Prenatal exposure to phthalates linked to higher risk of preterm birth and low birth weight

A study published in the journal The Lancet Planetary Health reveals that prenatal exposure to phthalate metabolites can increase the risk of preterm birth and low birth weight.

Study: Prenatal phthalate exposure and adverse birth outcomes in the USA: a prospective analysis of births and estimates of attributable burden and costs. Image Credit: Sibirian sun / Shutterstock

Background

Preterm birth and low birth weight are associated with many adverse consequences, including infant and childhood mortality, psychological, behavioral, and educational adversities in young adulthood, and cardiometabolic diseases in adulthood. In the United States, about 8% and 10% of infants suffered low birthweight and preterm birth, respectively, in 2020.

Many risk factors are associated with adverse birth outcomes, including maternal age, poor socioeconomic status, pre-eclampsia, and lack of prenatal care. Various synthetic chemicals, such as phthalates, are also known to increase the risk of birth adversities.

Phthalate and its metabolites are used in personal care products and food packaging. These chemicals have pro-inflammatory, pro-oxidative, and endocrine-disrupting activities. The crosstalk between these pathways can potentially disrupt hormonal regulation in pregnancy and induce placental insufficiency, pre-eclampsia, and premature membrane rupture.

In this study, scientists investigated the effects of prenatal phthalate exposure on birthweight and gestational age at birth. They also estimated phthalate-attributable adverse birth outcomes and associated costs.   

Study design

The scientists collected data from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program, which includes 69 unique pediatric cohorts from across the USA to identify environmental and preventable factors associated with low birthweight, preterm birth, and other birth complications.

The concentrations of 20 phthalate metabolites were measured in maternal urinary samples. The associations of these metabolites with gestational age at birth, birthweight, birth length, and birthweight for gestational age z-scores (age-independent assessment of a fetus growth) were analyzed in the study.

Important observations

The study was conducted on 5006 mother-child dyads identified from 13 cohorts in the ECHO program. The concentrations of phthalate metabolites in these mothers were similar to those detected in women of childbearing age in national surveys. A similar distribution of phthalates was observed across trimesters. The metabolites of di-2-ethylhexyl phthalate (DEHP) showed a strong correlation with one another. Mono-ethyl phthalate and phthalic acid showed the highest concentrations in maternal urinary samples. 

Higher concentrations of multiple phthalate metabolites were observed in non-Hispanic Black mothers. In contrast, Hispanic mothers showed higher concentrations of low-molecular-weight metabolites and lower concentrations of high-molecular-weight metabolites, DEHP, and phthalic acid.

An inverse association was observed between maternal age and concentrations of all metabolites. Moreover, a positive association was observed between maternal age, birth weight and length.

Impact of phthalates on birth outcomes

The study analysis revealed strong associations of phthalic acid, diisodecyl phthalate (DiDP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP) with gestational age, birth length, and birth weight. These associations were stronger than that observed for low- and high-molecular-weight metabolites and DEHP.

Overall, phthalate metabolites showed an association with low birth weight. The strongest associations were observed between the concentrations of phthalic acid, DiNP, DiDP, and DnOP and preterm birth and low birth weight. The magnitude of these associations was stronger in the third trimester compared to that in the first and second trimesters.   

The findings of sensitive analysis revealed that the association between DnOP and preterm birth is stronger for female infants than male infants. Moreover, the associations of phthalic acid, DiNP, and DnOP with many birth outcomes were stronger among non-Hispanic White mothers and college-educated mothers.   

Regarding phthalate-attributable adverse birth outcomes and associated costs, the study estimated 56,595 preterm birth cases in 2018, with associated costs of 3.84 billion USD. A sensitive analysis considering DiDP exposure revealed 57,017 to 79,947 attributable cases with associated costs of 3.86 billion USD to 5.42 billion USD. Similarly, for DiNP exposure, the analysis showed 76,838 to 120,116 attributable cases with associated costs of 5.21 billion USD to 8.14 billion USD.

Study significance

The study finds that prenatal exposure to phthalate metabolites can increase the risk of preterm birth and low birth weight. The pattern of associations observed in the study indicates that phthalate metabolites replacing DHEP in food packaging are responsible for the increase in preterm birth. This suggests a need to regulate chemicals with similar properties as a class.