Maternal risk factors and adverse birth outcomes associated with HELLP syndrome: a population-based study.

OBJECTIVES: We assessed the incidence, risk factors and adverse birth outcomes associated with elevated liver enzymes and low platelets (HELLP) syndrome. DESIGN: A retrospective population-based cohort study. SETTING: Canada (excluding Quebec), 2012/2013-2015/2016. POPULATION: Mothers with a singleton hospital live birth or stillbirth at ≥24 weeks' gestation (n = 1 078 323). METHODS: HELLP syndrome was identified using ICD-10-CA diagnostic code from delivery hospitalisation data. We used logistic regression to identify independent risk factors for HELLP syndrome by obtaining adjusted odds ratios (AOR) and 95% confidence intervals (CI), and to assess the associations with adverse outcomes. MAIN OUTCOME MEASURES: Adverse maternal (e.g. eclampsia) and fetal/neonatal outcomes (e.g. intraventricular haemorrhage, perinatal death). RESULTS: The incidence of HELLP syndrome was 2.5 per 1000 singleton deliveries (n = 2663). Risk factors included: age ≥35 years, rural residence, nulliparity, parity ≥4, pre-pregnancy and gestational hypertension and diabetes, assisted reproduction, chronic cardiac conditions, systemic lupus erythematosus, obesity, chronic hepatic conditions, placental disorders (e.g. fetomaternal transfusion) and congenital anomalies. PROM and age <25 years were inversely associated with HELLP syndrome (P-values <0.05). Women with the syndrome had a 10-fold higher maternal mortality (95% CI 1.6-84.3) and elevated severe maternal morbidity (9.6 versus 121.7 per 1000; AOR 12.5, 95% CI 11.1-14.1); and higher perinatal mortality (4.3 versus 21.0 per 1000; AOR 4.5, 95% CI 3.5-5.9) and perinatal mortality/severe neonatal morbidity (21.2 versus 202.4 per 1000; AOR 10.7, 95% CI 9.7-11.8). CONCLUSION: HELLP syndrome is associated with specific pre-pregnancy and pregnancy risk factors, higher rates of maternal death, and substantially higher severe maternal morbidity, perinatal mortality and severe neonatal morbidity. TWEETABLE ABSTRACT: HELLP syndrome is associated with higher maternal death rate, and substantially higher severe maternal and neonatal morbidity, and perinatal mortality.

Perinatal and maternal morbidity and mortality among term singletons following midcavity operative vaginal delivery versus caesarean delivery.

OBJECTIVE: To quantify severe perinatal and maternal morbidity/mortality associated with midcavity operative vaginal delivery compared with caesarean delivery. DESIGN: Population-based, retrospective cohort study. SETTING: British Columbia, Canada. POPULATION: Term, singleton deliveries (2004-2014) by attempted midcavity operative vaginal delivery or caesarean delivery in the second stage of labour, stratified by indication for operative delivery (n = 10 901 deliveries; 5057 indicated for dystocia, 5844 for fetal distress). METHODS: Multinomial propensity scores and mulitvariable log-binomial regression models were used to estimate adjusted rate ratios (ARR) and 95% confidence intervals (95% CI). MAIN OUTCOME MEASURES: Composite severe perinatal morbidity/mortality (e.g. convulsions, severe birth trauma and perinatal death) and severe maternal morbidity (e.g. severe postpartum haemorrhage, shock, sepsis and cardiac complications). RESULTS: Among deliveries with dystocia, attempted midcavity operative vaginal delivery was associated with higher rates of severe perinatal morbidity/mortality compared with caesarean delivery (forceps ARR 2.11, 95% CI 1.46-3.07; vacuum ARR 2.71, 95% CI 1.49-3.15; sequential ARR 4.68, 95% CI 3.33-6.58). Rates of severe maternal morbidity/mortality were also higher following midcavity operative vaginal delivery (forceps ARR 1.57, 95% CI 1.05-2.36; vacuum ARR 2.29, 95% CI 1.57-3.36). Among deliveries with fetal distress, there were significant increases in severe perinatal morbidity/mortality following attempted midcavity vacuum (ARR 1.28, 95% CI 1.04-1.61) and in severe maternal morbidity following attempted midcavity forceps delivery (ARR 2.34, 95% CI 1.54-3.56). CONCLUSION: Attempted midcavity operative vaginal delivery is associated with higher rates of severe perinatal morbidity/mortality and severe maternal morbidity, though these effects differ by indication and instrument. TWEETABLE ABSTRACT: Perinatal and maternal morbidity is increased following midcavity operative vaginal delivery.

International comparisons of preterm birth: higher rates of late preterm birth are associated with lower rates of stillbirth and neonatal death.

OBJECTIVE: To examine international rates of preterm birth and potential associations with stillbirths and neonatal deaths at late preterm and term gestation. DESIGN: Ecological study. SETTING: Canada, USA and 26 countries in Europe. POPULATION: All deliveries in 2004. METHODS: Information on preterm birth (<37, 32-36, 28-31 and 24-27 weeks of gestation) and perinatal deaths was obtained for 28 countries. Data sources included files and publications from Statistics Canada, the EURO-PERISTAT project and the National Center for Health Statistics. Pearson correlation coefficients and random-intercept Poisson regression were used to examine the association between preterm birth rates and gestational age-specific stillbirth and neonatal death rates. Rate ratios with 95% confidence intervals were estimated after adjustment for maternal age, parity and multiple births. MAIN OUTCOME MEASURES: Stillbirths and neonatal deaths ≥ 32 and ≥ 37 weeks of gestation. RESULTS: International rates of preterm birth (<37 weeks) ranged between 5.3 and 11.4 per 100 live births. Preterm birth rates at 32-36 weeks were inversely associated with stillbirths at ≥ 32 weeks (adjusted rate ratio 0.94, 95% CI 0.92-0.96) and ≥ 37 weeks (adjusted rate ratio 0.88, 95% CI 0.85-0.91) of gestation and inversely associated with neonatal deaths at ≥ 32 weeks (adjusted rate ratio 0.88, 95% CI 0.85-0.91) and ≥ 37 weeks (adjusted rate ratio 0.82, 95% CI 0.78-0.86) of gestation. CONCLUSIONS: Countries with high rates of preterm birth at 32-36 weeks of gestation have lower stillbirth and neonatal death rates at and beyond 32 weeks of gestation. Contemporary rates of preterm birth are indicators of both perinatal health and obstetric care services.

PP023. Unexpected random urinary protein: creatinine ratio results - Insightsfrom clinician-laboratory medicine collaboration.

INTRODUCTION: Proteinuria assessment is important in pregnancy, particularly in determining whether or not a woman has pre-eclampsia. The random protein to creatinine ratio (PrCr) has been recommended as a confirmatory test for dipstick proteinuria in pregnancy, defined as random PrCr ⩾30mg/mmol. However, it has been our clinical impression that women with normal pregnancy outcomes have fluctuating or persistently elevated PrCr values. OBJECTIVES: As the primary goal of proteinuria testing in pregnancy should be to identify women at increased risk of adverse outcomes, we sought to explore our clinical impression that an elevated PrCr is seen not infrequently in pregnancies with normal outcome. METHODS: In this prospective cohort study, consecutive inpatients or outpatients (attending high-risk maternity clinics) were evaluated at a tertiary care facility. Random midstream urine samples were obtained as part of normal clinical care. Urine protein was measured using a pyrocatechol violet molybdate dye-binding method, and urine creatinine by an enzymatic method, both on an automated analyser (Vitros® 5.1 FS or Vitros® 5600, Ortho-Clinical Diagnostics, Rochester, NY) followed by PrCr calculation. Maternal and perinatal outcomes were abstracted from the hospital case notes. RESULTS: 160 women (81.9% outpatients) were screened at one/more antenatal visits providing a total of 233 samples for analysis. Ninety one (39.1%) samples had a random PrCr ⩾30 mg/mmol. This result was more common when urinary creatinine concentration was <3mM [64 (94.1%)] compared with ⩾3mM [27 (16.4%)], even among the 32 (20.0%) women with known normal pregnancy outcome [(13 (92.9%) vs. 0 (0%), respectively] (Panel A). In dilution studies using the same automated analyser, urinary protein (at a concentration of 0.12g/L) was 'detected' in deionised, double-distilled water. Method-specific re-analysis of data from two other published cohorts from our centre revealed substantially less inflation of PrCr values in dilute 24h urine samples tested using a pyrogallol red dye-binding based protein assay. When results were categorized according to urinary creatinine <3mM vs. ⩾3mM, PrCr ⩾30mg/mmol occurred in 12 (66.7%) vs. 99 (55.3%) respectively (p=0.35) in a 24-h urine completeness cohort and 92 (73.6%) vs. 313 (64.9%) respectively (p=0.07) in a cohort of women hospitalised for pre-eclampsia (Panel B). CONCLUSION: Random urinary PrCr results may be inflated in dilute urines because of overestimation of proteinuria in a common pyrocatechol violet dye-based method. This inflation was reduced but not eliminated when the dye used was pyrogallol red. Analytical methods do matter in the assessment of proteinuria in pregnant women. It may be prudent to consider the potential for falsely positive PrCr ⩾30mg/mmol in dilute urine, and to order PrCr testing on first voided (concentrated) urines whenever possible.

PP024. Random urine albumin: Creatinine ratio in high-risk pregnancy - Is it clinically useful?

INTRODUCTION: The albumin:creatinine ratio (ACr) is the newest of available methods of proteinuria assessment in pregnancy. Published cut-offs for detection of ⩾0.3g/d proteinuria vary from 2mg/mmol to 8mg/mmol. Up to 20% of women have an elevated ACr in pregnancy but normal outcome. In addition, it is our impression that the urine albumin component of the ACr is frequently below the detection limit of the assay. OBJECTIVES: To evaluate the frequency with which a measurable ACr can be obtained in a high-risk outpatient maternity population. METHODS: In this prospective cohort study, consecutive inpatients or outpatients (attending primarily morning high-risk maternity clinics) were evaluated at a tertiary care facility. Random midstream urine samples were obtained as part of normal clinical care. In the hospital laboratory, urinary albumin was measured using an immunoturbidimetric method, and urinary creatinine by an enzymatic method, both on an automated analyser (Vitros® 5,1 FS or Vitros® 5600, Ortho-Clinical Diagnostics, Rochester NY). ACr was calculated for samples with measurable urine albumin, and for samples with albumin below the assay range, ACr was calculated using the assay cut-off for albumin of 6.00mg/L. RESULTS: One hundred and sixty women (81.9% outpatients) were screened at one/more antenatal visits, providing a total of 233 urine samples for analysis. 68 (29.2%) urine samples were dilute (i.e., had urinary creatinine <3mM); only 13 (19.1%) of these had measurable urinary albumin for calculation of the ACr. Overall, 117/233 samples (50.2%) had measurable urine albumin that could be used to calculate the ACr. 76 (65.0%) had ACr >2mg/mmol and 34 (29.1%) had ACr >8mg/mmol. For the 116/233 (49.8%) samples with urine albumin below the assay detection limit, ACr was calculated using 6.00mg/L as the value for urine albumin. All of the 55 dilute samples had an ACr >2mg/mmol and 3 (2.6%) had an ACr >8mg/mmol. If dilute samples were excluded, none of the remaining 61 samples had an ACr value >2mg/mmol. CONCLUSION: Among a population of pregnant women attending primarily morning high-risk maternity clinics, urine is often dilute and urine albumin is often below the assay detection limit. This combination may result in uninterpretable ACr values if an ACr cut-off of 2mg/mmol is used as the decision limit for proteinuria ⩾0.3g/d. ACr may be best performed on first voided (concentrated) urine if ACr is used to assess proteinuria in pregnancy.

PP025. Urinary dipstick proteinuria testing - Does automated strip analysis offer an advantage over visual testing?

INTRODUCTION: The visual urinary test strip is widely accepted for screening for proteinuria in pregnancy, given the convenience of the method and its low cost. However, test strips are known to lack sensitivity and specificity. The 2010 NICE (National Institute for Health and Clinical Excellence) guidelines for management of pregnancy hypertension have recommended the use of an automated test strip reader to confirm proteinuria (http://nice.org.uk/CG107). Superior diagnostic test performance of an automated (vs. visual) method has been proposed based on reduced subjectivity. OBJECTIVES: To compare the diagnostic test properties of automated vs. visual read urine dipstick testing for detection of a random protein:creatinine ratio (PrCr) of ⩾30mg/mmol. METHODS: In this prospective cohort study, consecutive inpatients or outpatients (obstetric medicine and high-risk maternity clinics) were evaluated at a tertiary care facility. Random midstream urine samples (obtained as part of normal clinical care) were split into two aliquots. The first underwent a point-of-care testing for proteinuria using both visual (Multistix 10SG, Siemens Healthcare Diagnostics, Inc., Tarrytown NY) and automated (Chemstrip 10A, Roche Diagnostics, Laval QC) test strips, the latter read by an analyser (Urisys 1100®, Roche Diagnostics, Laval QC). The second aliquot was sent to the hospital laboratory for analysis of urinary protein using a pyrocatechol violet molybdate dye-binding method, and urinary creatinine using an enzymatic method, both on an automated analyser (Vitros® 5,1 FS or Vitros® 5600, Ortho-Clinical Diagnostics, Rochester NY); random PrCr ratios were calculated in the laboratory. Following exclusion of dilute samples with urinary creatinine concentration <3mM (given inflation of PrCr values in dilute urine by our method), diagnostic test properties were determined for visual and automated dipstick proteinuria testing (⩾1+) for detection of a random PrCr ⩾30mg/mmol. RESULTS: 160 women (81.9% outpatients) were screened at one/more antenatal visits, providing a total of 233 urine samples for analysis. Both visual and automated read urinary dipstick testing showed low sensitivity (56.0% and 53.9%, respectively). Positive likelihood ratios (LR+) and 95% CI were 15.0 [5.9,37.9] and 24.6 [7.6,79.6], respectively. Negative LR (LR-) were 0.46 [0.29,0.71] and 0.47 [0.31,0.72], respectively. CONCLUSION: Automated dipstick urinalysis is not more sensitive than visual read urinalysis for detection of proteinuria in a primarily outpatient setting in pregnancy. Both have excellent LR+ but only fair to poor LR- as previously recognised for visual dipstick testing. Performance of automated strip analysis testing may vary with the test strips and analyser used.