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.