Treatment with oral beta-blockers during pregnancy complicated by maternal heart disease increases the risk of fetal growth restriction.

To investigate the effect on fetal growth of treatment with oral beta-blockers during pregnancy in women with congenital or acquired heart disease. Historical matched cohort study. Centre for Pregnant Women with Heart Disease, Copenhagen University Hospital, Denmark. A cohort of 175 women with heart disease, grouped according to beta-blocker treatment, and a cohort of 627 women from the overall population matched on seven birthweight-determining factors. Differences between groups were tested by simple descriptive statistics and assessed using standard hypothesis tests. Associations were estimated by correlational analysis and multivariable regression. Proportion of infants born small for gestational age (SGA). More of the infants exposed to beta-blockers were SGA compared with non-exposed infants (29.4 versus 15.3%; P < 0.05). After adjustment for birthweight-determining factors, beta-blocker treatment and maternal body mass index (BMI) were the only factors independently associated with SGA (the relative difference in expected birthweight was -8.6%; 95% CI -13.3 to -3.9%; P = 0.0004). After adjustment for BMI, beta-blocker treatment was associated with an increased risk of SGA (OR 2.65; 95% CI 1.15-6.10; P = 0.02). In a subgroup with isolated tachyarrhythmias, SGA infants were more frequent in the beta-blocker exposed group compared with the non-exposed group (31 versus 10%; P < 0.005). Beta-blocker treatment was the only independent predictor of SGA, adjusting for several factors influencing fetal growth (the relative difference in expected birthweight was -12.2%; 95% CI -19.9 to -3.9%; P = 0.001). In a historical cohort of pregnancies complicated by maternal heart disease, treatment with beta-blockers was found to be independently associated with an increased risk of delivering an SGA infant.

Ersbøll AS ，Hedegaard M ，Søndergaard L ，Ersbøll M ，Johansen M ... -  《-》

Beta-blockers increase the risk of being born small for gestational age or of being institutionalised during infancy.

To compare infant outcomes between mothers with hypertension treated by beta-blockers alone and by methyldopa alone during pregnancy. Historical cohort study. Saskatchewan, Canada. Women who delivered a singleton birth in Saskatchewan during the periods from 1 January 1980 to 30 June 1987 or from 1 January 1990 to 31 December 2005 (women who delivered between 1 July 1987 and 31 December 1989 were excluded because the information recorded on maternal drug use during pregnancy is incomplete) with a diagnosis of a hypertensive disorder during pregnancy, and who were dispensed only beta-blockers (n = 416) or only methyldopa (n = 1000). Occurrences of adverse infant outcomes were compared between women who received beta-blockers only and women who received methyldopa only during pregnancy, first in all eligible women, and then in women with chronic hypertension and in women with gestational hypertension or pre-eclampsia/eclampsia, separately. Multiple logistic regression analyses were performed to adjust for potential confounding. Small for gestational age (SGA) < 10th percentile, SGA < 3rd percentile, preterm birth, stillbirth, institutionalisation for respiratory distress syndrome (RDS), sepsis, seizure during infancy, and infant death. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for infants born to mothers with chronic hypertension who were dispensed beta-blockers only, as compared with infants born to mothers who were dispensed methyldopa only, during pregnancy were: 1.95 (1.21-3.15), 2.17 (1.06-4.44), and 2.17 (1.09-4.34), respectively, for SGA < 10th percentile, SGA < 3rd percentile, and being institutionalised during infancy. For infants born to mothers with chronic hypertension, compared with those treated by methyldopa alone, those treated by beta-blockers appear to be at increased rates of SGA and hospitalisation during infancy.

Xie RH ，Guo Y ，Krewski D ，Mattison D ，Walker MC ，Nerenberg K ，Wen SW ... -  《-》

The use of customised versus population-based birthweight standards in predicting perinatal mortality.

Zhang X ，Platt RW ，Cnattingius S ，Joseph KS ，Kramer MS ... -  《BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY》

Perinatal outcomes after in-utero exposure to beta-blockers in women with heart disease: Data from the ESC EORP registry of pregnancy and cardiac disease (ROPAC).

Beta-blockers are commonly used drugs during pregnancy, especially in women with heart disease, and are regarded as relatively safe although evidence is sparse. Differences between beta-blockers are not well-studied. In the Registry of Pregnancy And Cardiac disease (ROPAC, n = 5739), a prospective global registry of pregnancies in women with structural heart disease, perinatal outcomes (small for gestational age (SGA), birth weight, neonatal congenital heart disease (nCHD) and perinatal mortality) were compared between women with and without beta-blocker exposure, and between different beta-blockers. Multivariable regression analysis was used for the effect of beta-blockers on birth weight, SGA and nCHD (after adjustment for maternal and perinatal confounders). Beta-blockers were used in 875 (15.2%) ROPAC pregnancies, with metoprolol (n = 323, 37%) and bisoprolol (n = 261, 30%) being the most frequent. Women with beta-blocker exposure had more SGA infants (15.3% vs 9.3%, p < 0.001) and nCHD (4.7% vs 2.7%, p = 0.001). Perinatal mortality rates were not different (1.4% vs 1.9%, p = 0.272). The adjusted mean difference in birth weight was -177 g (-5.8%), the adjusted OR for SGA was 1.7 (95% CI 1.3-2.1) and for nCHD 2.3 (1.6-3.5). With metoprolol as reference, labetalol (0.2, 0.1-0.4) was the least likely to cause SGA, and atenolol (2.3, 1.1-4.9) the most. In women with heart disease an association was found between maternal beta-blocker use and perinatal outcomes. Labetalol seems to be associated with the lowest risk of developing SGA, while atenolol should be avoided.

Ramlakhan KP ，Roos-Hesselink JW ，Basso T ，Greenslade J ，Flint RB ，Krieger EV ，Shotan A ，Budts W ，De Backer J ，Hall R ，Johnson MR ，Parsonage WA ，ROPAC Investigators ... -  《-》

The impact of maternal celiac disease on birthweight and preterm birth: a Danish population-based cohort study.

Khashan AS ，Henriksen TB ，Mortensen PB ，McNamee R ，McCarthy FP ，Pedersen MG ，Kenny LC ... -  《-》