Objective To explore if the addition of pregnancy-associated plasma protein-A (PAPP-A) to maternal factors and biophysical markers yields a significant improvement in the detection of hypertensive disorders before the clinical onset of disease.Methods Prospective screening study for early preeclampsia (PE), late PE and gestational hypertension (GH) in women attending their first hospital visit at 11 +0 -13 +6 weeks of gestation. The performance of screening for PE and GH by combinations of maternal factors, uterine artery with the lowest pulsatility index (L-PI), mean arterial pressure (MAP) and serum PAPP-A was determined.Results There were 8061 unaffected controls, 37 of whom developed early PE, 128 with late PE and 140 with GH. Compared to the controls, in early PE and late PE MAP and uterine artery L-PI were increased and PAPP-A was decreased. In GH PAPP-A was not significantly different from controls. In screening for a combination of maternal factors, uterine artery L-PI, MAP and PAPP-A the detection rate of early PE was 83.8%, at a 5% false-positive rate. In the prediction of late PE and GH there was no significant improvement from the addition of PAPP-A to the combination of maternal factors, MAP and uterine artery L-PI. ConclusionMeasurement of PAPP-A improves the performance of screening for early PE provided by a combination of maternal factors and biophysical tests at 11-13 weeks.

Objective: To determine if combinations of maternal characteristics and measurements of parameters used in screening for aneuploidies at 11–13 weeks provide significant prediction of macrosomia. Method: Maternal characteristics, fetal nuchal translucency (NT), free β-human chorionic gonadotrophin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) were recorded at 11⁺⁰–13⁺⁶ weeks in 36,743 singleton pregnancies. Regression analysis was used to determine if in predicting macrosomia significant contributions are provided by maternal factors, fetal NT, free β-hCG and PAPP-A. Results: The risk for macrosomia increased with maternal weight and height and was higher in parous women with previous delivery of a macrosomic baby and in those with diabetes mellitus; the risk was lower in women of African and South Asian racial origins, in cigarette smokers and in those with chronic hypertension. In the macrosomic group compared to the unaffected group there were higher Δ-NT (0.167 vs. 0.116 mm), free β-hCG (1.010 vs. 0.964 MoM) and PAPP-A (1.103 vs. 1.003 MoM). Prediction of macrosomia provided by maternal factors was significantly improved by fetal NT, free β-hCG and PAPP-A (34.4 vs. 33.1% at a false-positive rate of 10%). Conclusion: Prediction of macrosomia is provided in the first trimester of pregnancy by a combination of maternal characteristics and measurements of parameters used in screening for aneuploidies.

Objective To estimate the risk of miscarriage associated with chorionic villus sampling (CVS). Methods This was a retrospective cohort study of women attending for routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation at one of eight fetal‐medicine units in Spain, Belgium and Bulgaria, between July 2007 and June 2018. Two populations were included: (1) all singleton pregnancies undergoing first‐trimester assessment at Hospital Clínico Universitario Virgen de la Arrixaca in Murcia, Spain, that did not have CVS (non‐CVS group); and (2) all singleton pregnancies that underwent CVS following first‐trimester assessment at one of the eight participating centers (CVS group). We excluded pregnancies diagnosed with genetic anomalies or major fetal defects before or after birth, those that resulted in termination and those that underwent amniocentesis later in pregnancy. We used propensity score (PS) matching analysis to estimate the association between CVS and miscarriage. We compared the risk of miscarriage of the CVS and non‐CVS groups after PS matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that are associated with CVS, in a similar way to that in which randomization operates in a randomized clinical trial. Results The study population consisted of 22 250 pregnancies in the non‐CVS group and 3613 in the CVS group. The incidence of miscarriage in the CVS group (2.1%; 77/3613) was significantly higher than that in the non‐CVS group (0.9% (207/22 250); P < 0.0001). The PS algorithm matched 2122 CVS with 2122 non‐CVS cases, of which 40 (1.9%) and 55 (2.6%) pregnancies in the CVS and non‐CVS groups, respectively, resulted in a miscarriage (odds ratio (OR), 0.72 (95% CI, 0.48–1.10); P = 0.146). We found a significant interaction between the risk of miscarriage following CVS and the risk of aneuploidy, suggesting that the effect of CVS on the risk of miscarriage differs depending on background characteristics. Specifically, when the risk of aneuploidy is low, the risk of miscarriage after CVS increases (OR, 2.87 (95% CI, 1.13–7.30)) and when the aneuploidy risk is high, the risk of miscarriage after CVS is paradoxically reduced (OR, 0.47 (95% CI, 0.28–0.76)), presumably owing to prenatal diagnosis and termination of pregnancies with major aneuploidies that would otherwise have resulted in spontaneous miscarriage. For example, in a patient in whom the risk of aneuploidy is 1 in 1000 (0.1%), the risk of miscarriage after CVS will increase to 0.3% (0.2 percentage points higher). Conclusions The risk of miscarriage in women undergoing CVS is about 1% higher than that in women who do not have CVS, although this excess risk is not solely attributed to the invasive procedure but, to some extent, to the demographic and pregnancy characteristics of the patients. After accounting for these risk factors and confining the analysis to low‐risk pregnancies, CVS seems to increase the risk of miscarriage by about three times above the patient's bac...

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