SPRING: an RCT study of probiotics in the prevention of gestational diabetes mellitus in overweight and obese women
Marloes Dekker Nitert
0
1
Helen L Barrett
0
1
Katie Foxcroft
2
Anne Tremellen
6
Shelley Wilkinson
5
6
Barbara Lingwood
1
Jacinta M Tobin
4
Chris McSweeney
3
Peter O'Rourke
8
H David McIntyre
7
Leonie K Callaway
0
2
0
School of Medicine, The University of Queensland
,
Herston
,
Australia
1
The UQ Centre for Clinical Research, The University of Queensland
,
RBWH campus, Butterfield street, Herston QLD 4029
,
Australia
2
The Royal Brisbane and Women's Hospital
,
Herston
,
Australia
3
CSIRO
,
St Lucia
,
Australia
4
Western Clinical School, The University of Melbourne
,
Melbourne
,
Australia
5
Department of Nutrition & Dietetics, Mater Mothers' Hospital
,
Brisbane
,
Australia
6
Mater Medical Research Institute, Mothers' & Babies Theme
,
South Brisbane
,
Australia
7
Mater Clinical School, The University of Queensland
,
South Brisbane
,
Australia
8
Statistics Unit, Queensland Institute of Medical Research
,
Herston
,
Australia
Background: Obesity is increasing in the child-bearing population as are the rates of gestational diabetes. Gestational diabetes is associated with higher rates of Cesarean Section for the mother and increased risks of macrosomia, higher body fat mass, respiratory distress and hypoglycemia for the infant. Prevention of gestational diabetes through life style intervention has proven to be difficult. A Finnish study showed that ingestion of specific probiotics altered the composition of the gut microbiome and thereby metabolism from early gestation and decreased rates of gestational diabetes in normal weight women. In SPRING (the Study of Probiotics IN the prevention of Gestational diabetes), the effectiveness of probiotics ingestion for the prevention of gestational diabetes will be assessed in overweight and obese women. Methods/design: SPRING is a multi-center, prospective, double-blind randomized controlled trial run at two tertiary maternity hospitals in Brisbane, Australia. Five hundred and forty (540) women with a BMI > 25.0 kg/m2 will be recruited over 2 years and receive either probiotics or placebo capsules from 16 weeks gestation until delivery. The probiotics capsules contain > 1x109 cfu each of Lactobacillus rhamnosus GG and Bifidobacterium lactis BB-12 per capsule. The primary outcome is diagnosis of gestational diabetes at 28 weeks gestation. Secondary outcomes include rates of other pregnancy complications, gestational weight gain, mode of delivery, change in gut microbiome, preterm birth, macrosomia, and infant body composition. The trial has 80% power at a 5% 2-sided significance level to detect a >50% change in the rates of gestational diabetes in this high-risk group of pregnant women. Discussion: SPRING will show if probiotics can be used as an easily implementable method of preventing gestational diabetes in the high-risk group of overweight and obese pregnant women.
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Background
The incidence of gestational diabetes mellitus (GDM),
diabetes mellitus first diagnosed during pregnancy, is
on the rise in concordance with the rise in overweight
and obesity in the obstetric population [1]. GDM is
associated with short term and long term morbidity for
mother and baby. In the short term, women with GDM
have an increased risk of developing preeclampsia and
delivery by Cesarean section [2,3]. For the infant,
maternal GDM increases the risk of excessive adiposity,
macrosomia (a birth weight of >4000 g), shoulder
dystocia, admittance to the neonatal intensive care unit and
neonatal hypoglycemia [4,5]. In the long term, maternal
GDM is associated with increased risk of obesity as well
as metabolic (type 2 diabetes) and cardiovascular disease
in both mother and baby [6-8]. While current therapy,
which is focused on normalizing blood glucose levels, is
variably successful in reducing the short term
complications of GDM, this may not be true for the
longer term complications [9]. Therefore, prevention of
GDM would be preferable.
The incidence of GDM is higher in women who are
overweight or obese prior to falling pregnant [10].
Strategies for the prevention of GDM have until now been
restricted to diet and exercise interventions, which
have had mixed results [11,12]. Many of these trials
have had small sample sizes and their methodological
heterogeneity complicates comparability. Additionally,
there are substantial barriers to pregnant women
engaging in intensive lifestyle intervention programs
[13,14].
The role of the gut microbiome as a modulator of
metabolic and inflammatory process is currently being
investigated. The gut microbiome is the composite of
bacterial species present in the gut. Many factors
influence the exact gut microbiome species composition in
adult life including antibiotic therapy in early life [15],
growth and inhibitory factors determined by diet, host
and microbial factors as well as luminal pH, osmolarity
and organism replication rates [16]. Gut microbiome
species have discrete capabilities in generating energy
for take-up by the host. The gut microbiome (...truncated)