Congenital Diaphragmatic Hernia Research Articles

Association of Fetal Lung Development Disorders with Adult Diseases: A Comprehensive Review.

Fetal lung development is a crucial and complex process that lays the groundwork for postnatal respiratory health. However, disruptions in this delicate developmental journey can lead to fetal lung development disorders, impacting neonatal outcomes and potentially influencing health outcomes well into adulthood. Recent research has shed light on the intriguing association between fetal lung development disorders and the development of adult diseases. Understanding these links can provide valuable insights into the developmental origins of health and disease, paving the way for targeted preventive measures and clinical interventions. This review article aims to comprehensively explore the association of fetal lung development disorders with adult diseases. We delve into the stages of fetal lung development, examining key factors influencing fetal lung maturation. Subsequently, we investigate specific fetal lung development disorders, such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), congenital diaphragmatic hernia (CDH), and other abnormalities. Furthermore, we explore the potential mechanisms underlying these associations, considering the role of epigenetic modifications, transgenerational effects, and intrauterine environmental factors. Additionally, we examine the epidemiological evidence and clinical findings linking fetal lung development disorders to adult respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and other respiratory ailments. This review provides valuable insights for healthcare professionals and researchers, guiding future investigations and shaping strategies for preventive interventions and long-term care.

Delivery Room Resuscitation of Infants with Congenital Diaphragmatic Hernia: Lessons Learned through Video Review

Introduction: Delivery room (DR) interventions for infants with congenital diaphragmatic hernia (CDH) are not well described. This study sought to describe timing and order of DR interventions and identify system factors impacting CDH DR resuscitations using a human factors framework. Methods: This was a single-center observational study of video-recorded CDH DR resuscitations documenting timing and order of interventions. The team used the Systems Engineering Initiative for Patient Safety (SEIPS) model to identify system factors impacting DR resuscitations and time to invasive ventilation. Results: We analyzed 31 video-recorded CDH resuscitations. We observed variability in timing and order of resuscitation tasks. The “Internal Environment” and “Tasks” components of the SEIPS model were prominent factors affecting resuscitation efficiency; significant room and bed spatial constraints exist, and nurses have a significant task burden. Additionally, endotracheal tube preparation was a prominent barrier to timely invasive ventilation. Conclusion: Video review revealed variation in event timing and order during CDH resuscitations. Standardization of the room setup, equipment, and event order and reallocation of tasks facilitate more efficient intubation and ventilation, representing targets for CDH DR improvement initiatives. This work emphasizes the utility of rigorous human factors review to identify areas for improvement during DR resuscitation.

Exercise-Induced Pulmonary Hypertension in Long-Term Survivors of Congenital Diaphragmatic Hernia

ObjectiveTo determine the prevalence of exercise-induced pulmonary hypertension (PH) among long-survivors of congenital diaphragmatic hernia (CDH) repair. Study designThis is a single-center, retrospective cohort study of CDH survivors who underwent exercise stress echocardiography (ESE) at Boston Children’s Hospital from January 2006 to June 2020. PH severity was assessed by echocardiogram at baseline and after exercise. Patients were categorized by right ventricular systolic pressure (RVSP) after exercise: Group 1 - no or mild PH; and Group 2 - moderate or severe PH (RVSP ≥ 60 mmHg or ≥ ½ systemic blood pressure). ResultsEighty-four patients with CDH underwent 173 ESE with median age 8.1 (4.8 – 19.1) years at first ESE. Sixty-four patients were classified as Group 1, 11 as Group 2, and 9 had indeterminate RVSP with ESE. Moderate to severe PH after exercise was found in 8 (10%) patients with no or mild PH at rest. Exercise-induced PH was associated with larger CDH defect size, patch repair, use of ECMO, supplemental oxygen at discharge, and higher WHO functional class. Higher VE/VCO2 slope, lower peak oxygen saturation, and lower percent predicted FEV1 and FEV1/FVC ratio were associated with Group 2 classification. ESE changed management in 9/11 Group 2 patients. PH was confirmed in all 5 Group 2 patients undergoing cardiac catheterization after ESE. ConclusionsAmong long-term CDH survivors, 10% had moderate-severe exercise-induced PH on ESE, indicating ongoing pulmonary vascular abnormalities. Further studies are needed to optimally define PH screening and treatment for patients with repaired CDH.

Congenital Diaphragmatic Hernia: Antenatal Sonographic Findings with Review of Literature

Congenital Diaphragmatic Hernia: Antenatal Sonographic Findings with Review of Literature

Diagnosis, management and long term cardiovascular outcomes of phenotypic profiles in pulmonary hypertension associated with congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm resulting in herniation of viscera into the chest. This condition is characterized by pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. PH is a key component of the pathophysiology of CDH in neonates and contributes to morbidity and mortality. Traditionally, PH associated with CDH (CDH-PH) is thought to be secondary to increased pulmonary arterial resistance and vasoreactivity resulting from pulmonary hypoplasia. Additionally, there is increasing recognition of associated left ventricular hypoplasia, dysfunction and elevated end diastolic pressure resulting in pulmonary venous hypertension in infants with CDH. Thus, hemodynamic management of these infants is complex and cautious use of pulmonary vasodilators such as inhaled nitric oxide (iNO) is warranted. We aim to provide an overview of different phenotypic profiles of CDH associated PH and potential management options based on current evidence and pathophysiology.

On the curious association of diaphragmatic hernia and Urban-Rifkin-Davis Syndrome (Autosomal Recessive Cutis Laxa-1C): A collective review of 16 cases

Background: Autosomal recessive cutis laxa type-1C is also known as Urban-Rifkin-Davis syndrome (URDS). It is known to affect cardiopulmonary, integumentary, gastrointestinal, musculoskeletal and genitourinary systems. However, its frequent association with congenital diaphragmatic hernia has not previously been highlighted. Case Presentation: A newborn male with cutis laxa presented with respiratory distress at birth. The cause of dyspnoea was perinatal strangulation of the stomach in hiatus hernia. After surgical repair of the hernia, his respiratory distress temporarily improved but kept recurring periodically by various mechanisms in sequence namely pulmonary hypertension, tracheomalacia, pulmonary emphysema and finally he succumbed to pneumothorax. Genetic analysis revealed his skin condition as autosomal recessive cutis laxa type-1C which is also known as URDS. Exome sequencing revealed a novel frameshift mutation c.426delC (p.Cys143Alafs*41) of the LTBP4 gene in the exon 5 of Chromosome 19. Conclusion: Out of the 28 cases of URDS reported in the world literature 57% had congenital diaphragmatic hernia (CDH) and 53% of them died during infancy. Such a high incidence of CDH is not observed in other subtypes of elastic disorders. Thus, congenital diaphragmatic defects appear to be a characteristic diagnostic feature of URDS in patients with cutis laxa.

Multicentre, randomised controlled trial of physiological-based cord clamping versus immediate cord clamping in infants with a congenital diaphragmatic hernia (PinC): statistical analysis plan

BackgroundInfants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial).DesignThe PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4–8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved.Trial registrationClinicalTrials.gov NCT04373902 (registered April 2020).

Neurodevelopmental Outcomes in Children After Fetoscopic Endoluminal Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia: Results From a Multidisciplinary Clinic

BackgroundWe compared early neurodevelopmental morbidity in young children with severe CDH who underwent FETO to those without fetal therapy. MethodsWe conducted a prospective study of severe CDH patients undergoing FETO (n = 18) at a single North American center from 2015 to 2021 (NCT02710968). Outpatient survivors (n = 12) were evaluated by a multidisciplinary team and compared to expectantly managed CDH patients. Neurodevelopmental outcomes were assessed using the Capute Scales [Clinical Linguistic and Auditory Milestone Scales (CLAMS) and Cognitive Adaptive Test (CAT)], with a developmental quotient (DQ) < 85 indicative of at-risk for delay. ResultsAt one year, 58% (n = 7) of FETO patients underwent evaluation, with notable concern for language delay (CLAMS median DQ, 80.1 [interquartile range, 67.6–86.7]). FETO scores improved by 24-months, whereas high severity/non-FETO scores declined [CLAMS median DQ (Difference in DQ), 92.3 (+12.2) vs. 77.1 (−13.4), respectively; p = 0.049]. On the initial CAT, FETO patients had concern for visual motor and problem-solving delays, with a median DQ of 81.3 (62.1–89.4). At 24-months, FETO patients had improving scores [Median CAT DQ, 90.8 (+9.5)], whereas high severity/non-FETO [87.5 (−3.0), p = 0.28] had declining scores. ConclusionThese initial data suggest that FETO is associated with favorable neurodevelopmental outcomes at 24-months compared to severe CDH under expectant management. Level of EvidenceIII.

Pleural Effusion and Chylothorax in Congenital Diaphragmatic Hernia-Risk Factors, Management and Outcome.

Background: Pleural effusion and chylothorax are common complications in the treatment of congenital diaphragmatic hernia (CDH). We set out to identify risk factors for chylothorax development in patients with CDH and to investigate the association of pleural effusion and chylothorax with neonatal morbidity and mortality. Methods: In this retrospective cohort study, we included 396 neonates with CDH treated at our institution between January 2013 and June 2019. Preoperative and postoperative chest radiographs and clinical data were evaluated and correlated with morbidity, complications and mortality. Results: Laboratory-confirmed chylothorax occurred in 58 (18.6%) of all CDH cases. Pleural effusion was frequently observed as a postoperative complication but also occurred as a pre-existing condition. Neonates with large defects of size C and D, patch repair, the need for presurgical and/or postsurgical ECMO support, pulmonary hypertension, liver-up phenomenon and lower relative fetal lung volume were associated with higher occurrences of chylothorax. After stepwise logistic regression, larger CDH defects (p < 0.0001) and the need for postsurgical ECMO (p = 0.0158) remained significant risk factors for CTX to occur (AUC 0.71). The same potential risk factors were used to assess their association with both presurgical and postsurgical pleural effusion. After stepwise logistic regression, only the need for presurgical ECMO remained significantly associated with presurgical PE (p < 0.01, AUC 0.65) and patch repair as the therapeutic intervention remained significantly associated with the occurrence of postsurgical PE (p < 0.0001, AUC 0.80). Patients with CTX had longer durations of both MV (p < 0.0001) and subsequent ventilatory assistance with spontaneous breathing (p = 0.0004), increased total lengths of hospitalization (p < 0.0001), increased durations of ECMO (p < 0.01) and increased incidences of CLD (p < 0.0001) compared to patients without CTX. No significant difference could be found for survival in both groups (p = 0.12). Conclusions: Our data suggest that the incidence of chylothorax is associated with large diaphragmatic defects, the need for postsurgical ECMO and the development of chronic lung disease, but not with survival.

Pulmonary vasculature development in congenital diaphragmatic hernia: a novel automated quantitative imaging analysis.

Impaired fetal lung vasculature determines the degree of pulmonary hypertension in the congenital diaphragmatic hernia (CDH). This study aims to demonstrate the morphometric measurements that differ in pulmonary vessels of fetuses with CDH. Nitrofen-induced CDH Sprague-Dawley rat fetuses were scanned with microcomputed tomography. The analysis of the pulmonary vascular tree was performed with artificial intelligence. The number of segments in CDH was significantly lower than that in the control group on the left (U = 2.5, p = 0.004) and right (U = 0, p = 0.001) sides for order 1(O1), whereas there was a significant difference only on the right side for O2 and O3. The pooled element numbers in the control group obeyed Horton's law (R2 = 0.996 left and R2 = 0.811 right lungs), while the CDH group broke it. Connectivity matrices showed that the average number of elements of O1 springing from elements of O1 on the left side and the number of elements of O1 springing from elements of O3 on the right side were significantly lower in CDH samples. According to these findings, CDH not only reduced the amount of small order elements, but also destroyed the fractal structure of the pulmonary arterial trees.

Thoracic Biometry in Patients with Congenital Diaphragmatic Hernia, a Magnetic Resonance Imaging Study.

This is a retrospective study investigating biometric measurements using magnetic resonance imaging (MRI) examinations in congenital diaphragmatic hernia (CDH). CDH is one of the more common causes of pulmonary hypoplasia, with grave consequences for the fetus. Inclusion criteria were patients diagnosed with CDH as the only observed anomaly, who underwent MRI examination after the second-trimester morphology ultrasound. The patients came from three university hospitals in Bucharest, Romania. In total, 19 patients were included in the study after applying exclusion criteria. Comparing the observed values of the thoracic transverse diameter, the thoracic anterior-posterior diameter, the thoracic circumference, the thoracic area, and the thoracic volume with values from the literature, we observed a predictive alteration of these parameters, with most showing Gaussian distribution. We observed statistical significance for most of our correlations, except between the observed and expected thoracic anterior-posterior diameters and the observed and expected thoracic volume values. This is very helpful when complex studies that can calculate the pulmonary volume cannot be obtained, as in the case of movement artifacts, and allows the clinicians to better assess the severity of the disease. MRI follow-up in CDH cases is a necessity, as it offers the most accurate thoracic biometry.

Prise en charge anténatale des fœtus porteurs d’une hernie de coupole diaphragmatique

Congenital diaphragmatic hernia (CDH) can be diagnosed prenatally and its severity assessed by fetal imaging. The prognosis of a fetus with CDH is based on whether or not the hernia is isolated, the measurement of lung volume on ultrasound and MRI, and the position of the liver. The birth of a child with CDH should take place in a center adapted to the care of such children, and in accordance with the recommendations defined by the French National Diagnosis and Care Protocol. It has recently been demonstrated that for moderate and severe forms of CDH, tracheal occlusion using a balloon placed in utero by fetoscopy (FETO) increases survival until discharge from the neonatal unit, but at the cost of an increased risk of prematurity. At the same time, advances in neonatal resuscitation and the standardization of follow-up of these children within the framework of the “Centre de référence maladies rares: hernie de coupole diaphragmatique” have improved the prognosis of these children and young adults.

Case Report: The Diaphragmatic Hernia: A Rare Cause of Intestinal Obstruction

We present the case of a 22-year-old patient, with congenital diaphragmatic hernia, diagnosed at an advanced stage due to an occlusive syndrome observed on the CT scan, revealing colonic distension upstream of a strangulated Bochdalek's diaphragmatic hernia. The patient underwent laparotomy, where the hernia was reduced, and the diaphragmatic rupture was closed. The purpose of this article is to highlight a rare cause of intestinal obstruction, which is strangulated diaphragmatic hernia, when the diagnosis and detection of complications are confirmed through CT scan, allowing for early management.

The RNA-binding protein quaking is upregulated in nitrofen-induced congenital diaphragmatic hernia lungs at the end of gestation.

The RNA-binding protein Quaking (QKI) increases during epithelial-to-mesenchymal transition and its expression is controlled by microRNA-200 family members. Here, we aimed to describe the expression of QKI in the developing lungs of control and nitrofen-induced congenital diaphragmatic hernia lungs (CDH). To investigate the expression of QKI, we dissected lungs from control and nitrofen-induced CDH rats on embryonic day 15, 18, 21 (E15, E18, E21). We performed immunofluorescence (IF) and quantitative reverse transcription PCR (RT-qPCR) for QKI expression. Additionally, we assessed Interleukin-6 (IL-6) abundance using IF. On E21, IF showed that the abundance of all three QKI isoforms and IL-6 protein was higher in CDH lungs compared to control lungs (QKI5: p = 0.023, QKI6: p = 0.006, QKI7: p = 0.014, IL-6: p = 0.045, respectively). Furthermore, RT-qPCR data showed increased expression of QKI5, QKI6, and QKI7 mRNA in E21 nitrofen lungs by 1.63 fold (p = 0.001), 1.63 fold (p = 0.010), and 1.48 fold (p = 0.018), respectively. Our data show an increase in the abundance and expression of QKI at the end of gestation in nitrofen-induced CDH lungs. Therefore, a disruption in the regulation of QKI during the late stage of pregnancy could be associated with the pathogenesis of abnormal lung development in CDH.

Use of surfactant beyond respiratory distress syndrome, what is the evidence?

Surfactant replacement therapy is currently approved by the United States Food and Drug Administration (FDA) for premature infants with respiratory distress syndrome (RDS) caused by surfactant deficiency due to immaturity. There is strong evidence that surfactant decreases mortality and air leak syndromes in premature infants with RDS. However, surfactant is also used "off-label" for respiratory failure beyond classic RDS. This review discusses current evidence for the use of off-label surfactant therapy for (1) term infants with lung disease such as meconium aspiration syndrome (MAS), pneumonia/sepsis, and congenital diaphragmatic hernia (2) premature infants after 72 h for acute respiratory failure, and (3) the use of surfactant lavage. At last, we briefly describe the use of surfactants for drug delivery and the current evidence on evaluating infants for surfactant deficiency.

Patches in Congenital Diaphragmatic Hernia: A systematic review.

This systematic review aims to evaluate current choice in practice and outcomes of biomaterials used in patch repair of congenital diaphragmatic hernia (CDH). Multiple biomaterials, both novel and combinations of pre-existing materials are employed in patch repair of large size CDH. Literature search was performed across Embase, Medline, Scopus, and Web of Science. Publications that explicitly reported patch repair, material used and recurrences following CDH repair were selected. Sixty-three papers were included, presenting data on 4598 patients of which 1811 (39.4%) were managed using 19 types of patches. Goretex® (GTX) (n=1259) was the most frequently employed patch followed by Surgisis® (n=164), Dualmesh® (n=114), Marlex®/GTX® (n=56), Tutoplast dura® (n=40), Dacron® (n=34), Dacron®/GTX® (n=32), Permacol® (n=24), Teflon® (n=24), Surgisis®/GTX® (n=15), Sauvage® Filamentous Fabric (n=13), Marlex® (n=9), Alloderm® (n=8), Silastic® (n=4), Collagen coated Vicryl® mesh (CCVM) (n=1), Mersilene® (n=1), and MatriStem® (n=1) Biomaterials were further subgrouped as: Synthetic non-resorbable (SNOR) (n=1458), Natural-resorbable (NR) (n=249), Combined natural and synthetic non-resorbable (NSNOR) (n=103), and Combined natural and synthetic resorbable (NSR) (n=1). Overall recurrence rate for patch repair was 16.8% (n=305). For patch types with n>20, recurrence rate was lowest in GTX/Marlex (3.6%), followed by Teflon (4.2%), Dacron (5.6%), GTX (13.8%), Permacol (16.0%), Tutoplast Dura (17.5%), Dualmesh (20.2%), SIS/GTX (26.7%), SIS (36.6%), and Dacron/GTX (37.5%).When analysed by biomaterial groups, recurrence was highest in NSR (100%), followed by NR (32.9%), NSNOR (17.5) and SNOR the least (14.0%). In this cohort, over one-third of CDH were closed using patches. To date, 19 patch types/variations have been employed for CDH closure. GTX is the most popular, employed in 70% of patients; however excluding smaller cohorts (n<20) GTX/Marlex is associated with the lowest recurrence rate (3.6%). SNOR was the material type least associated with recurrence while NSR experienced recurrence in every instance.

Diagnostics and features of the course of Meckel’s diverticulus of thoracic localization with combined developmental malformations

The paper presents literature data and our own results of surgical treatment of children with a rare form of Meckel’s diverticulum in combination with congenital diaphragmatic hernia and intestinal malrotation. Of the 47 children observed in the clinical bases of the Department of Hospital Surgery of the Tashkent Medical Pediatric Institute in 2010-2022, 1 child was diagnosed with this anomaly.

Postoperative intussusception after congenital diaphragmatic hernia repair: a report of 2 cases

Postoperative intussusception after congenital diaphragmatic hernia repair: a report of 2 cases

Relative Mediastinal Displacement Index (RMDI): A Prenatal MRI Indicator of Adverse Events in Fetuses With Isolated Left Congenital Diaphragmatic Hernia.

Extracorporeal membrane oxygenation (ECMO), has partly improved congenital diaphragmatic hernia (CDH) outcomes, yet the overall morbidity and mortality remain high. Existing prenatal indicators for CDH fetuses are operator-dependent, time-consuming, or less accurate, a new simple and accurate indicator to indicate adverse events in CDH patients is needed. To propose and assess the association of a new MRI parameter, the relative mediastinal displacement index (RMDI), with adverse events including in-hospital deaths or the need for ECMO in fetuses with isolated left CDH (iLCDH). Retrospective analysis. One hundred thirty-nine fetuses were included in the iLCDH group (24 with adverse events and 115 without) and 257 fetuses were included in the control group from two centers in Guangzhou. 3.0 T, T2WI-TRUFI; 1.5 T, T2WI-FIESTA. Three operators independently measured the , , and DH on the axial images. The calculation formula of the RMDI was ( + )/DH. The independent sample t test, Mann-Whitney U test, Chi-square test, Chi-square test continuity correction, Fisher's test, linear regression analysis, logistic regression analysis, intraclass correlation coefficient, receiver operating characteristic curve analysis, and Delong test. A P value <0.05 was considered statistically significant. The RMDI did not change with gestational age in the iLCDH group (with [P = 0.189] and without [P = 0.567] adverse events) and the control group (P = 0.876). There were significant differences in RMDI between the iLCDH group (0.89 [0.65, 1.00]) and the control group (-0.23 [-0.34, -0.16]). In the iLCDH group, RMDI was the only indicator left for indicating adverse events, and the best cutoff value was 1.105. Moreover, there was a significant difference in diagnostic accuracy between the RMDI (AUC = 0.900) and MSA (AUC = 0.820), LHR (AUC = 0.753), o/e LHR (AUC = 0.709), and o/e TFLV (AUC = 0.728), respectively. The RMDI is expected to be a simple and accurate tool for indicating adverse events in fetuses with iLCDH. 4 TECHNICAL EFFICACY: Stage 1.

The Association of Prenatal Diagnoses with Mortality and Long-Term Morbidity in Children with Specific Isolated Congenital Anomalies: A European Register-Based Cohort Study

ObjectivesTo compare 5-year survival rate and morbidity in children with spina bifida, transposition of great arteries (TGA), congenital diaphragmatic hernia (CDH) or gastroschisis diagnosed prenatally with those diagnosed postnatally.MethodsPopulation-based registers’ data were linked to hospital and mortality databases.ResultsChildren whose anomaly was diagnosed prenatally (n = 1088) had a lower mean gestational age than those diagnosed postnatally (n = 1698) ranging from 8 days for CDH to 4 days for TGA. Children with CDH had the highest infant mortality rate with a significant difference (p < 0.001) between those prenatally (359/1,000 births) and postnatally (116/1,000) diagnosed. For all four anomalies, the median length of hospital stay was significantly greater in children with a prenatal diagnosis than those postnatally diagnosed. Children with prenatally diagnosed spina bifida (79% vs 60%; p = 0.002) were more likely to have surgery in the first week of life, with an indication that this also occurred in children with CDH (79% vs 69%; p = 0.06).ConclusionsOur findings do not show improved outcomes for prenatally diagnosed infants. For conditions where prenatal diagnoses were associated with greater mortality and morbidity, the findings might be attributed to increased detection of more severe anomalies. The increased mortality and morbidity in those diagnosed prenatally may be related to the lower mean gestational age (GA) at birth, leading to insufficient surfactant for respiratory effort. This is especially important for these four groups of children as they have to undergo anaesthesia and surgery shortly after birth. Appropriate prenatal counselling about the time and mode of delivery is needed.