ECHO Study Finds Link Between Phthalate Exposure and Preterm Birth, Estimates Potential Costs

Authors: Leonardo Trasande, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of The Director, National Institutes of Health supported this research.

Why was this study needed?

Phthalates are widely used chemicals found in some consumer products, and previous research has linked phthalate exposure to preterm birth. In response, the use of di-2-ethylhexyl phthalate (DEHP), a common type of phthalate, has decreased in recent years. However, there is limited research on the effects of the replacement phthalates, and the costs associated with phthalate exposure remain unquantified. ECHO Cohort researchers wanted to learn about the potential connections between phthalates, their metabolites in the urine of pregnant individuals, and birth outcomes—including birth weight and length of pregnancy. The study also sought to estimate the potential costs associated with adverse birth outcomes.

What were the study results?

When the researchers grouped mothers based on the amount of DEHP metabolites (substances produced when the body breaks down DEHP) found in their urine, they found that the 10 percent with the highest levels had a 50 percent higher chance of giving birth before the 37th week of pregnancy compared to the 10 percent with the lowest levels.

Some common alternatives to DEHP were associated with even higher risk of preterm birth. Women exposed to the highest amounts of these alternative chemicals—phthalic acid, di-isodecyl phthalate (DIDP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP)—had twice the risk of preterm birth compared to those with little to no exposure to these alternatives.

Researchers estimated that the number of premature births in the U.S. that could be linked to phthalate exposure in 2018 was between 24,000 and 120,000, potentially costing between $1.6 billion and $8.1 billion in medical expenses over the lifetime of the children.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What was this study's impact?

This ECHO Cohort research examines the effect of phthalates on birth outcomes such as preterm birth and birth weight. These findings associated adverse birth outcomes with exposure to DEHP and its chemically similar substitutes, which can inform the development of policies, programs, and practices that can help prevent or lessen potentially harmful exposures during pregnancy.

Who was involved?

The study included 5,006 mother-child pairs from 13 ECHO Cohort Study Sites across the U.S. Researchers included individuals with information on up to 20 urinary phthalate metabolites. The pregnant participants were aged 25 to 34 at the time they gave birth.

What happened during the study?

The researchers analyzed levels of 20 phthalate metabolites in urine samples collected at three points during each participant’s pregnancy. They also investigated the differences between specific types of phthalates, comparing DEHP with several newer alternatives developed to replace it. Then, the team looked for associations between these metabolite levels and preterm births. They also calculated the number of premature births that could be linked to phthalate exposure and the possible associated costs over the lifetime of the child.

What happens next?

Future research could look at how exposure to replacement phthalates affects child development after birth. The European Union has prohibited the use of certain phthalates in some consumer products—as have California and a few other U.S. states.

Where can I learn more?

Access the full journal article, titled “Prenatal phthalate exposure and adverse birth outcomes in the USA: a prospective analysis of births and estimates of attributable burden and costs,” in The Lancet Planetary Health.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published February, 2024

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ECHO Study Finds Link Between Phthalate Exposure and Preterm Birth, Estimates Potential Costs

ECHO Study Finds Flame-Retardant Chemicals May Increase Risk Of Preterm Birth and Higher Birth Weight

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ECHO Study Finds Flame-Retardant Chemicals May Increase Risk Of Preterm Birth and Higher Birth Weight

Authors: Deborah Bennett, Jiwon Oh, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was this study needed?

Manufacturers commonly use flame-retardant chemicals known as organophosphate esters (OPEs) in products such as furniture, baby items, electronics, clothes, and building materials to prevent fires and make plastics more flexible. People can come into contact with OPEs in various ways, including swallowing or breathing indoor dust or absorbing it through the skin. Animal studies have revealed that OPEs can harm the growth and development of offspring. However, the connection between OPE exposure during pregnancy and birth outcomes has been unclear. ECHO researchers wanted to learn if there was a link between OPE levels in the urine of pregnant individuals and specific birth outcomes.

What were the study results?

Pregnant individuals exposed to specific classes of OPEs may face an increased risk of preterm birth, especially for baby girls and babies with higher birth weights. Three of these substances—diphenyl phosphate (DPHP), a combination of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate—were associated with shorter pregnancies and higher risks of preterm birth only among female infants. Among male infants, higher concentrations of DPHP were associated with longer pregnancies.

Babies born to mothers with detectable levels of three other OPE markers—bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate—tended to have higher birth weights compared to those whose mothers had no detectable levels of these substances.

Note: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What was this study's impact?

In the past decade, OPEs have been increasingly used as flame retardants after polybrominated diphenyl ether (PBDE) flame retardants were phased out due to health risks. ECHO research examines the potential impact of these now more widespread OPE chemicals on pregnancy outcomes such as preterm birth and birth weight. The findings can inform policies, programs, and practices to help decrease exposure.

Who was involved?

The study included 6,646 pregnant participants at 16 ECHO Cohort Study Sites across the U.S. and Puerto Rico.

What happened during the study?

Researchers measured a total of nine OPE markers in urine samples collected from 6,646 pregnant participants across 16 ECHO Cohort Study Sites—often during their third or second trimesters. The researchers then assessed birth outcomes, including the length of pregnancy and birth weight, using medical records or parent reports.

What happens next?

OPEs tend to stay in the human body for short periods, usually hours to days. To better understand how these chemicals might affect birth outcomes, researchers can use multiple measurements of urinary OPE biomarkers. This could help identify when the body might be more sensitive to these chemicals. Additionally, learning more about how people are exposed to these chemicals can help identify ways to reduce exposure, especially during pregnancy.

Where can I learn more?

Access the full journal article, titled “Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program,” in Environmental Health Perspectives.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published January 24, 2024

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ECHO Study Finds Flame-Retardant Chemicals May Increase Risk Of Preterm Birth and Higher Birth Weight

ECHO Researchers Characterize Children Born Preterm into Four Neurobehavioral Profiles

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ECHO Researchers Characterize Children Born Preterm into Four Neurobehavioral Profiles

Authors: Marie Camerota, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was the study needed?

Birth outcomes for infants born very preterm have steadily improved over the past several decades. More children born at earlier gestational ages are surviving into childhood, however, it is unclear how being born very preterm may influence neurodevelopmental or behavioral problems.

Outcomes of children born at a gestational age of less than 33 weeks (“very pre-term”) vary significantly, with some children showing few neurodevelopmental concerns and others showing significant impairment. Most prior research has looked at single outcomes—for example, whether a child born preterm had a lower neurodevelopmental score or higher levels of behavior problems. Understanding how these different outcomes may group together can help researchers and healthcare providers provide more comprehensive treatment plans for children born very preterm.

What were the study results?

Researchers found evidence for four different neurobehavioral profiles based on different combinations of cognitive, motor, and behavioral outcomes of children at the age of two. These profiles range from few or no developmental concerns to severe impairment in one or more domains. The study placed most children (about 85%) into one of two groups with no/mild developmental delay and a low prevalence of behavioral problems. The remaining 15% fell into one of two profiles with more serious neurodevelopmental problems with (5%) or without (10%) co-occurring behavior problems.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What was the study's impact?

This study helps researchers better understand outcomes for children following a very pre-term birth. The different groups of children this study described might require different types of follow-up services or interventions.

Who was involved?

This study included more than 2,000 babies who were born at less than 33 weeks gestational age and were evaluated at the age of two years. Pre-term children from three ECHO research sites in the U.S. were included in this analysis.

What happened during the study?

Researchers recruited children born less than 33 weeks gestational age into the ECHO Program shortly after they were born. When these children reached age two years, researchers conducted a neurodevelopmental assessment and a motor exam; parents completed questionnaires about their children’s behavior. ECHO researchers looked for patterns in these data to understand whether there were groups of children with similar strengths and weaknesses.

What happens next?

More research is needed to understand why some preterm children develop neurodevelopmental and/or behavioral problems and others do not. To do this, future studies may study risk factors in pregnancy, the perinatal period, and in early infancy.

Where can I learn more?

Access the full journal article, titled “Neurodevelopmental and behavioral outcomes of very preterm infants: latent profile analysis in the Environmental influences on Child Health Outcomes (ECHO) Program,” in Pediatric Research.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published September 12, 2023

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ECHO Researchers Characterize Children Born Preterm into Four Neurobehavioral Profiles

Preterm Birth and Family Hardship May Associated With Childhood Behavior Problems

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Preterm Birth and Family Hardship May Associated With Childhood Behavior Problems

Authors: Julie A. Hofheimer, Monica McGrath, Rashelle Musci, et al.

Who sponsored this study?

This research was supported by the Environmental influences on Child Health Outcomes (ECHO) Program, Office of The Director, National Institutes of Health.

Why was this study needed?

Emotional and behavioral difficulties during early childhood can predict later problems such as anxiety, depression, attention deficits, and aggression. This study aims to describe children’s behavioral development from 18 to 72 months of age, examining risk factors for continuing behavioral problems that can inform early interventions to improve behavioral and emotional regulation.

What were the study results?

Children born preterm, males, and those exposed to more family hardships had more behavioral difficulties that persisted over time, including anxiety/depression, attention deficits, and aggression. Other factors that increased the risk for behavioral difficulties in children were prenatal substance exposure and higher maternal psychosocial and economic difficulties during pregnancy. Some children who experienced fewer family hardships showed improved behavior over time when receiving early support. The researchers were able to identify early life factors that may increase a child’s risk for experiencing behavioral and emotional difficulties later in childhood.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What was the study's impact?

This study suggested that support and services for families to help them cope with newborn health challenges and other family hardships may help improve young children’s behavioral and emotional difficulties. Specifically, preterm births and prenatal substance exposures may be used to identify children who may benefit from early support. Individualized support to meet the specific needs of children may prevent later behavioral problems and improve future outcomes for vulnerable children and their families.

Who was involved?

The study included 3,934 children born between 1990 and 2019 and their mothers from 20 ECHO cohorts across the United States. About 80% of the children were born at term (at or beyond 37 weeks of gestation), and about 20% were born preterm (before 37 weeks of gestation).

What happened during the study?

The researchers collected caregiver self-reports, demographics, and medical and social environment information about the mothers and children before and during pregnancy and from infancy through age 6. Caregivers also completed the Child Behavior Checklist at multiple study visits to describe their child’s behavior at different ages. Researchers compared the trajectory of children’s scores for dysregulation behaviors (anxiety, depression, attention, and aggression) across the first six years of life. Researchers described three patterns of behavioral trajectories observed in these children 1) high and increased dysregulation (2.3%); 2) borderline and stable dysregulation (12.3%); and 3) low and decreasing dysregulation (85.6%).

What happens next?

Future ECHO studies may examine how the behavior of children continues to develop after six years of age. These new studies could focus on identifying additional risk and protective factors for emotional and behavioral well-being and patterns across middle childhood and adolescence.

Where can I learn more?

Access the full journal article, titled “Psychosocial and Neonatal Risk Factors Associated with Behavioral Dysregulation Trajectories Among Young Children from 18 through 72 Months of Age,” in JAMA Network Open.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published April 26, 2023

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Preterm Birth and Family Hardship May Associated With Childhood Behavior Problems

NIH Program Study Suggests Pregnant Women with Higher Levels of Oxidative Stress May Be More Likely to Deliver Preterm Babies

Posted on January 27, 2023August 27, 2025 by Jodi Snare

FOR IMMEDIATE RELEASE

Elevated levels of oxidative stress during pregnancy might be linked to a higher risk of preterm birth, according to a new study funded by the Environmental influences on Child Health Outcomes Program at the National Institutes of Health.

Oxidative stress, a process that can trigger cell damage, may contribute to poor prenatal health outcomes. “Previous research on this topic has involved fairly small, primarily White populations, which is not reflective of diversity in the U.S.,” said Stephanie Eick, PhD, MPH, an ECHO Program investigator at Emory University’s School of Public Health.

This study examined data from 1,916 racially, ethnically, and demographically diverse pregnant women from four ECHO cohorts across the U.S. and Puerto Rico. Researchers used urine samples collected during the second and third trimesters of pregnancy to measure oxidative stress biomarkers and evaluate any links between those biomarkers and preterm birth.

The researchers found a strong association between higher levels of oxidative stress biomarkers and preterm birth, particularly for participants who experienced sudden, unexpected preterm birth or preterm birth that occurred prior to 34 weeks. Further research is needed to understand the chemical mechanisms behind this association and identify the risk factors that contribute to high oxidative stress during pregnancy.

Dr. Eick and Rachel Morello-Frosch, PhD, MPH an ECHO Program investigator at the University of California, Berkeley, led this collaborative research published in the American Journal of Obstetrics and Gynecology.

Eick, S. et al. A pooled analysis of four birth cohorts examining urinary oxidative stress biomarkers and preterm birth. American Journal of Obstetrics and Gynecology. DOI:10.1016/j.ajog.2022.11.1282.

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About ECHO: ECHO is a nationwide research program supported by the NIH. Launched in 2016, ECHO aims to enhance the health of children for generations to come. ECHO investigators study the effects of a broad range of early environmental influences on child health and development. For more information, visit echochildren.org.

About the NIH: NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information, visit www.nih.gov.

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New ECHO Study Investigates the Relationship Between a Mother’s Oxidative Stress Levels and Preterm Birth

Posted on January 26, 2023April 2, 2025 by Jodi Snare

A collaborative research study led by Stephanie Eick, PhD, MPH of Emory University’s Rollins School of Public Health and Rachel Morello-Frosch PhD, MPH of the University of California, Berkeley found an association between elevated levels of oxidative stress and higher risk of preterm birth. This study examined data from 1,916 racially, ethnically, and demographically diverse pregnant participants from four ECHO cohorts across the United States and Puerto Rico. This research titled, “A pooled analysis of four birth cohorts examining urinary oxidative stress biomarkers and preterm birth,” is published in the American Journal of Obstetrics and Gynecology.

Oxidative stress is a process that can trigger cell damage and may contribute to poor prenatal health outcomes. “This is the largest study to date looking at the relationship between oxidative stress and preterm birth,” said Dr. Eick. “Previous research on this topic has involved fairly small, primarily White populations, which is not reflective of diversity in the US.”

The researchers measured oxidative stress biomarkers in urine samples from participants collected during the second and third trimesters of pregnancy. Then, they calculated the association between the oxidative stress biomarkers concentration for each participant and all preterm births (delivery prior to 37 weeks).

Results from this study showed a strong association between higher levels of oxidative stress biomarkers and preterm birth. This association was particularly true for participants who experienced preterm birth that was sudden and unexpected or occurred prior to 34 weeks.

Future research will investigate how the chemicals involved in oxidative stress may lead to preterm birth and identify what risk factors lead to higher oxidative stress during pregnancy.

Read the research summary.

ECHO Study Suggests Oxidative Stress Contributes to Mother’s Risk for Preterm Birth

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ECHO Study Suggests Oxidative Stress Contributes to Mother's Risk for Preterm Birth

Authors: Stephanie Eick, Rachel Morello-Frosch, et al.

Who sponsored this study?

Research reported in this publication was supported by the Environmental influences on Child Health Outcomes (ECHO) Program, Office of The Director, National Institutes of Health (NIH).

What were the study results?

Pregnant participants who had higher levels of oxidative stress biomarkers during pregnancy were more likely to deliver preterm babies. This association was stronger for participants who experienced preterm birth that was sudden and unexpected or occurred prior to 34 weeks.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What was the study's impact?

This study is the largest to date to look at the relationship between oxidative stress and preterm birth.

The study included a large group of racially, ethnically, and demographically diverse pregnant participants from across the mainland United States and Puerto Rico. The results from this study support prior findings that oxidative stress is higher among pregnant women who deliver preterm. The methods used in this study may help doctors identify pregnant women who may be at risk for preterm birth and plan targeted interventions.

Why was this study needed?

Oxidative stress is a process that can trigger cell damage and can play a role in the development of some diseases. Previous research has shown that oxidative stress in pregnant women may be linked to preterm birth. However, prior studies on this topic have involved small, primarily White populations, which does not reflect the diversity in the United States.

Who was involved?

This study involved 1,916 pregnant participants in the United States and Puerto Rico who were enrolled in one of four ECHO cohorts.

What happened during the study?

The researchers measured the levels of oxidative stress biomarkers from urine samples collected from participants during the second and third trimesters of pregnancy. They used these measurements to determine whether levels of oxidative stress were higher among participants who delivered their babies before 37 weeks (preterm birth).

What happens next?

Next, the researchers will study how exposure to environmental chemicals may lead to an increase in oxidative stress, ultimately leading to preterm birth. Future research will also identify what risk factors lead to higher oxidative stress during pregnancy.

Where can I learn more?

Access the full journal article, titled “A pooled analysis of four birth cohorts examining urinary oxidative stress biomarkers and preterm birth” in the American Journal of Obstetrics and Gynecology.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published November 15, 2022

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ECHO Study Suggests Oxidative Stress Contributes to Mother's Risk for Preterm Birth

New ECHO Research Reveals Depression is More Common Among New Mothers of Preterm Babies

Posted on June 17, 2022July 17, 2024 by Jodi Snare

New ECHO research reveals that increasing symptoms of depression may be more common among women who give birth to preterm babies compared to women who have their babies at full term. Mothers of preterm babies were also more likely to experience depression that lasted years after birth, and for many of these women, their symptoms of depression got worse over time. These findings resulted from a collaborative effort between ECHO researchers Danielle Roubinov, PhD of the University of California, San Francisco (UCSF) and Rashelle Musci, PhD of Johns Hopkins University, along with senior author Nicole Bush, PhD, of UCSF and other ECHO researchers.

Their research, titled “Trajectories of Depressive Symptoms Among Mothers of Preterm and Full-Term Infants in a National Sample,“ is published in Archives of Women’s Mental Health.

The research team collected data from approximately 11,300 women from 35 different ECHO cohorts across the United States that documented self-reported depression measures for women when they were pregnant and after they had their babies. Of these women, 11% had preterm births, and 89% had full-term babies. Follow-up assessments from the two groups of women were collected at least once within the first five years following childbirth to better understand the long-term trajectories of depressive symptoms s and potential opportunities for treatment.

“Having a baby is exciting, but it can also be stressful, and some women feel sad or anxious before and after their baby is born,” said Dr. Roubinov. “This period can be especially difficult for mothers when babies are born prematurely.”

Many mothers can struggle with their mental health after giving birth, and women who give birth prematurely may be particularly at risk of experiencing depressive symptoms related to the birth experience, neonatal care challenges, and ongoing concerns about the infant’s health and development.

“Currently, many doctors only ask women about how they feel when they are pregnant and for six months after birth,” said Dr. Musci. “This study showed us that we should be continuing to ask women about their mental health for years following their pregnancy while helping them to find the support they need.”

Future ECHO studies can add to this research by assessing intervention programs that can help support the mental health of new mothers, as maternal mental health is a critical influence on children’s development.

Learn more about depression during and after pregnancy through the Centers for Disease Control and Prevention and NIH.

Read the Research Summary.

O’Shea/Fry: Early Life Origins of Health Among Individuals Born Extremely Preterm

Early Life Origins of Health Among Individuals Born Extremely Preterm

ECHO Discovery Summary

Preterm Birth and Long-Term Health Outcomes

ECHO Researchers Dr. Michael O’Shea, MD, MPH of the UNC Chapel Hill Division of Neonatal-Perinatal Medicine and Dr. Rebecca Fry, PhD of the UNC Gillings School of Global Public Health gave a presentation about the Extremely Low Gestational Age Newborn (ELGAN) study. Dr. O’Shea and Dr. Fry presented the objectives of the ELGAN study and its findings in their presentation on ‘Early Life Origins of Health Among Individuals Born Extremely Preterm’.

The ELGAN Cohort focuses on researching mechanisms that could link preterm birth to long-term health outcomes, such as chronic health and developmental disorders. Through the ECHO Program, ELGAN has been able to expand to obesity, asthma, positive health (well-being, life satisfaction, global health), blood pressure, and renal (kidney) outcome areas. Dr. O’Shea provided an overview of the study, which has followed more than 1,000 babies born at least 3 months early, between 2002 and 2004, at 14 different hospitals in five states. The ELGAN study confirmed strong relationships between neonatal inflammation and neurodevelopmental outcomes, an area of ECHO research. Researchers have previously established that neonatal inflammation is associated with a broad suite of children’s health outcomes.

Another goal of ELGAN is to research perinatal influences on child health. One of the organs that researchers focused on was the placenta, which is important for the developing fetus. Dr. Fry emphasized that data from the study indicates placental weight is linked to both prenatal exposures and later life adverse health outcomes. This suggests the possibility that placenta epigenetics links early life exposures and later life outcome.

ELGAN is now studying the cohort’s teenagers’ health and well-being, including reasoning skills, behavior, emotions, sleep patterns, and overall quality of life. A key conclusion that both presenters highlighted is that similar studies are needed for diverse socioeconomic contexts and more recent birth cohorts. This will help lead to more indicative data for further findings in this area of neonatal and perinatal research. You can learn more about the ELGAN study and its research by watching the presentation.

Speakers:

Michael O’Shea, MD, MPH

Division of Neonatal-Perinatal Medicine

University of North Carolina at Chapel Hill

Speaker Bio: Michael O’Shea, MD, MPH, received his undergraduate, medical school, and masters degrees, as well as residency training in internal medicine and pediatrics at the University of North Carolina. He completed a fellowship in Neonatal-Perinatal Medicine at Duke University.

Rebecca Fry, PhD

UNC Gillings School of Global Public Health

Speaker Bio:

Dr. Rebecca Fry is the Carol Remmer Angle Distinguished Professor of Children’s Environmental Health at UNC-Chapel Hill. Dr. Fry is the Associate Chair in Environmental Sciences and Engineering at the Gillings School of Global Public Health, the Director of the UNC Superfund Research Program, and founding Director of the Institute for Environmental Health Solutions. Dr. Fry is trained in molecular biology with a MS, and PHD from Tulane University and post-doctoral training at Massachusetts Institute of Technology.

Date: Wednesday, February 10 , 1 to 2pm

Slides