There\'s a paucity of robust normal fractional limb and organ volume standards from a large and diverse ethnic population. The Fetal 3D Study was designed to develop research and clinical applications for fetal soft tissue and organ volume assessment. The NICHD Fetal Growth Studies (2009-2013) collected 2D and 3D fetal volumes. In the Fetal 3D Study (2015-2019), sonographers performed longitudinal 2D and 3D measurements for specific fetal anatomical structures in research ultrasounds of singletons and dichorionic twins. The primary aim was to establish standards for fetal body composition and organ volumes, overall and by maternal race/ethnicity, and determine whether these standards vary for twins versus singletons. We describe the study design, methods, and details about reviewer training. Basic characteristics of this cohort, with their corresponding distributions of fetal 3D measurements by anatomical structure, are summarized. This investigation is responsive to critical data gaps in understanding serial changes in fetal subcutaneous fat, lean body mass, and organ volume in association with pregnancy complications. In the future, this cohort can answer critical questions regarding the potential influence of maternal characteristics, lifestyle factors, nutrition, and biomarker and chemical data on longitudinal measures of fetal subcutaneous fat, lean body mass, and organ volumes.

Up until now, bovine fetometry has been entirely based on 2-dimensional ultrasonography. Fetal size is estimated by several linear measurements such as crown-rump length (CRL). However, the advent of 3-dimensional ultrasonography (3D-US) provides in vivo access to the volumes of the fetus and its amniotic sac. The objective of this preliminary observational study was to determine the variability of conceptus-related volumes using transrectal 3D-US in dairy cows and to identify factors affecting them. Furthermore, relationships between the gained measurements and calf birth weight were investigated. In total, 315 Simmental and Holstein-Friesian dairy cows were transrectally examined at d 42 after breeding using a portable ultrasound device (Voluson I, GE Healthcare). Gestational volumes including fetal volume (FV) and amniotic sac volume (ASV) were determined with the software tool VOCAL (Virtual Organ Computer-Aided Analysis, GE Healthcare), whereas amniotic fluid volume (AFV) values were derived from the subtraction of FV from ASV. The CRL was determined by means of 3-dimensional data. The mean values and standard deviations for FV, ASV, AFV, and CRL were 1.47 ± 0.25 cm3, 5.86 ± 1.22 cm3, 4.38 ± 1.02 cm3, and 2.38 ± 0.18 cm, respectively. All gestational volumes and CRL values were affected by breed. In Simmental cattle, larger concepti were observed compared with pregnancies derived from Holstein-Friesian animals. Parity affected only ASV and AFV, with heifers showing greater values than lactating cows. The CRL was positively associated with milk protein content. It was not possible to predict calf weight at birth by using FV, ASV, or AFV; however, tendencies were found for ASV and AFV. The present study was the first to adopt 3D-US volumetry to assess early pregnancy development in dairy cattle. Our results showed that this method could be used successfully to identify minor variations in conceptus growth.

The aim of this study was to investigate if transrectal three-dimensional (3D) ultrasound is a reliable technique to measure equine fetal volume (FV) during early gestation in mares. In total 149 warmblood mares were examined once transrectally on days 45 ± 1 of pregnancy with a portable 3D ultrasound device (Voluson® i, GE Healthcare, Zipf, Austria). The following measurements were performed: Two-dimensional (2D) and 3D crown-rump length (CRL), FV using Virtual Organ Computer-aided AnaLysis (VOCAL™) software with rotational angles of 6° and 30°. To analyze intra- and inter-observer reliability (intraclass correlation coefficient (ICC)) and agreement (Bland-Altman\'s limits of agreement (LoA)) of FV measurements, images from 60 horse fetuses were selected and repeatedly analyzed by the same examiner (A) and by a second examiner (B). The time for each ultrasound examination (2D and 3D) and for the FV measurements was recorded. The 3D measured CRL was larger (P < 0.001) than the 2D CRL. Repeated measurements of 3D CRL showed a higher reliability (ICC = 0.91 (0.88-0.94), P < 0.001) and agreement (mean = 0.13%, 95% LoA: 7.45 to +7.19) compared to reliability (ICC = 0.50 (0.36-0.61), P < 0.001) and agreement (mean = -1.54%, 95% LoA: 23.29 to +20.21) of the CRL measurement in 2D mode. For intra-observer examinations, reliability was highest when using a rotational angle of 30° (ICC = 0.98 (0.97-0.99), P < 0.001). The inter-observer reliability of 3D measurements was good (ICC = 0.85 (0.67-0.92), P < 0.001). The extra time needed to perform the 3D scan ranged from 1 to 9 min and FV measurements lasted 03:30 ± 00:46 and 08:10 ± 01:05, for rotational angles of 30° and 6°, respectively. In conclusion, this study showed a high level of intra- and inter-observer reliability and agreement for FV measurements using VOCAL™. Furthermore, the 6° and 30° rotational angles can be used interchangeably, but test duration, reliability and agreement were better with the 30° rotational step method. The CRL measurements obtained with 3D mode probably reflects the true CRL, compared to the 2D measured CRL.

OBJECTIVE: This study aimed to determine the relationship between birth weight, and maternal serum insulin-like growth factor-binding protein-1 (IGFBP-1) and kisspeptin-1 (KISS-1) levels, and first-trimester fetal volume (FV) based on three-dimensional ultrasonography.
METHODS: The study included 142 pregnant women at gestational week 11°-136. All fetuses were imaged ultrasonographically by the same physician. Maternal blood samples were collected at the time of ultrasonographic evaluation and analyzed for IGFBP-1 and KISS-1 levels via enzyme-linked immunosorbent assay (ELISA). Maternal and neonatal weights were recorded at birth. Birth weight ≤10th and the >90th percentiles was defined as small and large for gestational age (SGA and LGA), respectively.
RESULTS: Median crown-rump length (CRL), FV, and maternal serum IGFBP-1 and KISS-1 levels were 58.2 mm (35.3-79.2 mm), 16.3 cm3 (3.8-34.4 cm3), 68.1 ng mL-1 (3.8-377.9 mL-1), and 99.7 ng L-1 (42.1-965.3 ng L-1), respectively. First-trimester IGFBP-1 levels were significantly lower in the mothers with LGA neonates (p < .05). There was a significant positive correlation between CRL and FV, and between the IGFBP-1 and KISS-1 levels. IGFBP-1 levels and maternal weight at delivery were negatively correlated with neonatal birth weight. There was no correlation between CRL or FV and maternal IGFBP-1 or KISS1 levels (p > .05). The maternal IGFBP-1 level during the first trimester was a significant independent factor for SGA and LGA neonates (Odds ratio (OR): 0.011, 95%CI: 1.005-1.018, p < .001; and OR: 1.297, 95%CI: 1.074-1.566, p = .007, respectively). There was no significant relationship between SGA or LGA, and CRL, FV, or the KISS-1 level.
CONCLUSIONS: As compared to the maternal KISS-1 level, the maternal IGFBP-1 level during the first trimester might be a better biomarker of fetal growth. Additional larger scale studies are needed to further delineate the utility of IGFBP-1 as a marker of abnormal birth weight.

OBJECTIVE: To determine whether fetal volume (FV) measured by three-dimensional (3D) ultrasound was able to detect fetuses at risk of low birth weight (primary outcome) and/or preterm labor (secondary outcome).
METHODS: One hundred pregnant women carrying a singleton living pregnancy who were sure of dates, and had a dating scan, with gestational age between 11 weeks and 13 weeks+6 days coming for routine first trimester nuchal translucency (NT) were examined by both two-dimensional (2D) and 3D ultrasound (Vocal System) for crown-rump length (CRL) and FV then followed up regularly every 4 weeks until 28 weeks then biweekly until 36 weeks then weekly until delivery both clinically and by ultrasound biometry.
RESULTS: Eighty-seven cases had a normal outcome, while the remaining 13 cases had either preterm labor (four cases) or low-birth weight (nine cases). FV positively correlated with CRL (P=0.026), gestational age in weeks (P=0.002), neonatal body weight in grams (P=0.018) and neonatal body length at birth (P=0.04). A mean FV of 8.3 mm3 was association with neonatal complications (P=0.045). A cut-off point of 9 mm3 for FV was associated with 100% sensitivity for detection of the date of birth, while a cut-off point of 9.15 mm3 for FV was associated 100% sensitivity for detection of neonatal birth weight.
CONCLUSIONS: 3D assessment of FV in the first trimester provides an accurate method for predicting pregnancy outcome namely low birth weight and neonatal complications, however, it is a better positive predictor than a negative one.

Intra- and inter-observer reproducibility of fetal volume measurement by 3-D ultrasound scan (using VOCAL [Virtual Organ Computer-Aided Analysis] software) in 27 fetuses at 7 to 13 wk was studied. For intra-observer variability, the mean difference (MD) and 95% limits of agreement (95% LOA) at 12°, 18° and 30° were MD(12) = 0.097, 95% LOA(12) = -0.87 to +1.06; MD(18) = 0.07, 95% LOA(18) = -1.31 to +1.45; and MD(30) = -0.07, 95% LOA(30) = -1.55 to +1.41. The standard deviation of the differences (SD(DIF)) increased with crown-rump length at 12° (p = 0.0016), 18° (p = 0.0011) and 30° (p = 0.02). For inter-observer variability, MD(12) = 0.15, 95% LOA(12) = -1.65 to +1.95; MD(18) = 0.042, 95% LOA(18) = -1.79 to +1.87; and MD(30) = 0.19, 95% LOA(30) = -1.24 to +1.62. SDDIF increased with crown-rump length at 18° (p = 0.0084) and 30° (p = 0.0073). The accuracy of fetal volume measurement was not influenced by rotational angle or fetal size. Precision deteriorated for wider rotational angles and larger fetuses.