and many unknowns persist including what should be taught and by whom, what teaching methods and settings should be used, and how medical learners should be assessed. MATERIALS AND METHODS: Based on published studies, input from experts in the field, and elements from the framework developed by the National Academy of Medicine, we created a universal Social and Structural Determinants of Health Curriculum Assessment Tool (SSDH CAT) to assist medical educators to assess existing SSDH curricular content, ascertain critical gaps, and categorize educational methods, delivery, and assessment techniques and tools that could help inform curricular enhancements to advance the goal of training a health care workforce focused on taking action to achieve health equity. To test the usefulness of the tool, we applied the SSDH CAT to map SSDH-related curriculum at a US-based medical school. RESULTS: By applying the SSDH CAT to our undergraduate medical school curriculum, we recognized that our SSDH curriculum relied too heavily on lectures, emphasized knowledge without sufficient skill building, and lacked objective assessment measures. As a result of our curricular review, we added more skill-based activities such as using evidence-based tools for screening patients for social needs, and created and implemented a universal, longitudinal, experiential community health curriculum. DISCUSSION: We created a universal SSDH CAT and applied it to assess and improve our medical school's SSDH curriculum. The SSDH CAT provides a starting point for other medical schools to assess their SSDH content as a strategy to improve teaching and learning about health equity, and to inspire students to act on the SSDH.

The epidemiology of multifood allergy in the United States: A population-based study.

BACKGROUND: Immunoglobulin E (IgE)-mediated food allergies (FAs) are increasingly common among US children and adults. Not only can living with FA impose considerable physical health impacts, but it also imposes economic burden and can negatively affect quality of life. Limited data indicate that allergy to multiple foods (multi-FA) also may be common, but much remains unknown about its distribution and determinants. OBJECTIVE: To characterize the prevalence, characteristics, determinants, psychosocial burden, and distribution of multi-FA among a large, nationally representative sample of US children and adults. METHODS: A US population-based survey was administered. Estimates of multi-FA prevalence, conditional frequencies of multi-FA combinations, and associated factors were derived. Latent class analyses were conducted using 9 dichotomized indicators of specific FA prevalence, which were used to determine factors associated with latent class membership and characterize FA-related psychosocial burden within each class. RESULTS: Surveys were completed for 38,408 children and 40,443 adults. Among children and adults meeting established symptom-report criteria for FA, an estimated 40% and 48% had multi-FA, respectively. Among pediatric and adult populations with convincing FAs, the lifetime reported prevalence of physician-diagnosed atopic comorbidities increased significantly as the number of reported current convincing FAs increased, as did the proportion reporting multi-FA-related health care utilization and higher perceived psychosocial burden. Latent class analyses suggested the existence of the following 4 key latent phenotypes of multi-FA: milk and egg-dominant, seafood-dominant, peanut and tree nut-dominant, and broadly multi-food allergic. CONCLUSION: The US population-level burden of multi-FA is high among both children and adults, and data indicate the presence of 4 major phenotypes of multi-FA in both populations.

A Nonlinear Relation Between Maternal Red Blood Cell Manganese Concentrations and Child Blood Pressure at Age 6-12 y: A Prospective Birth Cohort Study.

BACKGROUND: Although manganese (Mn) is an essential trace element and a common component of most multivitamins on the market, an adverse effect on blood pressure (BP) has been reported in adults. In addition, the longitudinal relation between prenatal Mn status and childhood BP is still unknown. OBJECTIVE: This study investigated the association between prenatal Mn concentrations and risk of elevated BP at ages 3-12 y. METHOD: The analyses included 1268 mother-child dyads who were enrolled at birth and followed prospectively at the Boston Medical Center. Maternal RBC Mn concentrations were measured by inductively coupled plasma mass spectrometry, using RBCs collected within 1-3 d after delivery (reflecting late-pregnancy Mn exposure). Child elevated BP was defined as systolic or diastolic BP ≥90th percentile for a given age, sex and height. Multivariate logistic regression models were conducted. Path analysis was applied to mediation estimation. RESULTS: The median (IQR) maternal RBC Mn concentration was 37.5 (29.2-48.5) µg/L. The rate of child elevated BP at ages 3-12 y was 25%. Both the lowest and highest quartiles of maternal RBC Mn concentrations were associated with higher risk of elevated BP among children aged 6-12 y (OR: 1.52; 95% CI: 1.04, 2.21 and OR: 1.65; 95% CI: 1.13, 2.40, respectively) compared with those in the second and third quartiles. Gestational age and fetal growth mediated the association between low maternal RBC Mn (first quartile) and child elevated BP, explaining 25% of the association, but not for high (fourth quartile) maternal RBC Mn concentrations. No association was found between maternal RBC Mn concentrations and BP among children aged 3-5 y. CONCLUSION: We found a nonlinear association between maternal RBC Mn concentrations and elevated BP among children aged 6-12 y from a high-risk, predominantly minority population. Our findings warrant further investigation.

Gaining a deeper understanding of social determinants of preterm birth by integrating multi-omics data.

In the US, high rates of preterm birth (PTB) and profound Black-White disparities in PTB have persisted for decades. This review focuses on the role of social determinants of health (SDH), with an emphasis on maternal stress, in PTB disparity and biological embedding. It covers: (1) PTB disparity in US Black women and possible contributors; (2) the role of SDH, highlighting maternal stress, in the persistent racial disparity of PTB; (3) epigenetics at the interface between genes and environment; (4) the role of the genome in modifying maternal stress-PTB associations; (5) recent advances in multi-omics studies of PTB; and (6) future perspectives on integrating multi-omics with SDH to elucidate the Black-White disparity in PTB. Available studies have indicated that neither environmental exposures nor genetics alone can adequately explain the Black-White PTB disparity. Preliminary yet promising findings of epigenetic and gene-environment interaction studies underscore the value of integrating SDH with multi-omics in prospective birth cohort studies, especially among high-risk Black women. In an era of rapid advancements in biomedical sciences and technologies and a growing number of prospective birth cohort studies, we have unprecedented opportunities to advance this field and finally address the long history of health disparities in PTB. IMPACT: This review provides an overview of social determinants of health (SDH) with a focus on maternal stress and its role on Black-White disparity in preterm birth (PTB). It summarizes the available literature on the interplay of maternal stress with key biological layers (e.g., individual genome and epigenome in response to environmental stressors) and significant knowledge gaps. It offers perspectives that such knowledge may provide deeper insight into how SDH affects PTB and why some women are more vulnerable than others and underscores the critical need for integrating SDH with multi-omics in prospective birth cohort studies, especially among high-risk Black women.

In utero exposure to mercury and childhood overweight or obesity: counteracting effect of maternal folate status.

BACKGROUND: Low-dose mercury (Hg) exposure has been associated with cardiovascular diseases, diabetes, and obesity in adults, but it is unknown the metabolic consequence of in utero Hg exposure. This study aimed to investigate the association between in utero Hg exposure and child overweight or obesity (OWO) and to explore if adequate maternal folate can mitigate Hg toxicity. METHODS: This prospective study included 1442 mother-child pairs recruited at birth and followed up to age 15 years. Maternal Hg in red blood cells and plasma folate levels were measured in samples collected 1-3 days after delivery (a proxy for third trimester exposure). Adequate folate was defined as plasma folate ≥ 20.4 nmol/L. Childhood OWO was defined as body mass index ≥ 85% percentile for age and sex. RESULTS: The median (interquartile range) of maternal Hg levels were 2.11 (1.04-3.70) µg/L. Geometric mean (95% CI) of maternal folate levels were 31.1 (30.1-32.1) nmol/L. Maternal Hg levels were positively associated with child OWO from age 2-15 years, independent of maternal pre-pregnancy OWO, diabetes, and other covariates. The relative risk (RR = 1.24, 95% CI 1.05-1.47) of child OWO associated with the highest quartile of Hg exposure was 24% higher than those with the lowest quartile. Maternal pre-pregnancy OWO and/or diabetes additively enhanced Hg toxicity. The highest risk of child OWO was found among children of OWO and diabetic mothers in the top Hg quartile (RR = 2.06; 95% CI 1.56-2.71) compared to their counterparts. Furthermore, adequate maternal folate status mitigated Hg toxicity. Given top quartile Hg exposure, adequate maternal folate was associated with a 34% reduction in child OWO risk (RR = 0.66, 95% CI 0.51-0.85) as compared with insufficient maternal folate. There was a suggestive interaction between maternal Hg and folate levels on child OWO risk (p for interaction = 0.086). CONCLUSIONS: In this US urban, multi-ethnic population, elevated in utero Hg exposure was associated with a higher risk of OWO in childhood, and such risk was enhanced by maternal OWO and/or diabetes and reduced by adequate maternal folate. These findings underscore the need to screen for Hg and to optimize maternal folate status, especially among mothers with OWO and/or diabetes.

Expert Consensus on Inclusion of the Social Determinants of Health in Undergraduate Medical Education Curricula.

PURPOSE: Accreditation bodies have mandated teaching social determinants of health (SDH) to medical students, but there has been limited guidance for educators on what or how to teach, and how to evaluate students' competence. To fill this gap, this study aimed to develop an SDH curricular consensus guide for teaching SDH to medical students. METHOD: In 2017, the authors used a modified Delphi technique to survey an expert panel of educators, researchers, students, and community advocates about knowledge, skills, and attitudes (KSA) and logistics regarding SDH teaching and assessment. They identified the panel and ranked a comprehensive list of topics based on a scoping review of SDH education studies and discussions with key informants. A total of 57 experts were invited. RESULTS: Twenty-two and 12 panelists participated in Delphi rounds 1 and 2, respectively. The highest-ranked items regarding KSA were "Appreciation that the SDH are some of the root causes of health outcomes and health inequities" and "How to work effectively with community health workers." The panel achieved consensus that SDH should constitute 29% of the total curriculum and be taught continuously throughout the curriculum. Multiple-choice tests were ranked lowest as an assessment method, and patient feedback was ranked highest. Panelists noted that SDH content must be a part of standardized exams to be prioritized by faculty and students. CONCLUSIONS: An expert panel endorsed essential curricular content, teaching methods, and evaluation approaches that can be used to help guide medical educators regarding SDH curriculum development.

Inter-generational link of obesity in term and preterm births: role of maternal plasma acylcarnitines.

BACKGROUND/OBJECTIVES: Acylcarnitines, intermediates of fatty acid oxidation, are known to be involved in obesity and insulin resistance. Since maternal prepregnancy overweight or obesity (OWO) is a recognized major risk factor for offspring OWO, we hypothesized that maternal plasma acylcarnitines may play a role in inter-generational OWO. SUBJECTS/METHODS: This study included 1402 mother-child pairs (1043 term, 359 preterm) recruited at birth from 1998-2013 and followed prospectively up to age 18 years at the Boston Medical Center. The primary outcomes were child OWO defined as BMI ≥ 85th percentile for age and sex. The primary exposures were maternal prepregnancy OWO defined as BMI ≥ 25 kg/m2 and maternal acylcarnitine levels measured in plasma samples collected soon after delivery using liquid chromatography-tandem mass spectrometry (LC-MS) in a targeted manner. RESULTS: Approximately 40% of the children in this study were OWO by age 5. Maternal OWO had a significant association with childhood OWO, both in term and preterm births. ß-hydroxybutyryl-carnitine (C4-OH) levels were significantly and positively associated with child OWO among term births after adjustment for potential confounders and multiple-comparisons. Children born to OWO mothers in the top tertile C4-OH levels were at the highest risk of OWO: OR = 3.78 (95%CI: 2.47, 5.79) as compared with those born to non-OWO mothers in the lowest tertile (P for interaction of maternal OWO and C4-OH = 0.035). In a four-way decomposition of mediation/interaction analysis, we estimated that C4-OH levels explained about 27% (se = 0.08) of inter-generational OWO risk (P = 0.001). In contrast, these associations were not observed in preterm births. CONCLUSIONS: In this U.S. urban low-income birth cohort, we provide further evidence of the inter-generational link of OWO and reveal the differential role of C4-OH in explaining the inter-generational obesity between term and preterm births. Further investigations are warranted to better understand and prevent the inter-generational transmission of OWO.

Vitamin D Trajectories From Birth to Early Childhood and Elevated Systolic Blood Pressure During Childhood and Adolescence.

Vitamin D deficiency is associated with hypertension in adults. It is unknown to what degree vitamin D status in early life can affect blood pressure (BP) a decade later. This study investigated the effect of vitamin D trajectory through early life on systolic BP (SBP) in childhood. This is a prospective birth cohort study of 775 children enrolled from 2005 to 2012 and followed prospectively up to age 18 years at the Boston Medical Center, Boston, MA. Persistent low vitamin D status is defined as plasma 25(OH)D <11 ng/mL at birth and <25 ng/mL in early childhood. Elevated SBP is defined as SBP ≥75th percentile. Low vitamin D status at birth was associated with higher risk of elevated SBP at ages 3 to 18 years: odds ratio, 1.38; (95% CI, 1.01-1.87) compared to those with sufficient vitamin D. Low vitamin D status in early childhood was associated with a 1.59-fold (95% CI, 1.02-2.46) higher risk of elevated SBP at age 6 to 18 years. Persistent low vitamin D status from birth to early childhood was associated with higher risk of elevated SBP (odds ratio, 2.04; [95% CI, 1.13-3.67]) at ages 3 to 18 years. These results suggest that low vitamin D status and trajectory in early life were associated with increased risk of elevated SBP during childhood and adolescence. Our findings will help inform future clinical and public health strategies for vitamin D screening and supplementation in pregnancy and childhood to prevent or reduce risk of elevated BP across the lifespan and generations.

Teaching the Social Determinants of Health in Undergraduate Medical Education: a Scoping Review.

BACKGROUND: To provide optimal care, medical students should understand that the social determinants of health (SDH) impact their patients' well-being. Those charged with teaching SDH to future physicians, however, face a paucity of curricular guidance. OBJECTIVE: This review's objective is to map key characteristics from publications about teaching SDH to students in undergraduate medical education (UME). METHODS: In 2016, the authors searched PubMed, Embase, Web of Science, the Cochrane and ERIC databases, bibliographies, and MedEdPORTAL for articles published between January 2010 and November 2016. Four reviewers screened articles for eligibility then extracted and analyzed data descriptively. Scoping review methodology was used to map key concepts and curricular logistics as well as educator and student characteristics. RESULTS: The authors screened 3571 unique articles of which 22 were included in the final review. Many articles focused on community engagement (15). Experiential learning was a common instructional strategy (17) and typically took the form of community or clinic-based learning. Nearly half (10) of the manuscripts described school-wide curricula, of which only three spanned a full year. The majority of assessment was self-reported (20) and often related to affective change. Few studies objectively assessed learner outcomes (2). CONCLUSIONS: The abundance of initial articles screened highlights the growing interest in SDH in medical education. The small number of selected articles with sufficient detail for abstraction demonstrates limited SDH curricular dissemination. A lack of accepted tools or practices that limit development of robust learner or program evaluation was noted. Future research should focus on identifying and evaluating effective instructional and assessment methodologies to address this gap, exploring additional innovative teaching frameworks, and examining the specific contexts and characteristics of marginalized and underserved populations and their coverage in medical education.

Strategy for early identification of prediabetes in lean populations: New insight from a prospective Chinese twin cohort of children and young adults.

AIMS: To identify certain subgroups in young and lean populations, who may be at a high risk of developing prediabetes/diabetes, which is not captured by current BMI-based screening algorithms. METHODS: Incidence of prediabetes/diabetes was assessed using oral glucose tolerance tests among 1859 children and 1073 young adults from a prospective Chinese twin cohort. RESULTS: Over a 6-year follow-up, 507 (27.3%) children and 293 (27.3%) adults developed prediabetes/diabetes. Of the 800 incidents, 737(92.1%) and 644(80.5%) were lean at baseline and follow-up, respectively. Baseline fasting glucose in the top tertile of the normal range was associated with an increased risk of prediabetes/diabetes: odds ratio, 1.85 (95% CI 1.32-2.59) and 3.29 (95%CI 2.10-5.17) among normal weight and underweight children, respectively, and 2.74 (95% CI 1.78-4.23) and 3.08 (95% CI 1.69-5.58) among normal weight and overweight/obese adults, respectively, compared with the low tertile of fasting glucose. CONCLUSIONS: We showed that majority incident cases of prediabetes/diabetes were not overweight/obese (at baseline), who would have been missed by traditional screening algorithm emphasizing overweight/obesity. Our findings revealed that an upper end of normal fasting glucose was a simple and robust predictor of future higher risk of prediabetes/diabetes in this young and lean population.

Maternal Biomarkers of Acetaminophen Use and Offspring Attention Deficit Hyperactivity Disorder.

Previous studies have suggested a positive association between self-reported maternal acetaminophen use during pregnancy and risk of attention deficit hyperactivity disorder (ADHD) in offspring. We sought to examine the prospective association between maternal plasma biomarkers of acetaminophen intake and ADHD diagnosis in the offspring. This report analyzed 1180 children enrolled at birth and followed prospectively as part of the Boston Birth Cohort, including 188 with ADHD diagnosis based on electronic medical record review. Maternal biomarkers of acetaminophen intake were measured in plasma samples obtained within 1⁻3 days postpartum. Odds ratios for having ADHD diagnosis or other developmental disorders were estimated using multinomial logistic regression models, adjusting for pertinent covariables. Compared to neurotypical children, we observed significant positive dose-responsive associations with ADHD diagnosis for each maternal acetaminophen biomarker. These dose⁻responsive associations persisted after adjusting for indication of acetaminophen use and other pertinent covariates; and were specific to ADHD, rather than other neurodevelopmental disorders. In the stratified analyses, differential point estimates of the associations were observed across some strata of covariates. However, these differences were not statistically significant. Maternal acetaminophen biomarkers were specifically associated with increased risk of ADHD diagnosis in offspring. Additional clinical and mechanistic investigations are warranted.

A Prospective Birth Cohort Study on Early Childhood Lead Levels and Attention Deficit Hyperactivity Disorder: New Insight on Sex Differences.

OBJECTIVE: To investigate the prospective associations between early childhood lead exposure and subsequent risk of attention deficit hyperactivity disorder (ADHD) in childhood and its potential effect modifiers. STUDY DESIGN: We analyzed data from 1479 mother-infant pairs (299 ADHD, 1180 neurotypical) in the Boston Birth Cohort. The child's first blood lead measurement and physician-diagnosed ADHD was obtained from electronic medical records. Graphic plots and multiple logistic regression were used to examine dose-response associations between lead exposure and ADHD and potential effect modifiers, adjusting for pertinent covariables. RESULTS: We found that 8.9% of the children in the Boston Birth Cohort had elevated lead levels (5-10 µg/dL) in early childhood, which was associated with a 66% increased risk of ADHD (OR, 1.66; 95% CI, 1.08-2.56). Among boys, the association was significantly stronger (OR, 2.49; 95% CI, 1.46-4.26); in girls, the association was largely attenuated (P value for sex-lead interaction = .017). The OR of ADHD associated with elevated lead levels among boys was reduced by one-half if mothers had adequate high-density lipoprotein levels compared with low high-density lipoprotein, or if mothers had low stress compared with high stress during pregnancy. CONCLUSIONS: Elevated early childhood blood lead levels increased the risk of ADHD. Boys were more vulnerable than girls at a given lead level. This risk of ADHD in boys was reduced by one-half if the mother had adequate high-density lipoprotein levels or low stress. These findings shed new light on the sex difference in ADHD and point to opportunities for early risk assessment and primary prevention of ADHD.

Genome-wide DNA methylation associations with spontaneous preterm birth in US blacks: findings in maternal and cord blood samples.

Preterm birth (PTB) affects one in six Black babies in the United States. Epigenetics is believed to play a role in PTB; however, only a limited number of epigenetic studies of PTB have been reported, most of which have focused on cord blood DNA methylation (DNAm) and/or were conducted in white populations. Here we conducted, by far, the largest epigenome-wide DNAm analysis in 300 Black women who delivered early spontaneous preterm (sPTB, n = 150) or full-term babies (n = 150) and replicated the findings in an independent set of Black mother-newborn pairs from the Boston Birth Cohort. DNAm in maternal blood and/or cord blood was measured using the Illumina HumanMethylation450 BeadChip. We identified 45 DNAm loci in maternal blood associated with early sPTB, with a false discovery rate (FDR) <5%. Replication analyses confirmed sPTB associations for cg03915055 and cg06804705, located in the promoter regions of the CYTIP and LINC00114 genes, respectively. Both loci had comparable associations with early sPTB and early medically-indicated PTB, but attenuated associations with late sPTB. These associations could not be explained by cell composition, gestational complications, and/or nearby maternal genetic variants. Analyses in the newborns of the 110 Black women showed that cord blood methylation levels at both loci had no associations with PTB. The findings from this study underscore the role of maternal DNAm in PTB risk, and provide a set of maternal loci that may serve as biomarkers for PTB. Longitudinal studies are needed to clarify temporal relationships between maternal DNAm and PTB risk.