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ORIGINAL COMMUNICATION
Diet during pregnancy in relation to maternal weight
gain and birth size
P Lagiou
1,2
, RM Tamimi
2
, LA Mucci
2
, H-O Adami
2,3
, C-C Hsieh
2,4
and D Trichopoulos
1,2
*
1
Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Greece;
2
Department of Epidemiology, Harvard
School of Public Health, Boston, MA, USA;
3
Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden; and
4
University of Massachusetts Cancer Center, Worcester, MA, USA
Objective: Maternal weight gain has been consistently linked to birth weight but, beyond maternal energy intake, no
macronutrient has been associated with either of them. We have examined whether maternal energy-adjusted intake of
macronutrients is associated with either maternal weight gain or birth-size parameters.
Design: Cohort study.
Setting: University hospital in Boston, USA.
Subjects: A total of 224 pregnant women coming for their first routine prenatal visit. The women were followed through
delivery.
Interventions: None. Pregnant women’s dietary intake during the second trimester was ascertained at the 27th week of
pregnancy through a food frequency questionnaire.
Results: Intake of neither energy nor any of the energy-generating nutrients was significantly associated with birth size. In
contrast, maternal weight gain by the end of the second trimester of pregnancy was significantly associated with energy intake
( þ 0.9 kg/s.d. of intake; PB0.006) as well as energy-adjusted intake of protein ( þ 3.1 kg/s.d. of intake; Po10
-4
), lipids of animal
origin ( þ 2.6 kg/s.d. of intake; Po10
4
) and carbohydrates (5.2 kg/s.d. of intake; Po10
4
).
Conclusions: Although maternal weight gain is strongly associated with birth size, the indicated nutritional associations with
weight gain are not reflected in similar associations with birth-size parameters. The pattern is reminiscent of the sequence linking
diet to coronary heart disease (CHD) through cholesterol: diet has been conclusively linked to blood cholesterol levels and
cholesterol levels are conclusively linked to this disease, even though the association of diet with CHD has been inconclusive and
controversial.
Sponsorship: This study was supported in part by Grant No. CA54220 from the National Institutes of Health
European Journal of Clinical Nutrition (2004) 58, 231–237. doi:10.1038/sj.ejcn.1601771
Keywords: diet; pregnancy; birth weight; maternal weight gain
Introduction
Birth weight is an important correlate of neonatal and infant
health and has been recently associated with adult onset
diseases, including cardiovascular diseases (Rich-Edwards
et al, 1997), non-insulin dependent diabetes mellitus (Rich-
Edwards et al, 1999) and breast cancer (Potischman & Troisi,
1999). Several studies have examined sociodemographic,
reproductive and anthropometric factors in relation to birth-
size parameters. In particular, birth weight is higher among
offspring of women 17–35 y old in comparison to younger
and older women (Lee et al, 1988), among multiparae in
comparison to primiparae (Magnus et al, 1985) and among
women of higher rather than lower socioeconomic status
(Spencer et al, 1999). In contrast, smoking (England et al,
2001) and coffee consumption (Eskenazi et al, 1999) during
pregnancy have been linked to lower birth weight. Although
maternal weight gain has been consistently linked to birth
Received 5 February 2003; revised 20 March 2003;accepted 26 March
2003
*Correspondence: D Trichopoulos, Department of Epidemiology, Harvard
School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
E-mail: dtrichop@hsph.harvard.edu
Guarantor: D Trichopoulos.
Contributors: The study was executed by PL, RMT and LAM. The
original international study was conceived by H-OA, DT and CcH,
who also provided input in the analysis. All authors contributed to
the interpretation of the results and the preparation of the manu-
script.
European Journal of Clinical Nutrition (2004) 58, 231–237
&
2004 Nature Publishing Group All rights reserved 0954-3007/04 $
25.00
www.nature.com/ejcn
weight (Abrams & Selvin, 1995; Zhou & Olsen, 1997;
Thorsdottir & Birgisdottir, 1998; Shapiro et al, 2000; Lagiou
et al, 2003), the relation of energy-generating nutrients with
birth size after controlling for energy-intake has not been
adequately investigated. Indeed, the sequence from maternal
nutrition to maternal weight gain to birth weight is not
sustained by available data, except under extreme nutri-
tional deprivation (Susser, 1991). Notwithstanding findings
indicating that the consumption of marine omega-3 fatty
acids (Olsen, 1993) and monounsaturated lipids from olive
oil (Petridou et al, 1998) may be positively associated with
birth weight, the prevailing view is that qualitative aspects of
diet in developed countries are unlikely to be strongly
related to birth weight (Mathews et al, 1999).
We have examined the relation of the intake of energy and
energy-generating nutrients with maternal weight gain until
the 27th gestational week and with birth-size parameters in a
cohort of nonpre-eclamptic pregnant Caucasian women who
had singleton births after gestation lasting from 37 to 42
weeks, inclusive, in a major university hospital in Boston
USA from 1994 to 1995. We have restricted our study to this
group of women and newborns, because there would be too
few pre-eclamptic women or premature/overmature babies
to allow evaluation of possible subtle and complex interac-
tions. The hypothesis under investigation is that one or more
energy-generating nutrients may have differential effects on
birth weight, possibly mediated through differential effects
on maternal weight gain.
Materials and methods
Study subjects
The present investigation was undertaken using data from an
international prospective study on predictors of pregnancy
hormones among women in Boston, USA and Shanghai,
China (Lipworth et al, 1999). Since we have an inadequate
nutrient database for the Chinese diet at this time, we
present here data on dietary factors in relation to maternal
weight gain and birth-size variables for the US women only.
Between March 1994 and October 1995, 402 eligible
pregnant women were identified at the Beth Israel Hospital
in Boston. To be able to participate in the study, women had
to be Caucasian, less than 40-y old and have a parity of no
more than two. Women were not eligible if they had taken
any kind of hormonal medication during the index preg-
nancy, if they had a prior diagnosis of diabetes mellitus or
thyroid disease, or if the fetus had a known major anomaly.
A trained health professional met all pregnant women
coming for their first routine prenatal visit to the collaborat-
ing maternity clinic, ascertained whether the woman was
eligible to participate, explained to her the objectives of the
study and the requirements for participation, and obtained
informed consent. The procedures followed were in accor-
dance with the ethical standards for human experimentation
established by the Institutional Review Board at the Harvard
School of Public Health and Beth Israel Hospital.
Of 402 eligible women, 77 refused to participate, nine
were subsequently excluded because the index pregnancy
was terminated through a spontaneous or induced
abortion, two were excluded because of twin birth and
10 were lost to follow-up after the initial meeting. For
the present analysis, we excluded 23 women because they
had a pregnancy that lasted less than 37 or more than 42
weeks, 16 women because they had missing data for one or
more of the sociodemographic or reproductive factors
evaluated in this analysis and an additional 14 women
who developed pre-eclampsia. Of the remaining 251 women,
224 who had adequately completed the food frequency
questionnaire, so as to allow calculation of energy and
macronutrient intake, were eventually included in the
present study.
Information concerning the nondietary aspects of the
standard questionnaire administered and medical record
reviewing has been given in the earlier publication
(Lipworth et al, 1999). Dietary information was collected
through a semiquantitative food frequency questionnaire
covering an extensive list of foods and beverages, as well
as information on vitamin or multivitamin supplements.
This questionnaire was identical to the one used and
validated in the Nurses’ Health Study (Willett et al, 1985).
The questionnaire was mailed to the women 1 week prior
to their second routine visit to the maternity clinic,
which was around the 27th gestational week. It required
information on their dietary patterns during the second
trimester of pregnancy and it was checked for completeness
by trained interviewers during the women’s second visit.
Birth weight, height and head circumference were
measured at delivery by study collaborators, whereas mater-
nal weight gain was calculated as the difference between
weight measured at the 27th gestational week and prepreg-
nancy weight.
Statistical analysis
The statistical analyses were conducted using SAS Software
version 8.0 (SAS Institute, Cary, NC, USA). Following simple
cross-tabulations, the data were modeled through multiple
linear regression with dependent variables, alternatively,
birth weight, birth height, head circumference and maternal
weight gain until the 27th gestational age. Main exposure
variables were intake of energy and energy-generating
nutrients, and they were calculated from the dietary data
using the standard software used in the Nurses’ Health Study
(Romieu et al, 1990). Increments equal to 1 s.d. were used for
the nutritional variables to allow comparability among effect
estimates of these variables, which have different levels and
ranges of intake.
In studying the association of dietary intakes with
weight gain and pregnancy outcomes, several variables
with confounding potential were controlled for, namely
maternal age (categorically), maternal education (categori-
cally), parity (categorically), maternal height (continuously),
Diet, maternal weight gain and birth weight
P Lagiou et al
232
European Journal of Clinical Nutrition
prepregnancy body mass index (BMI) (continuously), preg-
ravid oral contraceptive (OC) use (categorically), smoking
during pregnancy (categorically), exact gestational age at
delivery (continuously) and gender of the baby (categori-
cally). Only six women reported alcohol intake and this
referred only to low frequencies and quantities; thus, alcohol
intake was not a possible confounder in these data. For all
women, gestational age at delivery was estimated as the
exact difference between the first day of last menstruation
and the date of delivery.
Results
Table 1 shows birth weight, length and head circumference
according to maternal characteristics and gender of off-
spring. Maternal characteristics were evaluated as possible
confounders of the association of energy and energy-
generating nutrients with birth-size characteristics. We
found positive associations of maternal height, prepreg-
nancy BMI, maternal weight gain and male gender with
birth-size parameters. Pregravid OC use was also positively
associated with birth-size parameters in this data set, whereas
Table 1 Birth weight, birth length and head circumference of babies born to 224 nonpre-eclamptic Caucasian women
a
in Boston USA (1994–1995)
after gestation lasting from 37 to 42 weeks, inclusive, according to maternal characteristics
Birth weight (g) Birth length (cm) Head circumference (cm)
Maternal characteristics N Mean (s.e.) N Mean (s.e.) N Mean (s.e.)
Maternal age (y)
18–24 5 3570 (1 6 0) 5 49.60 (1.54) 5 34.90 (0.29)
25–29 62 3478 (62) 62 50.19 (0.29) 62 34.35 (0.20)
30–34 138 3614 (39) 138 50.92 (0.20) 135 34.74 (0.15)
35+ 19 3489 (117) 19 50.15 (0.49) 19 34.11 (0.33)
Maternal education
High school graduate 36 3583 (77) 36 50.30 (0.42) 36 34.66 (0.24)
College graduate 92 3635 (48) 92 51.05 (0.24) 90 34.70 (0.16)
Higher 94 3490 (49) 94 50.32 (0.23) 93 34.46 (0.19)
Parity
1 138 3569 (40) 138 50.67 (0.20) 135 34.68 (0.13)
2 86 3558 (50) 86 50.56 (0.25) 86 34.44 (0.20)
Height (cm)
159 50 3473 (71) 50 50.26 (0.31) 50 34.18 (0.19)
160–164 53 3526 (71) 53 50.53 (0.28) 52 34.53 (0.20)
165–169 63 3599 (54) 63 50.70 (0.33) 62 34.70 (0.18)
170+ 56 3646 (58) 56 50.94 (0.32) 55 34.75 (0.30)
Prepregnancy BMI (kg/m
2
)
18 26 3468 (72) 26 50.30 (0.39) 26 34.07 (0.24)
19–21 109 3530 (45) 109 50.39 (0.23) 109 34.48 (0.18)
22–24 59 3681 (60) 59 51.41 (0.30) 59 35.01 (0.19)
25 30 3549 (102) 30 50.19 (0.41) 30 34.60 (0.27)
Weight gain up to 27th gestational week (kg)
7 42 3451 (66) 42 50.36 (0.33) 42 34.25 (0.22)
8–11 97 3514 (44) 97 50.50 (0.22) 96 34.46 (0.18)
12–14 34 3614 (67) 34 50.38 (0.38) 34 34.78 (0.28)
15+ 34 3787 (102) 34 51.49 (0.48) 32 35.28 (0.25)
Previous oral contraceptive use
Yes 172 3602 (37) 172 50.80 (0.18) 169 34.69 (0.13)
No 52 3438 (57) 52 50.00 (0.26) 52 34.23 (0.21)
Smoking in pregnancy
Yes 11 3555 (192) 11 49.55 (1.11) 11 33.82 (0.41)
No 211 3566 (32) 211 50.67 (0.15) 208 34.64 (0.11)
Gender of offspring
Male 114 3629 (40) 114 51.14 (0.22) 112 34.74 (0.17)
Female 110 3498 (48) 110 50.07 (0.21) 109 34.42 (0.14)
a
The numbers do not always add up because of missing values.
Diet, maternal weight gain and birth weight
P Lagiou et al
233
European Journal of Clinical Nutrition
no consistent effects were evident with respect to parity,
smoking during pregnancy, maternal age and educational
level.
In Table 2, pregnant women were distributed in quartiles
by intakes, alternatively, of energy, animal lipids, vegetable
lipids, carbohydrates and protein. Subsequently, we calcu-
lated mean differences (and standard errors) in birth weight,
birth length and head circumference between the first
quartile, taken as referent, and each of the subsequent
quartiles. Univariate regression-derived P-values for trend by
quartile groups were obtained. With respect to birth weight
and birth length, no substantial or significant trend with
intake of either energy or any of the energy-generating
nutrients was observed. In contrast, positive associations
were apparent between head circumference and intake of
either energy or any of the energy-generating nutrients. The
associations were significant with respect to intake of energy
or protein, but they were irregular and suggestive of possible
threshold effects. Interpretation of the apparent associations
and their irregularities is hindered by the fact that intake of
energy and energy-generating nutrients are highly corre-
lated.
In Table 3, the association of maternal intake of energy
and energy-generating nutrients with birth-size parameters is
examined. After adjustment for the possible confounders
indicated in Table 1, neither energy intake nor intake of any
of the energy-generating nutrients (after adjustment for
energy intake) was associated with any of the birth-size
parameters examined.
For Table 4, complete data for 207 pairs of mothers and
newborn were available, but their distributions by the
variables indicated in Table 1 were similar to the distribu-
tions given in Table 1. Again, pregnant women were
distributed in quartiles by intakes, alternatively, of energy,
animal lipids, vegetable lipids, carbohydrates and protein.
Subsequently, mean differences (and standard errors) in
maternal weight gain between the first quartile, taken as
referent, and each of the subsequent quartiles were calcu-
lated. Univariate regression-derived P-values for trend by
quartile groups were obtained. With the exception of
carbohydrates, significant positive associations with weight
gain were evident, but the possibility of confounding, either
mutual among the nutritional factors or by the nonnutri-
tional factors indicated in Table 1, cannot be excluded.
Table 5 shows the association of maternal intake of energy
and energy-generating nutrients with maternal weight gain.
After adjustment for the possible confounders indicated in
the footnote of the table, energy intake and energy-adjusted
intake of animal lipids and protein were significantly
positively associated with maternal weight gain, whereas a
significant inverse association was evident with respect to
carbohydrates. In an alternative model, we introduced
simultaneously the four energy-generating nutrients, but
we excluded energy intake to avoid collinearity. The
association of maternal weight gain with intake of carbohy-
drates (inverse) and with animal lipids and protein (positive)
persisted, although the partial regression coefficients were all
reduced (in absolute terms).
Table 2 Mean change and standard error (s.e.) in birth weight, birth length and head circumference by quartile
a
of intake of energy and energy-
generating nutrients
Q2 Q3 Q4
Q1 Mean change s.e. Mean change s.e. Mean change s.e. P-value trend
Birth weight(g)
Energy REF +149.0 87.9 17.1 87.9 +165.1 87.9 0.24
Animal lipids REF +132.3 88.4 4.9 88.4 +131.3 88.4 0.36
Vegetable lipids REF +65.1 88.9 4.2 88.9 +105.4 88.9 0.38
Carbohydrates REF +181.4 88.2 +51.3 88.2 +160.6 88.2 0.21
Protein REF +11.1 89.0 +79.7 89.0 +88.3 89.0 0.24
Birth length (cm)
Energy REF +0.15 0.44 0.40 0.44 +0.54 0.44 0.45
Animal lipids REF 0.01 0.44 0.46 0.44 +0.22 0.44 0.87
Vegetable lipids REF 0.20 0.44 0.11 0.44 +0.17 0.44 0.66
Carbohydrates REF +0.24 0.44 +0.16 0.44 +0.30 0.44 0.56
Protein REF 0.66 0.44 0.47 0.44 +0.26 0.44 0.49
Head circumference (cm)
Energy REF +0.53 0.31 +0.14 0.31 +0.92 0.31 0.02
Animal lipids REF +0.73 0.31 +0.33 0.31 +0.68 0.31 0.10
Vegetable lipids REF +0.10 0.32 0.03 0.32 +0.48 0.31 0.18
Carbohydrates REF +0.75 0.31 +0.47 0.31 +0.71 0.31 0.06
Protein REF +0.05 0.31 +0.31 0.31 +0.67 0.31 0.02
a
The 25th, 50th and 75th centiles were for energy 6386, 8345 and 10146 kJ, for animal lipids 27.4, 35.1 and 47.2 g, for vegetable lipids 16.9, 22.8 and 29.6 g, for
carbohydrates 208.2, 271.8 and 345.5 g and for protein 67.2, 86.3, and 113.4 g, respectively.
Data from 224 nonpre-eclamptic pregnancies lasting from 37 to 42 weeks, inclusive, in Boston USA, 1994–1995.
Diet, maternal weight gain and birth weight
P Lagiou et al
234
European Journal of Clinical Nutrition
Discussion
In an earlier paper (Lagiou et al, in press), examining non-
nutritional factors in relation to birth weight, we found, as
others have (Abrams & Selvin, 1995; Zhou & Olsen, 1997;
Thorsdottir & Birgisdottir, 1998; Shapiro et al, 2000), that
maternal weight gain is positively associated with birth
weight. Among Caucasian women, an increase in maternal
weight gain by 2 kg was associated with an increase of 37.1 g
(standard error 13.2 g) in birth weight, after adjustment for
possible confounding variables (Lagiou et al, in press). In the
present paper, we found that neither energy intake nor the
energy-adjusted intake of any of the energy-generating
nutrients, as ascertained at the end of the second trimester
of pregnancy, is significantly associated with any of the
studied birth-size parameters after adjustment for confound-
ing variables. In contrast, energy intake was significantly
positively associated with maternal weight gain through the
end of the second trimester of pregnancy and, after
controlling for energy intake, protein and lipids of animal
origin were also significantly positively associated with
Table 3 Partial regression coefficients showing changes in birth weight (g), birth length (cm) and head circumference (cm) per increments of one
standard deviation (s.d.)
a
of intake of energy and energy generating nutrients
b
Birth weight
change (g)
c
s.e. P-value
Adjusted birth weight
change (g)
d
s.e. P-value
Energy (per s.d.) +51.2 31.3 0.10 +7.8 28.8 0.79
Animal lipids (per s.d.) +6.5 48.3 0.89 +24.8 44. 5 0.58
Vegetable lipids (per s.d.) +55.1 46.7 0.24 6.9 42.2 0.87
Carbohydrates (per s.d.) 42.1 83.6 0.62 38.6 77.0 0.62
Protein (per s.d.) +3.5 68.8 0.96 +32.2 62.7 0.61
Birth length
change (cm)
c
s.e. P-value
Adjusted birth length
change (cm)
d
s.e. P-value
Energy (per s.d.) +0.15 0.16 0.34 0.06 0.14 0.66
Animal lipids (per s.d.) 0.002 0.24 0.99 +0.16 0.22 0.46
Vegetable lipids (per s.d.) +0.08 0.23 0.74 0.22 0.21 0.30
Carbohydrates (per s.d.) 0.11 0.42 0.79 0.20 0.38 0.61
Protein (per s.d.) +0.16 0.34 0.65 +0.32 0.31 0.31
Head circumference
change (cm)
c
s.e. P-value
Adjusted head circumference
change (cm)
d
s.e. P-value
Energy (per s.d.) +0.29 0.11 0.01 +0.15 0.11 0.16
Animal lipids (per s.d.) +0.01 0.17 0.95 +0.07 0.16 0.65
Vegetable lipids (per s.d.) +0.12 0.16 0.45 0.04 0.15 0.79
Carbohydrates (per s.d.) 0.13 0.29 0.65 0.16 0.28 0.56
Protein (per s.d.) +0.05 0.24 0.84 +0.16 0.23 0.47
a
s.d. for energy 3371.9 kJ/day, for animal lipids 19.6 g/day, for vegetable lipids 10.8 g/day, for carbohydrates 127.3 g/day and for protein 40.7 g/day
b
Total of 224 singleton, nonpre-eclamptic pregnancies, lasting from 37 to 42 weeks inclusive. Boston, USA, 1994–1995.
c
Adjusted for energy intake only (except for energy).
d
Adjusted for energy intake (except for energy), maternal age, maternal education, parity, maternal height, prepregnancy BMI, pregravid OC use, smoking during
pregnancy, exact gestational age at delivery and gender of the baby.
Table 4 Mean change and s.e. in maternal weight gain by quartile of intake of energy and energy-generating nutrients
Weight gain (kg)
Q2 Q3 Q4
Q1 Mean change s.e. Mean change s.e. Mean change s.e. P-value trend
Energy REF +0.79 0.97 0.12 0.95 +2.46 0.96 0.04
Animal lipids REF 0.18 0.96 +0.29 0.95 +2.82 0.94 0.003
Vegetable lipids REF 0.00 0.96 0.17 0.96 +2.80 0.96 0.007
Carbohydrates REF +0.62 0.98 0.007 0.98 +1.03 0.96 0.40
Protein REF 0.14 0.96 +0.51 0.98 +1.90 0.95 0.03
Data from 207 nonpre-eclamptic pregnancies lasting from 37 to 42 weeks, inclusive, in Boston USA, 1994–1995.
Diet, maternal weight gain and birth weight
P Lagiou et al
235
European Journal of Clinical Nutrition
maternal weight gain, whereas carbohydrates were signifi-
cantly inversely associated with it.
The strong associations between four of the five studied
nutritional variables and maternal weight gain, in combina-
tion with the strong positive association of the latter variable
with birth weight (and, indeed, birth length and birth head
circumferenceFTable 1) would have led to the prediction of
significant associations between the nutritional variables
and birth-size parameters. The absence of such associations is
intriguing. There is a biological precedent, however,
although in a different time scale. The relation of diet to
coronary heart disease (CHD) has been weak in most
epidemiological investigations, even though cholesterol
levels (both high- and low-density lipoprotein cholesterol)
are powerful predictors of CHD and are clearly associated
with diet (Willett, 1998). It appears that the effects of
nutritional variables are diluted by those of other determi-
nants of birth-size parameters, so that they might only be
detected in very large studies. Nevertheless, such effects are
likely to exist and, if they are dose-dependent and exposures
are extreme, they could even have physiological implica-
tions.
There have been earlier studies indicating that maternal
protein intake is positively associated with pregnancy weight
gain (Scholl et al, 1991; Kramer, 2000a) with birth weight
(Weigel et al, 1991; Godfrey et al, 1997) or both (Kramer,
2000b). Other studies indicate that maternal intake of fat
(Weigel et al, 1991) and carbohydrates (Godfrey et al, 1997)
is, respectively, positively and inversely associated with birth
weight. A study in rats showed that protein intake during
pregnancy is positively associated with pregnancy weight
gain and birth weight (Levy & Jackson, 1993). Finally, there
have been many reports indicating that overt malnutrition
and reduction in maternal energy intake are associated with
reduced pregnancy weight gain and birth weight (Susser,
1991; Alexy et al, 1997; Bergmann et al, 1997; Rondo &
Tomkins, 1999; Rush, 2001). Thus, the existing collective
evidence is not incompatible with our findings, which,
however, present a more integrated perspective.
Among the advantages of our study are its prospective
nature and its reliance on a validated food frequency
questionnaire. Weaknesses of the study include the moderate
size and the focus on pregnancy weight gain during the first
two trimesters. However, several reports have indicated that
maternal weight gain in the first and second trimester may
be stronger determinants of newborn size than weight gain
in the third trimester of pregnancy (Abrams & Selvin, 1995;
Brown et al, 2002; Guihard-Costa et al, 2002). In any case,
even if weight gain during the third trimester has its own
determinants and consequences, this does not affect the
findings of the present study. Prepregnancy weight was self-
reported, but there is evidence in the literature (Yu & Nagey,
1992) that self-reported prepregnancy weight is highly
correlated (rB0.9) with the objective measurement. A high
proportion of women were excluded, but most of these
exclusions were imposed by technical or administrative
reasons that were unlikely to have introduced selection bias.
The study group was not representative of the American
population, but representativeness is not a prerequisite for
validity in prospective cohort studies, the strength of which
stems from the lack of association between errors in exposure
and outcome ascertainment.
In conclusion, we have found evidence that, after adjust-
ment for energy intake, intake of protein and lipids of
animal origin is positively associated with weight gain
through the end of the second trimester of pregnancy,
whereas intake of carbohydrates is inversely associated with
it. Although weight gain is strongly associated with birth-size
parameters, the indicated nutritional associations are not
reflected in similar associations with birth-size variables. The
pattern is reminiscent of the sequence linking diet to CHD
through cholesterol and may be explained by the operation
of non-nutritional determinants of birth size.
References
Abrams B & Selvin S (1995): Maternal weight gain pattern and birth
weight. Obstet. Gynecol. 86,163–169.
Alexy B, Nichols B, Heverly MA & Garzon L (1997): Prenatal factors
and birth outcomes in the public health service: a rural/urban
comparison. Res. Nurs. Health 20, 61–70.
Bergmann MM, Flagg EW, Miracle-McMahill HL & Boeing H (1997):
Energy intake and net weight gain in pregnant women according
Table 5 Partial regression coefficients showing changes in maternal weight gain (kg) by the 27th gestational week per increments of 1 s.d. of intake of
energy and energy-generating nutrients
a
Weight gain
change
b
(kg) s.e. P-value trend
Adjusted weight gain
change
c
(kg) s.e. P-value trend
Energy (per s.d.) +1.29 0.33 0.0001 +0.91 0.33 0.006
Animal lipids (per s.d.) +3.01 0.46 o0.0001 +2.56 0.47 o0.0001
Vegetable lipids (per s.d.) +1.02 0.49 0.04 +0.77 0.48 0.11
Carbohydrates (per s.d.) 5.94 0.77 o0.0001 5.22 0.80 o0.0001
Protein (per s.d.) +3.58 0.72 o0.0001 +3.11 0.71 o0.0001
a
A total of 207 singleton, nonpre-eclamptic pregnancies, lasting from 37 to 42 weeks inclusive. Boston, USA, 1994–1995.
b
Adjusted for energy intake only (except for energy).
c
Adjusted for energy intake (except for energy), maternal age, maternal education, parity, maternal height, prepregnancy BMI, pregravid OC use, smoking during
pregnancy, exact gestational age at delivery and gender of the baby.
Diet, maternal weight gain and birth weight
P Lagiou et al
236
European Journal of Clinical Nutrition
to body mass index (BMI) status. Int. J. Obes. Relat. Metab. Disord.
21,1010–1017.
Brown JE, Murtaugh MA, Jacobs Jr DR & Margellos HC. (2002):
Variation in newborn size according to pregnancy weight change
by trimester. Am. J. Clin. Nutr. 76, 205–209.
England LJ, Kendrick JS, Wilson HG, Merritt RK, Gargiullo PM &
Zahniser SC (2001): Effects of smoking reduction during preg-
nancy on the birth weight of term infants. Am. J. Epidemiol. 154,
694–701.
Eskenazi B, Stapleton AL, Kharrazi M & Chee WY (1999): Associa-
tions between maternal decaffeinated and caffeinated coffee
consumption and fetal growth and gestational duration. Epide-
miology 10, 242–249.
Godfrey KM, Barker DJ, Robinson S & Osmond C (1997): Maternal
birthweight and diet in pregnancy in relation to the infant’s
thinness at birth. Br. J. Obstet. Gynaecol. 104, 663–667.
Guihard-Costa AM, Papiernik E, Grange G & Richard A (2002):
Gender differences in neonatal subcutaneous fat store in late
gestation in relation to maternal weight gain. Ann. Hum. Biol. 29,
26–36.
Kramer MS (2000a): High Protein Supplementation in Pregnancy.
Cochrane Database Syst Rev, Vol. 2, CD000105.
Kramer MS (2000b): Balanced Protein/Energy Supplementation in
Pregnancy. Cochrane Database Syst Rev, Vol. 2, CD000032.
Lagiou P, Hsieh CC, Trichopoulos D, Xu B, Wuu J, Mucci L, Tamimi R,
Adami HO & Cnattingius S (2003): Birth weight differences
between USA and China and their relevance to breast cancer
etiology. Int. J. Epidemiol. 32, 193–198.
Lee KS, Ferguson RM, Corpuz M & Gartner LM (1988): Maternal age
and incidence of low birth weight at term: a population study. Am.
J. Obstet. Gynecol. 158, 84–89.
Levy L & Jackson AA (1993): Modest restriction of dietary protein
during pregnancy in the rat: fetal and placental growth. J. Dev.
Physiol. 19, 113–118.
Lipworth L, Hsieh Cc, Wide L, Ekbom A, Yu SZ, Yu GP, Xu B,
Hellerstein S, Carlstrom K, Trichopoulos D & Adami HO (1999):
Maternal pregnancy hormone levels in an area with a high
incidence (Boston, USA) and in an area with a low incidence
(Shanghai, China) of breast cancer. Br. J. Cancer. 79, 7–12.
Magnus P, Berg K & Bjerkedal T (1985): The association of parity and
birth weight: testing the sensitization hypothesis. Early Hum. Dev.
12, 49–54.
Mathews F, Yudkin P & Neil A (1999): Influence of maternal nutrition
on outcome of pregnancy: prospective cohort study. BMJ 319,
339–343.
Olsen SF (1993): Consumption of marine n-3 fatty acids during
pregnancy as a possible determinant of birth weight. A review
of the current epidemiologic evidence. Epidemiol. Rev. 15,
399–413.
Petridou E, Stoikidou M, Diamantopoulou M, Mera E, Dessypris N &
Trichopoulos D (1998): Diet during pregnancy in relation to
birthweight in healthy singletons. Child Care Health Dev. 24,
229–242.
Potischman N & Troisi R (1999): In-utero and early life exposures
in relation to risk of breast cancer. Cancer Causes Control 10,
561–573.
Rich-Edwards JW, Stampfer MJ, Manson JE, Rosner B, Hankinson SE,
Colditz GA, Willett WC & Hennekens CH (1997): Birth weight and
risk of cardiovascular disease in a cohort of women followed up
since 1976. BMJ 315, 396–400.
Rich-Edwards JW, Colditz GA, Stampfer MJ, Willett WC, Gillman
MW, Hennekens CH, Speizer FE & Manson JE (1999): Birthweight
and the risk for type 2 diabetes mellitus in adult women. Ann.
Intern. Med. 130, 278–284.
Romieu I, Stampfer MJ, Stryker WS, Hernandez M, Kaplan L, Sober A,
Rosner B & Willett WC (1990): Food predictors of plasma beta-
carotene and alpha-tocopherol: validation of a food frequency
questionnaire. Am. J. Epidemiol. 131, 864–876.
Rondo PH & Tomkins AM (1999): Maternal and neonatal anthro-
pometry. Ann. Trop. Paediatr. 19,349–356.
Rush D (2001): Maternal nutrition and perinatal survival. Nutr. Rev.
59, 315–326.
Scholl TO, Hediger ML, Khoo CS, Healey MF & Rawson NL (1991):
Maternal weight gain, diet and infant birth weight: correla-
tions during adolescent pregnancy. J. Clin. Epidemiol. 44,
423–428.
Shapiro C, Sutija VG & Bush J (2000): Effect of maternal weight gain
on infant birth weight. J. Perinat. Med. 28, 428–431.
Spencer N, Bambang S, Logan S & Gill L (1999): Socioeconomic
status and birth weight: comparison of an area-based measure
with the Registrar General’s social class. J. Epidemiol. Commun.
Health 53, 495–498.
Susser M (1991): Maternal weight gain, infant birth weight, and diet:
causal sequences. Am. J. Clin. Nutr. 53, 1384–1396.
Thorsdottir I & Birgisdottir BE (1998): Different weight gain in
women of normal weight before pregnancy: postpartum weight
and birth weight. Obstet. Gynecol. 92, 377–383.
Weigel MM, Narvaez WM, Lopez A, Felix C & Lopez P (1991):
Prenatal diet, nutrient intake and pregnancy outcome in urban
Ecuadorian primiparas. Arch. Latinoam. Nutr. 41, 21–37.
Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J,
Hennekens CH & Speizer FE (1985): Reproducibility and validity of
a semiquantitative food frequency questionnaire. Am. J. Epidemiol.
122, 51–65.
Willett W. (1998): Diet and coronary heart disease. In Nutritional
Epidemiology, W Willett (ed). 2nd Edition, pp 414–466. New York:
Oxford University Press, 1998.
Yu SM & Nagey DA. (1992): Validity of self-reported pregravid
weight. Ann. Epidemiol. 2: 715–721.
Zhou W & Olsen J (1997): Gestational weight gain as a predictor of
birth and placenta weight according to pre-pregnancy body mass
index. Acta. Obstet. Gynecol. Scand. 76, 300–307.
Diet, maternal weight gain and birth weight
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