Antenatal corticosteroids (ACS) are a standard practice for improving survival and prognosis in premature infants. Their benefits in reducing mortality and morbidities like respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC) are well-documented. While ACS might improve gastrointestinal maturation, its effects on postnatal growth and nutrition in very preterm infants (VPIs) remain unclear. In China, approximately 200,000 VPIs (gestational age <32 weeks) are born annually, with an 87.6% survival rate. However, a significant proportion (47.3%) experience extrauterine growth restriction (EUGR), a condition linked to poor growth, neurodevelopmental issues, and cardiometabolic problems. A previous study suggested a small protective effect of ACS against EUGR, and another showed faster weight gain in very-low-birth-weight infants with ACS. However, ACS exposure rates in China are lower than in developed countries (75.6% vs. 80-90%). Given this gap and lack of data on the association between ACS and VPI nutrition, this study aimed to investigate the hypothesis that ACS improves postnatal growth and nutrition, reducing EUGR incidence in VPIs.

Existing literature supports the beneficial effects of antenatal corticosteroids (ACS) on reducing neonatal mortality and major morbidities in preterm infants. Studies have shown a positive correlation between ACS and improved gastrointestinal tract maturation. However, research specifically examining the impact of ACS on postnatal growth and nutritional status of very preterm infants is limited. Studies conducted in China have highlighted the high incidence of extrauterine growth restriction (EUGR) among very preterm infants. A few studies have suggested a potential association between ACS and reduced EUGR incidence or faster weight gain, but these studies were often retrospective and of limited sample size. This lack of comprehensive data underscores the need for large-scale studies to evaluate the impact of ACS on postnatal growth outcomes in very preterm infants, particularly in the context of the unique challenges faced in a large, diverse population like that in China.

This study involved a secondary analysis of data from a multicenter prospective survey on extrauterine growth restriction (EUGR) in very preterm infants (VPIs). Data were collected from 28 tertiary hospitals across seven regions of China between September 2019 and December 2020. The study included VPIs born at less than 32 weeks' gestational age, hospitalized for more than 14 days, and admitted within 24 hours of birth. Exclusion criteria included major congenital malformations, death during hospitalization, discharge against medical advice, incomplete data, and rescue or repeat courses of ACS. Antenatal steroid regimens consisted of either betamethasone or dexamethasone, with complete ACS defined as receiving all doses within a specified timeframe before delivery. Infants were categorized into no ACS, partial ACS, and complete ACS groups. Data collected included demographic characteristics, maternal pregnancy complications, postnatal growth and nutritional outcomes, and major morbidities and treatments. Postnatal growth indicators included weight, length, head circumference, greatest weight loss, days to regain birth weight, and EUGR incidence (defined as weight below the 10th percentile at discharge). Nutritional outcomes included enteral feeding start time, days to full enteral feeding, fasting days, breastfeeding, energy intake, amino acid and fat emulsion doses, and duration of parenteral nutrition. Major morbidities included RDS, BPD, PDA, sepsis, ROP, NEC, and IVH. Statistical analyses using SPSS 23.0 included chi-square tests, Mann-Whitney U tests, Kruskal-Wallis H tests, Bonferroni tests, multivariable linear regression, and multivariable logistic regression to assess associations between ACS and outcomes, adjusting for potential confounders. Dummy variables were used for ACS grouping in regression models. Subgroup analyses stratified by gestational age were also performed.

A total of 2,514 VPIs were included in the analysis. 77.9% received at least one dose of ACS, with 48.7% receiving complete ACS. Compared to the no ACS group, the any ACS group showed significantly earlier enteral feeding start time, shorter cumulative fasting time, and higher breastfeeding rate. The accumulated energy intake in the first week was significantly higher in the any ACS group. Multivariable linear regression revealed that only complete ACS was associated with significantly earlier enteral feeding initiation. Reduced cumulative fasting time was observed in both complete and partial ACS groups. Regarding postnatal growth, the any ACS group exhibited faster weight and length growth velocities, although head circumference growth did not differ. Complete ACS was associated with the fastest weight growth velocity and least dramatic decline in weight Z-score. The incidence of EUGR was significantly lower in the any ACS group (46.1% vs. 51.5%, P=0.022). Both complete and partial ACS were independently associated with a lower incidence of EUGR in multivariable logistic regression. Subgroup analysis showed a significant reduction in EUGR incidence with any ACS coverage in infants born at 24-27 and 30-31 weeks' gestational age. ACS was associated with lower incidence of RDS and shorter duration of invasive mechanical ventilation, potentially contributing to reduced BPD.

This study's findings demonstrate a clear association between antenatal corticosteroid (ACS) administration and improved postnatal growth outcomes in very preterm infants (VPIs). The observed improvements in enteral feeding, weight gain, and reduced extrauterine growth restriction (EUGR) support previous suggestions of ACS's role in gastrointestinal maturation. The stronger association with complete ACS highlights a potential dose-dependent effect. The reduced incidence of bronchopulmonary dysplasia (BPD) may be partly due to the earlier establishment of enteral nutrition enabled by ACS, as insufficient enteral nutrition is a known risk factor for BPD. The results underscore the importance of optimizing ACS administration and nutritional support strategies for VPIs, especially in settings with lower-than-optimal ACS coverage, as observed in this study’s Chinese cohort. The large sample size and multicenter design enhance the generalizability of the findings, although limitations related to the retrospective nature of the data analysis should be considered.

This large, multicenter study provides strong evidence that antenatal corticosteroids (ACS) improve postnatal growth outcomes in very preterm infants. Complete ACS administration is particularly beneficial, leading to earlier enteral feeding, faster weight gain, and a reduced risk of extrauterine growth restriction. These findings emphasize the need to increase ACS administration rates and implement standardized nutritional guidelines in clinical practice to optimize postnatal growth in this vulnerable population. Further research should focus on long-term growth outcomes and identifying specific subgroups of VPIs who would benefit most from ACS.

This study's limitations include its retrospective nature and the inability to fully control for all potential confounders. The exclusion of infants hospitalized for less than two weeks might have introduced selection bias. The lack of detailed data on specific ACS regimens (dosage, timing, type of steroid) limits the ability to precisely evaluate the impact of different administration protocols. Future studies with larger samples and more detailed data are needed to address these limitations and further explore the long-term effects of ACS on growth and development.