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Insights of Perinatal Endocrine Disruptors Exposure Influencing Maternal and Child Health

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A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Human Toxicology and Epidemiology".

Deadline for manuscript submissions: closed (10 April 2023) | Viewed by 26735

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Dr. Megan Romano

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Guest Editor

Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
Interests: childhood obesity; exposure assessment; perinatal epidemiology; environmental health; environmental epidemiology; gestational diabetes; endocrine disruptors

Dr. Caitlin Howe

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Guest Editor

Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
Interests: environmental mixtures; metals; nutrition; early growth; cardiometabolic health; epigenetics; DOHaD
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Dear Colleagues,

The perinatal period represents a window of extreme vulnerability for both mothers and the developing child. During pregnancy, women and the developing fetus are exposed to a wide array of environmental factors with implications for both short- and long-term health of mother and child. The importance of understanding the influence of individual endocrine disruptors, co-exposures, and multipollutant exposures on maternal and child health cannot be overstated. Exposure to environmental endocrine-disrupting chemicals, including bisphenol A, phthalates, organophosphate esters, pesticides, per- and polyfluoroalkyl substances, and many others, can cause complications of pregnancy and adversely affect other aspects of maternal health both during and following pregnancy. Likewise, these exposures in utero influence fetal development, birth outcomes, and many cardiovascular, metabolic, immunologic, respiratory, and neurological outcomes in childhood.

This Special Issue focuses on our current understanding and identification of gaps in the evidence base with respect to perinatal exposure to environmental endocrine-disrupting chemicals and their adverse effects on maternal health, fetal development, birth outcomes, and children’s health.

Dr. Megan Romano
Dr. Caitlin Howe
Guest Editors

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Keywords

perinatal exposure
endocrine disruptors
maternal and child health
fetal development
birth outcomes
environmental epidemiology

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Published Papers (7 papers)

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15 pages, 647 KiB

Open AccessArticle

Prenatal Cadmium Exposure and Maternal Sex Steroid Hormone Concentrations across Pregnancy

by Zorimar Rivera-Núñez, Megan Hansel, Camila Capurro, Danielle Kozlosky, Christina Wang, Cathleen L. Doherty, Brian Buckley, Pamela Ohman-Strickland, Richard K. Miller, Thomas G. O’Connor, Lauren M. Aleksunes and Emily S. Barrett

Toxics 2023, 11(7), 589; https://doi.org/10.3390/toxics11070589 - 6 Jul 2023

Viewed by 8568

Abstract

Cadmium exposure has been associated with adverse perinatal outcomes. One possible mechanism is endocrine disruption. Studies of non-pregnant adults suggest that cadmium impacts androgen production; here, we examined these associations during pregnancy. Participants in the Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort provided biospecimens and questionnaire data in each trimester (n = 272). We quantified urinary cadmium, serum total testosterone (TT), estrone, estradiol, and estriol and serum free testosterone (fT). In adjusted longitudinal models, we examined sex steroid concentrations across pregnancy in relation to specific gravity-adjusted, ln-transformed cadmium concentrations. Additionally, we examined trimester-specific associations and stratified models by fetal sex. Results are presented as percent change (%∆) in hormone concentrations. In longitudinal models, higher cadmium concentrations were associated with lower fT across pregnancy (%∆ = −5.19, 95%CI: −8.33, −1.93), with no differences in other hormones observed. In trimester-specific models, higher cadmium concentrations were associated with lower TT in trimester 2 (%∆ = −15.26, 95%CI: −25.15, −4.06) and lower fT in trimester 3 (%∆ = −14.35, 95%CI: −19.75, −8.59). Associations with TT were stronger in pregnancies carrying female fetuses. Maternal cadmium exposure may be associated with reduced testosterone in pregnancy. Additional work is necessary to understand how alterations in gestational testosterone activity may impact pregnancy and child health. Full article

(This article belongs to the Special Issue Insights of Perinatal Endocrine Disruptors Exposure Influencing Maternal and Child Health)

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13 pages, 831 KiB

Open AccessArticle

Associations of Maternal Urinary Concentrations of Phenols, Individually and as a Mixture, with Serum Biomarkers of Thyroid Function and Autoimmunity: Results from the EARTH Study

by Glen McGee, Maximilien Génard-Walton, Paige L. Williams, T. I. M. Korevaar, Jorge E. Chavarro, John D. Meeker, Joseph M. Braun, Maarten A. Broeren, Jennifer B. Ford, Antonia M. Calafat, Irene Souter, Russ Hauser and Lidia Mínguez-Alarcón

Toxics 2023, 11(6), 521; https://doi.org/10.3390/toxics11060521 - 9 Jun 2023

Cited by 3 | Viewed by 2735

Abstract

The associations between urinary phenol concentrations and markers of thyroid function and autoimmunity among potentially susceptible subgroups, such as subfertile women, have been understudied, especially when considering chemical mixtures. We evaluated cross-sectional associations of urinary phenol concentrations, individually and as a mixture, with serum markers of thyroid function and autoimmunity. We included 339 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2009–2015). We quantified four phenols in urine using isotope dilution high-performance liquid chromatography–tandem mass spectrometry, and biomarkers of thyroid function (thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4), and triiodothyronine (fT3, TT3)), and autoimmunity (thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (Ab)) in serum using electrochemoluminescence assays. We fit linear and additive models to investigate the association between urinary phenols—both individually and as a mixture—and serum thyroid function and autoimmunity, adjusted for confounders. As a sensitivity analysis, we also applied Bayesian Kernel Machine Regression (BKMR) to investigate non-linear and non-additive interactions. Urinary bisphenol A was associated with thyroid function, in particular, fT₃ (mean difference for a 1 log unit increase in concentration: −0.088; 95% CI [−0.151, −0.025]) and TT₃ (−0.066; 95% CI [−0.112, −0.020]). Urinary methylparaben and triclosan were also associated with several thyroid hormones. The overall mixture was negatively associated with serum fT₃ concentrations (mean difference comparing all four mixture components at their 75th vs. 25th percentiles: −0.19, 95% CI [−0.35, −0.03]). We found no evidence of non-linearity or interactions. These results add to the current literature on phenol exposures and thyroid function in women, suggesting that some phenols may alter the thyroid system. Full article

(This article belongs to the Special Issue Insights of Perinatal Endocrine Disruptors Exposure Influencing Maternal and Child Health)

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18 pages, 362 KiB

Open AccessEditor’s ChoiceArticle

Maternal Serum, Cord and Human Milk Levels of Per- and Polyfluoroalkyl Substances (PFAS), Association with Predictors and Effect on Newborn Anthropometry

by Maya Mahfouz, Mireille Harmouche-Karaki, Joseph Matta, Yara Mahfouz, Pascale Salameh, Hassan Younes, Khalil Helou, Ramzi Finan, Georges Abi-Tayeh, Mohamad Meslimani, Ghada Moussa, Nada Chahrour, Camille Osseiran, Farouk Skaiki and Jean-François Narbonne

Toxics 2023, 11(5), 455; https://doi.org/10.3390/toxics11050455 - 14 May 2023

Cited by 10 | Viewed by 3166

Abstract

Background: The understanding of per- and polyfluoroalkyl substances (PFAS) health effects is rapidly advancing among critical populations. Therefore, the objective of this study was to assess PFAS serum levels among Lebanese pregnant women, cord serum and human milk levels, their determinants, and effects on newborn anthropometry. Methods: We measured concentrations of six PFAS (PFHpA, PFOA, PFHxS, PFOS, PFNA and PFDA) using liquid chromatography MS/MS for 419 participants, of which 269 had sociodemographic, anthropometric, environmental and dietary information. Results: The percentage of detection for PFHpA, PFOA, PFHxS and PFOS was 36.3–37.7%. PFOA and PFOS levels (95th percentile) were higher than HBM-I and HBM-II values. While PFAS were not detected in cord serum, five compounds were detected in human milk. Multivariate regression showed that fish/shellfish consumption, vicinity to illegal incineration and higher educational level were associated with an almost twice higher risk of elevated PFHpA, PFOA, PFHxS and PFOS serum levels. Higher PFAS levels in human milk were observed with higher eggs and dairy products consumption, in addition to tap water (preliminary findings). Higher PFHpA was significantly associated with lower newborn weight-for-length Z-score at birth. Conclusions: Findings establish the need for further studies, and urgent action to reduce exposure among subgroups with higher PFAS levels. Full article

(This article belongs to the Special Issue Insights of Perinatal Endocrine Disruptors Exposure Influencing Maternal and Child Health)

15 pages, 1252 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Per- and Polyfluoroalkyl Substances (PFAS) Mixture during Pregnancy and Postpartum Weight Retention in the New Hampshire Birth Cohort Study (NHBCS)

by Yuting Wang, Caitlin Howe, Lisa G. Gallagher, Julianne Cook Botelho, Antonia M. Calafat, Margaret R. Karagas and Megan E. Romano

Toxics 2023, 11(5), 450; https://doi.org/10.3390/toxics11050450 - 10 May 2023

Cited by 3 | Viewed by 2172

Abstract

Per- and polyfluoroalkyl substances (PFAS), widely used in industrial and consumer products, are suspected metabolic disruptors. We examined the association between a PFAS mixture during pregnancy and postpartum weight retention in 482 participants from the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate, perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate, were quantified in maternal plasma collected at ~28 gestational weeks. Postpartum weight change was calculated as the difference between self-reported weight from a postpartum survey administered in 2020 and pre-pregnancy weight abstracted from medical records. Associations between PFAS and postpartum weight change were examined using Bayesian kernel machine regression and multivariable linear regression, adjusting for demographic, reproductive, dietary, and physical activity factors; gestational week of blood sample collection; and enrollment year. PFOS, PFOA, and PFNA were positively associated with postpartum weight retention, and associations were stronger among participants with a higher pre-pregnancy body mass index. A doubling of PFOS, PFOA, and PFNA concentrations was associated with a 1.76 kg (95%CI: 0.31, 3.22), 1.39 kg (−0.27, 3.04), and 1.04 kg (−0.19, 2.28) greater postpartum weight retention, respectively, among participants who had obesity/overweight prior to pregnancy. Prenatal PFAS exposure may be associated with increased postpartum weight retention. Full article

(This article belongs to the Special Issue Insights of Perinatal Endocrine Disruptors Exposure Influencing Maternal and Child Health)

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18 pages, 5446 KiB

Open AccessArticle

Gestational Exposure to Phthalates and Phthalate Replacements in Relation to Neurodevelopmental Delays in Early Childhood

by Seonyoung Park, Emily Zimmerman, Gredia Huerta-Montañez, Zaira Rosario-Pabón, Carmen M. Vélez-Vega, José F. Cordero, Akram Alshwabekah, John D. Meeker and Deborah J. Watkins

Toxics 2023, 11(1), 65; https://doi.org/10.3390/toxics11010065 - 11 Jan 2023

Cited by 13 | Viewed by 2579

Abstract

Phthalates have been linked to changes in child neurodevelopment. However, sex-specificity has been reported inconsistently, and little is known about the impact of recent phthalate replacement chemicals. Our analysis included mother–child pairs (N = 274) from the PROTECT birth cohort in Puerto Rico. Phthalate metabolites were measured in multiple maternal urine collected during pregnancy. Neurodevelopment was measured at 6, 12, and 24 months of age using the Battelle Developmental Inventory-2nd edition (BDI), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. Multivariable linear regression was used to examine associations between phthalate metabolite concentrations and BDI scores, adjusting for maternal age, maternal education, child age, and specific gravity. Sex-specificity was assessed with sex X exposure interaction terms and stratified models. Results show that all five domains were significantly associated with mono-3-carboxypropyl phthalate (MCPP) at age 24 months, suggesting a holistic developmental delay related to this metabolite. Sex-specificity existed for all timepoints (p-interaction < 0.2), in general, showing stronger associations among boys. For example, metabolites of a recent phthalate replacement, di-2-ethylhexyl terephthalate (DEHTP), were differentially associated with the adaptive domain (boys −7.53%/IQR, 95% CI: −14.58, −0.48 vs. girls −0.85%/IQR, 95% CI: −5.08, 3.37), and the cognitive domain (boys −6.05%/IQR, 95% CI: −10.88, −1.22 vs. girls −1.93%/IQR, 95%CI: −4.14, 0.28) at 6 months. To conclude, gestational exposure to phthalates and phthalate replacements was associated with neurodevelopmental delay across multiple domains, with differences by sex and child age. Full article

(This article belongs to the Special Issue Insights of Perinatal Endocrine Disruptors Exposure Influencing Maternal and Child Health)

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20 pages, 3298 KiB

Open AccessFeature PaperArticle

Associations between Phthalate Exposure and Gestational Age at Delivery in a Diverse Pregnancy Cohort

by Laura Sienas, Catherine Albright, Yu Ni, Adam Szpiro, Nicole R. Bush, Christine Loftus, Kurunthachalam Kannan, Frances Tylavsky, Catherine J. Karr, Kaja Z. LeWinn and Sheela Sathyanarayana

Toxics 2022, 10(12), 754; https://doi.org/10.3390/toxics10120754 - 3 Dec 2022

Cited by 4 | Viewed by 2510

Abstract

The association between prenatal phthalate exposure and late preterm birth (LPTB) is unclear. We examined singleton pregnancies (2006–2011) from a racially and socioeconomically diverse sample of women in the CANDLE cohort of the ECHO-PATHWAYS Consortium. Urine collected in the second and third trimester was analyzed for 14 phthalate metabolites. Multivariate logistic and linear regressions were performed for LPTB, defined as delivery 34–37 weeks, and gestational week, respectively. Models were controlled for socio-demographics, behavioral factors, clinical measurements, medical history, and phthalates in the other trimester. Effect modification by race and pregnancy stress, indicated by intimate partner violence (IPV), was investigated. We conducted a secondary analysis in women with spontaneous preterm labor. The rate of LPTB among 1408 women (61% Black, 32% White) was 6.7%. There was no evidence of decreased gestational age (GA) in association with any phthalate metabolite. Each two-fold increase in third trimester mono-benzyl phthalate (MBzP) was associated with 0.08 weeks longer gestational age (95% CI: 0.03, 0.12). When restricting to women with spontaneous labor, second trimester mono-n-butyl phthalate (MBP) was associated with 54% higher odds (95% CI: 2%, 132%) of LPTB. Associations were not modified by maternal race or IPV exposure. In conclusion, we observed mixed evidence concerning our hypothesis that prenatal phthalate exposure increases risk of LPTB, though secondary analyses suggest increased risk of spontaneous LPTB associated with MBP, which is consistent with a recent pooled analysis of 16 cohorts. Full article

(This article belongs to the Special Issue Insights of Perinatal Endocrine Disruptors Exposure Influencing Maternal and Child Health)

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25 pages, 7333 KiB

Open AccessFeature PaperReview

Per- and Polyfluoroalkyl Substances and Breastfeeding as a Vulnerable Function: A Systematic Review of Epidemiological Studies

by Amalie Timmermann, Oyemwenosa N. Avenbuan, Megan E. Romano, Joseph M. Braun, Janne S. Tolstrup, Laura N. Vandenberg and Suzanne E. Fenton

Toxics 2023, 11(4), 325; https://doi.org/10.3390/toxics11040325 - 29 Mar 2023

Cited by 17 | Viewed by 3682

Abstract

Milk formation in the breast during breastfeeding is a complex hormonally regulated process, potentially sensitive to the effects of endocrine-disrupting chemical exposures. The environmental chemicals, per- and polyfluoroalkyl substances (PFAS) are known endocrine disruptors. PFAS exposure have been associated with insufficient mammary gland development in mice and reduced breastfeeding duration in humans. The aim of this review was to gather the epidemiological evidence on the association between PFAS exposure and breastfeeding duration. Using PubMed and Embase, we performed a systematic literature search (on 23 January 2023) to identify epidemiological studies examining the association between maternal PFAS exposure and breastfeeding duration. Animal studies, reviews, and non-English studies were excluded. The risk of bias was assessed using the risk of bias in non-randomized studies of exposures tool. Estimates describing the association between PFAS exposure and the duration of breastfeeding were identified, and the data were synthesized separately for each type of PFAS and for the duration of exclusive and total breastfeeding. Six studies with between 336 and 2374 participants each were identified. PFAS exposure was assessed in serum samples (five studies) or based on residential address (one study). Five out of six studies found shorter total duration of breastfeeding with higher PFAS exposure. The most consistent associations were seen for perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA). The finding of a potential causal association between PFAS exposure and breastfeeding duration is in agreement with findings from experimental studies. Full article

(This article belongs to the Special Issue Insights of Perinatal Endocrine Disruptors Exposure Influencing Maternal and Child Health)

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