Objective  To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design  Systematic review and meta-analysis of cohort studies. Data sources  PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies  Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction  Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results  There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions  There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

https://www.bmj.com/content/bmj/353/bmj.i1753.full.pdf

Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

BackgroundOral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. MethodsWe performed a multicenter, randomized, double-blind, adaptive, phase 2–3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. ResultsOf 460 infants who underwent randomization, 456 received treat...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1404710

A Randomized, Controlled Trial of Oral Propranolol in Infantile Hemangioma

Earlier studies have reported the effectiveness of aspirin in preventing preeclampsia in women considered to be at moderate to high risk of developing this disorder. This current study was a meta-analysis of cohort studies examining risk factors for preeclampsia with the goal of estimating early in pregnancy (r16wk gestation) a woman’s risk of developing preeclampsia based on the presence of absence of various risk factors. Three practical estimates were generated: the absolute risk of developing preeclampsia in the presence or absence of a given risk factor; the relative risk in the presence or absence of a given risk factor, and the population attributable fraction (PAF) for preeclampsia in relation to each risk factor. On the basis of their analysis, the authors aimed to provide a list of risk factors that could be used to identify those women at high risk for developing preeclampsia. The PubMed and Embase databases were used to identify articles studying the association between preeclampsia and one or more risk factors in a previous pregnancy or in the current pregnancy. They specifically evaluated practical risk factors that were patient specific, easily remembered by the patient or found in previous medical records, and could be determined in the first trimester by the physician. Risk factors studied included: previous history of preeclampsia, placental abruption, intrauterine growth restriction (IUGR), or stillbirth; nulliparity; advanced maternal age; chronic hypertension; preexisting diabetes; high body mass index (BMI); kidney disease; lupus; antiphospholipid (aPL) antibody syndrome; multiple gestation, and assisted reproduction. The pooled preeclampsia event rate in the exposed and unexposed groups was calculated for each risk factor and pooled relative risk was calculated. Subsequently the PAF for each risk factor was calculated using the pooled relative risks. A total of 25,356,688 pregnancies from 92 studies were included in the meta-analysis. The mean pooled event rate for preeclampsia among all risk factors was 2.7% (SD=0.93%) for unexposed groups, while the mean pooled event rate for all exposed groups was 7.3% (SD= 4.6%). The highest pooled rate of preeclampsia was observed in women with aPL antibody syndrome [17.3%, 95% confidence Interval (CI), 6.8%-31.4%] while a previous history of preeclampsia had the highest pooled relative risk (8.4; 95% CI, 7.1-9.9). Chronic hypertension was the risk factor with the second highest pooled rate (16.0%; 95% CI, 12.6%-19.7%) and pooled relative risk (5.1%; 95% CI, 4.0%-6.5%) for preeclampsia. Preexisting diabetes, BMI >30, and pregnancy achieved by assisted reproduction were other risk factors with notably high pooled rates and relative risks. The presence of all but one of the risk factors evaluated (IUGR) was determined to significantly increase the risk of developing preeclampsia. Although aPL antibody syndrome was associated with the highest rate of preeclampsia it is a relatively uncommon disorder and therefore had one of the lowest PAFs for preeclampsia (0.18%; 95% CI, 0.08%-0.33%), whereas nulliparity, prepregnancy BMI >25, and prior preeclampsia were found to have the highest PAFs (32.3%; 95% CI, 27.4%-37.0%; 23.8%; 95% CI, 22.0%-25.6%; and 22.8%; 95% CI, 19.6%-26.3%, respectively). On the basis of their meta-analysis, the investigators identified multiple risk factors that could be used to identify early in pregnancy women who are at “high risk” of developing preeclampsia. They suggest this information could be used to develop a clinical prediction model that would be useful in determining those women who would benefit from aspirin prophylaxis during their pregnancies.

/pdf/clinical-risk-factors-for-preeclampsia-determined-in-early-seyf5wieqa.pdf

Clinical Risk Factors for Preeclampsia Determined in Early Pregnancy: Systematic Review and Meta-Analysis of Large Cohort Studies

Infantile hemangiomas (IHs) occur in as many as 5% of infants, making them the most common benign tumor of infancy. Most IHs are small, innocuous, self-resolving, and require no treatment. However, because of their size or location, a significant minority of IHs are potentially problematic. These include IHs that may cause permanent scarring and disfigurement (eg, facial IHs), hepatic or airway IHs, and IHs with the potential for functional impairment (eg, periorbital IHs), ulceration (that may cause pain or scarring), and associated underlying abnormalities (eg, intracranial and aortic arch vascular abnormalities accompanying a large facial IH). This clinical practice guideline for the management of IHs emphasizes several key concepts. It defines those IHs that are potentially higher risk and should prompt concern, and emphasizes increased vigilance, consideration of active treatment and, when appropriate, specialty consultation. It discusses the specific growth characteristics of IHs, that is, that the most rapid and significant growth occurs between 1 and 3 months of age and that growth is completed by 5 months of age in most cases. Because many IHs leave behind permanent skin changes, there is a window of opportunity to treat higher-risk IHs and optimize outcomes. Early intervention and/or referral (ideally by 1 month of age) is recommended for infants who have potentially problematic IHs. When systemic treatment is indicated, propranolol is the drug of choice at a dose of 2 to 3 mg/kg per day. Treatment typically is continued for at least 6 months and often is maintained until 12 months of age (occasionally longer). Topical timolol may be used to treat select small, thin, superficial IHs. Surgery and/or laser treatment are most useful for the treatment of residual skin changes after involution and, less commonly, may be considered earlier to treat some IHs.

https://pediatrics.aappublications.org/content/pediatrics/early/2018/12/20/peds.2018-3475.full.pdf

Clinical Practice Guideline for the Management of Infantile Hemangiomas.

With a prevalence of 2.6–4.5 %, infantile haemangiomas (IH) represent the most common tumour of infancy. While the majority of IH does not require therapy and regresses spontaneously, about 10 % of IH exhibit complications such as obstruction, ulceration or disfigurement. With the advent of oral propranolol, many conventional treatment options have become obsolete. This paper summarizes current recommendations for management of complicated IH. These recommendations have been written by an expert group after a consensus process including bibliographic review, several drafts of synthesis, meetings with quantitative voting system and redaction of an approved final manuscript.

Treatment of infantile haemangiomas: recommendations of a European expert group.

Background The aetiology and exact incidence of infantile haemangiomas (IHs) are unknown. Prior studies have noted immunohistochemical and biological characteristics shared by IHs and placental tissue. Objectives We investigated the possible association between placental anomalies and the development of IHs, as well as the demographic characteristics and other risk factors for IHs. Patients and methods Pregnant women (n = 578) were prospectively enrolled and their offspring followed for 9 months. Placental evaluations were performed and demographic data collected on all mother-infant pairs. Results We evaluated 594 infants: 34 haemangiomas [either IH or congenital (CH)] were identified in 29 infants, yielding an incidence of 4·5% for IH (27 infants) and 0·3% for CH (two infants). Placental anomalies were noted in almost 35% of haemangioma-related pregnancies, approximately twice the incidence noted in pregnancies with unaffected infants (P = 0·025). Other risk factors for IH included prematurity (P = 0·016) and low birth weight (P = 0·028). All IHs were present by 3 months of age, and cessation of growth had occurred in all by 9 months of age. Most occurred on the trunk. Of note, 20% of identified IHs were abortive or telangiectatic in nature, small focal lesions that did not proliferate beyond 3 months of age. Only one IH required intervention. Conclusions This is the first prospective American study to document the incidence of IHs in infants followed from birth to early infancy. The association with placental anomalies was statistically significant. The overall incidence mirrors prior estimates, but the need for treatment was lower than previously reported.

/pdf/prospective-study-of-infantile-haemangiomas-incidence-44906uqg71.pdf

Prospective Study of Infantile Haemangiomas: Incidence, Clinical Characteristics and Association With Placental Anomalies

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Prospective Study of Infantile Haemangiomas: Incidence, Clinical Characteristics and Association With Placental Anomalies