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Abstract
Background: Preterm birth (gestational age less than 37 weeks), the leading cause of infant morbidity and mortality worldwide, disproportionally impacts pregnancies in Puerto Rico. Organophosphate flame retardants (OPFRs) are used as flame retardants and plasticizers its exposure is widespread. Epidemiologic studies in humans of the endocrine-disrupting and reproductive effects of OPFRs are very limited but suggest that OPRFs have the capacity to disrupt growth and metabolism through endocrine-related mechanisms of action. Alterations in the delicate hormonal balance occurring during pregnancy may represent one possible mechanism linking OPFR exposure to adverse pregnancy outcomes. The purpose of this dissertation is to (1) Identify knowledge gaps on the role of flame retardant on adverse pregnancy outcomes and assess the current knowledge of the effects of flame retardants on adverse pregnancy outcomes; (2) Identify associations between prenatal exposure to OPFRs with gestational age and birth weight using the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort; and (3) Identify associations between OPFRs and 9 maternal thyroid and reproductive hormones using the PROTECT cohort.
Methods: For aim 1, a research protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to conduct a systematic review on prenatal exposure to OPFRs and its effects on adverse pregnancy outcomes, with a focus on preterm birth and low birth weight. Data for aims 2 & 3 of this dissertation came from the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort. OPFRs (>70% LOD) were measured in maternal urine and collected at two visits (~20 and 24 weeks of gestation). Multivariable linear regression was used to examine the associations between average OPFR levels across 2 time points in pregnancy with gestational duration and birth weight. Linear mixed models were used to assess the effect of 8 OPFRs and 9 serum hormones measured over two time points during pregnancy.
Results: The systematic review yielded 40 epidemiological studies meeting the pre-determined inclusion criteria. Of these studies, only 6 studies examined the associations between OPFRs and preterm birth/low birth weight and 4 studies examined other outcomes of interest (Aim 1). No associations were observed between OPFR metabolites, gestational age, and birth weight (Aim 2). For maternal hormones, increased levels of FT4 were associated with BCPP (%Δ:0.25, 95% CI: 0.05, 0.45) and BDCPP (%Δ:0.24, 95% CI: 0.07, 0.41) A decrease in FT4 was associated with DPhP (%Δ: -0.21, 95% CI: -0.37, -0.06). DPhP was associated with a decrease in T4(%Δ: -0.16, 95% CI: -0.31, -0.01) (Aim 3). Conclusions: Our study examined associations between multiple measures of OPFRs among a pregnant Puerto Rican population. Findings from our study highlight the role of OPFRs as possible endocrine disruptors and the urgent need for more research on emerging flame retardants, such as OPFRs.
Methods: For aim 1, a research protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to conduct a systematic review on prenatal exposure to OPFRs and its effects on adverse pregnancy outcomes, with a focus on preterm birth and low birth weight. Data for aims 2 & 3 of this dissertation came from the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort. OPFRs (>70% LOD) were measured in maternal urine and collected at two visits (~20 and 24 weeks of gestation). Multivariable linear regression was used to examine the associations between average OPFR levels across 2 time points in pregnancy with gestational duration and birth weight. Linear mixed models were used to assess the effect of 8 OPFRs and 9 serum hormones measured over two time points during pregnancy.
Results: The systematic review yielded 40 epidemiological studies meeting the pre-determined inclusion criteria. Of these studies, only 6 studies examined the associations between OPFRs and preterm birth/low birth weight and 4 studies examined other outcomes of interest (Aim 1). No associations were observed between OPFR metabolites, gestational age, and birth weight (Aim 2). For maternal hormones, increased levels of FT4 were associated with BCPP (%Δ:0.25, 95% CI: 0.05, 0.45) and BDCPP (%Δ:0.24, 95% CI: 0.07, 0.41) A decrease in FT4 was associated with DPhP (%Δ: -0.21, 95% CI: -0.37, -0.06). DPhP was associated with a decrease in T4(%Δ: -0.16, 95% CI: -0.31, -0.01) (Aim 3). Conclusions: Our study examined associations between multiple measures of OPFRs among a pregnant Puerto Rican population. Findings from our study highlight the role of OPFRs as possible endocrine disruptors and the urgent need for more research on emerging flame retardants, such as OPFRs.