Potential higher risk of tethered spinal cord in children after prenatal surgery for myelomeningocele:A systematic review and meta-analysis

Introduction We performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC. The objectives was to understand the incidence of secondary TSC after prenatal surgery for MMC compared to postnatal surgery for MMC. Material and methods On May 4, 2023, a systematic search was conducted in Medline, Embase, and the Cochrane Library to gather relevant data. Primary studies focusing on repair type, lesion level, and TSC were included, while non-English or non-Dutch reports, case reports, conference abstracts, editorials, letters, comments, and animal studies were excluded. Two reviewers assessed the included studies for bias risk, following PRISMA guidelines. TSC frequency in MMC closure types was determined, and the relationship between TSC occurrence and closure technique was analyzed using relative risk and Fisher's exact test. Subgroup analysis revealed relative risk differences based on study designs and follow-up periods. A total of ten studies, involving 2,724 patients, were assessed. Among them, 2,293 patients underwent postnatal closure, while 431 received prenatal closure for the MMC defect. In the prenatal closure group, TSC occurred in 21.6% (n = 93), compared to 18.8% (n = 432) in the postnatal closure group. The relative risk (RR) of TSC in patients with prenatal MMC closure versus postnatal MMC closure was 1.145 (95%CI 0.939 to 1.398). Fisher's exact test indicated a statistically non-significant association (p = 0.106) between TSC and closure technique. When considering only RCT and controlled cohort studies, the overall RR for TSC was 1.308 (95%CI 1.007 to 1.698) with a non-significant association (p = .053). For studies focusing on children up until early puberty (maximum 12 years follow-up), the RR for tethering was 1.104 (95%CI 0.876 to 1.391), with a non-significant association (p = 0.409). Conclusion and discussion This review found no significant increase in relative risk of TSC between prenatal and postnatal closure in MMC patients, but a trend of increased TSC in the prenatal group. More longterm data on TSC after fetal closure is needed for better counseling and outcomes in MMC.</p

Perinatal stabilisation of infants born with congenital diaphragmatic hernia: A review of current concepts

Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs into the chest. Pulmonary hypertension is a major contributor to both mortality and morbidity, however, treatment modalities are limited. Novel prenatal and postnatal interventions, such as fetal surgery and medical treatments, are currently under investigation. Until now, the perinatal stabilisation period immediately after birth has been relatively overlooked, although optimising support in these early stages may be vital in improving outcomes. Moreover, physiological parameters obtained from the perinatal stabilisation period could serve as early predictors of adverse outcomes, thereby facilitating both prevention and early treatment of these conditions. In this review, we focus on the perinatal stabilisation period by discussing the current delivery room guidelines in infants born with CDH, th

Implementation of Delayed Cord Clamping for 3 Min During Term Cesarean Sections Does Not Influence Maternal Blood Loss

Background: To assess maternal safety outcomes after a local protocol adjustment to change the interval of cord clamping to 3 min after term cesarean section.Design, Setting, and Patients: A retrospective cohort study in a tertiary referral hospital (Erasmus MC, Rotterdam). We included pregnant women who gave birth at term after cesarean section. A cohort (Nov 2016–Oct 2017) prior to the protocol implementation was compared to a cohort after its implementation (Nov 2017–Nov 2018). The study population covered 789 women (n = 376 pre-cohort; n = 413 post-cohort).Interventions: Implementation of a local protocol changing the interval of cord clamping to 3 min in all term births.Main outcome measures: Primary outcomes were the estimated maternal blood loss and the occurrence of postpartum hemorrhage (blood loss &gt;1,000 ml). Secondary outcomes included both maternal as well as neonatal outcomes.Results: Estimated maternal blood loss was not significantly different between the pre-cohort and post-cohort (400 mL [300–600] vs. 400 mL [300–600], p = 0.52). The incidence of postpartum hemorrhage (26 [6.9%] vs. 35 (8.5%), OR 1.24, 95% CI 0.73–2.11) and maternal blood transfusion (9 [2%] vs. 13 (3%), OR 1.33, 95% CI 0.56–3.14) were not different. Hemoglobin change was significantly higher in the post-cohort (−0.8 mmol/L [−1.3 to −0.5] vs. −0.9 mmol/L [−1.4 to −0.6], p = 0.01). In the post-cohort, neonatal hematocrit levels were higher (51 vs. 55%, p = 0.004) and need for phototherapy was increased (OR 1.95, 95% CI 0.99–3.84).Conclusion: Implementation of delayed cord clamping for 3 min in term cesarean sections was not associated with increased maternal bleeding complications

Increasing Respiratory Effort With 100% Oxygen During Resuscitation of Preterm Rabbits at Birth

Background: Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O2 may reduce the risk of hypoxia and increase respiratory effort at birth. Methods: Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% (n = 12) or 100% O2 (n = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O2 in kittens who started in 21% O2, and remained at 100% O2 for kittens who started the experiment in 100% O2. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Results: Initially, kittens receiving 21% O2 had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O2 [median (IQR) respiratory rate: 16 (4–28) vs. 38 (29–46) bpm, p = 0.001; variability in inter-breath interval: 33.3% (17.2–50.1%) vs. 27.5% (18.6–36.3%), p = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O2 (11/12 vs. 1/8, p = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O2. FRC was not different between study groups at both timepoints. Conclusion: Initiating resuscitation with 100% O2 resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are mandatory to confirm the benefit of this approach in terms of oxygenation. In addition, the ability to avoid hyperoxia after initiation of resuscitation with 100% oxygen, using a titration protocol based on oxygen saturation, needs to be clarified

Spontaneous breathing approach in mild congenital diaphragmatic hernia: A resuscitation algorithm

BackgroundInfants with a congenital diaphragmatic hernia (CDH) and expected mild pulmonary hypoplasia have an estimated survival rate of 90%. Current guidelines for delivery room management do not consider the individual patient's disease severity, but an individualized approach with spontaneous breathing instead of routine mechanical ventilation could be beneficial for the mildest cases. We developed a resuscitation algorithm for this individualized approach serving two purposes: improving the success rate by structuring the approach and providing a guideline for other centers.MethodsAn initial algorithm was discussed with all local stakeholders. Afterwards, the resulting algorithm was refined using input from international experts.ResultsEligible CDH infants: left-sided defect, observed to expected lung-to-head ratio ≥50%, gestational age at birth ≥37.0 weeks, and no major associated structural or genetic abnormalities. To facilitate fetal-to-neonatal transition, we propose to start stabilization with non-invasive respiratory support and to adjust this individually.ConclusionsInfants with mild CDH might benefit from an individualized approach for neonatal resuscitation. Herein, we present an algorithm that could serve as guidance for centers implementing this

Increasing Respiratory Effort With 100% Oxygen During Resuscitation of Preterm Rabbits at Birth

Background: Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O2 may reduce the risk of hypoxia and increase respiratory effort at birth. Methods: Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% (n = 12) or 100% O2 (n = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O2 in kittens who started in 21% O2, and remained at 100% O2 for kittens who started the experiment in 100% O2. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Results: Initially, kittens receiving 21% O2 had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O2 [median (IQR) respiratory rate: 16 (4–28) vs. 38 (29–46) bpm, p = 0.001; variability in inter-breath interval: 33.3% (17.2–50.1%) vs. 27.5% (18.6–36.3%), p = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O2 (11/12 vs. 1/8, p = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O2. FRC was not different between study groups at both timepoints. Conclusion: Initiating resuscitation with 100% O2 resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are mandatory to confirm the benefit of this approach in terms of oxygenation. In addition, the ability to avoid hyperoxia after initiation of resuscitation with 100% oxygen, using a titration protocol based on oxygen saturation, needs to be clarified

Oxygen Saturation Index in Neonates with a Congenital Diaphragmatic Hernia: A Retrospective Cohort Study

Introduction: The oxygenation index (OI) is a marker for respiratory disease severity and adverse neonatal outcomes. The oxygen saturation index (OSI) is an alternative that allows for continuous noninvasive monitoring, but evidence for clinical use in critically ill neonates is scarce. The aim of this study was to evaluate the OSI as compared to the OI in term neonates with a congenital diaphragmatic hernia (CDH). Methods: A single-center retrospective cohort study was conducted including all live-born infants with an isolated CDH between June 2017 and December 2020. Paired values of the OI and OSI in the first 24 h after birth were collected. The relation between OI and OSI measurements was assessed, taking into account arterial pH, body temperature, and preductal versus postductal location of oxygen saturation measurement or arterial blood sampling. The predictive values for pulmonary hypertension, need for extracorporeal membrane oxygenation therapy, and survival at discharge were evaluated. Results: Of 33 subjects included, 398 paired values of the OI (median 5.8 [3.3-17.2]) and OSI (median 7.3 [3.6-14.4]) were collected. The OI and OSI correlated strongly (r = 0.77, p < 0.001). The OSI values corresponding to the clinically relevant OI values (10, 15, 20, and 40) were 8.9, 10.9, 12.9, and 20.9, respectively. The predictive values of the OI and OSI were comparable for all adverse neonatal outcomes. No difference was found in the area under the receiver operating characteristic curves for the OI and the OSI for adverse neonatal outcomes. Conclusions: The OSI could replace the OI in clinical practice in infants with a CDH

Spontaneous breathing approach in mild congenital diaphragmatic hernia: a resuscitation algorithm

Background: Infants with a congenital diaphragmatic hernia (CDH) and expected mild pulmonary hypoplasia have an estimated survival rate of 90%. Current guidelines for delivery room management do not consider the individual patient's disease severity, but an individualized approach with spontaneous breathing instead of routine mechanical ventilation could be beneficial for the mildest cases. We developed a resuscitation algorithm for this individualized approach serving two purposes: improving the success rate by structuring the approach and providing a guideline for other centers. Methods: An initial algorithm was discussed with all local stakeholders. Afterwards, the resulting algorithm was refined using input from international experts. Results: Eligible CDH infants: left-sided defect, observed to expected lung-to-head ratio ≥50%, gestational age at birth ≥37.0 weeks, and no major associated structural or genetic abnormalities. To facilitate fetal-to-neonatal transition, we propose to start stabilization with non-invasive respiratory support and to adjust this individually. Conclusions: Infants with mild CDH might benefit from an individualized approach for neonatal resuscitation. Herein, we present an algorithm that could serve as guidance for centers implementing this

Prenatal stomach position and volume in relation to postnatal outcomes in left-sided congenital diaphragmatic hernia

OBJECTIVE: To examine the association between prenatal stomach position (SP) grade and stomach volume (SV) and the need for pulmonary hypertension (PH) treatment after birth in prenatally diagnosed left-sided congenital diaphragmatic hernia (CDH), live born >34 weeks. METHODS: In retrospect, SP grade and SV were determined in fetuses with isolated left-sided CDH from 19 weeks gestational age (GA) onwards at three different time periods (≤24 weeks' GA: US1, 24-30 weeks' GA: US2; ≥30 weeks' GA: US3). Primary outcome was need for treatment of PH after birth. Secondary analyses included the predictive value of SP and SV for other respiratory outcomes and postnatal defect size. RESULTS: A total of 101 fetuses were included. SP grade was significantly associated with need for treatment of PH (US1, US2, and US3: p < 0.02). Also, prenatal SP grade was positively associated with defect size and development of chronic lung disease (CLD) in survivors. No association was found between SV and respiratory morbidities or postnatal defect size. CONCLUSION: SP grade in left-sided CDH fetuses is associated with an increased need for PH treatment, a larger postnatal defect size and CLD in survivors. We consider SP determination a valuable contribution to the prenatal assessment of left-sided CDH