AbstractObjectiveSkeletal dysplasia is usually apparent in the second trimester. First trimester femur‐length/biparietal diameter (FL/BPD), FL/abdominal circumference (AC) and FL/foot for the screening of skeletal dysplasia were evalauted.MethodCase‐control study: pregnancies with molecular confirmation of skeletal dysplasia undergoing nuchal translucency (January_2007–December_2021). Controls included pregnancies without fetal abnormalities. Performance of FL/BPD, FL/AC and FL/foot was evaluated by receiver operating characteristic curves.ResultsTwenty‐eight skeletal dysplasia cases were identified; 17 (60.71%) corresponded to lethal types. Compared to 184 controls, cases had a lower median FL/BPD (0.34 [IQR 0.30–0.38] vs. 0.44 [IQR 0.39–0.48]; p < 0.001), FL/AC (0.13 [IQR 0.09–0.15] vs. 0.15 [IQR 0.13–0.16]; p = 0.001) and FL/foot (0.84 [IQR 0.76–0.91] vs. 1.01 [IQR 0.94–1.11]; p < 0.001). FL/BPD and FL/foot ratios had a superior area under the curve (0.846 and 0.853, respectively) than FL/AC (0.64). The probability of diagnosing skeletal dysplasia increased at least 9‐fold if FL/BPD <0.376 (OR 26.05, 95% CI 9.79–69.3; p < 0.001) and 14‐fold if FL/foot <0.891 (OR 39.46, 95% CI 14.17–109.9; p < 0.001). Low FL/BPD and FL/foot were associated significantly with lethal types compared to viable skeletal dysplasia.ConclusionsFirst trimester FL/BPD and FL/foot may be of clinical utility in the detection of skeletal dysplasia especially when there is another suspicious sonographic sign or when there is a relevant family history before overt second trimester sonographic markers become apparent.