udy by Lykke et al based on vital statistics registry data from Denmark (23), preterm birth (<37 weeks) was associated with a 2-fold increased risk of T2DM in mothers after adjusting for maternal age, year of delivery, and pregnancy complications. The median study follow-up time was approximately 15 years. Unlike our study, no adjustment was made for pre-pregnancy risk factors, such as overweight/obesity and family history, strong predictors of T2DM. Another study by Catov et al found 76% increased odds of metabolic syndrome among women with a previous preterm birth 8 years following pregnancy (24). We observed a very similar 2-fold increased risk of T2DM after a moderate preterm delivery (<37 weeks) in the first 10 years after pregnancy. However, we were able to follow our cohort for an additional 20 years, which indicated that the excess risk associated with a history of moderate preterm birth was limited to the first 10 years after pregnancy. The risk associated with very preterm birth, however, arose after the first decade following the first pregnancy and remained modestly elevated throughout the 35 years of follow-up. However, the weakening over time of relative risk associated with preterm delivery and infant birth weight may reflect the increasing prevalence of other T2DM risk factors with increasing age (study time), including high BMI and increased sedentary behaviors. Therefore, our findings may suggest that these pregnancy complications may be especially useful predictors of early-onset T2DM.The increased risk of T2DM among women who experience a preterm birth may be due to chronic low-level inflammation (25,26). Several studies suggest that chronic low-level inflammation precedes the onset of T2DM (26– 28). As such, preterm birth could signal a chronic state of inflammation and an increased risk of future development of T2DM. In addition, the association between macrosomia and T2DM, independent of GDM status, could be attributed to maternal hyperglycemia, which is less overt than GDM and can lead to fetal hyperglycemia, exaggerated fetal insulin response, and macrosomia. Therefore, macrosomia could simply indicate hyperglycemia in mothers, despite not meeting clinical definitions for a GDM diagnosis. In fact, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study found a continuous association between maternal hyperglycemia and increasing birth weight (15).Strengths of this study include use of a large cohort of nurses with detailed information on both pregnancy history and diabetes and information on pre-pregnancy and reproductive risk factors for diabetes. We were also able to control for GDM and HDOP as strong predictors of T2DM. In addition, this study had an average follow-up time after first birth of 22 years, which allowed for sufficient time for a substantial proportion of participants to develop the disease (approximately 4% of the population). Furthermore, we were able to explore these research questions by using different cut points in total study time. This technique allowed us to explore periods in which certain pregnancy complications may have the most predictive value for future development of T2DM. Future studies are needed to further explore and confirm these associations based on time since pregnancy.Our study has several limitations. First, data on gestational age and birth weight were unvalidated self-reports. However, validation studies demonstrated good self-report of related pregnancy factors (16,19). Also, several validation studies show moderate to high reliability of self-report of preterm birth and infant birth weight when compared with medical records (29–31). Second, we used categories of gestational age and birth weight instead of continuous measures, which may make it difficult to see subtle changes in disease risk. Furthermore, these categorizations prevented us from examining small-for-gestational age or large-for-gestational-age infants; as such we had to restrict our analysis of birth weight to term births. Thus, our finding of an early elevation in T2DM risk for women who delivered infants that were term low birth weight may not be generalizable to women who delivered preterm infants, who were small for gestational age. We also had limited power to examine recurrent complications in later pregnancies. Finally, we had limited ability to evaluate this association among minorities, who have both a higher prevalence of these pregnancy complications and T2DM.Women who experience a preterm birth or have an infant with nonnormal birth weight are not followed up for lifestyle intervention or disease prevention after re-entry into the standard health care system for nonpregnant women. Both the American Diabetes Association and American College of Obstetrics and Gynecology recommend screening for T2DM for women with a history of GDM (32,33). If our findings are replicated, women who experience a preterm birth or have a nonnormal birth-weight infant may benefit from additional follow-up and lifestyle intervention to reduce their subsequent risk of T2DM.
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