title: Lack of correlation between elevated maternal serum hCG during second-trimester biochemical screening and fetal congenital anomaly.
abstract: OBJECTIVE
  Isolated elevations in midtrimester maternal serum human chorionic gonadotrophin concentrations (MShCG) have been reported to be associated with a substantially increased likelihood of fetal congenital malformations. The reported malformations included a wide range of organ systems, originating at different embryologic developmental stages. The purpose of our study was to determine the significance of an isolated elevated MShCG (>2.5 MoM) in midtrimester for the detection of fetal structural anomalies in a large population.
  
  
  METHODS
  Among 10,144 women who underwent a biochemical triple screen at 15 to 18 weeks' gestation, 463 patients, who had an elevated MShCG, but normal alpha-fetoprotein (AFP) and unconjugated estriol (uE3) levels, were identified. Patients with an integrated calculated Down syndrome risk above 1:250 were excluded. Only nonsmokers, at ages <35 years, without a history of prior fetal anomalies were included. The control group consisted of 463 patients with normal serum analyte concentrations and Down syndrome risks below 1:250, who were matched for maternal age and date of biochemical screen. All patients underwent a detailed genetic sonogram in which an anatomic survey and multiple 'soft markers' for aneuploidy were looked for. Newborns were examined by a senior pediatrician trained in dysmorphology.
  
  
  RESULTS
  MShCG levels were 3.18 +/- 0.72 versus 0.99 +/- 0.43 MoM (p < 0.0001) in study and control groups respectively. Sonography revealed 8 versus 6 cases of major congenital anomalies among the 463 patients of their respective groups, and 39 versus 36 sonographic 'soft markers' for aneuploidy. Fetal karyotyping and neonatal examination for dysmorphology revealed 6 chromosomal anomalies (4 Down syndrome; 2 Turner syndrome) among the 8 major malformations in the study group, but none in the controls (p < 0.0001). Three of the 39 fetuses with 'soft markers' and elevated MShCG were found to have trisomy 21.
  
  
  CONCLUSIONS
  Isolated elevation of MShCG does not confer an increased risk of fetal congenital anomalies other than chromosomal abnormalities. However, elevated MShCG levels in combination with sonographic 'soft markers' for aneuploidy were associated with a high incidence of chromosomal anomalies, despite a normal biochemical triple screen risk estimate.
authors.affiliation: Department of Obstetrics and Gynecology, University G.d'Annunzio, Chieti, Italy. ccelen@tin.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Celentano
authors.forename: Paolo Emilio
authors.initials: PE
authors.lastname: Guanciali-Franchi
authors.forename: Marco
authors.initials: M
authors.lastname: Liberati
authors.forename: Chiara
authors.initials: C
authors.lastname: Palka
authors.forename: Donatella
authors.initials: D
authors.lastname: Fantasia
authors.forename: Elisena
authors.initials: E
authors.lastname: Morizio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calabrese
authors.forename: Liborio
authors.initials: L
authors.lastname: Stuppia
authors.forename: Siegfried
authors.initials: S
authors.lastname: Rotmensch
mesh_terms: D000328:Adult; D006063:Chorionic Gonadotropin / Q000097:blood*; D000013:Congenital Abnormalities / Q000097:blood*; D005260:Female; D005315:Fetal Diseases / Q000097:blood*; D006801:Humans; D008403:Mass Screening; D011247:Pregnancy; D011262:Pregnancy Trimester, Second
chemical_list: D006063:Chorionic Gonadotropin