Journal Club Papers
Paper 1: Scheduled birth at term for the prevention of pre-eclampsia (PREVENT-PE): an open-label randomised controlled trial.
Goadsby et al.
Lancet. (4 Dec 2025).
10.1016/S0140-6736(25)01207-3
Review contributed by Dr Hannah Gordon.
Preeclampsia is a leading cause of obstetric morbidity and mortality. While aspirin reduces the risk of preterm preeclampsia, this trial by Goadsby et al describes the first promising intervention to reduce the risk of term preeclampsia. The trial: This was a randomised controlled trial across two UK hospitals, investigating whether term preeclampsia can be prevented by planning birth among high-risk women. The population: Women with singleton pregnancies were recruited at 35-36 weeks’ gestation when presenting for routine fetal ultrasound. The intervention: Participants were randomised to usual care vs intervention, which included 1) an assessment of preeclampsia risk and 2) planned birth stratified across gestation by level of preeclampsia risk:
1. ≥1:2 risk - birth initiated at 37+0-2,
2. 1:3 to 1:5 risk - birth initiated at 38+0-2
3. 1:6 to 1:20 risk - - birth initiated at 39+0-2
4. 1: 21 to 1:50 risk - 40+0–2
5. <1 in 50 risk - ≥41 (per local policy)
Preeclampsia risk assessment was made using the Fetal Medicine Foundation competing-risks model, which considers maternal risk factors, mean arterial pressure and biochemical markers (sFLT-1, PLGF).
The outcome: A diagnosis of pre-eclampsia (defined by International Society for the Study of Hypertension in Pregnancy criteria)
The findings: Of 10,803 eligible women, 8,094 (74.9%) consented to be involved in the study, including 4,042 randomised to the intervention, and 4,058 to usual care.
Most women in the intervention group (78.1%; n=3152) were considered low risk for preeclampsia (<1:50).
65 (1.6%) women were in the highest risk group (predicted ≥1:2 chance of developing preeclampsia) and were allocated to planned birth at 37 weeks. A further 100 (2.5%) had birth planned at 38 weeks’, 318 (7.9%) at 39 weeks’ and 402 (10.0%) at 40 weeks’.
Among the intervention group, 3.9% (n=158) developed preeclampsia, compared with 5.6% (n=226) in the usual care group. The intervention conferred a 30% lower risk of developing preeclampsia (adjusted risk ratio (aRR) 0.70 [95% confidence interval: 0.58, 0.86]), without an increase in complications including emergency caesarean section or need for NICU admission.
There was also no increase in postpartum preeclampsia associated with the intervention, compared with usual care. There was a greater proportion of women with gestational hypertension (4.7%, n=188 intervention vs. 3.9%, n=157 usual care), though this was not statistically significant.
A 30% reduction in term preeclampsia is substantial by any measure. Based on this study, thirteen high-risk women require planned birth to prevent one case of term preeclampsia. Importantly, more than three quarters of women returned a low-risk screen, so when considering feasibility, 59 women must be screened to prevent one case of term preeclampsia. What remains to be seen, therefore, is how this intervention could be implemented in clinical practice, particularly when the biochemical markers it relies upon aren’t readily accessible across many sites. Nonetheless, this is an exciting study, potentially reducing the short- and long-term health burdens of preeclampsia for at-risk women and their infants.
Paper 2: Risk of infection and wound dehiscence after use of prophylactic antibiotics in episiotomy or second-degree tear (REPAIR study): single centre, double blind, placebo controlled randomised trial.
Perslev K et al.,
BMJ. October 2024.
DOI: https://doi.org/10.1136/bmj-2025-084312
Perineal injury following vaginal birth is common. In Australia, only 18% of women have an intact perineum following vaginal birth, 23% will undergo episiotomy and a further 32% will experience a second-degree tear. Wound complications, including dehiscence and infection, are significant concerns for women who sustain perineal injury.
Following the ANODE trial of 2019, which demonstrated a reduction in maternal infection with prophylactic antibiotics after instrumental birth, antibiotic prophylaxis has become widely used in this context. However, the evidence supporting prophylactic antibiotics to prevent wound complications after episiotomy or second-degree tears remains unclear.
The REPAIR trial aimed to evaluate whether prophylactic antibiotics reduce rates of perineal wound infection and dehiscence among women with an episiotomy or second-degree tear.
The trial: This was a double blinded, placebo-controlled trial that recruited Danish speaking women from a single centre in Denmark. The population and intervention: 442 women were randomized (1:1) to 3 doses of amoxicillin (500 mg) + clavulanic acid (125 mg) vs placebo. The first dose was given within 6 hours of birth and the subsequent doses at 8-hour intervals.
The outcome: The primary outcome was wound dehiscence (>5mm) or wound infection (ongoing infection with substantial purulent discharge or abscess) or both assessed by clinical consultation with participants in lithotomy. Participants were assessed between 4 and 14 days postpartum.
Before recruitment commenced the team noted that dehiscence of >5mm was common and may reflect the normal healing process. Thus, the team added a secondary outcome of ‘clinically relevant wound complications’ defined as dehiscence requiring clinical follow-up due to the extent (often >10mm), severity of pain or infection.
The findings: 433 women completed follow-up (2% drop out rate). Among these, wound complications occurred in 47/218 (21.6%) in the antibiotic group vs 62/215 (28.8%) in the placebo group, resulting in a non-significant risk reduction of 25% (RR 0.75 [95% CI 0.54, 1.04]).
For the secondary outcome, clinically relevant wound complications occurred among 19/218 (8.7%) in the antibiotic group vs 36/215 (16.7%) of the placebo group – a significant relative risk reduction of 48% (RR 0.52 [95% CI 0.31, 0.88]).
For exploratory outcomes: 1) median wound dehiscence was shorter in the antibiotic arm (7mm vs 10mm), 2) antibiotics were less commonly prescribed before or at the follow-up REPAIR visit in the antibiotic arm (3.7% vs 8.8%) and 3) women in the antibiotic arm more likely to rate their healing process as better than expected (48.6% vs 34.4%). There was no difference between the groups for urinary incontinence, pain scores and breastfeeding.
Whilst the primary outcome of wound dehiscence or infection was not reduced, this study showed a significant reduction in clinically important wound complications with antibiotic prophylaxis after episiotomy or second-degree perineal tears.
The results are indeed encouraging, however the generalisability of these findings beyond a single centre and a Danish-speaking population remains uncertain and requires further evaluation. Given the large number of women who experience episiotomy or second-degree tears, the potential contribution to antimicrobial resistance must also be carefully weighed before routine use of prophylactic antibiotics in this setting can be recommended.
Paper 3: Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.
Cluver et al. al.,
Cochrane Database of Systematic Reviews. 3 December 2025.
DOI: 10.1002/14651858.CD001059.pub6.
Review contributed by Jess Atkinson
Hypertensive disorders of pregnancy are among the leading causes of maternal and neonatal morbidity and mortality. Calcium supplementation was first proposed as a potential prophylactic measure for hypertensive disorders of pregnancy in the 1980s, and since then, several randomised trials have suggested benefit in this setting.
This updated Cochrane review sought to re-assess the role of calcium supplementation in preventing hypertensive disorders of pregnancy. This is the fifth update of a previously published Cochrane review; however, the authors designed a new protocol, search strategy, and updated key outcomes. Additionally, the authors employed a more stringent assessment of trial trustworthiness (the Trustworthiness in Randomised Controlled Trials checklist), due to ongoing concerns about data integrity in obstetric trials. Thus, all included studies in this update were considered to be of high-quality with verifiable trial information.
The study: Ten randomised control trials including 37,504 participants were included in this review. Notably, 20 previously included trials were excluded in this update due to changes in eligibility criteria (11 trials) or trustworthiness issues (9 trials).
The outcome: The primary maternal outcome was preeclampsia (any gestation).
The findings: The authors found that calcium supplementation did not significantly alter the risk of developing preeclampsia (RR 0.83, 95% CI 0.67, 1.04; n=15,364; low-certainty evidence). This result remained unchanged when restricting only to trials with ≥500 participants (RR 0.92, 95% CI 0.79, 1.05; n=14,730; high-certainty evidence).
There was no difference in the risk of maternal death or severe morbidity (RR 0.80, 95% CI 0.54, 1.19; moderate-certainty evidence), or adverse events (RR 2.16, 95% CI 0.43, 10.78; very low-certainty evidence).
The primary perinatal outcome was perinatal loss (stillbirth or neonatal death).
Calcium supplementation was not associated with any difference in the risk of perinatal loss (RR 0.93, 95% CI 0.64, 1.35; n=6832; low-certainty evidence), however, this evidence was uncertain. There was also no difference in the risk of stillbirth (RR 0.91, 95% CI 0.72, 1.15; moderate-certainty evidence) or neonatal death (RR 1.09, 95% CI 0.50, 2.38; very low-certainty evidence).
Calcium supplementation was not associated with any difference in the risk of preterm birth <37 weeks’ gestation (RR 0.83, 95% CI 0.65, 1.05; n=15,074; very low-certainty evidence). This result remained unchanged when restricting only to trials with ≥500 participants (RR 0.97, 95% CI 0.85, 1.11; n=14,429; high-certainty evidence).
There was no difference in outcomes when comparing low-dose vs high-dose calcium supplementation. Subgroup analysis also indicated no difference between women with adequate or low dietary calcium intake.
Overall, the results of this review suggest that calcium supplementation is not effective in preventing preeclampsia or related adverse outcomes. Most trials included women commencing calcium in mid-pregnancy, so the effect of early supplementation remains unclear. The authors conclude that additional large, randomised trials are unlikely to substantially alter their findings. Future research into alternative methods to prevent hypertensive disorders of pregnancy is needed.