Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-26T08:03:26.479Z Has data issue: false hasContentIssue false

Prenatal exposure to selective serotonin reuptake inhibitors and risk of childhood overweight

Published online by Cambridge University Press:  09 January 2012

L. E. Grzeskowiak*
Affiliation:
Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia
A. L. Gilbert
Affiliation:
Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia
J. L. Morrison
Affiliation:
Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia
*
*Address for Correspondence: Mr L. Grzeskowiak, Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide SA 5001, Australia. (Email [email protected])

Abstract

The objective was to investigate the association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and overweight in offspring at 4–5 years of age. We conducted a retrospective cohort study using linked records from the Women's and Children's Health Network in South Australia, Australia. Women were eligible to participate if they gave birth to singleton, live-born infants between September 2000 and December 2005. Women were excluded if they received a dispensing for an antidepressant other than SSRIs or an antipsychotic or an anti-epileptic or had a chronic medical condition. Of the 6560 eligible women, 71 received a dispensing for an SSRI (exposed), 204 had a reported psychiatric illness but did not receive a dispensing for any antidepressant (untreated psychiatric illness) and 6285 did not have a reported psychiatric illness and did not receive a dispensing for any antidepressant (unexposed). Childhood overweight was classified as a body mass index >85th percentile, based on age and sex. At 4–5 years of age, female offspring of exposed mothers were less likely to be overweight compared with female offspring of mothers with an untreated psychiatric illness [adjusted Prevalence Ratio (aPR) 0.23; 95% confidence interval (CI) 0.05–0.98] and female offspring of unexposed mothers (aPR 0.27; 0.07–0.99). No association with overweight was observed among male offspring of exposed mothers compared with male offspring of mothers with an untreated psychiatric illness (aPR 1.17; 0.54–2.51) and male offspring of unexposed mothers (aPR 0.93; 0.52–1.67). Further research is required to confirm these findings and examine the potential mechanisms behind the sex-specific differences.

Type
Original Article
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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

1.Mant, A, Rendle, VA, Hall, WD, et al. Making new choices about antidepressants in Australia: the long view 1975–2002. MJA. 2004; 181 (Suppl 7), 21S24S.Google Scholar
2.Emslie, G, Judge, R. Tricyclic antidepressants and selective serotonin reuptake inhibitors: use during pregnancy, in children/adolescents and in the elderly. Acta Psychiatr Scand. 2000; 101 (Suppl 403), 26S34S.CrossRefGoogle Scholar
3.Goldstein, BJ, Goodnick, PJ. Selective serotonin reuptake inhibitors in the treatment of affective disorders-III. Tolerability, safety and pharmacoeconomics. J Psychopharmacol. 1998; 12 (3 Suppl B), 55S87S.CrossRefGoogle ScholarPubMed
4.Andrade, SE, Raebel, MA, Brown, J, et al. Use of antidepressant medications during pregnancy: a multisite study. Am J Ostet Gynecol. 2008; 198, 194.e191194.e195.CrossRefGoogle ScholarPubMed
5.Masand, PS, Gupta, S. Selective serotonin-reuptake inhibitors: an update. Harv Rev Psychiatry. 1999; 7, 6984.CrossRefGoogle ScholarPubMed
6.Van Harten, J. Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clin Pharmcokinet. 1993; 24, 203220.CrossRefGoogle ScholarPubMed
7.Grzeskowiak, LE, Gilbert, AL, Morrison, JL. Investigating outcomes following the use of SSRIs for treating depression in pregnancy: a focus on methodological issues. Drug Saf. 2011; 34, 10271048.CrossRefGoogle ScholarPubMed
8.Lattimore, KA, Donn, SM, Kaciroti, N, et al. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis. J Perinatol. 2005; 25, 595604.CrossRefGoogle ScholarPubMed
9.Whitaker-Azmitia, PM. Serotonin and brain development: role in human developmental diseases. Brain Res Bull. 2001; 56, 479485.CrossRefGoogle ScholarPubMed
10.Blundell, JE, Halford, JCG. Serotonin and appetite regulation: implications for the pharmacological treatment of obesity. CNS Drugs. 1998; 9, 473495.CrossRefGoogle Scholar
11.Halford, JC, Harrold, JA, Lawton, CL, Blundell, JE. Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity. Curr Drug Targets. 2005; 6, 201213.CrossRefGoogle ScholarPubMed
12.Sargent, BJ, Henderson, AJ. Targeting 5-HT receptors for the treatment of obesity. Curr Opin Pharmacol. 2011; 11, 5258.CrossRefGoogle ScholarPubMed
13.Li, Q, Wichems, CH, Ma, L, et al. Brain region specific alterations of 5 HT2A and 5 HT2C receptors in serotonin transporter knockout mice. J Neurochem. 2003; 84, 12561265.CrossRefGoogle ScholarPubMed
14.Li, Q, Wichems, C, Heils, A, Lesch, KP, Murphy, DL. Reduction in the density and expression, but not G-protein coupling, of serotonin receptors (5-HT1A) in 5-HT transporter knock-out mice: gender and brain region differences. J Neurosci. 2000; 20, 78887895.CrossRefGoogle Scholar
15.Bouali, S, Evrard, A, Chastanet, M, et al. Sex hormone dependent desensitization of 5-HT1A autoreceptors in knockout mice deficient in the 5-HT transporter. Eur J Neurosci. 2003; 18, 22032212.CrossRefGoogle Scholar
16.Line, SJ, Barkus, C, Coyle, C, et al. Opposing alterations in anxiety and species-typical behaviours in serotonin transporter overexpressor and knockout mice. Eur Neuropsychopharmacol. 2011; 21, 108116.CrossRefGoogle ScholarPubMed
17.Üçeyler, N, Schütt, M, Palm, F, et al. Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity. Int J Obes. 2010; 34, 701711.CrossRefGoogle ScholarPubMed
18.Lisboa, SFS, Oliveira, PE, Costa, LC, Venancio, EJ, Moreira, EG. Behavioral evaluation of male and female mice pups exposed to fluoxetine during pregnancy and lactation. Pharmacology. 2007; 80, 4956.CrossRefGoogle ScholarPubMed
19.Oberlander, TF, Gingrich, JA, Ansorge, MS. Sustained neurobehavioral effects of exposure to SSRI antidepressants during development: molecular to clinical evidence. Clin Pharmacol Ther. 2009; 86, 672677.CrossRefGoogle ScholarPubMed
20.Chambers, CD, Anderson, PO, Thomas, RG, et al. Weight gain in infants breastfed by mothers who take fluoxetine. Pediatrics. 1999; 104, e61e66.CrossRefGoogle ScholarPubMed
21.Merlob, P, Stahl, B, Sulkes, J. Paroxetine during breast-feeding: infant weight gain and maternal adherence to counsel. Eur J Pediatr. 2004; 163, 135139.CrossRefGoogle ScholarPubMed
22.Moretti, M, Sharma, A, Bar-Oz, B, Koren, G, Ito, S. Fluoxetine and its effects on the nursing infant: a prospective cohort study [Abstract]. Clin Pharmacol Ther. 1999; 65, 141.CrossRefGoogle Scholar
23.Hendrick, V, Smith, LM, Hwang, S, Altshuler, LL, Haynes, D. Weight gain in breastfed infants of mothers taking antidepressant medications. J Clin Psychiatry. 2003; 64, 410412.CrossRefGoogle ScholarPubMed
24.Lewis, AJ, Galbally, M, Opie, G, Buist, A. Neonatal growth outcomes at birth and one month postpartum following in utero exposure to antidepressant medication. Aust N Z J Psychiatry. 2010; 44, 482487.CrossRefGoogle ScholarPubMed
25.Grzeskowiak, LE, Gilbert, AL, Morrison, JL. Hospital pharmacy dispensing records for pharmacoepidemiology research into late gestation exposure to antidepressants. J Pharm Pract Res. 2010; 40, 265268.CrossRefGoogle Scholar
26.Cole, TJ, Bellizzi, MC, Flegal, KM, Dietz, WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ. 2000; 320, 12401245.CrossRefGoogle ScholarPubMed
27. South Australian Pregnancy Record. Retrieved 7 July 2011 from http://www.health.sa.gov.au/pehs/pregnancy-record.htmGoogle Scholar
28.McLean, A, Scott, J, Keane, R, Sage, L, Chan, A. Validation of the 1994 South Australian Perinatal Data Collection Form, 2001. Pregnancy Outcome Unit, Epidemiology Branch, Department of Human Services: Adelaide, South Australia.Google Scholar
29.Blair, EM, Liu, Y, De Klerk, NH, Lawrence, DM. Optimal fetal growth for the Caucasian singleton and assessment of appropriateness of fetal growth: an analysis of a total population perinatal database. BMC Pediatr. 2005; 5, 13.CrossRefGoogle ScholarPubMed
30.Australian Bureau of Statistics. Socio-Economic Indexes for Areas (SEIFA) – Technical Paper. 2008; Report no. 2039.0.55.001. ABS, Canberra.Google Scholar
31.Greenland, S. Model-based estimation of relative risks and other epidemiologic measures in studies of common outcomes and in case–control studies. Am J Epidemiol. 2004; 160, 301305.CrossRefGoogle ScholarPubMed
32.Olds, TS, Tomkinson, GR, Ferrar, KE, Maher, CA. Trends in the prevalence of childhood overweight and obesity in Australia between 1985 and 2008. Int J Obes. 2010; 34, 5766.CrossRefGoogle ScholarPubMed
33.Jovanovic, H, Lundberg, J, Karlsson, P, et al. Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET. Neuroimage. 2008; 39, 14081419.CrossRefGoogle ScholarPubMed
34.Cosgrove, KP, Mazure, CM, Staley, JK. Evolving knowledge of sex differences in brain structure, function, and chemistry. Biol Psychiatry. 2007; 62, 847855.CrossRefGoogle ScholarPubMed
35.Yadav, VK, Oury, F, Suda, N, et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009; 138, 976989.CrossRefGoogle ScholarPubMed
36.Collin, M, Bäckberg, M, Önnestam, K, Meister, B. 5-HT1A receptor immunoreactivity in hypothalamic neurons involved in body weight control. Neuroreport. 2002; 13, 945951.CrossRefGoogle ScholarPubMed
37.Hutson, P, Dourish, C, Curzon, G. Evidence that the hyperphagic response to 8-OH-DPAT is mediated by 5-HT1A receptors. Eur J Pharmacol. 1988; 150, 361366.CrossRefGoogle Scholar
38.Cabrera, TM, Battaglia, G. Delayed decreases in brain 5-hydroxytryptamine2A/2C receptor density and function in male rat progeny following prenatal fluoxetine. J Pharmacol Exp Ther. 1994; 269, 637645.Google ScholarPubMed
39.Qu, Y, Villacreses, N, Murphy, DL, Rapoport, SI. 5-HT2A/2C receptor signaling via phospholipase A2 and arachidonic acid is attenuated in mice lacking the serotonin reuptake transporter. Psychopharmacology. 2005; 180, 1220.CrossRefGoogle ScholarPubMed
40.Moya, P, Fox, M, Jensen, C, et al. Altered 5-HT2C receptor agonist-induced responses and 5-HT2C receptor RNA editing in the amygdala of serotonin transporter knockout mice. BMC Pharmacol. 2011; 11, 3.CrossRefGoogle ScholarPubMed
41.Li, J, Olsen, J, Vestergaard, M, Obel, C, Baker, JL, et al. Prenatal stress exposure related to maternal bereavement and risk of childhood overweight. PLoS One. 2010; 5, e11896.CrossRefGoogle ScholarPubMed
42.Colvin, L, Slack Smith, L, Stanley, FJ, Bower, C. Dispensing patterns and pregnancy outcomes for women dispensed selective serotonin reuptake inhibitors in pregnancy. Birth Defects Res A Clin Mol Teratol. 2011; 91, 142152.CrossRefGoogle ScholarPubMed
43.Bakker, MK, Kolling, P, van den Berg, PB, de Walle, HEK, de Jong van den Berg, LTW. Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population-based cohort study from the Netherlands. Br J Clin Pharmacol Apr. 2008; 65, 600606.CrossRefGoogle ScholarPubMed
44.Alwan, S, Reefhuis, J, Rasmussen, SA, Friedman, JM. Patterns of antidepressant medication use among pregnant women in a United States population. J Clin Pharmacol. 2011; 51, 264270.CrossRefGoogle Scholar
45.Kallen, B. Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med. 2004; 158, 312316.CrossRefGoogle ScholarPubMed
46.Oberlander, TF, Warburton, W, Misri, S, Aghajanian, J, Hertzman, C. Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Arch Gen Psychiatry. 2006; 63, 898906.CrossRefGoogle ScholarPubMed
47.Chambers, CD, Johnson, KA, Dick, LM, Felix, RJ, Jones, KL. Birth outcomes in pregnant women taking fluoxetine. N Engl J Med. 1996; 335, 10101015.CrossRefGoogle ScholarPubMed
48.Oberlander, TF, Warburton, W, Misri, S, Aghajanian, J, Hertzman, C. Effects of timing and duration of gestational exposure to serotonin reuptake inhibitor antidepressants: population-based study. Br J Psychiatry. 2008; 192, 338343.CrossRefGoogle ScholarPubMed
49.Malm, H, Klaukka, T, Neuvonen, PJ. Risks associated with selective serotonin reuptake inhibitors in pregnancy. Obstet Gynecol. 2005; 106, 12891296.CrossRefGoogle ScholarPubMed
50.Ertel, KA, Koenen, KC, Rich-Edwards, JW, Gillman, MW, Myer, L. Maternal depressive symptoms not associated with reduced height in young children in a US prospective cohort study. PLoS One. 2010; 5, e13656.CrossRefGoogle ScholarPubMed
51.Barnett, LM, Van Beurden, E, Morgan, PJ, Brooks, LO, Beard, J. Childhood motor skill proficiency as a predictor of adolescent physical activity. J Adolesc Health. 2009; 44, 252259.CrossRefGoogle ScholarPubMed