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

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 Overview

• Status: Enrolling by invitation
• Conditions: Intrauterine Growth Restriction (IUGR)
• Intervention / Treatment: Dietary supplement: Small for gestational age (SGA) infants; Dietary supplement: Adequate for gestational age (AGA) infants

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 290

Contacts and Locations

Study Locations

• Portugal
  • Lisbon, Portugal, 1150-199
    • Unidade Local de Saúde São José

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Full term infants diagnosed with intrauterine growth restriction.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Dietary supplement: Small for gestational age (SGA) infants; Body composition assessment will be conducted using a Displacement Plethysmograph (Pea Pod, Cosmed, Italy), which is validated for newborns (Ellis et al., 2007). Subsequent assessments will be performed by the same observer at 1 week after discharge, 1 month and 3 months of age.; At birth and during body composition evaluations, anthropometric measurements (body weight, length and head circumference) will be measured.; 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, once a week, circa 4 cc of midfeeding breast milk during the noon feeding, as a systematic sampling of milk collected through 24 hours, in order to bring the conditions for expressing milk closer together for all mothers.
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.	Dietary supplement: Adequate for gestational age (AGA) infants; Body composition assessment will be conducted using a Displacement Plethysmograph (Pea Pod, Cosmed, Italy), which is validated for newborns (Ellis et al., 2007). Subsequent assessments will be performed by the same observer at 1 week after discharge, 1 month and 3 months of age.; At birth and during body composition evaluations, anthropometric measurements (body weight, length and head circumference) will be measured.; 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, once a week, circa 4 cc of midfeeding breast milk during the noon feeding, in order to bring the conditions for expressing milk closer together for all mothers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Centro Hospitalar de Lisboa Central
• Investigators: Principal Investigator: Manuela Cardoso, RDN, PhD, Unidade Local de Saúde São José

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: small for gestational age; fetal growth; intrauterine growth restriction; Doppler velocimetry; nutritional management
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Fetal Diseases; Growth Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Fetal Growth Retardation; Physiological Phenomena; Growth and Development; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena; Embryonic and Fetal Development; Morphogenesis; Fetal Development; Gestational Age
• Other Study ID Numbers: CHULC.CI.658.2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No