Nutrition and Micronutrients in Pregnancy

Advances in Maternal and Neonatal Health

Evidence of Nutritional Intervention Effectiveness

Maternal malnutrition
Folate Iron Iodine Vitamin A Zinc Calcium

Nutrition and Micronutrients in Pregnancy

Maternal Malnutrition and Pregnancy Outcome

Severe nutritional deprivation (Netherlands 194445)

Birth weight significantly influenced by starvation Perinatal mortality rate not affected No increase incidence of malformation In healthy women, state of near starvation is needed to affect pregnancy outcome Severe nutritional deprivation (Netherlands 194446)

Periconception: Decreased fertility, increased neural tube defect 1st trimester: Increased stillbirths, preterm births, early newborn deaths 3rd trimester: Low birth weight, small for gestational age, preterm birth
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Cunningham et al 1997; Susser and Stein 1994. Nutrition and Micronutrients in Pregnancy

Maternal Malnutrition and Pregnancy Outcome (continued)

Dietary restriction trials in pregnant women

High weight for height or high weight gain Inconclusive results to demonstrate or exclude effect on fetal growth or any significant effect on other outcomes Mixed result with nutritional supplementation trials

High protein: No evidence of benefit on fetal growth Balanced protein and energy: minimal increase in average birth weight (~30 g) and small decrease in incidence of small for gestational age newborns Women manifesting nutritional deficits can benefit from a balanced energy/protein supplementation

Enkin et al 2000; de Onis, Villar and Glmezoglu 1998. Nutrition and Micronutrients in Pregnancy 4

Folic Acid

Strong evidence that folic acid prevents preconceptionally recurrent and first occurent neural tube defects Increasing evidence that folic acid reduces risk of some other birth defects Improves the hematologic indices in women receiving routine iron and folic acid USPHS/CDC recommends for US women

400 g/day: All women in childbearing age 1 mg/day: Pregnant women 4 mg/day: Women with history of neural tube defect deliveries take folic acid 1 month prior to conception and during first trimester

Czeizel 1993; Czeizel and Dudas 1992; Mahomed et al 1998; MRC Vitamin Study Research Group 1991. Nutrition and Micronutrients in Pregnancy

Nutritional Supplementation and Anemia

WHO definition of severe anemia: Hemoglobin < 7 g/dL

Level of risk

Moderate anemia (Hgb 711 g/dL): Not increased Severe anemia: Significant risk Low birth weight newborns Premature newborns Perinatal mortality

Severe anemia associated with:

Increased maternal mortality and morbidity

Nutrition and Micronutrients in Pregnancy

Anemia and Obstetrical Hemorrhage

Anemia does not cause obstetrical hemorrhage (even severe anemia)

Etiology of obstetric hemorrhage

Early pregnancy: Abortion complications Mid/late pregnancy to delivery: Previa, abruption, atony, retained placenta, birth canal laceration Primary factors affecting outcome: Rapid intervention to prevent exsanguination Availability of skilled provider, drugs, blood and fluids There is no evidence that high levels of hemoglobin are beneficial in withstanding a hemorrhagic event.

Enkin et al 2000; Mahomed 2000a. Nutrition and Micronutrients in Pregnancy 7

Iron Supplementation

Iron requirements:

Average non-pregnant adult:

800 g iron lost/day + 500 g iron lost/day during menses Pregnant woman: Increased need

Expanded blood volume Fetal and placental requirements Blood loss during delivery Routine vs. selective iron supplementation:

Prevalence of nutritional anemia

Routine iron and folate supplementation where nutritional anemia is prevalent

Recommended dose: 60 mg elemental iron + 5 g folic acid
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Mahomed 2000b; WHO 1994. Nutrition and Micronutrients in Pregnancy

Iodine Supplementation

Iodine deficiency is a preventable cause of mental impairment

Iodine supplementation and fortification programs have been largely successful in decreasing iodine deficiency conditions
Population with high levels of mental retardation (e.g., some parts of China):

Supplementation may be effective at preconception up to mid-pregnancy period Form of iodine supplementation (iodinating food or oral/injectable iodine) depend on: Severity of iodine deficiency Cost Availability of different preparation

Enkin et al 2000; Mahomed and Glmezoglu 2000. Nutrition and Micronutrients in Pregnancy 9

Vitamin A

Indications for vitamin A supplementation:

Vertical transmission of HIV (ongoing) Infant survival Maternal anemia: Positive interaction with iron in reducing anemia Infection Maternal mortality: Vitamin A vs. placebo RR 0.60 (0.370.97) Beta-carotene vs. placebo RR 0.51 (0.300.86) Potential adverse effects of Vitamin A and related substances: Total daily dose > 10,000 IU before 7th week of gestation associated with birth defects: craniofacial, central nervous system, thymic cardiac Overall effectiveness and safety of vitamin A supplementation needs to be evaluated

Rothman et al 1995; Suharno et al 1993; West et al 1999. Nutrition and Micronutrients in Pregnancy

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Other Micronutrients: Calcium

Association between reduction in pregnancy induced hypertension (PIH) and calcium supplementation

Reduction of incidence of PIH Routine supplementation likely beneficial in women at high risk of developing PIH or have low dietary calcium intake High calcium doses (2 g/day) not associated with adverse events Need adequately sized and designed trials in different settings to confirm beneficial effects

Recommend increase in calcium intake through diet in women at risk of hypertension or low calcium areas

Bucher et al 1996; Kulier et al 1998; Lopez-Jaramillo et al 1997. Nutrition and Micronutrients in Pregnancy 11

Calcium Supplementation: Objective and Design

Objective: To assess effects of calcium in prevention of hypertensive disorders of pregnancy

Methods: Meta analysis of randomized controlled trial Outcomes:

Mothers: Hypertension +/- proteinuria, maternal death or serious morbidity, abruption, cesarean section, length of stay
Newborns: Preterm delivery, low birth weight/small for gestational age, neonatal intensive care unit admission, length of stay, still birth/death, disability, hypertension

Atallah, Hofmeyr and Duley 2000. Nutrition and Micronutrients in Pregnancy 12

Calcium Supplementation: Results

Mothers:

Hypertension+/-proteinuria: Less hypertension: RR 0.81 (0.740.89) Less pre-eclampsia: RR 0.70 (0.580.83) Better if low calcium intake, high risk Newborns:

Low birth weight: RR 0.83 (0.710.98), best for women at highest risk Chronic hypertension: RR 0.59 (0.390.91) No difference in preterm delivery, neonatal intensive care unit admission, stillbirth, death

Atallah, Hofmeyr and Duley 2000. Nutrition and Micronutrients in Pregnancy 13

Calcium Supplementation: Conclusions

Calcium decreases risk of hypertension, pre-eclampsia, low birth weight, and chronic hypertension in children
Recommend for high risk women with low calcium intake, if pre-eclampsia is important in the population Calcium has other health benefits not related to pregnancy:

Maintaining bone strength Proper muscle contraction Blood clotting Cell membrane function Healthy teeth

Atallah, Hofmeyr and Duley 2000. Nutrition and Micronutrients in Pregnancy 14

Summary of Nutritional Review Findings

Evidence of nutritional intervention effectiveness

Iron supplementation Periconceptional folic acid intake Iodine use Balanced energy/protein supplementation Calcium Confirmatory studies to examine effectiveness

Vitamin A Zinc

Nutrition and Micronutrients in Pregnancy

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References
Atallah AN, GJ Hofmeyr and L Duley. 2000. Calcium supplements during pregnancy for prevention of hypertensive disorders and related problems (Cochrane Review), in The Cochrane Library, Issue 3. Bucher HC et al. 1996. Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a meta-analysis of randomized controlled trials. JAMA 275(4): 11131117. Cunningham FG et al. 1997. Williams Obstetrics, 20th ed. Appleton & Lange: Stamford, Connecticut. Czeizel AE. 1993. Controlled studies of multivitamin supplementation on pregnancy outcomes. Ann N Y Acad Sci 678: 266275. Czeizel AE and I Dudas. 1992. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 327 (26): 183235.

de Onis M, J Villar and M Glmezoglu. 1998. Nutritional intervention to prevent intrauterine growth retardation: Evidence from randomized controlled trials. Eur J Clin Nutr 52(Suppl 1): S83S93.
Nutrition and Micronutrients in Pregnancy 16

References (continued)
Enkin M et al. 2000. A Guide to Effective Care in Pregnancy and Childbirth, 3rd ed. Oxford University Press: Oxford.
Kulier R et al. 1998. Nutritional interventions for the prevention of maternal morbidity. Int J Gyn Obstet 63: 231246. Lopez-Jaramillo P et al. 1997. Calcium supplementation and the risk of preeclampsia in Ecuadorian pregnant teenagers. Obstet Gynecol 90(2):162167.

Mahomed K. 2000a. Iron supplementation in pregnancy (Cochrane Review), in The Cochrane Library. Issue 4. Update Software: Oxford.
Mahomed K. 2000b. Iron and folate supplementation in pregnancy (Cochrane Review), in The Cochrane Library.Issue 4. Update Software: Oxford. Mahomed K and A Glmezoglu. 2000. Maternal iodine supplements in areas of deficiency (Cochrane Review), in The Cochrane Library. Issue 4. Update Software: Oxford.

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References (continued)
Mahomed K et al. 1998. Risk factors for pre-eclampsia among Zimbabwean women: maternal arm circumference and other anthropometric measures of obesity. Paediatr Perinat Epidemiol 12: 253262. Medical Research Council Vitamin Study Research Group. 1991. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338 (8760):131137. Rothman KJ et al. 1995. Teratogenicity of high vitamin A intake. N Engl J Med 333 (21): 13691373. Suharno D et al. 1993. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet 342: 13251328. Susser M and Z Stein. 1994. Timing in prenatal nutrition: A reprise of the Dutch famine study. Nutrition Reviews 52 (3): 8494. West Jr. KP et al. 1999. Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta carotene on mortality related to pregnancy in Nepal. Br Med J 318: 570575.

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