PMID- 37094650 OWN - NLM STAT- MEDLINE DCOM- 20230522 LR - 20231216 IS - 1096-0953 (Electronic) IS - 0013-9351 (Print) IS - 0013-9351 (Linking) VI - 229 DP - 2023 Jul 15 TI - Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study. PG - 115975 LID - S0013-9351(23)00767-3 [pii] LID - 10.1016/j.envres.2023.115975 [doi] AB - BACKGROUND: Pregnant persons are exposed ubiquitously to phthalates and increasingly to chemicals introduced to replace phthalates. In early pregnancy, exposure to these chemicals may disrupt fetal formation and development, manifesting adverse fetal growth. Previous studies examining the consequences of early pregnancy exposure relied on single spot urine measures and did not investigate replacement chemicals. OBJECTIVE: Characterize associations between urinary phthalate and replacement biomarkers in early pregnancy and fetal growth outcomes. METHODS: Analyses were conducted among 254 pregnancies in the Human Placenta and Phthalates Study, a prospective cohort with recruitment 2017-2020. Exposures were geometric mean concentrations of phthalate and replacement biomarkers quantified in two spot urine samples collected around 12- and 14-weeks of gestation. Outcomes were fetal ultrasound biometry (head and abdominal circumferences, femur length, estimated fetal weight) collected in each trimester and converted to z-scores. Adjusted linear mixed effects (single-pollutant) and quantile g-computation (mixture) models with participant-specific random effects estimated the difference, on average, in longitudinal fetal growth for a one-interquartile range (IQR) increase in individual (single-pollutant) or all (mixture) early pregnancy phthalate and replacement biomarkers. RESULTS: Mono carboxyisononyl phthalate and the sums of metabolites of di-n-butyl, di-iso-butyl, and di-2-ethylhexyl phthalate were inversely associated with fetal head and abdominal circumference z-scores. A one-IQR increase in the phthalate and replacement biomarker mixture was inversely associated with fetal head circumference (beta: -0.36 [95% confidence interval: -0.56, -0.15]) and abdominal circumference (-0.31 [-0.49, -0.12]) z-scores. This association was mainly driven by phthalate biomarkers. CONCLUSIONS: Urine concentrations of phthalate biomarkers, but not replacement biomarkers, in early pregnancy were associated with reductions in fetal growth. Though the clinical implications of these differences are unclear, reduced fetal growth contributes to excess morbidity and mortality across the lifecourse. Given widespread global exposure to phthalates, findings suggest a substantial population health burden resulting from early pregnancy phthalate exposure. CI - Published by Elsevier Inc. FAU - Stevens, Danielle R AU - Stevens DR AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA. FAU - Rosen, Emma M AU - Rosen EM AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA; Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA. FAU - Van Wickle, Kimi AU - Van Wickle K AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA; Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA. FAU - McNell, Erin E AU - McNell EE AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA; Curriculum in Toxicology and Environmental Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA. FAU - Bommarito, Paige A AU - Bommarito PA AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA. FAU - Calafat, Antonia M AU - Calafat AM AD - Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. FAU - Botelho, Julianne C AU - Botelho JC AD - Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. FAU - Sinkovskaya, Elena AU - Sinkovskaya E AD - Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA. FAU - Przybylska, Ann AU - Przybylska A AD - Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA. FAU - Saade, George AU - Saade G AD - Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA. FAU - Abuhamad, Alfred AU - Abuhamad A AD - Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA. FAU - Ferguson, Kelly K AU - Ferguson KK AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA. Electronic address: Kelly.ferguson2@nih.gov. LA - eng GR - T32 HL129982/HL/NHLBI NIH HHS/United States GR - ZIA ES103344/ImNIH/Intramural NIH HHS/United States GR - R01 HD086313/HD/NICHD NIH HHS/United States GR - T32 ES007018/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural DEP - 20230423 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 6O7F7IX66E (phthalic acid) RN - 0 (Phthalic Acids) RN - 0 (Environmental Pollutants) RN - 0 (Biomarkers) SB - IM MH - Pregnancy MH - Female MH - Humans MH - Prospective Studies MH - *Phthalic Acids/toxicity/metabolism MH - Fetal Development MH - Placenta/metabolism MH - *Environmental Pollutants/toxicity MH - Biomarkers MH - Environmental Exposure PMC - PMC10201455 MID - NIHMS1898892 OTO - NOTNLM OT - Endocrine disruptors OT - Fetal weight OT - Phthalic acid OT - Pregnancy OT - Prospective studies COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/04/25 00:41 MHDA- 2023/05/22 06:42 PMCR- 2024/07/15 CRDT- 2023/04/24 07:21 PHST- 2023/01/13 00:00 [received] PHST- 2023/04/14 00:00 [revised] PHST- 2023/04/21 00:00 [accepted] PHST- 2024/07/15 00:00 [pmc-release] PHST- 2023/05/22 06:42 [medline] PHST- 2023/04/25 00:41 [pubmed] PHST- 2023/04/24 07:21 [entrez] AID - S0013-9351(23)00767-3 [pii] AID - 10.1016/j.envres.2023.115975 [doi] PST - ppublish SO - Environ Res. 2023 Jul 15;229:115975. doi: 10.1016/j.envres.2023.115975. Epub 2023 Apr 23.