Exposure to phthalates during pregnancy is associated with an increased risk of hypertension and preeclampsia

A recent study published in Environment International examines the link between exposure to phthalates during pregnancy and the development of hypertensive disorders of pregnancy (HPD), such as pre-eclampsia / eclampsia (PE/E).

Rates of HRD in the United States have increased over the past several decades. According to a recent study based on data from the US National Inpatient Sample, the prevalence of GHD increased 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, pregnancy-related maternal mortality, maternal organ damage and cardiovascular disease. p>

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

The widespread use of phthalates increases the likelihood of exposure in pregnant women. Most of the available studies on phthalates exposure and the prevalence of PE or other HRDs have small samples, which requires further validation.

The objective of this study was to determine whether exposure to phthalates, either alone or in combination, increases the risk of GBS, particularly PE. This hypothesis was tested using eight cohorts of the Environmental Impacts on Children's Health (ECHO) study. ECHO includes 69 pediatric cohorts across the United States studying how environmental factors influence children's health.

Pregnant women from diverse geographic and sociodemographic backgrounds were recruited for the current study. Participants ranged in age from 18 to 40 years at delivery and provided detailed data on prenatal urinary phthalate biomarkers, as well as information on PE, eclampsia, gestational hypertension, and singleton pregnancy.

A total of 3,430 participants were recruited for this study. The average age of participants was 29 years, 51% were White, and 44% were Hispanic. Most participants had a college education and were married or living with a partner.

A significant increase in the risk of PE/E was observed with exposure to mono (3-carboxypropyl) phthalate (MCPP) and mono-benzyl phthalate (MBzP). In cohorts with more phthalate metabolites measured, 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 subsamples, these associations were stronger if the pregnancy involved a female fetus.

A significant increase in the risk of PE/E, particularly PE/E, was found with exposure to phthalates during pregnancy. Thus, maternal exposure to multiple phthalates, either individually or in combination, may be associated with the overall risk of GERD and PE/E.

It is important to note that the biological mechanisms underlying this association are not fully understood. However, previous studies suggest that phthalates may interfere with normal placental development and function, contributing to the development of PE/E. Phthalates may also alter placental epigenetics and gene expression, and cause morphological changes in placental size and shape.

Additional research is needed to better understand these associations and to develop effective and safe methods to reduce the risk of these adverse events.

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

Some limitations of the current study include a lack of data harmonization across cohorts. Additionally, not all urine samples were collected in the first morning void, which may have impacted the measured phthalate concentrations as voids collected at other times of the day may have contained different phthalate concentrations.

Another limitation is related to Type I error inflation, as this study tested multiple hypotheses. Due to this limitation, the focus was on correlations rather than strict statistical significance.