The National Standard for Normal Fetal Growth
|ClinicalTrials.gov Identifier: NCT00912132|
Recruitment Status : Completed
First Posted : June 3, 2009
Last Update Posted : October 26, 2017
|Condition or disease|
|Pregnancy Fetal Growth|
Summary and aims:
Normal fetal growth is a critical component of a healthy pregnancy and the long-term health of the offspring. Pivotal to understanding the dynamics of human fetal growth and to defining normal and abnormal fetal growth is the development of standards for fetal anthropometric parameters measured longitudinally throughout gestation, which, in turn, can be used to develop interval velocity curves and customized for genetic and physiological factors. We propose to conduct a multi-center prospective observational study (1) to establish a standard for normal fetal growth (velocity) and size for gestational age in the U.S. population; (2) to create an individualized standard for fetal growth potential; and (3) to improve accuracy of fetal weight estimation.
• Healthy, low-risk pregnant women (both obese and nonobese) between the ages of 18 and 40 from each of the following four self-identified race/ethnicity backgrounds: African American, Asian, Caucasian, and Hispanic.
- Observational cohort design where pregnant women are recruited prior to 13 weeks gestation and followed throughout pregnancy and delivery for women having livebirths.
- After a sonogram at enrollment (10-13 weeks), women were randomized to receive sonograms according to one of the following four schedules: schedule A: 16, 24, 30, 34, and 38 weeks; schedule B: 18, 26, 31, 35, and 39 weeks; schedule C: 20, 28, 32, 36, and 40 weeks; schedule D: 22, 29, 33, 37, and 41 weeks.
- An enrollment interview was followed by depression screening, physical activity, anthropometric assessment and ultrasonology screening for measurement of fetal growth, and at each of the 5 subsequent visits.
- Uterine artery and fetal Doppler studies at selected gestational weeks.
- Women were asked to provide blood samples at enrollment and at follow-up visits at 16-22 weeks, 24-29 weeks, and 34-37 weeks of gestation.
- Neonatal anthropometry completed for all infants within 12-24 hours after birth.
- Cord blood, plasma, and placenta samples were collected for a smaller subsample of newborns.
- Post-study evaluations: Women who were diagnosed with gestational diabetes during pregnancy were asked to return for a follow-up visit 6 weeks after delivery.
Final recruitment included 2,802 women with singleton pregnancies of which 2,334 were healthy, low-risk women with pre-pregnancy body mass indices (BMI) between 19-29.9 kg/m2. The racial/ethnic distribution of participating women were: Caucasians (n=614), African American (n=611), Hispanics (n=649), and Asians (n=460), and reflects natality characteristics of contemporary U.S. births. An additional 468 obese women (BMI 30-44.9 kg/m2) were also recruited.
The quality of the ultrasound measures was guaranteed by implementation of: (1) a comprehensive quality control protocol for ante hoc training and credentialing of all site sonographers, developed by the sonology center at Columbia University, and (2) a rigorous protocol for post hoc quality control, whereby a random sample of all scans, stratified by clinical site and visit, was re-measured for accuracy and reliability.
|Study Type :||Observational|
|Actual Enrollment :||2802 participants|
|Official Title:||The National Standard for Normal Fetal Growth|
|Study Start Date :||May 19, 2009|
|Actual Primary Completion Date :||August 25, 2013|
|Actual Study Completion Date :||August 25, 2013|
Low risk singleton cohort
Women with singleton gestations were enrolled between 8w0d and 13w6d and followed up to nine months (2009-2013) in this prospective cohort study. A sub-set of women with and without gestational diabetes were followed up to 6 weeks postpartum. Enrollment was based upon a predefined set of criteria including medical/reproductive history and pre-pregnancy body mass index. Women with a body mass index between 19.0-29.9 kg/m2 were in the low-risk cohort.
Women with singleton gestations were enrolled between 8w0d and 13w6d and followed up to nine months (2009-2013) in this prospective cohort study. A sub-set of women with and without gestational diabetes were followed up to 6 weeks postpartum. Enrollment was based upon a predefined set of criteria including medical/reproductive history and pre-pregnancy body mass index. Women with a body mass index between 30.0-44.9 kg/m2 were in the obese cohort.
- Establish a standard for normal fetal growth (velocity) and size for gestational age in the U.S. population. [ Time Frame: 3 years ]
Fetal growth trajectories were created using 2-D ultrasound fetal biometry including biparietal diameter, head circumference, humerus length, abdominal circumference, and femur length using standardized protocols. Estimated fetal weight (EFW) was calculated.
Fetal growth trajectories were created using linear mixed models with cubic splines for estimating racial/ethnic specific fetal growth curves for size, methods that accounted for the variation across individual fetuses. For EFW and each individual anthropometric parameter, we tested for overall differences in the racial/ethnic-specific curves using a likelihood-ratio test. When the global test was significant (<.05 level), we tested for week-specific differences by race/ethnicity using Wald tests at each week of gestation. These tests were conducted on the estimated curves with and without adjustment for maternal characteristics.
A fetal growth velocity standard by maternal race/ethnicity was also created.
- Create an individualized standard for fetal growth potential.Individualized and customized fetal growth models will be created using two- dimensional ultrasound measures. Individualized or customized definitions of small for gestational age or large for gestational age will be compared to the NICHD Fetal Growth Study singleton standard cut-points of 10th and 90th percentiles, respectively, to see if they improve detection of maternal and neonatal health outcomes.
- Improve accuracy of fetal weight estimation.Since the last ultrasound exam is scheduled at term, it was expected that many women would deliver within 3 days after the last ultrasound exam. A formula (or formulas) to estimate fetal weight will be created using a multiple linear regression to include not only the 2-D and 3-D sonographic measurements but also factors such as maternal height and weight, sex of the fetus, and glucose challenge test result. We will identify a formula that provides the best estimate of fetal weight, and apply that formula to a validation group. If the sample size allows, we will randomly split the whole cohort into two groups: one group for testing and the other for validation. If the statistical power is insufficient for splitting, we will use cross-validation.
- Construct an individualized standard for fundal height.We will reevaluate the sensitivity and specificity of the current approach to using fundal height to monitor fetal growth. We will produce an individualized standard for fundal height. We will compare the new standard with the current approach with regard to true positive and true negative values.
- Collect blood samples for an etiology study of gestational diabetes and a prediction study of fetal growth restriction and/or overgrowth.Blood samples were collected at enrollment, visit 1, visit 2 and visit 4.
- Collect placental tissues and cord blood in selected cases and controls for studies on the etiology of idiopathic fetal growth restriction.Placental tissue and cord blood at delivery were collected in selected IUGR cases and controls.
- Collect dietary intake data to study the association between nutrition and fetal growth.Food frequency questionnaire was collected at enrollment and 24-h dietary recall at visit 1, visit 2, visit 3, and visit 4.
Biospecimen Retention: Samples With DNA
- Maternal blood sample (serum, plasma, white blood cells, red blood cells and PAXgene RNA) at enrollment, 1st, 2nd, 4th follow-up visits, and postpartum
- Cord blood and placenta of offspring of consenting women collected at delivery
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00912132
|United States, Alabama|
|University of Alabama|
|Birmingham, Alabama, United States|
|United States, California|
|Fountain Valley Regional Hospital|
|Fountain Valley, California, United States, 92708|
|University of California-Long Beach|
|Long Beach, California, United States, 90806|
|University of California, Irvine Medical Center|
|Orange, California, United States, 92668|
|United States, Delaware|
|Christiana Care Health Services|
|Newark, Delaware, United States|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, New Jersey|
|Saint Peters University Hospital|
|New Brunswick, New Jersey, United States, 08901|
|United States, New York|
|New York Presbyterian Healthcare System|
|Flushing, New York, United States, 11355|
|New York, New York, United States, 10032-3784|
|United States, Rhode Island|
|Women and Infants|
|Providence, Rhode Island, United States, 02905|
|United States, South Carolina|
|Medical University of South Carolina|
|Charleston, South Carolina, United States|
|Principal Investigator:||Germaine M Louis, M.D.||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|