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Fetal Growth RestrictionNCT01369940

The NICHD Fetal Growth Study: Twin Gestations

An observational study of Fetal Growth Restriction and Growth Discordancy, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Normal growth and development of twins are important for the long-term health of the children. The purpose of this study was to empirically define the trajectory of fetal growth in dichorionic twins using longitudinal two-dimensional ultrasonography and to compare the fetal growth trajectories for dichorionic twins… Read more about this study

Who is it for?
Ages 18 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for
Fetal Growth Restriction, Growth Discordancy
How many people
171 participants
Where
9 sitesUnited States
Study dates
29 May 2011to 30 Sep 2014
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Study population: Women with dichorionic twin gestations, irrespective of the mode of conception, maternal medical history or obesity status, were enrolled from eight U.S. clinical centers. Women were enrolled between 8w0d and 13w6d, and accurate dating was required for enrollment. A total of 171 women were recruited, with 152 gestations resulting in live birth.

Who may be able to join

  • Twin, viable pregnancy
  • 8+0 13+6 weeks of gestation
  • Maternal age 18 - 45 years
  • Spontaneous pregnancy or pregnancy from ovulation induction or in-vitro fertilization with known date of transfer
  • Pregnancy from egg donor or embryo donor (record if anonymous or known source)
  • LMP-date and crown-rump length measurement match within certain number of days according to a standard scheme (for larger twin)
  • Expect to deliver at one of the participating hospitals

Who cannot join

  • Fetal reduction (medically induced only)
  • Congenital anomalies (structural or chromosomal)
  • Either twin with an increased nuchal translucency (>99th percentile for crown-rump length; i.e. 3.5 mm or more)
  • Monochorionic twins
  • Crown-rump length discordancy >10% in dichorionic twin pregnancies

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • National Institute of Child Health and Human Development (NICHD), 9000 Rockville

    Bethesda, Maryland, 20892

  • University of Alabama

    Birmingham, Alabama, 35233

  • Medical University of S. Carolina

    Charleston, South Carolina, 29425

  • Northwestern University

    Chicago, Illinois, 60611

  • University of California-Long Beach

    Long Beach, California, 90806

  • Columbia University

    New York, New York, 10032-3784

  • Christiana Care Health Services

    Newark, Delaware

  • University of California, Irvine Medical Center

    Orange, California, 92668

  • Women and Infants

    Providence, Rhode Island, 02905

Other trials in United States

About this study

Official title: NICHD Fetal Growth Study: Twin Gestations

Normal growth and development of twins are important for the long-term health of the children. The purpose of this study was to empirically define the trajectory of fetal growth in dichorionic twins using longitudinal two-dimensional ultrasonography and to compare the fetal growth trajectories for dichorionic twins with those based on a growth standard developed by our group for singletons. This knowledge may lead to interventions that could minimize or prevent pregnancy and newborn health problems in the future.

Read the detailed description

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.

Biospecimen Description:

  • 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
Keywords
Growth Discordancy, Fetal Growth, Twin Growth
Medical subject headings
Fetal Growth Retardation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01369940
Study groupRoleWhat they receive
NICHD Fetal Growth Study - Twin GestationsWomen 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fetal growth trajectories in dichorionic twin pregnancies

    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.

    Measured: 3 years

  2. Comparison of the fetal growth trajectories for dichorionic twins with singletons

    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.

    Measured: 3 years

  3. Incidence of fetal growth restriction (with small-for-gestational age as a proxy) in dichorionic twins (by zygosity)

    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.

    Measured: 3 years

  4. Comparison of singleton and twin gestations for maternal biomarkers of fetal growth

    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.

    Measured: 3 years

Secondary outcomes (6)

  1. Body composition

    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.

    Measured: 3 years

  2. Genetic and environmental factors affecting fetal growth

    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).

    Measured: 3 years

  3. Biospecimen repository

    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.

    Measured: 3 years

  4. Zygosity and growth trajectories

    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.

    Measured: 3 years

  5. Conception mode and growth trajectories

    Information on mode of conception was collected during the enrollment interview.

    Measured: 3 years

  6. Placental pathology and growth trajectories

    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.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jun 2011 (estimated)
  2. Study start29 May 2011
  3. Primary completion25 Aug 2013
  4. Study completion30 Sep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
171 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01369940
Sponsor's protocol ID
999911178
Other IDs
11-CH-N178
Status last verified
Sep 2017
First submitted
8 Jun 2011
Last updated
5 Sep 2017
Results posted
No

Publications

  • Grantz KL, Grewal J, Albert PS, Wapner R, D'Alton ME, Sciscione A, Grobman WA, Wing DA, Owen J, Newman RB, Chien EK, Gore-Langton RE, Kim S, Zhang C, Buck Louis GM, Hediger ML. Dichorionic twin trajectories: the NICHD Fetal Growth Studies. Am J Obstet Gynecol. 2016 Aug;215(2):221.e1-221.e16. doi: 10.1016/j.ajog.2016.04.044. Epub 2016 Apr 30.

    PubMed 27143399

  • Amyx MM, Albert PS, Bever AM, Hinkle SN, Owen J, Grobman WA, Newman RB, Chien EK, Gore-Langton RE, Buck Louis GM, Grantz KL. Intrauterine growth discordance across gestation and birthweight discordance in dichorionic twins. Am J Obstet Gynecol. 2020 Feb;222(2):174.e1-174.e10. doi: 10.1016/j.ajog.2019.08.027. Epub 2019 Aug 24.

    PubMed 31454510

Questions about this trial

What is this clinical trial studying?

An observational study of Fetal Growth Restriction and Growth Discordancy, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fetal growth trajectories in dichorionic twin pregnancies (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01369940, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2017.

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