First trimester screening of serum soluble fms-like tyrosine kinase-1 and placental growth factor predicting hypertensive disorders of pregnancy

AbstractObjectiveTo assess the accuracy of first trimester soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in predicting pregnancy hypertension and pre-eclampsia; and compare with the accuracy of routinely collected maternal and clinical risk factors.Study designIn this population-based cohort study, serum sFlt-1 and PlGF levels were measured in first trimester in 2,681 women with singleton pregnancies in New South Wales, Australia.Main outcome measuresPrediction of pregnancy hypertension and pre-eclampsia.ResultsThere were 213 (7.9%) women with pregnancy hypertension, including 68 (2.5%) with pre-eclampsia. The area under the curve (AUC) for both sFlt-1 and PlGF was not different from chance, but combined was 0.55 (P=0.005). Parity and previous diagnosed hypertension had better predictive accuracy than serum biomarkers (AUC=0.64, P<0.001) and the predictive accuracy for all maternal and clinical information was fair (AUC=0.70, P<0.001 for pregnancy hypertension and AUC=0.74, P<0.001 for pre-eclampsia). Adding sFlt-1 and PlGF to maternal risk factors did not improve the ability of the models to predict pregnancy hypertension or pre-eclampsia.ConclusionsMaternal first trimester serum concentrations of sFlt-1 and PlGF do not predict hypertensive disorders in pregnancy any better than routinely collected clinical and maternal risk factor information. Screening for sFlt-1 and PlGF levels in early pregnancy would not identify those pregnancies at-risk

First trimester screening of serum soluble fms-like tyrosine kinase-1 and placental growth factor predicting hypertensive disorders of pregnancy

AbstractObjectiveTo assess the accuracy of first trimester soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in predicting pregnancy hypertension and pre-eclampsia; and compare with the accuracy of routinely collected maternal and clinical risk factors.Study designIn this population-based cohort study, serum sFlt-1 and PlGF levels were measured in first trimester in 2,681 women with singleton pregnancies in New South Wales, Australia.Main outcome measuresPrediction of pregnancy hypertension and pre-eclampsia.ResultsThere were 213 (7.9%) women with pregnancy hypertension, including 68 (2.5%) with pre-eclampsia. The area under the curve (AUC) for both sFlt-1 and PlGF was not different from chance, but combined was 0.55 (P=0.005). Parity and previous diagnosed hypertension had better predictive accuracy than serum biomarkers (AUC=0.64, P<0.001) and the predictive accuracy for all maternal and clinical information was fair (AUC=0.70, P<0.001 for pregnancy hypertension and AUC=0.74, P<0.001 for pre-eclampsia). Adding sFlt-1 and PlGF to maternal risk factors did not improve the ability of the models to predict pregnancy hypertension or pre-eclampsia.ConclusionsMaternal first trimester serum concentrations of sFlt-1 and PlGF do not predict hypertensive disorders in pregnancy any better than routinely collected clinical and maternal risk factor information. Screening for sFlt-1 and PlGF levels in early pregnancy would not identify those pregnancies at-risk

Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes

Objective: To assess Ang-1, Ang-2 and the Ang-1/Ang-2 ratio levels in the first trimester of pregnancy, their association with adverse pregnancy outcomes; and their predictive accuracy. Study Design: This cohort study measured serum Ang-1 and Ang-2 levels in 4,785 women with singleton pregnancies attending first trimester screening in New South Wales, Australia. Multivariate logistic regression models were used to assess the association and predictive accuracy of serum biomarkers with subsequent adverse pregnancy outcomes (small for gestational age, preterm birth, preeclampsia, miscarriage >10 weeks and stillbirth). Results: Median (interquartile range) levels for Ang-1, Ang-2 and the Ang-1/Ang-2 ratio for the total population were 19.6 ng/ml (13.6-26.4), 15.5 ng/ml (10.3-22.7) and 1.21 (0.83-1.73), respectively. Maternal age, weight, country of birth and socio-economic status significantly affected Ang-1, Ang-2 and the Ang-1/Ang-2 ratio levels. After adjusting for maternal and clinical risk factors, women with low Ang-2 levels (90th centile) had increased risk of developing most adverse pregnancy outcomes. Compared to the Ang-1/Ang-2 ratio alone, maternal and clinical risk factors had better predictive accuracy for most adverse pregnancy outcomes. The exception was miscarriage [Ang-1/Ang-2 ratio area under ROC curve (AUC) =0.70; maternal risk factors AUC =0.58]. Overall, adding the Ang-1/Ang-2 ratio to maternal risk factors did not improve the ability of the models to predict adverse pregnancy outcomes. Conclusions: Our findings suggest that the Ang-1/Ang-2 ratio in first trimester is associated with most adverse pregnancy outcomes, but do not predict outcomes any better than clinical and maternal risk factor information.Australian National Health and Medical Research Council (NHMRC) Project Grant (#632653)

Acid suppressants for managing gastro-oesophageal reflux and gastro-oesophageal reflux disease in infants: a national survey

Objectives: To evaluate the diagnosis and management of reflux and gastro-oesophageal reflux disease (GORD) in infants aged <1 year presenting to general practitioners (GPs). Design, setting and participants: A nationally representative, prospective, cross-sectional survey of GP activity in Australia, 2006–2016 (Bettering the Evaluation And Care of Health Study). Annually, a random sample of around 1000 GPs recorded details for 100 consecutive visits with consenting, unidentified patients. Outcome measures: Diagnoses of reflux and GORD and their management including prescribing of acid-suppressant medicines (proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs)) and counselling, advice or education. Results: Of all infants’ visits, 512 (2.7%) included a diagnosis of reflux (n=413, 2.2%) or GORD (n=99, 0.5%). From 2006 to 2016, diagnostic rates decreased for reflux and increased for GORD. Prescribing of acid suppressants occurred in 43.6% visits for reflux and 48.5% visits for GORD, similar to rates of counselling, advice or education (reflux: 38.5%, GORD: 43.4% of visits). Prescribing of PPIs increased (statistically significant only for visits for reflux), while prescribing of H2RAs decreased. Conclusions: Overprescribing of acid suppressants to infants may be occurring. In infants, acid-suppressant medicines are no better than placebo and may have significant negative side effects; however, guidelines are inconsistent. Clear, concise and consistent guidance is needed. GPs and parents need to understand what is normal and limitations of medical therapy. We need a greater understanding of the influences on GP prescribing practices, of parents’ knowledge and attitudes and of the pressures on parents of infants with these conditions.Jane C Bell, Francisco J Schneuer, Christopher Harrison, Lyndal Trevena, Harriet Hiscock, Adam G Elshaug, Natasha Nassa

Maternal and neonatal outcomes of women with gestational diabetes and without specific medical conditions: an Australian population-based study comparing induction of labor with expectant management

Background/aims: To evaluate maternal birth and neonatal outcomes among women with gestational diabetes mellitus (GDM), but without specific medical conditions and eligible for vaginal birth who underwent induction of labour (IOL) at term compared with those who were expectantly managed. Materials and methods: Population-based cohort study of women with GDM, but without medical conditions, who had a singleton, cephalic birth at 38–41 completed weeks gestation, in New South Wales, Australia between January 2010 and December 2016. Women who underwent IOL at 38, 39, 40 weeks gestation (38-, 39-, 40-induction groups) were compared with those who were managed expectantly and gave birth at and/or beyond the respective gestational age group (38-, 39-, 40-expectant groups). Multivariable logistic regression analysis was used to assess the association between IOL and adverse maternal birth and neonatal outcomes taking into account potential confounding by maternal age, country of birth, smoking, residential location, residential area of socioeconomic disadvantage and birth year. Results: Of 676 762 women who gave birth during the study period, 66 606 (10%) had GDM; of these, 34799 met the inclusion criteria. Compared with expectant management, those in 38- (adjusted odds ratio (aOR) 1.11; 95% CI, 1.04–1.18), 39- (aOR 1.21; 95% CI, 1.14–1.28) and 40- (aOR 1.50; 95% CI, 1.40–1.60) induction groups had increased risk of caesarean section. Women in the 38-induction group also had an increased risk of composite neonatal morbidity (aOR 1.10; 95% CI, 1.01–1.21), which was not observed at 39- and 40-induction groups. We found no difference between groups in perinatal death or neonatal intensive care unit admission for births at any gestational age. Conclusion: In women with GDM but without specific medical conditions and eligible for vaginal birth, IOL at 38, 39, 40 weeks gestation is associated with an increased risk of caesarean section