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

Abstract

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.

National surveillance of severe microcephaly in Australia

“…Birth prevalence in Australia (4.01 per 10 5 live births; CI 2.60–5.92) was similar to that reported from INOPSU members using similar methods. Canada estimated a prevalence of 4.5 and the UK 5.5 per 10 5 live births 1,3 . Similar to Canada and the UK, a large proportion of our cohort had congenital anomalies, presented with abnormal neurological signs, and failed to reach developmental milestones 1,3 .…”

“…It became a public health concern in 2016, following an outbreak of Zika virus infection associated with microcephaly in the Americas 2 . In response to the international emergency declared by the World Health Organization, some members of the International Network of Paediatric Surveillance Units (INOPSU), including Canada, the United Kingdom (UK) and New Zealand, initiated surveillance for severe microcephaly, defined as an occipitofrontal circumference (OFC) ≥3 standard deviations (SDs) below the mean for age and sex 1–3 . Given the paucity of epidemiological information on this condition in Australia, the Australian Paediatric Surveillance Unit (APSU) undertook surveillance for microcephaly using a similar surveillance method, but using a cut‐off for microcephaly at an OFC of ≥2 SDs below the mean.…”

“…Recent publications of national data on severe microcephaly from the Canadian Paediatric Surveillance Program (CPSP) 1 and the British Paediatric Surveillance Unit (BPSU) 3 reported that children with severe microcephaly endure substantial morbidity and neurodisability. 1,3 In this report, we describe clinical, epidemiological and aetiological features of severe microcephaly in Australian infants and compare findings to those reported by the CPSP and BPSU.…”

“…1,3 Similar to Canada and the UK, a large proportion of our cohort had congenital anomalies, presented with abnormal neurological signs, and failed to reach developmental milestones. 1,3 Data from a large German cohort of infants with microcephaly highlighted serious longer-term comorbidities, including intellectual impairment (65%), epilepsy (43%) and ophthalmological disorders (30%) and a rate of structural brain anomalies (76%) higher than identified in our study (48%). 4 | 1735…”

“…2 In response to the international emergency declared by the World Health Organization, some members of the International Network of Paediatric Surveillance Units (INOPSU), including Canada, the United Kingdom (UK) and New Zealand, initiated surveillance for severe microcephaly, defined as an occipitofrontal circumference (OFC) ≥3 standard deviations (SDs) below the mean for age and sex. [1][2][3] Given the paucity of epidemiological information on this condition in Australia, the Australian Paediatric Surveillance Unit (APSU) undertook surveillance for microcephaly using a similar surveillance method, but using a cut-off for microcephaly at an OFC of ≥2 SDs below the mean.Recent publications of national data on severe microcephaly from the Canadian Paediatric Surveillance Program (CPSP) 1 and the British Paediatric Surveillance Unit (BPSU) 3 reported that children with severe microcephaly endure substantial morbidity and neurodisability. 1,3 In this report, we describe clinical, epidemiological and aetiological features of severe microcephaly in Australian infants and compare findings to those reported by the CPSP and BPSU.…”