BRAzil magnesium (BRAMAG) trial: a double-masked randomized clinical trial of oral magnesium supplementation in pregnancy.

BACKGROUND: There is conflicting evidence about the role of oral magnesium supplementation in the prevention of preterm birth and related adverse outcomes. The objective of this study was to compare magnesium citrate with placebo in the prevention of adverse perinatal and maternal outcomes among women at higher risk. METHODS: This multicenter, double-masked, placebo-controlled randomized superiority clinical trial compared oral magnesium citrate 300 mg to matched placebo, from 12 to 20 weeks' gestation until delivery. This trial was completed in three centers in northeastern Brazil. Eligible women were those with a singleton pregnancy and ≥ 1 risk factor, such as prior preterm birth or preeclampsia, or current chronic hypertension or pre-pregnancy diabetes mellitus, age > 35 years or elevated body mass index. The primary perinatal composite outcome comprised preterm birth < 37 weeks' gestation, stillbirth > 20 weeks, neonatal death or NICU admission < 28 days after birth, or small for gestational age birthweight < 3rd percentile. The co-primary maternal composite outcome comprised preeclampsia or eclampsia < 37 weeks, severe gestational hypertension < 37 weeks, placental abruption, or maternal stroke or death during pregnancy or ≤ 7 days after delivery. RESULTS: Analyses comprised 407 women who received magnesium citrate and 422 who received placebo. The perinatal composite outcome occurred among 75 (18.4%) in the magnesium arm and 76 (18.0%) in the placebo group - an adjusted odds ratio (aOR) of 1.10 (95% CI 0.72-1.68). The maternal composite outcome occurred among 49 (12.0%) women in the magnesium arm and 41 women (9.7%) in the placebo group - an aOR of 1.29 (95% CI 0.83-2.00). CONCLUSIONS: Oral magnesium citrate supplementation did not appear to reduce adverse perinatal or maternal outcomes in high-risk singleton pregnancies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02032186, registered January 9, 2014.

Could the erythrocyte indices or serum ferritin predict the therapeutic response to a trial with oral iron during pregnancy? Results from the Accuracy study for Maternal Anaemia diagnosis (AMA).

BACKGROUND: Treatment of maternal iron-deficiency anaemia can reduce risks of prematurity and low birth weight; hence a reliable diagnosis of maternal iron needs is critical. However, erythrocyte indices and serum ferritin have shown a weak correlation with iron status during pregnancy. This study verified the accuracy of those tests to predict the responsiveness to a therapeutic test with oral iron as reference standard for iron deficiency in pregnant women. METHODS: A prospective diagnostic study phase 3 was conducted in a single prenatal care center in Northeast Brazil. Between August 2011 and October 2012 a consecutive sampling included 187 women in their 2(nd)-3(rd) trimesters of low-risk pregnancy and having anaemia (haemoglobin <11.0 g/dL). Until December 2012, 139 women completed a trial with daily pills of ferrous sulfate (40 mg of iron), during 23 to 125 days. Haemoglobin (Hb), other erythrocyte indices and ferritin (index-tests) were assessed pre-treatment by automated analyzers. Hb was performed also post-treatment to assess the therapeutic response by its post-pretreatment differences. We estimated sensitivity (Se), specificity (Sp), predictive values (PV), likelihood ratios (LR), diagnostic Odds Ratio (OR), area under Receiver Operating Characteristic curve (AUC), accuracy ratio and agreement coefficient of the index-tests against an increase of at least 0.55 Hb Z-score (reference standard test). We calculated the Z-scores according to the reference population from Centers for Disease Control and Prevention. RESULTS: Hb had a mean increase of 0.24 Z-score after 30 iron pills (p 0.013). All index-tests demonstrated PV- above 70 %, PV+ around 40 %, LR around 1.0, and AUC of 0.5 to 0.6. Hb and haematocrit had Se of 50 % (95 % CI 40 to 70); and Sp of 59 % (95 % CI 43 to 74) and 47 % (95 % CI 38 to 57), respectively. Ferritin, Mean Corpuscular Volume, Mean Corpuscular Haemoglobin, Mean Corpuscular Haemoglobin Concentration and Red blood cell Distribution Width had Se below 40 % with Sp above 70 %. CONCLUSIONS: Erythrocyte indices and ferritin could not predict the iron needs of anemic pregnant women. Increases of Hb Z-scores after a short treatment with oral iron may be a reliable therapeutic test. TRIAL REGISTRATION: World Health Organization International Clinical Trials Registry Platform U1111-1123-2605; Brazilian Registry of Clinical Trials RBR-237wbg , registered 28 July 2011.

The Effect of a Maternal Double Megadose of Vitamin A Supplement on Serum Levels of Retinol in Children Aged under Six Months.

Objective. To measure concentrations of serum retinol in children after the use of maternal vitamin A double megadose supplements. Design. Randomized controlled clinical trial. Setting. The study was conducted at two maternity hospitals in the city of Recife, in the northeast region of Brazil between August 2007 and June 2009. Subjects and Methods. 276 children/mothers were recruited after birth and the women received a 200,000 IU capsule of vitamin A. After ten days they were randomly assigned to two treatment groups. One group received a second 200.000 IU capsule, while the other received a placebo. The concentrations of retinol in the serum of the children from each group were measured at 2, 4, and 6 months. Results. 173 children completed the study. There was no difference between the two treatment groups (P = 0.514). The mean base retinol level was lower than that at four and six months (P < 0.001). Conclusions. The maternal double megadose supplement had no additional effect on the serum retinol levels of the children, although concentrations of retinol in the children rose in the first six months of life. This trial is registered with NCT00742937.

Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000 IU of vitamin A.

BACKGROUND AND OBJECTIVE: Postpartum vitamin A supplementation is a strategy used to combat vitamin A deficiency and seems to reduce maternal/infant morbidity and mortality. However, studies have shown that a dose of 200 000 IU (World Health Organization [WHO] protocol) does not seem to provide adequate retinol levels in maternal breast milk, infant serum, and infant tissue. The objective of this study was to compare the effect of postpartum maternal supplementation with 400 000 IU (International Vitamin A Consultative Group protocol) compared with 200 000 IU of vitamin A on infant morbidity. METHODS: This was a randomized controlled, triple-blinded clinical trial conducted at 2 public maternity hospitals in Recife in northeastern Brazil. There were 276 mother-child pairs that were allocated to 2 treatment groups: 400 000 IU or 200 000 IU of vitamin A. They were followed up for >6 months to evaluate infant morbidity. RESULTS: Fever (rate ratio [RR]: 0.92 [95% confidence interval (CI): 0.75-1.14]), diarrhea (RR: 0.96 [95% CI: 0.72-1.28]), otitis (RR: 0.94 [95% CI: 0.48-1.85]), acute respiratory infection (RR: 1.03 [95% CI: 0.88-1.21]), the need for intravenous rehydration (RR: 2.08 [95% CI: 0.64-2.07]), and the use of antibiotic treatment (RR: 0.80 [95% CI: 0.43-1.47]) did not differ significantly between the 2 treatment groups. CONCLUSIONS: Our findings suggest that postpartum maternal supplementation with 400 000 IU of vitamin A does not provide any additional benefits in the reduction of illness in children aged <6 months; therefore, we do not support the proposal to increase the standard vitamin A dose in the existing WHO protocol.

Efeito da fortificação alimentar com ácido fólico na prevalência de defeitos do tubo neural / Efecto de la fortificación alimentaria con ácido fólico en la prevalencia de defectos del tubo neural / Effects of folic acid fortification on the prevalence of neural tube defects

OBJETIVO:Analisar o efeito de alimentos fortificados com ácido fólico na prevalência de defeitos de fechamento do tubo neural entre nascidos vivos. MÉTODOS: Estudo longitudinal de nascidos vivos do município de Recife (PE) entre 2000 e 2006. Os dados pesquisados foram obtidos do Sistema Nacional de Informações de Nascidos Vivos. Os defeitos de fechamento do tubo neural foram definidos de acordo com o Código Internacional de Doenças-10ª Revisão: anencefalia, encefalocele e espinha bífida. Compararam-se as prevalências nos períodos anterior (2000-2004) e posterior (2005-2006) ao período mandatório à fortificação. Analisou-se a tendência temporal das prevalências trimestrais de defeitos do fechamento do tubo neural pelos testes de Mann-Kendall e Sen's Slope. RESULTADOS: Não se identificou tendência de redução na ocorrência do desfecho (Teste de Mann-Kendall; p= 0,270; Sen's Slope =-0,008) no período estudado. Não houve diferença estatisticamente significativa entre as prevalências de defeitos do fechamento do tubo neural nos períodos anterior e posterior à fortificação dos alimentos com acido fólico de acordo com as características maternas. CONCLUSÕES: Embora não tenha sido observada redução dos defeitos do fechamento do tubo neural após o período mandatório de fortificação de alimentos com ácido fólico, os resultados encontrados não permitem descartar o seu benefício na prevenção desta malformação. São necessários estudos avaliando maior período e considerando o nível de consumo dos produtos fortificados pelas mulheres em idade fértil.

Effects of folic acid fortification on the prevalence of neural tube defects.

OBJECTIVE: To analyze the effect of folic acid-fortified foods on the prevalence of neural tube defects in live newborns. METHODS: Longitudinal study with newborns from the city of Recife, Northeastern Brazil, between 2000 and 2006. Data analyzed were obtained from the Sistema Nacional de Informações de Nascidos Vivos (National Information System on Live Births). Neural tube defects were defined in accordance with the International Classification of Diseases, 10th revision (ICD-10): anencephaly, encephalocele, and spina bifida. Prevalences from the periods before (2000-2004) and after (2005-2006) the mandatory fortification period were compared. Time trend of three-month prevalences of neural tube defects were analyzed using Mann-Kendall test and Sen's Slope estimator. RESULTS: Tendency towards reduction in the occurrence of outcome (Mann-Kendall test; p= 0.270; Sen's Slope estimator =-0.008) was not identified in the period studied. The difference between prevalences of neural tube defects in the periods before and after food fortification with folic acid was not statistically significant, according to maternal characteristics. CONCLUSIONS: Even though reduction in neural tube defects after the period of mandatory food fortification with folic acid was not observed, results found do not enable its benefit to prevent malformations to be ruled out. Studies assessing longer periods and considering the level of consumption of fortified products by women of fertile age are necessary.

Adherence and side effects of three ferrous sulfate treatment regimens on anemic pregnant women in clinical trials.

The objective of this study was to analyze adherence and side effects of three iron supplement regimens (ferrous sulfate) on anemic pregnant women. The clinical trial involved 150 women between the 16th and 20th gestational weeks, at low obstetric risk and with hemoglobin concentration of between 8.0 and 11.0 g/dL. Treatment was provided by ferrous sulfate with 60 mg of elemental iron during 16 (+/- 1) weeks, in three regimens: single tablet a week (n = 48); single tablet twice a week (n = 53) or single tablet a day (n = 49). The outcomes were adherence, assessed through interviews and by counting tablets, and side effects, according to patient information. The adherence showed a declining trend (92%, 83% and 71%; p = 0.010) and the side effects revealed a growing trend (40%, 45% and 71%; p = 0.002) as the dosage increased. Diarrhea and epigastric pain were significantly associated with the dose administered (p = 0.002). These results suggest that in anemic pregnant women, complaints are directly proportional and the compliance is inversely proportional to the amount of medicinal iron.

Adherence and side effects of three ferrous sulfate treatment regimens on anemic pregnant women in clinical trials / Adesão e efeitos colaterais em ensaio clínico comparando três esquemas de tratamento com sulfato ferroso em gestantes anêmicas

The objective of this study was to analyze adherence and side effects of three iron supplement regimens (ferrous sulfate) on anemic pregnant women. The clinical trial involved 150 women between the 16th and 20th gestational weeks, at low obstetric risk and with hemoglobin concentration of between 8.0 and 11.0g/dL. Treatment was provided by ferrous sulfate with 60mg of elemental iron during 16 (± 1) weeks, in three regimens: single tablet a week (n = 48); single tablet twice a week (n = 53) or single tablet a day (n = 49). The outcomes were adherence, assessed through interviews and by counting tablets, and side effects, according to patient information. The adherence showed a declining trend (92 percent, 83 percent and 71 percent; p = 0.010) and the side effects revealed a growing trend (40 percent, 45 percent and 71 percent; p = 0.002) as the dosage increased. Diarrhea and epigastric pain were significantly associated with the dose administered (p = 0.002). These results suggest that in anemic pregnant women, complaints are directly proportional and the compliance is inversely proportional to the amount of medicinal iron.

O objetivo deste estudo foi analisar a adesão e os efeitos colaterais de três esquemas de suplementação com sulfato ferroso em gestantes anêmicas. O ensaio clínico incluiu 150 mulheres entre a 16ª e 20ª semanas de gestação, de baixo risco obstétrico e com concentração de hemoglobina entre 8,0 e 11,0g/dL. A intervenção foi realizada com 60mg de ferro elementar, durante 16 (±1) semanas, em três esquemas: uma drágea semanal (n = 48); uma drágea duas vezes por semana (n = 53) ou uma drágea diariamente (n = 49). Os desfechos foram adesão, verificada por entrevista e contagem das drágeas, e efeitos colaterais auto-relatados pelas pacientes. A adesão apresentou tendência declinante (92 por cento, 83 por cento e 71 por cento; p = 0,010) e os efeitos colaterais, ascendente (40 por cento, 45 por cento e 71 por cento; p = 0,002) com o aumento da dose prescrita. Diarréia e dor epigástrica estiveram significativamente associadas à dose administrada (p = 0,002). Os resultados sugerem que em gestantes anêmicas as queixas e a adesão ao tratamento com sulfato ferroso são, respectivamente, direta e inversamente proporcionais à quantidade do ferro medicamentoso.

[Efficacy of iron supplementation with or without vitamin A for anemia control]. / Eficácia da suplementação de ferro associado ou não à vitamina A no controle da anemia em escolares.

This study aimed to evaluate the efficacy of weekly iron supplementation with or without vitamin A in the treatment of iron deficiency anemia, using an experimental, randomized, non-placebo-controlled design in 1999. 267 schoolchildren 6 to 14 years of age were randomized to two treatment groups: one group (144) received 200mg iron sulfate alone, with 40 mg of elemental iron, while the other (123) received the same iron supplementation dose plus 10,000 IU of vitamin A (both groups for 30 weeks). Final anemia prevalence was reduced from 48.4% to 17.7% (p < 0.001) in the group receiving iron supplementation alone and 58.1% to 14.3% (p < 0.001) in the group receiving iron plus vitamin A. There was no significant difference between the groups at the end of the study according to mean Hb (p = 0.355) and anemia (p = 0.479). There was a significant correction for iron deficiency anemia with weekly iron-alone supplementation, but with no additional advantage of vitamin A. New studies on the synergism between these two micronutrients are recommended.

Eficácia da suplementação de ferro associado ou não à vitamina A no controle da anemia em escolares / Efficacy of iron supplementation with or without vitamin A for anemia control

Com o objetivo de avaliar a eficácia da suplementação de ferro, associado ou não à vitamina A, na anemia ferropriva, administrado semanalmente, realizou-se ensaio clínico comunitário, randomizado, não controlado por placebo, em 1999. Uma amostra probabilística de 267 escolares de ambos os sexos com 6 a 14 anos de idade foram casualizados em bloco segundo dois tipos de intervenção: um grupo (144) recebeu 200mg de sulfato ferroso com (40mg de ferro elementar) e o outro (123) recebeu dose similar de sulfato ferroso associado a 10.000 UI de vitamina A, durante 30 semanas. A prevalência de anemia ao final foi reduzida de 48,4 por cento, para 17,7 por cento (p < 0,001), no grupo que recebeu sulfato ferroso, e de 58,1 por cento, para 14,3 por cento (p < 0,001), no grupo que recebeu sulfato ferroso associado à vitamina A. Não houve diferença significante entre os grupos, ao final do estudo, quanto às médias de Hb (p = 0,355) e à proporção de anêmicos (p = 0,479). Corrigiu-se significantemente a anemia ferropriva com suplementação semanal de sulfato ferroso, mas não houve vantagem adicional com a associação da vitamina A. Sugerem-se novos estudos sobre o sinergismo desses micronutrientes.

This study aimed to evaluate the efficacy of weekly iron supplementation with or without vitamin A in the treatment of iron deficiency anemia, using an experimental, randomized, non-placebo-controlled design in 1999. 267 schoolchildren 6 to 14 years of age were randomized to two treatment groups: one group (144) received 200mg iron sulfate alone, with 40mg of elemental iron, while the other (123) received the same iron supplementation dose plus 10,000 IU of vitamin A (both groups for 30 weeks). Final anemia prevalence was reduced from 48.4 percent to 17.7 percent (p < 0.001) in the group receiving iron supplementation alone and 58.1 percent to 14.3 percent (p < 0.001) in the group receiving iron plus vitamin A. There was no significant difference between the groups at the end of the study according to mean Hb (p = 0.355) and anemia (p = 0.479). There was a significant correction for iron deficiency anemia with weekly iron-alone supplementation, but with no additional advantage of vitamin A. New studies on the synergism between these two micronutrients are recommended.

Síndrome da rubéola congênita: perfil clínico de crianças usuárias do sistema único de saúde de Pernambuco, nordeste do Brasil / Congenital rubella syndrome: clinical profile of children seen at Public Health Institution in Pernambuco, Northeast of Brasil

O objetivo do estudo foi descrever caracteristicas clínicas de crianças portadoras de síndrome de rubéola congênita, usuárias do Sistema Ùnico de Saúde de Pernambuco. Trata-se de uma série de casos de crianças, com diagnóstico confirmado ou compatível de síndrome da rubéola congênita, avaliadas entre março de 2002 e setembro de 2003, em duas instituições de referência do Estado. Considerou-se caso confirmado, quando a criança apresentava malformação congênita e confirmação laboratorial de infecção rubéolica, e compatível, quando os resultados laboratoriais foram insuficientes e a criança apresentava duas complicações da doença, ou uma complicação associada `a infecção materna, confirmada por laboratório ou vínculo epidemiológico. Foram analisados os dados clínicos e realizadas as avaliações cardiologica, audiológica e oftalmológica. Foram avaliadas 84 crianças, sendo 25,0por cento casos confirmados e 75,0por cento compatíveis. A média das idades foi 51,4 ± 36,4 meses, com baixo peso ao nascer, em 40,5por cento das crianças. As anomalias mais frequentes foram surdez (86,9por cento), seguidas das lesões oculares (68,0por cento), neurológicas (60,7por cento) e cardiopatia congênita (54,8por cento). Foi encontrada catarata congênita em 48,8por cento, retardo mental em 40,5por cento, retinopatia pigmentar em 25,opor cento, microcefalia em 13,opor cento. O tempo médio para diagnóstico das complicações foi 238 dias. A alta freqüência de casos de rubéola congênita, com baixa taxa de casos confirmados neste estudo, revela necessidade de maior atenção dos profissionais de saúde às populações de risco para rubéola. Recomenda-se que os casos suspeitos de SRC sejam notificados e investigados, visando tratamento adequado.