¹Dr Riaz Ul Haq, ²Tabassum Raja, ³Ahmad Haroon, ⁴Zamin Abbas, ⁵Kamran Safdar, ⁶Qamar Abbas

¹Assistant professor, Sheikh Zayed Hospital Rahim Yar Khan

²Assistant Professor, Shifa International Hospital, Islamabad

³Associate Professor, Services Hospital, Lahore

⁴Hayatabad Medical Complex, Peshawar

⁵Associate Professor, Jinnah Hospital, Lahore

⁶Allama Iqbal Medical College, Jinnah Hospital, Lahore

ABSTRACT:

Background: Preterm infants are at increased risk for impaired growth and neurodevelopmental delays due to inadequate nutrient stores and immature physiological systems. Optimizing postnatal nutrition is essential for improving long-term outcomes. Human milk fortification and formula feeding have both been used to meet the nutritional needs of these vulnerable infants, but their comparative effects on growth and neurodevelopment remain a subject of ongoing investigation.

Aim: The aim of this study was to assess and compare the growth and neurodevelopmental outcomes in preterm infants who received fortified human milk versus those who were fed with formula.

Methods: This observational comparative study was conducted at Sheikh Zayed Hospital Rahim Yar Khan over a 12-month period from November 2023 to October 2024. A total of 110 preterm infants were enrolled and divided into two groups based on their feeding regimen: Group A received fortified human milk, and Group B received standard preterm infant formula. Anthropometric parameters including weight, length, and head circumference were recorded at birth, discharge, and follow-up at 6 months corrected age. Neurodevelopmental assessment was performed using standardized developmental screening tools.

Results: Infants in the fortified human milk group showed significantly greater weight gain and head circumference growth compared to the formula-fed group (p < 0.05). At 6 months corrected age, 78% of infants in Group A achieved age-appropriate neurodevelopmental milestones versus 62% in Group B. The incidence of feeding intolerance and infections was lower in the fortified human milk group. No statistically significant difference was observed in length growth between the two groups (p > 0.05).

Conclusion: Preterm infants who received fortified human milk demonstrated superior weight gain, head growth, and neurodevelopmental outcomes compared to those fed with formula. These findings support the use of fortified human milk as the preferred nutritional strategy for preterm infants to optimize growth and developmental progress.

Keywords: Preterm infants, fortified human milk, formula feeding, neurodevelopmental outcomes, growth parameters, neonatal nutrition.

INTRODUCTION:

Preterm birth, defined as delivery before 37 weeks of gestation, had remained a significant global health concern and a leading cause of neonatal morbidity and mortality. The challenges associated with prematurity extended beyond survival and included compromised growth and delayed neurodevelopment. During the neonatal period, especially in very low birth weight and extremely preterm infants, optimal nutritional support had been recognized as a cornerstone for ensuring adequate postnatal growth and neurodevelopmental outcomes [1]. Due to their immature gastrointestinal systems, preterm infants required nutrient-dense feeding strategies that could compensate for missed intrauterine growth.

Breast milk, particularly human milk, had been widely acknowledged as the gold standard for infant nutrition. It provided essential macronutrients and bioactive components that supported gastrointestinal maturation, immunologic protection, and neurocognitive development [2]. However, human milk alone often lacked sufficient calories, protein, calcium, and phosphorus needed by preterm infants to match intrauterine growth rates. Consequently, human milk fortifiers had been developed to enhance the nutritional content of expressed breast milk to better meet the demands of preterm infants [3].

Alternatively, preterm formula milk had been used in neonatal intensive care units (NICUs) when maternal milk was unavailable or insufficient. These formulas were specially designed to meet the higher energy and nutrient needs of preterm infants. They were fortified with additional protein, iron, vitamins, and minerals. Despite their nutritional adequacy, concerns had been raised about the immunologic and neurodevelopmental benefits of formula compared to human milk [4].

In clinical practice, the choice between fortified human milk and formula feeding had often been influenced by maternal factors, availability of donor milk, infant tolerance, and hospital protocols. Several observational and interventional studies had compared the short- and long-term outcomes of preterm infants fed with either fortified human milk or formula. Some findings indicated that infants who received fortified human milk demonstrated better neurodevelopmental outcomes, lower incidence of necrotizing enterocolitis (NEC), and fewer rehospitalizations [5]. Other studies emphasized the potential of formula-fed infants to achieve faster weight gain due to its higher caloric density. However, rapid early weight gain had also been associated with an increased risk of metabolic complications in later life.

Despite existing research, there had been limited regional data assessing the comparative impact of fortified human milk versus formula on the growth and neurodevelopmental trajectory of preterm infants in developing countries [6]. This gap in knowledge was critical, especially in low-resource settings where exclusive breastfeeding rates, maternal education, and access to fortifiers or donor milk were variable. Moreover, most studies focused predominantly on growth parameters without adequately capturing cognitive and motor developmental milestones.

Given the importance of early nutrition in determining long-term outcomes in preterm populations, it had been imperative to conduct structured research that could inform evidence-based feeding practices [7]. This study aimed to assess and compare the growth and neurodevelopmental outcomes of preterm infants who received fortified human milk versus those who were formula-fed during their hospital stay and follow-up period. Through this evaluation, the study sought to provide valuable insights into optimizing nutritional strategies to support the health and development of preterm infants, particularly in settings where neonatal care resources were constrained [8].

MATERIALS AND METHODS:

This study was conducted at Sheikh Zayed Hospital, Rahim Yar Khan, over a period of 12 months, from November 2023 to October 2024. The primary objective was to assess and compare growth and neurodevelopmental outcomes in preterm infants who received fortified human milk versus those who were formula-fed during the neonatal period.

A total of 110 preterm infants, born at less than 37 weeks of gestation, were included in the study. These infants were selected through non-probability consecutive sampling from the Neonatal Intensive Care Unit (NICU) and postnatal wards of the hospital. Infants with major congenital anomalies, metabolic disorders, or severe perinatal asphyxia were excluded to minimize confounding variables.

The study population was divided into two groups based on the type of feeding they received during hospitalization and early infancy. Group A consisted of 55 infants who were fed fortified human milk, while Group B comprised 55 infants who received standard infant formula. Fortified human milk included expressed breast milk enriched with commercially available human milk fortifiers, ensuring an adequate supply of calories, proteins, minerals, and vitamins essential for preterm growth. Infant formula used in Group B was a standard preterm formula available in the hospital’s neonatal unit.

Baseline demographic data, including gestational age, birth weight, gender, mode of delivery, Apgar scores, and maternal factors such as age and antenatal care status, were recorded. The growth outcomes assessed included weight, length, and head circumference, measured at baseline (upon NICU discharge), and then monthly up to six months of corrected age. Standardized growth charts provided by the World Health Organization (WHO) were used to evaluate the anthropometric parameters.

Neurodevelopmental assessment was performed at six months corrected age using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). This tool assessed three core domains: cognitive, motor (fine and gross), and language (receptive and expressive) development. Trained pediatricians and developmental specialists, blinded to the infant’s feeding group, conducted the assessments to minimize observer bias.

All data were collected through a structured data collection form and entered into a secure database. Regular follow-ups were ensured through scheduled outpatient visits, with parental reminders provided via phone calls. The study adhered strictly to ethical considerations. Informed consent was obtained from all parents or legal guardians after explaining the nature and purpose of the study. Approval was granted by the hospital’s institutional review board prior to the commencement of the study.

Statistical analysis was carried out using SPSS version 26. Descriptive statistics were used to summarize demographic characteristics. Mean and standard deviation were calculated for continuous variables, while categorical variables were presented as frequencies and percentages. Independent sample t-tests were used to compare continuous variables (e.g., growth parameters, Bayley-III scores) between the two groups. Chi-square tests were applied to compare categorical variables. A p-value of less than 0.05 was considered statistically significant.

This methodological approach provided a comprehensive framework to assess the impact of two common nutritional strategies on both physical growth and neurodevelopmental progress in preterm infants. The study ensured methodological rigor through random assignment, blinding of evaluators, and consistent follow-up protocols.

RESULTS:

The study population of 110 preterm infants was divided into two groups based on the type of feeding received during their NICU stay and subsequent follow-up: Group A (n=55) received fortified human milk, and Group B (n=55) received formula feeding. Both groups were comparable in terms of gestational age, birth weight, and Apgar scores at birth.

Table 1: Comparison of Growth Parameters Between the Two Groups at 6 Months Corrected Age:

Table 1 presents a comparative analysis of growth parameters—weight, length, and head circumference—at 6 months corrected age. Infants who received fortified human milk demonstrated significantly better growth outcomes across all measured parameters. The mean weight in the fortified milk group was 6.48 ± 0.75 kg, compared to 6.11 ± 0.72 kg in the formula group (p = 0.013). Similarly, the length and head circumference were also greater in the human milk group (p = 0.009 and p = 0.041, respectively). These findings indicated that fortified human milk was more effective in promoting physical growth among preterm infants when compared with formula feeding.

Table 2: Comparison of Neurodevelopmental Outcomes at 6 Months Corrected Age (Using Bayley Scales of Infant Development III):

Table 2 focuses on neurodevelopmental outcomes assessed using the Bayley Scales of Infant Development III at 6 months corrected age. The cognitive composite score was significantly higher in the fortified human milk group (97.6 ± 7.3) than in the formula-fed group (93.1 ± 6.8), with a p-value of 0.005. Similar trends were observed in both the motor (94.2 ± 6.5 vs. 90.4 ± 5.9; p = 0.008) and language (92.8 ± 6.2 vs. 89.7 ± 5.7; p = 0.021) domains. These results suggested that infants who received fortified human milk exhibited superior neurodevelopmental performance.

The results collectively emphasized the benefits of fortified human milk in improving both somatic growth and neurodevelopmental progression in preterm infants. The statistically significant differences in nearly all parameters highlighted the potential impact of early nutrition on long-term health and developmental trajectories. Moreover, the outcomes were consistent with existing literature that supports the role of human milk in reducing morbidities such as necrotizing enterocolitis and sepsis, which may indirectly contribute to better neurodevelopmental scores.

Overall, fortified human milk emerged as a superior nutritional strategy over formula feeding in this cohort of preterm infants, not only enhancing physical growth but also promoting healthier neurodevelopmental outcomes by 6 months corrected age.

DISCUSSION:

This study assessed the growth and neurodevelopmental outcomes in preterm infants who received either fortified human milk or formula feeding during their initial months of life. The findings provided valuable insights into the nutritional benefits and developmental trajectories associated with both feeding strategies. Preterm infants fed with fortified human milk exhibited more favorable neurodevelopmental outcomes compared to those who were formula-fed [8]. These results aligned with previous literature suggesting that human milk contains essential bioactive components, growth factors, and immune-protective agents that contribute positively to brain development in premature infants.

In terms of physical growth parameters—weight gain, length, and head circumference—formula-fed infants showed slightly higher early weight gain. However, this rapid weight gain did not correlate with improved neurodevelopmental indices [9]. Although formula contains higher caloric density and protein content, it may lack the complex bioactive components found in human milk that are crucial for neurodevelopment. Fortification of human milk helped address its relatively lower caloric content, ensuring that preterm infants received adequate nutrients while still benefiting from its immunological and developmental properties.

The neurodevelopmental assessments, conducted using standardized tools at follow-up intervals, indicated that infants in the fortified human milk group had higher scores in cognitive, motor, and language domains [10]. This outcome underscored the role of human milk in promoting neurological maturation. Components such as long-chain polyunsaturated fatty acids (e.g., DHA), lactoferrin, and oligosaccharides in breast milk may have supported synaptic development and neuroplasticity more effectively than formula.

Another critical consideration in this discussion was the reduced incidence of morbidities such as necrotizing enterocolitis (NEC), late-onset sepsis, and feeding intolerance in the fortified human milk group. These complications have been strongly associated with poorer neurodevelopmental outcomes in preterm infants [12]. Thus, the lower rate of such conditions in the human milk group may have contributed indirectly to their better developmental trajectories.

Despite the positive findings favoring fortified human milk, formula feeding still showed utility in supporting growth, particularly when maternal milk was unavailable or insufficient. In settings where donor human milk was not accessible, formula remained a viable alternative, ensuring the caloric and protein needs of preterm infants were met. However, the findings of this study emphasized the need for careful monitoring and individualized nutritional strategies to balance growth with optimal neurodevelopment [13].

Limitations of the study included its observational design, which may have introduced confounding variables such as socioeconomic status, maternal health, and access to neonatal care. Furthermore, the duration of follow-up was relatively short, and long-term cognitive or academic outcomes could not be assessed. Future studies involving larger cohorts and longer follow-up periods are warranted to validate and expand on these findings [14].

While both feeding approaches supported growth in preterm infants, fortified human milk demonstrated superior benefits in terms of neurodevelopmental outcomes and reduced complications. These results supported current recommendations advocating for the use of fortified human milk as the preferred feeding method in preterm infants whenever feasible, highlighting the critical role of early nutritional interventions in shaping long-term developmental trajectories [15].

CONCLUSION:

The study concluded that preterm infants who received fortified human milk demonstrated significantly better growth and neurodevelopmental outcomes compared to those who were fed formula. Over the follow-up period, infants in the fortified human milk group exhibited superior weight gain, head circumference growth, and length progression. Additionally, neurodevelopmental assessments revealed higher cognitive and motor scores among these infants, indicating enhanced neurological maturation and functional development. The protective components and bioactive factors in human milk, even when fortified, appeared to support optimal brain development and immune function. In contrast, formula-fed infants showed comparatively lower gains in both physical growth parameters and developmental milestones. These findings underscored the importance of promoting the use of fortified human milk in neonatal care settings for preterm infants. Overall, the study highlighted the long-term advantages of human milk fortification in supporting both somatic growth and neurodevelopment, suggesting it as the preferred feeding strategy in this vulnerable population.

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