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Kari Laine, MD, PhD; Tuija Heikkinen, MD; Ulla Ekblad, MD, PhD; Pentti Kero, MD, PhD

Arch Gen Psychiatry. 2003;60:720-726.

Background  Selective serotonin reuptake inhibitors (SSRIs) have gained wide acceptance in the treatment of mental disorders in pregnant women, but there seems to be an increased risk for neonatal adaptation problems after exposure to SSRIs in late pregnancy. We aimed to investigate the perinatal sequelae of infants exposed to SSRIs during their fetal life and the relationship of these symptoms to the cord blood monoamine and prolactin concentrations.

Methods  We conducted a prospective, controlled, follow-up study with 20 mothers taking 20 to 40 mg/d of either citalopram or fluoxetine for depression (n = 10) or panic disorder (n = 10) and their infants and 20 matched controls not receiving psychotropic medication for confounding obstetric characteristics. Maternal cord blood and infant citalopram, fluoxetine, and norfluoxetine, cord blood monoamine and metabolite, and prolactin concentrations were measured. The newborns underwent standard clinical examination and specific assessment of serotonergic symptoms during the first 4 days of life and at the ages of 2 weeks and 2 months.

Results  There was a statistically significant (P = .008, V = 15, n = 20 for both groups), 4-fold difference in the serotonergic symptom score during the first 4 days of life between the SSRI group and the control group. The SSRI-exposed infants had significantly lower cord blood 5-hydroxyindoleacetic acid (5-HIAA) concentrations (P = .02, t₃₁ = 2.57) compared with the control group. A significant inverse correlation (r_s = -0.66, P = .007, n = 15) was seen between the serotonergic symptom score and the umbilical vein 5-HIAA concentrations in the SSRI-exposed but not the control infants.

Conclusions  Infants exposed to SSRIs during late pregnancy are at increased risk for serotonergic central nervous system adverse effects, and the severity of these symptoms is significantly related to cord blood 5-HIAA levels.

From the Departments of Pharmacology and Clinical Pharmacology (Drs Laine and Heikkinen), Obstetrics and Gynaecology (Drs Heikkinen and Ekblad), and Pediatrics (Dr Kero), University of Turku and Turku University Central Hospital, Turku, Finland.

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