Fetal short femur length as a minor marker for fetal aneuploidies, skeletal dysplasia and intrauterine growth restriction: risk stratification for isolated and not isolated finding in different gestational age

Introduction. Fetal short femur is defined by a femur length below the 5th percentile or -2 DS for the gestational age. The finding of a short femur represents a diagnostic dilemma for the various differential diagnosis. It may be associated with skeletal dysplasia, aneuploidies or genetic syndromes. In the isolated form, it may be an early sign of placental insufficiency and growth delay, or a normal variant in constitutionally small fetuses. Aims of the study: The aim of this study was: to examine postnatal outcome of pregnancies complicated by a short femur length; to compare outcomes in pregnancies with an early diagnosis of short FL (< 24 weeks of gestation) with pregnancies where this sign arises later in gestation (> 25 weeks of gestation); to analyse outcome differences in isolated and non-isolated form. A secondary aim of our research was a proposal of a diagnostic algorithm as a tool to guide clinicians in the management and counselling of pregnancy with isolated and not isolated short femur length. For this purpose, a revision of current literature data on the argument was carried out. Materials and Methods: A longitudinal prospective cohort study was conducted. All singleton pregnancies with a diagnosis of fetal femur < 5 centile were enrolled in the study. Patients were divided into two groups: patients with diagnosis of FL < 5th percentile at 14-24 weeks (group A) and at 25-40 weeks (group B). The differences in pregnancy complications and outcomes between the two groups were analysed. A comparison of the results of isolated and non-isolated forms was also carried out. For the secondary aim of our study we reviewed the literature and used meta-analytic technique to estimate accuracy of this marker in the prediction of Down Syndrome, IUGR and skeletal dysplasia. Correlation with poor perinatal outcome was also evaluated. Results: We enrolled 147 cases of short femur length in singleton pregnancies. In 61 (41,49%) cases short femur was associated to other fetal anomalies, in 86/147 fetuses (58,5%) was classified as isolated. Abnormal fetal karyotype (27,3% vs 3.7% p: 0.02) and skeletal dysplasia (19,7% vs 3.7% p: 0.002) were more frequent in group A. Cases of multiple abnormalities was diagnosed in 9 cases in group A and in 6 cases in group B with a difference not statistically significant (13.6% vs 7.4% p < 0.193). Diagnosis of isolated short femur was more common in group B (79% vs 33,4%, p: 0.000). In group B diagnosis of IUGR was made in 44.4% vs 19.7% of group A (p:0.002). The SGA prevalence had a difference statistically significant between the two groups (7.6% vs 24.7% p:0.007). The percentage of live birth was significant lower than group B (34.8% vs 97,6%). A comparison based on presence of an isolated short femur and not isolate finding (Group 1: Isolated - Group 2 not isolated) was also carried out. Abnormal fetal karyotype and (24,6% vs 7,0% p: 0.004), skeletal dysplasia (24,6% vs 1.2% p: 0.004) were more frequent in non-isolated group. Diagnosis of IUGR and SGA was more common in isolated group (47,7% vs 13,1%, p: 0.000, 25,6% vs 4,9% p 0.001) (table 4). The percentage of live birth was significant lower in not isolated group (45.9% vs 86% p 0.00). A higher incidence of neonatal complication, postnatal surgery and neonatal death were notice in not isolated group compared to isolated (57,69% vs17.45% p 0.019; 27,92% vs 4,2% p:0.003). Meta-analysis showed a higher incidence of short femur length in Down Syndrome fetuses (375/1326 28,2%) compared with euploid group (5809/188935, 3.07%) with an OR 5.12 (95% CI, 4.47-5.87). A higher incidence of IUGR/SGA was found in isolated short femur (455/3108, 14,6%) compared with the control group (11634/222362, 5.23%) with an OR of 4.12 (CI 95% 3.70-4.58). Conclusions. The diagnosis of short FL is often a challenge in obstetrics. The results of our study could help clinicians in counseling these patients in presence of this ultrasound findings. The diagnosis of a non-isolated short femur length before 24 weeks of gestation is associated to poor pregnancy outcome. When a short femur arises late in gestation and in isolated form, pregnancy outcome is better in term of chromosomal abnormalities but high rate of IUGR, SGA and neonatal complication is possible.