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Serotonin and poor neonatal adaptation after antidepressant exposure in utero

  • Noera Kieviet (a1), Vera van Keulen (a1), Peter Marinus van de Ven (a2), Koert Melchior Dolman (a1), Martine Deckers (a3) and Adriaan Honig (a4) (a5)...

Abstract

Objective

Infants exposed to selective antidepressants (SADs) in utero are at risk to develop poor neonatal adaptation (PNA) postpartum. As symptoms are non-specific and the aetiology of PNA is unknown, the diagnostic process is hampered. We hypothesised that the serotonin metabolism plays a role in the aetiology of PNA.

Methods

In this controlled study, infants admitted postpartum from February 2012 to August 2013 were included and followed for 3 days. Infants exposed to SADs during at least the last 2 weeks of fetal life were included in the patient group (n=63). Infants not exposed to psychotropic medication and admitted postpartum for another reason were included in the control group (n=126). The neonatal urinary 5-hydroxyindoleacetid acid (5-HIAA) levels of SAD-exposed infants who developed PNA, SAD-exposed infants who did not develop PNA and control infants were compared.

Results

The course of the 5-HIAA levels over the first 3 days postpartum differed between infants with and without PNA (p≤0.001) with higher 5-HIAA levels in infants with PNA on day 1 (2.42 mmol/mol, p=0.001). Presence of maternal psychological distress modified this relationship.

Conclusions

A transient disturbance of the neonatal serotonergic system may play a role in the aetiology of PNA. Other factors, including the presence of maternal psychological distress, also seem to play a role.

Copyright

Corresponding author

Dr. Noera Kieviet, OLVG West, Department of Pediatrics, Jan Tooropstraat 164, 1061 AE Amsterdam, The Netherlands. Tel: +31 20 510 8790; Fax :+31 20 685 3059; E-mail: noera.kieviet@gmail.com

References

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1. Kieviet, N, Dolman, KM, Honig, A. The use of psychotropic medication during pregnancy: how about the newborn? Neuropsychiatr Dis Treat 2013;9:12571266.
2. Levinson-Castiel, R, Merlob, P, Linder, N, Sirota, L, Klinger, G. Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediatr Adolesc Med 2006;160:173176.
3. Sie, SD, Wennink, JMB, van Driel, JJ et al. Maternal use of SSRIs, SNRIs and NaSSAs: practical recommendations during pregnancy and lactation. Arch Dis Child Fetal Neonatal Ed 2012;97:F472F476.
4. Moses-Kolko, EL, Bogen, D, Perel, J et al. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA 2005;293:23722383.
5. Ferreira, E, Carceller, AM, Agogue, C et al. Effects of selective serotonin reuptake inhibitors and venlafaxine during pregnancy in term and preterm neonates. Pediatrics 2007;119:5259.
6. Ray, S, Stowe, ZN. The use of antidepressant medication in pregnancy. Best Pract Res Clin Obstet Gynaecol 2014;28:7183.
7. Ververs, T, Kaasenbrood, H, Visser, G, Schobben, F, de Jong-van den Berg, L, Egberts, T. Prevalence and patterns of antidepressant drug use during pregnancy. Eur J Clin Pharmacol 2006;62:863870.
8. Oberlander, TF, Misri, S, Fitzgerald, CE, Kostaras, X, Rurak, D, Riggs, W. Pharmacologic factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure. J Clin Psychiatry 2004;65:230237.
9. Laine, K, Heikkinen, T, Ekblad, U, Kero, P. Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry 2003;60:720726.
10. Klinger, G, Merlob, P. Selective serotonin reuptake inhibitor induced neonatal abstinence syndrome. Isr J Psychiatry Relat Sci 2008;45:107113.
11. Davidson, S, Prokonov, D, Taler, M et al. Effect of exposure to selective serotonin reuptake inhibitors in utero on fetal growth: potential role for the IGF-I and HPA axes. Pediatr Res 2009;65:236241.
12. Jansson, LM, Velez, M. Neonatal abstinence syndrome. Curr Opin Pediatr 2012;24:252258.
13. Field, T, Diego, M, Hernandez-Reif, M. Prenatal depression effects and interventions: a review. Infant Behav Dev 2010;33:409418.
14. Byatt, N, Deligiannidis, KM, Freeman, MP. Antidepressant use in pregnancy: a critical review focused on risks and controversies. Acta Psychiatr Scand 2013;127:94114.
15. 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.
16. Hilli, J, Heikkinen, T, Rontu, R et al. MAO-A and COMT genotypes as possible regulators of perinatal serotonergic symptoms after in utero exposure to SSRIs. Eur Neuropsychopharmacol 2009;19:363370.
17. Finnegan, LP, Kron, RE, Connaughton, JF, Emich, JP. Assessment and treatment of abstinence in the infant of the drug-dependent mother. Int J Clin Pharmacol Biopharm 1975;12:1932.
18. American Society of Health-System pharmacists. AHFS Drug Information 2012. ASHP, Maryland, United States, 2012.
19. Definition of ilicit drugs by the United Nations Office on Drugs and Crime. Available at www.unodc.org. Accessed August 1, 2015.
20. Roelofs-Thijssen, MAMA, Schreuder, MF, Hogeveen, M, van Herwaarden, AE. Reliable laboratory urinalysis results using a new standardised urine collection device. Clin Biochem 2013;46:12521256.
21. Boix, F, Wøien, G, Sagvolden, T. Short term storage of samples containing monoamines: ascorbic acid and glutathione give better protection against degradation than perchloric acid. J Neurosci Methods 1997;75:6973.
22. Hessels, J, Cairo, DW, Slettenhaar, M, Dogger, M. PeeSpot; urine home collection device Innovatieve methode voor verzamelen van portie urine. Ned Tijdschr Klin Chem Labgeneesk 2011;36:249251.
23. van Praag, HM. Psychofarmaca. Assen, the Netherlands, van Gorcum, 2001.
24. Berg, C, Backström, T, Winberg, S, Lindberg, R, Brandt, I. Developmental exposure to fluoxetine modulates the serotonin system in hypothalamus. PLoS One 2013;8:e55053.
25. Zigmond, AS, Snaith, RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983;67:361370.
26. Herrmann, C. International experiences with the Hospital Anxiety and Depression Scale – a review of validation data and clinical results. J Psychosom Res 1997;42:1741.
27. Dutch birgweight curves, Dutch perinatal registration.Available at www.perinatreg.nl. Accessed August 1, 2015.
28. Kieviet, N, van Ravenhorst, M, Dolman, KM et al. Adapted Finnegan scoring list for observation of anti-depressant exposed infants. J Matern Fetal Neonatal Med 2014:15.
29. Twisk, JWR. Applied Longitudinal Data Analysis for Epidemiology. Cambridge: Cambridge University Press, 2013.
30. Peters, DA. Maternal stress increases fetal brain and neonatal cerebral cortex 5-hydroxytryptamine synthesis in rats: a possible mechanism by which stress influences brain development. Pharmacol Biochem Behav 1990;35:943947.
31. Pawluski, JL, Galea, LAM, Brain, U, Papsdorf, M, Oberlander, TF. Neonatal S100B protein levels after prenatal exposure to selective serotonin reuptake inhibitors. Pediatrics 2009;124:e662e670.
32. Marc, DT, Ailts, JW, Campeau, DCA, Bull, MJ, Olson, KL. Neurotransmitters excreted in the urine as biomarkers of nervous system activity: validity and clinical applicability. Neurosci Biobehav Rev 2011;35:635644.
33. Esler, M, Lambert, E, Alvarenga, M et al. Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor. Stress 2007;10:295304.
34. Birkenhäger, TK, van den Broek, WW, Fekkes, D, Mulder, PG, Moleman, P, Bruijn, JA. Lithium addition in antidepressant-resistant depression: effects on platelet 5-HT, plasma 5-HT and plasma 5-HIAA concentration. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:10841088.
35. Sarrias, MJ, Cabré, P, Martínez, E, Artigas, F. Relationship between serotoninergic measures in blood and cerebrospinal fluid simultaneously obtained in humans. J Neurochem 1990;54:783786.
36. Tellez, MR, Mamikunian, G, O’Dorisio, TM, Vinik, AI, Woltering, EA. A single fasting plasma 5-HIAA value correlates with 24-hour urinary 5-HIAA values and other biomarkers in midgut neuroendocrine tumors (NETs). Pancreas 2013;42:405410.

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Serotonin and poor neonatal adaptation after antidepressant exposure in utero

  • Noera Kieviet (a1), Vera van Keulen (a1), Peter Marinus van de Ven (a2), Koert Melchior Dolman (a1), Martine Deckers (a3) and Adriaan Honig (a4) (a5)...

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