Maternal glycemic control in diabetic pregnancies and neurodevelopmental outcomes in preschool aged children. A prospective cohort study☆
Introduction
There are conflicting reports regarding the relationship between maternal glycemic control during diabetic pregnancy and neurodevelopmental outcomes of the offspring. Some studies found no association between maternal glycemic control and their children's intellect [[1], [2], [3]]. Others found an adverse association between poor maternal glycemic control and intellect [4,5], developmental quotient [6], hand-eye coordination [7], motor test scores [7,8], school grades [9] and cognitive scores in adult males [10]. However, participants in most of these studies were born in the 1960s through to 1990s and management of diabetes in pregnancy has evolved since that time [[11], [12], [13], [14], [15]]. Furthermore, many studies did not adjust for confounding factors such as obesity, parental education or socioeconomic status [1,2,[6], [7], [8],16], or were not large enough to compare outcomes between children of mothers with different types of diabetes.
The socioeconomic status of a child's family is a well-known influence on their development [17] and there is increasing evidence that maternal obesity has an adverse effect on their children's neurodevelopment [[18], [19], [20], [21], [22], [23], [24], [25], [26], [27]]. Obesity is associated with increased risk of diabetes in pregnancy [28] and with poorer socioeconomic status [29,30]. The variation in findings from previous studies could thus be due to confounding.
Reports of the effect of intrapartum glycemic control on risk of neonatal hypoglycemia also yield conflicting results. In cohorts with a high percentage of diabetic women maintaining blood glucose concentrations within target ranges of 3–6 mmol/L or 4–7 mmol/L during labor [31,32], no association was found between maternal intrapartum and neonatal blood glucose concentrations. However, other studies found higher maternal blood glucose concentrations during labor were associated with an increased likelihood of neonatal hypoglycemia [[33], [34], [35], [36], [37]], Since neonatal hypoglycemia can itself lead to adverse neurodevelopmental outcomes, it is possible that an interaction between maternal glycemic control and neonatal hypoglycemia determines later outcomes.
We sought to determine the relationship between maternal glycemic control during pregnancy and labor in diabetic pregnancy and offspring neurodevelopmental outcomes, accounting for a range of potential confounders and also any interaction with neonatal hypoglycemia.
Section snippets
Sample
Eligible children were born to mothers with either pre-existing or gestational diabetes who were part of a prospective cohort study, the CHYLD Study, which recruited infants at risk of neonatal hypoglycemia (maternal diabetes, late preterm birth between 32 and 36 weeks' gestation, birthweight less than 10th centile or <2500 g (small) or birthweight greater than 90th centile, or >4500 g (large)) between 2006 and 2010 at Waikato Hospital, Hamilton, New Zealand [38,39]. Children born ≥35 weeks'
Results
Primary outcome data were available for 196/229 (86%) eligible children (196/231, 85% of recruited children) (Fig. 1). The majority of children (155/196, 79%) were born to mothers with gestational diabetes. As expected, diabetes management varied by diabetes type (Table 1). Mothers with type 1 diabetes had the lowest BMI at booking, followed by those with gestational and then type 2 diabetes. Babies of mothers with gestational diabetes were born half a week later, on average, than those born to
Discussion
We sought to examine the relationship between maternal glycemic control in pregnancy and labor, and neurosensory impairment in the children of diabetic mothers. We found that maternal glycemic control in pregnancy and labor was not associated with offspring neurodevelopment at preschool ages.
Our findings agree with some studies which found no association between IQ at three years of age and maternal HbA1c [2,3], but are contrary to others, which found an association between HbA1c and offspring
Conclusions
Children born to mothers with diabetes during pregnancy have a high rate of neurosensory impairment at preschool ages, but this is not associated with measures of maternal glycemic control during pregnancy or the intrapartum period.
Sources of funding
RG held a research fellowship from the New Zealand Diabetes Foundation. The CHYLD study was supported by grant R01HD069622 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, by grant 10-399 from the Health Research Council of New Zealand, by the Auckland Medical Research Foundation, and by Gravida, National Research Centre for Growth and Development, New Zealand. The content is solely the responsibility of the authors and does not necessarily represent the
Author contributions
RG, JA had full access to all of the data in the study. RG, DH, JA, JH and TW were involved with the acquisition of data. RG, JA, JH, and CM were involved in the analysis, interpretation and statistical analysis of data.
RG, JA and JH drafted the manuscript and designed the tables. All authors critically revised the manuscript for important intellectual content and approved the final manuscript. JA is the guarantor of this work and takes responsibility for the contents of this article and the
Acknowledgements
We are grateful to the children and families who participated in the CHYLD study and The Children with Hypoglycemia and Their Later Development (CHYLD) Study Team:
Liggins Institute, The University of Auckland, Auckland, New Zealand: Judith Ansell, PhD, Anne Jaquiery, PhD, Kelly Jones, PhD, Sapphire Martin, BNurs, Christina McQuoid, DipEdPsych, Jenny Rogers, MHSc, Heather Stewart, Anna Tottman, MBBS, Kate Williamson, MBBS, Ellen Campbell, PhD, Coila Bevan, BA, Tineke Crawford, Kelly Fredell,
Conflict of interest statement
None declared.
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The results of this study were presented at the Perinatal Society of Australia and New Zealand Annual Congress, Canberra, 2nd–5th April 2017.