Johnson, Anthony

ImportanceEarly 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.ObjectiveTo assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks’ gestation to mitigate lethal pulmonary hypoplasia.Design, Setting, and ParticipantsProspective, 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.ExposureEnrolled 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 MeasuresThe primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement.ResultsThe 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 RelevanceSerial 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 RegistrationClinicalTrials.gov Identifier: NCT03101891

AbstractObjectiveTo evaluate inter‐rater agreement for sonographic classification of stomach position (as a surrogate for liver herniation) in fetal left congenital diaphragmatic hernia (LCDH) among: (i) fetal medicine specialists from the North American Fetal Therapy Network (NAFTNet) centers within and without the fetal endoscopic tracheal occlusion (FETO) consortium and in comparison to an expert external reviewer (ER1); and (iii) among two expert ERs (ER1 and ER2).MethodsForty‐eight physicians from 26 NAFTNet centers and 2 ERs were asked to assess 13 sonographic clips of isolated LCDH and classify stomach position as “intra‐abdominal,” “anterior left chest,” “mid to posterior left chest,” or “retro‐cardiac" based on the classification published by Basta et al.8 Interrater agreement was assessed by determining proportion of stomach position ratings concordant amongst NAFTNet participants and ER1. Agreement for stomach position between ERs was calculated using kappa statistics.ResultsAgreement for stomach position was 69% (39%–85%; n = 19) and 54% (23%–92%; n = 29) among FETO and non‐FETO NAFTNet participants, respectively, when compared to ER1. Most disagreement in stomach position was related to a discrepancy of one position. ERs were in agreement for stomach position in 5 of 13 cases (38.5%) and inter‐rater agreement was highest for “anterior” stomach position.ConclusionInterrater agreement for stomach position assessment in CDH was poor across NAFTNet and indeed amongst expert reviewers.

AbstractIntroductionPrenatal work‐up for congenital diaphragmatic hernia (CDH) is important for risk stratification, standardization, counseling, and optimal therapeutic choice. To determine current practice patterns regarding prenatal CDH work‐up, including prenatal ultrasound and magnetic resonance imaging (MRI) use, and to identify areas for standardization of such evaluation between fetal centers.MethodsA survey regarding prenatal CDH work‐up was sent to each member center of the North American Fetal Therapy Network (NAFTNet) (n = 36).ResultsAll responded. Sonographic measurement of lung‐to‐head ratio (LHR) was determined by all, 89% (32/36) of which routinely calculate observed‐to‐expected LHR. The method for measuring LHR varied: 58% (21/36) used a “trace” method, 25% (9/36) used “longest axis,” and 17% (6/36) used an “antero‐posterior” method. Fetal MRI was routinely used in 78% (28/36) of centers, but there was significant variability in fetal lung volume measurement. Whereas all generated a total fetal lung volume, the planes, methodology and references values varied significantly. All evaluated liver position, 71% (20/28) evaluated stomach position and 54% (15/28) quantified the degree of liver herniation. More consistency in workup was seen between centers offering fetal intervention.ConclusionPrenatal CDH work‐up and management differs considerably among North American fetal diagnostic centers, highlighting a need for its standardization.

AbstractObjectiveTo evaluate variability in antenatal sonographic prognostication of congenital diaphragmatic hernia (CDH) within the North American Fetal Therapy Network (NAFTNet).MethodsNAFTNet centre were invited to complete a questionnaire and participate in videoconference calls, during which participants were observed while measuring lung area by ultrasound using the anteroposterior (AP) method, longest method, and trace method. Each center identified 1–2 experienced fetal medicine specialist(s) or medical imaging specialists locally to participate in the study. Practices were compared among NAFTNet centre within and without the fetal endoscopic tracheal occlusion (FETO) consortium.ResultsNineteen participants from 9 FETO center and 30 participants from 17 non‐FETO center completed the survey and 31 participants were interviewed and observed while measuring sonographic lung area. All Centres measured observed‐to‐expected lung‐to‐head ratio (o/e LHR) or LHR for CDH prognostication. Image selection criteria for lung area measurement were consistent, including an axial section of the chest with clear lung borders and a 4‐chamber cardiac view. Lung area measurement methods varied across NAFTNet, with most centre using longest (4/9 FETO vs. 13/29 non‐FETO) or trace (3/9 FETO vs. 11/29 non‐FETO) method. Centres differed in expected reference ranges for o/e LHR determination and whether the lowest, highest or average o/e LHR was utilized.ConclusionVariability in antenatal sonographic prognostication of CDH was identified across NAFTNet, indicating a need for consensus‐based standardization.

AbstractObjectiveTo determine the antenatal sonographic lung area measurement method in left congenital diaphragmatic hernia (CDH) with the highest interrater agreement among North American Fetal Therapy Network (NAFTNet) centers within and outside the fetoscopic tracheal occlusion (FETO) consortium and in comparison with a European “expert” reviewer (ER).MethodsNineteen members from nine FETO consortium centers and 29 reviewers from 17 non‐FETO centers reviewed ultrasound clips of the chest from 13 fetuses with isolated left CDH and were asked to select a static plane for lung area measurement using anteroposterior (AP), longest, and trace methods. Interrater agreement in lung area measurements was determined using intraclass correlation coefficient (ICC). Bland‐Altman analysis was used to evaluate mean difference (bias) between NAFTNet reviewers and ER.ResultsAmong FETO centers, agreement was highest using trace (ICC 0.94; 95% CI, 0.83‐0.98), followed by longest (ICC 0.89; 95% CI, 0.75‐0.97) and lowest for A‐P (ICC 0.83; 95% CI, 0.67‐0.94). Similar trends were noted in non‐FETO centers. When compared with ER, bias was lowest for trace: 14 ± 38 mm2 and 19 ± 36 mm2 for FETO and non‐FETO centers, respectively.ConclusionThe trace method demonstrated the highest interrater agreement and lowest bias for lung area estimation in left CDH across NAFTNet.