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Cochrane Database of Systematic Reviews

Different intensities of glycaemic control for pregnant women with pre‐existing diabetes

Information

DOI:
https://doi.org/10.1002/14651858.CD008540.pub4Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 04 May 2016see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Pregnancy and Childbirth Group

Copyright:
  1. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Philippa Middleton

    Correspondence to: Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, Australia

    [email protected]

    [email protected]

  • Caroline A Crowther

    Liggins Institute, The University of Auckland, Auckland, New Zealand

  • Lucy Simmonds

    Ehrenberg‐Bass Institute, University of South Australia, Adelaide, Australia

Contributions of authors

Philippa Middleton drafted the protocol with assistance from Lucy Simmonds. Philippa Middleton and Lucy Simmonds assessed studies for inclusion/exclusion; carried out data extraction and assessed the risk of bias components. Philippa Middleton wrote and updated the review with editorial or clinical input or both from Caroline Crowther and Lucy Simmonds.

Sources of support

Internal sources

  • ARCH: Australian Research Centre for Health of Women and Babies, Robinson Research Institute, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Australia.

External sources

  • NHMRC: National Health and Medical Research Council, Australia Funding for the PCG Australian and New Zealand Satellite, Australia.

  • NIHR Cochrane Programme Grant Project: 13/89/05 – Pregnancy and childbirth systematic reviews to support clinical guidelines, UK.

Declarations of interest

None known.

Acknowledgements

Jessica Ainge Allen, Rachel Earl and Rebecca Tooher helped with drafting early versions of the protocol. Peter Muller for clinical input during the development of the 2012 update.

Denise Atherton for administrative assistance; Lynn Hampson for the literature search; Helen West for assistance with the 2015 revision.

Helen West's contribution to this project was supported by the National Institute for Health Research, via Cochrane Programme Grant funding to Cochrane Pregnancy and Childbirth. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Version history

Published

Title

Stage

Authors

Version

2016 May 04

Different intensities of glycaemic control for pregnant women with pre‐existing diabetes

Review

Philippa Middleton, Caroline A Crowther, Lucy Simmonds

https://doi.org/10.1002/14651858.CD008540.pub4

2012 Aug 15

Different intensities of glycaemic control for pregnant women with pre‐existing diabetes

Review

Philippa Middleton, Caroline A Crowther, Lucy Simmonds

https://doi.org/10.1002/14651858.CD008540.pub3

2010 Sep 08

Different intensities of glycaemic control for pregnant women with pre‐existing diabetes

Review

Philippa Middleton, Caroline A Crowther, Lucy Simmonds, Peter Muller

https://doi.org/10.1002/14651858.CD008540.pub2

2010 Jun 16

Different intensities of glycaemic control (tight versus very tight) for pregnant women with pre‐existing diabetes

Protocol

Philippa Middleton, Caroline A Crowther, Lucy Simmonds, Peter Muller

https://doi.org/10.1002/14651858.CD008540

Differences between protocol and review

2015 update

  1. We have updated the Background with some more recent data and references.

  2. We have added additional outcomes (Later development of cardiovascular disease (maternal); Length of postnatal stay (mother); Apgar score; and Childhood/adulthood diabetes) and reworded other outcomes to be in line with the list of core outcomes for diabetes in pregnancy.

  3. We have added some additional outcomes and labelled these as 'not prespecified' (chronic hypertension; transient hypertension; hypoglycaemic episodes; fetal distress; asphyxia; neonatal hypomagnesaemia).

  4. We have deleted the maternal primary outcome of hyperglycaemia requiring changes in management during pregnancy and the neonatal secondary outcome of macrosomia, as both are now redundant.

  5. 'Summary of findings' tables have been incorporated.

2012 review version

  1. The scope of the review has been expanded to include moderate and loose glycaemic control as well as tight and very tight control, resulting in a title change and changes to the objectives.

  2. The Methods were updated to current Pregnancy and Childbirth Group standard text.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Figures and Tables -
Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Figures and Tables -
Figure 3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 1 Caesarean section.
Figures and Tables -
Analysis 1.1

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 1 Caesarean section.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 2 Perinatal mortality.
Figures and Tables -
Analysis 1.2

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 2 Perinatal mortality.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 3 Serious perinatal morbidity.
Figures and Tables -
Analysis 1.3

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 3 Serious perinatal morbidity.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 4 Congenital fetal anomaly.
Figures and Tables -
Analysis 1.4

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 4 Congenital fetal anomaly.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 5 Pregnancy‐induced hypertension.
Figures and Tables -
Analysis 1.5

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 5 Pregnancy‐induced hypertension.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 6 Chronic hypertension: not prespecified.
Figures and Tables -
Analysis 1.6

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 6 Chronic hypertension: not prespecified.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 7 Glycaemic control ‐ Self‐monitored blood glucose (mean, mmol/L).
Figures and Tables -
Analysis 1.7

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 7 Glycaemic control ‐ Self‐monitored blood glucose (mean, mmol/L).

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 8 Glycaemic control ‐ Self‐monitored blood glucose tests/day.
Figures and Tables -
Analysis 1.8

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 8 Glycaemic control ‐ Self‐monitored blood glucose tests/day.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 9 Glycaemic control ‐ HbA1c (%): first trimester.
Figures and Tables -
Analysis 1.9

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 9 Glycaemic control ‐ HbA1c (%): first trimester.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 10 Glycaemic control ‐ HbA1c (%): second trimester.
Figures and Tables -
Analysis 1.10

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 10 Glycaemic control ‐ HbA1c (%): second trimester.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 11 Glycaemic control ‐ HbA1c (%): third trimester.
Figures and Tables -
Analysis 1.11

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 11 Glycaemic control ‐ HbA1c (%): third trimester.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 12 Glycaemic control ‐ Mean preprandial glucose (mmol/L).
Figures and Tables -
Analysis 1.12

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 12 Glycaemic control ‐ Mean preprandial glucose (mmol/L).

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 13 Glycaemic control ‐ Mean postprandial glucose (mmol/L).
Figures and Tables -
Analysis 1.13

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 13 Glycaemic control ‐ Mean postprandial glucose (mmol/L).

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 14 Glycaemic control ‐ Below FBG threshold (% days).
Figures and Tables -
Analysis 1.14

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 14 Glycaemic control ‐ Below FBG threshold (% days).

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 15 Hypoglycaemic episodes ‐ > 1 subjective (% of days): not prespecified.
Figures and Tables -
Analysis 1.15

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 15 Hypoglycaemic episodes ‐ > 1 subjective (% of days): not prespecified.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 16 Gestational weight gain (kg/week).
Figures and Tables -
Analysis 1.16

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 16 Gestational weight gain (kg/week).

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 17 Fetal distress: not prespecified.
Figures and Tables -
Analysis 1.17

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 17 Fetal distress: not prespecified.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 18 Gestational age at birth (weeks).
Figures and Tables -
Analysis 1.18

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 18 Gestational age at birth (weeks).

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 19 Birthweight (g).
Figures and Tables -
Analysis 1.19

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 19 Birthweight (g).

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 20 Apgar score.
Figures and Tables -
Analysis 1.20

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 20 Apgar score.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 21 Asphyxia: not prespecified.
Figures and Tables -
Analysis 1.21

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 21 Asphyxia: not prespecified.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 22 Neonatal hypocalcaemia.
Figures and Tables -
Analysis 1.22

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 22 Neonatal hypocalcaemia.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 23 Neonatal hypomagnesaemia: not prespecified.
Figures and Tables -
Analysis 1.23

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 23 Neonatal hypomagnesaemia: not prespecified.

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 24 Maternal hospitalisation (days).
Figures and Tables -
Analysis 1.24

Comparison 1 Very tight versus tight‐moderate glycaemic control, Outcome 24 Maternal hospitalisation (days).

Comparison 2 Tight versus moderate glycaemic control, Outcome 1 Pre‐eclampsia.
Figures and Tables -
Analysis 2.1

Comparison 2 Tight versus moderate glycaemic control, Outcome 1 Pre‐eclampsia.

Comparison 2 Tight versus moderate glycaemic control, Outcome 2 Caesarean section.
Figures and Tables -
Analysis 2.2

Comparison 2 Tight versus moderate glycaemic control, Outcome 2 Caesarean section.

Comparison 2 Tight versus moderate glycaemic control, Outcome 3 Perinatal mortality.
Figures and Tables -
Analysis 2.3

Comparison 2 Tight versus moderate glycaemic control, Outcome 3 Perinatal mortality.

Comparison 2 Tight versus moderate glycaemic control, Outcome 4 Transient maternal hypertension.
Figures and Tables -
Analysis 2.4

Comparison 2 Tight versus moderate glycaemic control, Outcome 4 Transient maternal hypertension.

Comparison 2 Tight versus moderate glycaemic control, Outcome 5 Hypoglycaemic epispodes ‐ first half of pregnancy: not prespecified.
Figures and Tables -
Analysis 2.5

Comparison 2 Tight versus moderate glycaemic control, Outcome 5 Hypoglycaemic epispodes ‐ first half of pregnancy: not prespecified.

Comparison 2 Tight versus moderate glycaemic control, Outcome 6 Large‐for‐gestational age (birthweight > 90th centile).
Figures and Tables -
Analysis 2.6

Comparison 2 Tight versus moderate glycaemic control, Outcome 6 Large‐for‐gestational age (birthweight > 90th centile).

Comparison 2 Tight versus moderate glycaemic control, Outcome 7 Respiratory distress syndrome.
Figures and Tables -
Analysis 2.7

Comparison 2 Tight versus moderate glycaemic control, Outcome 7 Respiratory distress syndrome.

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 1 Pre‐eclampsia.
Figures and Tables -
Analysis 3.1

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 1 Pre‐eclampsia.

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 2 Caesarean section.
Figures and Tables -
Analysis 3.2

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 2 Caesarean section.

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 3 Perinatal mortality.
Figures and Tables -
Analysis 3.3

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 3 Perinatal mortality.

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 4 Transient maternal hypertension.
Figures and Tables -
Analysis 3.4

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 4 Transient maternal hypertension.

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 5 Hypoglycaemic episodes ‐ in first half of pregnancy: not prespecified.
Figures and Tables -
Analysis 3.5

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 5 Hypoglycaemic episodes ‐ in first half of pregnancy: not prespecified.

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 6 Large‐for‐gestational age (birthweight > 90th centile).
Figures and Tables -
Analysis 3.6

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 6 Large‐for‐gestational age (birthweight > 90th centile).

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 7 Respiratory distress syndrome.
Figures and Tables -
Analysis 3.7

Comparison 3 Tight‐moderate versus loose glycaemic control, Outcome 7 Respiratory distress syndrome.

Summary of findings for the main comparison. Very tight versus tight‐moderate glycaemic control (maternal outcomes)

Very tight versus tight‐moderate glycaemic control (FBG target 3.33 to 5.0 versus 5.27 to 6.38 mmol/L)

Patient or population: pregnant women with pre‐existing type 1 diabetes
Setting: one study, USA
Intervention: very tight
Comparison: tight‐moderate glycaemic control

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with tight‐moderate glycaemic control

Risk with very tight glycaemic control

Pre‐eclampsia

not reported

Caesarean section

Study population

RR 0.92
(0.49 to 1.73)

22
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

FBG target 3.3 to 5.0 versus 5.27 to 6.38 mmol/L

667 per 1000

613 per 1000
(327 to 1000)

Perineal trauma

not reported

Gestational weight gain

The mean difference in gestational weight gain (kg/week) was 0

The mean difference in gestational weight gain (kg/week) was 0.02 kg/week more (0.23 fewer to 0.27 more)

22
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

FBG target 3.3 to 5.0 versus 5.27 to 6.38 mmol/L

Postnatal depression

not reported

Induction of labour

not reported

Later development of cardiovascular disease

not reported

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 One study with design limitations.

2 Wide confidence interval crossing the line of no effect, and small sample size.

Figures and Tables -
Summary of findings for the main comparison. Very tight versus tight‐moderate glycaemic control (maternal outcomes)
Summary of findings 2. Very tight versus tight‐moderate glycaemic control (infant outcomes)

Very tight versus tight‐moderate glycaemic control (FBG target 3.33 to 5.0 versus 5.27 to 6.38 mmol/L or FBG target < 4.44 versus < 5.55 mmol/L)

Patient or population: pregnant women with pre‐existing type 1 diabetes
Setting: 2 studies, both USA
Intervention: very tight
Comparison: tight‐moderate glycaemic control

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with tight‐moderate glycaemic control

Risk with very tight glycaemic control

Large‐for‐gestational age

not reported

Perinatal mortality

Study population

not estimable

22
(1 RCT)

⊕⊕⊝⊝
LOW 1 2

FBG target 3.33 to 5.0 versus 5.27 to 6.38 mmol/L

0 per 1000

0 per 1000
(0 to 0)

Serious perinatal morbidity

Study population

not estimable

22
(1 RCT)

⊕⊕⊝⊝
LOW 1 2

FBG target 3.33 to 5.0 versus 5.27 to 6.38 mmol/L

0 per 1000

0 per 1000
(0 to 0)

Neonatal hypoglycaemia

not reported

Childhood/adulthood adiposity

not reported

Childhood/adulthood diabetes

not reported

Childhood/adulthood neurosensory disability

not reported

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 One study with design limitations.

2 Small sample size, no events.

Figures and Tables -
Summary of findings 2. Very tight versus tight‐moderate glycaemic control (infant outcomes)
Summary of findings 3. Tight versus moderate glycaemic control (maternal outcomes)

Tight versus moderate glycaemic control (FBG target ≤ 5.6 mmol/L versus 5.6 to 6.7 mmol/L) ‐ Maternal outcomes

Patient or population: pregnant women with pre‐existing type 1 diabetes
Setting: 1 study, Saudi Arabia
Intervention: tight
Comparison: moderate glycaemic control

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with moderate glycaemic control

Risk with tight glycaemic control

Pre‐eclampsia

Study population

RR 5.29
(0.23 to 122.91)

45
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

FBG target ≤ 5.6 versus 5.6 to 6.7 mmol/L

Moderate: 0 out of 29 women, Tight: 1 out of 16 women.

not estimable

not estimable

Caesarean section

Study population

RR 1.21
(0.22 to 6.50)

45
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

FBG target ≤ 5.6 versus 5.6 to 6.7 mmol/L

103 per 1000

125 per 1000
(23 to 672)

Perineal trauma

not reported

Gestational weight gain

not reported

Postnatal depression

not reported

Induction of labour

not reported

Later development of cardiovascular disease

not reported

1 One study with design limitations.

2 Wide confidence interval crossing the line of no effect, few events and small sample size.

Figures and Tables -
Summary of findings 3. Tight versus moderate glycaemic control (maternal outcomes)
Summary of findings 4. Tight versus moderate glycaemic control (infant outcomes)

Tight versus moderate glycaemic control (FBG target ≤ 5.6 mmol/L versus 5.6 to 6.7 mmol/L) ‐ Infant outcomes

Patient or population: pregnant women with pre‐existing type 1 diabetes
Setting: 1 study, Saudi Arabia
Intervention: tight
Comparison: moderate glycaemic control

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with moderate glycaemic control

Risk with tight glycaemic control

Large‐for‐gestational age (birthweight > 90th centile)

Study population

not estimable

45
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

FBG target ≤ 5.6 versus 5.6 to 6.7 mmol/L

0 per 1000

0 per 1000
(0 to 0)

Perinatal mortality

Study population

not estimable

45
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

FBG target ≤ 5.6 versus 5.6 to 6.7 mmol/L

0 per 1000

0 per 1000
(0 to 0)

Serious perinatal morbidity

not reported

Neonatal hypoglycaemia

not reported

Childhood/adulthood adiposity

not reported

Childhood/adulthood diabetes

not reported

Childhood/adulthood neurosensory disability

not reported

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 One study with design limitations.

2 No events & small sample size.

Figures and Tables -
Summary of findings 4. Tight versus moderate glycaemic control (infant outcomes)
Summary of findings 5. Tight‐moderate versus loose glycaemic control (maternal outcomes)

Tight‐moderate versus loose glycaemic control (FBG ≤ 6.7 mmol/L versus 6.7 to 8.9 mmol/L) ‐ Maternal outcomes

Patient or population: pregnant women with pre‐existing type 1 diabetes
Setting: 1 study, Saudi Arabia
Intervention: tight‐moderate
Comparison: loose glycaemic control (mother)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with loose glycaemic control (mother)

Risk with Tight‐moderate

Pre‐eclampsia

Study population

RR 0.11
(0.01 to 0.99)

60
(1 RCT)

⊕⊕⊝⊝
LOW 1 2

FBG target ≤ 6.7 mmol/L versus 6.7 to 8.9 mmol/L

200 per 1000

22 per 1000
(2 to 198)

Caesarean section

Study population

RR 0.28
(0.10 to 0.78)

60
(1 RCT)

⊕⊕⊝⊝
LOW 1 3

FBG target ≤ 6.7 versus 6.7 to 8.9 mmol/L

400 per 1000

112 per 1000
(40 to 312)

Perineal trauma

not reported

Gestational weight gain

not reported

Postnatal depression

not reported

Induction of labour

not reported

Later development of cardiovascular disease

not reported

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 One study with design limitations.

2 Few events and small sample size.

3 Small sample size.

Figures and Tables -
Summary of findings 5. Tight‐moderate versus loose glycaemic control (maternal outcomes)
Summary of findings 6. Tight‐moderate versus loose glycaemic control (infant outcomes)

Tight‐moderate versus loose glycaemic control (FBG ≤ 6.7 mmol/L versus 6.7 to 8.9 mmol/L) ‐ Infant outcomes

Patient or population: pregnant women with pre‐existing type 1 diabetes
Setting: 1 study, Saudi Arabia
Intervention: tight‐moderate
Comparison: loose glycaemic control

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with loose glycaemic control

Risk with tight‐moderate glycaemic control

Large‐for‐gestational age (birthweight > 90th centile)

Study population

RR 0.01
(0.00 to 0.20)

60
(1 RCT)

⊕⊕⊝⊝
LOW 1 2

FBG target ≤ 6.7 versus 6.7 to 8.9 mmol/L

867 per 1000

9 per 1000
(0 to 173)

Perinatal mortality

Study population

RR 0.07
(0.00 to 1.37)

60
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 3

FBG target ≤ 6.7 versus 6.7 to 8.9 mmol/L

133 per 1000

9 per 1000
(0 to 183)

Serious perinatal morbidity

not reported

Neonatal hypoglycaemia

not reported

Childhood/adulthood adiposity

not reported

Childhood/adulthood diabetes

not reported

Childhood/adulthood neurosensory disability

not reported

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 One study with design limitations.

2 Small sample size.

3 Wide confidence interval crossing the line of no effect, few events and small sample size.

Figures and Tables -
Summary of findings 6. Tight‐moderate versus loose glycaemic control (infant outcomes)
Comparison 1. Very tight versus tight‐moderate glycaemic control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Caesarean section Show forest plot

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.49, 1.73]

1.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.49, 1.73]

2 Perinatal mortality Show forest plot

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Serious perinatal morbidity Show forest plot

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Congenital fetal anomaly Show forest plot

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

3.57 [0.19, 66.61]

4.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

3.57 [0.19, 66.61]

5 Pregnancy‐induced hypertension Show forest plot

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.40 [0.60, 3.25]

5.1 FBG target < 4.44 vs < 5.55 mmol/L

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.40 [0.60, 3.25]

6 Chronic hypertension: not prespecified Show forest plot

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.1 FBG target 3.33 to 5.0 mmol/L vs 5.27 to 6.38 mmol/L

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

7 Glycaemic control ‐ Self‐monitored blood glucose (mean, mmol/L) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

7.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L: first trimester

1

22

Mean Difference (IV, Fixed, 95% CI)

‐1.23 [‐2.19, ‐0.27]

7.2 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L: second trimester

1

22

Mean Difference (IV, Fixed, 95% CI)

‐0.99 [‐1.64, ‐0.34]

7.3 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L: third trimester

1

22

Mean Difference (IV, Fixed, 95% CI)

‐0.66 [‐1.60, 0.28]

8 Glycaemic control ‐ Self‐monitored blood glucose tests/day Show forest plot

1

22

Mean Difference (IV, Fixed, 95% CI)

1.60 [‐0.15, 3.35]

8.1 FBG target 3.33 to 5.0 vs 5.27 to 6.39 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

1.60 [‐0.15, 3.35]

9 Glycaemic control ‐ HbA1c (%): first trimester Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

9.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

‐1.20 [‐2.25, ‐0.15]

9.2 FBG target < 4.44 vs < 5.55 mmol/L

1

137

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.62, 0.62]

10 Glycaemic control ‐ HbA1c (%): second trimester Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

10.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐1.09, 0.09]

10.2 FBG target < 4.44 vs < 5.55 mmol/L

1

137

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.37, 0.57]

11 Glycaemic control ‐ HbA1c (%): third trimester Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

11.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐0.92, 0.32]

11.2 FBG target < 4.44 vs < 5.55 mmol/L

1

137

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.49, 0.29]

12 Glycaemic control ‐ Mean preprandial glucose (mmol/L) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

12.1 FBG target < 4.44 vs < 5.55 mmol/L: first trimester

1

137

Mean Difference (IV, Fixed, 95% CI)

‐0.39 [‐1.33, 0.55]

12.2 FBG target < 4.44 vs < 5.55 mmol/L: second trimester

1

137

Mean Difference (IV, Fixed, 95% CI)

‐0.27 [‐1.19, 0.65]

12.3 FBG target < 4.44 vs < 5.55 mmol/L: third trimester

1

137

Mean Difference (IV, Fixed, 95% CI)

‐0.34 [‐1.40, 0.72]

13 Glycaemic control ‐ Mean postprandial glucose (mmol/L) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

13.1 FBG target < 4.44 vs < 5.55 mmol/L: first trimester

1

137

Mean Difference (IV, Fixed, 95% CI)

‐0.94 [‐2.05, 0.17]

13.2 FBG target < 4.44 vs < 5.55 mmol/L: second trimester

1

137

Mean Difference (IV, Fixed, 95% CI)

‐0.56 [‐1.38, 0.26]

13.3 FBG target < 4.44 vs < 5.55 mmol/L: third trimester

1

137

Mean Difference (IV, Fixed, 95% CI)

‐0.11 [‐1.26, 1.04]

14 Glycaemic control ‐ Below FBG threshold (% days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

14.1 < 3.33 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

20.0 [7.00, 33.00]

14.2 < 2.78 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

17.0 [4.04, 29.96]

14.3 < 2.22 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

8.0 [‐3.56, 19.56]

15 Hypoglycaemic episodes ‐ > 1 subjective (% of days): not prespecified Show forest plot

1

22

Mean Difference (IV, Fixed, 95% CI)

22.0 [11.07, 32.93]

15.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

22.0 [11.07, 32.93]

16 Gestational weight gain (kg/week) Show forest plot

1

22

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.23, 0.27]

16.1 FBG target 3.3 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.23, 0.27]

17 Fetal distress: not prespecified Show forest plot

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.63, 2.11]

17.1 FBG target < 4.44 vs < 5.55 mmol/L

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.63, 2.11]

18 Gestational age at birth (weeks) Show forest plot

2

159

Mean Difference (IV, Fixed, 95% CI)

0.43 [‐0.23, 1.08]

18.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐2.44, 1.84]

18.2 FBG target < 4.44 vs < 5.55 mmol/L

1

137

Mean Difference (IV, Fixed, 95% CI)

0.5 [‐0.19, 1.19]

19 Birthweight (g) Show forest plot

2

159

Mean Difference (IV, Fixed, 95% CI)

‐2.62 [‐179.83, 174.59]

19.1 FBG target 3.33 to 5.0 vs 5.27 to 6.38 mmol/L

1

22

Mean Difference (IV, Fixed, 95% CI)

‐272.0 [‐803.99, 259.99]

19.2 FBG target < 4.44 vs < 5.55 mmol/L

1

137

Mean Difference (IV, Fixed, 95% CI)

31.0 [‐156.95, 218.95]

20 Apgar score Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

20.1 < 7 at 1 minute: FBG target < 4.44 vs < 5.55 mmol/L

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.40, 2.55]

20.2 < 7 at 5 minutes: FBG target < 4.44 vs < 5.55 mmol/L

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

21 Asphyxia: not prespecified Show forest plot

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.58, 1.78]

21.1 FBG target < 4.44 vs < 5.55 mmol/L

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.58, 1.78]

22 Neonatal hypocalcaemia Show forest plot

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.30, 1.03]

22.1 FBG target < 4.44 vs < 5.55 mmol/L

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.30, 1.03]

23 Neonatal hypomagnesaemia: not prespecified Show forest plot

1

127

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.25, 1.68]

23.1 FBG target < 4.44 vs < 5.55 mmol/L

1

127

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.25, 1.68]

24 Maternal hospitalisation (days) Show forest plot

1

137

Mean Difference (IV, Fixed, 95% CI)

10.60 [9.53, 11.67]

24.1 FBG target < 4.44 vs < 5.55 mmol/L

1

137

Mean Difference (IV, Fixed, 95% CI)

10.60 [9.53, 11.67]

Figures and Tables -
Comparison 1. Very tight versus tight‐moderate glycaemic control
Comparison 2. Tight versus moderate glycaemic control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pre‐eclampsia Show forest plot

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

5.29 [0.23, 122.91]

1.1 FBG target ≤ 5.6 mmol/L vs 5.6 to 6.7 mmol/L

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

5.29 [0.23, 122.91]

2 Caesarean section Show forest plot

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

1.21 [0.22, 6.50]

2.1 FBG target ≤ 5.6 vs 5.6 to 6.7 mmol/L

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

1.21 [0.22, 6.50]

3 Perinatal mortality Show forest plot

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.1 FBG target ≤ 5.6 vs 5.6 to 6.7 mmol/L

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Transient maternal hypertension Show forest plot

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.03, 13.66]

4.1 FBG target ≤ 5.6 vs 5.6 to 6.7 mmol/L

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.03, 13.66]

5 Hypoglycaemic epispodes ‐ first half of pregnancy: not prespecified Show forest plot

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

26.47 [1.61, 435.38]

5.1 FBG target ≤ 5.6 vs 5.6 to 6.7 mmol/L

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

26.47 [1.61, 435.38]

6 Large‐for‐gestational age (birthweight > 90th centile) Show forest plot

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.1 FBG target ≤ 5.6 vs 5.6 to 6.7 mmol/L

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

7 Respiratory distress syndrome Show forest plot

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.09, 9.24]

7.1 FBG target ≤ 5.6 v 5.6 to 6.7 mmol/L

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.09, 9.24]

Figures and Tables -
Comparison 2. Tight versus moderate glycaemic control
Comparison 3. Tight‐moderate versus loose glycaemic control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pre‐eclampsia Show forest plot

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 0.99]

1.1 FBG ≤ 6.7 mmol/L vs 6.7 to 8.9 mmol/L

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 0.99]

2 Caesarean section Show forest plot

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.28 [0.10, 0.78]

2.1 FBG target ≤ 6.7 vs 6.7 to 8.9 mmol/L

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.28 [0.10, 0.78]

3 Perinatal mortality Show forest plot

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.07 [0.00, 1.37]

3.1 FBG target ≤ 6.7 vs 6.7 to 8.9 mmol/L

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.07 [0.00, 1.37]

4 Transient maternal hypertension Show forest plot

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

1.81 [0.12, 27.07]

4.1 FBG target ≤ 6.7 vs 6.7 to 8.9 mmol/L

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

1.81 [0.12, 27.07]

5 Hypoglycaemic episodes ‐ in first half of pregnancy: not prespecified Show forest plot

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

5.22 [0.32, 86.28]

5.1 FBG target ≤ 6.7 vs 6.7 to 8.9 mmol/L

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

5.22 [0.32, 86.28]

6 Large‐for‐gestational age (birthweight > 90th centile) Show forest plot

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.01 [0.00, 0.20]

6.1 FBG target ≤ 6.7 vs 6.7 to 8.9 mmol/L

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.01 [0.00, 0.20]

7 Respiratory distress syndrome Show forest plot

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.17 [0.05, 0.59]

7.1 FBG target ≤ 6.7 vs 6.7 to 8.9 mmol/L

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.17 [0.05, 0.59]

Figures and Tables -
Comparison 3. Tight‐moderate versus loose glycaemic control