Racial Disparities in Medication Use During Pregnancy: Results from the NISAMI Cohort.

Purpose: This study aimed to evaluate racial disparities in medication use and associated factors among pregnant women receiving prenatal care at Brazilian Unified Health System primary care health units in the northeast region. Patients and Methods: A total of 1058 pregnant women in the NISAMI Cohort were interviewed between June 2012 and February 2014. Medicines used during pregnancy were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and ANVISA pregnancy risk categories. Prevalence ratios (crude and adjusted) and 95% confidence intervals (CIs) were estimated using Poisson regression with robust error variance. All analyses were stratified by race (Asian, black, brown/mixed, Brazilian indigenous, and white). Results: Approximately 84% of the pregnant women used at least one medication, with a lower proportion among white women. The most reported medications were antianemic preparations (71.08%; 95% CI 68.27-73.72%), analgesics (21.74%; 95% CI 19.36-24.32%), and drugs for functional gastrointestinal disorders (18.81%; 95% CI 16.57-21.28%). Approximately 29% of women took potentially risky medications during pregnancy, with a higher prevalence among Asian and white women. Factors associated with medication use during pregnancy include a greater number of prenatal consultations, higher education levels, health problems, and smoking. In addition, maternal age above 25 years, smoking status, and two or more previous pregnancies were associated with potentially risky medication use during pregnancy. Conclusion: A high prevalence of medication use during pregnancy was found; however, this prevalence was lower among white women. Nonetheless, black and brown women used antianemic preparations less frequently. This finding suggests that race is a factor of inequity in prenatal care, demanding public policies to mitigate it.

Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis.

Background: The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically, it starts with conventional synthetic DMARDs (csDMARDs), and depending on the patient's response to the treatment and the adverse events experienced, biological DMARDs (bDMARDs) are initiated. bDMARDs are more specific to inflammatory factors than csDMARDs and more efficient in inducing remission and low disease activity. Thus, this study aimed to assess the effectiveness of biological therapy in patients with rheumatoid arthritis in administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science databases were searched from inception to 21 October 2021, to identify observational studies that evaluated the effectiveness of biological therapy in patients with rheumatoid arthritis using administrative databases and real-world data. The methodological quality was assessed by the methodological index for non-randomized studies (MINORS). A fixed or random-effects model estimated risk ratios with 95% confidence intervals. The analysis was divided into four groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus TNFi (adalimumab, etanercept, and golimumab versus infliximab); bDMARDs versus Janus kinase inhibitors (JAKi); and bDMARDs monotherapy versus combination therapy (bDMARDs and MTX). Results: Twenty-one records were eligible for inclusion in this systematic review and meta-analysis; seven population-based cohorts, eight prospective, and six retrospective cohort studies. Overall, 182,098 rheumatoid arthritis patients were evaluated. In the meta-analysis, lower effectiveness was observed among TNFi users than in non-TNFi (RR: 0.88; 95% CI: 0.81-0.95; p < 0.01; I2 = 94.0%) and bDMARDs than in JAKi (RR: 0.86; 95% CI: 0.79-0.94; p < 0.01; I2 = 93.0%). Higher effectiveness among adalimumab, etanercept, and golimumab than in infliximab (RR: 1.19; 95% CI: 1.05-1.36; p < 0.01; I2 = 96.0%) was found. No significant differences in the effectiveness of bDMARD monotherapy compared to combination therapy (RR: 0.83; 95% CI: 0.68-1.00; p < 0.01; I2 = 81.0%) was observed. E-value analysis indicated that the estimates were not robust against unmeasured confounding. Conclusion: According to the available real-world data, our results suggest that biological therapy effectively treats patients with rheumatoid arthritis, indicating higher effectiveness with non-TNFi and JAKi than with TNFi. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID#CRD42020190838, identifier CRD42020190838.

Association between paracetamol use during pregnancy and perinatal outcomes: Prospective NISAMI cohort.

BACKGROUND: Paracetamol is widely used to manage fever and pain during pregnancy worldwide. However, paracetamol may affect the pregnant woman and fetus, once this drug crosses the placental barrier after therapeutic doses and may impair fetal liver function, affecting fetus growth and development. Thus, this study aimed to investigate the association between paracetamol use during pregnancy and perinatal outcomes as preterm birth, low birth weight, and small for gestational age. METHODS AND FINDINGS: Data from 760 pregnant women within the NISAMI Cohort between June 2012 and February 2014 were analyzed. Logistic regression was used to estimate the association among paracetamol use during pregnancy and preterm birth, low birth weight, and small for gestational age. Multivariate analyses were adjusted for socioeconomic, maternal, pregnancy, and newborn covariates. Around 14% of women were exposed to paracetamol during pregnancy. A decrease in paracetamol use throughout pregnancy was observed. Lower risk of low birth weight in infants born to women exposed to the drug (OR 0.21; IC 95% 0.01-0.99) was found. Paracetamol use during pregnancy was not statistically associated with preterm birth or small for gestational age. CONCLUSIONS: The findings of this study do not suggest an increased risk of perinatal outcomes. However, it should not be assumed that paracetamol is a risk-free medication and its use must be rational.

Polyunsaturated fatty acid consumption and weight gain during pregnancy: NISAMI Cohort study.

OBJECTIVES: Few studies have investigated the influence of polyunsaturated fatty acid consumption on excessive weight gain during pregnancy. Thus, we analyzed the association between the intake of polyunsaturated fatty acids (ω-6 and ω-3) and weight gain in women during pregnancy. METHODS: This is a cohort study of 250 pregnant women enrolled in municipal pre-natal services. Weight, height, and dietary intake of polyunsaturated fatty acids were evaluated at the baseline. The semi-quantitative food frequency questionnaire was employed to assess the main exposure. Gestational weight was measured in the first, second, and third trimesters. A dietary pattern involving the consumption of fatty acids was identified through factor analysis. A generalized estimating equation was used for the data analysis. RESULTS: The prevalence of excessive weight gain at the end of pregnancy was 35.2%. Consumption patterns 1 (salted meats, offal, vegetable oil, snacks, legumes, and oleaginous foods) and 2 (red meat, sausages, butter, margarine, mayonnaise, acarajé, caruru, vatapá, and refined cereals) revealed a risk for the accumulation of excess weight during pregnancy. Women who adhered to consumption patterns 1 (RR: 2.39; 95% CI: 1.44-3.94) and 2 (RR: 2.39; 95% CI: 1.44-3.94) were more susceptible to excess weight gain during pregnancy. CONCLUSIONS: Women who adhered to dietary patterns involving foods that are sources of ω-6 fatty acids and saturated fatty acids were more susceptible to gaining weight during pregnancy compared to those who adhered less to these patterns.

Investigation of maternal polymorphisms in genes related to glucose homeostasis and the influence on birth weight: a cohort study.

OBJECTIVES: To contribute to a better understanding of the maternal genetic mechanisms that influence obstetric outcomes and that are involved in maternal and child health, this study aimed to evaluate the association between maternal genetic variants and the offspring birth weight by analyzing single-nucleotide polymorphisms (SNPs) in genes related to glucose homeostasis. METHODS: Three polymorphisms were analyzed (GCK rs1799884, TCF7L2 rs7903146 and LEPR rs1137101) in 250 pregnant women who participated in a Brazilian prospective cohort study. Genotyping was performed by Real-Time Polymerase Chain Reaction (qPCR) using pre-designed TaqMan® SNP genotyping assays. Vitamin D dosage was performed by chemiluminescence. Variance, Pearson's chi-square test and multiple linear regression were used for the statistical analysis. RESULTS: It was possible to verify a significant association between birth weight and maternal GCK rs1799884 when obstetric outcomes, clinical and anthropometric characteristics were taken into consideration. The children of homozygous women for the minor allele GCK rs1799884 presented lower birth weight (ß = -335.25, 95% CI = -669.39; -1.17, p = 0.04). Furthermore, a direct link between a leptin receptor variant and gestational duration was found (p = 0.037). CONCLUSION: The variant GCK rs1799884 (mm) was associated with a reduction in newborn weight in the miscegenated Brazilian population.

Associations between Maternal Dietary Patterns and Infant Birth Weight in the NISAMI Cohort: A Structural Equation Modeling Analysis.

The mother's diet during pregnancy is associated with maternal and child health. However, there are few studies with moderation analysis on maternal dietary patterns and infant birth weight. We aim to analyse the association between dietary patterns during pregnancy and birth weight. A prospective cohort study was performed with pregnant women registered with the prenatal service (Bahia, Brazil). A food frequency questionnaire was used to evaluate dietary intake. Birth weight was measured by a prenatal service team. Statistical analyses were performed using factor analysis with a principal component extraction technique and structural equation modelling. The mean age of the pregnant women was 27 years old (SD: 5.5) and the mean birth weight was 3341.18 g. It was observed that alcohol consumption (p = 0.05) and weight-gain during pregnancy (p = 0.05) were associated with birth weight. Four patterns of dietary consumption were identified for each trimester of the pregnancy evaluated. Adherence to the "Meat, Eggs, Fried Snacks and Processed foods" dietary pattern (pattern 1) and the "Sugars and Sweets" dietary pattern (pattern 4) in the third trimester directly reduced birth weight, by 98.42 g (Confidence interval (CI) 95%: 24.26, 172.59) and 92.03 g (CI 95%: 39.88, 165.30), respectively. It was also observed that insufficient dietary consumption in the third trimester increases maternal complications during pregnancy, indirectly reducing birth weight by 145 g (CI 95%: -21.39, -211.45). Inadequate dietary intake in the third trimester appears to have negative results on birth weight, directly and indirectly, but more studies are needed to clarify these causal paths, especially investigations of the influence of the maternal dietary pattern on the infant gut microbiota and the impacts on perinatal outcomes.

Long-Chain Polyunsaturated Fatty Acid Concentrations and Association with Weight Gain in Pregnancy.

Lower concentrations of omega-3 (ω-3) and higher concentrations of omega-6 (ω-6) have been associated with excess weight in adults; however, the information on this relationship in pregnancy remains in its infancy. This study aimed to investigate the association between plasma levels of ω-3 and ω-6 long-chain polyunsaturated fatty acids (PUFAs) and weight gain during the gestational period. This is a prospective cohort study involving 185 pregnant women registered with the prenatal services of a municipality in the northeast of Brazil. The dosage of the serum concentration of fatty acids and the anthropometric measurements were carried out at the baseline, and the women's weight information in the first, second, and third trimesters was collected from their pregnancy cards. Serum fatty acids were determined with the help of gas chromatography. The response variable of this study is the latent variable weight gain in pregnancy, derived from three variables: gestational weight in the first, second, and third trimesters. The main exposure was the plasma concentrations of PUFAs. Structural equation modeling was used for the data analysis. The mean age of the pregnant women was 26.74 years old (SD: 5.96 years). Most of the women had not completed high school (84%) and had a low income (70.86%). It was observed that the ω-3 PUFAs, represented by ALA plasm (alpha-linolenic acid), DHA (docosahexaenoic acid), and the EPA/ALA ratio (eicosapentaenoic acid to alpha-linolenic acid ratio), were negatively associated with the weight gain during pregnancy construct (-0.20, -0.12, and -0.14, respectively). Meanwhile, the PUFAs represented by the ratio between the ω-6 category acids ARA and LA (arachidonic acid and linoleic acid) had a direct and positive association (0.22) with that construct. Excess maternal weight gain was associated with ω-3 and ω-6 plasma levels. The women with the greatest gestational weight gain were the ones that presented the highest ARA/LA ratio (ω-6) and the lowest plasma concentrations of ALA, DHA, and EPA/ALA ratio (ω-3).

Administrative Data Linkage in Brazil: Potentials for Health Technology Assessment.

Health technology assessment (HTA) is the systematic evaluation of the properties and impacts of health technologies and interventions. In this article, we presented a discussion of HTA and its evolution in Brazil, as well as a description of secondary data sources available in Brazil with potential applications to generate evidence for HTA and policy decisions. Furthermore, we highlighted record linkage, ongoing record linkage initiatives in Brazil, and the main linkage tools developed and/or used in Brazilian data. Finally, we discussed the challenges and opportunities of using secondary data for research in the Brazilian context. In conclusion, we emphasized the availability of high quality data and an open, modern attitude toward the use of data for research and policy. This is supported by a rigorous but enabling legal framework that will allow the conduct of large-scale observational studies to evaluate clinical, economical, and social impacts of health technologies and social policies.

Influence of vitamin D serum concentration, prenatal care and social determinants on birth weight: a northeastern Brazilian cohort study.

The relationship among social determinants, vitamin D serum concentration and the health and nutrition conditions is an important issue in the healthcare of pregnant women and newborns. Thus, the present study analyses how vitamin D, prenatal monitoring and social determinants are associated with birth weight. The cohort comprised 329 pregnant women, up to 34 weeks gestational age at the time of admission, who were receiving care through the prenatal services of Family Health Units. Structural equation modelling was used in the statistical analysis. The mean birth weight was 3340 (sd 0·545) g. Each nmol increase in maternal vitamin D serum concentration was associated with an increase in birth weight of 3·06 g. Prenatal healthcare with fewer appointments (ß -41·49 g, 95 % CI -79·27, -3·71) and late onset of care in the second trimester or third trimester (ß -39·24 g, 95 % CI -73·31, -5·16) favoured decreased birth weight. In addition, low socio-economic class and the practice of Afro-Brazilian religions showed a direct association with high vitamin D serum concentrations and an indirect association with high birth weight, respectively. High gestational BMI (ß 23·84, 95 % CI 4·37, 43·31), maternal education level (ß 24·52 g, 95 % CI 1·82, 47·23) and length of gestation (ß 79·71, 95 % CI 52·81; 106·6) resulted in high birth weight. In conclusion, maternal vitamin D serum concentration, social determinants and prenatal care, evaluated in the context of primary healthcare, directly determined birth weight.

Improving the comprehension of sarcopenic state determinants: An multivariate approach involving hormonal, nutritional, lifestyle and genetic variables.

It is known that sarcopenia is a multifaceted phenomenon, which involves genetic, nutritional, hormonal and living habits aspects. Then, an integrated analysis, as a multivariate approach, could improve the comprehension about the determinants of sarcopenic state in old adults. The present study aimed to investigate the interaction among serum vitamin D, daily caloric and protein intake, lifestyle habits, ACE I/D gene polymorphism and sarcopenic state in community-dwelling old adults. One hundred one community-dwelling old adults were clinically stratified as sarcopenic or non-sarcopenic. Serum vitamin D, daily caloric and protein intake, lifestyle habits (smoking, physical activity level and sedentary behavior) and ACE I/D gene polymorphism were recorded. A multivariate logistic regression technique was applied to investigate the interaction among the selected independent variables and the sarcopenic state. The independent variables age, smoking, serum Vitamin D and ACE I/D polymorphism achieved the statistical criteria to be inserted in the multivariate analysis. After a stepwise procedure from the multivariate logistic regression, the variables age, serum Vitamin D and ACE I/D polymorphism remained, together, in the final model. Sarcopenic state was significantly associated to older age, II-genotype and low serum Vitamin D in old adults from 60 years old.

Co-infection of sexually transmitted pathogens and Human Papillomavirus in cervical samples of women of Brazil.

BACKGROUND: Some sexually transmitted infectious agents, such as Chlamydia trachomatis and Herpes simplex, cause local inflammation, and could contribute to Human Papillomavirus (HPV) and cervical lesion progression. Thus, the aim of this study was to determine any association between the presence of microorganisms of gynecological importance, sexual behavior, clinical and demographical variables to the development and progress of cervical lesions. METHODS: One hundred and thirty-two women between 14 and 78 years and living at Vitória da Conquista, Bahia, Brazil, were included (62 individuals with cervical lesions and 70 without lesions). They answered a questionnaire to provide data for a socioeconomic and sexual activity profile. Samples of cervical swabs were collected and analyzed by PCR to detect genital microorganisms and HPV. Quantitative PCR was used to detect and quantify Ureaplasma urealyticum and Ureaplasma parvum. Univariate and multiple logistic regression were performed to measure the association with the cervical lesions, and an odds ratio (OR) with 95% confidence intervals (95%CI) were calculated. The Mann-Whitney U test was also used to compare the microorganism load in the case and control groups. The significance level was 5% in all hypotheses tested. RESULTS: Cervical lesions were associated with: women in a stable sexual relationship (OR = 14.21, 95%CI = 3.67-55.018), positive PCR for HPV (OR = 16.81, 95%CI = 4.19-67.42), Trichomonas vaginalis (OR = 8.566, 95%CI = 2.04-35.94) and Gardnerella vaginalis (OR = 6.13, 95%CI = 1.53-24.61), adjusted by age and qPCR for U. parvum. U. parvum load showed a statistical difference between the case and control groups (p-value = 0.002). CONCLUSION: Variables such as stable relationship, HPV, T. vaginalis, G. vaginalis were associated with cervical lesions in epidemiological studies. U. parvum load was higher in woman with cervical lesions compared with women without lesions. Additional studies are needed to better understand the role of these factors in cervical lesion development.

Off-label use and harmful potential of drugs in a NICU in Brazil: A descriptive study.

BACKGROUND: Neonates admitted to neonatal intensive care units (NICU) are exposed to a wide variety of drugs, most without any data on safety and efficacy. OBJECTIVE: To describe the drugs prescribed to different groups of neonates hospitalized in a NICU, and to analyze off-label use and harmful potential of drugs, in terms of the potential risks. METHODS: This was a six-month retrospective cohort study of drug use in a NICU, with neonates who were inpatients for a period of over 24 hours, and using prescription data from electronic medical records. Drug information found in the package leaflets, in the British National Formulary for Children 2012-2013, and in the Thomson Micromedex database were compared. Drugs and excipients considered potentially harmful were evaluated according to the literature. RESULTS: One hundred ninety-two neonates were included in the study, with a mean gestational age (GA) of 33.3 weeks (SD ± 4.3), 75.0 % were preterm, with an average of 18.8 days of hospitalization (SD ± 18.1), and a total of 3617 neonates-day. 3290 prescriptions were registered, on average 17.1 prescriptions/neonate (SD ± 17.9) and 8.8 drugs/neonate (SD ± 5.9). The number of prescriptions and drugs was higher in neonates with GA <31 weeks (p <0.05). Anti-infectives for systemic use, blood, alimentary tract and metabolism drug groups were more frequent, varying according to the GA. Neonates (99.5 %) were exposed to unlicensed drugs (UL) and off label use (OL), more frequently in GA <28 weeks (p <0.05). Most OL drugs used were indicated for newborns. 15 potentially harmful drugs were used in more than 70 % of the neonates, and most were OL; exposure to harmful excipients occurred in 91.6 % of the neonates, a percentage even higher when considering immature neonates. CONCLUSIONS: Immature neonates in a Brazilian NICU are exposed to a variety of OL, UL and potentially harmful drugs and excipients.

Prevalence of Mycoplasma genitalium and Mycoplasma hominis in urogenital tract of Brazilian women.

BACKGROUND: The role of Mycoplasma hominis and M. genitalium in urogenital tract infections remains unknown. Furthermore these mollicutes present a complex relationship with the host immune response. The role of inflammatory cytokines in infections also makes them good candidates to investigate bacterial vaginosis and mycoplasma genital infections. Therefore, the aim of this study was to detect the above-mentioned mollicutes by quantitative Polymerase Chain Reaction (qPCR) methodologies in vaginal swabs and dosage of cytokines. METHODS: Vaginal swabs and peripheral blood were collected from 302 women, including healthy individuals. The molecular findings were correlated with some individual behavioral variables, clinical and demographic characteristics, presence of other important microorganisms in vaginal swabs, and levels of interleukin (IL)-1ß and IL-6. RESULTS: M. hominis and M. genitalium were detected in 31.8% and 28.1% of samples, respectively. The qPCR results were associated with clinical signs and symptoms of the infections studied. The frequency of Trichomonas vaginalis, Gardnerella vaginalis, Neisseria gonorrhoeae and Chlamydia trachomatis was 3.0%, 21.5%, 42.4%, and 1.7% respectively. Increased levels of IL-1ß were associated with the presence of M. hominis and signs and/or symptoms of the genital infection of women studied. CONCLUSION: IL-1ß production was associated with the detection of M. hominis by qPCR. The sexual behavior of women studied was associated with the detection of mycoplasma and other agents of genital infections.

Adverse drug reactions in hospitalized children in Fortaleza, Brazil.

PURPOSE: To investigate the occurrence of adverse drug reactions (ADRs) and associated risk factors in a pediatric hospital in northeast Brazil, from August to December 2001. SUBJECTS/SETTING: Two hundred seventy two patients hospitalized for more than 24 hours. METHODS: Prospective cohort study. Daily visits were performed for inclusion or attendance of patients and collection of information on drug prescriptions and medical events. The visits were focused on the detection of adverse events. WHO categories were used to assess the imputability and severity of suspected ADRs. RESULTS: Two hundred sixty five patients (97%) were exposed to medicines during hospitalization; the most frequent diagnosis was pneumonia (30%), the therapeutic class most prescribed was anti-infectives for systemic use (26%). Of a total of 420 adverse events, 47 ADRs were detected in 33 of 265 children treated with drugs. The cumulative incidence of ADRs was 12.5% (33/265); incidence density was 8 events per 1000 patient days (33/4042 patient-days). The skin was the most affected organ (49%); the drugs more implicated were systemic antibiotic (53.2%). The ADRs were mild or moderate in 97.9% of cases; causality was probable in 57.5% and the majority of events were independent of the dose given (55.3%). In multivariate analysis, the risk of ADR increased with the number of drugs, male gender, and > or =3 previous hospitalization courses. CONCLUSION: ADRs are not uncommon among hospitalized children, particularly those with prior histories of hospitalization and concomitant use of several medicines.