Prediction of spontaneous preterm birth and preterm prelabor rupture of membranes using maternal factors, obstetric history and biomarkers of placental function at 11–13 weeks

Abstract

What are the novel findings of this work?We have demonstrated that first-trimester maternal serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) levels are reduced in cases of spontaneous preterm birth (sPTB) and preterm prelabor rupture of membranes (PPROM) at < 37 weeks, suggesting that placental insufficiency is implicated in the underlying pathophysiology of these complications. What are the clinical implications of this work?In addition to increased risks of fetal growth restriction and pre-eclampsia, low levels of maternal serum PAPP-A and PlGF are associated with increased risks of sPTB and PPROM. These findings may be useful in counseling women regarding their obstetric risks, and paving the way to the identification of effective personalized preventive measures for women at high risk of sPTB.

Angiogenic imbalance in pregnancies with preterm prelabor rupture of membranes between 34 and 37 weeks of gestation

“…9 Angiogenic imbalance represents one of the underlying pathologies of PPROM. 28 The angiogenic imbalance in the maternal circulation of women who later develop PPROM can be observed even in the first trimester of the pregnancy 32 and is further pronounced in the second and third trimesters of pregnancy. 8 Romero et al have recently shown that the earliest gestational age at which concentrations of PlGF, sFlt-1 and their ratio become different from uncomplicated pregnancy are gestational ages 30, 31 and 27 weeks, respectively.…”

First‐trimester prediction of preterm pre‐eclampsia and prophylaxis by aspirin: Effect on spontaneous and iatrogenic preterm birth

“…A smaller study of 11 437 women undergoing first‐trimester screening for preterm pre‐eclampsia by a combination of maternal risk factors, MAP, UtA‐PI and PAPP‐A, reported that in those with estimated risk of ≥1 in 50, compared with those with a risk <1 in 50, the odds ratio for iPTB was 6.0 (95% CI 4.29–8.43) and that for sPTB was 2.0 (95% CI 1.46–2.86) 11 . Another study of 9298 singleton pregnancies reported that first‐trimester biomarkers of placental function can be used to screen for sPTB; inclusion of PlGF and PAPP‐A improved the DR of sPTB at <37 weeks of gestation provided by maternal risk factors from 17% to 25%, at FPR of 10% 12 …”

“…11 Another study of 9298 singleton pregnancies reported that first-trimester biomarkers of placental function can be used to screen for sPTB; inclusion of PlGF and PAPP-A improved the DR of sPTB at <37 weeks of gestation provided by maternal risk factors from 17% to 25%, at FPR of 10%. 12 A Swedish register-based cohort study investigated the association between low-dose aspirin use and PTB among 22 127 women with a previous PTB and concluded that low-dose aspirin use was associated with a reduced risk for sPTB (relative risk [RR] 0.70; 95% CI 0.57-0.86) but had no significant effect on iPTB (RR 1.09; 95% CI 0.91-1.30). 13 A double-blind, placebo-controlled trial of low-dose aspirin (81 mg daily) versus placebo from 6 to 13 weeks of gestation until 36 weeks in 11 976 nulliparous women with singleton pregnancies found that aspirin was associated with an 11% reduction in the risk of PTB at <37 weeks of gestation (RR 0.89, 95% CI 0.81-0.98) but the study did not provide data as to whether the PTB was spontaneous or iatrogenic and whether there was any association with pre-eclampsia.…”

“…8 There is some contradictory evidence as to whether women at high risk of developing pre-eclampsia are also at increased risk of spontaneous (s) and iatrogenic (i) preterm birth (PTB) for reasons other than pre-eclampsia and whether the incidence of these conditions is also reduced by prophylactic use of aspirin. [9][10][11][12][13] The objectives of this study are: first, to compare the predictive performance of the FMF triple test and NICE guidelines for sPTB and iPTB, and second, to examine the impact of prophylactic use of aspirin in the prevention of these pregnancy complications.…”

Does Precision-Based Medicine Hold the Promise of a New Approach to Predicting and Treating Spontaneous Preterm Birth?

“…As a result, it is used to predict the need for delivery within 14 days, with a sensitivity (the ability of the test to identify true positives) and specificity (the ability of the test to identify true negatives) of 80% for both and positive and negative predictive values (the proportion of individuals with a positive test result who will deliver preterm or with a negative test result who will not deliver preterm) of 0.41 and 0.95, respectively (using the Triage MeterPro point-of-care analyzer that uses a fluorescence immunoassay) [57]. More recently, PLGF has been investigated as a potential biomarker for predicting spontaneous PTL, and this is discussed later in this review [58]. Prediction and prevention rely on identifying high-risk patients using their medical and obstetric history to determine risk factors.…”