Papers

Maternal nutrition in early and late pregnancy in relation to placental and fetal growth

^a Medical Research Council Environmental Epidemiology Unit (University of Southampton), Southampton General Hospital, Southampton SO16 6YD

Correspondence to: Dr Godfrey.

Abstract

Objective: To assess how nutrient intakes of mothers in early and late pregnancy influence placental and fetal growth.
Design: Prospective observational study.
Setting: Princess Anne Maternity Hospital, Southampton.
Subjects: 538 mothers who delivered at term.
Main outcome measures: Placental and birth weights adjusted for the infant's sex and duration of gestation.
Results: Mothers who had high carbohydrate intakes in early pregnancy had babies with lower placental and birth weights. Low maternal intakes of dairy and meat protein in late pregnancy were also associated with lower placental and birth weights. Placental weight fell by 49 g (95% confidence interval 16 g to 81 g; P=0.002) for each log g increase in intake of carbohydrate in early pregnancy and by 1.4 g (0.4 g to 2.4 g; P=0.005) for each g decrease in intake of dairy protein in late pregnancy. Birth weight fell by 165 g (49 g to 282 g; P=0.005) for each log g increase in carbohydrate intake in early pregnancy and by 3.1 g (0.3 g to 6.0 g; P=0.03) for each g decrease in meat protein intake in late pregnancy. These associations were independent of the mother's height and body mass index and of strong relations between the mother's birth weight and the placental and birth weights of her offspring.
Conclusion: These findings suggest that a high carbohydrate intake in early pregnancy suppresses placental growth, especially if combined with a low dairy protein intake in late pregnancy. Such an effect could have long term consequences for the offspring's risk of cardiovascular disease.

Introduction

Most low birthweight babies have a small placenta.^{1 2} The growth of the placenta precedes that of the fetus, and surgical restriction of placental growth in sheep causes retardation of fetal growth.³ Recent experimental studies in sheep have shown that high nutrient intakes in early pregnancy may also suppress placental growth, resulting in reduced placental and fetal size.⁴ In humans we know little about how nutrient intakes in early pregnancy relate to placental and fetal size. Whereas nutrient intakes in late pregnancy have been reported to have inconsistent effects on fetal size.^{5 6} their relation to placental size is largely unknown. Any such effects may be of long term importance in view of the associations between placental and birth size and adult cardiovascular disease.^{2 7} In a prospective study we have assessed the relations between the mother's nutrient intakes in early and late pregnancy and placental and fetal weight.

Subjects and methods

We approached all 655 white women aged 16 years or older with signleton pregnancies who registered under two consultants over one year and who attended the midwives' antenatal booking clinic at the Princess Anne Maternity Hospital in Southampton at less than 17 weeks' gestation. Twelve miscarried or had a termination of pregnancy, and seven delivered outside the district. Of the 636 remaining women, 596 (94%) agreed to participate.

The mothers were visited at home by a trained research nurse shortly after recruitment and again around 32 weeks' gestation (median duration of gestation 15.3 and 32.7 weeks, respectively). Mothers were asked about their menstrual and obstetric history, weight before pregnancy, and smoking habits and were requested to contact their parents and ascertain their own birth weight. Height was measured with a stadiometer. Social class was allocated according to the mother's current or last occupation.^{8 9} Social class could not be allocated for 15 mothers.

In early and late pregnancy a food frequency questionnaire was administered that assessed the average frequency of consumption of 100 foods or food groups in the three months preceding the visit. The nutrient content^{10 11 12 13} of a standard portion of each food¹⁴ was multiplied by its reported frequency of use to calculate average daily nutrient intake. The early pregnancy estimates have been validated against those determined from food diaries kept over four days.¹⁵

At birth the baby was weighed to the nearest 5 g with digital scales. The placenta was weighed on digital scales after trimming by stripping the amnion to the cord, cutting the chorion at the edge of the placenta, and removing the cord flush with the placenta. Duration of gestation was estimated from menstrual history and ultrasound scan data by using a standard algorithm.¹⁶

The study was approved by the local ethics committee. Of the 596 mothers recruited, 39 delivered before 259 days' (37 weeks') gestation and were excluded from this analysis in view of the strong dependence of birth weight on gestation. Three mothers were not visited in late pregnancy and placental weight was not recorded for 16, leaving 538 term pregnancies with complete data on nutrition and delivery (85% of the sample of 636).

Statistical analysis was by tabulation of means and paired t tests. Multiple linear regression was used to take account of the independent effects of separate variables. Levels of significance refer to regression analysis of continuous variables. Nutrient intakes were log transformed when necessary to satisfy assumptions of normality.

Results

Table 1 shows the characteristics of the 538 mothers and babies. Placental and birth weights rose with increasing gestational age at birth by 1.6 g/day and 21 g/day, respectively, and were higher in boys than girls. We adjusted both weights for the baby's sex and duration of gestation, and subsequent analyses use the adjusted values.

Table 1--Characteristics of 538 mothers and babies
----------------------------------------------------------------------
Mothers
No (%) primiparous                                     285 (53.0)
No (%) of smokers                                      139 (25.8)
Social class:
  No (%) I, II                                         144 (26.8)
  No (%) IIIN, IIIM                                    283 (52.6)
  No (%) IV, V                                         111 (20.7)
Mean (SD) height (m)*                                 1.63 (0.06)
Mean (SD) body mass index (kg/m2) before
  pregnancy*                                          23.1 (4.4)
Mean (SD) age (years)                                 26.4 (4.9)
Mean (SD) birth weight of mother (g)+                 3312 (534)
Babies (boys; girls)
Mean (SD) placental weight (g)                  544 (125); 522 (115)
Mean (SD) birth weight (g)                     3527 (496); 3344 (463)
Mean (SD) placental ratio (%)                  15.4 (2.8); 15.7 (2.9)
Mean (SD) gestation (days)                    281.4 (9.3); 281.2 (9.3)
----------------------------------------------------------------------
*Body mass index unknown for 10 mothers and height for two
mothers.
+Mother's own birth weight unknown for 47 mothers.

Table 2 shows the mothers' median daily nutrient intakes. Between early and late pregnancy a small fall in carbohydrate and rise in fat intakes resulted in a fall in the proportion of energy derived from carbohydrate (from 49.4% to 49.0%) and a corresponding rise in that derived from fat (from 35.7% to 36.4%). While intakes of dairy protein rose (from 20.5 g to 22.3 g/day) those of meat protein remained constant and those of cereal protein fell (from 34.7 g to 33.7 g/day). Intakes of iron and folate rose during pregnancy (table 2) because of higher intakes from supplements in late pregnancy.

Table 2--Median daily intakes (lower and upper quartile) of
the 538 mothers
----------------------------------------------------------------------
Intake                      Early pregnancy        Late pregnancy
----------------------------------------------------------------------
Energy (kcal)              2329 (1882, 2789)      2314 (1970, 2729)
Carbohydrate (g)          302.7 (245.7, 372.9)   301.9 (254.3, 360.6)
Fat (g)                    91.2 (74.2, 112.6)     93.2 (75.8, 111.9)
Protein (g)                87.2 (69.8, 101.3)     85.7 (72.4, 99.8)
Proportion (%) kcal
  carbohydrate             49.4 (46.2, 53.4)      49.0 (46.1, 52.2)
Proportion (%) kcal fat    35.7 (32.5, 38.7)      36.4 (33.3, 39.1)
Proportion (%) kcal
  protein                  14.7 (13.3, 16.5)      14.7 (13.3, 16.0)
Total sugars (g)          141.7 (109.9, 185.0)   151.5 (115.9, 189.1)
Starch (g)                150.3 (123.2, 190.0)   144.3 (116.9, 176.9)
Cereal protein (g)         34.7 (27.7, 42.0)      33.7 (27.2, 40.2)
Meat protein (g)           28.1 (19.0, 38.3)      28.3 (20.5, 37.3)
Dairy protein (g)          20.5 (15.2, 28.2)      22.3 (16.4, 28.9)
Iron (mg)                  15.5 (12.7, 21.2)      16.8 (13.2, 29.6)
Folate (µg)              315 (252, 397)          327 (260, 449)

NUTRIENT INTAKES IN EARLY PREGNANCY AND PLACENTAL AND BIRTH WEIGHTS

Table 3 shows mean placental and birth weights according to the mother's intakes of energy and macronutrients. Placental and birth weights were inversely related to energy intake in early pregnancy, falling by 38 g (95% confidence interval 5 g to 72 g; P=0.03) and 134 g (11 g to 256 g; P=0.03), respectively, for each log kcal increase in intake. These relations were largely dependent on an association with carbohydrate intake, placental weight falling by 41 g (10 g to 73 g; P=0.01) and birth weight by 143 g (28 g to 258 g; P=0.01) for each log g increase in carbohydrate. Division of carbohydrate into total sugars and starch showed that the relations with intakes of sugars (P=0.01 and P=0.02, respectively) were stronger than those with intakes of starch (P=0.09 and P=0.1).

Table 3--Mean placental weight and birth weight adjusted
for baby's sex and duration of gestation according to
mother's daily intakes in early and late pregnancy
------------------------------------------------------------
                    Placental     Birth
Intake              weight (g)  weight (g)  No of subjects
------------------------------------------------------------
Early pregnancy
Energy (kcal):
  </=2080              547       3468           180
  -2560                535       3446           173
  >2560                520       3412           185
Carbohydrate (g):
  </=265               554       3501           181
  -340                 531       3444           172
  >340                 517       3381           185
Fat (g):
  </=80                542       3456           191
  -105                 543       3461           165
  >105                 517       3409           182
Protein (g):
  </=76                537       3462           175
  -95                  536       3427           175
  >95                  528       3437           188
Late pregnancy
Energy (kcal):
  </=2080              537       3452           175
  -2560                531       3438           182
  >2560                534       3436           181
Carbohydrate (g):
  </=265               544       3492           170
  -340                 529       3427           190
  >340                 530       3409           178
Fat (g):
  </=80                538       3443           165
  -105                 530       3432           187
  >105                 534       3450           186
Protein (g):
  </=76                530       3419           173
  -95                  534       3453           189
  >95                  537       3452           176

Placental weight fell by 27 g (-2 g to 56 g; P=0.07) and birth weight by 101 g (-4 g to 207 g; P=0.06) for each log g increase in fat. Both were unrelated to the mother's intakes of protein, iron, or folate in early pregnancy. After carbohydrate intakes in early pregnancy were taken into account no more variance in placental and birth weights was explained when we also considered fat, protein, iron, or folate intakes in early pregnancy.

NUTRIENT INTAKES IN LATE PREGNANCY AND PLACENTAL AND BIRTH WEIGHTS

There were no significant univariate relations between the mother's nutrient intakes in late pregnancy and placental and birth weights (table 3). After the mother's carbohydrate intake in early pregnancy was taken into account, however, a low protein intake in late pregnancy was associated with decreased placental weight (P=0.02) and birth weight (P=0.01). Though the relation with placental weight reflected an association with dairy protein, there being no associations with either cereal (P=0.2) or meat protein (P=0.5), birth weight was more closely related to intakes of meat protein than those of dairy (P=0.2) or cereal protein (P=0.2). Thus placental weight fell by 49 g (16 g to 81 g; P=0.002) for each log g increase in carbohydrate intake in early pregnancy and by 1.4 g (0.4 g to 2.4 g; P=0.005) for each g decrease in dairy protein intake in late pregnancy (table 4). Birth weight fell by 165 g (49 g to 282 g; P=0.005) for each log g increase in carbohydrate intake in early pregnancy and by 3.1 g (0.3 g to 6.0 g; P=0.03) for each g decrease in meat protein intake in late pregnancy (table 5).

Table 4--Mean placental weight (g) adjusted for baby's sex
and duration of gestation according to mother's daily
intakes of carbohydrate in early pregnancy and dairy
protein in late pregnancy. Figures in parentheses are
numbers of subjects
----------------------------------------------------------------
Dairy protein
intake in late  Carbohydrate intake in early pregnancy (g/day)
pregnancy      -------------------------------------------------
(g/day)             </=265      -340       >340       All
----------------------------------------------------------------
</=18.5            539 (72)   507 (49)   494 (54)   516 (175)
-26.5              556 (73)   546 (63)   509 (48)   540 (184)
>26.5              582 (36)   533 (60)   536 (83)   544 (179)
All                554 (181)  531 (172)  517 (185)  534 (538)

Table 5--Mean birth weight (g) adjusted for baby's sex and
 duration of gestation according to the mother's daily
 intakes of carbohydrate in early pregnancy and meat
 protein in late pregnancy. Figures in parentheses are
 numbers of subjects
----------------------------------------------------------------
Meat protein
intake in late  Carbohydrate intake in early pregnancy (g/day)
pregnancy      -------------------------------------------------
(g/day)             </=265      -340       >340       All
----------------------------------------------------------------
</=23.5            3450 (71)  3419 (61)  3312 (43)  3405 (175)
-34.0              3539 (58)  3472 (56)  3359 (69)  3451 (183)
>34.0              3529 (52)  3443 (55)  3443 (73)  3468 (180)
All                3501 (181) 3444 (172) 3381 (185) 3442 (538)

Placental and birth weights fell by 15 g (1 g to 28 g; P=0.03) and 63 g (14 g to 112 g; P=0.01), respectively, for each log mg decrease in iron intake in late pregnancy and by 34 g (11 g to 57 g; P=0.004) and 98 g (15 g to 181 g; P=0.02) for each log µg decrease in folate. These relations largely reflected associations with iron and folate intakes from supplements and were independent of those with dietary carbohydrate and protein intakes.

MOTHER'S CHARACTERISTICS AND PLACENTAL AND BIRTH WEIGHTS

Primiparous mothers had placentas that were 29 g (8 g to 49 g; P=0.006) lighter and babies that were 121 g (48 g to 195 g; P=0.001) lighter than those of multiparous mothers. Placental and birth weights fell with decreasing maternal height (by 336 g/m (180 g/m to 492 g/m; P<0.0001) and 1541 g/m (977 g/m to 2105 g/m; P<0.0001), respectively) and, weakly, with decreasing maternal body mass index (g/weight(kg)/height(m)²) before pregnancy (by 1.6 g (-0.7 g to 3.9 g; P=0.2) and 8.1 g (-0.5 g to 16.6 g; P=0.06)). Though placental weight was similar in mothers who smoked and did not smoke (difference 1 g (-24 g to 22 g; P=0.9)), birth weight was 146 g (62 g to 229 g; P=0.0007) lower in mothers who smoked. After maternal height and smoking were taken into account, placental and birth weights were unrelated to maternal age and social class.

Multiple regression analyses showed that the relations between placental and birth weights and intakes of carbohydrate and dairy and meat protein were independent of the mother's height and body mass index and were similar in primiparous and multiparous mothers and in mothers who did or did not smoke.

MOTHER'S BIRTH WEIGHT

Of the 538 mothers, 491 (91%) ascertained their own birth weight. Placental and birth weights were strongly related to the mother's weight at birth (table 6), falling by 0.041 g (0.021 g to 0.061 g; P=0.0001) and 0.204 g (0.133 g to 0.276 g; P<0.0001), respectively, for each g decrease in the mother's birth weight. These relations were both little changed when we simultaneously took account of the mother's adult height (adjusted regression coefficients 0.033 for placental weight and 0.162 for birth weight) and were similar in primiparous and multiparous mothers and in mothers who smoked and did not smoke. Multiple regression analyses showed that the relations between placental and birth weights and the mother's dietary intakes were independent of her own weight at birth.

Table 6--Mean placental weight and birth weight adjusted
for baby's sex and duration of gestation according to
mother's own birth weight
---------------------------------------------------------
Mother's own      Placental     Birth
birth weight (g)  weight (g)  weight (g)  No of subjects
---------------------------------------------------------
</=2500              503         3309           28
-3000                510         3359          111
-3500                533         3394          180
-4000                550         3553          132
>4000                586         3705           40

Comparison of recalled birth weight with the actual weight recorded in the original obstetric records was possible for 136 mothers born in local hospitals. Actual birth weight averaged 32 g heavier than recalled birth weight (SD of difference 264 g); 84% differed by 250 g or less. Among the 136 mothers the relations between actual maternal birth weight and the offspring's placental and birth weights were similar to those with recalled birth weight.

PLACENTAL RATIO

The ratio of placental weight to birth weight (placental ratio) fell by 0.05% for each day increase in gestational age at birth and was 0.3% lower in boys than girls (table 1). The ratio, adjusted for gestation and sex, fell by 0.77% (0.01% to 1.53%; P=0.05) for each log g increase in early pregnancy carbohydrate intakes and by 0.025% (0.001% to 0.049%; P=0.04) for each g decrease in late pregnancy dairy protein intakes and was 0.66% (0.11% to 1.21%; P=0.02) higher in mothers who smoked than in those who did not smoke. The ratio also fell with decreasing folate intake in late pregnancy (P=0.05) but was unrelated to meat protein or iron intakes or to parity, height, body mass index, or the mother's birth weight.

Discussion

We have examined how the nutrient intakes in pregnancy of an unselected group of mothers delivering at term are related to placental and fetal size at birth. The 538 mothers represent 85% of the original sample approached. Their social class distribution (table 1) was similar to that of mothers in England and Wales.⁹

We administered a food frequency questionnaire to assess nutrient intakes over the first trimester and repeated this in late pregnancy. The estimates of energy intake given by the questionnaire were consistent with predicted requirements based on calculations of basal metabolic rate.^{15 17} Among those who did not have nausea in early pregnancy the questionnaire to assess intakes over the first trimester ranked mothers similarly to a four day food diary in the second trimester (rank correlation coefficient for energy 0.41),¹⁵ and nutrient intakes estimated by the two methods were similarly related to placental weight (unpublished observations). Though food frequency questionnaires give an assessment of diet useful in ranking the nutrient intakes of individual subjects,^{18 19 20} they can, however, be subject to bias^{21 22} and allow only cautious conclusions.

We have found that placental and fetal size at birth are associated with the mother's intakes of carbohydrate and protein. These relations could reflect an effect of total food intakes as it is difficult to disentangle the effects of highly correlated nutrients whose error of measurement may differ. Our analyses suggest, however, that carbohydrate and protein in early and late pregnancy may have specific and differing effects. High carbohydrate intakes in early pregnancy were associated with low placental and birth weights (table 3). Although this seems paradoxical, in sheep farming it is common practice for ewes to be put on rich pasture before they are mated and then on poor pasture for a period in early pregnancy.²³ Experimental studies in farm animals suggest that the scientific basis of this practice may lie partly in stimulation of placental growth by undernutrition in early pregnancy.^{4 24 25} Our data provide the first evidence that similar effects may occur in humans.

In late pregnancy low intakes of dairy protein in relation to carbohydrate were also associated with low placental weight (table 4). A recent reanalysis of a survey of diet in late pregnancy, carried out in Aberdeen, similarly showed that low intakes of animal protein in relation to carbohydrate were associated with low placental weight.²⁶ This survey, however, did not differentiate meat and dairy protein. Interestingly, follow up of the babies in this survey, now 40 years old, showed that low maternal intakes of animal protein in relation to carbohydrate not only led to decreased placental size but were also associated with raised blood pressure in adult life.²⁶ This parallels experimental studies in rats.²⁷

We found that low intakes of meat protein in late pregnancy were associated with lower birth weight (table 5). High protein intakes in late pregnancy have been associated with both positive and negative effects on birth weight.^{5 6 28} Supplements in which protein contributed less than 21% of energy have had beneficial effects on birth weight, whereas adverse effects have resulted from supplements with a higher protein density.⁶ Our results raise the possibility that both the source and density of the protein may be important.

High intakes of iron and folate from supplements late in pregnancy were associated with both higher placental and birth weights. While this could reflect a beneficial effect of supplementation the results of randomised trials of iron and folate supplementation suggest this is unlikely.^{29 30} One possibility is that the higher iron requirement of large babies leads to greater falls in maternal haemoglobin,³¹ making their mothers more likely to be supplemented.

Consistent with the results of other studies³² mothers who had low birth weights had babies with lower birth weights (table 6). Although our analyses were dependent on recalled birth weights, validation against labour ward records showed a high degree of agreement between recalled and actual weights. The effects of the mother's birth weight were largely independent of her adult height and at least as strong. We showed for the first time that the babies of low birthweight mothers had lower placental weights. This strong relation supports the hypothesis that maternal constraint of fetal growth may operate largely through constraint of placental growth,³³ perhaps as a consequence of impaired uterine or ovarian development during the mother's own fetal life.³⁴

One observational study cannot form the basis for changing dietary recommendations to pregnant women. The differing relations of nutrient intakes in early and late pregnancy to placental and fetal growth need replication in other studies. Our findings, however, do parallel those of experimental studies in sheep in which high nutrient intakes in early pregnancy have been shown to suppress placental and fetal growth.

We thank the mothers who gave us their time; the staff on the antenatal clinic, labour ward, and postnatal ward for their considerable assistance in the study; Mr T Wheeler and Professor E J Thomas for their guidance and for allowing us to include their patients; and Mr D Howe for advice and for performing ultrasound scans. The fieldwork was carried out by S Crofts, V Davill, J Hammond, L Greenaway, S Mitcham, and S White.

Funding: The Dunhill Trust and the Medical Research Council. KG was in receipt of a Medical Research Council training fellowship.

Conflict of interest: None.

1. McKeown T, Record RG. The influence of placental size on foetal growth according to sex and order of birth. J Endocrinol 1953;10:73-81. [Medline]
2. Barker DJP, Bull AR, Osmond C, Simmonds SJ. Fetal and placental size and risk of hypertension in adult life. BMJ 1990;301:259-62.
3. 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.
4. Robinson JS, Owens JA, De Barro T, Lok F, Chidzanja S. Maternal nutrition and fetal growth. In: Ward RHT, Smith SK, Donnai D, eds. Early fetal growth and development. London: Royal College of Obstetricians and Gynaecologists, 1994:317-34.
5. Slen SB. Wool production and body growth in sheep. In: Cuthbertson D, ed. Nutrition of animals of agricultural importance. Part 2. Assessment of and factors affecting the requirements of farm livestock. Oxford: Pergamon Press, 1969:827-48.
6. Rush D. Effects of changes in protein and calorie intake during pregnancy on the growth of the human fetus. In: Chalmers I, Enkin M, Keirse MJNC, eds. Effective care in pregnancy and childbirth. Vol I. Oxford: Oxford University Press, 1989:301-17.
7. Barker DJP. Fetal origins of coronary heart disease. BMJ 1995;311:171-4. [Free Full Text]
8. Office of Population Censuses and Surveys. Classification of occupations. London: HMSO, 1980.
9. Botting B, Cooper J. Analysing fertility and infant mortality by mother's social class as defined by occupation--part II. Population Trends 1993;74:27-33.
10. Holland B, Welch AA, Unwin ID, Buss DH, Paul AA, Southgate DAT. McCance and Widdowson's the composition of foods. 5th ed. Cambridge: Royal Society of Chemistry and Ministry of Agriculture, Fisheries and Food, 1991.
11. Holland B, Unwin ID, Buss DH. Cereals and cereal products. Third supplement to McCance and Widdowson's composition of foods. Cambridge: Royal Society of Chemistry and Ministry of Agriculture, Fisheries and Food, 1988.
12. Holland B, Unwin ID, Buss DH. Milk, milk products and eggs. Fourth supplement to McCance and Widdowson's composition of foods. Cambridge: Royal Society of Chemistry and Ministry of Agriculture, Fisheries and Food, 1989.
13. Holland B, Unwin ID, Buss DH. Vegetables, herbs and spices. Fifth supplement to McCance and Widdowson's composition of foods. Cambridge: Royal Society of Chemistry and Ministry of Agriculture, Fisheries and Food, 1991.
14. Crawley H. Food portion sizes. London: HMSO, 1988.
15. Robinson SM, Godfrey KM, Cox V, Osmond C, Barker DJP. Evaluation of a food frequency questionnaire used to assess nutrient intakes in pregnant women. Eur J Clin Nutr (in press).
16. Howe DT, Wheeler T, Osmond C. The influence of maternal haemoglobin and ferritin on mid-pregnancy placental volume. Br J Obstet Gynaecol 1995;102:213-19. [Medline]
17. Prentice AM, Spaaij CJK, Poppitt SD, Goldberg GR, van Raaij JMA. Energy requirements of pregnant and lactating women. Eur J Clin Nutr (in press).
18. Willett WC. Future directions in the development of food-frequency questionnaires. Am J Clin Nutr 1994;59suppl:171-4S.
19. Block G, Woods M, Potosky A, Clifford C. Validation of a self administered diet history questionnaire using multiple diet records. J Clin Epidemiol 1990;43:1327-35. [Medline]
20. Margetts BM, Cade JE, Osmond C. Comparison of a food frequency questionnaire with a diet record. Int J Epidemiol 1989;18:868-73. [Abstract/Free Full Text]
21. Bingham SA. The dietary assessment of individuals; methods, accuracy, new techniques and recommendations. Nutrition Abstracts and Reviews (Series A) 1987;57:705-42.
22. McKeigue P. Trans fatty acids and coronary heart disease: weighing the evidence against hardened fat. Lancet 1995;345:269-70. [Medline]
23. Thomas WJK, ed. Lowland sheep: production policies and practices. Exeter: University of Exeter, 1970.
24. McCrabb GJ, Egan AR, Hosking BJ. Maternal undernutrition during mid-pregnancy in sheep. Placental size and its relationship to calcium transfer during late pregnancy. Br J Nutr 1991;65:157-68. [Medline]
25. Heap FC, Lodge GA, Lamming GE. The influence of plane of nutrition in early pregnancy on the survival and development of embryos in the sow. J Reprod Fertil 1967;13:269-79. [Medline]
26. Campbell D, Hall MH, Barker DJP, Cross J, Shiell AW, Godfrey KM. Diet in pregnancy and the offspring's blood pressure 40 years later. Br J Obstet Gynaecol (in press).
27. Langley SC, Jackson AA. Increased systolic pressure in adult rats induced by fetal exposure to maternal low protein diets. Clin Sci (Colch) 1994;86:217-22.
28. Rosso P. Nutrition and metabolism in pregnancy. Oxford: Oxford University Press, 1990:175-84.
29. Mahomed K, Hytten F. Iron and folate supplementation in pregnancy. In: Chalmers I, Enkin M, Keirse MJNC, eds. Effective care in pregnancy and childbirth. Vol I. Oxford: Oxford University Press, 1989:301-17.
30. Hemminki E, Starfield B. Routine administration of iron and vitamins during pregnancy: review of controlled clinical trials. Br J Obstet Gynaecol 1978;85:404-10. [Medline]
31. Howe D. Maternal haemoglobin and birth weight in different ethnic groups. BMJ 1995;310:1601. [Free Full Text]
32. Emanuel I, Filakti H, Alberman E, Evans SJW. Intergenerational studies of human birthweight from the 1958 birth cohort. 1. Evidence for a multigenerational effect. Br J Obstet Gynaecol 1992;99:67-74. [Medline]
33. Ounsted M, Ounsted C. Maternal regulation of intra-uterine growth. Nature 1966;212:687-9.
34. Barker DJP, Gluckman PD, Robinson JS. Fetal origins of adult disease. Report of the first international study group, Sydney, 29-30 October 1994. Placenta 1995;16:317-20. [Medline]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Gluckman, P. D., Hanson, M. A., Cooper, C., Thornburg, K. L. (2008). Effect of In Utero and Early-Life Conditions on Adult Health and Disease. NEJM 359: 61-73 [Full text]  
• Jansson, N., Nilsfelt, A., Gellerstedt, M., Wennergren, M., Rossander-Hulthen, L., Powell, T. L, Jansson, T. (2008). Maternal hormones linking maternal body mass index and dietary intake to birth weight. Am. J. Clin. Nutr. 87: 1743-1749 [Abstract] [Full text]  
• Xue, F., Willett, W. C., Rosner, B. A., Forman, M. R., Michels, K. B. (2008). Parental characteristics as predictors of birthweight. Hum Reprod 23: 168-177 [Abstract] [Full text]  
• Olsen, S. F, Halldorsson, T. I, Willett, W. C, Knudsen, V. K, Gillman, M. W, Mikkelsen, T. B, Olsen, J., and The NUTRIX Consortium, (2007). Milk consumption during pregnancy is associated with increased infant size at birth: prospective cohort study. Am. J. Clin. Nutr. 86: 1104-1110 [Abstract] [Full text]  
• Langley-Evans, S C, Carrington, L J (2006). Diet and the developing immune system. Lupus 15: 746-752 [Abstract]  
• Phillips, D I. (2006). External influences on the fetus and their long-term consequences. Lupus 15: 794-800 [Abstract]  
• Regan, F. M., Cutfield, W. S., Jefferies, C., Robinson, E., Hofman, P. L. (2006). The Impact of Early Nutrition in Premature Infants on Later Childhood Insulin Sensitivity and Growth. Pediatrics 118: 1943-1949 [Abstract] [Full text]  
• Jansson, N., Pettersson, J., Haafiz, A., Ericsson, A., Palmberg, I., Tranberg, M., Ganapathy, V., Powell, T. L., Jansson, T. (2006). Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J. Physiol. 576: 935-946 [Abstract] [Full text]  
• Gale, C. R., Jiang, B., Robinson, S. M., Godfrey, K. M., Law, C. M., Martyn, C. N. (2006). Maternal Diet During Pregnancy and Carotid Intima-Media Thickness in Children. Arterioscler. Thromb. Vasc. Bio. 26: 1877-1882 [Abstract] [Full text]  
• Bloomfield, F H, Oliver, M H, Harding, J E (2006). The late effects of fetal growth patterns.. Arch. Dis. Child. Fetal Neonatal Ed. 91: F299-F304 [Abstract] [Full text]  
• Trujillo-Ortega, M. E, Mota-Rojas, D., Hernandez-Gonzalez, R., Velazquez-Armenta, E. Y., Nava-Ocampo, A. A, Ramirez-Necoechea, R., Becerril-Herrera, M., Alonso-Spilsbury, M. (2006). Obstetric and neonatal outcomes to recombinant porcine somatotropin administered in the last third of pregnancy to primiparous sows.. J Endocrinol 189: 575-582 [Abstract] [Full text]  
• Murphy, V. E., Smith, R., Giles, W. B., Clifton, V. L. (2006). Endocrine Regulation of Human Fetal Growth: The Role of the Mother, Placenta, and Fetus. Endocr. Rev. 27: 141-169 [Abstract] [Full text]  
• Gnanalingham, M G, Mostyn, A, Gardner, D S, Stephenson, T, Symonds, M E (2006). Developmental regulation of the lung in preparation for life after birth: hormonal and nutritional manipulation of local glucocorticoid action and uncoupling protein-2.. J Endocrinol 188: 375-386 [Abstract] [Full text]  
• Jiang, B., Godfrey, K. M., Martyn, C. N., Gale, C. R. (2006). Birth Weight and Cardiac Structure in Children. Pediatrics 117: e257-e261 [Abstract] [Full text]  
• Salsberry, P. J., Reagan, P. B. (2005). Dynamics of Early Childhood Overweight. Pediatrics 116: 1329-1338 [Abstract] [Full text]  
• Parker, E., Phillips, D. I. W., Cockington, R. A., Cull, C., Poulton, J. (2005). A common mitchondrial DNA variant is associated with thinness in mothers and their 20-yr-old offspring. Am. J. Physiol. Endocrinol. Metab. 289: E1110-E1114 [Abstract] [Full text]  
• Gurekian, C. N., Koski, K. G. (2005). Amniotic Fluid Amino Acid Concentrations Are Modified by Maternal Dietary Glucose, Gestational Age, and Fetal Growth in Rats. J. Nutr. 135: 2219-2224 [Abstract] [Full text]  
• Cagnacci, A., Pansini, F. S., Bacchi-Modena, A., Giulini, N., Mollica, G., De Aloysio, D., Vadora, E., Volpe, A., for the Emilia-Romagna Operative Group for the Men, (2005). Season of birth influences the timing of menopause. Hum Reprod 20: 2190-2193 [Abstract] [Full text]  
• Ashdown-Lambert, J. R (2005). A review of low birth weight: predictors, precursors and morbidity outcomes. The Journal of the Royal Society for the Promotion of Health 125: 76-83 [Abstract]  
• Wallace, J. M., Aitken, R. P., Milne, J. S., Hay, W. W. Jr. (2004). Nutritionally Mediated Placental Growth Restriction in the Growing Adolescent: Consequences for the Fetus. Biol. Reprod. 71: 1055-1062 [Abstract] [Full text]  
• Gluckman, P. D., Hanson, M. A. (2004). Living with the Past: Evolution, Development, and Patterns of Disease. Science 305: 1733-1736 [Abstract] [Full text]  
• Mitchell, E A, Robinson, E, Clark, P M, Becroft, D M O, Glavish, N, Pattison, N S, Pryor, J E, Thompson, J M D, Wild, C J (2004). Maternal nutritional risk factors for small for gestational age babies in a developed country: a case-control study. Arch. Dis. Child. Fetal Neonatal Ed. 89: F431-F435 [Abstract] [Full text]  
• Moore, V. M., Davies, M. J., Willson, K. J., Worsley, A., Robinson, J. S. (2004). Dietary Composition of Pregnant Women Is Related to Size of the Baby at Birth. J. Nutr. 134: 1820-1826 [Abstract] [Full text]  
• Mathews, F., Youngman, L., Neil, A. (2004). Maternal circulating nutrient concentrations in pregnancy: implications for birth and placental weights of term infants. Am. J. Clin. Nutr. 79: 103-110 [Abstract] [Full text]  
• Forrester, T. (2004). Historic and Early Life Origins of Hypertension in Africans. J. Nutr. 134: 211-216 [Abstract] [Full text]  
• Langley-Evans, A J, Langley-Evans, S C (2003). Relationship between maternal nutrient intakes in early and late pregnancy and infants weight and proportions at birth: prospective cohort study. The Journal of the Royal Society for the Promotion of Health 123: 210-216 [Abstract]  
• Edwards, C A, Osman, L M, Godden, D J, Campbell, D M, Douglas, J G (2003). Relationship between birth weight and adult lung function: controlling for maternal factors. Thorax 58: 1061-1065 [Abstract] [Full text]  
• Hobel, C., Culhane, J. (2003). Role of Psychosocial and Nutritional Stress on Poor Pregnancy Outcome. J. Nutr. 133: 1709S-1717 [Abstract] [Full text]  
• Gluckman, P. D., Pinal, C. S. (2003). Regulation of Fetal Growth by the Somatotrophic Axis. J. Nutr. 133: 1741S-1746 [Abstract] [Full text]  
• Khan, I. Y., Taylor, P. D., Dekou, V., Seed, P. T., Lakasing, L., Graham, D., Dominiczak, A. F., Hanson, M. A., Poston, L. (2003). Gender-Linked Hypertension in Offspring of Lard-Fed Pregnant Rats. Hypertension 41: 168-175 [Abstract] [Full text]  
• Duggleby, S. L, Jackson, A. A (2002). Higher weight at birth is related to decreased maternal amino acid oxidation during pregnancy. Am. J. Clin. Nutr. 76: 852-857 [Abstract] [Full text]  
• Margetts, B M, Mohd Yusof, S, Al Dallal, Z, Jackson, A A (2002). Persistence of lower birth weight in second generation South Asian babies born in the United Kingdom. J. Epidemiol. Community Health 56: 684-687 [Abstract] [Full text]  
• Gray, I. P., Cooper, P. A., Cory, B. J., Toman, M., Crowther, N. J. (2002). The Intrauterine Environment Is a Strong Determinant of Glucose Tolerance during the Neonatal Period, Even in Prematurity. J. Clin. Endocrinol. Metab. 87: 4252-4256 [Abstract] [Full text]  
• Bertin, E., Gangnerau, M.-N., Bellon, G., Bailbe, D., Arbelot De Vacqueur, A., Portha, B. (2002). Development of beta -cell mass in fetuses of rats deprived of protein and/or energy in last trimester of pregnancy. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283: R623-R630 [Abstract] [Full text]  
• Rahiala, E., Tenhola, S., Vanninen, E., Herrgard, E., Tikanoja, T., Martikainen, A. (2002). Ambulatory Blood Pressure in 12-Year-Old Children Born Small for Gestational Age. Hypertension 39: 909-913 [Abstract] [Full text]  
• Daenzer, M., Ortmann, S., Klaus, S., Metges, C. C. (2002). Prenatal High Protein Exposure Decreases Energy Expenditure and Increases Adiposity in Young Rats. J. Nutr. 132: 142-144 [Abstract] [Full text]  
• Moore, S. E, Collinson, A. C, Prentice, A. M (2001). Immune function in rural Gambian children is not related to season of birth, birth size, or maternal supplementation status. Am. J. Clin. Nutr. 74: 840-847 [Abstract] [Full text]  
• LUM, S., HOO, A.-F., DEZATEUX, C., GOETZ, I., WADE, A., DEROOY, L., COSTELOE, K., STOCKS, J. (2001). The Association between Birthweight, Sex, and Airway Function in Infants of Nonsmoking Mothers. Am. J. Respir. Crit. Care Med. 164: 2078-2084 [Abstract] [Full text]  
• MATHEWS, F, YUDKIN, P, NEIL, A (2001). Maternal nutrition and pregnancy outcome. Arch. Dis. Child. 85: 510d-510 [Full text]  
• Shiell, A. W., Campbell-Brown, M., Haselden, S., Robinson, S., Godfrey, K. M., Barker, D. J.P. (2001). High-Meat, Low-Carbohydrate Diet in Pregnancy: Relation to Adult Blood Pressure in the Offspring. Hypertension 38: 1282-1288 [Abstract] [Full text]  
• Barker, D. J P (2001). The malnourished baby and infant: Relationship with Type 2 diabetes. Br Med Bull 60: 69-88 [Abstract] [Full text]  
• Dezateux, C, Stocks, J, Wade, A M, Dundas, I, Fletcher, M E (2001). Airway function at one year: association with premorbid airway function, wheezing, and maternal smoking. Thorax 56: 680-686 [Abstract] [Full text]  
• Bertram, C., Trowern, A. R., Copin, N., Jackson, A. A., Whorwood, C. B. (2001). The Maternal Diet during Pregnancy Programs Altered Expression of the Glucocorticoid Receptor and Type 2 11{beta}-Hydroxysteroid Dehydrogenase: Potential Molecular Mechanisms Underlying the Programming of Hypertension in Utero. Endocrinology 142: 2841-2853 [Abstract] [Full text]  
• Whorwood, C. B., Firth, K. M., Budge, H., Symonds, M. E. (2001). Maternal Undernutrition during Early to Midgestation Programs Tissue-Specific Alterations in the Expression of the Glucocorticoid Receptor, 11{beta}-Hydroxysteroid Dehydrogenase Isoforms, and Type 1 Angiotensin II Receptor in Neonatal Sheep. Endocrinology 142: 2854-2864 [Abstract] [Full text]  
• Metges, C. C. (2001). Does Dietary Protein in Early Life Affect the Development of Adiposity in Mammals?. J. Nutr. 131: 2062-2066 [Abstract] [Full text]  
• Rao, S., Yajnik, C. S., Kanade, A., Fall, C. H. D., Margetts, B. M., Jackson, A. A, Shier, R., Joshi, S., Rege, S., Lubree, H., Desai, B. (2001). Intake of Micronutrient-Rich Foods in Rural Indian Mothers Is Associated with the Size of Their Babies at Birth: Pune Maternal Nutrition Study. J. Nutr. 131: 1217-1224 [Abstract] [Full text]  
• Kahn, H. S., Ravindranath, R., Valdez, R., Venkat Narayan, K. M. (2001). Fingerprint Ridge-Count Difference between Adjacent Fingertips (dR45) Predicts Upper-Body Tissue Distribution: Evidence for Early Gestational Programming. Am J Epidemiol 153: 338-344 [Abstract] [Full text]  
• Harding, J. (2001). The nutritional basis of the fetal origins of adult disease. Int J Epidemiol 30: 15-23 [Full text]  
• Yajnik, C. (2001). Commentary: Fetal origins of cardiovascular risk--nutritional and non-nutritional. Int J Epidemiol 30: 57-59 [Full text]  
• MURRAY, L. J., O'REILLY, D. P. J., BETTS, N., PATTERSON, C. C., SMITH, G. D., EVANS, A. E. (2000). Season and Outdoor Ambient Temperature: Effects on Birth Weight. Obstet Gynecol 96: 689-695 [Abstract] [Full text]  
• Symonds, M. E, Budge, H., Stephenson, T. (2000). Current topic: Limitations of models used to examine the influence of nutrition during pregnancy and adult disease. Arch. Dis. Child. 83: 215-219 [Full text]  
• Smith, J. T., Waddell, B. J. (2000). Increased Fetal Glucocorticoid Exposure Delays Puberty Onset in Postnatal Life. Endocrinology 141: 2422-2428 [Abstract] [Full text]  
• Steer, P. J (2000). Maternal hemoglobin concentration and birth weight. Am. J. Clin. Nutr. 71: 1285S-1287 [Abstract] [Full text]  
• Godfrey, K. M, Barker, D. J. (2000). Fetal nutrition and adult disease. Am. J. Clin. Nutr. 71: 1344S-1352 [Abstract] [Full text]  
• Huxley, R. R. (2000). NAUSEA AND VOMITING IN EARLY PREGNANCY: ITS ROLE IN PLACENTAL DEVELOPMENT. Obstet Gynecol 95: 779-782 [Abstract] [Full text]  
• Doyle, W., Crawford, M., Costeloe, K., Mathews, F., Yudkin, P., Neil, A. (2000). Maternal nutrition and birth weight. BMJ 320: 941a-941 [Full text]  
• Mathews, F., Yudkin, P., Neil, A. (1999). Influence of maternal nutrition on outcome of pregnancy: prospective cohort study. BMJ 319: 339-343 [Abstract] [Full text]  
• Wheeler, T., Evans, P.W., Anthony, F.W., Godfrey, K.M., Howe, D.T., Osmond, C. (1999). Relationship between maternal serum vascular endothelial growth factor concentration in early pregnancy and fetal and placental growth. Hum Reprod 14: 1619-1623 [Abstract] [Full text]  
• Godfrey, K. M., Matthews, N., Glazier, J., Jackson, A., Wilman, C., Sibley, C. P. (1998). Neutral Amino Acid Uptake by the Microvillous Plasma Membrane of the Human Placenta Is Inversely Related to Fetal Size at Birth in Normal Pregnancy. J. Clin. Endocrinol. Metab. 83: 3320-3326 [Abstract] [Full text]  
• Signorello, L. B., Trichopoulos, D. (1998). Perinatal determinants of adult cardiovascular disease and cancer. Scand J Public Health 26: 161-165 [Abstract]  
• Walker, B. R, McConnachie, A., Noon, J. P, Webb, D. J, Watt, G. C M (1998). Contribution of parental blood pressures to association between low birth weight and adult high blood pressure: cross sectional study. BMJ 316: 834-837 [Abstract] [Full text]  
• Falkner, B., Hulman, S., Kushner, H. (1998). Birth Weight Versus Childhood Growth as Determinants of Adult Blood Pressure. Hypertension 31: 145-150 [Abstract] [Full text]  
• Gardner, D. S., Jackson, A. A., Langley-Evans, S. C. (1997). Maintenance of Maternal Diet-Induced Hypertension in the Rat Is Dependent on Glucocorticoids. Hypertension 30: 1525-1530 [Abstract] [Full text]  
• Stanner, S A, Bulmer, K, Andres, C, Lantseva, O E, Borodina, V, Poteen, V V, Yudkin, J S (1997). Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study. BMJ 315: 1342-1348 [Abstract] [Full text]  
• Sayer, A A., Cooper, C, Barker, D J P (1997). Is lifespan determined in utero?. Arch. Dis. Child. Fetal Neonatal Ed. 77: 162F-164 [Full text]  
• Forsen, T, Eriksson, J G, Tuomilehto, J, Teramo, K, Osmond, C, Barker, D J P (1997). Mother's weight in pregnancy and coronary heart disease in a cohort of finnish men: follow up study. BMJ 315: 837-840 [Abstract] [Full text]  
• (1996). MATERNAL NUTRITION MIGHT AFFECT FETAL GROWTH. JWatch General 1996: 4-4 [Full text]