Drug exposure during pregnancy and fetal cardiac function – a systematic review

Abstract

Background:The aim of this systematic review was to describe the effects of drug exposure during pregnancy on fetal cardiac function. Methods: We searched MEDLINE, Embase, Cochrane and SCOPUS for studies assessing fetal cardiac function in drug-exposed human pregnancies. Risk of bias was assessed by the Risk Of Bias In Non-randomized Studies of Interventions (ROBIN-I) tool. Results: We included 32 studies on eight different drug groups. They included 51 outcome variables, which were all based on ultrasound techniques primarily assessing systolic function: pulsed wave Doppler, tissue Doppler imaging (TDI), and B-and M-mode. Overall, the risk of bias was moderate. β 2 agonists increased the systolic velocity in the ductus arteriosus and the fetal heart rate. β-blockers caused unchanged or decreased systolic velocity of the pulmonary trunk. Corticosteroids increased the velocity in the ductus arteriosus. Furthermore, in growth-restricted fetuses with an increased myocardial performance index (MPI′) on the right side, corticosteroids normalized this variable. Nonsteroidal anti-inflammatory drugs (NSAIDs), but not acetylsalicylic acid, increased the flow velocities in the ductus arteriosus, decreased the shortening fraction and increased the end-diastolic ventricular diameters. Metformin and insulin normalized the diastolic strain and global longitudinal strain in diabetic pregnancies. Highly active antiretroviral therapy (HAART) exposure increased the E/A ratio on the right side, prolonged the isovolumic relaxation time (IRT) and ejection time, shortened the isovolumic contraction time (ICT), and decreased left myocardial systolic peak velocities. Chemotherapy did not cause detectable changes. Conclusion: Six of the eight drug groups caused detectable changes in fetal cardiac function. However, the evidence was hampered by only a few studies for some drugs.

The protective effects of ritodrine against hypoxia/reoxygenation-induced injury in endometrial stromal cells

“…The most severe side effects of Ritodrine are the severe maternal side effects such as cardiac side effects, and even death. 44 Therefore, the future investigation has to be focused on the beneficial and side effects of Ritodrine on both endometrium and myometrium.…”

British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: comorbidity medications used in rheumatology practice

“…Clopidogrel is an antiplatelet agent that may sometimes be used with or instead of LDA to reduce cardiovascular risk. NICE guidance [40], four systematic reviews [16,[41][42][43] and a case report/review [44] evaluated LDA, NSAID and clopidogrel use in pregnancy.…”

“…A systematic review of the effects of various drugs on foetal cardiac function evaluated by ultrasound found that all NSAIDs (including COX2 inhibitors) increased constriction in the ductus arteriosus, within 4–30 h of exposure and resolved by 72 h of discontinuation [ 43 ]. In this study the critical gestational age (measured for indomethacin) increased from 5–10% of foetuses at weeks 26–27 to 50% at week 32.…”

Executive Summary: British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: comorbidity medications used in rheumatology practice

“…Recommendations were based on NICE guidance [40], four systematic reviews [16,[41][42][43], a case report/review [44], UKTIS [18], LactMed [20] and United States Food and Drug Administration (FDA) guidance [45], as shown in Supplementary Tables S5 and S6, available at Rheumatology online.…”