European Journal of Cardiovascular Medicine

Preterm infants born before 32 weeks’ gestation continue to represent a major contributor to neonatal morbidity and healthcare utilization worldwide [1]. Advances in antenatal care and neonatal intensive care have significantly improved survival among extremely and very preterm infants. However, many infants who survive the early high-risk period remain vulnerable to a range of short-term morbidities that contribute to prolonged hospitalization and increased healthcare burden.

Most published literature has focused on critically ill extremely and very preterm neonates, emphasizing early mortality and severe complications such as bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), severe intraventricular hemorrhage (IVH), and advanced retinopathy of prematurity (ROP) [2,3]. In contrast, there is a relative paucity of data describing the clinical characteristics and short-term outcomes of preterm infants who survive initial hemodynamic and respiratory instability, particularly from low- and middle-income countries where resource constraints and care practices may differ.

Even after apparent clinical stabilisation, preterm infants remain at risk for apnea of prematurity, sepsis, feeding difficulties, ROP, and extrauterine growth restriction (EUGR), with prematurity itself being a major underlying risk factor [2,4]. While caffeine therapy and appropriate respiratory support have been shown to reduce clinically apparent apnea and improve short-term respiratory outcomes, subtle respiratory instability and intermittent hypoxemia may persist and potentially influence neonatal morbidity and growth outcomes [5–7].

Understanding the clinical profile and early outcomes of these relatively stable yet vulnerable preterm infants is essential for optimizing post-stabilization care strategies, anticipating complications, and improving resource allocation. The present study aims to describe the clinical characteristics, morbidity profile, and short-term outcomes of extremely and very preterm infants born before 32 weeks’ gestation who survived the early neonatal period in a tertiary care setting.

Study Design and Setting
This was a single-centre observational study conducted in the neonatal intensive care unit (NICU) of a tertiary care teaching hospital in India over a period of 18 months.

Study Population
All preterm neonates born between 26⁰/₇ and 31⁶/₇ weeks’ gestation and admitted to the NICU during the study period were screened for eligibility.

Inclusion criteria were: gestational age <32 weeks; survival to 33 weeks’ postmenstrual age (PMA); clinically stable at 33 weeks’ PMA, defined as being hemodynamically stable and off all forms of respiratory support, including invasive ventilation, non-invasive ventilation, and supplemental oxygen; and availability of complete clinical records.

Exclusion criteria were: presence of major congenital anomalies; severe intraventricular hemorrhage (Grade III or IV); and death before achieving clinical stability. This cohort therefore represents a selected population of clinically stable extremely and very preterm infants rather than all infants born before 32 weeks’ gestation.

Sample Size Calculation
As this was an observational descriptive study including all eligible infants who met the inclusion criteria during the study period, a formal sample size calculation was not performed. All consecutive eligible infants were enrolled.

Data Collection
Data were collected prospectively using a structured proforma and included maternal characteristics (age, parity, antenatal care, mode of delivery, antenatal corticosteroid administration, and maternal morbidities), neonatal characteristics (gestational age, birth weight, sex, Apgar scores, and need for resuscitation), clinical course (respiratory support requirements and caffeine therapy), neonatal morbidities (sepsis, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity), and outcomes (duration of hospital stay, extrauterine growth restriction, and discharge status).

Definitions
Sepsis was defined as either culture-positive infection or clinically suspected sepsis based on clinical signs and laboratory parameters prompting antibiotic therapy [8]. Extrauterine growth restriction (EUGR) was defined as weight below the 10th percentile for postmenstrual age at discharge [9]. Bronchopulmonary dysplasia (BPD) was defined as oxygen requirement at 36 weeks’ PMA [10]. Necrotizing enterocolitis (NEC) was classified using modified Bell’s staging criteria [11]. Retinopathy of prematurity (ROP) requiring treatment was defined according to established guidelines [12].

Statistical Analysis
Data were analysed using descriptive statistics. Continuous variables are presented as mean ± standard deviation or median (interquartile range), and categorical variables as frequencies and percentages.

A total of 59 clinically stable extremely and very preterm infants were included. The mean maternal age was 28.0 ± 4.8 years, and 23.7% of mothers were primigravida. Antenatal corticosteroids were administered in 50.8% of cases. Maternal morbidities such as hypertension, antepartum haemorrhage, oligohydramnios, anaemia, and preterm premature rupture of membranes were present in 59.3% of mothers. The mean gestational age was 30.2 ± 1.4 weeks, with a mean birth weight of 1346 ± 292 g. Male neonates constituted 54.2% of the cohort. Resuscitation at birth was required in 15.3% of infants. The median Apgar score at 5 minutes was 8 (IQR 7–8) (Table 1).

Table 1: Baseline Maternal and Neonatal Characteristics

Sepsis (clinical and/or culture-positive) was observed in 45 neonates (76.3%), while culture-positive sepsis was confirmed in 5 (8.5%). Shock occurred in 9 infants (15.3%). Recurrence of apnea following discontinuation of caffeine therapy as per unit protocol was observed in 7 infants (11.9%). Hemodynamically significant patent ductus arteriosus was identified in 4 infants (6.8%). Bronchopulmonary dysplasia and necrotizing enterocolitis (Stage ≥II) were each observed in 1 neonate (1.7%). Infants with severe intraventricular hemorrhage were excluded; therefore, no cases of Grade III/IV IVH were observed. Retinopathy of prematurity requiring treatment was not observed in any infant (Table 2).

Table 2: Neonatal Morbidity Profile

All neonates required respiratory support during the early neonatal period, predominantly for respiratory distress syndrome (59/59, 100%). The mean duration of respiratory support (invasive and non-invasive) was 10.4 ± 9.8 days. Extrauterine growth restriction at discharge was observed in 16 infants (27.1%). The mean length of hospital stay was 36.0 ± 13.3 days. All neonates were successfully discharged home (59/59, 100%) (Table 3).

Table 3: Short-Term Outcomes

This single-centre descriptive observational study describes the clinical characteristics, neonatal morbidities, and short-term outcomes of clinically stable preterm infants born before 32 weeks’ gestation. By focusing on infants who survived early instability and achieved hemodynamic and respiratory stability by 33 weeks’ PMA, this study provides insight into a subgroup that is often underrepresented in neonatal outcome literature, particularly in low- and middle-income country settings.
The study population had a mean gestational age of approximately 30 weeks and a mean birth weight of around 1340 g, comparable to other cohorts reported from similar settings [2,3]. Antenatal corticosteroid exposure was observed in nearly half of the mothers. The relatively favourable respiratory outcomes observed in our cohort are consistent with evidence that antenatal corticosteroid administration accelerates fetal lung maturation and reduces respiratory morbidity and mortality among very and extremely preterm infants [13].
Despite respiratory stabilization, neonatal morbidity remained substantial. The incidence of clinically suspected sepsis in our cohort (76.3%) was higher than rates reported from Indian NICU surveillance studies such as the DeNIS collaboration (total sepsis 14.3%; culture-positive 6.2%) [14]. This difference likely reflects our broader definition including clinical sepsis, prolonged hospitalization in a selected cohort surviving to 33 weeks’ PMA, and the well-recognized low yield of blood cultures in low- and middle-income settings.

Importantly, severe morbidities such as necrotizing enterocolitis, severe intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity requiring treatment were infrequent in this cohort. This likely reflects both the exclusion of infants with severe early complications and the relatively higher gestational age of the population studied. The low incidence of BPD is noteworthy and may be related to antenatal corticosteroid exposure, predominant use of non-invasive ventilation strategies, and early optimization of respiratory support [10]. Recurrence of apnea was observed in 11.9% of infants following discontinuation of caffeine, consistent with previous reports demonstrating persistence or recurrence of apnea and respiratory instability after apparent clinical resolution, highlighting the need for continued monitoring before discharge [2,5,6].

In an Italian cohort of very low birth weight infants surviving beyond 33 weeks’ postmenstrual age, EUGR assessed using INTERGROWTH-21st standards was reported in 23.8% of infants [15], comparable to the 27.1% observed in our cohort, which was also evaluated using INTERGROWTH-21st criteria. In contrast, an Indonesian NICU study including a broader population of preterm infants reported a higher EUGR prevalence of approximately 47% at discharge [16]. These findings highlight that, even among clinically stable preterm infants, postnatal growth restriction remains common and necessitates ongoing NICU-based nutritional support and growth monitoring.

A mean hospital stay of approximately five weeks in our cohort is consistent with reports from both high-income and low- and middle-income settings, where preterm infants born before 32 weeks’ gestation who survive early neonatal instability typically require prolonged hospitalization [5,17]. All infants were successfully discharged home, reflecting favourable short-term survival outcomes in this selected cohort.

Strengths and Limitations
A key strength of this study is its focus on clinically stable extremely and very preterm infants, providing clinically relevant insights into morbidities that persist beyond the period of early critical illness. However, several limitations merit consideration. The single-centre design and relatively small sample size may limit the generalizability of the findings. In addition, the selected nature of the cohort, which excluded the sickest infants, may have resulted in an underestimation of the overall burden of morbidity among all preterm infants born before 32 weeks’ gestation. Finally, long-term neurodevelopmental outcomes were not assessed and represent an important area for future research

Clinically stable preterm infants born before 32 weeks’ gestation continue to experience a substantial burden of neonatal morbidity, particularly sepsis and extrauterine growth restriction, despite favourable short-term respiratory outcomes. These findings underscore the importance of sustained infection-prevention strategies, targeted nutritional optimization, and close clinical monitoring in this vulnerable population even after initial clinical stabilization.

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