prenatal exposure to ssris or untreated maternal depression and perinatal outcome

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84 Abstracts / Reproductive Toxicology 37 (2013) 77–87 Prenatal exposure to SSRIs or untreated maternal depression and perinatal outcome Heli Malm a,b,c,, Miia Artama c,d , Alan S. Brown e,f , Mika Gissler c,g,h , David Gyllenberg c,i , Susanna Hinkka-Yli-Salomäki c , Ian McKeague j , Andre Sourander c,e a Teratology Information, HUSLAB, Helsinki, Finland b Department of Clinical Pharmacology, Helsinki University and Helsinki University Central Hospital, Helsinki, Finland c University of Turku, Department of Child Psychiatry, Turku, Finland d The Finnish Cancer Registry, Helsinki, Finland e Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, NY, USA f Department of Epidemiology, Columbia University, Mailman School of Public Health, New York, NY, USA g National Institute for Health and Welfare, Helsinki, Finland h Nordic School of Public Health, Gothenburg, Gothenburg, Sweden i Helsinki University and Helsinki University Central Hospital, Chidl- ren’s Hospital, Department of Child Psychiatry, Helsinki, Finland j Mailman School of Public Health, Department of Biostatistics, Columbia University College of Physicians and Surgeons, New York, NY, USA Introduction: Use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with adverse peri- natal outcome, but the impact of maternal depression remains to be confirmed. Methods: This is a cohort study based on national registers in Finland: the Medical Birth Register, the Register of Congenital Malformations, the Hospital Discharge Register, the Drug Reim- bursement Register and the Population Register. The total study population includes 845,345 women and their live-born, singleton offspring born during January 1, 1996–December 31, 2010. Peri- natal outcome is compared between offspring exposed prenatally to SSRIs (n = 15,780) and offspring exposed prenatally to maternal depression but unexposed to antidepressants (n = 9679). Results: Mean gestational length was marginally shorter and mean birth weight marginally lower in the depression-only than in the SSRI-exposed group (39.1 gestational weeks vs. 39.2 gestational weeks and 3474.3 g vs. 3502.0 g; P < 0.0001 for both). Similarly, preterm (<37 gestational weeks) and very preterm birth (<32 ges- tational weeks) were both more common in the depression-only group (6.7% vs.5.7% and 1.3% vs. 0.9%, respectively; P = 0.001 for both), as was low birth weight (<2500 g) (4.6% vs. 3.8%; P = 0.002). No difference between the groups was observed in being born small for gestational age (2.5% in both groups). SSRI-exposed offspring were more likely to need treatment in neonatal care unit (15.4% vs. 12.2%; P < 0.0001), while persistent pulmonary hypertension of the newborn was not more common in SSRI-exposed (0.08% vs. 0.03% in the depression-only group; P = 0.19). The prevalence of major congenital anomalies did not differ between the groups (3.9% for both) and there was no difference in infant mortality < 1 year’s age (0.4% in SSRI-exposed vs. 0.5% in depression-only group; P = 0.13). Conclusions: Maternal depression-related factors other than SSRI use may predisposeto certain perinatal adverse outcomes. This study represents the epidemiological part of an interna- tional, collaborative research project in context with the Conte Center for the Neuroscience of Mental Disorders at Columbia Uni- versity (http://columbiapsychiatry.org). The study is funded by a NIH Grant P50MH090966 and the SacklerCenter. http://dx.doi.org/10.1016/j.reprotox.2013.02.023 Effects of ibuprofen, diclofenac, naproxen, and piroxicam on the course of pregnancy and pregnancy outcome: A prospective cohort study Kateˇ rina Nezvalová-Henriksen a,, Olav Spigset b,c , Hedvig M.E. Nordeng a,d a University of Oslo, Oslo, Norway b St Olav’s University Hospital, Trondheim, Norway c Norwegian University of Science and Technology, Trondheim, Norway d 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 often manifest during pregnancy. Studies have so far mainly focused on early exposure and the risk of miscarriage and cardiac defects or late exposure and the risk of premature closure of ductusarterio- sus. Most studies present their findings as a group effect, and data on the safety of individual NSAIDs remain scarce. Our aim was to assess the safety of ibuprofen, diclofenac, naproxen, and piroxi- cam with emphasis on immediate pregnancy outcomes (survival, malformations, birth weight, prematurity, haemorrhage, perinatal complication) and asthmatic symptoms in the 18 month old child. Methods: We used The Norwegian Mother and Child Cohort Study dataset to obtain information on maternal socio- demographic and medical characteristics, and the health of the child up to 18 months postpartum. The Norwegian Mother and Child Cohort Study is a nationwide prospective cohort study covering over 100 000 pregnancies. Its aim is to examine the effect of a vast array of exposures on pregnancy outcome and the health of the mother and child. Data stem from self-administered questionnaires. We used the Medical Birth Registry of Norway (MBRN) to obtain information on pregnancy outcome. The registry comprises all births in Norway and prospectively collects data on all deliveries using standardised forms. The datasets were linked via the maternal personal identification number. Associations between NSAID use and outcomes were identified using logistic regression 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 effect on infant survival, congenital malformation rate, or structural heart defect rate was found for any of the NSAIDs investigated. Ibupro- fen and diclofenac were associated with low birth weight (adjusted OR 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 associated with 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 18 months. Conclusions: The increased risk of low birth weight may partly have been caused by underlying inflammatory conditions and was reassuringly 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 effects. The finding of an increased risk of asthma after exposure to ibuprofen and diclofenac warrants further investigation. http://dx.doi.org/10.1016/j.reprotox.2013.02.024

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Page 1: Prenatal exposure to SSRIs or untreated maternal depression and perinatal outcome

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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