Diagnostic approach to fetal microcephaly

Microcephaly in utero is conventionally defined as a fetal head circumference (HC) 3SD below the mean for gestational age according to Jeanty et al.'s reference range. Prediction of microcephaly at birth (micB) based on conventional prenatal biometry is associated with a high percentage of false positive diagnoses and as a result, in countries in which it is an option, termination of pregnancy may be offered in cases that would have culminated in birth of a normocephalic child. A false negative diagnosis is rarer, but may lead to the birth of a symptomatic microcephalic child. In this review we present the results of our recent studies aimed at improvement of accurate prenatal detection of microcephaly including: (1), application of two new reference ranges for fetal HC in cases with a prenatal diagnosis of microcephaly based on the conventional reference; (2) assessment whether integration of additional parameters (stricter fetal HC cut-offs, small-for-gestational age (SGA), decreased HC/abdominal circumference and HC/femur length ratios, presence of associated malformations and family history) can improve prediction; (3), estimation of the difference between Z-scores of prenatal HC and the corresponding occipitofrontal circumference (OFC) at birth in order to propose an adjustment for better prediction of the actual OFC deviation at birth; (4), assessment whether micB diagnosis can be improved by accurate detection of false positive Fmic cases whose small HC is due to an acrocephalic-like head deformation by applying a new reference range of a vertical measurement of the fetal head: foramen magnum-to-cranium distance (FCD). The conventional and new reference ranges for fetal HC, all result in considerable over-diagnosis of fetal microcephaly (ranging from 43% to 33%). The use of the new references does not significantly improve micB prediction compared with the conventional one, whilst integrating additional parameters results in a better positive predictive value (PPV), but an increase in false negatives. The degree of Fmic severity is significantly over-estimated compared to the corresponding micB. The difference between the postnatal OFC deviation from the mean and the prenatal HC ranges from -0.74 SD to -1.95 SD for various fetal HC references. Application of the reference range for vertical cranial dimensions enables exclusion of fetuses with a small HC associated with a vertical cranial deformity without missing those with actual micB. Combining the fetal HC with the developed FCD criteria raised the PPV of micB to 78%. CONCLUSIONS: Prediction of micB can be improved by integrating additional parameters and by application of the FCD criteria, however the correct diagnosis of Fmic remains challenging. An algorithm for evaluation of fetal microcephaly is provided.