title: Timing of prenatal maternal exposure to severe life events and adverse pregnancy outcomes: a population study of 2.6 million pregnancies.
abstract: OBJECTIVE
  To identify the impact of timing of prenatal stress exposure on offspring risk for shortened gestational age, preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA), using a population-based sample.
  
  
  METHODS
  Swedish longitudinal population registries were linked to study all individuals born in Sweden from 1973 to 2004. Prenatal maternal stress exposure was defined as death of the father of the child or first-degree relative of the mother. Using linear and logistic regression, timing of stress exposure was examined across pregnancy, by month, and by novel periods created based on month of stress exposure findings.
  
  
  RESULTS
  A total of 2,618,777 live-born, singleton infants without congenital anomalies were included; 32,286 were exposed to prenatal maternal stress. Examining associations between stress exposure and outcome by the month revealed that risk increases midgestation, particularly after months 5 and 6. Combining months 1 to 4, 5 and 6, and 7 to 9 as potential periods of differing vulnerability, it was found that stress during period 2 (months 5 and 6) was associated with the greatest risk for shortened gestational age (-0.52 days, standard error = 0.15, p = .0006), PTB (odds ratio [OR], 1.24; 99% confidence interval [CI], 1.08-1.42), LBW (OR, 1.38; 99% CI, 1.19-1.61), and SGA (OR, 1.25; 99% CI, 1.05-1.49).
  
  
  CONCLUSIONS
  Risk for shortened GA, PTB, LBW, and SGA are greater post stress exposure during the 5th and/or 6th month of pregnancy. It may be beneficial to refine future analyses to these months. Possible mechanisms include alterations in the hypothalamic-pituitary-adrenal axis and associated stress-responsive molecular regulators.
authors.affiliation: Department of Psychology and Brain Sciences, Indiana University, 1101 E. 10th Street, Bloomington, IN 47405. qaclass@indiana.edu
authors.forename: Quetzal A
authors.initials: QA
authors.lastname: Class
authors.forename: Paul
authors.initials: P
authors.lastname: Lichtenstein
authors.forename: Niklas
authors.initials: N
authors.lastname: Långström
authors.forename: Brian M
authors.initials: BM
authors.lastname: D'Onofrio
mesh_terms: D000328:Adult; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008016:Life Change Events; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011263:Pregnancy Trimester, Third / Q000502:physiology; D011266:Pregnancy-Associated Plasma Protein-A / Q000502:physiology; D047928:Premature Birth / Q000503:physiopathology; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors
chemical_list: D011266:Pregnancy-Associated Plasma Protein-A