Corresponding author:
Dr Jack Milln
MRC/UVRI & LSHTM Uganda Research Unit, Plot 51-59, Nakiwogo Road, P. O. BOX 49, Entebbe, Uganda.
Tel.: +256 793 392872. No fax available
jackmilln@doctors.org.uk
Running title: Pregnancy outcomes associated with GDM in Uganda
ABSTRACT – as per BJOG template, 250 words (currently 248)
Objective: To determine whether hyperglycaemia in the gestational diabetes (GDM) range independently predicts adverse pregnancy outcomes in Uganda.
Design: Prospective observational cohort study.
Setting: Five major hospitals in urban/semi-urban central Uganda.
Sample: 237 women with gestational diabetes, 2,641 normoglycaemic controls.
Methods: Women were screened with oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. Cases of GDM were identified (WHO 2013 diagnostic criteria) and received standard care. Data was collected on maternal demographics, anthropometrics, prenatal management, umbilical cord c-peptide levels, and pregnancy outcomes. Participants with diabetes in pregnancy (DIP) were excluded from the analysis.
Outcomes: Primary outcomes: Birthweight large for gestational age (LGA; >90th centile) and perinatal death. Secondary outcomes: Caesarean delivery, preterm birth <37 weeks, umbilical cord c-peptide concentration >90th centile (>1.35 mcg/L), and neonatal admission.
Results: Women with GDM had a median of only two glucose measurements recorded in third trimester, and only one fifth received therapeutic management (mostly metformin, one participant received insulin).
GDM was not independently associated with LGA (adjusted odds ratio, aOR 1.12; 95% CI 0.81-1.56) or perinatal death (aOR 0.66; 95% CI 0.26-1.66), but increased the risk of Caesarean delivery. Mid-gestational BMI of >30kg/m2 was strongly associated with LGA, and mean arterial pressure >90 mmHg was the strongest predictor of perinatal death.
Conclusions: Even without active management, GDM was not associated with large birthweight or perinatal death in this population. Interventions that target blood pressure and obesity are likely to be more beneficial in improving LGA and perinatal mortality, than management of GDM.
Funding: Medical Research Council
Keywords: Gestational diabetes, Africa
Tweetable abstract: ‘GDM does not predict large birthweight or perinatal death in Uganda, despite low intensity management; interventions targeting blood pressure and obesity are likely more beneficial’
INTRODUCTION - 400 words for BJOG (currently 392)
Hyperglycaemia first detected in pregnancy (HIP) is currently classified, based on 75g oral glucose tolerance test (OGTT), as diabetes in pregnancy (DIP) or gestational diabetes mellitus (GDM), a milder form.1 While the association between DIP and poor pregnancy outcomes is clear2, the contribution of milder levels of hyperglycaemia in the GDM range (fasting glucose 5.1-7.0 mmol/L, 2-hour OGTT glucose level 8.5-11.0 mmol/L) has long been debated. Recently, the HAPO study showed hyperglycaemia within the GDM range was linearly associated with adverse pregnancy outcomes, notably large birthweight (>90thcentile).3 This has led to recent tightening of international diagnostic criteria for GDM in order to capture women with milder derangements in glucose control.4 Subsequently, some studies have shown that treating such mild levels hyperglycaemia is associated with modest improvement in outcomes, although in most cases this required intensive interventions such as insulin use, multiple daily self-monitoring of blood glucose5 or induction of labour.6,7
Both the HAPO and subsequent intervention studies were largely undertaken in high-income countries, and the benefits of these screening and management approaches may not necessarily directly translate to other populations, particularly those in resource poor settings, such as sub-Saharan Africa (SSA). The International Diabetes Federation (IDF) estimates that 1 in 6 women in the African region may be affected by hyperglycaemia in pregnancy, raising the profile of GDM on the international development agenda around NCD prevention and management.8 However, in most countries in SSA, screening and treatment of HIP is not common, and there is paucity of studies on screening, treatment and obstetric outcomes of HIP; loose recommendations are largely based on external evidence, or on small studies with heterogeneous methodologies and criteria.9–11 In these resource constrained settings, there is a clear need to develop optimal screening and management strategies that will identify and target women with HIP who are at significant risk of clinically relevant adverse obstetric outcomes.
The aim of this study was therefore to critically assess whether hyperglycaemia in the GDM range, obtained by OGTT, independently predicted poor pregnancy outcomes, particularly large birthweight (defined as >90th centile) and perinatal death, in women living in urban and peri-urban Uganda. Perinatal death was chosen as an outcome in our study due to the higher perinatal mortality rate in the SSA setting, compared to sites in the HAPO study. Other variables/exposures with potential to impact pregnancy outcomes were also explored.