How Prenatal Stress Timing Affects Infant Stress Response

Summary: New research shows that when stress occurs during pregnancy changes how it affects infant stress responses—and these effects differ by sex. The study found that stress in mid-pregnancy more strongly alters stress reactivity in girls, while stress experienced later in gestation has a greater impact on boys.

Researchers measured infants’ hormonal responses to a mild stressor and assessed temperament after tracking weekly prenatal stress. Their results challenge the idea that girls are universally more vulnerable to prenatal stress and emphasize that the timing of stress exposure is a key factor in early-life risk for later mental health problems.

Key Facts:

  • Timing Matters: Specific windows in mid and late pregnancy are especially influential in shaping infant stress biology and temperament.
  • Sex Differences: Girls appear most sensitive to stress in mid-gestation, while boys show greater sensitivity to stress during late gestation.
  • Measurable Infant Indicators: Researchers used salivary cortisol responses to a mild laboratory challenge and parent-reported temperament to assess infant biobehavioral reactivity.

Source: Michigan State University

Researchers from Michigan State University and the University of Michigan identify precise prenatal windows when maternal stress most strongly associates with infant stress reactivity and temperament.

Published in Psychoneuroendocrinology, this study offers the most detailed weekly assessment of prenatal stress to date, tracking expectant mothers from week 15 through week 41. By mapping stress week by week across pregnancy, the team located the gestational periods most closely linked to two early-life markers of later psychopathology: hypothalamic-pituitary-adrenal (HPA) axis reactivity and difficult temperament.

“Prenatal stress is well known to be connected to poorer mental and physical health outcomes later in life, and past studies have often emphasized greater effects on girls,” said Alytia Levendosky, lead investigator and professor in MSU’s Department of Psychology. “Our data show a more nuanced picture: the differences by sex are driven by timing, not simply greater vulnerability in one sex.”

The study enrolled 396 pregnant women drawn from a higher stress-risk population—participants were more likely to have low income and/or to have experienced intimate partner violence. From week 15 onward, women reported stress levels weekly via brief electronic surveys. This dense, repeated measurement allowed investigators to identify when prenatal stress most strongly predicted infant outcomes.

At six months of age, infants underwent a mild, standardized laboratory stress task during which researchers collected salivary cortisol samples before and after the challenge to evaluate HPA axis reactivity. Mothers also completed validated questionnaires describing their infant’s temperament.

Results revealed distinct sensitive windows. For girls, mid-gestation weeks—around weeks 20 and 29—were linked to altered HPA reactivity and to higher likelihood of difficult temperament. For boys, a sensitive period emerged in late gestation—around week 37—with stress during this time associated with differences in cortisol response. Temperament findings likewise showed mid- and late-gestation associations for girls and a broader mid-to-late gestation window for boys.

Earlier studies typically ended assessments by weeks 32–34, which likely missed the late-gestation window now identified for boys. “Extending our measurement through week 41 made it possible to pinpoint the later sensitivity for boys,” said Joseph Lonstein, study investigator and professor in MSU’s Department of Psychology. “These findings correct and refine our understanding of how prenatal stress affects boys and girls differently.”

The authors emphasize that these associations do not prove deterministic outcomes for individual children but rather highlight periods when the developing brain appears especially responsive to environmental influences. They call for additional research to clarify biological mechanisms and to understand how timing of exposure interacts with postnatal environments to shape developmental trajectories.

Funding currently supports continued follow-up of participating families through age four, with assessments already planned at 2.5 years and at 4 years. Amy Nuttall, co-author and associate professor in MSU’s Department of Human Development and Family Studies, expressed interest in extending follow-up further into childhood to observe how early patterns evolve over time.

About this stress and neurodevelopment research news

Author: Jack Harrison
Source: Michigan State University
Contact: Jack Harrison – Michigan State University
Image: Image credited to Neuroscience News

Original Research: Open access. “Pinpointing the timing of prenatal stress associated with infant biobehavioral reactivity” by Alytia Levendosky et al., Psychoneuroendocrinology. DOI: 10.1016/j.psyneuen.2025.107368


Abstract

Pinpointing the timing of prenatal stress associated with infant biobehavioral reactivity

Prenatal stress is linked to adverse biobehavioral outcomes in early childhood, but when during gestation these influences are strongest has been unclear. We investigated how the timing of maternal stress across pregnancy relates to two infant outcomes—HPA axis reactivity and difficult temperament—that are early indicators of risk for later psychopathology.

This study collected weekly stress ratings from 396 pregnant women between 15 and 41 weeks of gestation, providing a highly granular picture of prenatal stress exposure. At six months postpartum, infant salivary cortisol responses to a mild laboratory stressor were measured (n = 173), and mothers reported on infant temperament (n = 244).

Using machine learning approaches to examine both between-person and within-person effects, we identified distinct sensitive periods. For HPA axis reactivity, girls showed sensitive windows in mid-gestation (around weeks 20 and 29), while boys showed sensitivity in late gestation (around week 37). For difficult temperament, average maternal stress levels across pregnancy predicted outcomes, and specific sensitive periods were evident: mid and late gestation weeks for girls (weeks 20, 21, 25 and week 37) and a broader mid-to-late gestation range for boys (weeks 25, 27, 30, 34, 40).

These findings are the first to use weekly prenatal measurement across gestation to demonstrate sex-specific windows of sensitivity for infant biobehavioral markers linked to later risk for psychopathology. The results underscore that biological sex influences the timing of prenatal stress effects on early developmental outcomes and should inform future research and prevention efforts.