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Fetal growth velocity: the NICHD fetal growth studies

      Background

      Accurately identifying pregnancies with accelerated or diminished fetal growth is challenging and generally based on cross-sectional percentile estimates of fetal weight. Longitudinal growth velocity might improve identification of abnormally grown fetuses.

      Objective

      We sought to complement fetal size standards with fetal growth velocity, develop a model to compute fetal growth velocity percentiles for any given set of gestational week intervals, and determine association between fetal growth velocity and birthweight.

      Study Design

      This was a prospective cohort study with data collected at 12 US sites (2009 through 2013) from 1733 nonobese, low-risk pregnancies included in the singleton standard. Following a standardized sonogram at 10w0d–13w6d, each woman was randomized to 1 of 4 follow-up visit schedules with 5 additional study sonograms (targeted ranges: 16–22, 24–29, 30–33, 34–37, and 38–41 weeks). Study visits could occur ± 1 week from the targeted GA. Ultrasound biometric measurements included biparietal diameter, head circumference, abdominal circumference, and femur length, and estimated fetal weight was calculated. We used linear mixed models with cubic splines for the fixed effects and random effects to flexibly model ultrasound trajectories. We computed velocity percentiles in 2 ways: (1) difference between 2 consecutive weekly measurements (ie, weekly velocity), and (2) difference between any 2 ultrasounds at a clinically reasonable difference between 2 gestational ages (ie, velocity calculator). We compared correlation between fetal growth velocity percentiles and estimated fetal weight percentiles at 4-week intervals, with 32 (±1) weeks’ gestation for illustration. Growth velocity was computed as estimated fetal growth rate (g/wk) between ultrasound at that gestational age and from prior visit [ie, for 28–32 weeks’ gestational age: velocity = (estimated fetal weight 32–28)/(gestational age 32–28)]. We examined differences in birthweight by whether or not estimated fetal weight and estimated fetal weight velocity were <5th or ≥5th percentiles using χ2.

      Results

      Fetal growth velocity was nonmonotonic, with acceleration early in pregnancy, peaking at 13, 14, 15, and 16 weeks for biparietal diameter, head circumference, femur length, and abdominal circumference, respectively. Biparietal diameter, head circumference, and abdominal circumference had a second acceleration at 19–22, 19–21, and 27–31 weeks, respectively. Estimated fetal weight velocity peaked around 35 weeks. Fetal growth velocity varied slightly by race/ethnicity although comparisons reflected differences for parameters at various gestational ages. Estimated fetal weight velocity percentiles were not highly correlated with fetal size percentiles (Pearson r = 0.40–0.41, P < .001), suggesting that these measurements reflect different aspects of fetal growth and velocity may add additional information to a single measure of estimated fetal weight. At 32 (SD ± 1) weeks, if both estimated fetal weight velocity and size were <5th percentile, mean birthweight was 2550 g; however, even when size remained <5th percentile but velocity was ≥5th percentile, birthweight increased to 2867 g, reflecting the important contribution of higher growth velocities. For estimated fetal weight ≥5th percentile, but growth velocity <5th, birthweight was smaller (3208 vs 3357 g, respectively, P < .001).

      Conclusion

      We provide fetal growth velocity data to complement our previous work on fetal growth size standards, and have developed a calculator to compute fetal growth velocity. Preliminary findings suggest that growth velocity adds additional information over knowing fetal size alone.

      Key words

      Introduction

      Distinguishing fetal growth that is constitutionally small or large from growth that is pathologically restricted or increased presents one of the most significant challenges in obstetrics. Cross-sectional fetal measurements are typically compared to reference size-for-age curves, with a range of 10th–90th percentiles considered appropriate for gestational age (GA).
      • Battaglia F.C.
      • Lubchenco L.O.
      A practical classification of newborn infants by weight and gestational age.
      ACOG
      Fetal growth restriction. Practice bulletin no. 134.
      Yet, a single measurement can only indicate size.
      • Deter R.L.
      Evaluation of intrauterine growth retardation in the fetus and neonate: are simple-minded methods good enough?.
      At least 2 measurements separated in time are needed to estimate actual fetal growth.
      • Altman D.G.
      • Hytten F.E.
      Intrauterine growth retardation: let's be clear about it.

      Why was this study conducted?

      • Identifying pregnancies with accelerated or diminished fetal growth is challenging and generally based on cross-sectional percentile estimates of fetal weight. Longitudinal growth velocity might improve identification of abnormally grown fetuses.

      Key findings

      • We provide fetal growth velocity data to complement our fetal growth size standards and developed a calculator to compute fetal growth velocity. Estimated fetal weight growth velocity percentiles were not highly correlated with estimated fetal weight size percentiles, indicating that these measurements reflect different aspects of fetal growth. Preliminary findings suggest that growth velocity adds additional information over knowing fetal size alone.

      What does this add to what is known?

      • Until recently, there has been a lack of prospective studies with diverse populations and repeated ultrasound measurements to calculate fetal growth velocity. A calculator to compute fetal growth velocity percentiles for any given set of gestational week intervals may be clinically useful.
      Fetal growth velocity is the rate of fetal growth over a given time interval (eg, g/wk). Understanding whether fetal growth has deviated from a normal trajectory may have more clinical utility to distinguish constitutional from pathologic fetal growth abnormalities compared to using a particular threshold of fetal size from a single time measure.
      • Sovio U.
      • White I.R.
      • Dacey A.
      • Pasupathy D.
      • Smith G.C.
      Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study.
      Yet until recently, there has been a lack of longitudinal prospective studies with diverse populations that have collected repeated ultrasound measurements. The benefits of using growth velocity to categorize fetal growth and assess its contribution to birthweight have not been empirically demonstrated.
      The primary aim of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) fetal growth studies–singletons, a multicenter US prospective cohort study of pregnant women, was to establish fetal growth standards, for size and velocity, for 4 self-identified race/ethnic groups: non-Hispanic white, non-Hispanic black, Hispanic, and Asian or Pacific Islander. We previously published our fetal size standards.
      • Buck Louis G.M.
      • Grewal J.
      • Albert P.S.
      • et al.
      Racial/ethnic standards for fetal growth: the NICHD fetal growth studies.
      • Buck Louis G.M.
      • Grewal J.
      Clarification of estimating fetal weight between 10-14 weeks gestation, NICHD fetal growth studies.
      The objective of the present analysis were to complement the fetal size standards with fetal growth velocity for individual biometric parameters and estimated fetal weight (EFW). Understanding that clinicians see patients at unpredictably spaced time points, we developed a model to compute fetal growth velocity percentiles of a given fetus for any given set of gestational week intervals. Additionally, we investigated whether growth velocity had an independent association with birthweight over fetal size alone.

      Materials and Methods

      The NICHD Fetal Growth Studies–Singletons recruited women from 12 clinical sites from July 2009 through January 2013.
      • Buck Louis G.M.
      • Grewal J.
      • Albert P.S.
      • et al.
      Racial/ethnic standards for fetal growth: the NICHD fetal growth studies.
      Inclusion criteria included: maternal age 18–40 years; pregravid body mass index 19.0–29.9 kg/m2 calculated from recalled prepregnancy weight and height; viable singleton pregnancy between 8w0d–13w6d with gestational dating consistent with last menstrual period dating within a prescribed range per screening sonogram; and planning to deliver at participating hospitals. Women with prior adverse pregnancy outcomes, history of chronic diseases, conception using medical drugs or assisted reproductive technology, cigarette smoking, illicit drug use, or intake of ≥1 alcoholic drinks per day were excluded as previously described.
      • Buck Louis G.M.
      • Grewal J.
      • Albert P.S.
      • et al.
      Racial/ethnic standards for fetal growth: the NICHD fetal growth studies.
      Human subjects’ approval was obtained from all participating sites, the NICHD, and data-coordinating center, and all women gave informed consent prior to any data collection (ClinicalTrials.gov Identifier: NCT00912132).
      • Grewal J.
      • Grantz K.L.
      • Zhang C.
      • et al.
      Cohort profile: NICHD fetal growth studies–singletons and twins.
      Following a standardized sonogram at 10w0d–13w6d, each woman was randomized to 1 of 4 follow-up visit schedules with 5 additional study sonograms (targeted ranges: 16–22, 24–29, 30–33, 34–37, and 38–41 gestational weeks). Study visits could occur ± 1 week from the targeted GA.
      • Grewal J.
      • Grantz K.L.
      • Zhang C.
      • et al.
      Cohort profile: NICHD fetal growth studies–singletons and twins.
      Study sonographers underwent training and credentialing prior to enrollment and followed a standardized protocol. Ultrasound measurements were performed using standard operating procedures and identical equipment. Fetal biometry included head circumference (HC) and abdominal circumference (AC) using the ellipse function, and biparietal diameter (BPD), humerus length (HL), and femur length (FL) using the linear function measured at all study visits including 10w0d–13w6d. Voluson ultrasound machines were configured so that the sonographers were blinded to the measurements. EFW was computed from HC, AC, and FL using a formula of Hadlock et al.
      • Hadlock F.P.
      • Harrist R.B.
      • Sharman R.S.
      • Deter R.L.
      • Park S.K.
      Estimation of fetal weight with the use of head, body, and femur measurements–a prospective study.
      Measurements and images were captured in ViewPoint (GE Healthcare) and electronically transferred to the study’s imaging data-coordination center. Quality assurance was performed on 5% of the scans, and demonstrated correlations between the site sonographers and experts >0.99 for all biometric parameters and coefficients of variation ≤3%.
      • Hediger M.L.
      • Fuchs K.M.
      • Grantz K.L.
      • et al.
      Ultrasound quality assurance for singletons in the National Institute of Child Health and Human Development fetal growth studies.
      In-person interviews were conducted at each research visit to ascertain information on lifestyle, and reproductive and medical history. Demographic data; antenatal history; and labor, delivery, and neonatal course and outcomes were abstracted from the prenatal record, labor and delivery summary, and hospital and neonatal records by trained research personnel.

      Statistical analysis

      Ultrasonographic biometric measurements (BPD, HC, AC, HL, FL) and EFW were log-transformed to stabilize variances across GAs and to improve normal approximations for the error structures.

      Pinheiro JC, Bates DM. Mixed-effects models in S and S-plus. New York (NY): Springer Science–Business Media New York.

      For each biometric measurement and EFW we fit a linear mixed model with cubic splines for the fixed effects and a cubic polynomial for the random effects. Three-knot points (25th, 50th, 75th percentiles) were chosen at GAs that evenly split the distributions. The dependent variable is a log-transformed biometric measurement. From these we computed velocity percentiles in 2 ways: (1) the difference between 2 consecutive weekly measurements (ie, weekly velocity), and (2) the difference between any 2 ultrasounds at a clinically reasonable difference between 2 GAs (ie, velocity calculator).
      The velocity curves were defined as the mean change in each anthropometric measurement per week of GA. This weekly change was obtained from the fitted models by exponentiations of the predicted log mean estimates at each week and making the appropriate subtractions. From these models we were able to obtain percentiles on the relative change over each gestational week. These velocities were determined across GA from 11–41 weeks and for each racial/ethnic group. The 50th percentile velocity curves were computed as the average relative change for the average week-specific measurement. Weekly velocity percentiles were calculated as relative change using the ratio of the difference between the first measurement and the second measurement to adjust for the log transformation and allow results to be reported in the original scale; for detailed equations see Appendix.
      The growth velocity for EFW and each individual anthropometric parameter was tested for overall differences in racial/ethnic-specific curves using a likelihood-ratio test. When the global test was significant (<.05 level), we tested for week-specific differences by race/ethnicity using Wald tests at each week of gestation. These tests were conducted on the estimated curves with adjustment for maternal characteristics: age, height and pregravid weight, parity, full-time employment/student status (yes/no), marital status (married/living as married vs not), health insurance (private/managed vs Medicaid/other), income, education, and infant sex (male/female). All covariates were treated as continuous unless otherwise stated. Annual income (<$30,000; $30,000–39,999; $40,000–49,999; $50,000–74,999; $75,000–99,999; ≥$100,000) and education (<high school; high school or equivalent; some college or associate degree, bachelor’s degree; and master’s or higher degree) were analyzed categorically. We used multiple imputation (with 20 imputations) to account for missing covariate information when performing covariate-adjusted tests for week-specific racial/ethnic differences in the fetal growth curves.
      • Sterne J.A.
      • White I.R.
      • Carlin J.B.
      • et al.
      Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls.
      EFW percentiles were computed as previously reported for singleton fetal growth.
      • Buck Louis G.M.
      • Grewal J.
      • Albert P.S.
      • et al.
      Racial/ethnic standards for fetal growth: the NICHD fetal growth studies.
      We then compared fetal growth velocity percentiles and the EFW percentiles at 24, 28, 32, 36, and 40 (±1) weeks’ gestation to evaluate whether these 2 measures were correlated using the Pearson correlation coefficient (r). Growth velocity was computed as the estimated fetal growth rate (g/wk) between the ultrasound at that GA and from the prior visit [ie, for 28–32 weeks GA: velocity = (EFW 32–28)/(GA 32–28)].
      Understanding that clinicians see patients at unpredictably spaced time points, we developed a model so that the fetal growth velocity with corresponding percentiles can be computed for any given set of gestational weeks. Percentile distributions for this difference were constructed on the log scale using the linear mixed models that includes within and between women variation discussed above. These percentiles assessed the relative change in anthropometric measurement taken at any fixed set of 2 GA times, without having to observe all the time points in between. Thus, for any given set of 2 GA and anthropometric measurements the change percentile can be computed.
      We examined whether the maternal demographics, birthweight, and composite neonatal morbidity distributions differed by whether or not EFW and EFW velocity were each <5th percentile (both <5th percentile), EFW <5th percentile but velocity not, velocity <5th percentile but EFW not, and lastly, both >5th percentile. The χ2 or t tests for categorical and continuous data, respectively, were performed with significance defined as a 2-sided P < .05 using 32 weeks’ gestation for illustration purposes. The composite neonatal outcome included: metabolic acidosis (pH <7.1 and base deficit >12 mmol/L), neonatal intensive care unit stay >3 days, pneumonia, respiratory distress syndrome, persistent pulmonary hypertension, seizures, hyperbilirubinemia requiring exchange transfusion, intrapartum aspiration (meconium, amniotic fluid, blood), mechanical ventilation at term, necrotizing enterocolitis, hypoglycemia, hypoxic ischemic encephalopathy, periventricular leukomalacia, sepsis based on blood culture, bronchopulmonary dysplasia/chronic lung disease, retinopathy of prematurity, birth injury, or neonatal death.
      • Longo S.
      • Bollani L.
      • Decembrino L.
      • Di Comite A.
      • Angelini M.
      • Stronati M.
      Short-term and long-term sequelae in intrauterine growth retardation (IUGR).
      • Rosenberg A.
      The IUGR newborn.
      • Giapros V.
      • Drougia A.
      • Krallis N.
      • Theocharis P.
      • Andronikou S.
      Morbidity and mortality patterns in small-for-gestational age infants born preterm.
      • McIntire D.D.
      • Bloom S.L.
      • Casey B.M.
      • Leveno K.J.
      Birth weight in relation to morbidity and mortality among newborn infants.
      • King J.R.
      • Korst L.M.
      • Miller D.A.
      • Ouzounian J.G.
      Increased composite maternal and neonatal morbidity associated with ultrasonographically suspected fetal macrosomia.
      All analyses were implemented using SAS (Version 9.4; SAS Institute Inc, Cary, NC) or R (Version 3.4.2; http://www.R-project.org).

      Results

      Among the 2334 low-risk women enrolled, 169 (7%) exited the study; 356 (16%) were excluded due to pregnancy complications (eg, miscarriages, stillbirths, preterm delivery, hypertensive diseases, gestational diabetes); and 72 (4%) due to fetal or neonatal conditions (stillbirth, aneuploidy, or anomalies), resulting in 1737 pregnant women included in the standard. Four women did not have ultrasound data leaving 1733 for analysis. Of these women, 480 (28%) were non-Hispanic white, 423 (24%) were non-Hispanic black, 488 (28%) were Hispanic, and 342 (20%) were Asian or Pacific Islander. Additional demographic details are previously published.
      • Buck Louis G.M.
      • Grewal J.
      • Albert P.S.
      • et al.
      Racial/ethnic standards for fetal growth: the NICHD fetal growth studies.
      Average EFW growth velocity increased across gestation from 29 g/wk at 16 weeks, to 59 g/wk at 20 weeks, to 175 g/wk at 30 weeks, and 215 g/wk at 35 weeks, at which point it peaked. The 50th percentiles for weekly fetal growth velocity varied slightly by race/ethnicity for EFW (Figure 1) (global test P < .001) and BPD, HC, AC, FL, and HL (Figure 2) (global test P < .001 for all), although comparisons reflected differences for parameters at various GAs. Data for weekly growth velocity percentiles (5th, 10th, 50th, 90th, 95th) are presented in Table 1 with pairwise comparisons between racial/ethnic groups presented in Table 2. In general, the AC growth velocity increased in the first half of pregnancy until peaking on average around 16 weeks of gestation, with a second acceleration from 27–31 weeks, followed by steadily decreasing growth velocity for the remainder of pregnancy. Figure 2 illustrates the largest differences in fetal growth velocity by race/ethnicity was for the AC (Figure 2). The BPD and HC average growth velocities increased early in pregnancy peaking at approximately 13 and 14 weeks, respectively, with a second slight acceleration occurring from 19–22 weeks for BPD and 19–21 weeks for HC, followed by a decrease in growth velocity as pregnancy advanced. The long bone average growth velocities also increased in the first half of pregnancy, peaking at approximately 15 weeks for both the HL and FL, then steadily decreased over the rest of gestation. It is important to note that weekly fetal growth velocity was negative (reflecting measurement error) for the 5th and 10th percentiles for some of the anthropometric measurements at various gestational weeks. These findings were corroborated in simulations (data not presented) based on a previous approach.
      • Cheon K.
      • Albert P.S.
      • Zhang Z.
      The impact of random-effect misspecification on percentile estimation for longitudinal growth data.
      Figure thumbnail gr1
      Figure 1Estimated fetal weight (EFW) velocity (g/wk) by race/ethnicity and gestation, Eunice Kennedy Shriver National Institute of Child Health and Human Development fetal growth studies–singletons
      Velocity for EFW by maternal self-reported race/ethnicity. Velocity was computed using parameters from linear mixed model as discussed in “Materials and Methods” section.
      Grantz et al. Fetal growth velocity. Am J Obstet Gynecol 2018.
      Figure thumbnail gr2
      Figure 2Growth velocity (g/wk) of fetal anthropometric measurements by race/ethnicity and gestation, Eunice Kennedy Shriver National Institute of Child Health and Human Development fetal growth studies–singletons
      Velocity for individual fetal anthropometric parameters by self-reported race/ethnicity. Velocity was computed using parameters from linear mixed model as discussed in “Materials and Methods” section.
      AC, abdominal circumference; BPD, biparietal diameter; FL, femur length; HC, head circumference; HL, humerus length.
      Grantz et al. Fetal growth velocity. Am J Obstet Gynecol 2018.
      Table 1Race/ethnic-specific percentiles for fetal growth velocity of anthropometric measurements by gestational age, Eunice Kennedy Shriver National Institute of Child Health and Human Development fetal growth studies
      Gestational age, wkPercentile
      5th10th50th90th95th
      Biparietal diameter, mm–white
      112.42.63.44.24.4
      122.42.73.64.64.9
      132.32.63.84.95.3
      142.12.43.75.15.5
      151.72.13.65.25.6
      161.31.83.45.25.7
      170.91.43.35.25.7
      180.61.23.15.25.8
      190.41.03.15.36.0
      200.20.83.15.56.2
      210.00.73.15.76.4
      22–0.10.63.25.96.7
      23–0.30.43.16.06.9
      24–0.60.23.16.27.1
      25–0.80.03.16.37.2
      26–1.0–0.23.06.47.4
      27–1.3–0.43.06.57.5
      28–1.5–0.62.96.57.6
      29–1.8–0.82.86.67.7
      30–2.1–1.02.76.67.8
      31–2.4–1.32.66.67.8
      32–2.7–1.62.46.67.8
      33–3.0–1.92.26.67.8
      34–3.3–2.22.06.47.7
      35–3.7–2.51.86.37.6
      36–4.0–2.81.66.17.5
      37–4.3–3.11.36.07.4
      38–4.6–3.31.15.97.2
      39–4.8–3.61.05.77.1
      40–5.0–3.80.85.67.1
      41–5.2–3.90.75.67.0
      Head circumference, mm–white
      119.09.712.014.415.1
      129.210.012.815.716.6
      139.010.013.316.717.7
      148.49.513.317.318.5
      157.68.813.117.618.9
      166.57.912.717.719.2
      175.57.012.317.819.4
      184.56.111.917.919.7
      193.85.611.818.320.2
      203.35.211.918.920.9
      212.84.811.919.421.5
      222.24.311.919.822.1
      231.53.711.820.222.6
      240.73.111.620.523.1
      25–0.12.411.420.723.4
      26–0.91.711.020.823.6
      27–1.80.910.720.923.8
      28–2.80.010.220.923.9
      29–3.7–0.89.820.824.0
      30–4.7–1.79.320.623.9
      31–5.7–2.68.720.423.8
      32–6.7–3.58.120.123.6
      33–7.8–4.57.419.723.3
      34–8.8–5.56.619.222.9
      35–9.9–6.55.918.722.4
      36–10.9–7.45.118.221.9
      37–11.8–8.34.417.621.5
      38–12.6–9.03.817.221.1
      39–13.3–9.73.316.820.8
      40–13.8–10.22.916.620.5
      41–14.3–10.72.616.420.5
      Abdominal circumference, mm–white
      116.47.19.512.112.9
      126.77.510.513.714.6
      136.77.711.315.116.2
      146.57.611.816.317.6
      155.97.312.117.318.8
      165.26.712.218.119.8
      174.36.012.218.720.6
      183.45.312.119.321.4
      192.54.612.019.922.2
      201.73.912.020.623.1
      210.83.211.921.223.9
      22–0.22.411.821.724.6
      23–1.11.611.622.125.2
      24–2.10.811.422.625.9
      25–3.10.011.223.026.5
      26–4.0–0.811.023.427.1
      27–4.9–1.510.923.927.8
      28–5.6–2.110.924.528.5
      29–6.3–2.610.925.229.4
      30–6.9–3.111.126.030.3
      31–7.6–3.611.126.731.2
      32–8.4–4.211.127.332.0
      33–9.2–4.911.027.832.7
      34–10.2–5.710.828.233.3
      35–11.2–6.510.528.433.7
      36–12.3–7.510.028.634.0
      37–13.6–8.69.428.534.1
      38–14.9–9.88.728.234.0
      39–16.3–11.27.827.833.7
      40–17.9–12.66.727.233.2
      41–19.6–14.25.526.432.5
      Femur length, mm–white
      111.21.31.72.12.2
      121.51.72.32.93.1
      131.82.02.83.74.0
      141.82.13.24.44.8
      151.72.03.55.05.5
      161.31.73.55.45.9
      170.81.33.35.66.2
      180.20.83.15.76.4
      19–0.30.43.05.86.7
      20–0.60.12.96.17.0
      21–1.0–0.22.96.37.3
      22–1.4–0.52.86.57.6
      23–1.8–0.92.76.67.8
      24–2.2–1.22.66.88.0
      25–2.6–1.52.56.98.2
      26–3.0–1.92.47.08.4
      27–3.4–2.22.37.18.6
      28–3.7–2.42.27.38.8
      29–4.0–2.72.17.49.0
      30–4.2–2.92.17.69.3
      31–4.5–3.12.17.89.5
      32–4.8–3.32.07.99.7
      33–5.0–3.62.08.19.9
      34–5.3–3.81.98.210.0
      35–5.6–4.11.88.210.2
      36–5.9–4.31.78.310.3
      37–6.3–4.61.58.310.3
      38–6.6–4.91.48.210.3
      39–6.9–5.21.28.210.3
      40–7.2–5.51.08.110.2
      41–7.6–5.80.77.910.1
      Humerus length, mm–white
      111.31.41.82.12.3
      121.71.92.43.03.2
      132.02.22.93.84.0
      142.02.33.34.44.8
      151.82.13.44.95.3
      161.31.83.35.15.6
      170.81.33.15.15.7
      180.20.82.85.15.7
      19–0.30.32.65.15.8
      20–0.60.12.55.26.0
      21–0.9–0.22.55.46.2
      22–1.2–0.52.45.56.4
      23–1.6–0.82.35.66.6
      24–1.9–1.02.25.76.7
      25–2.2–1.32.15.76.8
      26–2.5–1.61.95.86.9
      27–2.8–1.81.85.87.0
      28–3.1–2.01.85.97.1
      29–3.3–2.21.76.07.3
      30–3.5–2.41.76.17.4
      31–3.7–2.61.66.27.5
      32–3.9–2.81.66.37.7
      33–4.1–2.91.56.37.8
      34–4.3–3.11.56.47.9
      35–4.5–3.31.46.58.0
      36–4.7–3.51.36.58.1
      37–5.0–3.71.26.58.1
      38–5.2–3.91.16.58.1
      39–5.5–4.10.96.48.0
      40–5.7–4.40.76.38.0
      41–6.1–4.70.56.17.8
      Estimated fetal weight, g–white
      114581314
      1256111618
      1378142123
      14911182629
      151114233337
      161417294246
      171721365257
      182025446470
      192329527785
      2025336192101
      21273670107118
      22283980124138
      23294290143159
      242944101163182
      252846113185207
      262748125209235
      272549138235264
      282350152263297
      292051167294332
      301651183327370
      311049198360408
      32044211392447
      33–1436221423484
      34–3223227451518
      35–545229474547
      36–81–16227493572
      37–111–41222508594
      38–142–67214520612
      39–175–95203529626
      40–209–124191535638
      41–244–155176539648
      Biparietal diameter, mm–black
      112.52.73.44.34.5
      122.52.73.74.75.0
      132.32.63.85.05.3
      142.02.43.75.15.6
      151.62.13.65.25.7
      161.21.73.45.25.7
      170.91.43.25.25.8
      180.61.13.15.35.9
      190.41.03.15.46.1
      200.20.83.25.66.3
      210.00.73.15.86.5
      22–0.20.53.15.96.7
      23–0.50.33.16.06.9
      24–0.70.13.06.27.1
      25–1.0–0.13.06.27.2
      26–1.2–0.32.96.37.3
      27–1.5–0.62.86.47.5
      28–1.7–0.82.86.57.6
      29–2.0–1.02.76.57.7
      30–2.3–1.22.66.67.7
      31–2.5–1.52.46.67.8
      32–2.9–1.82.36.57.8
      33–3.2–2.12.16.47.7
      34–3.6–2.41.86.37.6
      35–3.9–2.81.66.17.4
      36–4.3–3.11.35.97.3
      37–4.5–3.31.15.87.2
      38–4.7–3.41.15.87.2
      39–4.8–3.51.05.87.2
      40–4.8–3.51.15.97.4
      41–4.7–3.41.26.27.6
      Head circumference, mm–black
      119.29.912.314.915.6
      129.410.213.116.217.1
      139.010.013.517.218.2
      148.39.413.517.718.9
      157.28.513.117.919.3
      166.07.512.617.919.5
      174.96.512.118.019.7
      184.05.711.818.220.1
      193.45.211.818.720.7
      202.84.811.919.321.4
      212.14.211.819.722.0
      221.43.611.720.122.5
      230.62.911.420.422.9
      24–0.32.211.220.623.3
      25–1.21.410.920.723.6
      26–2.10.710.520.823.8
      27–3.0–0.110.220.924.0
      28–3.9–0.99.820.924.2
      29–4.7–1.79.421.024.3
      30–5.7–2.59.020.924.4
      31–6.6–3.48.420.724.3
      32–7.7–4.37.820.424.1
      33–8.8–5.47.020.023.7
      34–10.0–6.56.219.423.2
      35–11.1–7.65.318.722.6
      36–12.2–8.64.518.122.1
      37–12.9–9.33.917.721.7
      38–13.5–9.83.617.521.6
      39–13.8–10.13.417.521.6
      40–13.9–10.23.517.822.0
      41–13.9–10.03.918.422.6
      Abdominal circumference, mm–black
      115.96.69.512.513.4
      126.06.910.414.115.2
      135.86.911.115.516.8
      145.36.611.516.718.2
      154.66.111.717.719.4
      163.75.411.718.520.5
      172.74.611.619.221.4
      181.73.811.619.822.3
      190.73.011.520.523.2
      20–0.32.211.421.224.1
      21–1.31.311.221.824.9
      22–2.40.411.022.325.6
      23–3.5–0.510.822.726.3
      24–4.6–1.410.523.226.9
      25–5.6–2.210.323.727.6
      26–6.5–2.910.224.228.4
      27–7.3–3.610.224.929.2
      28–8.1–4.110.325.730.2
      29–8.6–4.510.526.631.4
      30–9.2–5.010.827.632.5
      31–10.0–5.510.928.433.6
      32–10.9–6.210.929.134.5
      33–11.9–7.110.729.635.2
      34–13.1–8.110.329.935.7
      35–14.4–9.39.730.036.0
      36–15.7–10.39.230.136.3
      37–16.7–11.28.930.436.7
      38–17.5–11.98.830.837.4
      39–18.1–12.38.931.638.3
      40–18.5–12.69.332.639.5
      41–18.8–12.610.034.141.2
      Femur length, mm–black
      111.31.41.82.22.4
      121.71.92.53.13.3
      132.02.23.14.04.3
      141.92.33.44.75.1
      151.72.13.55.25.7
      161.21.73.45.46.0
      170.61.13.25.56.2
      180.10.73.05.66.3
      19–0.30.32.95.86.6
      20–0.70.12.96.07.0
      21–1.1–0.22.96.37.3
      22–1.4–0.62.86.47.5
      23–1.8–0.92.76.67.8
      24–2.2–1.22.66.78.0
      25–2.6–1.52.56.98.2
      26–3.0–1.92.47.08.4
      27–3.3–2.12.37.18.6
      28–3.6–2.42.27.38.8
      29–3.9–2.62.27.59.0
      30–4.1–2.82.27.69.3
      31–4.4–3.02.17.89.5
      32–4.7–3.32.17.99.7
      33–5.0–3.52.08.09.9
      34–5.4–3.81.98.110.0
      35–5.7–4.11.78.110.0
      36–6.0–4.41.68.110.1
      37–6.2–4.61.58.210.2
      38–6.4–4.81.48.310.3
      39–6.6–4.91.58.410.5
      40–6.7–5.01.58.710.8
      41–6.8–5.01.79.011.2
      Humerus length, mm–black
      111.41.51.92.42.5
      121.82.02.63.33.5
      132.02.33.24.14.4
      142.02.33.54.85.2
      151.62.03.55.15.6
      161.11.53.35.25.8
      170.41.03.05.25.9
      18–0.10.52.75.26.0
      19–0.50.12.65.36.2
      20–0.9–0.12.65.56.4
      21–1.2–0.42.55.76.6
      22–1.6–0.82.45.86.8
      23–2.0–1.12.25.97.0
      24–2.3–1.42.15.97.1
      25–2.6–1.72.06.07.2
      26–3.0–1.91.96.17.3
      27–3.2–2.21.86.27.5
      28–3.5–2.41.76.27.6
      29–3.7–2.61.76.47.8
      30–3.9–2.71.76.58.0
      31–4.1–2.91.76.68.1
      32–4.4–3.11.66.78.3
      33–4.6–3.31.56.88.4
      34–4.8–3.51.46.88.4
      35–5.1–3.81.36.88.5
      36–5.3–4.01.26.98.5
      37–5.5–4.11.26.98.7
      38–5.6–4.21.27.18.9
      39–5.6–4.21.37.39.1
      40–5.6–4.11.57.79.6
      41–5.6–4.01.88.210.1
      Estimated fetal weight, g–black
      114591315
      1256111719
      1368152224
      14810192831
      151013233539
      161216294448
      171519365460
      181722436572
      191825507886
      2019275892102
      21192966107119
      22193175123138
      23193284141158
      24173394161181
      251534104182205
      261334115205232
      271034127230261
      28634141258293
      29234155288328
      30–333170320366
      31–1130183353404
      32–2323195385442
      33–3912203414477
      34–60–4207439509
      35–86–25205458535
      36–113–46202477559
      37–139–67200495584
      38–163–87200516611
      39–184–103202539641
      40–204–117209569678
      41–220–127221606722
      Biparietal diameter, mm–Hispanic
      112.32.53.34.14.4
      122.32.63.64.64.9
      132.22.53.74.95.2
      142.02.43.75.15.5
      151.72.13.65.25.6
      161.31.73.45.25.7
      170.91.43.35.25.8
      180.61.13.15.25.9
      190.30.93.15.46.0
      200.20.83.15.66.3
      210.00.73.15.76.5
      22–0.20.53.25.96.7
      23–0.40.43.16.16.9
      24–0.60.23.16.27.1
      25–0.90.03.16.37.3
      26–1.1–0.23.06.47.4
      27–1.4–0.52.96.57.6
      28–1.7–0.72.86.67.7
      29–1.9–0.92.76.67.7
      30–2.2–1.22.66.67.8
      31–2.5–1.42.56.67.8
      32–2.8–1.72.36.67.8
      33–3.2–2.02.16.57.8
      34–3.5–2.31.96.47.7
      35–3.9–2.71.76.27.6
      36–4.2–3.01.46.17.4
      37–4.4–3.21.36.07.4
      38–4.6–3.41.25.97.3
      39–4.7–3.51.15.97.3
      40–4.8–3.51.16.07.5
      41–4.8–3.51.26.27.7
      Head circumference, mm–Hispanic
      118.49.212.015.015.8
      128.59.512.916.517.6
      138.29.313.417.718.9
      147.58.813.518.519.9
      156.47.913.318.920.6
      165.26.812.819.121.0
      173.95.712.319.321.3
      182.84.711.919.521.7
      191.94.011.819.922.3
      201.23.511.820.623.1
      210.52.911.821.123.9
      22–0.32.311.721.724.6
      23–1.21.511.622.125.2
      24–2.10.811.422.525.7
      25–3.10.011.122.826.2
      26–4.1–0.910.823.026.6
      27–5.1–1.710.423.226.9
      28–6.1–2.610.023.327.1
      29–7.1–3.59.623.327.4
      30–8.1–4.49.123.327.5
      31–9.2–5.48.623.227.5
      32–10.3–6.48.023.027.4
      33–11.4–7.47.322.727.2
      34–12.6–8.56.522.326.9
      35–13.8–9.65.721.726.4
      36–14.9–10.64.921.125.9
      37–15.9–11.64.120.625.4
      38–16.7–12.43.520.225.0
      39–17.4–13.03.019.824.7
      40–18.0–13.62.619.624.5
      41–18.5–14.02.319.524.5
      Abdominal circumference, mm–Hispanic
      115.96.69.312.213.0
      126.17.010.313.814.8
      136.07.111.115.316.5
      145.76.911.616.618.0
      155.16.611.917.619.3
      164.36.012.118.520.4
      173.45.212.019.321.4
      182.44.411.919.922.3
      191.43.611.920.623.2
      200.42.911.821.324.1
      21–0.62.011.621.824.9
      22–1.71.111.422.425.6
      23–2.80.211.222.826.3
      24–3.8–0.710.923.326.9
      25–4.8–1.510.723.827.6
      26–5.8–2.310.624.328.3
      27–6.6–3.010.524.929.1
      28–7.4–3.510.625.630.1
      29–8.0–4.010.826.531.2
      30–8.6–4.411.027.532.3
      31–9.3–4.911.228.333.4
      32–10.2–5.611.229.034.3
      33–11.2–6.411.029.535.0
      34–12.4–7.410.629.835.5
      35–13.7–8.610.129.935.7
      36–15.0–9.89.429.935.9
      37–16.2–10.98.929.936.1
      38–17.4–11.88.429.936.3
      39–18.4–12.78.030.136.6
      40–19.3–13.57.830.437.0
      41–20.1–14.27.630.837.7
      Femur length, mm–Hispanic
      111.31.31.72.02.1
      121.61.82.32.93.0
      131.92.12.83.73.9
      141.92.23.24.34.7
      151.82.13.44.85.3
      161.41.83.45.15.6
      170.91.43.35.35.9
      180.41.03.15.46.0
      190.00.63.05.56.3
      20–0.30.32.95.76.6
      21–0.70.12.95.96.8
      22–1.1–0.22.86.17.1
      23–1.4–0.62.76.27.3
      24–1.8–0.92.66.37.5
      25–2.2–1.22.46.47.6
      26–2.5–1.52.36.57.8
      27–2.9–1.82.26.67.9
      28–3.1–2.02.26.88.1
      29–3.4–2.22.26.98.3
      30–3.6–2.42.17.18.6
      31–3.9–2.62.17.28.8
      32–4.1–2.82.17.49.0
      33–4.4–3.12.07.49.1
      34–4.7–3.31.87.59.2
      35–5.1–3.61.77.59.2
      36–5.4–3.91.57.59.2
      37–5.6–4.11.47.59.3
      38–5.8–4.31.47.59.4
      39–6.0–4.41.37.69.5
      40–6.1–4.51.47.89.7
      41–6.2–4.61.58.110.0
      Humerus length, mm–Hispanic
      111.31.41.82.22.3
      121.71.92.43.03.2
      132.02.23.03.84.1
      142.02.33.34.54.8
      151.72.13.44.95.3
      161.21.73.35.15.6
      170.71.23.05.05.7
      180.10.62.75.05.7
      19–0.40.32.65.05.8
      20–0.70.02.55.26.0
      21–1.0–0.32.45.46.2
      22–1.3–0.52.35.56.4
      23–1.6–0.82.25.66.6
      24–2.0–1.12.15.76.7
      25–2.3–1.42.05.76.8
      26–2.6–1.61.95.86.9
      27–2.9–1.91.85.87.1
      28–3.1–2.11.75.97.2
      29–3.4–2.31.76.07.3
      30–3.6–2.51.66.17.5
      31–3.8–2.61.66.27.6
      32–4.0–2.81.56.37.7
      33–4.2–3.01.56.37.8
      34–4.4–3.21.46.47.9
      35–4.7–3.41.36.47.9
      36–4.9–3.61.26.48.0
      37–5.1–3.81.16.58.0
      38–5.2–3.91.16.58.1
      39–5.4–4.01.06.58.2
      40–5.6–4.21.06.68.3
      41–5.7–4.30.96.78.4
      Estimated fetal weight, g–Hispanic
      113491315
      1246111719
      1368142124
      14810182730
      151012233538
      161215294348
      171419355459
      181622436673
      191825517988
      2019275993104
      21192967109122
      22193176126141
      23183286145163
      24173396165186
      251434107187212
      261234118212240
      27834131238270
      28434144267304
      29033159299341
      30–632175334382
      31–1429190369423
      32–2721203403464
      33–4310212435502
      34–65–6216462537
      35–93–29215484565
      36–124–54209501589
      37–154–79204518612
      38–184–103199534635
      39–211–126196552660
      40–237–146195574688
      41–261–164198600722
      Biparietal diameter, mm–Asian
      112.42.63.44.24.4
      122.52.73.64.64.9
      132.42.73.84.95.2
      142.22.53.85.15.5
      151.82.23.75.25.6
      161.51.93.55.25.7
      171.11.53.35.15.7
      180.71.23.15.15.7
      190.41.03.05.25.8
      200.30.93.15.46.0
      210.10.83.15.66.3
      220.00.63.15.76.5
      23–0.20.53.15.96.7
      24–0.40.33.16.06.9
      25–0.70.23.16.27.1
      26–0.90.03.06.37.2
      27–1.1–0.33.06.37.3
      28–1.4–0.52.96.47.4
      29–1.7–0.72.86.47.5
      30–2.0–1.02.66.47.5
      31–2.3–1.22.56.47.6
      32–2.5–1.52.36.47.6
      33–2.8–1.82.26.37.5
      34–3.1–2.02.06.27.5
      35–3.4–2.31.86.17.4
      36–3.7–2.61.66.07.3
      37–4.0–2.81.45.97.2
      38–4.3–3.11.25.87.1
      39–4.6–3.31.05.67.0
      40–4.8–3.60.85.56.8
      41–5.1–3.90.65.36.7
      Head circumference, mm–Asian
      119.29.811.914.114.8
      129.510.212.815.516.3
      139.410.313.316.517.4
      148.99.913.417.118.1
      158.19.213.217.418.6
      167.18.312.817.418.8
      176.07.412.317.418.9
      185.06.511.817.419.0
      194.25.811.617.619.3
      203.75.411.618.019.9
      213.35.111.718.520.5
      222.74.711.719.021.1
      232.14.211.619.321.6
      241.43.611.419.622.0
      250.72.911.219.822.3
      26–0.22.210.919.922.5
      27–1.01.510.519.922.6
      28–1.90.710.119.822.6
      29–2.9–0.29.519.622.6
      30–3.9–1.19.019.422.4
      31–4.8–2.08.419.122.3
      32–5.8–2.87.818.822.0
      33–6.7–3.77.218.521.8
      34–7.6–4.66.618.121.5
      35–8.5–5.45.917.721.1
      36–9.4–6.25.317.220.7
      37–10.4–7.14.616.720.2
      38–11.3–8.13.816.019.6
      39–12.4–9.12.915.318.9
      40–13.4–10.12.014.418.1
      41–14.5–11.21.013.617.2
      Abdominal circumference, mm–Asian
      116.26.89.312.012.7
      126.57.310.313.514.5
      136.57.511.114.916.1
      146.27.411.616.117.5
      155.77.011.917.118.7
      165.06.512.017.919.7
      174.15.812.018.620.5
      183.15.011.919.121.2
      192.24.211.719.622.0
      201.33.511.620.222.7
      210.42.711.520.723.4
      22–0.61.911.321.224.1
      23–1.61.111.121.624.7
      24–2.60.310.822.025.2
      25–3.5–0.510.622.425.8
      26–4.4–1.210.522.826.4
      27–5.2–1.910.423.327.1
      28–5.9–2.410.423.927.9
      29–6.5–2.810.524.728.8
      30–7.1–3.310.725.429.7
      31–7.8–3.810.726.130.6
      32–8.6–4.410.726.631.3
      33–9.5–5.210.527.031.9
      34–10.5–6.110.127.332.3
      35–11.6–7.09.727.432.6
      36–12.7–8.09.227.532.8
      37–13.7–8.88.927.633.1
      38–14.5–9.58.727.933.6
      39–15.1–10.08.728.434.2
      40–15.7–10.48.829.135.1
      41–16.1–10.79.130.136.3
      Femur length, mm–Asian
      111.31.31.62.02.0
      121.71.82.32.82.9
      132.02.22.93.63.8
      142.12.43.34.34.6
      152.02.33.54.85.2
      161.62.03.45.05.5
      171.11.53.25.15.6
      180.51.13.05.15.7
      190.10.72.85.25.9
      20–0.20.42.85.46.1
      21–0.50.22.85.66.4
      22–0.8–0.12.75.76.6
      23–1.1–0.32.75.96.9
      24–1.5–0.62.66.07.0
      25–1.8–0.92.56.17.2
      26–2.1–1.12.46.27.4
      27–2.4–1.42.36.37.5
      28–2.7–1.72.26.47.7
      29–3.0–1.92.26.67.9
      30–3.2–2.12.16.78.0
      31–3.5–2.32.16.88.2
      32–3.7–2.52.06.98.3
      33–4.0–2.71.96.98.4
      34–4.3–3.01.87.08.6
      35–4.5–3.21.87.18.7
      36–4.7–3.41.77.18.8
      37–5.0–3.61.67.28.8
      38–5.2–3.81.57.28.9
      39–5.5–4.01.47.29.0
      40–5.7–4.21.37.29.0
      41–6.0–4.51.27.39.1
      Humerus length, mm–Asian
      111.31.41.72.12.2
      121.81.92.42.93.1
      132.02.22.93.74.0
      142.12.43.34.44.7
      151.92.23.44.85.2
      161.41.83.34.95.4
      170.91.33.04.95.4
      180.30.82.74.85.4
      19–0.20.42.54.85.4
      20–0.50.12.44.95.6
      21–0.8–0.12.45.05.8
      22–1.0–0.32.35.26.0
      23–1.3–0.62.25.36.2
      24–1.6–0.82.25.46.3
      25–1.9–1.12.15.46.5
      26–2.2–1.32.05.56.6
      27–2.5–1.51.95.66.7
      28–2.7–1.81.85.66.8
      29–3.0–2.01.75.76.9
      30–3.2–2.21.65.77.0
      31–3.4–2.41.55.87.0
      32–3.6–2.51.55.87.1
      33–3.8–2.71.45.97.2
      34–4.0–2.91.46.07.3
      35–4.2–3.01.36.07.4
      36–4.3–3.11.36.17.5
      37–4.5–3.31.26.17.6
      38–4.7–3.51.16.17.6
      39–5.0–3.71.06.17.6
      40–5.2–4.00.86.07.5
      41–5.5–4.20.65.97.4
      Estimated fetal weight, g–Asian
      115591314
      1267111617
      1389142022
      141011182628
      151214233235
      161417284043
      171721344954
      182025426065
      192328497278
      202532578593
      2127356699109
      22293875114126
      23304184131145
      24314495149166
      253147105169188
      263049117191213
      273051129214239
      282852142239267
      292654155265298
      302354169294331
      311752182322364
      32948193350397
      33–241201376428
      34–1830207399457
      35–3715209419482
      36–58–2208437505
      37–82–21206452526
      38–106–40203466545
      39–131–61198479564
      40–157–83193492582
      41–184–105187506601
      Week corresponds to exact week (eg, 11 wk = 11.0 wk).
      Estimated fetal weight was calculated using Hadlock et al.
      • Hadlock F.P.
      • Harrist R.B.
      • Sharman R.S.
      • Deter R.L.
      • Park S.K.
      Estimation of fetal weight with the use of head, body, and femur measurements–a prospective study.
      Grantz et al. Fetal growth velocity. Am J Obstet Gynecol 2018.
      Table 2Pairwise race/ethnic P values for weekly fetal growth velocity of anthropometric measurements by gestational age, Eunice Kennedy Shriver National Institute of Child Health and Human Development fetal growth studies
      Gestational age, wkGlobalAsian vs blackAsian vs HispanicAsian vs whiteBlack vs HispanicBlack vs whiteHispanic vs white
      Biparietal diameter, mm
      111.0000.8700.3722.4844.1754.2406.7532
      121.0000.8621.2940.3628.2407.3026.7886
      131.0000.4863.1978.2134.3820.4208.8577
      14.3837.1052.0900.0640.7804.7155.9782
      15.0051.0009.0151.0022.2994.5838.5565
      16.0031.0005.0431.0027.0753.4018.2896
      17.7162.1194.7091.2052.1879.6941.3228
      181.0000.8817.5604.8132.6109.6490.3322
      19.2141.0357.1141.4514.5572.0815.2853
      20.0968.0161.0255.2010.8859.1396.2044
      21.2925.2149.0487.3500.4064.6878.2015
      22.7600.8122.2258.7177.1267.5191.3308
      23.3534.1917.6449.9282.0589.1771.5391
      24.2096.0478.9633.7395.0349.0638.7530
      25.0817.0136.7017.6669.0216.0209.9650
      26.0229.0038.5295.6818.0126.0048.7972
      27.0042.0012.4195.8237.0083.0007.5079
      28.0027.0036.4245.7966.0216.0004.2414
      29.0718.1315.6855.4086.2176.0120.1674
      30.3755.4884.9138.2870.5220.0626.1953
      31.4262.5810.9182.2534.6270.0710.1762
      32.1607.3751.7426.2421.5514.0268.1076
      33.0068.0514.3441.2826.2952.0011.0310
      34.0006.0016.0679.6914.1218<.0001.0127
      35.0266.0044.0753.6790.1922.0052.1113
      36.0323.0054.0766.3828.2523.0327.3145
      37.0099.0016.0448.1390.2095.0652.5580
      38.2100.0350.1725.0952.3721.5118.7721
      391.0000.6468.8073.3893.8062.6976.4979
      401.0000.8580.8528.6465.9986.4927.4767
      411.0000.6449.7087.7924.9188.4299.4831
      Head circumference, mm
      11.1044.3068.5486.4107.7279.0174.1152
      12.1577.5337.5668.2943.9669.0263.0721
      13.1792.9936.5869.1602.4925.0507.0299
      14.0240.2477.6064.0411.0546.1809.0040
      15.0002.0007.6280.0012<.0001.7234<.0001
      16.0003<.0001.7648.0038<.0001.1247.0032
      17.0806.0198.8082.2700.0134.1795.1923
      181.0000.6399.6275.9985.3132.5983.5907
      19.5930.0988.2730.2660.6614.5414.9287
      20.4231.0983.1749.0705.8705.8012.7091
      21.5842.8867.5106.1075.5617.0974.3515
      22.0575.1734.8401.2788.2561.0096.1995
      23.0129.0210.4293.5586.1499.0022.1590
      24.0044.0043.2681.7774.1027.0007.1442
      25.0015.0013.2051.8839.0722.0003.1308
      26.0004.0006.1882.8792.0484<.0001.1138
      27.0001.0005.2291.7403.0342<.0001.0999
      28.0011.0074.4741.4684.0550.0002.1316
      29.1850.3117.8731.2831.2445.0308.3725
      301.0000.9442.4888.2594.4513.2342.7318
      311.0000.8676.3966.2785.4879.3619.9037
      321.0000.9499.4210.3264.3788.2827.9471
      33.4473.3174.6546.4916.1612.0745.8640
      34.0673.0149.5943.9001.0638.0112.6459
      35.0452.0075.2321.4401.1512.0300.5755
      36.0548.0091.1619.3727.2883.0630.5280
      37.1113.0186.1286.4929.5004.0771.3483
      381.0000.6548.4691.7732.7725.4323.2806
      391.0000.3282.8306.3952.4663.8303.5600
      40.9307.1551.5849.3265.4227.5929.7294
      41.6551.1092.4896.3044.4160.5091.8135
      Abdominal circumference, mm
      111.0000.8308.9676.5573.7650.6459.4506
      121.0000.9908.9633.5559.9651.4251.4385
      13.9382.7016.9650.5415.6829.1564.4158
      14.0376.2731.9886.4919.1771.0063.3738
      15<.0001.0114.8970.3648.0016<.0001.3525
      16.0011.0034.6498.3729.0009.0002.6678
      17.0428.0576.5783.4974.0117.0071.9101
      18.1753.2909.4829.4061.0490.0292.9082
      19.1602.7728.2996.1623.0919.0267.6953
      20.0030.7069.1699.0233.0253.0005.2835
      21<.0001.3753.1697.0031.0110<.0001.0715
      22<.0001.2455.2767.0024.0201<.0001.0391
      23.0005.2351.4399.0072.0448<.0001.0460
      24.0019.2677.5565.0185.0783.0003.0638
      25.0056.3312.5951.0324.1133.0009.0892
      26.0162.4546.5500.0436.1511.0027.1320
      27.0851.7443.4135.0536.2196.0142.2430
      28.6160.6704.2438.1027.4563.2269.6531
      291.0000.2725.1864.3626.9077.7321.6024
      30.8562.1782.1427.5534.9869.3626.3096
      31.6473.1353.1079.5608.9671.2890.2425
      32.4196.0961.0699.4412.9133.2997.2360
      33.2232.0706.0372.2108.7948.4893.3274
      34.4633.2284.0814.0772.6738.7192.9238
      35.8970.7576.5156.1495.7684.3127.4355
      361.0000.9008.9086.2699.9883.3362.3061
      371.0000.8034.7533.5031.5621.6801.2956
      381.0000.6087.5031.6442.2275.2993.7835
      39.7977.6293.6215.3334.3189.1330.6418
      40.7461.6572.7208.2985.4115.1244.4881
      41.7577.6710.7802.2947.4692.1263.4309
      Femur length, mm
      11.0677.7544.0443.0211.0354.0113.8232
      12.1058.3783.0277.0176.0898.0540.9548
      13.0761.0711.0127.0136.3234.3901.8257
      14.0023.0004.0028.0098.6259.1624.4475
      15<.0001<.0001.0001.0129<.0001<.0001.0564
      16<.0001<.0001.0047.6480<.0001<.0001.0195
      17<.0001<.0001.7999.2277<.0001<.0001.1160
      18<.0001.0083.3346.0686<.0001<.0001.3191
      19.0066.6576.0486.0242.0032.0011.6993
      20.0323.8393.0161.0138.0062.0054.8911
      21.0372.5977.0981.0553.0137.0062.7362
      22.1869.2231.6663.3975.0799.0311.6479
      23.6597.1099.5377.8651.2800.1334.6407
      24.4515.0752.2021.3905.5419.3182.6720
      25.3542.0590.0907.1825.7704.5352.7255
      26.2872.0484.0479.0867.9433.7638.8101
      27.1946.0454.0324.0410.9382.9788.9595
      28.1976.0896.0572.0329.9003.6964.7787
      29.9440.4461.4041.1573.9934.5576.5253
      301.0000.9679.8773.6329.8451.6681.4961
      311.0000.8117.5661.9905.7522.8134.5570
      321.0000.7681.4712.7552.6836.9929.6816
      331.0000.9286.5574.5813.6217.6445.9873
      341.0000.5875.8561.5643.6910.2564.4182
      351.0000.3766.3746.8400.9334.2497.2317
      361.0000.3621.2651.9749.8913.3622.2610
      371.0000.4336.2203.7604.6869.6282.3597
      381.0000.9989.5483.5229.5405.5147.9635
      391.0000.5735.8323.6210.6906.2680.4377
      401.0000.4753.6192.7083.7876.2579.3494
      411.0000.4412.5355.7560.8388.2645.3249
      Humerus length, mm
      11.3523.8522.9748.0897.8640.0587.0596
      12.4189.4144.7705.0698.5673.2104.0872
      13.2874.0685.4913.0479.2117.8825.1554
      14.0014.0002.1672.0262.0099.0332.4058
      15<.0001<.0001.0053.0145<.0001<.0001.4808
      16<.0001<.0001.0005.2998<.0001<.0001.0119
      17<.0001<.0001.1189.5098.0003<.0001.0196
      18.0002.0270.9100.1355.0213<.0001.0761
      19.1350.5740.1227.0225.2230.0335.3957
      20.0236.1059.0096.0039.2037.1023.7333
      21.1770.6654.0737.0295.1204.0455.6738
      22.2829.3267.6413.3886.1232.0472.6761
      23.3042.0507.5096.7372.1646.0759.7170
      24.0746.0124.1747.2710.2111.1147.7592
      25.0282.0047.0751.1164.2474.1510.7939
      26.0142.0024.0411.0620.2711.1810.8244
      27.0122.0020.0328.0458.2942.2157.8600
      28.0648.0108.0756.0857.3803.3213.9214
      291.0000.3090.5374.5142.6422.6384.9888
      301.0000.8860.7291.7179.8420.8342.9977
      311.0000.5173.4540.3856.9344.8515.9151
      321.0000.3838.3702.2357.9919.7674.7710
      33.9431.4136.4388.1572.9584.5439.5057
      341.0000.9482.9838.2642.9293.2926.2269
      351.0000.4772.4080.8617.9449.3401.2673
      361.0000.3853.2932.8566.8788.4643.3570
      371.0000.5503.3059.7773.6714.7440.4462
      381.0000.5990.8527.9143.4530.4904.9278
      391.0000.2790.5729.8837.5666.3029.6436
      401.0000.2338.4292.8118.6529.3053.5528
      411.0000.2210.3775.7791.6989.3171.5256
      Estimated fetal weight, g
      11.3754.2569.2183.0626.8540.4098.5770
      12.5213.2988.2594.0869.8554.4283.6045
      13.9086.3690.3420.1514.8858.5089.6700
      141.0000.5153.5608.4171.9850.8502.8572
      151.0000.9312.6757.3281.5632.1949.5712
      16.0018.5595.0422.0003.2207.0102.1486
      17.0013.6562.0410.0002.1289.0020.1094
      18.0005.9288.0741.0004.0452<.0001.0745
      19<.0001.2445.1402.0004.0023<.0001.0241
      20<.0001.0143.2582<.0001<.0001<.0001.0012
      21<.0001.0007.4784<.0001<.0001<.0001<.0001
      22<.0001.0005.8811.0002.0002<.0001.0002
      23<.0001.0013.8340.0047.0021<.0001.0017
      24<.0001.0033.7138.0243.0082<.0001.0066
      25<.0001.0059.6973.0506.0150<.0001.0147
      26<.0001.0088.7779.0593.0163<.0001.0242
      27<.0001.0165.9797.0437.0126<.0001.0398
      28.0003.0951.5342.0330.0175<.0001.1210
      29.1261.6678.2204.0666.0934.0210.5557
      30.5364.7215.0894.0926.1942.2092.8980
      31.3154.5145.0526.0877.2145.3350.7072
      32.2157.4886.0360.0580.1668.2593.7192
      33.1579.7137.0376.0263.0856.0663.9937
      34.0638.5909.2599.0446.0973.0106.4040
      35.2008.2982.8518.3011.3762.0335.2027
      36.6105.2515.3986.6656.7519.1017.1847
      371.0000.2600.1703.9394.8087.2659.1704
      381.0000.7451.2485.5176.4104.7748.5296
      391.0000.7357.7016.5292.4702.3194.8294
      401.0000.5711.9765.5935.5525.2548.6171
      411.0000.5050.8829.6399.6076.2406.5359
      Week corresponds to exact week (eg, 11 wk = 11.0 wk).
      P values obtained by Wald test with adjustment for maternal age, height, weight, parity, job, marital status, insurance, income, education, and infant sex.
      Grantz et al. Fetal growth velocity. Am J Obstet Gynecol 2018.
      In clinical practice, patients may be seen at unpredictably spaced time intervals. Therefore, we created a calculator for any given set of 2 GAs and anthropometric measurements, where the EFW growth velocity with corresponding percentiles for a given fetus can be computed (Appendix). Table 3 presents an example for different scenarios for 2 ultrasounds obtained at 28–32 weeks, respectively, by self-reported maternal race/ethnicity. The results demonstrate that a fetus could have arrived at a given EFW at 32 weeks from different EFW growth velocities. If the change percentile is very small (eg, <5%) it is interpreted as no change in the measurement is unlikely in a healthy population, suggesting that this degree of fetal growth velocity may be problematic.
      Table 3Example of different scenarios for 2 ultrasounds obtained between 28–32 weeks of gestation by self-identified maternal race/ethnicity
      Non-Hispanic white
      28 wk EFW32 wk EFWEFW percentile at 32 wkVelocity percentile from 28–32 wk
      1354196050th5th
      1202196050th50th
      1067196050th95th
      Non-Hispanic black
      28 wk EFW32 wk EFWEFW percentile at 32 wkVelocity percentile from 28–32 wk
      1292183750th5th
      1134183750th50th
      996183750th95th
      Hispanic
      28 wk EFW32 wk EFWEFW percentile at 32 wkVelocity percentile from 28–32 wk
      1317187850th5th
      1150187850th50th
      1005187850th95th
      Asian and Pacific Islander
      28 wk EFW32 wk EFWEFW percentile at 32 wkVelocity percentile from 28–32 wk
      1267183050th5th
      1132183050th50th
      1011183050th95th
      EFW, estimated fetal weight.
      Grantz et al. Fetal growth velocity. Am J Obstet Gynecol 2018.
      To determine whether EFW growth velocity might provide information beyond cross-sectional measures, the correlation of growth velocity percentile with EFW percentile was assessed at 32 (±1) weeks of gestation for illustration (Figure 3). If the 2 measures were completely correlated, the points would line up in a 45-degree line on the figure. For all racial/ethnic groups, EFW growth velocity percentiles were not highly correlated with EFW size percentiles (Pearson r = 0.40–0.41, P < .001). Results were similar at 24, 28, 36, and 40 (±1) weeks’ gestation indicating that this low correlation persisted across gestation (data not shown). These findings suggest that these measurements reflect different aspects of fetal growth, so we investigated whether velocity could add additional information compared to a single measure of EFW in the ascertainment of abnormal growth. We also compared whether maternal demographics, birthweight, and a composite neonatal morbidity differed by whether or not EFW and velocity separately were below or above their prospective 5th percentile using 32 weeks of gestation (SD 1.5) for illustrative purposes, a time when an obstetrical ultrasound might be obtained to evaluate fetal growth in clinical practice (Table 4). Maternal height was slightly higher when EFW was ≥5th compared to <5th percentile, an association that did not vary much by whether fetal growth velocity was <5th percentile or ≥5th percentile (P = .044). Maternal body mass index was slightly lower if either EFW or velocity alone were <5th percentile (22.8 and 22.6, respectively) compared to when they were concordantly <5th percentile or ≥5th percentile (23.7 and 23.5, respectively). Birthweight was lightest when both EFW and growth velocity were <5th percentile (2550 g) followed by when EFW was <5th percentile and velocity was ≥5th percentile (2867 g). This observation suggests that lighter birthweight is associated with both EFW <5th percentile and a slower growth velocity. Still for EFW >5th percentile, birthweight was lighter when velocity was <5th percentile compared to ≥5th percentile (3208 vs 3357 g, respectively, P < .001) underscoring that slower growth velocity will negatively impact birthweight. Composite neonatal outcomes did not statistically differ by the groups, although the numbers were small (Table 4).
      Figure thumbnail gr3
      Figure 3Estimated fetal weight (EFW) velocity percentile by EFW percentile by race/ethnicity and gestation, Eunice Kennedy Shriver National Institute of Child Health and Human Development fetal growth studies–singletons
      EFW velocity percentile (x-axis) by EFW percentile (y-axis) for standard at 32 (±1) weeks of gestation for illustration. There was variation for all percentiles across all race/ethnic groups indicating that there was very little correlation, which suggests that growth velocity could add additional information to single time measure of EFW.
      Grantz et al. Fetal growth velocity. Am J Obstet Gynecol 2018.
      Table 4Characteristics by fetal growth velocity and estimated fetal weight percentile category for pregnancies with ultrasound at mean of 32 SD 1.5 weeks of gestation
      CharacteristicsTotal

      n = 1605
      Velocity <5th percentileVelocity ≥5th percentileP value
      EFW <5th percentile

      n = 14
      EFW ≥5th percentile

      n = 57
      EFW <5th percentile

      n = 62
      EFW ≥5th percentile

      n = 1472
      Race/ethnicity, no. (%).760
       Non-Hispanic white458 (28)2 (14)
      Because of rounding, percentages may not total 100
      17 (30)16 (26)423 (29)
       Non-Hispanic black387 (24)4 (29)12 (21)17 (27)354 (24)
       Hispanic448 (28)4 (29)12 (21)18 (29)414 (28)
       Asian and Pacific Islander312 (19)4 (29)16 (28)11 (18)281 (19)
      Height, mean (SD), cm163 (7)160 (6)164 (7)161 (6)163 (7).044
      Maternal prepregnancy BMI, mean (SD), kg/m223.4 (3)23.7 (4)22.6 (3)22.8 (3)23.5 (3).046
      Parity, no. (%).152
       0769 (48)7 (50)29 (51)22 (36)711 (48)
       1576 (36)3 (21)23 (40)30 (48)520 (35)
       ≥2260 (16)4 (29)5 (9)10 (16)241 (16)
      Infant sex, no. (%).305
       Male834 (52)7 (50)31 (54)25 (40)771 (52)
       Female771 (48)7 (50)26 (46)37 (60)701 (48)
      Birthweight, mean (SD), kg3325 (422)
      Birthweight was available for 1443 neonates
      2550 (295)3208 (382)2867 (420)3357 (405)<.001
      Composite neonatal outcome,
      Neonatal morbidities included: metabolic acidosis (pH <7.1 and base deficit >12 mmol/L), neonatal intensive care unit stay >3 d, pneumonia, respiratory distress syndrome, persistent pulmonary hypertension, seizures, hyperbilirubinemia requiring exchange transfusion, intrapartum aspiration (meconium, amniotic fluid, blood), neonatal death, mechanical ventilation at term, necrotizing enterocolitis, hypoglycemia, hypoxic ischemic encephalopathy, periventricular leukomalacia, sepsis based on blood culture, bronchopulmonary dysplasia/chronic lung disease, retinopathy of prematurity, and birth injury.13–17
      no. (%)
      .632
       No1536 (96)14 (100)53 (93)59 (95)1410 (96)
       Yes69 (4)0 (0)4 (7)3 (5)62 (4)
      Standard population as detailed in Buck Louis et al.
      • Buck Louis G.M.
      • Grewal J.
      • Albert P.S.
      • et al.
      Racial/ethnic standards for fetal growth: the NICHD fetal growth studies.
      BMI, body mass index; EFW, estimated fetal weight.
      Grantz et al. Fetal growth velocity. Am J Obstet Gynecol 2018.
      a Because of rounding, percentages may not total 100
      b Birthweight was available for 1443 neonates
      c Neonatal morbidities included: metabolic acidosis (pH <7.1 and base deficit >12 mmol/L), neonatal intensive care unit stay >3 d, pneumonia, respiratory distress syndrome, persistent pulmonary hypertension, seizures, hyperbilirubinemia requiring exchange transfusion, intrapartum aspiration (meconium, amniotic fluid, blood), neonatal death, mechanical ventilation at term, necrotizing enterocolitis, hypoglycemia, hypoxic ischemic encephalopathy, periventricular leukomalacia, sepsis based on blood culture, bronchopulmonary dysplasia/chronic lung disease, retinopathy of prematurity, and birth injury.
      • Longo S.
      • Bollani L.
      • Decembrino L.
      • Di Comite A.
      • Angelini M.
      • Stronati M.
      Short-term and long-term sequelae in intrauterine growth retardation (IUGR).
      • Rosenberg A.
      The IUGR newborn.
      • Giapros V.
      • Drougia A.
      • Krallis N.
      • Theocharis P.
      • Andronikou S.
      Morbidity and mortality patterns in small-for-gestational age infants born preterm.
      • McIntire D.D.
      • Bloom S.L.
      • Casey B.M.
      • Leveno K.J.
      Birth weight in relation to morbidity and mortality among newborn infants.
      • King J.R.
      • Korst L.M.
      • Miller D.A.
      • Ouzounian J.G.
      Increased composite maternal and neonatal morbidity associated with ultrasonographically suspected fetal macrosomia.

      Comment

      We present fetal growth velocity for BPD, HC, AC, FL, HL, and EFW by maternal race/ethnicity to complement previously published fetal size standards.
      • Buck Louis G.M.
      • Grewal J.
      • Albert P.S.
      • et al.
      Racial/ethnic standards for fetal growth: the NICHD fetal growth studies.
      • Buck Louis G.M.
      • Grewal J.
      Clarification of estimating fetal weight between 10-14 weeks gestation, NICHD fetal growth studies.
      Fetal growth velocity was nonmonotonic, with an acceleration early in pregnancy peaking at 13 weeks of gestation for BPD, 14 weeks for HC, 15 weeks for FL and HL, and 16 weeks for AC. The BPD and HC had a second acceleration in midpregnancy (19–22 and 19–21 weeks, respectively) and AC in the early third trimester (27–31 weeks). Conversely, long bone velocity (FL and HL) continued to slow. EFW velocity continued to accelerate peaking at approximately 35 weeks of gestation. A model to compute fetal growth velocity percentiles for any given set of gestational week intervals was also developed, since weekly velocity charts may not be that clinically useful. While an EFW size <5th percentile at 32 weeks’ gestation was associated with smaller birthweight, birthweight was additionally influenced by the EFW velocity prior to that visit. Birthweight was lighter if the fetal growth velocity was <5th compared to ≥5th percentile. Furthermore, EFW growth velocity percentiles were not highly correlated with EFW size percentiles, indicating that these measurements reflect different aspects of fetal growth.
      The finding that BPD and HC velocity first peaked in our study at 13 and 14 weeks of gestation, respectively, was similar to the BPD velocity peak at 13–16 weeks reported by Guihard-Costa et al
      • Guihard-Costa A.M.
      • Droulle P.
      • Larroche J.C.
      Growth velocity of the biparietal diameter, abdominal transverse diameter and femur length in the fetal period.
      in a study that included mixed (mostly cross-sectional and 25% with some longitudinal) measures. Similarly, they also found a second growth velocity acceleration for BPD. Our findings were somewhat different from the peak BPD velocity of 15–16 weeks of gestation reported in a longitudinal study by Fescina et al
      • Fescina R.H.
      • Ucieda F.J.
      • Cordano M.C.
      • Nieto F.
      • Tenzer S.M.
      • Lopez R.
      Ultrasonic patterns of intrauterine fetal growth in a Latin American country.
      of 30 fetuses and from the peak BPD and HC velocity at 17–18 weeks reported in another study by Bertino et al
      • Bertino E.
      • Di Battista E.
      • Bossi A.
      • et al.
      Fetal growth velocity: kinetic, clinical, and biological aspects.
      of 238 low-risk, uncomplicated pregnancies delivering at term. Our finding that AC growth velocity increased in the first half of pregnancy until it peaked on average around 16 weeks of gestation, with a second acceleration from 27–31 weeks, was somewhat similar to the study by Guihard-Costa et al
      • Guihard-Costa A.M.
      • Droulle P.
      • Larroche J.C.
      Growth velocity of the biparietal diameter, abdominal transverse diameter and femur length in the fetal period.
      where abdominal transverse diameter peaked at 13–16 weeks, and again around 25–28 weeks of gestation. However, our findings differ from the peak AC velocity at 22 weeks of gestation reported by Bertino et al
      • Bertino E.
      • Di Battista E.
      • Bossi A.
      • et al.
      Fetal growth velocity: kinetic, clinical, and biological aspects.
      and 32–34 weeks reported by Fescina et al.
      • Fescina R.H.
      • Ucieda F.J.
      • Cordano M.C.
      • Nieto F.
      • Tenzer S.M.
      • Lopez R.
      Ultrasonic patterns of intrauterine fetal growth in a Latin American country.
      The pattern of the long bone growth velocities increasing in the first half of pregnancy, peaking on average at 15 weeks of gestation, then steadily decreasing over the rest of gestation is also similar to the study by Bertino et al,
      • Bertino E.
      • Di Battista E.
      • Bossi A.
      • et al.
      Fetal growth velocity: kinetic, clinical, and biological aspects.
      although they found FL growth velocity peaked later around 20 weeks, and somewhat similar to the study by Guihard-Costa et al
      • Guihard-Costa A.M.
      • Droulle P.
      • Larroche J.C.
      Growth velocity of the biparietal diameter, abdominal transverse diameter and femur length in the fetal period.
      where FL growth velocity accelerated until 13–16 weeks of gestation, steadily decreased until 28 weeks, followed by an irregular decrease and then a rapid decrease >37 weeks. The differences in these results may be explained, in part, by differences in study populations. Modern ultrasound machines also have a narrower beam width accuracy resulting in shorter linear measurements, although it is unclear how this difference might affect velocity.
      • Okland I.
      • Bjastad T.G.
      • Johansen T.F.
      • Gjessing H.K.
      • Grottum P.
      • Eik-Nes S.H.
      Narrowed beam width in newer ultrasound machines shortens measurements in the lateral direction: fetal measurement charts may be obsolete.
      We also used modern statistics that were flexible enough to demonstrate accelerations and decelerations in fetal growth velocity based on an approach from Cheon et al
      • Cheon K.
      • Albert P.S.
      • Zhang Z.
      The impact of random-effect misspecification on percentile estimation for longitudinal growth data.
      that differed from prior publications.
      The direction of our findings on EFW are also generally consistent with a prior study in a single hospital in Scotland where EFW growth velocity peaked around 35 weeks of gestation, but the magnitudes were different.
      • Owen P.
      • Donnet M.L.
      • Ogston S.A.
      • Christie A.D.
      • Howie P.W.
      • Patel N.B.
      Standards for ultrasound fetal growth velocity.
      EFW growth velocity in our study was higher than reported in their investigation; for example at 35 weeks of gestation the EFW growth velocity was 230 g/wk in our non-Hispanic white group compared to 188 g/wk in the Scottish sample. These differences might be due to the inclusion of women with risk factors for fetal growth restriction in the Scottish sample, such as maternal smoking and pregnancy complications such as preterm delivery, while our study included only women with uncomplicated pregnancies and optimal outcomes. In addition, our findings regarding the low correlation of EFW size with EFW growth velocity are somewhat similar, although their conclusions were based on comparing the difference (velocity) to the average of the 2 measurements. We also compared the 2 measures in a slightly different manner using the EFW measurement vs velocity from the previous visit.
      The finding that fetal growth velocity was negative (representing measurement error) for the 5th and 10th percentiles for some of the anthropometric measurements at various gestational weeks suggests that assessing average weekly fetal growth velocity might be difficult in clinical practice. In light of these drawbacks, we have developed a calculator to compute fetal growth velocity with corresponding percentiles for a given fetus at any given set of gestational weeks, designed to enhance our assessment of fetal growth velocity. The calculator takes measurement error into account in a way by estimating the probability of how unusual fetal growth velocity is over a time period based on the NICHD fetal growth population. For very short intervals, detecting clinically meaningful changes is not possible since the measurement error in the measurements is larger than any reasonable change. For a larger interval, the clinically meaningful change would be larger and can more easily be separated from measurement error. Choosing the optimal interval is complicated and reflects the time of the measurements as well as the particular biometric measurement used. In particular cases, the calculator may be useful in making this decision. For example, if we wanted to calculate what time interval is needed to identify delayed growth based on no change in EFW, we can use the calculator with different start and end times with no change in EFW over the interval. The percentile for change will decrease as the length of the interval is increased. When this change percentile is very small (for example <5%) it is interpreted as no change in the measurement is unlikely in a healthy population, suggesting that this degree of delay may be problematic. Future work is needed to determine the optimal time intervals for clinical management.
      Some evidence suggests that growth velocity might be able to distinguish constitutionally small-for-GA fetuses from pathologic fetal growth restriction <10th percentile for EFW. In a prospective cohort study of 4512 women in the United Kingdom with research ultrasounds at 20, 28, and 32 weeks of gestation, for an EFW <10th percentile, neonatal morbidity (metabolic acidosis, 5-minute Apgar <7, or intensive neonatal care unit admission) was increased only if the fetal AC growth velocity was in the lowest decile compared to normal fetal growth velocity.
      • Sovio U.
      • White I.R.
      • Dacey A.
      • Pasupathy D.
      • Smith G.C.
      Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study.
      Our findings also suggest that EFW growth velocity adds additional information over knowing fetal size alone and future work is needed to determine whether velocity can improve prediction of birthweight and neonatal outcomes over isolated fetal size estimates.
      Limitations of our study reflect the observational design, including potential bias from the cohort selection or residual confounding. Also, we never observed the individual changes in growth per week, so the differences in size per week are extrapolated; however, the linear mixed models with cubic splines for the fixed effects and a cubic polynomial for the random effects are flexible enough to allow a robust calculation of growth at any point in gestation despite the fact that the percentage change in fetal weight differs at each gestational week and the time of the ultrasound examinations may be different in each patient. Further, model diagnostics demonstrated that major model assumptions such as the normality of the random effects and error distribution were met. The major strength of our study was the prospective collection of serial ultrasounds allowing the ability to assess fetal growth velocity in a racially/ethnically diverse obstetric cohort.
      In summary, we provide fetal growth velocity data to complement our previous work on fetal growth size standards and have developed a calculator to compute fetal growth velocity with corresponding percentiles for a given fetus at any given set of gestational weeks. Preliminary findings suggest that EFW growth velocity adds additional information over knowing fetal size alone. Additional research is needed to determine whether an abnormal fetal growth velocity percentile identifies fetuses and neonates at increased risk for morbidity and mortality, particularly in the setting of an otherwise appropriate-for-GA EFW size.

      Acknowledgment

      The authors acknowledge the research teams at all participating clinical centers, including Christina Care Health Systems, University of California–Irvine, Long Beach Memorial Medical Center, Northwestern University, Medical University of South Carolina, Columbia University, New York Presbyterian Queens, Saint Peter’s University Hospital, University of Alabama at Birmingham, Women and Infants Hospital of Rhode Island, Fountain Valley Regional Hospital and Medical Center, and Tufts University. The authors also acknowledge C-TASC and the EMMES Corporations for providing data and imaging support for this multisite study. This work would not have been possible without the assistance of GE Healthcare Women’s Health Ultrasound for their support and training on the Voluson and Viewpoint products over the course of this study.

      Appendix

      For a single longitudinal ultrasound measurement, we built a random effect model with cubic spline based on 3-knot points for fixed effects and cubic function for random effects as follow:
      Yij=θ0+θ1tij+θ2tij2+θ3tij3+θ4(tijδ1)+3+θ5(tijδ2)+3+θ6(tijδ3)+3+bi0+bi1tij+bi2tij2+bi3tij3+εij,
      (1)


      where Yij denotes log-transformed ultrasound measurement, tij is the jth gestational age for ith women, (tijδk)+3=max(0,(tijδk)3) is the knot sequence with δ1<δ2<δ3,(1,tij,tij2,tij3,(tijδ1)+3,(tijδ2)+3,(tijδ3)+3) is a truncated polynomial basis functions of degree 3, (θ0,θ1,θ2,θ3,θ4,θ5,θ6) is a corresponding vector of parameters and describes the overall fetal growth with a cubic spline function, and bi=(bio,bi1,bi2,bi3) denotes the random effects, where j=1,2,,ni,i=1,2,,I, ni denotes the number of repeated time points for ith women, and I denotes the number of women. Further, we assume that the residual errors εij are distributed with independent normal distributions with mean 0 and variance σε2. The random effects are assumed to have mean 0 and be correlated with each other. The random effects are interpreted as individual departures in an individual’s growth curve relative to the average fetal growth curve in the population. Further, the use of the model in (1) allows us to compute the ratio and velocity of 2 ultrasound measurements as follows:
      ri,jj=exp(YijˆYijˆ)andvi,jj=(ri,jj1)Yij/(tijtij),


      where Yij is an original scaled ultrasound measurement at time tij, Yijˆ is an estimated log-transformed ultrasound measurement at time tij, ri,jj is a ratio of 2 ultrasound measurements, and vi,jj is a velocity of 2 ultrasound measurements.

      References

        • Battaglia F.C.
        • Lubchenco L.O.
        A practical classification of newborn infants by weight and gestational age.
        J Pediatr. 1967; 71: 159-163
        • ACOG
        Fetal growth restriction. Practice bulletin no. 134.
        Obstet Gynecol. 2013; 121: 1122-1133
        • Deter R.L.
        Evaluation of intrauterine growth retardation in the fetus and neonate: are simple-minded methods good enough?.
        Ultrasound Obstet Gynecol. 1995; 6: 161-163
        • Altman D.G.
        • Hytten F.E.
        Intrauterine growth retardation: let's be clear about it.
        Br J Obstet Gynaecol. 1989; 96: 1127-1132
        • Sovio U.
        • White I.R.
        • Dacey A.
        • Pasupathy D.
        • Smith G.C.
        Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study.
        Lancet. 2015; 386: 2089-2097
        • Buck Louis G.M.
        • Grewal J.
        • Albert P.S.
        • et al.
        Racial/ethnic standards for fetal growth: the NICHD fetal growth studies.
        Am J Obstet Gynecol. 2015; 213: 449.e1-449.e41
        • Buck Louis G.M.
        • Grewal J.
        Clarification of estimating fetal weight between 10-14 weeks gestation, NICHD fetal growth studies.
        Am J Obstet Gynecol. 2017; 217: 96-101
        • Grewal J.
        • Grantz K.L.
        • Zhang C.
        • et al.
        Cohort profile: NICHD fetal growth studies–singletons and twins.
        Int J Epidemiol. 2018; 47 (25–25l)
        • Hadlock F.P.
        • Harrist R.B.
        • Sharman R.S.
        • Deter R.L.
        • Park S.K.
        Estimation of fetal weight with the use of head, body, and femur measurements–a prospective study.
        Am J Obstet Gynecol. 1985; 151: 333-337
        • Hediger M.L.
        • Fuchs K.M.
        • Grantz K.L.
        • et al.
        Ultrasound quality assurance for singletons in the National Institute of Child Health and Human Development fetal growth studies.
        J Ultrasound Med. 2016; 35: 1725-1733
      1. Pinheiro JC, Bates DM. Mixed-effects models in S and S-plus. New York (NY): Springer Science–Business Media New York.

        • Sterne J.A.
        • White I.R.
        • Carlin J.B.
        • et al.
        Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls.
        BMJ. 2009; 338: b2393
        • Longo S.
        • Bollani L.
        • Decembrino L.
        • Di Comite A.
        • Angelini M.
        • Stronati M.
        Short-term and long-term sequelae in intrauterine growth retardation (IUGR).
        J Matern Fetal Neonatal Med. 2013; 26: 222-225
        • Rosenberg A.
        The IUGR newborn.
        Semin Perinatol. 2008; 32: 219-224
        • Giapros V.
        • Drougia A.
        • Krallis N.
        • Theocharis P.
        • Andronikou S.
        Morbidity and mortality patterns in small-for-gestational age infants born preterm.
        J Matern Fetal Neonatal Med. 2012; 25: 153-157
        • McIntire D.D.
        • Bloom S.L.
        • Casey B.M.
        • Leveno K.J.
        Birth weight in relation to morbidity and mortality among newborn infants.
        N Engl J Med. 1999; 340: 1234-1238
        • King J.R.
        • Korst L.M.
        • Miller D.A.
        • Ouzounian J.G.
        Increased composite maternal and neonatal morbidity associated with ultrasonographically suspected fetal macrosomia.
        J Matern Fetal Neonatal Med. 2012; 25: 1953-1959
        • Cheon K.
        • Albert P.S.
        • Zhang Z.
        The impact of random-effect misspecification on percentile estimation for longitudinal growth data.
        Stat Med. 2012; 31: 3708-3718
        • Guihard-Costa A.M.
        • Droulle P.
        • Larroche J.C.
        Growth velocity of the biparietal diameter, abdominal transverse diameter and femur length in the fetal period.
        Early Hum Dev. 1991; 27: 93-102
        • Fescina R.H.
        • Ucieda F.J.
        • Cordano M.C.
        • Nieto F.
        • Tenzer S.M.
        • Lopez R.
        Ultrasonic patterns of intrauterine fetal growth in a Latin American country.
        Early Hum Dev. 1982; 6: 239-248
        • Bertino E.
        • Di Battista E.
        • Bossi A.
        • et al.
        Fetal growth velocity: kinetic, clinical, and biological aspects.
        Arch Dis Child Fetal Neonatal Ed. 1996; 74: F10-F15
        • Okland I.
        • Bjastad T.G.
        • Johansen T.F.
        • Gjessing H.K.
        • Grottum P.
        • Eik-Nes S.H.
        Narrowed beam width in newer ultrasound machines shortens measurements in the lateral direction: fetal measurement charts may be obsolete.
        Ultrasound Obstet Gynecol. 2011; 38: 82-87
        • Owen P.
        • Donnet M.L.
        • Ogston S.A.
        • Christie A.D.
        • Howie P.W.
        • Patel N.B.
        Standards for ultrasound fetal growth velocity.
        Br J Obstet Gynaecol. 1996; 103: 60-69