Methods

Quasi‐randomised trial.

Women were sequentially assigned to telemedicine and control groups (not randomised).

Period of study: not reported.

Participants

88 women with gestational diabetes in the telemedicine group and 115 in the control group;
17 women with type 1 diabetes in the telemedicine group and 15 in the control group.

Inclusion criteria: pregnant women with type 1 diabetes (enrolled in the study at their first visit after conception. Women with gestational diabetes included after a week from the diagnosis of gestational diabetes.

Exclusion criteria: not described.

Interventions

Intervention: automated telemedicine monitoring.

Control: conventional system.

Outcomes

Outcomes used in this review

1. Caesarean section.

2. Neonatal morbidity composite (presence of macrosomia (4000 g) and complications).

3. Gestational age at birth.

4. Use of additional insulin therapy.

5. Glycaemic control (maternal).

6. Weight gain.

7. Macrosomia.

8. Birthweight.

Notes

Setting: 12 diabetes clinics.

Country: Italy.

Funding: not mentioned.

Declarations of interest: not reported.

Comments: data for women with gestational diabetes and type 1 diabetes are presented separately.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: “Women were sequentially assigned to two groups: one patient was followed up using the telemedicine approach and the next using the conventional approach (usual care).”

Allocation concealment (selection bias)

High risk

No attempt was made to conceal allocation.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

No attempt was made to blind women or personnel. Women were aware of whether they were being monitored using telemedicine or usual care. However, the outcomes were measured objectively and would not have been influenced by blinding or not blinding.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

No blinding of outcome assessment. However, all outcomes were objectively measured.

Incomplete outcome data (attrition bias)
All outcomes

High risk

4/36 women with type 1 diabetes and 37/240 women with gestational diabetes were excluded because they did not complete questionnaires at the end of the study. It is unclear whether these were women with type 1 diabetes or gestational diabetes.

Selective reporting (reporting bias)

Unclear risk

This study was assessed from a published report, without the study protocol. The main outcomes were reported separately for type 1 diabetes and GDM, however some outcomes were not reported separately or were only reported in the text.

Other bias

High risk

The study did not use an intention‐to‐treat analysis. There is no sample size calculation, or information on whether groups were comparable at baseline. Women with type 1 diabetes only make up a small part of the whole study (32 out of 235 women).

Methods

Randomised, parallel‐group, open‐label, 2‐armed, active controlled trial.

Period of study: not mentioned.

Participants

Number randomised: 20.

Eligible were type 1 diabetes mellitus (IDDM) pregnant patients attending the Diabetes Unit specialising in the treatment of diabetes in pregnancy during the period of study.

Inclusion criteria: type 1 DM pregnant patients.

Exclusion criteria: not mentioned in the text.

Interventions

Intervention: DIANET system ‐ continuous automated monitoring system using a telemedicine system ‐ patient unit, diabetes workstation and the communication link (n = 10).

Control: conventional monitoring ‐ performed 3 or more tests of blood glucose per day using BM20‐800 strips (n = 10).

Outcomes

Outcomes used in this review

1. Gestational age at birth.

2. Insulin requirement at end of study.

3. Glycaemic control (maternal).

Notes

Setting: Diabetes Unit specialising in the treatment of diabetes in pregnancy.

Country: Italy.

Funding: not mentioned.

Declarations of interest: not reported.

Comments

1. No sample size estimation reported.

2. No type 2 DM pregnant patients included.

3. Patients enrolled at 9.5 + 10 weeks, study ended at 37.6 + 0.4 weeks.

4. Hypoglycaemic episodes were graded in categories of 1 (mild) to 4 (severe).

5. Trial not registered ??

6. Therapeutic adjustment by the Diabetes Unit was performed every week by a visit to the control group.

7. The experimental group had their data stored in DIANET system transmitted to the team weekly. This allowed feedback to both patients and clinicians.

8. Clinic visit for experimental group is once every 15‐30 days as they stayed at a longer distance from the clinics than the control group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote from report ‐ "Patients were consecutively chosen by 1 of the investigators. Stratified block randomisation was used to divide patients into 2 groups at baseline." The patients were randomly assigned to a control or DIANET group.

Comment: methods of sequence allocation not stated.

Allocation concealment (selection bias)

Unclear risk

Comment: not mentioned.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: no blinding of participants and personnel. However, this may not affect the results as all outcomes were objectively measured.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Comment: no blinding of outcome assessment. However, all outcomes were objectively measured.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: reported results of all participants (n = 20).

Selective reporting (reporting bias)

Low risk

As reported in the article all outcomes listed have been mentioned.

Other bias

Low risk

No obvious risk to other bias.

Methods

Multi‐centre, parallel randomised controlled trial – open‐label.

They ran 2 trials in parallel for pregnant participants and for participants planning a pregnancy.

Period of study: 25 March 2013 ‐ 22 March 2016.

We report the results for pregnant participants.

Participants

Number randomised: 325 (215 pregnant, 110 planning pregnancy).

Inclusion criteria: women aged 18‐40 years, with type 1 diabetes for a minimum of 12 months, receiving intensive insulin therapy via multiple daily injections or an insulin pump, who were pregnant or planning pregnancy.

Exclusion criteria: regular CGM users and women with severe nephropathy or medical conditions such as psychiatric illness requiring hospitalisation. Women using automatic insulin delivery options, such as low glucose suspend pumps, were not excluded.

Interventions

Intervention: real‐time CGM in addition to capillary glucose monitoring. CGM system was aGuardian REAL‐Time or MiniMed Minilink system, both Medtronic, Northridge CA. Participants were trained to use the study devices and instructed to use them daily by local diabetes or antenatal clinic teams. CGM users were advised to verify the accuracy of CGM measurements using their capillary glucose meter before insulin dose adjustment, as per the regulatory labelling instructions (n = 108).

Control: standard ‐ capillary glucose monitoring alone (home glucose monitoring). Participants in the control group continued their usual method of capillary glucose monitoring. Participants in both groups were advised to test capillary blood glucose levels at least 7 times daily (before and 1‐2 hours after meals and before bed) and given written instructions for how to use capillary or CGM measures for insulin dose adjustment, customised for methods of insulin delivery. Both groups had the same target glucose range of 3.5 to 7.8 mmol/L and same target HbA1c levels of no higher than 6.5% (48 mmol/mol) during pregnancy (n = 107).

Outcomes

Outcomes used in this review

1. Hypertensive disorders of pregnancy (including pre‐eclampsia, pregnancy‐induced hypertension, eclampsia).

2. Caesarean section.

3. Large‐for‐gestational age.

4. Mortality or morbidity composite (in the report this is defined as: pregnancy loss (miscarriage, stillbirth, and neonatal death); birth injury; neonatal glycaemia; hyperbilirubinaemia; respiratory distress; and high‐level neonatal care for more than 24 hours).

5. Weight gain during pregnancy (reported as median and IQR).

6. Behaviour changes associated with the intervention.

7. Sense of well‐being and quality of life (Questionnaires relating to fear of hypoglycaemia, coping with diabetes, quality of life, and satisfaction with monitoring device).

8. Glycaemic control during/end of treatment (as defined by trialists) (e.g. HbA1c, fructosamine, fasting blood glucose, post‐prandial blood glucose) ‐ HbA1c, total insulin dose.

9. Maternal hypoglycaemia (severe).

10. Miscarriage.

11. Postnatal weight retention or return to pre‐pregnancy weight – maternal weight gain (from entry to 34 weeks).

12. Cardiovascular health (as defined by trialists, including blood pressure, hypertension, cardiovascular disease, metabolic syndrome) ‐ hypertension.

13. Stillbirth.

14. Gestational age at birth – median (IQR).

15. Preterm birth (less than 37 weeks' gestation and less than 34 weeks' gestation).

16. Macrosomia (≥ 4000 g).

17. Small‐for‐gestational age (< 10th centile).

18. Birthweight and z‐score (birthweight g) mean (SD).

19. Head circumference (cm) mean (SD) and z‐score.

20. Length and z‐score (crown‐heel length (cm).

21. Adiposity (e.g. BMI, skinfold thickness) Sum of 4 skin folds (triceps, subscapular, biceps, flank).

22. Shoulder dystocia.

23. Respiratory distress syndrome.

24. Hypoglycaemia (variously defined).

25. Hyperbilirubinaemia.

26. Relevant biomarker changes associated with the intervention (e.g. cord c peptide, cord insulin) – Cord blood C‐peptide levels > 566 pmol/L, > 2725 pmol/L.

27. Major and minor anomalies – congenital anomaly.

28. Number of antenatal visits or admissions – number of hospital admissions.

29. Length of antenatal stay – maternal length of stay – days – median (IQR).

30. Neonatal intensive care unit length of stay greater than 24 hours.

31. Birth trauma (shoulder dystocia, bone fracture, nerve palsy) (not pre‐specified as a composite) – birth injury and shoulder dystocia.

32. Diabetic ketoacidosis – DKA – page 22 in supplementary file – table 19a.

Notes

Setting: 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland and the USA.

Country: Canada.

Funding: the trial was funded by Juvenile Diabetes Research Foundation (JDRF) grants #17‐2011‐533, and grants under the JDRF Canadian Clinical Trial Network, a public‐private partnership including JDRF and FedDev Ontario and supported by JDRF #80‐2010‐585. Metronic supplied the CGM sensors and CGM systems at reduced cost. HRM conducts independent research supported by the National Institute for Health Research (Career Development Fellowship, CDF‐2013‐06‐035), and is supported by Tommy’s charity. The funders had no role in the trial design, data collection, data analysis, or data interpretation.

Declarations of interest: 8 authors report grants from the Juvenile Diabetes Research Foundation during the conduct of the study. Two authors report personal fees from Novo Nordisk, Roche and Medtronic, outside the submitted work. 1 author reports personal fees from Abbott Diabetes Care and Medtronic (MiniMed Academia), outside the submitted work. 1 author sits on the Medtronic European Scientific Advisory Board. All remaining authors declare no completing interests.

Comments

1. A sample size calculation was reported.

2. They ran 2 trials in parallel for pregnant participants and for participants planning a pregnancy ‐ we report only on the trial of pregnant participants.

3. The study protocol was approved by the Health Research Authority, East of England Research Ethics Committee for all UK sites and at each individual centre for all other sites. Regional Ethical Committee.

4. All participants provided written informed consent.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Treatments allocated by a web‐based system using a computer‐generated randomisation list with permuted block sizes and stratified by method of insulin delivery (pump or multiple injections) and baseline HbA1c (< 7.5% vs ≥ 7.5% or 58 mmol/mol for the pregnancy trial).

Allocation concealment (selection bias)

Low risk

Randomisaton schedule created by a programming manager, encrypted, and maintained in a secure database – the co‐ordinating team and investigators had no access.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Used masked sensors – for control group – so suggests blinding and also HbA1c measures done at a central laboratory and were unavailable to participants and healthcare teams during the trial.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

All HbA1c measures done at a central laboratory. Samples were shipped after delivery and collection of cord blood and were unavailable to participants and healthcare teams during the trial.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Authors report that about 20% data were missing, lost to follow‐up.

For primary outcome – change in HbA1c – 82% (89/108) and 79% (84/107) included in analysis from CGM and home monitoring groups.

Also stated that "For the primary outcome, the patterns of change were similar between analyses of imputed and available HbA_1c data".

There is a study flow diagram and missing data appear balanced across groups.

Selective reporting (reporting bias)

Low risk

Cross‐checked the protocol with main published report and methods section – also checked Appendices in supplementary file – most of the outcomes appear to have been reported.

Other bias

Low risk

Groups balanced at baseline – differences noted in smoking, automated insulin delivery option, hypertension, severe hypoglycaemia in past year or during early pregnancy pre‐randomisation – but report states "any minor imbalances in baseline characteristics between CGM and control group participants were within the expected bounds for random allocation".

Methods

Randomised, parallel‐group, open‐label, 2‐armed, active controlled trial.

Period of study: 1 October 1979 ‐ 1 October 1982.

Participants

Number randomised: 100.

Eligible were type 1 diabetes mellitus (IDDM) and type 2 diabetes mellitus (NIDDM) pregnant patients attending the from 5 hospitals in Stockholm during the period of study.

Inclusion criteria: patients with a diagnosis of diabetes, either insulin‐dependent or non‐insulin‐dependent prior to pregnancy.

Exclusion criteria: not mentioned in text.

Interventions

Intervention: patients self‐monitored their blood glucose at home from the 32nd week until the 36th week of gestation. Weekly hospital visit from 32‐36 weeks and then hospitalised during the 37th week until delivery (n = 54).

Control: patients were hospitalised from 32nd week until delivery (n = 46).

Outcomes

Outcomes used in this review

1. Caesarean section.

2. Perinataly mortality (stillbirth and neonatal mortality).

3. Pre‐eclampsia.

4. Pregnancy‐induced hypertension.

5. Placental abruption.

6. Preterm birth < 37 weeks.

7. Respiratory distress syndrome.

8. Neonatal hypoglycaemia.

9. Neonatal jaundice.

10. HbA1c.

11. Major anomalies.

12. Antenatal hospital admission.

13. Neonatal hospital stay.

14. Feeding difficulties.

Notes

Setting: 5 hospitals in Stockholm.

Country: Sweden.

Funding: Expressens Perinatal forskningsfond, AIImanna Barnbordshusets Minnesfond, Svenska Diabetesstiftelsen, Nordisk Insulinfond, Swedish Medical Research Council (Project No. 3787), and Tielman's Fund for Pediatric Research.

Declarations of interest: not reported.

Comments

1. No sample size estimation reported.

2. Twins were included (2 pairs).

3. If complications occurred, home monitoring situation was interrupted.

4. The study was approved by the Regional Ethical Committee.

5. Informed consent was obtained from all participants.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: not mentioned.

Allocation concealment (selection bias)

Unclear risk

Comment: not mentioned.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: no blinding of participants and personnel. However, this may not affect the results as all outcomes were objectively measured.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Comment: no blinding of outcome assessment. Objective measurements used.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 1 excluded for severe drug addiction, 8 spontaneous abortions and 1 mother died.

Selective reporting (reporting bias)

Low risk

No obvious risk to selective reporting.

Other bias

Low risk

No obvious risk to other bias.

Methods

Randomised, parallel‐group, open‐label, 2‐armed, active controlled trial.

Period of study: not mentioned.

Participants

Number randomised: 61

Eligible were type 1 diabetes mellitus (IDDM) pregnant patients attending or referred to the Regional Joint Metabolic/Antenatal Clinic at the Royal Maternity Hospital, Belfast during the period of study.

Inclusion criteria: type 1 DM pregnant women at 16 weeks' gestation.

Exclusion criteria: women without results due to reasons such as: stillbirth, abortions, major congenital abnormalities.

Interventions

Intervention: pre‐prandial glucose monitoring (n = 31).

Control: post‐prandial glucose monitoring (n = 30).

Outcomes

Outcomes used in this review

1. Caesarean section.

2. Large‐for‐gestational age.

3. Perinatal mortality (stillbirth and neonatal mortality).

4. Pre‐eclampsia.

5. Weight gain during pregnancy.

6. Insulin dose.

7. Maternal glycaemic control (HbA1c, fasting blood glucose, post‐prandial blood glucose, fructosamine).  

8. Stillbirth.

9. Gestational age (at birth).

10. Preterm birth < 37 weeks.

11. Macrosomia.

12. Birthweight (kg).

13. Respiratory distress syndrome.

14. Neonatal hypoglycaemia.

15. Neonatal jaundice.

16. Cord IGF.

17. Neonatal glucose at age 1 hour.

18. Transient tachypnoea.

19. Neonatal intensive care admissions.

Notes

Setting: Regional Joint Metabolic/Antenatal Clinic at the Royal Maternity Hospital, Belfast.

Country: UK.

Funding: Department of Health and Social Sevices, Northern lreland, the Northern Ireland Mother and Baby Appeal, the Metabolic Unit Research Fund, Royal Victoria Hospital, Belfast, the Royal Maternity Hospital, Royal Victoria Hospital, Belfast, and the Irish Perinatal Society.

Declarations of interest: not reported.

Comments

1. No sample size estimation reported.

2. No type 2 DM pregnant patients included.

3. Only white women were included.

4. Patients were reviewed fortnightly or more frequently if clinically indicated.

5. Insulin doses were adjusted to achieve fasting glucose values between 60 mg/dL and 90 mg/dL (3.3 mmol/L and 5.0 mmol/L), pre‐prandial values between 60 mg/dL and 105 mg/dL (3.3 mmol/L and 5.9 mmol/L), and post‐prandial values less than 140 mg/dL (7.8 mmol/L).

6. Post‐prandial glucose monitoring may significantly reduce the incidence of pre‐eclampsia and neonatal triceps skinfold thickness compared with pre‐prandial monitoring.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote ‐ "Women were randomly assigned at 16 weeks' gestation to 1 of 2 blood glucose monitoring protocols".

Comment: method not mentioned.

Allocation concealment (selection bias)

Low risk

Quote ‐ "allocations were via a sealed envelope system, which the patient selected from a box at the clinic visit".

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: no blinding of participants and personnel.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Comment: no blinding of outcome assessment. However, all outcomes were objectively measured.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote ‐ "74 patients were recruited. 13 were excluded because they did not have results for analysis. This left 61 diabetic women (31 pre‐prandial and 30 post‐prandial monitoring) with results suitable for analysis".

Selective reporting (reporting bias)

Low risk

No obvious risk to selective reporting.

Other bias

Low risk

No obvious risk to other bias.

Methods

Randomised, parallel‐group, open‐label, 2‐armed, active controlled trial.

Period of study: September 2003 to 2006.

Participants

Number randomised: 71.

Eligible were type 1 (IDDM) and type 2 (NIDDM) diabetes mellitus pregnant patients attending 2 secondary care diabetic antenatal clinics in the UK during the period of study.

Inclusion criteria

1. Type 1 and type 2 DM pregnant women at 16 weeks' gestation.

2. Provided written informed consent.

3. Willing to wear a continuous glucose monitor.

Exclusion criteria

1. Women with severe medical or psychological comorbidity.

Interventions

Intervention: continuous glucose monitor which measured glucose in subcutaneous tissues every 10 seconds and an average value is stored every 5 minutes, providing up to 288 measurements per day (n = 38). The participants were required to wear the CGMS for 7 days at intervals of 4‐6 weeks. They were also advised to measure blood glucose at least 7 times a day.

Control: intermittent self‐monitoring of glucose levels (n = 33), at least 7 times a day (standard care).

Outcomes

Outcomes used in this review

1. Caesarean section.

2. Large‐for‐gestation age.

3. Perinatal mortality (stillbirth and neonatal mortality).

4. Pre‐eclampsia.

5. Maternal glycaemic control (HbA1c).

6. Miscarriage.

7. Neonatal mortality.

8. Gestational age at birth.

9. Preterm birth at < 37 weeks.

10. Macrosomia.

11. Birthweight.

12. Small‐for‐gestational age.

13. Neonatal hypoglycaemia.

14. Major and minor anomalies.

15. Neonatal intensive care admissions.

Notes

Setting: secondary care diabetic antenatal clinics.

Country: UK.

Funding: this was an investigator initiated study funded by the Ipswich Diabetes Centre Charity Research Fund. HRM also received salary support from Diabetes UK. The study equipment (6 x CGMS Gold monitors and 300 sensors) was donated free of charge by Medtronic UK. The research was sponsored by Ipswich Hospital NHS Trust and was independent of all the study funders.

Declarations of interest: 2 trial authors received honorariums for speaking at research symposiums sponsored by Medtronic in 2004 and 2005.

Comments

1. Sample size estimation was reported.

2. Both type 1 and type 2 DM pregnant patients were included.

3. The women were predominantly white European.

4. The continuous glucose monitor (CGM) to be worn up to 7 days at intervals of 4 to 6 weeks between 8 and 32 weeks' gestation.

5. In addition to the CGM, intermittent self‐monitoring of glucose levels was implemented in the intervention group.

6. Therapeutic adjustments to diet, exercise, and insulin regimens were discussed with the obstetric diabetes team, based on the combined intermittent capillary glucose and continuous glucose data for women allocated to CGM or the intermittent capillary glucose data alone for women allocated to standard antenatal care.

7. The women were advised to measure blood glucose levels at least 7 times a day and were provided with several targets: 3.5 mmol/L to 5.5 mmol/L before meals, < 7.8 mmol/L 1 hour after meals, and < 6.7 mmol/L 2 hours after meals.

8. The women were seen every 2‐4 weeks for up to 28 weeks, fortnightly until 32 weeks, and weekly thereafter, with assessments of fetal growth at 28, 32, and 36 weeks.

9. Short‐acting insulin analogues were used before meals with intermediate acting insulin, long‐acting analogues, or pump therapy. The women with type 2 diabetes were treated with insulin before pregnancy or as soon as pregnancy was confirmed.

10. Majority (90%) of women were White European, with the rest being Asian and others.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote ‐ "The study statistician used computer generated randomised numbers in blocks of 20".

Allocation concealment (selection bias)

Low risk

Quote ‐ "Concealed in sealed envelopes. Research nurses trained in accordance with good clinical practice guidelines provided the women with their group allocation".

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: no blinding of participants and personnel. However, this may not affect the results as all outcomes were objectively measured.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Comment: no blinding of outcome assessment. However, all outcomes were objectively measured.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: intention‐to‐treat analysis was applied.

Selective reporting (reporting bias)

Low risk

All expected outcomes appear to have been reported.

Other bias

Low risk

No obvious risk to other bias.

Methods

Randomised, parallel‐group, open‐label, 2‐armed, active controlled trial.

Period of study: not mentioned.

Participants

Number randomised: 25.

Eligible were type 1 diabetes mellitus (IDDM) pregnant patients attending the University Clinic of Endocrinology, Diabetes and Metabolic Disorders in Skopje during the period of study.

Inclusion criteria

1. On continuous subcutaneous insulin infusion (CSII) for at least 3 months before conception.

2. Singleton pregnancy.

Exclusion criteria

1. Not mentioned.

Interventions

Intervention: constant CGM ‐ 24 hours/day (n = 12).

Control: intermittent CGM ‐ 14 days per month (n = 13), measured blood glucose at least 6 times a day every second week (when not using the CGM).

Outcomes

Outcomes used in this review

1. Caesarean section rates.

2. Weight gain during pregnancy.

3. Maternal glycaemic control (HbA1c, mean blood glucose).

4. Severe hypoglycaemia (maternal).

5. Diabetic ketoacidosis.

6. Preterm birth < 37 weeks.

7. Macrosomia.

8. Neonatal hypoglycaemia.

Notes

Setting: University Clinic of Endocrinology, Diabetes and Metabolic Disorders in Skopje.

Country: Macedonia.

Funding: Macedonion Ministry of Health and the Health Care Fund of Macedonia.

Declarations of interest: the authors declared that they had no competing financial interests.

Comments

1. No sample size estimation reported.

2. No type 2 DM pregnant patients included.

3. All patients were followed for 1 to 3 weeks by a diabetologist and obstetrician.

4. The device could alert increased or decreased glucose levels, insulin pump was automatically suspend insulin delivery if necessary.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote ‐ "Patients were randomised into 2 groups".

Comment: method not mentioned.

Allocation concealment (selection bias)

Unclear risk

Not mentioned.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: no blinding of participants and personnel. However, this may not affect the results as all outcomes were objectively measured.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Comment: no blinding of outcome assessment. However, all outcomes were objectively measured.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Intention‐to‐treat analysis.

Selective reporting (reporting bias)

Low risk

All expected outcomes reported.

Other bias

Low risk

No obvious risk to other bias.

Methods

Randomised, parallel‐group, open‐label, 2‐armed, active controlled trial.

Period of study: 15 February 2009 to 15 February 2011.

Participants

Number randomised: 154.

Eligible were 123 type 1 (IDDM) and 31 type 2 (NIDDM) pregnant patients referred to the Centre for Pregnant Women with Diabetes, Rigshospitalet, before 14 completed gestational weeks.

Inclusion criteria

1. Type 1 and type 2 DM pregnant women before 14 completed weeks of gestation.

2. Provided written informed consent.

3. Willing to wear a CGM.

Exclusion criteria

1. Present use of real‐time CGM.

2. Severe mental or psychiatric barriers.

3. Diabetic nephropathy.

4. Severe concurrent comorbidity (e.g. severe psoriasis, previous gastric bypass surgery).

Interventions

Intervention: real time CGM for 6 days at pregnancy visits during 8, 12, 21, 27 and 33 weeks, in addition to routine pregnancy care.

Control: routine pregnancy care with self‐monitored plasma glucose measurements of 7 times daily.

Outcomes

Outcomes used in this review

1. Caesarean section.

2. Large‐for‐gestational age.

3. Pre‐eclampsia.

4. Pregnancy‐induced hypertension.

5. Miscarriage.

6. Preterm birth <37 weeks.

7. Neonatal hypoglycaemia.

Notes

Setting: Centre for Pregnant women with Diabetes, Rigshospitalet.

Country: Denmark.

Funding: 1 of the authors received financial support from the European Foundation of the Study of Diabetes and LifeScan, Rigshopitalet's Research Foundation, the Capital Region of Denmark, the Medical Facuty Foundation of Copenhagen Univeristy, Aase and Ejnar Danielsen Foundation, and Master Joiner Sophus Jacobsen and his wife Astrid Jacobsens' Foundation. 1 author holds stocks in Novo Nordisk. 1 author received financial support from Novo Nordisk Foundation. The real‐time CGM monitors and links were supplied, and glucose sensors were offered at a reduced price by Medtronic.

Declarations of interest: the authors declared no other potential conflicts of interest, other than those reported under 'funding'. interests.

Comments

1. Sample size estimation was reported.

2. Women gave written informed consent.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote ‐ "a computer generated randomization program was used".

Allocation concealment (selection bias)

Low risk

Quote ‐ "..treatment allocation was properly concealed using automated telephone allocation service (Paravox) provided by an independent organization".

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: no blinding of participants and personnel. However, this may not affect the results as all outcomes were objectively measured.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Comment: no blinding of outcome assessment. However, all outcomes were objectively measured.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote ‐ "Intention‐to‐treat analysis was carried out".

Selective reporting (reporting bias)

Low risk

All expected outcomes reported.

Other bias

Low risk

No obvious risk to other bias.

Methods

Randomised, parallel‐group, open‐label, 2‐armed, active controlled trial.

Period of study: not mentioned.

Participants

Number randomised: 13.

Eligible were type 1 (IDDM) diabetes mellitus pregnant patients attending King College's Hospital.

Inclusion criteria: type 1 DM pregnant women at 30‐31 weeks' gestation.

Exclusion criteria: not mentioned.

Interventions

Intervention: 1) glucometer group (n = 7) measured blood glucose at home ‐ 7 times a day, twice weekly (before and after each main meal and before bedtime).

Control: non‐meter group (n = 6) ‐ checked urine glucose 4 times daily, random blood glucose measured at the fortnightly clinic visits.

Outcomes

Outcomes used in this review

1. Maternal glycaemic control (post‐prandial blood glucose).

2. Birthweight.

Notes

Setting: King's College hospital.

Country: UK.

Funding: Medical Research Council Project Grant and the British Diabetic Association.

Declarations of interest: not reported.

Comments

1. Sample size estimation was not reported.

2. Type 2 DM pregnant patients were not included.

3. A third group (normal women, n = 8) was included for comparison.

4. The women were at 30‐31 weeks' gestation at the beginning of study.

5. Women in the intervention group had their diet and insulin dosage adjusted by telephone or clinic consultation.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: not mentioned.

Allocation concealment (selection bias)

Unclear risk

Comment: not mentioned.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: no blinding of participants and personnel. However, this may not affect the results as all outcomes were objectively measured.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Comment: no blinding of outcome assessment. However, all outcomes were objectively measured.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: iIntention‐to‐treat.

Selective reporting (reporting bias)

Low risk

All expected outcomes reported.

Other bias

Low risk

No obvious risk to other bias.

Methods

Randomised, parallel‐group, open‐label, 2‐armed, active controlled trial.

Period of study: 1 February 1980 to 16 September 1981.

Participants

Number randomised: 30.

Eligible were type 1 diabetes mellitus (IDDM) pregnant patients attending the High Risk Obstetric Clinic at the University of Iowa Hospitals and Clinics during the period of study.

Inclusion criteria: less than 20 weeks' gestation.

Exclusion criteria: not mentioned.

Interventions

Intervention: daily home glucose monitoring (n = 15) ‐ fasting, 2‐hour post‐prandial morning, afternoon and evening glucose values were measured daily.

Control: weekly venipuncture (n = 15) ‐ fasting, 2 hours after breakfast, and 2 hours after lunch glucose levels measured on 1 day each week.

Outcomes

Outcomes used in this review

1. Caesarean section.

2. Perinatal mortality.

3. Maternal glycaemic control (HbA1c).

4. Miscarriage.

5. Neonatal mortality.

6. Gestational age at birth.

7. Birthweight.

8. Respiratory distress syndrome.

9. Neonatal hypoglycaemia.

10. Neonatal jaundice.

11. Neonatal hypocalcaemia.

12. Neonatal polycythaemia.

13. Neonatal cord vein C‐peptide.

Notes

Setting: High Risk Obstetric Clinic at the University of Iowa Hospitals and Clinics, Iowa.

Country: USA.

Funding: Research Fellowship from the Iowa Affiliate of the American Diabetes Association.

Declarations of interest: not reported.

Comments

1. No sample size estimation reported.

2. No type 2 DM pregnant patients included.

3. Patients telephoned their physicians weekly to report their blood glucose values or possible complications.

4. Insulin was adjusted by the patients with physicians' consultation.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote ‐ "Patients were assigned to control and experimental groups using a random number sequence".

Allocation concealment (selection bias)

Unclear risk

Comment: not mentioned.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: no blinding of participants and personnel. However, this may not affect the results as all outcomes were objectively measured.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Comment: no blinding of outcome assessment. However, all outcomes were objectively measured.

Incomplete outcome data (attrition bias)
All outcomes

High risk

2 patients from each group had a first trimester spontaneous miscarriage and were excluded (2 out of 30 = 7%).

Selective reporting (reporting bias)

Low risk

All expected outcomes reported.

Other bias

Low risk

No obvious risk to other bias.

Methods

Nationwide multicentre, open‐label, parallel, pragmatic randomised controlled trial

Period of study: July 2011 to September 2015

Participants

Number randomised: 300 pregnant women type 1 (n = 109), type 2 (n = 82), or with gestational diabetes (n = 109).

Inclusion criteria: pregnant women with pre‐existing DM, at gestational age of before 16 weeks, or had GDM requiring insulin therapy before 30 weeks gestational age.

Exclusion criteria: women with multiple pregnancies, under 18 years of age, or who had severe medical or psychological comorbidity

Interventions

Intervention: CGM:iPro2 (Medtronic, Northridge, California) ‐ CGM in addition to standard care – self‐monitoring. Women allocated to CGM were instructed to use the device for 5‐7 days every 6 weeks and glucose profiles were obtained retrospectively, directly after each use and evaluated by the local endocrinologist. SMBG is required for calibration of CGM. Readings from the CGM are uploaded to a web‐based program; (n = 147 all women, 50 with T1DM, 40 T2DM).

Control: standard treatment ‐ self‐monitoring of blood glucose only (n = 153 all women, 97 with type 2 diabetes). All participants in both intervention and control groups performed SMBG (4‐8 times/day: at least fasting, after every meal, at bedtime and, preferably before every meal).

Outcomes

Outcomes used in this review

1. Hypertensive disorders of pregnancy (including pre‐eclampsia, pregnancy‐induced hypertension, eclampsia).

2. Caesarean section*.

3. Large‐for‐gestational age*.

4. Induction of labour*.

5. Glycaemic control during/end of treatment (as defined by trialists) (e.g. HbA1c, fructosamine, fasting blood glucose, post‐prandial blood glucose)*.

6. Instrumental vaginal birth*.

7. Neonatal mortality.

8. Gestational age at birth*.

9. Preterm birth*.

10. Macrosomia (≥ 4000 g).

11. Small‐for‐gestational age (< 10th centile)*.

12. Birthweight and z‐score (birthweight g) mean (SD)*.

13. Shoulder dystocia*.

14. Neonatal hypocalcaemia*.

15. Major and minor anomalies – congenital anomaly*.

16. Neonatal intensive care unit admission*.

17. Birth trauma (shoulder dystocia, bone fracture, nerve palsy) (not pre‐specified as a composite) – birth injury and shoulder dystocia*.

* outcome not reported separately for pre‐gestational and gestational diabetes

Notes

Setting: 22 hospitals (university, teaching and non‐teaching in the Netherlands and 1 university hospital in Belgium.

Country: the Netherlands.

Funding: the trial was funded by ZonMw, The Dutch Organization for Health Research and Development 80‐82310‐97‐11157. The funder had no role in the study design, data collection, data analysis, data interpretation or writing of the report. Continuous glucose monitors were purchased at a discounted price from Medtronic® and they had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Declarations of interest: 1 of the trial authors received a research grant from ZonMW (the Netherlands Organization for Health Research and Development) and a second author received research grants from Abbott, Dexcom, Medtronic and Sensonics, and also received personal fees from Roche Diabetes Care and Sensonics. A third author is supported by an NHMRC Practitioner Fellowshop (GNT1082548) and reports consultancy for ObsEVa, Merck and Guerbet. All other authors declare no support from any organization or conflict of interest.

Comments

1. A sample size calculation was reported.

2. They included both women with pre‐gestational diabetes (type 1 and type 2) and women with GDM. However, for most of our review outcomes, the data were not separated out by pre‐gestational and GDM women.

3. The study was approved by the ethics committee of the Academic Medical Centre Amsterda, (reference number MEC AMC 10/322) and by the boards of management of all participating hospitals.

4. Written consent was obtained from all participating women.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Web‐based computerised programme using 1:1 randomisation, stratified according to type of diabetes

Allocation concealment (selection bias)

Unclear risk

Not clearly described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

No blinding – but outcome measures mainly objective, so unlikely to be affected by lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

No blinding – but outcome measures mainly objective, so unlikely to be affected by lack of blinding

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

High number of patients refused continued use of the CGM after the first or second time – a total of 66% of participants used CGM according to study protocol. However, there was a clear flow of participants in trial profile figure and reasons for dropouts, withdrawal provided. Conducted analyses on intention‐to‐treat and per‐protocol basis; 4 drop‐outs from CGM group and 6 from standard group so primary analyses were carried out according to the intention‐to‐treat principle – 143/147 included from the (CGM group) and 147/153 (standard group in the intention‐to‐treat analysis).

Quite a high drop out rate – 95 women in the CGM group and 144 from the control group were included in the per‐protocol analyses. 48 discontinued intervention and 3 discontinued protocol for standard group leaving: 95/147 (66%) intervention group and 144/153 (98%) standard group

Selective reporting (reporting bias)

High risk

Maternal outcomes not reported

1. Severe hypoglycaemia

Neonatal outcomes not reported

1. Preterm birth < 37 weeks' gestation

2. Birth trauma

3. Culture proven sepsis

4. Respiratory distress syndrome

5. Bronchopulmonary dysplasia

6. Intraventricular haemorrhage

7. Necrotising enterocolitis

The above were outcomes in the methods of the full report – but were not presented in the results section.

The protocol also reported the following outcomes that were not reported in the results: mode of delivery, perinatal death, glucose variability, costs and resource utilisation

Other bias

Unclear risk

Baseline characteristics – groups were similar. Data not presented separately for pre‐gestational diabetes (type 1 and type 2 diabetes) and GDM patients for most of the outcomes.

Methods

Randomised, parallel‐group, open‐label, 2‐armed, active controlled trial.

Period of study: not mentioned.

Participants

Number randomised: 32.

Eligible were type 1 diabetes mellitus (IDDM) pregnant patients attending the Clinic of Gastroenterology and Metabolic Diseases of the Medical Academy in Warsaw during the period of study.

Inclusion criteria

1. Duration of pregnancy less than 16 weeks.

2. No diseases.

3. Acceptable intelligence level according to the modified Wechsler‐Bellevue Scale for Adults.

4. Glycaemic control in the range of HbA1c < 9.5%.

Exclusion criteria

1. Not mentioned.

Interventions

Intervention:

Telematic Management System (Central Clinical Unit and Patients' Teletransmission Modules) (n = 15) ‐ daily transfer of glycaemic data to diabetologist, at least 6 blood glucose measurements daily.

Control:

Standard care without Telematic Management System (n = 15), 6 blood glucose measurement daily and routine clinic visit every 3 weeks.

Outcomes

Outcomes used in this review

1. Gestational age at birth.

2. Maternal glycaemic control (HbA1c, mean blood glucose).  

3. Hypoglycaemia (maternal).

Notes

Setting: Clinic of Gastroenterology and Metabolic Diseases of the Medical Academy in Warsaw.

Country: Poland.

Funding: supported by grants from the Polish State Committee for Scientific Research, the Bayer Diagnostic Division Warsaw, and the Polish Cellular Telephony Centertel.

Declarations of interest: not reported.

Comments

1. No sample size estimation reported.

2. No type 2 DM pregnant patients included.

3. 2 participants in the intervention group were excluded as they had pneumonia and Meniere's disease not diagnosed before randomisation.

4. Intensive insulin treatment was provided with multi‐injection technique with 6 blood glucose measurements per day (before and 60 minutes after the 3 main meals).

5. Each patient was followed up every 3 weeks by the same diabetologist.

6. Patients from the intervention group had their blood glucose data transmitted to the diabetologist daily. Thus the diabetologist was able to examine the metabolic state and to intervene if necessary.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation stated but method of sequence generation not clear. Quote: "Before randomization written consent was taken........".

Allocation concealment (selection bias)

High risk

Not possible as the same diabetologist was seeing both groups and knew to which group the participant belonged (control group could access the diabetologist by phone any time).

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: no blinding of participants and personnel. However, this may not affect the results as all outcomes were objectively measured.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Comment: no blinding of participants and personnel. However, all outcomes were objectively measured.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants accounted for and all data reported.

Selective reporting (reporting bias)

Low risk

No obvious risk to selective reporting.

Other bias

Low risk

No obvious risk to other bias.