Expected small left heart size in the presence of congenital diaphragmatic hernia: Fetal values and Z-scores for infants confirmed to have no heart disease postnatally.

Objectives: In fetuses with left-sided congenital diaphragmatic hernia (CDH), left heart structures may appear small, but usually normalize after birth in the absence of structural cardiac anomalies. To decrease the possibility of an erroneous diagnosis of structural heart disease, we identify normal values for left heart structures in the presence of left CDH and secondarily investigate the relationship of left heart size and survival to neonatal hospital discharge. Methods: Left heart structures [mitral valve (MV) and aortic valve (AoV) annulus diameter, left ventricle (LV) length and width] were measured by fetal echocardiogram in fetuses with left CDH and no congenital heart disease. We generated linear regression models to establish the relationship of gestational age for each left heart structure using data from fetuses who survived after birth. We calculated z-scores (normalized to gestational age), and assessed the relationship of survival to the size of each structure. Results: One hundred forty-two fetuses underwent fetal echocardiogram (median 25 weeks' gestation, IQR 23, 27 weeks). Left heart structures were deemed small when using published normative data from unaffected fetuses (z-scores: MV -1.09 ± 1.35, AoV -2.12 ± 1.16, LV length -1.36 ± 1.24, LV width -4.79 ± 0.79). CDH-specific models derived from log-transformed values yielded left-shifted distributions, reflecting the small structures (mean z-score lower by: MV 0.99 ± 0.30, AoV 2.04 ± 0.38, LV length 1.30 ± 0.36, and LV width 4.69 ± 0.28; p < 0.0001 for all comparisons). Non-survivors had worse z-scores than survivors for all measurements, but this did not reach statistical significance. Conclusions: Log-transformed linear models generated new normative data for fetal left heart structures in left CDH, which may be used to allay antenatal concerns regarding structural left heart anomalies. There were no significant differences in z-scores between survivors and non-survivors, suggesting that in the absence of true structural disease, cardiac evaluation is not predictive in isolation and that causes of mortality are likely multifactorial in this population.

Characteristics of Extremely Low Gestational Age Newborns Undergoing Tracheotomy: A Secondary Analysis of the Trial of Late Surfactant Randomized Clinical Trial.

Importance: Tracheotomy is sometimes performed in extremely low gestational age newborns requiring prolonged ventilation. Studies suggest better neurodevelopmental outcomes in preterm newborns undergoing earlier tracheotomy (<120 days); however, guidelines for who should undergo tracheotomy and when to perform tracheotomy are unclear regarding infants receiving long-term positive-pressure support. Objective: To determine the characteristics associated with tracheotomy in high-risk, extremely low gestational age newborns. Design, Setting, and Participants: This secondary analysis of infants enrolled in the double-blind, randomized clinical trial known as the Trial of Late Surfactant (TOLSURF) was conducted from January 10, 2010, to September 3, 2013, in neonatal intensive care units. Participants included 511 premature infants (≤28 weeks' gestational age) who were intubated and mechanically ventilated anytime between 7 and 14 days of life. Infants were randomized to receive late surfactant plus inhaled nitric oxide or inhaled nitric oxide alone. All data were collected prospectively. A mixed-effects model, with patient-level random effects included to account for individual homogeneity, was used to compare mean airway pressure (MAP) during the first 120 days in infants who did not undergo tracheotomy vs those who underwent tracheotomy. The present analysis was conducted from July 1, 2015, to March 29, 2016. Exposures: Mean airway pressure, comorbidities of prematurity, airway stenosis, and airway malacia. Main Outcomes and Measures: Tracheotomy. Results: Of the 511 infants enrolled in TOLSURF, the mean (SD) gestational age was 25 (1.2) weeks, with a birth weight of 701 (165) g. Fifteen infants (2.9%) underwent tracheotomy. Among those undergoing tracheotomy, 7 infants (46.7%) had airway stenosis or malacia, none of whom died. Of the 8 infants who underwent tracheotomy without airway stenosis or malacia, 4 (50%) died. Mean age at tracheotomy was 126 days (95% CI, 108-144 days). In general, MAP increased over time in the group undergoing tracheotomy (+0.09 cm H2O/wk; 95% CI, 0.06-0.11 cm H2O/wk) but decreased in those who did not undergo tracheotomy (-0.20 cm H2O/wk; 95% CI, 0.19-0.21 cm H2O/wk; P < .001 for interaction). Conclusions and Relevance: In this cohort of high-risk, extremely low gestational age newborns, trends in MAP can be a clinical indicator for infants requiring long-term positive-pressure ventilation who are at highest risk for receiving tracheotomy. Knowledge of this information may identify infants who would benefit from earlier consideration for tracheotomy. Trial Registration: clinicaltrials.gov Identifier: NCT01022580.

Spleen Behind the Heart Complicates Lung-to-Head Ratio Measurement in Left-Sided Congenital Diaphragmatic Hernia.

In fetuses with left-sided congenital diaphragmatic hernia, intrathoracic herniation of the spleen is a common occurrence. The herniated spleen can reside posterior to the left atrium of the heart in the right hemithorax and is increasingly differentiated from the lung with the use of newer sonographic equipment. Estimation of the neonatal prognosis relies on accurate measurement of fetal lung size, particularly with commonly used measurements such as the lung-to-head ratio. Here we describe how herniation of the spleen behind the heart can complicate measurement of the lung-to-head ratio on sonography and lead to overestimation, with implications for perinatal prognostication and management.

Fetal Stomach Position Predicts Neonatal Outcomes in Isolated Left-Sided Congenital Diaphragmatic Hernia.

INTRODUCTION: We sought to determine the relationship between the degree of stomach herniation by antenatal sonography and neonatal outcomes in fetuses with isolated left-sided congenital diaphragmatic hernia (CDH). MATERIALS AND METHODS: We retrospectively reviewed neonatal medical records and antenatal sonography of fetuses with isolated left CDH cared for at a single institution (2000-2012). Fetal stomach position was classified on sonography as follows: intra-abdominal, anterior left chest, mid-to-posterior left chest, or retrocardiac (right chest). RESULTS: Ninety fetuses were included with 70% surviving to neonatal discharge. Stomach position was intra-abdominal in 14% (n = 13), anterior left chest in 19% (n = 17), mid-to-posterior left chest in 41% (n = 37), and retrocardiac in 26% (n = 23). Increasingly abnormal stomach position was linearly associated with an increased odds of death (OR 4.8, 95% CI 2.1-10.9), extracorporeal membrane oxygenation (ECMO; OR 5.6, 95% CI 1.9-16.7), nonprimary diaphragmatic repair (OR 2.7, 95% CI 1.4-5.5), prolonged mechanical ventilation (OR 5.9, 95% CI 2.3-15.6), and prolonged respiratory support (OR 4.0, 95% CI 1.6-9.9). All fetuses with intra-abdominal stomach position survived without substantial respiratory morbidity or need for ECMO. DISCUSSION: Fetal stomach position is strongly associated with neonatal outcomes in isolated left CDH. This objective tool may allow for accurate prognostication in a variety of clinical settings.

Short-Term Treprostinil Use in Infants with Congenital Diaphragmatic Hernia following Repair.

We describe 2 infants with congenital diaphragmatic hernia with severe pulmonary hypertension at 6 weeks. Treprostinil was used with rapid clinical improvement. Repeat cardiac catheterization showed dramatic improvement. Both infants were weaned off the drug, representing the first reports of successful short-term treprostinil use in neonates with congenital diaphragmatic hernia.

Fetal ultrasound markers of severity predict resolution of pulmonary hypertension in congenital diaphragmatic hernia.

OBJECTIVE: Congenital diaphragmatic hernia (CDH) results in morbidity and death from lung hypoplasia and persistent pulmonary hypertension (PH). We sought to define the relationship between fetal ultrasound markers of severity in CDH and the time to resolution of neonatal PH. STUDY DESIGN: We conducted a retrospective study of fetuses with an antenatal ultrasound scan and left-sided CDH cared for at the University of California San Francisco (2002-2012). Fetal liver position was classified on ultrasound scan as abdominal (entire liver within the abdomen) or thoracic (any portion of the liver within the thorax). Fetal stomach position was classified from least to most aberrant: abdominal, anterior left chest, mid-posterior left chest, or retrocardiac (right chest). Lung-to-head ratio (LHR) was determined from available scans at 20-29 weeks of gestational age (GA). Routine neonatal echocardiograms were performed weekly for up to 6 weeks or until PH resolved or until discharge. PH was assessed by echocardiogram with the use of a hierarchy of ductus arteriosus level shunt, interventricular septal position, and tricuspid regurgitant jet velocity. Days to PH-free survival was defined as the age at which pulmonary artery pressure was estimated to be <2/3 systemic blood pressure. Cox proportional hazards models adjusted for GA at birth, era of birth, fetal surgery, and GA at ultrasound scan (LHR model only), with censoring at 100 days. RESULTS: Of 118 patients, the following fetal markers were available: LHR (n = 53), liver position (n = 112), and stomach position (n = 80). Fewer infants experienced resolved PH if they had LHR <1 (P = .006), thoracic liver position (P = .001), or more aberrant stomach position (P < .001). There was also a decreased rate of resolution of PH in infants with LHR <1 (hazard ratio, 0.30; P = .007), thoracic liver position (hazard ratio, 0.38; P < .001), and more aberrant stomach position (hazard ratios, 0.28 [P = .002]; 0.1 [P < .001]; and 0.07 [P < .001]). CONCLUSION: Fetal ultrasound markers of CDH severity are predictive not only of death but also of significant morbidity. LHR <1, thoracic liver, and aberrant stomach position are associated with delayed time to resolution of PH in infants with CDH and may be used to identify fetuses at high risk of persistent PH.

Persistence of pulmonary hypertension by echocardiography predicts short-term outcomes in congenital diaphragmatic hernia.

OBJECTIVES: To describe the natural history of pulmonary hypertension (PH) and the risk of death and pulmonary morbidity associated with the persistence of PH through the neonatal hospitalization for these infants. STUDY DESIGN: We performed a retrospective cohort study of infants with congenital diaphragmatic hernia (CDH) cared for at University of California San Francisco (2002-2012). Infants with other major anomalies or syndromes were excluded (n = 43). Clinical echocardiograms were performed weekly for up to 6 weeks or until PH resolved off respiratory support or until hospital discharge. Echocardiograms were re-read by a blinded reviewer and categorized by severity of elevation in estimated pulmonary arterial pressure. PH was defined as ≥2/3 systemic blood pressure. Severity was determined by a hierarchy of ductus arteriosus level shunt, interventricular septal position, and tricuspid regurgitant jet velocity. RESULTS: Of 140 infants with ≥1 echo, 98 resolved their PH prior to death/discharge. Mean time to resolution was 18 days (median 14 days, IQR 8, 21 days). Those with persistence of PH had a higher rate of extracorporeal membrane oxygenation (P < .001) and death (P < .001), and fewer ventilator-free days (P < .001). Persistence of PH at 14 days predicted mortality (area under the receiver operating characteristic curve 0.87) and adverse respiratory outcomes (area under the receiver operating characteristic curve 0.80-0.83). CONCLUSIONS: The majority of infants with CDH resolve PH between 1 and 3 weeks of life. At 2 weeks of age, severity of PH by echocardiogram strongly predicts short-term pulmonary morbidity and death. Further evaluation of physiological alterations during that time may lead to novel therapies for severe CDH.

Multi-institutional practice patterns and outcomes in uncomplicated gastroschisis: a report from the University of California Fetal Consortium (UCfC).

BACKGROUND/PURPOSE: Gastroschisis is a resource-intensive birth defect without consensus regarding optimal surgical and medical management. We sought to determine best-practice guidelines by examining differences in multi-institutional practices and outcomes. METHODS: Site-specific practice patterns were queried, and infant-maternal chart review was retrospectively performed for gastroschisis infants treated at 5 UCfC institutions (2007-2012). The primary outcome was length of stay. Univariate analysis was done to assess variation practices and outcomes by site. Multivariate models were constructed with site as an instrumental variable and with sites grouped by silo practice pattern adjusting for confounding factors. RESULTS: Of 191 gastroschisis infants, 164 infants were uncomplicated. Among uncomplicated patients, there were no deaths and only one case of necrotizing enterocolitis. Bivariate analysis revealed significant differences in practices and outcomes by site. Despite wide variations in practice patterns, there were no major differences in outcome among sites or by silo practice, after adjusting for confounding factors. CONCLUSIONS: Wide variability exists in institutional practice patterns for infants with gastroschisis, but poor outcomes were not associated with expeditious silo or primary closure, avoidance of routine paralysis, or limited central line and antibiotic durations. Development of clinical pathways incorporating these practices may help standardize care and reduce health care costs.

B-type natriuretic peptide: prognostic marker in congenital diaphragmatic hernia.

BACKGROUND: B-type natriuretic peptide (BNP) has not been evaluated in newborns with congenital diaphragmatic hernia (CDH). We hypothesized that BNP and severity of pulmonary hypertension (PH) would predict clinical outcome in these infants. METHODS: We measured BNP levels and assessed severity of PH by echocardiography at 1 d and 1 wk of life. Outcome was classified by status at 56 d (or prior discharge): Good (n = 13) if alive on room air and Poor (n = 14) if expired or receiving respiratory support. We estimated area under the curve (AUC) and 95% confidence interval (CI). RESULTS: BNP levels were higher at 1 d in newborns with Poor outcome (median 220 pg/ml vs. 55 pg/ml, P < 0.01). At 1 wk, there was no significant difference in BNP level (median 547 pg/ml vs. 364 pg/ml, P = 0.70, for Poor and Good outcomes). At 1 d, BNP level predicted outcome (AUC = 0.91, 95% CI = 0.77-1.0), but this relationship dissipated by 1 wk (AUC = 0.55, 95% CI = 0.31-0.79). Severity of PH did not predict outcome at 1 d (AUC = 0.51, 95% CI = 0.27-0.74), but prediction improved at 1 wk (AUC = 0.80, 95% CI = 0.61-0.99). CONCLUSION: BNP is a strong predictor of clinical outcome in newborns with CDH at 1 d of life.