Fetal Cardiology

Postnatal circulation in patients with aortic stenosis undergoing fetal aortic valvuloplasty: systematic review and meta-analysis. Vorisek CN, Zurakowski D, Tamayo A, Axt-Fliedner R, Siepmann T, Friehs I.Ultrasound Obstet Gynecol. 2021 Nov 2. doi: 10.1002/uog.24807. Online ahead of print. PMID: 34726817   Take Home Message Fetal aortic balloon valvuloplasty (FAV) is feasible with very low rate of maternal complications. FAV can be successful in the vast majority of the cases (82%). Successful FAV results in biventricular circulation in about 50% of liveborn infants. Further controlled trials with standardized inclusion criteria and long term follow up are needed to evaluate the true effect of FAV in the type of postnatal circulation and quality of life achieved. Commentary from Dr. Anna Tsirka (Hartford, CT, USA), section editor of Pediatric and Fetal Cardiology Journal Watch Introduction The current standard treatment of HLHS remains palliative surgery resulting in univentricular circulation (UVC). Despite improved postnatal surgical and clinical management of HLHS, morbidity and mortality rates in patients with UVC remain high.  Fetal aortic valvuloplasty aims to improve fetal hemodynamics, prevent myocardial damage, and promote biventricular circulation (BVC). This study is a systematic review of the literature and meta-analysis of eligible studies investigating the type of postnatal circulation achieved in patients with AS undergoing FAV.   Methods This analysis reviewed studies investigating the type of postnatal circulation achieved following FAV in patients diagnosed prenatally with AS. Only original papers published in peer-reviewed journals in the English language after 2000 were included. Studies with (median) follow-up less than 1 year after birth were excluded from review. Seven articles met the criteria and were included in the systematic review and meta-analysis. The flowchart below summarizes the selection review process.     Results A total of 266 subjects from seven studies were included. The sample size of the included studies ranged from 8 to 100. There were no maternal deaths, and maternal complication was noted in two cases: in one case placental abruption occurred following FAV, resulting in delivery at 25 weeks’ gestation, and in another maternal preeclampsia occurred at 34 weeks, unrelated to FAV. The table below summarizes the outcomes of all pregnancies after FAV, regardless of technical success (infant death is defined death after the neonatal period):     The following table displays the prevalence of BVC or UVC in 182 cases with prenatal diagnosis of aortic stenosis that had technically successful fetal aortic valvuloplasty and were liveborn:     Discussion The current meta-analysis shows that FAV is successful in 82% of pregnancies, and of those 97.7% deliver a liveborn infant. Of all cases of live birth after FAV, 46% achieved BVC, and 44% UVC. Of those with successful BAV, 52% achieved BVC, 40% UVC and 8% died. None of these studies included a control group, and none of them were randomized. Well-designed international collaborative RCTs with evaluation of outcomes beyond the neonatal period to conclusively determine the postnatal circulation outcome following FAV are needed.   

Antidepressant use in pregnancy and severe cardiac malformations: Danish register-based study. Kolding L, Ehrenstein V, Pedersen L, Sandager P, Petersen OB, Uldbjerg N, Pedersen LH.BJOG. 2021 Nov;128(12):1949-1957. doi: 10.1111/1471-0528.16772. Epub 2021 Jun 22. PMID: 34036715   Take Home Message This is a nation-wide registry study in Denmark of the association of antidepressant use in the first trimester of pregnancy with the development of congenital heart disease. The use of antidepressants in the first trimester results in a prevalence of cardiac malformations in 12/1000 pregnancies. The use of SSRIs in the first trimester of pregnancy may increase the risk for non-severe cardiac malformations but NOT of severe cardiac malformations, while the use of venlafaxine (a SNRI) in the first trimester increases the risk for severe cardiac malformations and specifically HLHS 17-fold, although the risk is still low (4.4/1000). The risk of severe malformations may be underestimated in studies that only involve live births, as termination is not accounted for. Commentary from Dr. Anna Tsirka (Hartford, CT, USA), section editor of Pediatric and Fetal Cardiology Journal Watch Introduction Depression is a very common comorbidity in pregnancy, affecting 6-15% of pregnant women. Antidepressants are commonly prescribed in pregnancy. The most commonly prescribed agents are selective serotonin reuptake inhibitors (SSRIs) followed by serotonin-norepinephrine reuptake inhibitors (SNRIs). Serotonin is a signaling molecule involved in embryogenesis. Several studies have shown increased incidence of septal defects, RVOT abnormalities and Ebstein’s anomalies in liveborn infants, while little is known about the effects of SNRIs in the development of CHD. All studies investigating these effects to date are limited to live births. The current study evaluates the association between first trimester use of SSRIs and SNRis and risk of cardiac malformations among clinically recognized pregnancies over 11 weeks, regardless of survival.   Methods This was a prevalence study based on routinely collected data from nationwide registries in Denmark that register pregnancies, terminations, deliveries, malformations diagnosed both prenatally and postnatally and prescriptions. The study population included all pregnancies alive at 11 weeks between November of 2007 and February of 2014. The individuals were categorized in 3 groups in terms of exposure to antidepressants: unexposed, exposed and former users. Medications were classified as any antidepressant, SSRI, SNRI, tricyclic antidepressants (TCA) and other.   Results Of 364012 singleton pregnancies, 1.1% of pregnant women had exposure to antidepressants in the first trimester using the criterion of at least 2 filled prescriptions, while 3.2% based on at least one filled prescription. The prevalence of former use of antidepressants without use during the pregnancy was 1.8%. The prevalence of cardiac malformations (CM), both severe (SCM) and non-severe (non-SCM) among 1st trimester users of antidepressants was 12/1000. Among the SCM, 24 % were terminated, and would not have been captured in studies of live births. The prevalence rate (PR) of SCM in pregnancies exposed to any antidepressant (AD) adjusted for all other variables evaluated was 1.31 (95% CI 0.78–2.22). The PR was 2.13 (95% CI 0.89–5.13) for exposure to venlafaxine, and 1.09 (95% CI 0.52–2.30) for SSRIs . Venlafaxine (SNRI) the majority of exposed cases represented HLHS, with a crude PR of 17.4 (95% CI 6.41–47.2) and an absolute risk of 4.4/1000 (95% CI 0.2 to 9.1/1000). The fully adjusted PRs for non-SCM were 1.65 (95% CI 1.31–2.08) for any antidepressant, 1.38 (95% CI 1.00–1.92) for SSRIs, and 1.73 (95% CI 1.08–2.77) for venlafaxine. As venlafaxine resulted in a significant increase in the development of HLHS, and those fetuses were more likely to be aborted in Denmark, the association would not have been evident if only live births were evaluated. A typical analysis restricted to live births yielded the PRs for venlafaxine 0.62 (95% CI 0.09–4.40) and for SSRIs 1.87 (95% CI 1.00–3.48). The number needed to harm (NNH) for venlafaxine was 307 for SCM and 225 for HLHS. For non-SCM, the NNH was 162 for SSRI and 90 for venlafaxine.   SCMNon SCM   Discussion First trimester exposure to antidepressants is associated with a 30% increase in severe cardiac malformations, and a 65% increase in the prevalence of non-severe cardiac malformations. Specifically, SSRIs were associated with increase in non-SCM, while venlafaxine increases the prevalence of SCM and especially HLHS with a PR of over 17. It is important to note however that still the absolute risk is low at 4.4/1000 and risk and benefit should be taken into consideration when treatment decisions are being made. Given the high termination rate in the Danish population of fetuses with HLHS, this association would not have been discovered in a study evaluating only live births.