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Early Determinants of Child Health

Edwina Yeung
  • Edwina Yeung, PhD, ScM, Senior Investigator, Epidemiology Branch, DiPHR
  • Diane Putnick, PhD, Statistician
  • Priscilla Clayton, PhD, Postdoctoral Fellow
  • Xuanxuan Zhu, PhD, Visiting Fellow

As with every new generation, exposures at the population level shift as society advances and changes. Worldwide demographic trends of couples delaying childbearing have led to rising use of fertility treatment to conceive and have increased the prevalence of chronic conditions prior to pregnancy. Our research agenda aims to understand the health impacts of such trends under the Developmental Origins of Health and Disease (DOHaD) concept, which hypothesizes that adaptations in response to early exposures influence long-term health. If one envisions a health trajectory that begins at conception, this research is answering what and where the levers are that change these trajectories. The ultimate goal of this research is to understand, in a comprehensive way, how healthy children continue to grow into healthy adults, as it is increasingly realized that cardio-metabolic, pulmonary, developmental, mental health, and other outcomes are inter-related. Our research includes examining exposures in the perinatal and postnatal windows through infancy and beyond, while acknowledging the importance of social context. Our research also seeks to determine the underlying mechanisms with regard to developmental programming by examining DNA methylation.

In 2025, our team continued research using the Upstate KIDS study. This study followed more than 6,000 babies born between 2008 and 2010. Nearly one in three of these children were conceived using fertility treatments. The goal of the study is to learn whether fertility treatments affect children’s growth and development. We also use data from this study to work on other health concerns and with other research teams around the world.

Health of children conceived by fertility treatment

There has been long-standing concern, from couples and health care providers, that children conceived using fertility treatment grow and develop differently than children not conceived by these technologies. Some of the concern stems from observations that children conceived by assisted reproductive technologies (ART) have lower birthweight and gestational age, known risk factors for many later health outcomes. The increased risk that these perinatal outcomes confer for heart disease, along with elevated blood pressure, has been particularly consistent across different populations. Mechanisms specific to ART include the potential for epigenetic changes during the implementation of these technologies, including culture media. Using the Upstate KIDS cohort, we previously evaluated the long-term cardio-metabolic risk of children conceived by fertility treatment, both by ART and by fertility drugs, finding no differences [Yeung et al. Fertil Steril 2022;121:793]. Due to the smaller number of children agreeing to Upstate KIDS clinic visits hailing from all over New York State, the findings were pursued using the larger cohort of children with information from 7–9 years as reported by mothers at their physician visits [Reference 1]. The results remained similar, with no concerns for BMI or blood pressure after conception using fertility treatments. Overall, the body of evidence from Upstate KIDS has reassured parents and clinicians that ART in particular do not lead to detriments in childhood health.

Examining DNA methylation as a DOHaD mechanism

In collaboration with international researchers in the Pregnancy And Childhood Epigenetics (PACE) consortium, we participated in several investigations of newborn and childhood DNA methylation to decipher how they may explain differences in development and child health. These studies examined how experiences during pregnancy may affect how genes work in newborn babies and children. One study confirmed that maternal sustained smoking during pregnancy contributes to unique newborn DNA methylation signatures. However, paternal smoking, other secondhand smoke, or maternal past smoking all contributed to fewer apparent differences in DNA methylation at birth in blood samples [Reference 2]. Another study found that mothers with asthma during pregnancy were more likely to have babies with DNA methylation changes linked to genes involved in lung health and asthma risk [Reference 3]. The team continues to lead a project following on previous findings on the impact of parental age on DNA methylation and to contribute to other investigations in the consortium.

Early nutrition

Early complementary feeding may have consequences for subsequent eating habits and childhood growth. Understanding these relationships may inform better evidence-based guidelines on when to introduce and feed certain foods in infancy. We previously confirmed the findings that breastfeeding and delaying introduction of certain complementary foods is associated with long-term childhood body mass index (BMI). In 2025, using Upstate KIDS data, we examined whether timing of introducing certain foods such as fruits and vegetables affected the child's own intake of such and their overall dietary patterns before (three years old) and after school age (seven to nine years old). We evaluated dietary patterns according to a composite Youth Healthy Eating Index score, with higher scores denoting better diet quality (e.g., more fruits and vegetables, less sugar-sweetened beverages, etc.). We found that waiting too long to introduce some food items such as fruits and vegetables was associated with lower daily intake. It was also in turn associated with lower diet quality [Reference 4]. These findings suggest that decisions around when to introduce healthy foods can have longer-term consequences.

However, the timing of introduction of complementary foods is complicated by the many recommendations that are available. The American Academy of Pediatrics recommends introduction around six months of age, but many parents base decisions on other factors such as signs of development. From over 5,400 children with information in Upstate KIDS, we found that signs of developmental readiness contributed to earlier introduction to complementary foods than the recommended age of feeding at six months [Reference 5]. Factors included whether they could sit without support, reached for items, frequently put items in their mouths, had a good appetite, or had steady head control, factors that individually and in combination were associated with higher likelihood of introducing complementary foods and beverages before six months. While racial differences in the timing of complementary feeding were observed, the perceived developmental readiness of infants played a role in these differences. That raises the question as to how best to create clear and consistent guidance on which developmental signs matter most to support healthy habits and long-term growth.

Paternal contribution of perinatal health

We continued to recruit couples into the Study of Pregnancy and Neonatal Health (SPAN) at four study sites, in order to investigate paternal contributions to the developmental origins of health and disease. While much research has been devoted to maternal exposures, information on paternal factors is greatly lacking, despite evidence of potential epigenetic pathways in animal models. The data collected will uniquely answer important questions about how paternal obesity and other cardio-metabolic risk factors affect fetal growth, placental factors, and neonatal outcomes.

Publications

  1. Yeung E, Lin T, Putnick DL, Mendola M. Fertility treatment and cardio-metabolic risk factors in middle childhood. Reproductive BioMedicine Online 2025 doi: 10.1016/j.rbmo.2025.104846
  2. Hoang TT, Cosin-Tomas M, Lee Y, Monasso G, Xu Z, Shaobo S, Zeng X, Starling AP, Reimann B, Röder S, Zillich L, Jima DD, Thio CHL, Pesce G, Kersten ETG, Breeze CE, Burkholder AB, Lee M, Ward JM, BIOS Consortium, Alfano R, Deuschle M, Duijts L, Ghassabian A, Herrera LCG, Jaddoe VWV, Motsinger-Reif AA, Lie RT, Nawrot TS, Page CM, Send TS, Sharp G, Stein DJ, Streit F, Sunyer J, Wilcox AJ, Zar HJ, Koppelman GH, Annesi-Maesano I, Corpeleijn E, Snieder H, Hoyo C, Hüls A, Sirignano L, Witt SH, Herberth G, Plusquin M, Dabelea D, Yeung E, Wiemels JL, Richmond RC, Taylor JA, Felix JF, Håberg SE, Bustamante M, London SJ. Prenatal smoking exposures and epigenome-wide newborn methylation. Environ Health Perspect 2025 doi: 10.1289/EHP16303;online ahead of print
  3. Pedersen CET, Hoang TT, Jin J, Starnawska A, Granell R, Elliott HR, Huels A, Zar HJ, Stein DJ, Zhang Y, Dekker HT, Duijts L, Felix JF, Sangüesa J, Bustamante M, Casas M, Vrijheid M, Kadalayil L, Rezwan FI, Arshad H, Holloway J, Röder S, Zenclussen AC, Herberth G, Staunstrup NH, Horsdal HT, Mill J, Hannon E, iPSYCH-MINERvA Group, Annesi-Maesano I, Pesce G, Baïz N, Heude B, Hosseinian-Mohazzab S, Breton CV, Harlid S, Harbs J, Domellof M, West C, Yeung E, Zeng X, Nystad E, Håberg SE, Magnus MC, Schendel D, London SJ, Bønnelykke K. Maternal asthma and newborn DNA methylation. Clin Epigenetics 2025 17(1):79
  4. Clayton PK, Putnick DL, Lin TC, Yeung EH. Influence of infant feeding practices on childhood dietary patterns in Upstate KIDS. Appetite 2025 209:107967
  5. Putnick DL, Ghassabian A, Clayton PK, Sundaram R, Yeung EH. Developmental readiness for complementary feeding: associations with initiation before age 6 months. J Pediatr 2025 286:114722

Collaborators

  • Erin Bell, PhD, University at Albany School of Public Health, Albany, NY
  • Akhgar Ghassabian, MD, PhD, NYU Langone Health, New York, NY
  • Weihua Guan, PhD, University of Minnesota, Minneapolis, MN
  • Karin Fox, PhD, University of Texas Medical Branch, Galveston, TX
  • Brenna Hughes, MD, Duke University School of Medicine, Durham, NC
  • Stephanie London, MD, DrPH, Integrative Genomic Epidemiology Group, NIEHS, Durham, NC
  • George L. Maxwell, MD, Inova Health System, Fairfax, VA
  • Pauline Mendola, PhD, University at Buffalo, Buffalo, NY
  • Daniel Molina, PhD, Technical Resources International, Inc., Bethesda, MD
  • Robert Silver, MD, University of Utah, Salt Lake City, UT
  • Alan Tita, MD, The University of Alabama at Birmingham, Birmingham, AL
  • Timothy Wen, MD, University of California San Diego, San Diego, CA

Contact

For more information, email yeungedw@mail.nih.gov or visit https://irp.nih.gov/pi/edwina-yeung.