Summary

A recent UK study showed that a single prophylactic dose of antibiotics offered to mothers within 6 hours of delivery prevents almost half of infections. But, apart from challenges in the choice of antibiotics and development of drug resistance, whether India may follow the same needs due deliberation.

If hospitals give a single dose of preventative antibiotics to all women after child birth involving forceps delivery or vacuum extraction, it could prevent almost half of maternal infection including sepsis. This is equivalent to over 7000 maternal infections annually in the UK and around 5000 in the USA.

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On May 13, 2019, The Lancet journal published the results of the first randomised trial of its kind in the UK. The UK study which involved 3420 women from 27 obstetric units also found that a policy of universal prophylaxis after birth could help to reduce antibiotic use by 17%.

In a press release, the lead researcher Professor Marian Knight from the University of Oxford, UK asserted that “these findings highlight the urgent need to change current WHO antibiotic guidelines and other guidance from organisations in the UK, North America, and Australasia, that do not recommend routine antibiotic prophylaxis for assisted childbirth”.

“Pregnancy-associated infection is a major cause of death and serious illness. Almost 1 in 5 women develop an infection after assisted vaginal delivery and our results show that this could be reduced by almost half by a single dose of prophylactic antibiotic,” she clarified.

Assisted vaginal births without antibiotic prophylaxis lead to infection rates of around 16% worldwide, and up to 25% after caesarean section. According to the researchers sepsis causes 11% of maternal deaths globally.

They noted that:

• In 2016, an estimated 19,500 women died because of pregnancy-related infections. This burden is not limited to countries of low and middle income
• 5% of maternal deaths in high-income settings are due to infection, and in the USA this figure has been estimated to be as high as 13%
• For every woman that dies from pregnancy-related infection, 70 women have severe infection and survive, often with long-term health consequences
• Maternal infection remains under-recognized and undertreated, and hence is the focus of a WHO global study and awareness campaign

The research team quoted a recent Cochrane review of 95 trials which showed that giving antibiotics before caesarean section reduced wound infection and endometritis (the inflammation of the inner lining of the uterus –endometrium-) which is the most common cause of infection after child birth and serious maternal infection by 60 to 70%, and the use of antibiotics during caesarean section is widely recommended. In contrast, evidence on the use of prophylactic antibiotics in assisted vaginal birth is limited to a small trial of 393 women.

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The new study provided more evidence. The researchers investigated whether a single dose of antibiotics prevented maternal infection in the 6 weeks after assisted vaginal birth in 3,420 women (aged 16 years and older) giving birth in 27 hospital obstetric units across the UK.

Between March 2016 and June 2018, researchers randomly assigned women to receive intravenous amoxicillin and clavulanic acid (1,715 women) or placebo (saline; 1,705) within 6 hours of operative vaginal delivery. They also assessed the effect of using prophylaxis on overall antibiotic use. They identified suspected or confirmed maternal infection within 6 weeks of giving birth by a new prescription for antibiotics, confirmed systemic infection on culture, or endometritis.

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The researchers estimated that the total average National Health Service (NHS) costs 6 weeks after birth were £52.60 less per women in those who received the single dose of antibiotic compared to women given placebo (£102.50 vs £155.10).

“With increasing recognition of the need to reduce unnecessary caesarean births, the incentive to minimise the harms associated with other types of assisted delivery are even greater,” Professor Knight cautioned in the press release.

“This simple intervention could also be used to prevent maternal infections in low- and middle-income countries in which intravenous antibiotics are available.” she added

In a linked comment in the journal, Dr. Vincenzo Berghella from Thomas Jefferson University, USA, conceded that the new study is “practice changing”

“The main strengths of this study are that it is large, methodologically well done, covers an important clinical issue, and is practice changing. Only one small study had been previously done on this issue. Other strengths are the use of only one dose of antibiotics, limiting the effect on microbiota of both mother and baby (effect through breastfeeding). Risks of negative effects on the baby, such as necrotising enterocolitis or asthma, can be minimised if the antibiotic is given after delivery, and this antibiotic has been shown to be safe for infant breastfeeding.” he clarified.

“This large multicentre trial was adequately powered to robustly examine the effect of antibiotic prophylaxis after operative vaginal birth. It showed a clear reduction in the proportion of women who had a confirmed or suspected infection after operative vaginal birth in the intervention group, as well as lower proportions of women with perineal wound infection, perineal pain, or perineal wound breakdown after antibiotic prophylaxis, which, to the best of our knowledge, has not previously been shown.”, the researchers explained.

Responding to Science Media Centre, Dr Dimitrios Siassakos, Associate Professor and Reader in Obstetrics, University College London (UCL) accepted the results and raised a few queries:

“This paper presents the findings of a large study with potentially significant repercussions. Should all women who have an assisted childbirth (forceps or ventouse) receive prophylactic antibiotics to reduce their risk of infection from now on?"

“The study results show that giving antibiotics within 6 hours after birth reduces the need for antibiotics later, and 17% overall, at the expense of one serious allergic reaction out of more than 1,000 women."

“Is this difference in antibiotic need good enough to make us give antibiotics to all women from tomorrow, considering that it might increase resistance to antibiotics?"

“Women who received antibiotics for prevention were half as likely, compared to those who did not, to report a breakdown of their perineal wound, but without difference in their likelihood to report painful sexual intercourse. They were less likely to report it was painful to feed the baby but not more likely to breastfeed. What might be key, before any decision is made to introduce routine antibiotic use to clinical practice, guidelines, and training for assisted childbirth, is to investigate what these differences mean to women, especially in the long term. It is also important to investigate whether earlier administration of the antibiotics, before as opposed to after birth, will have a greater effect on the risk of infection, balancing the risks of resistance to antibiotics.” He highlighted the need for more research.

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India’s approach

India’s health issues are daunting. According to a report from the National Institution for Transforming India (NITI), the maternal mortality ratio (MMR) for (20014-2016) varied from 46 per 100,000 for Kerala to 237 per 100,000 for Assam. The MMR values are above 100 per 100,000 for 12 States. The infant mortality rate varied from 8 per 1000 live births for Goa to 47 per 1000 live births for Madhya Pradesh.

Though the blinded randomised trial in the UK has demonstrated the benefits of a single prophylactic dose of antibiotics within 6 hours of delivery, whether India may follow the same needs due deliberation. The choice of the antibiotics is challenging. Long term impact and antibiotic drug resistance needs consideration. Dr. Dimitrios Siassakos in his commentary asks for more research.

Competent Indian professional groups must deliberate on various issues and decide on the acceptability or otherwise of appropriate protocols for India. The paper on which this review is based is an excellent example of a scientifically robust study which showed that a single prophylactic dose of antibiotics offered to mothers within six hours of delivery prevents almost half of infections and saves in the use of a significant amount of antibiotics later. The issues are the challenges in the choice of antibiotics, development of drug resistance among others.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

Dr K S Parthasarathy is a former Secretary of the Atomic Energy Regulatory Board. He is accessible at ksparth@gmail.com