Prenatal small head circumference: Which biomarkers best predict microcephaly?

OBJECTIVES

Prenatal ultrasound detection of a small head circumference (US-SHC) is a key indicator of microcephaly. This retrospective study (2015-2024) aimed to determine the incidence of SHC at birth (b-SHC) and microcephaly at 6 months, and to identify prenatal biomarkers.

METHODS

We included 55 fetuses with us-SHC and median postnatal follow-up of 28 months (range: 7-112).

RESULTS

Among the 47 fetuses with available outcomes, b-SHC was confirmed in 31 (66%), while persistent microcephaly at 6 months was observed in 16 of 34 (47%) liveborns. Fetal brain MRI, particularly cerebral biparietal and occipitofrontal diameters below the third percentile, accurately predicted b-SHC, with a positive predictive value (PPV) of 83% and a negative predictive value (NPV) of 82% but were less effective for persistent microcephaly (PPV 53%, NPV 75%). Prenatal deceleration in HC growth was a key predictor of both b-SHC (OR = 13.86, p = 0.028) and persistent microcephaly (OR = 13.00, p = 0.025). A genetic etiology was identified in 44% (7/16) of infants with confirmed microcephaly; chromosomal microarray had a 12% (5/43) diagnostic yield.

CONCLUSIONS

Prenatal us-SHC predicted postnatal microcephaly in nearly half of cases. Prenatal HC growth deceleration emerged as a biomarker of persistent microcephaly.