Gestational diabetes, glucose intolerance with onset or first recognition during pregnancy,
is a rising problem worldwide. Both non‐pharmacological and pharmacological approaches
to the prevention of gestational diabetes have been, and continue to be explored.
Myo‐inositol, an isomer of inositol, is a naturally occurring sugar commonly found
in cereals, corn, legumes and meat. It is one of the intracellular mediators of the
insulin signal and correlated with insulin sensitivity in type 2 diabetes. The potential
beneficial effect on improving insulin sensitivity suggests that myo‐inositol may
be useful for women in preventing gestational diabetes. To assess if antenatal dietary
supplementation with myo‐inositol is safe and effective, for the mother and fetus,
in preventing gestational diabetes. We searched the Pregnancy and Childbirth Group's
Trials Register, ClinicalTrials.gov , WHO ICTRP (2 November 2015) and reference
lists of retrieved studies. We sought published and unpublished randomised controlled
trials, including conference abstracts, assessing the effects of myo‐inositol for
the prevention of gestational diabetes mellitus (GDM). Quasi‐randomised and cross‐over
trials were not eligible for inclusion, but cluster designs were eligible. Participants
in the trials were pregnant women. Women with pre‐existing type 1 or type 2 diabetes
were excluded. Trials that compared the administration of any dose of myo‐inositol,
alone or in a combination preparation were eligible for inclusion. Trials that used
no treatment, placebo or another intervention as the comparator were eligible for
inclusion. Two review authors independently assessed trials for inclusion, risk of
bias and extracted the data. Data were checked for accuracy. We included four randomised
controlled trials (all conducted in Italy) reporting on 567 women who were less than
11 weeks' to 24 weeks' pregnant at the start of the trials. The trials had small sample
sizes and one trial only reported an interim analysis. Two trials were open‐label.
The overall risk of bias was unclear. For the mother, supplementation with myo‐inositol
was associated with a reduction in the incidence of gestational diabetes compared
with control (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.29 to 0.64; three
trials; n = 502 women). Using GRADE methods this evidence was assessed as low with
downgrading due to unclear risk of bias for allocation concealment in two of the included
trials and lack of generalisability of findings. For women who received myo‐inositol
supplementation, the incidence of GDM ranged from 8% to 18%; for women in the control
group, the incidence of GDM was 28%, using International Association of Diabetes and
Pregnancy Study Groups Consensus Panel 2010 criteria to diagnose GDM. Two trials reported
on hypertensive disorders of pregnancy , a primary maternal outcome of this review.
There was no clear difference in risk of hypertensive disorders of pregnancy between
the myo‐inositol and control groups (average RR 0.43, 95% CI 0.02 to 8.41; two trials;
n = 398 women; Tau 2 = 3.23; I 2 = 69%). Using GRADE methods, this evidence was
assessed as very low , with downgrading due to wide confidence intervals with very
low event rates, a small sample size, and lack of blinding and unclear allocation
concealment methods, and a lack of generalisability. For women who received myo‐inositol
the risk of hypertensive disorders of pregnancy ranged from 0% to 33%; for women in
the control group the risk was 4%. For the infant, none of the included trials reported
on the primary neonatal outcomes of this systematic review ( large‐for‐gestational
age , perinatal mortality , mortality or morbidity composite ). In terms of this
review's secondary outcomes, there was no clear difference in the risk of caesarean
section between the myo‐inositol and control groups (RR 0.95, 95% CI 0.76 to 1.19;
two trials; n = 398 women). Using GRADE methods, this evidence was assessed as low
, with downgrading due to unclear risk of bias in one trial and lack of generalisability.
For women who received myo‐inositol supplementation, the risk of having a caesarean
section ranged from 34% to 54%; for women in the control group the was 45%. There
were no maternal adverse effects of therapy in the two trials that reported on this
outcome (the other two trials did not report this outcome). Two trials found no clear
difference in the risk of macrosomia between infants whose mothers received myo‐inositol
supplementation compared with controls (average RR 0.35, 95% CI 0.02 to 6.37; two
trials; n = 398 infants;Tau 2 = 3.33; I 2 = 73%). Similarly, there was no clear
difference between groups in terms of neonatal hypoglycaemia (RR 0.36, 95% CI 0.01
to 8.66) or shoulder dystocia (average RR 2.33, 95% CI 0.12 to 44.30, Tau 2 = 3.24;
I 2 = 72%). There was a lack of data available for a large number of maternal and
neonatal secondary outcomes, and no data for any of the long‐term childhood or adulthood
outcomes, or for health service cost outcomes. Evidence from four trials of antenatal
dietary supplementation with myo‐inositol during pregnancy shows a potential benefit
for reducing the incidence of gestational diabetes. No data were reported for any
of this review's primary neonatal outcomes. There were very little outcome data for
the majority of this review's secondary outcomes. There is no clear evidence of a
difference for macrosomia when compared with control. The current evidence is based
on small trials that are not powered to detect differences in outcomes including perinatal
mortality and serious infant morbidity. All of the included studies were conducted
in Italy which raises concerns about the lack of generalisability of the evidence
to other settings. There is evidence of inconsistency and indirectness and as a result,
many of the judgements on the quality of the evidence were downgraded to low or
very low quality (GRADEpro Guideline Development Tool). Further trials for this promising
antenatal intervention for preventing gestational diabetes are encouraged and should
include pregnant women of different ethnicities and varying risk factors and use of
myo‐inositol (different doses, frequency and timing of administration) in comparison
with placebo, diet and exercise or pharmacological interventions. Outcomes should
include potential harms including adverse effects. What is the issue? This review
aimed to investigate if myo‐inositol is an effective antenatal dietary supplement
for preventing gestational diabetes in pregnant women. Women who develop gestational
diabetes have a higher risk of experiencing complications during pregnancy and birth,
as well as developing diabetes later on in life. The babies of mothers who have gestational
diabetes can be larger than they should be potentially causing injuries to the babies
at birth. These babies are at risk of diabetes even as young children or young adults.
Why is this important? The number of women being diagnosed with gestational diabetes
is increasing around the world so finding simple and cost‐effective ways to prevent
women developing gestational diabetes is important. Myo‐inositol is a naturally occurring
sugar found in cereals, corn, green vegetables and meat that has a role in the body's
sensitivity to insulin. What evidence did we find? We searched for studies on 2 November
2015 and included four small randomised controlled trials involving a total of 567
women who were less than 11 weeks' to 24 weeks' pregnant at the start of the trials.
The quality of the evidence was assessed as low or very low and the overall risk
of bias was unclear. Myo‐inositol was associated with a reduction in the rate of gestational
diabetes ( low quality evidence ), reducing the incidence from 28% in women who did
not take the supplement, to between 8% and 18% in the women who took it. There was
no difference between groups in terms of the number of women who had hypertensive
disorders of pregnancy (including pre‐eclampsia, eclampsia and abnormally high blood
pressure during pregnancy) ( very low quality evidence ). The trials did not provide
any information about the number of babies that died (either before being born or
shortly afterwards) or babies that were large‐for‐gestational age. There were no maternal
adverse effects of therapy in the two trials that reported on this outcome (the other
two trials did not mention this). This review did not find any impact on other outcomes
such as the risk of having a caesarean section ( low quality evidence ), a large baby,
obstructed labour when the baby's shoulder becomes stuck (shoulder dystocia) or a
baby with low blood glucose levels. This may be due to the trials being too small
to detect differences in these outcomes and the outcomes not being reported by all
trials. All four trials were from Italy. The included trials did not report on a large
number of other mother and baby outcomes listed in this review and nor were there
any data relating to longer‐term outcomes for the mother or the infant, or the cost
of health services. What does this mean? Myo‐inositol as a dietary supplement during
pregnancy shows promise in preventing gestational diabetes but there is not enough
evidence at this stage to support its routine use. Further large, well‐designed, randomised
controlled trials are required to assess the effectiveness of myo‐inositol in preventing
gestational diabetes and improving other health outcomes for mothers and their babies.
Ideally, future studies should consider involving women from different ethnicities
and with differing risk factors for gestational diabetes. It would be useful for future
studies to consider the ways that myo‐inositol can be used (different doses, frequency
and when to take it) and compare the intervention with a placebo control, diet and
exercise or pharmacological interventions. We recommend that future studies utilise
the outcomes listed in this review and that potential harms, including adverse effects
are included.