Project 2

Project Leaders: Laura Glynn, PhD and Curt A. Sandman, PhD

Glynn Early Human Development Lab146

SIGNIFICANCE: A significant contribution to childhood and adult health and disease risk is attributable to developmental processes during fetal life. The fetus receives many signals from the mother, and we and others have published many studies that fetal exposure to maternal adversity has harmful effects on infant and child development and may even contribute to risk for disease later in life.

We will examine the consequences of several instances of fetal and infant exposure to fragmented signals. It is unknown if inconsistent maternal signals during pregnancy influence later development. We will examine the influence on the fetus of daily, weekly and monthly changes in maternal mood, including anxiety and depression, during pregnancy. We will follow mothers and their infants after birth to determine if the mismatch between fetal and infant exposures to maternal mood makes a significant contribution to later emotional and cognitive development. We also will examine the influence of the most dominant signal in fetal life, the beat of the mother’s heart. The human fetus is exposed to 25,000,000 heartbeats during its time in the womb and it is known that the fetal brain responds to each beat. It is not known, but will be tested in our Center, if fragmented or inconsistent patterns of maternal heartbeats alter the fetal brain in ways that increase vulnerabilities to emotional and cognitive deficits in early development. We will test the hypothesis that these early experiences influence male and female fetuses differently.


Discovering early predictors of mental and cognitive illness is crucial for understanding the underlying processes and for developing early interventions. It is known that developmental processes during fetal life in response to a variety of environmental influences contribute to cognitive and emotional outcome. However, the precise nature of the exposure and the mechanisms by which early environmental signals influence life-long cognitive and emotional outcomes are unknown.

Building on data from Project 1, the goal of Project 2 it to test if exposures to fragmented patterns of maternal signals influence cognitive and emotional outcomes during adolescence. We employ two separate cohorts: One maternal/child cohort has been followed since they were 15 week old fetuses; they are now approaching adolescence. The second, new cohort will be followed from 15 weeks gestation through 12 months postpartum with refined measures of maternal fragmentation and infant development.

We accomplish our goal via 4 aims:

Aim 1 tests the hypothesis that fetal exposure to fragmented maternal emotional states increases vulnerabilities to cognitive and emotional deficits during early development.

Serial measures of maternal depression and anxiety are collected at regular intervals during gestation. In collaboration with the Computational Core, profiles of fragmentation are calculated for each woman at daily, weekly and monthly intervals. We then test the novel hypothesis that fetal exposure to maternal fragmented emotional states will result in increased incidence of emotional lability and cognitive impairment in infants and child/adolescents (with Project 3 and Project 4).

Aim 2 tests the novel hypothesis that fragmented patterns of maternal heart beats is a salient signal that increases vulnerabilities to cognitive and emotional deficits during early development.

Fragmented patterns of maternal heart rate are characterized for each pregnant mother using time series analysis in our existing cohorts at regular gestational intervals. The effects of fetal exposure to fragmented maternal signals are assessed on emotional and cognitive measures during infancy and early childhood (with Project 3 and 4) and periadolescent brain structure and function (Project 4 and Imaging Core).

Aim 3 shifts the focus to the consistency between prenatal and postnatal maternal emotional states and tests the hypothesis that inconsistency between pre- and postnatal maternal emotional states will increase the vulnerability to cognitive and emotional deficits in 1 year-old children.

Serial measures of maternal mood that are collected during gestation are compared with identical measures at regular intervals postpartum. In collaboration with Projects 3, 4 and the Computational and Imaging Cores we examine the persisting influence of consistent pre and postnatal mood states on behavior and the brain. There is evidence that sex specific patterns are formed very early in human development and there is evidence from our studies that male and female fetuses respond differently to environmental signals and that these variations persist and may result in differential risk for developing emotional, cognitive and structural brain impairments.

In Aim 4, we test the hypothesis that fetal vulnerability to fragmentation and unpredictability is sex-dependent.

Our findings will provide the first information regarding the consequences of exposure to fragmented maternal signals during the most vibrant period of development on cognitive and emotional vulnerabilities in infants, children and adolescents. Parallel studies in rodents (Project 1), will provide the neurobiological mechanisms involved. Together, the findings will be integrated by the computational core into models to predict adolescent behavior that portend mental illness.

Project Publications
  • Is there a viability-vulnerability tradeoff? Sex differences in fetal programming. Sandman CA, Glynn LM, Davis EP. J Psychosom Res. 2013 Oct;75(4):327-35.
  • Grant K-A, Sandman CA, Wing DA, Dmitrieva J, Davis, EP. Prenatal programming of postnatal susceptibility to memory impairments: A developmental double jeopardy. Psychological Science. 2015; 26:1054-62.
  • Curt A. Sandman. Mysteries of the human fetus revealed. Research in Child Dev. 2015; 124-137.
  • Stout SA, Espel EV, Sandman CA, Glynn LM & Davis EP. Fetal programming of children’s obesity risk. Psychoneuroendocrinology. 2015; 53:29-39.
  • Sandman CA, Buss C, Head K, Davis EP. Fetal exposure to maternal depressive symptoms is associated with cortical thickness in late childhood. Biol. Psychiatry. 2014; 77:324-334.
  • Espel EV, Glynn LM, Sandman CA, & Davis EP. Longer gestation among children born full term influences cognitive and motor development. PLoS One. 2014; 9:e113758.
  • Sandman CA, Glynn LM, Davis EP. Is there a viability-vulnerability trade off? Sex differences in fetal programming.  Psychosom Res. 2013; 75:327-35.
  • Baram TZ, Davis EP, Obenaus A, Sandman CA, Small SL, Solodkin A, Stern H. Fragmentation and Unpredictability of Early-Life Experience in Mental Disorders. Am J Psychiatry. 2012; 169:907-15.

You can read the Project 2 Summary for a non-technical explanation.