Ultrasound diagnosis of microcephaly: a comparison of three reference curves and postnatal diagnosis

  • Lucas Augusto Monteiro de Castro Doin TrigoEmail author
  • Joao Renato Benini-Junior
  • Luiz Gustavo Oliveira Brito
  • Sergio Tadeu Martins Marba
  • Eliana Amaral
Maternal-Fetal Medicine



To evaluate which reference curve (RC)—Snijders, Intergrowth 21st (IG21) and World Health Organization (WHO)—is more accurate for microcephaly diagnosis.


Retrospective cohort study with more than 30,000 exams in more than 11,000 women. Microcephaly was confirmed by a neonatologist at birth and positive predictive values (PPVs) and misdiagnosis were assessed.


A total of 71 cases were confirmed as microcephaly at birth. IG21 and Snijders PPVs showed to be more significant over WHO’s (p < 0.001), without difference between them (p = 0.39). All RC were superimposed and did not show significant difference. When evaluated in different fragments, three trends were observed (until 30 weeks, between 30 and 36 and after 36 weeks of gestational age), with the latter interval showing a significant difference between IG21 and WHO (p = 0.0079). Conversely, WHO exhibited only one misdiagnosis, a much lower rate than Snijders, who missed eight cases and IG21, nine.


WHO’s RC appears to misdiagnose fewer cases, which could be useful for a population screening, while IG21’s RC presented a more significant PPV, being more useful for a more precise final diagnosis in reference centers.


Microcephaly Reference values Fetal development Growth curve Diagnosis 


Author contributions

LT, EA: Protocol/project development, data collection or management, data analysis, manuscript writing/editing. JRB, STM: Project development, data collection or management. LGB: Data management, data analysis, manuscript writing/editing.


The first author received a Master of Sciences scholarship from Coordination for the Improvement of Higher Education Personnel (CAPES).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was performed in accordance with the 1964 Helsinki Declaration and received Institutional Board Review for being performed.

Informed consent

Informed consent was not required as it was a retrospective study and all information were de-identified.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynaecology, School of Medical SciencesUniversity of CampinasCampinasBrazil
  2. 2.Department of Paediatrics, School of Medical SciencesUniversity of CampinasCampinasBrazil
  3. 3.BarcelonaSpain

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