Survey of Neonatal Management After Amnioinfusion for Anhydramnios.

This survey study reports on use of renal replacement therapy, hemodynamic support, sedation, neuroimaging, and extracorporeal membrane oxygenation at Renal Anhydramnios Fetal Therapy trial sites for neonates with either bilateral renal agenesis or fetal kidney failure.

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Racial and Ethnic Disparities in Outcomes Among Newborns with Congenital Diaphragmatic Hernia.

Importance: There is some data to suggest that racial and ethnic minority infants with congenital diaphragmatic hernia (CDH) have poorer clinical outcomes. Objective: To determine what patient- and institutional-level factors are associated with racial and ethnic differences in CDH mortality. Design, Setting, and Participants: Multicenter cohort study of 49 US children's hospitals using the Pediatric Health Information System database from January 1, 2015, to December 31, 2020. Participants were patients with CDH admitted on day of life 0 who underwent surgical repair. Patient race and ethnicity were guardian-reported vs hospital assigned as Black, Hispanic (White or Black), or White. Data were analyzed from August 2021 to March 2022. Exposures: Patient race and ethnicity: (1) White vs Black and (2) White vs Hispanic; and institutional-level diversity (as defined by the percentage of Black and Hispanic patients with CDH at each hospital): (1) 30% or less, (2) 31% to 40%, and (3) more than 40%. Main Outcomes and Measures: The primary outcomes were in-hospital and 60-day mortality. The study hypothesized that hospitals managing a more racially and ethnically diverse population of patients with CDH would be associated with lower mortality among Black and Hispanic infants. Results: Among 1565 infants, 188 (12%), 306 (20%), and 1071 (68%) were Black, Hispanic, and White, respectively. Compared with White infants, Black infants had significantly lower gestational ages (mean [SD], White: 37.6 [2] weeks vs Black: 36.6 [3] weeks; difference, 1 week; 95% CI for difference, 0.6-1.4; P < .001), lower birthweights (White: 3.0 [1.0] kg vs Black: 2.7 [1.0] kg; difference, 0.3 kg; 95% CI for difference, 0.2-0.4; P < .001), and higher extracorporeal life support use (White: 316 patients [30%] vs Black: 69 patients [37%]; χ21 = 3.9; P = .05). Black infants had higher 60-day (White: 99 patients [9%] vs Black: 29 patients [15%]; χ21 = 6.7; P = .01) and in-hospital (White: 133 patients [12%] vs Black: 40 patients [21%]; χ21 = 10.6; P = .001) mortality . There were no mortality differences in Hispanic patients compared with White patients. On regression analyses, institutional diversity of 31% to 40% in Black patients (hazard ratio [HR], 0.17; 95% CI, 0.04-0.78; P = .02) and diversity greater than 40% in Hispanic patients (HR, 0.37; 95% CI, 0.15-0.89; P = .03) were associated with lower mortality without altering outcomes in White patients. Conclusions and Relevance: In this cohort study of 1565 who underwent surgical repair patients with CDH, Black infants had higher 60-day and in-hospital mortality after adjusting for disease severity. Hospitals treating a more racially and ethnically diverse patient population were associated with lower mortality in Black and Hispanic patients.

Design and Protocol of the Renal Anhydramnios Fetal Therapy (RAFT) Trial.

PURPOSE: Anhydramnios secondary to anuria before 22 weeks of gestational age and congenital bilateral renal agenesis before 26 weeks of gestational age are collectively referred to as early-pregnancy renal anhydramnios. Early-pregnancy renal anhydramnios occurs in at least 1 in 2000 pregnancies and is considered universally fatal when left untreated because of severe pulmonary hypoplasia precluding ex utero survival The Renal Anhydramnios Fetal Therapy (RAFT) trial is a nonrandomized, nonblinded, multicenter clinical trial designed to assess the efficacy, safety, and feasibility of amnioinfusions for patients with pregnancies complicated by early-pregnancy renal anhydramnios. The primary objective of this study is to determine the proportion of neonates surviving to successful dialysis, defined as use of a dialysis catheter for ≥14 days. METHODS: A consortium of 9 North American Fetal Therapy Network (NAFTNet) centers was formed, and the RAFT protocol was refined in collaboration with the NAFTNet Scientific Committee. Enrollment in the trial began in April 2020. Participants may elect to receive amnioinfusions or to join the nonintervention observational expectant management group. Eligible pregnant women must be at least 18 years of age with a fetal diagnosis of isolated early-pregnancy renal anhydramnios. FINDINGS: In addition to the primary study objective stated above, secondary objectives include (1) to assess maternal safety and feasibility of the serial amnioinfusion intervention (2) to perform an exploratory study of the natural history of untreated early pregnancy renal anhydramnios (3) to examine correlations between prenatal imaging and lung specific factors in amniotic fluid as predictive of the efficacy of serial percutaneous amnioinfusions and (4) to determine short- and long-term outcomes and quality of life in surviving neonates and families enrolled in RAFT IMPLICATIONS: The RAFT trial is the first clinical trial to investigate the efficacy, safety, and feasibility of amnioinfusions to treat the survival-limiting pulmonary hypoplasia associated with anhydramnios. Although the intervention offers an opportunity to treat a condition known to be almost universally fatal in affected neonates, the potential burdens associated with end-stage kidney disease from birth must be acknowledged. CLINICALTRIALS: gov identifier: NCT03101891.

Implementation Process and Evolution of a Laparotomy-Assisted 2-Port Fetoscopic Spina Bifida Closure Program.

INTRODUCTION: Prenatal closure of open spina bifida via open fetal surgery improves neurologic outcomes for infants in selected pregnancies. Fetoscopic techniques that are minimally invasive to the uterus aim to provide equivalent fetal benefits while minimizing maternal morbidities, but the optimal technique is undetermined. We describe the development, evolution, and feasibility of the laparotomy-assisted 2-port fetoscopic technique for prenatal closure of fetal spina bifida in a newly established program. METHODS: We conducted a retrospective cohort study of women consented for laparotomy-assisted fetoscopic closure of isolated fetal spina bifida. Inclusion and exclusion criteria followed the Management of Myelomeningocele Study (MOMS). Team preparation involved observation at the originating center, protocol development, ancillary staff training, and surgical rehearsal using patient-matched models through simulation prior to program implementation. The primary outcome was the ability to complete the repair fetoscopically. Secondary maternal and fetal outcomes to assess performance of the technique were collected prospectively. RESULTS: Of 57 women screened, 19 (33%) consented for laparotomy-assisted 2-port fetoscopy between February 2017 and December 2019. Fetoscopic closure was completed in 84% (16/19) cases. Over time, the technique was modified from a single- to a multilayer closure. In utero hindbrain herniation improved in 86% (12/14) of undelivered patients at 6 weeks postoperatively. Spontaneous rupture of membranes occurred in 31% (5/16) of fetoscopic cases. For completed cases, median gestational age at birth was 37 (range 27-39.6) weeks and 50% (8/16) of women delivered at term. Vaginal birth was achieved in 56% (9/16) of patients. One newborn had a cerebrospinal fluid leak that required postnatal surgical repair. CONCLUSION: Implementation of a laparotomy-assisted 2-port fetoscopic spina bifida closure program through rigorous preparation and multispecialty team training may accelerate the learning curve and demonstrates favorable obstetric and perinatal outcomes.

Obstetrician patterns of steroid administration for the prenatal management of congenital pulmonary airway malformations.

BACKGROUND: Congenital pulmonary airway malformation (CPAM) is the most common prenatally-diagnosed lung malformation. This lesion, classified as macrocystic or microcystic, can lead to significant fetal compromise. Management options include observation, maternal antenatal steroid administration, and fetal surgical intervention. Current evidence suggests that microcystic (but not macrocystic) lesions and those with a cyst volume ratio (CVR) >1.6 are responsive to steroid therapy. The objective of this study was to identify patterns of prenatal steroid administration for the management of CPAMs and to identify characteristics of CPAMs prompting steroid administration. METHODS: An 18-question survey was distributed to obstetricians from the Pregnancy-Related Care Research Network (PRCRN) and the North American Fetal Therapy Network (NAFTNet), from January to April 2019, to capture antenatal steroid prescribing patterns. RESULTS: Response rates were 28.3% (138/487) for PRCRN and 63.3% (19/30) for NAFTNet. Among PRCRN members, 16.8% administered prenatal steroids, with most (77.2%) doing so for both microcystic and macrocystic CPAMs; corresponding percentages for NAFTNet members were 90.9% and 52.6%. Two thirds (65.6%) of obstetricians who administer steroids do so for a CVR > 1.6, without evidence of mediastinal shift or hydrops fetalis. CONCLUSIONS: There is a lack of consensus among obstetricians as to the CPAM characteristics that should prompt administration of prenatal steroids. Many surveyed obstetricians do not use cyst type or CVR to guide decision-making regarding steroid therapy.

Single-Center Outcome of Fetoscopic Tracheal Balloon Occlusion for Severe Congenital Diaphragmatic Hernia.

OBJECTIVE: To assess feasibility and maternal and infant outcome after fetoscopic tracheal balloon occlusion in patients with severe congenital diaphragmatic hernia. METHODS: We conducted a prospective cohort study of fetuses with congenital diaphragmatic hernia and observed/expected lung/head ratio less than 30%. Eligible women had planned fetoscopic tracheal balloon occlusion at 26 0/7-29 6/7 weeks of gestation and balloon removal 4-6 weeks later. Standardized prenatal and postnatal care was at a single institution. Fetoscopic tracheal balloon occlusion details, lung growth, obstetric complications, birth outcome, and infant outcome details until discharge were evaluated. RESULTS: Of 57 women screened, 14 (25%) were enrolled between 2015 and 2019. The congenital diaphragmatic hernia was left in 12 (86%); the pre-fetoscopic tracheal balloon occlusion observed/expected lung/head ratio was 23.2% (range 15.8-29.0%). At a median gestational age of 28 5/7 weeks (range 27 3/7-29 6/7), fetoscopic tracheal balloon occlusion was successful in all cases, and balloons remained in situ. Removal was elective in 10 (71%) patients, by ultrasound-guided needle puncture in eight (57%), and occurred at a median of 33 4/7 weeks of gestation (range 32 1/7-34 4/7; median occlusion 34 days, range 17-44). The post-fetoscopic tracheal balloon occlusion observed/expected lung/head ratio increased to a median of 62.8% (44.0-108) and fell to a median of 46.6% (range 30-92) after balloon removal (all Mann Whitney U, P<.003). For prevention of preterm birth, all patients received vaginal progesterone; 11 (79%) required additional tocolytics, three (21%) had vaginal pessary placement for cervical shortening, and five (36%) had amnioreduction for polyhydramnios. Median gestational age at birth was 39 2/7 weeks (range 33 6/7-39 4/7), with term birth in eight (57%) patients. Twelve (86%) neonates required high-frequency ventilation, and seven (50%) required extracorporeal membrane oxygenation for a median of 7 days (range 3-19). All neonates needed patch repair. Neonatal survival was 93% (n=13, 95% CI 49-100%), and survival to hospital discharge was 86% (n=12, 95% CI 44-100%). CONCLUSION: Fetoscopic tracheal balloon occlusion for severe congenital diaphragmatic hernia was feasible in our single-center setting, with few obstetric complications and favorable infant outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02710968.

Risks of preterm birth among non-Hispanic black and non-Hispanic white women: Effect modification by maternal age.

BACKGROUND: Preterm birth (PTB) disproportionately affects African American compared with Caucasian women, although reasons for this disparity remain unclear. Some suggest that a differential effect of maternal age by race/ethnicity, especially at older maternal ages, may explain disparities. OBJECTIVE: To determine whether the relationship between maternal age and preterm birth varies by race/ethnicity among primiparae non-Hispanic blacks (NHB) and non-Hispanic whites (NHW). METHODS: A cross-sectional study of 367 081 singleton liveborn first births to NHB and NHW women in California from 2008 to 2012 was conducted. Rate ratios (RR) were estimated for PTB and its subtypes-spontaneous and clinician-initiated-after adjusting for confounders through Poisson regression. Universal age/race reference groups (NHW, 25-29 years) and race-specific reference groups (NHW or NHB, 25-29 years) were used for comparisons. RESULTS: Among all women, RR of PTB was highest at the extremes of age (<15 and ≥40 years). Among NHBs, the risk of PTB was higher than among NHWs at all maternal ages (adjusted RR of PTB 1.38-2.93 vs 0.98-2.38). However, using race-specific reference groups, the risk of PTB for NHB women (RR 0.91-1.88) vs NHW women (RR 0.98-2.39) was nearly identical at all maternal ages, with overlapping confidence intervals. Analyses did not demonstrate substantial divergence of risk with advancing maternal age. PTB, spontaneous PTB, and clinician-initiated PTB demonstrated similar risk patterns at younger but not older maternal ages, where risk of clinician-initiated PTB increased sharply for all women. CONCLUSIONS: Primiparae NHBs demonstrated increased risk of PTB, spontaneous PTB, and clinician-initiated PTB compared with NHWs at all maternal ages. However, RRs using race-specific reference groups converged across maternal ages, indicating a similar independent effect of maternal age on PTB by race/ethnicity. A differential effect of maternal age does not appear to explain disparities in preterm birth by race/ethnicity.

Detection of Nicotine and Nicotine Metabolites in Units of Banked Blood.

OBJECTIVES: To determine the concentrations of nicotine and nicotine metabolites in RBC units as a means to estimate the point prevalence of exposure within the healthy donor pool. METHODS: Segments from 105 RBC units were tested for the presence of nicotine, cotinine, or trans-3'-hydroxycotinine by liquid chromatography-tandem mass spectrometry. RESULTS: Of the 20 (19%) units that contained detectable concentrations of nicotine, cotinine, or trans-3'-hydroxycotinine, 19 (18.1%) contained concentrations consistent with the use of a nicotine-containing product within 48 hours of specimen collection. One RBC unit contained nicotine concentrations consistent with passive exposure. CONCLUSIONS: Chemicals from nicotine-containing products are detectable within the US RBC supply. Further investigation is needed to determine the risks of transfusion-associated exposure to nicotine and other tobacco-associated chemicals among vulnerable patient populations such as neonates.

Routine postnatal chest x-ray and intensive care admission are unnecessary for a majority of infants with congenital lung malformations.

BACKGROUND: Postnatal evaluation of prenatally identified congenital lung malformations (CLMs) often includes a chest x-ray (CXR) and neonatal intensive care unit (NICU) admission for observation. With current efforts aimed at prioritizing value and resource utilization, we sought to assess the utility of this practice in infants with known CLMs. We hypothesized that CXR and NICU admission are overused and could be deferred in the majority of cases. METHODS: Clinical and radiographic data for infants with CLM from 2007 to 2016 were reviewed with IRB approval. Regression models were developed for respiratory support (RS), symptoms within 30 days of discharge (Sx30), and abnormal CXR. Predictors included initial symptoms (IS), birth weight (BW), gestational age (GA), cyst-volume-ratio (CVR) and abnormal CXR. Odds ratios (ORs) and ROC curves were generated for significant predictors (p < 0.05). RESULTS: Fifty-eight infants were identified. Eight were excluded because birth or surgery occurred outside of our institution. Another four were excluded for requiring immediate surgery, leaving forty-six for full analysis. All infants underwent initial CXR and NICU admission, and 22 (47.8%) had an abnormal CXR. Higher CVR (OR = 6.69, p = 0.024) and lower BW (OR = 0.27, p = 0.028) both increased the odds of an abnormal CXR. Applying optimal ROC cutoffs for CVR and BW would have safely eliminated 21 of 46 CXRs, increasing CXR sensitivity from 48% to 68%. For RS and Sx30, no variable, including abnormal CXR, significantly predicted outcomes. Twenty-seven infants (59%) had a NICU stay of <24 h and only three patients (6.8%) developed Sx30. CONCLUSIONS: Both CXR and NICU admission appear to be overused in infants with CLM. CXR result did not predict need for respiratory support or symptoms following discharge, and thus may not aid in the initial evaluation or in the prediction of future care needs. Using CVR and birth weight can guide CXR use and optimize its sensitivity. Need for NICU admission could not be predicted, but a majority of infants spent <24 h in the NICU without intervention, suggesting that NICU admission was likely not needed for all infants in this setting. LEVEL OF EVIDENCE: Study of diagnostic test, Level II evidence.

With a simple calculation, the fraction of platelets remaining can be used to estimate the residual hemoglobin S percentage in sickle cell disease patients undergoing automated red blood cell exchange.

OBJECTIVES: Automated red blood cell exchange (RBX) is an important treatment for patients with sickle cell disease (SCD). Although not specifically targeted for removal, platelets (PLTs) are collected along with red blood cells during RBX. We sought to determine whether the pre- and post- RBX PLT counts could be used to derive the post-procedure hemoglobin S% (HgbS%). METHODS: Using the pre- and post- RBX lab values of 59 SCD patients undergoing 112 RBX procedures over 1 year, we derived mathematical formulas which estimate the post-RBX HgbS% based on the pre-RBX HgbS%, the pre- and post- RBX PLT, and a correction factor. RESULTS: For patients with pre-RBX HgbS > 40%, the mathematically derived post-RBX HgbS% was statistically indistinguishable from the measured post-RBX HgbS%. CONCLUSIONS: Using a simple formula, pre- and post-RBX platelet counts can provide a rapid approximation of the measured post-RBX HgbS% in patients with SCD.