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Licensed Unlicensed Requires Authentication Published by De Gruyter July 25, 2019

Early pregnancy reference intervals; 29 serum analytes from 4 to 12 weeks’ gestation in naturally conceived and uncomplicated pregnancies resulting in live births

  • Jesper Friis Petersen ORCID logo EMAIL logo , Lennart J. Friis-Hansen , Andreas Kryger Jensen , Anders Nyboe Andersen and Ellen C.L. Løkkegaard



Pregnancy introduces major physiological changes that also alter biochemical analytes. Maternal and perinatal health can be optimized by early intervention and therefore, pregnancy-specific reference intervals (RIs) for the local population are warranted. While the second and third trimester-specific changes are well described, the first trimester is less well characterized. We therefore wanted to facilitate early detection of abnormalities by generating first trimester reference values for 29 common analytes.


In a prospective early pregnancy (PEP) cohort (2016–2017), 203 pregnant women were recruited from 4 to 8 weeks’ gestation. Consecutive blood samples were drawn every 2 weeks until an ongoing second trimester pregnancy (n = 164) or a miscarriage (n = 39) occurred. After exclusion of women with complicated pregnancies or deliveries (n = 42), 122 women were included. The serum samples collected at <6, 6–8, 8–10, 10–12 and >12 weeks’ gestation were analyzed for 29 common analytes. Subsequently the RIs were calculated according to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations (2.5–97.5th percentiles) and compared with the conventional RIs for non-pregnant women.


Human chorionic gonadotropin (hCG), progesterone (P4), estradiol (E2), pregnancy-associated plasma protein A (PAPP-A), cancer antigen 125 (CA125), thyroid stimulating hormone (TSH), creatinine (CREA) and albumin (ALB) showed an early pregnancy-dependent change compared with conventional limits. For ALB the change was seen at 5.5 weeks’ gestation.


We report gestational age-specific RIs available from the early part of the first trimester applicable to everyday clinical care of pregnant women. Well-known alterations of RIs seen in later trimesters are also observed in the first.

Corresponding author: Jesper Friis Petersen, MD, Department of Obstetrics and Gynecology, North Zealand Hospital, University of Copenhagen, Dyrehavevej 29, 3400 Hillerød, Denmark


This study received invaluable practical assistance from the staff of the Departments of Clinical Biochemistry and Clinical Research at North Zealand Hospital, and from the data management of Steen Rasmussen, MSC.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Grants from the North Zealand Hospital Research Council, the Gangsted Foundation, the Foundation for Development of Danish Private Practice, the Tvergaard Foundation, the AP Møller Foundation, the Foundation from Danish Doctors Pension and Copenhagen University made this research possible. No funders were involved in the design, acquisition, analysis or interpretation of data prior to submission.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2019-05-14
Accepted: 2019-06-17
Published Online: 2019-07-25
Published in Print: 2019-11-26

© 2019 Walter de Gruyter GmbH, Berlin/Boston

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