Reference intervals for clinical biochemistry and haematology tests during normal pregnancy

Abstract

Background Pregnancy induces physiological changes which affect biochemical and haematological parameters. As the significance of laboratory test results change throughout pregnancy, the reference interval (RI) or key result interpretive guide, should be specific to pregnancy. This study sought to establish trimester-specific-RIs for routine biochemical and haematological tests in healthy white European women with singleton pregnancies with comparison to RIs for non-pregnant European adults.
 Methods A retrospective analysis of a prospective longitudinal single-centre study of healthy pregnant women conducted between November 2018 and December 2020 in a tertiary academic hospital with approximately 3000 births annually. Inclusion criteria: signed informed consent, age≥18years, white European, body mass index (BMI)<25kg/m2, blood pressure<140/90mmHg, non-smoker, no previous pathology or gestational diabetes. Trimester defined as, T1:up to 13weeks+6days, T2:14-27weeks+6days, T3:≥28-41weeks+6days. Baseline demographics, anthropometric and laboratory measurements were recorded. In total, 31 biochemical and 10 haematological ISO15189:2012 accredited tests were measured using Roche Cobas® and Sysmex XN-9100™ analysers respectively. RIs were established according to the International Federation of Clinical Chemistry (IFCC) recommended method.
 Results Apparently healthy pregnant women (n=124) with bio-banked serum samples in each trimester were recruited. At the booking visit, 49.2% (n=61) of participants were nulliparous, with median: age of 34.4(IQR: 31.3-37.3) years, gestational age of 89(IQR:84-93) days, BMI of 22.5(IQR:21.0-23.7) kg/m2, systolic and diastolic blood pressure of 116(110-125) mmHg and 67 (61-75) mmHg respectively. 
 Conclusions Normative trimester-specific biological intervals for routinely requested biochemical and haematological medical laboratory tests were established. These RIs will be invaluable to result interpretation and the management of pregnant women. 

Pregnancy-specific reference intervals: should we exclude women based on body mass index?

“…We read with interest the article by Groenendijk et al, in which normative pregnancy-specific levels are reported for 41 routine haematological and biochemical tests. 1 We appreciated this well-executed reference study for its rigorous approach to investigating partitioning by gestational age. However, we have concerns about the use of body mass index (BMI) as an exclusion criterion.…”

Subjects used to calculate pregnancy-specific reference intervals must exclude those who are overweight or obese

“…There is much confusion in the letter from Dockree et al commenting on the reference intervals during normal pregnancy paper. 1,2 The values used in determining reference intervals are always selected from disease-free subjects. Adding people to these calculations with known characteristics that make a disease diagnosis likely is unwise and serves no legitimate clinical purpose.…”