Congenital diaphragmatic hernia (CDH) is a complex malformation characterised by a triad of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. Much of the mortality and morbidity in CDH is largely accounted for by PH, especially when persistent beyond the neonatal period and refractory to available treatment. Gentle ventilation, haemodynamic optimisation and pulmonary vasodilation constitute the foundations of neonatal treatment of CDH-related PH (CDH-PH). Moreover, early prenatal diagnosis, the ability to assess severity and the developmental nature of the condition generate the perfect rationale for fetal therapy. Shortcomings of currently available clinical therapies in combination with increased understanding of CDH pathophysiology have spurred experimental drug trials, exploring new therapeutic mechanisms to tackle CDH-PH. We herein discuss clinically available neonatal and fetal therapies specifically targeting CDH-PH and review the most promising experimental treatments and future research avenues.

<p><strong>OBJECTIVES: </strong>To determine which patients with congenital diaphragmatic hernia (CDH) and pulmonary hypertension (PH) benefit from inhaled nitric oxide (iNO) treatment by comparing characteristics and outcomes of iNO responders to nonresponders.</p>

<p><strong>STUDY DESIGN: </strong>We performed a retrospective chart review of infants with CDH treated at our center between 2011 and 2016. In a subset of patients, iNO was initiated for hypoxemia or echocardiographic evidence of extrapulmonary right to left shunting. Initial post-treatment blood gases were reviewed, and patients were classified as responders (increased PaO &gt;20&nbsp;mm Hg) or nonresponders. Baseline characteristics, echocardiograms and outcomes were compared between groups with Fisher exact tests and Mann-Whitney t tests, as appropriate.</p>

<p><strong>RESULTS: </strong>During the study period, 95 of 131 patients with CDH (73%) were treated with iNO. All patients with pretreatment echocardiograms (n&nbsp;=&nbsp;90) had echocardiographic evidence of PH. Thirty-eight (40%) patients met treatment response criteria. Responders had significant improvements in PaO (51&nbsp;±&nbsp;3 vs 123&nbsp;±&nbsp;7&nbsp;mm Hg, P &lt; .01), alveolar-arterial gradient (422&nbsp;±&nbsp;30 vs 327&nbsp;±&nbsp;27&nbsp;mm Hg, P &lt; .01), and PaO to FiO ratio (82&nbsp;±&nbsp;10 vs 199&nbsp;±&nbsp;15&nbsp;mm Hg, P &lt; .01). Nonresponders were more likely to have left ventricular systolic dysfunction (27% vs 8%, P&nbsp;=&nbsp;.03) on echocardiogram. Responders were less likely to require extracorporeal membrane support (50 vs 24%, P&nbsp;=&nbsp;.02).</p>

<p><strong>CONCLUSIONS: </strong>iNO treatment is associated with improved oxygenation and reduced need for ECMO in a subpopulation of patients with CDH with PH and normal left ventricular systolic function.</p>

<p><strong>BACKGROUND/PURPOSE: </strong>Prostaglandin E1 (PGE) has been used to maintain ductus arteriosus patency and unload the suprasystemic right ventricle (RV) in neonates with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension (PH). Here we evaluate the PH response in neonates with CDH and severe PH treated with PGE.</p>

<p><strong>METHODS: </strong>We performed a retrospective chart review of CDH infants treated at our center between 2011 and 2016. In a subset, PGE was initiated for echocardiographic evidence of severe PH, metabolic acidosis, or hypoxemia. To assess PH response, we evaluated laboratory data, including B-type natriuretic peptide (BNP) and echocardiograms before and after PGE treatment. Categorical and continuous data were analyzed with Fisher's exact tests and Mann-Whitney t-tests, respectively.</p>

<p><strong>RESULTS: </strong>Fifty-seven infants were treated with PGE a mean 17 ± 2 days. BNP levels declined after 1.4 ± 0.2 days of treatment and again after 5.2 ± 0.6 days. After 6 ± 0.8 days of treatment, echocardiographic estimates of severe PH by tricuspid regurgitation jet velocity, ductus arteriosus direction, and ventricular septum position also improved significantly. Treatment was not associated with postductal hypoxemia or systemic hypoperfusion.</p>

<p><strong>CONCLUSIONS: </strong>In patients with CDH and severe PH, PGE is well tolerated and associated with improved BNP and echocardiographic indices of PH, suggesting successful unloading of the RV.</p>

<p><strong>TYPE OF STUDY: </strong>Treatment study.</p>

<p><strong>LEVEL OF EVIDENCE: </strong>Level III.</p>

<p><strong>OBJECTIVE: </strong>The Management of Myelomeningocele Study (MOMS) compared prenatal with postnatal surgery for myelomeningocele (MMC). The present study sought to determine how MOMS influenced the clinical recommendations of pediatric neurosurgeons, how surgeons' risk tolerance affected their views, how their views compare to those of their colleagues in other specialties, and how their management of hydrocephalus compares to the guidelines used in the MOMS trial.</p>

<p><strong>METHODS: </strong>A cross-sectional survey was sent to all 154 pediatric neurosurgeons in the American Society of Pediatric Neurosurgeons. The effect of surgeons' risk tolerance on opinions and counseling of prenatal closure was determined by using ordered logistic regression.</p>

<p><strong>RESULTS: </strong>Compared to postnatal closure, 71% of responding pediatric neurosurgeons viewed prenatal closure as either "very favorable" or "somewhat favorable," and 51% reported being more likely to recommend prenatal surgery in light of MOMS. Compared to pediatric surgeons, neonatologists, and maternal-fetal medicine specialists, pediatric neurosurgeons viewed prenatal MMC repair less favorably (p &lt; 0.001). Responders who believed the surgical risks were high were less likely to view prenatal surgery favorably and were also less likely to recommend prenatal surgery (p &lt; 0.001). The management of hydrocephalus was variable, with 60% of responders using endoscopic third ventriculostomy in addition to ventriculoperitoneal shunts.</p>

<p><strong>CONCLUSIONS: </strong>The majority of pediatric neurosurgeons have a favorable view of prenatal surgery for MMC following MOMS, although less so than in other specialties. The reported acceptability of surgical risks was strongly predictive of prenatal counseling. Variation in the management of hydrocephalus may impact outcomes following prenatal closure.</p>

<p><strong>OBJECTIVES: </strong>The ethics of maternal-fetal surgery involves weighing the importance of potential benefits, risks, and other consequences involving the pregnant woman, fetus, and other family members. We assessed clinicians' ratings of the importance of 9 considerations relevant to maternal-fetal surgery.</p>

<p><strong>METHODS: </strong>This study was a discrete choice experiment contained within a 2015 national mail-based survey of 1200 neonatologists, pediatric surgeons, and maternal-fetal medicine physicians, with latent class analysis subsequently used to identify groups of physicians with similar ratings.</p>

<p><strong>RESULTS: </strong>Of 1176 eligible participants, 660 (56%) completed the discrete choice experiment. The highest-ranked consideration was of neonatal benefits, which was followed by consideration of the risk of maternal complications. By using latent class analysis, we identified 4 attitudinal groups with similar patterns of prioritization: "fetocentric" (n = 232), risk-sensitive (n = 197), maternal autonomy (n = 167), and family impact and social support (n = 64). Neonatologists were more likely to be in the fetocentric group, whereas surgeons were more likely to be in the risk-sensitive group, and maternal-fetal medicine physicians made up the largest percentage of the family impact and social support group.</p>

<p><strong>CONCLUSIONS: </strong>Physicians vary in how they weigh the importance of social and ethical considerations regarding maternal-fetal surgery. Understanding these differences may help prevent or mitigate disagreements or tensions that may arise in the management of these patients.</p>

<p><strong>BACKGROUND: </strong>While prenatal surgery historically was performed exclusively for lethal conditions, today intrauterine surgery is also performed to decrease postnatal disabilities for non-lethal conditions. We sought to describe physicians' attitudes about prenatal surgery for lethal and non-lethal conditions and to elucidate characteristics associated with these attitudes.</p>

<p><strong>METHODS: </strong>Survey of 1200 paediatric surgeons, neonatologists and maternal-fetal medicine specialists (MFMs).</p>

<p><strong>RESULTS: </strong>Of 1176 eligible physicians, 670 (57%) responded (range by specialty, 54%-60%). In the setting of a lethal condition for which prenatal surgery would likely result in the child surviving with a severe disability, most respondents either disagreed (59%) or strongly disagreed (19%) that they would recommend the surgery. Male physicians were twice as likely to recommend surgery for the lethal condition, as were physicians who believe that abortion is morally wrong (OR 1.75; 95% CI 1.0 to 3.05). Older physicians were less likely to recommend surgery (OR 0.57; 95% CI 0.36 to 0.88). For non-lethal conditions, most respondents agreed (66% somewhat, 4% strongly) that they would recommend prenatal surgery, even if the surgery increases the risk of prematurity or fetal death. Compared with MFMs, surgeons were less likely to recommend such surgery, as were physicians not affiliated with a fetal centre, and physicians who were religious (ORs range from 0.45 to 0.64).</p>

<p><strong>CONCLUSION: </strong>Physician's attitudes about prenatal surgery relate to physicians' beliefs about disability as well as demographic, cultural and religious characteristics. Given the variety of views, parents are likely to receive different recommendations from their doctors about the preferable treatment choice.</p>

<p>Venoarterial (VA) extracorporeal life support (ECLS) for neonatal respiratory failure is associated with increased mortality compared with venovenous (VV) ECLS. It is unclear whether this is a causal relationship or reflects differences in baseline disease severity between infants managed with these two strategies. Our objective was to identify clinical variables associated with the preferential selection of VA over VV ECLS, as these may confound the association between VA ECLS and increased mortality. We identified documented indications for preferential VA selection through chart review. We then assessed how the presence of common indications impacted mortality. Thirty-nine cases met eligibility. Severity of hypotension/degree of inotropic support and ventricular dysfunction on echocardiogram before cannulation were the most common specific indications for preferential VA ECLS. Mortality was 12.5% when neither high inotropic support nor ventricular dysfunction was present. Mortality rose to 20% with high inotropic support and 25% with ventricular dysfunction present alone and to 50% when both were present. We conclude that severe hypotension and ventricular dysfunction before ECLS cannulation are common indications for VA ECLS that likely influence survival. Research assessing the impact of ECLS cannulation mode on survival should adjust for baseline differences between groups for these important variables.</p>

<p><strong>OBJECTIVE: </strong>Examine how pediatric and obstetrical subspecialists view benefits and burdens of prenatal myelomeningocele (MMC) closure.</p>

<p><strong>STUDY DESIGN: </strong>Mail survey of 1200 neonatologists, pediatric surgeons and maternal-fetal medicine specialists (MFMs).</p>

<p><strong>RESULTS: </strong>Of 1176 eligible physicians, 670 (57%) responded. Most respondents disagreed (68%, 11% strongly) that open fetal surgery places an unacceptable burden on women and their families. Most agreed (65%, 10% strongly) that denying the benefits of open maternal-fetal surgery is unfair to the future child. Most (94%) would recommend prenatal fetoscopic over open or postnatal MMC closure for a hypothetical fetoscopic technique that had similar shunt rates (40%) but decreased maternal morbidity. When the hypothetical shunt rate for fetoscopy was increased to 60%, physicians were split (49% fetoscopy versus 45% open). Views about burdens and fairness correlated with the likelihood of recommending postnatal or fetoscopic over open closure.</p>

<p><strong>CONCLUSION: </strong>Individual and specialty-specific values may influence recommendations about prenatal surgery.Journal of Perinatology advance online publication, 15 June 2017; doi:10.1038/jp.2017.75.</p>

<p><strong>INTRODUCTION: </strong>The Management of Myelomeningocele Study (MOMS) compared prenatal with postnatal surgery for fetal myelomeningocele (MMC). We sought to understand how subspecialists interpreted the trial results and whether their practice has changed.</p>

<p><strong>MATERIALS AND METHODS: </strong>Cross-sectional, mailed survey of 1,200 randomly selected maternal-fetal medicine (MFM) physicians, neonatologists, and pediatric surgeons.</p>

<p><strong>RESULTS: </strong>Of 1,176 eligible physicians, 670 (57%) responded. Compared to postnatal closure, 33% viewed prenatal closure as "very favorable" and 60% as "somewhat favorable." Most physicians reported being more likely to recommend prenatal surgery (69%), while 28% were less likely to recommend pregnancy termination. In multivariable analysis, neonatologists were more likely to report prenatal closure as "very favorable" (OR 1.6; 95% CI: 1.03-2.5). Pediatric surgeons and neonatologists were more likely to recommend prenatal closure (OR 2.1; 95% CI: 1.3-3.3, and OR 2.9; 95% CI: 1.8-4.6) and less likely to recommend termination (OR 3.8; 95% CI: 2.2-6.7, and OR 4.7; 95% CI: 2.7-8.1). In addition, physicians with a higher tolerance for prematurity were more likely to report prenatal closure as "very favorable" (OR 1.02; 95% CI: 1.00-1.05).</p>

<p><strong>DISCUSSION: </strong>In light of the MOMS trial, the vast majority of pediatric subspecialists and MFMs view prenatal MMC closure favorably. These attitudes vary by specialty and risk tolerance.</p>