Dane A. De Silva

Magnesium sulphate for the management of preeclampsia and eclampsia in low and middle income countries: a systematic review of tested dosing regimens.

OBJECTIVE To review systematically the magnesium sulphate (MgSO4) dosing regimens tested in low and middle income countries (LMICs) for women with preeclampsia (prevention) and/or eclampsia (treatment). DATA SOURCES We searched Medline, EMBASE, IPA, CINAHL, CDSR, and CENTRAL databases for relevant English language publications. STUDY SELECTION Our search yielded 753 publications, of which 26 (10 randomized controlled trials and 16 observational studies) evaluated MgSO4 for preeclampsia and/or eclampsia in World Bank-classified LMICs. DATA EXTRACTION Independent, by two authors. DATA SYNTHESIS Twenty-five studies were conducted in hospital settings and one in the community. Rates of eclampsia were usually < 5% (median 3.0%, range 0.0% to 26.5%) even when MgSO4 was administered for eclampsia. When dosage varied from the standard Pritchard or Zuspan regimens, almost all (n = 22) reduced the dose or duration of treatment, most commonly because of concerns about maternal safety, cost, or resource availability. Four trials of a loading dose only (4 g IV + 10 g IM) versus loading plus maintenance dosing of 5 g/4 hr IM found no difference in eclampsia recurrence (RR 1.64; 95% CI 0.48 to 5.65, n = 396). One study documented less eclampsia recurrence associated with community administration of a MgSO4 loading dose before referral to a care facility versus treatment in a care facility (RR 0.23; 95% CI 0.11 to 0.49, n = 265). CONCLUSION Use of MgSO4 for eclampsia treatment and prevention has been well-studied in LMICs, but concern remains about potential toxicity. Further studies are needed to identify the minimum effective dosage of MgSO4 for management of preeclampsia and eclampsia and whether MgSO4 loading can be safely administered in the community.

Effect of Magnesium Sulphate on Fetal Heart Rate Parameters: A Systematic Review

OBJECTIVE To examine the potential effects of intravenous magnesium sulphate (MgSO4) administration on antepartum and intrapartum fetal heart rate (FHR) parameters measured by cardiotocography (CTG) or electronic fetal monitoring (EFM). METHODS We undertook a systematic review of randomized controlled trials, observational studies, and case series. Studies were reviewed independently by two reviewers and qualitatively analyzed with regard to CTG/EFM parameters (baseline FHR, variability and acceleration-deceleration patterns), types of participants, interventions offered, and outcomes reported. RESULTS Of 18 included studies, two were RCTs (72 women); 12 were prospective observational studies (269 women), 10 of which were of a pre- and post-intervention design; one was a prospective cohort study (36 women) and three were retrospective cohort studies (555 women). Lower baseline FHR was associated with MgSO4 exposure in seven of nine relevant studies. Decreased FHR variability was reported in nine of 12 relevant studies. Reductions in reactivity or acceleration pattern were seen in four of six relevant studies without an increase in decelerative patterns. All changes were small and not associated with adverse clinical outcomes. CONCLUSION Maternal administration of MgSO4 for eclampsia prophylaxis/treatment, tocolysis or fetal neuroprotection appears to have a small negative effect on FHR, variability, and accelerative pattern, but is not sufficient clinically to warrant medical intervention.

Random urine albumin:creatinine ratio in high-risk pregnancy - Is it clinically useful?

We evaluated the frequency of measurable albuminuria (⩾6.00mg/L) for albumin:creatinine ratios (ACr) among 160 consecutive women attending high-risk clinics. Of last urine samples before delivery, 76 had measurable albuminuria and 41/76 (53.9%) had ACr ⩾2mg/mmol of which 7.3% had normal pregnancy outcome. 84 samples had albuminuria <6.00mg/L and 43/84 (51.2%) had ACr ⩾2mg/mmol of which 25.6% had normal pregnancy outcome (p=0.025). Excluding 48/160 (30.0%) dilute samples (urinary creatinine <3mM), no samples with unmeasurable albuminuria had ACr ⩾2mg/mmol. In pregnancy, urine is often dilute and without measurable albuminuria, leading to a clinically relevant proportion of false positive results by ACr.

Prediction of adverse maternal outcomes from pre-eclampsia and other hypertensive disorders of pregnancy: A systematic review

BACKGROUND The hypertensive disorders of pregnancy are a leading cause of maternal and perinatal mortality and morbidity. The ability to predict these complications using simple tests could aid in management and improve outcomes. We aimed to systematically review studies that reported on potential predictors of adverse maternal outcomes among women with a hypertensive disorder of pregnancy. METHODS We searched MEDLINE, Embase and CINAHL (inception - December 2016) for studies of predictors of severe maternal complications among women with a hypertensive disorder of pregnancy. Studies were selected in a two-stage process by two independent reviewers, excluding those reporting only on adverse fetal outcomes. We extracted data on study and test(s) characteristics and outcomes. Accuracy of prediction was assessed using sensitivity, specificity, likelihood ratios and area under the receiver operating curve (AUROC). Strong evidence of prediction was taken to be a positive likelihood ratio >10 or a negative likelihood ratio <0.1, and for multivariable models, an AUROC ≥0.70. Bivariate random effects models were used to summarise performance when possible. RESULTS Of 32 studies included, 28 presented only model development and four examined external validation. Tests included symptoms and signs, laboratory tests and biomarkers. No single test was a strong independent predictor of outcome. The most promising prediction was with multivariable models, especially when oxygen saturation, or chest pain/dyspnea were included. CONCLUSION Future studies should investigate combinations of tests in multivariable models (rather than single predictors) to improve identification of women at high risk of adverse outcomes in the setting of the hypertensive disorders of pregnancy.

Urinary Dipstick Proteinuria Testing: Does Automated Strip Analysis Offer an Advantage Over Visual Testing?

OBJECTIVE To compare the diagnostic test properties of automated and visually read urine dipstick screening for detection of a random protein:creatinine ratio (PrCr) ≥ 30 mg/mmol. METHODS Urine samples were collected prospectively from 160 women attending high-risk maternity clinics at a tertiary care facility. Samples were divided into two aliquots; one aliquot was tested using two different urine test strips, one read visually and one by an automated reader. A second aliquot of the same urine was analyzed for urinary protein and creatinine. Performance of visual and automated dipstick results (proteinuria ≥ 1+) were compared for detection of PrCr ≥ 30 mg/mmol using non-dilute urine samples (urinary creatinine ≥ 3 mmol/L). RESULTS Both urine test strips showed low sensitivity (visual 56.0% and automated 53.8%). Positive likelihood ratios were 15.0 for visual dipstick testing (95% CI 5.9 to 37.9) and 24.6 for automated (95% CI 7.6 to 79.6). Negative likelihood ratios were 0.46 for visual dipstick testing (95% CI 0.29 to 0.71) and 0.47 for automated (95% CI 0.31 to 0.72). CONCLUSION Automated dipstick testing was not superior to visual testing for detection of proteinuria in pregnant women in a primarily outpatient setting. Sensitivity may depend on the test strips and/or analyzer used.

Magnesium Sulphate for Eclampsia and Fetal Neuroprotection: A Comparative Analysis of Protocols Across Canadian Tertiary Perinatal Centres.

BACKGROUND Magnesium sulphate (MgSO4) has been recommended for fetal neuroprotection to prevent cerebral palsy, with national societies adopting new guidelines for its use. A knowledge translation project to implement Canadian guidelines is ongoing. Discussion about MgSO4 for fetal neuroprotection could not occur distinct from MgSO4 for eclampsia prophylaxis and treatment. Thus, in order to explore standardization of MgSO4 use in Canada, we sought to compare local protocols for eclampsia and fetal neuroprotection across tertiary perinatal centres. METHODS Twenty-five Canadian tertiary perinatal centres were asked to submit their protocols for use of MgSO4 for eclampsia prophylaxis/treatment and fetal neuroprotection. Information abstracted included date of protocol, definitions of indications for treatment, details of MgSO4 administration, maternal and fetal monitoring, antidote for toxicity, and abnormal signs requiring physician attention. Descriptive analyses were used to compare site protocols with known definitions of preeclampsia. Data from the Canadian Perinatal Network (CPN) were used to verify what was done in clinical practice. RESULTS Twenty-two of the 25 centres submitted protocols for eclampsia prevention/treatment. Eleven of these provided a definition of preeclampsia that warranted treatment; five of the 22 advised treatment of severe preeclampsia only. Criteria for treatment and monitoring procedures varied across centres. Sixteen of the 22 sites with protocols had data from the CPN. Of 635 women with pre-eclampsia, 422 (66.5%) received MgSO4. Twenty of 25 centres provided protocols for fetal neuroprotection. Definitions of indications were consistent across sites, except for gestational age cut-off. CONCLUSION This study suggests that local protocols are often inconsistent with published evidence. While this may be related to local institutional practices, relevant processes must be put in place to maximize uniformity of practice and improve patient care.

Determinants of magnesium sulphate use in women hospitalized at <29 weeks with severe or non-severe pre-eclampsia

Objective Magnesium sulphate is recommended by international guidelines to prevent eclampsia among women with pre-eclampsia, especially when it is severe, but fewer than 70% of such women receive magnesium sulphate. We aimed to identify variables that prompt Canadian physicians to administer magnesium sulphate to women with pre-eclampsia. Methods Data were used from the Canadian Perinatal Network (2005–11) of women hospitalized at <29 weeks’ who were thought to be at high risk of delivery due to pre-eclampsia (using broad Canadian definition). Unadjusted analyses of relative risks were estimated directly and population attributable risk percent (PAR%) calculated to identify variables associated with magnesium sulphate use. A multivariable model was created and a generalized estimating equation was used to estimate the adjusted RR that explained magnesium sulphate use in pre-eclampsia. The adjusted PAR% was estimated by bootstrapping. Results Of 631 women with pre-eclampsia, 174 (30.1%) had severe pre-eclampsia, of whom 131 (75.3%) received magnesium sulphate. 457 (69.9%) women had non-severe pre-eclamspia, of whom 291 (63.7%) received magnesium sulphate. Use of magnesium sulphate among women with pre-eclampsia could be attributed to the following clinical factors (PAR%): delivery for ‘adverse conditions’ (48.7%), severe hypertension (21.9%), receipt of antenatal corticosteroids (20.0%), maternal transport prior to delivery (9.9%), heavy proteinuria (7.8%), and interventionist care (3.4%). Conclusions Clinicians are more likely to administer magnesium sulphate for eclampsia prophylaxis in the presence of more severe maternal clinical features, in addition to concomitant antenatal corticosteroid administration, and shorter admission to delivery periods related to transport from another institution or plans for interventionist care.

Fetal, Infant and Maternal Outcomes among Women with Prolapsed Membranes Admitted before 29 Weeks Gestation.

Background Few studies have examined fetal, infant and maternal mortality and morbidity among pregnant women at very early gestation with an open cervix and prolapsed membranes. We carried out a study describing the outcomes of women hospitalized with prolapsed membranes at 22–28 weeks’ gestation. Methods We prospectively recruited women with singleton pregnancies admitted at 22–28 weeks’ gestation to tertiary hospitals of the Canadian Perinatal Network between 2005 and 2009. Time-to-delivery, perinatal death, neonatal intensive care unit (NICU) admission, severe neonatal morbidity and severe maternal morbidity were compared between women admitted at 22–25 vs. 26–28 weeks gestation. Logistic regression was used to estimate adjusted odds ratios (AOR) and 95% confidence intervals. Results 129 women at 22–25 weeks gestation and 65 women at 26–28 weeks gestation were admitted to hospital and the median time-to-delivery was 4 days in both groups. Stillbirth rates were 12.4% vs 4.6% among women admitted at earlier vs later gestation (AOR 2.8, 95% CI 0.5–14.8), while perinatal death rates were 38.0% vs 6.1% (AOR 14.1, 95% CI 3.5–59.0), respectively. There were no significant differences in NICU admission and severe morbidity among live-born infants; 89.4% and 82.3% died or were admitted to NICU, (P value 0.18), and 53.9% vs 44.0% of NICU infants had severe neonatal morbidity (P value 0.28). Antibiotics, tocolysis and cerclage did not have a significant effect on perinatal death. Maternal death or severe maternal morbidity occurred in 8.5% and 6.2% of women admitted at 22–25 vs 26–28 weeks (AOR 1.2, 95% CI 0.4–4.2). Conclusion Perinatal mortality among women with prolapsed membranes at very early gestation is high, although significantly lower among those admitted at a relatively later gestational age. Rates of adverse maternal outcomes are also high. This information can be used to counsel women with prolapsed membranes at 22 to 28 weeks gestation.