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The effect of maternal diabetes during pregnancy on offspring health in childhood

Presented at the Neonatal Society 2010 Summer Meeting (programme).

Philipps L, Santhakumaran S, Hyde MJ, Prior E, Logan K, Gale CRK, Modi N

Neonatal Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK

Background: The prevalence of gestational diabetes has risen from 2.1 to 4.1% over the last 20 years. While gestational diabetes has traditionally been associated with macrosomia, we have suggested that the offspring of the diabetic mother may be more accurately described as adipose, rather than necessarily macrosomic (1). To date, studies of later childhood outcomes of the diabetic pregnancy have been small, of limited power and findings have been contradictory.

Aim: We conducted a systematic review to evaluate the effect of maternal diabetes on offspring body mass index (BMI) z-score. Secondary outcomes were (i) fasting blood glucose concentration (ii) systolic blood pressure (iii) diastolic blood pressure and (iv) low density lipoprotein (LDL) concentration.

Methods: A literature search was conducted in Pubmed using pre-defined search terms. Studies were included if they measured one of the outcomes of interest in controls and offspring of diabetic mothers (ODM) between 2 -16 years old. All types of maternal diabetes (insulin dependent, non-insulin dependent, gestational) were considered as exposures. Reference lists were searched for further potential studies. Efforts were made to contact the author to obtain further information if required. Where studies were comparable in exposure definition and outcome measure, a meta-analysis was carried out in RevMan5 using the inverse variance method. This was carried out separately for adjusted and unadjusted results. Where heterogeneity was present a random effects meta-analysis was carried out, otherwise a fixed effects analysis was performed. Forest plots were used to illustrate results and funnel plots were to investigate publication bias.

Results: 27 studies were eligible for inclusion in the review; of these data were available for 16. Comparing all forms of diabetes with controls, the meta-analysis found the unadjusted mean BMI z-score to be 0.26 higher in the ODM group (Fig. 1). The offspring of mothers with gestational diabetes (excluding all pre-pregnancy diabetes) had increased BMI z-scores of 0.27 (95% CI 0.04, 0.50; p = 0.01; 6 studies; ODM n = 687 controls n = 26253), offspring of maternal type 1 diabetes alone, compared to controls, had increased BMI z-score of 0.44, just falling short of significance (95% CI -0.03, 0.91, p = 0.07; 3 studies; ODM n = 178 controls n = 117). Combining studies which controlled for maternal BMI and other factors, there was no difference in adjusted mean BMI z-score in the ODM (all diabetes) group (95% CI -0.13, 0.26; p = 0.49; 3 studies; ODM n = 204 controls n = 11206). Systolic blood pressure was 4.5 mmHg higher in ODM group than controls (95% CI 2.02, 7.00, p = 0.0004; 7 studies; ODM n = 368 controls n = 1726). There were no significant differences in fasting blood glucose concentration, diastolic blood pressure or low density lipoprotein (LDL) concentration.

Conclusion: This meta-analysis shows a clear association between gestational diabetes and increased offspring BMI z-score in childhood. However, this relationship appears to be attenuated when corrected for maternal BMI suggesting that both maternal obesity and diabetes affect offspring outcome. The absence of an identifiable difference in blood glucose and LDL concentration is not surprising given the young age of the offspring when studied. However the identification of higher systolic blood pressure is of concern.

1. Logan, K. et al. (2009) Arch Dis Child. 94 (1): A13

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