Early Lung Function Trajectories: Comparison Between Infants With and Without Intrauterine Growth Restriction. (ELFIGO)

Early Lung Function Trajectories: Comparison Between Infants With Intrauterine Growth Restriction and Appropriately Grown Ones.

During intrauterine life, some babies are smaller or grow less than expected. This fetal growth abnormality, called fetal growth restriction (FGR), can be diagnosed by ultrasound. Since there are currently no curative treatments for this condition, nor methods to optimize the growth of babies in the womb, the only effective strategy is intensive monitoring of fetal conditions, accompanied by early planning of delivery.

The diagnosis of early FGR (i.e. diagnosed before 32 weeks of gestation) confers a greater risk of short- and long-term respiratory problems.

The study aims to examine the association between parameters that can be assessed during pregnancy by ultrasound, such as the estimate of lung volumes, the thickness and contractility of the diaphragm, and cardiac kinetics, and any perinatal complications and respiratory function in the first years of life of premature infants, both with and without evidence of fetal growth pathology. Therefore, the study is divided into two phases: a prenatal and a postnatal phase.

The study includes two groups of patients:

1. Study group: Fetuses and preterm infants with a prenatal history of FGR;
2. Control group: Preterm infants without a prenatal history of FGR followed during neonatal follow-up.

Pregnant women with fetuses with FGR are followed at the Ultrasound clinics dedicated to Growth Pathology.

These pregnancies usually receive weekly ultrasound monitoring, which includes a Doppler study of the maternal and fetal circulation and an estimate of fetal weight every two weeks. Cardiotocographic monitoring is also planned once or twice a week, depending on fetal well-being.

The child will be assessed from a respiratory point of view during hospitalization and subsequently in the outpatient clinic, as required by clinical practice.

He/she will undergo respiratory function tests. Visits are scheduled at 3, 6, 12 and 24 months of corrected age, during which at least two respiratory function tests will be performed.

In addition, routine clinical data (personal data, medical history, blood tests, biological and instrumental tests) present in the medical record of the child will be collected.

Data from preterm infants without fetal growth restriction will be collected after informed consent. These infants are routinely followed at our Institution and undergo clinical assessment and lung function tests in the first two years of life as previously indicated.

Study Overview

• Status: Recruiting
• Conditions: Preterm Infant; Intrauterine Growth Retardation (IUGR); Respiratory Monitoring; Lung Function Tests
• Intervention / Treatment: Diagnostic test: fetal ultrasound to assess lungs, heart and diaphragm

• Study Type: Observational
• Enrollment (Estimated): 54

Contacts and Locations

• Study Contact: Name: Stefano Nobile, MD, PhD, MSc; Phone Number: +390630156937; Email: stefano.nobile@policlinicogemelli.it

Study Locations

• Italy
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Gemelli IRCCS
    • Contact: Stefano Nobile, MD, PhD, MSc; Phone Number: +390630156937; Email: stefano.nobile@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Fetuses and Infants born before 32 weeks of gestation, with and without fetal growth restriction

Description

Inclusion Criteria:

• Fetuses and Infants born before 32 weeks of gestation, with and without fetal growth restriction

Exclusion Criteria:

• Lack of informed consent
• Need for palliative care
• Major malformations

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Infants born preterm with history of IUGR; preterm infants with history of intrauterine growth restriction	Diagnostic test: fetal ultrasound to assess lungs, heart and diaphragm; The potential association between fetal ultrasound parameters (estimation of lung volumes, diaphragmatic thickness and contractility, cardiac thickness and kinetics), perinatal complications and respiratory function in the first years of life will be studied. Variables include: neonatal complications, non-invasive markers of respiratory status during neonatal admission (e.g. peripheral oxygen saturation/rfaction of inspired oxygen ratio among others), lung function tests in the first two years of life.; Other Names: lung function tests
Infants born preterm without history of IUGR; preterm infants without history of intrauterine growth restriction	Diagnostic test: fetal ultrasound to assess lungs, heart and diaphragm; The potential association between fetal ultrasound parameters (estimation of lung volumes, diaphragmatic thickness and contractility, cardiac thickness and kinetics), perinatal complications and respiratory function in the first years of life will be studied. Variables include: neonatal complications, non-invasive markers of respiratory status during neonatal admission (e.g. peripheral oxygen saturation/rfaction of inspired oxygen ratio among others), lung function tests in the first two years of life.; Other Names: lung function tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchopulmonary dysplasia	Respiratory support at 36 weeks post-menstrual age	36 weeks post-menstrual age
Death	occurrence of death during NICU admission or afterwards	2 years of life
Lung function data	Data from the Tidal breathing flow volume test and multiple breath nitrogen washout	2 years of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral oxygen saturation/fraction on inspired oxygen ratio (SFR)	non-invasive ratio between peripheral oxygen saturation/fraction on inspired oxygen ratio	16 weeks of life
Peripheral oxygen saturation/fraction on inspired oxygen ratio divided by mean airway pressure (SFR/P)	non-invasive ratio between peripheral oxygen saturation/fraction on inspired oxygen ratio and mean airway pressure	16 weeks of life

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Stefano Nobile, MD, PhD, MSc, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications and helpful links

General Publications

• Nobile S, Marchionni P, Carnielli VP. Neonatal outcome of small for gestational age preterm infants. Eur J Pediatr. 2017 Aug;176(8):1083-1088. doi: 10.1007/s00431-017-2957-1. Epub 2017 Jun 28.
• Jensen EA, Foglia EE, Dysart KC, Simmons RA, Aghai ZH, Cook A, Greenspan JS, DeMauro SB. Adverse effects of small for gestational age differ by gestational week among very preterm infants. Arch Dis Child Fetal Neonatal Ed. 2019 Mar;104(2):F192-F198. doi: 10.1136/archdischild-2017-314171. Epub 2018 May 5.
• D'Agostin M, Di Sipio Morgia C, Vento G, Nobile S. Long-term implications of fetal growth restriction. World J Clin Cases. 2023 May 6;11(13):2855-2863. doi: 10.12998/wjcc.v11.i13.2855.
• Arigliani M, Stocco C, Valentini E, De Pieri C, Castriotta L, Ferrari ME, Canciani C, Driul L, Orsaria M, Cattarossi L, Cogo P. Lung function between 8 and 15 years of age in very preterm infants with fetal growth restriction. Pediatr Res. 2021 Sep;90(3):657-663. doi: 10.1038/s41390-020-01299-0. Epub 2021 Jan 19.
• Nobile S, Marchionni P, Gidiucci C, Correani A, Palazzi ML, Spagnoli C, Rondina C; Marche Neonatal Network; Carnielli VP. Oxygen saturation/FIO2 ratio at 36 weeks' PMA in 1005 preterm infants: Effect of gestational age and early respiratory disease patterns. Pediatr Pulmonol. 2019 May;54(5):637-643. doi: 10.1002/ppul.24265. Epub 2019 Jan 27.
• Salem Y, Willers CC, Amylidi-Mohr S, Kentgens AC, Stranzinger E, Latzin P, Raio L, Yammine S. Low Birth Weight and Impaired Later Lung Function: Results from a Monochorionic Twin Study. Ann Am Thorac Soc. 2022 Nov;19(11):1856-1864. doi: 10.1513/AnnalsATS.202112-1349OC.

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: April 2, 2025
• First Submitted That Met QC Criteria: April 2, 2025
• First Posted (Actual): April 9, 2025

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: preterm birth; pulmonary function test; intrauterine growth retardation; lung volume measurements; oxygen saturation/physiology
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Fetal Diseases; Growth Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Premature Birth; Fetal Growth Retardation; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Respiratory System; Respiratory Function Tests
• Other Study ID Numbers: 6642

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