Publications

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children's health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO's rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children.

Increasing diverse engagement in the Society for Epidemiologic Research (SER) will positively impact the field of epidemiology. As the largest and longest-running epidemiologic society in North America, SER has long been a pioneer in promoting diversity and inclusion. A recent survey of SER members, however, showed there is still room for improving diversity, inclusion, representation, and participation in the Society. In this commentary, as members of both the SER and the Johns Hopkins Bloomberg School of Public Health Department of Epidemiology's Inclusion, Diversity, Equity, Anti-Racism, and Science (Epi IDEAS) Working Group, we recommend 4 goals for the SER Annual Meeting and beyond: 1) convene epidemiologic researchers with diverse backgrounds and ideas; 2) promote an inclusive environment at the SER Annual Meeting; 3) develop, compile, and disseminate best practices to honor diversity in epidemiologic research; and 4) increase prioritization of health disparities research and methods. We also suggest strategies for achieving these goals so that SER can better include, support, and elevate members from historically disadvantaged groups. While our recommendations are tailored specifically to SER, the greater epidemiologic and academic communities could benefit from adopting these goals and strategies within their professional societies and conferences.

IMPORTANCE: Maternal preeclampsia may be one of the early risk factors for childhood and adolescence elevated blood pressure (BP). It is unknown whether the intergenerational association between maternal preeclampsia and offspring BP differs by cord blood vitamin D levels.

OBJECTIVE: To assess the associations between maternal preeclampsia and offspring systolic BP (SBP) across childhood and adolescence and to test whether these associations vary by cord blood 25-hydroxyvitamin D [25(OH)D] concentrations (a biomarker of in utero vitamin D status).

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzed 6669 SBP observations from 754 mother-child pairs from the Boston Birth Cohort, who were enrolled from December 1998 to June 2009. Data were analyzed from October 2019 to March 2020.

EXPOSURES: Physician-diagnosed maternal preeclampsia. Plasma 25(OH)D concentrations measured in cord blood samples collected at delivery.

MAIN OUTCOMES AND MEASURES: Repeated SBP measures between 3 and 18 years of age. The SBP percentile was calculated based on the 2017 American Academy of Pediatrics hypertension guidelines. Mean difference in SBP percentile in children born to mothers with vs without preeclampsia was compared across different cord blood 25(OH)D levels.

RESULTS: There were 6669 SBP observations from the 754 children; 50.0% were female and 18.6% were born preterm. Of the 754 mothers, 62.2% were Black and 10.5% had preeclampsia. Median cord blood 25(OH)D was 12.2 (interquartile range, 7.9-17.2) ng/mL. Maternal preeclampsia was associated with 5.34 (95% CI, 1.37-9.30) percentile higher SBP after adjusting for confounders. This association varied by quartiles of cord blood 25(OH)D concentrations: the differences in SBP percentile comparing children born to mothers with vs without preeclampsia were 10.56 (95% CI, 2.54-18.56) for quartile 1 (lowest), 7.36 (95% CI, -0.17 to 14.88) for quartile 2, 4.94 (95% CI, -3.07 to 12.96) for quartile 3, and -1.87 (95% CI, -9.71 to 5.96) for quartile 4 (highest). When cord blood 25(OH)D was analyzed continuously, children born to mothers with preeclampsia had 3.47 (95% CI, 0.77-6.18) percentile lower SBP per 5 ng/mL 25(OH)D increment. These associations did not differ by child sex or developmental stages.

CONCLUSIONS AND RELEVANCE: In this study of a US high-risk birth cohort, maternal preeclampsia was associated with higher offspring SBP from early childhood to adolescence. These associations were attenuated by higher cord blood 25(OH)D levels in a dose-response fashion. Additional studies, including clinical trials, are warranted.

BACKGROUND: Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants.

METHOD: In this prospective study (Nurture: recruitment 2013-2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months.

RESULTS: Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend = 0.006) with infants exposed to ≥ 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value < 0.05).

CONCLUSIONS: Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months.

BACKGROUND: Potentially driven by the lack of mother-to-infant transmission of microbiota at birth, cesarean delivery has been associated with higher risk of offspring obesity. Yet, no studies have examined when delivery-mode differences in adiposity begin to emerge. In this study, we examine differences in infant weight and adiposity trajectories from birth to 12 months by delivery mode.

METHODS: From 2013 to 2015, we recruited pregnant women into the Nurture Study and followed up their 666 infants. We ascertained maternal delivery method and infant birth weight from medical records. We measured weight, length, and skinfold thicknesses (subscapular, triceps, abdominal) when infants were 3, 6, 9, and 12 months of age. The main outcome, infant weight-for-length z score, was derived based on the WHO Child Growth Standards. We used linear regression models to assess the difference at each time point and used linear mixed models to examine the growth rate for infant weight and adiposity trajectories. We controlled for maternal age, race, marital status, education level, household income, smoking status, maternal pre-pregnancy body mass index, and infant birth weight.

RESULTS: Of the 563 infants in our final sample, 179 (31.8%) were cesarean delivered. From birth to 12 months, the rate of increase in weight-for-length z score was 0.02/month (p = 0.03) greater for cesarean-delivered than vaginally-delivered infants. As a result of more rapid growth, cesarean-delivered infants had higher weight-for-length z score (0.26, 95% CI: 0.05, 0.47) and sum of subscapular and triceps (SS + TR) skinfold thickness (0.95 mm, 95% CI: 0.30, 1.60)-an indicator for overall adiposity-at 12 months, compared to vaginally-delivered infants.

CONCLUSIONS: Compared to vaginal delivery, cesarean delivery was associated with greater offspring rate of weight gain over the first year and differences in adiposity that appear as early as 3 months of age. Monitoring cesarean-delivered infants closely for excess weight gain may help guide primordial prevention of obesity later in life.

Background Preeclampsia is a leading contributor to maternal and perinatal morbidity and mortality. In mice experiments, manganese (Mn) and selenium (Se) are protective whereas cadmium (Cd) is promotive for preeclampsia. Epidemiologic findings on these chemical elements have been inconsistent. To confirm experimental findings in mice, we examined associations of trace minerals (Mn and Se) and heavy metals (Cd, lead [Pb], and mercury [Hg]) with preeclampsia in a birth cohort. Methods and Results A total of 1274 women from the Boston Birth Cohort (enrolled since 1998) had complete data on the exposures and outcome. We measured Mn, Se, Cd, Pb, and Hg from red blood cells collected within 24 to 72 hours after delivery. We ascertained preeclampsia diagnosis from medical records. We used Poisson regression with robust variance models to estimate prevalence ratios (PRs) and 95% CIs. A total of 115 (9.0%) women developed preeclampsia. We observed evidence of a dose-response trend for Mn (P for trend<0.001) and to some extent for Cd (P for trend=0.009) quintiles. After multivariable adjustment, a 1 SD increment in Mn was associated with 32% lower risk of developing preeclampsia (PR=0.68; 95% CI, 0.54-0.86), whereas a 1 SD increment in Cd was associated with 15% higher risk of preeclampsia (PR=1.15; 95% CI, 0.98-1.36). Null associations were observed for Se, Pb, and Hg. Conclusions Findings from our cohort, consistent with evidence from mice experiments and human studies, indicate that women with lower blood concentration of Mn or higher Cd are more likely to develop preeclampsia.

Exposure to ambient air pollution has been associated with greater risk of elevated blood pressure (BP) in adults and children. Recent evidence suggests that air pollution exposure in pregnancy may also portend increased risk for the next generation; however, few studies have examined this relationship. We conducted a prospective study of 1293 mothers in the Boston Birth Cohort (enrolled 1998-2012) and their children who had follow-up visits between 3 and 9 years of age and complete exposure and outcome data. Our primary exposure, ambient particulate matter ≤2.5 µm (PM2.5) concentration during pregnancy, was estimated by matching mother's residential address to the US Environmental Protection Agency's air quality monitors. We defined our primary outcome child systolic BP (SBP) percentile according to US reference (Fourth Report) and classified elevated BP as SBP ≥90th percentile. Our multivariable-adjusted cubic spline showed a sharp increase in offspring SBP percentile and risk for elevated BP when third-trimester PM2.5 concentration was ≥13 μg/m3 The highest versus lowest tertile of third-trimester PM2.5 exposure was associated with a 4.85 (95% confidence interval: 1.38-8.37) percentile increase in child SBP or a 1.61 (95% confidence interval: 1.13-2.30) times higher risk of child elevated BP. A 5-μg/m3 increment in PM2.5 during the third trimester was associated with a 3.49 (95% confidence interval: 0.71-6.26) percentile increase in child SBP or a 1.47 (95% confidence interval: 1.17-1.85) times higher risk of elevated BP. Our findings suggest that exposure to ambient PM2.5 during the third trimester of pregnancy is associated with elevated BP in children, ages 3 to 9 years.

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Patients with chronic hepatitis B superinfected with HEV may progress to liver failure. Babao Dan (BD) is a traditional Chinese medicine widely used as an auxiliary option for the treatment of chronic hepatitis and liver cancer in China. This study aimed to evaluate the effect of BD on the management of HEV infection in a rabbit model. Sixty-two specific-pathogen-free (SPF) rabbits were divided randomly into five groups and treated with BD or placebo for 2 weeks. All rabbits were inoculated intravenously with rabbit HEV after initial administration. Then, rabbits were administered BD or ribavirin or placebo at 2 weeks post-inoculation (wpi) until faecal virus shedding showed negative. The duration of faecal virus shedding and levels of HEV RNA in faeces were reduced, and anti-HEV antibodies were detected in all rabbits in groups treated with BD before or after inoculation. Ribavirin treatment rapidly cleared HEV infection in SPF rabbits, but anti-HEV antibodies remained negative in 50 % of rabbits treated with ribavirin. These results indicate that ribavirin treatment was more effective in clearing HEV infection, while administration of BD before or after inoculation was effective in clearing HEV infection. Further clinical studies are warranted.