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Page 1: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Micronutrients

2007

Page 2: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Micronutrient Status

• Important throughout the reproductive years:– Periconceptual period– Pregnancy– Lactation– Inter-pregnancy interval

Page 3: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Multiple Micronutrient Deficiencies Occur with Poor Diets

• Most historic research on iron, folate, iodine

• Increasing understandings about less recognized deficiencies.

• Nutrients deficiencies interact: example vitamin A supplements can decrease rates of iron deficiency anemia in some populations.

Page 4: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Vitamins and Minerals

• Increased needs in pregnancy associated with:– DNA/RNA synthesis– Increased blood volume– bone mineralization & structure– Increased energy metabolism

Page 5: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Vitamins and Minerals

• Some nutrients of special concern due to low dietary levels in the population & extra demands of pregnancy

• IOM report, 1990:• Vitamins B6, D, E• iron• calcium• zinc• magnesium

Page 6: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 7: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 8: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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)

Page 9: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Vitamins and Minerals

• Vitamin and mineral needs are increased by:– alcohol consumption– tobacco use– multiple fetuses

Page 10: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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 2002

Page 11: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 12: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

High levels of retinol intake during the first trimester of pregnancy result from use of over-the-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.

Page 13: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 14: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 15: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 16: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Vitamin A RDA - 2001

• Non Pregnant = 700 mg RAE (retinol activity equivalents)

• Pregnant – Age 14-18: g 750– Age 19-30: g 770– Age 31-50: g 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 g/day preformed vitamin A– Age 19-50: 3,000 g/day preformed vitamin A

Page 17: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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 gIU)/day

• UL for pregnancy and non-pregnant– 50 g (2000 IU)/day– Excess associated with fetal hypercalcemia,

aortic stenosis, abnormal skull development/premature closure of fontanel

Page 18: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Vitamin D: Emerging Understandings

• Maternal vitamin D status associated with bone mineralization in 9 year olds

• Some preliminary observational reports find that vitamin D status is association with risk of: – Autoimmune diseases such as multiple

sclerosis & rheumatoid arthritis– Malignancies

Page 19: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Copyright ©2006 CMA Media Inc. or its licensors

Hollis, B. W. et al. CMAJ 2006;174:1287-1290

Fig. 2: The endocrine, paracrine and intracrine functions of vitamin D

Page 20: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Vitamin D: Emerging Understandings

• Widespread deficiencies

• Disparities

Page 21: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Vitamin D Deficiency in Selected Populations

• Van der Meer et al. Am J Clin Nutr. 2006• Chart review of serum 25-hydroxyvitamin D

status of 358 pregnant women in the Netherlands

• Used conservative estimates (<25 nmol/l for vitamin D deficiency– Deficiency cutoff based on array of biomarkers

adversely affected by vit D is <80 nmol/l.

Page 22: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

TABLE 2 Mean serum 25-hydroxyvitamin D [25(OH)D] concentrations in subjects and proportions of subjects with deficiency or with concentrations under the detection limit

1 Means compared by using ANOVA and Dunnett’s test; vitamin D data were log transformed and weighted by inverse cell variances. 2 Deficiency = < 25 nmol 25(OH)D/L. 3 Means compared by using logistic regression. 4 Under the detection limit = <7 nmol 25(OH)D/L. 5 ± SD (all such values). 6 P 0.001. 7 P 0.05.

25(OH)D conc1

25(OH)D deficiency2,3

25(OH)D under the detection

limit3,4

n (%) n (%)

Western (reference) (n = 105)

52.7 ± 21.65 8 (8) 1 (1)

Turkish (n = 79) 15.2 ± 12.16 66 (84)6 17 (22)6

Moroccan (n = 69) 20.1 ± 13.56 56 (81)6 3 (4)

Other non-Western (n = 105)

26.3 ± 25.96 62 (59)6 9 (9)7

Page 23: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 24: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Vitamin D status Classification (Simhan, cont.)

• Serum 25(0H)D (25 hydroxy vitamin D)– Deficiency = <37.5 nmol/ L– Insufficiency = between 37/5 and 80

nmol/L– Sufficiency = > 80nmol/L

Page 25: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Prevalence of Vitamin D DeficiencyInsufficiency Deficiency

White Infants 42 10

White Mothers 56 5

Black Infants 47 29

Black Mothers 51 46

Page 26: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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 pre-eclampsia (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 random-effects models (RR 0.44, 95% CI 0.16 to 1.22, three trials, 510 women).”

Page 27: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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.”

Page 28: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Water Soluble Vitamins - C

• Potential for dependency in the newborn (reported with vitamin C and B6)

• Vitamin C is actively transported across placenta as well as simple diffusion so potential for high fetal levels exists

• High maternal vitamin C levels associated with false positive tests for urinary glucose as well as cramps, nausea, and diarrhea

Page 29: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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 scurvey 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

Page 30: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 31: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 32: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 33: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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).”

Page 34: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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).”

Page 35: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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.”

Page 36: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Emerging Findings: B Vitamin Deficiencies and Homocysteinemia in

Pregnancy ( Allen, AJCN, 2005)• Low intakes of folate, riboflavin, B6, B12 are

associated with elevated Hcy • Elevated plasma homocysteine (Hcy) is

associated with increased risk of:– Placental abruption– Still-births– VLBW– Preterm delivery– Preeclampsia– Neural tube defect

Page 37: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval
Page 38: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Potential Mechanisms for Adverse Impact of Hcy in Pregnancy

• Hcy increases oxygen free radical concentrations, increases oxidative stress and placental ischemia

• Hcy causes inflammatory response

• Hypermethylation of DNA/altered gene expression

• Hcy is thronbogenic

Page 39: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 40: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

B6 – adverse effects

• Inconclusive studies of toxicity have linked to:– Congenital defects

– B6 dependency

– Antilactogenic effects

Page 41: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 42: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Folic Acid - NTD

• NTD - 2,500 births per year in US.• 50-70% may be preventable with

adequate maternal folic acid status.• Etiologies and pathways remain

unknown.• Some population groups - Mexican

Americans, Native Americans - at higher risk.

Page 43: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Folic Acid - Recommendations

• 1992 - USPHSD: 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.

Page 44: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Folic Acid: Fortification

• 0.14 mg per 100g cereal grain products• 0.035 mg per slice of bread• 0.10 mg per serving breakfast cereal• Low level consumers can have intakes of

0.23-0.25 mg.• Women with low intake range of

recommended food group servings will consume 0.5 mg per day total folate.

Page 45: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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.

Page 46: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

MMWR, September 2005

Page 47: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

MMWR - Knowledge and use of folic acid, Annual Reports from March of Dimes Gallup

Survey

1995 1997 2003 2004 2005

Taking FA 25% 30% 32% 40% 33%

Aware of FA 52% 66% 79% 77% 84%

Know that FA prevents birth defects

5% 11% 21% 24% 25%

Know that FA should be taken before pregnancy

2% 6% 10% 12% 7%

Page 48: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Folate Status in Women of Childbearing Age, by Race/Ethnicity:

MMWR, January 2007

                                                                                

Page 49: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

"Why do you not take any vitamin or mineral supplements on a daily basis?"

(2005 survey)

• forgetting to take supplements (28%)

• perceiving they do not need them (16%)

• believing they get needed nutrients and vitamins from food (9%).

Page 50: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

"For what specific need would you start taking a vitamin or mineral

supplement?" (2005 survey)• being sick or in poor health (20%)• a doctor's recommendation (20%)• the need for energy (9%)• being pregnant (8%)• being deficient in any vitamins or minerals (7%)• balancing the diet (6%)• keeping bones strong (6%)• 11% cited no specific need that would motivate them

to begin taking a vitamin or supplement. • Among women who reported not consuming a

vitamin or mineral supplement daily, 31% indicated they had received a doctor's recommendation.

Page 51: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

MMWR, September2005

Page 52: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

MMWR, May 2004

Page 53: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Emerging Issues: It’s 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

Page 54: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic

Acid, Biotin, and Choline (1999)

1999 Nonpregnant

1999pregnant

1989pregnant

Thiamin,mg 1.1 1.4 1.5

Riboflavin,mg

1.1 1.4 1.6

Niacin, mg 14 18 17

B6 mg 1.3 2.0 2.2

Folate, mcg 400 600 400(180 np)

B12, mcg 2.4 2.4 2.2

Page 55: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic

Acid, Biotin, and Choline (1999)

Non-pregnant(AI)

Pregnant(AI)

Pantothenicacid, mg

5 6

Biotin, mcg 30 30

Choline, mg 425 450

Page 56: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Iron

• General statements

• RDA

• Routine Supplementation

• Screening

• Treatment for Iron Deficiency Anemia

Page 57: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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 developing countries maternal iron status is often

found to predict infant iron status.– Some studies find that maternal iron deficiency is

associated with preterm delivery• In US postpartum iron deficiency anemia is

common in WIC mothers (27% overall, 48% non-Hispanic blacks)– Postpartum anemia is associated with postpartum

depression

Page 58: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 59: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 60: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Absorbed Iron Requirements

Stage Basal Losses

Erythrocyte Mass (mg/day)

Fetus and placenta (mg/day_

Total absorbed requirement

T1 0.896 0.27 1.2

T2 0.896 2.7 1.20 4.7

T3 0.896 2.7 2.00 5.6

Page 61: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Dietary Iron Requirements During Pregnancy

Stage Absorbed Iron Requirement

Absorpbtion (%)

Requirement (mg/day)

T1 1.2 18 6.4

T2 4.7 25 18.8

T3 5.6 25 22.4

Page 62: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

US Preventative Services Task Force

Prevalence: Hgb < 10 g/dl is present in 20-40% 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

Page 63: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

US Preventative Services Task Force: Iron Supplementation in

PregnancySafety: 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.

Page 64: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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 does increase side effects and decrease

compliance.• Recommendation: Small dose (30mg) after 12

weeks for all pregnant women.

Page 65: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Cochrane Review of 20 Trials- 1999

• “Iron supplementation appears to prevent low haemoglobin at birth or at six weeks post-partum.”

• “Iron supplementation had no detectable effect on any substantial measures of either maternal or fetal outcome.”

Page 66: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 67: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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.

Page 68: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Emerging Iron Issues (Zimmerman, Lancet, 2007)

• Selective plan breeding & genetic engineering are promising new approaches to improve dietary iron quality in populations consuming “monotonous” plant based diet.

Page 69: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Yes No Maybe Not enough evidence

IOM - NAS (1990)

Nat'l Perinatal Epi Proj. - Oxford

US Surgeon General (1988)

US preventive Services Task Force (1993)

FASEB (1991)

USPHS Ex. Panel on Prenatal care (1989)

Cochran Review (1999)

CDC (1998)

Recommendations for Routine Iron Supplementation in Pregnancy

Page 70: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Zinc - Adapted from Janet King 1999

• Severe maternal zinc deficiency is teratogenic in rats

• Zinc is available to the fetus from maternal tissues

• Both survey and experimental research on zinc in human pregnancy have inconclusive results due to issues of study design

Page 71: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Zinc - cont.

• Kirksey et al. AJCN, 1994: – Low income Egyptian women– Only 2 mg zinc available when look at

phytate-zinc molar ratio– 20% of variance of birthweight attributed to

plasma Zn in second trimester– 39% of variance of birthweight attributed to

maternal weight at 3 mos. gest.... and plasma Zn in second trimester

Page 72: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Zinc

• Poor maternal zinc status:– limits fetal growth– influences length of gestation– increases risk of maternal complications

Page 73: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Zinc Absorption in Pregnancy(Fung et al, AJCN, 1997)

Dietary Znmg/day

%absorbed

Amountabsorbedmg/d

Pre-pregnancy

9.7 14.6 1.4

24-36weeks

11.8 18.9 2.2

34-36weeks

12.4 19.4 2.4

Note: In 2001 IOM stated that evidence for compensatory increases in zinc absorbtion was not strong

Page 74: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Zinc Absorption

• Reduced by:– phytate– supplemental iron

• GI diseases– Crohn’s– diarrhea disease– intestinal by-pass

Page 75: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Zinc metabolism

• Needs increased by hepatic sequestering and increased urinary losses:– trauma– infection– smoking– alcoholism– chronic strenuous exercise

Page 76: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Cochrane Collection: Zinc& Pregnancy April, 2007

• Background : low serum zinc levels may be associated with – prolonged labor

– Atonic postpartum hemorrhage

– PIH

– Preterm labor

– Post-term pregnancy

Page 77: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Cochrane Collection: Zinc

• 17 RCTS; >9,000 women

• Outcomes– Lower risk of preterm birth (RR, 0.86, 0.76-

0.98)

– No consistent impact on other outcomes

– The highest impact was found in studies among low-income women

Page 78: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Cochrane Collection: Zinc

• Conclusions: “The 14% relative reduction in preterm birth for zinc compared with placebo was primarily in the group of studies involving women of low income and this has some relevance in areas of high perinatal mortality. There was no convincing evidence that zinc supplementation during pregnancy results in other useful and important benefits. Since the preterm association could well reflect poor nutrition, 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.”

Page 79: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 80: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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 increases in preparation for third trimester demands

• 1,25(OH)2D concentrations increase in pregnancy

Page 81: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Calcium Absorption

Stage Absorption

Non- pregnant 27%

5-6 months ofpregnancy

54%

Term 42%

Page 82: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 83: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Total BodyBMD (g/cm2)

TrabecularBMD (mg/ cm3)

Prepregnancy 1.156 162.9

Postdelivery 1.162 163.7

EL 1.153 147.7

Postmenses 1.143 164.3

Page 84: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and

Fluoride (1999)Institute of Medicine (IOM

• Dietary calcium intake does not appear to influence changes in maternal bone mass during pregnancy

• There is a lack of a relationship between the number of previous pregnancies and BMD.

• Some studies find a positive relationship between number of children born and radial BMD, total body calcium, and risk of hip fracture.

Page 85: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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.”

Page 86: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Dietary calcium and pregnancy-induced

hypertension: is there a relation?

Ritchie LD, King, JC. Am J Clin Nutr. 2000:71(suppl):1371S-4S

Page 87: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Effect of routine calcium supplementation during pregnancy on relative risk (RR) of preeclampsia

Subgroup Typical RR (95% CI)

Low-risk (n = 6 trials) 0.79 (0.65, 0.94)

High-risk2 (n = 4 trials) 0.22 (0.11, 0.43)

Adequate-calcium diet 0.86 (0.71, 1.05)(900 mg/d)(n = 4 trials)

Low-calcium diet (<900 mg/d) (n = 6 trials) 0.32 (0.21, 0.49)

Those at high risk: teenagers, had had preeclampsia previously, had increased sensitivity to angiotension II, or had preexisting hypertension.

Page 88: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Effect of routine calcium supplementation during pregnancy on relative risk (RR) of high blood pressure

Subgroup Typical RR (95% CI)

Low-risk (n = 6 trials) 0.84 (0.76, 0.92)

High-risk2 (n = 3 trials) 0.35 (0.21, 0.57)

Adequate-calcium diet (900 mg/d) (n = 4 trials) 0.90 (0.81, 0.99)

Low-calcium diet 0.49 (0.38, 0.62) (<900 mg/d) (n = 5 trials)

.

Page 89: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Review Conclusions

• “Ca supplementation during pregnancy for women with deficient calcium intake is a promising preventive strategy for preeclampsia.”

Page 90: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Emerging Issues: Calcium

• “There is evidence to support associations between maternal calcium intake in pregnancy and offspring blood pressure at ages 1-9.”

(Bergel, BMC Pediatri, 2007)

Page 91: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and

Fluoride (1999)Institute of Medicine (IOM)

1999 non-pregnant(19-31)

1999pregnant

1989RDA(25-50)

Calcium(mg)

1000 (AI) 1000 (AI) 1200

Phosphorus(mg)

700 (RDA) 700 (RDA) 1200

Magnesium(mg)

310 (RDA) 350 (RDA) 320

Vitamin D(mcg)

5 (AI) 5 (AI) 10

Fluoride(mg)

3 (AI) 3 (AI) none

Page 92: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Calcium: IOM Recommendations

• If intake is < 600 mg:– Encourage increased dietary sources– Consider supplemental calcium

Page 93: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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.

Page 94: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Cochrane Collection: Magnesium

• Main results: 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.

Page 95: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

Cochrane Collection: Magnesium

• Reviewers' conclusions: There is not enough high quality evidence to show that dietary magnesium supplementation during pregnancy is beneficial.

Page 96: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

2004 DRI for Sodium• AI for pregnancy is the same as that for non-

pregnant 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

Page 97: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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

Page 98: Micronutrients 2007. Micronutrient Status Important throughout the reproductive years: –Periconceptual period –Pregnancy –Lactation –Inter-pregnancy interval

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.