Fetal growth velocity references from a Chinese population–based fetal growth study

Intrauterine growth marks the starting point of a 1000-day early life growth period. The quality of this growth can profoundly affect the likelihood of a child fulfilling their developmental potential [1, 2], and is closely related to health and disease in adults [3‐5]. Fetal ultrasound measurements during pregnancy are the main indicators of the quality of intrauterine growth. Comparison with fetal size curves determines whether the fetus has a size appropriate for gestational age [6]. Ultrasound measurements below the 10th percentile of the fetal size curve denote small–for–gestational age (SGA) status; they are important diagnostic criteria for fetal growth restriction (FGR) [7‐9], which increases the risk of adverse perinatal outcomes. Several fetal size curves have been developed for clinical practice [10‐12]. Choosing a chart that is appropriate for the genetic background and living environment of the population to which it is applied could improve the diagnostic power of SGA and FGR.

Traditional fetal size curves can assess fetal size at a specific time point, but provide little insight into dynamic changes occurring during the growth process. Fetal growth velocity, defined as the growth per unit time (e.g., g/week), can provide more insight into the growth process during a given period. A retrospective study of 4,285 singleton pregnancies showed that 74% of antepartum fetal deaths were not SGA at the time of the last ultrasound examination [13]. Compared to traditional fetal size curves, fetal growth velocity improved the sensitivity of predictions of antepartum fetal death (26.1 vs. 56.5%) [13]. Although several fetal growth velocity charts have been published [14‐19], there are none specifically intended for the Chinese population. This is the first study to develop a fetal growth velocity chart for the Chinese population.

Data were obtained from the Chinese Fetal Growth Study, a multi–center cohort study involving 24 hospitals in 18 provinces in China, which aimed to establish a fetal growth chart suitable for the Chinese population. The objective of the present study was to develop a fetal growth velocity chart for estimating fetal weight, biparietal diameter (BPD), abdominal circumference (AC), head circumference (HC), and femur diaphysis length (FDL) in the Chinese population. To facilitate clinical application, we devised a model to determine whether the fetal growth velocity between any two gestational weeks was below a given percentile on the velocity chart. Furthermore, we explored the association between fetal growth velocities in the bottom 10th percentile and adverse outcomes.

To our knowledge, this study is the first to attempt to develop a fetal growth velocity chart specific to the Chinese population. We established fetal growth velocity reference charts for EFW, AC, FDL, HC, and BPD according to gestational weeks. EFW velocity was shown to increase beginning at 12 gestational weeks, reaching a maximum velocity of 211.71 g/week at 35 gestational weeks, followed by a gradual decrease to 127.04 g/week at 40 gestational weeks. The other four biometric parameters showed similar patterns characterized by accelerations in the early second trimester peaking at 13 gestational weeks for BPD and HC, 14 gestational weeks for AC, and 15 gestational weeks for FDL. BPD and HC experienced a second acceleration in the mid and late second trimester, at 19–24 and 19–21 gestational weeks, respectively. Compared to traditional fetal size curves, we found that fetal growth velocities in the bottom 10th percentile provided more information associated with neonatal complications and preterm birth < 37 weeks.

EFW velocity was previously reported by the NICHD fetal growth study [18] in a US population, and by Guihard–Costa et al. [16] in a French population; the median EFW velocity patterns were similar to our findings. Both studies observed that EFW velocity peaked at around 35 gestational weeks, with maximum velocities of 220.66 and 209 g/week, respectively. However, after 36 gestational weeks, the EFW velocity of the NICHD fetal growth study decreased slower than in our study, resulting in a higher EFW velocity at the end of pregnancy relative to this study. This difference in third trimester EFW velocity may be due to the fact that the pregravid BMI of our Chinese mothers was lower than that of Asian American mothers, which limited fetal growth in the third trimester [26, 27].

In general, the patterns of BPD, HC, AC, and FDL velocities in our findings were consistent with previous studies. The NICHD fetal growth study and Guihard–Costa et al. reported acceleration of BPD, HC, and FDL velocities in the early second trimester, with peaks around 13–15 gestational weeks. However, the BPD velocity in the early second trimester reported here was higher than in both of the previous studies. The maximum velocity of HC was similar to Guihard–Costa et al., and higher than that of the NICHD fetal growth study, while the NICHD fetal growth study had the highest maximum velocity of FDL. The INTERGROWTH–21st project reported that fetal growth velocities from 16 gestational weeks, so the first acceleration seen in our study was not present in theirs; otherwise, the fetal growth velocities were similar, except for AC velocity. In our study, AC velocity decreased rapidly during the late third trimester, from 10.09 mm/week at 33 weeks to 4.69 mm/week at 40 weeks. In contrast, the AC velocity in the NICHD fetal growth study and INTERGROWTH–21st project did not exhibit this sharp decrease in the third trimester, and in fact showed a third acceleration after 38 weeks in the case of the NICHD fetal growth study. In addition to these above publications, two other studies also reported fetal growth velocities. Bertino et al. [14] reported the velocities of AC, FDL, HC, and BPD in an Italian population in 1996, which showed similar velocity curves to our population. However, their curves only showed one period of acceleration and peaked later than those of our participants. Fescina et al. [28] reported that, in a Latin American population, BPD velocity peaked at 13 weeks, decreased at around 15 weeks, stabilized from 15 to 30 weeks, and decreased again after 30 weeks [29]. We speculate that differences in fetal growth velocity can be partially explained by differences in genetic background and living environment between study populations. Higher AC and EFW velocities may be related to higher pregravid BMI in some populations [30, 31]; however, we note that epidemiological surveys showed that, due to lower maternal pregravid BMI, Chinese babies had lower birth weights than American and Chinese American babies [26, 27]. Furthermore, these studies employed different ultrasound equipment, participant inclusion criteria, and modeling methods, all of which may have affected fetal growth velocity trajectories.

Our findings showed that, compared to traditional fetal size curves, fetal growth velocity curves could provide additional information for associated with neonatal complications and preterm birth < 37 weeks. Moreover, sensitivity analysis showed that EFW velocity in the bottom 10th percentile was significantly associated with more adverse perinatal outcomes (including preterm birth < 37 weeks, admitted to NICU, neonatal complications) in the AGA group than the LGA and SGA groups. Hendrix et al. [32] reported similar findings, i.e., decreased fetal growth velocities between around 20 and 32 weeks were significantly associated with adverse neonatal outcomes (neonatal asphyxia, sepsis, respiratory distress syndrome, and transient shortness of breath) in AGA neonates. In a prospective cohort of 3977 pregnant women, Sovio et al. [33] found that, compared to EFW velocity alone in the bottom 10th percentile, AC velocity in the lowest decile was also associated with a higher relative risk of SGA and other adverse perinatal outcomes. Deter et al. [34], in a retrospective observational study of 126 pregnant women, found that the AC velocity of fetuses with restricted third–trimester growth was significantly lower than that of fetuses with normal growth. These reduced fetal growth velocities may indicate placental insufficiency, with both Kennedy et al. [35] and MacDonald et al. [36] reporting that reduced EFW and AC velocity in the third trimester was associated with a cerebroplacental ratio < 5th percentile at 36 gestational weeks, neonatal acidosis (umbilical artery pH < 7.15 at birth), and low neonatal body fat percentage (< 4.2% for males and < 5.8% for females). Summarizing our findings and the above–mentioned studies, fetal growth velocity curves can provide additional information for obstetric clinical practice, which could aid the identification of potentially high–risk AGA neonates.

There were some limitations to the present study. First, as it relied on real–world clinical data, the ultrasound examinations were non–uniformly distributed from 12 to 40 gestational weeks, with most pregnant women receiving three ultrasound examinations at around 22, 30, and 37 gestational weeks (consistent with the national policy of antenatal care in China [37], which recommends at least three ultrasound examinations for fetal anthropometry at the above times points). Therefore, the interval between two adjacent ultrasound examinations for most pregnant women exceeded 4 weeks, such that the fetal growth velocities calculated for the last two ultrasound examinations may have been slower than the actual velocities. Considering the above issues, we chose to calculate the derivative of the percentiles of the growth curve to obtain the percentiles of the velocity curves. The advantage of this method is that it can make full use of the data in our cohort and can estimate the instantaneous velocity at a given time point. However, in clinical practice, the instantaneous velocity is difficult to obtain, obstetricians usually calculate the average speed in 2 weeks for pregnancy monitoring, which is somewhat different from the velocity references in our study.

Here, we presented the first fetal growth velocity charts specific to the Chinese population. Our findings revealed modest differences in fetal growth velocities between Chinese populations and other populations. We recommend the utilization of fetal growth standards, including growth velocity curves, designed specifically for the population to which they are applied. More importantly, we found that fetal growth velocity lower than the 10th percentile provided more information to understand the risk of adverse perinatal outcomes, especially in AGA neonates. Finally, we suggest that future researchers consider adding fetal growth velocity to existing multivariable models to improve the accuracy of predictions of adverse perinatal outcomes.