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Early Provision of Maternal Colostrum by the Oropharyngeal Route to Preterm Infants

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Early Provision of Maternal Colostrum by the Oropharyngeal Route to Preterm Infants Early Provision of Maternal Colostrum by the Oropharyngeal route to Preterm Infants By Amna Widad Ahmed Nasuf Division of Child Health, Obstetrics and Gynaecology School of Medicine Faculty of Medicine and Health Sciences University of Nottingham Thesis submitted to the University of Nottingham for the degree of Doctor of Philosophy March 2019 Dedication This thesis is dedicated to the memory of my wonderful parents i Abstract Preterm infants are those born before 37 completed weeks of gestation. Worldwide, about one million children die each year due to complications of prematurity and survivors may face lifelong disabilities. Approximately 50% of neonatal deaths and 17% of deaths among children under five are affected by prematurity. Colostrum is the first milk produced by the mother within the early few days after birth. Colostrum is very rich in immunological and growth factors that indicates its primary functions are protective and trophic. Oropharyngeal administration of colostrum (OPC) is a novel route that involves coating the infant’s oropharynx with a small amount of colostrum (0.1 to 0.5 ml) during the early neonatal period. Immune and growth factors in colostrum might interact with the oropharyngeal mucosal-associated lymphoid tissues to modulate the infant’s immune system and promote intestinal growth, potentially reducing infection and necrotising enterocolitis (NEC), improving survival and health outcomes. Ultimately OPC could provide a potential target to prevent mortality and morbidities of preterm and sick infants. This thesis aimed to investigate whether OPC administration during the early neonatal period prevents deaths, improves health outcomes and promotes the growth of preterm infants. To achieve the aim of this thesis; initially, an online survey targeted neonatal professionals was performed to evaluate the current practice and perception of OPC administration in the UK neonatal units. Oropharyngeal colostrum has been introduced into UK neonatal practice despite a lack of high-quality evidence regarding its efficacy and safety. OPC practice was variable, frequently without written guidelines. A Cochrane systematic review was conducted to synthesis and appraise the currently available randomised controlled trials (RCTs), which evaluated if early OPC given within the first 48 hours has a positive impact in preterm infants (< 37 weeks gestation) compared with control. Six RCTs were eligible for inclusion in this systematic review. Meta-analysis showed that early OPC could shorten the time to reach full enteral feeds ii but did not reduce the incidence of late-onset infection (LOI), NEC and death nor the length of hospital stay. Available evidence is insufficient due to lack of participants and very low quality to demonstrate the benefits effects of OPC for preterm infants. The third study, a matched case-control study evaluated the effects of OPC administration on the short-term health outcomes in preterm (≤ 32 weeks) infants. Eligible infants who were admitted to the Nottingham neonatal units after the implementation of OPC in the care of preterm infants, and received OPC, compared with those who were admitted before the use of OPC in the units. Preterm infants who received OPC within the first 96 hours of life achieved full enteral feeding (150 ml/Kg/day for consecutive 72 hours) earlier than those infants who did not receive OPC. A higher rate of receiving breast milk at discharge to home was also observed. However, the two groups had a similar length of hospital stay, weight Z-score at hospital discharge, and incidences of NEC, LOI and deaths. Finally, a non-randomised observational study evaluated the response of gut hormones to OPC administration in preterm (< 37 weeks of gestation) and ill infants requiring neonatal intensive care (NIC). Preliminary results demonstrated a rising trend in plasma gut hormone concentrations in response to OPC administration in the participant preterm and full-term infants. This study is ongoing, and more infants are required before final conclusions can be elicited. In conclusion, OPC administration is a potentially feasible intervention that shortens time to attain full enteral feeds in preterm infants. Given the high risk for preterm infants and the benefits of maternal colostrum, OPC may have preventive implications for improving the health outcomes of this vulnerable population. This work expands the current knowledge about the use of OPC in the care of preterm and sick newborn infants and could benefit efforts to improve preterm birth outcomes by informing guidelines, clinical decision and future research. Larger, well-designed, high-quality research with sufficient power are needed to assess the efficacy and safety of this intervention. iii Acknowledgments All Praise to my God for offering me the chance, the power and endurance to complete this project. Thanks to Tripoli University and the Libyan Ministry of Higher Education for sponsoring and funding my PhD study. Thanks also go to the Libyan Cultural affair in the UK for facilitating administrative aspect throughout my study. I want to express my sincere gratitude to my supervisor, Dr Jon Dorling, for his generous guidance, positive appreciation and encouragement throughout my study. With his support, I successfully overcame many obstacles. I am grateful to my second supervisor, Prof Helen Budge for her valuable feedback and highly appreciate her generous assistance in solving a financial issue with the university. I would also like to thank Dr Don Sharkey for his support and being a second supervisor. I want to extend my appreciation to all the staff at the Academic Division of Child Health, particularly to Prof Michael Symonds for his wise leadership and treating me with every respect. Thanks also go to the team of the Academic Division of Obstetrics & Gynaecology, University of Nottingham. Many thanks to the Neonatal Networks staff who provided the contact details of their neonatal units as well as all those neonatal professionals who participated in my survey study. Great thanks go to Dr Elda Dermyshi and Dr Tng Chang for undertaken the Blinded Endpoint Review for my case-control study. I am grateful to the parents who generously agreed for their babies to participate in my gut hormone study. Thanks also go to all the staff of the Nottingham neonatal service who supported this study, particularly, Dr Karen Norman for her help in the study recruitment and Mrs Stella Tilling for facilitating administrative aspects. Special thanks to Dr Elda Dermyshi and Dr Tng Chang for their role in the study recruitment and kind assistance. I also need to thank Dr Lesia Kurlak, Dr Hiten Mistry, and Mrs Layla Albustanji for iv processing the blood samples. Many thanks to Dr Ian Bloor and Mr Mark Pope for undertaken the laboratory analysis of the gut hormones study. Through my work, I have been fortunate to have had the opportunity to meet very wonderful friends. Reham Alagle, I owe boundless gratitude to you, but words can never express how grateful I am to you. Dr Zenab Elfzzani, thank you for being a good companion throughout my study. Lyla Albustanji, thanks for your kind help and prayers. I am thankful to my friend Intisar Aboshagour for her care and sympathy. Sincere appreciation goes to Mis Fatheia Abdulghani, the Chief Nurse in Tripoli Children Hospital, and Mrs Souad Bridan who they are always beside me when I need. Many thanks go to all the nurses’ staff of the neonatal unit at Tripoli Children Hospital, Libya. Special gratitude goes to Dr Nancy Garofalo (Pritzker School of Medicine, University of Chicago) for her kind cooperation. Finally, my sincere thanks go to all my family members. Their love, encouragements and continuous prayer have made me stronger each day on completing my study. Thanks to an exceptional person, my husband, Faisal for his continued love, support and understanding for making the completion of this thesis possible. I appreciate my beloved son Azzam for bearing with me during this journey. Great thanks go to my beloved daughter Yasmin who suffered a lot being separated from us. Many thanks to my sisters, who are an affectionate heart and wise counsellors, for their incredible support, kindness and valuable prayers. My brother Abd Almageed, thank you for your kind support, you helped me to keep things in perspective. Special thanks go to my lovely neighbour, Zaira, her daughter and son (Saida & Nasser), who gave me a fulfilling family life while I am far from my home. Finally, thanks go to all who have contributed by anyway to accomplish this project. v Declaration The work in this thesis was completed within the Academic Division of Child Health, Obstetrics and Gynaecology at the University of Nottingham (Queen Medical Centre campus), between October 2014 and March 2019. Unless where specified, this report demonstrates my own work that achieved under the supervision of Dr Jon Dorling and Professor Helen Budge. To the best of my knowledge, this thesis is an accurate illustration of the work performed, and no other study is reproducing this work, has been carried out within the University of Nottingham. Amna Widad Ahmed Nasuf March 2019 vi Presentations & Publications Oral presentations Nasuf A, Budge H, Ojha S, Dorling J. Oropharyngeal administration of mother’s own colostrum to preterm infants: a survey of neonatal professionals. Trent Paediatric Society meeting on the 13th November 2015. Nasuf A. Budge H, Dorling J. Golden Milk: could it change the future for millions? M & HS Faculty Postgraduate Research Forum, School of Medicine, University of Nottingham. June 2015. Nasuf A, Budge H, Ojha S, Dorling J. Oropharyngeal administration of mother’s own colostrum to preterm infants: a survey of neonatal professionals. Sue Watson Postgraduate Presentation Prize, School of Medicine, University of Nottingham. October 2016 Poster Presentations Nasuf A, Budge H, Ojha S, Dorling J. Oropharyngeal administration of mother’s own colostrum to preterm infants: a survey of neonatal professionals. 9TH Annual Midlands and East Newborn & Perinatal conference.
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