Incidence, aetiology and neurodisability associated with severe microcephaly: a national surveillance study

ObjectiveTo determine the incidence, causes and neurodevelopmental impact of severe microcephaly (head circumference <-3SD) up to age 2 years. DesignBinational active paediatric surveillance study undertaken in 2017-2018 to identify and characterise new diagnoses of severe microcephaly. SettingUK and Ireland. ParticipantsInfants aged under 12 months at diagnosis. InterventionsObservational study. Main outcome measuresIncidence, aetiology and neurodevelopmental outcomes at age 2 years. ResultsFifty-nine infants met the case definition, of whom 30 (51%) were girls; 24 (41%) were born preterm (<37 weeks' gestation); and 34 (58%) were of 'white' ethnicity. Eight (14%) children died before 12 months of age. Incidence of severe microcephaly was 5.5 per 100 000 infants (95% CI 4.0 to 7.3). Higher relative risk (RR) was associated with preterm birth (RR 7.7, 95% CI 3.8 to 15.1) and British Asian ethnicity (RR 3.6, 95% CI 1.6 to 7.8). Microcephaly was mainly due to genetic causes (59%), brain ischaemia/hypoxia (10%) and congenital infection (8%), and 19% remained undetermined. Each child was referred on average to eight specialists, and 75% had abnormal brain imaging. By 2 years of age, 55 children experienced neurodevelopmental abnormalities, including feeding problems (68%), motor delay (66%), visual impairment (37%), hearing loss (24%) and epilepsy (41%). ConclusionsAlthough severe microcephaly is uncommon, it is associated with high mortality, complex multimorbidity and neurodisability, thus representing a significant ongoing burden for families and healthcare services. Potentially preventable causes include preterm birth, hypoxic/ischaemic brain injury and congenital infections. Clinical guidelines are essential to standardise aetiological investigation and optimise multidisciplinary management.