title: Prenatal alcohol exposure patterns and alcohol-related birth defects and growth deficiencies: a prospective study.
abstract: BACKGROUND
  The physical features of fetal alcohol syndrome include smooth philtrum, thin vermillion border, short palpebral fissures, microcephaly, and growth deficiencies on weight and height. However, little is known about the specific quantities of alcohol exposure, pattern of drinking, timing of exposure, and magnitude of risk for each of these features.
  
  
  METHODS
  Using data on 992 subjects collected prospectively in California between 1978 and 2005, we examined the patterns and timing of alcohol exposure in relation to these features. Structural features were assessed by a dysmorphologist who performed a blinded physical examination of all infants. Patterns of drinking were evaluated by drinks per day, number of binge episodes, and maximum number of drinks. Timing of exposure was evaluated 0 to 6 weeks postconception, 6 to 12 weeks postconception, first trimester, second trimester, and third trimester.
  
  
  RESULTS
  Higher prenatal alcohol exposure in every pattern was significantly associated with the incidence of smooth philtrum but not with short palpebral fissures. The strongest associations were with timing of exposure in the second half of the first trimester (RR 1.25, 95% CI 1.14 to 1.36 for average number of drinks per day; RR 1.17, 95% CI 1.09 to 1.26 for maximum number of drinks in 1 episode). Similarly, thin vermillion border was most strongly associated with exposure in the second half of the first trimester. Findings with respect to timing of exposure were similar for microcephaly and reduced birth weight. However, reduced birth length was increased with exposure in any trimester. These associations were linear, and there was no evidence of a threshold.
  
  
  CONCLUSIONS
  Reduced birth length and weight, microcephaly, smooth philtrum, and thin vermillion border are associated with specific gestational timing of prenatal alcohol exposure and are dose-related without evidence of a threshold. Women should continue to be advised to abstain from alcohol consumption from conception throughout pregnancy.
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, USA. sawada@ucsd.edu
authors.forename: Haruna Sawada
authors.initials: HS
authors.lastname: Feldman
authors.forename: Kenneth Lyons
authors.initials: KL
authors.lastname: Jones
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lindsay
authors.forename: Donald
authors.initials: D
authors.lastname: Slymen
authors.forename: Hillary
authors.initials: H
authors.lastname: Klonoff-Cohen
authors.forename: Kelly
authors.initials: K
authors.lastname: Kao
authors.forename: Smriti
authors.initials: S
authors.lastname: Rao
authors.forename: Christina
authors.initials: C
authors.lastname: Chambers
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology; D000328:Adult; D000428:Alcohol Drinking / Q000453:epidemiology; D000437:Alcoholism / Q000150:complications; D001724:Birth Weight; D001827:Body Height; D002140:California / Q000453:epidemiology; D003625:Data Collection; D005145:Face / Q000002:abnormalities; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D005865:Gestational Age; D006130:Growth Disorders / Q000139:chemically induced*; D006257:Head / Q000033:anatomy & histology; D006801:Humans; D007231:Infant, Newborn; D008046:Lip / Q000002:abnormalities; D016015:Logistic Models; D008831:Microcephaly / Q000139:chemically induced / Q000453:epidemiology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D012959:Socioeconomic Factors