Maternal preconception exposure to phthalates was associated with increased risk of preterm birth, according to a study of 420 births to subfertile couples over a 13-year period.
Previous studies have shown increased risk of preterm birth associated with prenatal exposure to phthalates, which are commonly found in a range of household and commercial products as well as medical equipment and some pharmaceuticals.
“Our results suggest that female exposure to [4 di(2-ethylhexyl) phthalate] DEHP before conception might be an unrecognized risk factor for adverse pregnancy outcomes, often overlooked in clinical practice,” wrote Yu Zhang of the department of environmental health at Harvard T.H. Chan School of Public Health, Boston, and colleagues.
The prospective cohort study evaluated preconception urinary levels of phthalates and phthalate substitutes in 419 women and 229 men participating in the Environment and Reproductive Health (EARTH) study, a cohort of couples seeking fertility care at the Massachusetts General Hospital Fertility Center. The study cohort gave birth during 2005-2018. The average gestational age of the 420 singleton children born to this cohort was 39 weeks, with 8% (n = 34) born preterm.
Adjusted models showed that maternal preconception urinary concentrations of phthalates and of cyclohexane-1, 2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH), a metabolite of a nonphthalate plasticizer substitute, were associated with a 50% and 70% increased risk of preterm birth, respectively (P = .01, .11), according to results published in JAMA Network Open .
Sensitivity analysis showed that maternal preconception MHiNCH concentrations above the median were associated with a fourfold increased risk of preterm birth (risk ratio, 4.02; P = .08), Maternal preconception MHiNCH concentrations were associated with an average 2-day reduction in gestational age (P = .02).
Covariate-adjusted models found that paternal urinary phthalate metabolite concentrations were associated with an increased risk of preterm birth (RR, 1.41; P = .09), but this association was attenuated toward zero (RR, 1.06) in models that accounted for maternal preconception phthalate concentrations. Sensitivity analysis of 228 couples found the associations of maternal preconception phthalate metabolite concentrations and preterm birth remained robust in three different models: a twofold increased risk in covariate-adjusted models (P < .001); an almost fivefold increased risk in adjusting for prenatal levels (RR, 4.98; P < .001); and a twofold risk (P = .001) in adjusting for paternal levels. “Couple-based analyses confirmed the results for an association between maternal preconception DEHP concentrations and increased risk of preterm birth,” the investigators said.
“To our knowledge, this is the first study evaluating couples’ exposure to phthalate metabolites during the preconception window and its association with preterm birth,” the researchers wrote. “Our findings support a novel hypothesis: Maternal phthalate exposure during the critical period before conception may be associated with shorter gestation.”
“This study is consistent with several, but not all, prior studies supporting maternal prenatal exposure to phthalates increase preterm birth,” said Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida, Orlando. “The uniqueness of the current study was the assessment of couples’ exposures and the outcome, though paternal exposure to phthalates did not demonstrate a significant association.”
Dr. Trolice noted that about 25% of women in the study were smokers, but the study didn’t adjust for tobacco use and phthalate exposure, and 85% of the women were white. He urged caution in applying the study results in practice, adding that the study didn’t adjust for method of conception. “Assisted reproductive technology, multiple gestation, and advanced age are all known risk factors for preterm birth,”
The National Institute of Environmental Health Science funded the study. Two study coauthors received grants from the NIEHS, one coauthor received grants from the National Institutes of Health, and one received a grant from the Canadian Institutes of Health Research. No other disclosures were reported. Dr. Trolice has no financial relationships to disclose.
SOURCE: Zhang Y et al. JAMA Network Open. 2020; doi: 10.1001/jamanetworkopen.2020.2159.