Rohan D’Souza

Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis

Aims To review maternal and foetal outcomes in women with mechanical heart valves (MHVs) treated with vitamin-K antagonists (VKAs), first-trimester heparin followed by VKAs (sequential treatment), low molecular weight heparin (LMWH) and unfractionated heparin (UFH) during pregnancy, in order to inform practice. Methods and results Medline, Embase and Central were searched from inception until February 2016. Two reviewers independently screened 1786 titles, reviewed 110 full-texts and extracted data and assessed risk-of-bias from 46 articles. Pooled incidence (95% confidence intervals) was calculated for maternal and foetal outcomes. Included studies had a moderate or high risk-of-bias. With VKAs, sequential treatment and LMWH, maternal mortality occurred in 0.9% (0.4–1.4), 2.0% (0.8–3.1) and 2.9% (0.2–5.7), thromboembolic complications in 2.7% (1.4–4.0), 5.8% (3.8–7.7) and 8.7% (3.9–13.4), livebirths in 64.5% (48.8–80.2), 79.9% (74.3–85.6) and 92.0% (86.1–98.0) and anticoagulant-related foetal/neonatal adverse events (embryopathy or foetopathy) in 2.0% (0.3–3.7), 1.4% (0.3–2.5) and 0%, respectively. When UFH is used throughout pregnancy, 11.2% (2.8–19.6) suffered thromboembolic complications. Foetal loss and adverse events occurred with first-trimester warfarin doses ⩽ 5 mg/day, although there were more livebirths [83.6% (75.8–91.4) vs. 43.9% (32.8–55.0)] and fewer foetal anomalies [2.3% (0.7–4.0) vs. 12.4% (3.3–21.6)] with lower doses than with warfarin > 5 mg/day. Conclusions VKAs are associated with fewest maternal complications but also with fewest livebirths. Sequential treatment does not eliminate anticoagulant-related foetal/neonatal adverse events. LMWH is associated with the highest number of livebirths. The safety of UFH throughout pregnancy and first-trimester warfarin  ⩽ 5 mg/day remains unconfirmed.

The Collagenopathies: Review of Clinical Phenotypes and Molecular Correlations

Genetic defects of collagen formation (the collagenopathies) affect almost every organ system and tissue in the body. They can be grouped by clinical phenotype, which usually correlates with the tissue distribution of the affected collagen subtype. Many of these conditions present in childhood; however, milder phenotypes presenting in adulthood are increasingly recognized. Many are difficult to differentiate clinically. Precise diagnosis by means of genetic testing assists in providing prognosis information, family counseling, and individualized treatment. This review provides an overview of the current range of clinical presentations associated with collagen defects, and the molecular mechanisms important to understanding how the results of genetic testing affect medical care.

Maternal blood endotoxin activity in pregnancies complicated by preterm premature rupture of membranes

Abstract Objective: To compare maternal blood endotoxin activity (EA) in women with preterm premature rupture of membranes (PPROM) with gestational age (GA) matched controls; to evaluate serial EA till birth in PPROM and its correlation with latency to delivery. Methods: We followed singleton preterm pregnancies from admission with PPROM until birth. Uncomplicated, GA-matched pregnancies served as controls. Demographics, birth and neonatal outcomes were collected. EA (EAA™) was assessed serially in PPROM and at study entry in controls. EA was compared using Mann Whitney and Wilcoxon tests, p value <.05 was considered significant. Results: We recruited 20 cases of PPROM and 20 controls. Demographics were similar between groups. Mean GA of PPROM was 29.0 ± 2.2 weeks and median latency was 7.5 (IQR 14.1) weeks. Median EA at admission following PPROM was significantly elevated over controls (0.43 (0.18) versus 0.36 (0.2); p < .02). Overall there was no difference in median EA at admission and in labor (0.43 (0.18) versus 0.33 (0.21); p = .2) following PPROM. However, on comparing cases with latency to delivery ≤7 days (n = 10) versus >7 days (n = 10), there was a significant drop in EA in the latter group (0.44 (0.2) versus 0.34 (0.2); p < .004). Conclusions: EA in PPROM represents a promising biomarker in predicting the clinical evolution of preterm birth.

Measurement properties of comorbidity indices in maternal health research: a systematic review

BackgroundMaternal critical illness occurs in 1.2 to 4.7 of every 1000 live births in the United States and approximately 1 in 100 women who become critically ill will die. Patient characteristics and comorbid conditions are commonly summarized as an index or score for the purpose of predicting the likelihood of dying; however, most such indices have arisen from non-pregnant patient populations. We sought to systematically review comorbidity indices used in health administrative datasets of pregnant women, in order to critically appraise their measurement properties and recommend optimal tools for clinicians and maternal health researchers.MethodsWe conducted a systematic search of MEDLINE and EMBASE to identify studies published from 1946 and 1947, respectively, to May 2017 that describe predictive validity of comorbidity indices using health administrative datasets in the field of maternal health research. We applied a methodological PubMed search filter to identify all studies of measurement properties for each index.ResultsOur initial search retrieved 8944 citations. The full text of 61 articles were identified and assessed for final eligibility. Finally, two eligible articles, describing three comorbidity indices appropriate for health administrative data remained: The Maternal comorbidity index, the Charlson comorbidity index and the Elixhauser Comorbidity Index. These studies of identified indices had a low risk of bias. The lack of an established consensus-building methodology in generating each index resulted in marginal sensibility for all indices. Only the Maternal Comorbidity Index was derived and validated specifically from a cohort of pregnant and postpartum women, using an administrative dataset, and had an associated c-statistic of 0.675 (95% Confidence Interval 0.647–0.666) in predicting mortality.ConclusionsOnly the Maternal Comorbidity Index directly evaluated measurement properties relevant to pregnant women in health administrative datasets; however, it has only modest predictive ability for mortality among development and validation studies. Further research to investigate the feasibility of applying this index in clinical research, and its reliability across a variety of health administrative datasets would be incrementally helpful. Evolution of this and other tools for risk prediction and risk adjustment in pregnant and post-partum patients is an important area for ongoing study.