Association between adverse pregnancy outcome and placental biomarkers in the first trimester: A prospective cohort study

Abstract

AbstractObjectiveTo determine the inter‐relationships between five first‐trimester biomarkers (pregnancy associated plasma protein A [PAPP‐A], alpha‐fetoprotein [AFP], beta human chorionic gonadotrophin [beta‐hCG], placenta growth factor [PlGF] and soluble fms‐like tyrosine kinase receptor‐1 [sFlt‐1]) and a range of adverse pregnancy outcomes (APOs).DesignProspective cohort study of nulliparous singleton pregnancy.SettingCambridge, UK.Population or Sample4056 pregnancy outcome prediction study participants.MethodsThe biomarker concentrations were measured in maternal serum at ~12 weeks of gestation. Univariable analysis of APOs was performed using logistic regression. Multivariable analysis used best subsets logistic regression with cross‐validation.Main outcome measuresPre‐eclampsia (PE), small for gestational age (SGA), including severe SGA (birthweight <3rd), fetal growth restriction (FGR), preterm birth (PTB, both induced and spontaneous [iPTB and sPTB, respectively]), pre‐viable loss and stillbirth, plus combinations of outcomes.ResultsLower values of PAPP‐A, PlGF and sFlt‐1 and higher values of AFP were associated with FGR (OR for 1 SD higher value 0.59 [95% CI 0.48–0.74], OR 0.56 [95% CI 0.44–0.70], OR 0.68 [95% CI 0.54–0.87] and OR 1.53 [95% CI 1.25–1.88]), severe SGA (OR 0.59 [95% CI 0.49–0.72], OR 0.71 [95% CI 0.57–0.87], OR 0.74 [95% CI 0.60–0.91] and OR 1.41 [95% CI 1.17–1.71]), sPTB (OR  0.61 [95% CI 0.50–0.73], OR 0.79 [95% CI 0.66–0.96], OR 0.57 [95% CI 0.47–0.70] and OR 1.41 [95% CI 1.18–1.67]) and iPTB (OR  0.72 [95% CI 0.57–0.91], OR 0.62 [95% CI 0.49–0.78], OR 0.71 [95% CI 0.56–0.90] and OR 1.44 [95% CI 1.16–1.78]), respectively. When combinations of biomarkers were assessed, PAPP‐A and AFP were independently associated with severe SGA; PAPP‐A alone with PE + PTB; PlGF alone with severe PE; PlGF, beta‐hCG, AFP and PAPP‐A with the combination of PE and SGA; AFP and sFlt‐1 with sPTB; and AFP and PlGF with iPTB.ConclusionsCombinations of first‐trimester placental biomarkers are associated with APOs. However, the patterns vary for different types of APO, indicating heterogeneity in the underlying pathophysiological pathways.