Bibliography Tag: birth cohort studies

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

Chiu, 2017

Chiu, Y. H.,”Pesticide Residues in Fruits and Vegetables: Assessment and Their Associations With Reproductive Health Outcomes;” Dissertation at Harvard Universiry, (Doctor of Science in Nutrition and Epidemiology); 2017.


According to the Dietary Guideline, consumption of fruits and vegetables (FVs) are recommended throughout the lifespan, including during pregnancy. FVs, on the other hand, can serve as a vehicle of exposure to pesticide residues. In the US, Environmental Protection Agency (EPA) is responsible for regulating pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act and the Food Quality Protection Act. While majority of the produce sampled through the US Department of Agriculture had residues below the EPA limits, there is a growing concern whether chronic exposure to these pesticide residues may have adverse health effects, especially among susceptible populations such as pregnant women. Yet, such research is scarce. This dissertation focuses on the assessment of pesticide residues in FVs and evaluates their associations with pregnancy outcomes.

We previously have developed the Pesticide Residue Burden Score (PRBS) based on selfreported diet and national surveillance data on food pesticide residues to characterize dietary exposure over the past year. In Chapter 1, we evaluated the association of the PRBS with urinary pesticide metabolites in the Environment and Reproductive Health (EARTH) Study. We found intake of high pesticide residues FVs was positively associated with urinary concentrations of pesticide biomarkers, suggesting that PRBS can characterize dietary exposure to select pesticides.

In Chapter 2, we assessed the relation between preconception intake of high and low FVs and assisted reproductive technology outcomes in EARTH study. We found that intake of high pesticide residues FVs was associated with lower probability of clinical pregnancy and live birth, while intake of low pesticide residue FVs had the opposite relations among women undergoing infertility treatment. This is the first report of such relation in humans.

In Chapter 3, we examine the association between maternal intake of high and low pesticide residue FVs with birth outcomes in a pre-birth cohort. We found that maternal intake of high pesticide residue FVs during the first trimester was associated with higher risks of small-for-gestational-age among white women, while these exposures was associated with large-for-gestational-age among nonwhite women.

In conclusion, this work demonstrated the usefulness of PRBS in assessing pesticide residue intake through FVs. Using this method, these studies suggest exposure to pesticide residues may adversely affect pregnancy and birth outcomes.


Yamamoto et al., 2016

Yamamoto, M., Fujita, M., Mori, C., & Hata, A.; “Survey of motivation to participate in a birth cohort;” Journal of Human Genetics, 2016, 61(9), 787-791; DOI: 10.1038/jhg.2016.60.


For a longitudinal prospective cohort study to be successful, participants’ motivation to provide information must be maintained. Therefore, this study aimed to identify items that effectively promote participants’ motivation. Questionnaires were mailed to 4541 mothers and expectant mothers in Chiba Prefecture, Japan who participated in a nationwide birth cohort. A total of 2387 (52.6%) responses were received. The following items were identified as primary motivating factors among our cohort: “benefits to the participants’ children”, “monetary compensation” and “contribution to a better future environment”. More than 30% of the respondents expressed a lack of understanding regarding the study purpose and requirements for participation. About 14% were concerned about the leakage of personal information, and 13% felt burdened by having to make a long-term commitment to the study. Cluster analysis identified four groups, two of which, one with extremely low levels of motivation and the other motivated by only money or goods, lacked an understanding of the study and tended to be concerned about the associated risks and burdens. Participants in these groups were considered to be at a high risk of dropout. Therefore, implementing measures to provide participants with a better understanding of cohort studies could lead to more successful results. FULL TEXT

Oya et al., 2016

Oya, N., Ito, Y., Hioki, K., Asai, Y., Aoi, A., Sugiura, Y., Ueyama, J., Oguri, T., Kato, S., Ebara, T., & Kamijima, M.; “Quantitative analysis of organophosphate insecticide metabolites in urine extracted from disposable diapers of toddlers in Japan;” International Journal of Hygiene and Environmental Health, 2017, 220(2 Pt A), 209-216; DOI: 10.1016/j.ijheh.2016.10.009.



Epidemiological studies linking insecticide exposure to childhood neurodevelopment have been gaining global attention. Despite the rapid development of the central nervous system in early childhood, studies regarding the biological monitoring of insecticide exposure in diapered children are limited. In this study, we aimed to clarify the concentrations of organophosphate (OP) insecticide metabolites in toddler urine extracted from disposable diapers in Japan.


We recruited diapered children from the Aichi regional subcohort participants of the Japan Environment and Children’s Study (JECS) at the time of their 18-month checkup. A total of 116 children wore designated disposable diapers overnight, which were then sent as refrigerated cargo. The urine was extracted from the diapers using acetone and analyzed by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) to determine the concentrations of six dialkyl phosphates (DAPs) (i.e., dimethyl phosphate [DMP], dimethyl thiophosphate [DMTP], dimethyl dithiophosphate [DMDTP], diethyl phosphate [DEP], diethyl thiophosphate [DETP], and diethyl dithiophosphate [DEDTP]). DAP absorption into the diapers was quantified to calculate the urinary DAP concentrations.


The DAP recovery using the developed method yielded between 54.2% (DEDTP) and 101.4% (DEP). Within-run precision expressed as the relative standard deviation was between 2.4% and 14.7%, and the between-run precision was between 3.1% and 8.5%. A Bland-Altman analysis confirmed the agreement between the results obtained by the developed method and by the measurements for the corresponding urine without diaper absorption. The geometric means (GM) of urinary DMP, DMTP, DMDTP, DEP, DETP, and total DAPs (SigmaDAP) were 3.6, 3.9, 0.9, 6.0, 0.6mug/L, and 137.6 nmol/L, respectively. The GM of DEDTP was not calculated due to its low detection rate.


We successfully established a method to measure the DAP concentrations in urine extracted from diapers and this is the first report of these pesticide concentrations in diapered children in Japan.


Michikawa et al., 2018

Michikawa, T., Nitta, H., Nakayama, S. F., Yamazaki, S., Isobe, T., Tamura, K., Suda, E., Ono, M., Yonemoto, J., Iwai-Shimada, M., Kobayashi, Y., Suzuki, G., Kawamoto, T., Japan, Environment, & Children’s Study, Group; “Baseline Profile of Participants in the Japan Environment and Children’s Study (JECS);” Journal of Epidemiology, 2018, 28(2), 99-104; DOI: 10.2188/jea.JE20170018.



The Japan Environment and Children’s Study (JECS), known as Ecochil-Chosa in Japan, is a nationwide birth cohort study investigating the environmental factors that might affect children’s health and development. We report the baseline profiles of the participating mothers, fathers, and their children.


Fifteen Regional Centres located throughout Japan were responsible for recruiting women in early pregnancy living in their respective recruitment areas. Self-administered questionnaires and medical records were used to obtain such information as demographic factors, lifestyle, socioeconomic status, environmental exposure, medical history, and delivery information. In the period up to delivery, we collected bio-specimens, including blood, urine, hair, and umbilical cord blood. Fathers were also recruited, when accessible, and asked to fill in a questionnaire and to provide blood samples.


The total number of pregnancies resulting in delivery was 100,778, of which 51,402 (51.0%) involved program participation by male partners. Discounting pregnancies by the same woman, the study included 95,248 unique mothers and 49,189 unique fathers. The 100,778 pregnancies involved a total of 101,779 fetuses and resulted in 100,148 live births. The coverage of children in 2013 (the number of live births registered in JECS divided by the number of all live births within the study areas) was approximately 45%. Nevertheless, the data on the characteristics of the mothers and children we studied showed marked similarity to those obtained from Japan’s 2013 Vital Statistics Survey.


Between 2011 and 2014, we established one of the largest birth cohorts in the world.