Hostname: page-component-745bb68f8f-lrblm Total loading time: 0 Render date: 2025-02-02T03:44:54.888Z Has data issue: false hasContentIssue false
  • English
  • Français

Associations of antenatal glucocorticoid exposure with mental health in children

Published online by Cambridge University Press:  28 January 2019

Elina Wolford Open the ORCID record for Elina Wolford [Opens in a new window] ,
Marius Lahti-Pulkkinen ,
Polina Girchenko ,
Jari Lipsanen ,
Soile Tuovinen ,
Jari Lahti ,
Kati Heinonen ,
Esa Hämäläinen ,
Eero Kajantie  and
Anu-Katriina Pesonen
...Show all authors
Elina Wolford*
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Marius Lahti-Pulkkinen
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
Polina Girchenko
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Jari Lipsanen
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Soile Tuovinen
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Jari Lahti
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland Folkhälsan Research Centre, Helsinki, Finland
Kati Heinonen
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Esa Hämäläinen
Affiliation:
Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland
Eero Kajantie
Affiliation:
National Institute for Health and Welfare, Helsinki, Finland Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
Anu-Katriina Pesonen
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Pia M. Villa
Affiliation:
Obstetrics and Gynaecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
Hannele Laivuori
Affiliation:
Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
Rebecca M. Reynolds
Affiliation:
University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
Katri Räikkönen
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
*
Author for correspondence: Elina Wolford, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Synthetic glucocorticoids, to enhance fetal maturation, are a standard treatment when preterm birth before 34 gestational weeks is imminent. While morbidity- and mortality-related benefits may outweigh potential neurodevelopmental harms in children born preterm (<37 gestational weeks), this may not hold true when pregnancy continues to term (⩾37 gestational weeks). We studied the association of antenatal betamethasone exposure on child mental health in preterm and term children.

Methods

We included 4708 women and their children, born 2006–2010, from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction Study with information on both antenatal betamethasone treatment and child mental and behavioral disorders from the Finnish Hospital Discharge Register from the child's birth to 31 December 2016. Additional follow-up data on mother-reported psychiatric problems and developmental milestones were available for 2640 children at 3.5 (s.d. = 0.07) years-of-age.

Results

Of the children, 187 were born preterm (61 betamethasone-exposed) and 4521 at term (56 betamethasone-exposed). The prevalence of any mental and behavioral, psychological development, emotional and behavioral, and comorbid disorders was higher in the betamethasone-exposed, compared to non-exposed children [odds ratio 2.76 (95% confidence interval 1.76–4.32), 3.61 (2.19–5.95), 3.29 (1.86–5.82), and 6.04 (3.25–11.27), respectively]. Levels of psychiatric problems and prevalence of failure to meet the age-appropriate development in personal-social skills were also higher in mother-reports of betamethasone-exposed children. These associations did not vary significantly between preterm and term children.

Conclusions

Antenatal betamethasone exposure may be associated with mental health problems in children born preterm and in those who end up being born at term.

Keywords

Betamethasonedevelopmental milestonesglucocorticoidsmental healthpsychiatric problems
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 2 , January 2020 , pp. 247 - 257
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Achenbach, TM and Rescorla, LA (2000) Manual for the ASEBA Preschool Forms & Profiles. Burlington, VT: University of Vermont, Research Center for Children, Youth, & Families.Google Scholar
Alexander, N, Rosenlöcher, F, Stalder, T, Linke, J, Distler, W, Morgner, J and Kirschbaum, C (2012) Impact of antenatal synthetic glucocorticoid exposure on endocrine stress reactivity in term-born children. Journal of Clinical Endocrinology and Metabolism 97, 3538–3544.CrossRefGoogle ScholarPubMed
Alexander, N, Rosenlöcher, F, Dettenborn, L, Stalder, T, Linke, J, Distler, W, Morgner, J, Miller, R, Kliegel, M and Kirschbaum, C (2016) Impact of antenatal glucocorticoid therapy and risk of preterm delivery on intelligence in term-born children. The Journal of Clinical Endocrinology & Metabolism 101, 581–589.CrossRefGoogle ScholarPubMed
Asztalos, E, Willan, A, Murphy, K, Matthews, S, Ohlsson, A, Saigal, S, Armson, A, Kelly, E, Delisle, M-F, Gafni, A, Lee, S, Sananes, R, Rovet, J, Guselle, P and Amankwah, K (2014) Association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5). BMC Pregnancy and Childbirth 14, 272.CrossRefGoogle Scholar
Austin, PC (2011) An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behavioral Research 46, 399–424.CrossRefGoogle ScholarPubMed
Beck, A, Steer, R and Brown, G (1996). Manual for the Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation.Google Scholar
Blencowe, H, Cousens, S, Oestergaard, MZ, Chou, D, Moller, A-B, Narwal, R, Adler, A, Vera Garcia, C, Rohde, S, Say, L and Lawn, JE (2012) National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 379, 2162–2172.CrossRefGoogle ScholarPubMed
Boes, AD, McCormick, LM, Coryell, WH and Nopoulos, P (2008) Rostral anterior cingulate cortex volume correlates with depressed mood in normal healthy children. Biological Psychiatry 63, 391–397.CrossRefGoogle ScholarPubMed
Burgess, N, Maguire, EA and O'Keefe, J (2002) The human hippocampus and spatial and episodic memory. Neuron 35, 625–641.CrossRefGoogle ScholarPubMed
Charkaluk, M-L, Rousseau, J, Calderon, J, Bernard, JY, Forhan, A, Heude, B and Kaminski, M (2017) Ages and stages questionnaire at 3 years for predicting IQ at 5–6 years. Pediatrics 139, e20162798.CrossRefGoogle ScholarPubMed
Conover, JC and Yancopoulos, GD (1997) Neurotrophin regulation of the developing nervous system: analyses of knockout mice. Reviews in the Neurosciences 8, 13–27.CrossRefGoogle ScholarPubMed
Damsted, SK, Born, AP, Paulson, OB and Uldall, P (2011) Exogenous glucocorticoids and adverse cerebral effects in children. European Journal of Paediatric Neurology 15, 465–477.CrossRefGoogle ScholarPubMed
Davis, EP, Sandman, CA, Buss, C, Wing, DA and Head, K (2013) Fetal glucocorticoid exposure is associated with preadolescent brain development. Biological Psychiatry 74, 647–655.CrossRefGoogle ScholarPubMed
Filgueiras, A, Pires, P, Maissonette, S and Landeira-Fernandez, J (2013) Psychometric properties of the Brazilian-adapted version of the Ages and Stages Questionnaire in public child daycare centers. Early Human Development 89, 561–576.CrossRefGoogle ScholarPubMed
Geuze, E, Vermetten, E and Bremner, JD (2005) MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Molecular Psychiatry 10, 160–184.CrossRefGoogle ScholarPubMed
Girchenko, P, Hämäläinen, E, Kajantie, E, Pesonen, A-K, Villa, P, Laivuori, H, Räikkönen, K, Entringer, S, Buss, C, Wadhwa, PD, Hämäläinen, E, Kajantie, E, Pesonen, A-K, Villa, PM, Laivuori, H and Räikkönen, K (2017) Prediction and prevention of preeclampsia and intrauterine growth restriction (PREDO) study. International Journal of Epidemiology 46, 1380–1381.Google ScholarPubMed
Goldenberg, RL, Culhane, JF, Iams, JD and Romero, R (2008) Epidemiology and causes of preterm birth. The Lancet 371, 75–84.CrossRefGoogle ScholarPubMed
Gyamfi-Bannerman, C, Thom, EA, Blackwell, SC, Tita, ATNN, Reddy, UM, Saade, GR, Rouse, DJ, McKenna, DS, Clark, EASS, Thorp, JM, Chien, EK, Peaceman, AM, Gibbs, RS, Swamy, GK, Norton, ME, Casey, BM, Caritis, SN, Tolosa, JE, Sorokin, Y, VanDorsten, JP and Jain, L (2016) Antenatal betamethasone for women at risk for late preterm delivery. The New England Journal of Medicine 374, 1311–1320.CrossRefGoogle ScholarPubMed
Hodyl, NA, Crawford, TM, McKerracher, L, Lawrence, A, Pitcher, JB and Stark, MJ (2016) Antenatal steroid exposure in the late preterm period is associated with reduced cord blood neurotrophin-3. Early Human Development 101, 57–62.CrossRefGoogle ScholarPubMed
Ilg, L, Kirschbaum, C, Li, S-C, Rosenlöcher, F, Miller, R and Alexander, N (2018) Persistent effects of antenatal synthetic glucocorticoids on endocrine stress reactivity from childhood to adolescence. The Journal of Clinical Endocrinology & Metabolism. doi: 10.1210/jc.2018-01566.Google Scholar
Jarde, A, Morais, M, Kingston, D, Giallo, R, MacQueen, GM, Giglia, L, Beyene, J, Wang, Y and McDonald, SD (2016) Neonatal outcomes in women with untreated antenatal depression compared with women without depression. JAMA Psychiatry 73, 826.CrossRefGoogle ScholarPubMed
Kamath-Rayne, BD, Rozance, PJ, Goldenberg, RL and Jobe, AH (2016) Antenatal corticosteroids beyond 34 weeks gestation: what do we do now? American Journal of Obstetrics and Gynecology 215, 423–430.CrossRefGoogle ScholarPubMed
Kapoor, A, Petropoulos, S and Matthews, SG (2008) Fetal programming of hypothalamic-pituitary-adrenal (HPA) axis function and behavior by synthetic glucocorticoids. Brain Research Reviews 57, 586–595.CrossRefGoogle ScholarPubMed
Kerstjens, JM, Bos, AF, ten Vergert, EMJ, de Meer, G, Butcher, PR and Reijneveld, SA (2009) Support for the global feasibility of the ages and stages questionnaire as developmental screener. Early Human Development 85, 443–447.CrossRefGoogle ScholarPubMed
Khalife, N, Glover, V, Taanila, A, Ebeling, H, Järvelin, M-R and Rodriguez, A (2013) Prenatal glucocorticoid treatment and later mental health in children and adolescents. PLoS ONE 8, e81394.CrossRefGoogle ScholarPubMed
Lahti, M, Savolainen, K, Tuovinen, S, Pesonen, A-K, Lahti, J, Heinonen, K, Hämäläinen, E, Laivuori, H, Villa, PM, Reynolds, RM, Kajantie, E and Räikkönen, K (2017) Maternal depressive symptoms during and after pregnancy and psychiatric problems in children. Journal of the American Academy of Child & Adolescent Psychiatry 56, 30–39.CrossRefGoogle ScholarPubMed
Lee, BK, Lessler, J and Stuart, EA (2011) Weight trimming and propensity score weighting. PLoS ONE 6, e18174.CrossRefGoogle ScholarPubMed
Lupien, SJ, McEwen, BS, Gunnar, MR and Heim, C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews. Neuroscience 10, 434–445.CrossRefGoogle ScholarPubMed
March of Dimes, PMNCH S the C, WHO (2012). Born too soon. The Global Action Report on Preterm Birth. CP Howson, MV Kinney, JE Lawn Eds. World Health Organization Publ. Geneva, 1–126.Google Scholar
Modi, N, Lewis, H, Al-Naqeeb, N, Ajayi-Obe, M, Doré, CJ and Rutherford, M (2001) The effects of repeated antenatal glucocorticoid therapy on the developing brain. Pediatric Research 50, 581–585.CrossRefGoogle ScholarPubMed
Noguchi, K (2014) Glucocorticoid induced cerebellar toxicity in the developing neonate: implications for glucocorticoid therapy during bronchopulmonary dysplasia. Cells 3, 36–52.CrossRefGoogle ScholarPubMed
Noorlander, CW, de Graan, PNE, Middeldorp, J, Van Beers, JJBC and Visser, GHA (2006) Ontogeny of hippocampal corticosteroid receptors: effects of antenatal glucocorticoids in human and mouse. Journal of Comparative Neurology 499, 924–932.CrossRefGoogle ScholarPubMed
Noorlander, CW, Tijsseling, D, Hessel, EVS, de Vries, WB, Derks, JB, Visser, GHA and de Graan, PNE (2014) Antenatal glucocorticoid treatment affects hippocampal development in mice. PLoS ONE 9, e85671.CrossRefGoogle ScholarPubMed
O'Halloran, CJ, Kinsella, GJ and Storey, E (2012) The cerebellum and neuropsychological functioning: a critical review. Journal of Clinical and Experimental Neuropsychology 34, 35–56.CrossRefGoogle ScholarPubMed
Pavlík, A, Buresová, M and Burešová, M (1984) The neonatal cerebellum: the highest level of glucocorticoid receptors in the brain. Developmental Brain Research 12, 13–20.CrossRefGoogle Scholar
Pihkala, J, Hakala, T, Petri, V and Raivio, K (1989) Uudet suomalaiset sikiön kasvukäyrät. Duodecim; Laaketieteellinen Aikakauskirja 105, 1540–1546.Google Scholar
Radloff, LS (1977) The CES-D scale: a self-report depression scale for research in the general population. Applied Psychological Measurement 1, 385–401.CrossRefGoogle Scholar
Reul, JMHM and De Kloet, ER (1985) Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology 117, 2505–2511.CrossRefGoogle ScholarPubMed
Reynolds, RM and Seckl, JR (2012) Antenatal glucocorticoid treatment: are we doing harm to term babies? Journal of Clinical Endocrinology and Metabolism 97, 3457–3459.CrossRefGoogle ScholarPubMed
Rosenberg, TJ, Garbers, S, Lipkind, H and Chiasson, MA (2005) Maternal obesity and diabetes as risk factors for adverse pregnancy outcomes: differences among 4 racial/ethnic groups. American Journal of Public Health 95, 1545–1551.CrossRefGoogle ScholarPubMed
Saccone, G and Berghella, V (2016) Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ (Clinical Research Ed.) 355, i5044.Google ScholarPubMed
Seckl, JR and Meaney, MJ (2004) Glucocorticoid programming. Annals of the New York Academy of Sciences 1032, 63–84.CrossRefGoogle ScholarPubMed
Squires, J, Bricker, D and Potter, L (1997) Revision of a parent-completed development screening tool: ages and stages questionnaire. Pediatric Psychology 22, 313–328.CrossRefGoogle Scholar
Steenis, LJP, Verhoeven, M, Hessen, DJ and van Baar, AL (2015) Parental and professional assessment of early child development: the ASQ-3 and the Bayley-III-NL. Early Human Development 91, 217–225.CrossRefGoogle ScholarPubMed
Stutchfield, P (2005) Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ 331, 662–660.CrossRefGoogle ScholarPubMed
Stutchfield, PR, Whitaker, R, Gliddon, AE, Hobson, L, Kotecha, S and Doull, IJM (2013) Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean section (ASTECS trial). Archives of Disease in Childhood. Fetal and Neonatal Edition 98, F195–F200.CrossRefGoogle Scholar
Sund, R (2012) Quality of the Finnish hospital discharge register: a systematic review. Scandinavian Journal of Public Health 40, 505–515.CrossRefGoogle ScholarPubMed
Sweet, DG, Carnielli, V, Greisen, G, Hallman, M, Ozek, E, Plavka, R, Saugstad, OD, Simeoni, U, Speer, CP, Vento, M, Visser, GHA and Halliday, HL (2017) European consensus guidelines on the management of respiratory distress syndrome – 2016 update. Neonatology 111, 107–125.CrossRefGoogle ScholarPubMed
The American College of Obstetricians and Gynecologists (2016) ACOG practice bulletin 171: management of preterm labor. Obstetrics & Gynecology 128, e155–e164.CrossRefGoogle Scholar
Tuovinen, S, Lahti-Pulkkinen, M, Girchenko, P, Lipsanen, J, Lahti, J, Heinonen, K, Reynolds, RM, Hämäläinen, E, Kajantie, E, Laivuori, H, Pesonen, A-K, Villa, PM and Räikkönen, K (2018) Maternal depressive symptoms during and after pregnancy and child developmental milestones. Depression and Anxiety 35, 732–741.CrossRefGoogle ScholarPubMed
Uotila, J, Vuorela, P, Koistinen, E, Nupponen, I, Nuutila, M, Raudaskoski, T, Tammela, O and Varesmaa-Korhonen, L and Working group set up by the Finnish Medical Society Duodecim and the Finnish Gynecologial Association (2011) Preterm Birth: Current Care Guidelines. Helsinki: The Finnish Medical Society Duodecim.Google Scholar
van der Voorn, B, Wit, JM, van der Pal, SM, Rotteveel, J and Finken, MJJ (2015) Antenatal glucocorticoid treatment and polymorphisms of the glucocorticoid and mineralocorticoid receptors are associated with IQ and behavior in young adults born very preterm. The Journal of Clinical Endocrinology & Metabolism 100, 500–507.CrossRefGoogle ScholarPubMed
Supplementary material: File

Wolford et al. supplementary material

Tables S1-S2, Figure S1 and Supplementary Text

Download Wolford et al. supplementary material(File)
File 1.1 MB