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Fiona Mathews Division of Public Health and Primary Health Care,
Institute of Health Sciences, University of Oxford, PO Box 777, Oxford
OX3 7LF
Correspondence to: F Mathews Department of Zoology, University
of Oxford, Oxford OX1 3PS fmathews{at}ermine.ox.ac.uk
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Abstract |
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Objective:
To investigate the relations of maternal
diet and smoking during pregnancy to placental and birth weights at term.
Design:
Prospective cohort study.
Setting:
District general hospital in the south of England.
Participants:
693 pregnant nulliparous white women
with singleton pregnancies who were selected from antenatal booking clinics with stratified random sampling.
Main outcome measures:
Birth and placental weights at term.
Results:
Placental and birth weights were unrelated to the intake of any macronutrient. Early in pregnancy, vitamin C was
the only micronutrient independently associated with birth weight after
adjustment for maternal height and smoking. Each ln mg increase in
vitamin C was associated with a 50.8 g (95% confidence interval
4.6 g to 97.0 g) increase in birth weight. Vitamin C, vitamin E, and
folate were each associated with placental weight after adjustment for
maternal characteristics. In simultaneous regression, however, vitamin
C was the only nutrient predictive of placental weight: each ln mg
increase in vitamin C was associated with a 3.2% (0.4 to 6.1) rise in
placental weight. No nutrient late in pregnancy was associated with
either placental or birth weight.
Conclusions:
Concern over the impact of maternal
nutrition on the health of the infant has been premature. Maternal
nutrition, at least in industrialised populations, seems to have only a
small effect on placental and birth weights. Other possible
determinants of fetal and placental growth should be investigated.
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Key messages
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Introduction |
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Barker and colleagues have shown strong associations between infant and placental size and the risk of later chronic disease, such as cardiovascular disease and diabetes. 1 2 On the basis of data from animal studies and cross country comparisons, poor maternal nutrition has been implicated as one of the key "adverse environmental influences in utero," which could lead to compromised fetal and placental growth and adverse long term consequences.1 Their observational studies of British women also suggest that maternal diet is an important determinant of infant and placental size.3-5 The "Barker hypothesis" has led to calls for improvements in maternal diet, which have generated some concern among obstetricians.6
Although there is widespread recognition of the importance of adequate
maternal nutrition during pregnancy in developing countries, there is
considerable uncertainty about its role in industrialised countries,
where profound malnutrition is uncommon. Even near starvation, such as
occurred during the "Dutch hunger winter," reduced mean birth
weight by only 300 g.7 The evidence from adequately
nourished populations is conflicting. Observational studies have found
only weak and inconsistent associations between intake of
macronutrients and infant size,
3 5 8 9
and few data are
available for micronutrients.9-11 In supplementation trials, micronutrients have not been shown to have important impact on
mean birth or placental weights.10-13 Protein and energy
supplementation have produced both increases and decreases in birth
weight, with high density protein supplements seeming to reduce birth
weight.
14 15
The results of such trials are difficult to
generalise, however, as intakes are often increased well beyond normal
levels. In addition, trials are usually designed to detect changes in
adverse outcomes of pregnancy rather than in birth weights within the
normal range. We therefore conducted a large scale observational study
in an attempt to elucidate the role of maternal nutrition in pregnancy. We set out to detect differences in birth weight between women with
high and low intakes of nutrients early in pregnancy.2
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Participants and methods |
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Full details of the survey methods are reported elsewhere.16 Briefly, healthy white nulliparous women attending antenatal clinics in Portsmouth between May 1994 and February 1996 were stratified by smoking status, and simple random selection was carried out within each stratum (details on request). Of the 1002 women invited to participate, 963 were recruited. The sampling procedure resulted in the prevalence of smoking among respondents being similar to nationally representative samples of pregnant women. 17 18
Sample size
To detect a 150 g difference in mean birth weight (SD 500 g)
between the two extreme thirds of nutrient intake (two sided
=0.05,
power=90%) required a sample of 750 women. The expected difference was
based on the results of a pilot study. To allow for non-completion of
the food diary we aimed to recruit 1000 women.
Data collection
Structured interviews were conducted by trained researchers during
visits to antenatal clinics. Social class was based on the woman's
most recent occupation.19 Height, weight, blood pressure,
and blood count were as measured routinely. Women were classified as
smokers if they reported smoking or if their serum cotinine
concentration was greater than 14 ng/ml.
20 21
Statistical analysis
Over the ranges studied, placental and birth weights showed linear
relations with gestational age and were also associated with sex. For
clarity, and for comparison with other studies,3-5
individual measurements were adjusted to the mean gestational age and
sex of the cohort. All subsequent analyses used these adjusted values.
2 tests. Tests of significance were
two tailed. The sociodemographic variables considered were smoking
status; cigarettes smoked in day before interview (0 and approximately
equal groups: 1-8; 9-16;
17); maternal age at booking (days);
reported weight before conception (kg); maternal weight (kg) at
booking; maternal height (m); body mass index (kg/m2)
before conception; body mass index at booking; diastolic blood pressure
at booking; haemoglobin concentration at booking (g/dl); social class
in three groups (I and II; III non-manual and III manual; IV and V);
and education in three groups (higher than O level (>GCSE); O level
(GCSE grades A-C); and less than O level (GCSE grades D and E)).
The fit of multiple linear regression models was ascertained by
examination of residuals. Placental weights were ln transformed to
satisfy the assumptions of normality; total intakes of all micronutrients were ln transformed to reduce the leverage of outlying values. Transformation did not materially affect the results. Maternal
variables were considered for inclusion if they were significantly
(P<0.05) associated with nutrient intake or pregnancy outcome in
univariate analysis or if this association had been reported elsewhere.
Each model was built by using a combination of forced entry and forward
stepwise procedures (criterion for entry was P<0.05 and for removal
P>0.10).
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Results |
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Of the 963 women recruited, 917 had live singleton deliveries in Portsmouth. Food diaries were completed by 739 (80.6%) of these women ("respondents"). To permit comparisons with the results of Godfrey et al 4 5 the 46 respondents who delivered before 259 days' gestation were excluded. The results obtained from the entire cohort did not differ from those presented for term deliveries, and no nutrient was associated with preterm delivery.21
Table 1 shows the characteristics of the 693 mothers and babies. The nulliparous women in our cohort were sociodemographically similar to those studied by Godfrey et al 4 5 and their social class distribution was comparable with a nationally representative sample of mothers.26
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Table 2 shows nutrient intakes (from food and supplements) in early and later pregnancy. Nutrient intakes from
food alone as well as totals including supplements are shown for iron
and folate as supplements made a substantial contribution to intakes
for these nutrients.
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In
univariate analyses maternal height, weight before conception, weight
at booking, self reported smoking status, and smoking status validated
by cotinine measurements were all predictive of birth weight
(P<0.001). In multiple regression, however, the only independent
predictors of birth weight were smoking status validated by cotinine
measurement (P<0.001) and maternal height (P<0.001). Smoking
predicted a 104 g (95% confidence interval 47 g to 161 g)
decrease in birth weight, and each 10 cm of additional height
predicted a 172 g (129 g to 215 g) increase in birth weight. In
univariate analyses placental weight was associated with maternal
height (P=0.033), weight before pregnancy (P=0.002) and weight at
booking (P=0.001) but with no other maternal characteristics. In
multiple regression maternal height was the only independent predictor
of placental weight (P<0.001), with each 10 cm of additional height
predicting a 5% (2% to 8%) increase in placental weight.
Nutrient intakes in early pregnancy and birth weights
Birth
weight was positively associated with intakes of vitamin C, vitamin E,
and total folate but with no other nutrient (table 3). After adjustment
for maternal smoking and height, birth weight remained associated only
with vitamin C (P=0.031). There was no interaction between smoking and
vitamin C intake. These findings were unaltered by simultaneous
adjustment for energy intake.
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Placental weight was positively associated with vitamin
C, vitamin E, and total folate (table 4) and remained so after
adjustment for maternal height. Simultaneous adjustment for energy
intake did not alter these relations. As intakes of vitamin C, vitamin
E, and folate were correlated, the independent effect of each nutrient
was investigated. After adjustment for vitamin C intake no other
nutrient independently predicted placental weight.
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The 624 respondents to the food frequency questionnaire
were similar to the whole cohort in their nutritional intakes early in
pregnancy, placental and infant weights, and associations between early
pregnancy nutrition and outcome. No nutrient in late pregnancy was
significantly associated with any outcome, and this remained true after
adjustment for other maternal factors.
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Discussion |
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In this large and detailed study we found no clinically important effects of maternal nutrition on the placental or birth weight of infants born at term. Dietary intake and smoking status were measured as accurately as possible, and account was taken of maternal characteristics that might confound associations between dietary intake and infant size. The inclusion of only nulliparous women also removed the possible confounding effect of parity.
Vitamin C, but no other nutrient, was positively related to birth weight, with about a 100 g difference between the lowest and highest thirds of intake. The significance of this relation, however, was considerably reduced after adjustment for smoking and maternal height. Vitamin C showed some association with placental weight, but again this relation was weaker after adjustment for maternal height. As in previous research, there was no association between any nutrient in later pregnancy and placental or birth weights. 3 4 9
Comparison with Barker's data
Our findings differ from those of Barker and colleagues, who
studied a cohort with similar social class and age distributions. In
early pregnancy, Godfrey et al found significant negative relations
between energy intake and placental and birth weights.4
These relations were largely due to strong associations between the
outcomes and carbohydrate intakes. It is notable that the median values
and the variability of all nutrient intakes, particularly carbohydrate
and energy, were much higher than in our study. For example, the median
intakes of energy and carbohydrate were 9.8 MJ (2346 kcals) and 303 g,
respectively4 compared with 8.5 MJ (2044 kcals) and 256 g
in our cohort. The interquartile ranges for carbohydrate and energy
consumption were about two thirds greater (125 g v
74.5 g and 3.8 MJ v 2.3 MJ, respectively). This
increased variability resulted mainly from an extended right hand tail
in the distribution of intakes.
a 7 day food diary
suffers less measurement error
than food frequency methods.23-25 It is notable that both
the median values and variability in nutrient intakes in our study with
food diaries were similar to those obtained by Barker's group when
their subjects completed a 4 day food diary; their data, however, were
not analysed in relation to outcome measures.27 Further,
the variability in our data was almost the same as that for women in
the national dietary and nutritional survey of British adults (7 day
weighed diary).28
In later pregnancy we, like Godfrey et al, used a food frequency
questionnaire. In neither study was any individual nutrient found to
predict pregnancy outcome. Godfrey et al, however, found that low
intake of meat protein later in pregnancy, in conjunction with high
carbohydrate early in pregnancy, was associated with reduced birth and
placental weights.4 This observation contrasts with their
earlier report that diets with a high proportion of energy from animal
protein were associated with reduced birth weight.3 In our
study, combinations of nutrients were not investigated, given the lack
of main effects for carbohydrate, protein, and total energy; the high
correlation between carbohydrate and protein intakes (0.62 in diary and
0.72 in food frequency questionnaire); and the likelihood of
"positive" findings due to multiple significance testing.
Maternal malnutrition may be an important determinant of fetal growth
in developing countries. Our work suggests that among the reasonably
well nourished women of industrialised countries, however, maternal
diet in pregnancy has, at most, a small impact on placental and birth
weights. We are currently analysing stored serum samples from our
cohort to help to clarify the relation of maternal nutrition to the
outcome of pregnancy.
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Acknowledgments |
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We thank Dr R Smith for performing the cotinine analyses; Mr J Bevan and colleagues for permission to include their patients in the study; the midwifery and support staff at St Mary's Hospital Portsmouth for their assistance; Mrs L Willis and Mrs L McRoberts for help in data collection and management; Dr T Key and colleagues for permission to base the food diary and the food frequency questionnaire on those used in the EPIC study; Mr R Fraser for helpful comments; and all the women who participated in the research.
Contributors: FM was the principal investigator. She designed the study, obtained funding, supervised research staff, collected data from pregnant women, measured infants, coded and entered food diaries, performed statistical analyses, and prepared the paper for publication. PY was involved in design of the study and had a major input to the statistical analysis, interpretation of results, and writing of the paper. AN participated in designing the study, obtaining funding, and supervision of the project and contributed to interpretation of the results and preparation of the paper. FM is the guarantor.
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Footnotes |
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Funding: The Sir Jules Thorn Charitable Trust and Oxford University Medical Research Fund.
Competing interests: None declared.
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References |
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| 2. | Barker DJP, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341: 938-941[Medline]. |
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(Accepted 25 May 1999)
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