Josephine van Dongen

Chapter 2 28 Eligibility All infants hospitalized in a par ticipating hospital and aged less than 14 weeks were screened for eligibility, which includes infants with 1) one of the following diagnoses (i.e. medical risk conditions): preterm bir th (gestational age < 36 weeks; low bir thweight < 2500 grams; presence of a severe congenital disorder ( eFigure 1 ), and 2) receiving care in a par ticipating hospital between 6-14 weeks of postnatal age. Parents of eligible infants were approached for par ticipation in the cohort study, and asked for informed consent ( eFigure 2 ). Data collection For all eligible children, irrespective of cohor t par ticipation, we collected the following data: date of bir th, gender, gestational age, bir thweight, presence of congenital disorder and any contra-indications for rotavirus vaccination 15 . This allowed us to evaluate differences between par ticipants and non-par ticipants. Medical risk conditions were classified into; premature, SGA (based on the 10th percentile cut off for Dutch boys and girls 16,17 ) and congenital disorder. Low, intermediate and high socioeconomic status (SES) was based on highest family educational level 18 . Ethnicity was defined by parental origin and divided into three categories, European, non- European and mixed 19. Single parent households are combined in either of first two categories. A baseline parental questionnaire detailed SES, ethnicity, household composition, pregnancy and labor, and was filled upon enrollment.Thereafter, parents received a monthly questionnaire until the end of follow up, at 18 months of age ( eFigure 2 ).The monthly questionnaire contained the following items: occurrence of gastrointestinal and respiratory symptoms during the previous month, any doctor’s visit or hospitalization, administration of vaccinations and occurrence of adverse events, type of feeding and daycare attendance. For all cohor t par ticipants, medical char ts were reviewed for additional data on hospitalizations, diagnoses, medication and other suppor tive therapy at 6 weeks, 5 months and 18 months of age. Follow up for AGE AGE was defined as acute watery or looser than normal stools, more than three times within in a 24 hour period, and/or acute forceful vomiting 20 . At enrollment, parents received verbal instructions concerning these AGE criteria, and on a plasticized instruction card. Parents of par ticipants were instructed to instantly repor t if their child developed symptoms of AGE during the follow-up period. For each AGE episode, parents kept a standardized symptom 7-day diary, based on the Modified Vesikari Severity (MVS) Scale 21,22 ( eTable 1 ). Parents were requested to collect a fecal sample, as soon as possible after AGE onset. Fecal samples were packed in biosafety envelopes and send by regular mail to the central laboratory for PCR testing (see supplement). On day 14 after AGE onset, an additional questionnaire was filled