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

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function

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Estradiol and progesterone levels in early pregnancy after natural, estradiol + progesterone or gonadotrophin stimulated frozen embryo transfer cycle: a randomised controlled trial protocol

“…A statistical power analysis was performed for sample size estimation based on data from previous studies regarding serum estradiol levels in early, naturally conceived pregnancies 8. The median serum estradiol level at gestational week 7 is 3.3 nmol/L.…”

“…A statistical power analysis was performed for sample size estimation based on data from previous studies regarding serum estradiol levels in early, naturally conceived Open access pregnancies. 8 The median serum estradiol level at gestational week 7 is 3.3 nmol/L. Using the assumed clinically relevant effect size of 20% absolute increase in serum estradiol levels in estradiol-treated FET, with a two-sided significance level of 0.05 and with 80% power, the projected sample size needed is n=83 women.…”

Reference intervals for clinical biochemistry and haematology tests during normal pregnancy

“…8,9 The clinical risk of such practice is not insignificant with the potential to lead to patient misdiagnosis and/or mismanagement; therefore, ideally laboratories should establish/provide pregnancy-specific RIs for biochemical and haematological parameters across all three trimesters. 10…”