Bibliography Tag: birth cohort studies

Eaton et al., 2022

Eaton JL, Cathey AL, Fernandez JA, Watkins DJ, Silver MK, Milne GL, Velez-Vega C, Rosario Z, Cordero J, Alshawabkeh A, Meeker JD; “The association between urinary glyphosate and aminomethyl phosphonic acid with biomarkers of oxidative stress among pregnant women in the PROTECT birth cohort study;” Ecotoxicology and Environmental Safety, 2022, 233:113300; DOI: 10.1016/j.ecoenv.2022.113300.

Background: Glyphosate is a widely used herbicide in global agriculture. Glyphosate and its primary environmental degradate, aminomethyl phosphonic acid (AMPA), have been shown to disrupt endocrine function and induce oxidative stress in in vitro and animal studies. To our knowledge, these relationships have not been previously characterized in epidemiological settings. Elevated urinary levels of glyphosate and AMPA may be indicative of health effects caused by previous exposure via multiple mechanisms including oxidative stress.

Methods: Glyphosate and AMPA were measured in 347 urine samples collected between 16 and 20 weeks gestation and 24-28 weeks gestation from pregnant women in the PROTECT birth cohort. Urinary biomarkers of oxidative stress, comprising 8-isoprostane-prostaglandin-F2α (8-iso-PGF2α), its metabolite 2,3-dinor-5,6-dihydro-15-F2 t-isoprostane (8-isoprostane metabolite) and prostaglandin-F2α (PGF2α), were also measured. Linear mixed effect models assessed the association between exposures and oxidative stress adjusting for maternal age, smoking status, alcohol consumption, household income and specific gravity. Potential nonlinear trends were also assessed using tertiles of glyphosate and AMPA exposure levels.

Results: No significant differences in exposure or oxidative stress biomarker concentrations were observed between study visits. An interquartile range (IQR) increase in AMPA was associated with 9.5% (95% CI: 0.5-19.3%) higher 8-iso-PGF2α metabolite concentrations. Significant linear trends were also identified when examining tertiles of exposure variables. Compared to the lowest exposure group, the second and third tertiles of AMPA were significantly associated with 12.8% (0.6-26.5%) and 15.2% (1.8-30.3%) higher 8-isoprostane metabolite, respectively. An IQR increase in glyphosate was suggestively associated with 4.7% (-0.9 to 10.7%) higher 8-iso-PGF2α.

Conclusions: Urinary concentrations of the main environmental degradate of glyphosate, AMPA, were associated with higher levels of certain oxidative stress biomarkers. Associations with glyphosate reflected similar trends, although findings were not as strong. Additional research is required to better characterize the association between glyphosate exposure and biomarkers of oxidative stress, as well as potential downstream health consequences.


Rauh et al., 2012

Rauh, V. A., Perera, F. P., Horton, M. K., Whyatt, R. M., Bansal, R., Hao, X., Liu, J., Barr, D. B., Slotkin, T. A., & Peterson, B. S.; “Brain anomalies in children exposed prenatally to a common organophosphate pesticide;” Proceedings of the National Academy of Sciences, 2012, 109(20), 7871-7876; DOI: 10.1073/pnas.1203396109.


Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9-11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure x IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose-response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain.  FULL TEXT

Rauh et al., 2011

Rauh, Virginia, Arunajadai, Srikesh, Horton, Megan, Perera, Frederica, Hoepner, Lori, Barr, Dana B, & Whyatt, Robin; “Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide;” Environmental Health Perspectives, 2011, 119(8), 1196-1201; DOI: 10.1289/ehp.1003160.


BACKGROUND: In a longitudinal birth cohort study of inner-city mothers and children (Columbia Center for Children’s Environmental Health), we have previously reported that prenatal exposure to chlorpyrifos (CPF) was associated with neurodevelopmental problems at 3 years of age.

OBJECTIVE: The goal of the study was to estimate the relationship between prenatal CPF exposure and neurodevelopment among cohort children at 7 years of age.

METHODS: In a sample of 265 children, participants in a prospective study of air pollution, we measured prenatal CPF exposure using umbilical cord blood plasma (picograms/gram plasma) and 7-year neurodevelopment using the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). Linear regression models were used to estimate associations, with covariate selection based on two alternate approaches.

RESULTS: On average, for each standard deviation increase in CPF exposure (4.61 pg/g), Full-Scale intelligence quotient (IQ) declined by 1.4% and Working Memory declined by 2.8%. Final covariates included maternal educational level, maternal IQ, and quality of the home environment. We found no significant interactions between CPF and any covariates, including the other chemical exposures measured during the prenatal period (environmental tobacco smoke and polycyclic aromatic hydrocarbons).

CONCLUSIONS: We report evidence of deficits in Working Memory Index and Full-Scale IQ as a function of prenatal CPF exposure at 7 years of age. These findings are important in light of continued widespread use of CPF in agricultural settings and possible longer-term educational implications of early cognitive deficits.


Rappazzo et al., 2018

Rappazzo, K. M., Warren, J. L., Davalos, A. D., Meyer, R. E., Sanders, A. P., Brownstein, N. C., & Luben, T. J.; “Maternal residential exposure to specific agricultural pesticide active ingredients and birth defects in a 2003-2005 North Carolina birth cohort;” Birth Defects Research, 2018; DOI: 10.1002/bdr2.1448.


BACKGROUND: Previously we observed elevated odds ratios (ORs) for total pesticide exposure and 10 birth defects: three congenital heart defects and structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems. This analysis examines association of those defects with exposure to seven commonly applied pesticide active ingredients.

METHODS: Cases were live-born singleton infants from the North Carolina Birth Defects Monitoring Program linked to birth records for 2003-2005; noncases served as controls (total n = 304,906). Pesticide active ingredient exposure was assigned using a previously constructed metric based on crops within 500 m of residence, dates of pregnancy, and likely chemical application dates for each pesticide-crop combination. ORs (95% CI) were estimated with logistic regression for categories of exposure compared to unexposed. Models were adjusted for maternal race/ethnicity, age at delivery, education, marital status, and smoking status.

RESULTS: Associations varied by birth defect and pesticide combinations. For example, hypospadias was positively associated with exposures to 2,4-D (OR50th to <90th percentile : 1.39 [1.18, 1.64]), mepiquat (OR50th to <90th percentile : 1.10 [0.90, 1.34]), paraquat (OR50th to <90th : 1.14 [0.93, 1.39]), and pendimethalin (OR50th to <90th : 1.21 [1.01, 1.44]), but not S-metolachlor (OR50th to <90th : 1.00 [0.81, 1.22]). Whereas atrial septal defects were positively associated with higher levels of exposure to glyphosate, cyhalothrin, S-metolachlor, mepiquat, and pendimethalin (ORs ranged from 1.22 to 1.35 for 50th to <90th exposures, and 1.72 to 2.09 for >90th exposures); associations with paraquat were null or inconsistent (OR 50th to <90th: 1.05 (0.87, 1.27).

CONCLUSION: Our results suggest differing patterns of association for birth defects with residential exposure to seven pesticide active ingredients in North Carolina.

Ferguson et al., 2019

Ferguson, K. K., Rosario, Z., McElrath, T. F., Velez Vega, C., Cordero, J. F., Alshawabkeh, A., & Meeker, J. D.; “Demographic risk factors for adverse birth outcomes in Puerto Rico in the PROTECT cohort;” Plos One, 2019, 14(6), e0217770; DOI: 10.1371/journal.pone.0217770.


Preterm birth is a major public health problem, especially in Puerto Rico where the rates are among the highest observed worldwide, reaching 18% in 2011. The Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) study is an ongoing investigation of environmental factors that contribute to this condition. In the present analysis, we sought to examine common risk factors for preterm birth and other adverse birth outcomes which have not been characterized previously in this unique population. Pregnant women from the PROTECT cohort are recruited from the heavily contaminated Northern coast of the island of Puerto Rico and are free of pre-existing conditions like diabetes. We examined associations between basic demographic, behavioral (e.g., tobacco and alcohol use), and pregnancy (e.g., season and year of delivery) characteristics as well as municipality of residence in relation to preterm birth (<37 weeks gestation), postterm birth (>/=41 weeks gestation), and small and large for gestational age in univariate and multivariate logistic regression models. Between 2011 and 2017, 1028 live singleton births were delivered as part of the PROTECT cohort. Of these, 107 (10%) were preterm. Preterm birth rates were higher among women with low socioeconomic status, as indicated by education level and income, and among women with high pre-pregnancy body mass index (BMI). Odds ratios of small for gestational age delivery were higher for women who reported tobacco use in pregnancy and lower for women who delivered in the hurricane and dengue season (July-October). Overall, in pregnant women residing in Puerto Rico, socioeconomic status was associated with preterm birth but few other factors were associated with this or other adverse outcomes of pregnancy. Research to understand environmental factors that could be contributing to the preterm birth epidemic in Puerto Rico is necessary. FULL TEXT

Silver et al., 2021

Silver, M. K., Fernandez, J., Tang, J., McDade, A., Sabino, J., Rosario, Z., Velez Vega, C., Alshawabkeh, A., Cordero, J. F., & Meeker, J. D.; “Prenatal Exposure to Glyphosate and Its Environmental Degradate, Aminomethylphosphonic Acid (AMPA), and Preterm Birth: A Nested Case-Control Study in the PROTECT Cohort (Puerto Rico);” Environmental Health Perspectives, 2021, 129(5), 57011; DOI: 10.1289/EHP7295.


BACKGROUND: Glyphosate (GLY) is the most heavily used herbicide in the world. Despite nearly ubiquitous exposure, few studies have examined prenatal GLY exposure and potentially adverse pregnancy outcomes. Preterm birth (PTB) is a risk factor for neonatal mortality and adverse health effects in childhood.

OBJECTIVES: We examined prenatal exposure to GLY and a highly persistent environmental degradate of GLY, aminomethylphosphonic acid (AMPA), and odds of PTB in a nested case-control study within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort in northern Puerto Rico.

METHODS: GLY and AMPA in urine samples collected at 18+/-2 (Visit 1) and 26+/-2 (Visit 3) wk gestation (53 cases/194 randomly selected controls) were measured using gas chromatography tandem mass spectrometry. Multivariable logistic regression was used to estimate associations with PTB (delivery <37wk completed gestation).

RESULTS: Detection rates in controls were 77.4% and 77.5% for GLY and 52.8% and 47.7% for AMPA, and geometric means (geometric standard deviations) were 0.44 (2.50) and 0.41 (2.56) mug/L for GLY and 0.25 (3.06) and 0.20 (2.87) mug/L for AMPA, for Visits 1 and 3, respectively. PTB was significantly associated with specific gravity-corrected urinary GLY and AMPA at Visit 3, whereas associations with levels at Visit 1 and the Visits 1-3 average were largely null or inconsistent. Adjusted odds ratios (ORs) for an interquartile range increase in exposure at Visit 3 were 1.35 (95% CI: 0.99, 1.83) and 1.67 (95% CI: 1.26, 2.20) for GLY and AMPA, respectively. ORs for Visit 1 and the visit average were closer to the null.

DISCUSSION: Urine GLY and AMPA levels in samples collected near the 26th week of pregnancy were associated with increased odds of PTB in this modestly sized nested case-control study. Given the widespread use of GLY, multiple potential sources of AMPA, and AMPA’s persistence in the environment, as well as the potential for long-term adverse health effects in preterm infants, further investigation in other populations is warranted.


Kokroko et al., 2020

Kokroko, J., Kogut, K., Harley, K., & Eskenazi, B.; “Prenatal beta-Hexachlorocyclohexane (beta-HCH) Exposure and 7-Year Child IQ in the CHAMACOS Birth Cohort;” Neurotoxicity Research, 2020, 37(3), 553-563; DOI: 10.1007/s12640-020-00160-w.


Fetal and infant exposures to beta-hexachlorocyclohexane (beta-HCH) occur through placental and breastmilk transfers. No studies have examined the relationship between beta-HCH and child intelligence quotient (IQ). This study examined associations between in utero beta-HCH exposure and cognitive development in 7-year-old children. Data from women and children (n = 256) participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort study were evaluated. We assessed exposure to beta-HCH by measuring maternal serum concentration during pregnancy. We administered the Wechsler Intelligence Scale for Children (WISC), Fourth Edition, to children at age 7. Analyses were adjusted for maternal age, country of birth, work status, parity, and other pesticide exposures, language used for child cognitive assessment, and duration of breastfeeding. Higher serum beta-HCH concentrations were associated with higher cognitive scores across all unadjusted models for the full-scale and sub-scale cognitive tests. In the adjusted models, a 10-fold increase in serum beta-HCH concentration was associated with a 4.5-point increase in Working Memory IQ score (95% CI, 0.6 to 8.3; p = 0.02). We observed no significant interaction by length of breastfeeding or sex on associations. Our findings suggest that prenatal exposure to beta-HCH is not adversely related to IQ at age 7 in a cohort of Mexican American children with fairly high exposure in utero as measured by maternal serum levels. Future research must replicate these findings in other study cohorts of women and children.

Shah and Kingdom, 2011

Shah, Prakesh, & Kingdom, John; “Long-term neurocognitive outcomes of SGA/IUGR infants;” Obstetrics, Gynaecology & Reproductive Medicine, 2011, 21(5), 142-146; DOI: 10.1016/j.ogrm.2011.02.004.


With advances in the management of preterm neonates, the chances of survival have increased even among those who are intrauterine growth restricted (IUGR) or who are born small for gestational age (SGA). However, infants who are IUGR/SGA are considered at higher risk of physical and neurodevelopmental abnormalities, although the reported impacts of IUGR and SGA status at birth on neurodevelopmental outcomes in long-term outcomes studies have varied. In particular, some reports have indicated gradual improvement in neurodevelopmental functions over time in these infants. We have therefore reviewed all the available reports describing neurodevelopmental outcomes of preterm and term SGA infants beyond 5 years of age. Preterm SGA infants are at increased risk of impairment in neuromotor, cognitive, behavioural and scholastic attainments compared with preterm non-SGA infants. On the other hand, term SGA infants had problems in scholastic/vocational attainments compared with term non SGA infants, while adverse neuromotor, cognitive and behavioural outcomes were not consistently observed at higher rates. Limitations regarding the validity of studies of long-term outcomes of SGA infants are discussed and a potential approach is suggested. FULL TEXT

Haas et al., 2015

Haas, D. M., Parker, C. B., Wing, D. A., Parry, S., Grobman, W. A., Mercer, B. M., Simhan, H. N., Hoffman, M. K., Silver, R. M., Wadhwa, P., Iams, J. D., Koch, M. A., Caritis, S. N., Wapner, R. J., Esplin, M. S., Elovitz, M. A., Foroud, T., Peaceman, A. M., Saade, G. R., Willinger, M., Reddy, U. M., & NuMo, M. b study; “A description of the methods of the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b);” American Journal of Obstetrics & Gynecology, 2015, 212(4), 539 e531-539 e524; DOI: 10.1016/j.ajog.2015.01.019.


OBJECTIVE: The primary aim of the “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” is to determine maternal characteristics, which include genetic, physiologic response to pregnancy, and environmental factors that predict adverse pregnancy outcomes.

STUDY DESIGN: Nulliparous women in the first trimester of pregnancy were recruited into an observational cohort study. Participants were seen at 3 study visits during pregnancy and again at delivery. We collected data from in-clinic interviews, take-home surveys, clinical measurements, ultrasound studies, and chart abstractions. Maternal biospecimens (serum, plasma, urine, cervicovaginal fluid) at antepartum study visits and delivery specimens (placenta, umbilical cord, cord blood) were collected, processed, and stored. The primary outcome of the study was defined as pregnancy ending at <37+0 weeks’ gestation. Key study hypotheses involve adverse pregnancy outcomes of spontaneous preterm birth, preeclampsia, and fetal growth restriction.

RESULTS: We recruited 10,037 women to the study. Basic characteristics of the cohort at screening are reported.

CONCLUSION: The “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” cohort study methods and procedures can help investigators when they plan future projects.


Buckley et al., 2020

Buckley, J. P., Barrett, E. S., Beamer, P. I., Bennett, D. H., Bloom, M. S., Fennell, T. R., Fry, R. C., Funk, W. E., Hamra, G. B., Hecht, S. S., Kannan, K., Iyer, R., Karagas, M. R., Lyall, K., Parsons, P. J., Pellizzari, E. D., Signes-Pastor, A. J., Starling, A. P., Wang, A., Watkins, D. J., Zhang, M., Woodruff, T. J., & program collaborators for, Echo; “Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program;” Journal of exposure science & environmental epidemiology, 2020, 30(3), 397-419; DOI: 10.1038/s41370-020-0211-9.


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. FULL TEXT