Factors of poor prognosis in newborns with a prenatal diagnosis of gastroschisis in Bogota, Colombia

Variables

Maternal variables: age, parity, diagnosis of gestational diabetes, hypertensive disorders during pregnancy, and body mass index (BMI).

Fetal ultrasound variables: diagnosis of fetal growth restriction (fetal weight below the 3rd percentile), oligohydramnios (amniotic fluid index below 5 cm), polyhydramnios (amniotic fluid index above 25 cm), and intra-abdominal bowel dilation (IABD) on ultrasound.

Perinatal and neonatal variables: gestational age at delivery, mode of delivery, Apgar score at 5 min, birth weight, size of abdominal wall defect, type of surgical management, time until abdominal wall closure, days of hospitalization from birth to discharge, duration of stay in the neonatal intensive care unit (NICU), days on mechanical ventilation, need for parenteral nutrition, and the total number of days until the start of full enteral feedings.

Databases

The databases used correspond to the mandatory notification registry of congenital defects in Colombia for live births with gastroschisis and datasets from the hospitalization registry in neonatal units of the following hospitals: Hospital Universitario de La Samaritana, Hospital Universitario Clínica San Rafael, Hospital Simón Bolívar, Clínica Palermo, Clínica Universitaria Colombia, Hospital Universitario San José, Clínica Colsubsidio, and Hospital Universitario De San Ignacio during the period from January 01, 2011 to December 2022.

Bias

A multi-center study was conducted, which included patients from eight hospitals in Bogotá. This approach allowed for an increased sample size and participant diversity, potentially reducing selection bias. Additionally, it was ensured that controls came from the same source as the cases. For this purpose, databases from the mandatory notification registry of congenital defects in Colombia for live births with gastroschisis and medical records from the NICU of each institution were used.

To mitigate information bias, a review of records was conducted by two different reviewers at the time of data entry. This helped ensure that the data were accurate and complete. Furthermore, specialists at each center were trained to consider the same diagnostic ultrasound criteria. This training aimed to ensure consistency in diagnoses across the centers.

Sample size

Data from the study conducted by Fullerton et al. in North America was used to calculate the sample size. The hypothetical proportions were set with a 35 % exposure rate among controls, a 61.76 % exposure rate among cases, and an odds ratio (OR) of 3.76 for polyhydramnios leading to intestinal atresia[15]. The sample size was calculated using the formula for unmatched case-control studies, considering a confidence level of 90 % and a power of 80 %. The result indicated a minimum number of 44 cases needed for the study.

Statistical analysis

The data were collected using Microsoft Excel, version 2019, and analyzed using the STATA SE 17 software. Study subjects were selected through simple random sampling from the list of patients treated during the research period.

Qualitative variables were summarized in terms of frequencies and percentages. Regarding quantitative variables, normality was assessed using the Shapiro-Wilk test. In cases where the data distribution was normal, results were presented in terms of means and standard deviations. When the distribution was not normal, results were presented in terms of median and interquartile range.

Subsequently, a bivariate analysis was conducted to assess the association between predictor variables and the adverse outcome. For normally distributed quantitative variables, the Student’s t test was used. For non-normally distributed quantitative variables, the Mann-Whitney U test was applied. The Pearson chi-square test was employed for qualitative variables. Statistical significance was considered at p<0.05. Following this, a logistic regression test was performed, adjusting for the preterm birth variable to mitigate potential confounding factors.

Ethics backgrounds

The study followed the World Medical Association Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects [16]. Our retrospective study is based on a historical database where patients’ data were stored anonymized. The study was considered of no risk to patients according to Article 11 of Resolution No 008430 of 1993, of the Colombian Ministry of Health [17]. The protocol was reviewed and approved by the Ethics Committees of all the participating institutions; no informed consent was required.

Main results

Our study has identified prenatal ultrasonographic evidence of IABD between 20 and 25 mm as prognostically unfavorable for intestinal complications. Moreover, oligohydramnios emerged as a precursor for perinatal mortality. In terms of postnatal surgical intervention, staged reductions using a silo were correlated with increased mortality risks.

Strengths and limitations

One of the main strengths lies in our sample’s multi-center origin, enhancing our findings’ representativeness and allowing for more robust generalizations. In addition, the sample size provides a solid foundation for statistical analysis, enhancing the reliability of our results. The rigorous data collection and randomness of the sample ensure the reliability of our data and help minimize potential biases in our research.

Regarding the limitations of our study, is that we cannot assert definitive associations due to the lack of statistical significance in some of our results. Nevertheless, our study is a valuable first step in this research field. The current limitations can serve as a basis for future studies to delve into aspects that we have not been able to address conclusively.

The retrospective nature of this study, coupled with the reliance on clinical records for data collection, represents inherent limitations; considering that not all data on the variable of the size of the abdominal wall defect were found. In the case of fetal growth restriction, no record of the calculation formula for estimating prenatal fetal weight was found, given that abdominal circumference is less sensitive in cases of abdominal wall defects. However, the presence of the condition was confirmed with neonatal weight, which reduced this bias.

In summary, our strengths support the quality and credibility of our study, while our weaknesses point out areas for future research and improvement.

Interpretation

In the realm of prenatal diagnostics, IABD has emerged as a pivotal marker for assessing the risk of complex conditions. Our observations indicate that fetuses with IABD measurements of 20–25 mm are at a considerably higher risk for intestinal complications, with an OR of 3.22 (95 % CI 1.26–8.23), a finding consistent with Nitzsche et al., who identified a cutoff point of 18 mm as a predictor for complex gastroschisis [19]. This aligns with the systematic analysis by D’Antonio et al., which found an association between IABD and bowel atresia, with an OR of 5.48 (95 % CI 3.1–9.8) [20], and is further corroborated by a comprehensive review that predicts higher IABD in fetuses with complex gastroschisis, with a risk ratio (RR) of 3.01 (95 % CI 2.22–4.07) [21]. Meanwhile, an IABD of less than 20 mm has been identified as a protective factor, associated with improved neonatal outcomes and fewer intestinal complications (OR 0.20; 95 % CI 0.06–0.6). Consequently, the termination of pregnancy in fetuses with intestinal dilatations less than 20 mm would not be recommended, in accordance with guidelines from the Fetal Medicine Foundation [22].

As for oligohydramnios, a study of 101 patients with gastroschisis suggested that oligohydramnios was not a statistically significant predictor for complex gastroschisis [23]. Similarly, the research presented by Johnston et al., indicated that oligohydramnios does not appear to worsen the prognosis for neonates with gastroschisis [24]. However, in contrast to these findings, our study found that oligohydramnios is indeed a poor prognostic risk factor, associated with a higher rate of neonatal death (OR 4.95; 95 % CI 1.15–21.32, p=0.04). This discrepancy in findings highlights the complexity of prenatal prognostication in gastroschisis and underscores the need for further research. It may also point to the potential influence of other confounding variables that were not accounted for in previous studies, or it might suggest variability in the impact of oligohydramnios on neonatal outcomes across different populations.

The optimal gestational age for delivering fetuses with gastroschisis has been controversial. Prat et al., in 2017, advocated allowing gestation to proceed as close to term as possible except in fetuses with bowel loop deterioration or other fetal or maternal causes indicating the need for delivery [25]. This stance is akin to the recommendations of the Fetal Medicine Foundation, which advises ending the pregnancy at 38 weeks or earlier if there is evidence of poor growth, fetal hypoxia, or dilatation of the intra-abdominal bowel [22]. Sparks et al. recommends delivery at 37 weeks, considering that, beyond that gestational age, mortality increases with expectant management (RR 1.90; 95 % CI 1.73–2.08) at 39 weeks [26]. Our findings highlight improved neonatal outcomes for full-term births, which acted as a protective factor against adverse neonatal prognosis (OR 0.77; 95 % CI 0.28–2.14), death (OR 0.54; 95 % CI 0.14–2.11), and intestinal complications (OR 0.77; 95 % CI 0.28–2.14), even though the results did not reach statistical significance.

In terms of surgical management, our findings indicate that primary closure with suturing is associated with lower mortality and improved neonatal prognosis compared to delayed closure with a silo (OR 0.31; 95 % CI 0.10–0.96) compared to delayed closure using a silo (OR 3.48; 95 % CI 1.10–10.96). This is in line with literature suggesting that primary reduction is associated with fewer days on mechanical ventilation, without affecting the type or duration of ventilation or oxygen requirements [3]. Additionally, Tauriainen et al. underscore that complications from silo correlate with adverse outcomes, highlighting the risks of managing gastroschisis with silo [14].