title: Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study.
abstract: Human chorionic gonadotropin (hCG) is a pregnancy hormone secreted by the placental synctiotrophoblast cell layer that has been linked to fetal growth and various placental, uterine and fetal functions. In order to investigate the effects of hCG on clinical endpoints, knowledge on reference range (RR) methodology and determinants of gestational hCG levels is crucial. Moreover, a better understanding of gestational hCG physiology can improve current screening programs and future clinical management. Serum total hCG levels were determined in 8195 women participating in the Generation R Study. Gestational age specific RRs using 'ultrasound derived gestational age' (US RRs) were calculated and compared with 'last menstrual period derived gestational age' (LMP RRs) and a model-based RR. We also investigated which pregnancy characteristics were associated with hCG levels. Compared to the US RRs, the LMP RRs were lower, most notably for the median and lower limit levels. No considerable differences were found between RRs calculated in the general population or in uncomplicated pregnancies only. Maternal smoking, BMI, parity, ethnicity, fetal gender, placental weight and hyperemesis gravidarum symptoms were associated with total hCG. We provide gestational RRs for total hCG and show that total hCG values and RR cut-offs during pregnancy vary depending on pregnancy dating methodology. This is likely due to the influence of hCG on embryonic growth, suggesting that ultrasound based pregnancy dating might be less reliable in women with high/low hCG levels. Furthermore, we identify different pregnancy characteristics that influence total hCG levels considerably and should therefore be accounted for in clinical studies.
authors.affiliation: The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands. t.korevaar@erasmusmc.nl.|Department of Internal Medicine, Erasmus Medical Centre, Room D 430, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. t.korevaar@erasmusmc.nl.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands. t.korevaar@erasmusmc.nl.
authors.forename: Tim I M
authors.initials: TI
authors.lastname: Korevaar
authors.affiliation: Department of Clinical Chemistry, Erasmus Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Room D 430, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.|Department of Obstetrics and Gynecology, Erasmus Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.affiliation: The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Clinical Chemistry, Erasmus Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schalekamp-Timmermans
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Room D 430, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: W Edward
authors.initials: WE
authors.lastname: Visser
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology Pediatrics, Erasmus Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Child and Adolescent Psychiatry, Erasmus Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Room D 430, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Room D 430, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Medici
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Room D 430, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. r.peeters@erasmusmc.nl.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands. r.peeters@erasmusmc.nl.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D006063:Chorionic Gonadotropin / Q000097:blood*; D005260:Female; D005865:Gestational Age; D006801:Humans; D009426:Netherlands; D010920:Placenta; D011247:Pregnancy / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D012016:Reference Values; D012959:Socioeconomic Factors
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; D011266:Pregnancy-Associated Plasma Protein-A
keywords: Determinants; Pregnancy; Reference range; hCG