Birth Weight, Growth, and Blood Pressure
An Annual Follow-up Study of Children Aged 5 Through 21 Years
Abstract Associations between birth weight and blood pressure have been found in children and adults. In this longitudinal study, the objective was to assess the relation between birth weight and blood pressure level and the change in blood pressure from childhood and young adolescence into adulthood. A cohort of 483 children from a middle-class community in the town of Zoetermeer in the Netherlands had annual measurements of blood pressure during an average follow-up period of 14 years. For 330 of these participants, initially aged 5 through 21 years, birth weight data were collected, which were related to blood pressure level and blood pressure change. An inverse association between birth weight and systolic blood pressure was found, with adjustment for current body height and weight, sex, and use of alcohol, cigarettes, and oral contraceptives. This inverse association was found for the total follow-up in 5- to 37- year-olds (regression coefficient: −2.4 mm Hg/kg; 95% confidence interval: −3.9 to −1.0, as well as in most individual age groups: 5 through 9 years (−0.6 mm Hg/kg, −3.2 to 2.0); 10 through 14 years (−2.5 mm Hg/kg, −4.7 to −0.4); 15 through 19 years (−3.1 mm Hg/kg, −4.9 to −1.2); 20 through 24 years (−2.7 mm Hg/kg, −4.6 to −0.9); 25 through 29 years (−2.0 mm Hg/kg, −3.9 to −0.01); and 30 through 37 years (−1.9 mm Hg/kg, −4.6 to 0.7). For diastolic blood pressure, there appeared to be an inverse association with birth weight in the age group of 30 through 37 years, both unadjusted (−2.0 mm Hg/kg, −4.6 to 0.5) and adjusted for risk factors other than sex (−2.3 mm Hg/kg, −4.7 to 0.1), although these findings were of borderline statistical significance. The results were independent of gestational age and were similar in the group of subjects with low birth weight but normal gestational age (−2.7 mm Hg/kg, −4.3 to −1.0). In relation to systolic blood pressure, birth weight showed a significant interaction with body mass index (regression coefficient, 0.02; SE=0.01; P=.05). There was no relation between birth weight and change in systolic or diastolic blood pressure with age. Our longitudinal study shows that birth weight is consistently inversely associated with systolic blood pressure level from childhood to young adulthood and with diastolic blood pressure in young adulthood. Birth weight is not related to change of blood pressure with increasing age. Low birth weight in combination with high current body mass index seems to be of particular importance in the development of high blood pressure.
Impaired prenatal and early postnatal growth and development may be an important risk factor for cardiovascular and other chronic disease later in life. Both ecological studies and longitudinal studies of individuals have shown relations between an adverse intrauterine environment and cardiovascular disease.1 2 3 4 Blood pressure has been suggested as one possible link between compromised intrauterine life and cardiovascular disease. In several studies, an inverse relation between birth weight, as an indicator of intrauterine circumstances, and blood pressure in children, adolescents, and adults was found,5 6 7 8 9 although other studies reported no or a positive association, particularly in adolescents.10 11 12 Recently, a U-shaped relation between birth weight and blood pressure was reported in infants and young children.13 The inverse relation between systolic blood pressure and birth weight may become stronger or amplified with increasing age.9 This possibility was suggested in a recent study showing a more rapid increase of systolic blood pressure in children of lower birth weight.14 There are only sparse longitudinal data from childhood to adulthood on the relation between birth weight and blood pressure.
We studied the relation between birth weight and blood pressure in a longitudinal study conducted from childhood into adulthood. Data are from a cohort of youngsters, initially aged 5 through 21 years, who were annually examined for an average of 14 years. In particular, we examined the relation of birth weight to level of blood pressure at different ages and to blood pressure change with increasing age.
Between 1975 and 1978, the total population aged 5 years and over in two districts of Zoetermeer, a suburban town in the western part of the Netherlands, was invited to participate in a study of chronic disease risk indicators.15 Of 5670 eligible children aged 5 through 21 years, 4649 (82% response) took part in the study. From this group, a random sample of 596 children was selected for annual follow-up in a study of cardiovascular risk factors and their determinants. The present study was based on 483 (81% response) subjects who took part in the yearly follow-up (252 males and 231 females). The average follow-up period was 14 years (range, 3 to 18 years). In 1991, 352 subjects still participated in the study.
A random-zero sphygmomanometer (Hawksley) was used to measure blood pressure according to a standardized protocol13 on the left arm of a sitting subject after a resting period of about 15 minutes. Diastolic pressure was based on the fifth Korotkoff phase. A cuff of 23 cm×10 or 14 cm was used, depending on the arm circumference. The largest cuff was usually used in children aged over 10 years. At each annual examination, two blood pressure readings were taken, and the average was used for analysis. Throughout the follow-up period, blood pressure measurements were performed by the same research assistant; annual measurements were performed in the same month of the year and usually at the same time of day. Serum total cholesterol was measured with an automated enzymatic method, using the Boehringer Mannheim CHOD-PAP reagent kit.16 Body height and weight were measured without shoes and heavy clothing. At each examination, a questionnaire about lifestyle factors was completed.
Birth Data Collection
To obtain birth data, a questionnaire was sent to the parents of the children. Questions were asked about birth weight (in grams), birth height (in centimeters), placental weight (in grams), gestational age, complications during pregnancy, and whether or not the mother had smoked during pregnancy. The addresses of 33 parents could not be found, and two children died during follow-up. Of the 448 questionnaires sent, 353 (78.8% response) were returned to the investigators. Of the 353 returned questionnaires, 330 had usable data on birth weight. The analysis included a total of 327 subjects on whom there were birth weight data and sufficient follow-up data on blood pressure and possible confounders. In 59% of the returned questionnaires, the parents reported the birth weight as they remembered it (59% of these reported birth weights to the nearest 100 g). In 19%, parents obtained the birth weight from a maternity center (55% reported to the nearest 100 g). In 22%, parents took the birth weight from birth announcements (43% reported to the nearest 100 g).
The data were analyzed by using an unbalanced repeated-measurements analysis (BMDP 5V). The linear regression model included repeated measurements of blood pressure as the dependent variable and birth weight as well as other constant and time-varying covariates as independent variables. This analysis, as well as the analysis for the complete data, was done within the age groups 5 through 9, 10 through 14, 15 through 19, 20 through 24, 25 through 29, 30 through 37, and 5 through 37 years. In all analyses, an unstructured covariance matrix was used.
The relation between change of blood pressure over time and birth weight was studied by using a linear regression model, with blood pressure (repeated measures) as the dependent variable and age, birth weight, and the interaction term birth weight×age as independent variables. The basic model can be written as Blood Pressure=α+β0×Age+β1×Birth Weight×Age+β2×Birth Weight, whereby (α+β2×Birth Weight) is the intercept and (β0+β1×Birth Weight) is the slope of blood pressure change over time.
Subjects were on average 13 years old on entry into the study cohort, with 72% of subjects under 16 years of age. The characteristics of the subjects with available birth weight data on entry into the cohort and pregnancy data are shown in Table 1⇓. Both birth weight and birth height were slightly higher in boys than in girls.
Table 2⇓ shows the results of the repeated-measures analysis of the relation between blood pressure and birth weight. There was no association between systolic blood pressure and birth weight in any of the age groups if sex only was entered into the model. When additional adjustment was made for current body weight, body height, and use of alcohol, cigarettes, and oral contraceptives, statistically significant inverse relations were found between systolic blood pressure and birth weight. This relation was almost entirely due to the adjustment for current body weight and height. An adjusted analysis of the group as a whole yielded a statistically significant inverse relation between systolic blood pressure and birth weight. No clear trend in the strength of the association over age groups was observed. A separate analysis on the relation between systolic blood pressure and birth weight showed a statistically significant interaction between birth weight and body mass index (BMI) (regression coefficient, 0.02; SE=0.01; P=.05). This finding suggests that systolic blood pressure is highest in those with low birth weight and high current BMI.
Fig 1⇓ shows the annual height- and weight-standardized mean systolic blood pressure by tertiles of birth weight (low, ≤3200 g; medium, 3200 to 3600 g; high, ≥3600 g). The standardized systolic blood pressure was persistently higher in subjects in the lower-birth-weight tertile.
In preterm subjects (n=41), defined as a gestation period of 37 weeks or less, the relation between systolic blood pressure and birth weight over the total follow-up period could not be shown. In term subjects (n=281), defined as a gestation period of more than 37 weeks, this relation was similar to that found in the group as a whole (regression coefficient, −2.67 mm Hg/kg; SE=0.83; P=.0012). Inclusion of gestational age in the full model (second column, Table 2⇑), using all data from the complete follow-up period, yielded similar results (regression coefficient, −2.14 mm Hg/kg; SE=0.78; P=.0062). Additional adjustment for maternal smoking during pregnancy (n=70) and complications during pregnancy (particularly maternal hypertension [n=64]) did not change the relation between systolic blood pressure and birth weight (regression coefficient, −2.28 mm Hg/kg; SE=0.81; P=.005).
Up to age 29, there was no association of diastolic blood pressure with birth weight. However, between ages 30 and 37, there was an inverse relation (Table 2⇑). There was no interaction between birth weight and BMI (or body weight or height) in relation to diastolic blood pressure.
The change of blood pressure with age was assumed linear within the periods 5 through 20 years and 20 through 37 years (Fig 1⇑). The analysis of blood pressure change was therefore performed separately for these two periods. For systolic blood pressure, there was interaction between birth weight and age (regression coefficient, 0.03; SE=0.01; P=.02), indicating an effect of birth weight on the slope of systolic blood pressure over time. However, this effect was negligible compared with the effect of birth weight on the level of systolic blood pressure. This is graphically shown in Fig 2⇓, in which intercepts of and change in systolic and diastolic blood pressures are shown in subjects with a birth weight of 2.5 kg and subjects with a birth weight of 4.5 kg. The analysis over the age period of 20 through 37 years showed similar results. Further adjustments for other variables in this analysis did not materially change the results.
To evaluate the effect of misclassification due to reporting birth weights from memory, additional analyses were performed on birth weight and systolic blood pressure in subjects (41% of total number) whose parents reported birth weights from either maternity center cards or birth announcements. The results of the fully adjusted repeated-measures analysis restricted to these subjects were essentially similar (regression coefficient, −1.76 mm Hg/kg; SE=0.88; P=.0465).
There were no secular trends in either blood pressure levels or body weight and height during follow-up. Mean systolic blood pressure levels in 15- through 20-year-olds measured before 1983 were 114.6, 117.3, 118,3, 120.8, 120.2, and 122.2 mm Hg, respectively. Levels in the same age groups measured after 1983 were 114.4, 117.5, 118.7, 120.3, 121.4, and 122.6 mm Hg (all observations based on n>100). There was a small secular trend in birth weight. Subjects who reached the age of 15 before 1983 (n=138) had a mean (SE) birth weight of 3.39 (0.05) kg, and those who reached that age after 1983 (n=82) had a birth weight of 3.52 (0.06) kg. Similarly, for 20-year-olds, the mean birth weights were 3.42 (0.06) kg (n=117) and 3.46 (0.05) kg (n=136), respectively. However, separate analyses taking the date of birth into account did not change the relation between birth weight and blood pressure level nor blood pressure change (data not shown). The change in body weight in 15- through 20-year-olds measured before 1983 (n=164) seemed to be slightly lower than in 15- through 20-year-olds measured from 1983 onward (n=58): 1.7 (0.1) kg/y versus 1.9 (0.2) kg/y, although the difference was not statistically significant (P=.21).
The results of this longitudinal study show a strong and consistent inverse association between birth weight and systolic blood pressure after adjustment for, particularly, current body height and weight. This association persists from adolescence into adulthood. The systolic blood pressure was highest in subjects with low birth weight and high current body mass. An inverse relation between birth weight and diastolic blood pressure also appeared to be present in adulthood. There was no association between birth weight and the change in systolic and diastolic blood pressures with increasing age.
Before these results are interpreted, some methodological aspects of the study should be discussed. Differential loss to follow-up and selection in the collection of birth data are not likely to have biased the results. Mean systolic and diastolic blood pressures or mean weight did not differ between responders and nonresponders. Furthermore, the birth data were obtained without reference to the annual blood pressure measurements. At the time of birth of most of the subjects in the present study, there was no national registry of birth data, nor are these available from vital statistics. Furthermore, a large proportion of children in the Netherlands were, and still are, born at home. Accurate birth weight data may be obtained from maternity center cards and from personal birth announcements. Although the recall from memory of, particularly, birth weights by mothers, as opposed to other prenatal and postnatal characteristics, has been shown to be reliable,17 it may be expected to affect precision. Imprecision in the self-reported birth weights occurred, as there were many rounded-off numbers, in particular from parents reporting birth weight from memory. However, analyses restricted to subjects whose parents reported birth weights from maternity center cards or birth announcements yielded even stronger inverse associations between birth weight and systolic blood pressure below age 25 than for the total group, despite the smaller sample (41% of the total). Therefore, this misclassification is most likely to be random and underestimates the real association between birth weight and blood pressure. There were no secular trends in blood pressure, body weight, and height that could explain the findings. Youngsters of a specific age who were born later had higher birth weights but similar blood pressure levels.
Our results are in line with earlier cross-sectional and longitudinal reports on an inverse relation between birth weight and blood pressure in populations of different age, ranging from infancy to adult life.5 8 9 13 14 18 Matthes et al,12 in a retrospective cohort study comparing low- and higher-birth-weight subjects with respect to later blood pressure, found no association. This may partly be explained by a U-shaped relation between birth weight and blood pressure that was reported in infancy,13 but also, in adolescence, high birth weight was related to high blood pressure.11
The present study is the first to demonstrate the longitudinal association between birth weight and blood pressure from childhood into adulthood within the same group of subjects. The dependency of the relation between systolic blood pressure and birth weight on BMI confirms the results of a study in 50-year-old men.19 Recently, another study on incident coronary heart disease showed that an increased risk is restricted to those with low birth weight and high BMI in adulthood.20 Our study suggests that by childhood and adolescence, high systolic blood pressure may already occur, particularly in those with low birth weight and high current BMI.
The results were independent of gestational age as a confounder in the relation between birth weight and blood pressure. Further, the relation was present in subjects born at term regarding systolic blood pressure. This would indicate that it is attained birth weight that is related to blood pressure, possibly as a reflection of hampered intrauterine growth rate. Maternal smoking and complications during pregnancy did not explain the results. Children of mothers with hypertension during pregnancy have been reported to have higher blood pressure and lower birth weight.21 In our data, reported maternal hypertension during pregnancy did not explain the results. A number of mechanisms, such as maternal malnutrition,22 could link a compromised intrauterine environment to reduced fetal growth and high blood pressure. An adverse environment during critical periods of development may lead to permanent changes in the body’s structure, physiology, and metabolism,21 22 such as changes in the fetal structure of blood vessels. In a recent study, lower arterial compliance in subjects who were small at birth was reported.18 Alternatively, low-birth-weight babies may experience an accelerated increase in blood pressure during the first months after birth.23 Several studies on newborn infants report a positive relation between birth weight and blood pressure within the first week after birth but an inverse relation 3 months later.13 19 24 These findings lead to the question of whether the birth weight/blood pressure relation persists from birth or whether blood pressure rises more rapidly in low-birth-weight children. A number of studies have reported that the inverse blood pressure/birth weight relation becomes stronger or is “amplified” with increasing age.6 9 14 Whincup et al14 showed amplification of the relation in children. Although the age group analysis in our younger groups (5 through 14 years) indicated such amplification, we did not find clear support for amplification in the older groups. On the basis of the cross-sectional age-group analyses of systolic blood pressure, we conclude that the effects show a decrease from around puberty to young adulthood, rather than an increase. This is supported by the somewhat higher increase of systolic blood pressure with age in the high-birth-weight subjects, given their lower initial levels.
The associations in the present study were, as in other studies, found only after adjustment for current body height and weight and other risk factors as confounders in the relation between birth weight and blood pressure. It must be borne in mind that current body size may to some extent also be an intermediate variable between birth weight and blood pressure, in which case, adjustment could lead to artificial relations. However, current size measured long after birth is not easily conceived of as only an intermediate variable. Furthermore, the effect of adjustment for current size in the birth weight/systolic blood pressure relation was rather different from the effect in the birth weight/diastolic blood pressure relation.
Although the findings of this study are important with regard to the etiology of high blood pressure, the public health implications for adult blood pressure management are limited, because the adjusted associations are obviously not appropriate for identification of high-risk groups. Also, with this adjustment, the relation between high birth weight and high current weight resulting in high blood pressure that was found elsewhere13 is cancelled out. However, our study points out the particular importance of low birth weight in combination with high current BMI in the development of high blood pressure in adolescence and young adulthood.
In conclusion, our longitudinal study shows that birth weight is consistently inversely associated with systolic blood pressure level from childhood to young adulthood and to diastolic blood pressure in young adulthood. Birth weight is not related to change of blood pressure with increasing age. Low birth weight in combination with high current BMI seems to be of particular importance in the development of high blood pressure.
The EPOZ follow-up study was financially supported by the Netherlands Prevention Fund. Joke R. Jansen is gratefully acknowledged for her technical assistance in the project.
- Received July 23, 1996.
- Revision received August 23, 1996.
- Accepted January 9, 1997.
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Leon DA, Koupilova I, Lithell HO, Berglund L, Mohsen R, Vågerö D, Lithell U-B, McKeigue PM. Failure to realize growth potential in utero and adult obesity in relation to blood pressure in 50 year old Swedish men. BMJ. 1996;312:401-406.
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