European Journal of Cardiovascular Medicine

Late preterm (LPT) infants, defined as those born between 34 weeks 0/7 days and 36 weeks 6/7 days of gestation, constitute a significant and growing subgroup within the spectrum of preterm births. Although these infants are often physiologically and physically close to term neonates, emerging evidence highlights that their organ systems—particularly the lungs, brain, liver, and immune system—remain immature at birth. This immaturity predisposes them to increased risk of complications in the early neonatal period as well as in long-term developmental outcomes [1]. Globally, LPT infants represent nearly 74% of all preterm births and approximately 8% of all live births [2,3].

Over the past two decades, the incidence of late preterm births has risen, largely due to increased obstetric interventions, such as labor inductions and cesarean deliveries, often driven by concerns for fetal well-being or maternal comorbidities [4]. Advances in fetal monitoring, prenatal screening, and assisted reproductive technologies have contributed to more frequent early deliveries. Despite their increasing numbers, LPT infants have historically received less clinical attention than extremely or very preterm infants. They are frequently managed in postnatal wards without neonatal intensive care unit (NICU) admission, under the assumption that they are functionally similar to term neonates [1,5].

However, data from large population-based studies challenge this assumption. Teune et al. [1] demonstrated that LPT infants face higher risks of respiratory distress, hypoglycemia, jaundice, feeding difficulties, and sepsis—even in the absence of severe prematurity. Similarly, Bird et al. [6] and McLaurin et al. [7] found that LPT infants have higher rates of hospital readmissions, greater healthcare utilization, and elevated healthcare costs during the first year of life. These findings suggest that late preterm birth imposes a measurable burden on both the healthcare system and families, despite the initial perception of “near-normalcy.”

Furthermore, longitudinal studies have drawn attention to persistent morbidities and neurodevelopmental challenges in LPT infants. According to Dong and Yu [8], long-term consequences of late prematurity can include growth restriction, cognitive delays, and learning difficulties. Natarajan and Shankaran [9] similarly emphasized that LPTs, though often overlooked, are at risk for short- and long-term neurodevelopmental impairments, including behavioral and academic challenges.

Despite compelling global evidence, there is a scarcity of region-specific data from Asia, where the majority of preterm births occur. The World Health Organization reports that out of the 15 million preterm births annually, over 54% take place in Asia [2,3]. Yet, few studies from this region have comprehensively examined the outcomes of LPT infants beyond the immediate neonatal period. While Jaiswal et al. [10] explored early neonatal morbidities among late preterms in India, there remains a critical knowledge gap regarding long-term outcomes such as growth patterns, feeding issues, morbidity trends, and mortality beyond discharge.

With this background, the current study was undertaken to evaluate the physical growth, feeding difficulties, morbidity, and mortality of late preterm infants up to 12 months of age and compare these outcomes with term infants. Importantly, our study exclusively included apparently healthy late preterms who were not admitted to NICU and were discharged early, thereby reflecting real-world postnatal ward practices in resource-limited settings. Through this prospective cohort approach, we aim to generate region-specific evidence that can inform follow-up care guidelines, parental counseling, and early interventions for late preterm infants in India and similar settings.

AIMS AND OBJECTIVES

Aim:
To evaluate growth and morbidity outcomes of apparently healthy late preterm infants up to 12 months of age, in comparison with term infants.

Objectives:

1. To compare growth parameters (weight, length, and head circumference) and corresponding Z-scores at 12 months using WHO standards.
2. To assess and compare the morbidity profile including feeding difficulties, infections, and hospitalizations during the first year.
3. To evaluate and compare hemoglobin and serum ferritin levels at 12 months of age between the two groups.

This prospective cohort study was conducted in the Department of Pediatrics, Government Medical College, Ongole, Andhra Pradesh, after obtaining ethical clearance from the Institutional Ethical Committee. The study aimed to evaluate the physical growth, morbidity, and mortality outcomes of apparently healthy late preterm infants up to 12 months of age and compare them with term infants. The primary objective was to assess weight-for-age (WFA), length-for-age (LFA), weight-for-length (WFL), and head circumference-for-age (HFA) using WHO Multicenter Growth Reference Standards, while secondary objectives included evaluating the morbidity profile (diarrhea, pneumonia, fever, hospitalizations), feeding difficulties, and hematological indicators such as hemoglobin and serum ferritin levels.

All neonates born between August 2021to December 2021 in the hospital were screened for eligibility. Infants born between 34 weeks 0/7 days and 36 weeks 6/7 days of gestation, appropriate for gestational age (AGA), not requiring NICU admission for more than 48 hours, and residing within a 20 km radius were enrolled as cases (late preterm group). Infants with major congenital anomalies, multiple gestation, or whose families were unable or unwilling to attend follow-up visits were excluded. The control group consisted of the next consecutively born healthy term infant (37 weeks 0/7 to 41 weeks 6/7 gestation), who met the same inclusion criteria and consented for follow-up.

Gestational age was assessed using the mother’s last menstrual period (LMP), first-trimester ultrasonography, or, when unavailable, the New Ballard Score. Anthropometric measurements were recorded at 12 months of age during scheduled follow-up visits, which were aligned with the national immunization schedule. Weight was recorded using a calibrated digital weighing machine (Dolphin India, 5g precision), length was measured using an infantometer (range 0–100 cm, 1 mm precision), and head circumference was measured using a non-stretchable retractable measuring tape. Each parameter was recorded by two trained investigators throughout the study to maintain consistency.

Z-scores for WFA, LFA, WFL, and HFA were calculated using the WHO Anthropometric Calculator (version 3.2.2), and children with Z-scores below -2 SD were categorized as underweight, stunted, or wasted, respectively. At each follow-up, morbidity data including episodes of diarrhea, fever, pneumonia, hospitalizations, and feeding-related issues were recorded using a structured proforma. Feeding difficulties were sub-categorized as infant-related (poor latching, excessively sleepy baby) or maternal (low milk output, flat/inverted nipples). Exclusive breastfeeding, bottle feeding, and diluted feeding practices were documented as per WHO definitions.

At 12 months, hemoglobin and serum ferritin were assessed using standard laboratory techniques. Serum ferritin was measured using a one-step enzyme immunoassay with fluorescent detection (Biomeriux, France). Data were analyzed using STATA version 12.0. Continuous variables were compared using Student’s unpaired t-test or Wilcoxon Rank-Sum test as appropriate, and categorical variables using Chi-square or Fisher’s exact test. Logistic regression analysis was performed using growth indicators (WFA, LFA, WFL, HFA) as dependent variables and sex, maternal weight and height, exclusive breastfeeding, socioeconomic status (classified by Modified Kuppuswami scale), and rehospitalization as covariates. A p-value <0.05 was considered statistically significant.

Baseline Characteristics of Term and Late Preterm Neonates

The comparison of baseline characteristics between term (n = 200) and late preterm neonates (n = 190) reveals statistically significant differences in key birth parameters. Late preterm infants had significantly lower mean birth weight (2.42 kg vs. 2.94 kg), length (48.51 cm vs. 51.66 cm), head circumference (33.60 cm vs. 36.75 cm), and gestational age (36.96 weeks vs. 40.32 weeks), with all differences being highly significant (P < 0.001). These findings underscore the expected growth limitations in late preterm neonates at birth. Although the proportion of male infants was slightly higher in the late preterm group (54.4%) compared to the term group (50%), the difference was not statistically significant. Vaginal delivery was nearly equal in both groups (57.4% vs. 59.5%). Maternal characteristics such as age and height were comparable between groups, while maternal weight was significantly higher in the late preterm group (66.36 kg vs. 64.68 kg; P = 0.007). Hemoglobin levels showed no meaningful difference. Socioeconomic status revealed a slightly higher percentage of lower status among term infants (38%) compared to late preterm infants (32%). Overall, these data confirm that late preterm neonates are born with significantly reduced anthropometric measures and marginally higher maternal weight, emphasizing their potential vulnerability from birth.

FIGURE 1 : Comparison of Birth Parameters (Weight, Length, Head Circumference).

FIGURE 2  : Growth Parameters at 12 Months (Weight, Length, Head Circumference).

FIGURE 3  : Sex Distribution in Term vs Late Preterm Infants.

TABLE II

Growth Outcomes of Term and Late Preterm Infants at 12 Months

At 12 months of age, late preterm infants demonstrated significantly poorer growth outcomes compared to term infants. The mean weight of late preterm infants was substantially lower (7.0 kg) than that of term infants (8.8 kg), with a significant adjusted odds ratio (OR) of 1.2 (95% CI: 1.1–1.4; P < 0.001). Similarly, the mean length was considerably shorter in late preterms (65.2 cm vs. 72.8 cm), with an OR of 3.0 (2.2–3.8; P < 0.001). Head circumference also remained significantly lower in late preterm infants (43.0 cm vs. 44.0 cm; P < 0.001), suggesting suboptimal neurodevelopmental growth. Annual weight gain and weekly weight gain were both significantly reduced in the late preterm group, highlighting slower physical development (P < 0.001). While length gain over the year was statistically comparable between the two groups (P = 0.968), head circumference gain was paradoxically greater in late preterms (10.9 cm vs. 9.0 cm; P < 0.001), though this did not translate into normalized absolute head circumference values. These findings underscore the lasting impact of late preterm birth on infant growth trajectories and emphasize the need for close monitoring and nutritional support during early life in this vulnerable population.

TABLE III

Growth Outcomes of Late Preterm Infants at 12 Months of Age (Adjusted)

Notes:

• Adjusted for sex, maternal weight, maternal height, re-hospitalization, exclusive breastfeeding, and socioeconomic status.
• Odds ratios are for late preterm infants compared to term infants.

At 12 months of age, late preterm infants exhibited significantly higher odds of undernutrition and suboptimal growth when compared to term infants. The crude odds of being underweight were markedly elevated at 5.88 (95% CI: 3.57–5.78), and even after adjusting for potential confounders such as sex, maternal weight and height, hospitalization, exclusive breastfeeding, and socioeconomic status, the adjusted odds remained significantly high at 4.30 (95% CI: 1.68–10.92). Similarly, crude odds for stunting, wasting, and reduced head circumference were also elevated in the late preterm group, with values of 3.68, 3.78, and 3.57 respectively. However, after adjustment, the significance of these associations diminished, with adjusted odds ratios decreasing to 1.26 for stunting, 1.47 for wasting, and 1.37 for head circumference, all with confidence intervals crossing unity, suggesting statistical non-significance. These findings indicate that while late preterm birth is strongly associated with underweight status at one year, the relationships with stunting, wasting, and head growth may be influenced by other modifiable postnatal factors.

TABLE IV
Morbidity Profile of Term and Late Preterm Infants Till 1 Year of Age .
(Term n = 157, Late Preterm n = 158)

Feeding-Related Issues

Morbidity Profile

Hematological Parameters

Late preterm infants exhibited a significantly higher morbidity burden compared to term infants during the first year of life. Feeding-related challenges were notably more prevalent among late preterms, including greater difficulty in initiating breastfeeding (29.2% vs. 16.7%; P = 0.014), trouble latching (16.6% vs. 4.7%; P = 0.004), and increased need for medical consultation regarding feeding (15.3% vs. 7.4%; P = 0.045). Additionally, exclusive breastfeeding rates were lower (61.2% vs. 72.9%; P = 0.046), while bottle feeding was more frequent (53.2% vs. 39.4%; P = 0.023).

In terms of general morbidity, late preterm infants had significantly more episodes of diarrhea (median 1.93 vs. 1.20; P = 0.0005) and fever (median 1.40 vs. 1.00; P = 0.0143), and a higher rate of jaundice requiring phototherapy (41.2% vs. 28.1%; P = 0.008). Hospitalization rates were more than double in late preterms (26.6% vs. 12.7%; P = 0.022). Hematological assessments also showed that late preterms had lower hemoglobin levels (8.30 g/dL vs. 8.72 g/dL; P = 0.0111) and reduced serum ferritin (73.4 vs. 94.6 ng/mL; P < 0.001), indicating a higher risk of iron deficiency. Overall, this profile reflects the increased vulnerability of late preterm infants to both nutritional and infectious morbidities, underscoring the need for early identification, close monitoring, and supportive care in this high-risk group.

Our study highlights that apparently healthy late preterm infants—even in the absence of major neonatal morbidities at birth—remain biologically and clinically vulnerable compared to term counterparts. Notably, our data show that LPT infants had significantly higher risk of being underweight by 12 months of age. Although length gain was comparable between groups, both weight and head circumference remained consistently lower in LPTs. The adjusted odds ratio for underweight status was statistically significant, suggesting that growth faltering may persist despite early discharge and apparent neonatal well-being.

Our findings echo those of Santos et al. [11], who reported increased odds of underweight, stunting, and wasting among late preterm infants at both 12 and 24 months of age. However, in our cohort, only underweight status reached significance after adjustment, likely due to our deliberate exclusion of late preterms who required NICU care—unlike Santos et al., who included all LPTs. Similarly, Goyal et al. [12] demonstrated persistence of underweight status at 6 and 12 months among late preterms, even after excluding small-for-gestational-age infants. Our results align with their conclusion that late preterm birth itself is a determinant of growth vulnerability, independent of birth weight or neonatal complications.

In terms of feeding-related issues, we observed that LPT infants had significantly higher prevalence of breastfeeding initiation difficulties, trouble latching, and need for medical consultations, alongside reduced rates of exclusive breastfeeding. This supports findings from Boyle et al. [13], who demonstrated lower breastfeeding rates and increased postnatal support needs in LPTs, even without NICU admission. This may reflect neurodevelopmental immaturity and poor oral coordination in late preterms.

Our study also documented increased morbidity in late preterms, particularly diarrhea, fever, jaundice requiring phototherapy, and hospitalization during the first year of life. These findings align with Escobar et al. [14], who found that LPTs were 1.5 to 3 times more likely to be rehospitalized than term infants—primarily due to jaundice and feeding difficulties. Similarly, Tan et al. [15] reported significantly higher rates of neonatal complications in LPTs, including jaundice (41.1% vs 12.2%), sepsis, anemia, and hypoglycemia—all consistent with clinical patterns seen in our cohort. We also noted lower hemoglobin and serum ferritin levels at one year among LPTs, further supporting the risk of nutritional deficiencies.

Additionally, Shah and Saini [6] reported higher NICU admissions, respiratory distress (36.5% vs 12.5%), and neonatal jaundice (26.9% vs 9.6%) among late preterms in their Indian cohort, further affirming our observations. Though we did not examine maternal outcomes directly, similar patterns of increased obstetric intervention were seen in our sample, indicating possible shared etiological factors.

Brown et al. [16] added another layer by exploring biological determinants that mediate gestational age effects. Their study showed that gestational age interacts with placental and hypoxic factors to increase neonatal morbidity risk. In our study, even without detailed biological modeling, LPTs demonstrated consistently poorer growth and health outcomes, supporting gestational age as an independent risk factor.

A strength of our study lies in the focus on healthy LPTs who were not admitted to NICU. This reflects a population often deemed low-risk and rarely followed systematically. However, limitations include absence of neurodevelopmental assessment, ~20% loss to follow-up, and lack of gestational correction at 12 months—though our unit protocol and previous studies [11,12] followed similar methods.

In conclusion, our findings reinforce that late preterm infants, even when clinically stable at discharge, are not equivalent to term infants in terms of growth, nutrition, and morbidity risk. Early identification and targeted interventions for this group are essential to reduce the risk of adverse outcomes in infancy and beyond.

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