Strategies to reduce vertical transmission of multi-drug resistant pathogens to neonates (NeoVT-AMR)

Major progress has been made over the last two decades in reducing deaths in young children from the world's poorest countries, however death rates in newborn babies remain high. Bacterial infection is one of the commonest causes of illness and death in newborn babies across the world but is particularly problematic in low income settings. Resistance to commonly used antibiotics is increasingly seen in infections affecting young babies, and in some countries this is resulting in babies developing serious infections which cannot be treated with locally available antibiotics. Cheap, effective, readily available strategies to reduce neonatal infections are urgently required. Babies are often infected by bacteria that colonise their skin shortly after they are born. One method of reducing infection in young babies could therefore be to apply antiseptics to the birth canal of women in labour and to the skin of newborn babies to reduce the number of bacteria found on babies' skin. Finding out whether antiseptic use could reduce the number of babies developing infections will need a large, complex trial over multiple sites, but currently the best antiseptic regime to use for such a trial is not known. Our proposed study sets out to provide this information.
We plan to compare two different antiseptics which are used routinely in hospitals in the care of babies and women in labour: chlorhexidine (CHG) and octenidine (OCT). We will look at how well these two antiseptics reduce the amount of bacterial present when they are applied to the birth canal of a mother and to the skin of a baby. We will also compare different frequencies of applying the antiseptics to determine which schedule works best.
The study will enroll women and babies presenting to a government hospital in Malawi, one of the poorest countries in the world, and will allocate them to receive one of the antiseptic regimes. The number of bacteria present in the birth canal (women) and skin (babies) after antiseptic is applied will be tested using skin swabs. This study will carefully collect data on whether antiseptic causes skin irritation or any other problems, and will collect data from women about how acceptable it is to have antiseptic applied whilst they are in labour. The information we collect as part of this study will help decide how we design a future large study to see if antiseptics can reduce the number of serious infections occurring in young babies.

Neonatal infection is a leading cause of morbidity and mortality in children from in low income countries, and rates of antimicrobial resistance (AMR) in causative organisms are rising rapidly. Strategies to reduce the incidence of neonatal sepsis are urgently required. Early onset neonatal infection (EOS) often results from transmission of pathogenic organisms from labouring mothers to their infants. Application of antiseptic to the genital tract of labouring women and neonates is potentially a cheap, practical, scale-able intervention to reduce transmission of organisms from mother to child and to reduce EOS, however equipoise exists regarding the effectiveness of such an intervention, particularly for resistant organisms. A large-scale clinical trial is required to address this question, but additional data on optimal antiseptic regimes to be tested are required. This pilot study aims to identify the antiseptic strategy to be tested in such a trial.
The proposed study will be conducted in a government hospital in Malawi, a very low-income country. It is a randomised controlled trial consisting of two independent strata: labouring women (maternal strata) and unselected neonates (neonatal strata). Each strata will be a 3x2 factorial trial testing the following factors and a control arm:
- Antiseptic (3 levels): chlorhexidine (1%), chlorhexidine (2%), octenidine (0.1%) in both strata. Antiseptic will be applied to the skin of neonates and to the perineum and vagina of women.
- Frequency (2 levels): single application in both strata plus 4 hourly in maternal strata and 24 hourly in neonatal strata
The study outcomes will be change in vaginal and perineal bacterial load in colony forming units (CFU) in the maternal strata and change in skin bacterial load in CFU the neonatal strata. In addition, safety data will be collected on skin and mucous membrane integrity, temperature stability in neonates and on the tolerability and acceptability of the intervention.

This study will identify the optimal antiseptic strategy for labouring women and neonates to be tested in a larger clinical trial of interventions to prevent neonatal sepsis. It is part of a programme of work to identify pragmatic, scale-able interventions that can be used in clinical practice to protect neonates in low income countries from serious infection. Neonatal sepsis has huge long-term consequences for both affected infants, their families and the health care system around them, and has a significant social and economic impact on communities in low income countries. Prevention of neonatal sepsis is a therefore a global health priority. Potential long-term beneficiaries of this research include neonates and their families, health care workers, and health systems. Results from this study and from research leading on from it will inform public health and infection prevention and control (IPC) strategy at local, national and international levels.
This study is part of a global effort to address the escalating challenge of antimicrobial resistance (AMR). Reducing AMR will require multifaceted approaches including reducing antibiotic consumption and interrupting transmission of resistant organisms between individuals. This study will provide data to inform antiseptic use to reduce transmission of pathogenic bacteria from mothers to infants, including resistant gram-negative bacteria which are emerging as a major global cause of serious neonatal infections. High quality data on optimal antiseptics to reduce transmission of resistant organisms will be invaluable both clinically, and to inform ongoing research strategy.
This is a clinical study which will be conducted in the maternity and neonatal units of a busy government hospital in a low-income country. It will provide opportunities for education and training on IPC for health care providers and for the families of new-born infants. Qualitative assessments of the acceptability and feasibility of the interventions will be an integral part of the study. These will be shared with local clinical teams to support the development of successful, locally appropriate, IPC guidelines.
This is one step in a programme of work designed to reduce the burden of neonatal sepsis. A clinical trial will follow on from this study, and the trial will need to be completed and the results disseminated, before any positive findings could be incorporated into policy. This process will take a number of years. However, the findings of this study in relation to the effect of antiseptics on neonatal skin bacterial load and maternal genital bacterial load will be of use in and of themselves, and these findings will be disseminated as soon as the study is closed and results analysed.