Boston Birth Cohort Research Articles

Preeclampsia Across Pregnancies and Associated Risk Factors: Findings From a High-Risk US Birth Cohort.

BackgroundPreeclampsia increases women's risks for maternal morbidity and future cardiovascular disease. The aim of this study was to identify opportunities for prevention by examining the association between cardiometabolic risk factors and preeclampsia across 2 pregnancies among women in a high‐risk US birth cohort.Methods and ResultsOur sample included 618 women in the Boston Birth Cohort with index and subsequent pregnancy data collected using standard protocols. We conducted log‐binomial univariate regression models to examine the association between preeclampsia in the subsequent pregnancy (defined as incident or recurrent preeclampsia) and cardiometabolic risk factors (ie, obesity, hypertension, diabetes mellitus, preterm birth, low birth weight, and gestational diabetes mellitus) diagnosed before and during the index pregnancy, and between index and subsequent pregnancies. At the subsequent pregnancy, 7% (36/540) had incident preeclampsia and 42% (33/78) had recurrent preeclampsia. Compared with women without obesity, women with obesity had greater risk of incident preeclampsia (unadjusted risk ratio [RR], 2.2 [95% CI, 1.1–4.5]) and recurrent preeclampsia (unadjusted RR, 3.1 [95% CI, 1.5–6.7]). Preindex pregnancy chronic hypertension and diabetes mellitus were associated with incident, but not recurrent, preeclampsia (hypertension unadjusted RR, 7.9 [95% CI, 4.1–15.3]; diabetes mellitus unadjusted RR, 5.2 [95% CI, 2.5–11.1]. Women with new interpregnancy hypertension versus those without had a higher risk of incident and recurrent preeclampsia (incident preeclampsia unadjusted RR, 6.1 [95% CI, 2.9–13]); recurrent preeclampsia unadjusted RR, 2.4 [95% CI, 1.5–3.9]).ConclusionsIn this diverse sample of high‐risk US women, we identified modifiable and treatable risk factors, including obesity and hypertension for the prevention of preeclampsia.

In Utero Exposure to Heavy Metals and Trace Elements and Childhood Blood Pressure in a U.S. Urban, Low-Income, Minority Birth Cohort.

Background:In utero exposure to heavy metals lead (Pb), mercury (Hg), and cadmium (Cd) may be associated with higher childhood blood pressure (BP), whereas trace elements selenium (Se) and manganese (Mn) may have protective antioxidant effects that modify metal-BP associations.Objectives:We examined the individual and joint effects of in utero exposure to Pb, Hg, Cd, Se, and Mn on childhood BP.Methods:We used data from the Boston Birth Cohort (enrolled 2002–2013). We measured heavy metals and trace elements in maternal red blood cells collected 24–72 h after delivery. We calculated child BP percentile per the 2017 American Academy of Pediatrics Clinical Practice Guideline. We used linear regression models to estimate the association of each metal, and Bayesian kernel machine regression (BKMR) to examine metal coexposures, with child BP between 3 to 15 years of age. Results:Our analytic sample comprised 1,194 mother-infant pairs (61% non-Hispanic Black, 20% Hispanic). Hg and Pb were not associated with child systolic BP (SBP). Se and Mn were inversely associated with child SBP percentiles, which, on average, were 6.23 points lower with a doubling of Se (95% CI: , ) and 2.62 points lower with a doubling of Mn (95% CI: , ). BKMR models showed similar results. Although Cd was not associated with child SBP overall, the inverse association between Mn and child SBP was stronger at higher levels of Cd (). Consistent with this finding, in utero exposure to cigarette smoke modified the Mn–child SBP association. Among children whose mothers smoked during pregnancy, a doubling of Mn was associated with a 10.09-point reduction in SBP percentile (95% CI: , ), compared with a 1.49-point reduction (95% CI: , 1.24) in children whose mothers did not smoke during pregnancy ().Conclusion:Se and Mn concentrations in maternal red blood cells collected 24–72 h after delivery were associated with lower child SBP at 3 to 15 years of age. There was an interaction between Mn and Cd on child SBP, whereby the protective association of Mn on child SBP was stronger among mothers who had higher Cd. The association of Mn and child SBP was also modified by maternal cigarette smoking—a source of Cd—during pregnancy. Optimizing in utero Se levels, as well as Mn levels in women who had high Cd or smoked during pregnancy, may protect offspring from developing high BP during childhood. https://doi.org/10.1289/EHP8325

Invited Perspective: Metal Mixtures and Child Health: The Complex Interplay of Essential and Toxic Elements.

Invited Perspective: Metal Mixtures and Child Health: The Complex Interplay of Essential and Toxic Elements.

Abstract MP64: Higher Visit-to-Visit Blood Pressure Variability In Early And Middle Childhood Is Associated With Higher Blood Pressure In Adolescence

Background: In young adults, higher blood pressure (BP) and visit-to-visit BP variability are independent risk factors for incident cardiovascular disease. No studies have examined if BP and visit-to-visit BP variability during early and middle childhood are independently associated with elevated BP during adolescence. Addressing this question can provide targets for primordial prevention of high BP. Hypotheses: Higher BP and BP variability in early and middle childhood are independently associated with higher BP in adolescence. Methods: We studied 476 children in the Boston Birth Cohort (enrolled 1998-2016) who had BP measured in early (1 to <6 y) or middle childhood (6 to <13y) and in adolescence (13 to <18 y). We modelled visit-to-visit BP variability using variability independent of the mean (VIM). We used linear regression models to examine the associations of mean BP and BP VIM in early and middle childhood (exposures) with mean BP in adolescence (outcome) and adjusted for potential confounders (see Table footnote). Results: After multivariable adjustment, a 1-SD higher level of systolic BP (SBP) in early and middle childhood was associated with a 1.89 (95% CI: 1.03, 2.75) and a 4.31 (95% CI: 3.58, 5.03) mmHg higher SBP in adolescence, respectively. A 1-SD higher level of SBP VIM in early and middle childhood was associated with a 1.46 (95% CI: 0.54, 2.38) and a 0.89 (95% CI: 0.05, 1.73) mmHg higher SBP in adolescence, respectively. Higher diastolic BP (DBP) in early and middle childhood was also associated with higher adolescence DBP, but the magnitude was smaller in comparison with SBP results ( Table ). Childhood DBP VIM was not associated with DBP in adolescence. Conclusion: In this prospective US predominantly minority birth cohort, both BP levels and variability during early and middle childhood are associated with higher BP in adolescence. Our findings underscore the need for health professionals to collect early-life BP data to facilitate opportunities for the primordial prevention of high BP in adolescence and beyond.

Abstract MP47: Maternal Trimethylamine-n-oxide Is Associated With Risk Of Gestational Diabetes Mellitus In A Low-income, Urban, Multi-ethnic Population

Introduction: Trimethylamine-N-oxide (TMAO) is a metabolite influenced by gut microbiota composition and diet (e.g. eggs and red meat). While TMAO has been associated with type 2 diabetes in adults, it is still unclear whether TMAO is associated with risk of gestational diabetes (GDM). Results from the two case-control studies conducted on this topic in China were mixed, with one showing a U-shaped association and the other showing a linear association between TMAO and GDM. There is need to examine this association in a distinct population, in which the sources of TMAO may vary. Hypothesis: We hypothesized that higher TMAO concentration in both maternal and umbilical cord blood plasma (collected within 24-72 hours of birth) is associated with higher odds of GDM. Methods: We used data from the women in the Boston Birth Cohort (enrolled from 1998 to 2013) and fitted logistic regression models to examine the association of maternal and cord blood TMAO concentration with odds of GDM. TMAO was inversely normalized and was modeled in tertiles and as a continuous variable. GDM was diagnosed by a physician; women with pre-pregnancy diabetes were excluded from analyses. Final models were adjusted for covariates (see Table footnote). Results: Among our analytic sample (n=1405 participants), 1248 contributed maternal blood and 865 contributed cord blood. A total of 123 women developed GDM. Before and after adjustment for covariates, higher concentration of TMAO in maternal blood was associated with higher odds of GDM. After adjustment for potential confounders, the highest vs. lowest tertile of TMAO was associated with 1.75 times (95% CI 1.04, 2.96) the odds of GDM (Table). We found no association between cord blood TMAO and GDM (Table). Conclusion: In a population of predominantly low-income, urban mothers, higher maternal TMAO concentration measured in maternal blood (but not cord), was associated with higher odds of GDM. Our findings need to be replicated in prospective cohort studies that measure TMAO in early pregnancy.

Abstract 077: In Utero Exposure To Metal Mixtures And Offspring Blood Pressure: An Analysis Of The Boston Birth Cohort Using Bayesian Kernel Machine Regression

Background: In utero exposure to metals lead (Pb), cadmium (Cd), and mercury (Hg) may be associated with higher childhood systolic blood pressure (SBP), while trace elements manganese (Mn) and selenium (Se) may have protective, antioxidant effects that modify metal-SBP associations. No study has examined how in utero co-exposure to these metals affect offspring SBP. Objectives: To examine the individual and joint effects of in utero exposure to Cd, Pb, Hg, Mn, and Se on offspring SBP. Methods: We used data from the Boston Birth Cohort (enrolled 2002-2013). We measured metals in maternal red blood cells collected 24-72 hours after delivery. We calculated child age-, sex-, and height-specific SBP percentile per 2017 American Academy of Pediatrics guidelines. We used linear regression models to estimate associations of each metal, and Bayesian kernel machine regression (BKMR) to examine metal co-exposures, with child SBP between 3 to 15 years of age. Results: Our analytic sample comprised 1194 mother-child pairs (61% Black, 20% Hispanic). Hg and Pb were not associated with child SBP. Se and Mn were inversely associated with child SBP: each log2(Se) and log2(Mn) increment was associated with a 6.23 (95% CI: 0.96-11.51) and a 2.62 (95% CI: 0.04-5.20) percentile lower child SBP, respectively. BKMR models showed similar results ( Panel A ). While Cd was not overall associated with child SBP, there was an antagonistic interaction between Cd and Mn (P-interaction = 0.036): the association of Mn and lower child SBP was stronger with higher levels of Cd ( Panel B ). Consistent with this finding, in utero exposure to cigarette smoke (a major source of Cd) modified the association of Mn and child SBP: among children born mothers who smoked cigarette in pregnancy, each log2(Mn) increment was associated with a 10.09 (95% CI: 2.15-18.03) percentile lower SBP ( Panel C ). Conclusion: Optimizing in utero Se levels, as well as Mn levels in pregnant women who had high Cd or smoked during pregnancy, may protect offspring from developing high BP during childhood.

Abstract 051: Pre-pregnancy Cardiometabolic Risk Factors, Mediterranean Style Diet, And Risk Of Preeclampsia In The Boston Birth Cohort

Background: Preeclampsia carries high acute and chronic maternal and fetal morbidity and mortality. It is still unclear how pre-pregnancy conditions affect preeclampsia risk, and whether diet reduces risk. We examined associations of pre-pregnancy hypertension, obesity, and diabetes with preeclampsia, and investigated if a Mediterranean-style diet associates with lower risk. Methods: We used data from the Boston Birth Cohort, which comprises racially/ethnically diverse, urban, low-income mothers. We obtained maternal demographic and dietary intake frequencies via interviewer-administered questionnaires within 24-72 hours after birth. We extracted additional pregnancy-related clinical information, including physician diagnosis of preexisting conditions and preeclampsia from medical records. We created tertiles of a Mediterranean-style diet score previously created by our group. We performed logistic regression to assess associations of pre-pregnancy conditions and Mediterranean style diet with odds of preeclampsia. Results: Of 8,507 women in the sample, 849 developed preeclampsia. 47% were black, 28% were Hispanic, and the remaining were white/other. After multivariable adjustment (see table), pre-pregnancy hypertension had the strongest association with preeclampsia (OR 7.81; 95% CI 6.25-9.76), followed by obesity (OR 1.67; 95% CI: 1.41-1.99). Pre-pregnancy diabetes was not associated with preeclampsia after adjustment for obesity and hypertension (table). A higher Mediterranean-style diet score associated with lower preeclampsia odds, but it did not attenuate associations of hypertension or obesity with preeclampsia (table). Conclusions: Pre-pregnancy hypertension and obesity are independently associated with higher preeclampsia odds. Self-report of adherence to Mediterranean-style diet was also associated with lower preeclampsia odds, but this did not mediate risk among obese and hypertensive women. Strategies to prevent preeclampsia among high-risk women are needed.

Maternal pre-pregnancy weight and early life lower respiratory tract infections in a low-income urban minority birth cohort

The prevalence of maternal obesity has increased dramatically with adverse consequences on infant health. Prior studies have reported associations between maternal obesity and childhood wheeze, asthma as well as lower respiratory tract infections (LRTI). However, studies examining the association of obesity with early-life LRTIs in low-income urban minority populations are still lacking. This is a critical gap because both obesity and infant respiratory morbidity are more prevalent and severe in these communities. We examined mother‐child dyads from the Boston Birth Cohort (BBC) to define the longitudinal association of maternal pre‐pregnancy BMI and LRTI in infancy, defined as the presence of bronchiolitis, bronchitis, or pneumonia during the first year of life (< 12 months of age). A total of 2,790 mother‐child dyads were included in our analyses. Infants born to pre-pregnancy obese mothers (n = 688, 25%) had 1.43 increased odds (adjOR = 1.43, 95% CI 1.08–1.88, p = 0.012) of developing LRTI during the first year of life when compared with newborns born to normal-weight mothers after adjusting by relevant LRTI risk factors. Notably, infants born to overweight mothers (n = 808, 29%) followed a similar trend (adjOR = 1.31, 95% CI 1.00–1.72, p = 0.048). Our study demonstrated that maternal pre-pregnancy obesity is an independent risk factor for the development of LRTI during infancy in a low-income urban minority birth cohort.

22566 Identifying metabolic mechanisms linking prenatal acetaminophen exposure to childhood attention-deficit hyperactivity disorder

ABSTRACT IMPACT: This study has implications for understanding early developmental mechanisms of ADHD and for guidelines regarding safe use of acetaminophen during pregnancy. OBJECTIVES/GOALS: Prenatal acetaminophen exposure has been associated with childhood attention-deficit hyperactivity disorder (ADHD), but the underlying mechanism is unknown. This prospective birth cohort study aims to identify linkages between specific metabolites in umbilical cord plasma and the association of prenatal acetaminophen exposure and ADHD. METHODS/STUDY POPULATION: The sample was a subset of the Boston Birth Cohort that included 583 mother-newborn dyads followed at Boston Medical Center from 1998 to 2018. Metabolites were measured from cord plasma collected at birth. Based on existing literature, the analyses focused on candidate metabolites involved in neuroendocrine, inflammation, and oxidative stress pathways. The outcome was physician-diagnosed ADHD between the ages of 3 and 16 years. Exploratory analyses and multiple logistic regressions were used to examine the association of these candidate metabolites with both unmetabolized cord plasma acetaminophen levels and with incident risk of ADHD, adjusting for covariates of maternal and child characteristics. RESULTS/ANTICIPATED RESULTS: Of the 583 children, 257 had ADHD and 326 had neurotypical development. Two promising results have been found thus far. 5-methoxytryptophol (5-MTX), a neuroendocrine molecule which also has antioxidant and immunomodulatory properties, was inversely associated with acetaminophen and ADHD risk. For children below the median cord 5-MTX level, the odds of ADHD were 3.29 (95% CI [1.56, 7.16], p=0.002) for the third tertile of acetaminophen compared to the first tertile. This association attenuated among those above the median 5-MTX level: 2.23 (95% CI [0.98, 5.21], p=0.059), suggesting a protective effect. Tryptophan, an essential amino acid and precursor of serotonin, was positively associated with acetaminophen and ADHD. Next steps include mediation analysis with tryptophan and analyses for other metabolites. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study identifies cord plasma metabolites as possible modifiers or mediators linking prenatal acetaminophen exposure and childhood ADHD, which may offer insight into a mechanistic pathway. The study findings have implications for FDA, clinical, and public health guidelines regarding safe use of acetaminophen during pregnancy.

Overweight is associated with early puberty in boys and girls

It has been clear that overweight and obesity in childhood is associated with onset of puberty at a younger age in girls. For boys, this has been less clear and study results have been variable. One issue is that defining onset of puberty may be more difficult in boys compared with girls. In this volume of The Journal, Chen et al used data from the Boston Birth Cohort Study to evaluate this question. They used age at peak height velocity as a marker of puberty. They found that overweight or obesity from age 2-7 years is associated with earlier onset of puberty in boys as well as in girls. However, those with overweight or obesity at age 2-4 years who became normal weight at age 5-7 had normal timing of puberty. This suggests that interventions to achieve normal weight from age 5-6 years could impact timing of puberty and avoid the deleterious impact of early onset of puberty. Article page 221 ▸ Trajectory of Body Mass Index from Ages 2 to 7 Years and Age at Peak Height Velocity in Boys and GirlsThe Journal of PediatricsVol. 230PreviewTo examine the associations between body mass index (BMI) at 2-4 years and 5-7 years and age at peak height velocity (APHV), an objective measure of pubertal timing, among boys and girls from predominantly racial minorities in the US that have been historically underrepresented in this research topic. Full-Text PDF

Antenatal and neonatal factors contributing to extra uterine growth failure (EUGR) among preterm infants in Boston Birth Cohort (BBC).

ObjectiveIdentify antenatal and neonatal factors associated with primary outcome of EUGR.Methods1063 preterm infants from a subset of the BBC were included in this prospective cohort study. Regression analysis was carried out to evaluate associations of EUGR with antenatal factors and neonatal factors.Results6.1% of the infants had in-utero growth restriction (IUGR) at birth and 21.7% of infants had EUGR. The adjusted odds ratio for EUGR status were significant for birth weight (OR 0.99, p = 0.00, CI 0.99–0.99), for GA at birth (OR 4.58, p = 0.00, CI 3.25–6.44), for PDA (OR 2.9, p = 0.02, CI 1.17–7.1), for NEC (OR 5.14, p = 0.012, CI 1.44–18.3) and for day of life of reaching full feeds (OR 1.04, p = 0.001, CI 1.01–1.06).ConclusionThis study highlights important factors associated with EUGR. Additional studies are needed to gain further insight.

Relationship of Preeclampsia With Maternal Place of Birth and Duration of Residence Among Non-Hispanic Black Women in the United States.

Preeclampsia is one of the leading causes of maternal mortality in the United States. It disproportionately affects non-Hispanic Black (NHB) women, but little is known about how preeclampsia and other cardiovascular disease risk factors vary among different subpopulations of NHB women in the United States. We investigated the prevalence of preeclampsia by nativity (US born versus foreign born) and duration of US residence among NHB women. We analyzed cross-sectional data from the Boston Birth Cohort (1998-2016), with a focus on NHB women. We performed multivariable logistic regression to investigate associations between preeclampsia, nativity, and duration of US residence after controlling for potential confounders. Of 2697 NHB women, 40.5% were foreign born. Relative to them, US-born NHB women were younger, in higher percentage current smokers, had higher prevalence of obesity (body mass index ≥30 kg/m2) and maternal stress, but lower educational level. The age-adjusted prevalence of preeclampsia was 12.4% and 9.1% among US-born and foreign-born women, respectively. When further categorized by duration of US residence, the prevalence of all studied cardiovascular disease risk factors except for diabetes was lower among foreign-born NHB women with <10 versus ≥10 years of US residence. Additionally, the odds of preeclampsia in foreign-born NHB women with duration of US residence <10 years was 37% lower than in US-born NHB women. In contrast, the odds of preeclampsia in foreign-born NHB women with duration of US residence ≥10 years was not significantly different from that of US-born NHB women after adjusting for potential confounders. The prevalence of preeclampsia and other cardiovascular disease risk factors is lower in foreign-born than in US-born NHB women. The healthy immigrant effect, which typically results in health advantages for foreign-born women, appears to wane with longer duration of US residence (≥10 years). Further research is needed to better understand these associations.

Prenatal exposure to mercury and precocious puberty: a prospective birth cohort study

Abstract STUDY QUESTION Is in utero exposure to mercury associated with the risk of precocious puberty? SUMMARY ANSWER Prenatal exposure to high levels of mercury was associated with increased risk of precocious puberty, which was strengthened by concomitant maternal cardiometabolic conditions and adverse birth outcomes. WHAT IS KNOWN ALREADY The developing fetus is sensitive to mercury, a well-known endocrine disruptor which impacts the endocrine and reproductive system. STUDY DESIGN, SIZE, DURATION This study included 1512 mother–child pairs from the Boston Birth Cohort, a longitudinal cohort which recruited at birth and followed prospectively up to 21 years of age. PARTICIPANTS/MATERIALS, SETTING, METHODS Mother–child pairs, from a predominantly urban minority population, were enrolled from 2002 to 2013. Prenatal exposure was assessed by maternal mercury concentration in red blood cells (RBCs) collected at 1–3 days after delivery. Precocious puberty was defined based on International Classification of Disease codes. Cox proportional hazards models were applied to the association between maternal mercury concentrations and the risk of precocious puberty. MAIN RESULTS AND THE ROLE OF CHANCE The median (interquartile range) of maternal mercury concentrations among children with and without precocious puberty were 3.4 (1.9–4.6) µg/l and 2.0 (1.0–3.7) µg/l, respectively. Compared to those in the lowest tertile for mercury, the highest tertile was associated with increased risk of precocious puberty, with an adjusted hazard ratio (HR) of 2.41, 95% CI: 1.16–5.03. In addition, concomitant maternal cardiometabolic conditions and adverse birth outcomes strengthened the effects of mercury on the risk of precocious puberty. The highest risk of precocious puberty was observed among children who had adverse birth outcomes and whose mothers had high RBC-mercury concentrations along with cardiometabolic conditions, with an HR of 4.76 (95% CI: 1.66–13.60) compared to children with favorable profiles of all three risk factors. LIMITATIONS, REASONS FOR CAUTION Precocious puberty was defined based on medical records, not on a direct assessment, which may have led to underdiagnosis and the inability to make a subclassification. The study included a predominately urban, low-income, minority population and as such our findings may not be widely generalizable. WIDER IMPLICATIONS OF THE FINDINGS Prenatal Hg exposure was associated with an increased risk of precocious puberty. This risk was strengthened by concomitant maternal cardiometabolic conditions during pregnancy and adverse birth outcomes. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the NIH/National Institute of Environmental Health Sciences, NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Joint Associations of Maternal-Fetal APOL1 Genotypes and Maternal Country of Origin With Preeclampsia Risk

Preeclampsia, which disproportionately affects Black women, is a leading cause of preterm delivery and risk for future hypertension and chronic kidney disease (CKD). Apolipoprotein L1 (APOL1) kidney risk alleles, common among Black individuals, contribute substantially to CKD disparities. Given the strong link between preeclampsia and CKD, we investigated whether maternal and fetal APOL1 risk alleles can jointly influence preeclampsia risk, and explored potential modifiers of the association between APOL1 and preeclampsia. Nested case-control study. 426 Black mother-infant pairs (275 African Americans and 151 Haitians) from the Boston Birth Cohort. Maternal and fetal APOL1 risk alleles. Preeclampsia. Logistic regression models with adjustment for demographic characteristics were applied to analyze associations between fetal and maternal APOL1 risk alleles and risk of preeclampsia and to investigate the effects of modification by maternal country of origin. Fetal APOL1 risk alleles tended to be associated with an increased risk of preeclampsia, which was not statistically significant in the total genotyped population. However, this association was modified by maternal country of origin (P<0.05 for interaction tests): fetal APOL1 risk alleles were significantly associated with an increased risk of preeclampsia among African Americans under recessive (odds ratio [OR], 3.6 [95% CI, 1.3-9.7]; P=0.01) and additive (OR, 1.7 [95% CI, 1.1-2.6]; P=0.01) genetic models but not in Haitian Americans. Also, maternal-fetal genotype discordance at the APOL1 locus was associated with a 2.6-fold higher risk of preeclampsia (P<0.001) in African Americans. Limited sample size in stratified analyses; self-reported maternal country of origin; pre-pregnancy estimated glomerular filtration rate (eGFR) and proteinuria data in mothers were not collected; unmeasured confounding social and/or environmental factors; no replication study. This study supports the hypothesis that fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in a recessive mode of inheritance in African Americans and suggests that maternal-fetal genotype discordance is also associated with this risk. These conclusions underscore the need to better understand maternal-fetal interaction and their genetic and environmental factors as contributors to ethnic disparities in preeclampsia.

Cord Blood Plasma Metabolome-wide Associations With Height From Birth to Adolescence.

Although the maternal intrauterine metabolic environment has been recognized to have a profound impact on fetal growth and development with lifelong health implications, to our knowledge, there have been few large-scale birth cohort studies linking the cord metabolome (reflecting both the maternal and fetal metabolic state) with postnatal height measurements across the pediatric age range. Using data from the Boston Birth Cohort, an ongoing prospective birth cohort, this study investigated the association of cord plasma metabolites with children's height from birth to adolescence. Height was analyzed as attained height and longitudinal trajectories. Distinctive cord metabolite types were associated with attained height at different developmental windows: triacylglycerols [TAGs], diacylglycerols [DAGs], cholesterol ester [CEs], phospholipids, amino acids [AAs], acylcarnitines [ACs], and nucleotides in early (age 0-4 years) and middle (age 6-12 years) childhood; various metabolite types other than TAGs in later childhood (after age 14 years). Functional principal component analysis on children's repeated height measurements summarized two typical height trajectory components: loadings on first eigenfunction [FPC1] representing overall height by age, and loadings on second eigenfunction [FPC2] representing speed of pubertal height growth. Although only one cord metabolite was correlated with FPC1 after accounting for multiple testing, the study found 27 metabolites with significant overall effect on FPC2 among females and 18 among males. These metabolites were mostly phospholipids (including phosphatidylethanolamines [PEs], phosphatidylethanolamine plasmalogens [PE_Ps], phosphatidylcholines [PCs], lysophosphatidylethanolamines [LPEs], and lysophosphatidylcholines [LPCs]), AAs, and nucleotides. Their associations with height differed between overweight/obesity (OWO) and non-OWO children, especially among females. In this prospective study of US understudied urban, low-income, racially diverse children, we demonstrated that cord plasma metabolites were significantly associated with postnatal attained height at different age windows as well as height trajectories from birth to adolescence. We also revealed how these associations differed by children's sex and OWO status. Our findings help elucidate metabolic pathways underlying fetal origins of height growth across developmental stages. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Trajectory of Body Mass Index from Ages 2 to 7 Years and Age at Peak Height Velocity in Boys and Girls

To examine the associations between body mass index (BMI) at 2-4years and 5-7years and age at peak height velocity (APHV), an objective measure of pubertal timing, among boys and girls from predominantly racial minorities in the US that have been historically underrepresented in this research topic. This study included 1296 mother-child dyads from the Boston Birth Cohort, a predominantly Black and low-income cohort enrolled at birth and followed prospectively during 1998-2018. The exposure was overweight or obesity, based on Centers for Disease Control and Prevention reference standards. The outcome was APHV, derived using a mixed effects growth curve model. Multiple regression was used to estimate the overweight or obesity-APHV association and control for confounders. Obesity at 2-4years was associated with earlier APHV in boys (B in years, -0.19; 95% CI, -0.35 to -0.03) and girls (B, -0.22; 95% CI, -0.37 to -0.07). Obesity at 5-7years was associated with earlier APHV in boys (B, -0.18; 95% CI, -0.32 to -0.03), whereas overweight and obesity at 5-7years were both associated with earlier APHV in girls (overweight: B, -0.24; 95% CI, -0.40 to -0.08; obesity: B, -0.27; 95% CI, -0.40 to -0.13). With BMI trajectory, boys with persistent overweight or obesity and girls with overweight or obesity at 5-7years, irrespective of overweight or obesity status at 2-4years, had earlier APHV. This prospective birth cohort study found that overweight or obesity during 2-7years was associated with earlier pubertal onset in both boys and girls. The BMI trajectory analyses further suggest that reversal of overweight or obesity may halt the progression toward early puberty.

Abstract 15564: What Pre-pregnancy, Pregnancy, and Inter-pregnancy Cardiometabolic Factors Contribute to Increased Risk of Recurrent Preeclampsia?: A Longitudinal Analysis in the Boston Birth Cohort

Introduction: Women with recurrent preeclampsia represent a group at uniquely high risk for maternal and perinatal morbidity, as well as future cardiovascular complications. The aim of this study is to examine the association of cardiometabolic risk factors with recurrent preeclampsia in the subsequent pregnancy. Methods: The Boston Birth Cohort is a racially/ethnically diverse birth cohort with over 8500 women. We identified 618 women with repeat pregnancies. Of those, 78 women had preeclampsia in the index pregnancy, and of those, 33 had recurrent preeclampsia in the subsequent pregnancy. We used log-binomial regression to examine the association between pre-pregnancy, pregnancy, and inter-pregnancy cardiometabolic risk factors (e.g., obesity, hypertension, diabetes mellitus, preterm birth, low birth weight, and gestational diabetes mellitus) and recurrent risk of preeclampsia. Results: Among the 78 women who had preeclampsia in their index pregnancy, the recurrence rate of preeclampsia was 42.3%. Several maternal risk factors were associated with this recurrent risk. Compared to women with pre-(index) pregnancy normal weight, the risk of recurrent preeclampsia was 3 times higher for women with pre-(index) pregnancy overweight (RR 3.0 [95% CI: 1.4 to 6.6]) or obesity (RR 3.1 [95% CI: 1.5 to 6.7). Compared to women without new inter-pregnancy chronic hypertension, women with new inter-pregnancy chronic hypertension had a 2-fold higher risk of recurrent preeclampsia (RR 2.4 [95% CI: 1.5 to 3.9]). Conclusions: Pre-(index) pregnancy obesity and new inter-pregnancy chronic hypertension was highly associated with recurrent preeclampsia in the subsequent pregnancy. Clinical and public health programs focused on reducing preconception obesity and reducing risk of hypertension in both the pre-pregnancy and inter-pregnancy periods may help reduce recurrent preeclampsia, which, in turn may help prevent or reduce subsequent cardiovascular disease.

Abstract 16555: The Relationship of Preeclampsia and Maternal Region of Birth and Duration of Residence in Non-US Born Black Women

Introduction: Preeclampsia is a risk factor for cardiovascular disease (CVD) and disproportionately effects black women. Few studies have explored the prevalence of CVD risk factors and preeclampsia risk in non-US-born black women. We investigated the differential risk of preeclampsia by maternal birth country and duration of stay in US-born vs non-US-born black women residing in US. Methods: We analyzed data from 2967 black women (US-born and non-US-born) in the Boston Birth Cohort (1998 - 2016). Maternal sociodemographic characteristics and key CVD risk factors (hypertension, obesity, diabetes, smoking) were characterized in the two groups. We performed multivariate logistic regression to investigate the prevalence of preeclampsia by maternal birth country and the duration of stay in the US (&lt;10 years and ≥ 10 years) after controlling for explanatory variables. In all analyses, US-born black women were used as the reference group. Results: Of the study group, 40.5% were non-US-born (42% Caribbean, 36% from Sub-Saharan Africa and 21% from other regions). US-born black women were younger and had higher baseline prevalence of obesity (BMI≥ 30Kg/m2), multiparity, pregestational diabetes, smoking, maternal stress, lower educational level, and single marital status. As compared to US-born black women, non-US-born women had a 26% lower risk of preeclampsia. When further categorized by their duration of residence in the US, the prevalence of preeclampsia in non-US-born women with duration of stay &lt;10 years was 8.5%, compared to 9.3% in those with duration of stay beyond 10 years (Figure). Conclusions: As compared to US-born blacks, the prevalence of CVD risk factors and preeclampsia is lower in non-US-born blacks. The "healthy immigrant effect” which typically results in health advantages for foreign born women, tends to wane with increasing duration of US residence (≥ 10 years). Further research on the impact of CVD risk factors on preeclampsia is needed.

A prospective birth cohort study on cord blood folate subtypes and risk of autism spectrum disorder

We previously reported that extremely high concentrations of maternal plasma folate were associated with increased risk of autism spectrum disorder (ASD) in children. This study explored whether specific types of folate in cord blood have differential association with ASD. In the Boston Birth Cohort (BBC), we assessed the association between cord blood unmetabolized folic acid (UMFA), 5-methyl tetrahydrofolate (THF), and total folate and a child's ASD risk. In a subset, we explored whether the association between UMFA and ASD risk can be affected by the dihydrofolate reductase (DHFR) genotype and cord plasma creatinine. We also examined prenatal correlates of cord UMFA concentrations. This report included 567 BBC children (92 ASD, 475 neurotypical), who were recruited at birth and prospectively followed at the Boston Medical Center. ASD was defined from International Classification of Diseases (ICD)-9 and ICD-10 codes documented in electronic medical records. Children with cord UMFA in the highest, versus lowest quartile, had a greater ASD risk (adjusted OR, aORquartile4: 2.26; 95% CI: 1.08, 4.75). When stratified by race/ethnicity, the association was limited to 311 (45 ASD) Black children (aORquartile4: 9.85; 95% CI: 2.53, 38.31); a test of interaction between race/ethnicity and cord UMFA concentrations was significant (P=0.007). The UMFA-ASD association in Black children slightly attenuated after adjusting for cord plasma creatinine (P=0.05). There was no significant association between cord 5-methyl THF, total folate, DHFR genotype, and ASD risk. Cord total folate and maternal supplement intake during second trimester were associated with higher cord UMFA. Higher concentrations of cord UMFA, but not 5-methyl THF or total folate, were associated with a greater risk of ASD in Black children. This study in a preterm-birth-enriched cohort raises more questions than it could answer and underscores the need for additional investigations on the sources and role of cord UMFA in children's neurodevelopmental outcomes and underlying mechanisms.

Postpartum plasma metabolomic profile among women with preeclampsia and preterm delivery: implications for long-term health

BackgroundPreeclampsia and preterm delivery (PTD) are believed to affect women’s long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population.MethodsThis study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing.ResultsA total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P < 1.3 × 10−4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia.ConclusionIn this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women’s future cardiometabolic health.