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ObjectiveTo identify the association between birth weight (BW)-for-gestational age (GA) and pulmonary hypertension (PHTN) at 36 weeks in infants with moderate-severe bronchopulmonary dysplasia (BPD).Study DesignIn this retrospective cohort study, we followed 138 premature infants (≤28wks) with moderate and severe BPD (NIH consensus definition) born at Prentice Women’s Hospital between 2005 and 2009. BW percentiles were calculated using the Fenton growth curve for premature infants. PHTN was determined using a standardized algorithm of echocardiogram review at 36 weeks. Logistic regression was used to evaluate the associations between BW percentile subgroups and PHTN, taking into account antenatal and neonatal factors that were related to PHTN.ResultsPHTN was associated with small BW-for-GA, ranging from thresholds of <10th to <25th percentile (P<0.001). These associations remained significant when comparing BW <25th percentile to the reference group (50–89th percentile); after adjustment for GA, gender, multiple gestation, race/ethnicity (OR=4.2; 95% CI=1.5, 12.1); and after further adjustment for maternal vascular disease, intrauterine infection, oligohydramnios, and relevant postnatal factors (OR=5.7; 95% CI=1.5, 21.2). Longitudinal follow-up of this cohort showed a trend towards higher morbidity and death among PHTN infants with BW <25th percentile.ConclusionBW-for-GA is an important predictor of PHTN in premature infants with moderate/severe BPD. Our findings contribute to the growing evidence supporting fetal mechanisms of later onset pulmonary vascular disease.

Background-Ebstein anomaly and tricuspid valve dysplasia are rare congenital tricuspid valve malformations associated with high perinatal mortality. The literature consists of small, single-center case series spanning several decades. We performed a multicenter study to assess the outcomes and factors associated with mortality after fetal diagnosis in the current era. Methods and Results-Fetuses diagnosed with Ebstein anomaly and tricuspid valve dysplasia from 2005 to 2011 wereincluded from 23 centers. The primary outcome was perinatal mortality, defined as fetal demise or death before neonatal discharge. Of 243 fetuses diagnosed at a mean gestational age of 27±6 weeks, there were 11 lost to follow-up (5%), 15 terminations (6%), and 41 demises (17%). In the live-born cohort of 176 live-born patients, 56 (32%) died before discharge, yielding an overall perinatal mortality of 45%. Independent predictors of mortality at the time of diagnosis were gestational age <32 weeks (odds ratio, 8.6; 95% confidence interval, 3.5-21.0; P<0.001), tricuspid valve annulus diameter z-score (odds ratio, 1.3; 95% confidence interval, 1.1-1.5; P<0.001), pulmonary regurgitation (odds ratio, 2.9; 95% confidence interval, 1.4-6.2; P<0.001), and a pericardial effusion (odds ratio, 2.5; 95% confidence interval, 1.1-6.0;© 2015 American Heart Association, Inc.Circulation characterized by apical displacement of the valve or leaflet deformation, respectively. 3 In severe cases of dysplasia, the tricuspid valve orifice may become unguarded. 4,5 Although there is a broad morphologic spectrum, these malformations lead to the same hemodynamic burden, namely, tricuspid regurgitation (TR) and its pathophysiological sequelae. Although older children and adults with EA/TVD may be asymptomatic for years, the diagnosis of EA/TVD in the perinatal period carries a poor prognosis. In the fetus, severe TR may lead to cardiomegaly, hydrops, and arrhythmia, with demise rates as high as 48%.6 Among prenatally diagnosed patients who survive to live birth, hemodynamic instability, cyanosis, and respiratory compromise are common. Although neonatal mortality approached 80 to 85% in early series, 7,8 various single-center series have reported reduced mortality in the past 2 decades, ranging from 17% to 56%. 9-12 Clinical Perspective on p 489Fetal risk factors for perinatal mortality have been identified, including lack of antegrade flow across the pulmonary valve and retrograde duct flow 9-12 and fetal distress. 12However, studies were limited by small sample sizes, with Yu et al 12 reporting the largest series to date with 46 prenatally diagnosed patients. The prognostic value of indices of cardiomegaly, such as the cardiothoracic area (CTA) ratio and the right atrial area index, has been mixed. [9][10][11][12][13] Importantly, hemodynamic factors with potentially important influences on perinatal mortality, such as right ventricular pressure and the presence of pulmonary regurgitation (PR), have not been investigated.Since our understanding of fetuses diagnose...

Background-Using fetal magnetocardiography (fMCG), we characterize for the first time the electrophysiological patterns of initiation and termination of reentrant fetal supraventricular tachycardia (SVT), the most common form of life-threatening fetal arrhythmia. Methods and Results-In contrast to the expectation that reentrant SVT is initiated by spontaneous premature atrial contractions (PACs) and is terminated by spontaneous block, 5 distinct patterns of initiation and 4 patterns of termination were documented, with the most common patterns of initiation involving reentrant PACs. Waveform morphology and timing, including QRS and ventriculoatrial interval, were assessed. This enabled detection of such phenomena as Wolff-Parkinson-White syndrome, QRS aberrancy, and multiple reentrant pathways that were crucial for defining the rhythm patterns. In addition, fMCG actocardiography revealed an unexpectedly strong association between fetal trunk movement and the initiation and termination of SVT, suggesting that autonomic influences play a key role. Conclusions-This study demonstrates that the patterns of initiation and termination of fetal SVT are more diverse than is generally believed and that the most common patterns of initiation involve reentrant PACs. The ability to discern such patterns can help elucidate the underlying mechanisms and guide antiarrhythmic drug therapy. fMCG provides a noninvasive means of analyzing complex tachyarrhythmia in utero, with efficacy approaching that of postnatal electrocardiographic rhythm monitoring.

Introduction Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy, and BPD-associated pulmonary hypertension (PH) is a serious complication that can negatively impact later childhood health. There is growing evidence that lung injury leading to BPD and PH is due to chronic fetal hypoxia-ischemia. The purpose of this study was to investigate whether placental pathologic changes of maternal vascular underperfusion (MVU) are associated with BPD, and further increased with PH. Methods We conducted a 5-year retrospective cohort study of premature infants born ≤28 weeks. BPD was defined as persistent oxygen requirement at 36 weeks corrected gestational age. PH was identified using a standardized algorithm of echocardiogram review. Archived placental slides underwent standardized masked histopathologic review. Logistic regression modeling was performed, taking into account important maternal and infant covariates. Results Among 283 births, 121 had MVU, of which 67 (55%) developed BPD, and 24 (20%) had PH. Among the common neonatal complications of extreme prematurity, BPD was the only outcome that was increased with MVU (P<0.001). After adjustment for birth weight, fetal growth restriction, preeclampsia and other factors, infants with MVU were more likely to develop BPD (adjusted odds ratio=2.6; 95% confidence interval=1.4, 4.8). Certain MVU sublesions (fibrinoid necrosis/acute atherosis and distal villous hypoplasia/small terminal villi) were increased with PH (P<0.001). Discussion Placental MVU may identify BPD infants who were exposed to intrauterine hypoxia-ischemia, which increases their risk for development of PH disease. Conclusions Our findings have important implications for providing earlier and more effective therapies for BPD.

Second-degree AVB, isolated 3 degrees AVB, and 3 degrees AVB associated with structural cardiac disease manifest distinctly different electrophysiological characteristics and outcome. Fetuses with 2 degrees AVB or isolated 3 degrees AVB commonly exhibited complex, changing heart rate and rhythm patterns; all 19 delivered fetuses are alive and healthy. Fetuses with structural cardiac disease and 3 degrees AVB exhibited largely monotonous heart rate and rhythm patterns and poor prognosis. Junctional ectopic tachycardia and/or ventricular tachycardia may be characteristic of an acute stage of heart block.

Background-Fetal tachycardia complicated by ventricular dysfunction and hydrops fetalis carries a significant risk of morbidity and mortality. Transplacental digoxin is effective therapy in a small percentage, but there is no consensus with regard to antiarrhythmic treatment if digoxin fails. This study evaluates the safety, efficacy, and outcome of amiodarone therapy for digoxin-refractory fetal tachycardia with heart failure. Methods and Results-Fetuses with incessant tachycardia and either hydrops fetalis (nϭ24) or ventricular dysfunction (nϭ2) for whom digoxin monotherapy and secondary antiarrhythmic agents (nϭ13) were not effective were treated transplacentally with a loading dose of oral amiodarone for 2 to 7 days, followed by daily maintenance therapy for Ͻ1 to 15 weeks. Digoxin therapy was continued throughout gestation. Newborns were studied by transesophageal pacing or ECG monitoring to determine the mechanism of tachycardia. Three fetuses were delivered urgently in tachycardia during amiodarone loading, and 3 required additional antiarrhythmic agents for sustained cardioversion. Amiodarone or amiodarone combinations converted 14 of 15 (93%) with reentrant supraventricular tachycardia, 2 of 2 with ventricular or junctional ectopic tachycardia, and 3 of 9 (33%) with atrial flutter. Amiodarone-related adverse effects were transient in 5 infants and 8 mothers. Mean gestational age at delivery was 37 weeks, with 100% survival. Conclusions-Orally administered amiodarone is safe and effective treatment for drug-refractory fetal tachycardia, specifically reentrant supraventricular tachycardia, junctional ectopic, or ventricular tachycardia, even when accompanied by hydrops fetalis or ventricular dysfunction.

Objective To assess whether cord blood biomarkers associated with placental maternal vascular underperfusion (MVU) are predictive of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH). Study design Premature infants enrolled in a longitudinal cohort study were randomly sampled from 4 gestational age strata (n = 190, range 23–36 weeks). Fifteen factors from a human angiogenesis panel were measured in cord blood using multiplex immunoassay. Multivariate linear regression was used to compare biomarker levels according to placental histologic MVU, taking into account acute/chronic inflammation and fetal vascular pathology. Biomarkers associated with MVU were further evaluated in the subgroup of extremely low gestational age infants (gestational age ≤ 28 weeks; n = 48), and measured by enzyme-linked immunoassay in an additional 39 infants to determine associations with BPD (defined using the National Institutes of Health workshop criteria) and PH (identified by echocardiogram at 36 weeks of gestation). Results Cord blood placental growth factor (PIGF), granulocyte-colony stimulating factor (G-CSF), and vascular endothelial growth factor-A were decreased with MVU (P < .003), and decreased with BPD-PH (P < .05). The findings were validated for PIGF and G-CSF in 39 additional extremely low gestational age infants. In the combined group (n = 87), PIGF was decreased in infants with BPD-PH (n = 21) versus controls without PH (median 3 pg/mL [IQR 2–7] vs median 15 pg/mL [IQR 6–30], respectively; P < .001). G-CSF was similarly decreased with BPD-PH (median, 55 pg/mL [IQR 38–85] vs median 243 pg/mL [IQR 48–1593], respectively; P = .001). Receiver operator curve analysis revealed that decreased PIGF and G-CSF were predictive of BPD-PH (area under the curve 0.83 and 0.76, respectively). Conclusions Cord blood angiogenic factors that are decreased with placental MVU may serve as predictors of BPD-PH.