The effect of maternal HMB supplementation on bone mechanical and geometrical properties, as well as histomorphometry and immunolocalization of VEGF, TIMP2, MMP13, BMP2 in the bone and cartilage tissue of the humerus of their newborn piglets.

The presented experiment focuses on assessing the impact of HMB (hydroxy-ß-methobutyrate) supplementation of mothers during pregnancy on the development of the skeletal system of their offspring. For this purpose, an experiment was carried out on 12 clinically healthy sows of the Great White Poland breed, which were divided randomly into two groups the control and the HMB group. All animals were kept under standard conditions and received the same feed for pregnant females. In contrast, females from the HMB group between 70 and 90 days were supplemented with 3-hydroxy-3-methylbutyle in the amount of 0.2g/kg b.w/day. Immediately after birth, the piglets were also divided into groups based on: sex, and presence or lack HMB supplementation, and subsequently were euthanized and humerus bones from all piglets were collected. Mother's HMB supplementation during pregnancy affected the multiple index of their offspring. The higher humerus mass and length was observed with the greater effect in males. Maternal supplementation also influenced on the geometrical and mechanical properties of the humerus as in the case of mass, this effect was higher in males. Also, the collagen structure of the compacted and trabecular bone changed under the HMB addition. Maternal supplementation also affected the expression of selected proteins in growth cartilage and trabecular bone. The obtained results show that the administration to the mother during pregnancy by the HMB significantly affects the development of the humerus in many ways. The obtained results also confirm the utility of such experiments in understanding of the importance of the pregnancy diet as an develop and adaptable factor of offspring organisms and are the base for further research in that area as well as in the protein markers expression area.

Differences in fetal fractional limb volume changes in normal and gestational diabetic pregnancies: an exploratory observational study.

OBJECTIVE: Fetal fractional limb volume has been proposed as a useful measure for quantifying fetal soft tissue development. The aim of this study was to investigate the growth of fractional arm volume (AVol) and fractional thigh volume (TVol) of fetuses with maternal gestational diabetes (GDM) compared with those of fetuses with normal glucose tolerance (NGT). We hypothesised fetal fractional limb volume would be larger in the GDM group than in the NGT group in late gestation. DESIGN: Exploratory observational study. SETTING: Saitama Municipal Hospital. SAMPLE: A total of 165 (125 NGT and 40 GDM) singleton Japanese pregnant women. METHODS: AVol and TVol were assessed between 20 and 37 weeks' gestation as cylindrical limb volumes based on 50% of the fetal humeral or femoral diaphysis length. Women were diagnosed as GDM based on the criteria of the Japan Society of Obstetrics and Gynecology. MAIN OUTCOME MEASURES: AVol and TVol were compared between women with NGT and those with GDM at each gestational age period (2-week intervals from 20 to 37 weeks' gestation). RESULTS: Overall, 287 ultrasound scans were performed (NGT group, 205 scans; GDM group, 82 scans). There was no significant difference of AVol between the groups before 32 weeks' gestation. AVol was significantly larger in the GDM group than in the NGT group after 32 weeks' gestation (P < 0.05). TVol was not statistically different between the groups across gestation. CONCLUSIONS: Detection of variations in fetal AVol may provide greater insight into understanding the origins of altered fetal body proportion in GDM. TWEETABLE ABSTRACT: AVol, but not TVol, is significantly larger in fetuses with GDM than in those with NGT after 32 weeks' gestation.

Association of Maternal Obesity With Longitudinal Ultrasonographic Measures of Fetal Growth: Findings From the NICHD Fetal Growth Studies-Singletons.

Importance: Despite the increasing prevalence of pregravid obesity, systematic evaluation of the association of maternal obesity with fetal growth trajectories is lacking. Objective: To characterize differences in fetal growth trajectories between obese and nonobese pregnant women, and to identify the timing of any observed differences. Design, Setting, and Participants: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons study enrolled cohorts of pregnant women at 12 US health care institutions. Obese women (with prepregnancy body mass index > 30) and nonobese women (prepregnancy body mass indexes, 19-29.9) without major chronic diseases were recruited between 8 weeks and 0 days' gestation and 13 weeks and 6 days' gestation. A mixed longitudinal randomization scheme randomized participants into 1 of 4 schedules for 2-dimensional and 3-dimensional ultrasonograms to capture weekly fetal growth data throughout the remainder of their pregnancies. Main Outcomes and Measures: On each ultrasonogram, fetal humerus length, femur length, biparietal diameter, head circumference, and abdominal circumference were measured. Fetal growth curves were estimated using linear mixed models with cubic splines. Median differences in the fetal measures at each gestational week of the obese and nonobese participants were examined using the likelihood ratio and Wald tests after adjustment for maternal characteristics. Results: The study enrolled 468 obese and 2334 nonobese women between 8 weeks and 0 days' gestation and 13 weeks and 6 days' gestation. After a priori exclusion criteria, 443 obese and 2320 nonobese women composed the final cohort. Commencing at 21 weeks' gestation, femur length and humerus length were significantly longer for fetuses of obese woman than those of nonobese women. Differences persisted in obese and nonobese groups through 38 weeks' gestation (median femur length, 71.0 vs 70.2 mm; P = .01; median humerus length, 62.2 vs 61.6 mm; P = .03). Averaged across gestation, head circumference was significantly larger in fetuses of obese women than those of nonobese women (P = .02). Fetal abdominal circumference was not greater in the obese cohort than in the nonobese cohort but was significantly larger than in fetuses of normal-weight women (with body mass indexes between 19.0-24.9) commencing at 32 weeks (median, 282.1 vs 280.2 mm; P = .04). Starting from 30 weeks' gestation, estimated fetal weight was significantly larger for the fetuses of obese women (median, 1512 g [95% CI, 1494-1530 g] vs 1492 g [95% CI, 1484-1499 g]) and the difference grew as gestational age increased. Birth weight was higher by almost 100 g in neonates born to obese women than to nonobese women (mean, 3373.2 vs 3279.5 g). Conclusions and Relevance: As early as 32 weeks' gestation, fetuses of obese women had higher weights than fetuses of nonobese women. The mechanisms and long-term health implications of these findings are not yet established.

Ossification center of the humeral shaft in the human fetus: a CT, digital, and statistical study.

PURPOSE: The knowledge of the development of the humeral shaft ossification center may be useful both in determining the fetal stage and maturity and for detecting congenital disorders, as well. This study was performed to quantitatively examine the humeral shaft ossification center with respect to its linear, planar, and volumetric parameters. MATERIALS AND METHOD: Using methods of CT, digital image analysis, and statistics, the size of the humeral shaft ossification center in 48 spontaneously aborted human fetuses aged 17-30 weeks was studied. RESULTS: With no sex differences, the best-fit growth dynamics for the humeral shaft ossification center was modeled by the following functions: y = -78.568 + 34.114 × ln (age) ± 2.160 for its length, y = -12.733 + 5.654 × ln(age) ± 0.515 for its proximal transverse diameter, y = -4.750 + 2.609 × ln (age) ± 0.294 for its middle transverse diameter, y = -10.037 + 4.648 × ln (age) ± 0.560 for its distal transverse diameter, y = -146.601 + 11.237 × age ± 19.907 for its projection surface area, and y = 121.159 + 0.001 × (age)4 ± 102.944 for its volume. CONCLUSIONS: With no sex differences, the ossification center of the humeral shaft grows logarithmically with respect to its length and transverse diameters, linearly with respect to its projection surface area, and fourth-degree polynomially with respect to its volume. The obtained morphometric data of the humeral shaft ossification center are considered normative for respective prenatal weeks and may be of relevance in both the estimation of fetal ages and the ultrasonic diagnostics of congenital defects.

Cross-sectional study of fetal long-bone length in an Iranian population at 17-25 weeks of gestation.

OBJECTIVE: To construct improved reference charts for fetal long bones in an Iranian setting and to compare them with previous studies. METHODS: The present prospective cross-sectional study included singleton fetuses assessed by ultrasonography at 17-25 weeks of gestation at the Comprehensive Medical Genetics Center, Shahid Soltani, Shiraz, Iran between May 1, 2012, and February 28, 2014. Exclusion criteria included conditions that could affect fetal growth. Fetal long bones (femur, humerus, tibia, fibula, ulna, and radius) were measured with ultrasonography and biometric charts were produced. Regression models were fitted to estimate bone lengths. The models produced were compared with those from previous studies in other populations. RESULTS: There were 660 singleton fetuses included and 660 femur, 633 humerus, 512 tibia, 498 fibula, 505 ulna, and 498 radius biometric measurements were recorded. The models generated to predict the length of the tibia, fibula, ulna, and radius from the length of the femur and humerus demonstrated a high goodness of fit when the predicted lengths were plotted against the actual lengths. Comparisons of mean lengths with previous studies suggested that long-bone length was affected by maternal ethnicity. CONCLUSION: The equations generated could be used to predict long-bone length in an Iranian population and ethnicity should be considered when using fetal long-bone length as a prenatal diagnostic tool.

Risk of Adverse Outcomes in Euploid Pregnancies With Isolated Short Fetal Femur and Humerus on Second-Trimester Sonography.

OBJECTIVES: The purpose of this study was to evaluate pregnancies with isolated short fetal femur and humerus on second-trimester sonography. Short fetal long bones are known to be associated with aneuploidy and structural anomalies. In this study, we wanted to show the risk of adverse pregnancy outcomes in euploid and nonanomalous pregnancies. METHODS: Singleton pregnancies with short femur and humerus were included. Pregnancies with normal fetal bone lengths and age-matched mothers were selected as controls. RESULTS: The study group included 30 pregnancies with short fetal femur and humerus, and the control group included 60 normal pregnancies. The overall odds ratio for an adverse pregnancy outcome in the study group was 24.9. Preterm delivery occurred significantly more frequently (odds ratio, 20.8; P < .001), and one-third of pregnancies were complicated by preeclampsia. In the group with short long bones, the odds ratio for a pathologic umbilical Doppler flow pattern was 45.2 (P < .001), and birth weight was significantly lower (P < .001). Also, 3 (10.3%) stillbirths and 4 (13.3%) cases of early neonatal death were recorded in this group. These complications were not recorded in the control group. The risk of emergency cesarean delivery was significantly higher in the group with short long bones (odds ratio, 11.8; P < .001). CONCLUSIONS: The risk of adverse pregnancy outcomes is significant in euploid and nonanomalous pregnancies with isolated short long bones. Close follow-up is needed during pregnancy.

Maternal 25-hydroxyvitamin D level and fetal bone growth assessed by ultrasound: a systematic review.

OBJECTIVES: To assess systematically the role of maternal vitamin D levels in fetal bone growth. METHODS: PubMed, EMBASE and Cochrane databases were searched using the search words [Vitamin D] in combination with [fetal, fetus, intrauterine, or prenatal AND growth, development, bone, femur, or humerus]; [crown-rump length]; or [ultrasonography, prenatal]. Criteria for inclusion in this systematic review were data on maternal serum 25-hydroxyvitamin D (25(OH)D) during pregnancy and measurement of fetal growth by ultrasound. RESULTS: We identified 750 publications initially, from which five observational studies were selected for inclusion in the final review. The parameters studied were humerus length (HL) and femur length (FL) and their Z-scores, femoral volume, femoral distal metaphyseal cross-sectional area (CSA), femoral proximal metaphyseal diameter (PMD), femoral mid-shaft diameter and crown-rump length. In one study, 25(OH)D was associated directly with FL; in another study 25(OH)D only correlated with FL and HL Z-scores when calcium intake was insufficient. Two studies found no association between 25(OH)D and FL, but detected a direct association with femoral PMD, and an inverse relation with femoral distal metaphyseal CSA, respectively. CONCLUSIONS: Observational studies investigating the role of maternal vitamin D levels in fetal bone growth are sparse. Their evidence suggests that low maternal 25(OH)D levels may affect fetal bone growth under certain circumstances, especially in cases of simultaneous low calcium intake. Further studies are necessary.

Normal range for fetal urine production rate customized by biometry.

OBJECTIVE: The aim of this study was to develop a nomogram for fetal urine production (UPR) using biometric parameters. METHODS: A cross-sectional study was performed in 110 normal singleton fetuses with gestational ages ranging from 20 to 40 weeks. UPR was measured using tridimensional ultrasound (3-DUS) virtual organ computer-aided analysis. UPR (ml/h) was calculated during the filling phase using the equation, UPR = (VFB2-VFB1)/time. The values for UPR were plotted as a function of fetal biometry (femur, humerus, abdominal circumference, and head circumference and biparietal diameter) to obtain a nomogram for each parameter. RESULTS: A total of 110 normal singleton fetuses with gestational age between 20 and 40 weeks were investigated. Five of them were excluded because the image quality was insufficient for correct visualization of the bladder contour. Linear regression analysis of UPR as a function of femur, humerus, abdominal circumference, and head circumference and biparietal diameter generated curves that represents the normal range for UPR by fetal biometry, and expressed by the following equations: (1) Humerus length (HL): ln (UPR) = -5.9546 + 0.0958 × HL (mm); (R(2) 0.6422); (2) abdominal circumference: ln (UPR) = -1.0981 + 0.158 × AC (mm); (R(2) 0.6328); (3) femur length: ln (UPR) = -1.5133 + 0.0803 × FL (mm); (R(2) 0.6611); (4) biparietal diameter ln (UPR) = -7.8779 + 0.2368 × BPD-0.0012 × DBP(2); (R(2) 0.7066). Although BPD has the highest correlation coefficient (R(2) 0.7066) there was no statistical significant difference between the parameters investigated for UPR prediction. CONCLUSION: The use of biometric parameters for prediction of fetal UPR seems to be useful and can avoid the necessity of building local nomograms for different populations. The same strategy should be considered to other fields in fetal medicine.

Normal ranges for fetal femur and humerus diaphysis length during the second trimester in an Iranian population.

OBJECTIVES: Shortening of the fetal long bones is a sonographic soft marker for screening of Down syndrome in the second trimester that can be influenced by ethnicity. The purpose of this study was to provide normal reference ranges for femur and humerus diaphysis length during the second trimester of pregnancy in an Iranian population. METHODS: This cross-sectional study was performed on 3011 singleton fetuses at 15 to 28 weeks' menstrual age. The relationship between menstrual age and both femur and humerus diaphysis length was determined, and percentile values for each menstrual week were provided. RESULTS: The median femur diaphysis length ranged from 18.05 mm at 15 menstrual weeks to 52.20 mm at 28 menstrual weeks, and the mean humerus diaphysis length ranged from 17.65 mm at 15 menstrual weeks to 48.10 mm at 28 menstrual weeks. There was a linear relationship between menstrual age and both femur diaphysis length (R² = 0.957) and humerus diaphysis length (R² = 0.941). CONCLUSIONS: We have provided normal reference ranges for femur and humerus diaphysis length during the second trimester of pregnancy in an Iranian population.

Cartilage-specific ß-catenin signaling regulates chondrocyte maturation, generation of ossification centers, and perichondrial bone formation during skeletal development.

The WNT/ß-catenin signaling pathway is a critical regulator of chondrocyte and osteoblast differentiation during multiple phases of cartilage and bone development. Although the importance of ß-catenin signaling during the process of endochondral bone development has been previously appreciated using a variety of genetic models that manipulate ß-catenin in skeletal progenitors and osteoblasts, genetic evidence demonstrating a specific role for ß-catenin in committed growth-plate chondrocytes has been less robust. To identify the specific role of cartilage-derived ß-catenin in regulating cartilage and bone development, we studied chondrocyte-specific gain- and loss-of-function genetic mouse models using the tamoxifen-inducible Col2Cre(ERT2) transgene in combination with ß-catenin(fx(exon3)/wt) or ß-catenin(fx/fx) floxed alleles, respectively. From these genetic models and biochemical data, three significant and novel findings were uncovered. First, cartilage-specific ß-catenin signaling promotes chondrocyte maturation, possibly involving a bone morphogenic protein 2 (BMP2)-mediated mechanism. Second, cartilage-specific ß-catenin facilitates primary and secondary ossification center formation via the induction of chondrocyte hypertrophy, possibly through enhanced matrix metalloproteinase (MMP) expression at sites of cartilage degradation, and potentially by enhancing Indian hedgehog (IHH) signaling activity to recruit vascular tissues. Finally, cartilage-specific ß-catenin signaling promotes perichondrial bone formation possibly via a mechanism in which BMP2 and IHH paracrine signals synergize to accelerate perichondrial osteoblastic differentiation. The work presented here supports the concept that the cartilage-derived ß-catenin signal is a central mediator for major events during endochondral bone formation, including chondrocyte maturation, primary and secondary ossification center development, vascularization, and perichondrial bone formation.

Development of fetal trabecular micro-architecture in the humerus and femur.

It is widely accepted that during postnatal development trabecular bone adapts to the prevailing loading environment via modelling. However, very little is known about the mechanisms (whether it is predominantly modelling or remodelling) or controls (such as whether loading influences development) of fetal bone growth. In order to make inferences about these factors, we assessed the pattern of fetal trabecular development in the humerus and femur via histomorphometric parameter quantification. Growth and development (between 4 and 9 months prenatal) of trabecular architecture (i.e. thickness, number and bone volume fraction) was compared across upper and lower limb bones, proximal and distal regions, and sexes. The data presented here indicate that during prenatal development trabeculae became thicker and less numerous, whilst bone volume fraction remained constant. This partly mimics the pattern of early postnatal development (0-2 years) described by other researchers. Thickness was reported to increase whilst number reduced, but bone volume fraction decreased. This is perhaps because the balance of bone modelling (deposition vs. resorption) changes post partum. Published histological data suggest that bone deposition slows after birth, while resorption rates remain constant. Hence, fetal development may be characterized by relatively high rates of modelling and, particularly, bone deposition in comparison to postnatal. With respect to measures of thickness, number and bone volume fraction prenatal development was not bone, site, or sex specific, whilst postnatally these measures of architecture diverge. This is despite reported developmental variation in the frequency, speed and amplitude of fetal movements (which begin after 11 weeks and continue until birth), and probably therefore loading induced by muscular contractions. This may be because prenatal limb bone micro-architecture follows a generalised predetermined growth trajectory (or genetic blueprint), as appears to be the case for gross distribution of trabecular tissue.

Chondrocyte-specific ablation of Osterix leads to impaired endochondral ossification.

Osterix (Osx) is an essential transcription factor required for osteoblast differentiation during both intramembranous and endochondral ossification. Endochondral ossification, a process in which bone formation initiates from a cartilage intermediate, is crucial for skeletal development and growth. Osx is expressed in differentiating chondrocytes as well as osteoblasts during mouse development, but its role in chondrocytes has not been well studied. Here, the in vivo function of Osx in chondrocytes was examined in a chondrocyte-specific Osx conditional knockout model using Col2a1-Cre. Chondrocyte-specific Osx deficiency resulted in a weak and bent skeleton which was evident in newborn by radiographic analysis and skeletal preparation. To further understand the skeletal deformity of the chondrocyte-specific Osx conditional knockout, histological analysis was performed on developing long bones during embryogenesis. Hypertrophic chondrocytes were expanded, the formation of bone trabeculae and marrow cavities was remarkably delayed, and subsequent skeletal growth was reduced. The expression of several chondrocyte differentiation markers was reduced, indicating the impairment of chondrocyte differentiation and endochondral ossification in the chondrocyte-specific Osx conditional knockout. Taken together, Osx regulates chondrocyte differentiation and bone growth in growth plate chondrocytes, suggesting an autonomous function of Osx in chondrocytes during endochondral ossification.

Biophysical stimuli induced by passive movements compensate for lack of skeletal muscle during embryonic skeletogenesis.

In genetically modified mice with abnormal skeletal muscle development, bones and joints are differentially affected by the lack of skeletal muscle. We hypothesise that unequal levels of biophysical stimuli in the developing humerus and femur can explain the differential effects on these rudiments when muscle is absent. We find that the expression patterns of four mechanosensitive genes important for endochondral ossification are differentially affected in muscleless limb mutants, with more extreme changes in the expression in the humerus than in the femur. Using finite element analysis, we show that the biophysical stimuli induced by muscle forces are similar in the humerus and femur, implying that the removal of muscle contractile forces should, in theory, affect the rudiments equally. However, simulations in which a displacement was applied to the end of the limb, such as could be caused in muscleless mice by movements of the mother or normal littermates, predicted higher biophysical stimuli in the femur than in the humerus. Stimuli induced by limb movement were much higher than those induced by the direct application of muscle forces, and we propose that movements of limbs caused by muscle contractions, rather than the direct application of muscle forces, provide the main mechanical stimuli for normal skeletal development. In muscleless mice, passive movement induces unequal biophysical stimuli in the humerus and femur, providing an explanation for the differential effects seen in these mice. The significance of these results is that forces originating external to the embryo may contribute to the initiation and progression of skeletal development when muscle development is abnormal.

Bilateral asymmetry of the humerus during growth and development.

The development of handedness throughout growth can be investigated by using bilateral asymmetry of the humerus as a proxy for this trait. A large skeletal sample of nonadults from English archaeological sites was examined using standard metric techniques to assess when right-sided asymmetry first appears in the human skeleton. Results of this work indicate a change in directional asymmetry during growth and development, with infants and young children exhibiting no significant asymmetry and older children and adolescents demonstrating right-sidedness. This trend is consistent with what has been observed in previous studies of upper limb asymmetry in skeletal material and behaviorally in living children, adding further strength to the premise that biomechanical forces strongly influence bilateral asymmetry in the upper limb bones. Variability in the magnitude of asymmetry between different features of the humerus was also noted. This characteristic can be explained by differing degrees of genetic canalization, with length and articular dimensions being more strongly canalized than diaphyseal properties.

Second trimester fetal nasal bone length in a low-risk Turkish population.

OBJECTIVE: To define normal values of second trimester fetal nasal bone length (NBL) in a low-risk Turkish population. METHOD: Prenatal records of singleton fetuses who underwent second trimester ultrasonographic examination in the 16 to 23 weeks of pregnancy were retrospectively analyzed for NBL and biometric measurements (BPD, FL and HL). The relationship among NBL and gestational age (GA), biparietal diameter (BPD), femur length (FL) and humerus length (HL) was determined. Additionally, percentile values of NBL for each gestational week were provided. RESULTS: A total of 1467 fetuses were included in this study. There was a significant linear association among NBL and GA (R(2) = 0.709), BPD (R(2) = 0.752), FL (R(2) = 0.742) and HL (R(2) = 0.747). Fifth percentile values of fetal NBL were 3.11 mm for 16th, 3.50 mm for 17th, 3.70 mm for 18th, 4.10 mm for 19th, 4.50 mm for 20th, 4.62 mm for 21st, 5.24 mm for 22nd and 5.37 mm for 23rd gestational weeks. CONCLUSION: The study provides normal ranges of NBL between 16 and 23 weeks of pregnancy in a low-risk Turkish population. Future studies with larger sample sizes including pregnancies carrying high risk for aneuploidy are needed to define cut-off values for NBL.

Multidimensional standard curve for the development process of human fetuses.

The present paper considers a multidimensional view of the standard for the development process of human fetuses. An efficient method by which to find a multidimensional standard curve for the development process of human fetuses is proposed in which a logistic function with three parameters is utilized as an underlying model and a nonlinear regression method is applied. The proposed method also identifies an approximate prediction region, which can be efficiently applied to diagnose fetal malformation.

The effect of fetal gender in predicting Down syndrome using long bone ultrasonographic measurements.

OBJECTIVE: To determine if fetal gender affects the screening efficiency of short femur and humerus lengths in the prediction of trisomy 21. METHODS: Retrospective cohort study of 62 111 patients presenting for ultrasound from 1990 to 2006. Short humerus and femur lengths were defined using (1) biparietal diameter (BPD) to femur/humerus length (FL/HL) ratios > 1.5 standard deviations above the mean, (2) the observed to expected (O/E) ratio of femur length ≤ 0.91 or humerus length ≤ 0.89, and (3) femur and humerus lengths < 5th percentile. The sensitivity, specificity, and likelihood ratios were calculated for the association of short FL/HL and trisomy 21 stratified by gender. RESULTS: Both BPD/long bone ratios as well as O/E ratios demonstrated a statistically significant higher specificity for the detection of trisomy 21 in female fetuses. This difference was most clinically significant when using the O/E ratio, which yielded a specificity of 82.6% in males and 90.6% in females for short femur, and 69.7% in males and 77.9% in females for short humerus, when these markers were evaluated as isolated findings. CONCLUSION: Gender-specific differences in the effectiveness of both short femur and humerus lengths for the prediction of trisomy 21 may exist, but their presence and magnitude are largely dependent on the formula used.

Do race-specific definitions of short long bones improve the detection of down syndrome on second-trimester genetic sonograms?

OBJECTIVE: The purpose of this study was to determine whether the use of race-specific definitions of short femur and humerus lengths improves Down syndrome detection. METHODS: This was a retrospective cohort study over 16 years. For each self-reported maternal race (white, African American, Hispanic, and Asian), we evaluated the efficiency of Down syndrome detection using published race-specific formulas compared with a standard formula for short femur and humerus lengths (observed versus expected lengths < or =0.91 and < or =0.89, respectively). The sensitivity, specificity, and 95% confidence intervals for each parameter were compared. Screening performance was compared by areas under the receiver operating characteristic curves. RESULTS: Of 58,710 women, 209 (0.3%) had a diagnosis of a fetus with Down syndrome. Although the race-based formula increased sensitivity in each population, the increase was statistically significant only in the white population, whereas a decrease in specificity was statistically significant in all 4 populations, as denoted by nonoverlapping confidence intervals. The area under the receiver operating characteristic curve for the model using the race-specific definition of short femur length was 0.67 versus 0.65 compared with the standard definition, and for humerus length it was 0.70 versus 0.71. CONCLUSIONS: The use of race-based formulas for the determination of short femur and humerus lengths did not significantly improve the detection rates for Down syndrome.