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.

Calcium supplementation for prevention of primary hypertension.

BACKGROUND: Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of the review to evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure. OBJECTIVES: To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the prevention of primary hypertension. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to September 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and the US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: The 2020 updated search identified four new trials. We included a total of 20 trials with 3512 participants, however we only included 18 for the meta-analysis with 3140 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was: mean difference (MD) -1.37 mmHg, 95% confidence interval (CI) -2.08, -0.66; 3140 participants; 18 studies; I2 = 0%, high-certainty evidence; and MD -1.45, 95% CI -2.23, -0.67; 3039 participants; 17 studies; I2 = 45%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years was: MD -1.86, 95% CI -3.45, -0.27; 452 participants; eight studies; I2 = 19%, moderate-certainty evidence; MD -2.50, 95% CI -4.22, -0.79; 351 participants; seven studies ; I2 = 54%, moderate-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those 35 years or older was: MD -0.97, 95% CI -1.83, -0.10; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence; MD -0.59, 95% CI -1.13, -0.06; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for women was: MD -1.25, 95% CI -2.53, 0.03; 1915 participants; eight studies; I2 = 0%, high-certainty evidence; MD -1.04, 95% CI -1.86, -0.22; 1915 participants; eight studies; I2 = 4%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for men was MD -2.14, 95% CI -3.71, -0.59; 507 participants; five studies; I2 = 8%, moderate-certainty evidence; MD -1.99, 95% CI -3.25, -0.74; 507 participants; five studies; I2 = 41%, moderate-certainty evidence, respectively. The effect was consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was: MD -0.02, 95% CI -2.23, 2.20; 302 participants; 3 studies; I2 = 0%, moderate-certainty evidence with doses less than 1000 mg; MD -1.05, 95% CI -1.91, -0.19; 2488 participants; 9 studies; I2 = 0%, high-certainty evidence with doses 1000 to 1500 mg; and MD -2.79, 95% CI -4.71, 0.86; 350 participants; 7 studies; I2 = 0%, moderate-certainty evidence with doses more than 1500 mg. The effect on diastolic blood pressure was: MD -0.41, 95% CI -2.07, 1.25; 201 participants; 2 studies; I2 = 0, moderate-certainty evidence; MD -2.03, 95% CI -3.44, -0.62 ; 1017 participants; 8 studies; and MD -1.35, 95% CI -2.75, -0.05; 1821 participants; 8 studies; I2 = 51%, high-certainty evidence, respectively. None of the studies reported adverse events. AUTHORS' CONCLUSIONS: An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

Geographic Variations in Test Reactivity for the Serological Diagnosis of Trypanosoma cruzi Infection.

Chagas disease is a neglected disease caused by Trypanosoma cruzi parasites. Most diagnosis is based on serological tests, but the lack of a gold standard test complicates the measurement of test performance. To overcome this limitation, we used samples from a cohort of well-characterized T. cruzi-infected women to evaluate the reactivity of two rapid diagnostic tests and one enzyme-linked immunosorbent assay (ELISA). Our cohort was derived from a previous study on congenital transmission of T. cruzi and consisted of 481 blood/plasma samples from Argentina (n = 149), Honduras (n = 228), and Mexico (n = 104), with at least one positive T. cruzi PCR. Reactivity of the three tests ranged from 70.5% for the Wiener ELISA to 81.0% for the T-Detect and 90.4% for the Stat-Pak rapid tests. Test reactivity varied significantly among countries and was highest in Argentina and lowest in Mexico. When considering at least two reactive serological tests to confirm seropositivity, over 12% of T. cruzi infection cases from Argentina were missed by serological tests, over 21% in Honduras, and an alarming 72% in Mexico. Differences in test performance among countries were not due to differences in parasitemia, but differences in antibody levels against ELISA antigens were observed. Geographic differences in T. cruzi parasite strains as well as genetic differences among human populations both may contribute to the discrepancies in serological testing. Improvements in serological diagnostics for T. cruzi infections are critically needed to ensure an optimum identification of cases.

Calcium supplementation for prevention of primary hypertension.

BACKGROUND: Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of the review to evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure. OBJECTIVES: To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the prevention of primary hypertension. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to September 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and the US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: The 2020 updated search identified four new trials. We included a total of 20 trials with 3512 participants, however we only included 18 for the meta-analysis with 3140 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was: mean difference (MD) -1.37 mmHg, 95% confidence interval (CI) -2.08, -0.66; 3140 participants; 18 studies; I2 = 0%, high-certainty evidence; and MD -1.45, 95% CI -2.23, -0.67; 3039 participants; 17 studies; I2 = 45%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years was: MD -1.86, 95% CI -3.45, -0.27; 452 participants; eight studies; I2 = 19%, moderate-certainty evidence; MD -2.50, 95% CI -4.22, -0.79; 351 participants; seven studies ; I2 = 54%, moderate-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those 35 years or older was: MD -0.97, 95% CI -1.83, -0.10; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence; MD -0.59, 95% CI -1.13, -0.06; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for women was: MD -1.25, 95% CI -2.53, 0.03; 1915 participants; eight studies; I2 = 0%, high-certainty evidence; MD -1.04, 95% CI -1.86, -0.22; 1915 participants; eight studies; I2 = 4%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for men was MD -2.14, 95% CI -3.71, -0.59; 507 participants; five studies; I2 = 8%, moderate-certainty evidence; MD -1.99, 95% CI -3.25, -0.74; 507 participants; five studies; I2 = 41%, moderate-certainty evidence, respectively. The effect was consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was: MD -0.02, 95% CI -2.23, 2.20; 302 participants; 3 studies; I2 = 0%, moderate-certainty evidence with doses less than 1000 mg; MD -1.05, 95% CI -1.91, -0.19; 2488 participants; 9 studies; I2 = 0%, high-certainty evidence with doses 1000 to 1500 mg; and MD -2.79, 95% CI -4.71, 0.86; 350 participants; 7 studies = 8; I2 = 0%, moderate-certainty evidence with doses more than 1500 mg. The effect on diastolic blood pressure was: MD -0.41, 95% CI -2.07, 1.25; 201 participants; 2 studies; I2 = 0, moderate-certainty evidence; MD -2.03, 95% CI -3.44, -0.62 ; 1017 participants; 8 studies; and MD -1.35, 95% CI -2.75, -0.05; 1821 participants; 8 studies; I2 = 51%, high-certainty evidence, respectively. None of the studies reported adverse events. AUTHORS' CONCLUSIONS: An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

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.

Sequential inactivated (IPV) and live oral (OPV) poliovirus vaccines for preventing poliomyelitis.

BACKGROUND: Poliomyelitis mainly affects unvaccinated children under five years of age, causing irreversible paralysis or even death. The oral polio vaccine (OPV) contains live attenuated virus, which can, in rare cases, cause a paralysis known as vaccine-associated paralytic polio (VAPP), and also vaccine-derived polioviruses (VDPVs) due to acquired neurovirulence after prolonged duration of replication. The incidence of poliomyelitis caused by wild polio virus (WPV) has declined dramatically since the introduction of OPV and later the inactivated polio vaccine (IPV), however, the cases of paralysis linked to the OPV are currently more frequent than those related to the WPV. Therefore, in 2016, the World Health Organization (WHO) recommended at least one IPV dose preceding routine immunisation with OPV to reduce VAPPs and VDPVs until polio could be eradicated. OBJECTIVES: To assess the effectiveness, safety, and immunogenicity of sequential IPV-OPV immunisation schemes compared to either OPV or IPV alone. SEARCH METHODS: In May 2019 we searched CENTRAL, MEDLINE, Embase, 14 other databases, three trials registers and reports of adverse effects on four web sites. We also searched the references of identified studies, relevant reviews and contacted authors to identify additional references. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, controlled before-after studies, nationwide uncontrolled before-after studies (UBAs), interrupted time series (ITS) and controlled ITS comparing sequential IPV-OPV schedules (one or more IPV doses followed by one or more OPV doses) with IPV alone, OPV alone or non-sequential IPV-OPV combinations. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 21 studies: 16 RCTs involving 6407 healthy infants (age range 96 to 975 days, mean 382 days), one ITS with 28,330 infants and four nationwide studies (two ITS, two UBA). Ten RCTs were conducted in high-income countries; five in the USA, two in the UK, and one each in Chile, Israel, and Oman. The remaining six RCTs were conducted in middle-income countries; China, Bangladesh, Guatemala, India, and Thailand. We rated all included RCTs at low or unclear risk of bias for randomisation domains, most at high or unclear risk of attrition bias, and half at high or unclear risk for conflict of interests. Almost all RCTs were at low risk for the remaining domains. ITSs and UBAs were mainly considered at low risk of bias for most domains. IPV-OPV versus OPV It is uncertain if an IPV followed by OPV schedule is better than OPV alone at reducing the number of WPV cases (very low-certainty evidence); however, it may reduce VAPP cases by 54% to 100% (three nationwide studies; low-certainty evidence). There is little or no difference in vaccination coverage between IPV-OPV and OPV-only schedules (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.96 to 1.06; 1 ITS study; low-certainty evidence). Similarly, there is little or no difference between the two schedule types for the number of serious adverse events (SAEs) (RR 0.88, 95% CI 0.46 to 1.70; 4 studies, 1948 participants; low-certainty evidence); or the number of people with protective humoral response P1 (moderate-certainty evidence), P2 (for the most studied schedule; two IPV doses followed by OPV; low-certainty evidence), and P3 (low-certainty evidence). Two IPV doses followed by bivalent OPV (IIbO) may reduce P2 neutralising antibodies compared to trivalent OPV (moderate-certainty evidence), but may make little or no difference to P1 or P2 neutralising antibodies following an IIO schedule or OPV alone (low-certainty evidence). Both IIO and IIbO schedules may increase P3 neutralising antibodies compared to OPV (moderate-certainty evidence). It may also lead to lower mucosal immunity given increased faecal excretion of P1 (low-certainty evidence), P2 and P3 (moderate-certainty evidence) after OPV challenge. IPV-OPV versus IPV It is uncertain if IPV-OPV is more effective than IPV alone at reducing the number of WPV cases (very low-certainty evidence). There were no data regarding VAPP cases. There is no clear evidence of a difference between IPV-OPV and OPV schedules for the number of people with protective humoral response (low- and moderate-certainty evidence). IPV-OPV schedules may increase mean titres of P1 neutralising antibodies compared to OPV alone (low- and moderate-certainty evidence), but the effect on P2 and P3 titres is not clear (very low- and moderate-certainty evidence). IPV-OPV probably reduces the number of people with P3 poliovirus faecal excretion after OPV challenge with IIO and IIOO sequences (moderate-certainty evidence), and may reduce the number with P2 (low-certainty evidence), but not with P1 (very low-certainty evidence). There may be little or no difference between the schedules in number of SAEs (RR 0.92, 95% CI 0.60 to 1.43; 2 studies, 1063 participants, low-certainty evidence). The number of persons with P2 protective humoral immunity and P2 neutralising antibodies are probably lower with most sequential schemes without P2 components (i.e. bOPV) than with trivalent OPV or IVP alone (moderate-certainty evidence). IPV (3)-OPV versus IPV (2)-OPV One study (137 participants) showed no clear evidence of a difference between three IPV doses followed by OPV and two IPV doses followed by OPV, on the number of people with P1 (RR 0.98, 95% CI 0.93 to 1.03), P2 (RR 1.00, 95% CI 0.97 to 1.03), or P3 (RR 1.01, 95% CI 0.97 to 1.05) protective humoral and intestinal immunity; all moderate-certainty evidence. This study did not report on any other outcomes. AUTHORS' CONCLUSIONS: IPV-OPV compared to OPV may reduce VAPPs without affecting vaccination coverage, safety or humoral response, except P2 with sequential schemes without P2 components, but increase poliovirus faecal excretion after OPV challenge for some polio serotypes. Compared to IPV-only schedules, IPV-OPV may have little or no difference on SAEs, probably has little or no effect on persons with protective humoral response, may increase neutralising antibodies, and probably reduces faecal excretion after OPV challenge of certain polio serotypes. Using three IPV doses as part of a IPV-OPV schedule does not appear to be better than two IPV doses for protective humoral response. Sequential schedules during the transition from OPV to IPV-only immunisation schedules seems a reasonable option aligned with current WHO recommendations. Findings could help decision-makers to optimise polio vaccination policies, reducing inequities between countries.

Odon device for instrumental vaginal deliveries: results of a medical device pilot clinical study.

BACKGROUND: A prolonged and complicated second stage of labour is associated with serious perinatal complications. The Odon device is an innovation intended to perform instrumental vaginal delivery presently under development. We present an evaluation of the feasibility and safety of delivery with early prototypes of this device from an early terminated clinical study. METHODS: Hospital-based, multi-phased, open-label, pilot clinical study with no control group in tertiary hospitals in Argentina and South Africa. Multiparous and nulliparous women, with uncomplicated singleton pregnancies, were enrolled during the third trimester of pregnancy. Delivery with Odon device was attempted under non-emergency conditions during the second stage of labour. The feasibility outcome was delivery with the Odon device defined as successful expulsion of the fetal head after one-time application of the device. RESULTS: Of the 49 women enrolled, the Odon device was inserted successfully in 46 (93%), and successful Odon device delivery as defined above was achieved in 35 (71%) women. Vaginal, first and second degree perineal tears occurred in 29 (59%) women. Four women had cervical tears. No third or fourth degree perineal tears were observed. All neonates were born alive and vigorous. No adverse maternal or infant outcomes were observed at 6-weeks follow-up for all dyads, and at 1 year for the first 30 dyads. CONCLUSIONS: Delivery using the Odon device is feasible. Observed genital tears could be due to the device or the process of delivery and assessment bias. Evaluating the effectiveness and safety of the further developed prototype of the BD Odon Device™ will require a randomized-controlled trial. TRIAL REGISTRATION: ANZCTR ACTRN12613000141741 Registered 06 February 2013. Retrospectively registered.

Barriers and facilitators to the implementation of antenatal syphilis screening and treatment for the prevention of congenital syphilis in the Democratic Republic of Congo and Zambia: results of qualitative formative research.

BACKGROUND: The impact of untreated syphilis during pregnancy on neonatal health remains a major public health threat worldwide. Given the high prevalence of syphilis during pregnancy in Zambia and Democratic Republic of Congo (DRC), the Preventive Congenital Syphilis Trial (PCS Trial), a cluster randomized trial, was proposed to increase same-day screening and treatment of syphilis during antenatal care visits. To design an accepted and feasible intervention, we conducted a qualitative  formative research. Our objective was to identify context-specific  barriers and facilitators to the implementation of antenatal screening and treatment during pregnancy. METHODS: Qualitative research included in-depth semi-structured interviews with clinic administrators, group interviews with health care providers, and focus groups with pregnant women in primary care clinics (PCCs) in Kinshasa (DRC) and Lusaka (Zambia). RESULTS: A total of 112 individuals participated in the interviews and focus groups. Barriers for the implementation of syphilis testing and treatment were identified at the a) system level: fragmentation of the health system, existence of ANC guidelines in conflict with proposed intervention, poor accessibility of clinics (geographical and functional), staff and product shortages at the PCCs; b) healthcare providers' level: lack of knowledge and training about evolving best practices, reservations regarding same-day screening and treatment; c) Pregnant women level: late enrollment in ANC, lack of knowledge about consequences and treatment of syphilis, and stigma. Based on these results, we developed recommendations for the design of the PCS Trial intervention. CONCLUSION: This research allowed us to identify barriers and facilitators to improve the feasibility and acceptability of a behavioral intervention. Formative research is a critical step in designing appropriate and effective interventions by closing the "know-do gap".

Supply kits for antenatal and childbirth care during antenatal care and delivery: a mixed-methods systematic review, the qualitative approach.

Antenatal care reduces maternal and perinatal mortality and morbidity through the detection and treatment of some conditions, but its coverage is less than optimal within certain populations. Supply kits for maternal health were designed to overcome barriers present when providing care during pregnancy and childbirth particularly to women from underserved population.We conducted a mixed-methods systematic review on the use of supply kits. This manuscript presents the findings from qualitative studies that reported barriers, facilitators, and user's recommendation in the adoption and implementation of any type of kit designed to be used during pregnancy or childbirth.This review included eight studies, and seven were implemented in developing countries. Most studies assessed the implementation of clean delivery kits to be used during labour and delivery, and contributed to gain insights into factors that may hinder or foster the use of kits.Clean delivery kits were conceived to cope with barriers related mainly to access. The most important barrier identified were those related to the socio-cultural and the lack of knowledge dimension such as who held the decision-making authority in the household, as well as popular beliefs behind the idea that birth preparation could bring bad luck, may prevent clients from adhering to their use. In addition, financial constraints and limited understanding of the instructions of use were accessibility barriers found. On the other hand, once used, clean delivery kits for maternal health were accepted by women and health workers. Convenience, hygienic components, and avoidance of delays in receiving care were viewed as satisfactory features.Supply kits are mostly affordable and easily deployable. Increasing awareness among the population about the offered kits and providing information on their benefits emerges as a critical step to foster use in settings where kits are available. Implementation of this strategy requires low complexity resources and could make the use of kits an accepted alternative to increase the use of evidence-based interventions and thus improve quality of care during pregnancy, childbirth and neonatal period mainly at the community level in low income countries and remote areas with low access.

Supply kits for antenatal and childbirth care: a systematic review.

INTRODUCTION: It is critical to increase the uptake of interventions proven to be effective to improve maternal and perinatal outcomes. Supply kits have been suggested to be a feasible strategy designed to ensure timely availability and effective follow-up of care. OBJECTIVE: We conducted a systematic review to summarize the evidence on the uptake, effectiveness and safety of supply kits for maternal care. SEARCH STRATEGY: MEDLINE, the Cochrane Pregnancy and Childbirth Group's Trials Register, Campbell Collaboration, Lilacs, Embase and unpublished studies were searched. SELECTION CRITERIA: Studies that reported the efficacy, safety and use of supply kits for maternal healthcare were eligible. Participants were pregnant women or in childbirth. Supply kits were defined as a collection of medicines, supplies or instruments packaged together with the aim of conducting a healthcare task. DATA COLLECTION AND ANALYSIS: Two reviewers independently performed the screening, data extraction, and methodological and quality assessment. MAIN RESULTS: 24 studies were included: 4 of them were systematic reviews and 20 primary studies. Eighteen studies evaluated a so-called "clean delivery kit". In all but two studies, the kits were used by more than half of the participants. A meta-analysis was deemed inappropriate due to the heterogeneity in study design, in the components of the interventions implemented, in the content of the kits, and in outcomes. Nine studies assessed neonatal outcomes and found statistically significant reductions in cord infection, sepsis and tetanus-related mortality in the intervention group. Three studies showed evidence of reduced neonatal mortality (OR 0.52, 0.60 and 0.71) with statistically significant confidence intervals in all cases. Four studies reported odd ratios for maternal mortality, but only one showed evidence of a statistically significant decrease in this outcome but it was ascribed to hand washing prior to childbirth and not with the use of kits. CONCLUSION: This review suggests potential benefits in the use of supply kits to improve maternal and neonatal health. However, the observational nature of the studies, the heterogeneity and the use of kits incorporated within complex interventions limit the interpretation of the findings.

Zika virus infection in pregnant women in Honduras: study protocol.

BACKGROUND: Although there is increasing evidence for a relationship between symptomatic Zika virus (ZIKV) maternal infection, and microcephaly, a firm causal relation has yet to be established by epidemiologic studies. Studies also need to be conducted in recently infected settings. Our objectives are to assess the frequency of ZIKV infection during pregnancy in Honduras and the association of microcephaly with ZIKV infection. METHODS/DESIGN: We will perform a prospective study enrolling pregnant women at their first antenatal visit and following them up until delivery. At the time of enrollment, women will be interviewed to collect socio-demographic data, data needed to locate them for potential additional follow-up, and data about ZIKV symptoms during pregnancy. We will also collect maternal blood as soon as possible after enrollment. A probable maternal ZIKV infection will be defined as positive for maternal ZIKV IgM. A confirmed maternal ZIKV infection will be defined as positive for ZIKV IgM confirmed by plaque reduction neutralization test. Microcephaly at birth will be defined as an occipito-frontal circumference <2SD for sex and gestational age. Our objective is to enroll 2000 pregnant women. In a first step, we will follow a case cohort design and only analyze blood samples for cases and a sub-cohort of 200 women randomly selected. Blood samples for the entire population will be analyzed at a later stage if funds are available. DISCUSSION: This protocol was designed to be implemented with minimal resources. It allows a cohort to be built, which could be a foundation for future in-depth and follow-up studies.

Systematic review and meta-analysis of respiratory syncytial virus infection epidemiology in Latin America.

Respiratory syncytial virus (RSV) is a frequent cause of acute respiratory infection and the most common cause of bronchiolitis in infants. The aim of this systematic review and meta-analysis was to obtain a comprehensive epidemiological picture of the data available on disease burden, surveillance, and use of resources in Latin America. Pooled estimates are useful for cross-country comparisons. Data from published studies reporting patients with probable or confirmed RSV infection in medical databases and gray literature were included from 74 studies selected from the 291 initially identified. When considering all countries, the largest pooled percentage RSV in low respiratory tract infection patients was found in the group between 0 and 11 months old, 41.5% (95% CI 32.0­51.4). In all countries, percentages were increasingly lower as older children were included in the analyses. The pooled percentage of RSV in LRTIs in the elderly people was 12.6 (95% CI 4.2­24.6). The percentage of RSV infection in hospitalized newborns was 40.9% (95% CI 28.28­54.34). The pooled case fatality ratio for RSV infection was 1.74% (95% CI 1.2­2.4) in the first 2 years of life. The average length of stay excluding intensive care unit admissions among children with risk factors for severe disease was 12.8 (95% CI 8.9­16.7) days, whereas it averaged 7.3 (95% CI 6.1/8.5) days in otherwise healthy children.We could conclude that infants in their first year of age were the most vulnerable population. To our knowledge, this is the first systematic review on RSV disease burden and use of health resources in Latin America.

Calcium supplementation for prevention of primary hypertension.

BACKGROUND: Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure. As small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges, this review intends to evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure. OBJECTIVES: To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people. SEARCH METHODS: We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, EMBASE and ClinicalTrials.gov for randomised controlled trials up to October 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Group's Specialised Register. We also reviewed reference lists from retrieved studies and contacted authors of relevant papers. We applied no language restrictions. SELECTION CRITERIA: We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. MAIN RESULTS: We included 16 trials with 3048 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was mean difference (MD) -1.43 mmHg (95% confidence interval (CI) -2.15 to -0.72) and -0.98 mmHg (95%CI -1.46 to -0.50) respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years (7 trials with 399 participants) was -2.11 mmHg (95%CI -3.58 to -0.64) / -2.61 mmHg (95% CI -3.74, -1.49). The effect on systolic and diastolic blood pressure for those 35 years or more (9 trials with 2649 participants) was -0.96 mmHg (95%CI -1.83 to -0.09) / -0.59 mmHg (95%CI -1.13 to -0.06). The effect on systolic and diastolic blood pressure for women (6 trials with 1823 participants) was -1.45 mmHg (95% CI -2.78 to -0.12) / -0.92 mmHg (95% CI -1.71 to -0.14). The effect on systolic and diastolic blood pressure for men (5 trials with 617 participants) was -2.07 (95%CI -3.56 to -0.59] / -1.91 (95%CI -2.80 to -1.02).The quality of evidence for each of these outcomes was high. The effect is consistent in both genders regardless of baseline calcium intake.The effect on systolic blood pressure was 0.08 mmHg (95% CI -2.16 to 2.32) with doses less than 1000 mg, -1.14 mmHg (95% CI -2.01 to -0.27) with 1000 - 1500 mg, and -2.79 mmHg (95% CI -4.71 to -0.86) with more than 1500 mg. The effect on diastolic blood pressure was -0.54 mmHg (95% CI -2.23 to 1.15), -0.71 mmHg (95% CI -1.37 to -0.06) and -1.43 mmHg (95% CI -2.22 to -0.64) respectively. The quality of evidence for each of these outcomes was high.None of the studies reported adverse events. AUTHORS' CONCLUSIONS: An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. These results should be interpreted with caution, since the proposed biological mechanism explaining the relationship between calcium and blood pressure has not been fully confirmed. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease.There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

Implementation of evidence-based antenatal care in Mozambique: a cluster randomized controlled trial: study protocol.

BACKGROUND: Antenatal care (ANC) reduces maternal and perinatal morbidity and mortality directly through the detection and treatment of pregnancy-related illnesses, and indirectly through the detection of women at increased risk of delivery complications. The potential benefits of quality antenatal care services are most significant in low-resource countries where morbidity and mortality levels among women of reproductive age and neonates are higher.WHO developed an ANC model that recommended the delivery of services scientifically proven to improve maternal, perinatal and neonatal outcomes. The aim of this study is to determine the effect of an intervention designed to increase the use of the package of evidence-based services included in the WHO ANC model in Mozambique. The primary hypothesis is that the intervention will increase the use of evidence-based practices during ANC visits in comparison to the standard dissemination channels currently used in the country. METHODS: This is a demonstration project to be developed through a facility-based cluster randomized controlled trial with a stepped wedge design. The intervention was tailored, based on formative research findings, to be readily applicable to local prenatal care services and acceptable to local pregnant women and health providers. The intervention includes four components: the provision of kits with all necessary medicines and laboratory supplies for ANC (medical and non-medical equipment), a storage system, a tracking system, and training sessions for health care providers. Ten clinics were selected and will start receiving the intervention in a random order. Outcomes will be computed at each time point when a new clinic starts the intervention. The primary outcomes are the delivery of selected health care practices to women attending the first ANC visit, and secondary outcomes are the delivery of selected health care practices to women attending second and higher ANC visits as well as the attitude of midwives in relation to adopting the practices. This demonstration project is pragmatic in orientation and will be conducted under routine conditions. DISCUSSION: There is an urgent need for effective and sustainable scaling-up approaches of health interventions in low-resource countries. This can only be accomplished by the engagement of the country's health stakeholders at all levels. This project aims to achieve improvement in the quality of antenatal care in Mozambique through the implementation of a multifaceted intervention on three levels: policy, organizational and health care delivery levels. The implementation of the trial will probably require a change in accountability and behaviour of health care providers and we expect this change in 'habits' will contribute to obtaining reliable health indicators, not only related to research issues, but also to health care outcomes derived from the new health care model. At policy level, the results of this study may suggest a need for revision of the supply chain management system. Given that supply chain management is a major challenge for many low-resource countries, we envisage that important lessons on how to improve the supply chain in Mozambique and other similar settings, will be drawn from this study. TRIAL REGISTRATION: Pan African Clinical Trial Registry database. Identification number: PACTR201306000550192.

Mode of childbirth in low-risk pregnancies: Nicaraguan physicians' viewpoints.

To explore attitudes of physicians attending births in the public and private sectors and at the managerial level toward cesarean birth in Nicaragua. A qualitative study was conducted consisting of four focus groups with 17 physicians and nine in-depth interviews with decision-makers. Although study participants listed many advantages of vaginal birth and disadvantages of cesarean birth, they perceived that the increase in the cesarean birth rate in Nicaragua has resulted in a reduction in perinatal morbidity and mortality. They ascribed high cesarean birth rates to a web of interrelated provider, patient, and health system factors. They identified five actions that would facilitate a reduction in the number of unnecessary cesarean operations: establishing standards and protocols; preparing women and their families for labor and childbirth; incorporating cesarean birth rate monitoring and audit systems into quality assurance activities at the facility level; strengthening the movement to humanize birth; and promoting community-based interventions to educate women and families about the benefits of vaginal birth. Study participants believe that by performing cesarean operations they are providing the best quality of care feasible within their context. They do not perceive problems with their current practice. The identified causes of unnecessary cesarean operations in Nicaragua are multifactorial, so it appears that a multi-layered strategy is needed to safely reduce cesarean birth rates. The recent Nicaraguan Ministry of Health guidance to promote parto humanizado ("humanization of childbirth") could serve as the basis for a collaborative effort among health care professionals, government, and consumer advocates to reduce the number of unnecessary cesarean births in Nicaragua.

Trypanosoma cruzi Infection in Pregnancies without Congenital Transmission Is Associated with Reduced Fetal Growth: A Cross-Sectional Study in Argentina, Honduras, and Mexico.

We aimed to measure the association between Trypanosoma cruzi infection in pregnancy and reduced fetal growth in the absence of T. cruzi congenital transmission. We conducted a cross-sectional study of secondary data of all singleton live births between 2011 and 2013 in five hospitals from Argentina, Honduras, and Mexico. We excluded newborns with T. cruzi infection. Noninfected pregnant people were those without any positive rapid tests. The main study outcomes were birth weight, head circumference, and length for gestational age and sex. Logistic regression models were adjusted for country, age, education level, and obstetric history. Of the 26,544 deliveries, 459 (1.7%) pregnant people were found by rapid tests to be positive for T. cruzi. Of these, 320 were positive by enzyme-linked immunosorbent assay and 231 had a positive polymerase chain reaction (PCR) test. Uninfected newborns from T. cruzi-infected pregnant people were more likely to have birth weights below the 5th and 10th percentiles and head circumferences below the 3rd and 10th percentiles. Among T. cruzi-infected pregnant people diagnosed by PCR, the odds ratios were 1.58 for birth weight below the 10th percentile (95% CI, 1.12-2.23) and 1.57 for birth weight below the 5th percentile (95% CI, 1.02-2.42). Higher T. cruzi parasitic loads in pregnancy had a stronger association with reduced fetal growth (both in birth weight and head circumference), with an odds ratio of 2.31 (95% CI, 1.36-3.91) for a birth weight below the 5th percentile. The association shows, irrespective of causality, that newborns of pregnancies with T. cruzi have an increased risk of reduced fetal growth. We recommend further studies to assess other potential confounders and the causality of these associations.

Congenital transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico: study protocol.

BACKGROUND: Trypanosoma cruzi has been divided into Discrete Typing Units I and non-I (II-VI). T. cruzi I is predominant in Mexico and Central America, while non-I is predominant in most of South America, including Argentina. Little is known about congenital transmission of T. cruzi I. The specific aim of this study is to determine the rate of congenital transmission of T. cruzi I compared to non-I. METHODS/DESIGN: We are conducting a prospective study to enroll at delivery, 10,000 women in Argentina, 7,500 women in Honduras, and 13,000 women in Mexico. We are measuring transmitted maternal T. cruzi antibodies by performing two rapid tests in cord blood (Stat-Pak, Chembio, Medford, New York, and Trypanosoma Detect, InBios, Seattle, Washington). If at least one of the results is positive, we are identifying infants who are congenitally infected by performing parasitological examinations on cord blood and at 4-8 weeks, and serological follow-up at 10 months. Serological confirmation by ELISA (Wiener, Rosario, Argentina) is performed in cord and maternal blood, and at 10 months. We also are performing T. cruzi standard PCR, real-time quantitative PCR and genotyping on maternal venous blood and on cord blood, and serological examinations on siblings. Data are managed by a Data Center in Montevideo, Uruguay. Data are entered online at the sites in an OpenClinica data management system, and digital pictures of data forms are sent to the Data Center for quality control. Weekly reports allow for rapid feedback to the sites.

[Prevalence of gastroesophageal reflux disease in Uruguay]. / Prevalencia de la enfermedad por reflujo gastroesofágico en Uruguay.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common condition, with wide geographical differences worldwide. There are no epidemiological data on this disease for Uruguay. OBJECTIVE: To estimate the prevalence of GERD in two adult populations in Uruguay (urban and hospital) through the Gastroesophageal reflux disease Questionnaire (GerdQ) questionnaire and evaluation of typical symptoms. MATERIAL AND METHOD: A descriptive, cross-sectional study was carried out through the use of two diagnostic methods administered in two settings: an urban and a hospital setting. The first method consisted of administration of the standardized GerdQ structured questionnaire and the other consisted of evaluating the typical symptoms of GERD. A total of 1141 persons from the urban population, with a mean age of 52 years (± 18 years), and 163 persons from a gastroenterology polyclinic, with a mean age of 53 years (± 16 years), were included. RESULTS: The prevalence of GERD in Uruguay was 4.69%, (95% CI 2.92-6.46%) when the GerdQ questionnaire was used, but increased to 14.14% (95% CI 12.57-15.71) when only typical symptoms were considered. In the hospital sample, the prevalence was 11.66% (95% CI 6.42-16.89%) and 20.25% (95% CI 14.01-26.48), respectively. CONCLUSION: The prevalence obtained in the urban population of Uruguay with the GerdQ questionnaire in the symptomatic (hospital) population was more than double that in the general population, 11.66% and 4.69%, respectively. Evaluation of symptoms, pyrosis and/or regurgitation systematically yields a higher prevalence. Consensus on the definition of GERD and on the instrument used for its diagnosis are essential to interpret and compare epidemiological studies.