Placental growth factor measurements in the assessment of women with suspected Preeclampsia: A stratified analysis of the PARROT trial.

OBJECTIVE: Placental growth factor testing decreases time to recognition of preeclampsia and may reduce severe maternal adverse outcomes. This analysis aims to describe the clinical phenotype of women by PlGF concentration, and to determine the mechanism(s) underpinning the reduction in severe maternal adverse outcomes in the PARROT trial, in order to inform how PlGF testing may be optimally used within clinical management algorithms. STUDY DESIGN: This was a planned secondary analysis from the PARROT trial that compared revealed PlGF testing and management guidance with usual care in the assessment of women with suspected preterm preeclampsia. MAIN OUTCOME MEASURES: Maternal and perinatal outcomes following stratification of women by trial group, and measured PlGF concentration. RESULTS: 1006 women were included. PlGF < 100 pg/ml identified women with more marked hypertension, increased adverse maternal outcomes and preterm delivery rates, and higher rates of small for gestational age infants. There was a reduction in adverse maternal outcomes in women whose results were revealed when PlGF levels were 12-100 pg/ml compared to usual care (3.8% vs 6.9%; aOR 0.15(95% CI 0.03-0.92). There was no significant difference in gestation at delivery between concealed or revealed groups in any PlGF categories. CONCLUSION: Low PlGF concentrations are associated with severe preeclampsia. The reduction in severe adverse maternal outcomes may be mediated through quicker diagnosis and intensive surveillance, as recommended by the management algorithm for those at increased risk. PlGF is particularly beneficial in those who test 12-100 pg/ml, as these may be women with silent multi-organ disease who otherwise may go undetected.

Pregnancy in women known to be living with a single kidney.

There is a paucity of data on pregnancy outcome in women living with a single kidney from all causes. Current thinking is extrapolated from living kidney donors, a group biased by strict selection criteria. We present a cohort of 26 women with a solitary functioning kidney; 11 women had an acquired single kidney of whom only 1 was a living donor and 15 had a congenital single kidney. Median time living with a single kidney was 28 years. None booked with hypertension or proteinuria. Urinary tract infection complicated 50% of pregnancies. Worryingly, 35% developed pre-eclampsia, gestational proteinuria or gestational hypertension. We propose pre-conceptual counselling, education on how to protect their single kidney, pre eclampsia prophylaxis with low-dose aspirin and close monitoring for urinary tract infection, hypertension and proteinuria with lower thresholds for pharmaceutical management. We have devised a Patient Information leaflet - 'Living with a single kidney, pregnancy and beyond'.

Quantitative Fetal Fibronectin at 18 Weeks of Gestation to Predict Preterm Birth in Asymptomatic High-Risk Women.

OBJECTIVE: To compare quantitative fetal fibronectin measurement from 18 to 21 weeks of gestation to measurement at 22-27 weeks of gestation for the prediction of spontaneous preterm birth. METHODS: In a prospective cohort study, we studied the accuracy of cervicovaginal fluid quantitative fetal fibronectin concentrations measured between 18 0/7 weeks of gestation and 21 6/7 weeks of gestation in high-risk asymptomatic women to predict spontaneous preterm birth before 34 weeks of gestation. Predefined fibronectin thresholds were 10 or greater, 50 or greater, and 200 ng/mL or greater. Diagnostic accuracy of the early test (n=898) was compared with the standard test performed between 22 0/7 and 27 6/7 weeks of gestation (n=691) in the same cohort. Subgroup analysis was performed according to cervical length measurement. RESULTS: Of 898 women, 8.7% delivered spontaneously before 34 weeks of gestation. Only 3.8% of the women with concentrations less than 10 ng/mL (65% of test results) delivered before 34 weeks of gestation. A concentration threshold of 10 ng/mL measured at 18 and 22 weeks of gestation had comparably high sensitivity (early 0.71, 95% confidence interval 0.60-0.81; standard 0.76, 0.63-0.87) and negative predictive value (early 0.96, 0.94-0.98; standard 0.97, 0.95-0.99) for delivery before 34 weeks of gestation. Specificity was also comparable (early 0.69, 0.65-0.72; standard 0.70, 0.66-0.74). A threshold of 200 ng/mL had high specificity (early 0.96, 0.94-0.98; standard 0.96, 0.94-0.97) with lower sensitivity (early 0.26, 0.17-0.37; standard 0.35, 0.22-0.49). Consideration of cervical length strengthened prediction. CONCLUSION: Quantitative cervicovaginal fetal fibronectin measured from 18 to 21 weeks of gestation has similar predictive value as measurement at 22-27 weeks of gestation for prediction of spontaneous preterm birth. Low fibronectin concentrations are associated with spontaneous preterm birthrates approaching population background levels.

Quantitative fetal fibronectin to predict preterm birth in asymptomatic women at high risk.

OBJECTIVE: To evaluate the diagnostic accuracy of cervicovaginal fluid quantitative fetal fibronectin, measured by a bedside analyzer, to predict spontaneous preterm birth before 34 weeks of gestation. METHODS: We conducted a prospective masked observational cohort study of cervicovaginal fluid quantitative fetal fibronectin concentration in asymptomatic women at high risk of spontaneous preterm birth (n=1,448; 22-27 6/7 weeks of gestation) measured using a rapid bedside analyzer. The routine qualitative result (positive-negative) was made available to clinicians at the time of testing, but the quantitative result remained blinded until after delivery. RESULTS: Spontaneous preterm birth (less than 34 weeks of gestation) increased from 2.7%, 11.0%, 14.9%, 33.9%, and 47.6% with increasing concentration of fetal fibronectin (less than 10, 10-49, 50-199, 200-499, and 500 ng/mL or greater, respectively). A threshold of 200 ng/mL had a positive predictive value of 37.7 (95% confidence interval [CI] 26.9-49.4) with specificity 96% (95% CI 95.3-97.3). Women with a fetal fibronectin concentration of less than 10 ng/mL had a very low risk of spontaneous preterm birth at less than 34 weeks of gestation (2.7%), no higher than the background spontaneous preterm birth rate of the general hospital population (3.3%). The quantitative fetal fibronectin test predicted birth at less than 34 weeks of gestation with an area under the curve (AUC) of 0.78 (95% CI 0.73-0.84) compared with the qualitative test AUC 0.68 (95% CI 0.63-0.73). Quantitative fetal fibronectin discriminated risk of spontaneous preterm birth at less than 34 weeks of gestation among women with a short cervix (less than 25 mm); 9.5% delivered prematurely less than 10 ng/mL compared with 55.1% greater than 200 ng/mL (P<.001). DISCUSSION: Alternative risk thresholds (less than 10 ng/mL and greater than 200 ng/mL) improve accuracy when using quantitative fetal fibronectin measurements to define risk of spontaneous preterm birth. This is particularly relevant for asymptomatic women with a short cervix. LEVEL OF EVIDENCE: II.

Deranged liver function tests in pregnancy: the importance of postnatal follow-up.

We report an asymptomatic 40-year-old woman with persistently deranged liver function tests found incidentally in the first trimester of her second pregnancy. No cause was apparent clinically, serologically or with imaging studies until a new finding of hepatomegaly led to a repeat ultrasound scan six weeks following delivery. A mass in the region of the common hepatic duct was confirmed to be a cholangiocarcinoma, with vascular invasion precluding curative surgical resection. This case highlights the need for close vigilance of patients with unexplained and persistently abnormal liver function tests, antenatally and postdelivery.