BMJ 1999;319:1403-1407 ( 27 November )

Papers

Growth in utero and during childhood among women who develop coronary heart disease: longitudinal study

T Forsén, research fellow a,  J G Eriksson, senior researcher a,  J Tuomilehto, professor a,  C Osmond, statistician b,  D J P Barker, director b. 

a National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit, Mannerheimintie 166, Helsinki, Finland, b Medical Research Council Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD

Correspondence to: D J P Barker david.barker{at}mrc.soton.ac.uk

    Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References

Objective: To examine whether women who develop coronary heart disease have different patterns of fetal and childhood growth from men in the same cohort who develop the disease.
Design: Follow up study of women whose body size at birth was recorded and who had an average of 10 measurements of height and weight during childhood.
Setting: Helsinki, Finland.
Subjects: 3447 women who were born in Helsinki University Central Hospital during 1924-33 and who went to school in Helsinki.
Main outcome measures: Hazard ratios for hospital admission for or death from coronary heart disease.
Results Coronary heart disease among women was associated with low birth weight (P=0.08 after adjustment for gestation, P=0.007 after adjustment for placental weight) and was more strongly associated with short body length at birth (P=0.001 and P<0.0001, respectively). The hazard ratio for women developing coronary heart disease increased by 10.2% (95% confidence interval 4.3 to 15.7) for each cm decrease in length at birth. The effect of short length at birth was greatest in women whose height "caught up" after birth so that as girls they were tall. Such girls tended to have tall mothers. In contrast, men in the same cohort who developed the disease were thin at birth rather than short, showed "catch up" growth in weight rather than height, and their mothers tended to be overweight rather than tall.
Conclusion: Coronary heart disease among both women and men reflects poor prenatal nutrition and consequent small body size at birth combined with improved postnatal nutrition and "catch up" growth in childhood. The disease is associated with reductions in those aspects of body proportions at birth that distinguish the two sexes---short body length in women and thinness in men.


Key messages

  • Coronary heart disease in women is associated with low birth weight but more strongly with short body length at birth

  • Among men in the same cohort coronary heart disease is also associated with low birth weight but more strongly with thinness at birth

  • In the whole cohort body proportions at birth differed in the two sexes: the girls were short and the boys were thin

  • These differences may reflect intrinsic sex differences in rates of fetal growth at similar levels of maternal nutrition

  • The slower fetal growth of females may underlie their lower rates of coronary heart disease



    Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References

In both men and women the development of coronary heart disease has been shown to be associated with low birth weight in relation to the length of gestation.1-3 An interpretation of this is that coronary heart disease originates through adaptations that the fetus makes when it is undernourished.4 These adaptations include alterations in metabolism, hormonal output, and the distribution of cardiac output, and they may be combined with slowing of growth.5 Birth weight is a crude marker of fetal growth, as the same birth weight may be the outcome of many different paths of growth.6 Insights into the fetal adaptations that lead to coronary heart disease have come from studying body proportions at birth. Thinness at birth and shortness at birth---outcomes of different paths of reduced fetal growth---have been found to be associated with different biological risk factors for coronary heart disease.4 Placental weight has also been found to be an independent predictor of coronary heart disease in some studies. 7 8

We have previously described death rates from coronary heart disease among a group of men who were born in Helsinki during 1924-33. 8 9 Their body size at birth was recorded in detail. As expected coronary heart disease was associated with low birth weight, after adjustment for gestation, but was more strongly associated with thinness at birth, measured by a low ponderal index (birth weight/length3). The growth of these men through childhood and their living conditions were also recorded. This allowed us to examine for the first time the association between childhood growth and death from coronary heart disease, taking into account size at birth. We found that the highest death rates from coronary heart disease occurred in boys who were thin at birth but whose weight caught up so that they had an above average body mass from the age of 7 years.

We report here findings among the corresponding cohort of women born in the same hospital over the same period of time. The tempo of fetal and childhood growth differs in boys and girls. 10 11 Hence the paths of early growth that lead to coronary heart disease may differ in the two sexes.

    Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References

We studied a sample of women who were born at the University Central Hospital during 1924-33 and who went to school in the city of Helsinki; 60% of all births in the city occurred in this hospital. Details of the birth records kept there have been previously described.8 Data on the mothers include age, parity, height, and date of last menstrual period, together with body weight measured on admission in labour. Data on their newborn babies include birth weight, length, head circumference, and placental weight. We studied women who were born at the hospital and who went to school in the city of Helsinki and were still resident in Finland in 1971. School health records for all children attending school in Helsinki are stored in the city archive. Details of these records have been described previously.9 They include an average of 10 (SD 4) measurements of length and weight between the ages of 6 and 16 years, recorded at periodic medical examinations. They also include the number of other people living in the child's home---recorded at the time of first examination---and the number of rooms. Since 1971 all residents of Finland have been assigned a unique personal identification number.

From the birth and school health records and identification numbers we identified 3688 women who fulfilled the criteria. Of these women, 241 subsequently emigrated, and the date of emigration was not always recorded. We therefore excluded them from the study to leave 3447.

By using the personal identification number we identified all hospital admissions and deaths among the women during 1971-95. Because death rates from coronary heart disease are much lower among women than men we ascertained fatal and non-fatal coronary disease rather than fatal disease alone, as in our study of men. All hospital admissions in Finland are recorded in the national hospital discharge register. All deaths are recorded in the national mortality register. Causes of hospital admissions or deaths were recorded according to ICD-8 (international classification of diseases, 8th revision) until 1986; thereafter ICD-9 was used until 1995. The first three digits from the cause of admission or death were used to identify the occurrence of coronary heart disease (ICD-8 and ICD-9 codes 410-414). Using the father's occupation, which was on the birth records, we grouped the men according to a social classification used by the Central Statistical Office. Overall, 85% of the fathers were labourers, and 11% were classified as lower middle class. Together these constitute the lower social class as opposed to the upper social class.

Statistical analysis---We examined the trends in hazard ratios with maternal, neonatal, and childhood measurements. Tests for trend were based on Cox's proportional hazards model. We converted each measurement of height, weight, and body mass index for each girl to a Z score.12 We interpolated between successive Z scores with a piecewise linear function and so obtained a Z score at each birthday from age 7 to 15 years. We back transformed these Z scores to obtain the corresponding height, weight, and body mass index at these ages.

    Results
Top
Abstract
Introduction
Methods
Results
Discussion
References

Maternal, neonatal, and childhood characteristics of the 3447 women are shown in table 1. Of these women, 247 had been admitted to hospital for coronary heart disease, of whom 35 died from the disease. A further 32 had died without admission to hospital. We therefore analysed data on 279 women with coronary heart disease. The annual death rate at ages 45 to 64 years was 0.8 per 1000 compared with 3.9 per 1000 in men.


                              
View this table:
[in this window]
[in a new window]
 

Table 1. Maternal, neonatal, and childhood characteristics of 3447 women born at Helsinki University Central Hospital during 1924-33 


                              
View this table:
[in this window]
[in a new window]
 

Table 2. Hazard ratios for coronary heart disease according to size at birth and height at age 7 years

Size at birth
Table 2 shows hazard ratios for coronary heart disease according to size at birth. The ratios fell with increasing birth weight, although this was not significant. Hazard ratios were not related to the length of gestation, but adjustment for gestation strengthened the association with birth weight. Hazard ratios fell more steeply with increasing length. The hazard ratio for developing coronary heart disease increased by 10.2% (95% confidence interval 4.3 to 15.7) for each cm decrease in length at birth, adjusted for gestation. There were no trends with head circumference or ponderal index.

Hazard ratios tended to rise with increasing placental weight, although this trend was not significant. There was, however, a significant rise with an increasing ratio of placental weight to birth weight (P=0.01, adjusted for gestation). In a simultaneous analysis with birth weight, placental weight, and gestational age the hazard ratios fell with increasing birth weight (P=0.007) but rose with increasing placental weight (P=0.03). There were stronger trends in a simultaneous analysis of birth length, placental weight, and gestational age, the hazard ratios falling with increasing birth length (P<0.0001) and rising with increasing placental weight (P=0.02). The hazard ratios increased by 13.8% (7.5 to 19.6) for each cm decrease in length at birth and increased by 14.8% (2.6 to 28.3) for each 100 g increase in placental weight. The trends with length and placental weight were similar for fatal and non-fatal disease.

Table 3 shows hazard ratios according to length and placental weight. Because the relative size of the body and placenta change during gestation we excluded preterm babies. Compared with women who were longest at birth but had the lowest placental weight, whose hazard ratio was set at 1.0, the highest ratio, 5.2, was in women who were short at birth but had heavy placentas.


                              
View this table:
[in this window]
[in a new window]
 

Table 3. Hazard ratios for coronary heart disease according to length at birth and placental weight in women born at term. Number of cases in parentheses

Growth in childhood
At each age from 7 to 15 years the mean heights and weights of women who developed coronary heart disease were below those of all other women. At 7 years, for example, their height was 0.42 cm less and their weight 0.20 kg less. At no age, however, were the differences significant. At birth their length was 0.17 SD below average; while at 7 and 15 years their heights were only 0.08 SD and 0.02 SD below average, respectively. Therefore their heights and weights had largely "caught up" between birth and 15 years. Table 4 shows the combined effects of length at birth and height in childhood on hazard ratios for coronary heart disease. Height at 7 years is used but the findings with all other ages are similar. The hazard ratio for women who were longest at birth and tallest as children is set at 1.0. The fall in risk of coronary heart disease with increasing length at birth was steeper among women who were tallest as girls. This interaction between birth length and childhood height was significant (P=0.02). At no age in childhood was body mass index related to later coronary heart disease.


                              
View this table:
[in this window]
[in a new window]
 

Table 4. Hazard ratios for coronary heart disease according to length at birth, adjusted for gestation and placental weight, and height at age 7 years. Numbers of cases in parentheses

Maternal characteristics
The mothers' heights and their weights and body mass indices during pregnancy were unrelated to the occurrence of coronary heart disease in their daughters. When, however, we divided the mothers according to their height, using the median height of 1.58 metres as in our previous analysis, we found that the interactive effects of short length at birth and tallness in childhood on coronary heart disease was stronger among the daughters of taller women (P=0.006 for interaction between birth length and height at 7 years in daughters of tall women). As expected, taller mothers tended to have taller daughters, the correlation coefficient between mother's height and daughter's height at 7 years being 0.36.

Crowding in the home and social class during childhood
An examination of the average number of inhabitants and rooms in the homes where the girls grew up showed that 47% of them lived in homes with only one room (see table 1). We used the ratio of the number of inhabitants to the number of rooms as an index of crowding. Table 5 shows that families living in less crowded homes were of higher social class, and the daughters were taller at all ages. Coronary heart disease, however, was unrelated to the number of inhabitants, number of rooms, crowding, or social class in childhood.


                              
View this table:
[in this window]
[in a new window]
 

Table 5. Crowding in home, fathers' social class, daughters' heights at age 7 years, and hazard ratios for coronary heart disease

Sex differences in fetal growth
In comparison with the men in the cohort the women had smaller head circumferences at birth (34.3 cm v 34.9 cm), shorter body lengths at birth (49.7 cm v 50.2 cm), and lower birth weights (3315 g v 3443 g). Mean placental weights, however, were similar (628 g v 634 g). During childhood the heights and weights of the men and women were similar until adolescence when, as expected, women became shorter and heavier. Table 6, which gives the percentage of girls among term babies according to length at birth and placental weight, shows that the small differences in average body size at birth between the sexes conceal large differences in proportionate size. Short body length in relation to high placental weight, the pattern which predicts coronary heart disease in women (table 3), is much more common among girls than boys (P<0.0001; table 6). In contrast, table 7 shows that thinness at birth in relation to a large head circumference is much more common among boys than girls (P<0.0001); and it is thinness at birth that predicts coronary heart disease in men.


                              
View this table:
[in this window]
[in a new window]
 

Table 6. Percentage of girls among term babies according to length and placental weight. Number of babies in parentheses


                              
View this table:
[in this window]
[in a new window]
 

Table 7. Percentage of boys among term babies according to head circumference and ponderal index. Number of babies in parentheses



    Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References

In this study in Finland we have examined the paths of fetal and childhood growth that are associated with the later development of coronary heart disease in women. We found that these paths of growth differed from those of men in the same birth cohort who developed coronary heart disease. Because women have much lower rates of coronary heart disease we combined death and hospital discharge rates, whereas in our report on men we described only death rates.9 Among the women, however, the paths of growth associated with fatal and non-fatal disease were similar.

Our study was restricted to women who were born in Helsinki University Central Hospital. This would introduce a bias only if the associations between size at birth, childhood growth, and coronary heart disease differed between those born in the hospital and those born outside the hospital. The fathers of 85% of the women were classed as labourers. The women may therefore not be representative of all women living in Helsinki, although we know that in the early years of this century around 60% of men in the city were labourers. We ascertained coronary heart disease through the national mortality and national hospital discharge registers. The validity of these records has previously been reported. 13 14

Sex differences in fetal growth and coronary heart disease
In keeping with findings among women in the United Kingdom,1 Sweden,2 the American nurses' study,3 and India15 we found that coronary heart disease among women in the Helsinki cohort was associated with low birth weight (table 2). This trend was of only borderline significance, after adjustment for length of gestation, but it became strongly significant after adjustment for placental weight (table 3). Low birth weight therefore predicts coronary heart disease in both women and men. Our analysis of body proportions at birth, however, has shown that the paths of intrauterine growth that led to low birth weight and later coronary heart disease differed between the two sexes in the same cohort. The women were born short in length while the men were born thin; these associations being much stronger than those with birth weight. Stunting and thinness at birth may represent two different responses to fetal undernutrition, and published findings suggest that the long term consequences of these responses differ. While both have been found to be associated with raised blood pressure in later life, 16 17 stunting is associated with persistent changes in liver function, including raised serum cholesterol concentration18 and plasma fibrinogen,19 while thinness is associated with features of the insulin resistance syndrome including impaired glucose tolerance and dyslipidaemia.20

We found that the paths of fetal growth among women and men in this cohort differed. The small sex differences in average body measurements at birth (table 1) concealed large differences in body proportions (tables 6 and 7). Girls tended to be short in relation to their placental size; boys tended to be thin in relation to their head circumference. As the girls and boys were born to the same group of mothers these differences in body proportions must reflect intrinsic differences between the sexes in their paths of growth at similar levels of maternal nutrition. The rate of fetal growth of girls and boys is known to differ from an early stage of gestation, even from before implantation. 10 11 21 Girls grow more slowly. Because different parts of the body grow at different phases of gestation, sex differences in growth rates could lead to differences in body proportions at birth. In animals the rate of intrauterine growth is known to modify the effects of a brief period of maternal undernutrition on the offspring's body composition at birth. 22 23

Sex differences in childhood growth and coronary heart disease
In both women and men the effects of reduced fetal growth on the risk of coronary heart disease were increased by accelerated or "catch up" growth. Among women the effect of being short at birth was greatest in those who were tall in childhood (table 4). Men who were thin at birth increased their risk by having an above average body mass index in childhood. The risk among women was not influenced by body mass in childhood, and risk among men was not influenced by height. In our previous report we discussed several possible reasons why catch up growth could be associated with adverse outcomes in later life.9 One speculation is based on the observation that restricted fetal growth leads to permanently reduced cell numbers in tissues such as kidney, in which there is no further cell replication after birth.24 Postnatal catch up growth could be deleterious either because overgrowth of a limited cell mass disrupts cell function or because large body size imposes an excessive metabolic demand on a limited cell mass.

The childhood heights of the women were related to their mothers' heights, and the interaction between short length at birth and tallness in childhood in increasing the risk of coronary heart disease was stronger in the daughters of taller mothers. This could reflect both nutritional and genetic influences, the nutritional benefits associated with a taller, heavier mother being either direct effects during lactation or better availability of food after weaning. We used the level of crowding in the home as an index of living conditions. Women who grew up in less crowded homes were taller at all ages. The level of crowding was not, however, related to later coronary heart disease (table 5). Our findings therefore suggest that it is good nutrition and genetic influences rather than living conditions and low rates of infection that lead to catch up growth in height and increased risk of later coronary heart disease in women. A similar suggestion came from our analyses of the men, among whom catch up in weight was associated with high maternal body mass.9 We conclude that coronary heart disease among both the women and men in our study reflected poor prenatal nutrition combined with improved postnatal nutrition.

Sex differences in coronary heart disease
We have found that coronary heart disease among women and men is associated with the body proportions at birth that distinguish the two sexes. Women who develop coronary heart disease were short at birth, particularly in relation to placental weight; the men were thin. It has been suggested that the growth of every human fetus is constrained by the mother through her limited capacity to deliver nutrients to it.25 In the light of this, coronary disease could represent the outcome of more severe constraint to which female and male fetuses respond differently because female fetuses grow more slowly. By the time of birth the girls have become short and the boys thin. The long term changes in physiology and metabolism associated with shortness and thinness at birth are different, and so too it seems are the adverse effects of catch up growth in height and weight during childhood. The lower rates of coronary heart disease among women may originate in their slower rates of growth in utero.

    Acknowledgments

We thank Terttu Nopanen, Tiina Saarinen, Hillevi Öfverström-Anttila, Liisa Toivanen, Arja Purtonen, Tiina Valle, Hanna Pehkonen, and Ulla Tarvainen for abstracting the data from the records. Sigrid Rosten was responsible for data management.

Contributors: All the authors took part in the design and analysis of the study and jointly wrote the paper. The data abstraction and linkage were supervised by JGE and TF. JGE, CO, and DJPB will act as guarantors for the paper.

    Footnotes

Funding: British Heart Foundation, Jahnsson Foundation, Finska Läkaresällskapet, Orion Corporation Research Foundation, and Finnish Foundation for Cardiovascular Research.

Competing interests: None declared.

    References
Top
Abstract
Introduction
Methods
Results
Discussion
References

1. Osmond C, Barker DJP, Winter PD, Fall CHD, Simmonds SJ. Early growth and death from cardiovascular disease in women. BMJ 1993; 307: 1519-1524.
2. Leon D, Lithell HO, Vagero D, Koupilova I, Mohsen R, Berglund L, et al. Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15000 Swedish men and women born 1915-29. BMJ 1998; 317: 241-245[Abstract/Free Full Text].
3. Rich-Edwards JW, Stampfer MJ, Manson JE, Rosner B, Hankinson SE, Colditz GA, et al. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976. BMJ 1997; 315: 396-400[Abstract/Free Full Text].
4. Barker DJP. Fetal origins of coronary heart disease. BMJ 1995; 311: 171-174[Free Full Text].
5. Barker DJP. Mothers, babies and health in later life. 2nd ed. Edinburgh: Churchill Livingstone, 1998.
6. Harding JE, Johnston BM. Nutrition and fetal growth. Reprod Fertil Dev 1995; 7: 539-547[Medline].
7. Martyn CN, Barker DJP, Osmond C. Mothers' pelvic size, fetal growth, and death from stroke and coronary heart disease in men in the UK. Lancet 1996; 348: 1264-1268[Medline].
8. Forsén T, Eriksson JG, Tuomilehto J, Teramo K, Osmond C, Barker DJP. Mother's weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study. BMJ 1997; 315: 837-840[Abstract/Free Full Text].
9. Eriksson JG, Forsén T, Tuomilehto J, Winter PD, Osmond C, Barker DJP. Catch up growth in childhood and death from coronary heart disease: longitudinal study. BMJ 1999; 318: 427-431[Abstract/Free Full Text].
10. Tanner JM. Foetus into man. 2nd ed. Castlemead: Ware, 1989.
11. Pedersen JF. Ultrasound evidence of sexual difference in fetal size in first trimester. BMJ 1980; 281: 1253.
12. Royston P. Constructing time-specific reference ranges. Stat Med 1991; 10: 675-690[Medline].
13. Mahonen M, Salomaa V, Brommels M, Molarius A, Miettinen H, Pyorala K, et al. The validity of hospital discharge register data on coronary heart disease in Finland. Eur J Epidemiol 1997; 13: 403-415[Medline].
14. Rapola JM, Virtamo J, Korhonen P, Haapakoski J, Hartman AM, Edwards BK, et al. Validity of diagnoses of major coronary events in national registers of hospital diagnoses and deaths in Finland. Eur J Epidemiol 1997; 13: 133-138[Medline].
15. Stein CE, Fall CHD, Kumaran K, Osmond C, Cox V, Barker DJP. Fetal growth and coronary heart disease in South India. Lancet 1996; 348: 1269-1273[Medline].
16. Barker DJP, Godfrey KM, Osmond C, Bull A. The relation of fetal length, ponderal index and head circumference to blood pressure and the risk of hypertension in adult life. Paediatr Perinat Epidemiol 1992; 6: 35-44[Medline].
17. Martyn CN, Barker DJP, Jespersen S, Greenwald S, Osmond C, Berry C. Growth in utero, adult blood pressure, and arterial compliance. Br Heart J 1995; 73: 116-121[Abstract/Free Full Text].
18. Barker DJP, Martyn CN, Osmond C, Hales CN, Fall CHD. Growth in utero and serum cholesterol concentrations in adult life. BMJ 1993; 307: 1524-1527.
19. Martyn CN, Meade TW, Stirling Y, Barker DJP. Plasma concentrations of fibrinogen and factor VII in adult life and their relation to intra-uterine growth. Br J Haematol 1995; 89: 142-146[Medline].
20. Lithell HO, McKeigue PM, Berglund L, Mohsen R, Lithell UB, Leon DA. Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50-60 years. BMJ 1996; 312: 406-410[Abstract/Free Full Text].
21. Garn SM, Burdi AR, Babler WJ. Male advancement in prenatal head development. Am J Phys Anthropol 1974; 41: 353-359[Medline].
22. Harding J, Liu L, Evans P, Oliver M, Gluckman P. Intrauterine feeding of the growth retarded fetus: can we help? Early Hum Dev 1992; 29: 193-197[Medline].
23. Widdowson EM, McCance RA. The effect of finite periods of undernutrition at different ages on the composition and subsequent development of the rat. Proc Roy Soc Lond B 1963; 158: 329-342[Medline].
24. Pitts GC. Cellular aspects of growth and catch-up growth in the rat: a reevaluation. Growth 1986; 50: 419-436[Medline].
25. Ounsted M, Scott A, Ounsted C. Transmission through the female line of a mechanism constraining human fetal growth. Ann Hum Biol 1986; 13: 143-151[Medline].

(Accepted 24 August 1999)

© BMJ 1999
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to StumbleUpon StumbleUpon   Add to Technorati Technorati    What's this?

Relevant Articles

Longitudinal study of birth weight and adult body mass index in predicting risk of coronary heart disease and stroke in women
Janet W Rich-Edwards, Ken Kleinman, Karin B Michels, Meir J Stampfer, JoAnn E Manson, Kathryn M Rexrode, Eileen N Hibert, and Walter C Willett
BMJ 2005 330: 1115. [Abstract] [Full Text] [PDF]

Slower fetal development may protect women from heart disease
BMJ 1999 319: 0. [Full Text]

This article has been cited by other articles:

  • Ceelen, M., van Weissenbruch, M. M., Prein, J., Smit, J. J., Vermeiden, J. P.W., Spreeuwenberg, M., van Leeuwen, F. E., Delemarre-van de Waal, H. A. (2009). Growth during infancy and early childhood in relation to blood pressure and body fat measures at age 8-18 years of IVF children and spontaneously conceived controls born to subfertile parents. Hum Reprod 24: 2788-2795 [Abstract] [Full text]  
  • Risnes, K. R., Romundstad, P. R., Nilsen, T. I. L., Eskild, A., Vatten, L. J. (2009). Placental Weight Relative to Birth Weight and Long-term Cardiovascular Mortality: Findings From a Cohort of 31,307 Men and Women. Am J Epidemiol 170: 622-631 [Abstract] [Full text]  
  • Rohrmann, S., Sutcliffe, C. G., Bienstock, J. L., Monsegue, D., Akereyeni, F., Bradwin, G., Rifai, N., Pollak, M. N., Agurs-Collins, T., Platz, E. A. (2009). Racial Variation in Sex Steroid Hormones and the Insulin-Like Growth Factor Axis in Umbilical Cord Blood of Male Neonates. Cancer Epidemiol. Biomarkers Prev. 18: 1484-1491 [Abstract] [Full text]  
  • Zhang, H., Meyer, K. D., Zhang, L. (2009). Fetal Exposure to Cocaine Causes Programming of Prkce Gene Repression in the Left Ventricle of Adult Rat Offspring. Biol. Reprod. 80: 440-448 [Abstract] [Full text]  
  • Meyer, K. D., Zhang, L. (2009). Short- and long-term adverse effects of cocaine abuse during pregnancy on the heart development. Ther Adv Cardiovasc Dis 3: 7-16 [Abstract]  
  • Fraser, A., Hughes, R., McCarthy, A., Tilling, K., Davies, D., Rumley, A., Lowe, G. D. O., Davey Smith, G., Ben-Shlomo, Y. (2008). Early Life Growth and Hemostatic Factors: The Barry Caerphilly Growth Study. Am J Epidemiol 168: 179-187 [Abstract] [Full text]  
  • Fei, C., McLaughlin, J. K., Tarone, R. E., Olsen, J. (2008). Fetal Growth Indicators and Perfluorinated Chemicals: A Study in the Danish National Birth Cohort. Am J Epidemiol 168: 66-72 [Abstract] [Full text]  
  • Rajaleid, K, Manor, O, Koupil, I (2008). Does the strength of the association between foetal growth rate and ischaemic heart disease mortality differ by social circumstances in early or later life?. J. Epidemiol. Community Health 62: e6-e6 [Abstract] [Full text]  
  • Mittendorfer-Rutz, E, Wasserman, D, Rasmussen, F (2008). Fetal and childhood growth and the risk of violent and non-violent suicide attempts: a cohort study of 318 953 men. J. Epidemiol. Community Health 62: 168-173 [Abstract] [Full text]  
  • Baker, J. L., Olsen, L. W., Sorensen, T. I.A. (2007). Childhood Body-Mass Index and the Risk of Coronary Heart Disease in Adulthood. NEJM 357: 2329-2337 [Abstract] [Full text]  
  • Grigore, D., Ojeda, N. B., Robertson, E. B., Dawson, A. S., Huffman, C. A., Bourassa, E. A., Speth, R. C., Brosnihan, K. B., Alexander, B. T. (2007). Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293: R804-R811 [Abstract] [Full text]  
  • Carlsen, S M, Jacobsen, G, Romundstad, P (2006). Maternal testosterone levels during pregnancy are associated with offspring size at birth.. Eur J Endocrinol 155: 365-370 [Abstract] [Full text]  
  • Fernandez-Twinn, D. S., Ekizoglou, S., Wayman, A., Petry, C. J., Ozanne, S. E. (2006). Maternal low-protein diet programs cardiac beta-adrenergic response and signaling in 3-mo-old male offspring. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291: R429-R436 [Abstract] [Full text]  
  • Johnsson, J. I, Bohlin, T. (2006). The cost of catching up: increased winter mortality following structural growth compensation in the wild. Proc R Soc B 273: 1281-1286 [Abstract] [Full text]  
  • Giustarini, E, Pinchera, A, Fierabracci, P, Roncella, M, Fustaino, L, Mammoli, C, Giani, C (2006). Thyroid autoimmunity in patients with malignant and benign breast diseases before surgery.. Eur J Endocrinol 154: 645-649 [Abstract] [Full text]  
  • Wiles, N. J., Peters, T. J., Heron, J., Gunnell, D., Emond, A., Lewis, G., for the ALSPAC Study Team, (2006). Fetal Growth and Childhood Behavioral Problems: Results from the ALSPAC Cohort. Am J Epidemiol 163: 829-837 [Abstract] [Full text]  
  • Ekelund, U., Ong, K., Linne, Y., Neovius, M., Brage, S., Dunger, D. B, Wareham, N. J, Rossner, S. (2006). Upward weight percentile crossing in infancy and early childhood independently predicts fat mass in young adults: the Stockholm Weight Development Study (SWEDES). Am. J. Clin. Nutr. 83: 324-330 [Abstract] [Full text]  
  • Jiang, B., Godfrey, K. M., Martyn, C. N., Gale, C. R. (2006). Birth Weight and Cardiac Structure in Children. Pediatrics 117: e257-e261 [Abstract] [Full text]  
  • McMullen, S., Langley-Evans, S. C. (2005). Sex-Specific Effects of Prenatal Low-Protein and Carbenoxolone Exposure on Renal Angiotensin Receptor Expression in Rats. Hypertension 46: 1374-1380 [Abstract] [Full text]  
  • Lawlor, D. A., Ronalds, G., Clark, H., Davey Smith, G., Leon, D. A. (2005). Birth Weight Is Inversely Associated With Incident Coronary Heart Disease and Stroke Among Individuals Born in the 1950s: Findings From the Aberdeen Children of the 1950s Prospective Cohort Study. Circulation 112: 1414-1418 [Abstract] [Full text]  
  • Barrenas, M.-L., Jonsson, B., Tuvemo, T., Hellstrom, P.-A., Lundgren, M. (2005). High Risk of Sensorineural Hearing Loss in Men Born Small for Gestational Age with and without Obesity or Height Catch-Up Growth: A Prospective Longitudinal Register Study on Birth Size in 245,000 Swedish Conscripts. J. Clin. Endocrinol. Metab. 90: 4452-4456 [Abstract] [Full text]  
  • Kajantie, E., Osmond, C., Barker, D. J., Forsen, T., Phillips, D. I., Eriksson, J. G (2005). Size at birth as a predictor of mortality in adulthood: a follow-up of 350 000 person-years. Int J Epidemiol 34: 655-663 [Abstract] [Full text]  
  • Rich-Edwards, J. W, Kleinman, K., Michels, K. B, Stampfer, M. J, Manson, J. E, Rexrode, K. M, Hibert, E. N, Willett, W. C (2005). Longitudinal study of birth weight and adult body mass index in predicting risk of coronary heart disease and stroke in women. BMJ 330: 1115- [Abstract] [Full text]  
  • Ekholm, K., Carstensen, J., Finnstrom, O., Sydsjo, G. (2005). The Probability of Giving Birth among Women Who Were Born Preterm or with Impaired Fetal Growth: A Swedish Population-based Registry Study. Am J Epidemiol 161: 725-733 [Abstract] [Full text]  
  • Racasan, S., Braam, B., Koomans, H. A., Joles, J. A. (2005). Programming blood pressure in adult SHR by shifting perinatal balance of NO and reactive oxygen species toward NO: the inverted Barker phenomenon. Am. J. Physiol. Renal Physiol. 288: F626-F636 [Abstract] [Full text]  
  • Zhang, L. (2005). Prenatal Hypoxia and Cardiac Programming. Reproductive Sciences 12: 2-13 [Abstract]  
  • Schooling, M., Leung, G. M, Janus, E. D, Ho, S. Y., Hedley, A. J, Lam, T. H. (2004). Childhood migration and cardiovascular risk. Int J Epidemiol 33: 1219-1226 [Abstract] [Full text]  
  • Barker, D.J.P. (2004). The Developmental Origins of Adult Disease. J. Am. Coll. Nutr. 23: 588S-595S [Abstract] [Full text]  
  • Bagby, S. P. (2004). Obesity-Initiated Metabolic Syndrome and the Kidney: A Recipe for Chronic Kidney Disease?. J. Am. Soc. Nephrol. 15: 2775-2791 [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]  
  • Saw, S-M, Tong, L, Chia, K-S, Koh, D, Lee, Y-S, Katz, J, Tan, D T H (2004). The relation between birth size and the results of refractive error and biometry measurements in children. Br J Ophthalmol 88: 538-542 [Abstract] [Full text]  
  • Pouta, A., Hartikainen, A.-L., Sovio, U., Gissler, M., Laitinen, J., McCarthy, M. I., Ruokonen, A., Elliott, P., Jarvelin, M.-R. (2004). Manifestations of Metabolic Syndrome After Hypertensive Pregnancy. Hypertension 43: 825-831 [Abstract] [Full text]  
  • Skidmore, P. M.L., Hardy, R. J., Kuh, D. J., Langenberg, C., Wadsworth, M. E. J. (2004). Birth Weight and Lipids in a National Birth Cohort Study. Arterioscler. Thromb. Vasc. Bio. 24: 588-594 [Abstract] [Full text]  
  • Forsen, T, Osmond, C, Eriksson, J G, Barker, D J P (2004). Growth of girls who later develop coronary heart disease. Heart 90: 20-24 [Abstract] [Full text]  
  • Raphael, D. (2003). Barriers to addressing the societal determinants of health: public health units and poverty in Ontario, Canada. HEALTH PROMOT INT 18: 397-405 [Abstract] [Full text]  
  • Kuh, D, Ben-Shlomo, Y, Lynch, J, Hallqvist, J, Power, C (2003). Life course epidemiology. J. Epidemiol. Community Health 57: 778-783 [Abstract] [Full text]  
  • Hack, M., Schluchter, M., Cartar, L., Rahman, M., Cuttler, L., Borawski, E. (2003). Growth of Very Low Birth Weight Infants to Age 20 Years. Pediatrics 112: e30-38 [Abstract] [Full text]  
  • Horta, B L, Barros, F C, Victora, C G, Cole, T J (2003). Early and late growth and blood pressure in adolescence. J. Epidemiol. Community Health 57: 226-230 [Abstract] [Full text]  
  • Kajantie, E., Fall, C. H. D., Seppala, M., Koistinen, R., Dunkel, L., Yliharsila, H., Osmond, C., Andersson, S., Barker, D. J. P., Forsen, T., Holt, R. I. G., Phillips, D. I. W., Eriksson, J. (2003). Serum Insulin-like Growth Factor (IGF)-I and IGF-Binding Protein-1 in Elderly People: Relationships with Cardiovascular Risk Factors, Body Composition, Size at Birth, and Childhood Growth. J. Clin. Endocrinol. Metab. 88: 1059-1065 [Abstract] [Full text]  
  • Yliharsila, H., Eriksson, J. G., Forsen, T., Kajantie, E., Osmond, C., Barker, D. J.P. (2003). Self-Perpetuating Effects of Birth Size on Blood Pressure Levels in Elderly People. Hypertension 41: 446-450 [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]  
  • Gunnarsdottir, I., Birgisdottir, B. E, Thorsdottir, I., Gudnason, V., Benediktsson, R. (2002). Size at birth and coronary artery disease in a population with high birth weight. Am. J. Clin. Nutr. 76: 1290-1294 [Abstract] [Full text]  
  • Barker, D., Eriksson, J., Forsen, T, Osmond, C (2002). Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol 31: 1235-1239 [Abstract] [Full text]  
  • Blake, K V, Gurrin, L C, Beilin, L J, Stanley, F J, Kendall, G E, Landau, L I, Newnham, J P (2002). Prenatal ultrasound biometry related to subsequent blood pressure in childhood. J. Epidemiol. Community Health 56: 713-718 [Abstract] [Full text]  
  • Williams, S., Poulton, R. (2002). Birth Size, Growth, and Blood Pressure between the Ages of 7 and 26 Years: Failure to Support the Fetal Origins Hypothesis. Am J Epidemiol 155: 849-852 [Abstract] [Full text]  
  • Regidor, E., Gutierrez-Fisac, J. L, Calle, M E., Navarro, P., Dominguez, V. (2002). Infant mortality at time of birth and cause-specific adult mortality among residents of the region of Madrid born elsewhere in Spain. Int J Epidemiol 31: 368-374 [Abstract] [Full text]  
  • Parsons, T. J, Power, C., Manor, O. (2001). Fetal and early life growth and body mass index from birth to early adulthood in 1958 British cohort: longitudinal study. BMJ 323: 1331-1335 [Abstract] [Full text]  
  • Victora, C. G, Barros, F. C, Horta, B. L, Martorell, R. (2001). Short-term benefits of catch-up growth for small-for-gestational-age infants. Int J Epidemiol 30: 1325-1330 [Abstract] [Full text]  
  • Eriksson, J. (2001). Commentary: Early catch-up' growth is good for later health. Int J Epidemiol 30: 1330-1331 [Full text]  
  • Tucker, K. L., Buranapin, S. (2001). Nutrition and Aging in Developing Countries. J. Nutr. 131: 2417S-2423 [Abstract] [Full text]  
  • Matte, T. D, Bresnahan, M., Begg, M. D, Susser, E. (2001). Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study. BMJ 323: 310-314 [Abstract] [Full text]  
  • Eriksson, J G, Forsén, T, Tuomilehto, J, Osmond, C, Barker, D J P (2001). Early growth and coronary heart disease in later life: longitudinal study. BMJ 322: 949-953 [Abstract] [Full text]  
  • Victora, C. G, Barros, F. C (2001). Commentary: The catch-up dilemma-- relevance of Leitch's 'low-high' pig to child growth in developing countries. Int J Epidemiol 30: 217-220 [Full text]  
  • Wamala, S. P, Lynch, J., Kaplan, G. A (2001). Women's exposure to early and later life socioeconomic disadvantage and coronary heart disease risk: the Stockholm Female Coronary Risk Study. Int J Epidemiol 30: 275-284 [Abstract] [Full text]  
  • Binns, C. W., Lee, M., Scott, J. A. (2001). The Fetal Origins of Disease Hypothesis: Public Health Implications for the Asia-Pacific Region. Asia Pac J Public Health 13: 68-73 [Abstract]  
  • Wahlbeck, K., Forsen, T., Osmond, C., Barker, D. J. P., Eriksson, J. G. (2001). Association of Schizophrenia With Low Maternal Body Mass Index, Small Size at Birth, and Thinness During Childhood. Arch Gen Psychiatry 58: 48-52 [Abstract] [Full text]  
  • Eriksson, J., Forsen, T., Tuomilehto, J., Osmond, C., Barker, D. (2000). Fetal and Childhood Growth and Hypertension in Adult Life. Hypertension 36: 790-794 [Abstract] [Full text]  
  • Hu, X.W, Levy, A, Hart, E.J, Nolan, L.A, Dalton, G.R, Levi, A.J (2000). Intra-uterine growth retardation results in increased cardiac arrhythmias and raised diastolic blood pressure in adult rats. Cardiovasc Res 48: 233-243 [Abstract] [Full text]  
  • Dietz, W. H (2000). Birth weight, socioeconomic class, and adult adiposity among African Americans. Am. J. Clin. Nutr. 72: 335-336 [Full text]  
  • Forsen, T., Eriksson, J., Tuomilehto, J., Reunanen, A., Osmond, C., Barker, D. (2000). The Fetal and Childhood Growth of Persons Who Develop Type 2 Diabetes. ANN INTERN MED 133: 176-182 [Abstract] [Full text]  

Rapid Responses:

Read all Rapid Responses

Sex differences in programming of CVD
Simon Langley-Evans
bmj.com, 4 Apr 2000 [Full text]
Authors' reply
D J P Barker
bmj.com, 12 Apr 2000 [Full text]
Re: Authors' reply
Simon Langley-Evans
bmj.com, 10 May 2000 [Full text]
Access jobs at BMJ Careers
Whats new online at Student BMJ