The National Standard for Normal Fetal Growth
Condition: Pregnancy; Fetal Growth
Study type: Observational

Summary: 
      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 growth. The
      study's purpose was to establish standards for normal fetal growth and size for gestational
      age for 4 racial/ethnic groups of pregnant women with the eventual creation of individualized
      standards for fetal growth and improvements in fetal weight estimation. These data for a
      contemporary cohort of pregnant women should provide data for clinical management.
    

Detailed description: 
      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.

      Eligibility:

      • 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.

      Design:

        -  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.

      Enrollment:

      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.

      Quality Control:

      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Women with singleton gestations (n=2,802) were enrolled from 12 U.S. clinical centers.
        Women were enrolled between 8w0d and 13w6d gestation, as measured by last menstrual period
        dating consistent with obstetrical ultrasonology.
      
Biospecimen description: 
      -  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
    
Keywords: Fetal Growth; Pregnancy