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Year : 2023  |  Volume : 28  |  Issue : 2  |  Page : 122-127

Assessment of antenatal and postnatal prognostic indicators in the outcome of neonatal congenital diaphragmatic hernia: A prospective observational study

1 Department of Pediatric Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
2 Department of Neonatology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
3 Department of Obstetrics and Gynaecology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

Date of Submission30-Jul-2022
Date of Decision09-Oct-2022
Date of Acceptance26-Oct-2022
Date of Web Publication30-Nov-2022

Correspondence Address:
Bikash Kumar Naredi
Department of Pediatric Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry - 605 006
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiaps.jiaps_105_22

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Context: Despite advances in neonatal intensive care, surgical methods, and anesthesia, congenital diaphragmatic hernia (CDH) is still associated with significant mortality. Predicting which babies will have poorer outcomes is essential to identify the high-risk babies and to give targeted care and accurate prognosis to the parents, especially in a resource crunch set-up. Aims: The aim of this study is to evaluate the antenatal and postnatal prognostic factors in neonatal CDH that can be used to predict the outcome. Settings and Design: This was a prospective observational study in a tertiary care center. Subjects and Methods: Neonates presented with CDH within 28 days of life were included in the study. Bilateral disease, recurrent diseases, and babies operated outside were excluded from the study. The data were collected prospectively, and babies were followed until discharge or death. Statistical Analysis Used: Data were expressed in mean with standard deviation or median with range based on normality. All the data were analyzed using the SPSS software version 25. Results: Thirty babies with neonatal CDH were studied. There were three right-sided cases. The male-to-female ratio was 2.3:1, and 93% of babies were antenatally diagnosed. Seventeen out of the 30 babies underwent surgery. Nine (52.9%) underwent laparotomy, and 8 (47%) underwent thoracoscopic repair. Overall mortality was 53.3%, and operative mortality was 17.6%. Demographic characteristics were comparable between expired versus survived babies. The significant predictors of outcome identified were – Persistent pulmonary hypertension (PPHN), mesh repair, high-frequency oscillatory ventilation (HFOV), use of inotropes, 5-min APGAR, ventilator index (VI), and HCO3 levels. Conclusions: We conclude that the prognostic indicators associated with poor prognosis are low 5-min APGAR, high VI, low HCO3 levels in venous blood gas analysis, mesh repair, HFOV, inotropes usage, and PPHN. None of the antenatal factors studied showed any statistical significance. Further prospective studies with a larger sample size are recommended to confirm the findings.

Keywords: Congenital anomaly, congenital diaphragmatic hernia, prognostic indicators

How to cite this article:
Deivasigamani A, Naredi BK, Jindal B, Sambandan K, Govindarajan K, Plakkal N, Gowda M. Assessment of antenatal and postnatal prognostic indicators in the outcome of neonatal congenital diaphragmatic hernia: A prospective observational study. J Indian Assoc Pediatr Surg 2023;28:122-7

How to cite this URL:
Deivasigamani A, Naredi BK, Jindal B, Sambandan K, Govindarajan K, Plakkal N, Gowda M. Assessment of antenatal and postnatal prognostic indicators in the outcome of neonatal congenital diaphragmatic hernia: A prospective observational study. J Indian Assoc Pediatr Surg [serial online] 2023 [cited 2023 Mar 29];28:122-7. Available from: https://www.jiaps.com/text.asp?2023/28/2/122/362388

   Introduction Top

Congenital diaphragmatic hernia (CDH) is a significant challenge faced by pediatric surgeons. The advances and the routine use of antenatal ultrasound have led to the early diagnosis in the antenatal period as early as 25 weeks of gestation. Almost 60% of the cases are antenatally diagnosed now.[1] However, CDH is associated with considerable morbidity and mortality and is a substantial burden to neonatal intensive care units (ICUs).[2],[3] The overall survival in CDH is still around 65% despite all those advances.[4],[5] There is a significant amount of hidden mortality associated with CDH cases in the form of termination of pregnancies after early antenatal diagnosis and stillbirths. There is also considerable variation among studies due to various referral policies and case selection bias, and most of the large sample studies are retrospective in nature.[6],[7] Our current study is a prospective study that includes both antenatal and postnatal prognostic factors. The aim is to evaluate the antenatal and postnatal prognostic factors in neonatal CDH that can be used as prognostic indicators to predict the outcome. The primary objective is to assess the relationship between antenatal and postnatal prognostic factors in predicting 30-day mortality. Secondary outcomes include the duration of hospitalization, time to achieve full feeds postoperatively, number of days of ventilation, and time to preoperative stabilization.

   Subjects and Methods Top

This is a prospective observational study conducted between August 2019 and August 2021 in our tertiary care center. All antenatally detected CDH cases presenting before 28 days of life to our institution were included in the study. Babies with bilateral disease and those who were operated on elsewhere were excluded from the study. Once the baby was delivered and shifted to the ICU, the postnatal prognostic factors were recorded using the data collection pro forma. All babies were followed up, and data were collected prospectively. The course and associated anomalies were recorded. The presence of primary pulmonary hypertension (PHN) and the requirement of inotropes and other pharmacological agents like sildenafil were recorded. Among those babies who underwent surgery, intraoperative findings such as the type of surgery, size of the defect, presence of sac, and contents were recorded. The type of diaphragmatic defect is assessed by visual inspection during surgery and assigned by the operating surgeon into one of the four types from A to D.[8] Pulmonary hypoplasia is defined as the presence of hypoplastic lungs noted during surgery.

Lung-to-head ratio (LHR) is calculated by the following method. First, the fetal lung area is calculated in the antenatal ultrasound, in the transverse section of the fetal chest demonstrating the 4-chamber view of the heart and multiplying the longest diameter and the longest perpendicular of the contralateral lung. The value is divided by the head circumference, which gives the LHR.[1] The O/E LHR (observed/expected LHR) was also documented if available.

PHN measured postnatally is defined as a mean arterial pressure of >25 mmHg. PHN is diagnosed by the difference between the preductal and postductal saturation and a two-dimensional echocardiogram (2D ECHO) showing a right atrium and ventricular dilatations. Right ventricular systolic pressures were measured if facilities were available.[9]

The ventilator index (VI) was calculated, as described by Bohn et al. by the following formula from the ventilator parameters.[10]

VI = (RR × [PIP − PEEP] × PaCo2)/1000

All babies were followed up till discharge or death. All the parameters were assessed at the end of the study to find out the prognostic value of each parameter in predicting the outcome.

The data that followed normal distribution were expressed in the mean with standard deviation, and data that did not follow normal distribution were represented in the median with range. The Mann–Whitney U-test was performed for data that did not follow the normal distribution, and the independent Student's t-test was performed for data that followed a normal distribution. A P < 0.05 was considered statistically significant. Statistical analysis was performed using IBM Corp. Released 2017. (IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY).

   Results Top

During the study period of 2 years, we managed 30 neonates with the diagnosis of CDH. Demographic details of the patients are given in [Table 1]. The LHR was available for 10 babies, and the median LHR was 1.275. The prognostic factors and their statistical significance on the primary outcome mortality are given in [Table 2] and [Table 3].
Table 1: Demographic details of the overall study population and differences between the survived and expired babies

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Table 2: Categorical values studied and their significance as predictors of mortality

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Table 3: Continuous variables studied and their significance in predicting mortality

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The types of surgical approaches were either laparotomy (52.9%) or thoracoscopy (47.0%). None of the thoracoscopic surgeries was converted to open repair. While comparing thoracoscopic repair with open repair, the thoracoscopy showed a significantly decreased length of hospitalization (P = 0.024) and shorter time to reach full feeds (P = 0.02) postoperatively. The mean days of total oxygen therapy (P = 0.09) and postoperative hospital stay (P = 0.08) were also less but did not reach statistical significance. However, there was no effect on the primary outcome mortality by the type of surgical approach (P = 0.576).

Mesh repair with polytetrafluoroethylene patch was required in two babies with a large defect where suture repair was not feasible without increased tension. Both the babies expired due to reasons not directly related to mesh complications. One baby died due to severe sepsis, and another baby expired due to inadvertent injury to the ventricle, causing pericardial tamponade, and required sternotomy and repair, but the baby expired in the postoperative period. The difference was statistically significant (P = 0.02).

The VI is a useful index to assess the ventilator requirements, and a higher VI is thought to be associated with a poorer prognosis. In our study, the VI showed a significant effect on mortality (P = 0.05). Among the blood gas analysis parameters, HCO3 alone significantly affected mortality, as low HCO3 values or acidosis were associated with higher mortality (P = 0.015). There is a significant difference between the two groups regarding high-frequency oscillatory ventilation (HFOV) usage with a P = 0.02. There were 15 babies with PHN in the expired group versus only three in the survived group (P = 0.00). All 16 babies in the expired group required inotropic support, but among the 14 babies who survived, only 10 required inotropic support. The difference was statistically significant (P = 0.03).

There was only one case of recurrence among the 17 cases operated on during the study period (5.8%). There were only three cases of surgical site infection postsurgery, and all of them were following laparotomy and repair. The median duration of keeping an intercostal drain tube was 4.50 days. The median length of hospitalization was 17.50 days, and the median postoperative hospital stay was 14.00 days. The median days to reach full feeds postoperative was 8 days, the median days of total ventilation were 7 days, and the median duration of total oxygen therapy was 9.5 days.

Five of the 17 babies operated on were noted to have sacs (29.4%). The median size of the defect in its largest dimension was 4.00 cm. The most common content of hernia was the small bowel (94%). Five out of the 17 babies operated on were noted to have a liver as part of the content of hernia (29.4%). The stomach was noted in 8 (47%) babies with small bowel followed by large bowel, respectively, in 16 and 12 (94% and 70.5%) babies. Spleen is noted in 11 babies. However, no significant difference was noted in the distribution of the size of the defect, the presence of sac, or the content of hernia between the expired versus survived babies, even in those with liver or stomach as content.

   Discussion Top

CDH is one of the leading causes of perinatal morbidity and mortality. Predicting the outcome of a baby with a diagnosis of CDH is difficult, and it is highly variable.[11]

The lower the gestational age and the birth weight, the more the risk of mortality.[12] In our study population, the mean gestational age was 38.30 ± 1.236 weeks, and the mean birth weight was 2.63 ± 0.34 kg. There was only one preterm baby in our study population (3.33%) with no significant difference in mortality in relation to gestational age at birth and birth weight, with P = 0.108 and 0.673, respectively.

The LHR has been studied as an important predictor of outcomes in CDH. A value of more than 1.35 is said to be associated with a better prognosis. In our study, only 10 (35.7%) patients had an LHR value in their antenatal ultrasound report. There was no statistically significant association between LHR and mortality (P = 0.831). This may be attributed to the lesser number of patients with available LHR values.

The 5-minute APGAR score is one of the predictors of mortality noted in other studies.[13] There was a statistically significant effect on mortality between the two groups when compared in terms of the 5-min APGAR score (P = 0.001).

CDH most commonly occurs on the left side. The right-sided CDH is thought to be having poorer prognosis than the left-sided CDH. In their study published in 2016 by Partridge et al., 17% of the total population had right-sided CDH. They noted an increased requirement for supplemental oxygen and an increased incidence of PHN in right-sided CDH compared to left-sided CDH.[14] However, there was no statistically significant difference in mortality with right-sided CDH. In our study population, there was no significant difference between right-sided versus left-sided CDH in terms of mortality (P = 0.586). We also compared the duration of oxygen therapy, the presence of PHN, as well as the use of inotropes between the left and right-sided CDH and found no statistically significant difference between the two groups.

There were no major cyanotic congenital cardiac anomalies in our study population. There were minor cardiac anomalies such as ventricular septal defect, small foramen ovale, and patent ductus arteriosus, and we found no statistically significant increased risk of mortality due to the presence of congenital cardiac anomalies (P = 1.000). However, there was a difference in the median duration of oxygen therapy between those with cardiac anomalies and those without cardiac anomalies.

Of the 30 babies in our study population, only 17 (56.7%) babies underwent surgery for CDH. The babies were taken for surgery when hemodynamically stable with minimal or no inotrope support and when the blood gas analysis was within normal range. Thirteen babies died during stabilization and before any surgical procedure could be performed. The time to stabilization is taken as the duration (in days) between the presentations of the baby till the baby is taken up for the surgical procedure. The mean time to stabilization is 4.00 ± 3.79 days.

The overall mortality was 53.3% (16 out of 30 cases), and the operative mortality was 17.6%, as three out of 17 operated babies died during the study period. Among those who died, two of them were following thoracoscopic surgery, and one following laparotomy repair. We compared the thoracoscopy group and the laparotomy group with various outcomes studied. There was no significant difference between the thoracoscopic repair versus the laparotomy repair in terms of mortality (P = 0.576). However, when comparing the median days to full feeds, there is a significant difference between the thoracoscopic and the laparotomy group (P = 0.02). The median days of postoperative stay are also significantly lower in the thoracoscopic group (P = 0.005). Similar results were found by Tanaka et al. in 2013 who reported shorter hospital stays and early commencement of feeds in thoracoscopic repair compared to open CDH repair.[15],[16] There was no surgical site infection following thoracoscopic surgeries. There was a significantly lower median length of hospitalization and median postoperative hospital stay in thoracoscopic repair with P = 0.022 and 0.005, respectively.

A study published by the CDH study group in 2007 showed that the defect size affects the mean length of hospitalization and total duration of mechanical ventilation.[8] However, in our study, the length of hospitalization was lesser in defects with smaller sizes, but it was not statistically significant. Zamora et al. in their retrospective review noted better outcomes in babies with sacs in CDH.[17] However, in our study, there was no statistically significant difference in mortality between those babies with the sac and those without the sac (P = 0.191).

Mullassery et al. in their systematic review with meta-analysis noted lower survival rates when the liver is noted as the content of the hernia.[18] However, there was no statistically significant effect on mortality in terms of the contents noted in the hernia.

Among the 30 babies in the study population, 18 babies had developed PHN. There was a significant difference in the distribution of persistent PHN (PPHN) between the expired and the survived babies (P = 0.000). The use of inotropic support was also noted as a predictor of mortality and poor outcome (P = 0.037). Nine out of the 17 babies operated on were stated to have hypoplastic lungs (52.9%). However, there is no statistically significant effect on mortality (P = 1.00).

HFOV is used as a rescue measure when babies require high pressures and high FiO2 in conventional ventilation. Among the 30 babies in our study population, 23 were placed on HFOV during the hospital stay. There is a statistically significant difference in mortality in terms of the use of HFOV (P = 0.02).

The pH, HCO3 levels, and PaCO2 levels were analyzed and compared between the babies who survived and babies who expired. The difference in bicarbonate levels in venous blood gas analysis (HCO3) was found to be statistically significant (P = 0.015). The mean VI was 37.72 and the median was 29.61 (P = 0.05).

On univariate analysis, the various antenatal and postnatal factors which were identified as predictors of poor outcomes based on the statistical significance are the following:

  • Low 5-min APGAR
  • Surgical site infection
  • Mesh repair
  • Presence of PPHN
  • Use of inotropes
  • Use of HFOV
  • Low HCO3 levels in venous blood gas
  • High VI.

However, among the above predictors, only 5-min APGAR, presence of PPHN, and HCO3 values showed statistical significance in multivariate logistic regression. [Table 4].
Table 4: Multivariate logistic regression analysis

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None of the antenatal prognostic factors have shown any significance in our current study; hence conclusions could not be made on those antenatal factors.

Limitations of our study were smaller sample size and lack of standardization of surgical technique between various surgeons and the diagnosis of PPHN by indirect assessment using 2D ECHO.

   conclusion Top

Based on our findings, we conclude that the prognostic indicators associated with poor prognosis in CDH are low 5-min APGAR, high VI, low HCO3 levels in venous blood gas analysis, use of mesh repair, use of HFOV, use of inotropes, and presence of PPHN. None of the antenatal factors studied showed any statistical significance. Further prospective studies with a larger sample size are recommended to confirm the findings and overcome the limitations of our study.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Datin-Dorriere V, Rouzies S, Taupin P, Walter-Nicolet E, Benachi A, Sonigo P, et al. Prenatal prognosis in isolated congenital diaphragmatic hernia. Am J Obstet Gynecol 2008;198:80.e1-5.  Back to cited text no. 1
Colvin J, Bower C, Dickinson JE, Sokol J. Outcomes of congenital diaphragmatic hernia: A population-based study in Western Australia. Pediatrics 2005;116:e356-63.  Back to cited text no. 2
Bent DP, Nelson J, Kent DM, Jen HC. Population-based validation of a clinical prediction model for congenital diaphragmatic hernias. J Pediatr 2018;201:160-5.e1.  Back to cited text no. 3
Stevens TP, van Wijngaarden E, Ackerman KG, Lally PA, Lally KP, Congenital Diaphragmatic Hernia Study Group. Timing of delivery and survival rates for infants with prenatal diagnoses of congenital diaphragmatic hernia. Pediatrics 2009;123:494-502.  Back to cited text no. 4
Long AM, Bunch KJ, Knight M, Kurinczuk JJ, Losty PD, BAPS-CASS. Early population-based outcomes of infants born with congenital diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed 2018;103:F517-22.  Back to cited text no. 5
Skari H, Bjornland K, Haugen G, Egeland T, Emblem R. Congenital diaphragmatic hernia: A meta-analysis of mortality factors. J Pediatr Surg 2000;35:1187-97.  Back to cited text no. 6
Gallot D, Boda C, Ughetto S, Perthus I, Robert-Gnansia E, Francannet C, et al. Prenatal detection and outcome of congenital diaphragmatic hernia: A French registry-based study. Ultrasound Obstet Gynecol 2007;29:276-83.  Back to cited text no. 7
Congenital Diaphragmatic Hernia Study Group, Lally KP, Lally PA, Lasky RE, Tibboel D, Jaksic T, et al. Defect size determines survival in infants with congenital diaphragmatic hernia. Pediatrics 2007;120:e651-7.  Back to cited text no. 8
Bossone E, D'Andrea A, D'Alto M, Citro R, Argiento P, Ferrara F, et al. Echocardiography in pulmonary arterial hypertension: From diagnosis to prognosis. J Am Soc Echocardiogr 2013;26:1-14.  Back to cited text no. 9
Bohn D, Tamura M, Perrin D, Barker G, Rabinovitch M. Ventilatory predictors of pulmonary hypoplasia in congenital diaphragmatic hernia, confirmed by morphologic assessment. J Pediatr 1987;111:423-31.  Back to cited text no. 10
Langham MR Jr., Kays DW, Ledbetter DJ, Frentzen B, Sanford LL, Richards DS. Congenital diaphragmatic hernia. Epidemiology and outcome. Clin Perinatol 1996;23:671-88.  Back to cited text no. 11
Casaccia G, Ravà L, Bagolan P, di Ciommo VM. Predictors and statistical models in congenital diaphragmatic hernia. Pediatr Surg Int 2008;24:411-4.  Back to cited text no. 12
Skari H, Bjornland K, Frenckner B, Friberg LG, Heikkinen M, Hurme T, et al. Congenital diaphragmatic hernia in Scandinavia from 1995 to 1998: Predictors of mortality. J Pediatr Surg 2002;37:1269-75.  Back to cited text no. 13
Partridge EA, Peranteau WH, Herkert L, Rendon N, Smith H, Rintoul NE, et al. Right versus left-sided congenital diaphragmatic hernia: A comparative outcomes analysis. J Pediatr Surg 2016;51:900-2.  Back to cited text no. 14
Tanaka T, Okazaki T, Fukatsu Y, Okawada M, Koga H, Miyano G, et al. Surgical intervention for congenital diaphragmatic hernia: Open versus thoracoscopic surgery. Pediatr Surg Int 2013;29:1183-6.  Back to cited text no. 15
Tyson AF, Sola R Jr., Arnold MR, Cosper GH, Schulman AM. Thoracoscopic versus open congenital diaphragmatic hernia repair: Single tertiary center review. J Laparoendosc Adv Surg Tech A 2017;27:1209-16.  Back to cited text no. 16
Zamora IJ, Cass DL, Lee TC, Welty S, Cassady CI, Mehollin-Ray AR, et al. The presence of a hernia sac in congenital diaphragmatic hernia is associated with better fetal lung growth and outcomes. J Pediatr Surg 2013;48:1165-71.  Back to cited text no. 17
Mullassery D, Ba'ath ME, Jesudason EC, Losty PD. Value of liver herniation in prediction of outcome in fetal congenital diaphragmatic hernia: A systematic review and meta-analysis. Ultrasound Obstet Gynecol 2010;35:609-14.  Back to cited text no. 18


  [Table 1], [Table 2], [Table 3], [Table 4]


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