In Vitro Fertilization (IVF) and Prenatal Effects Independent of Genetics

Leveraging IVF to Identify Prenatal Effects Independent of Shared Maternal-Child Genes

This study examines how maternal stress during pregnancy affects infant brain and behavioral development, focusing on whether these effects are due to the prenatal environment or shared genes. By comparing IVF pregnancies using donor eggs/embryos (no shared genetics) with non-donor IVF pregnancies, the investigators aim to understand how stress influences the baby's development independent of genetic factors.

Participants will complete questionnaires, provide blood samples, and take part in placenta and cord blood collection, fetal monitoring, and newborn brain activity assessments.

Aim 1: The influence of maternal distress on perinatal neurobehavioral development.

Hypotheses: Independent of IVF group status, higher maternal AL will be associated with higher 3rd trimester FHR reactivity, lower FHR variability, AND lower FHR-movement coupling

Aim 2: Maternal distress affecting placenta gene methylation.

Hypotheses: Independent of IVF group status, maternal AL will be associated with placenta differential DNA methylation in glucocorticoid-regulating genes (FKBP5 and HSD11B2),

Aim 3: Maternal experiences associated with unique placenta transcriptomic profiles.

Hypotheses: Independent of IVF group status, maternal AL and well-being each will be associated with unique placenta gene expression in pro-inflammatory genes

Study Overview

• Status: Recruiting
• Conditions: Child Development; Maternal Distress
• Intervention / Treatment: Other: Prenatal maternal psychosocial and biological assessment protocol

Detailed Description

To rigorously test the Developmental Origins of Health and Disease (DOHaD) research model, this project will leverage the spectacular scientific advancements of in vitro fertilization (IVF) and compare maternal prenatal distress effects between IVF donor oocyte/embryo and non-donor oocyte pregnancies. This will be the first study to use multidisciplinary (neurobehavioral, epigenetic, transcriptomic) methods with adoption-at-conception pregnant individuals to determine whether prenatal programming can be detected independent of shared maternal-child genes.

Decades of prospective DOHaD research with birthing individuals and their genetic children, including reports from our group, support the prenatal programming hypothesis that pregnant individuals' mental health affects the next generation's. Seminal, population-based studies using parent reports, such as the Avon Longitudinal Study of Parents and Children (ALSPAC), showed pregnant women in the top 15% for anxiety symptoms had children with nearly twice the risk of mental health disorders across ages 4-13 after controlling for confounders including postpartum depression. In our work and others' using objective assessments, maternal prenatal distress associated with higher 3rd trimester fetal heart rate (FHR) reactivity, from EEG in newborns lower high- frequency power and greater frontal asymmetry (itself associated with adult depression), and decrements in NIH ToolBox executive functioning and motor skills at 4-8 years old. However, for each of these findings, shared maternal-child genes cannot be ruled out. Animal models - in which the genetic background and stress exposure can be manipulated - show prenatal stress leads to anxious and depressed behavioral phenotypes independent of genetic inheritance, though limitations in the applicability to humans include: stressors' ecological validity, differences in gestational biology, and developmental timing. Genetically-informed studies, including those with donor IVF participants, show mixed evidence for prenatal distress effects. However, designs are frequently retrospective, including in IVF research, such that medical confounds also are not well controlled. Mechanistic approaches, such as our work and others' work focused on the placenta, a gestational organ at the maternal-fetal interface, show maternal distress associated with epigenetic regulation of placenta glucocorticoid and pro-inflammatory genes and child outcomes; to date, no study using IVF to circumvent genetic confounding has included mechanistic approaches. Finally, most DOHaD science concerns maternal distress effects; to advance prenatal programming research and enhance its relevance for clinical interventions, maternal social connection and other aspects of well-being also should be examined. Our study will address these design limitations and aim to identify maternal prenatal distress effects independent of shared maternal-child genes.

In a longitudinal study of 2nd trimester pregnant individuals (60 donor oocyte/embryo,120 non-donor oocyte), n=180 post attrition, protocol is: Zoom-based psychosocial questionnaires 24-28 weeks (Pregnancy Session 1); laboratory session for maternal EKG, blood pressure, blood draw (immune markers), psychosocial questionnaires, fetal neurobehavior 34-38 weeks (Pregnancy Session 2); collect placenta and cord blood (cortisol); newborn EEG in hospital; medical record data; and, methods: placenta targeted/genome-wide methylation, gene expression, distress, Allostatic Load (AL): Test three aims, identifying, independent of IVF group status.

• Study Type: Observational
• Enrollment (Estimated): 360

Contacts and Locations

• Study Contact: Name: Khadija Jones, MPH; Phone Number: 917-817-1490; Email: kj2660@cumc.columbia.edu
• Study Contact Backup: Name: Catherine Monk, PhD; Phone Number: 917-543-6031; Email: cem31@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center/New York Presbyterian Hospital
      • Contact: Khadija Jones, MPH; Phone Number: 917-817-1490; Email: kj2660@cumc.columbia.edu
      • Principal Investigator: Catherine Monk, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This five-year study will recruit and enroll approximately 200 pregnant individuals, ages 18-50 years, using IVF (120 homologous, 60 donor oocyte/embryo) and their offspring to achieve a post-attrition sample size of n=180. While based in Washington Heights, the sample reflects individuals undergoing IVF, not the general neighborhood. Based on Columbia Fertility Center data and national IVF trends, the investigators expect participants to be mostly Non-Hispanic/Latinx. While the investigators aim for inclusivity and diversity, non-English speakers will not be enrolled due to study team language constraints.

Description

Inclusion Criteria:

1. Individuals at 18-28 gestational weeks with donor and homologous IVF pregnancies, ages 18-50.
2. Participants must be patients receiving their perinatal health care through Columbia University Irving Medical Center's Department of OB/GYN and delivering at New York-Presbyterian Morgan Stanley Children's Hospital.
3. Participants must be patients delivering at Columbia University Irving Medical Center's Department of OB/GYN and delivering at New York-Presbyterian Morgan Stanley Children's Hospital.
4. Participants will include the offspring of patients receiving care and delivering at the above institutions.
5. Enrollment Location(s): Columbia University Irving Medical Center's Department of OB/GYN, delivering at New York-Presbyterian Morgan Stanley Children's Hospital.

Exclusion Criteria:

1. Identified addiction disorder
2. Severe psychiatric condition (defined as symptoms that significantly impair daily functioning and are untreated or not effectively managed)
3. Multiple fetal pregnancy
4. Known chromosomal, genetic, or major fetal malformations (unlikely due to routine preimplantation genetic testing)
5. Inflammatory conditions including rheumatoid arthritis, lupus, and multiple sclerosis
6. Not planning to deliver at a CUIMC-affiliated hospital

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Donor Oocyte/Embryo IVF Pregnancies; This cohort includes pregnant individuals who conceived through in vitro fertilization (IVF) using donor oocytes or embryos, and are therefore not genetically related to the fetus. Participants follow the same study protocol as the non donor oocyte cohort, with enrollment in the second trimester and data collection through delivery and early postpartum. The purpose of including this cohort is to evaluate the effects of maternal prenatal distress and well-being on perinatal development independent of shared maternal-child genetics. Data collection includes psychosocial questionnaires, maternal physiological monitoring, blood draws for immune and transcriptomic analyses, placental and cord blood collection at delivery, newborn physiological monitoring during the postpartum hospital stay, and birth outcomes obtained from the electronic health record (EHR).	Other: Prenatal maternal psychosocial and biological assessment protocol; This is not a therapeutic or experimental intervention. The data-collection protocol includes structured psychosocial questionnaires, physiological monitoring, maternal blood draws, placental and cord blood collection, and newborn physiological monitoring. These procedures are used to observe associations between maternal prenatal distress and infant outcomes. All participants undergo the same assessments; no clinical treatment or behavioral manipulation is delivered.
Non-Donor Oocyte IVF Pregnancies; This cohort includes pregnant individuals who conceived through IVF using their own oocytes, and are therefore genetically related to the fetus. Participants follow the same study protocol as the donor oocyte cohort, with enrollment in the second trimester and data collection through delivery and early postpartum. This group serves as a comparison to assess whether observed associations between maternal prenatal distress, biological markers, and infant neurodevelopment are attributable to intrauterine (environmental) influences or shared genetic factors. Data collection includes psychosocial questionnaires, maternal physiological monitoring, blood draws for immune and transcriptomic analyses, placental and cord blood collection at delivery, newborn physiological monitoring during the postpartum hospital stay, and birth outcomes obtained from the electronic health record (EHR)	Other: Prenatal maternal psychosocial and biological assessment protocol; This is not a therapeutic or experimental intervention. The data-collection protocol includes structured psychosocial questionnaires, physiological monitoring, maternal blood draws, placental and cord blood collection, and newborn physiological monitoring. These procedures are used to observe associations between maternal prenatal distress and infant outcomes. All participants undergo the same assessments; no clinical treatment or behavioral manipulation is delivered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fetal heart rate (FHR)	This is to measure 3rd trimester fetal heart rate (FHR) reactivity. Change in FHR in response to maternal response to the Stroop task, indicating greater fetal autonomic response associated with maternal distress. Units: Beats per minute (bpm). Greater FHR indicates higher stress.	At Pregnancy Session 2 (approximately 34-36 weeks of pregnancy)
Standard deviation of fetal heart rate	This is to measure fetal heart rate (FHR) variability, reflecting less vagal modulation of the heart associated with maternal distress. Units: Standard deviation of beats per minute. Lesser standard deviation (SD) indicates lower stress.	At Pregnancy Session 2 (approximately 34-36 weeks of pregnancy)
Cross correlation of fetal movement and heart rate change	This is to measure fetal heart rate (FHR)-movement coupling, reflecting central nervous system regulation. Units: Cross correlation value. Lower value indicates lower coupling.	At Pregnancy Session 2 (approximately 34-36 weeks of pregnancy)
Average percent DNA methylation of the FKBP5 gene in placental tissue	This is to measure FKBP5 DNA Methylation. Units: proportion of methylated vs unmethylated. Greater percent indicates higher methylation.	At delivery (approximately 37-40 weeks)
Average percent DNA methylation of the HSD11B2 gene in placental tissue	This is to measure HSD11B2 DNA Methylation. Units: proportion of methylated vs unmethylated. Greater percent indicates higher methylation.	At delivery (approximately 37-40 weeks)
Relative expression of key pro-inflammatory markers in placental tissue	This is to measure expression of Pro-Inflammatory Placental Genes. Units: Gene expression. Greater value indicates greater expression.	At delivery (approximately 37-40 weeks)

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of California, Los Angeles
• Investigators: Principal Investigator: Catherine Monk, PhD, Columbia University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030

Study Registration Dates

• First Submitted: December 18, 2025
• First Submitted That Met QC Criteria: December 18, 2025
• First Posted (Actual): December 22, 2025

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: IVF; Maternal Health; Child development; Developmental Origins of Health and Disease (DOHaD)
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Prenatal Injuries; Prenatal Exposure Delayed Effects; Developmental Origins of Health and Disease
• Other Study ID Numbers: AAAV4123; 1R01HD118949-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No