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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Small for gestational age (SGA) infants | Full-term SGA infants are defined by a birth weight below the 3rd percentile on the Fenton et al. (2025) growth charts. |
| |
| Adequate for gestational age (AGA) infants | Full-term AGA infants are defined by a birth weight equal to or above the 3rd percentile on the curves of Fenton et al. (2025), and are associated with intrauterine growth restriction and/or Doppler velocimetry abnormalities. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Small for gestational age (SGA) infants | Dietary Supplement |
|
| Measure | Description | Time Frame |
|---|---|---|
| Body composition assessment - Fat mass (FM) | Fat mass will be assessed using air-displacement plethysmography (Pea Pod, Cosmed, Italy) and expressed in kilograms. Unit of measure: Kilograms (kg) | Fat mass will be assessed 1 week after discharge, 1 month of age and 3 months of age |
| Body composition assessment - Fat-free mass (FFM) | Body composition will be assessed using air-displacement plethysmography (Pea Pod, Cosmed, Italy) and expressed in kilograms. Unit of measure: Kilograms (kg) | Fat-free mass will be assessed 1 week after discharge, 1 month of age and 3 months of age |
| Body composition assessment - Fat mass index (FMI) | Fat mass index (FMI) will be calculated by dividing fat mass (kg), obtained from air-displacement plethysmography, by length squared (m²). Formula: FMI (kg/m²) = fat mass (kg) / [length (m)]² Unit of Measure: kg/m² | Fat mass index will be calculated 1 week after discharge, 1 month of age and 3 months of age |
| Body composition assessment - Adiposity (%FM) | Adiposity will be assessed as fat mass percentage (%FM). Fat mass will be measured using air-displacement plethysmography (Pea Pod, Cosmed, Italy), and adiposity will be calculated as: %FM = [fat mass (kg) / body weight (kg)] × 100 Unit of Measure: Percentage (%) | Adiposity will be assessed 1 week after discharge, 1 month of age and 3 months of age |
| Measure | Description | Time Frame |
|---|---|---|
| Neonatal anthropometry - Body weight | Body weight will be measured using a calibrated neonatal scale. Unit of measure: Kilograms (kg) | At birth, 1 week after discharge, 1 month of age and 3 months of age |
| Neonatal anthropometry - Length |
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Inclusion Criteria:
Exclusion Criteria:
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Full term infants diagnosed with intrauterine growth restriction.
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| Name | Affiliation | Role |
|---|---|---|
| Manuela Cardoso, RDN, PhD | Unidade Local de Saúde São José | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Unidade Local de Saúde São José | Lisbon | 1150-199 | Portugal |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20624208 | Background | Pinto E, Severo M, Correia S, dos Santos Silva I, Lopes C, Barros H. Validity and reproducibility of a semi-quantitative food frequency questionnaire for use among Portuguese pregnant women. Matern Child Nutr. 2010 Apr;6(2):105-19. doi: 10.1111/j.1740-8709.2009.00199.x. | |
| 27399768 | Background | Goswami I, Rochow N, Fusch G, Liu K, Marrin ML, Heckmann M, Nelle M, Fusch C. Length Normalized Indices for Fat Mass and Fat-Free Mass in Preterm and Term Infants during the First Six Months of Life. Nutrients. 2016 Jul 8;8(7):417. doi: 10.3390/nu8070417. |
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Breast milk from mothers
|
| Adequate for gestational age (AGA) infants | Dietary Supplement |
|
|
Length will be measured using an infantometer. Unit of measure: Centimeter (cm)
| Length will be measured at birth, 1 week after discharge, 1 month of age and 3 months of age |
| Neonatal anthropometry - Head circumference | Head circumference will be measured using a non-stretchable measuring tape. Unit of measure: Centimeter (cm) | Head circumference will be measured at birth, 1 week after discharge, 1 month of age and 3 months of age |
| Breast milk energy content | Energy content of breast milk will be measured using the Miris® Human Milk Analyzer (Miris AB, Uppsala, Sweden). Mothers will be asked to save, once a week, circa 4 cc of midfeeding breast milk. Unit of measure: kcal/dL | Weekly from birth until 3 months of age |
| Breast milk macronutrient concentration | Breast milk macronutrient concentrations, including raw protein, true protein, fat, carbohydrates and ashes will be measured using the Miris® Human Milk Analyzer (Miris AB, Uppsala, Sweden). Mothers will be asked to save, once a week, circa 4 cc of midfeeding breast milk. Unit of measure: g/dL | Weekly from birth until 3 months of age |
| Mothers dietary habits - Mother energy intake | Maternal dietary intake during the second and third trimesters of pregnancy will be assessed using a semi-quantitative food frequency questionnaire validated for Portuguese pregnant women. Reported frequencies and standard portion sizes will be converted to estimated energy intake. Unit of measure: kcal/day | Assessed once at recruitment, within the first week after birth |
| Maternal dietary habits - Maternal macronutrient intake | Maternal intake of protein, fat, and carbohydrates during the second and third trimesters of pregnancy will be estimated using a semi-quantitative Food Frequency Questionnaire validated for Portuguese pregnant women. Reported food frequencies and portion sizes will be converted into estimated daily macronutrient intake. Unit of measure: g/day | Assessed once at recruitment, within the first week after birth |
| Prenatal fetal biometry and Doppler percentiles | Prenatal fetal biometry and Doppler measurements will be retrieved from obstetric ultrasound records and recorded as percentiles for gestational age, according to the reference standards used in the clinical ultrasound reports. Parameters will include abdominal circumference, femur length, head circumference, estimated fetal weight, and pulsatility index percentiles for the umbilical artery, middle cerebral artery, ductus venosus, and uterine arteries. Unit of Measure: Percentile | Assessed retrospectively during the study period |
| Maternal demographic and clinical variables - Maternal age | Maternal age will be determined from the maternal date of birth recorded in clinical records or reported at recruitment. Unit of Measure: Years | At birth (time of recruitment) |
| Mother's demographic and clinical variables - Maternal height | Maternal height will be retrieved from clinical records or reported by the mother at recruitment. Unit of Measure: Meters (m) | At birth (time of recruitment) |
| Mother's demographic and clinical variables - Pre-pregnancy weight | Maternal pre-pregnancy weight will be retrieved from clinical records or reported by the mother at recruitment. Unit of Measure: Kilograms (kg) | At birth (time of recruitment) |
| Mother's demographic and clinical variables - Postpartum weight | Maternal postpartum weight will be reported by the mother during follow-up. Unit of Measure: Kilograms (kg) | From recruitment until 3 months after birth |
| Mother's demographic and clinical variables - Pregnancy related medical conditions | Pregnancy-related medical conditions will be retrieved from clinical records, including diabetes mellitus (type 1 or type 2), gestational diabetes, gestational hypertension, pre-eclampsia, chronic renal disease, systemic lupus erythematosus, and anaemia. Unit of Measure: Presence or absence of condition | Assessed retrospectively during the study period |
| 17209182 | Background | Ellis KJ, Yao M, Shypailo RJ, Urlando A, Wong WW, Heird WC. Body-composition assessment in infancy: air-displacement plethysmography compared with a reference 4-compartment model. Am J Clin Nutr. 2007 Jan;85(1):90-5. doi: 10.1093/ajcn/85.1.90. |
| 36986263 | Background | Cardoso M, Virella D, Papoila AL, Alves M, Macedo I, E Silva D, Pereira-da-Silva L. Individualized Fortification Based on Measured Macronutrient Content of Human Milk Improves Growth and Body Composition in Infants Born Less than 33 Weeks: A Mixed-Cohort Study. Nutrients. 2023 Mar 22;15(6):1533. doi: 10.3390/nu15061533. |
| 33477964 | Background | Cardoso M, Virella D, Macedo I, Silva D, Pereira-da-Silva L. Customized Human Milk Fortification Based on Measured Human Milk Composition to Improve the Quality of Growth in Very Preterm Infants: A Mixed-Cohort Study Protocol. Int J Environ Res Public Health. 2021 Jan 19;18(2):823. doi: 10.3390/ijerph18020823. |
| 30513944 | Background | Czosnykowska-Lukacka M, Krolak-Olejnik B, Orczyk-Pawilowicz M. Breast Milk Macronutrient Components in Prolonged Lactation. Nutrients. 2018 Dec 3;10(12):1893. doi: 10.3390/nu10121893. |
| ID | Term |
|---|---|
| D005317 | Fetal Growth Retardation |
| ID | Term |
|---|---|
| D005315 | Fetal Diseases |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006130 | Growth Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D005865 | Gestational Age |
| ID | Term |
|---|---|
| D047109 | Fetal Development |
| D005314 | Embryonic and Fetal Development |
| D009024 | Morphogenesis |
| D048788 | Growth and Development |
| D010829 | Physiological Phenomena |
| D055703 | Reproductive Physiological Phenomena |
| D012101 | Reproductive and Urinary Physiological Phenomena |
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