Neurodevelopmental assessment of normocephalic children born to Zika virus exposed and unexposed pregnant people.

BACKGROUND: Studies examining the association between in utero Zika virus (ZIKV) exposure and child neurodevelopmental outcomes have produced varied results. METHODS: We aimed to assess neurodevelopmental outcomes among normocephalic children born from pregnant people enrolled in the Zika in Pregnancy in Honduras (ZIPH) cohort study, July-December 2016. Enrollment occurred during the first prenatal visit. Exposure was defined as prenatal ZIKV IgM and/or ZIKV RNA result at enrollment. Normocephalic children, >6 months old, were selected for longitudinal follow-up using the Bayley Scales of Infant and Toddler Development (BSID-III) and the Ages & Stages Questionnaires: Social-Emotional (ASQ:SE-2). RESULTS: One hundred fifty-two children were assessed; after exclusion, 60 were exposed and 72 were unexposed to ZIKV during pregnancy. Twenty children in the exposed group and 21 children in the unexposed group had a composite score <85 in any of the BSID-III domains. Although exposed children had lower cognitive and language scores, differences were not statistically significant. For ASQ:SE-2 assessment, there were not statistically significant differences between groups. CONCLUSIONS: This study found no statistically significant differences in the neurodevelopment of normocephalic children between in utero ZIKV exposed and unexposed. Nevertheless, long-term monitoring of children with in utero ZIKV exposure is warranted. IMPACT: This study found no statistically significant differences in the neurodevelopment in normocephalic children with in utero Zika virus exposure compared to unexposed children, although the exposed group showed lower cognitive and language scores that persisted after adjustment by maternal age and education and after excluding children born preterm and low birth weight from the analysis. Children with prenatal Zika virus exposure, including those normocephalic and have no evidence of abnormalities at birth, should be monitored for neurodevelopmental delays. Follow-up is important to be able to detect developmental abnormalities that might not be detected earlier in life.

Microcephaly Outcomes among Zika Virus-Infected Pregnant Women in Honduras.

The impact of Zika virus (ZIKV) infection on pregnancies shows regional variation emphasizing the importance of studies in different geographical areas. We conducted a prospective study in Tegucigalpa, Honduras, recruiting 668 pregnant women between July 20, 2016, and December 31, 2016. We performed Trioplex real-time reverse transcriptase-PCR (rRT-PCR) in 357 serum samples taken at the first prenatal visit. The presence of ZIKV was confirmed in seven pregnancies (7/357, 2.0%). Nine babies (1.6%) had microcephaly (head circumference more than two SDs below the mean), including two (0.3%) with severe microcephaly (head circumference [HC] more than three SDs below the mean). The mothers of both babies with severe microcephaly had evidence of ZIKV infection. A positive ZIKV Trioplex rRT-PCR was associated with a 33.3% (95% CI: 4.3-77.7%) risk of HC more than three SDs below the mean.

Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): a non-inferiority randomized controlled trial study protocol.

BACKGROUND: Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for preconceptional treatment to reduce parasitic load. The fear of treatment-related side effects limits the implementation of the Argentine guideline recommending BZN 60d/300 mg (or equivalent) treatment of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60d/300 mg course is not yet established. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed. METHODS AND DESIGN: We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150 mg/day (30d/150 mg) vs. BZN 60d/300 mg. We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at 6 months postpartum, and follow them up with the following specific aims: Specific aim 1: to measure the effect of BZN 30d/150 mg compared to 60d/300 mg preconceptional treatment on parasitic load measured by the frequency of positive Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately and 10 months after treatment. Specific aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment interruption. TRIAL REGISTRATION: ClinicalTrials.gov . Identifier: NCT03672487 . Registered 14 September 2018.

Using Prenatal Blood Samples to Evaluate COVID-19 Rapid Serologic Tests Specificity.

INTRODUCTION: Background cross-reactivity with other coronaviruses may reduce the specificity of COVID-19 rapid serologic tests. The vast majority of women attend prenatal care, which is a unique source of population-based blood samples appropriate for validation studies. We used stored 2018 serum samples from an existing pregnancy cohort study to evaluate the specificity of COVID-19 serologic rapid diagnostic tests. METHODS: We randomly selected 120 stored serum samples from pregnant women enrolled in a cohort in 2018 in Tegucigalpa, Honduras, at least 1 year before the COVID-19 pandemic. We used stored serum to evaluate four lateral flow rapid diagnostic tests, following manufacturers' instructions. Pictures were taken for all tests and read by two blinded trained evaluators. RESULTS: We evaluated 120, 80, 90, and 90 samples, respectively. Specificity for both IgM and IgG was 100% for the first two tests (95% confidence intervals [CI] 97.0-100 and 95.5-100, respectively). The third test had a specificity of 98.9% (95% CI 94.0-100) for IgM and 94.4% (95% CI 87.5-98.2) for IgG. The fourth test had a specificity of 88.9% (95% CI 80.5-94.5) for IgM and 100% (95% CI 96.0-100) for IgG. DISCUSSION: COVID-19 serologic rapid tests are of variable specificity. Blood specimens from sentinel prenatal clinics provide an opportunity to validate serologic tests with population-based samples.

Measurement of Head Circumference: Implications for Microcephaly Surveillance in Zika-Affected Areas.

Worldwide recognition of the Zika virus outbreak in the Americas was triggered by an unexplained increase in the frequency of microcephaly. While severe microcephaly is readily identifiable at birth, diagnosing less severe cases requires comparison of head circumference (HC) measurement to a growth chart. We examine measured values of HC and digit preference in those values, and, by extension, the prevalence of microcephaly at birth in two data sources: a research study in Honduras and routine surveillance data in Uruguay. The Zika in Pregnancy in Honduras study enrolled pregnant women prenatally and followed them until delivery. Head circumference was measured with insertion tapes (SECA 212), and instructions including consistent placement of the tape and a request to record HC to the millimeter were posted where newborns were examined. Three indicators of microcephaly were calculated: (1) HC more than 2 standard deviations (SD) below the mean, (2) HC more than 3 SD below the mean (referred to as "severe microcephaly") and (3) HC less than the 3rd percentile for sex and gestational age, using the INTERGROWTH-21st growth standards. We compared these results from those from a previous analysis of surveillance HC data from the Uruguay Perinatal Information System (Sistema Informático Perinatal (SIP). Valid data on HC were available on 579 infants, 578 with gestational age data. Nine babies (1.56%, 95% CI 0.71-2.93) had HC < 2SD, including two (0.35%, 95% CI 0.04-1.24) with HC < 3SD, and 11 (1.9%, 95% CI, 0.79-3.02) were below the 3rd percentile. The distribution of HC showed strong digit preference: 72% of measures were to the whole centimeter (cm) and 19% to the half-cm. Training and use of insertion tapes had little effect on digit preference, nor were overall HC curves sufficient to detect an increase in microcephaly during the Zika epidemic in Honduras. When microcephaly prevalence needs to be carefully analyzed, such as during the Zika epidemic, researchers may need to interpret HC data with caution.