Correspondence

Glucose Regulation in Young Adults with Very Low Birth Weight

N Engl J Med 2007; 357:616-617August 9, 2007

Article

To the Editor:

Hovi et al. (May 17 issue)1 report that young adults who had a very low birth weight have higher indexes of glucose intolerance and higher blood pressure than do those who were born at term. Although the authors report that maternal preeclampsia occurred significantly more frequently in the very-low-birth-weight group (35 of 166) than in the term group (13 of 172, P<0.001), they did not adjust their comparisons for this variable.

In our tertiary neonatal intensive care unit in an urban area in northern Italy, from 2000 to 2006, glucose intolerance (fasting glucose level, >215 mg per deciliter)2 was recorded in 74 of 469 neonates with a very low birth weight. Hyperglycemia occurred in 22 of 92 (23.9%) of those with a history of maternal preeclampsia,3 as compared with 52 of 377 (13.8%) without maternal preeclampsia (95% confidence interval [CI], 1.12 to 3.44; P=0.02).

Preeclampsia and insulin resistance may be associated in pregnant women,4 putting stress on the fetus and causing the onset of fetal hormonal responses, possibly involving blood pressure and glucose regulation. Since circumstances during the fetal period may have lifelong programming effects on various body functions and susceptibility to disease, our data suggest that preeclampsia — rather than very low birth weight itself — might account for early disturbances in glucose regulation.

Paolo Manzoni, M.D.
Maria Grazia Baù, M.D.
Daniele Farina, M.D.
Sant'Anna Obstetrics and Neonatology Hospital, 10126 Turin, Italy
paolomanzoni@hotmail.com

4 References

1. 1

   Hovi P, Andersson S, Eriksson JG, et al. Glucose regulation in young adults with very low birth weight. N Engl J Med 2007;356:2053-2063
   Full Text | Web of Science | Medline

2. 2

   Cowett RM, Farrag HM. Selected principles of perinatal-neonatal glucose metabolism. Semin Neonatol 2004;9:37-47
   CrossRef | Medline

3. 3

   Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1-S22
   Web of Science | Medline

4. 4

   Montoro MN, Kjos SL, Chandler M, Peters RK, Xiang AH, Buchanan TA. Insulin resistance and preeclampsia in gestational diabetes mellitus. Diabetes Care 2005;28:1995-2000
   CrossRef | Web of Science | Medline

Author/Editor Response

Manzoni et al. raise the important issue of maternal preeclampsia, which is a frequent reason for prematurity. Previous reports suggest that offspring of mothers with preeclampsia have higher-than-normal blood pressure in childhood1 and impaired glucose regulation in adulthood.2 In our study, we decided not to present results adjusted for preeclampsia because such an adjustment would not have altered the results. We here present numerical data to support this decision.

Young adults born to mothers with preeclampsia had glucose and insulin concentrations similar to those of the rest of the subjects. However, their systolic blood pressure was increased by 3.8 mm Hg (95% CI, 0.2 to 7.4). After adjustment for preeclampsia, very low birth weight was associated with an increase in the fasting insulin level of 16.7% (95% CI, 4.2 to 30.6), an increase in the 2-hour glucose level of 6.4% (95% CI, 0.3 to 12.7), and an increase in systolic blood pressure of 4.4 mm Hg (95% CI, 1.7 to 7.1). These estimates are similar to those we reported without adjustment for preeclampsia. Also, when we excluded subjects with a history of maternal preeclampsia, the effects of very low birth weight remained similar and statistically significant. Therefore, we conclude that maternal preeclampsia did not explain the association of very low birth weight with impaired glucose regulation and higher blood pressure.

Petteri Hovi, M.D.
National Public Health Institute, FI-00300 Helsinki, Finland

Sture Andersson, M.D., Ph.D.
Hospital for Children and Adolescents, FI-00029 HUS Helsinki, Finland

Eero Kajantie, M.D., Ph.D.
National Public Health Institute, FI-00300 Helsinki, Finland

2 References

1. 1

   Tenhola S, Rahiala E, Martikainen A, Halonen P, Voutilainen R. Blood pressure, serum lipids, fasting insulin, and adrenal hormones in 12-year-old children born with maternal preeclampsia. J Clin Endocrinol Metab 2003;88:1217-1222
   CrossRef | Web of Science | Medline

2. 2

   Thomas C, Hypponen E, Power C. Prenatal exposures and glucose metabolism in adulthood: are effects mediated through birth weight and adiposity? Diabetes Care 2007;30:918-924
   CrossRef | Web of Science | Medline