Objective Reference values are usually defined based on blood samples from healthy men or nonpregnant women. This is not optimal as many biological markers changes during pregnancy and adequate reference values are of importance for correct clinical decisions. There are only few studies on the variations of laboratory tests during normal pregnancies, especially during the first two trimesters. It is thus a need to establish such reference values.Design Longitudinal study of laboratory markers in normal pregnancies.Setting Uppsala University Hospital, Sweden.Population Healthy pregnant females.Methods We have studied 25 frequently used laboratory tests during 52 normal pregnancies. Each woman was sampled up to nine times and the samples were divided according to collection time into the following groups: gestational week 7-17; week 17-24; week 24-28; week 28-31; week 31-34; week 34-38; predelivery (0-2 weeks before delivery) and postpartum (>6 weeks after delivery). The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values.Results Reference intervals are reported for plasma alanine aminotransferase, albumin, alkaline phosphatase, pancreas amylase, apolipoprotein A1, apolipoprotein B, aspartate aminotransferase, bilirubin, calcium, chloride, creatinine, cystatin C, ferritin, g-glutamyltransferase, iron, lactate dehydrogenase, magnesium, phosphate, potassium, sodium, transferrin, triglycerides, thyroidstimulating hormone, urate and urea during these pregnancy periods.Conclusions Most of the analytes change during normal pregnancy. It is thus of importance to use special reference values during pregnancy.

The objective of this study was to establish reference intervals and decision limits for the interpretation of the acute phase proteins alpha(1)-acid glycoprotein (orosomucoid), alpha(1)-antitrypsin, C-reactive protein (CRP), haptoglobin and albumin, IgA, IgG and IgM during pregnancy by longitudinal sampling from 52 healthy women with normal pregnancies. Each woman was sampled in weeks 7-17; weeks 17-24; weeks 24-28; weeks 28-31; weeks 31-34; weeks 34-38 and predelivery (-14-0 days prior to delivery) and postpartum (>6 weeks after delivery). The 2.5th and 97.5th percentiles were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. Reference values for alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, albumin, haptoglobin, CRP, IgA, IgG and IgM are reported. Most of these proteins changed during normal pregnancy, as a reflection of the major physiological and biochemical changes that occur in pregnancy. A laboratory test result from a pregnant woman should be compared with pregnancy-specific reference intervals.

To study the role of inflammation throughout normal pregnancy and postpartum, 37 women with normal pregnancies, including normal neonatal outcome, participated. Blood and urine samples were collected from each woman at least six times during pregnancy and postpartum. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and urinary levels of a prostaglandin-F2α (PGF2α ) metabolite were measured. Median, 25th to 75th centile and average change per gestational week of IL-6, TNF-α and the PGF2α metabolite were measured. Levels of IL-6 increased significantly throughout pregnancy and remained high postpartum. No change in TNF-α could be seen. The PGF2α metabolite levels increased significantly throughout pregnancy and decreased postpartum. These results suggest that mild but significant inflammatory activity is involved in the development of normal pregnancy, which might have important physiological roles.

This longitudinal study demonstrates how sFlt1, PlGF and the sFlt1:PlGF ratio fluctuate throughout normal pregnancy and postpartum and may serve as a reference against which these factors can be studied in complicated pregnancies. VEGF-A levels were more often detectable postpartum.

This study investigates oxidative stress and antioxidants in normal human pregnancy and post-partum period. Thirty-seven healthy women with normal pregnancies were included. Both urinary and serum samples were collected throughout the pregnancy and post-partum period. Oxidative stress was estimated by measuring the reliable in vivo marker, namely 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha,) an F(2)-isoprostane) and antioxidant status was evaluated by measuring alpha- and gamma-tocopherol in serum samples. Pregnancy was associated with successively increased levels of 8-iso-PGF(2alpha) with advancing gestational age. The median post-partum value corresponded to the values observed in early gestation and a significant decrease was observed from late pregnancy to the post-partum period. Lipid-adjusted alpha- and gamma-tocopherol levels decreased with advancing gestational age. This longitudinal study suggests that mild oxidative stress is involved in normal human pregnancy.