Risk of Preterm Birth Due to Phenol Exposure Specific to Female Infants
Key findings
- This prospective study of 386 pregnant women investigated associations between preterm birth and prenatal urinary phenol concentrations, exploring the timing of vulnerability across gestation and potential modification by fetal sex
- Preterm birth was linked to middle and late pregnancy concentrations of bisphenol A (BPA), but only for women carrying female fetuses; findings were similar for third-trimester BPA and first-trimester paraben concentrations
- BPA concentrations were higher across all gestational weeks in women whose infants were born preterm compared with those who delivered at term
- From gestational week 21 to 29, that association between preterm birth and BPA was significant among women with female infants and not women with male infants
- The sex differences observed in this study may be attributable to differences between female and male fetuses in the expression of endocrine receptors
Prenatal exposure to phenols has been linked to preterm birth, although the results of human studies are inconsistent. Phenols such as bisphenol A (BPA), benzophenones, triclosan and parabens are endocrine-disrupting chemicals so widely used in food packaging, personal care products and numerous other consumer products that exposure is considered ubiquitous.
Subscribe to the latest updates from Endocrinology Advances in Motion
Carmen Messerlian, PhD, research fellow in the Vincent Center for Reproductive Biology and Department of Obstetrics and Gynecology at Massachusetts General Hospital, and colleagues have reported preliminary evidence that preterm birth is associated with urinary concentrations of BPA in mid- to late pregnancy and paraben in early pregnancy. Intriguingly, these associations were detected only for female infants, as explained in Fertility and Sterility.
Methods
The Mass General Fertility Center is conducting a prospective study called EARTH (Environment and Reproductive Health), investigating how nutrition and environmental exposures in men and women influence fertility, gestation and neonatal outcomes. This analysis included 386 female participants who gave birth to a singleton infant between 2005 and 2018 and had at least one urine sample quantified for phenols during pregnancy.
The researchers applied two methodological approaches:
- Determining whether trimester-specific phenol biomarker concentrations predicted preterm birth
- Analyzing phenol concentrations across gestational weeks, comparing women whose infants were born preterm and women with infants born full-term
The team stratified both types of analyses by infant sex.
Trimester-specific Associations
After adjustment for covariates, the researchers detected positive or suggestive positive associations between preterm birth and:
- Second-trimester urinary BPA concentrations (RR, 1.24); this association was significant for female infants (RR, 1.40) but not male infants
- Third-trimester BPA concentrations among female infants (RR, 1.91) but not male infants
- First-trimester paraben concentrations (RR, 1.17) among female infants (RR, 1.46) but not male infants
- First-trimester bisphenol S concentrations (RR, 1.25); the results were not stratified by infant sex because of the small sample size
Preterm vs. Full-term Births
The results of the second analytical approach were:
- Across gestational weeks, BPA concentrations were higher among women with infants born preterm than those of women who delivered at full term
- From gestational week 21 to 29, this pattern of association for BPA was significant among women with female infants and not women with male infants
- For the other phenols examined, no meaningful patterns emerged
Women With Complete Data
As a sensitivity analysis, the researchers restricted the sample to the 239 women who provided urine samples in all three trimesters. The trimester-specific findings of links between phenol concentrations and preterm birth were consistent with the primary analyses.
Notably, the association between second-trimester BPA concentration and preterm birth was strengthened and became significant (RR, 1.70).
Commentary
How environmental phenols may influence the length of gestation is still unclear. The leading hypotheses implicate inflammation, oxidative stress and endocrine disruption.
The sex differences observed in this study may be attributable to differences between female and male fetuses in the expression of endocrine receptors. Also, previous studies have shown that female fetuses are more sensitive to inflammation. How fetal sex influences the effect of phenols and other environmental chemicals on preterm birth is a rich subject for further exploration.
view original journal article Subscription may be required
Learn more about the Mass General Fertility Center
Refer a patient to the Department of Obstetrics & Gynecology