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Supplement: Nutrition as a Preventive Strategy against Adverse Pregnancy Outcomes

Some Thoughts on Body Mass Index, Micronutrient Intakes and Pregnancy Outcome ¹

Yasmin Neggers^*,2 and Robert L. Goldenberg

^* University of Alabama, Department of Human Nutrition, University of Alabama, Tuscaloosa, AL 35487 and University of Alabama at Birmingham, Center for Research in Women's Health, Birmingham, AL 35233

² To whom correspondence should be addressed. E-mail: yneggers{at}ches.ua.edu.

	ABSTRACT

TOP ABSTRACT LITERATURE CITED

 
A low prepregnancy body mass index is one of strongest predictors of adverse pregnancy outcomes such as preterm birth and fetal growth retardation. A low body mass interacts with other risk factors such as smoking and stress to increase risk of these outcomes, whereas zinc supplementation and low-dose aspirin increase birth weight in thin but not normal-size women. The association between maternal thinness and adverse pregnancy outcomes may be mediated more by a low plasma volume than by decreased protein or energy status. Maternal micronutrient status may partially mediate plasma volume expansion in pregnancy. Therefore, improving maternal micronutrient status may reduce adverse outcomes through this mechanism.

KEY WORDS: • body mass index • plasma volume • preterm birth • fetal growth retardation • micronutrients

Maternal nutritional status both before and during pregnancy is a well-recognized determinant of birth outcomes (1). Only two indicators of maternal nutritional status during pregnancy have shown consistent positive association with infant birth weight: maternal prepregnancy weight for height and weight gain during pregnancy (2). Body mass index (BMI) ³, defined as wt/ht², is a simple, useful index for evaluating prepregnancy nutritional status in clinical settings. In 1990 the United States Institute of Medicine established new weight gain recommendations for women during pregnancy using BMI as the preferred way to classify women into prepregnancy weight categories (3). Although prepregnancy BMI has a genetic as well as nutritional component, a low prepregnancy BMI is considered a marker for minimal tissue nutrient reserves (4). Women with low prepregnancy weight for height or BMI are at increased risk for a number of adverse pregnancy outcomes, including preterm birth and intrauterine growth retardation (IUGR) (5).

BMI and pregnancy outcomes: birth weight, intrauterine growth retardation and preterm delivery

In developed countries an interaction between prepregnancy weight and weight gain during pregnancy has been reported: underweight women with weight gain in excess of 12 kg and overweight women with weight gains limited to 6–11 kg tend to have the best pregnancy outcome (6). Spinillo et al. (7) reported a prepregnancy BMI < 19.5 and a second and third trimester weight gain <0.37 kg/wk to be associated with a significantly increased risk of spontaneous preterm delivery. The risk of spontaneous preterm delivery was associated with a low second or third trimester weight gain with a BMI 19.5 (odds ratio [OR] 5.63; 95% confidence interval [CI]: 2.35–13.8) compared with those with BMI > 19.5 (OR 2.45; 95% CI: 1.60–3.75). Similarly, Schieve et al. (4) reported that women with low prepregnancy BMI were at increased risk of preterm delivery only if they failed to gain weight at an adequate rate during pregnancy. However, low prepregnancy BMI alone has also been independently implicated as a risk factor for preterm delivery. In a matched case-control study of idiopathic preterm labor in Canada, Kramer et al. (8) reported an OR of 2.06 (95% CI: 1.77–3.34) for preterm delivery in women with a prepregnancy BMI < 19.8. In a large cohort of Hispanic women in the United States, Siega-Riz et al. (5) tested BMI cut points cited in the Institute of Medicine report (3) for their ability to predict preterm birth. Women with a prepregnancy BMI < 19.1 had a significantly increased risk of delivering preterm (relative risk 1.7, p < 0.05; positive predictive value 10.4%). Although the relative risks were not statistically significant, there was a trend toward a decreased risk of preterm birth with higher BMI. Prepregnancy weight status based on BMI alone was an indicator of preterm birth only for women with a low BMI.

In a large prospective study of predominantly black indigent women to examine the risk factors associated with IUGR and preterm delivery (9), except for a history of preterm delivery, a low prepregnancy weight (< 50 vs 85 kg) had the strongest relationship with preterm delivery with an adjusted odds ratio (AOR) of 2.72 (p < 0.05). Also, there was a 3-fold increase in risk of IUGR (AOR 3.0, p < 0.05) in women with low prepregnancy weight after adjustments were made for other confounders. The risk of IUGR in women with low prepregnancy weight was larger than all the other independent risk factors in the multiple regression model (Table 1). In a study to evaluate measures of maternal lean mass and fat reserves as predictors of infant birth size, the maternal prepregnancy weight was the best predictor for nearly every neonatal measurement considered (2).

Studies conducted by Goldenberg et al. (11– 13) have indicated an association between several risk factors for IUGR and BMI. For example, smoking and psychosocial stress during pregnancy and protective factors such as aspirin use and zinc supplementation during pregnancy were significantly associated with IUGR only in women with low BMI.

A poor psychosocial profile during pregnancy in both smokers and nonsmokers was a significant predictor of IUGR only in thinner women (pregnancy BMI < 22). The risk of IUGR was not significant in women with a poor psychosocial profile in either smokers or nonsmokers with BMI 22 (13). In thinner women who smoked and had a poor psychosocial profile during pregnancy, the rate and the relative risk of IUGR was substantially higher (mean % IUGR = 31.5; AOR 1.65; 95% CI: 1.06–2.57) than for heavier women who smoked and had a poor psychosocial profile (mean % IUGR = 11.1; AOR 1.04; 95% CI: 0.50–2.15) (Table 2). Thus, a higher BMI seems to protect against the adverse effect of stress and smoking in this population of poor and primarily black women.

In a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of zinc supplementation (25 mg zinc/d, starting at 19 wk gestation) on pregnancy outcome, infants of women in the zinc supplemented group had a significantly higher birth weight (126 g, p = 0.03) than did infants of women in the placebo group (11) (Table 3). However, in the thinner women (BMI < 26), zinc supplementation was associated with a 248 g higher birth weight. Zinc supplementation had virtually no effect in heavier women (BMI 26).

Considerable evidence suggests a role for micronutrients in pregnancy outcomes (14– 16). Even in a developed country like the United States, a substantial proportion of women of childbearing age consumes diets that provide less than the recommended amounts of micronutrients, particularly, zinc, folate, calcium and iron (17, 18). In south Asia, iron deficiency and anemia affect 50% or more of pregnant women. The prevalence of folic acid deficiency may be up to 30–50% and zinc deficiency is likely to be widespread (14). However, nutrition intervention studies have not provided unequivocal evidence of an association between micronutrient intakes and pregnancy outcomes such as birth weight, IUGR, preterm delivery and pregnancy-induced hypertension (19, 20). Study population, sample size and study design showed considerable methodological variation across these studies. Also, many of these studies were conducted in women not at great risk for low micronutrient intakes and were therefore less likely to demonstrate a positive association between micronutrient intakes and pregnancy outcome.

In a systematic review of randomized clinical trials to evaluate nutritional interventions to prevent IUGR, Onis et al. (19) concluded that perhaps with the exception of balanced protein and energy supplementation, no effective nutritional intervention has been demonstrated. However, they recommended that interventions such as with zinc, folate and magnesium supplements during pregnancy merit further research.

Ramakrishan et al. (20) published an extensive review of the relationship between micronutrient status and pregnancy outcome. This review was not restricted to randomized controlled trials and also included cross-sectional, prospective, case-control studies. Their key conclusions were that 1) significant evidence, mostly from developed countries, shows improved pregnancy outcomes from supplementation with zinc, calcium and magnesium; 2) vitamin A supplements may be associated with reduced maternal mortality and increased birthweight; 3) although the prevention of neural tube defects with folate supplementation and increases in hemoglobin with iron supplementation are well documented, evidence demonstrating whether folic acid and iron supplementation reduce other adverse pregnancy outcomes is limited; 4) vitamin C deficiency may have a role in the etiology of preterm delivery; and 5) severe maternal iodine deficiency results in mental retardation and cretinism but evidence is weak in the case of marginal iodine deficiency.

Because in developing countries the prevalence of both poor pregnancy outcome (20% of infants are low birth weight compared with 6% in developed countries) and multiple micronutrient deficiencies are common, well-designed randomized clinical trials in high risk women with low prepregnancy BMI are needed to evaluate the role of micronutrients related to poor pregnancy outcomes.

Prepregnancy BMI, birth weight and micronutrient intakes

The mechanisms of association between prepregnancy BMI and IUGR and preterm delivery are not clear, but throughout the literature there is an assumption that the relationship between a low prepregnancy BMI and adverse pregnancy outcomes is mediated by protein-energy availability. However, there are reasons to believe protein-energy malnutrition may not provide the full explanation (21, 22). For example, the effect of reduced prepregnancy weight on fetal growth was still present when underweight women were able to gain weight at a normal rate throughout pregnancy (23, 24). It is likely that a normal gestational weight gain indicates a positive energy balance. If maternal energy intake directly affects fetal growth, then it is hard to explain why similar weight gains result in larger infants in women with a normal prepregnancy weight than in women with a low prepregnancy weight. One explanation for the lower mean infant birth weight in women with low prepregnancy weight may be that the fetus was prevented from receiving an adequate supply of nutrients from the mother because of changes in maternal hemodynamic status (22).

In a study comparing the plasma volume in underweight, normal-weight and overweight women with similar weight gains during pregnancy, underweight women had smaller total plasma volume than did normal and overweight women both early and late in pregnancy (22). As expected, the mean birth weight of infants of underweight women was significantly lower than those of the other two groups. During pregnancy no differences in plasma volume expansion were observed between underweight and normal-weight women. It was concluded that because weight gain was similar in all groups, maternal weight and plasma volume increased proportionately. The authors suggest that this supports a key role for maternal plasma volume in fetal growth. Based on the results of their clinical studies, Rosso et al. (22) proposed that in underweight women, a low plasma volume during early pregnancy will result in a proportionately reduced cardiac output. A lower cardiac output would result in a lower uteroplacental blood flow and hence a decrease in transfer of nutrients to the fetus and a reduction in fetal growth.

Some evidence shows that in underweight women, micronutrient intake during pregnancy may be associated with maternal plasma volume and infant birth weight. In a supplementation study conducted in Chile by Mardones-Santander et al. (25) in underweight women (mean BMI = 20.2), infant birth weight was significantly higher in the group that received energy (milk powder) and a micronutrient supplement than the group that received energy supplement alone. Also, the percentage of IUGR infants was significantly lower in the group that received energy plus a micronutrient supplement than the group that received only energy supplement. The higher weight gain during pregnancy in the micronutrient group was attributed to a larger plasma volume expansion during pregnancy. A later analysis of this data indicated that the risk for IUGR in the group that received micronutrient plus energy supplement was significantly lower (OR 0.62; 95% CI: 0.46–0.83; p = 0.03) than the group that received only energy supplement (26). These investigators suggested that in malnourished underweight women, lower volume expansion related to decreased micronutrient status might be associated with reduced fetal growth.

In a recent prospective study conducted in India in underweight women (mean prepregnancy BMI = 18.1), increased infant birth weight was strongly associated with consumption of foods rich in micronutrients (vitamins A and C, folacin, calcium and iron) whereas energy and protein intakes were not associated with birth size (27). Women who consumed green leafy vegetables, fruits or milk products 3–4 times/wk compared with women who consumed these foods <1 time/wk had infants with a significantly higher mean birth weight (green leafy vegetables: 2742 vs. 2601 g, fruits: 2721 vs. 2598 g, milk products: 2704 vs. 2618 g). Because the mean birth weight in this study was low (mean = 2665, SD ± 358 g), an increase in birth weight of 139, 122 and 86 g with increased consumption of micronutrient-rich green leafy vegetables, fruits and milk products, respectively, is of biological significance. Thus, in undernourished women with low prepregnancy BMI, a lack of association of birth weight with energy and protein intakes but a strong association with micronutrient intakes suggests that micronutrients may be one of the limiting factors for fetal growth.

It can be concluded that in developed countries, prepregnancy BMI is a significant predictor of fetal growth. The effect of some protective factors (aspirin use and zinc supplements) on IUGR and preterm birth is largely present in women with a low prepregnancy BMI. By contrast, a higher prepregnancy BMI seems to protect against factors such as smoking and stress that reduce birth weight.

In developing countries, where deficiencies of multiple micronutrients are common, some evidence indicates that increasing micronutrient intakes, either by supplementation or by increased consumption of micronutrient-rich foods, is associated with significant increase in birth size and a reduction of IUGR in women with a low prepregnancy BMI. It is plausible that in these undernourished women both low prepregnancy BMI and a low plasma volume may be associated with poor micronutrient status. This combination may thus result in a decreased transfer of nutrients from mother to fetus and may have an adverse effect on fetal growth.

In conclusion, there is need for

• research to further clarify the mechanism of association between prepregnancy BMI and IUGR and preterm delivery and
  
• well-designed randomized controlled trials in high-risk women with low prepregnancy BMI, preferably in developing countries (where multiple micronutrient deficiencies are common) to evaluate the role of micronutrients related to poor pregnancy outcomes.
  

	FOOTNOTES

 
¹ Manuscript prepared for the USAID-Wellcome Trust workshop on "Nutrition as a preventive strategy against adverse pregnancy outcomes," held at Merton College, Oxford, July 18–19, 2002. The proceedings of this workshop are published as a supplement to The Journal of Nutrition. The workshop was sponsored by the United States Agency for International Development and The Wellcome Trust, UK. USAID's support came through the cooperative agreement managed by the International Life Sciences Institute Research Foundation. Supplement guest editors were Zulfiqar A. Bhutta, Aga Khan University, Pakistan, Alan Jackson (Chair), University of Southampton, England, and Pisake Lumbiganon, Khon Kaen University, Thailand.

³ Abbreviations used: AOR, adjusted odds ratio; BMI, body mass index; CI, confidence interval; IUGR, intrauterine growth retardation; OR, odds ratio.

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