Methods

RCT.

Participants

137 pregnant women and their infants.

Recruited: July 1978 to June 1989.

Setting: Perinatal Treatment Center, University of Cincinnati, Ohio, USA.

Inclusion criteria: women with type 1 diabetes enrolled in the trial before 9 weeks' gestation.

Exclusion criteria: infants whose birth dates were discrepant by 2 weeks or more from the estimated gestational age.

Severity of diabetes:

Very tight glycaemic control target: 31 White class B‐C; 37 White class D‐RT.

Tight‐moderate glycaemic control target: 38 White class B‐C; 31 White class D‐RT.

Duration of diabetes (years):

Very tight glycaemic control target: 11.9 (6.1).

Tight glycaemic control target: 11.3 (7.1).

Interventions

Very tight glycaemic control target (n = 68):

Target of FBG < 80 mg/dL (< 4.44 mmol/L); 1.5 hour postprandial BG < 120 mg/dL (< 6.66 mmol/L).

Admitted to hospital immediately on trial entry to achieve strict control; seen weekly throughout pregnancy.

Tight glycaemic control target (standard management) (n = 69):

Target of FBG < 100 mg/dL (< 5.55 mmol/L); postprandial BG < 140 mg/dL (< 7.77 mmol/L).

Only admitted to hospital if, after 1 week of outpatient management, the criteria for control of blood glucose were not met; seen biweekly in the first trimester, and weekly thereafter.

ALL WOMEN: all women received a twice‐daily insulin dose including both a short‐acting and an intermediate acting insulin, with dietary regulation; blood glucose was monitored with a reflectance meter (Ames dextrometer).

All women were admitted to hospital for the 28th week of gestation and again at 1 to 4 weeks before anticipated birth to evaluate and optimise serum glucose control.

Outcomes

HbA1c (first, second, third trimester).

Mean preprandial glucose (first, second, third trimester).

Mean postprandial glucose (first, second, third trimester).

Pregnancy‐induced hypertension.

Maternal length of hospital stay.

Infant serum calcium concentrations ‐ hypocalcaemia defined as serum total of < 8.0 mg/dL (2.00 mmol/L) in term infants (at least 37 weeks GA); and < 7.0 mg/dL (1.75 mmol/L) in preterm infants.

Infant serum magnesium concentrations ‐ hypomagnesaemia defined as serum magnesium concentration < 1.6 mg/dL (0.66 mmol/L).

Perinatal asphyxia (defined as presence of late decelerations in fetal heart rate or prolonged fetal bradycardia (fetal distress) and/or 1 minute Apgar scores < 7).

Birthweight.

GA.

Apgar score.

Fetal distress.

Notes

Mimouni 1987 appears to be an interim report of the trial.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"randomly assigned" ‐ no further information.

Allocation concealment (selection bias)

Unclear risk

"randomly assigned" ‐ no further information.

Blinding (performance bias and detection bias)
All outcomes

High risk

Not feasible to blind the intervention, although blinded assessment of outcomes would have been possible.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up reported.

Selective reporting (reporting bias)

High risk

None of the primary review outcomes of perinatal mortality or serious perinatal morbidity, pre‐eclampsia, hyperglycaemia requiring treatment and caesarean birth were reported; many secondary review outcomes also not reported (e.g. large‐for‐gestational age).

Other bias

Low risk

No apparent evidence of other bias.

Methods

RCT.

Participants

60 pregnant women with type 1 diabetes; aged between 24 and 40 years; parity between 3 to 8.

Setting: King Fahad Hospital, Alkhobar, Saudi Arabia.

Inclusion criteria:

White classification B and C for type 1 diabetes.

Exclusion criteria:

Women with any other medical complications; women who presented after the first trimester.

Interventions

Tight glycaemic control target (n = 16):

Target of 5.6 mmol/L or below*.

Moderate glycaemic control target (n = 29):

Target between 5.6 and 6.7 mmol/L*.

Loose glycaemic control (n = 15):

Target between 6.7 and 8.9 mmol/L*.

*paper does not specify if this was fasting blood glucose, but we have assumed that it is

ALL WOMEN: were admitted to hospital during the first trimester to regulate their diet and insulin requirements (average stay of 8 days); had insulin doses of 1 unit for each 0.6 mmol/L above the set target and adjusted as required; were reviewed every 2 weeks in the clinic for routine antenatal care, glycosuria and bacteriuria; were readmitted to hospital at 20 and 28 weeks' GA to readjust insulin dose, ultrasound follow‐up of biparietal diameter; were asked to count up to 10 fetal movements every day from 28 weeks' GA; were readmitted to hospital at 36 weeks' GA for insulin dose readjustment, ultrasonography, fetal movement count, biweekly oestriol estimation and electronic fetal monitoring.

At 38 weeks' GA, women with no contraindication for vaginal birth had their cervix evaluated and PGE2 sublingual tablets were administered to women who had an unfavourable cervix.

Outcomes

Fasting, 2‐hour postprandial and midnight blood glucose concentrations.

Length of hospital stay.

Ultrasound follow‐up of fetal biparietal diameter, head and abdominal circumferences; and femoral length at 30 and 28 weeks' GA.

Weekly serum oestriol estimation and electronic fetal monitoring (biochemical and physical tests) from 28 weeks' GA.

Perinatal mortality.

Pre‐eclampsia.

Caesarean section.

Maternal hypoglycaemia in first half of pregnancy.

Transient maternal hypotension.

Respiratory distress syndrome.

Birthweight > 90th centile.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"allocated at random" ‐ no further details.

Allocation concealment (selection bias)

Unclear risk

"allocated at random" ‐ no further details.

Blinding (performance bias and detection bias)
All outcomes

High risk

Not feasible to blind the intervention, although blinded assessment of outcomes would have been possible.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up reported.

Selective reporting (reporting bias)

High risk

Primary review outcomes of congenital anomalies and maternal hyperglycaemia requiring treatment not reported; many secondary review outcomes not reported.

Other bias

Unclear risk

Numbers randomised per group are imbalanced (16:29:15). This may have been due to 1:2:1 randomisation but this was not mentioned in the paper.

Methods

RCT.

Participants

26 pregnant women with type 1 diabetes who presented for antenatal care before 13 weeks' GA.

Recruited from 1 April 2000 to 31 March 2003.

Type 1 diabetes was identified on clinical grounds, including requirement for insulin and/or a history of abrupt onset of diabetes, diabetic ketoacidosis or both.

Setting: Department of Obstetrics and Gynaecology, Kaiser Permanente Hospital, Bellflower, CA, USA.

Interventions

Very tight glycaemic control target (n = 13 women and babies):

Fasting and pre‐meal glucose targets of 60 to 90 mg/dL (3.33 to 5.0 mmol/L); and 1 hour post‐meal targets of 120 to 140 mg/dL (6.66 to 7.77 mmol/L).

Tight glycaemic control target (n = 9 women and babies):

Fasting and pre‐meal glucose targets of 95 to 115 mg/dL (5.27 to 6.38 mmol/L); and 1 hour post‐meal targets of 155 to 175 mg/dL (8.6 to 9.71 mmol/L).

ALL WOMEN: were instructed in diet, insulin administration and glucose self‐monitoring; diet caloric content was based on ideal prepregnancy weight (40% carbohydrates, 20% fat and 40% protein).

For women using multiple injections, combinations of intermediate acting (NPH) and either regular insulin or insulin lispro were used to control maternal glycaemia. Women using continuous insulin infusion (insulin pumps) were trained to adjust their basal and bolus doses of insulin lispro to achieve the target values for their respective group.

Women were given written and verbal instructions in the daily adjustment of their insulin doses to achieve target glucose values for their assigned group.

Outcomes

Perinatal mortality.

Serious perinatal morbidity.

Capillary plasma glucose (self‐monitored 7 times a day with a memory‐based portable glucose meter).

Hypoglycaemic symptoms (self‐reported nervousness, tremulousness and peri‐oral numbness).

HbA1c measured each trimester.

BMI.

Maternal weight gain.

Chronic hypertension.

GA (weeks).

Caesarean.

Birth defects.

Birthweight.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"computer‐generated block randomization."

Allocation concealment (selection bias)

Unclear risk

"computer‐generated block randomization."

Blinding (performance bias and detection bias)
All outcomes

High risk

"open label"; not feasible to blind the intervention, although blinded assessment of outcomes would have been possible.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

4/26 (15.4%) ‐ all 4 were from the very tight glycaemic control target group (2 women had first trimester abortions, 1 was excluded because she had participated in an earlier pregnancy and 1 left the study because of not attending appointments).

Selective reporting (reporting bias)

High risk

Primary review outcomes of pre‐eclampsia and maternal hyperglycaemia requiring treatment and serious perinatal morbidity not reported; many secondary review outcomes not reported.

Other bias

Low risk

No apparent evidence of other bias.