Papers

Size at birth, maternal nutritional status in pregnancy, and blood pressure at age 17: population based analysis

^a Department of Internal Medicine, Carmel Hospital, Haifa, Israel, ^b Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA, ^c Department of Internal Medicine, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Hashomer, Israel, ^d Department of Neonatology, Bikur Cholim Hospital, Jerusalem, Israel, ^e Department of Obstetrics and Gynecology, Sheba Medical Center

Correspondence to: Dr Seidman

	Abstract

Top Abstract Introduction Subjects and methods Results Discussion References

Objective: To assess the effect of size at birth, maternal nutrition, and body mass index on blood pressure in late adolescence.
Design: Population based analysis of birth weight corrected for gestational age, mother's weight before pregnancy and weight gain in pregnancy, obtained from the Jerusalem perinatal study, and blood pressure and body mass index at age 17, available from military draft records.
Setting: Jerusalem, Israel.
Subjects: 10 883 subjects (6684 men and 4199 women) born in Jerusalem during 1974-6 and subsequently drafted to the army.
Main outcome measures: Systolic and diastolic blood pressures measured at age 17 and their correlation with birth weight, size at birth, mother's body mass index and weight gain during pregnancy, and height and weight at age 17.
Results: Systolic and diastolic blood pressures were significantly and positively correlated with body weight, height, body mass index at age 17, and with mother's body weight and body mass index before pregnancy, but not with birth weight or mother's weight gain in pregnancy.
Conclusion: Variables reflecting poor intrauterine nutrition, including low maternal body mass index before pregnancy, poor maternal weight gain in pregnancy, and being born small for gestational age, were not associated with a higher blood pressure in late adolescence.

	Introduction

Top Abstract Introduction Subjects and methods Results Discussion References

Several studies have shown a significant inverse relation between blood pressure and birth weight,^{1 2 3 4 5 6} which may be a result of fetal adaptations to an adverse environment, particularly undernutrition.⁷ Data showing a strong association between maternal nutritional status in pregnancy and blood pressure at 10-12 years of age support this contention,⁸ and further confirmation comes from study of the influence of mother's diet in late pregnancy on their offspring's adult blood pressure.⁹ However, not all investigators have confirmed this association.^{10 11 12 13} In addition, the hypothesis that high blood pressure has early nutritional origins was not supported by a study assessing the effect of poor nutrition in infants born before term on later high blood pressure.¹⁴

Previous studies examining prenatal effects on blood pressure defined intrauterine growth retardation as birth weight below 2500 g.¹⁵ A more accurate assessment of intrauterine growth is provided by size at birth considered in relation to gestational age, rather than birth weight alone. Also, in this study we assessed maternal nutritional status during pregnancy on the basis of body weight before pregnancy corrected for height and weight gain in pregnancy.

We aimed to evaluate the effects of being born small or large for gestational age, and of the mother's nutritional status, on systolic and diastolic blood pressure at 17 years of age. The large computerised dataset allowed adjustment for height and weight of the subjects and their mothers as well as for birth order, ethnic origin, and socioeconomic factors.

	Subjects and methods

Top Abstract Introduction Subjects and methods Results Discussion References

Data on 11 428 infants born between November 1974 and February 1976 were obtained from the computerised records of the Jerusalem study on oral contraceptive use,¹⁶ one of the interlocking epidemiologic studies making up the Jerusalem perinatal study, the design and methods of which have been reported.¹⁷ Variables included birth weight and gestational age recorded at the time of delivery, as well as detailed sociodemographic information. Socioeconomic status was assessed by area of residence (classified by municipal tax level areas¹⁷) and mother's educational attainment (years of schooling). Ethnic origin was defined according to father's country of birth. Gestational age was determined, in women with regular menstrual cycles,¹⁸ according to the date of the last menstrual period acquired through individual interviews with all mothers on the day after delivery.¹⁹ The perinatal data were matched to measurements made at age 17 obtained from the computerised records of the Israel defence forces' draft medical examination, using the subject's seven digit identification number assigned at the time of draft.²⁰ The adequacy of the match was confirmed by comparing sex and mother's identity number. Complete information on all variables was available on 10 883 (95.2%) of the subjects. Only 38.6% of our study population (4201 subjects) were women, as women who declare themselves to be orthodox religious are exempted from military service.²⁰ We thus analysed and presented the results separately for men and women. Only a negligible minority (124, <2%) of male subjects (those in hospital because of severe chronic and psychiatric disease and long term prisoners) were not examined and consequently were excluded from the study.

Subjects' birth weights were stratified in fifths for gestational age, on the basis of growth curves determined for our entire study population, to avoid a bias that may be caused by use of growth curves developed for a different population.

Blood pressure was measured in the sitting position in the right arm with a Bauman sphygmomanometer with appropriate cuff size. The end point for diastolic blood pressure was the disappearance of the Korotkoff sounds (phase V). The examiners were not aware of the perinatal data. Standing height was measured without shoes to the nearest centimetre, and body weight without clothes was determined to the nearest 100 g.

Regression coefficients with 95% confidence intervals were calculated by multiple linear regression analysis (SAS Institute, Cary, NC) to control for the effects of the studied independent variables. The variables included in the regression model were birth weight corrected for gestational age, birth order, ethnic origin, social status, height and body mass index (kg/m²) at 17 years of age, and mother's educational attainment, body mass index, and weight gain in pregnancy.

	Results

Top Abstract Introduction Subjects and methods Results Discussion References

Systolic and diastolic blood pressure at age 17 correlated significantly with body weight and height, body mass index, and mother's body weight and body mass index before pregnancy, but not with birth weight or mother's weight gain in pregnancy (table 1). After adjustment for birth weight, mother's body mass index, body weight at age 17, and ethnic origin by a multiple regression analysis model, systolic and diastolic blood pressure and body weight were positively associated (table 2). Birth weight and Western and Israeli ethnic origin were negatively associated with blood pressure (table 2). Birth order, social status, and mother's and father's educational attainment were not included in the final regression model as they did not influence blood pressure significantly.

The mean systolic and diastolic blood pressures increased with adolescent body mass index group in young women and young men (tables 3 and 4). The fifth of birth weight for gestational age was not associated the mean systolic or diastolic blood pressure at age 17 (tables 3 and 4). Adjustment for body weight at age 17 and mother's weight before pregnancy, body mass index, weight gain in pregnancy, and ethnic origin in a multiple regression model did not change these associations.

After adjustment for the above variables, mother's body mass index was positively associated with blood pressure while weight gain in pregnancy had little influence on blood pressure at age 17 (for details, see extra tables available on the internet at www.bmj.com). Furthermore, subjects born to women with low body mass index before pregnancy, or those who gained little weight in pregnancy, did not have a higher mean systolic or diastolic blood pressure.

	Discussion

Top Abstract Introduction Subjects and methods Results Discussion References

Adverse intrauterine conditions, suggested by small size for gestational age, were not associated with high blood pressure at age 17. Birth weight was positively, rather than negatively, correlated with blood pressure. This finding is in agreement with our previous study on 33 545 subjects born a decade earlier, in which low birth weight was poorly correlated with blood pressure in late adolescence.¹⁰ The present study has an advantage over the previous series, because an accurate estimation of gestational age was available, better reflecting intrauterine growth than birth weight alone. More importantly, maternal nutritional status during pregnancy could be assessed, and low weight and body mass index before pregnancy, as well as poor weight gain in pregnancy, were not associated with high blood pressure. In fact, the mother's body mass index before pregnancy and weight gain in pregnancy had an independent positive effect on blood pressure at 17 years of age.

Conflicting findings
Since we first reported, in 1991, that intrauterine environment, as shown by birth weight, has little effect on blood pressure in 17 year old subjects,¹⁰ additional studies have confirmed our observation in 15, 16, and 18 year olds.^{11 12 13} The weak association between birth weight and blood pressure in teenagers has subsequently been attributed to perturbation of blood pressure tracking during this period of rapid growth,⁷ but subjects who are 17 and 18 years old are probably well past the pubertal growth spurt.

Law et al noted that babies who are small at birth, and not just premature, tend to have raised blood pressure during adult life.³ In contrast to the previous four studies assessing birth weight in adolescence,^{10 11 12 13} in the present study we were able to determine the appropriateness of size at birth in relation to the gestational age. We were also able to correct for multiple confounding factors such as body mass index and mother's body mass index, socioeconomic status, and ethnic origin. Even so, our findings do not support an inverse relationship between size at birth and blood pressure. In a previous study that found an inverse association in children 5 to 7 years of age, social class, educational attainment and mother's body mass index corrected for the child's body mass index were not related to blood pressure.²¹

The finding that girls born large for gestational age have a higher incidence of raised systolic blood pressure at age 17 may be a chance finding due to analysis of multiple subgroups. Laurer et al, though, have found that children with a high birth weight had higher blood pressure up to the age of 4 years⁴; conversely, Whincup et al found an inverse relation between birth weight and blood pressure, especially prominent in girls.⁵

We found a strong positive association between body mass index and blood pressure, as observed in many other populations.²² However, subjects who were small at birth and became overweight were not at higher risk of high blood pressure, as has recently been suggested.²³

Limitations
Our study was limited by several factors. Firstly, as length at birth was not recorded, we were unable to calculate the body mass index at birth. A previous study using this body mass index at birth to determine symmetrical (light and short) and asymmetrical (light and of normal length) delayed intrauterine growth did not find an association with systolic or diastolic blood pressure at age 18 years.⁹ Secondly, we did not obtain placental weights. This factor has been found to be strongly related to systolic and diastolic blood pressure in adults,² but a recent study showed that birth weight, rather than placental ratio (ratio of placental weight to birth weight), is the early life factor most importantly related to blood pressure in childhood.⁵

Use of body mass index
Godfrey et al found a link between maternal triceps skinfold thickness and the blood pressure in 77 children at 10-12 years of age.⁸ They speculated that fetal undernutrition may lead to adaptive changes, with long term consequences that initiate higher blood pressure. We did not find that the mother's low body mass index and poor weight gain in pregnancy was associated with a higher mean systolic or diastolic blood pressure at late adolescence. Body mass index may be a less accurate measure of nutritional status than skinfold thickness. However, maternal body mass index and weight gain in pregnancy are positively and significantly associated with birth weight.²⁴ Furthermore, a recent longitudinal study showed that in non-obese women the correlation between body mass index and percentage of body fat remains during pregnancy.²⁵ In addition, our results are based on a much larger population and a longer follow up period. Therefore, it seems that the hypothesis that the initiating effect of adult high blood pressure is fetal nutrition in utero still demands more epidemiological evidence.²⁶

	Acknowledgements

Funding: None.

Conflict of interest: None

	References

Top Abstract Introduction Subjects and methods Results Discussion References

1. Whincup PH, Cook DG, Shaper AG. Early influences on blood pressure: a study of children aged 5-7 years. BMJ 1989;299:587-91.
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. Law CM, de Swiet M, Osmond C, Fayers PM, Barker DJ, Cruddas AM, et al. Initiation of hypertension in utero and its amplification throughout life. BMJ 1993;306:24-7.
4. Launder LJ, Hofman A, Grabbee DE. Relation between birth weight and blood pressure: longitudinal study of infants and children. BMJ 1993;307:1451-4.
5. Whincup P, Cook D, Papacosta O, Walker M. Birth weight and blood pressure: cross sectional and longitudinal relations in childhood. BMJ 1995;311:773-6. [Abstract/Free Full Text]
6. Forrester TE, Wilks RJ, Bennet FI, Simeon D, Osmond C, Allen M, et al. Fetal growth and cardiovascular risk factors in Jamaican schoolchildren. BMJ 1996;312:156-60. [Abstract/Free Full Text]
7. Law C. Fetal influences on adult hypertension. J Hum Hypertens 1995;9:649-51. [Medline]
8. Godfrey KM, Forrester T, Barker DJP, Jackson AA, Landman JP, Hall J St E, et al. Maternal nutritional status in pregnancy and blood pressure in childhood. Br J Obstet Gynaecol 1994;101:398-403.
9. Cambell DM, 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 1996;103:273-80. [Medline]
10. Seidman DS, Laor A, Gale R, Stevenson DK, Mashiach S, Danon YL. Birth weight, current body weight and blood pressure in late adolescence. BMJ 1991;302:1235-7.
11. Macintyre S, Watt G, West P, Ecob R. Correlates of blood pressure in 15 year olds in the west of Scotland. J Epidemiol Community Health 1991;45:143-7.
12. Williams S, St. George IM, Silva PA. Intrauterine growth retardation and blood pressure at age seven and eighteen. J Clin Epidemiol 1992;45:1257-73.
13. Matthes JNA, Lewis PA, Davies DP, Bethel JA. Relation between birth weight at term and systolic blood pressure in late adolescence. BMJ 1994;308:1074-7. [Abstract/Free Full Text]
14. Lucas A, Morley R. Does early nutrition in infants born before term programme later blood pressure? BMJ 1994;309:302-8.
15. Law CM, Barker DJP. Fetal influences on blood pressure. J Hypertens 1994;12:1329-32. [Medline]
16. Harlap S, Davies AM. The pills and births: the Jerusalem study. Bethesda, MD: National Institute of Child Health and Human Development, 1978.
17. Harlap S, Davies AM, Grover NB, Prywes R. The Jerusalem perinatal study: the first decade 1964-1973. Isr J Med Sci 1977;13:1073-82.
18. Dann PM. The search for perinatal definitions and standards. Acta Paediatr Scand Suppl 1985;319:7-16.
19. Kark JD, Kedem R, Revach M. Medical examination of Israeli 17-year-olds before military service as a national resource for health information. Isr J Med Sci 1986;12:318-25.
20. Harlap S. Gender of infants conceived on different days of the menstrual cycle. N Engl J Med 1979;300;1445-8.
21. Whincup PH, Cook DG, Papacosta O. Do maternal and intrauterine factors influence blood pressure in childhood? Arch Dis Child 1992;67:1423-9.
22. Jones DW, Kim JS, Andrew ME, Kim SJ, Hong YP. Body mass index and blood pressure in Korean men and women: the Korean national blood pressure survey. J Hypertens 1994;12:1433-7. [Medline]
23. Paneth N, Susser M. Early origin of coronary heart disease (the "Barker hypothesis). BMJ 1995;310:411-2.
24. Seidman DS, Ever-Hadani P, Gale R. The effect of maternal weight gain in pregnancy and birth weight. Obstet Gynecol 1989:74:240-6.
25. Lindsay CA, Huston L, Amini SB, Catalano PM. Longitudinal changes in the relationship between body mass index and percent body fat in pregnancy. Obstet Gynecol 1997;89:377-82.
26. Fall CHD, Osmond C, Barker DJP, Clark PMS, Hales CN, Stirling Y, et al. Fetal and infant growth and cardiovascular risk factors in women. BMJ 1995;310:428-32. [Abstract/Free Full Text]

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

Related Article

Patient and public involvement in clinical trials

Hazel Thornton
BMJ 2008 336: 903-904. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Thornton, H. (2008). Patient and public involvement in clinical trials. BMJ 336: 903-904 [Full text]  
• Webb, A. L, Conlisk, A. J, Barnhart, H. X, Martorell, R., Grajeda, R., Stein, A. D (2005). Maternal and childhood nutrition and later blood pressure levels in young Guatemalan adults. Int J Epidemiol 34: 898-904 [Abstract] [Full text]  
• Jarvelin, M.-R., Sovio, U., King, V., Lauren, L., Xu, B., McCarthy, M. I., Hartikainen, A.-L., Laitinen, J., Zitting, P., Rantakallio, P., Elliott, P. (2004). Early Life Factors and Blood Pressure at Age 31 Years in the 1966 Northern Finland Birth Cohort. Hypertension 44: 838-846 [Abstract] [Full text]  
• Conlisk, A. J., Barnhart, H. X., Martorell, R., Grajeda, R., Stein, A. D. (2004). Maternal and Child Nutritional Supplementation Are Inversely Associated with Fasting Plasma Glucose Concentration in Young Guatemalan Adults. J. Nutr. 134: 890-897 [Abstract] [Full text]  
• Falkner, B., Hulman, S., Kushner, H. (2004). Effect of Birth Weight on Blood Pressure and Body Size in Early Adolescence. Hypertension 43: 203-207 [Abstract] [Full text]  
• Innes, K. E., Byers, T. E., Marshall, J. A., Baron, A., Orleans, M., Hamman, R. F. (2003). Association of a Woman's Own Birth Weight with Her Subsequent Risk for Pregnancy-induced Hypertension. Am J Epidemiol 158: 861-870 [Abstract] [Full text]  
• Olausson, H., Uvnas-Moberg, K., Sohlstrom, A. (2003). Postnatal oxytocin alleviates adverse effects in adult rat offspring caused by maternal malnutrition. Am. J. Physiol. Endocrinol. Metab. 284: E475-E480 [Abstract] [Full text]  
• Lawlor, D. A., Ebrahim, S., Davey Smith, G. (2002). Is There a Sex Difference in the Association between Birth Weight and Systolic Blood Pressure in Later Life? Findings from a Meta-Regression Analysis. Am J Epidemiol 156: 1100-1104 [Abstract] [Full text]  
• Adair, L. S., Kuzawa, C. W., Borja, J. (2001). Maternal Energy Stores and Diet Composition During Pregnancy Program Adolescent Blood Pressure. Circulation 104: 1034-1039 [Abstract] [Full text]  
• Malaspina, D., Harlap, S., Fennig, S., Heiman, D., Nahon, D., Feldman, D., Susser, E. S. (2001). Advancing Paternal Age and the Risk of Schizophrenia. Arch Gen Psychiatry 58: 361-367 [Abstract] [Full text]  
• Aviv, A. (2001). Hypothesis : Pulse Pressure and Human Longevity. Hypertension 37: 1060-1066 [Abstract] [Full text]  
• IJzerman, R. G., Stehouwer, C. D. A., Boomsma, D. I. (2000). Evidence for Genetic Factors Explaining the Birth Weight-Blood Pressure Relation : Analysis in Twins. Hypertension 36: 1008-1012 [Abstract] [Full text]  
• Leon, D. A., Johansson, M., Rasmussen, F. (2000). Gestational Age and Growth Rate of Fetal Mass Are Inversely Associated with Systolic Blood Pressure in Young Adults: An Epidemiologic Study of 165,136 Swedish Men Aged 18 Years. Am J Epidemiol 152: 597-604 [Abstract] [Full text]  
• Steer, P. J (2000). Maternal hemoglobin concentration and birth weight. Am. J. Clin. Nutr. 71: 1285S-1287 [Abstract] [Full text]  
• Mi, J., Law, C., Zhang, K.-L., Osmond, C., Stein, C., Barker, D. (2000). Effects of Infant Birthweight and Maternal Body Mass Index in Pregnancy on Components of the Insulin Resistance Syndrome in China. ANN INTERN MED 132: 253-260 [Abstract] [Full text]  
• Williams, S., Poulton, R. (1999). Twins and maternal smoking: ordeals for the fetal origins hypothesis? A cohort study. BMJ 318: 897-897 [Abstract] [Full text]  
• Pharoah, P O D, Stevenson, C J, West, C R (1998). Association of blood pressure in adolescence with birthweight. Arch. Dis. Child. Fetal Neonatal Ed. 79: 114F-118 [Abstract] [Full text]  
• Tonkiss, J., Trzcinska, M., Galler, J. R., Ruiz-Opazo, N., Herrera, V. L. M. (1998). Prenatal Malnutrition-Induced Changes in Blood Pressure : Dissociation of Stress and Nonstress Responses Using Radiotelemetry. Hypertension 32: 108-114 [Abstract] [Full text]