Exposure to phthalates during pregnancy linked to increased risk of hypertension and preeclampsia

A recent Environment International study investigates the association between pregnancy phthalate exposure and the development of hypertensive disorders of pregnancy (HDP), such as preeclampsia/eclampsia (PE/E).

Study: Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program. Image Credit: SeventyFour / Shutterstock.com

Hypertension during pregnancy

Over the past several decades, the rates of HDP have increased in the United States. One recent study based on the U.S. National Inpatient Sample indicated an increase in the prevalence of HDP from 13.3% in 2017 to 15.9% in 2019.

Gestational hypertension and PE/E are characterized by high blood pressure during pregnancy, which significantly increases the risk of various complications, including intrauterine growth restriction, preterm birth, maternal pregnancy-related mortality, maternal organ damage, and cardiovascular diseases.

HDP is a multifactorial condition associated with genetic factors, as well as environmental factors, such as chemical exposure. To date, few studies have indicated an association between phthalate exposure and the incidence of pregnancy-induced hypertension and PE.

What are phthalates?

Phthalates are chemical compounds used in many products, such as plastics, food packaging, and personal care items. Some common types of high molecular weight phthalates used in flexible polyvinyl chloride (PVC) pipes, home furnishings, and food packaging include di-isodecyl phthalate (DiDP), di-2-ethylhexyl phthalate (DEHP), benzylbutyl phthalate (BzBP), and diisononyl phthalate (DiNP). Comparatively, di-n-butyl phthalate (DnBP) and diethyl phthalate (DEP) are low molecular weight phthalates used in personal care products and certain medications.

The widespread use of phthalates increases the likelihood of their exposure to pregnant women. Most available studies on phthalate exposure and PE or other HDP incidence have small sample sizes, which require further validation.

It is imperative to investigate the potential effect of phthalate exposure among pregnant women, as these data could provide valuable insights into developing preventive strategies to reduce the burden of HDP.

About the study

The present study hypothesized that phthalate exposure, both individually and as a mixture, increases the risk of HDP, particularly PE. This hypothesis was tested using eight cohorts of the Environmental Influences on Child Health Outcomes (ECHO) study. ECHO hosts 69 pediatric cohorts throughout the United States designed to study how environmental factors affect child health.

For the current study, pregnant women from diverse geographical and sociodemographic backgrounds were selected. Individuals between 18 and 40 years of age during the delivery provided detailed data on prenatal measures of urinary phthalate exposure biomarkers, and PE, eclampsia, gestational hypertension, and singleton pregnancies were included in the study.

Study findings

A total of 3,430 participants were selected for the current study. The mean age of the participants was 29, 51% of whom were White and 44% Hispanic. Most study participants were college-educated and married or living with their partner.

A significantly increased risk of PE/E in relation to mono (3-carboxypropyl) phthalate (MCPP) and mono-benzyl phthalate (MBzP) was observed. In cohorts with more measured phthalate metabolites, higher concentrations of MBzP, MCPP, mono-carboxy isononyl phthalate (MCiNP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-carboxy isooctyl phthalate (MCiOP) were associated with an increased risk of PE/E. In some sub-samples, these associations were stronger if a female fetus was being carried by the pregnancy.

Conclusions

A significantly higher risk of HDP, particularly PE/E, was associated with phthalate exposure during pregnancy. Thus, maternal exposure to several phthalates, both alone and in combination, could be associated with overall HDP and PE/E.

Importantly, the underlying biological mechanisms responsible for this association are not fully understood. Nevertheless, previous research suggests that phthalates may interfere with normal placental development and function, thereby contributing to the development of PE/E. Phthalates may also alter placental epigenetics and gene expression, as well as induce morphological changes in the size and shape of the placenta.

Additional research is needed to better understand these associations, as well as develop effective and safe interventions to mitigate the risk of such adverse conditions.

The key strengths of this study include the diverse study population, large sample size, use of multiple urine samples from several participants, consideration of sensitive and specific biomarkers of exposure, and rigorous statistical analysis.

Some limitations of the current study include the lack of harmonizing data across multiple cohorts. Furthermore, not all urine samples were collected as first morning voids, which may have affected the measured phthalate concentrations, as voids in other parts of the day could have different phthalate concentrations.

Another limitation is related to the inflation of type I errors, as multiple hypotheses were tested in this study. Due to this limitation, the focus was primarily on correlations rather than strict statistical significance.