Uterine Rupture Following Misoprostol Induction of Labour at 36 Weeks Gestation in an Unscarred Uterus

Case report of a 33-year-old G5P3+1SA diagnosed with an intrauterine foetal death at 36 weeks gestation and induction of labour started with 400 ug of misoprostol vaginally, which was complicated by a uterine rupture with subsequent referral and management in our facility. Intra-operative findings during laparotomy revealed uterine rupture with a macerated still birth intra-abdominally and moderate hemoperitoneum. Uterine rupture in an unscarred uterus following unsuccessful induction is an adverse effect that needs to be monitored and also requiring high index of suspicion to be diagnosed. A missed diagnosis of a uterine rupture during induction of labour could result in maternal mortality due to shock from severe hemoperitoneum. Incidence of uterine rupture following misoprostol induction is rarely recorded due to its use in gynaecological practice which has been off label, hence there is need to document this occurrence experienced in our facility.

Most of the pooled effect provided by studies, with low risk of bias ("A") -1 Most of the pooled effect provided by studies with moderate ("B") or high ("C") risk of bias. Studies with high risk of bias weighs <40% -2 Most of the pooled effect provided by studies with moderate ("B") or high ("C") risk of bias. Studies with high risk of bias weighs ≥40% Note: Low risk of bias (no limitations or minor limitations) -"A" Moderate risk of bias (serious limitations or potentially very serious limitations including unclear concealment of allocation or serious limitations, excluding limitations on randomization or concealment of allocation) -"B" High risk of bias (Limitations for randomization, concealment of allocation, including small blocked randomization (<10) or other very serious, crucial methodological limitations) -"C" The confidence interval is precise according to the figure below.
The total cumulative study population is not very small (i.e. sample size is more than 300 participants) and the total number of events is more than 30. RR -1 One of the above-mentioned conditions is not fulfilled.
-2 The two above-mentioned are not fulfilled.
Note: If the total number of events is less than 30 and the total cumulative sample size is appropriately large (e.g. above 3000 patients, consider not downgrading the evidence). If there are no events in both intervention and control groups, the quality of evidence in the specific outcome should be regarded as very low. PUBLICATION BIAS 0 No evident asymmetry in the funnel plot or less than five studies to be plotted.
-1 Evident asymmetry in funnel plot with at least five studies.

PART 2. GRADE TABLES
Note about the GRADE tables Each GRADE table relates to one specific comparison. The evidence summarized in the tables is derived from a larger body of data extracted primarily from Cochrane reviews, which in many cases contained multiple comparisons. Additional background data can be made available upon request.

Induction of labour at term and beyond
Source of evidence: Gülmezoglu AM, Crowther CA, Middleton P. Induction of labour for improving birth outcomes for women at or beyond term.    3 95% confidence intervals ranging from appreciable benefit to appreciable harm. 3 There is some asymmetry in the funnel plot, but it is unlikely to be due to publication bias (low heterogeneity, not statistically significant results etc.).

20
4 95% confidence intervals ranging from appreciable benefit to negligible harm.
5 Besides the asymmetry in the funnel plot, individual studies results are not statistically significant and there is very low heterogeneity between studies.
6 Very small study population or very rare events.   Not pooled 1 Only one small, underpowered trial.

22
2 Anything from a 54% reduction to a 75% increase.
3 No events in 3 trials and 39 events in one trial. Heterogeneity not applicable.
4 Anything from a 55% reduction to a 45% increase.
6 No events in two underpowered trials. Relative effect not pooled.
7 Three small and underpowered trials.
10 Anything from a 73% reduction to a 29% increase.
11 No events in only one small, underpowered trial. Relative effect not pooled. 1 Only one small, underpowered trial.
2 Anything from a 97% reduction to a 2.11-fold increase.
3 No events in only one trial. Relative effect not pooled.    1 In the funnel plot, the results of individual studies were asymmetric, and there was severe heterogeneity in the I2 test, suggesting publication bias.

33
2 5 out 9 studies have serious or potentially very serious limitations.
3 Moderate heterogeneity that can be associated with publication bias.
4 Evident asymmetry in the funnel plot.
5 95% confidence interval ranging from appreciable benefit to negligible harm.
6 95% confidence interval ranging from appreciable benefit to appreciable harm. 7 95% confidence interval ranging from appreciable benefit to appreciable harm associated with very small sample size.
8 Only one study provided evidence in this outcome. This study has potentially very serious limitations.   2 Most of the pooled effect comes from studies with moderate risk of bias.
3 95% confidence interval ranging from negligible benefit to appreciable harm, with very rare events.  3 There is a positive correlation between misoprostol dose and the occurrence of the outcome, which can explain the overall severe heterogeneity observed.

42
4 The pooled estimate is imprecise (95% confidence interval ranging from appreciable benefit to negligible harm), certainly affected by the heterogeneity between groups. Nevertheless, the correlation between misoprostol dose and the occurrence of the outcome seems to be less affected by the imprecision. 3 95% confidence interval ranging from appreciable benefit to appreciable harm with rare events.       2 Most of the evidence from studies with moderate risk of bias.

48
3 Most of evidence comes from studies with moderate or high risk of bias.
4 95% confidence interval ranging from negligible benefit to appreciable harm. 5 95% confidence interval ranging from appreciable harm with very rare events.
6 Most of the evidence comes from studies with high risk of bias.   1 Most of the evidence comes from studies with moderate risk of bias.

62
2 95% confidence interval ranging from negligible benefit to appreciable harm in a very small study population.
3 Evidence comes from studies with moderate and high risk of bias.
4 95% confidence interval ranging from appreciable benefit to negligible harm.
5 Evidence comes from a study with moderate risk of bias.  2 95% confidence interval ranging from negligible benefit to appreciable harm in a very small study population.
3 95% confidence interval ranging from appreciable benefit to appreciable harm in a very small study population.
4 95% confidence interval ranging from negligible benefit to appreciable harm with rare events.
5 The evidence comes from studies with moderate risk of bias.      2 Severe heterogeneity between trials (I2=69%).

69
3 Imprecise confidence intervals.   2 Very small study population or very rare events.

79
3 Most of the evidence is from studies with moderate risk of bias.       1 Most of the evidence from studies with moderate risk of bias.

84
2 95% confidence intervals ranging from appreciable benefit to negligible harm in a very small study population.
3 95% confidence interval ranging from appreciable benefit to appreciable harm in a population with very rare events. Table 2.10.5. Vaginal misoprostol versus prostaglandin F2 α for induction of labour in women with fetal anomaly or after fetal death 98