Lecture 3, 2006 Macro and Micronutrients. Carbohydrate Protein Lipids Vitamins and Minerals:...

Lecture 3, 2006Macro and Micronutrients

• Carbohydrate• Protein• Lipids• Vitamins and Minerals:

– General– Vitamins– Iron– Zinc– Calcium– Magnesium

2002 DRI for Carbohydrate

• In general all DRIs for carbohydrate based on brain glucose utilization.

• RDA for adults and children = 130 g/day

• Median intake ~:– Men: 200-330 g/day– Women: 180-230 g/day

2002 DRI for Carbohydrate in Pregnancy

• Fetal brain needs a minimum of 33 g/day• EAR for pregnancy (all ages) = 135 g/day• RDA for pregnancy (all ages) = 175 g/day

– CV is 15% based on variations in brain glucose utilization

– RDA = EAR plus twice CV

EAR: Estimated Average Requirement

CV: coefficient of variation (used when insufficient data to determine standard deviation)

2002 DRI for Fiber in Pregnancy

• “There is no evidence to suggest the beneficial effects of fiber in reducing risk of CHD is different from non-pregnant adolescent girls and women.”

• AI = 28 g/day (14 g/1,000 kcal x median kcal intake for group)

• AI for non-pregnant women is 25 g/day

Protein - old RDAs

• 1980: an additional 30 g for pregnancy

• 1989:– Protein RDA is 0.8 per kg for non-pregnant

woman– Additional 10 g for pregnancy

Protein - 1989 RDA

Category G proteinFemale 15-18 44Female 19-24 46Female 25-50 50Pregnant 60Lactating first 6 mos. 65Lactating second 6 mos. 62

2002 RDA

EAR for Protein in Pregnancy

• EAR = 21 g/day above protein needs at prepregnancy weight

• EAR Per kg– Increased amount on a per kg basis is 0.22

g/protein/kg/day– EAR for non-pregnant = 0.66 g protein/kg

per day– EAR for pregnancy = 0.88 g/kg/day

RDA for Protein for Pregnancy

• 1.1 g/kg/day or 25 g/day additional protein

• RDA for women aged 19-50 is 0.80 or 46 g/day

• RDA is 71g protein per day

Reference woman is 57 kg

RDA to Diet

• RDAs calculated using high quality reference proteins like egg, meat, milk or fish

• However, even with adjustments for lower quality proteins most women in the US who are meeting energy needs with reasonable food choices, will meet protein needs.

Vegan Diet & Protein Intake

Food Gprotein

#servings

Total gprotein

Totalkcal

Grains 3 11 33 880

Vegetables 4 2 8 100

Beans 15 2 cups 30 550

Total 71 1450

Protein Intakes

• Range in US is 75 to 110 g per day for women

Energy and Protein

• If energy needs are not met by diet then protein will be used for energy

• RDA calculations assume adequate energy intake

Protein Supplementation

• In developing countries protein and energy supplements may improve pregnancy outcomes when women are undernourished

• There is little evidence that protein supplementation affects outcome in developed countries

Adverse Effects of Protein Supplementation

• Several human and animal studies of protein supplementation have found adverse effects including retarded fetal growth, increase in prematurity, and increased neonatal deaths.

Cochrane Collection: Energy and Protein Intake in Pregnancy (Kramer et al, 2004)

• objectives: To assess the effects of advice to increase or reduce energy or protein intake, or of actual energy or protein supplementation or restriction during pregnancy on energy and protein intakes, gestational weight gain, and the outcome of pregnancy

Cochrane Collection: High protein supplementation in pregnancy

• Selection criteria: acceptably controlled trials of dietary advice to increase or reduce energy or protein intake, or of actual energy or protein supplementation or restriction, during pregnancy.

Results: dietary advice to increase energy and protein intakes

• 5 trials, 1134 women

• Dietary advice increased intakes

• No consistent benefit was observed for pregnancy outcomes

Results: Balanced Energy/Protein Supplementation


• Modest increase in maternal weight gain and mean birth weight

• Reduction risk for SGA

• Reduced risk of stillbirth and neonatal death

• No significant effects on preterm birth

Results: High Protein Supplementation

• Two trials, 1076 women

• Small, nonsignificant increase in maternal weight gain and nonsignificant reduction in birth weight

• Increased risk of SGA

• Nonsignificant increased risk of neonatal death

Results: Energy/protein restriction for overweight women


• Reduced maternal weight gain

• Reduced mean birth weight

• No effect on pregnancy induced hypertension or pre-eclampsia

Lipids

• General lipid recommendations for pregnancy

• Essential fatty acids & LCPUFA

• Trans FA

Lipids: Maternal

• Metabolism changes to:– meet increased maternal needs for energy

and hormones precursors– to insure adequate fetal accretion

• Serum cholesterol rises 25-40%

• Triglycerides rise 200-400%

Lipids: Maternal Recommendations, 2002 DRI

• 30% of kcals from fat is a reasonable goal in pregnancy.– There is no need to try to affect the

physiological rise in blood lipids

Essential and LCPUFA

Important Fatty Acids

LNA -linolenic 18:3n-3

LA Linoleic 18:2n-6

EPA Eicosapentaenoic 20:5n-3

ARA Arachidonic 20:4n-6

DHA Docosahexanoic 22:6n-3

Background: LCPUFA

• Dietary sources of n-3 and n-6 fatty acids are essential.

• Fetal ability to elongate and desaturate fatty acids is limited.

• Conversion of LNA to DHA is highly variable among individual infants.

Innis. J Peds. 2003

Fetal Implications• Human brain is lipid based; ~ 60% of dry

weight• 30% of fetal CNS tissue is LCPUFA with n-3

to n-6 ratio of 2:1• Fetal brain development starts early &

experiences “growth spurt” during last trimester and 1st 6 months of life

• In 3rd trimester, storage of LCPUFA in fetal adipose tissue if adequate maternal sources

• Adequacy of LCPUFA associated with CNS and retinal function.

Arterburn et al, Am J Clin Nutr, 2006

Background: Placental Transfer

• The fetus is totally dependent on maternal intake and placental transfer.

• The placenta selectively transports LCPUFA

• Concentrations of DHA and ARA are 300 to 400 fold higher in fetal vs maternal plasma phospholipids

Innis. J Peds. 2003

Maternal LCPUFA status maters to the Infant

• Women with higher plasma ARA and DHA during pregnancy have infants with higher ARA and DHA

• Higher n-6 and n-3 status at birth results in higher ARA and DHA for several weeks.

Maternal LCPUFA Status matters to the Pregnancy

• Eicosanoids derived from LCPUFA (prostaglandins, thromboxanes, prostacylcins, leukotrienes) play vital roles in pregnancy

• The ideal ratio of n-3 to n-6 remains unknown

• Dietary sources of EFA - both n-3 and n-6 are important

PIH and n-3 Fatty Acids

• Possible biological pathway: – Vasoconstriction and epithelial damage of

PIH is associated with imbalance of TXA2

(vasoconstrictor) and PGI2 (vasodilator)

• If increased dietary intake of n-3:– EPA competes with Arachadonic Acid for

enzymes so may have lower production of TXA2 and higher production of PGI3 (vasodilator)

PIH and n-3 Fatty Acids

• Epidemiological Studies:– several studies have found that women with PIH

have lower levels of n-3– lower incidence of PIH in fish eating populations

• RCT– “Compelling evidence for a beneficial effect of n-3

fatty acids on preeclampsia from recent prospective, double-blind studies is lacking (Jensen, Am J Clin Nutr, 2006)

N-3 and Prolonged Gestation

• Faroe Islands: – high birthweights– longer gestations– diet high in marine oils

• Theory: n-3 interference with uterine prostaglandin production

N-3 and Prolonged Gestation

• Supplementation study: – increased gestational length by 4 days

– prolonged bleeding times & increased blood loss at delivery

N-3 and Maternal Depression (Jensen, AJCN, 2006)

• “Recent observational trials and open-label trials of n-3 FA supplementation appears promising.”

• “At present, however, there is a paucity of data from controlled studies supporting the efficacy of n-3 FA in the prevention or treatment of depression during pregnancy or the postpartum period.”

N-3 intake and Depression by Country (Hibbeln, AJCN, 2006)

% of energy from dietary n-3 LCFA

Postpartum Depression (%)

Brazil 0.052 24

Germany 0.084 25

Ireland 0.090 14

USA 0.103 12

Sweden 0.139 9

Canada 0.146 13

Japan 0.374 2

Iceland 0.435 5

N-3 intake and Depression by Country (Hibbeln, AJCN, 2006)

• In model with 20 countries, correlation between postpartum depression rates and energy from n-3 FA was r=-0.78, p<0.001)

Infant visual function/neural development (Jensen, 2006)

• Observational studies find both positive associations and no association.

• Small intervention studies: possible associations with attention & distractibility and visual functioning.

Essential Fatty Acids in Mothers and

Their Neonates (Hornstra, AJCN, 2000)

• Maternal essential fatty acid status declines during pregnancy (absolute plasma levels in-crease, but non-essential increase more).

• Pregnancy may cause maternal DHA depletion/mobilization from maternal stores. (Implications for close pregnancy spacing)

• Essential PUFA status of newborns is restricted by that of the mother and may not be optimal.

• Maternal PUFA supplementation affects neonatal PUFA status.

• Maternal linoleate intake during pregnancy is negatively related to neonatal head circumference.

• In preterm infants positive relationship between DHA in umbilical artery and birth weight. Length, and OFC.

Hornstra - Implications

• Hunter-gatherer diet more rich in LCPUFA.

• Humans evolved with limited ability to elongate and desaturate EFA?

• Limitations require special consideration during increased requirements of fetal development, lactation, and neonatal development.

Are n-3 fatty acids essential nutrients for fetal and infant development? (Nettleton, JADA 1993)

• Fetal and infant nutrition may be enhanced by encouraging pregnant and lactating women to consume seafood regularly (2-3 meals per week)

• Poultry and plant sources of n-3 may be useful if seafood is impossible

• Avoid extreme dietary rations of n-6 to n-3 by using olive and canola in addition to corn and safflower oil.

Washington State Fish Advisory for Mercury for

Women of Childbearing Age and Children Under Six • Do not eat any shark, swordfish, tilefish, king mackerel or

either fresh caught or frozen tuna steaks. • Limit the amount of canned tuna you eat, based on your

bodyweight. General guidelines are: – Women of childbearing age should limit the amount of

canned tuna they eat to about one can per week (six ounces).

– Children under six should eat less than one half a can of tuna (three ounces) per week. Specific weekly limits for children under six range from one ounce for a twenty pound child, to three ounces for a child weighing about sixty pounds.

– Choose chunk light tuna over albacore white to further reduce your exposure to mercury.

– Find out about fish advisories.

http://www.doh.wa.gov/fish/FishAdvMercury.htm

http://www.doh.wa.gov/fish/FishAdvMercury.htm

• For freshwater bass:– Woman of childbearing age and children under six

should limit their consumption of freshwater bass (largemouth and smallmouth) to no more than 2 meals/month. Additional information can be obtained from the "Statewide Bass Advisory" report and the "Freshwater Largemouth and Smallmouth Bass Consumption Advisory Due to Mercury Contamination" fact sheet

http://www.doh.wa.gov/ehp/oehas/publications%20pdf/statewide_%20bass_%20advisory-2003.pdf

http://www.doh.wa.gov/ehp/oehas/Bass%20FactSheet.pdf



• Health problems caused by mercury are:– Babies whose mothers ate fish contaminated with

mercury during pregnancy, are at greater risk for changes to their nervous systems. These changes can affect their ability to learn.

Health problems, cont.

• In adults, several neurological signs and symptoms are among the common features of chronic high-dose exposures to methylmercury in adults. These can include peripheral neuropathy (tingling in the hands and feet), tremor, problems walking, dizziness, visual and hearing difficulties, and memory impairment (NRC 2000, ATSDR 1999). These symptoms are generally not associated with the level of exposure to methylmercury through the consumption of fish in the U.S. Mercury has been shown to accumulate in the heart. Recent findings investigating chronic low-dose exposures have been associated with changes in blood-pressure and abnormal heart function (Salonen et al. 1995, Sorensen et al 1999) as well as increased risk of heart-attack (Guallar et al. 2002).

What about other contaminants?

• Mercury in fish is a big concern, but fish might also contain other contaminants. Some kinds of pesticides and chemicals called "PCBs" also get into fish. PCBs and pesticides are mostly found in the skin and fatty part of fish, so if you cut and cook fish in ways that remove the skin and fat, you can lower the amount of pesticides and PCBs in your food.

Recent Recommendations for Fish Intake in Pregnancy

• Consumer Reports, July 2006: – “Given the uncertainties about the safety of even

chunk-light tuna, we think it’s prudent for pregnant women to avoid canned tuna entirely.”

– Women of childbearing age who aren’t pregnant: “Mercury can linger in the body after you stop eating fish, so we advise these women to eat no more than about 3 chunk-light cans per week or one can of solid-light or white tuna.”

What about Salmon?

• Foran et al. Journal of Nutrition, 2005• Risk Benefit Ratios• Benefit carcinogenic risk ratio (BCRR)• Benefit noncarcinogenic risk ratio

(BNRR)• In general Wild salmon:

– have low contaminant contributions– have lower levels of n-3 FA

Essential Fatty Acids Requirements in Pregnancy

• FAO recommends 4.5% of daily energy as EFA (essential fatty acids) in pregnancy and 6% in lactation– If kcals are inadequate energy based

recommendations may be misleading

2002 DRI for n-6 Fatty Acids in Pregnancy

• AI = 13 g/day linoleic acid

• Based on median linoleic acid intake of pregnant women in US where deficiency is “basically non-existent.”

• AI for non-pregnant women = 12 g/day

2002 DRI for N-3 Fatty Acids in Pregnancy

• Demand driven by:– fetus– placental tissue– secretion during lactation

• AI = 1.3 g/day of -linolenic acid – Based on median -linolenic acid intake of

pregnant women in US where deficiency is “basically non-existent.”

– non-pregnant AI=1.1 g/day -linolenic acid

– DHA and EPA can contribute toward total n-3

Trans Fatty Acids

• Side product of catalytic hydrogenation of vegetable oils and biohydrogenation in the rumen of animals

• Animal studies show discrimination against transport of trans FA across the placenta, but some are transported.

• Trans FA inhibit elongation of EFA• Trans FA in plasma of human preterm

infants was found to be inversely associated with LCPUFA

Trans Fatty Acids

• Infant formula has few trans FA, breastmilk content reflects maternal diet.

• What to recommend?

Trans Fatty Acids

“It may be prudent to reduce maternal intake of trans fatty acids as much as possible, even if negative effects of trans fatty acids on fetal development cannot yet be ascertained.”

Carlson et at. AJCN, 1997

Macronutrient 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.

Vitamins and Minerals

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


• Some nutrients of special concern due to low dietary levels in the population

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

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

*for adolescent and adult women of reproductive age


• Risks for low vitamin and mineral status include:– low income– restricted energy intake– adolescence– vegan (Ca, B12, D, zinc)– Non white status (Ca)


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

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

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 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.

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: 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

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

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

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

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.

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

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).”

• “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.”

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

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

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

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).”

• “Women supplemented with vitamin C were at decreased risk 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

• Conclusion: “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.”

• Note: a Cochrane review on the impact of antioxidants on risk of preeclampsia is underway.

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

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

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

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

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.

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.

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.

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.

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%

"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%).

"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.

MMWR, September 2005

MMWR, September2005

MMWR, September 2005

MMWR, May 2004

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

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

Iron

• General statements

• RDA

• Routine Supplementation

• Screening

• Treatment for Iron Deficiency Anemia

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

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

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

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

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

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.

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.

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.”

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

Emerging Concerns about Iron Supplements (Scholl, AJCN, 2005)

• 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.

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

Iron: US Preventative Health Services Task Force (1997):

Screening• Screening for iron deficiency anemia using hemoglobin

or hematocrit is recommended for pregnant women and for high-risk infants

• The exact prevalence of iron deficiency anemia among pregnant women is uncertain:

– <2% of nonpregnant women aged 20-44 years may have iron deficiency anemia.

– low-income, pregnant U.S. populations: a low hemoglobin level and/or low hematocrit is present in 6% of white women and 17% of black women during the first trimester and in 25% of white women and 46% of black women during the third trimester.7


Screening• The high rates of anemia in pregnant women may not

be attributable to iron deficiency, however. In a large cohort of urban, low-income, mostly minority pregnant women, only 12.5% of anemic women were iron deficient

• Screening criteria for pregnancy:

– WHO: menstruating women, <12 g/dL; pregnant women, <11 g/dL

– CDC: <11 g/dL during the first and third trimesters and <10.5 g/dL in the second trimester


Screening• There is little evidence evaluating adverse effects from the

mild degree of anemia that is most often detected by screening asymptomatic persons in developed countries.

– In a Swedish cohort, anemic women (Hgb <12 g/dL) reported no increase in reported infections, fatigue, or other symptoms, but they were significantly more likely to report low work productivity compared to nonanemic women.

– In a small, randomized placebo-controlled trial of Welsh women with anemia (hemoglobin <10.5 g/dL) detected by population-based screening, iron therapy did not result in clinically or statistically significant improvements in psychomotor function tests, symptoms, or subjective well-being, despite increased hemoglobin concentrations.

Iron: US Preventative Health Services Task Force: Screening

• A hemoglobin analysis or hematocrit is recommended for pregnant women at their first prenatal visit

• There is insufficient evidence to recommend for or against repeated prenatal testing for anemia in asymptomatic pregnant women lacking evidence of

medical or obstetrical complications • Compared to other diagnostic tests, serum ferritin

has the best sensitivity and specificity for detecting

iron deficiency in patients found to be anemic.

Iron Deficiency Anemia: Recommended Guidelines for the Prevention, Detection, and Management

Among U.S. Children and Women of Childbearing Age (1994)

Institute of Medicine (IOM)

A. Screen for anemia at the first prenatal visit and treat as appropriate

1. If T1, Hgb & ferritin: Future eval if Hgb < 9.0 g/dl or between 9.0 and 10.9 with ferritin > 30

2. Do not treat with Fe when Hgb > 11.0 g.dl and serum ferritin is > 20 mcg/l

3. 30 mg Fe supp. If Hgb between 9.0-10.9 and ferritin 12-20 or Hgb > 11.0 and ferritin , 20 < 20

http://www4.nationalacademies.org/iom/iomhome.nsf




4. 60-120 mg Fe if Hgb 9.0-10.9 and ferritin is < 12

5. If no response to Fe supp. Refer for additional eval.

Note: Blacks Hgb 0.80 less, also adjust for high altitude and cigarette smoking





B. Screen for anemia at the second trimester visit and treat as appropriate

• Recommendation for supplement and referral are similar to first trimester, but upper Hgb cutoffs are 10.4 for upper level of supplementation and 10.5 for lower





C. Screen for anemia at the third trimester visit and treat as appropriate

D. Screen high-risk women for anemia at the 4-6 week postpartum visit

• E. Advise on diet at each prenatal visit

• 1. Eat a varied diet of iron





E. Advise on diet at each prenatal visit1. Eat a varied diet of iron rich foods

2. Items that inhibit absorption of iron (tea, coffee, whole-grain cereals[particularly bran], unleavened whole-grain breads and dried beans) should be consumer separately from iron rich foods.


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

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

Zinc

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

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

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

Cochrane Collection: Zinc, May 1997

• Background and objectives: It has been suggested that low serum zinc levels may be associated with abnormalities of labor, although this has not yet been established. The objective of this review was to assess the effect of zinc supplementation in pregnancy on maternal and fetal mortality and morbidity.

Cochrane Collection: Zinc

• Main results: Five trials were included. Apart from possible reduction in induction of labor in the supplemented group, no differences were detected between routine supplementation of zinc and placebo or no zinc in pregnancy.

Cochrane Collection: Zinc

• Reviewers' conclusions: There is not enough evidence to evaluate the use of routine zinc supplementation in pregnancy

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 increases in preparation for third trimester demands

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

Calcium Absorption

Stage Absorption

Non- pregnant 27%

5-6 months ofpregnancy

54%

Term 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 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

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.



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.”


Dietary calcium and pregnancy-induced

hypertension: is there a relation?

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

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.

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)

.

Review Conclusions

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


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


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.


• 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.


• 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 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

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.

Lecture 3, 2006 Macro and Micronutrients. Carbohydrate Protein Lipids Vitamins and Minerals:...

Documents

Transcript of Lecture 3, 2006 Macro and Micronutrients. Carbohydrate Protein Lipids Vitamins and Minerals:...