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Micronutrients
2011
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 inadequacy in pregnancy: biology,
Outcomes,
and interventions. Dror and Allen, Nutr Rev. 2010
• Some evidence for role of vitamin D in: fetal
brain development, fetal bone mineralization,
immune function.
• Potential long term impact of fetal vitamin D
exposure from epi studies of birth season:
diabetes, MS, some cancers, schizophrenia.
• Previous findings of supravalvular arotic
stenosis with high vitamin D related to
exaggerated response of those with Williams
Syndrome to oral vitamin D supplements.
Vitamin D: Emerging
Understandings
• Widespread deficiencies
• Disparities
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
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
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).
6P
0.001.
7P
0.05.
1
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
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
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 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
• (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
Cochrane, Vitamin C & E
Supplementation
Intervention
Fetal/neonatal
loss
Control
2.6%
2.3%
SGA
20.6%
20%
Pre-term
19.5%
18%
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
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 - 2,500 births per year in US; 1/1000
births
• 50-70% may be preventable with adequate
maternal folic acid status.
• NTD etiologies and folic acid pathways may
be multiple mechanisms:
– 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 & non-Hispanic whites
compared to black and asian
• 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.”
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.
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.
Folate Status in Women of
Childbearing Age, by Race/Ethnicity:
MMWR, January 2007
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/
Racial/Ethnic Differences in the Birth
Prevalence of Spina Bifida --- United States,
1995—2005 (MMWR, 2009)
• “Additional public health efforts targeting
women with known risk factors (e.g.,
obesity and certain genetic factors)
likely are needed to further reduce the
prevalence of spina bifida in the United
States.”
• Hispanic and non-Hispanic black
women are less likely to consume
supplements with folic acid than nonHispanic white women.
• Hispanic women have a 15%-25%
higher rate of pregnancies affected by
neural tube defects than women of
other races and ethnicities.
http://www.cdc.gov/features/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
"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%).
• Among women who reported not consuming a
vitamin or mineral supplement daily, 31%
indicated they had received a doctor's
recommendation.
Remember to take folic acid
every day:
Do it with another daily activity such as:
•Brushing your teeth
•Having breakfast
•Getting ready to go to bed
Place your vitamins where you can see them:
•In your purse
•On your desk
•On the kitchen counter
http://www.cdc.gov/features/folicacid
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
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
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
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 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 does 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 - 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 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
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
Cochrane Collection: Zinc
Supplementation
• 17 RCTS; >9,000 women
• Outcomes
– Lower risk of preterm birth (RR, 0.86, 0.760.98)
– No consistent impact on other outcomes
– The highest impact was found in studies
among low-income women
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.”
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
• 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.
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.
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
(900 mg/d)(n = 4 trials)
0.86 (0.71, 1.05)
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.
Ritchie LD, King, JC. Am J Clin Nutr. 2000:71(suppl):1371S-4S
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)
Dietary Reference Intakes for Calcium,
Phosphorus, Magnesium, Vitamin D, and
Fluoride (1999)Institute of Medicine (IOM)
Calcium
(mg)
Phosphorus
(mg)
Magnesium
(mg)
Vitamin D
Fluoride
(mg)
2010 nonpregnant
2010
Pregnant
1999 nonpregnant
1999
1989
pregnant RDA
1000 (RDA)
1000 (RDA)
1000 (AI)
1000 (AI) 1200
700 (RDA)
1200
5 (mcg, AI)
700
(RDA)
350
(RDA)
5 (AI)
3 (AI)
3 (AI)
none
310 (RDA)
600 (RDA IU) 600 (RDA,
IU)
320
10
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.