Characteristics of children of the Microcephaly Epidemic Research Group Pediatric Cohort who developed postnatal microcephaly.

The number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was - 0.098 (95% CI % - 0.117 to - 0.080), of weight was: - 0.010 (95%-CI - 0.033 to 0.014) and of height was: - 0.023 (95%-CI - 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern.

The economic burden of congenital Zika Syndrome in Brazil: an overview at 5 years and 10 years.

BACKGROUND: The aim of this paper is to estimate the economic burden of children with congenital Zika Syndrome (CZS) in Brazil over 5-10 years. METHODS: We conducted a modelling study based on data collected in a case-control study in Brazil, including children with CZS (cases) and typically developing children (controls), born in 2015 and 2016. In total, 484 participants were recruited in two sites, Recife and Rio de Janeiro. Social and economic information was collected in a survey from the carers of cases and controls, and detailed healthcare utilisation was recorded for each child in the Rio de Janeiro cohort prospectively in a database. We used this information to estimate the cost per child with severe, moderate and no CZS and incremental cost per child with severe and moderate versus no CZS from a disaggregated societal perspective. These estimates were incorporated into an economic burden model to estimate the incremental burden of the CZS epidemic in Brazil over 5 years and 10 years. FINDINGS: The societal cost per child with severe CZS was US$50 523 to 10 years of age (born in 2015 and 2016), substantially higher than the costs for moderate CZS (US$29 283) and without CZS (US$12 331). The incremental economic burden of severe versus no CZS in Brazil over 10 years was US$69.4 million from the household and US$129.0 million from the government perspective. For moderate CZS, these figures amounted to US$204.1 million and US$86.6 million. Over 10 years, 97% of the total societal economic cost of severe CZS is borne by the government, but only 46% for moderate CZS. INTERPRETATION: The economic burden of CZS is high at the household, provider and government levels. The compensatory government payments helped to alleviate some of the additional costs incurred by families with a child qualifying for the disability benefits, and could be scaled to include the children with moderate CZS.

Neighbourhood-level income and Zika virus infection during pregnancy in Recife, Pernambuco, Brazil: an ecological perspective, 2015-2017.

Zika virus (ZIKV) infections during pregnancy can lead to adverse neurodevelopmental and clinical outcomes in congenitally infected offspring. As the city of Recife in Pernambuco State, Brazil-the epicentre of the Brazilian microcephaly epidemic-has considerable disparities in living conditions, this study used an ecological approach to investigate the association between income at the neighbourhood level and the risk of ZIKV infections in pregnant individuals between December 2015 and April 2017. The spatial distribution of pregnant individuals with ZIKV infection was plotted on a map of Recife stratified into four categories based on mean monthly income of household heads. Additionally, a Poisson regression model with robust variance was fitted to compare proportions of ZIKV infections among pregnant individuals in relation to the mean monthly income of household heads, based on the 2010 census data, across 94 neighbourhoods in Recife. The results provide evidence that the risk of ZIKV infection to pregnant individuals was higher among those residing in lower-income neighbourhoods: relative to neighbourhoods that had a mean monthly income of ≥5 times minimum wage, neighbourhoods with <1 and 1 to <2 times minimum wage had more than four times the risk (incidence rate ratio, 95% CI 4.08, 1.88 to 8.85 and 4.30, 2.00 to 9.20, respectively). This study provides evidence of a strong association between neighbourhood-level income and ZIKV infection risks in the pregnant population of Recife. In settings prone to arboviral outbreaks, locally targeted interventions to improve living conditions, sanitation, and mosquito control should be a key focus of governmental interventions to reduce risks associated with ZIKV infections during pregnancy.

Epidemic preparedness: Prenatal Zika virus screening during the next epidemic.

Zika virus (ZIKV) is a vectorborne infectious agent of global public health significance due to its potential to cause severe teratogenic outcomes. The question of whether health systems should consider adopting screening programmes for ZIKV infections during pregnancy warrants consideration. In this analysis, we apply the Wilson-Jungner framework to appraise the potential utility of a prenatal ZIKV screening programme, outline potential screening strategies within the case-finding pathway, and consider other epidemiological factors that may influence the planning of such a screening programme. Our evaluation of a potential prenatal ZIKV screening programme highlights factors affirming its usefulness, including the importance of Congenital Zika Syndrome as a public health problem and the existence of analogous congenital prenatal screening programmes for STORCH agents (syphilis, toxoplasmosis, others (eg, human immunodeficiency virus, varicella-zoster virus, parvovirus B19), rubella, cytomegalovirus, and herpes simplex virus). However, our assessment also reveals key barriers to implementation, such as the need for more accurate diagnostic tests, effective antiviral treatments, increased social service capacity, and surveillance. Given that the reemergence of ZIKV is likely, we provide a guiding framework for policymakers and public health leaders that can be further elaborated and adapted to different contexts in order to reduce the burden of adverse ZIKV-related birth outcomes during future outbreaks.

Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia.

INTRODUCTION: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean. METHODS AND ANALYSIS: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach. ETHICS AND DISSEMINATION: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities.

"Life Is Taking Me Where I Need to Go": Biographical Disruption and New Arrangements in the Lives of Female Family Carers of Children with Congenital Zika Syndrome in Pernambuco, Brazil.

The congenital Zika syndrome (CZS) epidemic in Brazil turned the spotlight on many other factors beyond illness, such as poverty, gender, and inequalities in health care. Women were the emblematic subjects in this study, not only because Zika virus is a vertical transmission disease, but also because women-in Brazil and elsewhere-typically represent the primary carers of children. This is a qualitative analytic study using semi-structured interviews with 23 female family carers of children with CZS in Brazil. Through the concept of biographical disruption, we analysed some of the social impacts experienced by women involved in caring for affected children. We identified that the arrival of a child with disabilities resulted in biographical disruption similar to that experienced by people with chronic illnesses. Social support networks were configured through an alliance between women from different generations, revealing solidarity networks, but also highlighting the absence of the state in tackling these social vulnerabilities. Tracing the pathways of these biographical narratives enables us to understand how women have acted to defend the value of their disabled children in a society structured on the model of body normativity and inequality. These results may provide clues to a more inclusive society, which confronts systems of gender oppression and the sexual division of labour focused on women.

Hope and trust in times of Zika: the views of caregivers and healthcare workers at the forefront of the epidemic in Brazil.

This article investigates how hope and trust played out for two groups at the forefront of the Zika epidemic: caregivers of children with congenital Zika syndrome and healthcare workers. We conducted 76 in-depth interviews with members of both groups to examine hope and trust in clinical settings, as well as trust in public institutions, in the health system and in the government of Brazil. During and after the Zika epidemic, hope and trust were important to manage uncertainty and risk, given the lack of scientific evidence about the neurological consequences of Zika virus infection. The capacity of healthcare workers and caregivers to trust and to co-create hope seems to have allowed relationships to develop that cushioned social impacts, reinforced adherence to therapeutics and enabled information flow. Hope facilitated parents to trust healthcare workers and interventions. Hope and trust appeared to be central in the establishment of support networks for caregivers. At the same time, mistrust in the government and state institutions may have allowed rumours and alternative explanations about Zika to spread. It may also have strengthened activism in mother's associations, which seemed to have both positive and negative implications for healthcare service delivery. The findings also point to distrust in international health actors and global health agenda, which can impact community engagement in future outbreak responses in Brazil and other countries in Latin America.

The frequency and clinical presentation of Zika virus coinfections: a systematic review.

BACKGROUND: There is limited knowledge on the influence of concurrent coinfections on the clinical presentation of Zika virus (ZIKV) disease. METHODS: To better understand the types, frequencies and clinical manifestations of ZIKV coinfections, we did a systematic review of four databases (PubMed, Embase, Web of Science, LILACS) without restrictions for studies on ZIKV coinfections confirmed by nucleic acid (quantitative real-time-PCR) testing of ZIKV and coinfecting pathogens. The review aimed to identify cohort, cross-sectional, case series and case report studies that described frequencies and/or clinical signs and symptoms of ZIKV coinfections. Conference abstracts, reviews, commentaries and studies with imprecise pathogen diagnoses and/or no clinical evaluations were excluded. RESULTS: The search identified 34 articles from 10 countries, comprising 2 cohort, 10 cross-sectional, 8 case series and 14 case report studies. Coinfections were most frequently reported to have occurred with other arthropod-borne viruses (arboviruses); out of the 213 coinfections described, ZIKV infections co-occurred with chikungunya in 115 cases, with dengue in 68 cases and with both viruses in 19 cases. Other coinfecting agents included human immunodeficiency, Epstein-Barr, human herpes and Mayaro viruses, Leptospira spp, Toxoplasma gondii and Schistosoma mansoni. ZIKV-coinfected cases primarily presented with mild clinical features, typical of ZIKV monoinfection; however, 9% of cases in cohort and cross-sectional studies were reported to experience complications. CONCLUSION: Based on the evidence collated in this review, coinfections do not appear to strongly influence the clinical manifestations of uncomplicated ZIKV infections. Further research is needed to confirm whether risk of severe complications is altered when ZIKV infection co-occurs with other infections. PROSPERO REGISTRATION NUMBER: CRD42018111023.

Association between microcephaly, Zika virus infection, and other risk factors in Brazil: final report of a case-control study.

BACKGROUND: A Zika virus epidemic emerged in northeast Brazil in 2015 and was followed by a striking increase in congenital microcephaly cases, triggering a declaration of an international public health emergency. This is the final report of the first case-control study evaluating the potential causes of microcephaly: congenital Zika virus infection, vaccines, and larvicides. The published preliminary report suggested a strong association between microcephaly and congenital Zika virus infection. METHODS: We did a case-control study in eight public maternity hospitals in Recife, Brazil. Cases were neonates born with microcephaly, defined as a head circumference of 2 SD below the mean. Two controls without microcephaly were matched to each case by expected date of delivery and area of residence. We tested the serum of cases and controls and the CSF of cases for detection of Zika virus genomes with quantitative RT-PCR and for detection of IgM antibodies with capture-IgM ELISA. We also tested maternal serum with plaque reduction neutralisation assays for Zika and dengue viruses. We estimated matched crude and adjusted odds ratios with exact conditional logistic regression to determine the association between microcephaly and Zika virus infection. FINDINGS: We screened neonates born between Jan 15 and Nov 30, 2016, and prospectively recruited 91 cases and 173 controls. In 32 (35%) cases, congenital Zika virus infection was confirmed by laboratory tests and no controls had confirmed Zika virus infections. 69 (83%) of 83 cases with known birthweight were small for gestational age, compared with eight (5%) of 173 controls. The overall matched odds ratio was 73·1 (95% CI 13·0-∞) for microcephaly and Zika virus infection after adjustments. Neither vaccination during pregnancy or use of the larvicide pyriproxyfen was associated with microcephaly. Results of laboratory tests for Zika virus and brain imaging results were available for 79 (87%) cases; within these cases, ten were positive for Zika virus and had cerebral abnormalities, 13 were positive for Zika infection but had no cerebral abnormalities, and 11 were negative for Zika virus but had cerebral abnormalities. INTERPRETATION: The association between microcephaly and congenital Zika virus infection was confirmed. We provide evidence of the absence of an effect of other potential factors, such as exposure to pyriproxyfen or vaccines (tetanus, diphtheria, and acellular pertussis, measles and rubella, or measles, mumps, and rubella) during pregnancy, confirming the findings of an ecological study of pyriproxyfen in Pernambuco and previous studies on the safety of Tdap vaccine administration during pregnancy. FUNDING: Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations.

Social and economic impacts of congenital Zika syndrome in Brazil: Study protocol and rationale for a mixed-methods study.

Global concern broke out in late 2015 as thousands of children in Brazil were born with microcephaly, which was quickly linked to congenital infection with Zika virus (ZIKV). ZIKV is now known to cause a wider spectrum of severe adverse outcomes-congenital Zika syndrome (CZS)-and also milder impairments. This study aimed to explore the social and economic impacts of CZS in Brazil. Data was collected through mixed methods across two settings: Recife City and Jaboatão dos Guararapes in Pernambuco State (the epicentre of the epidemic), and the city of Rio de Janeiro (where reports of ZIKV infection and CZS were less frequent). Data was collected May 2017-January 2018. Ethical standards were adhered to throughout the research. In-depth qualitative interviews were conducted with: mothers and other carers of children with CZS (approximately 30 per setting), pregnant women (10-12 per setting), men and women of child-bearing age (16-20 per setting), and health professionals (10-12 per setting). Thematic analysis was undertaken independently by researchers from at least two research settings, and these were shared for feedback. A case-control study was undertaken to quantitatively explore social and economic differences between caregivers of a child with CZS (cases) and caregivers with an unaffected child (controls). We aimed to recruit 100 cases and 100 controls per setting, from existing studies. The primary caregiver, usually the mother, was interviewed using a structured questionnaire to collect information on: depression, anxiety, stress, social support, family quality of life, health care and social service use, and costs incurred by families. Multivariable logistic regression analyses were used to compare outcomes for cases and controls. Costs incurred as a result of CZS were estimated from the perspective of the health system, families and society. Modelling was undertaken to estimate the total economic burden of CZS from those three perspectives.

Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study.

BACKGROUND: The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy. METHODS: We did this case-control study in eight public hospitals in Recife, Brazil. Cases were neonates with microcephaly. Two controls (neonates without microcephaly), matched by expected date of delivery and area of residence, were selected for each case. Serum samples of cases and controls and cerebrospinal fluid samples of cases were tested for Zika virus-specific IgM and by quantitative RT-PCR. Laboratory-confirmed Zika virus infection during pregnancy was defined as detection of Zika virus-specific IgM or a positive RT-PCR result in neonates. Maternal serum samples were tested by plaque reduction neutralisation assay for Zika virus and dengue virus. We estimated crude odds ratios (ORs) and 95% CIs using a median unbiased estimator for binary data in an unconditional logistic regression model. We estimated ORs separately for cases with and without radiological evidence of brain abnormalities. FINDINGS: Between Jan 15, 2016, and May 2, 2016, we prospectively recruited 32 cases and 62 controls. 24 (80%) of 30 mothers of cases had Zika virus infection compared with 39 (64%) of 61 mothers of controls (p=0·12). 13 (41%) of 32 cases and none of 62 controls had laboratory-confirmed Zika virus infection; crude overall OR 55·5 (95% CI 8·6-∞); OR 113·3 (95% CI 14·5-∞) for seven cases with brain abnormalities; and OR 24·7 (95% CI 2·9-∞) for four cases without brain abnormalities. INTERPRETATION: Our data suggest that the microcephaly epidemic is a result of congenital Zika virus infection. We await further data from this ongoing study to assess other potential risk factors and to confirm the strength of association in a larger sample size. FUNDING: Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations.

Incidence and risk factors for intimate partner violence during the postpartum period.

OBJECTIVE To estimate the incidence and identify risk factors for intimate partner violence during postpartum. METHODS This prospective cohort study was conducted with women, aged between 18-49 years, enrolled in the Brazilian Family Health Strategy in Recife, Northeastern Brazil, between 2005 and 2006. Of the 1.057 women interviewed during pregnancy and postpartum, 539 women, who did not report violence before or during pregnancy, were evaluated. A theoretical-conceptual framework was built with three levels of factors hierarchically ordered: women's and partners' sociodemografic and behavioral characteristics, and relationship dynamics. Incidence and risk factors of intimate partner violence were estimated by Poisson Regression. RESULTS The incidence of violence during postpartum was 9.3% (95%CI 7.0;12.0). Isolated psychological violence was the most common (4.3%; 95%CI 2.8;6.4). The overlapping of psychological with physical violence occurred at 3.3% (95%CI 2.0;5.3) and with physical and/or sexual in almost 2.0% (95%CI 0.8;3.0) of cases. The risk of partner violence during postpartum was increased for women with a low level of education (RR = 2.6; 95%CI 1.3;5.4), without own income (RR = 1.7; 95%CI 1.0;2.9) and those who perpetrated physical violence against their partner without being assaulted first (RR = 2.0; 95%CI 1.2;3.4), had a very controlling partner (RR = 2.5; 95%CI 1.1;5.8), and had frequent fights with their partner (RR = 1.7; 95%CI 1.0;2.9). CONCLUSIONS The high incidence of intimate partner violence during postpartum and its association with aspects of the relationship's quality between the couple, demonstrated the need for public policies that promote conflict mediation and enable forms of empowerment for women to address the cycle of violence.

Postnatal depression in women after unsuccessful attempted abortion.

A population-based cohort study investigated postnatal depression in Brazilian women who attempted an abortion. Participants' views and actions on abortion were assessed during pregnancy and postnatal depression was evaluated with the Edinburgh Postnatal Depression Scale. An unsuccessful abortion attempt was associated with postnatal depression (adjusted OR = 1.6, 95% CI 1.0-2.5). In Brazil abortion is illegal under most circumstances.

Violence against women by their intimate partner during pregnancy and postnatal depression: a prospective cohort study.

BACKGROUND: Partner violence against women is common during pregnancy and might have an adverse effect on the mental health of women after delivery. We aimed to investigate the association of postnatal depression with psychological, physical, and sexual violence against women by their intimate partners during pregnancy. METHODS: In a prospective cohort study undertaken in Recife, northeastern Brazil, between July, 2005, and December, 2006, we enrolled pregnant women (aged 18-49 years) in their third trimester of pregnancy who were attending primary health-care clinics. The women were interviewed during pregnancy and after delivery. The form of partner violence in pregnancy was assessed with a validated questionnaire, and the Edinburgh postnatal depression scale was used to measure postnatal depression. Associations were estimated with odds ratios (ORs), adjusted for confounding factors contributing to the association between postnatal depression and intimate partner violence. FINDINGS: 1133 pregnant women were eligible for inclusion in the study, of whom 1045 had complete data for all variables and were included in the analysis. 270 women (25.8%, 95% CI 23.2-28.6) had postnatal depression. The most common form of partner violence was psychological (294 [28.1%, 25.4-31.0]). Frequency of psychological violence during pregnancy was positively associated with occurrence of postnatal depression, and although this association was attenuated after adjustment, women reporting the highest frequency of psychological violence were more likely to have postnatal depression even after adjustment (adjusted OR 2.29, 95% CI 1.15-4.57). Women who reported physical or sexual violence in pregnancy were more likely to develop postnatal depression (OR 3.28, 2.29-4.70), but this association was substantially reduced after adjustment for psychological violence and confounding factors. INTERPRETATION: Psychological violence during pregnancy by an intimate partner is strongly associated with postnatal depression, independently of physical or sexual violence. This finding has important policy implications since most social policies focus on prevention and treatment of physical violence. FUNDING: Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, e Insumos Estratégicos, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brazil).