European Journal of Clinical Nutrition (1999) 53, 970±971 ß 1999 Stockton Press. All rights reserved 0954±3007/99 $15.00 http://www.stockton-press.co.uk/ejcn
Letter to the Editor Nutritional interventions to prevent intrauterine growth retardation: evidence from randomized controlled trials. Paper by de Onis, Villar and GuÈlumezoglu: Nutritional interventions to prevent intrauterine growth retardation: evidence from randomized controlled trials. Eur J Clin Nutr (1998); 52 (Suppl 1): S83-S93. In our opinion the paper of de Onis et al contains a misinterpretation of the results of the so-called Santiago study (Mardones-Santander et al, 1988). In that paper we reported a randomized controlled trial of food supplementation during pregnancy that was done in Santiago, Chile. The possible effects of the regular Chilean supplementation with full cream milk powder (`Purita' or product P) were compared with those of a milk-based product designed in the Netherlands (`Vita Nova' or product VN) when the third author of this letter was working at Melkunie Holland. The product concept of the experimental product VN was based upon the assumption that malnourishment is not restricted to proteins and calories, but that also the possible low levels of the homeostasis regarding micronutrients should be taken into consideration. So the VN formula contains a balanced addition of micronutrients (National Academy of Sciences, 1980). The caloric content of VN was about the same as that of P, whereas the protein content was lower. The rather small supply of protein from each product was negligible when compared to the protein content in the diet of women consuming both products. Mean (plusmn; s.d.) total daily protein consumptions from the diet and from the products were: 45.8 g ( 5.4) vs 5.3 g ( 0.5) in the VN group and 44.5 g ( 5.0) vs 9.7 g ( 1.0) in the P group. The total ®gures of protein consumption are adequate to somewhat low according to international recommendations, including the corrections for digestibility for women weighing on average 47 kg at the beginning of pregnancy and 59 ± 60 kg at the end of pregnancy (World Health Organization, 1985). It seems to us, as explained in the above mentioned paper, that the differences on micronutrients consumption between the two groups of women are of far more biological importance than those related to protein consumption. Nevertheless, de Onis et al preferred to follow the suggestion of Kramer (Kramer, 1993, Kramer, 1997), and they looked just the protein supply from the supplements as important to de®ne them as adequate. The new 'correct supplement' according to Kramer is that having iso-caloric or balanced protein supply (that is providing as < 25% of its total energy content) and the non-balanced supplement is the one that provides more protein than above mentioned. Although that decision is in agreement with what we also expected to be the `correct intervention' (that is the VN product), that supplement was not assigned to the experimental group but curiously to the control group in the renaming of the design of our study. In other words, they decided to call our experimental group as control and vice versa. De Onis et al concluded, similarly to Kramer, that intrauterine growth retardation was increased and therefore
the mean birth weight was reduced in the experimental group. The conclusion is wrong because the 'correct intervention' (VN) when included in the original experimental group of our study had a reduced ®gure for intrauterine growth retardation and an increased mean birth weight when compared to the P group. It seems to us that this may be an involuntary mistake. The results with the new formula VN were in fact surprisingly better than with the product P. When calculations of the typical odds ratios (OR) are performed using the data of our study in the original form (that is allocating women receiving VN to the experimental group), results are totally different than those presented by de Onis et al. In the case of intrauterine growth retardation, the OR (with 95% C1) for its reduction is calculated here for the entire group of women and also stratifying by pregnancy complications as the effect of the intervention was different in this sub-group of women. The result of the ®rst one is 0.62 (0.46 ± 0.83); showing that VN delivery has one the highest reductions of the undesired outcome as compared to the interventions presented by de Onis et al. This OR was wrongly calculated (exchanging the experimental and control groups) in the paper of de Onis et al. The strati®ed OR calculated by using the Mentel-Haenszel estimator is 0.56 (0.41 ± 0.78), a ®gure that is similar to the OR of women without pregnancy complications who show an OR for the reduced risk with the new intervention of 0.47 (0.32 ± 0.68). These two OR are also not presented in the paper of de Onis et al and are much lower than those from the other nutritional interventions indicated by them for the prevention of intrauterine growth retardation. The 95% C1 for the three new OR presented here are much narrower than those presented by de Onis et al, meaning a higher statistical signi®cance. Although de Onis et al concluded that to date there is lack of evidence that micronutrients in the VN product could affect the outcomes examined, we would prefer to say that this trial produced new evidence in this regard. In our trial the data suggested that the greater mean birth weight of infants from the VN group was associated to greater maternal ¯uid retention and not with greater deposition of solid body components. We have recently published the results of a study which shows that maternal total body water, and therefore fat-free-mass, was near term the most important variable in¯uencing birth weight (MardonesSantander, 1998). Therefore, the apparent maternal greater ¯uid retention in the experimental group (VN women) can now be seen as clearly feasible. Other authors have also considered the plausible interpretation of the results that we gave in the 1988 paper. Mervyn Susser, in a critical survey of all supplementation studies based upon the protein-calorie model, gives credit to the positive effects found in the Santiago study, and ®nds the approach promising (Susser, 1991). He pointed out that in the experimental group (VN) `the weight gain change
Letter to the Editor
must have to do with ¯uid retention . . . If in this experiment ¯uid retention is the key to maternal weight gain and birthweight changes, presumably speci®c micronutrients underlie these phenomena'. The subcommittee on dietary intake and nutrient supplements during pregnancy of the Institute of Medicine, National Academy of Sciences of USA, concluded that in the Santiago study 'the relatively high increment in birth weight relative to maternal weight gain may have resulted from the increased supply of micronutrients. Greater rates of weight gain in those with similar energy intakes may have been caused by greater maternal ¯uid retention and plasma expansion' (National Academy of Sciences, 1990) We have also demonstrated the bene®ts on public health and on the budget for the National Health Services of VN delivery (Mardones-Santander, 1991) Dr Francisco Mardones-Santander Dr Pedro Rosso Dick Uiterwaal and Dr Guillermo Marshall Marcoleta 352, Santiago, Chile E-mail:
[email protected]
References Kramer MS. Effects of energy and protein intakes on pregnancy outcome: an overview of the research evidence from controlled trials. Am. J. Clin. Nutr. 1993; 58: 627 ± 635. Kramer MS. Isocaloric balanced protein supplementation in pregnancy. In: Neilson JP, Crowther CA, Hodnett ED, Hofmeyr GJ, Keirse MJNC (eds.) Pregnancy and Childbirth Module of The Cochrane Database of Systematic Reviews. Available in the Cochrane Library (database on disk and CDROM). The Cochrane Collaboration: Issue 2. Updated Software: Oxford, Updated quarterly. Mardones-Santander F, Rosso P, Stekel A, Ahumada E, Llaguno S, Pizarro F, Salinas J, Vial I and Walter T. Effect of a milk-based food supplement on maternal nutritional status and fetal growth in underweight Chilean women. Am. J. Clin. Nutr. 1988; 47: 413 ± 419. Mardones-Santander F, Rosso P, Zamora R, Mardones-Restat F, Uiterwaal D, and GonzaÂlez N. Cost-effectiveness of a nutrition intervention of pregnant women. Nutr. Res. 1991; 11: 295 ± 307. Mardones-Santander F, Salazar G, Rosso P, Villarroel L Maternal body composition near term and birth weight. Obstetr. Gynecol. 1998; 91: 873 ± 877. National Academy of Sciences, 1980. Recommended Dietary Allowances. Additional recommended micronutrients during pregnancy. Washington, D.C.: National Academy Press. National Academy of Sciences, 1990. Institute of Medicine, Nutrition during pregnancy. Washington, D.C.: National Academy Press, pp 161. Susser M Am. J. Clin. Nutr. 1991; 53: 1384 ± 1396. World Health Organization (1985). Technical Report Series No. 24. Report of a Joint FAO/WHO/UNU Expert Consultation. Energy and protein requirements. Geneva: WHO.
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