PurposeA pilot systematic evidence review to establish methodology utility in rare genetic diseases, support clinical recommendations, and identify important knowledge gaps.MethodsBroad-based published/gray-literature searches through December 2015 for studies of males with confirmed mucopolysaccharidosis type II (any age, phenotype, genotype, family history) treated with enzyme replacement therapy or hematopoietic stem cell transplantation. Preset inclusion criteria employed for abstract and full document selection, and standardized methods for data extraction and assessment of quality and strength of evidence.ResultsTwelve outcomes reported included benefits of urinary glycosaminoglycan and liver/spleen volume reductions and harms of immunoglobulin G/neutralizing antibody development (moderate strength of evidence). Less clear were benefits of improved 6-minute walk tests, height, early treatment, and harms of other adverse reactions (low strength of evidence). Benefits and harms of other outcomes were unclear (insufficient strength of evidence). Current benefits and harms of hematopoietic stem cell transplantation are unclear, based on dated, low-quality studies. A critical knowledge gap is long-term outcomes. Consensus on selection of critical outcomes and measures is needed to definitively evaluate treatment safety and effectiveness.ConclusionMinor methodology modifications and a focus on critical evidence can reduce review time and resources. Summarized evidence was sufficient to support guidance development and highlight important knowledge gaps.

ObjectiveAngiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE.Material and MethodsWe measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) levels in women with PE (n=35) compared to controls with no hypertensive disorders (NHD) (n=43) among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in Haiti. We divided the preeclamptic women into two groups, early onset (≤ 34 weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight <2500 grams, or fetal/neonatal death) in women with PE subgroups as compared to NHD groups separated by week of admission. Data are presented as median (25th-75th centile), n (%), and proportions.ResultsAmong patients with PE, most (24/35) were admitted at term. Adverse outcome rates in PE were much higher among the early onset group compared to the late onset group (100.0% vs. 54.2%, P=0.007). Plasma angiogenic factors were dramatically altered in both subtypes of PE. Angiogenic factors also correlated with adverse outcomes in both subtypes of PE. The median sFlt1/PlGF ratios for subjects with early onset PE with any adverse outcome vs. NHD <=34 weeks with no adverse outcome were 703.1 (146.6, 1614.9) and 9.6 (3.5, 58.6); P<0.001). Among late onset group the median sFlt1/PlGF ratio for women with any adverse outcome was 130.7 (56.1, 242.6) versus 22.4 (10.2, 58.7; P=0.005) in NHD >34 weeks with no adverse outcome.ConclusionPE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation.

Lower median birth weight among euthyroid women with high FT4 is not associated with adverse pregnancy outcomes. Further investigation is indicated to determine how the variations in thyroid hormone concentration influence birth weight.

IntroductionPreeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome.MethodsWomen evaluated for suspected PE at a tertiary hospital (2009–2012) had pregnancy outcomes categorized as ‘referent’ or ‘severe’, based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were considered ‘unclassified’. Soluble fms-like tyrosine kinase (sFlt1) and placental growth factor (PlGF) were subjected to bivariate discriminant modeling, allowing patient-specific risks to be assigned for severe outcomes.ResultsThree hundred twenty-eight singleton pregnancies presented at ≤34.0 weeks' gestation. sFlt1 and PlGF levels were adjusted for gestational age. Risks above 5 : 1 (10-fold over background) occurred in 77% of severe (95% CI 66 to 87%) and 0.7% of referent (95% CI <0.1 to 3.8%) outcomes. Positive likelihood ratios for the modeling and validation datasets were 19 (95% CI 6.2–58) and 15 (95% CI 5.8–40) fold, respectively.ConclusionsThis validated model assigns patient-specific risks of any severe outcome among women attending PE triage. In practice, women with high risks would receive close surveillance with the added potential for reducing unnecessary preterm deliveries among remaining women. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.

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