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Migraine affects up to 25% of women of reproductive age. In the majority of these women, migraine improves progressively during pregnancy, but symptoms generally recur shortly after delivery. As suboptimally treated migraine in pregnancy could have negative consequences for both mother and fetus, the primary aim of clinicians should be to provide optimal treatment according to stage of pregnancy, while minimising possible risks related to drug therapy. Nonpharmacological approaches are always first-line treatment, and should also be used to complement any required drug treatment. Paracetamol is the preferred drug for acute treatment throughout pregnancy. If paracetamol is not sufficiently effective, sporadic use of sumatriptan can be considered. NSAIDs such as ibuprofen can also be used under certain circumstances, though their intake in the first and third trimesters is associated with specific risks and contraindications. Preventive treatment should only be considered in the most severe cases. In women contemplating pregnancy, counselling is essential to promote a safe and healthy pregnancy and postpartum period for the mother and child, and should involve a dialogue addressing maternal concerns and expectations about drug treatment. This Review summarizes current evidence of the safety of the most common antimigraine medications during pregnancy and breastfeeding, and provides treatment recommendations for use in clinical practice.

To investigate the individual effects of ibuprofen, diclofenac, naproxen, and piroxicam on pregnancy outcome.Cohort study.Norwegian population.A total of 90 417 women and singleton child pairs.The Norwegian Mother and Child Cohort Study and Medical Birth Registry of Norway data sets were used.Infant survival, congenital malformations, structural heart defects, neonatal complications, haemorrhage during pregnancy and postpartum, asthma at age of 18 months.One or more of the four nonsteroidal anti-inflammatory drugs (NSAIDs) were used by 6511 pregnant women (7.2%). No effect on rates of infant survival, congenital malformation, or structural heart defects was found. The use of ibuprofen in the second trimester was significantly associated with low birthweight (adjusted OR 1.7, 95% CI 1.3-2.3), and ibuprofen use in the second and third trimesters was significantly associated with asthma in 18-month-old children (adjusted OR 1.5, 95% CI 1.2-1.9; adjusted OR 1.5, 95% CI 1.1-2.1). The use of diclofenac in the second trimester was significantly associated with low birthweight (adjusted OR 3.1, 95% CI 1.1-9.0), whereas diclofenac use in the third trimester was significantly associated with maternal vaginal bleeding (adjusted OR 1.8, 95% CI 1.1-3.0). No associations with other neonatal complications were found.The lack of associations with congenital malformations is reassuring. The significant association between diclofenac and ibuprofen use late in pregnancy, and maternal bleeding and asthma in the child, respectively, is consistent with their pharmacological effects. The increased risk of low birthweight may partly have been caused by underlying inflammatory conditions, and was reassuringly similar to the expected baseline risk of low birthweight.

Background Up to 10% of women are exposed to selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Information on their effect on birthweight and gestational age remains conflicting. The aim of this sibling-controlled prospective cohort study is to address shared geneticand family-level confounding to investigate the effects of prenatal SSRI exposure and maternal depression on birthweight and gestational age. Methods We used the Norwegian Mother and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). Our study population consisted of 27 756 siblings; 194 were prenatally exposed to SSRIs and 27 500 were unexposed to any antidepressant medication. Random and fixed effects analysis with propensity score adjustment was used to evaluate the effectson birthweight and gestational age. Results SSRI exposure during two or more trimesters was associated with a decrease in birthweight of 205 g [95% confidence interval (CI) -372 to - 38] and a decrease in gestational length of 4.9 days (95% CI - 9.1 to - 1.4). Neither maternal SSRI use in one trimester, lifetime history of major depression nor depressive symptoms during pregnancy were associated with these pregnancy outcomes (for non-pharmacologically treated depression in two periods in pregnancy, +5 g (95% CI - 56 to + 67) and +4.9 days (95% CI - 4.7 to + 14.7), respectively). Conclusions Prenatal exposure to SSRIs during two or more trimesters may decrease birthweight and gestational length. Our results indicate that neither maternal depression nor shared genetics and family environment fully explain this association.

Background Guidelines on codeine safety during pregnancy rely on small studies with inconsistent results, and associations between codeine use during pregnancy and increased risk of congenital malformations remain unsubstantiated. Objectives Our objective was to analyze the effect of codeine on pregnancy outcome. Methods Pregnancy outcomes of 2,666 women who used codeine during pregnancy were compared with 65,316 women who used no opioids during pregnancy. Information on maternal sociodemographic and medical characteristics, potential confounders, and pregnancy outcome was obtained from The Norwegian Mother and Child Cohort Study [den norske Mor & barn-undersøkelsen (MoBa)] data set and the Medical Birth Registry of Norway (MBRN) data set. The data sets were linked via the maternal personal identification number. Associations between codeine therapy and pregnancy outcomes were identified using logistic regression analyses. Results No significant differences were found in the survival rate [adjusted odds ratio (OR) 0.9, 95% confidence interval (CI) 0.6–1.5] or the congenital malformation rate (adjusted OR 0.9, 95% CI 0.8–1.1) between codeine-exposed and unexposed infants. Codeine use anytime during pregnancy was associated with planned Cesarean delivery (adjusted OR 1.4, 95% CI 1.2–1.7; P

Little is known about factors associated with migraine pharmacotherapy during pregnancy. Of 60 435 pregnant women in a population-based cohort, 3480 (5.8%) reported having migraine during the first 5 months of pregnancy. Of these, 2525 (72.6%) reported using migraine pharmacotherapy, mostly non-narcotic analgesics (54.1%) and triptans (25.4%). After adjustment for sociodemographic factors and comorbidities in logistic regression analysis, high pregestational body mass index [odds ratio (OR) 1.3, 95% confidence interval (CI) 1.2, 1.4], sleep < 5 h (OR 1.6, 95% CI 1.3, 1.9), being on sick-leave (OR 1.3, 95% CI 1.2, 1.5) and acute back/shoulder/neck pain (OR 0.6, 95% CI 0.6, 0.7) were associated with migraine pharmacotherapy during pregnancy. Many women need drug treatment for migraine during pregnancy, and the choice of pharmacotherapy during this period may be influenced by maternal sociodemographic factors and comorbidities.

Migraine affects up to 25% of women of reproductive age. In the majority of these women, migraine improves progressively during pregnancy, but symptoms generally recur shortly after delivery. As suboptimally treated migraine in pregnancy could have negative consequences for both mother and fetus, the primary aim of clinicians should be to provide optimal treatment according to stage of pregnancy, while minimising possible risks related to drug therapy. Nonpharmacological approaches are always first-line treatment, and should also be used to complement any required drug treatment. Paracetamol is the preferred drug for acute treatment throughout pregnancy. If paracetamol is not sufficiently effective, sporadic use of sumatriptan can be considered. NSAIDs such as ibuprofen can also be used under certain circumstances, though their intake in the first and third trimesters is associated with specific risks and contraindications. Preventive treatment should only be considered in the most severe cases. In women contemplating pregnancy, counselling is essential to promote a safe and healthy pregnancy and postpartum period for the mother and child, and should involve a dialogue addressing maternal concerns and expectations about drug treatment. This Review summarizes current evidence of the safety of the most common antimigraine medications during pregnancy and breastfeeding, and provides treatment recommendations for use in clinical practice.

Knowledge on triptan safety during pregnancy remains limited to their class effect or studies on sumatriptan. Our aim was to evaluate the individual effect of four most frequently used triptans on several pregnancy outcomes. We used the Norwegian prescription database to access information on triptans redeemed by pregnant women living in Norway between 2004 and 2007. This database was linked to the Medical Birth Registry of Norway covering every institutional delivery in Norway and providing information on pregnancy, delivery, maternal and neonatal health. Estimates of associations with pregnancy outcomes were obtained by Generalised Estimation Equations analysis. Of the 181,125 women in our study, 1,465 (0.8 %) redeemed triptans during pregnancy, and 1,095 (0.6 %) redeemed triptans before pregnancy only (disease comparison group). The population comparison group comprised the remaining 178,565 women. Using this group as reference, we found no associations between triptan redemption during pregnancy and congenital malformations. Second trimester redemption was associated with postpartum haemorrhage (adjusted OR 1.57; 95 % CI 1.19–2.07). The disease comparison group had an increased risk of major congenital malformations (adjusted OR 1.48; 95 % CI 1.11–1.97), low birth weight (adjusted OR 1.39; 95 % CI 1.08–1.81), and preterm birth (adjusted OR 1.30; 95 % CI 1.06–1.60). The association of triptans with postpartum hemorrhage could be attributable to decreased platelet agreeability occurring in severe migraine. Likewise, the increased risk of major congenital malformations and other adverse pregnancy outcomes in the disease comparison group might be attributable to migraine severity.

Objective.—To evaluate the safety of triptan therapy during pregnancy. Background.—Information on the safety of triptan therapy during pregnancy is scarce and only available for sumatriptan, naratriptan, and rizatriptan. No associations with congenital malformations have been detected so far, but one study found a significant association between sumatriptan exposure during pregnancy and prematurity. Methods.—The study population consisted of 69,929 pregnant women and their newborn children for whom data on drug exposure and pregnancy outcome were available. Information on triptan therapy and potential socio-demographic and medical confounding factors was obtained from the Norwegian Mother and Child Cohort Study. Information on congenital malformations and other adverse pregnancy outcomes was obtained from the Norwegian Medical Birth Registry. The datasets were linked via the women’s personal identification number. Pearson’s c 2 tests and logistic regression analyses were used to identify associations between triptan therapy and pregnancy outcome. Results.—No significant associations between triptan therapy during the first trimester and major congenital malformations (unadjusted OR: 1.0; 95% CI 0.8-1.3, adjusted OR: 1.0; 95% CI 0.7-1.2) or other adverse pregnancy outcomes were found. Triptan therapy during the second and/or third trimesters was significantly associated with atonic uterus (unadjusted OR: 1.5; 95% CI 1.1-1.9, adjusted OR: 1.4; 95% CI 1.1-1.8), and blood loss >500 mL during labor (unadjusted OR: 1.3; 95% CI 1.1-1.5, adjusted OR: 1.3; 95% CI 1.1-1.5). Conclusions.—Triptan therapy during pregnancy was not associated with an overall increased risk of congenital malformations. It cannot, however, be excluded that a difference in the risk between triptan use and individual or rare congenital malformations may exist. A slight increase in the risk of atonic uterus and hemorrhage was associated with triptan use during the second and/or third trimesters. Although the present findings are reassuring, confirmation in independent studies is warranted.

We would like to bring your attention to an error in the article “The effects of codeine on pregnancy outcome: results from a large population-based cohort study” published in Eur J Clin Pharmacology volume 67, year 2011, pages 1253–1261. The error was purely technical and led to some double counting and misclassification. We found one new statistically significant pregnancy outcome (atonic uterus) related to codeine exposure as shown in the tables below. This relationship was borderline significant in the old analysis (lower limit of the confidence interval 1.0). The outcome is directly biologically linked to postpartum hemorrhage, which was found to be significantly associated with codeine both in the previous analysis and in the new one. Otherwise, the odds ratios remained virtually unaltered as did the maternal socio-demographic and medical characteristics. No significant differences were found in the survival rate [adjusted odds ratio (OR) 0.9, 95 % confidence interval (CI) 0.6–1.5] or the congenital malformation rate (adjusted OR 0.9, 95 % CI 0.7–1.2) between codeine-exposed and unexposed infants. Codeine use anytime during pregnancy was associated with planned Cesarean delivery (adjusted OR 1.6, 95 % CI 1.3–2.0; P