Journal Club Papers
The UK based National Institute for Health and Care Excellence (NICE) recently updated their guidance for threatened miscarriage:
- “Offer vaginal micronised progesterone 400 mg twice daily to women with an intrauterine pregnancy confirmed by a scan, if they have vaginal bleeding and have previously had a miscarriage.
- If a fetal heartbeat is confirmed, continue progesterone until 16 completed weeks of pregnancy.”
These recommendations were spurred by encouraging results of a recent randomized clinical trial, which was included in an updated Cochrane meta-analysis of progesterone for preventing miscarriage. We’ve summarised the findings of this meta-analysis below.
This Cochrane meta-analysis included randomized clinical trials assessing progestogen treatment for preventing miscarriage among women with threatened or recurrent miscarriage. The primary outcome was livebirth and secondary outcomes included miscarriage <24 weeks.
- 7 randomized clinical trials, involving 5,682 women, were included. 3 arms assessed vaginal progesterone, 2 used dydrogesterone, 1 oral progesterone and 1 used 17-hydroxyprogesterone.
Women with threatened miscarriage (early pregnancy bleeding):
- No effect of vaginal progesterone (2 studies; N=4,090; relative risk 1.03 [95% CI 1.00, 1.07]; high certainty evidence) or dydrogesterone (2 studies; RR 0.98 [95% CI 0.89, 1.07]; moderate certainty evidence) was found for live birth rates when compared with placebo treated women.
- Among a subgroup analysis of women with a threatened miscarriage and one or more previous miscarriages, vaginal progesterone increased livebirth rates compared with placebo (RR 1.08 [95% CI 1.02, 1.15]; 36 more live births per 1000; high certainty evidence).
- Among women with threatened miscarriage and no previous miscarriage, vaginal progesterone has no effect on livebirth rates (RR 0.99 [95% CI 0.94, 1.04]; high certainty evidence).
- Neither vaginal progesterone nor dydrogesterone were found to alter the risk of miscarriage (<24 weeks) compared with placebo.
Women with recurrent miscarriage (3 or more miscarriages) without threatened miscarriage in current pregnancy:
- Based on one trial (N=826), vaginal progesterone was not found to improve livebirth rates (RR 1.04 [95% CI 0.95, 1.15]; high certainty evidence) nor was dydrogesterone (RR 1.00 [95% CI 0.23, 4.36]; very low certainty evidence).
- Neither vaginal progesterone nor dydrogesterone reduced the risk of miscarriage <24 weeks among this group.
From these findings it is clear that progesterone will not prevent every miscarriage but may have modest benefit for a subgroup of women with early pregnancy bleeding and a history of miscarriage (potentially 36 more live births per 1000). RCOG have advised that these findings will also be included in the updated Green Top Guideline on recurrent miscarriage. RANZCOG are yet to update their guidance on progesterone support of the luteal phase and in the first trimester.
Using data on births in California between 2007-2012, this study compared severe maternal and neonatal morbidity outcomes by mode of birth among women with a prolonged second stage of labour.
- Comparisons were made between a) successful operative vaginal birth and b) caesarean delivery after failed operative vaginal birth with c) caesarean delivery without attempted operative birth (reference group).
- Outcomes (using ICD-9 codes) included:
- Severe maternal morbidity: acute cardiac event, renal failure, heart failure, sepsis, blood transfusion.
- Severe unexpected neonatal morbidity: neonatal death, transfer of care, severe birth trauma, severe hypoxia etc.
- Low risk nulliparous women at term with singleton, vertex livebirths were included.
- Multivariable logistic regression was used to correct for known confounders.
- Among the cohort of 9,239 births, 74.1% (6,851) were successful operative deliveries, 3.3% (301) were failed operative vaginal births and 22.6% (2,087) were caesarean deliveries without attempts at operative delivery.
- Key findings:
1. Successful operative birth group:
- Most were vacuum-assisted (90.4%).
- Compared with caesarean delivery (without operative birth attempt), successful operative birth was associated with a 45% reduction in severe maternal morbidity (adjusted OR 0.55, 95%CI 0.39-0.78) – mostly blood transfusion and endometritis – but no difference in severe unexpected neonatal morbidity (adjusted OR 0.99, 95%CI 0.78-1.26).
2. Failed operative birth group:
- Most were vacuum-assisted (47.4%) or combined vacuum-forceps births (30.9%) – ALL combined vacuum-forceps births failed.
- Women who had a failed operative birth were more likely to have comorbidities, and birthweight >4000g.
- Compared with caesarean delivery (without operative birth attempt), failed operative birth (and subsequent caesarean) was associated with a 214% increase in severe maternal morbidity (adjusted OR 2.14, 95%CI 1.20-3.82) and a 78% increase in severe neonatal morbidity (adjusted OR 1.78, 95%CI 1.09-2.86).
- Combined vacuum-forceps births contributed substantially to the failed operative birth group (54/301 failed operative births) and the risks of adverse outcome with failed operative birth were attenuated when combined vacuum-forceps births were removed from the analysis.
- The rate of 3rd/4th degree tears with successful operative birth was 15.6% but this was not included as part of the composite maternal outcome.
This study highlights the benefits of successful operative birth but also the importance of minimising failed operative births by careful patient selection, optimising operator skill and avoiding combined vacuum-forceps births to reduce maternal and neonatal morbidity.
(Contributed by Alexandra Roddy-Mitchell, Mercy Perinatal Research Midwife and PhD scholar.)
This English population-based linkage study aimed to quantify the magnitude of socioeconomic and ethnic inequalities on adverse pregnancy outcomes using a large cohort of 1,155,981 singleton births from 24 – 42 weeks’ gestation.
The authors used population attributable fractions to estimate the proportion each adverse pregnancy outcome that was attributable to socioeconomic status and ethnicity.
- Socioeconomic status measured by quintiles of area-level deprivation:
- Socioeconomic deprivation accounted for an adjusted attributable fraction of 12.4% for stillbirths, 10.1% for preterm birth and 16.5% for fetal growth restriction.
- Importantly, all outcomes demonstrated a dose-response association with socioeconomic deprivation, with the risk of each adverse outcome increasing with quintile of increasing socioeconomic deprivation.
- Ethnicity was categorised into: White, South Asian, Black, Mixed and Other:
- Ethnicity accounted for an adjusted attributable fraction of 12.6% for stillbirth, 1.2% for preterm birth and 19.5% for fetal growth restriction (meaning 19.5% of all cases of fetal growth restriction may be attributable to ethnicity).
- For stillbirth, white women had the smallest risk at 0.34%; Black women had the greatest, at 0.70% (p<0.0001).
- The risk of preterm birth was less varied: 6.0% for White women, 6.5% for South Asian women and 6.6% for Black women (p<0.0001).
- The risk of fetal growth restriction was lowest for White women, at 1.4%; and greatest for South Asian women, at 3.5% (p<0.0001).
- Combined effects of socioeconomic deprivation and ethnicity:
- Black women living in the most deprived areas had the greatest attributable fraction for stillbirth at 63.7% (95% CI 58.1, 68.6), when compared with white women living in the least deprived areas.
- South Asian women living in the most deprived areas had greatest attributable fraction of preterm birth at 35.3% (95% CI 33.2, 37.4) and fetal growth restriction at 71.7% (95% CI 70.1, 73.1).
These findings highlight the clear impact of socioeconomic and racial inequities on adverse pregnancy outcomes, with 12% of stillbirths, 10% of preterm births and 16% of fetal growth restricted births attributed to social deprivation and similar results for ethnicity.
An astounding 63.7% of stillbirths among Black women living in the most deprived areas would not have occurred if all these women had the same risk as White women living in the least deprived areas. These disparities demonstrate the need for political, public health and healthcare provider action to champion health equity, improving women’s social circumstances, support and health throughout their life course.