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effects. The finding of an increased risk of asthma after exposure toibuprofen and diclofenac warrants further investigation.

http://dx.doi.org/10.1016/j.reprotox.2013.02.024

4 Abstracts / Reproductive

renatal exposure to SSRIs or untreated maternal depressionnd perinatal outcome

eli Malm a,b,c,∗, Miia Artama c,d, Alan S. Brown e,f,ika Gissler c,g,h, David Gyllenberg c,i,

usanna Hinkka-Yli-Salomäki c, Ian McKeague j,ndre Sourander c,e

Teratology Information, HUSLAB, Helsinki, FinlandDepartment of Clinical Pharmacology, Helsinki University andelsinki University Central Hospital, Helsinki, FinlandUniversity of Turku, Department of Child Psychiatry, Turku, FinlandThe Finnish Cancer Registry, Helsinki, FinlandDepartment of Psychiatry, Columbia University College of Physiciansnd Surgeons, New York State Psychiatric Institute, New York, NY, USADepartment of Epidemiology, Columbia University, Mailman Schoolf Public Health, New York, NY, USANational Institute for Health and Welfare, Helsinki, FinlandNordic School of Public Health, Gothenburg, Gothenburg, SwedenHelsinki University and Helsinki University Central Hospital, Chidl-en’s Hospital, Department of Child Psychiatry, Helsinki, FinlandMailman School of Public Health, Department of Biostatistics,olumbia University College of Physicians and Surgeons, New York,Y, USA

Introduction: Use of selective serotonin reuptake inhibitorsSSRIs) during pregnancy has been associated with adverse peri-atal outcome, but the impact of maternal depression remains toe confirmed.

Methods: This is a cohort study based on national registersn Finland: the Medical Birth Register, the Register of Congenital

alformations, the Hospital Discharge Register, the Drug Reim-ursement Register and the Population Register. The total studyopulation includes 845,345 women and their live-born, singletonffspring born during January 1, 1996–December 31, 2010. Peri-atal outcome is compared between offspring exposed prenatallyo SSRIs (n = 15,780) and offspring exposed prenatally to maternalepression but unexposed to antidepressants (n = 9679).

Results: Mean gestational length was marginally shorter andean birth weight marginally lower in the depression-only than in

he SSRI-exposed group (39.1 gestational weeks vs. 39.2 gestationaleeks and 3474.3 g vs. 3502.0 g; P < 0.0001 for both). Similarly,reterm (<37 gestational weeks) and very preterm birth (<32 ges-ational weeks) were both more common in the depression-onlyroup (6.7% vs.5.7% and 1.3% vs. 0.9%, respectively; P = 0.001 foroth), as was low birth weight (<2500 g) (4.6% vs. 3.8%; P = 0.002).o difference between the groups was observed in being born small

or gestational age (2.5% in both groups). SSRI-exposed offspringere more likely to need treatment in neonatal care unit (15.4% vs.

2.2%; P < 0.0001), while persistent pulmonary hypertension of theewborn was not more common in SSRI-exposed (0.08% vs. 0.03%

n the depression-only group; P = 0.19). The prevalence of majorongenital anomalies did not differ between the groups (3.9% foroth) and there was no difference in infant mortality < 1 year’s age0.4% in SSRI-exposed vs. 0.5% in depression-only group; P = 0.13).

Conclusions: Maternal depression-related factors other thanSRI use may predisposeto certain perinatal adverse outcomes.

This study represents the epidemiological part of an interna-ional, collaborative research project in context with the Conteenter for the Neuroscience of Mental Disorders at Columbia Uni-ersity (http://columbiapsychiatry.org). The study is funded by aIH Grant P50MH090966 and the SacklerCenter.

ttp://dx.doi.org/10.1016/j.reprotox.2013.02.023

ology 37 (2013) 77–87

Effects of ibuprofen, diclofenac, naproxen, and piroxicam onthe course of pregnancy and pregnancy outcome: A prospectivecohort study

Katerina Nezvalová-Henriksen a,∗, Olav Spigset b,c,Hedvig M.E. Nordeng a,d

a University of Oslo, Oslo, Norwayb St Olav’s University Hospital, Trondheim, Norwayc Norwegian University of Science and Technology, Trondheim, Norwayd National Institute of Health, Oslo, Norway

Introduction: NSAIDs form the basis of first-line therapy for con-ditions such as headache and musculoskeletal diseases that oftenmanifest during pregnancy. Studies have so far mainly focused onearly exposure and the risk of miscarriage and cardiac defects orlate exposure and the risk of premature closure of ductusarterio-sus. Most studies present their findings as a group effect, and dataon the safety of individual NSAIDs remain scarce. Our aim was toassess the safety of ibuprofen, diclofenac, naproxen, and piroxi-cam with emphasis on immediate pregnancy outcomes (survival,malformations, birth weight, prematurity, haemorrhage, perinatalcomplication) and asthmatic symptoms in the 18 month old child.

Methods: We used The Norwegian Mother and Child CohortStudy dataset to obtain information on maternal socio-demographic and medical characteristics, and the health ofthe child up to 18 months postpartum. The Norwegian Motherand Child Cohort Study is a nationwide prospective cohort studycovering over 100 000 pregnancies. Its aim is to examine theeffect of a vast array of exposures on pregnancy outcome and thehealth of the mother and child. Data stem from self-administeredquestionnaires. We used the Medical Birth Registry of Norway(MBRN) to obtain information on pregnancy outcome. The registrycomprises all births in Norway and prospectively collects data onall deliveries using standardised forms. The datasets were linkedvia the maternal personal identification number. Associationsbetween NSAID use and outcomes were identified using logisticregression analyses.

Results: Of the 90 417 women included in the study, 6511 (7.2%)used one or more of the four NSAIDs during pregnancy. No effecton infant survival, congenital malformation rate, or structural heartdefect rate was found for any of the NSAIDs investigated. Ibupro-fen and diclofenac were associated with low birth weight (adjustedOR 1.7, 95% CI 1.3–2.3 and adjusted OR 3.1, 95% CI 1.1–9.0, respec-tively). Use of diclofenac during the 3rd trimester was associatedwith maternal vaginal bleeding (adjusted OR 1.8, 95% CI 1.1–3.0).Furthermore, infants exposed to ibuprofen during the 2nd trimester(adjusted OR 1.5, 95% CI 1.2–1.9) or 3rd trimester (adjusted OR 1.5,95% CI 1.1–2.1) had an increased risk of asthma at the age of 18months.

Conclusions: The increased risk of low birth weight may partlyhave been caused by underlying inflammatory conditions and wasreassuringly similar to the general baseline risk of low birth weight.The significant association between diclofenac use late in preg-nancy and maternal bleeding is consistent with its pharmacological