Development of Italian Fetal Growth Charts (METRICS)

Fetal Growth Curves and Doppler Velocimetry in the Italian Population, Multicenter Study

There is an ongoing international discussion regarding which fetal growth charts should be used. As a matter of fact, an extensive and clinically significant variability among different growth charts has been proved, even between studies of the highest methodological quality. Indeed, methodological aspects such as the study population, data collection, curve modeling and others are of crucial importance for the final outcome of the process. Beside the discussion on methodological issues, there is also an ongoing discussion regarding whether one international standard might be adequate to assess fetal growth all around the globe, or are there some differences related to ethnicity supporting the adoption of growth charts constructed based on national data, or even the customization. Recently, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) Practice Guidelines on Ultrasound Assessment of Fetal Biometry and Growth recommended the application of "prescriptive biometry charts, obtained prospectively, truly population-based and derived from studies with the lowest possible methodological bias", and called for the practitioners' awareness regarding national or even local reference charts. Such awareness requires an exploratory and preliminary analysis of the impact of different charts by applying reference values to local findings.

On these grounds, there is an urgent need for a nationwide study for the prospective collection of data and the construction of methodologically robust national growth and Doppler standards.

Study Overview

• Status: Recruiting
• Conditions: Growth Charts
• Intervention / Treatment: Other: Ultrasound evaluation

Detailed Description

There is an ongoing international discussion regarding which fetal growth charts should be used. As a matter of fact, an extensive and clinically significant variability among different growth charts has been proved, even between studies of the highest methodological quality. Indeed, methodological aspects such as the study population, data collection, curve modeling and others are of crucial importance for the final outcome of the process. Beside the discussion on methodological issues, there is also an ongoing discussion regarding whether one international standard might be adequate to assess fetal growth all around the globe, or are there some differences related to ethnicity supporting the adoption of growth charts constructed based on national data, or even the customization.

Recently, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) Practice Guidelines on Ultrasound Assessment of Fetal Biometry and Growth recommended the application of "prescriptive biometry charts, obtained prospectively, truly population-based and derived from studies with the lowest possible methodological bias", and called for the practitioners' awareness regarding national or even local reference charts. Such awareness requires an exploratory and preliminary analysis of the impact of different charts by applying reference values to local findings.

A recent multicentric Italian study promoted by the Italian Society of Ultrasound in Obstetrics and Gynecology (SIEOG), assessed the application of WHO growth charts published in 2006 and the Intergrowth 21 (IG-21st) growth charts in a large Italian cohort (n=7347) of low risk women with uneventful pregnancy. According to the results of the study the IG-21st standards identified the smallest proportion of fetuses below the 10th centile and the largest proportion of fetuses above the 90th centile, respectively. The proportion of fetuses with head circumference (HC), abdominal circumference (AC) and femur length (LF) above 90th centile was 29.9%, 32.5 and 46%, respectively. While the WHO references seem to be the closest to observed 10th centile, the proportion of fetuses above 90th centile was also higher than expected for an appropriate distribution of centiles, but smaller compared with IG-21st standards: 22.8%, 21.3% and 31.9% for HC, AC and LF, respectively. Overall, these data suggest that there might be differences linked to ethnic origin and not fully explained by maternal, socio-economic or other methodological factors as already suggested by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and World Health Organization (WHO) groups.

These data suggest that, despite indisputable advantages that IG-21st growth standards might offer, immediate application into clinical practice might result into an under-diagnosis of small for gestational age fetuses and, especially, in an over-diagnosis of large for gestational age fetuses with major consequences for clinical practice. The WHO growth references seem to be more suitable for our population, although they might also over-estimate the proportion of large for gestational age fetuses. On the other hand, existing national growth charts lack crucial biometric parameters and centiles. This is of major importance, if we consider that recent consensus criteria suggested AC and estimated fetal weight (EFW) below the 3rd centile as independent criteria for the diagnosis fetal growth restriction.

On these grounds, there is an urgent need for a nationwide study for the prospective collection of data and the construction of methodologically robust national growth and Doppler standards.

• Study Type: Observational
• Enrollment (Estimated): 2500

Contacts and Locations

• Study Contact: Name: Tamara Stampalija, MD; Phone Number: +390403785486; Email: tamara.stampalija@burlo.trieste.it

Study Locations

• Italy
  • Trieste, Italy, 34137
    • Recruiting
    • Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"
    • Contact: Tamara Stampalija, MD; Phone Number: 0403785486; Email: tamara.stampalija@burlo.trieste.it
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Not yet recruiting
      • Fondazione Policlinico Agostino Gemelli - IRCCS City Rome
      • Contact: Alessandra Familiari, MD; Phone Number: +39 0630151; Email: alessandra.familiari@policlinicogemelli.it
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Not yet recruiting
      • Fondazione IRCSS Ca Granda, Policlinico di Milano
      • Contact: Enrico Ferrazzi, MD; Phone Number: +39 0255031; Email: enrico.ferrazzi@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Healthy women with singleton uncomplicated pregnancy

Description

Inclusion Criteria:

1. Age >18 years and ≤40 years
2. body mass index (BMI) 18-30 kg/m2
3. singleton pregnancy
4. the first day of the last menstrual period (LMP) known and the cycle reported to be regular, lasting 28 days ±4 days and a crown rump length (CRL) measured in early pregnancy
5. no history of chronic health problems
6. no long-term medication (including fertility treatment)
7. no environmental or economic constraints likely to impede fetal growth
8. not smoking currently or in the previous 6 months
9. no alcohol consumption
10. no history of recurrent miscarriages
11. no previous preterm delivery (<37 week) or birthweight < 2,500 grams
12. no evidence in the present pregnancy of congenital disease or fetal anomaly at study entry

Exclusion Criteria:

1. multiple pregnancy
2. fetuses with congenital structural or chromosomal anomalies including increased nuchal translucency (>99°centile)
3. fetal death
4. women with disorders that may affect fetal growth (pre-existing hypertension, diabetes mellitus, renal disease)
5. drug assumption (low dose aspirin, etc)
6. smoking
7. delivery <37 weeks
8. pregnancy complications (hypertensive disorders of pregnancy, infections, gestational diabetes, other diseases)
9. pregnancies conceived by assisted reproductive technology
10. Abnormal uterine arteries Doppler (if performed)
11. First trimester PAPP-A<0.3 MoM

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant women; Healthy women with singleton uncomplicated pregnancy	Other: Ultrasound evaluation; Fetal ultrasound evaluation will be collected longitudinally during the prenatal period from the weeks 14 every 4-5 weeks, for a total of maximum 6 ultrasound scans

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal growth evaluation	Construction of national normal fetal growth reference charts	From the weeks 14 of gestational age to delivery

Collaborators and Investigators

• Sponsor: IRCCS Burlo Garofolo
• Investigators: Study Chair: Tamara Stampalija, Institute for Maternal and Child Health IRCCS Burlo Garofolo

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2021
• Primary Completion (Estimated): July 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: March 7, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): June 13, 2024
• Last Update Submitted That Met QC Criteria: June 12, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Doppler; biometry; Fetal growth charts
• Other Study ID Numbers: RC 24/20

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