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Long-Term Neurodevelopmental Outcome Measures in Preterm Infants: A Systematic Review Nurul Purnamasari; Ririn Azhari
The International Journal of Medical Science and Health Research Vol. 16 No. 3 (2025): The International Journal of Medical Science and Health Research
Publisher : International Medical Journal Corp. Ltd

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.70070/jtxw1843

Abstract

Introduction: Advances in neonatal care have significantly increased the survival of preterm infants, shifting the focus to long-term neurodevelopmental outcomes. Infants born before 37 weeks of gestation are at an elevated risk for a wide spectrum of impairments due to the interruption of critical in-utero brain development. This systematic review synthesizes the current evidence on long-term neurodevelopmental outcomes in preterm infants and the measures used for their assessment. Methods: This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of MEDLINE, Embase, CINAHL, PsycINFO, Scopus, Web of Science, and the Cochrane Library was performed to identify observational studies and randomized controlled trials that reported neurodevelopmental outcomes in preterm infants assessed at or after 12 months of age, compared to term-born controls or other preterm subgroups. Two independent reviewers performed study selection, data extraction, and risk of bias assessment using the Cochrane Risk of Bias 2 (RoB 2) tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. A narrative synthesis was conducted, with results grouped by neurodevelopmental domain. Results: The search yielded 4,720 unique records, from which 8 studies met the inclusion criteria, encompassing a total of 72,974 preterm-born children. The evidence confirms a clear gradient of risk, with the prevalence and severity of impairment increasing with decreasing gestational age. Preterm infants demonstrate significantly higher rates of adverse outcomes across all major domains. Key findings include a pooled prevalence of overall neurodevelopmental impairment of 16% and cerebral palsy of 5% in low- and middle-income countries. Cognitive delays were the most frequently reported outcome, with preterm children scoring, on average, 11-13 points lower on IQ scales than their term-born peers. Increased risks were also consistently found for motor impairments, language delays, academic difficulties, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and internalizing and externalizing behavioral problems. A wide array of assessment tools was identified, with the Bayley Scales of Infant and Toddler Development and Wechsler Intelligence Scales being the most common. Discussion: The findings underscore the substantial and persistent burden of neurodevelopmental morbidity following preterm birth. The heterogeneity of assessment tools across studies presents a significant challenge for synthesizing evidence and comparing outcomes. The data suggest a developmental cascade, where early motor and language deficits may contribute to later cognitive and behavioral challenges. The necessity for long-term surveillance is highlighted by "sleeper effects," where some impairments only manifest later in childhood as academic and social demands increase. Conclusion: Preterm birth is a major risk factor for a wide spectrum of long-term neurodevelopmental impairments. Comprehensive, multidisciplinary follow-up programs using validated and context-appropriate assessment tools are essential for early identification and intervention to optimize the developmental potential of this vulnerable population.
Responsive versus Scheduled Interval Feeding for Preterm and Low Birth Weight Infants: A Systematic Review Nurul Purnamasari; Ririn Azhari
The International Journal of Medical Science and Health Research Vol. 16 No. 3 (2025): The International Journal of Medical Science and Health Research
Publisher : International Medical Journal Corp. Ltd

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.70070/ev8p0z60

Abstract

Introduction: Optimal feeding for preterm and low birth weight (LBW) infants is critical for growth and development, yet the ideal feeding strategy remains debated. This systematic review evaluates the effects of responsive (cue-based) feeding compared with traditional scheduled interval feeding on a comprehensive range of outcomes in this vulnerable population. Methods: Following PRISMA guidelines, we conducted a systematic search of CENTRAL, MEDLINE, EMBASE, and CINAHL for randomized controlled trials (RCTs) comparing responsive versus scheduled feeding in preterm (<37 weeks' gestation) or LBW (<2500 g) infants. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the Cochrane RoB 2 tool. Data were synthesized using random-effects meta-analysis for homogeneous outcomes, with results reported as mean difference (MD) or risk ratio (RR) with 95% confidence intervals (CI). A narrative synthesis was performed for heterogeneous data. The certainty of evidence was assessed using the GRADE framework. Results: Nine RCTs involving over 650 infants were included. Meta-analysis revealed that responsive feeding resulted in a slower rate of weight gain compared to scheduled feeding (MD −1.36 g/kg/day, 95% CI −2.44 to −0.29; low certainty) but significantly reduced the time to achieve full oral feeding (MD −5.53 days, 95% CI −6.80 to −4.25; low certainty). There was no consistent or statistically significant effect on the overall duration of hospital admission (MD −1.42 days, 95% CI −5.43 to 2.59; very low certainty). Data on critical outcomes, including long-term neurodevelopment, parental satisfaction, breastfeeding duration, and specific adverse events like necrotizing enterocolitis, were systematically absent across the included trials. Most included studies were small and possessed methodological limitations, primarily a high risk of bias due to lack of blinding. Discussion: The evidence highlights a central clinical trade-off: responsive feeding appears to accelerate the acquisition of oral feeding skills at the potential cost of slower short-term weight gain. The lack of a corresponding reduction in hospital stay suggests that other discharge criteria, such as achieving a specific weight, may negate the benefits of earlier feeding proficiency. A profound misalignment exists between the developmental philosophy of responsive feeding and the predominantly biomedical outcomes measured in existing trials. Conclusion: The current evidence, which is of low to very low certainty, is insufficient to recommend the universal adoption of responsive feeding over scheduled feeding to improve growth or shorten hospitalization for preterm and LBW infants. Responsive feeding appears to be a safe alternative that may hasten the transition to full oral feeding. High-quality, large-scale RCTs that measure patient- and family-centered outcomes are urgently needed.
The Relation Between 25-Hydroxyvitamin D Levels and Sepsis in Neonatal Intensive Care Unit Infants: A Comprehensive Systematic Review Nurul Purnamasari; Ririn Azhari
The International Journal of Medical Science and Health Research Vol. 16 No. 4 (2025): The International Journal of Medical Science and Health Research
Publisher : International Medical Journal Corp. Ltd

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.70070/zhjype47

Abstract

Introduction: Neonatal sepsis is a leading cause of morbidity and mortality worldwide, characterized by a dysregulated host immune response to infection. Vitamin D, recognized for its potent immunomodulatory functions, has been implicated as a potential modifiable risk factor. This systematic review aims to comprehensively evaluate the association between 25-hydroxyvitamin D levels and the incidence and severity of sepsis in infants admitted to the Neonatal Intensive Care Unit (NICU). Methods: A systematic search of PubMed, Scopus, and the Cochrane Library was conducted to identify observational (case-control and cohort) studies assessing maternal, cord, or neonatal 25(OH)D levels in NICU infants with and without sepsis. Data on study characteristics, participant demographics, vitamin D status, and a minimum of 15 clinical and laboratory outcomes were extracted. The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Results: The review included a robust selection of observational studies. A consistent and statistically significant association was found between lower 25(OH)D levels and the presence of neonatal sepsis. Neonates with sepsis had markedly lower mean 25(OH)D concentrations compared to non-septic controls across multiple studies. Furthermore, low maternal and cord blood 25(OH)D levels were identified as significant independent risk factors for developing neonatal sepsis, with neonates born to vitamin D-deficient mothers having substantially increased odds of infection. Vitamin D deficiency was also significantly associated with increased sepsis severity, longer hospital and NICU stays, greater need for mechanical ventilation and inotropic support, and adverse laboratory profiles, including elevated C-reactive protein (CRP) and lower platelet counts. Discussion: The evidence strongly suggests that pre-existing vitamin D deficiency is a critical predisposing factor for neonatal sepsis, rather than merely a consequence of the acute illness. The immunomodulatory role of vitamin D—enhancing innate antimicrobial defenses while tempering excessive inflammation—provides a strong biological rationale for these clinical findings. Low vitamin D status appears to impair the neonate's ability to mount an effective yet controlled immune response, thereby increasing susceptibility to infection and the risk of progression to severe sepsis and organ dysfunction. Methodological challenges, including variability in 25(OH)D assays and the unmeasured influence of Vitamin D Binding Protein (VDBP), are important limitations in the current literature. Conclusion: There is a robust association between vitamin D deficiency and an increased risk and severity of neonatal sepsis. Optimizing perinatal vitamin D status represents a promising preventative strategy. High-quality, large-scale randomized controlled trials are urgently needed to establish causality and to formulate evidence-based guidelines for vitamin D supplementation in pregnant women and high-risk neonates for the prevention of sepsis.