- Click here for explanation of classification scheme.

To evaluate the maternal and neonatal complication rates of mild gestational hyperglycaemia (MGH) compared to a control group in France.

 

• The study population was drawn from 15 public maternity units in northern France between February and September 1992.  
• Women who had only 1 of the 4 OGTT values above Carpenter and Coustan’s criteria, i.e. fasting> 5.3 mmol/l; 1 h > mmol/l; 2 h > 8.6 mmol/l; > 3 h 7.8 mmol/l were defined as MGH, mild gestational hyperglycaemia.
• The study received ethical approval from institutional committee responsible for human experimentation.
• All women received verbal information on the study from their obstetricians and gave written consent to participate on admission to obstetric unit before the delivery.
• The women in the control group (n=112) was defined by a 50-g glucose challenge test below 7.2 mmol/l.

• Thirteen women were excluded from the analysis of maternal and neonatal complications because of twin pregnancies (n=5), high blood pressure pre-pregnancy (n=6), asthma (n=1), and haemochromatosis (n=1).
• Pre-pregnancy diabetes
• GDM
• Timing: If the 1-h glucose value was > 7.2 mmol/l, the test was considered positive and the woman was recalled as soon as possible for a 3-h,100-g OGTT after an overnight fast of at least 8 h.

Recruitment method was not detailed

Design Prospective Cohort

Blinding used :

• The control group was recruited at the admission before delivery, so the adverse outcomes did not affect the woman's or obstetricians's decision.
• The MGH group was recruited just after the OGTT. The patients did not know that they had a borderline glucose intoerance but the results were not blinded from the obstetricians. This fact could have influenced the medical decision for Caesarean section and the rate of prematurity. Therefore, each record with Caesarean section and prematurity was reviewed after the delivery by two obstetricians; the OGTT results were blinded from the two obstetricians. In every reviewed case they found an obstetrical reason for the Caesarean section other than MGH.

Intervention  (infant) If venous laboratory blood glucose was below 1.7 mmol/l, hypoglycaemia was diagnosed and treatment given. 

Statistical Analysis 

• With an alpha risk of 5%, a power of 80%, 1 LGA rate of 25% in MGH groups and a rate of 10% in the control group, the number of subjects in each group were 97.
• All analyses were performed with SAS software (SAS Institute, Cary, NC).
• Maternal and neonatal outcomes (expressed as percentage of affected women or newborns) in the two groups were compared with the X² or Fisher’s exact test.
• Student’s t-tests were used for quantitative data.
• Multivariate logistic regression was used to take confounding factors into account. 

Timing of Measurements: hypoglycaemic infants in the two groups were identified by at least one capillary blood glucose test at birth, at 2 h of life and then three times a day for 48h, before feeding.

Dependent Variables

Diagnostic criteria:

• Women, in public maternity units, were routinely screened between the 24^th and 28^th weeks of gestation by the use of a 50-g oral glucose load with venous plasma sampling at 1 h, in the fed or fasting state.
• If the 1-h glucose value was > 7.2 mmol/l, the test was considered positive and the woman was recalled as soon as possible for a 3-h, 100-g OGTT after an overnight fast of at least 8 h.
• Maternal glucose determinations were done in hospital or private laboratories, using the glucose oxidase method in 99.8% of cases. The different laboratories participated in an external quality assessment during the study period. The coefficient of variation for glucose values was 5.2%.
• Infant blood glucose level was measured with a reflectance meter which was the same in each centre. If capillary blood glucose was below 1.7 mmol/l, venous laboratory blood glucose was determined. If venous laboratory blood glucose was below 1.7 mmol/l, hypoglycemia was diagnosed and treatment given. If there were clinical signs of hypoglycaemia but no venous laboratory blood glucose test was performed, it was considered as hypoglycaemia.
• Pregnancy induced hypertension defined as a diastolic blood pressure above 85 mmHg on two occasions. Included: - preeclampsia-defined by such hypertension plus proteinuria above 0.5 g/24 h on  two occasions
• Caesarean section
• Shoulder dystocia was defined as a difficulty in delivery of the anterior shoulder of the infant, as described by the delivering clinician, necessitating manoeuvres other than downward traction and episiotomy for delivery
• Macrosomia  was defined as birth weight> 4000g
• Large for gestational age (LGA)-birth weight above the 90^th percentile, on the basis of standard growth curves for the French population according to gestational and sex (AUDIPOG study).
• Small for gestational age (SGA)-birth weight below the 10^th percentile, on the basis of standard growth curves for the French population according to gestational and sex (AUDIPOG study).
• Pathological deliveries were defined as fetal and maternal abnormalities during labour  
• Hypoglycaemia infants in the two groups were identified by at least one capillary blood glucose test at birth, at 2 h of life and then three times a day for 48h, before feeding
• Hyperbilirubinaemia was screened for on the third day of life. The definition of hyperbilirubinaemia was according to Cockington curves :    

Birth weight< 1,500 g, bilirubinaemia>88 mg/l

Birth weight between 1,500g and 2,000g, bilirubinaemia >114 mg/l

Birth weight between 2,001g and 2,500g, bilirubinaemia >141 mg/l

Birth weight >2,500g,  bilirubinaemia >158 mg/l

• Respiratory distress
• Transfer to neonatal care unit
• Malformations
• Mortality
• Prematurity- was defined by a gestational age less than 37 weeks.
• 1-min Apgar score<7 defines as a low apgar score
• 5-min Apgar score <7
• Adverse maternal and fetal outcome

Independent Variables

• Age(years)
• BMI (kg/m ² )
• BMI> 27
• Multiparity
• Gestational age-based on the last menstrual period, combined with early ultrasonographic assessment in 80.6% of cases.
• Higher educational status
• Foreigners
• Risk factors

Control Variables

 

Initial N: 131 MGH group, 108 in control group

Attrition (final N):  as above

Age: See Table 1

Ethnicity: not mentioned

Other relevant demographics: see Results

Anthropometrics

Location: Department of Endocrinology and Daibetology, Clonque Marc Linquette Chru Lille, Lille, France.

Women with MGH were significantly older and more obese than the controls (Table 1)   

Table 1 Maternal characteristics in mild gestational hyperglycemia (MGH) and the control group

Maternal   Characteristics	MGH	Control group	P value
n	131	108	-
Age (years)	28.8+ 5.8	27.0+ 5.2	P <0.05
BMI (kg/m2)	24.8+ 4.8	23.0+ 3.9	P<0.01
BMI>27	26.9	13.9	P<0.05
Multiparity	60.0	63.0	0.73
Higher educational status	46.0	45.7	0.96
Foreigners	13.1	8.5	0.26
Risk factors	47.3	26.9	P<0.01

Data are n, %, or means + SD. BMI, body mass index

The rate of pregnancy hypertension and Caesarean section were different between the MGH and control group (10.8%vs 4.6%; 17.6% vs. 10.2%) but the difference was not statistically significant. 

The rate of macrosomia (defined by a weight of 4,000 g or more) was significantly different between the two groups (P=0.05). After adjustment for pre-pregnancy body mass index >27, maternal age >35, multiparity and educational level, the difference was not statistically significant (Table 2). 

Women with MGH had a higher rate of LGA compared the control group (22.15 and 11.4%; P<0.05).  After adjustment for pre-pregnancy body mass index >27, maternal age >35, multiparity and educational level, the significant relationship between LGA and MGH persisted (odds ratio 2.50; 95% CI9 1.16-5.40; P<0.05)(Table 2). 

Table 2 Maternal and neonatal complications in mild gestational hyperglycemia (MGH) and the control group 

Maternal characteristics	MGH	Control group	P value
n	131	108	-
Pregnancy induced hypertension	10.8	4.6	0.08
Caesarean section	17.6	10.2	0.10
Pathological deliveries	7.6	2.8	0.10
Shoulder dystocia	0.8	3.7	0.18
Birth weight > 4000 g	16.0	7.6	0.05
Large for gestational age (LGA)	22.1	11.4	<0.05
Small for gestational age	4.6	9.5	0.13
Hypoglycaemia	18.3	12.5	0.23
Hyperbilirubinaemia	1.7	0	0.50
Respiratory distress	1.5	0.9	1.00
Transfer to neonatal care unit	5.4	2.8	0.52
Malformations	3.1	0.0	0.13
Mortality	0.8	0.0	1.00
Prematurity	5.3	3.7	0.76
1-min Apgar score<7	4.7	0.0	<0.05
5-min Apgar score <7	1.6	0.0	0.20
Adverse maternal and fetal outcome	53.4	28.75	<0.01

Data are n or %. Adverse maternal and fetal outcome was defined as the presence of one or more of the following: pregnancy –induced hypertension, pathological deliveries, shoulder dystocia, mortality, malformations, LGA, low 1-minute Apgar score, respiratory distress, hyperbilirubinaemia, and hypoglycaemia.

Other Findings

 

 

• Mild gestational hyperglycemia was more frequently associated with adverse maternal and fetal outcome than in the controls (53.4% vs. 28.7%; P<0.01).
• The study suggested that the increased rate of adverse maternal and fetal outcome, especially LGA, was associated with untreated mild gestational hyperglycaemia during pregnancy is independent of confounding factors.
• The rates of adverse matewrnal and fetal outcome were similar in MGH groups with and without risk factors, and significantly different from the control group. These results favour systematic screening but a specific study of this question is necessary.
• The study confirmed the increased rate of adverse maternal and fetal outcome associated with untreated mild gestational hyperglycaemic women. The compications seen were probably a result of the metabolic status; it is tempting to postulate that the mechanism of fetal macrosomia in the study group may be maternal hyperglycaemia leading to fetal hyperinsulinism. Hyperinsulinism is involved hyperbilirubinaemia, respiratory distress, and hypoglycaemia.
• In conclusion, even minor maternal glucose abnormalities can be associated with LGA infants, and other gestational complications. Therapeutic trials with economical evaluation in this population of mild gestational hyperglycaemia are necessary, in order to prove better outcomes when treated.

Analytical longitudinal surveys refer to what epidemiologists term prospective or cohort studies. A Cohort Study is a study in which patients who presently have a certain condition and/or receive a particular treatment are followed over time and compared with another group who are not affected by the condition under investigation. Studies of this kind provide a better opportunity than one time cross sectional studies to examine whether certain behaviors do in fact lead to (or cause) the disease.                 

The limitations and critique of the study, as stated by the authors appear to be very appropriate.