1. Nutrition and Micronutrients in Pregnancy Advances in Maternal and Neonatal Health

2. 2Nutrition and Micronutrients in Pregnancy Evidence of Nutritional Intervention Effectiveness Maternal malnutrition Folate Iron Iodine Vitamin A Zinc Calcium

3. 3Nutrition and Micronutrients in Pregnancy Maternal Malnutrition and Pregnancy Outcome Severe nutritional deprivation (Netherlands 1944–45) 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 1944–46) 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 Cunningham et al 1997; Susser and Stein 1994.

4. 4Nutrition 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 Gülmezoglu 1998.

5. 5Nutrition and Micronutrients in Pregnancy 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.

6. 6Nutrition and Micronutrients in Pregnancy Nutritional Supplementation and Anemia WHO definition of severe anemia: Hemoglobin < 7 g/dL Level of risk Moderate anemia (Hgb 7–11 g/dL): Not increased Severe anemia: Significant risk Severe anemia associated with: Low birth weight newborns Premature newborns Perinatal mortality Increased maternal mortality and morbidity

7. 7Nutrition 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.

8. 8Nutrition and Micronutrients in Pregnancy 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 Mahomed 2000b; WHO 1994.

9. 9Nutrition 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 Gülmezoglu 2000.

10. 10Nutrition and Micronutrients in Pregnancy 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 (0.37–0.97) –Beta-carotene vs. placebo RR 0.51 (0.30–0.86) 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.

11. 11Nutrition and Micronutrients in Pregnancy 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.

12. 12Nutrition and Micronutrients in Pregnancy 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.

13. 13Nutrition and Micronutrients in Pregnancy Calcium Supplementation: Results Mothers: Hypertension+/-proteinuria: –Less hypertension: RR 0.81 (0.74–0.89) –Less pre-eclampsia: RR 0.70 (0.58–0.83) –Better if low calcium intake, high risk Newborns: Low birth weight: RR 0.83 (0.71–0.98), best for women at highest risk Chronic hypertension: RR 0.59 (0.39–0.91) No difference in preterm delivery, neonatal intensive care unit admission, stillbirth, death Atallah, Hofmeyr and Duley 2000.

14. 14Nutrition and Micronutrients in Pregnancy 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.

15. 15Nutrition and Micronutrients in Pregnancy 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

16. 16Nutrition and Micronutrients in Pregnancy 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): 1113–1117. Cunningham FG et al. 1997. Williams Obstetrics, 20 th ed. Appleton & Lange: Stamford, Connecticut. Czeizel AE. 1993. Controlled studies of multivitamin supplementation on pregnancy outcomes. Ann N Y Acad Sci 678: 266–275. 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): 1832–35. de Onis M, J Villar and M Gülmezoglu. 1998. Nutritional intervention to prevent intrauterine growth retardation: Evidence from randomized controlled trials. Eur J Clin Nutr 52(Suppl 1): S83–S93.

17. 17Nutrition and Micronutrients in Pregnancy References (continued) Enkin M et al. 2000. A Guide to Effective Care in Pregnancy and Childbirth, 3 rd ed. Oxford University Press: Oxford. Kulier R et al. 1998. Nutritional interventions for the prevention of maternal morbidity. Int J Gyn Obstet 63: 231–246. Lopez-Jaramillo P et al. 1997. Calcium supplementation and the risk of preeclampsia in Ecuadorian pregnant teenagers. Obstet Gynecol 90(2):162–167. 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 Gülmezoglu. 2000. Maternal iodine supplements in areas of deficiency (Cochrane Review), in The Cochrane Library. Issue 4. Update Software: Oxford.

18. 18Nutrition and Micronutrients in Pregnancy 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: 253–262. Medical Research Council Vitamin Study Research Group. 1991. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338 (8760):131–137. Rothman KJ et al. 1995. Teratogenicity of high vitamin A intake. N Engl J Med 333 (21): 1369–1373. Suharno D et al. 1993. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet 342: 1325–1328. Susser M and Z Stein. 1994. Timing in prenatal nutrition: A reprise of the Dutch famine study. Nutrition Reviews 52 (3): 84–94. 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: 570–575.