title: Fetal growth and risk of stillbirth: a population-based case-control study.
abstract: BACKGROUND
  Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.
  
  
  RESULTS
  We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.
  
  
  CONCLUSIONS
  Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies. Please see later in the article for the Editors' Summary.
authors.affiliation: University of Texas Medical Branch at Galveston, United States of America.
authors.forename: Radek
authors.initials: R
authors.lastname: Bukowski
authors.affiliation: RTI International, Research Triangle Park, North Carolina, United States of America.
authors.forename: Nellie I
authors.initials: NI
authors.lastname: Hansen
authors.affiliation: The Pregnancy and Perinatology Branch, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Marian
authors.initials: M
authors.lastname: Willinger
authors.affiliation: The Pregnancy and Perinatology Branch, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Uma M
authors.initials: UM
authors.lastname: Reddy
authors.affiliation: RTI International, Research Triangle Park, North Carolina, United States of America.
authors.forename: Corette B
authors.initials: CB
authors.lastname: Parker
authors.affiliation: Brown University School of Medicine, Providence, Rhode Island, United States of America.
authors.forename: Halit
authors.initials: H
authors.lastname: Pinar
authors.affiliation: University of Utah School of Medicine and Intermountain Health Care, Salt Lake City, Utah, United States of America.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Silver
authors.affiliation: University of Texas Health Science Center at San Antonio, United States of America.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Dudley
authors.affiliation: Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, United States of America.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Stoll
authors.affiliation: University of Texas Medical Branch at Galveston, United States of America.
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.affiliation: RTI International, Research Triangle Park, North Carolina, United States of America.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Koch
authors.affiliation: Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Rowland Hogue
authors.affiliation: University of Utah School of Medicine and Intermountain Health Care, Salt Lake City, Utah, United States of America.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Varner
authors.affiliation: University of Texas Health Science Center at San Antonio, United States of America.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Conway
authors.affiliation: Brown University School of Medicine, Providence, Rhode Island, United States of America.
authors.forename: Donald
authors.initials: D
authors.lastname: Coustan
authors.affiliation: Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Goldenberg
mesh_terms: D000328:Adult; D001724:Birth Weight; D016022:Case-Control Studies; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D005865:Gestational Age; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D050498:Live Birth / Q000453:epidemiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology*; D012307:Risk Factors; D050497:Stillbirth / Q000453:epidemiology*; D014481:United States / Q000453:epidemiology; D055815:Young Adult
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