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Title Growth Parameter Catch-up Patterns and Neurodevelopmental Outcomes in Very Low Birth Weight Twins: A Korean Neonatal Network Cohort Study
Author Jiyoon Jeong
작성자 정지윤
Background Very low birth weight (VLBW) infants are at high risk for postnatal growth failure and adverse neurodevelopmental outcomes. Head circumference growth is considered an important marker of brain growth and has been associated with later neurodevelopmental outcomes (Ghods et al., Journal of Perinatal Medicine, 2011; Hong et al., BMC Pediatrics, 2023). Twin infants are commonly born preterm and may show different postnatal growth patterns compared with singleton infants. Although previous KNN research evaluated birthweight discordance and neonatal outcomes in VLBW twins (Yum et al., Pediatrics and Neonatology, 2023), catch-up patterns of weight, length/height, and head circumference in VLBW twins and their association with neurodevelopmental outcomes have not been fully evaluated.
Aim / Hypothesis To evaluate postnatal catch-up patterns of weight, length/height, and head circumference in VLBW twin infants and to investigate their association with neurodevelopmental outcomes. Among VLBW twin infants, catch-up of weight, length/height, and head circumference may occur differently. Failure of head circumference catch-up, defined by z-score criteria, is associated with increased risk of neurodevelopmental impairment.
Inclusion Criteria - Infants registered in the KNN registry - Twin infants who survived to discharge - Available anthropometric data at birth and follow-up - Available neurodevelopmental outcome data at 18–24 months corrected age for the primary analysis
Exclusion Criteria - Multiple gestations other than twins - Major congenital anomalies or chromosomal abnormalities - Death before discharge - Missing essential anthropometric or neurodevelopmental outcome data - Implausible anthropometric values after data review
Study Design Statistical methods Multicenter retrospective cohort study using prospectively collected data from the KNN registry. Growth parameters will include weight, length/height, and head circumference at birth, discharge, 18–24 months corrected age, and 3 years of age, if available. All anthropometric measurements will be converted into age- and sex-specific z-scores using appropriate growth references. Catch-up growth will be primarily defined as recovery to z-score ≥ -2 at follow-up. Changes in z-scores from birth or discharge to follow-up will also be evaluated as secondary growth indicators. Baseline characteristics and outcomes will be compared among groups according to catch-up growth pattern. Continuous variables will be compared using t-test, ANOVA, Mann–Whitney U test, or Kruskal–Wallis test, as appropriate. Categorical variables will be compared using chi-square test or Fisher’s exact test. Multivariable logistic regression will be used to evaluate the association between catch-up growth pattern and neurodevelopmental impairment. Models will adjust for gestational age, sex, birth weight z-score, small for gestational age status, major neonatal morbidities, and center effect when appropriate. For twin pairs in whom both co-twins are available, exploratory within-pair analyses may be performed.
Primary Outcomes 1. Identification and characterization of z-score-based catch-up growth patterns of weight, length/height, and head circumference in VLBW twin infants. 2. Association between growth catch-up patterns and neurodevelopmental impairment at 18–24 months corrected age. 3. Association between growth catch-up patterns and neurodevelopmental impairment at 3 years of age, if available.
Secondary Outcomes and Definitions 1. Comparison of individual components of neurodevelopmental impairment according to catch-up growth patterns, including developmental delay, cerebral palsy, visual impairment, and hearing impairment. 2. Comparison of neurodevelopmental outcomes according to catch-up failure of each growth parameter: weight, length/height, and head circumference. 3. Exploratory within-pair comparison of catch-up growth patterns and neurodevelopmental outcomes among twin pairs in whom both co-twins are available. Definitions: 1. Catch-up failure: z-score < -2 at follow-up. 2. Neurodevelopmental impairment: developmental delay, cerebral palsy, visual impairment, or hearing impairment based on available KNN follow-up variables.
Protocols Following the study design described above
Funding Not applicable

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