Maternal Nutrition in Pregnancy: Implications for the Long-Term Health of the Fetus
July 2000; Volume 2; 49-53
By Fiona Mathews, DPhil
Interest in the role of maternal nutrition during pregnancy has increased since the demonstration that folic acid supplementation prevents up to 70% of recurrent neural tube defects.1 Now, women are encouraged to increase their periconceptional folate intake, and prenatal nutritional supplements are marketed both in the United States and Europe.
Aside from preventing congenital abnormalities, maternal nutrition may affect both fetal and placental growth. There is widespread recognition of the need for adequate maternal nutrition during pregnancy in the Third World, where many women not only suffer clinical deficiencies, but also undertake strenuous manual labor well into the third trimester. However, considerable uncertainty exists about the role of maternal nutrition in industrialized countries. During the wartime "Hunger Winter" in Holland, sudden and severe nutritional deprivation was associated with a reduction in mean birth weight of 300 g.2 The incidence of preterm delivery and other adverse outcomes was also increased.3 Yet where overt undernutrition is rare, such as in the United States, the evidence is conflicting.
Micronutrients have not been shown to have an important impact on mean birth or placental weights in supplementation trials.4-7 Protein and energy supplementation have produced both increases and decreases in birth weight, with high-density protein supplements appearing to reduce birth weight.8,9 The results of such trials are difficult to generalize, since intakes often are elevated well beyond normal levels. In addition, they are usually designed to detect changes in adverse pregnancy outcomes rather than in birth weights within the normal range. Observational studies have found only weak and inconsistent associations between macronutrient intake and infant size,10-13 and few data are available for micronutrients.4,5,13 Particular problems in the interpretation of such work include small or unrepresentative samples,13-15 presentation of data only for women with adverse outcomes and controls,16 and the use of methods unsuitable for the assessment of most micronutrient intakes. Nevertheless, Professor David Barker and colleagues from the MRC Environmental Epidemiology Unit, Southampton, UK, propose not only that maternal nutrition is one of the major determinants of fetal and placental growth, but also that its impact extends beyond the immediate well-being of the infant into adulthood.
"The Barker Hypothesis"
Barker and colleagues postulate that maternal undernutrition during pregnancy is one of the key "adverse environmental influences in utero" that can compromise fetal growth and development.17 They argue that this in turn can predispose individuals to chronic diseases of adulthood. Socioeconomic inequalities in health could therefore be perpetuated across generations via the poor dietary intakes of women in lower social classes.
In the late 1980s, the group noted that standardized mortality ratios from coronary heart disease were highly and positively correlated (R = 0.73) with perinatal and infant mortality rates earlier in the century.17,18 Further refinement of the hypothesis occurred following a series of historical cohort studies. Delivery records (which in some hospitals included neonatal anthropometry and infant feeding data) of individuals born before World War II indicated that low birth weight was associated with subsequent hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and mortality from coronary heart disease.19-22 Variations in newborn ponderal index and the ratio of placental:birth weight were also linked to hypertension and cardiovascular disease in adulthood; low abdominal circumference at birth was linked with high serum cholesterol levels later in life.23-26 The causal pathways proposed for the long-term impact of fetal development on disease risk include the elevation of fetal blood pressure to maintain perfusion through an abnormally large placenta and the permanent compromise of liver development in infants who were thin at birth.
Most evidence implicating maternal nutrition as a key part of the programming hypothesis is drawn from animal studies. For example, undernutrition of pregnant rats has been reported to stunt the offspring’s growth permanently, whereas the manipulation of diet after birth had no effect on the growth deficit.27 Barker’s group has argued more recently that undernutrition at particular stages in gestation results in specific patterns of altered placental and fetal growth, which can be recognized at delivery and associated with later disease.
It is suggested that in the second trimester, when in normal pregnancy the placenta grows more rapidly than the fetus, fetal undernutrition disturbs the relationship of fetal to placental growth. The infant suffers reduced birth weight, while placental growth is normal or greater than expected. In previously well-nourished sheep, undernutrition early in pregnancy enlarges placental size; this hypertrophy may be an adaptation to extract more nutrients from the maternal circulation.28 Similarly, localized placental hypertrophy can be induced experimentally in sheep by reducing the number of implantation sites.29 Compensatory growth at the remaining sites appears to prevent any retardation of fetal growth, and has been interpreted as a sensitive, early response of the fetus to reduced nutrient supply. In humans, this pattern of disturbed placental:fetal growth is associated with hypertension, NIDDM, and coronary heart disease in later life.17,19,23
Barker also has argued that undernutrition in the third trimester causes fetal growth to be sacrificed to maintain placental growth, and this wasting may cause the infant to be thin at birth. If the period of undernutrition is protracted, the growth rate of the fetus may also be slowed irreversibly, leading to a disproportionally short infant. This type of growth pattern has been associated with raised LDL cholesterol and fibrinogen levels in later life and increased mortality from coronary heart disease and thrombotic stroke.30
The "Barker hypothesis" has attracted much controversy. The vague nature of the hypothesis (that maternal factors influence fetal growth, which in turn determines the infant’s future risks of certain adult diseases) makes conventional testing difficult. With so many possible exposure and outcome variables, it is to be expected that specific examples of the hypothesis holding true might be emphasized, with little attention being paid to cases where it does not. It has also been argued that too little consideration has been given to postnatal environmental factors and possible selection biases, which may explain the associations with coronary heart disease.31-33 In contrast to the focus on the group’s retrospective studies, there have been few attempts to determine whether maternal nutrition has been correctly identified as a major determinant of fetal and placental growth. Yet there have already been calls, in the lay press, for improvements to maternal diet, and concern is mounting among obstetricians about the possible ramifications of endorsing dietary change.34
Evidence for the Role of Maternal Nutrition
Two large detailed observational studies have specifically attempted to investigate the relationships between maternal nutrition and infant and placental size at birth. Barker’s group used food-frequency questionnaires to assess dietary intakes35 while Mathews et al used a food diary at 16 weeks gestation and a food-frequency questionnaire at 28 weeks.36 The two projects were conducted in neighboring cities in the South of England, had similar sample sizes and social and age-class distributions, evaluated dietary intake in both the second and third trimesters, and excluded preterm deliveries from the analysis. The women in each project were similar in terms of social class to nationally representative samples of British women, and included women who receive unemployment benefits.
Barker’s group reported significant relationships between energy and carbohydrate intakes and placental and birth weights.35 However, Mathews et al found no association between intakes of any macronutrient early in pregnancy and placental weight, birth weight, or placental ratio.36 Furthermore, they found no significant relationships between any outcome and intakes of any individual nutrient as assessed at approximately 28 weeks gestation. This finding is in agreement with the work of others.10,13,35
However, Godfrey et al reported that the combination of low dairy protein intakes in later pregnancy and high carbohydrate intakes early in pregnancy were associated with small placental size and thinness at birth.35 In contrast, low intakes of meat protein late in pregnancy in conjunction with high carbohydrate intake early in pregnancy were linked to reduced birth weight. In a previously reported study, they found that simultaneously high meat protein and low carbohydrate intakes in the third trimester were associated with reduced birth weight.10 These findings are difficult to interpret, particularly given the high correlation between protein and carbohydrate intakes, and the lack of a priori hypotheses about different types of protein. Nevertheless, they resulted in speculation in the press about the possible adverse consequences of a maternal vegetarian diet during pregnancy. In the work of Mathews et al, none of the relationships reported were altered by adjustment for total energy intake, and given the lack of main effects for carbohydrate intake, further investigation of these previous findings was not pursued.36
There has been concern about the potential confounding effects of maternal smoking in studies of the Barker hypothesis.33 Smokers have a poorer dietary intake of many micronutrients than do nonsmokers,37-39 and even when intakes are equivalent, the concentration of circulating antioxidants is lower among smokers than nonsmokers. Mathews et al therefore validated maternal self-reports of smoking status using serum cotinine. Maternal smoking was strongly associated with reduced birth weight, but not with alterations to the placental weight or the placental:birth weight ratio.36 After accounting for smoking and height, vitamin C intake early in pregnancy was the only nutrient associated with placental and birth weights. The placental:birth weight ratio was negatively associated with the use of preconceptional folic acid supplements, but not with any other factor. However all these relationships were weak (after adjustment for the effects of maternal height and smoking, the expected mean difference in birth weight for infants with mothers in the upper and lower thirds of intake was only approximately 70 g), and seem unlikely to be of clinical importance, even in the light of the "Barker hypothesis."
Conclusion
Lay literature about nutrition during pregnancy has made extraordinary claims for the importance of maternal diet, including postulated roles in preventing intrauterine growth retardation, preterm delivery, and infertility.40-42 Folic acid is clearly important in the prevention of neural tube defects.1 However, the role of maternal diet in determining the size of term infants born to relatively well-nourished women remains unproven. With the exception of iron-deficiency anemia (which has been associated with a threefold increase in the risk of low birth weight, and a twofold increase in preterm delivery),43 there is also little convincing evidence of a role for maternal diet in the etiology of intrauterine growth restriction or preterm delivery.4,5,44
This does not invalidate the public health message about maternal nutrition. Moreover, pregnant women who are young or smoke have been found to have poor micronutrient intakes.44 For example, in a large cohort of pregnant British smokers, vitamin C intake in the highest tertile of age was 50% more than in the lowest age tertile, and carotenoid intakes were more than 30% higher.36
Further, women who did not smoke had intakes of these nutrients 15-20% higher than those of smokers in the same age group. Encouraging pregnant women to follow a healthy diet is likely to be of considerable benefit to their own long-term health if not to that of their fetuses.
Dr. Mathews is an epidemiologist in the Department of Zoology at the University of Oxford, UK.
References
1. MRC Vitamin Study Research Group. Prevention of neural tube defects: Results of the Medical Research Council vitamin study. Lancet 1991;338:131-137.
2. Antonov AN. Children born during the siege of Leningrad in 1942. J Paediatr 1947;30:250-259.
3. Stein Z. Famine and Human Development: The Dutch Hunger Winter of 1944-45. New York: Oxford Univer-sity Press; 1975.
4. Kramer MS. Determinants of low birth weight: Methodological assessment and meta-analysis. Bull World Health Organ 1987;65:663-737.
5. Mathews F. Antioxidant nutrients in pregnancy: A systematic review of the literature. Nutr Res Rev 1996; 9:175-195.
6. Mahomed K. Routine zinc supplementation in pregnancy. In: Enkin MW, et al., eds. Pregnancy and Childbirth Module. Cochrane Database of Systematic Reviews. Oxford: Update Software; 1993.
7. Mahomed K. Routine folate supplementation in pregnancy. In: Enkin MW, et al., eds. Pregnancy and Childbirth Module. Cochrane Database of Systematic Reviews. Oxford: Update Software; 1993.
8. Rush D. Effect of changes in protein and calorie intake during pregnancy on the growth of the human fetus. In: Chalmers I, et al., eds. Effective Care in Pregnancy and Childbirth. Oxford: Oxford University Press; 1989:255-280.
9. Kramer MS. High protein supplementation in pregnancy. In: Enkin MW, et al., eds. Pregnancy and Childbirth Module. Cochrane Database of Systematic Reviews. Oxford: Update Software; 1994.
10. Campbell DM, et al. Diet in pregnancy and the offspring’s blood pressure 40 years later. Br J Obstet Gynaecol 1996;103:273-280.
11. Godfrey K, et al. Maternal birthweight and diet in pregnancy in relation to the infant’s thinness at birth. Br J Obstet Gynaecol 1997;104:663-667.
12. Susser M. Maternal weight gain, infant birth weight, and diet: Causal sequences. Am J Clin Nutr 1991;53:1384-1396.
13. Haste FM, et al. The effect of nutritional intake on outcome of pregnancy in smokers and non-smokers.
Br J Nutr 1991;65:347-354.
14. Haste FM, et al. Nutrient intakes during pregnancy: Observations on the influence of smoking and social class. Am J Clin Nutr 1990;51:29-36.
15. Black AE, et al. The nutrient intakes of pregnant and lactating mothers of good socio-economic status in Cambridge, UK: Some implications for recommended daily allowances of minor nutrients. Br J Nutr 1986;56:59-72.
16. Doyle W, et al. The association between maternal diet and birth dimensions. J Nutr Med 1990;1:9-17.
17. Barker DJ. Fetal and Infant Origins of Adult Disease. London: BMJ Publishing; 1992.
18. Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1986;1:1077-1081.
19. Barker DJ, et al. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989;298:564-567.
20. Hales CN, et al. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 1991;303:1019-1022.
21. Osmond C, et al. Early growth and death from cardiovascular disease in women. BMJ 1993;307:1519-1524.
22. Barker DJ, et al. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993;341:938-941.
23. Barker DJ, et al. Fetal and placental size and risk of hypertension in adult life. BMJ 1990;301:259-262.
24. Barker DJ, et al. The relation of fetal length, ponderal index and head circumference to blood pressure and the risk of hypertension in adult life. Paediatr Perinat Epidemiol 1992;6:35-44.
25. Barker DJ, et al. The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. BMJ 1993;306:422-426.
26. Barker DJ, et al. Growth in utero and serum cholesterol concentrations in adult life. BMJ 1993;307: 1524-1527.
27. Blackwell BN, et al. Further studies on growth and feed utilization in progeny of underfed mother rats. J Nutr 1969;97:79-84.
28. Robinson JS, et al. Maternal nutrition and fetal growth. In: Ward RHT et al., eds. Early Fetal Nutrition and Development. London: RCOG Press; 1994:317-334.
29. Owens JA, Robinson JS. The effect of experimental manipulation of placental growth and development. In: Cockburn F., ed. Fetal and Neonatal Growth. Chichester: Wiley; 1988:49-77.
30. Barker DJ. Fetal origins of coronary heart disease. BMJ 1995;311:171-174.
31. Ben-Shlomo Y, Smith GD. Deprivation in infancy or adult life: Which is more important for mortality risk? Lancet 1991;337:530-534.
32. Heart disease: In the beginning. Lancet 1992;339: 1386-1387.
33. Paneth N, Susser M. Early origins of coronary heart disease. BMJ 1995:310:411-412.
34. Fraser R Sr., Cresswell J Sr. What should obstetricians be doing about the Barker hypothesis? Br J Obstet Gynaecol 1997;104:645-647.
35. Godfrey K, et al. Maternal nutrition in early and late pregnancy in relation to placental and fetal growth. BMJ 1996;312:410-414.
36. Mathews F, et al. Influence of maternal nutrition on outcome of pregnancy: Prospective cohort study. BMJ 1999;319:339-343.
37. Bolton-Smith C, et al. Antioxidant vitamin intakes assessed using a food-frequency questionnaire: Correlation with biochemical status in smokers and non-smokers. Br J Nutr 1991;65:337-346.
38. Cade JE, Margetts BM. Relationship between diet and smoking: Is the diet of smokers different? J Epidemiol Community Health 1991;45:270-272.
39. Margetts BM, Jackson AA. Interactions between people’s diet and their smoking habits: The dietary and nutritional survey of British adults. BMJ 1993;307:1381-1384.
40. Kamen B, Kamen S. The Kamen Plan for Total Nutrition During Pregnancy. Appleton Century Crofts: New York; 1981.
41. Barnes B, Bradley SG. FORESIGHT, The Association for the Promotion of Preconceptional Care: Planning for a Healthy Baby. Vermilion: London; 1992:54-76.
42. Wynn M, Wynn A. The Case for Preconceptional Care of Men and Women. Bicester UK: A B Academic Publishers; 1991:64-84.
43. Scholl T, et al. Anaemia vs. iron deficiency: Increased risk of preterm delivery in a prospective study. Am J Clin Nutr 1992;55:985-988.
44. Mathews F, et al. Are cotinine assays of value in predicting adverse pregnancy outcome? Ann Clin Biochem 1999;36:468-476.
45. Mathews F, et al. Nutrient intakes during pregnancy: The influence of smoking status and age. J Epidemiol Comm Health 2000;54:17-23.
July 2000; Volume 2; 49-53
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content