Background: Iron and folic acid supplementation have been recommended in pregnancy for anaemia prevention, and may improve other maternal, pregnancy, and infant outcomes. Objectives: To examine the effects of daily oral iron supplementation during pregnancy, either alone or in combination with folic acid or with other vitamins and minerals, as an intervention in antenatal care. Search methods: We searched the Cochrane Pregnancy and Childbirth Trials Registry on 18 January 2024 (including CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform, conference proceedings), and searched reference lists of retrieved studies. Selection criteria: Randomised or quasi-randomised trials that evaluated the effects of oral supplementation with daily iron, iron + folic acid, or iron + other vitamins and minerals during pregnancy were included. Data collection and analysis: Review authors independently assessed trial eligibility, ascertained trustworthiness based on pre-defined criteria, assessed risk of bias, extracted data, and conducted checks for accuracy. We used the GRADE approach to assess the certainty of the evidence for primary outcomes. We anticipated high heterogeneity amongst trials; we pooled trial results using a random-effects model (average treatment effect). Main results: We included 57 trials involving 48,971 women. A total of 40 trials compared the effects of daily oral supplements with iron to placebo or no iron; eight trials evaluated the effects of iron + folic acid compared to placebo or no iron + folic acid. Iron supplementation compared to placebo or no iron. Maternal outcomes: Iron supplementation during pregnancy may reduce maternal anaemia (4.0% versus 7.4%; risk ratio (RR) 0.30, 95% confidence interval (CI) 0.20 to 0.47; 14 trials, 13,543 women; low-certainty evidence) and iron deficiency at term (44.0% versus 66.0%; RR 0.51, 95% CI 0.38 to 0.68; 8 trials, 2873 women; low-certainty evidence), and probably reduces maternal iron-deficiency anaemia at term (5.0% versus 18.4%; RR 0.41, 95% CI 0.26 to 0.63; 7 trials, 2704 women; moderate-certainty evidence), compared to placebo or no iron supplementation. There is probably little to no difference in maternal death (2 versus 4 events, RR 0.57, 95% CI 0.12 to 2.69; 3 trials, 14,060 women; moderate-certainty evidence). The evidence is very uncertain for adverse effects (21.6% versus 18.0%; RR 1.29, 95% CI 0.83 to 2.02; 12 trials, 2423 women; very low-certainty evidence) and severe anaemia (Hb < 70 g/L) in the second/third trimester (< 1% versus 3.6%; RR 0.22, 95% CI 0.01 to 3.20; 8 trials, 1398 women; very low-certainty evidence). No trials reported clinical malaria or infection during pregnancy. Infant outcomes: Women taking iron supplements are probably less likely to have infants with low birthweight (5.2% versus 6.1%; RR 0.84, 95% CI 0.72 to 0.99; 12 trials, 18,290 infants; moderate-certainty evidence), compared to placebo or no iron supplementation. However, the evidence is very uncertain for infant birthweight (MD 24.9 g, 95% CI -125.81 to 175.60; 16 trials, 18,554 infants; very low-certainty evidence). There is probably little to no difference in preterm birth (7.6% versus 8.2%; RR 0.93, 95% CI 0.84 to 1.02; 11 trials, 18,827 infants; moderate-certainty evidence) and there may be little to no difference in neonatal death (1.4% versus 1.5%, RR 0.98, 95% CI 0.77 to 1.24; 4 trials, 17,243 infants; low-certainty evidence) or congenital anomalies, including neural tube defects (41 versus 48 events; RR 0.88, 95% CI 0.58 to 1.33; 4 trials, 14,377 infants; low-certainty evidence). Iron + folic supplementation compared to placebo or no iron + folic acid. Maternal outcomes: Daily oral supplementation with iron + folic acid probably reduces maternal anaemia at term (12.1% versus 25.5%; RR 0.44, 95% CI 0.30 to 0.64; 4 trials, 1962 women; moderate-certainty evidence), and may reduce maternal iron deficiency at term (3.6% versus 15%; RR 0.24, 95% CI 0.06 to 0.99; 1 trial, 131 women; low-certainty evidence), compared to placebo or no iron + folic acid. The evidence is very uncertain about the effects of iron + folic acid on maternal iron-deficiency anaemia (10.8% versus 25%; RR 0.43, 95% CI 0.17 to 1.09; 1 trial, 131 women; very low-certainty evidence), or maternal deaths (no events; 1 trial; very low-certainty evidence). The evidence is uncertain for adverse effects (21.0% versus 0.0%; RR 44.32, 95% CI 2.77 to 709.09; 1 trial, 456 women; low-certainty evidence), and the evidence is very uncertain for severe anaemia in the second or third trimester (< 1% versus 5.6%; RR 0.12, 95% CI 0.02 to 0.63; 4 trials, 506 women; very low-certainty evidence), compared to placebo or no iron + folic acid. Infant outcomes: There may be little to no difference in infant low birthweight (33.4% versus 40.2%; RR 1.07, 95% CI 0.31 to 3.74; 2 trials, 1311 infants; low-certainty evidence), comparing iron + folic acid supplementation to placebo or no iron + folic acid. Infants born to women who received iron + folic acid during pregnancy probably had higher birthweight (MD 57.73 g, 95% CI 7.66 to 107.79; 2 trials, 1365 infants; moderate-certainty evidence), compared to placebo or no iron + folic acid. There may be little to no difference in other infant outcomes, including preterm birth (19.4% versus 19.2%; RR 1.55, 95% CI 0.40 to 6.00; 3 trials, 1497 infants; low-certainty evidence), neonatal death (3.4% versus 4.2%; RR 0.81, 95% CI 0.51 to 1.30; 1 trial, 1793 infants; low-certainty evidence), or congenital anomalies (1.7% versus 2.4; RR 0.70, 95% CI 0.35 to 1.40; 1 trial, 1652 infants; low-certainty evidence), comparing iron + folic acid supplementation to placebo or no iron + folic acid. A total of 19 trials were conducted in malaria-endemic countries, or in settings with some malaria risk. No studies reported maternal clinical malaria; one study reported data on placental malaria. Authors' conclusions: Daily oral iron supplementation during pregnancy may reduce maternal anaemia and iron deficiency at term. For other maternal and infant outcomes, there was little to no difference between groups or the evidence was uncertain. Future research is needed to examine the effects of iron supplementation on other maternal and infant health outcomes, including infant iron status, growth, and development.
Resumir la evidencia sobre las asociaciones de la anemia materna y el uso de hierro prenatal con hematológica materna y los resultados adversos del embarazo; y para evaluar posibles relaciones exposición-respuesta de dosis de hierro, la duración de uso, y la concentración de hemoglobina en período prenatal con los resultados del embarazo.
DISEÑO: Revisión sistemática y meta-análisis
FUENTES DE DATOS: Búsquedas de PubMed y Embase de estudios publicados hasta mayo de 2012 y las referencias de los artículos de revisión.
SELECCIÓN DE ESTUDIOS Ensayos aleatorios de uso de hierro prenatal y estudios de cohorte prospectivos de anemia prenatal; Se excluyeron los estudios transversales y de casos y controles cruzados.
RESULTADOS: 48 ensayos aleatorios (17 793 mujeres) y 44 estudios de cohortes (1 851 682 mujeres) fueron incluidos. El uso del hierro aumentado materna significa la concentración de hemoglobina por 4,59 (95% intervalo de confianza 3,72-5,46) g / L en comparación con los controles y redujo significativamente el riesgo de anemia (riesgo relativo 0,50, 0,42 a 0,59), la deficiencia de hierro (0,59, 0,46 a 0,79) , la anemia por deficiencia de hierro (0,40, 0,26-0,60), y el bajo peso al nacer (0,81, 0,71 hasta 0,93). El efecto del hierro sobre el parto prematuro no fue significativa (riesgo relativo 0,84, 0,68 a 1,03). El análisis de los estudios de cohorte mostró un riesgo significativamente mayor de bajo peso al nacer (odds ratio ajustada 1,29, 1,09 a 1,53) y el nacimiento prematuro (1,21, 1,13 a 1,30) con la anemia en el primer o segundo trimestre. El análisis de la exposición-respuesta indicó que por cada aumento de 10 mg de hierro dosis / día, hasta 66 mg / día, el riesgo relativo de la anemia materna fue de 0,88 (0,84-0,92) (p para la tendencia lineal <0,001). El peso al nacer se incrementó en 15,1 (6,0-24,2) g (p para la tendencia lineal = 0,005) y el riesgo de bajo peso al nacer disminuyó en un 3% (riesgo relativo 0,97, 0,95 a 0,98) por cada aumento de 10 mg en dosis / día (p para la tendencia lineal <0,001). Duración de uso no se asoció significativamente con los resultados después del ajuste para la dosis. Además, para cada 1 g / L aumento de la hemoglobina media, peso al nacer aumentó en un 14,0 (6,8-21,8) g (P para la tendencia lineal = 0,002); Sin embargo, la media de la hemoglobina no se asoció con el riesgo de bajo peso al nacer y parto prematuro. No se observó ninguna evidencia de un efecto significativo sobre la duración de la gestación, nacimientos pequeño para la edad gestacional y la longitud al nacer.
CONCLUSIONES: El uso prenatal diaria de hierro mejoraron sustancialmente el peso al nacer de una manera dosis-respuesta lineal, probablemente conduce a una reducción en el riesgo de bajo peso al nacer. Una mejora en prenatal significa la concentración de hemoglobina aumentó linealmente peso al nacer.
INTRODUCCIÓN: La deficiencia de hierro es la deficiencia nutricional más prevalente en el mundo, especialmente durante el embarazo. De acuerdo con la literatura, la anemia, anemia muy grave, se asocia con un mayor riesgo de mortalidad materna. También pone a las madres en riesgo de múltiples complicaciones perinatales. Numerosos estudios realizados en el pasado han evaluado el impacto de la suplementación con hierro y ácido fólico, pero los datos relativos a la eficacia y la calidad de la evidencia de estas intervenciones son escasas. Este artículo pretende abordar el impacto de hierro con y sin suplementación con folato sobre la anemia materna y proporciona una calidad específica de acuerdo con los resultados del Niño de la Salud de Referencia sobre Epidemiología (CHERG) directrices.
MÉTODOS: Se realizó una revisión sistemática de ensayos aleatorios publicados y cuasialeatorios en PubMed y la Cochrane Library de acuerdo con las directrices CHERG. Los estudios seleccionados suplementación diaria de hierro empleado con o sin ácido fólico en comparación con ninguna intervención / placebo, y también en comparación suplementación intermitente con el régimen diario. Los estudios fueron resumidos y clasificados de acuerdo a diseño del estudio, las limitaciones específicas de intervención y los efectos de los resultados. Normas CHERG se aplicaron para evaluar el impacto de estas intervenciones sobre la anemia por deficiencia de hierro durante el embarazo. Se formularon recomendaciones para las vidas salvadas Herramienta (LIST).
RESULTADOS: Tras la evaluación de los títulos de 3550, 31 fueron seleccionados para la evaluación con criterios CHERG. La suplementación con hierro diaria resultó en el 73% de reducción en la incidencia de la anemia a término (RR = 0,27, IC 95%: 0,17 a 0,42; modelo de efectos aleatorios) y el 67% de reducción de la anemia por deficiencia de hierro a término (RR = 0,33, IC 95% : 0,16 a 0,69; modelo aleatorio), en comparación con ninguna intervención / placebo. Para esta intervención, ambos resultados fueron clasificados como evidencia "moderada" de calidad. La suplementación diaria con hierro y ácido fólico se asoció con un 73% de reducción de la anemia a término (RR = 0,27, IC 95%: 0,12 a 0,56; modelo aleatorio) con un grado de calidad de "moderado". El efecto de la misma intervención en la anemia por deficiencia de hierro no fue significativa (RR = 0,43, IC 95%: 0,17 a 1,09; modelo aleatorio) y se calificó como evidencia de "baja" calidad. No hubo diferencia en las tasas de anemia a término con hierro y ácido fólico intermitente versus hierro y ácido fólico a diario suplementos (RR = 1,61, IC 95%: 0,82 -3,14; modelo aleatorio).
CONCLUSIÓN: La aplicación de las normas CHERG, se recomienda una reducción del 73% en la anemia a término con el hierro al día (solo) o suplementos de hierro / ácido fólico (combinado) vs ninguna intervención o placebo; para su inclusión en la Lista Modelo. Dada la escasez de estudios de hierro intermitente o la suplementación con hierro y ácido fólico, especialmente en los países en desarrollo, se recomienda una mayor evaluación de esta intervención en comparación con el régimen de suplementación diaria.
Background: Iron and folic acid supplementation have been recommended in pregnancy for anaemia prevention, and may improve other maternal, pregnancy, and infant outcomes. Objectives: To examine the effects of daily oral iron supplementation during pregnancy, either alone or in combination with folic acid or with other vitamins and minerals, as an intervention in antenatal care. Search methods: We searched the Cochrane Pregnancy and Childbirth Trials Registry on 18 January 2024 (including CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform, conference proceedings), and searched reference lists of retrieved studies. Selection criteria: Randomised or quasi-randomised trials that evaluated the effects of oral supplementation with daily iron, iron + folic acid, or iron + other vitamins and minerals during pregnancy were included. Data collection and analysis: Review authors independently assessed trial eligibility, ascertained trustworthiness based on pre-defined criteria, assessed risk of bias, extracted data, and conducted checks for accuracy. We used the GRADE approach to assess the certainty of the evidence for primary outcomes. We anticipated high heterogeneity amongst trials; we pooled trial results using a random-effects model (average treatment effect). Main results: We included 57 trials involving 48,971 women. A total of 40 trials compared the effects of daily oral supplements with iron to placebo or no iron; eight trials evaluated the effects of iron + folic acid compared to placebo or no iron + folic acid. Iron supplementation compared to placebo or no iron. Maternal outcomes: Iron supplementation during pregnancy may reduce maternal anaemia (4.0% versus 7.4%; risk ratio (RR) 0.30, 95% confidence interval (CI) 0.20 to 0.47; 14 trials, 13,543 women; low-certainty evidence) and iron deficiency at term (44.0% versus 66.0%; RR 0.51, 95% CI 0.38 to 0.68; 8 trials, 2873 women; low-certainty evidence), and probably reduces maternal iron-deficiency anaemia at term (5.0% versus 18.4%; RR 0.41, 95% CI 0.26 to 0.63; 7 trials, 2704 women; moderate-certainty evidence), compared to placebo or no iron supplementation. There is probably little to no difference in maternal death (2 versus 4 events, RR 0.57, 95% CI 0.12 to 2.69; 3 trials, 14,060 women; moderate-certainty evidence). The evidence is very uncertain for adverse effects (21.6% versus 18.0%; RR 1.29, 95% CI 0.83 to 2.02; 12 trials, 2423 women; very low-certainty evidence) and severe anaemia (Hb < 70 g/L) in the second/third trimester (< 1% versus 3.6%; RR 0.22, 95% CI 0.01 to 3.20; 8 trials, 1398 women; very low-certainty evidence). No trials reported clinical malaria or infection during pregnancy. Infant outcomes: Women taking iron supplements are probably less likely to have infants with low birthweight (5.2% versus 6.1%; RR 0.84, 95% CI 0.72 to 0.99; 12 trials, 18,290 infants; moderate-certainty evidence), compared to placebo or no iron supplementation. However, the evidence is very uncertain for infant birthweight (MD 24.9 g, 95% CI -125.81 to 175.60; 16 trials, 18,554 infants; very low-certainty evidence). There is probably little to no difference in preterm birth (7.6% versus 8.2%; RR 0.93, 95% CI 0.84 to 1.02; 11 trials, 18,827 infants; moderate-certainty evidence) and there may be little to no difference in neonatal death (1.4% versus 1.5%, RR 0.98, 95% CI 0.77 to 1.24; 4 trials, 17,243 infants; low-certainty evidence) or congenital anomalies, including neural tube defects (41 versus 48 events; RR 0.88, 95% CI 0.58 to 1.33; 4 trials, 14,377 infants; low-certainty evidence). Iron + folic supplementation compared to placebo or no iron + folic acid. Maternal outcomes: Daily oral supplementation with iron + folic acid probably reduces maternal anaemia at term (12.1% versus 25.5%; RR 0.44, 95% CI 0.30 to 0.64; 4 trials, 1962 women; moderate-certainty evidence), and may reduce maternal iron deficiency at term (3.6% versus 15%; RR 0.24, 95% CI 0.06 to 0.99; 1 trial, 131 women; low-certainty evidence), compared to placebo or no iron + folic acid. The evidence is very uncertain about the effects of iron + folic acid on maternal iron-deficiency anaemia (10.8% versus 25%; RR 0.43, 95% CI 0.17 to 1.09; 1 trial, 131 women; very low-certainty evidence), or maternal deaths (no events; 1 trial; very low-certainty evidence). The evidence is uncertain for adverse effects (21.0% versus 0.0%; RR 44.32, 95% CI 2.77 to 709.09; 1 trial, 456 women; low-certainty evidence), and the evidence is very uncertain for severe anaemia in the second or third trimester (< 1% versus 5.6%; RR 0.12, 95% CI 0.02 to 0.63; 4 trials, 506 women; very low-certainty evidence), compared to placebo or no iron + folic acid. Infant outcomes: There may be little to no difference in infant low birthweight (33.4% versus 40.2%; RR 1.07, 95% CI 0.31 to 3.74; 2 trials, 1311 infants; low-certainty evidence), comparing iron + folic acid supplementation to placebo or no iron + folic acid. Infants born to women who received iron + folic acid during pregnancy probably had higher birthweight (MD 57.73 g, 95% CI 7.66 to 107.79; 2 trials, 1365 infants; moderate-certainty evidence), compared to placebo or no iron + folic acid. There may be little to no difference in other infant outcomes, including preterm birth (19.4% versus 19.2%; RR 1.55, 95% CI 0.40 to 6.00; 3 trials, 1497 infants; low-certainty evidence), neonatal death (3.4% versus 4.2%; RR 0.81, 95% CI 0.51 to 1.30; 1 trial, 1793 infants; low-certainty evidence), or congenital anomalies (1.7% versus 2.4; RR 0.70, 95% CI 0.35 to 1.40; 1 trial, 1652 infants; low-certainty evidence), comparing iron + folic acid supplementation to placebo or no iron + folic acid. A total of 19 trials were conducted in malaria-endemic countries, or in settings with some malaria risk. No studies reported maternal clinical malaria; one study reported data on placental malaria. Authors' conclusions: Daily oral iron supplementation during pregnancy may reduce maternal anaemia and iron deficiency at term. For other maternal and infant outcomes, there was little to no difference between groups or the evidence was uncertain. Future research is needed to examine the effects of iron supplementation on other maternal and infant health outcomes, including infant iron status, growth, and development.