Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Risk factors and prognostic models for preterm birth

Tussen 2000 en 2007 vond een significante afname plaats van zowel het risico op vroeggeboorte als het risico op perinatale sterfte. Dit toont Jelle Schaaf aan in zijn onderzoek. Er blijkt wel verschil te zijn tussen etnische groepen. Zo blijken donkere vrouwen van Afrikaanse afkomst een hoger risico op vroeggeboorte te hebben dan blanke vrouwen, maar weer een lager risico op neonatale complicaties. Mediterrane vrouwen hebben zowel een verlaagd risico op vroeggeboorte als een verlaagd risico op neonatale complicaties. Vergeleken met Europese blanke vrouwen hebben de overige etnische groepen een verlaagd risico op neonatale complicaties na vroeggeboorte. Bij een identieke zwangerschapsduur lijken pasgeborenen van Afrikaanse, Zuid-Aziatische, mediterrane en Oost-Aziatische moeders beter bestand te zijn tegen de schadelijke impact van vroeggeboorte. Een eerdere vroeggeboorte vormt een van de belangrijkste risicofactoren voor een volgende vroeggeboorte

Development of a prognostic model for predicting spontaneous singleton preterm birth

Objective: To develop and validate a prognostic model for prediction of spontaneous preterm birth. Study design: Prospective cohort study using data of the nationwide perinatal registry in The Netherlands. We studied 1,524,058 singleton pregnancies between 1999 and 2007. We developed a multiple logistic regression model to estimate the risk of spontaneous preterm birth based on maternal and pregnancy characteristics. We used bootstrapping techniques to internally validate our model. Discrimination (AUC), accuracy (Brier score) and calibration (calibration graphs and Hosmer-Lemeshow C-statistic) were used to assess the model's predictive performance. Our primary outcome measure was spontaneous preterm birth at <37 completed weeks. Results: Spontaneous preterm birth occurred in 57,796 (3.8%) pregnancies. The final model included 13 variables for predicting preterm birth. The predicted probabilities ranged from 0.01 to 0.71 (IQR 0.02-0.04). The model had an area under the receiver operator characteristic curve (AUC) of 0.63(95% Cl 0.63-0.63), the Brier score was 0.04 (95% Cl 0.04-0.04) and the Hosmer Lemeshow C-statistic was significant (p <0.0001). The calibration graph showed overprediction at higher values of predicted probability. The positive predictive value was 26% (95% Cl 20-33%) for the 0.4 probability cut-off point. Conclusions: The model's discrimination was fair and it had modest calibration. Previous preterm birth, drug abuse and vaginal bleeding in the first half of pregnancy were the most important predictors for spontaneous preterm birth. Although not applicable in clinical practice yet, this model is a next step towards early prediction of spontaneous preterm birth that enables caregivers to start preventive therapy in women at higher risk. (C) 2012 Elsevier Ireland Ltd. All rights reserve

Trends in preterm birth in singleton deliveries in a Hong Kong population

To examine trends in preterm birth and its relationship with perinatal mortality in Hong Kong. In a retrospective cohort study, data were reviewed from singletons delivered between 1995 and 2011 at a university teaching hospital. Trends in preterm birth (between 24 and 36 weeks of pregnancy), perinatal mortality, and subtypes of preterm birth (spontaneous, iatrogenic, and following preterm premature rupture of membranes [PPROM]) were examined via linear regression. There were 103 364 singleton deliveries, of which 6722 (6.5%) occurred preterm, including 1835 (1.8%) early preterm births (24-33 weeks) and 4887 (4.7%) late preterm births (34-36 weeks). Frequency of preterm birth remained fairly consistent over the study period, but that of spontaneous preterm birth decreased by 25% (β=-0.83; P <0.001), from 4.5% to 3.8%. Frequency of preterm birth following PPROM increased by 135% (β=0.82; P <0.001), from 0.7% to 1.7%. The perinatal mortality rate decreased from 56.7 to 37.0 deaths per 1000 deliveries before 37 weeks (β=-0.16; P=0.54). Early preterm birth contributed to 16.0% of all deaths. Although the overall rate of preterm birth in Hong Kong has remained constant, the frequencies of its subtypes have changed. Overall perinatal mortality is gradually decreasing, but early preterm birth remains a major contributo

Recurrence risk of low Apgar score among term singletons: a population-based cohort study

To examine the risk of recurrence of low Apgar score in a subsequent term singleton pregnancy. Population-based cohort study. The Netherlands. A total of 190,725 women with two subsequent singleton term live births between 1999 and 2007. We calculated the recurrence risk of low Apgar score after adjustment for possible confounders. Women with an elective cesarean delivery, fetus in breech presentation or a fetus with congenital anomalies were excluded. Results were reported separately for women with a vaginal delivery or a cesarean delivery at first pregnancy. Prevalence of birth asphyxia, a 5-min Apgar score <7. The risk for an Apgar score of <7 in the first pregnancy was 0.99% and overall halved in the subsequent pregnancies (0.50%). For those with asphyxia in the first pregnancy, the risk of recurrence of a low Apgar score in the subsequent pregnancy was 1.1% (odds ratio 2.1, 95% confidence interval 1.4-3.3). This recurrence risk was present in women with a previous vaginal delivery (odds ratio 2.1, 95% confidence interval 1.2-3.5) and in women with a previous cesarean delivery (odds ratio 3.8, 95% confidence interval 1.7-8.5). Among women with a small-for-gestational-age infant in the subsequent pregnancy and a previous vaginal delivery, the recurrence risk was 4.8% (adjusted odds ratio 5.8, 95% confidence interval 2.0-16.5). Women with birth asphyxia of the first born have twice the risk of renewed asphyxia at the next birth compared to women without birth asphyxia of the first born. This should be incorporated in the risk assessment of pregnant wome

Ethnic and racial disparities in the risk of preterm birth: a systematic review and meta-analysis

The aim of this study is to present a systematic review of available literature on the effect of maternal ethnicity (Africans/blacks, Asians, Hispanics, others) on the risk of preterm birth (PTB). Studies investigating ethnicity (or race) as a risk factor for PTB were included if performing adjustments for confounders. A meta-analysis was performed, and data were synthesized using a random effects model. Forty-five studies met the inclusion criteria. Black ethnicity was associated with an increased risk of PTB when compared with whites (range of adjusted odds ratios [ORs] 0.6 to 2.8, pooled OR 2.0; 95% confidence interval [CI] 1.8 to 2.2). For Asian ethnicity, there was no significant association (range of adjusted ORs 0.6 to 2.3). For Hispanic ethnicity, there also was no significant association (range of adjusted ORs 0.7 to 1.5). Ethnic disparities in the risk of PTB were clearly pronounced among black women. Future research should focus on preventative strategies for ethnic groups at high risk for PTB. Information on ethnic disparities in risk of PTB-related neonatal morbidity and mortality is lacking and is also a topic of interest for future researc

Recurrence risk of preterm birth in subsequent singleton pregnancy after preterm twin delivery

OBJECTIVE: The purpose of this study was to investigate the recurrence risk of preterm birth ( <37 weeks' gestation) in a subsequent singleton pregnancy after a previous nulliparous preterm twin delivery. STUDY DESIGN: We included 1957 women who delivered a twin gestation and a subsequent singleton pregnancy from the Netherlands Perinatal Registry. We compared the outcome of subsequent singleton pregnancy of women with a history of preterm delivery to the pregnancy outcome of women with a history of term twin delivery. RESULTS: Preterm birth in the twin pregnancy occurred in 1075 women (55%) vs 882 women (45%) who delivered at term. The risk of subsequent spontaneous singleton preterm birth was significantly higher after preterm twin delivery (5.2% vs 0.8%; odds ratio, 6.9; 95% confidence interval, 3.1-15.2). CONCLUSION: Women who deliver a twin pregnancy are at greater risk for delivering prematurely in a subsequent singleton pregnanc

Recurrence of small-for-gestational-age pregnancy: analysis of first and subsequent singleton pregnancies in The Netherlands

OBJECTIVE: Small-for-gestational-age (SGA) neonates are at increased risk of adverse pregnancy outcome. Our objective was to study the recurrence rate of SGA in subsequent pregnancies. STUDY DESIGN: A prospective national cohort study of all women with a structurally normal first and subsequent singleton pregnancy from 1999-2007. SGA was defined as birthweight 32 weeks' gestation. CONCLUSION: Women with SGA in their first pregnancy have a strongly increased risk of SGA in the subsequent pregnancy and first pregnancy SGA delivers a significant contribution to the total number of second pregnancy SGA case

Antenatal prediction of neonatal mortality in very premature infants

To develop a prognostic model for antenatal prediction of neonatal mortality in infants threatening to be born very preterm ( <32 weeks). Nationwide cohort study in The Netherlands between 1999 and 2007. We studied 8500 singletons born between 25(+0) and 31(+6) weeks of gestation where fetus was alive at birth without congenital anomalies. We developed a multiple logistic regression model to estimate the risk of neonatal mortality within 28 days after birth, based on characteristics that are known before birth. We used bootstrapping techniques for internal validation. Discrimination (AUC), accuracy (Brier score) and calibration (graph, c-statistics) were used to assess the model's predictive performance. Neonatal mortality occurred in 766 (90 per 1000) live births. The final model consisted of seven variables. Predictors were low gestational age, no antental corticosteroids, male gender, maternal age ≥35 years, Caucasian ethnicity, non-cephalic presentation and non-3rd level of hospital. The predicted probabilities ranged from 0.003 to 0.697 (IQR 0.02-0.11). The model had an AUC of 0.83, the Brier score was 0.065. The calibration graph showed good calibration, and the test for the Hosmer Lemeshow c-statistic showed no lack of fit (p=0.43). Neonatal mortality can be predicted for very preterm births based on the antenatal factors gestational age, antental corticosteroids, fetal gender, maternal age, ethnicity, presentation and level of hospital. This model can be helpful in antenatal counselin