The Barker hypothesis (1) relates small size at birth to adult health outcomes, including coronary artery disease, hypertension, and diabetes, although the distinction has not always been made between prematurity and intrauterine growth restriction as causes of low birth weight. Previous work (24) has shown a correlation between a mother’s own growth restriction (weighing less than the 10th percentile for gestational age at her own birth) and the probability of being diagnosed with diabetes during her pregnancy. This study was designed to further evaluate that hypothesis.

A data file was created by the Vital Statistics Branch of the Department of Health, Commonwealth of Pennsylvania. This linked all females born at term in Pennsylvania in 1974 (the first year in which birth certificates requested an assessment of gestational age) who delivered singleton full-term live-born infants in the state between January 1 1999 and 31 December 2000. Members of the 1974 birth cohort were classified as small for gestational age (SGA) or appropriate for gestational age (AGA), using the 10th percentile of a contemporaneous U.S. population as the cutoff (5). The 10th percentile varies by race; as such, this distinction was preserved. Gestational age was assigned by the physician or midwife completing the birth certificate, either by clinical, menstrual, or ultrasound criteria. The study design duplicates that used for this birth-year cohort when they were evaluated at a median age of 21 years (1).

During their pregnancies in 1999–2000, subjects were dichotomized as diabetic or nondiabetic using a checkbox on the birth certificate. Specific information as to criteria for diagnosis was not available; typically, however, the classification includes either a diagnosis of diabetes made before pregnancy (pregestational diabetes) or a diagnosis of gestational diabetes made after a 3-h glucose tolerance test performed in the late second or early third trimester. The birth certificate does not distinguish gestational from pregestational diabetes. If a woman delivered more than one infant during the study period, only the later birth was included. Data were analyzed by χ2 using the EpiInfo 2002 statistical package (Centers for Disease Control and Prevention, Atlanta, GA.)

Of 74,494 females born in Pennsylvania in 1974, 7,802 were matched to births of live full-term infants in 1999–2000. The overall rate of diabetes during subjects’ pregnancies from 1999 to 2000, at ages 24–26 years, was 2.5% for blacks and 3.0% for whites. Table 1 shows no difference in the diabetes rate between women who had been SGA or AGA at birth.

Earlier work (1) has shown a tripling of the risk of pregnancy diabetes among mothers who themselves had been born SGA. In fact, women from both ends of the birth weight spectrum have higher rates of gestational diabetes than those between 2,500 and 4,000 g (2). Adjustment for prepregnancy BMI increases the odds ratio further, which suggests that women who had been SGA at birth but subsequently become overweight carry a particularly high risk of gestational diabetes.

The mechanism of association remains unclear, however. In settings of diminished intrauterine resources, lesser degrees of fetal growth occur, which may program both infant size at birth and differences in fuel handling. The SGA fetus develops less pancreatic endocrine tissue (6) and fewer β-cells, affecting the capability for insulin secretion; in addition, shunting of blood away from muscle, viscera, and adipose tissue may lead to the development of fewer insulin receptors. Alternatively, the fetal insulin hypothesis (7) proposes that insulin resistance, primarily genetically determined, accounts for both a lesser degree of insulin-mediated growth as a fetus and a greater predisposition to diabetes as an adult.

Regardless of the underlying hypothesis, the findings were surprising. A correlation was expected between having been SGA at birth and having diabetes during pregnancy at a median age of 25 years; however, the anticipated relationship did not materialize. Rates of diabetes in this population averaged 3% but did not differ between those women who had been AGA and those who had been SGA at birth. The overall rate was nearly twice as high as that in the 21-year-old Pennsylvania population studied previously (2), where the prevalence was 1.6% but in which a significant effect had been seen among the SGA mothers.

A small case-control study (8) accords with the findings presented here. Among Australian women who had been diagnosed with gestational diabetes, no difference was noted in their own birth weight compared with a control group without gestational diabetes. The diagnosis of gestational diabetes does not completely correspond, since criteria of the Australasian Diabetes in Pregnancy Society differ from those of the American Diabetes Association. It did, however, appear that among women diagnosed with gestational diabetes, postprandial glucose levels were higher among women born SGA than those born AGA (169 vs. 156 mg/dl), which may suggest more insulin resistance among women who had been SGA at birth.

The discrepancy in findings between this and the earlier Pennsylvania study (2) remains unexplained. The SGA distribution was somewhat different between the two (9% in 1995–1996 vs. 7% in 1999–2000). Although all subjects in both studies were born in 1974, and the same SGA cutoff value was applied, fewer SGA women delivered babies in 1999–2000, increasing the probability of a type 2 error. In keeping with the design of the original study, in which the 1974 birth cohort was analyzed at a median age of 21, no distinction was drawn between those individuals who were adequate for gestational age and those who in fact were large for gestational age (birth weight >90th percentile.) Thus, it is possible that the inclusion of the heaviest birth weight group, who may be more likely to be diabetic, confounded the results of the AGA group. It is difficult, however, to assume this happened only at age 25 years, while having no effect at age 21 years. Differences in the proportions of type 1, type 2, and gestational diabetes may account for the discrepancy but are impossible to track from the data available. Further analyses, such as the 1974 birth cohort ages, may clarify whether an association with low maternal birth weight and diabetes in pregnancy is in fact valid.

Table 1—

Risk of diabetes during pregnancy by woman’s own birthweight

Diabetes (n)No diabetes (n)Diabetes risk (%)RR (95% CI)P
Black      
 AGA 25 914 2.7 1.0  
 SGA 78 1.3 0.46 (0.02–3.31) 0.71 
White      
 AGA 188 6,138 3.0 1.0  
 SGA 16 442 3.5 1.18 (0.71–1.94) 0.53 
Total      
 AGA 213 7,052 2.9 1.0  
 SGA 17 520 3.2 1.08 (0.63–1.83) 0.76 
Diabetes (n)No diabetes (n)Diabetes risk (%)RR (95% CI)P
Black      
 AGA 25 914 2.7 1.0  
 SGA 78 1.3 0.46 (0.02–3.31) 0.71 
White      
 AGA 188 6,138 3.0 1.0  
 SGA 16 442 3.5 1.18 (0.71–1.94) 0.53 
Total      
 AGA 213 7,052 2.9 1.0  
 SGA 17 520 3.2 1.08 (0.63–1.83) 0.76 
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.