Fetal growth velocity standards from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project

Abstract

Background: Human growth is susceptible to damage from insults, particularly during periods of rapid growth. Identifying those periods and the normative limits that are compatible with adequate growth and development are the first key steps toward preventing impaired growth.

Objective: This study aimed to construct international fetal growth velocity increment and conditional velocity standards from 14 to 40 weeks' gestation based on the same cohort that contributed to the INTERGROWTH-21^st Fetal Growth Standards.

Study design: This study was a prospective, longitudinal study of 4321 low-risk pregnancies from 8 geographically diverse populations in the INTERGROWTH-21^st Project with rigorous standardization of all study procedures, equipment, and measurements that were performed by trained ultrasonographers. Gestational age was accurately determined clinically and confirmed by ultrasound measurement of crown-rump length at <14 weeks' gestation. Thereafter, the ultrasonographers, who were masked to the values, measured the fetal head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length in triplicate every 5 weeks (within 1 week either side) using identical ultrasound equipment at each site (4-7 scans per pregnancy). Velocity increments across a range of intervals between measures were modeled using fractional polynomial regression.

Results: Peak velocity was observed at a similar gestational age: 16 and 17 weeks' gestation for head circumference (12.2 mm/wk), and 16 weeks' gestation for abdominal circumference (11.8 mm/wk) and femur length (3.2 mm/wk). However, velocity growth slowed down rapidly for head circumference, biparietal diameter, occipitofrontal diameter, and femur length, with an almost linear reduction toward term that was more marked for femur length. Conversely, abdominal circumference velocity remained relatively steady throughout pregnancy. The change in velocity with gestational age was more evident for head circumference, biparietal diameter, occipitofrontal diameter, and femur length than for abdominal circumference when the change was expressed as a percentage of fetal size at 40 weeks' gestation. We have also shown how to obtain accurate conditional fetal velocity based on our previous methodological work.

Conclusion: The fetal skeleton and abdomen have different velocity growth patterns during intrauterine life. Accordingly, we have produced international Fetal Growth Velocity Increment Standards to complement the INTERGROWTH-21^st Fetal Growth Standards so as to monitor fetal well-being comprehensively worldwide. Fetal growth velocity curves may be valuable if one wants to study the pathophysiology of fetal growth. We provide an application that can be used easily in clinical practice to evaluate changes in fetal size as conditional velocity for a more refined assessment of fetal growth than is possible at present (https://lxiao5.shinyapps.io/fetal_growth/). The application is freely available with the other INTERGROWTH-21^st tools at https://intergrowth21.tghn.org/standards-tools/.

Keywords: correlation models; fetal growth; fetal growth velocity; fetal velocity standards; longitudinal study.

Figure 1

Increments in fetal HC, AC, and FL (mm/wk) according to gestational age (weeks) for all of the sites combined The fitted 3rd, 50th, and 97th centiles are superimposed. AC, abdominal circumference; FL, femur length; HC, head circumference. Ohuma et al. Fetal growth velocity standards. Am J Obstet Gynecol 2021.

Figure 2

Median fetal velocity increments for HC (green), AC (red), and FL (blue) expressed as a percentage of attained fetal size at 40 weeks’ according to INTERGROWTH-21^st Fetal Standards Adapted from Papageorghiou et al. AC, abdominal circumference; FL, femur length; HC, head circumference; INTERGROWTH-21st, International Fetal and Newborn Growth Consortium for the 21st Century. Ohuma el al. Fetal growth velocity standards. Am J Obstet Gynecol 2021.

Figure 3

Screenshots of the fetal velocity app showing 4 example plots of longitudinal fetal growth evaluation based on observed and predicted measurements for a fetus A, Normal fetus based on head circumference. B, Possible microcephaly based on head circumference. C, A fetus within 2 standard deviations. D, Possible case of macrosomia based on abdominal circumference. All measurements were compared with the published international INTERGROWTH-21st Fetal (Distance) Growth Standards. INTERGROWTH-21st, International Fetal and Newborn Growth Consortium for the 21st Century. Adapted from Papageorghiou et al. Ohuma et al. Fetal growth velocity standards. Am J Obstet Gynecol 2021.

Figure 3

Screenshots of the fetal velocity app showing 4 example plots of longitudinal fetal growth evaluation based on observed and predicted measurements for a fetus A, Normal fetus based on head circumference. B, Possible microcephaly based on head circumference. C, A fetus within 2 standard deviations. D, Possible case of macrosomia based on abdominal circumference. All measurements were compared with the published international INTERGROWTH-21st Fetal (Distance) Growth Standards. INTERGROWTH-21st, International Fetal and Newborn Growth Consortium for the 21st Century. Adapted from Papageorghiou et al. Ohuma et al. Fetal growth velocity standards. Am J Obstet Gynecol 2021.

Supplemental Figure 1

Increments in BPD and OFD (mm/wk) according to gestational age (weeks) for all of the sites combined The fitted 3rd, 50th, and 97th centiles are superimposed. Adapted from Papageorghiou et al. BPD, biparietal diameter; OFD, occipitofrontal diameter. Ohuma et al. Fetal growth velocity standards. Am J Obstet Gynecol 2021.

Supplemental Figure 2

Median velocity increments in BPD (green) and OFD (red) according to gestational age expressed as a percentage of the attained fetal size at 40 weeks’ gestation according to the published international INTERGROWTH-21st Fetal (Distance) Growth Standards BPD, biparietal diameter; INTERGROWTH-21st, International Fetal and Newborn Growth Consortium for the 21st Century; OFD, occipitofrontal diameter. Adapted from Papageorghiou et al. Ohuma et al. Fetal growth velocity standards. Am J Obstet Gynecol 2021.