Intrauterine growth restriction (IUGR) refers to the abnormal growth of the fetus during pregnancy, defined as cases wherein the size of the fetus is below the 10th percentile [1, 2, 3]. The causes of IUGR can vary, but most are associated with chromosomal abnormalities, malnutrition of the pregnant individuals, complications due to pregnancy, or a lack of adequate oxygen supply to the fetus. It affects 3–10% of all pregnancies, and regarding the perinatal mortality rate, fetuses with IUGR have a four to eight times higher risk rate than normal births. Even if the infant survives, the mortality rate reaches 50%. Thus, early detection of IUGR is crucial in determining the delivery timing and neonatal care after delivery [4].

When morphologically classifying IUGR, it can be clinically divided into symmetrical types, characterized by reduced fetus’ head, femur length, abdominal circumference, and weight; and asymmetrical types, characterized by a normal head shape compared with the body. Symmetrical IUGR is caused by a relative decrease in cell proliferation from the early stage of pregnancy, resulting from genetic defects, congenital intrauterine infection, or chromosomal abnormalities; the size of the head and body becomes proportionally smaller, most commonly appearing before 28 weeks of pregnancy. Asymmetrical IUGR is almost always expressed in the third trimester and is caused by uteroplacental insufficiency, wherein oxygen and nutrients are not appropriately supplied, and brain size reduction rarely occurs [5, 6]. Almost 70% of IUGR is asymmetric, and normal growth is possible if adequate nutrition is provided after birth. Therefore, an immediate response after delivery can be ensured via predicting IUGR by classifying it into one of the two types [7, 8].

Fetal biometric parameters are mainly measured using ultrasound as a screening test for diagnosing IUGR, and accurately measuring gestational age plays a crucial role in determining the timing of labor induction and cesarean section. Gestational age is generally predicted by measuring the biparietal diameter, abdominal circumference (AC), and femur length [9, 10, 11, 12]. Yet, these simple parameters are significantly affected when redistribution of cardiac output occurs along with the brain-sparing effect in fetuses with IUGR. Thus, presenting various markers is necessary to complement conventional fetal biometric parameter measurements [13, 14].

According to previous studies, IUGR can increase diastolic blood flow in the fetal cerebral artery in the third trimester, cause a notch in the umbilical artery, and increase resistance in the uterine artery of the pregnant individual [15, 16, 17, 18, 19]. However, the cerebellum is not affected by the growth restriction since there is no change in blood flow in the cerebellum; thus, the transverse cerebellar diameter (TCD) is the most reliable independent biometric parameter when evaluating actual gestational age, which is used to evaluate fetal growth. Fetal AC is a biometric parameter first affected by the decrease in hepatic glycogen and subcutaneous fat accumulation in IUGR, which can be used in combination with TCD for growth changes and IUGR evaluation in normal fetuses with unknown gestational age [15, 16, 17, 18, 19]. The ratio of fetal TCD to AC is a reliable predictor for evaluating fetal growth, with several countries having suggested ratios suitable for their demographic. Therefore, this study aimed to evaluate the relationship between fetal TCD and AC and compare it with previous reports in other countries to determine the normal TCD/AC ratio for Korean fetuses. Our objectives were to establish a reference value for the TCD/AC ratio for Korean fetuses and to assess its effectiveness in early detection and management of IUGR.

A simple regression analysis was performed to understand the functional relationship between TCD and AC and gestational age and determine the effect of the two variables on gestational age. TCD showed a high correlation with gestational age (r = 0.982, p 0.001), increasing as gestational age increased. The regression equation to predict gestational age was gestational age (GA) = 5.847 + 7.216 $\times$ TCD, indicating a correlation of determination of 0.965. AC also increased as gestational age increased (r = 0.965, p 0.001), and the regression equation to predict gestational age was GA = 5.934 + 0.952 $\times$ AC, with a correlation of determination of 0.951. The correlation coefficient between TCD and AC was 0.961, showing a high correlation (Table 1).

The TCD/AC ratio exhibited a minimum value of 11.25, a maximum value of 14.97, and a total mean of 13.26. As shown in Table 2, the TCD/AC ratio was classified into the 5th, 10th, 50th, 90th, and 95th percentiles depending on gestational age. The TCD/AC ratio based on gestational age indicated a constant value, as shown in Fig. 1, and Table 3 (Ref. [23, 24, 25, 26, 27, 28, 29, 30, 31]) shows the normal standard values of the TCD/AC ratio for each country in previous studies.

Fig. 1.

Scatter diagram showing the relationship between TCD/AC ratio and gestational age in normal pregnancy cases. TCD, transverse cerebellar diameter; AC, abdominal circumference.

IUGR is one of the causes of increased perinatal morbidity, including fetal asphyxia, meconium aspiration, emergency cesarean delivery, and mortality [32]. Fetuses with IUGR are at approximately twice the risk of stillbirth than those with normal growth, accounting for 1.5% of all fetuses, and the risk increases even more if growth restriction is severe. Since fetal size reflects pathophysiology, IUGR refers to poor growth, as well as all conditions related to fetal development, including fetal maturity and wellbeing [33]. Therefore, the main purpose of prenatal care is to identify the cause and determine the optimal delivery timing by monitoring fetal wellbeing when IUGR is suspected. When IUGR is defined as being below the 10th percentile of birth weight, the growth curve standard used in Korea uses data from abroad that does not consider racial and sociocultural characteristics. Hence, using it as a Korean standard is not appropriate. Although studies evaluating fetal growth according to gestational age have been steadily performed in Korea, most studies simply measured biometric parameters using ultrasound [34, 35, 36, 37]. Additionally, these parameters may affect the accuracy of growth evaluation due to fetal growth and deformation caused by external pressure on the skull. However, TCD was found to be the most accurate variable for predicting gestational age, even under extreme fetal growth restriction, in the TCD nomogram; this is because the TCD is not easily deformed owing to blood preservation in the cerebellum, even in the presence of IUGR [34, 35, 36, 37].

Regarding IUGR, it has been reported that evaluating the TCD/AC ratio as a variable that may cause early deformation is a reliable and sensitive method for predicting IUGR [38]. Based on this previous study, the present study attempted to suggest a standard value for the independent TCD/AC ratio of Korean fetuses and explore its role as a marker for predicting IUGR. As a result, the mean TCD/AC ratio among 1011 normal fetuses was determined to be 13.26, indicating a constant value regardless of the change in gestational age. IUGR can be predicted at values above the 95th percentile, with the 95th percentile in this study determined to be 14.39. Thus, close observation is required to evaluate fetal growth when the TCD/AC ratio value exceeds 14.39. Exploring the study on the Western population in Table 2, the TCD/AC ratio in the normal control group showed a distribution of 13.17–14.79, which was higher than the results of our study in the Korean population. This finding is thought to reflect the difference in biological ratio between races. Most previous studies showed that the TCD/AC ratio cutoff value for IUGR was 15.40–16.00; this is 1.70–2.10 higher than that of the normal control group, indicating that the TCD/AC ratio is an ideal variable for predicting IUGR based on previous studies [23, 24, 25, 26, 27, 28, 29, 30, 31].

As this study was conducted retrospectively, a limitation arises from the inability to conduct a prospective comparison between the control group identified in previous studies and the IUGR experimental group, which may lead to biased results. Therefore, a prospective study on a larger scale is needed in the future. However, this study is significant as it is the first of its kind in Korea, where few studies have been attempted. Moreover, as the number of low-birth-weight infants due to advanced maternal age increases, it is expected that the results of this study will be used as an auxiliary means for predicting IUGR.

This study presented the mean percentile value of the TCD/AC ratio among 1011 Korean fetuses between 19–34 weeks of gestation. The TCD/AC ratio had a mean value of 13.26, regardless of gestational age, with a 95th percentile value of 14.39. Therefore, the suggested TCD/AC ratio can be used as a useful variable to evaluate normal fetal growth and predict IUGR.

AC, abdominal circumference; IUGR, intrauterine growth restriction; TCD, transverse cerebellar diameter.

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

SHY and DYL designed the research study. SHY performed the research. DYL analyzed the data. Both authors contributed to editorial changes in the manuscript. Both authors read and approved the final manuscript. Both authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The retrospective review of data for this study was approved by the Institutional Review Board (IRB) of the Catholic University of Pusan (CUPIRB-2022-01-003). Ultrasonography was conducted with the pregnant participants’ consent, and data measured by one examiner were used for analysis.

This research received no external funding.

The authors declare no conflict of interest.