title: Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial.
abstract: BACKGROUND
  The ORACLE II trial compared the use of erythromycin and/or amoxicillin-clavulanate (co-amoxiclav) with that of placebo for women in spontaneous preterm labour and intact membranes, without overt signs of clinical infection, by use of a factorial randomised design. The aim of the present study--the ORACLE Children Study II--was to determine the long-term effects on children after exposure to antibiotics in this clinical situation.
  
  
  METHODS
  We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study and who were eligible for follow-up with a structured parental questionnaire to assess the child's health status. Functional impairment was defined as the presence of any level of functional impairment (severe, moderate, or mild) derived from the mark III Multi-Attribute Health Status classification system. Educational outcomes were assessed with national curriculum test results for children resident in England.
  
  
  RESULTS
  Outcome was determined for 3196 (71%) eligible children. Overall, a greater proportion of children whose mothers had been prescribed erythromycin, with or without co-amoxiclav, had any functional impairment than did those whose mothers had received no erythromycin (658 [42.3%] of 1554 children vs 574 [38.3%] of 1498; odds ratio 1.18, 95% CI 1.02-1.37). Co-amoxiclav (with or without erythromycin) had no effect on the proportion of children with any functional impairment, compared with receipt of no co-amoxiclav (624 [40.7%] of 1523 vs 608 [40.0%] of 1520; 1.03, 0.89-1.19). No effects were seen with either antibiotic on the number of deaths, other medical conditions, behavioural patterns, or educational attainment. However, more children whose mothers had received erythromycin or co-amoxiclav developed cerebral palsy than did those born to mothers who received no erythromycin or no co-amoxiclav, respectively (erythromycin: 53 [3.3%] of 1611 vs 27 [1.7%] of 1562, 1.93, 1.21-3.09; co-amoxiclav: 50 [3.2%] of 1587 vs 30 [1.9%] of 1586, 1.69, 1.07-2.67). The number needed to harm with erythromycin was 64 (95% CI 37-209) and with co-amoxiclav 79 (42-591).
  
  
  CONCLUSIONS
  The prescription of erythromycin for women in spontaneous preterm labour with intact membranes was associated with an increase in functional impairment among their children at 7 years of age. The risk of cerebral palsy was increased by either antibiotic, although the overall risk of this condition was low.
  
  
  BACKGROUND
  UK Medical Research Council.
authors.affiliation: Reproductive Sciences Section, Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK. oracle@leicester.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Kenyon
authors.forename: K
authors.initials: K
authors.lastname: Pike
authors.forename: D R
authors.initials: DR
authors.lastname: Jones
authors.forename: P
authors.initials: P
authors.lastname: Brocklehurst
authors.forename: N
authors.initials: N
authors.lastname: Marlow
authors.forename: A
authors.initials: A
authors.lastname: Salt
authors.forename: D J
authors.initials: DJ
authors.lastname: Taylor
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects* / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis / Q000009:adverse effects*; D002547:Cerebral Palsy / Q000453:epidemiology / Q000209:etiology; D002648:Child; D046688:Child Mortality; D004522:Educational Status; D004739:England / Q000453:epidemiology; D004917:Erythromycin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006304:Health Status; D006801:Humans; D016015:Logistic Models; D008297:Male; D007752:Obstetric Labor, Premature / Q000188:drug therapy*; D034161:Pelvic Infection / Q000517:prevention & control*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control*; D011297:Prenatal Exposure Delayed Effects; D016896:Treatment Outcome
chemical_list: D004917:Erythromycin; D019980:Amoxicillin-Potassium Clavulanate Combination