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A Test of the Barker Hypothesis

Mark A. Klebanoff, MD, MPH; Niels J. Secher, MD; Birgitte R. Mednick, PhD; Charlotte Schulsinger, MD

Arch Intern Med. 1999;159:1607-1612.

Background  Whether individuals who were small at birth are at increased risk of developing cardiovascular disease (the Barker hypothesis) is a topic of great controversy. Although an increased risk has been suggested by several reports, the reports have been criticized for being based on ill-defined populations, for the large numbers of subjects who were unavailable for follow-up, and for inadequate control of socioeconomic status.

Objective  To determine whether a woman's weight and gestational age at birth predict the development of hypertension during her subsequent pregnancies.

Design  Prospective observational study.

Subjects  Women born in Copenhagen, Denmark, as subjects in the Danish Perinatal Study (1959-1961) were traced through the Danish Population Register. Information was obtained on their pregnancies from 1974 to 1989.

Main Outcome Measures  Onset of hypertension in pregnancy, defined by the presence of a systolic blood pressure of 140 mm Hg or greater or a diastolic blood pressure of 90 mm Hg or greater on 2 visits at or after 140 days' gestation.

Results  Hypertension developed in 11.3% of the pregnant women who were small for gestational age at birth, compared with 7.2% of the pregnant women who were not small for gestational age at birth (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.6), and in 9.4% of the pregnancies in women who were preterm at birth, compared with 7.6% of pregnancies in women who were not preterm at birth (OR, 1.3; 95% CI, 0.8-2.0). After adjustment for adult body mass index, smoking, birth order, and hypertension in the subjects' own mothers, the ORs for small-for-gestational-age women and preterm women to develop hypertension during pregnancy were 1.8 (95% CI, 1.1-2.8) and 1.5 (95% CI, 0.96-2.5), respectively.

Conclusion  These results support the Barker hypothesis, while addressing many of the methodological criticisms of previous investigations.

From the Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md (Dr Klebanoff); the Perinatal Epidemiology Research Unit, Department of Gynecology and Obstetrics, Aarhus University, Aarhus, Denmark (Dr Secher); the Department of Educational Psychology, University of Southern California, Los Angeles (Dr Mednick); and the Institut for Sygdomsforebyggelse, University of Copenhagen, Copenhagen, Denmark (Dr Schulsinger).

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