Normal Femur Length Research Articles

307: Short femur length: A biomarker for spontaneous preterm birth?

Abnormal fetal growth patterns are associated with indicated preterm birth (iPTB). Recently, data has suggested that spontaneous preterm birth (sPTB) may also have sonographically detectable fetal growth characteristics, specifically the femur length (FL) component of fetal biometry. Our objective was to test the association of short FL at different gestational ages for the risk of PTB. This is a prospective cohort study of patients followed longitudinally across pregnancy at a tertiary care academic center with the primary aim of detecting novel markers of preterm birth. Fetal biometry measurements were collected from ultrasounds across pregnancy. sPTB was rupture of membranes or preterm labor resulting in delivery < 37 weeks (wks). iPTB was any maternal or fetal indication leading to delivery < 37 wks. Single FL measurements from growth assessments were tested for the association with PTB in four-week time windows (16 to 19+6 wks; 20-23+6 wks; 24-27+6 wks; 28-31+6 wks). ‘Short FL’ was defined < 25th percentile. Fischer’s exact tests were performed comparing the incidence of short FL between preterm versus term, and between sPTB versus iPTB. A time-to-event analysis, with delivery being the event, was performed to obtain hazard ratio for short FL and time to delivery. 125 patients with PTB were included; 58 sPTB and 67 iPTB. Short FL is significantly associated with the risk for PTB. The time windows of 16 to 20 weeks (p=0.01) and 28 to 32 weeks (p< 0.01) are of particular importance (Figure 1). Using survival analysis, there is a significantly decreased time to delivery amongst women with a short FL detected at 16-20 weeks and 28-32 weeks with fetuses with short FL three times more likely to deliver before those with normal FL (Figure 2) p< 0.001. There was no difference in risk for sPTB or iPTB with short FL < 25%ile. Short FL detected from 16-20 weeks and 28-32 weeks are associated with a significant increase in PTB. Further studies to examine whether short FL could be an important component of a clinical risk prediction and stratification for PTB.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Midtrimester isolated short femur and perinatal outcomes: A systematic review and meta-analysis.

Fetal femur length below the expected value has been described as a marker of aneuploidy, skeletal dysplasia, intrauterine growth restriction and small-for-gestational-age neonate. The aim of this systematic review and meta-analysis was to evaluate the strength of association between isolated short femur length and intrauterine growth restriction or small-for-gestational-age, and perinatal adverse outcomes. PubMed, EMBASE and Medline were searched from the inception of each database to May 2018. Selection criteria included prospective and retrospective cohort studies of singleton pregnancies between 18 and 28weeks of gestation, with sonographic finding of isolated short femur length, without any structural chromosomal abnormality. The meta-analysis was performed by computing odds ratios using both fixed and random-effects models. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. Six studies including 3078 cases of isolated short femur length (study group) and 222303 normal femur length (control group) were included. The prevalence of intrauterine growth restriction or small-for-gestational-age in the study group was 14.2%, compared with 5.2% in the control group (odds ratio of 4.04, 95% confidence interval 3.63-4.50). Isolated short femur length was associated with a higher incidence of low birthweight (study group: 22.10% vs control group: 8.57%, odds ratio 3.24, 95% confidence interval 2.34-4.48), Apgar <7 at 5minutes (study group: 3.98% vs control group: 1.79%, odds ratio 3.56, 95% confidence interval 1.87-6.77), preterm birth (study group: 12.16% vs control group: 8.16%, odds ratio 3.09, 95% confidence interval 1.57-6.08), fetal death (study group: 1.83% vs control group: 0.44%, odds ratio 6.48, 95% confidence interval 3.70-11.35) and neonatal intensive care unit admission (study group: 15.34% vs control group: 14.81%, odds ratio 2.11, 95% confidence interval 0.56-7.93). There is a significant association between isolated short femur length and intrauterine growth restriction or small-for-gestational-age and poor perinatal outcome.

Resultados perinatales en fetos del segundo trimestre con fémur corto aislado

Antecedentes: El hallazgo ecográfico de fémur corto (longitud menor del percentil 5) en la valoración ecográfica rutinaria del feto del segundo trimestre plantea un desafío diagnóstico y de manejo. Clásicamente ha sido asociado a cromosomopatías y displasia esquelética. Existen pocos reportes que valoran los resultados perinatales de los fetos con fémur corto en el examen del segundo trimestre. Objetivos: Determinar la asociación de fetos con fémur corto aislado en fetos del segundo trimestre y recién nacidos con restricción del crecimiento intrauterino (RCIU) y su asociación con otros resultados perinatales adversos. Diseño: Estudio de cohorte retrospectivo. Institución: Unidad de Medicina Fetal, Instituto Nacional Materno Perinatal, Lima, Perú. Participantes: Gestantes de 16 a 28 semanas. Intervenciones: Para cumplir con el tamaño muestral, se seleccionó los fetos evaluados durante el periodo de tres años (2006 a 2008) que cumplieron los criterios de inclusión. Se clasificó los fetos de 278 gestantes de 16 a 28 semanas en dos grupos: 89 con longitud de fémur corto aislado como único hallazgo, sin RCIU al momento de la evaluación (casos), y 189 fetos con longitud de fémur normal (controles). Se excluyó las gestantes cuyos fetos tenían anormalidades cromosómicas o estructurales y aquellas gestaciones con embarazos múltiples. Se realizó un análisis univariado mostrando porcentajes y medidas de tendencia central y un análisis bivariado con la prueba t, para las variables continuas, y la prueba exacta de Fisher, para las variables categóricas. Principales medidas de resultados: Asociación del fémur corto fetal con complicaciones fetales y maternas. Resultados: El grupo de fetos con fémur corto aislado tuvo recién nacidos con peso promedio significativamente menor que las gestantes de fetos con longitud de fémur normal, con una diferencia estadística y clínicamente significativa de 412,3 g (P=0,000), encontrándose un mayor porcentaje de recién nacidos con RCIU en 14,6% versus 6,8% en el grupo control (p=0,000). Calculamos un OR de 2,32 (IC95%:1,03 a 5,23) para RCIU. Además, se observó que las gestantes con fetos de fémur corto aislado desarrollaron hipertensión gestacional (11,2% versus 4,8%, p=0,046) y preeclampsia (11,2% versus 2,1%, p=0,001). Asimismo, hubo mayor número de casos con puntaje de Ápgar &lt;7 a los 5 minutos en el grupo de fetos con fémur corto (4,5% versus 0,5%, p=0,02). Igualmente, hubo dos casos de muerte perinatal en el grupo de fetos con fémur corto aislado. Conclusiones: El fémur corto, como hallazgo ecográfico aislado en fetos del segundo trimestre, está asociado a recién nacidos con RCIU y con gestaciones complicadas con hipertensión gestacional o preeclampsia. Este es la cohorte más grande publicada hasta el momento de fetos con fémur corto aislado.

Fetal isolated short femur in the second trimester and adverse pregnancy outcomes

This study aims to evaluate the association of isolated short femur (ISF) in the second trimester ultrasound with adverse pregnancy outcomes. All obstetric scans between 16 and 24 weeks of gestation from 1 January 2006 to 1 June 2012 were retrospectively evaluated. Multiple pregnancies, major congenital or chromosomal anomalies and subjects with incomplete outcome data were excluded. Femur length (FL) measurement from the earliest scan of singleton pregnancies was selected. An ISF was defined as a FL less than the tenth percentile in a fetus with an abdominal circumference greater than or equal to the tenth percentile. The primary outcomes were small for gestational age (SGA), birth weight below the third and fifth percentiles, low birth weight (LBW), preterm birth (PTB) and preeclampsia (PE). A 5-min Apgar score of less than 7 and a neonatal intensive care unit admission were secondary outcomes. Of the 4992 eligible fetuses, 312 (6%) had an ISF. Mothers in the short femur group were shorter and had a lower prepregnancy and delivery weight than the group with normal FL (p < 0.05). Multiple logistic regression revealed a significant increase in birth weight below fifth percentile, SGA, LBW infants and PTB (<32, <34 and <37 weeks) in the ISF group (p < 0.05). The incidence of PE was similar in both groups. Isolated short femur in the second trimester increases the risk of LBW, SGA and PTB, but not of PE.

Outcome of Fetuses with Diagnosis of Isolated Short Femur in the Second Half of Pregnancy

Objectives. To assess the outcome of fetuses with isolated short femur detected at 19–41 weeks and determine to what extent this incidental finding should be a cause of concern in fetuses with a normal previous follow-up. Methods. 156 fetuses with isolated short femur were compared with a control group of 637 fetuses with normal femur length. FL values were converted into Z-scores and classified into 4 groups: control group: Z-score over −2, group 1: Z-score between −2 and −3, group 2: Z-score between −3 and −4, and group 3: Z-score below −4. FL values were plotted with the curves representing Z-scores −2, −3, and −4. To assess fetal outcome, the frequency of SGA, IUGR, abnormal umbilical Doppler (AUD), Down's syndrome, and skeletal dysplasia was determined for each group after delivery, and the relative risk in comparison with the control group was obtained. Finally, ROC curves were drawn in order to evaluate the FL diagnostic ability for the conditions appearing with increased frequency. Results. SGA, IUGR, and AUD were more frequent in the fetuses with short femur. Conversely, none of them presented Down's syndrome or skeletal dysplasia. According to ROC analysis, FL measurement behaved as a good diagnostic test for SGA and IUGR. Conclusions. A short femur diagnosis in a fetus with an otherwise normal follow-up determines just a higher risk of being small (SGA or IUGR).

Perinatal outcomes after sonographic detection of isolated short femur in the second trimester

To determine the association of fetal isolated short femur in the second-trimester ultrasound (US) examination with perinatal outcomes such as small-for-gestational age (SGA) and low-birth weight (LBW) neonates. This is a retrospective cohort study in fetuses routinely assessed by US examination at 18 to 24 weeks during 2006-2009. A fetal isolated short femur was defined as femur length below the 5th percentile and with no chromosomal or structural abnormalities. Fetuses with abdominal circumference below the 5th percentile at the time of US examination were excluded. Each case of short femur was matched with three controls according to gestational age at the time of the US examination. Sixty-one fetuses met the inclusion criteria. Both the group of women carrying a fetus with isolated short femur and that of women carrying a fetus with normal femur length had similar general and obstetric characteristics. Women carrying a fetus with isolated short femur were significantly more likely to deliver a SGA neonate (19.7% versus 8.7%, p < 0.05) and a LBW neonate (19.7% versus 7.1%, p < 0.05) than women carrying a fetus with normal femur length. Logistic regression analysis found odds ratios for SGA and LBW of 2.6 (95% confidence interval, 1.1-5.9) and 2.9 (95% confidence interval, 1.2-7.1), respectively. Isolated short femur in the second-trimester US examination is associated with a subsequent delivery of SGA and LBW neonates.

Association of isolated short femur in the mid‐trimester fetus with perinatal outcome

To evaluate the prevalence of fetal isolated short femur in a cohort of women screened for Down syndrome by the integrated test, and to compare the outcome of fetuses with isolated short femur in the mid-trimester with that of fetuses with normal femur length (controls). This was a retrospective cohort study of 1262 women booked for antenatal care and delivery at University College London Hospital. All women had integrated testing in the late first and early second trimesters and a detailed anomaly scan in the mid-trimester. All scan reports, screening results and neonatal data were analyzed statistically. The fetal femur was short (< 5(th) percentile) in 5.1% of patients and 4.7% had isolated short femur. In pregnancies with isolated short femur, the birth weight was significantly lower and there were higher rates of small-for-gestational age (SGA) and low birth weight (LBW) infants, compared with controls (P < 0.01). The odds ratios for SGA and LBW in pregnancies with isolated short femur were 3.0 (95% CI, 1.5-5.9) and 2.60 (95% CI, 1.1-6.2), respectively. Isolated short femur was associated significantly with low levels of pregnancy-associated plasma protein-A (P = 0.001). Isolated short femur in the mid-trimester fetus is associated with fetal growth restriction and SGA. In the context of normal Down syndrome screening and a normal anomaly scan, this marker should be regarded as a predictor for SGA, and fetal growth should be monitored during these pregnancies.

Sonographic identification of second-trimester fetuses with Down's syndrome.

Fetuses with Down's syndrome are more likely than normal fetuses to have a thickened nuchal skin fold and relatively short femurs on ultrasound examination in the second trimester. We evaluated these measures in more than 5500 fetuses, including 28 who were later found to have Down's syndrome by means of amniocentesis with cytogenetic analysis. Normal femur length was established as a function of biparietal diameter in 192 of the normal fetuses. We found that with use of a nuchal skin-fold thickness of 6 mm or more and a ratio of actual to expected femur length of 0.91 or less, fetuses with Down's syndrome could be identified with a sensitivity of 75 percent and a specificity of 98 percent. When other anomalies, such as an atrioventricular canal and meconium peritonitis, were added to these two criteria, the sensitivity of sonographic detection of Down's syndrome in the second-trimester fetus rose to 82 percent. The potential predictive value of these sonographic signs far exceeds that of advanced maternal age and low alpha-fetoprotein levels, which currently identify only 10 to 30 percent of affected fetuses. We recommend that fetuses with a thickened nuchal skin fold or shortened femurs on ultrasound examination be evaluated for Down's syndrome by amniocentesis and cytogenetic analysis.

In utero analysis of heterozygous achondroplasia: variable time of onset as detected by femur length measurements.

Seven cases of heterozygous achondroplasia were examined in utero. Although the head shape and growth were normal, the initially normal femur length showed a decrease in growth and fell below the lower 99 per cent confidence limit in all cases. The time of presentation of achondroplasia varied between 21 and 27 gestational weeks. This study suggests that the diagnosis of achondroplasia can be reasonably made when the femur is abnormally short. When the femoral length is appropriate prior to 30 weeks, more caution should be taken in interpretation. Because of the variability in presentation, the fetus could be normal or still could be affected.