The NICHD Fetal Growth Study: Twin Gestations
|ClinicalTrials.gov Identifier: NCT01369940|
Recruitment Status : Completed
First Posted : June 9, 2011
Last Update Posted : September 5, 2017
|Condition or disease|
|Fetal Growth Restriction Growth Discordancy|
A prospective cohort of 171 women with twin gestations was recruited from eight U.S. sites from 2012 to 2013. After an initial sonogram at 11w0d-13w6d where dichorionicity was confirmed, women were randomized to one of two serial ultrasonology schedules. Ultrasound measurements at each follow-up visit included standard fetal biometrics ((BPD, HC, AC, FL); estimated fetal weight was calculated using a Hadlock formula. Growth curves and percentiles were estimated using linear mixed models with cubic splines. Percentiles were compared statistically at each gestational week between the twins and 1,731 singletons in the Fetal Growth Studies-Singletons cohort.
In addition to 2-D ultrasound measures for analyzing fetal growth, this study recorded maternal anthropometrics and a brief interview to capture changes in health status, stress and depression, and physical activity at each follow-up visit. Four blood draws at baseline and at targeted gestational ages for the eventual identification of biomarkers indicative of fetal growth were collected. After delivery, neonatal anthropometric measures were assessed for each twin, placental biospecimens were collected, and select information about the obstetrical course and newborn status were abstracted from medical charts. These exposures and outcomes provide opportunities to further compare singleton and twin gestations with respect to maternal biomarkers of fetal growth, well-being and maternal nutritional status using banked biospecimens to determine if the biomarkers ranges established for singletons are applicable to twin gestations.
- Maternal blood sample (serum, plasma, white blood cells, red blood cells and PAXgene RNA) at enrollment, 1st, 3rd, 5th follow-up visits, and delivery
- Cord blood and placentas for consenting women collected at delivery
- Placenta sample or buccal swab (determining zygosity by DNA probe for same sex pairs), collected at delivery
|Study Type :||Observational|
|Actual Enrollment :||171 participants|
|Official Title:||NICHD Fetal Growth Study: Twin Gestations|
|Study Start Date :||May 29, 2011|
|Actual Primary Completion Date :||August 25, 2013|
|Actual Study Completion Date :||September 30, 2014|
NICHD Fetal Growth Study - Twin Gestations
Women with dichorionic twin gestations were enrolled between 8w0d and 13w6d and followed up to nine months (2012-2013) in this prospective cohort study.
Intervention: No intervention
- Fetal growth trajectories in dichorionic twin pregnancies [ Time Frame: 3 years ]
Fetal growth trajectories in dichorionic twin pregnancies were created using two- and selected three-dimensional ultrasound measures. Measures included maternal anthropometric measurements and 2D fetal biometry (BPD, HC, AC, FL) using standardized protocols.
Women were recruited during the first trimester and followed until delivery. Each woman had seven scheduled ultrasound examinations, one at enrollment and six during follow-up visits. Women were randomized to receive sonograms according to one of the following two schedules: schedule A: 16, 20, 24, 28, 32 and 35 weeks or schedule B: 18, 22, 26, 30, 34 and 36 weeks.
- Comparison of the fetal growth trajectories for dichorionic twins with singletons [ Time Frame: 3 years ]The primary analysis compared fetal growth trajectories for dichorionic twins with 1,737 singleton gestations included in the NICHD Fetal Growth Studies - Singleton standard. For modeling twin trajectories, we used linear mixed models with a cubic spline mean structure and a random effects structure that included linear, quadratic, and cubic random effects for the twin pair and an intercept term for the individual fetus within twin pair. The linear mixed models were also used to test for overall differences (i.e., global tests) between the twin and singleton trajectories (for EFW and other measurements) using likelihood ratio tests of interaction terms between spline mean structure terms and twin-singleton indicator variables.
- Incidence of fetal growth restriction (with small-for-gestational age as a proxy) in dichorionic twins (by zygosity) [ Time Frame: 3 years ]Using small-for-gestational age as a proxy for growth restriction, we evaluated the percentage of dichorionic twins who would be classified below the 10th percentile using the study-generated singleton non-Hispanic white standard.
- Comparison of singleton and twin gestations for maternal biomarkers of fetal growth [ Time Frame: 3 years ]Longitudinal data will compare singleton and twin gestations with respect to maternal biomarkers of fetal growth, well-being and maternal nutritional status using banked biospecimens to determine if the biomarkers ranges established for singletons are applicable to twin gestations.
- Body composition [ Time Frame: 3 years ]Pending the results of a validation study, measures of fetal fat and lean body mass from 2D ultrasound and/or fractional volumes from 3D will be assessed.
- Genetic and environmental factors affecting fetal growth [ Time Frame: 3 years ]Twin gestations offer an opportunity to differentiate genetic from environmental etiologies of developmental disorders, and to gain insight by investigating the role of shared factors versus factors affecting each of the twins independently. This involves comparing results of within cohort versus within twin pairs. The shared factors include maternal nutrition and gestational age, and the non-shared factors are those that affect each twin (e.g., placental placement, growth trajectory).
- Biospecimen repository [ Time Frame: 3 years ]The available bank of de-identified specimens will be used to add to our understanding of the determinants associated with fetal growth trajectories or adverse outcomes. The repository will be important for exploring possible epigenetic mechanisms and other specific hypotheses investigators may have.
- Zygosity and growth trajectories [ Time Frame: 3 years ]Placental samples for zygosity determination were obtained for all like-sex twin pairs. In the event that placental samples were not able to be obtained for like-sex twin pairs, a buccal swab from each infant was obtained prior to discharge, preferably in the first 48 hours of life. Both placenta zygosity samples and buccal swab samples were sent in real time to the Columbia Placenta Pathology Laboratory for zygosity testing. The research nurse provided women her with zygosity results when the information was available within three months following delivery.
- Conception mode and growth trajectories [ Time Frame: 3 years ]Information on mode of conception was collected during the enrollment interview.
- Placental pathology and growth trajectories [ Time Frame: 3 years ]The gross anatomy of the placentas (weight, cord length, diameter of the cord, and other gross morphology) were documented by the clinical site's participating pathologist. Photographs of placentas were taken by trained research personnel. Placental samples were obtained according to a standardized protocol. Eventual analysis may include proteomics, DNA analyses (e.g., comparative genomic hybridization, genomics, and assessment of the methylome), RNA expression, and microRNA levels. Also, analysis may include immunocytochemistry, histopathologic and biochemical / molecular studies. Once the research specimens were obtained, the remaining placenta was submitted to the clinical pathology department for processing and analysis.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01369940
|United States, Alabama|
|University of Alabama|
|Birmingham, Alabama, United States, 35233|
|United States, California|
|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, Maryland|
|National Institute of Child Health and Human Development (NICHD), 9000 Rockville|
|Bethesda, Maryland, United States, 20892|
|United States, New York|
|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 S. Carolina|
|Charleston, South Carolina, United States, 29425|
|Principal Investigator:||Germaine M Louis, M.D.||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|