Ultrasound Unit, Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel.
Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.
Ultrasound Obstet Gynecol. 2016 May;47(5):586-92. doi: 10.1002/uog.15801.
To evaluate the prediction of microcephaly at birth (micB) using established and two new reference ranges for fetal head circumference (HC) and to assess whether integrating additional parameters can improve prediction.
Microcephaly in utero was defined as a fetal HC 3SD below the mean for gestational age according to Jeanty et al.'s reference range. The records of cases with fetal microcephaly (Fmic) were evaluated for medical history, imaging findings, biometry and postnatal examination/autopsy findings. Microcephaly was confirmed at birth (micB) by an occipitofrontal circumference (OFC) or a brain weight at autopsy 2SD below the mean for gestational age. The new INTERGROWTH-21(st) Project and a recent Israeli reference for fetal growth were applied for evaluation of the Fmic positive predictive value (PPV) for diagnosis of micB cases. Optimal HC cut-offs were determined for each of the new references with the aim of detecting all micB cases whilst minimizing the number of false positives found to have a normal HC at birth. We also assessed the difference between the Z-scores of the prenatal HC and the corresponding OFC at birth, the frequency of small-for-gestational age (SGA), decreased HC/abdominal circumference (AC) and HC/femur length (FL) ratios, the prevalence of associated malformations and family history.
Forty-two fetuses were diagnosed as having Fmic according to the Jeanty reference, but micB was confirmed in only 24 (PPV, 57.1%). The optimal INTERGROWTH and Israeli reference HC cut-offs for micB diagnosis were mean - 3SD and mean - 2.3SD, resulting in a statistically non-significant improvement in PPV to 61.5% and 66.7%, respectively. The presence of a family history of microcephaly, SGA, associated malformations and application of stricter HC cut-offs resulted in a higher PPV of micB, although not statistically significant and with a concurrent increase in the number of false-negative results. The deviation of the HC from the mean, by all references, was significantly larger compared with the actual deviation of the OFC at birth, with mean differences between the corresponding Z-scores of -1.15, -1.95 and -0.74 for the Jeanty, INTERGROWTH and Israeli references, respectively.
The evaluated reference ranges all result in considerable over-diagnosis of fetal microcephaly. The use of the two new HC reference ranges did not significantly improve micB prediction compared with that of Jeanty et al., whilst use of additional characteristics and stricter HC cut-offs could improve the PPV with an increase in false negatives. The postnatal OFC deviates significantly less from the mean compared with the prenatal HC, and we propose that adjustment for this would enable better prediction of the actual OFC deviation at birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
评估使用已建立的和两个新的胎儿头围（HC）参考范围来预测出生时的小头畸形（micB），并评估是否整合其他参数可以提高预测能力。
根据 Jeanty 等人的参考范围，宫内小头畸形定义为胎儿 HC 低于相应胎龄平均值的 3SD。评估小头畸形胎儿（Fmic）的病历、影像学发现、生物测量学和产后检查/尸检发现。出生时的小头畸形（micB）通过头围（OFC）或尸检时大脑重量低于相应胎龄平均值的 2SD 来确认。新的 INTERGROWTH-21(st) 项目和最近的以色列胎儿生长参考用于评估 Fmic 阳性预测值（PPV），以诊断 micB 病例。应用每个新参考的最佳 HC 截止值，目的是检测所有 micB 病例，同时将出生时 HC 正常但被错误诊断为小头畸形的病例数量最小化。我们还评估了产前 HC 和出生时相应 OFC 的 Z 分数之间的差异、小于胎龄儿（SGA）的频率、HC/腹围（AC）和 HC/股骨长度（FL）比值的降低、相关畸形的患病率和家族史。
根据 Jeanty 参考，42 例胎儿被诊断为 Fmic，但只有 24 例 micB 得到证实（PPV，57.1%）。用于 micB 诊断的最佳 INTERGROWTH 和以色列参考 HC 截止值分别为平均值-3SD 和平均值-2.3SD，这导致 PPV 统计学上无显著提高，分别为 61.5%和 66.7%。存在小头畸形家族史、SGA、相关畸形和应用更严格的 HC 截止值可提高 micB 的 PPV，但无统计学意义，同时假阴性结果的数量也会增加。所有参考标准的 HC 偏差明显大于出生时实际 OFC 的偏差，Jeanty、INTERGROWTH 和以色列参考标准的相应 Z 分数之间的平均差异分别为-1.15、-1.95 和-0.74。
评估的参考范围都导致胎儿小头畸形的过度诊断。与 Jeanty 等人相比，使用两种新的 HC 参考范围并不能显著提高 micB 的预测能力，而使用其他特征和更严格的 HC 截止值可以提高 PPV，但假阴性结果的数量也会增加。产后 OFC 与平均值的偏差明显小于产前 HC，我们建议对此进行调整，以便更好地预测出生时实际 OFC 的偏差。
