Determination of Clinical Phenotypes of Intrauterine Growth Restriction in Term Infants Based on Body Composition

Determination of Clinical Phenotypes of Intrauterine Growth Restriction in Term Infants Based on Body Composition. A Potential Contribution to Nutritional Management.

Intrauterine growth restriction (IUGR) is defined as the inability of the fetus to fulfill its genetic growth potential. "Small for gestational age" (SGA) is the most commonly used indicator for diagnosing IUGR. However, this definition does not consider intrauterine growth trajectory or physical characteristics at birth. SGA is based on the relationship between birth weight and gestational age, and does not address anthropometric measurements at birth or prenatal indicators, such as biometric, biophysical, and Doppler velocimetry abnormalities. SGA infants may constitute intrauterine growth restricted as well as constitutionally small infants. This distinction can be made more accurately by complementary assessment of body composition. The clinical meaning of each group identified by body composition will be assessed by the evolution until 3-months of age. The feeding pattern and composition will be considered a major postnatal exposure. Accurate classification of IUGR profiles is essential to ensure appropriate nutritional intervention.

Study design: This is a single-center prospective observational, cohort study of full-term infants born with intrauterine growth restriction (IUGR) and their lactating mothers.

Study period: A consecutive recruitment of participants will be conducted over 18 months (from November 19, 2025). Eligible children, whose parents accepted the invitation to participate, will be recruited in a follow-up study until they are 3 months old.

Settings: Neonatology Unit, Prenatal Diagnostic Center and Human Milk Bank at Maternidade Dr. Alfredo da Costa, Unidade Local de Saúde São José, Lisbon. Nutrition Laboratory of Hospital Dona Estefânia, Unidade Local de Saúde São José, Lisbon, Portugal.

Variables in study:

• Mother's retrieved demographic and clinical variables will include: mother's age, height, reported body weight closer to the beginning of pregnancy, body weight gain during pregnancy, pathological conditions during pregnancy (diabetes mellitus type I and type II, gestational diabetes, gestational hypertension, hypertension, pre-eclampsia, chronic renal disease, systemic lupus erythematosus, anaemia or other conditions).
• Obstetrics' Doppler velocimetry serial ultrasounds will be analysed. The data retrieved will include gestational age at ultrasound date, fetal abdominal circumference, femur length, head circumference, estimated fetal weight, pulsatility index of umbilical artery, middle cerebral artery, venous duct and uterine artery.
• Mothers dietary habits: A semi-quantitative food frequency questionnaire consisting of 86 food items, validated for Portuguese pregnant women, will be applied one week after birth to assess food intake during the second and third trimesters of pregnancy.
• Breast milk macronutrient and energy content: The breast milk macronutrient and energy content will be analyzed using the Miris® Human Milk analyzer (Miris AB, Uppsala, Sweden). Mothers will be asked to save circa 4 cc of midfeeding breast milk during the noon feeding, as a systematic sampling of milk collected through 24 hours, in order to minimize daily variability of breast milk composition. Before each use, the analyzer will be calibrated using the standard calibration solution. The breast milk composition will be expressed in densities: Kcal/dL of energy and g/dL of fat, total and true protein, carbohydrates, and ashes.
• Neonatal variables: gestational age at birth, sex, parity, birth weight, height and head circumference, gestational age adequacy.
• Body composition assessment: Body composition assessment will be conducted using a Displacement Plethysmograph (Pea Pod, Cosmed, Italy), which is validated for newborns. Subsequent assessments will be performed by the same observer at 1 week after discharge, 1 month and 3 months of age (+/- 1 week). The equipment automatically provides fat mass (FM), fat-free mass (FFM) and fat mass percentage (%FM). The same observer will measure length, and this measurement will be used to calculate the fat mass index (FMI). Adiposity will be defined by %FM (FM (kg)/body mass (kg)) and FMI (FM (kg)/length (m²)).

Estimate of sample size: Assuming the highest probability (2:1) of reduced adiposity in small-for-gestational-age (SGA) infants with reduced fat-free mass (FFM), SGA infants with reduced adiposity, appropriate-for-gestational-age (AGA) infants with fetal growth deceleration and/or Doppler velocimetry abnormalities with reduced FFM, and AGA infants with fetal growth deceleration and/or Doppler velocimetry abnormalities with reduced adiposity, and considering a 95% confidence interval, the expected sample size is 145 SGA infants and 145 AGA infants.

Comparison groups: Body composition will be compared between the following IUGR profiles: SGA infants without fetal growth deceleration or Doppler velocimetry abnormalities; SGA with fetal growth deceleration or Doppler velocimetry abnormalities; AGA with fetal growth deceleration or Doppler velocimetry abnormalities; SGA with reduced FFM (Fat-free-mass); SGA with reduced adiposity; AGA with fetal growth deceleration and/or Doppler velocimetry abnormalities with reduced FFM. AGA with fetal growth deceleration and/or Doppler velocimetry abnormalities with reduced adiposity.

Inclusion Criteria:

• IUGR and term GA (37+0/7 to 41+6/7 weeks of gestation)

Exclusion Criteria:

• Eligible fetuses with congenital malformations
• Eligible fetuses with genetic mutations.
• Eligible infants with congenital malformations
• Eligible intants with inborn errors of metabolism.
• Infants who become ill and require hospitalization during the study period
• Infants who die during the study period
• Parents or legal guardians who do not agree to participate
• Parents or legal guardians who abandon the study.