Tuesday, March 29, 2016

EID Journal: Microcephaly in Infants, Pernambuco State, Brazil, 2015

Credit EID Journal

# 11,207

The EID Journal has published an early retrospective - prospective study on the incidence and severity of Microcephaly in Pernambuco State, Brazil which was started late last summer after rates of microcephalic births began to rise noticeably. 

Cases recruited (n=104) for this study were born between late April and mid-November 2015. Note: This study had a cutoff date in late November, and so many of the epidemiological details cited are now several months out of date. 

This study was not designed to prove a causal relationship between maternal Zika virus infection and microcephalic birth defects, although it does note the temporal association with Brazil's Zika outbreak and growing suspicions of a link.

This study is hampered by a number of limitations.

  • Zika testing not available - mothers were asked if they recalled having a febrile rash illness sometime during their pregnancy. 
  • Testing for non-Zika infectious agents (toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis aka ToRCHeS agents) was completed for fewer than half the study cohort 
  • Brain scans were only performed on slightly more than half of the study cohort

Despite these limitations, this report does provide us with a closer look at the most severe end of the spectrum of defects affecting newborns in Northeastern Brazil.  As has been discussed previously, the full spectrum of congenital injury occurring in Brazil may take months or years to document and appreciate.

I've posted a few excerpts, but follow the link to read the full dispatch.

Volume 22, Number 6—June 2016


Microcephaly in Infants, Pernambuco State, Brazil, 2015


We studied the clinical characteristics for 104 infants born with microcephaly in the delivery hospitals of Pernambuco State, Brazil, during 2015. Testing is ongoing to exclude known infectious causes. However, microcephaly peaked in October and demonstrated central nervous system abnormalities with brain dysgenesis and intracranial calcifications consistent with an intrauterine infection.

In April 2015, Zika virus was identified in Brazil (1,2). In August, an increased incidence of microcephaly was detected in Pernambuco State. In November, the Brazilian Ministry of Health declared a relationship between the microcephaly epidemic and Zika virus infection during pregnancy (3) on the basis of accumulating evidence (Technical Appendix[PDF - 140 KB - 2 pages]). Since then, several reports of Zika virus–associated microcephaly have been published (46). 

As of December 12, 2015, a total of 2,401 suspected cases of microcephaly had been reported (including 29 stillbirths) in 549 municipalities in 20 states in Brazil; Pernambuco reported the most (874 cases) (7). In comparison, an annual mean of 156 microcephaly cases were reported in Brazil (through the routine birth notification system) during 2010–2014, including 9 in Pernambuco (7). We describe preliminary findings of 104 microcephaly cases in Pernambuco from the 2 hospitals to which infants with suspected cases were referred. 


Microcephaly among the 104 newborns peaked in October 2015 and demonstrated severe central nervous system abnormalities with brain dysgenesis and intracranial calcifications consistent with an intrauterine infection. Although we initially lacked Zika virus testing and completed only partial testing for ToRCHeS infections, the timing on the microcephaly and the history of rash in more than half of the pregnant mothers suggest an outbreak of congenital microcephaly caused by a congenital infection. 

Since our study was completed, less clinically detailed and more surveillance-oriented data have been published from the national reporting system (11). These data include the case-infants reported here and the reported occurrence of the 2015–2016 microcephaly cases, especially in Pernambuco. They highlight the temporal relationship between the preceding Zika virus transmission and the abrupt increase in prevalence of microcephaly at birth.

Our study focused on the clinical findings of 1 cohort, demonstrating a high proportion of calcifications and malformations of cortical development in infants with microcephaly and with severe microcephaly. Such malformations have commonly been observed in cases of intrauterine infections caused by cytomegalovirus and toxoplasmosis (12); more severe anomalies (e.g., lissencephaly) occur in infants whose mothers were infected before weeks 16–18 of pregnancy (13). The finding of intracranial calcifications predominantly in the cortical/subcortical parenchyma suggests a scan pattern distinct from that of other congenital infections, although further studies including comprehensive diagnostic testing for Zika virus and other known infectious causes of congenital central nervous system defects are needed to confirm this pattern.

Our study had several limitations. First, as previously noted, this study was preliminary, and Zika virus testing was not yet available. Second, personnel and laboratory resources were insufficient for ToRCHeS testing of more than half of the case-infants reported here; however, we collected blood and cerebrospinal fluid samples for future testing. Third, limited resources restricted the number of brain scans to slightly more than half of these infants. Fourth, the data on rash during pregnancy was collected postpartum and could be subject to recall bias. 

Nevertheless, a case–control study has been under way in Pernambuco since December 2015, supported by the Brazilian Ministry of Health and the Pan American Health Organization, to establish an association between microcephaly and Zika virus (primary hypothesis) and explore other infectious or noninfectious causes.

Although the ToRCHeS testing was incomplete, our findings suggest an outbreak of severe microcephaly in Pernambuco that peaked in October 2015. Our data, in conjunction with recent surveillance summaries from Brazil (11), are consistent with the timing of the Zika virus epidemic. Our findings illustrate the most severe end of the spectrum of defects affecting newborns. Other manifestations and complications in infants born to mothers infected with Zika virus during pregnancy will be described through close follow-up of these children. The government of Brazil plans to expand the support system for affected children. Further studies will define the proportion of congenital defects according to the gestational age of infection and describe the clinical outcomes.

The Microcephaly Epidemic Research Group comprises experts from several institutions in response to the public health emergency. The main goals of the group are research development and epidemiologic data analysis.

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