Preterm birth, defined as delivery before 37 weeks of gestation, represents a significant global health challenge and is a leading cause of neonatal morbidity and mortality. It affects approximately 11 % of all live births worldwide, placing millions of infants at increased risk for both short- and long-term health complications ^{1 - 4} . The survival and development of these vulnerable infants are intricately linked to the quality of care they receive during the neonatal period, particularly with respect to nutrition. Adequate and timely nutritional intervention is essential for promoting optimal growth, brain development, and physiological maturation during this critical time of early life ^{5 - 8} .

Due to the immaturity of their gastrointestinal and neurological systems, preterm infants have distinct nutritional requirements compared to full-term newborns. Early nutritional support not only influences immediate growth parameters such as weight, length, and head circumference but also contributes significantly to long-term cognitive, motor, and social-emotional development ^{9 - 11} . Emerging research highlights the importance of nutrient-enriched feeding strategies in the neonatal intensive care unit (NICU), especially during the first 1000 days of life, a period considered critical for brain development ^{12 , 13} .

Breastfeeding is widely recognized as the gold standard for infant nutrition. Human milk contains not only the macronutrients and micronutrients necessary for physical growth but also a complex array of bioactive compounds, including immunoglobulins, enzymes, hormones, long-chain polyunsaturated fatty acids, and human milk oligosaccharides, which collectively support neurodevelopment, immune function, and gastrointestinal health ^{14 - 16} . Studies have demonstrated that preterm infants who receive breast milk shows improved brain volume, enhanced functional connectivity, and better performance on cognitive assessments later in life ^{17 , 18} .

Nonetheless, exclusive breastfeeding is not always feasible for mothers of preterm infants. Maternal health complications, stress, lactation difficulties, and limited access to lactation support often result in inadequate milk supply, leading to the need for supplementation or substitution with formula. Preterm formulas are specifically designed to address the elevated nutritional needs of preterm infants and are fortified with higher levels of protein, calories, vitamins, and minerals ¹⁹ . Some evidence suggests that formula feeding may lead to faster short-term growth ²⁰ , yet concerns persist regarding its association with higher risks of necrotizing enterocolitis and the absence of critical neuroprotective and immunological factors found in breast milk ^{21 , 22} .

Although numerous studies have explored the individual benefits of breastfeeding and formula feeding, few have provided comprehensive, head-to-head comparisons of their impact on both growth trajectories and developmental outcomes in preterm populations. This gap in the literature leaves clinicians and parents with limited evidence-based guidance when making critical decisions about feeding strategies in the NICU and during early infancy ^{12 , 13} .

Therefore, the objective of this study was to conduct a longitudinal comparative analysis of early breastfeeding versus formula feeding in preterm infants, focusing on their effects on physical growth and developmental outcomes over a 24-month period. By examining validated growth indicators and standardized developmental assessments, this research aims to generate evidence that supports informed nutritional decision-making for preterm infants during a critical stage of life.

This study employed a comparative longitudinal design, a widely used approach in pediatric and neonatal research, to assess the effects of early breastfeeding versus formula feeding on growth and developmental outcomes in preterm infants ^{9 - 11} . Two cohorts of preterm infants one predominantly breastfed and the other predominantly formula-fed were followed from birth until 24 months of corrected age to evaluate differences in physical growth and neurodevelopmental progression.

The study population consisted of preterm infants born at less than 37 weeks of gestation, with birth weights ranging from 500 to 2500 g. These inclusion criteria align with international definitions of preterm birth and low birth weight ²³ . Infants were enrolled if they were medically stable and able to tolerate enteral feeding within the first week of life, which is consistent with clinical guidelines for initiating neonatal nutrition ²² . Exclusion criteria included the presence of major congenital anomalies, gastrointestinal conditions impairing oral feeding, or significant metabolic and endocrine disorders, all of which are known to influence feeding tolerance and developmental trajectories ¹⁹ .

Growth parameters weight, length, and head circumference were recorded at baseline (within the first week of life), then monthly for the first six months, and subsequently every two months until 24 months corrected age. Measurements were interpreted using the Fenton growth chart, a validated tool specifically designed to assess growth in preterm infants ²⁴ .

Developmental progress was evaluated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), a standardized and widely recognized tool for assessing early cognitive, motor, and social-emotional development ^{25 , 26} . Assessments were conducted at 6, 12, and 24 months of corrected age by trained developmental specialists.

The primary independent variable was feeding type, classified as either breastfeeding (exclusive or predominantly breast milk) or formula feeding (exclusive or predominantly preterm formula). Dependent variables included continuous measures of physical growth (weight, length, and head circumference) and domain-specific BSID-III scores (cognitive, motor, and social-emotional development).

Statistical analyses were conducted using repeated measures ANOVA to assess growth trajectories across time between groups. Independent t-tests were used to compare group means at specific time points. Multiple linear regression models were employed to evaluate developmental scores while adjusting for potential confounders such as gestational age and birth weight ^{12 , 13} . Chi-square tests were used for comparisons involving categorical variables.

The study was conducted in accordance with ethical principles outlined in the Declaration of Helsinki ²⁷ Written informed consent was obtained from the parents or legal guardians of all participants. The research protocol was reviewed and approved by the institutional ethics committee, and all data were anonymized and securely stored to protect participant confidentiality.

The growth trajectories of preterm infants in both breastfeeding and formula-feeding groups were analyzed using weight, length, and head circumference measurements collected at eight time points: baseline (0 months), 1, 2, 3, 6, 12, 18, and 24 months. Table 1 and Figure 1.

Table 1 Table 1 Growth data for breastfeeding vs. formula feeding groups Table 1 Growth data for breastfeeding vs. formula feeding groups

Time point (months)	Weight (g) (breastfeeding)	Weight (g) (formula feeding)	Length (cm) (breastfeeding)	Length (cm) (formula feeding)	Head circumference (cm) (breastfeeding)	Head circumference (cm) (formula feeding)
0	1800	1850	42	4	30	31
1	2200	2250	46	47	32	33
2	2700	2750	50	51	34	35
3	3200	3300	54	55	36	37
6	5000	5200	60	61	39	40
12	7500	7600	70	71	44	45
18	9000	9200	80	81	46	47
24	11000	11500	90	91	48	49

Figure 1 provides a visual comparison of the weight, length, and head circumference growth trajectories across the breastfeeding and formula-feeding groups. Both groups demonstrated consistent increases in growth parameters over time, with the formula-fed group exhibiting marginally higher values for weight, length, and head circumference at most intervals. However, these differences were not statistically significant (p > 0.05).

Table 2 Table 2 Developmental outcomes (BSID scores) for breastfeeding vs. formula feeding groups Table 2 Developmental outcomes (BSID scores) for breastfeeding vs. formula feeding groups

Time point (months)	Cognitive development (breastfeeding)	Cognitive development (formula feeding)	Motor development (breastfeeding)	Motor development (formula feeding)	Social-emotional development (breastfeeding)	Social-emotional development (formula feeding)
6	85	84	80	79	83	82
12	90	89	85	84	88	87
24	100	98	95	93	95	94

Figure 1 Figure 1 Head circumference growth comparison Figure 1 Head circumference growth comparison

The developmental outcomes of preterm infants were assessed at 6, 12, and 24 months using the Bayley Scales of Infant and Toddler Development (BSID). Measurements included cognitive, motor, and social-emotional domains. Table 2.

This study compared the effects of early breastfeeding and formula feeding on the growth and developmental outcomes of preterm infants over a 24-month period. The findings indicate that both feeding practices effectively support physical growth and early development, with no statistically significant differences in measured parameters such as weight, length, and head circumference. These outcomes contribute to the growing body of evidence suggesting that both feeding strategies can be viable under appropriate clinical guidance ¹⁷ .

The observed growth trajectories are consistent with previous studies showing that formula-fed preterm infants may exhibit slightly higher weight and length gains in early months, although such differences often lack statistical significance ²⁰ . The current findings suggest that advances in the nutritional formulation of preterm-specific formulas have narrowed the gap in growth outcomes between formula-fed and breastfed preterm infants.

Despite these improvements, breastfeeding continues to be the recommended practice due to its long-term health benefits and unique biological components. Breast milk is rich in long-chain polyunsaturated fatty acids, oligosaccharides, and immunoglobulins, which contribute not only to physical growth but also to the development of the immune system and central nervous system ²⁸ . Moreover, human milk has been consistently associated with a lower incidence of necrotizing enterocolitis, a life-threatening condition in preterm infants ²¹ .

In terms of developmental outcomes, the study found that both groups showed comparable progress across cognitive, motor, and social-emotional domains. However, breastfed infants demonstrated slightly higher cognitive and social-emotional scores at 24 months. This observation aligns with findings from longitudinal studies indicating modest but consistent neurodevelopmental advantages in breastfed preterm infants, which are often attributed to neuroprotective compounds present in breast milk ⁵ .

Although formula feeding meets nutritional requirements and supports typical developmental trajectories, it lacks certain bioactive substances naturally found in breast milk, such as growth factors and enzymes that support neural development. These missing components may explain the marginal cognitive benefits observed among breastfed infants ⁶ .

From a clinical perspective, the results support the continued promotion of breastfeeding in neonatal care. However, when breastfeeding is not possible due to maternal illness, low milk supply, or other challenges formula feeding remains a practical and effective alternative. It is important for healthcare providers to offer individualized support and consider supplemental options such as donor milk or human milk fortifiers to optimize nutritional care ¹⁹ .

Finally, while this study offers valuable insights, further research is needed to investigate the long-term cognitive, emotional, and behavioral outcomes associated with early feeding practices. Future studies should also examine the effects of mixed feeding and fortified breast milk to provide a more.