Journal Club Papers
Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial. Cluver et al. BMJ. 2021.
This randomized placebo-controlled trial, led by our very own (Cathy Cluver, Sue, and Stephen), examined metformin to treat preterm preeclampsia.
- 180 women diagnosed with preterm preeclampsia between 26+0 – 31+6 weeks gestation were treated with 3g of oral metformin (extended release) or placebo daily until delivery.
- The primary outcome was prolongation of gestation.
- The median time from randomization to delivery was 17.7 days (IQR 5.4 – 29.4 days) for the metformin arm vs 10.1 days (IQR 3.3 – 24.1 days) for the placebo arm; median difference of 7.6 days (p-value 0.057).
- In a pre-specified analysis excluding women who stopped taking the trial drug (13 in the metformin group and 15 in the placebo group) the median time from randomization to delivery was 17.5 days (IQR 5.4 – 28.7 days) in the metformin arm vs 7.9 days (3.0 – 22.2 days) in the placebo arm; significant median difference of 9.6 days.
- In a further pre-specified analysis excluding women who reduced the dose of trial drug (34 in the metformin group and 11 in the placebo) the median time from randomization to delivery was 16.3 days (IQR 4.8 – 28.8 days) in the metformin arm vs 4.8 days (IQR 2.5 – 15.4 days) in the placebo arm; significant median difference of 11.5 days.
- Secondary composite maternal, fetal and neonatal outcomes did not differ between the metformin and placebo arms.
- Among exploratory outcomes, birthweight was non-significantly increased in the metformin arm compared with placebo (1620g vs 1510g) and the total length of admission to any neonatal until was non-significantly reduced in the metformin arm compared with placebo (18 vs 30 days, median difference of 12 days).
- Women in the metformin arm, compared with the placebo arm, experienced more diarrhoea (33% vs 6%) and a non-significant increase in nausea (21% vs 11%). No serious adverse events related to the trial drug were recorded.
These findings suggest metformin may be associated with a clinically meaningful prolongation of gestation among women with preterm preeclampsia. Importantly, these findings also provide evidence that preterm preeclampsia is treatable. Given the borderline significance, further trials are needed to confirm these findings in a larger cohort before metformin is rolled out as a treatment for preterm preeclampsia.
Short-term outcomes: Planned mode of delivery after previous caesarean section and short-term outcomes. Fitzpatrick et al. 2019. PLoS Med.
Review contributed by Dr Hannah Gordon
This population-based linkage study used Scottish data on 74,043 women who had term singleton births between 2002 and 2015, and a history of one or more caesarean sections.
- Among this cohort, 45,579 (61.6%) women were planned for an elective repeat caesarean section and 28,464 (38.4%) planned and were eligible for a VBAC. The majority of the planned VBAC group had a history of one previous caesarean section (96.6%, n=27,509), and 3.4% (n=955) had two or more.
- 71.6% (n=20,375) of planned VBAC cases had a successful vaginal birth and the remaining 28.4% (n=8,089) required an emergency caesarean section in labour
- Compared with elective repeat caesarean section, planned VBAC was associated with higher odds of:
- Uterine rupture (0.04% vs 0.24%; adjusted Odds Ratio (aOR) 7.33; 95% CI 3.88-13.88)
- Blood transfusion (aOR 2.29; 95% CI 1.88-2.79)
- Sepsis (aOR 1.82; 95% CI 1.25-2.65)
- Surgical injury (aOR 2.96; 95% CI 1.83-4.77)
- Adverse perinatal outcomes (8.0% vs 6.4%; aOR 1.22; 95% CI 1.15-1.30) including admission to a neonatal unit, need for neonatal resuscitation with drugs and/or intubation, APGAR score <7 at 5 minutes, and intrapartum stillbirth or neonatal death.
- The risks associated with planned VBAC were higher with labour induction.
- Conversely, compared with elective repeat caesarean section, VBAC was associated with higher rates of breastfeeding at discharge from hospital (aRR 1.18; 95% CI 1.16-1.20) and at 6-8 weeks postpartum (aRR 1.29; 95% CI 1.26-1.32).
- Importantly it is worth noting that absolute risk of serious maternal morbidity remained low: 0.8% of women undergoing elective repeat caesarean section vs 1.8% of planned VBAC patients.
This population-based cohort study, aimed to provide counsel for women about planned VBAC. The maternal and neonatal outcomes are broadly in keeping with previously published Australian data (Crowther et al, PLOS Med, 2012).
Compared with the success rate of 43.2% found by Crowther et al, 71.6% of women in this study current cohort had a successful VBAC. This reinforces the importance of antenatal identification of women suitable for VBAC and to ensure patients are making informed choices about their planned mode of delivery.
Childhood outcomes: Planned mode of birth after previous caesarean section and special educational needs in childhood: a population-based record linkage cohort study. Fitzpatrick et al. BJOG 2021.
The same authorship team who penned paper 2 undertook another linkage study looking at long term outcomes. Examining a similar Scottish cohort of term singleton children born to mothers after a VBAC or an elective caesar (after a prior caesar) and a child's risk of having a record of special educational needs (SENs).
- The cohort included 44,892 children born in Scotland between 2002-2011.
- The outcome included any diagnosis of special education needs recorded between age 4-11 for children attending primary or special school.
- Compared with elective repeat caesarean section, children born following planned VBAC had a similar risk of having a record of any SENs (19.24 vs 17.63%; aOR 1.04; 95%CI 0.99-1.09).
- Planned VBAC following labour induction did not significantly alter this risk, although planned VBAC with labour induction was associated with an increased risk of sensory impairment (1.18 vs 0.78%; aOR 1.60; 95%CI 1.09-2.34) – which the authors acknowledge may be the result of multiple comparisons or residual confounding.
This study provides reassurance that planned mode of birth after caesarean section does not affect special education needs in childhood.