Caffeine intake during pregnancy and adverse outcomes: An integrative review.

Caffeine intake during pregnancy is common. Caffeine crosses the placenta, raising concerns about its possible deleterious effects on the developing embryo/fetus. Studies on this subject show conflicting results, and still there is no consensus on the recommended dose of caffeine during pregnancy. We performed an integrative review with studies from six databases, using broad MESH terms to allow the identification of publications that addressed the outcomes of caffeine use during pregnancy, with no date limit for publications, in English and Portuguese language. The research returned 16,192 articles. After removing duplicates, screening by title, abstract and full-text, we evaluated 257 and included 59 articles. We found association between caffeine intake and pregnancy loss, low birth weight, cardiac and genital anomalies, higher body mass, and neurodevelopmental and neurobehavioral outcomes. The effects were often dose dependent. No association with prematurity has been demonstrated, but one study showed a small reduction in gestational age with increasing doses of caffeine intake. Defining a safe dose for caffeine intake during pregnancy is a challenging task due to the heterogeneity in study designs and results, as well as the difficulty of reliably assessing the amount of caffeine consumed. In some studies, exposures below the recommended level of caffeine intake during pregnancy (200 mg/day), as suggested by the guidelines, were associated with pregnancy loss, low birth weight, cardiac and genital anomalies, higher body mass, and neurodevelopmental and neurobehavioral outcomes. Well-designed studies with reliable quantification of caffeine intake are needed to assess the safety of low doses during pregnancy.

Coronavirus disease 2019 population-based prevalence, risk factors, hospitalization, and fatality rates in southern Brazil.

OBJECTIVES: To assess population-based prevalence, risk factors, hospitalization, and infection fatality rates (IFR) associated with COVID-19. METHODS: We conducted two household surveys among the non-institutionalized adult population from May 30 to June 17, 2020, in Lajeado, an 84,000-inhabitant industrial city in southern Brazil. Primary outcome was prevalence of SARS-CoV-2 infection. Secondary outcomes were COVID-19-related hospitalizations and deaths occurring up to June 20, 2020. We summarized prevalence rates across surveys with meta-analysis. We assessed age-range IFR and hospitalization rate and regressed these rates over age strata using nonlinear (exponential) coefficients of determination (R2). RESULTS: Summarized overall prevalence was 3.40% (95% CI, 2.74-4.18), 34% lower in older adults ≥60 years. Prevalence was 14.3 and 5.4 times higher among household contacts and meat-precessing plant (MPP) workers, respectively. IFR ranged from 0.08% (0.06-0.11) to 4.63% (2.93-7.84) in individuals 20-39 years and ≥60 years, respectively. R2 for hospitalization rate and IFR over age were 0.98 and 0.93 (both p-values <0.0001), respectively. CONCLUSIONS: This is the first population-based study in Brazil to estimate COVID-19 prevalence, hospitalization, and fatality rates per age stratum. Rates were largely age-dependent. Household contacts and MPP workers are at higher risk of infection. Our findings are valuable for health-policy making and resource allocation to mitigate the pandemic.

Fetal Alcohol Spectrum Disorders: Health Needs Assessment in Brazil.

BACKGROUND: Fetal alcohol syndrome (FAS) is a disorder caused by alterations in embryo-fetal development due to prenatal alcohol exposure. It is estimated that between 0.5 and 2 per 1,000 individuals are born with FAS every year. In Brazil, there are few studies addressing the extent of the problem of FAS/fetal alcohol spectrum disorders (FASD); these studies are confined to limited geographic areas. Therefore, we decided to perform a health needs assessment for FAS/FASD in Brazil. METHODS: To estimate the prevalence of FAS and FASD in Brazil, we used information from the literature, which estimates between 0.5 and 2/1,000 births per year for FAS and 10 to 50/1,000 for FASD. RESULTS: We estimated that approximately 1,500 to 6,000 children are born with FAS every year. Considering the whole population, the prevalence would be 95,377 to 380,000 affected people. However, when we consider FASD as a whole, we estimate that between 1,900,000 and 9,500,000 Brazilians might suffer the more severe consequences of alcohol exposure during pregnancy and be living with FASD. CONCLUSION: The results of the current study indicate that FAS and FASD are prevalent disorders in Brazil, and more policies targeting alcohol intake during pregnancy must be developed.

CD4+ T Lymphocytes Subsets in Early Life: Does Exclusive Breastfeeding Promote Allergy?

Breastfeeding provides ideal nutrition and passive immunization for growing infants, protecting them from potentially fatal infectious diseases. Exclusive breastfeeding is recommended for at least six months and should be continued complementarity for another year. One of the justifications for this recommended practice is the prevention of allergic diseases, which has been controversial for many years. Here we reviewed data regarding breastfeeding practices and hypothesized that exclusive breastfeeding for long periods may affect the availability of helper T lymphocyte 1-polarizing antigens in babies. This fact could favor helper T lymphocyte 2 (TH2) phenotype development and consequently increase the incidences of allergies, although we have found no consistent evidence in the literature supporting or denying that breastfeeding plays a role in allergic diseases. The literature mostly presents inconsistencies and/or methodological issues precluding a final answer to this issue. The development of the adaptive immune system depends on exposure to antigens that elicit the production of specific cytokines and activates T lymphocyte populations. It is believed that a promotion of the TH2 phenotype to the detriment of another lymphocyte subset takes place, although the exact knowledge about when this process begins is still under investigation. Therefore, the recent increase in allergy incidence might be partly explained by breastfeeding practices in the world and by the hypothesis presented here, affecting the baby's immune system development through selective antigen availability.

Efficacy and safety of intravenous laronidase for mucopolysaccharidosis type I: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of IV laronidase for MPS I. METHODS: A systematic literature review was performed by searching the ClinicalTrials.gov, MEDLINE/PubMed, EMBASE, LILACS, and Cochrane Library databases, limited to clinical trials published until December 31, 2016. The first inclusion criterion was being a randomized controlled trial (RCT). If < five RCTs were identified, open-label and nonrandomized trials, controlled or uncontrolled (quasi-experimental), including ≥ five patients, and evaluating relevant outcomes defined a priori, would also be included. For meta-analysis, primary inferences were based on random-effects models. Assessment of article quality was performed in accordance with the GRADE criteria. The Cochrane Risk of Bias tool was used to examine the risk of bias for RCTs. RESULTS: The selection phase retrieved 632 articles. During the first phase of selection, 158 had the abstract or full text read for assessment of eligibility, of which nine (two RCTs) were included for qualitative synthesis. Four papers were included in the meta-analysis, which was performed for the following outcomes: occurrence of treatment-emergent or infusion-related adverse events (65%; 95%CI 53, 76), mild in most cases; development of IgG antibodies to laronidase (88%; 95%CI 67, 100); apnea-hypopnea index (not significant-NS), urinary glycosaminoglycans (GAGs) [mean change -65.5 µg/mg creatinine (95%CI -68.8, -62.3)], liver size [mean change -31.03% (95%CI -36.1, -25.9)], left ventricular mass index (LVMI) [mean change -1.8 (95%CI -2.32, -0.25)], and distance covered in the 6-minute walk test (NS). Among the outcomes not included in meta-analysis, we found evidence for benefit of laronidase only on shoulder flexion. CONCLUSIONS: Our findings suggest that IV laronidase effectively reduces urinary GAGs excretion, hepatomegaly and LVMI, and can improve shoulder flexion in MPS I patients. Laronidase appears to be safe in the studied population.

[Prevalence of congenital abnormalities identified in fetuses with 13, 18 and 21 chromosomal trisomy]. / Prevalência das malformações congênitas identificadas em fetos com trissomia dos cromossomos 13, 18 e 21.

PURPOSE: To describe the prevalence of malformations found in fetuses with trisomy of chromosomes 13, 18 and 21 by identifying the most frequent within each condition. METHODS: A retrospective cross-sectional study with the analysis of trisomy cases of chromosomes 13, 18 and 21 diagnosed through fetal karyotype obtained by amniocentesis/cordocentesis, between October 1994 and May 2014, at a Teaching Hospital in Brazil Southern Region. Malformations identified through morphological ultrasonography were described and, subsequently, confirmed in newborn examinations and/or fetal autopsy. The results were analyzed using Fisher's test and analysis of variance (ANOVA), with a 5% level of significance (p=0.05). RESULTS: Sixty-nine cases of trisomy were diagnosed among 840 exams; nine were excluded due to outcome outside Hospital de Clínicas de Porto Alegre or incomplete records, remaining 60 cases (nine cases of chromosome 13 trisomy, 26 of chromosome 18, and 25 of chromosome 21). In all three groups, heart disease occurred in most cases; the ventricular septal defect was more prevalent and occurred in 66.7% of the trisomy 13 group. Gastrointestinal abnormalities were more prevalent in the trisomy 18 group, especially omphalocele (38.5%; p<0.01). Genitourinary anomalies were more significantly frequent in the trisomy 13 group (pyelectasis, 55.6% - p<0.01; ambiguous genitalia, 33.3% - p=0.01). Central nervous system defects were identified in all cases of trisomy 13. Facial cracks were significantly more prevalent among fetuses with trisomy 13 (66.7%; p<0.01). Hand and feet malformations significantly differed among the trisomy groups. Hand defects occurred in 50% of trisomy 18 cases, and in 44.4% of all trisomy 13 cases (p<0.01); congenital clubfoot was more common in the trisomy 18 group, being detected in 46.2% of fetuses (p<0.01). The abnormalities were found in 50.9, 27.3 and 21.7% of trisomy 18, 13 and 21 cases respectively. CONCLUSION: Many fetal malformations identified at ultrasound are suggestive of trisomy and represent an important tool for etiologic diagnosis and prenatal and pre-conception genetic counseling.

Impact on pregnancies in south Brazil from the influenza A (H1N1) pandemic: cohort study.

INTRODUCTION: The emergence of a new subtype of the influenza virus in 2009 generated interest in the international medical community, the media, and the general population. Pregnant women are considered to be a group at risk of serious complications related to the H1N1 influenza virus. The aim of this study was to evaluate the outcomes and teratogenic effects of pregnancies exposed to the H1N1 virus during the Influenza A epidemic that occurred in the state of Rio Grande do Sul in 2009. METHODS: This is an uncontrolled prospective cohort study of pregnant women with suspected symptoms of Influenza A who were reported in the Information System for Notifiable Diseases-Influenza (SINAN-Influenza) during the epidemic of 2009 (database from the state of Rio Grande do Sul, Brazil). There were 589 cases of pregnant women with suspected infection. Among these, 243 were tested by PCR and included in the analysis. The main outcome measures were: maternal deaths, pregnancy outcome, stillbirths, premature births, low birth weight, congenital malformations, and odds ratios for H1N1+ and non-H1N1 pregnant women. RESULTS: There were one hundred and sixty-three (67%) confirmed cases of H1N1, 34 cases (14%) of seasonal Influenza A and 46 (19%) who were negative for Influenza A. There was no difference between the three groups in clinical parameters of the disease. There were 24 maternal deaths--18 of them had H1N1. There were 8 stillbirths--5 were children of H1N1 infected mothers. There were no differences in perinatal outcomes. CONCLUSIONS: The present data do not indicate an increase in teratogenic risk from exposure to the influenza A (H1N1) virus. These results will help to strengthen the data and clarify the health issues that arose after the pandemic.