||In most developing countries, low birth weight (LBW: Birth weight < 2500 g), infant morbidity and mortality remain major public health problems. These problems are caused by a complex series of genetic and environmental exposures during and after pregnancy, including inadequate maternal nutrition and infections. The main focus in this thesis is the nutritional aspects, but maternal malaria is also mentioned.
In developing countries, dietary intakes of pregnant women in general are considered insufficient to cover the increased micronutrient requirements during pregnancy. Prenatal supplementation with iron and folic acid has been recommended for decades by the who to prevent maternal anaemia; however, even though iron supplementation has consistent positive effects on maternal iron status and anaemia, little or no effects has been demonstrated for infant outcomes. Based on the potential benefits of multi-micronutrient supplementation for both mothers and their infants, UNICEF has proposed that a prenatal multi-micronutrient supplement would be more efficacious than the existing iron and folic acid supplement for maternal as well as infant outcomes. The proposed supplement contains one recommended dietary allowance (rda) of nine vitamins (including folic acid) and five minerals (including iron). However, the optimal micronutrient intakes may be higher in a population with low nutrient bioavailability from diet and frequent infections which can lead to reduced dietary intake, reduced absorption, and increased losses of micronutrients.
Even though maternal micronutrient status is associated with pregnancy outcome, there is no scientific evidence from randomised controlled trials in developing countries with a high risk of micronutrient deficiencies, that such a supplement will in fact improve pregnancy outcome. Therefore we investigated the effects on birth weight and peri- and neonatal mortality of daily supplementation in the second half of 2100 pregnancies with one (mn-1) or two (mn-2) recommended dietary allowances (rda) of 15 micronutrients compared with iron and folic acid alone (control) in a randomised, controlled, double masked intervention study. the study was carried out from primo 2001 to ultimo 2002 in a semi-urban area in Bissau, the capital of guinea-bissau, west africa. Transmission of p. falciparum malaria occurs in all seasons, whereas prevalence of hiv-1 is low. women less than 37 weeks pregnant attending antenatal care or identified through a monthly pregnancy surveillance in the study area were invited to participate in the study.
Those willing to participate were randomised to take daily one of three different supplements until delivery. The mean birth weight was higher among women who were offered multi-micronutrients (b="63;" 95 % c.i. [-9; 134] g in mn-1 and 99 [28; 170] g in mn-2). Our data suggest a dose-response relationship between birth weight and multi-micronutrient supplementation with doses up to two rda. There was an interaction between intervention and maternal anaemia (p="0.06)" due to a higher effect of mn-2 among anaemic women (30% with haemoglobin below 100 g/l), in which mn-2 increased birth weight with 218 [81; 354] g compared to anaemic controls, with a corresponding decreased risk of lbw of 69 [27; 87]%. Peri- or neonatal mortality was not different between the intervention groups. Other important determinants of birth weight were maternal body composition and mild to moderate malaria parasitaemia. Arm muscle area (AMA) and hip circumference had independent effects on birth weight. AMA below the mean was associated with 76 [18; 135] g lower birth weight compared to ama at or above the mean, and similarly, women whose hip circumference was in the lowest and the three central quintiles had babies of 136 [34; 238] g and 79 [1; 156] g lower birth weight compared to women whose hip circumference was in the upper quintile. Mild to moderate malaria parasitaemia at inclusion was associated with 59 [2; 115] g lower birth weight compared to no parasitaemia. Severe parasitaemia was treated at inclusion and was not associated with birth weight.
Low (< 70 g/l) and high haemoglobin (> 116 g/L) and malaria parasitaemia are highlighted among the other determinants of perinatal mortality. Low haemoglobin was associated with 2.83 [0.85; 9.44] times and high haemoglobin with 2.03 [1.26; 3.28] times higher risk of perinatal mortality compared to women with normal haemoglobin (100-116 g/L). Moderate malaria parasitaemia at inclusion despite prophylactic intake of chloroquine during the rest of the pregnancy was associated with 1.62 [1.01; 2.59] times higher risk of perinatal mortality compared to no parasitaemia.
It is recommended that all pregnant women in malaria endemic areas, regardless of gravidity and parasitaemia, should receive standard chloroquine treatment at their first antenatal visit, followed by prophylaxis during the rest of pregnancy. Determinants of high haemoglobin in pregnancy should be identified as it was a strong predictor of perinatal mortality. Based on existing knowledge, the scientific evidence is still too weak to change international recommendations from the existing iron and folic acid prenatal supplement into the supplement containing one RDA of 15 micronutrients being promoted by UNICEF.
The results from the present study suggested that two rather than one RDA should be considered in a future prenatal multi-micronutrient supplement, and in two other recent trials there were no effects on birth weight of one RDA. Even though there are no indications of adverse effects of the supplement, with limited health budgets it can not be advised to change recommendations into a more expensive supplement as long as there is no hard evidence for better survival or less morbidity. Therefore effects on functional medium and long term outcomes such as infant morbidity and mortality, and psychomotor development, should also be evaluated. Further, dietary intake or chronic infections may influence the effect of supplementation. Efficacy studies with concomitant micronutrient supplementation and interventions for various infections (such as intestinal parasites, syphilis, malaria, and HIV) should be conducted.