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Little data exist on the safety of H2-blockers during pregnancy. A computerized database of medications dispensed from 1998 to 2007 to all women registered in the 'Clalit' health maintenance organization, in the Southern District of Israel, was linked with computerized databases containing maternal and infant hospitalization records from the district hospital. The following confounders were controlled for: parity, maternal age, ethnic group, maternal diabetes, smoking, and peripartum fever. Also, therapeutic pregnancy termination data were analyzed. A total of 117 960 infants were born during the study period, 84 823 of them (72%) to women registered at Clalit; 1148 of the latter were exposed to H2-blockers during the first trimester of pregnancy. Exposure to H2-blockers was not associated with an increased risk for congenital malformations (adjusted odds ratio [OR] = 1.03, 95% confidence interval [CI]: 0.80-1.32); also, no such association was found when therapeutic pregnancy terminations were included in the analysis (adjusted OR = 1.17, 95% CI: 0.93-1.46). Exposure to H2-blockers was not associated with perinatal mortality, premature delivery, low birth weight, or low Apgar scores. [ABSTRACT FROM AUTHOR]

Objective:  The ductus arteriosus normally closes after birth. Histamine 2 receptor antagonist (H 2 RA) has been associated with patent ductus arteriosus (PDA). We aimed to study the characteristics of term infants with PDA and their possible association with prenatal exposure to antacids-proton pump inhibitors (PPIs) and H 2 RA., Study Design:  This was a population-based matched case-control study of mothers registered at "Clalit" Health Maintenance Organization (HMO) and their infants born at "Soroka" University Medical Center (SUMC) between 2001 and 2018. Cases are defined as term infants born with PDA diagnosed by echocardiography and registered in the postdelivery discharge form. Each case was matched with four term newborns without PDA diagnosis. Exposure window was defined by the timing of first purchase of H 2 RA or PPI during pregnancy and based on information from a computerized medication database (Clalit HMO, SUMC)., Results:  PDA was diagnosed in 1,884 term infants (4.9%). Characteristics included a significantly higher percentage of lack of prenatal care, cesarean section, in vitro fertilization, polyhydramnios, oligohydramnios, Apgar 1 minute <5, and prenatal exposure to H 2 RA (odds ratio [OR] 4.18) and PPIs (OR 3.50; all p  < 0.001). PDA association with exposure window was similar in each trimester (1.5-2%) for both H 2 RA and PPI., Conclusion:  PDA incidence in term infants in our population was greater than previously reported. PPI and H 2 RA are both antiacids with different mechanisms of action. The similar OR for exposure to one as well as the other, and the lack of influence of the initial exposure period, are compatible with bias., Key Points: · Term newborns with PDA have different characteristics than newborns without PDA.. · Prenatal exposure to PPIs or H2RA is associated with greater risk of PDA in term newborns.. · The possible effect mechanism of PPIs on the ductus is unclear and understudied.., Competing Interests: None declared., (Thieme. All rights reserved.)

We aimed to confirm or reject previous reports on the association of prenatal antibiotic exposure and development of epilepsy in offspring by accounting for known and unidentified confounding factors. In a retrospective cohort investigation, we enrolled children aged 3-18 years born between 1998 and 2012 at a single regional hospital and their mothers. A computerized medication database was linked with hospital records. The exposed group included children whose mothers purchased 1 or more antibiotic medications for use during pregnancy. Epilepsy was defined by epilepsy diagnosis and/or by chronic dispensing of antiepileptic drugs. We analyzed maternal exposure to antibiotics 2 years after delivery (but not during pregnancy and/or the 2 years following delivery) as part of the specificity analysis. We enrolled 88 899 children and their 74 416 mothers. The group exposed prenatally to antibiotics comprised 36 622 children (41.2%). Of them, 326 (0.9%) developed epilepsy compared with 370 of 52 277 (0.7%) in the unexposed group (relative risk [RR], 1.24; 95% confidence interval [CI], 1.07-1.44: P = .004). Exposure during the first, second, and third trimesters was characterized by incidence of epilepsy in 0.8% (P = .943), 0.9% (P = .266), and 0.9% (P = .073) of children, respectively, compared with the unexposed group, with an RR of 1.01 (95%CI, 0.83-1.23), 1.12 (95%CI, 0.92-1.36), and 1.19 (95%CI, 0.98-1.45), respectively. Similarly, prenatal exposure by antibiotic class was associated with epilepsy. Nevertheless, the specificity analysis strongly suggested the possibility of confounding by indication. Our findings indicated that pregnant women should receive the indicated antibiotic treatment with no fear of the development of epilepsy in their children., (© 2020, The American College of Clinical Pharmacology.)

Introduction: Enoxaparin is widely used during pregnancy as pregnancy is a hypercoagulable state; however, its fetal safety has scarcely been investigated., Objective: Our study aimed to examine fetal safety following enoxaparin exposure during pregnancy., Methods: A population-based, retrospective cohort study was performed by linking computerized databases, including the drug dispensing registries of Clalit Health Services in Israel and maternal and infant hospital records, between 1998 and 2009. Multivariate logistic regression models were used to examine associations between first- and third-trimester exposure to enoxaparin, major malformations, and other adverse birth outcomes, adjusted for confounders., Results: From a total of 109,473 singleton pregnancies, 418 and 572 were exposed to enoxaparin during the first and third trimesters, respectively. Exposure to enoxaparin during the first trimester of pregnancy was not associated with an increased risk of major congenital malformations [adjusted odds ratio (aOR) 1.1, 95% confidence interval (CI) 0.8-1.6], while exposure during the third trimester was not associated with an increased risk of low birth weight (aOR 1.1, 95% CI 0.8-1.4), low Apgar score (aOR 0.9, 95% CI 0.4-1.8), or risk of perinatal mortality (aOR 0.6, 95% CI 0.1-2.9)., Conclusion: Exposure to enoxaparin during pregnancy was not associated with an increased risk of major malformations in general or according to organ systems. Nonetheless, risk for specific malformations cannot be ruled out.

Fetal exposure to H2 blockers (H2 Bs) or proton pump inhibitors (PPIs) has been reported to be associated with asthma in children. We evaluated the risk of asthma in offspring following prenatal H2 Bs. We enrolled 91 428 children and their mothers who resided in southern Israel during 1998-2011. The computerized medications database was linked with records from the district hospital. Of the eligible children, 11 227 developed asthma, and overall 5.5% had been exposed to H2 Bs or PPIs prenatally. The risk of developing asthma was slightly higher in the group exposed to H2 Bs or PPIs (RR, 1.09; P = .023). At greater risk were children whose mothers purchased these medications more than 3 times (RR, 1.22; P = .038) or exposed to >20 defined daily doses or prenatally exposed to lansoprazole. The statistical association was significant and depended on magnitude of exposure and specific medication, but the absolute risk was low. The association between maternal consumption of H2 Bs or PPIs and asthma and childhood remained statistically significant 2 years after delivery, raising the possibility of confounding by the indication phenomenon. In view of the findings, a causal relationship could not be ascertained, and an unidentified etiological factor could be operative., (© 2015, The American College of Clinical Pharmacology.)

Air pollution has been shown to increase frequency of asthma attacks, as usually measured by hospitalisation rates. We hypothesise that purchase of asthma reliever medications will reflect a broader association between the environmental exposure and asthma exacerbations. In a time series analysis, we estimated the association of dust storms with mild asthma manifestations, as indicated by medication purchases, during 2005-2011. We compared our results with the estimation of the association of dust storms with hospitalisations due to asthma and asthma-like symptoms. We detected 289 dust storms characterised by high levels of particulate matter <10 μm in diameter. We identified 42,920 children with asthma, wheezing or asthma-like symptoms, of whom 2418 were hospitalised. We observed a higher risk of asthma medication purchase on the day of a mild dust storm (relative risk 1.05, 95% CI 1.00-1.10). The next peak in drug purchases was 3 days later and was more pronounced among Bedouin-Arab children. Stratified analyses showed higher risks for hospitalisation among Bedouin-Arab children; especially among children living in temporary houses (relative risk 1.33, 95% CI 1.04-1.71). We observed an increased risk of asthma medication purchase associated with mild dust storms. The risk observed for hospitalisation was more pronounced among the rural Bedouin-Arab population., (Copyright ©ERS 2015.)

Macrolide antibiotics are largely used in pregnancy for different bacterial infections. Their fetal safety has been studied by several groups, yielding opposing results. In particular, there have been studies claiming an association between macrolides and cardiovascular malformations. Exposure in early infancy has been associated with pyloric stenosis and intussusception. This has led to an avoidance in prescribing macrolides to pregnant women in several Scandinavian countries. The Objectives of the present study was to investigate the fetal safety of this class of drug by linking a large administrative database of drug dispensing and pregnancy outcome in Southern Israel. A computerized database of medications dispensed from 1999 to 2009 to all women registered in the Clalit health maintenance organization in southern Israel was linked with two computerized databases containing maternal and infant hospitalization records. Also, medical pregnancy termination data were analyzed. The following confounders were controlled for: maternal age, ethnicity, maternal pregestational diabetes, parity, and the year the mother gave birth or went through medical pregnancy termination. First- and third-trimester exposures to macrolide antibiotics as a group and to individual drugs were analyzed. During the study period there were 105,492 pregnancies among Clalit women that met the inclusion criteria. Of these, 104,380 ended in live births or dead fetuses and 1,112 in abortion due to medical reasons. In the first trimester of pregnancy, 1,033 women were exposed to macrolides. There was no association between macrolides and either major malformations [odds ratio (OR), 1.08; 95% confidence interval (CI), 0.84 to 1.38)] or specific malformations, after accounting for maternal age, parity, ethnicity, prepregnancy diabetes, and year of exposure. During the third trimester of pregnancy, 959 women were exposed to macrolides. There was no association between such exposure and perinatal mortality, low birth weight, low Apgar score, or preterm delivery. Similarly, no associations were demonstrated with pyloric stenosis or intussusception. Use of macrolides in the first trimester of pregnancy is not associated with an increased risk of major malformations. Exposure in the third trimester is not likely to increase neonatal risks for pyloric stenosis or intussusception in a clinically meaningful manner.

Objective: Despite high rates of hypertension in pregnancy, the effects of hypertension have not been separated appropriately from the effects of the medications that are used. We evaluated the safety of exposure to antihypertensive medications during pregnancy, while accounting for disease effects., Study Design: A population-based retrospective cohort study was performed that compared all pregnancies of women with hypertension who were either exposed or unexposed to antihypertensive medications. A computerized database of the medications that were dispensed to pregnant women from 1998-2008 was linked with computerized databases that contained maternal and infant hospitalization records from the district hospital during the same period., Results: During the study period, 100,029 deliveries occurred; of those, 1964 pregnant women experienced chronic hypertension, and 620 neonates (0.6%) were exposed to at least 1 antihypertensive medication (methyldopa or atenolol) during pregnancy. A higher rate of intrauterine growth restriction (7.2% vs 2.1%, respectively; adjusted odds ratio [OR], 4.37; 95% confidence interval [CI], 3.00-6.36; P < .001), small for gestational age (3% vs 1.7%, respectively; adjusted OR, 2.23; 95% CI, 1.27-3.92; P = .005), and preterm deliveries (<37 weeks, 22.9% vs 8.0%, respectively; adjusted OR, 3.69; 95% CI, 2.90-4.69; P < .001) were noted among the pregnancies of women who were exposed to antihypertensive medications during the third trimester. Importantly, a similar association was detected when we compared women with chronic hypertension who were not treated during pregnancy (n = 1074) to women who had no chronic hypertension and who were unexposed to antihypertensive medications (n = 97,820)., Conclusion: Chronic hypertension with or without treatment during pregnancy is an independent and significant risk factor for adverse perinatal outcomes such as intrauterine growth restriction, small for gestational age, and preterm delivery., (Copyright © 2013 Mosby, Inc. All rights reserved.)