Circulating SPINT1 is a biomarker of pregnancies with poor placental function and fetal growth restriction.

Placental insufficiency can cause fetal growth restriction and stillbirth. There are no reliable screening tests for placental insufficiency, especially near-term gestation when the risk of stillbirth rises. Here we show a strong association between low circulating plasma serine peptidase inhibitor Kunitz type-1 (SPINT1) concentrations at 36 weeks' gestation and low birthweight, an indicator of placental insufficiency. We generate a 4-tier risk model based on SPINT1 concentrations, where the highest risk tier has approximately a 2-5 fold risk of birthing neonates with birthweights under the 3rd, 5th, 10th and 20th centiles, whereas the lowest risk tier has a 0-0.3 fold risk. Low SPINT1 is associated with antenatal ultrasound and neonatal anthropomorphic indicators of placental insufficiency. We validate the association between low circulating SPINT1 and placental insufficiency in two other cohorts. Low circulating SPINT1 is a marker of placental insufficiency and may identify pregnancies with an elevated risk of stillbirth.

Determination of haemoglobin derivatives in aged dried blood spot to estimate haematocrit.

Introduction Dried blood spot (DBS) sample applications now encompass analytes related to clinical diagnosis, epidemiological studies, therapeutic drug monitoring, pharmacokinetic and toxicokinetic studies. Haematocrit (Hct) and haemoglobin (Hb) at very high or low concentrations may influence the accuracy of measurement quantification of the DBS sample. In this study, we aimed to predict the Hct of the punched DBS through primary spectrophotometric estimation of its haemoglobin-derivative (Hb-drv) content. Methods Formic acid solution was used to elute Hb-drv content of 3.2 mm spotted blood from its dry matrix. Direct spectrometry measurement was utilised to scan the extracted Hb-drv in the visible spectrum range of 520-600 nm. The linear relationship between an individual's Hct percentage and Hb-drv concentration was applied to estimate the Hct level of the blood spot. De-identified whole blood samples were used for the method development and evaluation studies. Results The Hb-drv estimation is valid in samples >2 months old. Method validation experiments DBS demonstrate linearity between 82.5 and 207.5 g/L, average coefficient of variation of 3.6% (intra-assay) and 7.7% (inter-assay), analytical recovery of 84%, and a high positive correlation (r=0.88) between Hb-drv and the original whole blood Hct. The Bland-Altman difference plot demonstrates a mean difference of 2.4% between the calculated DBS Hct and the directly measured Hct from fresh whole bloods. Conclusions We have successfully developed a simple Hb-drv method to estimate Hct in aged DBS samples. This method can be incorporated into DBS analytical work-flow for the in-situ estimation of Hct and subsequent correction of the analyte of interest as required.

Longitudinal assessment of thyroid function in pregnancy.

BACKGROUND: Trimester-specific reference intervals (RIs) for thyroid function tests are lacking for Beckman Dxl 800 analysers. We aimed to establish RIs for thyroid stimulating hormone (TSH), free thyroxine (fT4) and to track intraindividual changes in thyroid function throughout pregnancy. METHODS: One hundred and thirty healthy women without antithyroid peroxidase antibodies were followed longitudinally. Thyroid function was determined at trimester-1 (T1): 9-13 weeks; trimester-2 (T2): 22-26 weeks; trimester-3 (T3): 35-39 weeks and postpartum (PP): 8-12 weeks. A subgroup (n = 47) was used to track intraindividual changes using PP as non-pregnant state (baseline). RESULTS: For trimesters 1-3, TSH (median (2.5th, 5th, 95th and 97.5th percentile)) was 0.77 (0.03, 0.05, 2.33, 3.05), 1.17 (0.42, 0.47, 2.71, 3.36) and 1.35 (0.34, 0.42, 2.65, 2.83) mIU/L, respectively. Free T4 (mean (95%CI)) was 10.7 (5.9-15.5), 8.1 (4.9-11.3), 7.8 (4.5-11.0) pmol/L, respectively. In T2 and T3, 36% and 41% of the fT4 values, respectively, fell below the non-pregnancy lower normal limit. In the subgroup assessed for longitudinal changes, of the women with baseline TSH ≤ median, 71-75% remained at or below the corresponding median for trimesters 1-3. Of the women with baseline fT4 ≤ median, 69-81% also remained at or below the corresponding median for trimesters 1-3. High correlation was observed at different trimesters and baseline for TSH (Spearman's r: 0.593-0.846, P < 0.001) and for fT4 (r: 0.480-0.739, P < 0.001). CONCLUSIONS: Use of trimester-specific RIs would prevent misclassification of thyroid function during pregnancy. In the majority of women, TSH and fT4 tracked on the same side of the median distribution, from a non-pregnant baseline, throughout pregnancy.