Article : Prevalence of microcephaly in Europe: population based study

Joan K Morris, professor of medical statistics1, Judith Rankin, professor of maternal and perinatal epidemiology2, Ester Garne, consultant paediatrician3, Maria Loane, reader in public health4, Ruth Greenlees, EUROCAT database manager4, Marie-Claude Addor, clinical geneticist5, Larraitz Arriola, epidemiologist6, Ingeborg Barisic, professor of paediatrics and medical genetics7, Jorieke E H Bergman, clinical geneticist8, Melinda Csaky-Szunyogh, head of department9, Carlos Dias, coordinator and invited assistant professor10, Elizabeth S Draper, professor of perinatal and paediatric epidemiology11, Miriam Gatt, consultant in public health medicine12, Babak Khoshnood, medical epidemiologist13, Kari Klungsoyr, professor14, Jennifer J Kurinczuk, director15, Catherine Lynch, specialist in public health medicine16, Robert McDonnell, consultant in public health medicine17, Vera Nelen, director18, Amanda J Neville, senior research fellow19, Mary T O’Mahony, specialist in public health medicine20, Anna Pierini, researcher21, Hanitra Randrianaivo, scientific director22, Anke Rissmann, head of department23, David Tucker, CARIS manager24, Christine Verellen-Dumoulin, professor25, Hermien E K de Walle, senior epidemiologist8, Diana Wellesley, consultant and honorary senior lecturer in clinical genetics26, Awi Wiesel, head of epidemiology27, Helen Dolk, professor of epidemiology and health services research

Objectives To provide contemporary estimates of the prevalence of microcephaly in Europe, determine if the diagnosis of microcephaly is consistent across Europe, and evaluate whether changes in prevalence would be detected using the current European surveillance performed by EUROCAT (the European Surveillance of Congenital Anomalies).

Design Questionnaire and population based observational study.

Setting 24 EUROCAT registries covering 570 000 births annually in 15 countries.

Participants Cases of microcephaly not associated with a genetic condition among live births, fetal deaths from 20 weeks’ gestation, and terminations of pregnancy for fetal anomaly at any gestation.

Main outcome measures Prevalence of microcephaly (1 Jan 2003-31 Dec 2012) analysed with random effects Poisson regression models to account for heterogeneity across registries.

Results 16 registries responded to the questionnaire, of which 44% (7/16) used the EUROCAT definition of microcephaly (a reduction in the size of the brain with a skull circumference more than 3 SD below the mean for sex, age, and ethnic origin), 19% (3/16) used a 2 SD cut off, 31% (5/16) were reliant on the criteria used by individual clinicians, and one changed criteria between 2003 and 2012. Prevalence of microcephaly in Europe was 1.53 (95% confidence interval 1.16 to 1.96) per 10 000 births, with registries varying from 0.4 (0.2 to 0.7) to 4.3 (3.6 to 5.0) per 10 000 (χ2=338, df=23, I2=93%). Registries with a 3 SD cut off reported a prevalence of 1.74 per 10 000 (0.86 to 2.93) compared with those with the less stringent 2 SD cut off of 1.21 per 10 000 (0.21 to 2.93). The prevalence of microcephaly would need to increase in one year by over 35% in Europe or by over 300% in a single registry to reach statistical significance (P<0.01).

Conclusions EUROCAT could detect increases in the prevalence of microcephaly from the Zika virus of a similar magnitude to those observed in Brazil. Because of the rarity of microcephaly and discrepant diagnostic criteria, however, the smaller increases expected in Europe would probably not be detected. Clear diagnostic criteria for microcephaly must be adopted across Europe.