Phthalates and Phenols: Toxic for Mother and Baby

Evidence continues to accrue that prenatal exposure to some synthetic chemicals in the environment is associated with adverse pregnancy outcomes and negative effects on the neonatal metabolome and neurobehavior scores.

Although ubiquitous compounds such as phthalates and phenols affect several aspects of general human and reproductive health, preventing or reducing exposure is especially important for pregnant women.

These pro-inflammatory chemicals are embedded everywhere in household and personal care products — from flooring and food containers to shampoos, packaging, foods, and medications. Ingestible, inhalable, and absorbable, they yield metabolites measurable in urine and blood. In the body they can block or interact with human hormones to the detriment of maternal, fetal, and neonatal health.

“Phthalates and phenols act as endocrine-disrupting chemicals that can interfere with hormonal pathways critical for a healthy pregnancy,” Misa Hayasaka, MD, of the Department of Obstetrics and Gynecology at Eastern Virginia Medical School in Norfolk, Virginia, told Medscape Medical News. “Several biological mechanisms have been proposed, including placental dysfunction, oxidative stress, inflammation, and metabolic dysregulation.”

In a study published recently in O&G Open, Hayasaka and colleagues found prenatal exposure to phthalates and phenols was associated with an increased risk for preterm birth, small-for-gestational-age birth weight, and gestational diabetes.

Her group used datasets from the ECHO Research Program, launched by the National Institutes of Health in 2016, to investigate how prenatal and early-life environmental exposure affects child health and development. The ECHO cohort includes longitudinal data on more than 30,000 pregnancies and 50,000 children from 69 cohorts across the United States and Puerto Rico.

Higher concentrations of specific phthalates and phenols (particularly bisphenols) were associated with an increased risk for preterm birth. In addition, bisphenols and mono-isononyl phthalate were associated with an elevated risk for small-for-gestational-age birth weight. “By applying a harmonized analytic approach across a large, diverse, multicohort dataset, our study helps clarify the associations between prenatal exposure to specific phthalates and phenols and key pregnancy outcomes,” Hayasaka said.

Other Studies

Other research has identified similar harms, including a 2024 study by Leonardo Trasande and colleagues reporting that prenatal benzophenone-3 and methylparaben exposures in a large diverse American sample were associated with decreases in birth weight and increases in small-for-gestational-age neonates.

Another study found adverse effects in newborns, with prenatal phthalate exposure linked to lower Apgar scores. Furthermore, prenatal phthalate metabolite levels measured at 26 weeks’ gestation have been linked to nonoptimal reflexes in 5-week-old male infants on NICU Network Neurobehavioral Scale scores.

In another recent analysis published in Nature Communications, Susan S. Hoffman, a doctoral student in the Department of Epidemiology at Emory University in Atlanta, and colleagues evaluated associations between prenatal phthalate metabolites and adverse effects on newborns. These effects included perturbations of the newborn metabolome and infant neurobehavioral functioning in a cohort of 216 mother-newborn pairs enrolled in the Atlanta African American Maternal-Child Cohort during 2016-2018.

“These plasticizers can cross the placental barrier, so we wanted to see how exposure during pregnancy might impact babies’ biology shortly after birth,” Hoffman told Medscape Medical News. “We knew that pregnant women are often exposed to products containing these chemicals, and our sample did have higher levels than the general population.”

Her group found these chemicals perturbed or disrupted specific biological processes such as the metabolism of tryptophan and tyrosine and affected neonatal neurobehavioral scores.

Hoffman’s group quantified eight phthalate metabolites in prenatal urine samples collected between 8 and 14 weeks’ (visit 1; n=216) and 24 and 30 weeks’ gestation (visit 2; n=145), as well as metabolite features in newborn dried-blood spot samples collected at delivery.

Many of the pathways identified in the full study sample were involved in oxidative stress and acute and systemic inflammatory response, including vitamin K, H, B6, B5, E, and B3 metabolism in addition to the metabolism of tyrosine and tryptophan. Furthermore, compared with the US general adult population from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, the study population of African American mothers had higher mean levels of the phthalate metabolites monoethyl phthalate mono(2-ethylhexyl) phthalate. In general, women are more likely to have higher urinary concentrations of such metabolites than men because they are more likely to use personal care products, cosmetics, and scented household cleaners. Black individuals may have higher concentrations than White individuals because of use of hair straighteners, and they may live in areas with more environmental toxins.

“Taken together, these results support the existence of environmental disparities in phthalate exposures and suggest that we need further regulation on phthalates targeted at pregnant people generally and especially pregnant African American people,” Hoffman and associates wrote. They suggested that elements of racism in targeted product marketing may be at play.

Reducing Risk

Hoffman advised clinicians to tell pregnant women to read all product labels and choose personal-care and household products free of phthalates and phenols whenever possible. “They should opt for glass or stainless steel, not plastic containers, and never heat plastic containers in the microwave,” she said.

But, she cautioned, “We need large-scale studies before we can be clear about this. We hope that with stronger support for testing we can offer clinical guidelines and perhaps treatments in a few years.”

In clinical practice, Nathaniel G. DeNicola, MD, MSHP, an ob/gyn based in Yorba Linda, California, an environmental health expert, and liaison to the American Academy of Pediatrics Executive Council on Environmental Health, advises his pregnant patients to take a broad approach to reducing toxic chemical exposure rather than “a whack-a-mole style targeting specific chemicals such as phthalates.” That involves food and personal product choices.

For example, he told Medscape Medical News, “Pregnant women need to stay hydrated and should always carry water with them, but not in plastic bottles.” Food purchased in plastic packaging should be transferred to nonplastic containers for storage.

Fresh and whole food as recommended by the USDA Dietary Guidelines should be the nutritional norm. “Pregnant women should especially avoid fast food since the ingredients are often stored in containers with chemicals in them that can leach into the food.” Scent-free personal products are the wise choice because phthalates are used to stabilize fragrances in perfumes, lotions, and other cosmetics.

At the wider population level, reducing exposure will probably require coordinated efforts across sectors, Hayasaka said. “In the United States, specific phthalates are already restricted in children’s products under federal regulations. Expanding similar regulatory frameworks to cover other consumer products — especially those commonly used by pregnant individuals — may be a useful strategy for reducing exposure at the population level.”

Public education is essential, because many people may still be unaware how widespread these chemicals are in everyday products, she added. “Continued research on exposure sources and health effects will be critical for guiding evidence-based policies that protect maternal and child health.”

The American College of Obstetricians and Gynecologists has recommended that obstetric-care clinicians include questions about environmental exposures in patient histories during prepregnancy and prenatal care and that environmental health should be integrated into ob/gyn training and practice.

Hoffman’s research was supported by the National Institute of Health and the Environmental Protection Agency. Hoffman is supported by the National Institute of Environmental Health Sciences Training Program in Environmental Health and Toxicology. DeNicola, Hayasaka, and Hoffman had no relevant financial conflicts of interest.