Cost effectiveness of the sFlt1/PlGF ratio test as an adjunct to the current practice of evaluating suspected preeclampsia in the United States.

OBJECTIVE: Preeclampsia is a major obstetric disorder that can lead to severe maternal, fetal and infant outcomes. In women with suspected preeclampsia, measurement of the soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) ratio has been shown to have a high negative predictive value (>97%). Our aim was to estimate the value to the US healthcare system of adopting this test into clinical practice. STUDY DESIGN: An economic model was developed for the evaluation of suspected preeclampsia from a US payer perspective using data from a US observational study of 459 women evaluated between 23 and 34.6 weeks. Test results were not available to clinicians. The model compares two strategies for managing suspected preeclampsia: standard care versus a biomarker-informed pathway utilizing the sFlt1/PlGF ratio. RESULTS: Utilization of the sFlt1/PlGF ratio test reduced the number of women admitted for suspected preeclampsia by 34-49%. Despite fewer admissions, a higher proportion of women admitted to hospital subsequently developed preeclampsia, and the proportion of women not admitted who would subsequently develop preeclampsia remained low (3.2%-6.7%). Cost savings arising from a reduction in admissions are estimated to be $1050 in the base case; varying the hospitalization cost ±25% would lead to savings in the range $771 to $1330 per patient at 2020 prices. CONCLUSION: Adopting the sFlt1/PlGF ratio test as an adjunct to clinical criteria improves the assessment of risk in women presenting with suspicion of preeclampsia and has the potential to safely reduce unnecessary admissions and save costs.

Novel mutation in CCBE 1 as a cause of recurrent hydrops fetalis from Hennekam lymphangiectasia-lymphedema syndrome-1.

Whole exome sequencing (WES) was used to determine the etiology of recurrent hydrops fetalis in this case of Hennekam lymphangiectasia-lymphedema syndrome-1. WES is a useful approach for diagnosing rare single-gene conditions with nonspecific phenotypes and should be considered early in the diagnostic process of investigating fetal abnormalities.

Abnormal uterine artery Doppler velocimetry predicts adverse outcomes in patients with abnormal analytes.

OBJECTIVES: Our aim was to determine if uterine artery (UtA) Doppler studies would risk-stratify women with abnormal serum analytes on prenatal genetic screening into those at baseline and increased risk for preeclampsia and small-for-gestational age (SGA). STUDY DESIGN: This retrospective cohort study examined outcomes of patients with ⩾one abnormal analyte (PAPP-A<0.3, hCG>3.0, AFP>2.5, inhibin>2.0, or unconjugated estriol<0.3MoM). At approximately 24weeks, we assessed UtA pulsatility index (PI). MAIN OUTCOME MEASURES: Preeclampsia, preterm preeclampsia, SGA (birthweight (BW) <10%) and intrauterine growth restriction (IUGR) (BW<3%). RESULTS: We identified 132 patients with ⩾one abnormal analyte, UtA Doppler screening, and delivery outcomes. Twenty-four (18%) had an elevated UtA PI (PI>1.6); preeclampsia occurred in 16 (12%) and 26 (20%) delivered a SGA neonate. Abnormal UtA Doppler PI increased the likelihood of a composite outcome of preeclampsia or SGA from 27% to 71% (LR 6.48 (2.93, 14.30)); a negative UtA Doppler PI reduced the likelihood to 18% (LR 0.57 (0.42, 0.78)). Abnormal UtA Doppler PI increased the likelihood of a more severe composite outcome of preterm preeclampsia or IUGR from 11% to 39% (LR 5.49 (3.03, 9.97)); a negative UtA Doppler study reduced the likelihood to 4% (LR 0.35 (0.16, 0.80)). CONCLUSIONS: In patients with abnormal serum analytes, abnormal UtA Doppler PI is significantly associated with preeclampsia or SGA and improves the prediction of these adverse outcomes by 9-15-fold. Providers can incorporate UtA Doppler PI into an abbreviated surveillance regimen; they can be reassured that a normal study markedly decreases the risk of a severe early adverse outcome.

The role of natural antibodies in atherogenesis.

Atherosclerosis is now widely recognized as a chronic inflammatory disease that involves innate and adaptive immune responses. Both cellular and humoral components of the immune system have been implicated in atherogenesis. Natural antibodies can be considered humoral factors of innate immunity, and their functional role in health and disease has been reexamined in recent years. Natural antibodies exhibit a remarkably conserved repertoire that includes a broad specificity for self-antigens. For this reason, they are believed to be a product of natural selection and have been suggested to play an important role in "housekeeping" functions. Recent evidence has revealed that oxidation-specific epitopes are important and maybe immunodominant targets of natural antibodies, suggesting an important function for these antibodies in the host response to consequences of oxidative stress, for example, to the oxidative events that occur when cells undergo apoptosis. This review will focus on these recent findings and discuss the emerging evidence for an important role of natural antibodies in atherogenesis.