Micronutrients 2012 Micronutrient Status • Important throughout the reproductive years: – Periconceptual period – Pregnancy – Lactation – Inter-pregnancy interval Multiple Micronutrient Deficiencies Occur with Poor Diets • Usually not isolated deficiencies • Nutrients deficiencies interact: example vitamin A supplements can decrease rates of iron deficiency anemia in some populations. Vitamins and Minerals • Risks for low vitamin and mineral status include: – low income – restricted energy intake – adolescence – vegan (Calcium, B12, D, zinc) – Non white status (Calcium) Vitamins and Minerals • Vitamin and mineral needs are increased by: – alcohol consumption – tobacco use – multiple fetuses Proposed Criteria for Selecting the WIC Food Package – IOM, 2004 Highest Priority Nutrients* • Calcium • Iron • Magnesium • Vitamin E • Fiber • Potassium Also Consider • • • • • Vitamin A Vitamin C Vitamin D Vitamin B6 Folate *for adolescent and adult women of reproductive age Proposed Criteria for Selecting the WIC Food Package – IOM, 2004 Nutrients of concern with regard to excessive intake • Sodium • Food energy • Total fat Nutrients to limit in the diet • Saturated fat • Cholesterol • Trans fatty acids Vitamins and Minerals • Increased needs in pregnancy associated with: – DNA/RNA synthesis – Increased blood volume – bone mineralization & structure – Increased energy metabolism The issue of Vitamin-Mineral Supplements • The consumption of more food to meet energy needs and the increased absorption and efficiency of nutrient utilization that occurs in pregnancy are generally adequate to meet the needs for most nutrients. However, vitamin and mineral supplementation is appropriate for some nutrients and situations. Nutrition and lifestyle for a healthy pregnancy outcome .J AM Diet Assoc 2008 Cochrane: Multiple-micronutrient supplementation for women during pregnancy, 2006 • Nine trials (15,378 women): Bangladesh, Nepal, Zimbabwe, Chicago, Guinea-Bissau, Pakistan, Tanzania, Mexico. • When compared with supplementation of two or less micronutrients or no supplementation or a placebo, multiple-micronutrient supplementation resulted in a statistically significant decrease in the number of low birthweight babies (relative risk (RR) 0.83; 95% confidence interval (CI) 0.76 to 0.91), small-forgestational-age babies (RR 0.92; 95% CI 0.86 to 0.99) and in maternal anaemia (RR 0.61; CI 0.52 to 0.71). Just Iron and Folic Acid? • “these differences lost statistical significance when multiple-micronutrient supplementation was compared with iron folic acid supplementation alone.” • Further research: 1) beneficial maternal or fetal effects and 2) assess the risk of excess supplementation and potential adverse interactions between the micronutrients. Fat Soluble Vitamins • Placental transport is by simple diffusion, so fetus is not protected against high maternal intakes • Excess Vitamin A is associated with multiple congenital anomalies – concerns appear to start at 8,000 IU – ACOG and AAP define excessive as > 1,600 RE (twice the RDA) – 1 IU = 0.3 RE all trans retinol High levels of retinol intake during the first trimester of pregnancy result from use of overthe-counter vitamin/mineral supplements (Voyles et al. JADA, Sept., 2000) • N=64 women recruited at initial prenatal visit to obstetrics office in university town. • Household income and educational levels were higher than national averages. • Women completed questionnaires and three day food records. • 2 physicians in office prescribed routine prenatal vitamins, the third did not. Voyles, cont. - Adherence • 23% who were prescribed vitamins did not take them. • 26 % who were prescribed vitamins took OTC supplements instead. • 58% of those who were not prescribed took over the counter supplements. • 9 of 10 women who had excessive intakes took OTC supplements Voyles, Retinol Intakes (n=64) • 20 had intakes < 800 RE • 34 had intakes between 800 and 1,600 RE • 10 had intakes > 1,600 RE • Mean intake of vitamin A from food sources alone was 159% of the RDA Voyles, Applications • Most women can meet vitamin A needs with food alone. • Supplements need to be carefully considered: • many women taking OTC supps before pregnancy • IOM recommendation is to avoid supps with vitamin A in first trimester Vitamin A RDA - 2001 • Non Pregnant = 700 mg RAE (retinol activity equivalents) • Pregnant – Age 14-18: mg 750 – Age 19-30: mg 770 – Age 31-50: mg 770 • Increase based on accumulation of vitamin A in the newborn’s liver (usually about half of total body vitamin A) • UL for pregnancy – Age 14-18: 2,800 mg/day preformed vitamin A – Age 19-50: 3,000 mg/day preformed vitamin A Vitamin D DRI - 1997 • “Women, whether pregnant or not, who receive regular exposure to sunlight do not need vitamin D supplementation.” • AI for pregnancy and non-pregnancy – 14-50: 5.0 mg (200 IU)/day • UL for pregnancy and non-pregnant – 50 mg (2000 IU)/day – Excess associated with fetal hypercalcemia, aortic stenosis, abnormal skull development/premature closure of fontanel Vitamin D DRI: 2010 • RDA for pregnant and non- pregnant women ages 19-30 = 600 IU/day • Population goal: mean 25 OHD levels above 50 nmol/L (20 ng/mL) • “This thorough review found that information about the health benefits beyond bone health- benefits often reported in the media – were from studies that provided often mixed and inconclusive results, and could not be considered reliable.” Tolerable Upper Limit • Upper level intake = 4,000 IU/day • “starting point of 10,000 IU/day reflects first data concerning adverse effects related to allcause mortality, falls and fractures, and CVD risk.” • “Intake values in the range of 4,000 IU/day would not appear to cause serum 25OHD levels to exceed 125 to 150 nmol/L, a concentration which is at the high end of the range of serum levels associated with nadir risk of outcomes such as all-cause mortality.” Fig. 2: The endocrine, paracrine and intracrine functions of vitamin D Hollis, B. W. et al. CMAJ 2006;174:1287-1290 Copyright ©2006 CMA Media Inc. or its licensors Vitamin D in Pregnancy: current concepts. (Urrutia & Thorp. Current Opinion, 2012) • Placenta has enzyme responsible for vit. D activation and vit D receptors • Maternal serum active vit. D increases up to two fold in second and third trimester • Review of 78 studies: “Clinical studies establishing an association between vit D levels and adverse pregnancy outcomes such as preeclampsia, gestational diabetes, LBW, preterm, cesarean delivery and infectious diseases have conflicting results – likely due to paucity of RCT, low sample size, poor adjustment for confounding.” Vitamin D: Emerging Understandings • Widespread deficiencies • Disparities High Prevalence of Vitamin D Deficiency in Black and White Women Living in the Northern US (Simhan, J Nutr, 2007) • 200 Black, 200 white women in Pittsburg • >90% taking prenatal vitamins • Increase in status from winter to summer: – White: 0.23 nmol/l – Black: 0.16 nmol/l Prevalence of Vitamin D Deficiency % Insufficient % Deficient White Infants 42 10 White Mothers 56 5 Black Infants 47 29 Black Mothers 51 46 Prevalence of Vitamin D Insufficiency & Clinical Associations among Veiled E African Women in WA. Reed. J women’s health, 2007 • N=75, • All had low 25(OH)D, • Study done in Seattle in March and April Reed, et al. Vitamin E Supplementation in Pregnancy: Cochrane, 2005 • “Women supplemented with vitamin E in combination with other supplements compared with placebo were at decreased risk of developing clinical preeclampsia (RR 0.44, 95% CI 0.27 to 0.71, three trials, 510 women) using fixed-effect models; however, this difference could not be demonstrated when using randomeffects models (RR 0.44, 95% CI 0.16 to 1.22, three trials, 510 women).” Vitamin E Supplementation in Pregnancy: Cochrane, 2005 • “There were no differences between women supplemented with vitamin E compared with placebo for any of the secondary outcomes.” • Author’s conclusions: “The data are too few to say if vitamin E supplementation either alone or in combination with other supplements is beneficial during pregnancy.” Vitamin C RDA - 2000 • Maternal plasma vitamin C concentration falls in pregnancy, so additional vitamin C is needed to assure transfer to the fetus. • 7 mg vitamin C prevents scurvy in infants so RDA for pregnancy was increased by 10 mg over non-pregnant. • RDA • 14-18: 80 mg vitamin C • 19-30: 85 mg vitamin C • 31-50: 85 mg vitamin C UL for Vitamin C in Pregnancy • Vitamin C is actively transported from maternal to fetal blood, but toxic effects are not well documented and UL is the same for pregnant and non-pregnant. • TUL – 14-18: 1,800 mg vitamin C – 19 and older: 2,000 mg vitamin C • (Note: High maternal vitamin C levels associated with false positive tests for urinary glucose as well as cramps, nausea, and diarrhea). Cochrane: Vitamin C Supplementation in Pregnancy (2005) • 5 trials involving 766 women • Three trials supplemented women with 1000 mg vitamin C per day and two trials supplemented women with 500 mg vitamin C per day Cochrane: Vitamin C Supplementation in Pregnancy (2005) • No difference was seen between women supplemented with vitamin C alone or in combination with other supplements compared with placebo for: – Stillbirth – Perinatal death – Birthweight Cochrane: Vitamin C Supplementation in Pregnancy (2005) • Results re preeclampsia were unclear due to heterogeneity of studies. • “Women supplemented with vitamin C were at decreased risk of preeclampsia when using a fixed-effect model (RR 0.47, 95% CI 0.30 to 0.75, four trials, 710 women), however this difference could not be demonstrated when using a random-effects model (RR 0.52, 95%CI 0.23 to 1.20, four trials, 710 women).” Cochrane: Vitamin C Supplementation in Pregnancy (2005) • “Women supplemented with vitamin C compared with placebo were at increased risk of giving birth preterm (RR 1.38, 95% CI 1.04 to 1.82, three trials, 583 women).” Cochrane: Vitamin C Supplementation in Pregnancy • Conclusions: – “The data are too few to say if vitamin C supplementation either alone or in combination with other supplements is beneficial during pregnancy. – “Preterm birth may have been increased with vitamin C supplementation.” Combined vitamin C & E supplementation during pregnancy for preeclampsia prevention: Cochran, 2007 • 4 RCTs, n=4680 • All trials: vitamin C dose = 1,000 mg, vitamin E dose 400 mg • “Combined vitamin C and E supplementation during pregnancy does not reduce the risk of preeclampsia, foetal or neonatal loss, SGA, or pre-term birth.” • Combined vitamin C and E supplementation should be discouraged Water Soluble Vitamins - B6 • Inconclusive studies have linked to: – depression in pregnancy – decreased apgars with low maternal status – one study found good results for women with severe nausea who were treated with 25 mg each 8 hours • RDA for pregnancy (1998) – 1.9 mg/day for all ages APGAR SCORE • Devised by Virginia Apgar • “backronym” – Appearance (skin color) – Pulse (heart rate) – Grimace (reflex irritability) – Activity (muscle tone) – Respiration B6 – adverse effects • Inconclusive studies of toxicity have linked to: – Congenital defects – B6 dependency – Antilactogenic effects UL for B6 • UL for non-pregnant adults = 100 mg/day • UL for pregnancy – 14-18: 80 mg/day – 19 and older: 100 mg/day Pyridoxine (vitamin B6) supplementation in pregnancy (Cochran, 2006) • Five trials (1646 women) • “There is not enough evidence to detect clinical benefits of vitamin B6 supplementation in pregnancy and/or labour other than one trial suggesting protection against dental decay.” Folic Acid - NTD • NTD – currently 3,000 pregnancies affected by spina bifida/anencephaly per year in US; • 50-70% may be preventable with adequate maternal folic acid status. • ~ 1,000 more babies are born healthy since fortification • Multiple mechanisms for NTD etiologies – Main function of folate is participation in onecarbon transfers, important in methylation rx and purine/pyrimidine synthesis, regulation DNA synthesis & function; affects important events in embryogenesis Risk of NTD is Higher With • Maternal obesity /diabetes • Hx of previous child or relative with NTD • In Hispanic women – Lower blood folate levels – Less likely to consume fortified foods – Less likely to know about folic acid • Use of some antiseizure meds (valproic acid, carbamazepine) Folic Acid - Recommendations • 1992 - USPHS: women of childbearing age consume 400 mcg folic acid per day. • 1998 - IOM: women consume 400 mcg synthetic folic acid per day from supplements or fortified foods. • January 1998 - USFDA: fortification of the food supply at 140 mcg/100 grams of flour. • May, 2009 – USPSTF “recommends that all women planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400-800mg) of folic acid.” Neural tube defect rates per 10,000 population, by race/ethnicity and fortification period status --- National Birth Defects Prevention Network, 1995--2007 MMWR. August 13, 2010 / 59(31);980-984 After mandatory fortification began in 1998, NTD prevalence declined 30%– 40% among the three largest racial and ethnic groups. Folic Acid Supplements • Dietary folate is about half as absorbable as synthetic folic acid. • Public health recommendations have focused on message to all women of childbearing age to take a supplement of synthetic folic acid • Recently, 5-methyl-tetrahydrofolate (5-MTHF) has been proposed as an alternative to folic acid supplementation . Cochrane, 2010: Effects and safety of periconceptional folate supplementation for preventing birth defects – • 5 trials, 6105 women (1949 hx of NTD) • protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.15 to 0.52. MMWR - Knowledge and use of folic acid, Annual Reports from March of Dimes Gallup Survey 1995 1997 2003 2004 2005 2007 Taking FA 25% 30% 32% 40% 33% 40% Aware of FA 52% 66% 79% 77% 84% 81% 5% 11% 21% 24% 25% 2% 6% 10% 12% 7% Know that FA prevents birth defects Know that FA should be taken before pregnancy 12% http://www.cdc.gov/datastatistics/2008/folicacid/ Additional Opportunities to Prevent NTD with Folic Acid Fortification – MMWR – August 2010 • Most concerns re excess intake of folic acid associated with excessive supplement use rather than fortification. • Hispanic women may need additional folic acid: – Consider fortification of corn masa flour Emerging Issues: Is it more than folate? • NTD and B12 (Ray, Epidemiology, 2007) – In the presence of folate fortification, women with the lowest B12 status have 190% increased risk of NTD compared to those with the highest B12 status FIGURE 1 Choline and folate metabolic pathways intersect Zeisel, S. H Am J Clin Nutr 2009;89:673S-677S Copyright ©2009 The American Society for Nutrition Choline too… • Major source of methyl groups in the diet • Critical during fetal development – Stem cell proliferation & apoptosis – Alters brain and spinal cord function/influences risk of NTD & lifelong memory – Low choline diet increases risk of NTD – Helps maintain normal homocysteine concentrations (high hcy associated with NTD) Zeisel. Ann Rev Nutr. 2006 Pre- and Postnatal Health: Evidence of Increased Choline Needs (Caudill, JADA 2010) • Human fetus receives large amount of choline during gestation • In animal models pregnancy depletes hepatic choline • Neonates have blood choline levels three times higher than maternal levels • Majority of pregnant/lactating women not consuming recommended levels. • Prenatal vitamins have no choline Funded by Egg Nutrition Center & National Cattlemen’s Beef Association Single Carbon Metabolism: Zeisel AJCN Supplement, 2009 • Significant proportion of population consuming low levels of folate and choline • Could result in altered methelation & related epigenetic effects on gene expression • Infant not protected from inadequate intake of mother • Research needs before routine supplementation: – Impact of common genetic variants on nutrient requirements – Risk of excessive intake/supplementation Iron • • • • • General statements RDA Routine Supplementation Treatment for Iron Deficiency Anemia Emerging Issues How does maternal/infant iron metabolism illustrate each construct of the life course framework? • Timeline • Timing • Environment • Equality Iron Endowment at birth: maternal iron status and other influences. Viteri F. Nutrition Reviews. 2011 Iron • Iron stores at conception predict risk of iron deficiency anemia in later pregnancy. • Studies of the impact of iron deficiency are inconsistent due to study design and populations • In US postpartum iron deficiency anemia is common in WIC mothers (27% overall, 48% non-Hispanic blacks) – Postpartum anemia is associated with postpartum depression RDA for Iron, 2001 • Non Pregnant – 19-50: 18 mg/day • Pregnant – 14-50: 27 mg/day • UL (based primarily on GI effects) – 14-50: 45 mg/day Estimated Deposition of Iron: IOM 2001 Stage Fetus Umbilicus and Placenta Total (mg) T1 25 5 30 T2 75 25 100 T3 145 45 190 Total 245 75 320 Absorbed Iron Requirements Stage Basal Losses T1 0.896 T2 0.896 T3 0.896 Erythrocyte Mass (mg/day) Fetus and placenta (mg/day_ Total absorbed requirement 0.27 1.2 2.7 1.20 4.7 2.7 2.00 5.6 Dietary Iron Requirements During Pregnancy Stage Absorbed Iron Requirement Absorption (%) Requirement (mg/day) T1 1.2 18 6.4 T2 4.7 25 18.8 T3 5.6 25 22.4 US Preventative Services Task Force Prevalence: Hgb < 10 g/dl is present in 2040% of pregnant women, due largely to expansion of blood volume. Burden: observational data confirm modest associations between severe anemia and adverse maternal and infant outcomes. Efficacy: Trials find improved hematological indices not improved clinical outcomes US Preventative Services Task Force: Iron Supplementation in Pregnancy Safety: Unintentional overdosing, hemochromatosis, GI symptoms Compliance: Prescribed Fe supps taken correctly by 70%, not at all by 10% Recommendation: Evidence is insufficient to recommend for or against routine iron supplementation during pregnancy. IOM • Pregnancy requires an additional 6 mg Fe/day in T2 and T3 • Fe deficiency is common in pregnancy • Fe supps maintain Hgb levels during pregnancy. • Percentage of iron absorbed declines as the amount given increases. • High doses increase side effects and decrease compliance. • Recommendation: Small dose (30mg) after 12 weeks for all pregnant women. Cochrane 2010: Effects and safety of preventive oral iron or iron+folic acid supplementation for women during pregnancy • 49 trials; 23,200 pregnant women • daily iron supplementation associated with increased haemoglobin levels in maternal blood both before and after birth & reduced risk of anaemia at term – no difference between women receiving intermittent or daily supplementation • Side effects and haemoconcentration (a haemoglobin level greater than 130 g/L) were more common among women who received daily iron or iron+folic acid supplementation than among those who received no treatment or placebo. Author’s Conclusions: • Prenatal supplementation with iron or iron+folic acid provided either daily or weekly is effective to prevent anaemia and iron deficiency at term • No evidence of reduction in substantive maternal and neonatal adverse clinical outcomes (low birthweight, delayed development, preterm birth, infection, postpartum haemorrhage) • Side effects & may suggest the need for revising iron doses and schemes of supplementation during pregnancy Centers for Disease Control. Recommendations to prevent and control iron deficiency in the United States. MMWR.1998;47:1-36. • No conclusive evidence for benefit of universal iron supplementation • Recommend 30 mg/d starting at first prenatal visit because many women have reduced Fe stores with pregnancy • For Tx of low hct or hbg: 60-120 mg/d – If no response evaluate mean cell volume and serum ferritin Recommendations for Routine Iron Supplementation in Pregnancy Yes No IOM - NAS (1990) Nat'l Perinatal US Surgeon Epi Proj. General Oxford (1988) FASEB (1991) CDC (1998) Maybe USPHS Ex. Panel on Prenatal care (1989) Not enough evidence US preventive Services Task Force (1993) Cochran Review (1999) Emerging Iron Issues (Scholl, AJCN, 2005 & Rao, Semi fetal neonatal med) • Oxidant Mediated Tissue Injury – Iron overload can lead to oxidative stress – Iron overload can increase risk of type 2 diabetes – Increased maternal iron stores are associated with excretion of 8-OH-dG, a marker of oxidative damage to DNA in the maternal-fetal unit. Zinc (Zinc Supplementation for improving pregnancy and infant outcome. Mori et al. Cochran Library, 2012) • Mild to moderate Zn deficiency common in low income women in developing countries • Low serum Zn may be associated with prolonged labour, HDP, prematurity labor, post-term pregnancies Zinc (Zinc Supplementation for improving pregnancy and infant outcome. Mori et al. Cochran Library, 2012) • “evidence for a 14%relative reduction in preterm birth for zinc compared with placebo was primarily represented by trials involving women of low income.” • “no convincing evidence that zinc supplementation during pregnancy results in other useful and important benefits. • “studies to address ways of improving the overall nutritional status of populations in impoverished areas, rather than focusing on micronutrient and or zinc supplementation in isolation, should be an urgent priority.” Zinc Absorption in Pregnancy(Fung et al, AJCN, 1997) Dietary Zn % mg/day absorbed Pre9.7 pregnancy 24-36 11.8 weeks 34-36 12.4 weeks 14.6 Amount absorbed mg/d 1.4 18.9 2.2 19.4 2.4 Note: In 2001 IOM stated that evidence for compensatory increases in zinc absorbtion was not strong Zinc Absorption • Reduced by: – phytate – supplemental iron • GI diseases – Crohn’s – diarrhea disease – intestinal by-pass Zinc metabolism • Needs increased by hepatic sequestering and increased urinary losses: – trauma – infection – smoking – alcoholism – chronic strenuous exercise Zinc RDA, 2001 • Increased RDA based on average daily rates of zinc accumulation in pregnancy • Non-pregnant woman – 19-50: 8 mg • Pregnant woman – 14-18: 12 mg – 19-50: 11 mg Calcium • Fetus requires 25 to 30 g calcium • Most fetal calcium accretion in third trimester • Maternal absorption, increases early in pregnancy and maternal Ca stores increase in preparation for third trimester demands • 1,25(OH)2D concentrations increase in pregnancy Calcium Absorption Stage Absorption Non- pregnant 27% 5-6 months of pregnancy Term 54% 42% A longitudinal study of calcium homeostasis during human pregnancy and lactation (Ritchie et al, AJCN, 1998) • N=14, white, middle-upper income well nourished women who consumed ~1200 g Ca daily • Exams: • • • • • • prepregnancy T1 (8-10 weeks of pregnancy T2 (23-26 weeks) T3 (34-36 weeks) EL (6-10 weeks postpartum) 5-2 months post menses Total Body BMD (g/cm ) 2 Trabecular BMD (mg/ cm ) 3 Prepregnancy 1.156 162.9 Postdelivery 1.162 163.7 EL 1.153 147.7 Postmenses 1.143 164.3 Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride (1999)Institute of Medicine (IOM “Adaptive maternal responses to fetal calcium needs include an enhanced efficiency of absorption, which is modulated through changes in calciotropic hormones. Thus, provided that dietary calcium intake is sufficient for maximizing bone accretion rates in the nonpregnant state, the AI does not have to be increased during pregnancy.” Cochrane, 2006: Ca supplementation during pregnancy for preventing hypertensive disorders and related problems • 12 studies • “Ca supplementation appears to almost halve the risk of pre-eclampsia and to reduce the rare occurrence of the composite outcome “death or serious morbidity. There were not other clear benefits or harms.” • Effect greatest for high risk women and those with low Ca intake. Other Issues: Calcium • No benefits for Ca supplementation in prevention of preterm birth or LBW. (Buppasiri et al. Cochrane, 2011.) • “There is evidence to support associations between maternal calcium intake in pregnancy and offspring blood pressure at ages 1-9.” (Bergel, BMC Pediatri, 2007) Recommended Intakes 2010 nonpregnant 2010 Pregnant 1999 nonpregnant 1999 preg. 1989 RDA 1000 (RDA) 1000 (RDA) 1000 (AI) 1000 (AI) 1200 Phosphorus (mg) 700 (RDA) 700 (RDA) 1200 Magnesium (mg) 310 (RDA) 350 (RDA) 320 5 (mcg, AI) 5 (AI) 10 3 (AI) 3 (AI) none Calcium (mg) Vitamin D 600 (RDA, IU) 600 (RDA, IU) Fluoride (mg) 1 mcg vitamin D = 40 IU Calcium: IOM Recommendations • If intake is < 600 mg: – Encourage increased dietary sources – Consider supplemental calcium Cochrane Collection: Magnesium • Background and objectives: Many women, especially those from disadvantaged backgrounds, have intakes of magnesium below recommended levels. Magnesium supplementation during pregnancy may be able to reduce fetal growth retardation and pre-eclampsia, and increase birthweight. The objective of this review was to assess the effects of magnesium supplementation during pregnancy on maternal, neonatal and pediatric outcomes. Cochrane : Magnesium • Six trials involving 2637 women were included. Only one of these trials was judged to be of high quality. Compared with placebo, oral magnesium treatment from before the 25th week of gestation was associated with a lower incidence of preterm birth (odds ratio 0.71, 95% confidence interval 0.52 to 0.95). There was also less maternal hospitalization during pregnancy, fewer cases of antepartum hemorrhage, a lower incidence of low birthweight and small for gestational age infants. Poor quality trials are likely to have resulted in a bias favoring magnesium supplementation. Cochrane Collection: Magnesium • Reviewers' conclusions: There is not enough high quality evidence to show that dietary magnesium supplementation during pregnancy is beneficial. 2004 DRI for Sodium • AI for pregnancy is the same as that for nonpregnant adolescent girls and women: – Age 14-18: 1.5 g/day – Age 19-30: 1.5 g/day – Age 31-50: 1.5 g/day • UL is also the same (“inadequate data to support a different intake level for Na intake in pregnant women) – Age 19-50: 2.3 g/day – > 95% of men and 75% of women exceed this level 2004 DRI for Water • AI based on total water (drinking water, beverages and food). • Pregnant women ages 14-50: 3.0 L/day (includes ~10 cups as total beverages) • Non-pregnant women aged 19-50: 2.7 L/day 2004 DRI for Potassium • Pregnant women have increased ability to conserve K in the face of high Na diet. • Overall accretion during pregnancy is small. • AI is the same as for non-pregnant: 4.7 g/day. – Current median intake in US women is 2.1-2.3 g/day. • No UL is set because danger is low for healthy women during normal pregnancy.