Liggins Institute, The University of Auckland, Auckland, New Zealand.
Department of Paediatrics: Child and Youth Health, The University of Auckland, Auckland, New Zealand.
Cochrane Database Syst Rev. 2023 Feb 15;2(2):CD011507. doi: 10.1002/14651858.CD011507.pub3.
Gestational diabetes with onset or first recognition during pregnancy is an increasing problem worldwide. Myo-inositol, an isomer of inositol, is a naturally occurring sugar commonly found in cereals, corn, legumes and meat. Myo-inositol is one of the intracellular mediators of the insulin signal and correlates with insulin sensitivity in type 2 diabetes. The potential beneficial effect of improving insulin sensitivity suggests that myo-inositol may be useful for women in preventing gestational diabetes. This is an update of a review first published in 2015.
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 Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO ICTRP (17 March 2022) and the reference lists of retrieved studies.
We included published and unpublished randomised controlled trials (RCTs) including cluster-RCTs and conference abstracts, assessing the effects of myo-inositol for the prevention of gestational diabetes in pregnant women. We included studies that compared any dose of myo-inositol, alone or in a combination preparation, with no treatment, placebo or another intervention. Quasi-randomised and cross-over trials were not eligible. We excluded women with pre-existing type 1 or type 2 diabetes.
Two review authors independently assessed studies for inclusion, assessed risk of bias and extracted the data. We checked the data for accuracy. We assessed the certainty of the evidence using the GRADE approach.
We included seven RCTs (one conducted in Ireland, six conducted in Italy) reporting on 1319 women who were 10 weeks to 24 weeks pregnant at the start of the studies. The studies had relatively small sample sizes and the overall risk of bias was low. For the primary maternal outcomes, meta-analysis showed that myo-inositol may reduce the incidence of gestational diabetes (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.31 to 0.90; 6 studies, 1140 women) and hypertensive disorders of pregnancy (RR 0.34, 95% CI 0.19 to 0.61; 5 studies, 1052 women). However, the certainty of the evidence was low to very low. For the primary neonatal outcomes, only one study measured the risk of a large-for-gestational-age infant and found myo-inositol was associated with both appreciable benefit and harm (RR 1.40, 95% CI 0.65 to 3.02; 1 study, 234 infants; low-certainty evidence). None of the included studies reported on the other primary neonatal outcomes (perinatal mortality, mortality or morbidity composite). For the secondary maternal outcomes, we are unclear about the effect of myo-inositol on weight gain during pregnancy (mean difference (MD) -0.25 kilogram (kg), 95% CI -1.26 to 0.75 kg; 4 studies, 831 women) and perineal trauma (RR 4.0, 95% CI 0.45 to 35.25; 1 study, 234 women) because the evidence was assessed as being very low-certainty. Further, myo-inositol may result in little to no difference in caesarean section (RR 0.91, 95% CI 0.77 to 1.07; 4 studies, 829 women; low-certainty evidence). None of the included studies reported on the other secondary maternal outcomes (postnatal depression and the development of subsequent type 2 diabetes mellitus). For the secondary neonatal outcomes, meta-analysis showed no neonatal hypoglycaemia (RR 3.07, 95% CI 0.90 to 10.52; 4 studies; 671 infants; very low-certainty evidence). However, myo-inositol may be associated with a reduction in the incidence of preterm birth (RR 0.35, 95% CI 0.17 to 0.70; 4 studies; 829 infants). There were insufficient data for a number of maternal and neonatal secondary outcomes, and no data were reported for any of the long-term childhood or adulthood outcomes, or for health service utilisation outcomes.
AUTHORS' CONCLUSIONS: Evidence from seven studies shows that antenatal dietary supplementation with myo-inositol during pregnancy may reduce the incidence of gestational diabetes, hypertensive disorders of pregnancy and preterm birth. Limited data suggest that supplementation with myo-inositol may not reduce the risk of a large-for-gestational-age infant. The current evidence is based on small studies that were not powered to detect differences in outcomes such as perinatal mortality and serious infant morbidity. Six of the included studies were conducted in Italy and one in Ireland, which raises concerns about the lack of generalisability to other settings. There is evidence of inconsistency among doses of myo-inositol, the timing of administration and study population. As a result, we downgraded the certainty of the evidence for many outcomes to low or very low certainty. Further studies for this promising antenatal intervention for preventing gestational diabetes are encouraged and should include pregnant women of different ethnicities and varying risk factors. Myo-inositol at different doses, frequency and timing of administration, should be compared with placebo, diet and exercise, and pharmacological interventions. Long-term follow-up should be considered and outcomes should include potential harms, including adverse effects.
妊娠糖尿病是一种在全球范围内发病率不断上升的疾病，其定义为妊娠期间或首次诊断的糖尿病。肌醇，是肌醇的一种同分异构体，是一种天然存在于谷物、玉米、豆类和肉类中的糖。肌醇是胰岛素信号的细胞内介质之一，与 2 型糖尿病的胰岛素敏感性相关。改善胰岛素敏感性的潜在有益作用表明，肌醇可能对预防妊娠糖尿病的女性有用。这是对首次发表于 2015 年的综述的更新。
评估在母亲和胎儿中，产前补充肌醇是否安全有效，是否可预防妊娠糖尿病。
我们检索了 Cochrane 妊娠与分娩试验注册库、ClinicalTrials.gov、世卫组织国际临床试验注册平台（2022 年 3 月 17 日）和检索到的研究的参考文献列表。
我们纳入了已发表和未发表的随机对照试验（RCT），包括整群 RCT 和会议摘要，评估了肌醇用于预防孕妇妊娠糖尿病的效果。我们纳入了比较肌醇的任何剂量（单独或与组合制剂）与无治疗、安慰剂或其他干预的研究。准随机和交叉试验不符合纳入标准。我们排除了患有 1 型或 2 型糖尿病的孕妇。
两名综述作者独立评估研究纳入情况、评估偏倚风险并提取数据。我们检查了数据的准确性。我们使用 GRADE 方法评估证据的确定性。
我们纳入了 7 项 RCT（1 项在爱尔兰进行，6 项在意大利进行），共纳入 1319 名 10 周到 24 周妊娠的孕妇。这些研究样本量相对较小，整体偏倚风险较低。对于主要的母亲结局，meta 分析表明，肌醇可能降低妊娠糖尿病的发病率（风险比（RR）0.53，95%置信区间（CI）0.31 至 0.90；6 项研究，1140 名女性）和妊娠高血压疾病（RR 0.34，95%CI 0.19 至 0.61；5 项研究，1052 名女性）。然而，证据的确定性为低至极低。对于主要的新生儿结局，只有一项研究测量了巨大儿的风险，发现肌醇与益处和危害都有关（RR 1.40，95%CI 0.65 至 3.02；1 项研究，234 名婴儿；低确定性证据）。纳入的研究均未报告其他主要新生儿结局（围产期死亡率、死亡率或发病率复合结局）。对于次要的母亲结局，我们不清楚肌醇对妊娠期间体重增加的影响（平均差值（MD）-0.25 千克，95%CI-1.26 至 0.75 千克；4 项研究，831 名女性）和会阴创伤（RR 4.0，95%CI 0.45 至 35.25；1 项研究，234 名女性），因为证据被评估为极低确定性。此外，肌醇可能对剖宫产的影响较小或无影响（RR 0.91，95%CI 0.77 至 1.07；4 项研究，829 名女性；低确定性证据）。纳入的研究均未报告其他次要的母亲结局（产后抑郁和随后发生 2 型糖尿病）。对于次要的新生儿结局，meta 分析表明，肌醇不会导致新生儿低血糖（RR 3.07，95%CI 0.90 至 10.52；4 项研究；671 名婴儿；极低确定性证据）。然而，肌醇可能与早产发生率降低有关（RR 0.35，95%CI 0.17 至 0.70；4 项研究；829 名婴儿）。有一些次要的母婴结局的数据不足，没有任何数据报告长期儿童或成年结局，或卫生服务利用结局。
来自 7 项研究的证据表明，在妊娠期间补充肌醇可能降低妊娠糖尿病、妊娠高血压疾病和早产的发生率。有限的数据表明，肌醇补充可能不会降低巨大儿的风险。目前的证据基于样本量较小的研究，这些研究没有足够的能力来检测围产期死亡率和严重婴儿发病率等结局的差异。纳入的研究中有 6 项在意大利进行，1 项在爱尔兰进行，这引起了对研究结果在其他环境中缺乏普遍性的关注。肌醇的剂量、给药时间和研究人群存在不一致的证据。因此，我们将许多结局的证据确定性降级为低或极低。我们鼓励对这种有前途的预防妊娠糖尿病的产前干预措施进行进一步研究，应包括不同种族和不同风险因素的孕妇。应该比较不同剂量、频率和时间的肌醇与安慰剂、饮食和运动以及药物干预。应该考虑长期随访，并应包括潜在的危害，包括不良反应。
