Vaginal progesterone scores at par with cerclage for preventing preterm births in women with previous mishap and short cervix: a comparison meta-analysis

Vaginal progesterone fares equal with cerclage for preventing preterm births in women who have a short cervix and history of previous mid-trimester miscarriage (MTM) and/or preterm labor (PTL) reports the results of an updated comparison meta-analysis published in July issue of American Journal of Obstetrics and Gynecology.

In a recent update by WHO, every year 15 million babies are born before 37 weeks of gestation and the figures continue to rise. Prematurity is the leading cause of death in children under 5 years of age and is responsible for causing about 1 million deaths worldwide.

In addition, prematurity is a major contributor towards lifelong neurological morbidities such as intellectual disability, cerebral palsy, hearing and visual impairments, and a higher risk of chronic diseases in adulthood.

Women with a previous history of PTL and a short cervix (≤25) face a 3-fold increased risk of recurrent preterm births as compared to women with a cervical length >25 mm in the midtrimester.

The efficacy of vaginal progesterone and cerclage in preventing PTL is a hotly debated topic, but to date, only 2 small RCTs have been conducted to compare these two treatment modalities. However, the sample size was too small to detect any treatment differences.

The 2016 multicenter double-blind randomized placebo-controlled OPPTIMUM trial refuted the claim that progesterone reduces the risk of PTL and helps decrease the associated neonatal morbidity and mortality.

Hence, this adjusted indirect comparison meta-analysis was performed which usually, but not always, provides results similar to head-to-head randomized controlled trials.

An updated literature search of MEDLINE, EMBASE, CINAHL, LILACS, the Cochrane Central Register of Controlled Trials, conference proceedings and research registers of ongoing trials was performed from their inception to March 31, 2018.

All the RCTs comparing vaginal progesterone to placebo/no treatment or cerclage to no cerclage in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic cervical length <25 mm was included in the meta-analysis.

The researchers looked at prevention of preterm birth <35 weeks of gestation and perinatal mortality as the primary outcomes.

Five trials comparing vaginal progesterone vs placebo (265 women), 5 comparing cerclage vs no cerclage (504 women) and the OPPTIMUM study were included in the analysis.

The daily dose of vaginal progesterone used in the trials varied from 90 to 200 mg, and the treatment was administered from 18–25 to 34–36 weeks of gestation. Thirty women in two RCTs underwent a cerclage after randomization.

In direct comparison, the use of vaginal progesterone reduced the risk of preterm birth <35 weeks by 32%, <32 weeks of gestation by 40%, neonatal sepsis by 62%, neonatal morbidity by 71%, and admission to NICU by 54%.

The use of cerclage reduced the risk of preterm birth <35 weeks by 30%, <32 weeks of gestation by 34%, composite neonatal morbidity and mortality by 36%, and birthweight <1500 g by 36%.

Both interventions together were associated with a nonsignificant ∼36% reduction in the rate of perinatal death.

Adjusted indirect comparison meta-analyses didn’t show any differences between vaginal progesterone and cerclage in preventing preterm births and perinatal deaths.

The study has several advantages such as the use of individual patient data, similar patient demographics, and low rates of bias. There were few limitations such as the absence of data on respiratory distress syndrome in the OPPTIMUM study, some women with cerclage received 17-OHPC that could have affected the results and non-reporting of maternal side effects in the individual patient data (IPD) meta-analysis.

In the absence of adequately powered, high-quality, randomized controlled trials comparing vaginal progesterone and cerclage, our indirect comparison treatment meta-analysis provides the best available evidence regarding the comparative efficacy of the 2 interventions.

This meta-analysis results have huge implications in clinical practice. Both progesterone or cerclage show similar efficacy in preventing recurrent preterm births in patients with singleton pregnancy and short cervix. Thus, besides efficacy, the decision to use one intervention over other is based on physician preferences, cost-effectiveness, and maternal side effects.

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A C-section rate of approximately 19 percent seems to be ideal for the health of both women and newborns.

All generalization are false including the recent statement by India’s Union women and Child Development Minister about bringing down the C-section rate to 10%. The minister recently asked the health minister to issue a mandate to all the hospitals displaying the C-section rates. She took this action in response to a Change.org petition against hospitals and doctors profiteering by pushing women towards surgical deliveries instead of natural vaginal birth.

The petition has received 1.3 lakh signatures so far, a number that is not much looking at the total population of the country.

"We have entered into an area, very sorry to say, in the last 20 years, where doctors care more about money than about patients' health. We would like the hospitals to display data on how many cesarean section deliveries they have done," said the Minister.

"The normal Cesarean delivery rate in a country would not be more than 10 percent, because it is usually done as a last resort. In this country, it is extremely high because it brings the doctor more money," she further added.

Well, you cannot generalize and mandate a uniform C-section rate for all the hospitals in all the states across country. It all depends upon the healthcare infrastructure, geographical location, access to prenatal care and surgical expertise and the needs of individual woman.

Pointing a finger at the obstetrician and asking her to stop doing C-section is like treating a symptom instead of going into the root of problem. A hospital can have a C-section rate as high as 70% if it a tertiary care high risk hospital.

A review of trends around the world shows that currently about 18.6% of births take place by Cesarean section.  The rates vary from as low as 2% to as high as 50%. In U.S.A, about 1.3 million babies are delivered by Cesarean every year, which roughly equals to every 1 in every 3 children born in US(33%).

The WHO recommends that the ‘ideal’ rate of C-section for optimum maternal and fetal outcome should be around 10-15%.This was  based on the  observation that some countries with the lowest perinatal mortality rates had cesarean delivery rates that were less than 10 per 100 live births. The study also has insufficient data and relied upon average C-section rate from multiple previous year.

However, new study recently examined the relationship between C-section rates and maternal and neonatal mortality in 194 countries around the globe concluded that C-section rate up to 19 percent is associated with lower maternal and neonatal outcome. C-section delivery rates above 19 percent showed no further improvement in maternal and neonatal mortality rates.[1] Researchers used mathematical modeling to impute C-section rates for countries where data was missing and to account for other contributing factors such as health expenditure.

Latin America and the Caribbean region has the highest CS rates (40.5%) while some countries in Africa have the lowest (7%). Brazil occupies the top slot with a rate that exceeds 50% (55.6%).

The  study  found out that in countries with very low C-section rate, people did not have access to basic healthcare and surgical facilities resulting in high maternal and neonatal morbidity and mortality. In fact, a study by WHO concluded that in countries with C-section rate < 10%, there is an additional need for 0.8 – 3.2 million CS every year to improve maternal and neonatal mortality and morbidity. [2]

Dr. Thomas Weiser, an assistant professor of surgery at Stanford School of Medicine says “As countries increase the number of C-sections they provide, mortality goes down— but only to a point, when the C-section rate tops 19 percent, benefits for maternal and infant health plateau.

Increasing C-section rates in recent years are due to modern technology of continuous FHS monitoring in labor room which is a two-way sword, practicing defensive medicine, rise in on-demand C-sections beside other maternal and perinatal factors that come into play.

According to ACOG " Safe reduction of the rate of primary cesarean deliveries, is the only way to  lower  the repeat  cesarean section rate and total cesarean rate."

To conclude, it is impossible to form a policy regarding relationship between delivery methods and birth outcomes. Each case must be decided taking into consideration social, medical, obstetrical and healthcare factors.

Our goal as an obstetrician should be to see that every woman who needs a C-section should get one and every woman who does not need a C-section should not get one.

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[1] http://jamanetwork.com/journals/jama/fullarticle/2473490

[2] http://www.who.int/healthsystems/topics/financing/healthreport/30C-sectioncosts.pdf

Revisiting the 30 years old doctrine of Cesarean Delivery Rate.

Revisiting the 30 years old doctrine of Cesarean Delivery Rate. 

The World Health Organization (WHO) recommended in 1985 that cesarean delivery rates should not exceed 10 to 15 per 100 live births to optimize maternal and neonatal outcomes.

A study by Molina G. et al published in December edition of JAMA concludes that higher Higher Cesarean Delivery Rates May Be OK.

This cross sectional, ecological study was carried out to estimate the contemporary relationship between national levels of cesarean delivery and maternal and neonatal mortality.

Data was collected from all 194 WHO member states from year 2005 to 2012, including cesarean section rates, health expenditure per capita, fertility rate, and life expectancy.

For the 118 countries for which 2012 data were not available, the 2012 cesarean delivery rate was imputed from other years.

The main outcome studied was the relationship between population-level cesarean delivery rate and maternal mortality ratios (maternal death from pregnancy related causes during pregnancy or up to 42 days postpartum per 100,000 live births) or neonatal mortality rates (neonatal mortality before age 28 days per 1000 live births).

Among the 172 countries with observed data, variability in the international cesarean delivery rate between countries ranged from  (12.6 per 100 live birth to  24.0 per 100 live births; South Sudan had the lowest cesarean delivery rate (0.6%), while Brazil had the highest (55.6%).

Mean National Estimates for Countries According to Cesarean Delivery Rates, With Total Volume of Cesarean Deliveries for Each Category---JAMA December 1, 2015, Vol 314, No. 21

In 2013, almost one third of the babies in US were delivered by LSCS, while Canada and Australia have a CS rate of 27.3 and 32.3 respectively.

CS rates are rising globally and it is driven by number of factors like almost complete elimination of vaginal breech delivery, as well as a significant decrease in operative vaginal deliveries and vaginal birth after cesarean. Many women also specifically request cesarean delivery.

Increased level of fetal surveillance has led to increase in intrapartum CS due to presumed fetal distress, but it has not improved the overall rate of perinatal mortality and cerebral palsy.

The estimated global number of cesarean deliveries for 2012 was 22.9 million, yielding a global cesarean delivery rate estimate of 19.4 per 100 live births, which was higher than recommended 10% to 15% by WHO.

The authors say that due to ecological nature of the study it can only document association and no cause and effect result can be inferred.

The study is important as it challenges a 30 year old message that a cesarean rate of less than 15% should be an optimal target of all health care institutions.

Hence, National cesarean delivery rates of up to approximately 19 per 100 live births were associated with lower maternal or neonatal mortality among WHO member states. Previously recommended national target rates for cesarean deliveries may be too low.

It also suggests that efforts to reduce cesarean section rates may not improve patient outcomes.

In an accompanying editorial, Mary E. D'Alton, MD, and Mark P. Hehir, MD, from Columbia University College of Physicians and Surgeons in New York City write that "The optimal level of cesarean delivery cannot be as simple as a one-fits-all figure to be applied to all institutions and health care systems, and the obstetrical community must accept the fact that 'the appropriate' cesarean delivery rate remains unknown. However, it is not whether the cesarean delivery rate is high or low that really matters, but rather whether appropriate performance of cesarean delivery is part of a system that delivers optimal maternal and neonatal care after consideration of all relevant patient and health system information."

References:

1. http://jama.jamanetwork.com/article.aspx?articleid=2473490

2. http://jama.jamanetwork.com/article.aspx?articleid=2473470

3. http://www.un.org/millenniumgoals/maternal.shtml

4. United Nations sustainable development knowledge platform. Open Working Group proposal for sustainable development goals. https://sustainabledevelopment.un.org/sdgsproposal. Accessed December, 2015

5. World Health Organization.  Appropriate technology for birth. Lancet. 1985;2(8452):436-437.
   PubMed

6. World Bank. World development indicators. http://data.worldbank.org/indicator. Accessed December, 2015

7. http://www.medscape.com/viewarticle/855283