Background
High dose (HD) insulin therapy was previously considered an indication by our obstetrics team for induction of labour around 38 weeks’ gestation in GDM pregnancies. We investigated whether HD insulin therapy is associated with adverse pregnancy outcomes and neonatal complications.
Methods
This was a retrospective, observational study of prospectively collected data. Singleton pregnancies of GDM women (diagnosed by ADIPS 2014 criteria), delivered from March 2016 to May 2022 were included. Women presenting at >36 weeks’ gestation, having <2 clinical reviews, or with last weight measured >4weeks before delivery were excluded. Initial exploratory analysis demonstrated an inflection point for most adverse pregnancy outcomes at >50 units/day. Patients were grouped as HD (≥50 units insulin/day) versus low dose (LD) (<50 units insulin/day or diet managed). Clinical outcomes assessed included early delivery (<37weeks), caesarean section, large for gestational age infant (LGA, >90th percentile), small for gestational age (SGA, <10th percentile), neonatal hypoglycaemia (<2.6mmol/L), jaundice (requiring phototherapy) and shoulder dystocia. Univariate analyses included independent sample t-tests (continuous variables) and chi-square analyses (categorical variables). Logistic regression models were undertaken to adjust for baseline characteristics differences. Statistical significance p<0.05. Metformin was not used.
Results
HD insulin therapy was significantly associated with increased maternal age, gravida, parity, pre-pregnancy BMI, gestational weight gain (GWG) following first presentation, fasting, 1-hour and 2-hour blood glucose (on 75g OGTT) and lower gestational age at delivery. The HD insulin group were more likely to have excessive GWG (according to the Institute of Medicine weight gain targets), have prior GDM, prior macrosomia and family history of diabetes. There were more South Asian and less East/South-East Asian women in the HD group. There were no significant differences in proportions of European or Middle Eastern ethnicities. On univariate analyses, HD women were more likely to have early delivery [10.1 vs 6.0%, OR 1.8 (95% CI 1.0 – 3.2), p<0.05], caesarean section (53.6 vs 34.1%, OR 2.2 (95% CI 1.6 – 3.2), p<0.001], LGA infant [20.3 vs 10.9%, OR 2.1 (95% CI 1.3 – 3.2), p< 0.001] and neonatal hypoglycaemia [23.9 vs 19.2, OR 3.1 (95% CI 2.4 – 4.7), p<0.001] compared to the LD group. Following adjustments, only neonatal hypoglycaemia remained significant [adjusted OR 2.1 (95% CI 1.2 – 3.6), p<0.01].
Conclusion
On univariate analyses, HD insulin therapy was associated with increased risk of early delivery, caesarean section, LGA and neonatal hypoglycaemia. Following adjustment, a two-fold increased risk of neonatal hypoglycaemia remained, but other outcomes were no longer significant.
Table 1. Outcomes According to High vs Low dose Group
|
|
High dose Insulin >50 units/day n (%) Total = 138 |
Low dose (Diet controlled or Insulin < 50 units/day n (%) Total = 1830 |
Unadjusted Odds Ratio (95% CI) |
Adjusted Odds Ratio (95% CI) |
|
Premature Delivery (<37 weeks) |
14 (10.1) |
109 (6.0) |
1.8 (1.0 – 3.2)* |
1.0 (0.4 – 2.2) |
|
Caesarean Section |
74 (53.6) |
624 (34.1) |
2.2 (1.6 – 3.2)*** |
1.5 (1.0 – 2.3) |
|
LGA |
28 (20.3) |
200 (10.9) |
2.1 (1.3 – 3.2)*** |
1.1 (0.6 – 2.0) |
|
SGA |
6 (4.3) |
153 (8.4) |
0.5 (0.2 – 1.1) |
0.7 (0.3 – 1.8) |
|
Neonatal Hypoglycaemia |
33 (23.9) |
169 (9.2) |
3.1 (2.0 – 4.7)*** |
2.1 (1.2 - 3.6)** |
|
Neonatal Jaundice |
9 (6.5) |
89 (4.9) |
1.4 (0.7 - 2.8) |
0.9 (0.4- 2.2) |
|
Shoulder Dystocia |
1 (0.7) |
10 (0.5) |
1.3 (0.2 – 10.5) |
1.8 (0.1 – 29.1) |
*p<0.05, **p<0.01, ***p<0.001