Clinical trial NCT01369940: The NICHD Fetal Growth Study: Twin Gestations
Official title: NICHD Fetal Growth Study: Twin Gestations
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Fetal Growth Restriction
Growth Discordancy
Keywords: Growth Discordancy
Fetal Growth
Twin Growth
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2011-06-09
Enrollment: 171
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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 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.

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

Eligibility criteria: INCLUSION CRITERIA:

* 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

EXCLUSION CRITERIA:

* 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

Primary outcomes:
measure: Fetal growth trajectories in dichorionic twin pregnancies
timeFrame: 3 years
measure: Comparison of the fetal growth trajectories for dichorionic twins with singletons
timeFrame: 3 years
measure: Incidence of fetal growth restriction (with small-for-gestational age as a proxy) in dichorionic twins (by zygosity)
timeFrame: 3 years
measure: Comparison of singleton and twin gestations for maternal biomarkers of fetal growth
timeFrame: 3 years
Secondary outcomes:
measure: Body composition
timeFrame: 3 years
measure: Genetic and environmental factors affecting fetal growth
timeFrame: 3 years
measure: Biospecimen repository
timeFrame: 3 years
measure: Zygosity and growth trajectories
timeFrame: 3 years
measure: Conception mode and growth trajectories
timeFrame: 3 years
measure: Placental pathology and growth trajectories
timeFrame: 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Long Beach
country: United States
facility: University of California-Long Beach
state: California
city: Orange
country: United States
facility: University of California, Irvine Medical Center
state: California
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Bethesda
country: United States
facility: National Institute of Child Health and Human Development (NICHD), 9000 Rockville
state: Maryland
city: New York
country: United States
facility: Columbia University
state: New York
city: Providence
country: United States
facility: Women and Infants
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of S. Carolina
state: South Carolina
Study officials:
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Germaine M Louis, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.