Use of antihistamines before or during pregnancy and risk of early-onset pre-eclampsia in allergic women: a population-based cohort study.

OBJECTIVE: We have previously found that allergy is a risk factor for early-onset pre-eclampsia. The aim of this study was to assess the association between pregestational maternal use of antihistamines and early-onset pre-eclampsia. DESIGN: A population-based cohort study. SETTING AND PARTICIPANTS: All women giving birth in Norway 2004-2016, including 692 487 pregnancies. Data from the Medical Birth Registry of Norway were linked with data from the Norwegian Prescription Database. Prescriptions of antihistamines were divided into three groups: before pregnancy (<6 months), early pregnancy (<20 weeks) and late pregnancy (20-36 weeks). ORs with 95% CIs for pre-eclampsia <34 and <37 weeks by antihistamine use were estimated by logistic regression and stratified on multiple pregnancy and parity. Predicted proportions (%) with 95% CIs were estimated. INTERVENTIONS: Use of antihistamines in relation to pregnancy in allergic women. MAIN OUTCOME MEASURES: Development of early-onset pre-eclampsia. RESULTS: 2997 (0.43%) and 5769 (0.83%) women had pre-eclampsia <34 and <37 weeks, respectively. Use of antihistamines before and in early pregnancy was associated with a risk of developing early-onset pre-eclampsia that was comparable to the background population (OR 1.0, 95% CI 0.8 to 1.2 and OR 0.9, 95% CI 0.7 to 1.1, respectively). Antihistamine use only in late pregnancy was not treated as exposure, but as an indicator of allergy, and was associated with an increased risk of early-onset pre-eclampsia (OR 1.8, 95% CI 1.5 to 2.2). Predicted proportions of pre-eclampsia <34 weeks were significantly lower in women using antihistamines before (0.41%, 95% CI 0.34 to 0.49) and in early pregnancy (0.37%, 95% CI 0.31 to 0.44), compared with women using antihistamines after placentation (0.69%, 95% CI 0.57 to 0.83). Results were similar for pre-eclampsia <37 weeks. CONCLUSIONS: Antihistamine use before or during placentation was associated with reduced risk of developing early-onset pre-eclampsia in allergic women compared with women using antihistamines after placentation.

Maternal complications in pregnancy and childbirth for women with epilepsy: Time trends in a nationwide cohort.

OBJECTIVE: Obstetric trends show changes in complication rates and maternal characteristics such as caesarean section, induced labour, and maternal age. To what degree such general time trends and changing patterns of antiepileptic drug use influence pregnancies of women with epilepsy (WWE) is unknown. Our aim was to describe changes in maternal characteristics and obstetric complications in WWE over time, and to assess changes in complication risks in WWE relative to women without epilepsy. METHODS: This was a nationwide cohort study of all first births in the Medical Birth Registry of Norway, 1999-2016. We estimated maternal characteristics, complication rates, and risks for WWE compared to women without epilepsy. Main maternal outcome measures were hypertensive disorders, bleeding in pregnancy, induction of labour, caesarean section, postpartum hemorrhage, preterm birth, small for gestational age, and epidural analgesia. Time trends were analyzed by logistic regression and comparisons made with interaction analyses. RESULTS: 426 347 first births were analyzed, and 3077 (0.7%) women had epilepsy. In WWE there was an increase in proportions of induced labour (p<0.005) and use of epidural analgesia (p<0.005), and a reduction in mild preeclampsia (p = 0.006). However, the risk of these outcomes did not change over time. Only the risk of severe preeclampsia increased significantly over time relative to women without epilepsy (p = 0.006). In WWE, folic acid supplementation increased significantly over time (p<0.005), and there was a decrease in smoking during pregnancy (p<0.005), but these changes were less pronounced than for women without epilepsy (p<0.005). CONCLUSIONS: During 1999-2016 there were important changes in maternal characteristics and complication rates among WWE. However, outcome risks for WWE relative to women without epilepsy did not change despite changes in antiepileptic drug use patterns. The relative risk of severe preeclampsia increased in women with epilepsy.

Hypertensive pregnancy complications in women with epilepsy and antiepileptic drugs: a population-based cohort study of first pregnancies in Norway.

OBJECTIVES: To estimate the risk of hypertensive pregnancy complications in women with epilepsy, with and without antiepileptic drugs, and assess the risk associated with the four most common antiepileptic drugs. DESIGN: A population-based cohort study using linked data from the Medical Birth Registry of Norway and the Norwegian Prescription Database. Women with epilepsy with and without antiepileptic drugs were compared with women without epilepsy. SETTING: Norway, 2004-2012. PARTICIPANTS: All first pregnancies of women with epilepsy and women without epilepsy were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Main outcome measures were hypertensive pregnancy complications: a compound variable of any hypertensive disorder, gestational hypertension, mild pre-eclampsia, severe pre-eclampsia, early onset pre-eclampsia, eclampsia and HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). RESULTS: In total, 1778 pregnancies in women with epilepsy and 221 662 in women without epilepsy were analysed. 682 of the women with epilepsy used antiepileptic drugs, the most common in monotherapy being: lamotrigine (n=280), carbamazepine (n=94), levetiracetam (n=71) and valproate (n=51). There was an increased risk of any hypertensive disorder in women with epilepsy (adjusted OR (aOR) 1.2, 95% CI 1.0 to 1.5) and in the subcategory using valproat (aOR 2.9, 95% CI 1.3 to 6.4). The most frequent hypertensive complication was mild pre-eclampsia and the risk was increased in women with epilepsy (aOR 1.4, 95% CI 1.1 to 1.8) and women with epilepsy with valproat (aOR 3.3, 95% CI 1.2 to 9.4). CONCLUSIONS: Women with epilepsy have an increased risk of mild pre-eclampsia, but not for the severe types of hypertensive pregnancy complications. Lamotrigine and levetiracetam do not predispose for mild pre-eclampsia, whereas valproate was associated with an increased risk of mild pre-eclampsia.