title: Maternal psychiatric disease and epigenetic evidence suggest a common biology for poor fetal growth.
abstract: BACKGROUND
  We sought to identify and characterize predictors of poor fetal growth among variables extracted from perinatal medical records to gain insight into potential etiologic mechanisms. In this process we reevaluated a previously observed association between poor fetal growth and maternal psychiatric disease.
  
  
  METHODS
  We evaluated 449 deliveries of >36 weeks gestation that occurred between 9/2008 and 9/2010 at the Women and Infants Hospital in Providence Rhode Island. This study group was oversampled for Small-for-Gestational-Age (SGA) infants and excluded Large-for-Gestational-Age (LGA) infants. We assessed the associations between recorded clinical variables and impaired fetal growth: SGA or Intrauterine Growth Restriction (IUGR) diagnosis. After validating the previously observed association between maternal psychiatric disease and impaired fetal growth we addressed weaknesses in the prior studies by explicitly considering antidepressant use and the timing of symptoms with respect to pregnancy. We then evaluated DNA methylation levels at 27 candidate loci in placenta from a subset of these deliveries (n = 197) to examine if epigenetic variation could provide insight into the mechanisms that cause this co-morbidity.
  
  
  RESULTS
  Infants of mothers with prenatal psychiatric disease (Depression, Anxiety, OCD/Panic) had increased odds of poor fetal growth (ORadjusted = 3.36, 95%CI: 1.38-8.14). This relationship was similar among those who were treated with antidepressants (ORadjusted = 3.69, 95%CI: 1.31-10.45) and among those who were not (ORadjusted = 3.19, 95%CI: 1.30-7.83). Among those with a history of psychiatric disease but no active disease in pregnancy the ORadjusted was 0.45 (95%CI: 0.09-2.35). A locus near the transcription start site of the leptin receptor (cg21655790) had methylation levels that were decreased in the presence of: 1) SGA/IUGR, and 2) active but not resolved psychiatric disease (among mothers not on antidepressants).
  
  
  CONCLUSIONS
  These results validate and further characterize the association between maternal psychiatric disease and poor fetal growth. Because the association appears to depend on active psychiatric disease, this suggests a transient and potentially modifiable pathophysiology. The molecular findings in this study suggest that altered leptin signaling may be involved in the biological mechanisms that link prenatal maternal psychiatric symptoms and poor fetal growth.
authors: Institute for Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH, USA. timothyhciesielski@gmail.com.|Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. timothyhciesielski@gmail.com.
authors: Timothy H
authors: TH
authors: Ciesielski
authors: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. Carmen.J.Marsit@Dartmouth.edu.|Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. Carmen.J.Marsit@Dartmouth.edu.
authors: Carmen J
authors: CJ
authors: Marsit
authors: Institute for Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH, USA. Scott.Williams@Dartmouth.edu.|Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. Scott.Williams@Dartmouth.edu.
authors: Scott M
authors: SM
authors: Williams
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000150:complications* / Q000235:genetics; D019175:DNA Methylation; D003866:Depressive Disorder / Q000150:complications* / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000235:genetics; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development; D016017:Odds Ratio; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000523:psychology*; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D054411:Receptors, Leptin / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; D054411:Receptors, Leptin