Prevalence and clinical profiles of disproportionate and proportionate microcephaly in China: a population-based cross-sectional study

Abstract

BackgroundGuangzhou is a large city with a climate that is conducive to transmission of the dengue virus, and it is also at high risk of a zika epidemic. Viral, bacterial, and parasitic infections can lead to microcephaly, but data on microcephaly in China are limited. This study aimed to estimate the prevalence of microcephaly and the clinical spectrum of disproportionate and proportionate microcephaly in Guangzhou, China. MethodsA prospective surveillance study of microcephaly at birth was conducted at four perinatal health-care centres from February 2017 to August 2017 in Guangzhou, China. The Intergrowth-21st head circumference (HC) curves were used as the reference. Microcephaly was defined as a HC of more than 3 SD below the mean for sex and gestational age. Based on the neonates' HCs and birth weights, the study group was subdivided into those with disproportionate microcephaly, proportionate microcephaly, or normocephaly. Poisson exact 95% CIs of the prevalence of microcephaly were estimated. Maternal characteristics (including infection) and neonatal characteristics were examined for differences between microcephaly and normocephaly, and the association of neonatal complications with disproportionate and proportionate microcephaly was assessed using Poisson regression, in comparison with equivalent data for normocephaly. FindingsA total of 19 854 births were included, of which 88 had microcephaly, giving a prevalence of 0·44% (95% CI 0·35%–0·55%). Compared to women who delivered a baby with normocephaly, women who delivered a baby with microcephaly were younger (mean 29·1 (SD 5·1) years vs 30·3 (4·7) years, p=0·0222), had a higher proportion of nulliparity (60·2% vs 40·5%, p=0·0002), a higher prevalence of gestational hypertension (8·0% vs 2·3%, p=0·0004), and a shorter gestation length (mean 37·2 (SD4·1) weeks vs 39·0 (1·6) weeks, p<0·0001). The rates of maternal and neonatal infectious and parasitic diseases were not significantly higher in microcephaly than in normocephaly. The prevalence of disproportionate and proportionate microcephaly was 0·10% (95% CI 0·058%–0·15%) and 0·35% (95% CI 0·27%–0·44%), respectively. The proportion of women who were carriers of viral hepatitis B was higher in disproportionate microcephaly than in normocephaly (42·9% vs 7·3%, p=0·0107), whereas in proportionate microcephaly it was comparable to normocephaly (15·2% vs 7·3%, p=0·0471). Disproportionate microcephaly was associated with a substantially higher risk of stillbirth (adjusted RR [aRR] 44·1, 95% CI 6·1, 317·5), an Apgar score of <7 at 1 min (60·1, 7·5, 481·0), fetal growth restriction (8·6, 1·6, 47·0), and hyperbilirubinemia (2·1, 1·2, 3·7), than normocephaly. The risk of congenital heart disease was higher in proportionate microcephaly than in normocephaly (2·9, 0·5, 15·7) but was not significantly higher in disproportionate microcephaly than normocephaly (3·1, 1·6, 6·3). InterpretationExtrapolated to the near 18 million annual births in China, there may be an estimated 79 200 microcephaly cases each year. Disproportionate microcephaly is associated with substantially higher risk of severe adverse outcomes. Maternal carrier of viral hepatitis B is identified as a new risk factor for disproportionate microcephaly, but the mechanism is unclear and should be studied further. FundingThe National Natural Science Foundation of China (numbers 81673181 and 81703244), the National Key Research and Development Program of China (numbers 2016YFC1000205 and 2016YFC1000304), the European Union Horizon 2020 Research and Innovation Programme under ZIKAlliance (number 73458), and the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases programme (number ANR-10-LABX-62-IBEID).