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Current Psychiatry Reports
Published in: Current Psychiatry Reports 11/2018

01-11-2018 | Sex and Gender Issues in Behavioral Health (CN Epperson and L Hantsoo, Section Editors)

Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent Literature

Authors: Susanna Sutherland, Steven M. Brunwasser

Published in: Current Psychiatry Reports | Issue 11/2018

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Abstract

Purpose of Review

To evaluate the degree to which recent studies provide evidence that the effects of prenatal maternal stress (PNMS) on child health outcomes vary depending on the child’s biological sex. In this review, we used a broad definition of stress, including negative life events, psychological stress, and established stress biomarkers. We identified 50 peer-reviewed articles (published January 2015–December 2017) meeting the inclusion criteria.

Recent Findings

Most articles (k = 35) found evidence of either sex-specific associations (significant in one sex but not the other) or significant PNMSxstress interactions for at least one child health outcome. Evidence for sex-dependent effects was strongest in the group of studies evaluating child neural/nervous system development and temperament as outcomes.

Summary

There is sufficient evidence of sex-dependent associations to recommend that researchers always consider the potential role of child sex in PNMS programming studies and report descriptive statistics for study outcomes stratified by child biological sex.
Appendix
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Literature
1.
Kim D, Bale T, Epperson C. Prenatal programming of mental illness: current understanding of relationship and mechanisms. Curr Psychiatry Rep. 2015;17:5.CrossRef
2.
Stein A, Pearson R, Goodman S, Rapa E, Rahman A, McCallum M, et al. Effects of perinatal mental disorders on the fetus and child. Lancet. 2014;384:1800–19.CrossRef
3.
Entringer S, Buss C, Wadhwa P. Prenatal stress, development, health and disease risk: a psychobiological perspective—2015 Curt Richter Award Paper. Psychoneuroendocrinology. 2015;62:366–75.CrossRef
4.
5.
Accortt EE, Cheadle ACD, Dunkel SC. Prenatal depression and adverse birth outcomes: an updated systematic review. Matern Child Health J. 2015;19:1306–37.CrossRef
6.
Pearson J, Tarabulsy G, Bussières E-L. Foetal programming and cortisol secretion in early childhood: a meta-analysis of different programming variables. Infant Behav Dev. 2015;40:204–15.CrossRef
7.
Graignic-Philippe R, Dayan J, Chokron S, Jacquet A-Y, Tordjman S. Effects of prenatal stress on fetal and child development: a critical literature review. Neurosci Biobehav Rev. 2014;43:137–62.CrossRef
8.
9.
Beijers R, Buitelaar JK, de Weerth C. Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis. Eur Child Adolesc Psychiatry. 2014;23:943–56.CrossRef
10.
Coussons-Read M. Effects of prenatal stress on pregnancy and human development: mechanisms and pathways. Obstet Med. 2013;6:52–7.CrossRef
11.
12.
Sandman C, Glynn L, Davis E. Is there a viability–vulnerability tradeoff? Sex differences in fetal programming. J Psychosom Res. 2013;75:327–35.CrossRef
13.
DiPietro J, Voegtline K. The gestational foundation of sex differences in development and vulnerability. Neuroscience. 2017;342:4–20.CrossRef
14.
Carpenter T, Grecian S, Reynolds R. Sex differences in early-life programming of the hypothalamic–pituitary–adrenal axis in humans suggest increased vulnerability in females: a systematic review. J Dev Orig Health Dis. 2017;8:244–55.CrossRef
15.
Bale T. Sex differences in prenatal epigenetic programing of stress pathways. Stress. 2011;14:348–56.CrossRef
16.
Clifton V. Sex and the human placenta: mediating differential strategies of fetal growth and survival. Placenta. 2010;31:S33–9.CrossRef
17.
Glover V, Hill J. Sex differences in the programming effects of prenatal stress on psychopathology and stress responses: an evolutionary perspective. Physiol Behav. 2012;106:736–40.CrossRef
18.
Bale T. The placenta and neurodevelopment: sex differences in prenatal vulnerability. Dialogues Clin Neurosci. 2016;18:459–64.PubMedPubMedCentral
19.
Rosenfeld C. Sex-specific placental responses in fetal development. Endocrinology. 2015;156:3422–34.CrossRef
20.
Gabory A, Roseboom T, Moore T, Moore L, Junien C. Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics. Biol Sex Differ. 2013;4:5.CrossRef
21.
Aiken C, Ozanne S. Sex differences in developmental programming models. Reproduction. 2013;145:R1–13.CrossRef
22.
• Kingsbury M, Weeks M, MacKinnon N, Evans J, Mahedy L, Dykxhoorn J, et al. Stressful life events during pregnancy and offspring depression: evidence from a prospective cohort study. J Am Acad Child Adolesc Psychiatry. 2016;55:709–16. This large study found no evidence of a sex-dependent association between prenatal stress and offspring depression in adolescence. CrossRef
23.
24.
Gaillard R, Rifas-Shiman S, Perng W, Oken E, Gillman M. Maternal inflammation during pregnancy and childhood adiposity. Obesity. 2016;24:1320–7.CrossRef
25.
Mansell T, Vuillermin P, Ponsonby A-L, Collier F, Saffery R, Ryan J. Maternal mental well-being during pregnancy and glucocorticoid receptor gene promoter methylation in the neonate. Dev Psychopathol. 2016;28:1421–30.CrossRef
26.
Giesbrecht G, Campbell T, Letourneau N. Sexually dimorphic adaptations in basal maternal stress physiology during pregnancy and implications for fetal development. Psychoneuroendocrinology. 2015;56:168–78.CrossRef
27.
Koutra K, Roumeliotaki T, Kyriklaki A, Kampouri M, Sarri K, Vassilaki M, et al. Maternal depression and personality traits in association with child neuropsychological and behavioral development in preschool years: mother-child cohort (Rhea Study) in Crete, Greece. J Affect Disord. 2017;217:89–98.CrossRef
28.
Lee A, Chiu Y-H, Rosa M, Cohen S, Coull BA, Wright R, et al. Association of prenatal and early childhood stress with reduced lung function in 7-year-olds. Ann Allergy Asthma Immunol. 2017;119:153–9.CrossRef
29.
Rash J, Campbell T, Letourneau N, Giesbrecht G. Maternal cortisol during pregnancy is related to infant cardiac vagal control. Psychoneuroendocrinology. 2015;54:78–89.CrossRef
30.
Simcock G, Kildea S, Elgbeili G, Laplante D, Stapleton H, Cobham V, et al. Age-related changes in the effects of stress in pregnancy on infant motor development by maternal report: the Queensland Flood Study. Dev Psychobiol. 2016;58:640–59.CrossRef
31.
Liu G, Dancause K, Elgbeili G, Laplante D, King S. Disaster-related prenatal maternal stress explains increasing amounts of variance in body composition through childhood and adolescence: Project Ice Storm. Environ Res. 2016;150:1–7.CrossRef
32.
33.
Davis E, Head K, Buss C, Sandman C. Prenatal maternal cortisol concentrations predict neurodevelopment in middle childhood. Psychoneuroendocrinology. 2017;75:56–63.CrossRef
34.
Braithwaite E, Murphy S, Ramchandani P. Effects of prenatal depressive symptoms on maternal and infant cortisol reactivity. Arch Womens Ment Health. 2016;19:581–90.CrossRef
35.
Entringer S, Buss C, Rasmussen J, Lindsay K, Gillen D, Cooper D, et al. Maternal cortisol during pregnancy and infant adiposity: a prospective investigation. J Clin Endocrinol Metab. 2017;102:1366–74.PubMed
36.
St-Hilaire A, Steiger H, Liu A, Laplante D, Thaler L, Magill T, et al. A prospective study of effects of prenatal maternal stress on later eating-disorder manifestations in affected offspring: Preliminary indications based on the project ice storm cohort. Int J Eat Disord. 2015;48:512–6.CrossRef
37.
• Quarini C, Pearson R, Stein A, Ramchandani P, Lewis G, Evans J. Are female children more vulnerable to the long-term effects of maternal depression during pregnancy? J Affect Disord. 2016;189:329–35. This study found that prenatal depression was associated with elevated odds of depression among 18-year-old girls, whereas there was a tendency for reduced odds for exposed boys. CrossRef
38.
Gilman SE, Cherkerzian S, Buka SL, Hahn J, Hornig M, Goldstein JM. Prenatal immune programming of the sex-dependent risk for major depression. Transl Psychiatry. 2016;6:e822, 1–8.CrossRef
39.
Bendiksen B, Aase H, Diep L, Svensson E, Friis S, Zeiner P. The associations between pre- and postnatal maternal symptoms of distress and preschooler’s symptoms of ADHD, oppositional defiant disorder, conduct disorder, and anxiety. J Atten Disord. 2015.
40.
Maselko J, Sikander S, Bangash O, Bhalotra S, Franz L, Ganga N, et al. Child mental health and maternal depression history in Pakistan. Soc Psychiatry Psychiatr Epidemiol. 2016;51:49–62.CrossRef
41.
• Bandoli G, Coles C, Kable J, Wertelecki W, Granovska I, Pashtepa A, et al. Assessing the independent and joint effects of unmedicated prenatal depressive symptoms and alcohol consumption in pregnancy and infant neurodevelopmental outcomes. Alcohol Clin Exp Res. 2016;40:1304–11. This paper found that, in combination with prenatal alcohol exposure, prenatal depression was associated with increased motor and cognitive development deficits in infant girls but not boys. CrossRef
42.
• Fineberg A, Ellman L, Schaefer C, Maxwell S, Shen L, Chaudhury N, et al. Fetal exposure to maternal stress and risk for schizophrenia spectrum disorders among offspring: differential influences of fetal sex. Psychiatry Res. 2016;236:91–7. This study found that, among boys, prenatal stress was associated with significantly increased odds of schizophrenia spectrum disorders, whereas there was a trend for reduced odds among girls. CrossRef
43.
Giesbrecht G, Letourneau N, Campbell T. Sexually dimorphic and interactive effects of prenatal maternal cortisol and psychological distress on infant cortisol reactivity. Dev Psychopathol. 2017;29:805–18.CrossRef
44.
• Braithwaite E, Pickles A, Sharp H, Glover V, O’Donnell K, Tibu F, et al. Maternal prenatal cortisol predicts infant negative emotionality in a sex-dependent manner. Physiol Behav. 2017a;175:31–6. This study showed infant girls exposed to maternal cortisol exhibited elevated negative emotionality, whereas cortisol-exposed boys exhibited attenuated negative emotionality. CrossRef
45.
• Kaitz M, Mankuta D, Rokem A, Faraone S. Relation between maternal antenatal anxiety and infants’ weight depends on infants’ sex: a longitudinal study from late gestation to 1-month post birth. J Psychosom Res. 2015;79:620–7. This paper found that male fetuses and neonates weighed more than their female counterparts only when exposed to third trimester maternal anxiety. CrossRef
46.
Doyle C, Werner E, Feng T, Lee S, Altemus M, Isler J, et al. Pregnancy distress gets under fetal skin: maternal ambulatory assessment & sex differences in prenatal development. Dev Psychobiol. 2015;57:607–25.CrossRef
47.
Simcock G, Elgbeili G, Laplante D, Kildea S, Cobham V, Stapleton H, et al. The effects of prenatal maternal stress on early temperament: the 2011 Queensland Flood Study. J Dev Behav Pediatr. 2017c;38:310–21.CrossRef
48.
Simcock G, Laplante D, Elgbeili G, Kildea S, Cobham V, Stapleton H, et al. Infant neurodevelopment is affected by prenatal maternal stress: the QF2011 Queensland Flood study. Infancy. 2017a;22:282–302.CrossRef
49.
Yong Ping E, Laplante D, Elgbeili G, Hillerer K, Brunet A, O’Hara M, et al. Prenatal maternal stress predicts stress reactivity at 2½ years of age: the Iowa Flood Study. Psychoneuroendocrinology. 2015;56:62–78.CrossRef
50.
Braithwaite E, Murphy S, Ramchandani P, Hill J. Associations between biological markers of prenatal stress and infant negative emotionality are specific to sex. Psychoneuroendocrinology. 2017b;86:1–7.CrossRef
51.
Braithwaite E, Kundakovic M, Ramchandani P, Murphy S, Champagne F. Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation. Epigenetics. 2015;10:408–17.CrossRef
52.
Lebel C, Walton M, Letourneau N, Giesbrecht G, Kaplan B, Dewey D. Prepartum and postpartum maternal depressive symptoms are related to children’s brain structure in preschool. Biol Psychiatry. 2016;80:859–68.CrossRef
53.
Vangeel E, Pishva E, Hompes T, van den Hove D, Lambrechts D, Allegaert K, et al. Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for GABBR1. Clin Epigenetics. 2017;9:107.CrossRef
54.
Zhu P, Hao J-H, Tao R-X, Huang K, Jiang X-M, Zhu Y-D, et al. Sex-specific and time-dependent effects of prenatal stress on the early behavioral symptoms of ADHD: a longitudinal study in China. Eur Child Adolesc Psychiatry. 2015;24:1139–47.CrossRef
55.
Herbison C, Allen K, Robinson M, Newnham J, Pennell C. The impact of life stress on adult depression and anxiety is dependent on gender and timing of exposure. Dev Psychopathol. 2017;29:1443–54.CrossRef
56.
Frith A, Naved R, Persson L, Frongillo E. Early prenatal food supplementation ameliorates the negative association of maternal stress with birth size in a randomised trial. Matern Child Nutr. 2015;11:537–49.CrossRef
57.
• Pickles A, Sharp H, Hellier J, Hill J. Prenatal anxiety, maternal stroking in infancy, and symptoms of emotional and behavioral disorders at 3.5 years. Eur Child Adolesc Psychiatry. 2017;26:325–34. This study found that prenatal pregnancy-specific anxiety was associated with increased internalizing and externalizing symptoms in preschool boys and girls, but that maternal-infant stroking buffered against this effect only in girls. CrossRef
58.
• Lee A, Chiu Y-H, Rosa M, Jara C, Wright R, Coull B, et al. Prenatal and postnatal stress and asthma in children: temporal-and sex-specific associations. J Allergy Clin Immunol. 2016;138:740–7. This paper found that prenatal stress was associated with increased risk for asthma in preschoolers among boys but not girls and that prenatal and postnatal stress in combination was predictive of asthma in girls. CrossRef
59.
Rosa M, Just A, Ortiz M, Schnaas L, Svensson K, Wright R, et al. Prenatal and postnatal stress and wheeze in Mexican children: sex-specific differences. Ann Allergy Asthma Immunol. 2016;116:306–312.e1.CrossRef
60.
Stinson L, Stroud L, Buka S, Eaton C, Lu B, Niaura R, et al. Prospective evaluation of associations between prenatal cortisol and adulthood coronary heart disease risk: the New England family study. Psychosom Med. 2015;77:237–45.CrossRef
61.
• Soe N, Wen D, Poh J, Li Y, Broekman B, Chen H, et al. Pre- and post-natal maternal depressive symptoms in relation with infant frontal function, connectivity, and behaviors. PLOS ONE. 2016;11:e0152991. This paper showed that, among girls only, increases in depressive symptoms from 32-week gestation to 3 months postpartum was associated with greater frontal lobe activity and right frontal asymmetry in infant. CrossRef
62.
Plamondon A, Akbari E, Atkinson L, Steiner M, Meaney M, Fleming A. Spatial working memory and attention skills are predicted by maternal stress during pregnancy. Early Hum Dev. 2015;91:23–9.CrossRef
63.
Wen D, Poh J, Ni S, Chong Y-S, Chen H, Kwek K, et al. Influences of prenatal and postnatal maternal depression on amygdala volume and microstructure in young children. Transl Psychiatry. 2017;7:e1103.CrossRef
64.
Gholipoor R, Saboory E, Ghazavi A, Kiyani A, Roshan-Milani S, Mohammadi S, et al. Prenatal stress potentiates febrile seizure and leads to long-lasting increase in cortisol blood levels in children under 2years old. Epilepsy Behav. 2017;72:22–7.CrossRef
65.
Stroud L, Papandonatos G, Parade S, Salisbury A, Phipps M, Lester B, et al. Prenatal major depressive disorder, placenta glucocorticoid and serotonergic signaling, and infant cortisol response. Psychosom Med. 2016;78:979–90.CrossRef
66.
Moss K, Simcock G, Cobham V, Kildea S, Elgbeili G, Laplante D, et al. A potential psychological mechanism linking disaster-related prenatal maternal stress with child cognitive and motor development at 16 months: the QF2011 Queensland Flood Study. Dev Psychol. 2017;53:629–41.CrossRef
67.
Simcock G, Kildea S, Elgbeili G, Laplante DP, Cobham V, King S. Prenatal maternal stress shapes children’s theory of mind: the QF2011 Queensland Flood Study. J Dev Orig Health Dis. 2017b;8:483–92.CrossRef
68.
Mina T, Räikkönen K, Riley S, Norman J, Reynolds R. Maternal distress associates with placental genes regulating fetal glucocorticoid exposure and IGF2: role of obesity and sex. Psychoneuroendocrinology. 2015;59:112–22.CrossRef
69.
van den Heuvel M, Johannes M, Henrichs J, Van den Bergh B. Maternal mindfulness during pregnancy and infant socio-emotional development and temperament: the mediating role of maternal anxiety. Early Hum Dev. 2015;91:103–8.CrossRef
70.
• Kim D-J, Davis E, Sandman C, Sporns O, O’Donnell B, Buss C, et al. Prenatal maternal cortisol has sex-specific associations with child brain network properties. Cereb Cortex. 2017;27:5230–41. This paper showed that, among girls only, prenatal exposure to maternal cortisol was associated with brain network patterns that mediated the association between prenatal cortisol and internalizing symptoms in childhood. PubMed
71.
VanderWeele T. Explanation in causal inference: methods for mediation and interaction. Oxford: Oxford University Press; 2015.
72.
VanderWeele T, Knol M. A tutorial on interaction. Epidemiol Methods. 2014;3:33–72.
73.
Edwards R, Hans S. Prenatal depressive symptoms and toddler behavior problems: the role of maternal sensitivity and child sex. Child Psychiatry Hum Dev. 2016;47:696–707.CrossRef
74.
75.
Arnett A, Pennington B, Willcutt E, DeFries J, Olson R. Sex differences in ADHD symptom severity. J Child Psychol Psychiatry. 2015;56:632–9.CrossRef
76.
Abel K, Drake R, Goldstein J. Sex differences in schizophrenia. Int Rev Psychiatry. 2010;22:417–28.CrossRef
77.
Bale T, Epperson C. Sex differences and stress across the lifespan. Nat Neurosci. 2015;18:1413–20.CrossRef
78.
Davis E, Sandman C. The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Dev. 2010;81:131–48.CrossRef
79.
Brown CH, Sloboda Z, Faggiano F, Teasdale B, Keller F, Burkhart G, et al. Methods for synthesizing findings on moderation effects across multiple randomized trials. Prev Sci. 2013;14:144–56.CrossRef
Metadata
Title
Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent Literature
Authors
Susanna Sutherland
Steven M. Brunwasser
Publication date
01-11-2018
Publisher
Springer US
Published in
Current Psychiatry Reports / Issue 11/2018
Print ISSN: 1523-3812
Electronic ISSN: 1535-1645
DOI
https://doi.org/10.1007/s11920-018-0961-4

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