Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2023 Apr 1.
Published in final edited form as: Am J Obstet Gynecol. 2021 Dec 11;226(4):576–587.e2. doi: 10.1016/j.ajog.2021.12.006

Unified standard for fetal growth: the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies

Katherine L Grantz 1, Jagteshwar Grewal 2, Sungduk Kim 3, William A Grobman 4, Roger B Newman 5, John Owen 6, Anthony Sciscione 7, Daniel Skupski 8, Edward K Chien 9, Deborah A Wing 10, Ronald J Wapner 11, Angela C Ranzini 12, Michael P Nageotte 13, Sabrina Craigo 14, Stefanie N Hinkle 15, Mary E D’Alton 16, Dian He 17, Fasil Tekola-Ayele 18, Mary L Hediger 19, Germaine M Buck Louis 20, Cuilin Zhang 21, Paul S Albert 22
PMCID: PMC9554735  NIHMSID: NIHMS1838850  PMID: 34906542

OBJECTIVE:

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies–Singletons developed fetal growth standards in a contemporary, race and ethnicity diverse, and healthy multisite population in the United States.1 The study revealed differences in fetal growth, represented as size-for-gestational-age, by maternally self-reported race and ethnicity, demonstrable as early as 10 to 16 weeks’ gestation.2,3 Based on these findings, fetal growth standards stratified by race and ethnicity were developed because pooling results among self-identified racial and ethnic groups may differentially classify growth at the extremes, namely small for gestational age (SGA) or large for gestational age (LGA).4,5 For example, the study-derived standard based solely on the White racial and ethnic group classified up to 15% of fetuses born to non-White mothers as SGA (estimated fetal weight [EFW] of <fifth percentile).2,3 Since that time, there has been recognition that inclusion of self-reported race and ethnicity in clinical algorithms may create unintended consequences for diagnosis and intervention.6,7 In addition, if an individual does not identify as one of the specified racial and ethnic groups, then a unified standard may be more useful as a first step in the diagnostic process. We sought to create a contemporary, unified fetal growth standard, including all healthy participants in the NICHD Fetal Growth Studies–Singletons, weighted to represent the US population of pregnant women, to supplement our previous work and compare with (1) our previous racial- and ethnic-specific standards3 and (2) the Hadlock reference8 because the Society for Maternal-Fetal Medicine (SMFM) recommends the use of “population-based fetal growth references (such as Hadlock).”9

STUDY DESIGN:

Analyses included the same sample used for the racial- and ethnic-specific standards,1 composed of 1737 pregnant individuals without obesity with low-risk antenatal profiles from 12 US clinical sites (2009–2013) who delivered at ≥37 weeks’ gestation.1,2 Statistical analysis included 1732 eligible women (99.7%) with ultrasound measurements, of which 27.7%, 24.4%, 28.1%, and 19.8% self-identified as non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, and Asian or Pacific Islander (Asian), respectively. To approximate a nationally representative standard, the study sample was weighted back to a US population distribution of pregnant women using the natality statistics from 2011, which was the midpoint of the enrollment years (Supplement).10 Human subjects’ approval was obtained from all participating sites, and all women provided informed consent. A total of 6 research ultrasounds were performed measuring fetal biparietal diameter, head circumference (HC), abdominal circumference (AC), humerus, and femur length (FL). EFW was calculated from HC, AC and FL.11 The individual measurements, HC-to-AC ratio, and EFW were log-transformed to stabilize variances across gestational ages and improve normal approximations for error structures. Linear mixed models with cubic splines for the fixed and random effects were used to flexibly model fetal growth trajectories.12 Models were weighted on race and ethnicity for the unified standard and unweighted to estimate racial- and ethnic-specific EFW curves for comparison with the unified standard. Of note, 3-knot points (25th, 50th, and 75th percentiles) were chosen at gestational ages that evenly split the distributions. Percentiles were estimated on the basis of the assumed normal distribution of the random effects and error structure. Estimated curves (10th, 50th, and 90th percentiles) were determined across gestational age from the 10th to the 40th week (except for EFW, which started at 15 weeks). All analyses were implemented using the SAS software (version 9.4; SAS Institute Inc, Cary, NC) or R (version 3.1.2; R Foundation for Statistical Computing, Vienna, Austria; http://www.R-project.org). To assess the clinical relevance and impact on the classification of SGA, the unified standard was compared with the Hadlock et al8 (1991) reference commonly used in clinical practice. The differences in fetal growth classification between the unified standard and our previously developed racial and ethnic standards and the Hadlock reference were calculated for an EFW of <10th percentile (SGA).3 Statistical testing for comparison of the curves was not performed as each of the standards was constructed using the same dataset.

RESULTS:

The racial and ethnic representations in the analytical sample after weighting were as follows: 55.0% for NHW, 12.4% for NHB, 24.5% for Hispanic, and 8.1% for Asian. The weighted mean±standard deviation age was 28.9±5.2 years, and the prepregnancy body mass index was 23.4±2.9 kg/m2. In the weighted sample, 49.1% were nulliparous, 83.1% were married or living as married, 79.5% had education beyond high school, 56.7% had an income of ≥$75,000, 71.2% had commercial health insurance, and 75.3% were employed or full-time students. The unified and racial- and ethnic-specific EFW curves3 are presented in the Figure, A. The 50th percentile of the unified EFW curve was lower than that of the NHW group, similar to the Hispanic group, and higher than that for the Asian and NHB groups (statistical testing not performed). For example, at 39 weeks’ gestation, the 50th percentile EFWs were 3344 g for unified, 3502 g for NHW, 3330 g for Hispanic, 3263 g for Asian, and 3256 g for NHB. The unified standard classified more fetuses whose mothers identified as NHB, Hispanic, and Asian and fewer of those born to NHW mothers as being <10th percentile for EFW (Figure, B) than the racial- and ethnic-specific standards. Using the unified standard between 22 weeks’ gestation and term, more than 10% of fetuses born to NHB, Hispanic, and Asian mothers were classified as <10th percentile, using cutoffs from the racial- and ethnic-specific standards. For example, at 32 weeks’ gestation, a time when ultrasounds are often obtained, 5% of NHW, 14% of NHB, 12% of Hispanic, and 14% of Asian fetuses would be classified as <10th percentile based on the unified standard. Data for the unified standard percentiles (3rd, 5th, 10th, 50th, 90th, 95th, and 97th) for all measurements, HC and AC, and EFW are presented in the Table. The unified curve had a lower 50th percentile EFW than the Hadlock curve throughout gestation (Figure, C). A similar difference in classification of SGA fetuses would occur using the Hadlock reference, although the pattern differed slightly (Figure, D). Once more, at 32 weeks’ gestation, 6% of NHW, 15% of NHB, 13% of Hispanic, and 15% of Asian fetuses would have been classified as <10th percentile using the Hadlock reference.

FIGURE. EFW in the NICHD Fetal Growth Studies.

FIGURE

Open in a new tab

A, Distribution of EFW by a unified multiracial and ethnic group, 4 individual races and ethnicities, and gestational age (NICHD Fetal Growth Studies—Singletons). Estimated 10th, 50th, and 90th percentiles for fetal measurements by the entire cohort with race and ethnicity weighted using 2011 natality data and self-reported race and ethnicity, as estimated from linear mixed models with log-transformed outcomes and cubic splines. B, Percentage of fetuses with an EFW <10th percentile by racial and ethnic group, unified multiracial and ethnic group standard, and gestational age. The difference between racial- and ethnic-specific curves and the 10% referent line reflects the amount of differential classification attributed to using the unified multiracial or ethnic standard. C, Unified curve compared with the Hadlock reference. D, Percentage of fetuses with an EFW <10th percentile by racial and ethnic, group, Hadlock reference, and gestational age. The difference between racial- and ethnic-specific curves and the 10% referent line reflects the amount of differential classification attributed to using the Hadlock reference. Adapted from Hadlock.8

TABLE.

Percentiles for fetal measurements and EFW by gestational age, NICHD Fetal Growth Studies unified chart

Biparietal diameter (mm)
Gestational age (wk) 3rd 5th 10th 50th 90th 95th 97th
10 10.4 10.6 10.9 12.0 13.3 13.6 13.9
11 13.4 13.6 14.0 15.4 16.9 17.4 17.7
12 16.6 16.9 17.3 19.0 20.9 21.4 21.8
13 19.9 20.3 20.8 22.7 24.9 25.5 25.9
14 23.3 23.7 24.3 26.5 28.9 29.6 30.1
15 26.6 27.0 27.7 30.1 32.7 33.5 34.0
16 29.8 30.2 30.9 33.5 36.4 37.2 37.8
17 32.8 33.3 34.0 36.8 39.8 40.7 41.3
18 35.7 36.2 37.0 39.9 43.1 44.0 44.7
19 38.6 39.2 40.0 43.0 46.3 47.3 48.0
20 41.5 42.1 43.0 46.2 49.6 50.6 51.3
21 44.5 45.0 46.0 49.3 52.9 53.9 54.6
22 47.4 48.0 48.9 52.4 56.2 57.3 58.0
23 50.3 50.9 51.9 55.6 59.4 60.6 61.4
24 53.2 53.9 54.9 58.7 62.7 63.9 64.7
25 56.0 56.7 57.8 61.7 65.9 67.2 68.0
26 58.8 59.5 60.6 64.7 69.1 70.4 71.2
27 61.5 62.2 63.4 67.6 72.2 73.5 74.4
28 64.1 64.8 66.0 70.5 75.2 76.6 77.5
29 66.5 67.3 68.6 73.2 78.1 79.6 80.5
30 68.9 69.7 71.0 75.8 80.9 82.4 83.4
31 71.1 72.0 73.3 78.3 83.6 85.2 86.2
32 73.2 74.1 75.5 80.6 86.1 87.7 88.8
33 75.1 76.0 77.5 82.8 88.4 90.1 91.2
34 76.8 77.8 79.2 84.7 90.5 92.3 93.4
35 78.3 79.3 80.8 86.4 92.4 94.2 95.3
36 79.6 80.6 82.1 87.9 94.0 95.8 97.0
37 80.7 81.7 83.3 89.2 95.4 97.3 98.5
38 81.7 82.7 84.3 90.3 96.7 98.6 99.9
39 82.5 83.6 85.2 91.3 97.8 99.8 101.1
40 83.3 84.4 86.1 92.3 98.9 100.9 102.2
Head circumference (mm)
Gestational age (wk) 3rd 5th 10th 50th 90th 95th 97th
10 39.4 40.2 41.4 46.1 51.3 52.9 53.9
11 50.0 51.0 52.5 58.2 64.5 66.4 67.7
12 61.5 62.6 64.4 71.1 78.5 80.8 82.3
13 73.5 74.8 76.8 84.5 93.0 95.5 97.2
14 85.7 87.1 89.4 98.0 107.4 110.2 112.1
15 97.8 99.4 101.9 111.2 121.4 124.5 126.5
16 109.6 111.3 114.0 124.0 134.8 138.1 140.2
17 121.1 122.9 125.7 136.2 147.6 151.0 153.3
18 132.3 134.2 137.1 148.1 159.9 163.5 165.8
19 143.5 145.4 148.5 159.8 172.0 175.6 178.0
20 154.8 156.8 159.9 171.6 184.1 187.8 190.3
21 166.1 168.2 171.4 183.4 196.2 200.0 202.5
22 177.5 179.6 182.9 195.1 208.1 212.0 214.5
23 188.7 190.9 194.3 206.7 220.0 223.9 226.4
24 199.8 202.0 205.5 218.1 231.5 235.5 238.1
25 210.7 212.9 216.4 229.3 242.9 246.9 249.5
26 221.2 223.4 227.0 240.1 253.9 257.9 260.6
27 231.2 233.6 237.2 250.5 264.5 268.6 271.3
28 240.9 243.3 247.0 260.5 274.8 279.0 281.7
29 250.0 252.4 256.2 270.0 284.6 288.9 291.7
30 258.6 261.1 264.9 279.1 294.0 298.4 301.3
31 266.5 269.1 273.0 287.6 302.9 307.4 310.3
32 273.7 276.4 280.5 295.4 311.2 315.8 318.9
33 280.2 283.0 287.2 302.6 318.9 323.6 326.8
34 286.0 288.8 293.1 309.1 325.9 330.8 334.1
35 290.9 293.8 298.3 314.8 332.2 337.3 340.6
36 295.1 298.0 302.7 319.7 337.7 343.0 346.5
37 298.5 301.6 306.4 324.0 342.6 348.1 351.7
38 301.3 304.5 309.4 327.6 346.9 352.6 356.3
39 303.5 306.8 311.9 330.7 350.7 356.6 360.4
40 305.2 308.6 313.9 333.3 354.0 360.1 364.1
Abdominal circumference (mm)
Gestational age (wk) 3rd 5th 10th 50th 90th 95th 97th
10 30.9 31.5 32.4 36.1 40.1 41.3 42.1
11 39.1 39.8 41.0 45.4 50.3 51.8 52.8
12 48.2 49.1 50.5 55.8 61.6 63.3 64.5
13 58.1 59.1 60.7 66.9 73.6 75.6 77.0
14 68.5 69.7 71.5 78.5 86.1 88.4 90.0
15 79.2 80.5 82.6 90.4 98.9 101.5 103.2
16 90.1 91.5 93.8 102.4 111.8 114.6 116.4
17 101.0 102.6 105.1 114.4 124.5 127.6 129.6
18 111.8 113.5 116.2 126.2 137.1 140.4 142.6
19 122.6 124.4 127.3 138.0 149.6 153.1 155.4
20 133.3 135.2 138.3 149.7 162.0 165.7 168.1
21 143.8 145.9 149.2 161.2 174.3 178.1 180.7
22 154.2 156.4 159.9 172.6 186.3 190.4 193.1
23 164.4 166.7 170.3 183.7 198.1 202.4 205.3
24 174.3 176.7 180.5 194.6 209.8 214.3 217.3
25 184.0 186.5 190.5 205.3 221.2 226.0 229.1
26 193.4 196.1 200.3 215.8 232.6 237.6 240.9
27 202.7 205.6 210.0 226.3 244.0 249.2 252.7
28 212.0 215.0 219.6 236.9 255.4 260.9 264.6
29 221.4 224.5 229.4 247.6 267.1 273.0 276.8
30 230.8 234.1 239.3 258.5 279.2 285.4 289.4
31 240.3 243.7 249.2 269.5 291.4 298.0 302.3
32 249.6 253.3 259.1 280.5 303.7 310.6 315.2
33 258.7 262.6 268.7 291.3 315.9 323.3 328.1
34 267.4 271.5 277.9 301.9 327.8 335.6 340.8
35 275.6 279.9 286.7 311.9 339.3 347.5 353.0
36 283.2 287.7 294.8 321.4 350.3 358.9 364.7
37 290.3 295.1 302.5 330.4 360.8 370.0 376.0
38 297.1 302.1 309.9 339.1 371.1 380.8 387.1
39 303.6 308.9 317.0 347.7 381.3 391.5 398.2
40 310.1 315.5 324.1 356.3 391.6 402.3 409.3
Femur length (mm)
Gestational age (wk) 3rd 5th 10th 50th 90th 95th 97th
10 1.7 1.7 1.9 2.4 3.0 3.2 3.3
11 2.9 3.0 3.2 4.1 5.1 5.4 5.7
12 4.6 4.8 5.1 6.4 8.0 8.5 8.8
13 6.8 7.0 7.5 9.3 11.5 12.2 12.7
14 9.3 9.6 10.2 12.5 15.4 16.3 17.0
15 12.0 12.4 13.1 16.0 19.5 20.7 21.4
16 14.7 15.2 16.1 19.5 23.5 24.8 25.7
17 17.4 18.0 18.9 22.7 27.3 28.7 29.7
18 20.0 20.6 21.7 25.8 30.7 32.3 33.3
19 22.5 23.2 24.3 28.7 33.9 35.6 36.7
20 25.0 25.7 26.9 31.6 37.0 38.7 39.9
21 27.5 28.3 29.6 34.4 40.1 41.8 43.0
22 30.1 30.9 32.2 37.2 43.0 44.8 46.0
23 32.6 33.4 34.7 39.9 45.8 47.6 48.8
24 35.0 35.9 37.2 42.4 48.4 50.2 51.5
25 37.4 38.3 39.7 44.9 50.9 52.7 54.0
26 39.7 40.6 42.0 47.3 53.3 55.1 56.3
27 42.0 42.9 44.3 49.6 55.5 57.3 58.5
28 44.2 45.1 46.5 51.8 57.7 59.4 60.6
29 46.4 47.3 48.7 54.0 59.8 61.5 62.7
30 48.6 49.5 50.9 56.1 61.9 63.6 64.8
31 50.7 51.6 53.0 58.2 63.9 65.6 66.8
32 52.7 53.6 55.0 60.2 65.9 67.7 68.8
33 54.6 55.5 56.9 62.2 67.9 69.6 70.8
34 56.4 57.3 58.7 64.0 69.9 71.6 72.8
35 58.0 58.9 60.4 65.8 71.7 73.5 74.7
36 59.4 60.3 61.8 67.4 73.5 75.4 76.6
37 60.6 61.6 63.2 68.9 75.3 77.2 78.4
38 61.6 62.6 64.3 70.3 76.9 78.9 80.2
39 62.4 63.4 65.1 71.5 78.4 80.5 81.9
40 62.9 64.0 65.8 72.4 79.7 81.9 83.4
Humerus length (mm)
Gestational age (wk) 3rd 5th 10th 50th 90th 95th 97th
10 1.8 1.8 2.0 2.5 3.1 3.3 3.5
11 3.1 3.2 3.4 4.3 5.3 5.7 5.9
12 4.9 5.1 5.4 6.7 8.3 8.9 9.2
13 7.2 7.4 7.9 9.7 12.0 12.7 13.2
14 9.8 10.1 10.7 13.1 16.0 16.9 17.5
15 12.5 12.9 13.6 16.5 20.0 21.1 21.9
16 15.1 15.7 16.5 19.8 23.9 25.1 26.0
17 17.6 18.2 19.2 22.9 27.3 28.7 29.7
18 20.0 20.6 21.6 25.6 30.4 31.8 32.9
19 22.2 22.9 23.9 28.2 33.1 34.7 35.7
20 24.4 25.1 26.2 30.6 35.8 37.4 38.5
21 26.6 27.4 28.5 33.1 38.4 40.0 41.1
22 28.8 29.6 30.8 35.4 40.8 42.5 43.6
23 30.9 31.7 32.9 37.7 43.1 44.8 45.9
24 33.0 33.8 35.1 39.8 45.3 47.0 48.1
25 35.0 35.8 37.1 41.9 47.3 49.0 50.1
26 37.0 37.8 39.0 43.8 49.2 50.9 52.0
27 38.8 39.6 40.9 45.7 51.0 52.6 53.7
28 40.6 41.4 42.7 47.4 52.7 54.3 55.4
29 42.3 43.1 44.4 49.1 54.3 55.9 57.0
30 44.0 44.8 46.1 50.7 55.9 57.5 58.5
31 45.6 46.4 47.7 52.3 57.5 59.0 60.0
32 47.1 47.9 49.2 53.9 59.0 60.5 61.6
33 48.5 49.3 50.6 55.3 60.5 62.0 63.1
34 49.9 50.7 52.0 56.8 62.0 63.5 64.6
35 51.1 51.9 53.2 58.1 63.5 65.1 66.1
36 52.2 53.0 54.4 59.4 64.9 66.6 67.7
37 53.1 54.0 55.4 60.6 66.3 68.1 69.2
38 53.9 54.8 56.2 61.7 67.6 69.4 70.6
39 54.4 55.4 56.9 62.6 68.8 70.7 71.9
40 54.6 55.6 57.2 63.2 69.8 71.8 73.1
Head circumference to abdominal circumference ratio
Gestational age (wk) 3rd 5th 10th 50th 90th 95th 97th
10 1.174 1.188 1.209 1.290 1.375 1.401 1.417
11 1.172 1.186 1.207 1.286 1.370 1.395 1.412
12 1.165 1.178 1.199 1.277 1.359 1.384 1.400
13 1.153 1.166 1.187 1.263 1.344 1.368 1.383
14 1.138 1.151 1.171 1.246 1.325 1.349 1.364
15 1.122 1.134 1.154 1.227 1.305 1.328 1.343
16 1.104 1.117 1.136 1.208 1.284 1.306 1.321
17 1.088 1.100 1.119 1.189 1.264 1.286 1.300
18 1.072 1.084 1.103 1.172 1.246 1.267 1.282
19 1.059 1.071 1.089 1.158 1.23 1.252 1.266
20 1.048 1.060 1.079 1.147 1.219 1.240 1.254
21 1.040 1.052 1.070 1.138 1.210 1.231 1.245
22 1.033 1.045 1.064 1.131 1.203 1.225 1.239
23 1.028 1.04 1.058 1.126 1.198 1.220 1.234
24 1.023 1.035 1.053 1.122 1.194 1.216 1.230
25 1.018 1.03 1.048 1.117 1.191 1.212 1.227
26 1.012 1.024 1.043 1.113 1.187 1.208 1.223
27 1.006 1.018 1.037 1.107 1.182 1.204 1.218
28 0.998 1.010 1.029 1.100 1.175 1.198 1.212
29 0.988 1.000 1.019 1.091 1.167 1.189 1.204
30 0.976 0.988 1.008 1.08 1.156 1.179 1.194
31 0.963 0.975 0.995 1.067 1.144 1.167 1.183
32 0.948 0.961 0.981 1.053 1.131 1.155 1.170
33 0.933 0.946 0.966 1.039 1.118 1.141 1.157
34 0.918 0.931 0.951 1.024 1.104 1.127 1.143
35 0.902 0.915 0.935 1.010 1.09 1.114 1.130
36 0.887 0.900 0.920 0.995 1.076 1.101 1.117
37 0.872 0.885 0.905 0.981 1.063 1.088 1.104
38 0.856 0.869 0.89 0.967 1.050 1.075 1.091
39 0.84 0.854 0.875 0.952 1.037 1.062 1.079
40 0.825 0.838 0.859 0.938 1.024 1.050 1.067
EFW (g)
Gestational age (wk) 3rd 5th 10th 50th 90th 95th 97th
15 90 93 96 111 128 133 137
16 114 117 121 140 161 168 172
17 142 146 152 175 202 210 216
18 177 181 189 218 251 262 269
19 218 223 233 268 310 323 331
20 265 272 283 327 378 393 404
21 319 328 341 394 456 475 487
22 380 391 407 471 544 567 582
3 449 462 481 557 644 671 690
24 526 541 564 653 756 789 810
25 612 629 656 760 881 919 945
26 706 726 757 879 1020 1064 1094
27 810 833 869 1010 1174 1225 1259
28 924 950 992 1154 1344 1403 1443
29 1048 1078 1126 1313 1532 1600 1646
30 1184 1218 1273 1488 1738 1816 1869
31 1330 1369 1431 1676 1962 2052 2112
32 1483 1528 1599 1876 2202 2304 2373
33 1643 1692 1772 2086 2455 2570 2649
34 1804 1860 1949 2301 2716 2846 2935
35 1963 2025 2124 2516 2980 3126 3225
36 2116 2185 2295 2728 3243 3406 3517
37 2264 2339 2460 2937 3506 3687 3809
38 2406 2488 2619 3142 3768 3968 4103
39 2542 2631 2774 3344 4032 4251 4400
40 2672 2769 2924 3546 4299 4540 4704
Open in a new tab

Note that week corresponds to the exact week (eg, 15 weeks=15.0 weeks). EGW was calculated from head circumference, abdominal circumference, and femur length using the Hadlock 1985 formula.11

CONCLUSION:

We provided a unified, multiethnic, fetal growth standard to supplement our previous work.2,3 This unified curve for EFW falls below that for the fetuses of NHW women and above those for the fetuses of NHB, Hispanic, and Asian women. The unified multiracial and ethnic fetal standard compared with our racial- and ethnic-specific standards classified different percentages of fetuses as SGA, as expected.5 Although a unified fetal standard might be more practical for sonographic assessment in diverse and heterogeneous populations, it will classify different percentages of fetuses as SGA and LGA among racial and ethnic groups. When applying the standard to a local population, these findings mean that it may perform differently concerning the risks of perinatal morbidity and mortality, with long-term health implications.

Numerous ultrasound-based fetal weight references are used clinically.13 The NICHD Fetal Growth Studies addressed earlier methodologic limitations, for example, retrospective or cross-sectional designs coupled with limited and non-diverse samples without careful consideration of biases (selection, information, and residual confounding), all impacting their utility and feasibility for clinical use.8,14-18 Of note, the following 2 other diverse, contemporary international studies with longitudinal fetal measurements have offered alternative fetal growth standards: (1) the International Fetal and Newborn Growth Consortium for the 21st Century and (2) the World Health Organization Multicentre Growth Reference Study.19,20 Despite the 2 international studies and our including women with similar low-risk antenatal profiles, percentiles for fetal measurements and EFW varied significantly.21 The reason for demonstrated differences in fetal growth across geographic populations is not entirely clear as the determinants of fetal growth are not fully known.22,23 Variation in fetal growth reflects multiple maternal and paternal characteristics, including genetic factors and external factors, such as altitude, nutrition, stressors, and other environmental conditions.24-29 Country of inhabitance, for example, is the most important factor predicting adverse infant outcomes, compared with customizing for additional maternal and fetal characteristics.30 This observation underscores the importance of US-specific standards in clinical practice. We weighted our racial- and ethnic-specific standards to approximate their distribution in the general population using the natality data to construct a unified US standard. Ideally, we would use weights reflecting racial and ethnic distribution among women eligible to be included in the standard (low antenatal risk); however, such population data are not available. US professional societies do not currently recognize a national reference or standard for fetal growth. The American College of Obstetricians and Gynecologists does not specify one, whereas the SMFM recommends the use of “population-based fetal growth references (such as Hadlock).”9,31,32 However, the Hadlock reference is cross-sectional (ie, fetal measurements taken at a single examination, and each fetus is only represented once), so it is less precise in assessing velocity.8,33 Furthermore, the Hadlock reference was derived from a single hospital and included only White gravidas, less stringently screened for antenatal risk (eg, smokers not excluded). Moreover, it does not reflect the diversity in the US obstetrical population, as demonstrated by the differences between EFW unified and Hadlock curves and different percentages of fetuses classified as SGA compared with racial- and ethnic-specific standards. Our US-based fetal standard should apply to the current US population. However, given that we have shown differential classification at the extremes, clinical protocols may need to be adapted for use in local populations to avoid unnecessary follow-up and as a diagnostic tool for perinatal morbidity and mortality. Future studies evaluating short-term and long-term offspring health of the unified standards compared with the racial- and ethnic-specific standards are warranted. Ultimately, randomized trials are needed to establish which fetal growth standard is superior in improving outcomes.

Supplementary Material

supplement

ACKNOWLEDGMENTS

The authors acknowledge the research teams at all participating clinical centers, including ChristinaCare Health Systems; University of California, Irvine; Long Beach Memorial Medical Center; Northwestern University; Medical University of South Carolina; Columbia University; NewYork-Presbyterian Queens; Saint Peters’ University Hospital; University of Alabama at Birmingham; Women & Infants Hospital of Rhode Island; Fountain Valley Regional Hospital and Medical Center; and Tufts University. Furthermore, the authors acknowledge the Clinical Trials and Surveys Corporation and the Emmes Company in 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 throughout the study.

This research was supported, in part, by the Division of Population Health, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; and, in part, with Federal funds for the NICHD Fetal Growth Studies – Singletons under Contract Numbers: HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, and HHSN275201000009C. P.S.A., K.L.G., J.G., S.K., F.T.A. and C.Z. have contributed to this work as part of their official duties as employees of the United States Federal Government.

Footnotes

D.A.W. has been a consultant for Parsagen, for which she received no compensation. The other authors report no conflict of interest.

This study is registered on ClinicalTrials.gov.

Contributor Information

Katherine L. Grantz, Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Drive, MSC 7004, Bethesda, MD 20892.

Jagteshwar Grewal, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

Sungduk Kim, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

William A. Grobman, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Roger B. Newman, Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC.

John Owen, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL.

Anthony Sciscione, Department of Obstetrics and Gynecology, ChristianaCare Health System, Newark, DE.

Daniel Skupski, Department of Obstetrics and Gynecology, NewYork-Presbyterian Queens, Flushing, NY.

Edward K. Chien, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Women & Infants Hospital of Rhode Island, Providence, RI; Cleveland Clinic Cleveland, OH.

Deborah A. Wing, Division of Maternal-Fetal Medicine, Department of Obstetrics-Gynecology, University of California, Irvine, School of Medicine, Irvine Orange County, CA, Fountain Valley Regional Hospital and Medical Center Fountain Valley, CA.

Ronald J. Wapner, Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY.

Angela C. Ranzini, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Women and Infants Hospital of Rhode Island, Providence, RI; Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, St Peter’s University Hospital, New Brunswick, NJ.

Michael P. Nageotte, Department of Obstetrics and Gynecology, Miller Children’s Hospital/Long Beach Memorial Medical Center, Long Beach, CA.

Sabrina Craigo, Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA.

Stefanie N. Hinkle, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Mary E. D’Alton, Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY.

Dian He, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; The Prospective Group, Fairfax County, VA.

Fasil Tekola-Ayele, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health.

Mary L. Hediger, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

Germaine M. Buck Louis, Office of the Dean, College of Health and Human Services, George Mason University, Fairfax County, VA.

Cuilin Zhang, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

Paul S. Albert, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

REFERENCES

  • 1.Grewal J, Grantz KL, Zhang C, et al. Cohort profile: NICHD Fetal Growth Studies–singletons and twins. Int J Epidemiol 2018;47. 25–25l. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Buck Louis GM, Grewal J, Albert PS, et al. Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies. Am J Obstet Gynecol 2015;213:449.e1–41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Buck Louis GM, Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies’ Research Team, Grewal J Clarification of estimating fetal weight between 10-14 weeks gestation, NICHD Fetal Growth Studies. Am J Obstet Gynecol 2017;217: 96–101. [DOI] [PubMed] [Google Scholar]
  • 4.Epidemiology Branch. Fetal growth calculator. Eunice Kennedy Shriver National Institute of Child Health and Human Development.. 2020. Available at: https://www.nichd.nih.gov/fetalgrowthcalculator. Accessed February 11, 2021. [Google Scholar]
  • 5.Albert PS, Grantz KL. Fetal growth and ethnic variation. Lancet Diabetes Endocrinol 2014;2:773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Vyas DA, Eisenstein LG, Jones DS. Hidden in plain sight - reconsidering the use of race correction in clinical algorithms. N Engl J Med 2020;383:874–82. [DOI] [PubMed] [Google Scholar]
  • 7.Norris KC, Eneanya ND, Boulware LE. Removal of race From estimates of kidney function: first, do no harm. JAMA 2021;325:135–7. [DOI] [PubMed] [Google Scholar]
  • 8.Hadlock FP, Harrist RB, Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology 1991;181:129–33. [DOI] [PubMed] [Google Scholar]
  • 9.Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Martins JG, Biggio JR, Abuhamad A. Society for Maternal-Fetal Medicine Consult Series #52: diagnosis and management of fetal growth restriction: (replaces Clinical Guideline Number 3, April 2012). Am J Obstet Gynecol 2020;223:B2–17. [DOI] [PubMed] [Google Scholar]
  • 10.National Center for Health Statistics. Vital statistics natality birth data. National Bureau of Economic Research. 2011. Available at: https://www.nber.org/data/vital-statistics-natality-data.html. Accessed March 28, 2019. [Google Scholar]
  • 11.Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body, and femur measurements–a prospective study. Am J Obstet Gynecol 1985;151:333–7. [DOI] [PubMed] [Google Scholar]
  • 12.Pinheiro JC, Bates DM. Mixed-effects models in S and S-PLUS. New York, NY: Springer Science+Business Media; 2000. [Google Scholar]
  • 13.Grantz KL. Fetal growth curves: is there a universal reference? Obstet Gynecol Clin North Am 2021;48:281–96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Altman DG, Chitty LS. Charts of fetal size: 1. Methodology. Br J Obstet Gynaecol 1994;101:29–34. [DOI] [PubMed] [Google Scholar]
  • 15.Nasrat H, Bondagji NS. Ultrasound biometry of Arabian fetuses. Int J Gynaecol Obstet 2005;88:173–8. [DOI] [PubMed] [Google Scholar]
  • 16.Salomon LJ, Duyme M, Crequat J, et al. French fetal biometry: reference equations and comparison with other charts. Ultrasound Obstet Gynecol 2006;28:193–8. [DOI] [PubMed] [Google Scholar]
  • 17.Snijders RJ, Nicolaides KH. Fetal biometry at 14-40 weeks’ gestation. Ultrasound Obstet Gynecol 1994;4:34–48. [DOI] [PubMed] [Google Scholar]
  • 18.Ioannou C, Talbot K, Ohuma E, et al. Systematic review of methodology used in ultrasound studies aimed at creating charts of fetal size. BJOG 2012;119:1425–39. [DOI] [PubMed] [Google Scholar]
  • 19.Stirnemann J, Villar J, Salomon LJ, et al. International estimated fetal weight standards of the INTERGROWTH-21st Project. Ultrasound Obstet Gynecol 2017;49:478–86. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Kiserud T, Piaggio G, Carroli G, et al. The World Health Organization fetal growth charts: a multinational longitudinal study of ultrasound biometric measurements and estimated fetal weight. PLoS Med 2017;14:e1002220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Grantz KL, Hediger ML, Liu D, Buck Louis GM. Fetal growth standards: the NICHD fetal growth study approach in context with INTERGROWTH-21st and the World Health Organization Multicentre Growth Reference Study. Am J Obstet Gynecol 2018;218:641–55. e28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Lunde A, Melve KK, Gjessing HK, Skjaerven R, Irgens LM. Genetic and environmental influences on birth weight, birth length, head circumference, and gestational age by use of population-based parentoffspring data. Am J Epidemiol 2007;165:734–41. [DOI] [PubMed] [Google Scholar]
  • 23.Kramer MS. Determinants of low birth weight: methodological assessment and meta-analysis. Bull World Health Organ 1987;65:663–737. [PMC free article] [PubMed] [Google Scholar]
  • 24.Gardosi J. Customized fetal growth standards: rationale and clinical application. Semin Perinatol 2004;28:33–40. [DOI] [PubMed] [Google Scholar]
  • 25.Gluckman PD, Hanson MA, Buklijas T. A conceptual framework for the developmental origins of health and disease. J Dev Orig Health Dis 2010;1:6–18. [DOI] [PubMed] [Google Scholar]
  • 26.Frisancho AR. Developmental functional adaptation to high altitude: review. Am J Hum Biol 2013;25:151–68. [DOI] [PubMed] [Google Scholar]
  • 27.Tekola-Ayele F, Workalemahu T, Amare AT. High burden of birthweight-lowering genetic variants in Africans and Asians. BMC Med 2018;16:70. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Tekola-Ayele F, Zhang C, Wu J, et al. Trans-ethnic meta-analysis of genome-wide association studies identifies maternal ITPR1 as a novel locus influencing fetal growth during sensitive periods in pregnancy. PLoS Genet 2020;16:e1008747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Tekola-Ayele F, Ouidir M, Shrestha D, et al. Admixture mapping identifies African and Amerindigenous local ancestry loci associated with fetal growth. Hum Genet 2021;140:985–97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Mikolajczyk RT, Zhang J, Betran AP, et al. A global reference for fetal-weight and birthweight percentiles. Lancet 2011;377:1855–61. [DOI] [PubMed] [Google Scholar]
  • 31.American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins–Obstetrics and the Society forMaternal-FetalMedicin. ACOG Practice Bulletin No. 204: fetal growth restriction. Obstet Gynecol 2019;133:e97–109. [DOI] [PubMed] [Google Scholar]
  • 32.Macrosomia: ACOG Practice Bulletin, Number 216. Obstet Gynecol 2020;135:e18–35. [DOI] [PubMed] [Google Scholar]
  • 33.Grantz KL, Kim S, Grobman WA, et al. Fetal growth velocity: the NICHD Fetal Growth Studies. Am J Obstet Gynecol 2018;219:285.e1–36. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

supplement
NIHMS1838850-supplement-supplement.docx (21.3KB, docx)

RESOURCES