Maternal thyroid dysfunction and depressive symptoms during pregnancy and child behavioral and emotional problems - an ECHO multi-cohort investigation

Nora K Moog; Maxwell Mansolf; Phillip Sherlock; Jennifer J Adibi; Emily S Barrett; Sonja Entringer; Akhgar Ghassabian; Jean M Kerver; John D Meeker; Emily Oken; Nigel Paneth; Hyagriv N Simhan; Deborah J Watkins; Pathik D Wadhwa; Thomas G O'Connor; Claudia Buss; program collaborators for Environmental influences on Child Health Outcomes

doi:10.1016/j.jad.2025.03.163

Maternal thyroid dysfunction and depressive symptoms during pregnancy and child behavioral and emotional problems - an ECHO multi-cohort investigation

J Affect Disord. 2025 Jul 1:380:475-486. doi: 10.1016/j.jad.2025.03.163. Epub 2025 Mar 26.

Authors

Nora K Moog¹, Maxwell Mansolf², Phillip Sherlock², Jennifer J Adibi³, Emily S Barrett⁴, Sonja Entringer⁵, Akhgar Ghassabian⁶, Jean M Kerver⁷, John D Meeker⁸, Emily Oken⁹, Nigel Paneth⁷, Hyagriv N Simhan¹⁰, Deborah J Watkins⁸, Pathik D Wadhwa¹¹, Thomas G O'Connor¹², Claudia Buss⁵; program collaborators for Environmental influences on Child Health Outcomes

Affiliations

¹ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: nora.moog@charite.de.
² Department of Medical Social Sciences, Northwestern University, Feinberg School of Medicine, 420 E Superior St, Chicago, IL 60611, USA.
³ Department of Epidemiology, University of Pittsburgh School of Public Health, 130 De Soto St, Pittsburgh, PA 15261, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee Women's Hospital, University of Pittsburgh, 300 Halket St, Pittsburgh, PA 15213, USA.
⁴ Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Environmental and Occupational Health Sciences Institute, 683 Hoes Ln W, Piscataway, NJ 08854, USA.
⁵ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Charitéplatz 1, 10117 Berlin, Germany; Department of Pediatrics, University of California, Irvine, School of Medicine, 1001 Health Sciences Rd, Orange, California 92697, USA.
⁶ Department of Pediatrics, NYU Grossman School of Medicine, 550 1(st) Ave, New York, NY 10016, USA; Department of Population Health, NYU Grossman School of Medicine, 550 1(st) Ave, New York, NY 10016, USA.
⁷ Departments of Epidemiology & Biostatistics and Pediatrics & Human Development, College of Human Medicine, Michigan State University, 804 Service Rd, East Lansing, MI 48824, USA.
⁸ Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
⁹ Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, 401 Park Dr, Boston, MA 02215, USA.
¹⁰ Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee Women's Hospital, University of Pittsburgh, 300 Halket St, Pittsburgh, PA 15213, USA.
¹¹ Department of Pediatrics, University of California, Irvine, School of Medicine, 1001 Health Sciences Rd, Orange, California 92697, USA; Departments of Psychiatry and Human Behavior, Obstetrics and Gynecology, and Epidemiology, University of California, Irvine, School of Medicine, 1001 Health Sciences Rd, orange, California 92697, USA.
¹² Departments of Psychiatry, Psychology, Obstetrics and Gynecology, and Neuroscience, University of Rochester, 601 Elmwood Ave, Rochester, New York 14642, USA.

PMID: 40154801
DOI: 10.1016/j.jad.2025.03.163

Abstract

Background: Maternal thyroid dysfunction and maternal depression during pregnancy may increase the risk of child behavioral and emotional problems. We sought to investigate the independent and interactive associations of these two risk factors with child behavior problems.

Methods: We combined data from four cohorts in the Environmental influences on Child Health Outcomes (ECHO) program (N = 949). Maternal thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [fT4], thyroid peroxidase autoantibodies [TPO-Ab], fT4/TSH ratio) was measured predominantly during the first half of pregnancy. We harmonized maternal depression into a continuous measure of antepartum depressive symptomatology and a dichotomous measure reflecting (history of) clinical depression. Child internalizing and externalizing problems were harmonized to the T-score metric of the Child Behavior Checklist. We used multiple linear regression and random effects meta-analysis to assess the average relationship between each predictor and outcome, and the variability in these relationships across cohorts.

Results: Across cohorts, antepartum depressive symptomatology was positively associated with both internalizing (meta B = 2.879, 95 % CI 1.87-3.89, p < .001) and externalizing problems (meta B = 1.683, 95 % CI 0.67-2.69, p = .001). None of the indicators of maternal thyroid function was associated with child behavior problems across cohorts. TPO-Ab concentrations were positively associated with child externalizing problems only in offspring of depressed mothers (meta B = 3.063, 95 % CI 0.73-5.40, p = .010).

Conclusions: This study supports the importance of maternal antepartum mental health for child behavior across diverse populations. However, we found little empirical evidence for an association between maternal thyroid function within the normal range during pregnancy and child behavioral problems.

Keywords: Child behavior problems; Depression; Pregnancy; Prenatal exposure; Thyroid hormones.

MeSH terms

Adult
Autoantibodies / blood
Child
Child Behavior Disorders* / diagnosis
Child Behavior Disorders* / epidemiology
Child Behavior Disorders* / etiology
Child Behavior Disorders* / psychology
Child, Preschool
Cohort Studies
Depression* / psychology
Depressive Disorder* / psychology
Female
Humans
Male
Pregnancy
Pregnancy Complications* / blood
Pregnancy Complications* / psychology
Prenatal Exposure Delayed Effects*
Problem Behavior* / psychology
Risk Factors
Thyroid Diseases* / epidemiology
Thyroid Diseases* / psychology
Thyroid Function Tests
Thyrotropin / blood
Thyroxine / blood

Substances

Thyrotropin
Thyroxine
Autoantibodies