Nutritional supplementation and the outcome of pregnancy. I. Birth weight 1 - 3 J. O. Mora, B. de Paredes, M. Wagner, L. de Navarro, J. Suescun, N. Christiansen, and M. G. Herrera 4
ABSTRACT Colombian women at risk of malnutrition were enrolled in a health care program and randomly assigned to supplementation and control groups at the beginning of the third trimester of pregnancy. The net dietary intake increments resulting from supplementation amounted to 155 cal and 20 g of protein per day. Supplementation had a significant effect on the mean birth weight of male infants, but not that of female infants; the mechanisms responsible for the sex differences remain to be elucidated. The randomized trial design of the experiment and the documented similarity between the experimental and control groups at the onset permit the conclusion that the observed differences were caused by the food supplementation program. The effect of snpplementation on maternal weight gain and the association of the laller with birth weight strongly suggest that improved maternal nutrition mediated the effect on birth weight. Am. J. Cfin. Nutr. 32: 455-462, 1979.
The relationship of maternal nutrition to human fetal growth and development has been the subject of several recent reviews (1-3); it remains controversial. In animals maternal malnourishment significantly affects offspring size, survival rates, and subsequent growth and behavior. However, the dietary restrictions used in these experiments was greater than is commonly seen in humans and, in addition, species differences preclude extrapolation of these fmdings to man. In humans birth weight has been used as an index of fetal development and newborn well-being. Acute and severe maternal malnourishment of limited duration during wartime has been found associated with reduced birth weight. Provision of adequate diets during the last trimester compensated for nutritional deprivation earlier in pregnancy (4-7). Other studies have confirmed the correlation of severe maternal malnutrition with diminished birth weight; the latter, in turn, appears to be associated with perinatal mortality, neurological disorders, impaired physical growth, mental retardation, and poor school performance (8-10). The effect of chronic moderate maternal malnutrition is less clear (11-13). Problems arise in the evaluation ofnutritional status during pregnancy and in controlling for other environmental factors associated
with malnutrition which may affect fetal growth. There is a significant association between maternal weight gain during pregnancy and birth weight (14-16). However, associations between birth weight and variables such as prepregnancy weight, age, height, and panty of mother suggest that fetal growth and development is also influenced by prepregnancy factors (1, 2, 7, 18). Dietary supplementation during pregnancy has yielded contradictory results due in part to the problems encountered in selection of 'From the Department of Nutrition, Harvard School of Public Health, Boston, Massachusells, 02115, the Colombian Institute of Family Welfare, Bogota, Colombia, and the Institute of Nutrition, Justus Liebig University, Giessen, Germany. 'Supported in part by National Institute of Child Health and Human Development Grant ROI-HD06774OIAl; Ford Foundation Grant 740-0348; The German Research Foundation; and the Fund for Research and Teaching, Department of Nutrition, Harvard School of Public Health. J Address reprint requests to: Dr. M. G. Herrera, Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, Mass. 02115. 4 A collaborative research project of the Colombian Institute of Family Welfare, the Department of Nutrition, Harvard School of Public Health, and the Institute of Nutrition, Justus Liebig University, Giessen, Germany.
The American Journal of Clinical Nutrition 32: FEBRUARY 1979, pp. 455-462. Printed in U.S.A.
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455
· 456
MORA ET AL. EXPERIMENTAl POPULATION Famllres at risk of malnutrltion (456)
I Random Assignment
I
I
I
I
I A (90)
B
-Health Care
-Perlodie measurement
o (82)
(86)
-Heal th care
-Heel I th cafe
-Periodic measure-
-Periodic measure-
ment -Food supplemen-
ment -Food suppternenl:atl on frorn 6 mos of pr~gnancy to 6 mas of II f.
tatlan from 6 mas to 3 years of life
Al
c
(82l
-Health l:are -Pe r 1ad i c mellsurem~nt
-Food supp lernentatiQn from 6 rnos of pregnancy to
3
yei!!rs
of 11 f.
01 (58)
(58)
-A + psychological stimul21t ion from o to 3 years of life
-D + psychological
still'lul.atton frcm
a
to 3 years of 11 Fe
FIG. 1. Experimental design.
appropriate controls (I, 2, 19-23). Matching poses almost insurmountable difficulties under field conditions and designs that rely on self-selection result in problems of interpretation. With these considerations in mind, a prospective, randomized treatment trial was designed utilizing food supplementation as the intervention. Design and methods The data reported here pertain to the prenatal and perinatal phase of a longitudinal study of malnutrition and its relationship to physical and cognitive development carried out in Bogota, Colombia: Families with children in the poor southern barrios of the city were selected for the study according to the following criteria: 1) the mother was in the first or second trimester of pregnancy and 2) malnutrition was present in at least 50% of children under 5 years of age." Four surveys made of the entire zone at 6month intervals yielded 522 families who met the selection criteria. Ninety-six (17%) eligi-
ble families were not enrolled: 39 because of change of address, 34 due to abortion, and 23 because they elected not to participate. Sociological data from 57 of these 96 families compared with similar data from the participants showed no significant differences, thus arguing against selection bias in enrollment. The 456 families enrolled were randomly assigned to six experimental groups as shown in Figures I and 2. Until the time of birth, groups A, B, and Al merge as the control group receiving no supplementation; groups C, D, and DI together represent the supplemented sample. All families in the study were enrolled in a uniform, health-care program consisting of free medical care for the mother during pregnancy and delivery as well as pediatric care for all children under 7 years old. Prescribed medicines were provided free. Families in all study groups were subjects of the same social, health, and physical growth, and intellectual development measurements throughout the study. " Malnutrition was defined as tess than 85% in weight for age.
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NUTRITIONAL SUPPLEMENTATION AND BIRTH WEIGHT
Food supplementation was initiated at the beginning of the third trimester of pregnancy of families in groups C, D, and D 1. Supplements were provided in amounts sufficient to meet a substantial proportion of the recommended dietary allowances for the pregnant mother and for all members of the family (Table 1). The food was distributed weekly in a field unit similar to a neighborhood store independent of the health center where the medical program operated in order to minimize contact between supplemented and unsupplemented groups. Pregnant women were instructed to continue consuming their usual diet in addition to the supplement. Empty containers had to be returned in order to qualify for the next weekly supply and food utilization was monitored through random home visits by project personnel. Dietary intake was measured by the 24-hr recall method at the beginning of the study and again two months later. Leng~h of gestation was calculated from SIX
BIRTH MONTHS
A
D
c~,
THREE NO. OF FAMlllE.S YEA.RS
=t=t=======j
ENTERED
tl
90
I
82
~~::::::::= ;
I
II
SUPPLEMENTATION
~
EARLY EDUCATION (Stimulation)
8a
82 58 56
FlG. 2. Intervention schedule.
457
the 1st day of last menstruation. In 12 cases gestational age had to be estimated on the basis of successive measurements of uterine height because the date of last menstruation was uncertain. All mothers in the sample were weighed initially at about 25 weeks of gestation, and monthly thereafter. One hundred seventeen subjects were weighed during labor before rupture of the membranes. The first and last recorded maternal weight during the third trimester were used to estimate the average weekly weight gain. Two-thirds of the women in the sample were delivered at the University Hospital, San Juan de Dios, where specially-trained project personnel collected information on the birth and carried out anthropometric measurements on the newborn. A calibrated scale (Toledo) with a 13,500 g capacity and 20 g sensitivity was used for determination of birth weight. The remaining one-third of the sample delivered at other maternity hospitals or at home where weighing the newborn was not possible. Out of a total of 456 families, seven were lost to follow-up before delivery (change of address in four cases, decision to withdraw in three cases). There were 10 stillbirths and six multiple pregnancies. Thus a sample of 433 singletons were born to mothers in the study. Two hundred ninety-seven were weighed at the University Hospital immediately after birth and again 25 and 31 hr thereafter and at 15 days of age. One hundred ten of the remaining 136 were weighed by project personnel: 13 at 25 hr, eight at 31 hr, and 89 at 15 days of age. In order to estimate birth
TABLE I Nutritional supplements provided per capita per day for women during the last trimester of pregnancy Supplements
Grams
Dry skim milk EnriChed bread Vegetable oil Vitamin mineral supplement
60 150 20
TOTAL
230
Percentage of RDA"
Calories
214 466 176
Protein
Vitamin A
Iron
g
lU
mg
21.6
18
0.4
16.8
6
2.6
6000
15.0 18.0
856
38.4
6024
39
60
100
" Recommended Dietary Allowances (National Research Council, 1968).
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100
458
MORA ET AL.
weights of these 110, a regression equation was computed from the data on the 242 children on whom weight data were available at birth, 25 hr, 31 hr, and IS days. The correlations of birth weight with the other weight measurements were 0.98, 0.98, and 0.87, respectively. Thus, birth weight is available on 407 infants. Inclusion of the subsample with the estimated weights did not alter the results ofthe analysis. No associations were found between birth weight and mother's age (r = 0.007), height (r = 0.11) and parity (r = 0.02) in the total sample. Therefore, birth weight was not adjusted for these variables. Results Table 2 summarizes the socioeconomic, demographic, and nutritional characteristics of the sample by group. No significant differences between experimental and control groups were found in variables related to birth weight that could confound the intervention effect.
Calorie and protein intake for the supplemented group, before and during supplementation are shown in Table 3. The mean intake increment was 155 cal and 20 g of protein; increments in calorie intake among mothers pregnant with males tended to be larger than among those pregnant with females, but the difference did not reach significance. Mean birth weight for the total sample and for the 339 full-term children by sex and supplementation group are shown in Table 4. There were differences of 51 and 50 g between the unsupplemented and the supplemented groups which failed to reach significance. Among full-term males, however, supplementation resulted in increment of birth weight of 95 g which was significant by the one-tail t test (P < 0.05). There was no supplementation effect on the length ofgestation. Since duration of supplementation among women who delivered prematurely was associated with length of gestation, only fullterm birth weights were analysed by weeks of supplementation. Supplementation effects on
TABLE 2 Characteristics of the experimental groups before supplementation Supplemented (n - 207)
Unsupplemented
Variables
(n - 200)
Family size Family income (US$ monthly) Per capita income (US$ monthly) Family food expenses (US$ monthly) Mother Age Height (em) Daily calorie intake Daily protein intake (g) No. of previous pregnancies Education (median years completed)
mean
SD
mean
SD
5.9 50.9 9.7 27.7
2.5 25.4 6.1 13.4
5.2 46.9 9.9 26.2
2.0 205 4.8 12.6
26.9 149.9 1556 35.8 4.2 2.96
6.1 5.3 641 22.6 3.2
25.6 149.9 1623 35.5 3.6 3.01
5.4 5.5 635 19.2 2.6
TABLE 3 Calorie and protein intake of the supplemented group, before and during supplementation, by sex of the newbom" Females
Males
x
Calorie intake Before After
112 95
Protein intake Before After
112 95
n
1586 1771 35.1 55.7
SD
588 553 19.8 22.6
x
108 90 108 90
1637 1760 34.7 55.1
Both sexes
SD
660 590 18.1 2 \.6
n
220 185 220 185
24-Hr recall dietary surveys before beginning supplementation and 8 weeks thereafter.
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x
SD
1611 1766
623 570
34.9 55.4
19.0 22.1
NUTRITIONAL SUPPLEMENTATION AND BIRTH WEIGHT
459
TABLE 4 Mean birth weight (g) by sex and supplementation group for the total sample and for full-term newborns" Females
Males
x
SD
BOlh
x
SD
se~es
x
SD
Supplementation group A. Total sample Unsupplemented Supplemented Total
93 107 200
2951 3040 2999
411 414 414
107 100 207
2905 2911 2908
374 322 349
200 207 407
2927 2978 2953
392 377 385
B. Full-term Unsupplemented Supplemented Total
74 95 169
2966 3061 3019
322 374 354
88 82 170
2942 2935 2939
303 320 310
162 177 339
2953 3003 2979
311 355 335
n Differences between supplemented and unsupplemented groups. The difference between supplemented and unsupplemented full-term males was 95 g (single tail I test P < 0.05). Differences between sexes are significant (I test P < 0.05) among the supplemented groups.
3600
•
{41l (54)
3400 g
....
3200
..,'" W
3000
0-
2BOO
" ....'"
m
*
(101)
(74)
i47J 18Bf 1351
176) (162)
2600 2400
o
MALES UNSUPPLEMENTED
FEMALES
~
rn
BOTH SEXES
SUPPLEMENTED
13 WEEKS
FIG. 3. Birth weight of full-term children, by sex and supplementation group. Asterisk, difference with corresponding unsupplemented group is statistically significant (P < 0.05) by the single tail I test.
birth weight were related to duration of treatment and offspring sex. Among males a difference of 105 g was found between the unsupplemented group and those receiving supplementation for 13 weeks or more (single tail t test P < 0.05). Males receiving less than 13 weeks of supplementation weighed 102 g more than the controls: 102 g (P < 0.05) (Fig. 3). The difference in birth weight between males receiving less than 13 weeks of supplementation and controls was not significant. No supplementation effect on birth weight was found among females. It is noteworthy that among the unsupplemented, birth weight was similar for both sexes, while a significant difference of 126 g in-favor ofmales appeared in the supplemented group (P < 0.05). Sup-
plementation tended to reduce the proportion of low birth weights (2500 gor less) among males but not among females (Table 5). The l, however, was not significant. Parallel differences were found in mean weight gain of full-term mothers during the last trimester of pregnancy (Fig. 4). Weight gain of mothers pregnant with males was significantly higher when they were supplemented than when they were not. The difference between those supplemented 13 weeks or more and the controls amounted to 140 g! week. However, no differences in weight gain were found between supplemented and unsupplemented groups among mothers pregnant with females. Finally, a clear association was found between weight gain during the last trimester of pregnancy and birth weight irrespective of sex (Fig. 5). Discussion The results presented above show that maternal supplementation during the last trimester of pregnancy had a small but significant effect on the birth weight of male infants. The randomized trial design of the experiment and the documented similarity between experimental and control groups at the onset permit the conclusion that the observed differences were caused by the food supplementation program and not by confounding variables. The effect of supplementation on maternal weight gain and the association of the latter with birth weight strongly suggest that improved maternal nutrition mediated the effect on birth weight.
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MORA ET AL.
460
TABLE 5 Proportion oflow birth weight babies by sex and supplementation group for the total sample and for full-term newborns" Unsupplemented
To..1
Supplemented
l.OW/n
%
LBW/n
%
l.OWI"
%
Males Females Total
12/93 10/107 22/200
12.9 9.3 11.0
6/107 12/100 18/207
5.6 12.0 8.7
18/200 22/207 40/407
9.0 10.6 9.8
B. Full-term Males Females Total
8/74 6/88 14/162
10.8 6.8 8.6
4/95 8/82 12/177
4.2 9.8 6.8
12/169 14/170 26/339
7.1 8.2 7.7
A. Total sample
"Full-term defined as >37 and