Early Nutrition and Heart Structure and Function in Preterm Infants During the First Year of Life

This prospective observational study will investigate the association between early nutritional exposure during the neonatal period and cardiac structure and function during the first year of life in preterm infants.

**Study Setting and Population**

The study will be conducted at the Department of Pediatric Medicine, Assiut University Hospital and El-Eman General Hospital, Assiut, Egypt. The study population will include preterm infants born before 37 completed weeks of gestation who are admitted to the neonatal unit within 24 hours of birth, have adequate nutritional records, and whose parents provide written informed consent. Infants must be available for follow-up echocardiographic assessment at 12 months of corrected age.

**Eligibility Criteria**

Infants with major congenital heart disease, known congenital cardiomyopathy, major chromosomal or genetic abnormalities, congenital anomalies, or infections associated with or potentially affecting cardiac disease will be excluded. Infants with inadequate nutritional records, those whose parents refuse written consent, and those without follow-up at one year will also be excluded.

**Nutritional Exposure Groups**

The protocol describes the following feeding groups:

1. Preterm infants receiving early complementary feeding at 17 weeks.
2. Preterm infants receiving late complementary feeding after 26 weeks.
3. Preterm infants receiving breastfeeding.
4. Preterm infants receiving artificial feeding.
5. Preterm infants receiving both breast milk and artificial feeding.

Nutritional exposure will be evaluated in relation to cardiac and growth outcomes. The final operational definitions and classification of feeding groups will follow the study protocol.

**Data Collection**

Maternal information will include maternal age, parity, mode of conception, obstetric history and complications, antenatal corticosteroid and magnesium sulfate administration, and mode of delivery.

Neonatal information will include sex, gestational age, singleton or multiple birth, birth weight, length, head circumference, small-for-gestational-age, appropriate-for-gestational-age or large-for-gestational-age classification, Apgar scores, and resuscitation requirements. Neonatal complications will include respiratory distress syndrome, surfactant use, duration of ventilation, and length of hospital stay.

Anthropometric measurements, including weight, length, and head circumference, will be recorded at birth, 36 weeks of postmenstrual age, hospital discharge, and 12 months of corrected age. Appropriate growth z-scores will be calculated using relevant reference standards.

**Echocardiographic Assessment**

Echocardiography will be performed at birth, 6 months, and approximately 12 months of corrected age (±2 weeks) by a single trained pediatric cardiologist blinded to the feeding group.

Cardiac structural measurements will include left ventricular end-diastolic and end-systolic dimensions, septal and posterior wall thickness, left ventricular mass index, relative wall thickness, left ventricular sphericity index, left atrial size, right ventricular basal dimension, and aortic root dimensions.

Cardiac functional measurements will include left ventricular ejection fraction and global longitudinal strain; mitral E/A ratio, septal and lateral e', E/e' ratio, and isovolumetric relaxation time; tricuspid annular plane systolic excursion, tricuspid S', right ventricular fractional area change, right ventricular free-wall strain, pulmonary acceleration time, and septal configuration. Patent foramen ovale and patent ductus arteriosus, if identified, will be documented as incidental findings.

**Study Outcomes and Statistical Analysis**

The primary objective is to investigate the association between early nutritional strategies and cardiac structure and function at 12 months of corrected age.

Secondary objectives include comparing left ventricular mass index z-scores, other echocardiographic parameters, and anthropometric outcomes among feeding groups, and developing a predictive model to identify early nutritional and clinical factors associated with left ventricular mass index at 12 months.

Data will be analyzed using the Statistical Package for the Social Sciences (SPSS). Continuous variables will be summarized as mean ± standard deviation or median and interquartile range, as appropriate. Categorical variables will be presented as frequencies and percentages. Comparisons will use one-way analysis of variance or the Kruskal-Wallis test, with appropriate post hoc correction, and the chi-square test or Fisher's exact test for categorical variables. Multivariable linear regression will be used for the predictive model. A p-value below 0.05 will be considered statistically significant.

Written informed consent will be obtained from parents or legal guardians, and participant information will be handled confidentially by the research team.