Sri Lankan children with abdominal pain predominant functional gastrointestinal disorders:their autonomic functions, gastric motility and the therapeutic value of prokinetic drug- domperidone

Abstract

Abdominal pain- predominant functional gastrointestinal disorders (AP-FGIDs) are an important cause of recurrent abdominal pain. Despite the high prevalence, underlying pathophysiology of this condition is poorly understood and effective treatment options are lacking. This thesis has assessed the epidemiology of AP-FGIDs in Sri Lankan children aged 5-12 years, the role of gastric motility and autonomic functions in its pathophysiology and the therapeutic value of gastroprokinetic drug domperidone in its management.An epidemiological study was conducted in 653 children aged 5 - 12 years in four randomly selected schools in Gampaha district, Sri Lanka. Data were collected using a parental questionnaire. In this study, the prevalence of AP-FGIDs were 12.6%. The girls had a higher prevalence than boys (15.1% vs.9.7,p=0.037). The majority of the children suffered from moderate to severe pain (83.1%) and had disturbances in their normal function (78.1 %). Thirty-nine percent of affected children had sought medical care for their symptoms and health care consultation negatively correlated with emotional functioning (r= -0.312, p=0.014) and school functioning (r= -0.349, p=0.005) domains of health related quality of life assessment A significantly higher family impact was seen in the parents ~f affected children (78.97 vs. 86.86, p=0.011 ). The total score obtained for the family impact module negatively correlated with the frequency of pain episode (r= -0.205, p=0.008) and severity of pain (r= -0. 266, p=0.002). Main gastric motility parameters assessed (gastric emptying rate [45.65 vs. 59.55 in controls], amplitude [48.65 vs. 58.17] and frequency of antral contractions [8.29 vs.9.44], and antral motility index [4.08 vs. 6.41]) using a non-invasive ultrasound method was significantly lower in affected children and correlated with pain characteristics (p<0.05). Assessment of cardio-vagal autonomic functions showed low parasympathetic activity in patients when compared with control, but failed to show a correlation with gastric motility. The occurrence of functional extrinsic denervation, the maladaptive parasympathetic division was proposed as contributing factors to impairment of gastric motility and symptoms generation in AP-FGIDs. Eighty-nine completed the trial at 8 weeks (Placebo 42 [20 boys), Domperidone 47[14 boys)) and 79 completed the 6 month follow up. When the primary outcomes were assessed at 8 weeks, the domperidone group had significantly higher number of cllildren with patient reported general improvement [37 (74%) vs. 25 {50%) in the placebo group, p=0.013), while no such difference was observed in cure [22 (44%) in the domperidone group and 14 (28%) in the placebo group, p=0.09]. At 6 month follow up 30 (60%) in the domperidone group and 19 (38%} in the placebo group reported cure (p=0.028) and 44 (88%) lo the domperidone group and 33 (66%) in the placebo group showed improvement of overall clinical condition (p=0.009). When assessing secondary outcomes at 8 weeks, the domperidone group reported reduction in abdominal pain severity (54.1% vs. 24.7"/o, p =0.008) and improvement in antral motility index (27.5% vs. 7.2%,p=0.029). In conclusion, AP-FGIDs are a common disorder among 5-12 year aged children in Sri Lanka affecting approximately 13%. AP-FGIDs cause a poor health related quality of life, has a significant impact on the family and results in a high health care consultation. The presence of gastric motor abnormalities in affected children, which correlated with symptoms indicates the possible pathophysiological role of abnormal gastrointestinal motility in the generation of symptoms. Domperidone has a favorable effect on improving symptoms of AP-FGIDs in children.