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Original research
Small head circumference at birth: an 8-year retrospective cohort study in China
  1. Shiliang Liu1,2,3,
  2. Yanmei Pan2,
  3. Nathalie Auger4,
  4. Wen Sun2,3,
  5. Lijuan Dai2,
  6. Sihui Li3,
  7. Sushan Xie2,
  8. Shi Wu Wen5,
  9. Dunjin Chen2
  1. 1 Maternal, Chid and Youth Heath Division, Centre for Surveillance and Applied Research, Public Health Agency of Canada, Ottawa, Ontario, Canada
  2. 2 The Provincial Key Laboratory for Major Obstetric Disease, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
  3. 3 School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  4. 4 University of Montreal Hospital Research Centre, Montreal, Quebec, Canada
  5. 5 Ottawa Hospital Research Institute, Universityof Ottawa, Ottawa, Ontario, Canada
  1. Correspondence to Dr Dunjin Chen; chendunjin{at}


Objective Head circumference is considered a reliable assessment of the volume of the underlying brain. We sought to identify risk factors (maternal factors or antenatal antecedents) for microcephaly and to assess the effects of microcephaly on neonatal outcomes.

Design Retrospective cohort study.

Setting Data for all births in 2009-2017 were obtained from the Guangzhou Maternal-Fetal Care Database.

Participants All singleton liveborn infants between 33 and 42 weeks’ gestation (n=45 663) were categorised using the Intergrowth-21st standard for microcephaly.

Main outcome measures Prevalence of mild, absolute and relative microcephaly at birth. We estimated associations of (1) maternal characteristics including Cantonese origin, parity, exposure to teratogens, TORCH infections (ie, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus), in vitro fertilisation conception, pre-eclampsia and maternal congenital anomalies with risk of each category of microcephaly, and (2) microcephaly with risk of in-hospital mortality and severe morbidity.

Results A total of 2709 infants had a head circumference z-score >2 SD, resulting in an overall prevalence of microcephaly of 59.3 per 1000 infants, consisting of mild (54.1 per 1000), absolute (2.8 per 1000) and relative microcephaly (2.4 per 1000). In multiple logistic regression, absolute microcephaly was associated with in utero exposure to teratogens (OR 4.2, 95% CI 2.0 to 8.8) and TORCH agents (OR 3.2, 95% CI 1.1 to 9.5). Mild microcephaly was associated with Cantonese descent (OR) 1.5, 95% CI 1.3 to 1.7) and primiparity (OR 1.7, 95% CI 1.5 to 2.0). Absolute microcephaly was associated with a significantly higher odds of neonatal seizure (OR 8.7, 95% CI 1.1 to 69.1). Mild microcephaly was not associated with adverse neonatal outcomes overall.

Conclusions Cantonese origin, exposure to teratogens, pre-eclampsia and TORCH infection may be risk factors for microcephaly. The high prevalence of relative microcephaly and associated poor outcomes suggests that high-risk women merit closer clinical management and follow-up to maximise fetal head development during pregnancy.

  • microcephaly
  • brain development
  • risk factor
  • substance use

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  • Contributors This study was carried out in collaboration of the Public Health Agency of Canada with the Third Affiliated Hospital of Guangzhou Medical University in China, where the lead author holds an adjunct professorship.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No data are available. All data relevant to the study are included in the article or uploaded as supplementary information.

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