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BEDREHELSE-Bedre helse og livskvalitet

Neurodevelopment of children exposed in utero to psychotropic drugs: a population-based cohort study

Awarded: NOK 3.3 mill.

Paracetamol exposure during pregnancy and child neurodevelopment: Paracetamol is used extensively during pregnancy, but studies regarding the potential neurodevelopmental sequelae of fetal paracetamol exposure are lacking. The aim of this study was therefore to study neurodevelopmental and behavioral outcomes after prenatal exposure to paracetamol. We used the prospective Norwegian Mother and Child Cohort Study. The mothers were asked to report on their use of paracetamol at gestational weeks 17 and 30 and 6 months post-partum. We used data on 48 631 children whose mothers returned the 3-year follow-up questionnaire. Within this sample were 2919 same-sex sibling pairs which were used to adjust for familial and genetic factors. We modeled psychomotor development (communication, fine and gross motor development), externalizing and internalizing behavior problems, and temperament (emotionality, activity, sociability, and shyness) based on prenatal paracetamol exposure using generalized linear regression, adjusting for a number of factors, including febrile illness, infections, and co-medication use during pregnancy. The sibling-control analysis revealed that children exposed to prenatal paracetamol for more than 28 days had poorer gross motor development, communication, externalizing behavior, internalizing behavior, and higher activity level. Children exposed prenatally to short-term use of paracetamol (1-27 days) also had poorer gross motor outcomes, but the effects were smaller than with long-term use. Ibuprofen exposure was not associated with neurodevelopmental outcomes. If replicated these findings suggest limiting long term use of paracetamol during pregnancy. Prenatal antidepressant exposure and child behavior: During their childbearing years up to 20% of women experience depression or other mood disorders. The safety of antidepressant use during pregnancy is therefore an important issue. Potential adverse effects of prenatal antidepressant exposure on child development are still debated. The possibility that associations are due to genetic or family environmental risks rather than antidepressant use per se cannot easily be ruled out in conventional studies. Our objective was therefore to evaluate the association between prenatal antidepressant exposure and behavioral problems in a sibling controlled study. This study used data on 10 902 sibling pairs identified from the population-based Norwegian Mother and Child Cohort Study recruited between 1999 and 2008. The mothers were asked to report antidepressant use at gestational weeks 17 and 30 and 6 months post-partum. Externalizing and internalizing behavioral problems were assessed by validated questionnaires sent to mothers 18- and 36-months postpartum. We performed sibling-control analyses to determine potential effects of antidepressant exposure. The results showed that prenatal exposure to antidepressants was associated with increased levels anxiety after adjusting for differences between pregnancies in symptoms of maternal depression. The effect of antidepressant exposure on anxiety symptoms was controlled for important potential confounders such as genetic effects, family environment and variation in symptoms of maternal depression between the womans pregnancies. The effect of prenatal antidepressant exposure was specific to anxiety, and not associated with emotional reactivity, somatic complaints, sleep problems, attention problems or aggression in the siblings. The study also found evidence that maternal depression was independently associated with child behaviour problems. The results of this study indicate that both antidepressant use and depression during pregnancy can have a negative effect on the child regardless of genetic or environmental factors that the child shares with siblings, such as their upbringing. The study has also taken into consideration the possibility that pregnant women who take antidepressants might take larger amounts of other medicines, or more alcohol. Taken together, these findings form a strong basis for identifying and implementing non-medical interventions to reduce antenatal depression whenever possible.However, in the case of severe depression, medical treatment may be necessary. The potential risks observed in the child must be balanced against the benefit of the mother remaining stable in her condition for both mother and baby. Brandlistuen, R.E, Ystrøm, E., Eberhard-Gran, M., Nulman, I., Koren, G. & Nordeng, H. (2015). Behavioural effects of fetal antidepressant exposure in a Norwegian cohort of discordant siblings. International Journal of Epidemiology 2015, Vol. 44, No. 4

Every year approximately 3000 children in Norway (5%) are exposed to psychotropic drugs during fetal life. Therapy with psychotropic drugs during pregnancy involves weighing possible risk of fetal exposure to medication against the potential adverse effec ts of untreated maternal mental disorder to both mother and child. Assessments of neurodevelopment risks of exposure to psychotropic drugs during fetal life are largely derived from small casus-control or cohort studies, all of which have inherent methodo logical limitations. Studies investigating neurodevelopment after exposure to psychotropic drugs during pregnancy are warranted. Our study will take the advantage of using the existing linkage between the Norwegian Mother and Child Cohort Study (MoBa-stu dy, www.fhi.no/morogbarn) and the Medical Birth Registry of Norway to identify children exposed to psychotropic medications during fetal life, and study child neurodevelopmental outcomes with a wide battery of validated psychometric instruments up to 3 ye ars of age. We will include a disease control group of children of women who have psychiatric illness who did not use the psychotropic medication in question during pregnancy, and a control group of children of women without psychiatric illness and drug u se during pregnancy. Using the latest quality assured Moba data files and requiring that the woman has completed questionnaires at pregnancy week 18 and 30 and information about the child is available at 36 months, we expect to include 40 000 women in the study and over 2000 exposed children. Different appropriate regression analysis will be used to analyze the association between medication exposures and psychomotor, temperament and behavioural outcomes. This study represents a unique possibility to expl ore the neurodevelopmental outcomes in children exposed to psychotropic drugs during fetal life, using a prospective, longitudinal, population based approach.

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BEDREHELSE-Bedre helse og livskvalitet