Necrotizing Enterocolitis and Bowel Perforation in Very Preterm Infants - Long-term Follow up

Intestinal Perforation, Necrotizing Enterocolitis, Premature Infant Disease

necrotizing enterocolitis, bowel perforation, preterm infant, long-term follow-up, quality of life

Necrotizing enterocolitis (NEC) is a gastrointestinal syndrome characterized by transmural inflammation and necrosis of the large and/or small bowel and subsequent intramural gas-forming organisms into the intestinal wall. Some preterm infants also develop spontaneous intestinal perforations (SIP) without the classical bowel inflammation/necrosis seen in NEC. NEC and SIP can be challenging to differentiate. Severe cases of both conditions require surgery and often bowel resection, but mortality due to SIP seems lower. Studies looking at long-term prognosis of infants with NEC and bowel perforation have mainly assessed outcome until 2-7 years of age. The primary school years is a vulnerable period for ex-preterm children. Disruption in learning and social integration is of great importance for their quality of life (QoL), but little data exist in this age group. Moreover, nutritional deficits (e.g. cobalamin- or iron-deficiency may impact cognitive development, but this has not been investigated in this high-risk population in school age. Authors of a recent systematic review on gastrointestinal sequel after NEC-surgery thus called for more high-quality studies assessing long-term follow-up. In this project we will study the long-term impact of surgery for NEC and bowel perforation in preterm infants, both with a quality of life (QoL) perspective and with a focus on development, growth, nutrition and persistent gastrointestinal problems.

INTRODUCTION Necrotizing enterocolitis (NEC) is a gastrointestinal syndrome characterized by transmural inflammation and necrosis of the large and/or small bowel and subsequent intramural gas-forming organisms into the intestinal wall. The incidence of NEC is inversely related to birth weight and gestational age (GA), with the majority of affected being very preterm infants (GA \< 32 weeks), and in particular extremely preterm infants (GA \< 28 weeks). In Scandinavia, the rates of NEC in extremely preterm infants is 6-9% (1-3). NEC is a devastating condition and one of the four main causes of mortality in neonatal intensive care units (NICUs) (4). Some preterm infants also develop spontaneous intestinal perforations (SIP) without the classical bowel inflammation/necrosis seen in NEC. NEC and SIP can be challenging to differentiate. Severe cases of both conditions require surgery and often bowel resection, but mortality due to SIP seems lower (5). The clinical onset of NEC is usually in the second or third week of life. Typical symptoms and signs are a distended abdomen, periumbilical erythema, bloody stools, feeding intolerance and a generally unstable infant. However, the signs are non-specific, and the diagnosis is usually based on radiographic findings such as intramural bowel gas (6, 17, 18). The severity is classified by modified Bells criteria (18, 19). Stage I refers to suspected, but unconfirmed NEC. Stage II is radiographically confirmed NEC requiring medical therapy including broad-spectrum antibiotics and supportive care. Stage III patients demonstrate clinical signs of bowel necrosis, peritonitis, and septic shock, or radiographic findings of bowel perforation. These patients often receive surgery in addition to intensive care. The mortality rate of NEC is between 20-40%; highest in immature infants and/or stage III disease (20, 21). Survivors of severe NEC (stage III) require long and often very intensive medical therapy that cause suffering for both patients and their families (18, 20). Moreover, medical therapy of patients with NEC requires huge resources for the neonatal unit and the health care system (20). Those who survive NEC have an increased risk of later gut-associated problems (e.g. short bowel syndrome and strictures) (18, 22), and neurodevelopmental disability (20, 23). Similar results have been observed in follow-up studies after SIP, but less data is available for this condition (23). Although significant progress has been made in our understanding of NEC/SIP over the last decade, many questions remain regarding the long-term prognosis and optimal follow-up. Studies looking at long-term prognosis of infants with NEC and bowel perforation have mainly assessed outcome until 2-7 years of age (20, 24). The primary school years is a vulnerable period for ex-preterm children. Disruption in learning and social integration is of great importance for their quality of life (QoL), but little data exist in this age group (25). Moreover, nutritional deficits (e.g. cobalamin- or iron-deficiency (26, 27) may impact cognitive development, but this has not been investigated in this high-risk population in school age. Authors of a recent systematic review on gastrointestinal sequel after NEC-surgery thus called for more high-quality studies assessing long-term follow-up (28). In this project we will study the long-term impact of surgery for NEC and bowel perforation in preterm infants, both with a quality of life (QoL) perspective and with a focus on development, growth, nutrition and persistent gastrointestinal problems. AIM to collect long-term follow-up data on QoL, growth, development, biochemical nutritional status and persistent gastrointestinal symptoms among survivors of surgical NEC or bowel perforation in the neonatal period, in order to identify areas where we can improve or optimize follow-up. RESEARCH QUESTION What is the long-term outcome of preterm infants surviving surgical NEC or bowel perforation in the neonatal period?

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