Effects of emerging SARS-CoV-2 on total and cause-specific maternal mortality: A natural experiment in Chile during the peak of the outbreak, 2020-2021.

This study estimated the effects of the COVID-19 pandemic on maternal mortality in Chile between 2020 and 2021. A natural experiment was conducted using official data on maternal deaths and live births (LBs) between 1997 and 2021. The effects of the SARS-CoV-2 outbreak were evaluated using interrupted time series (ITS) and an autoregressive integrated moving average (ARIMA) model to forecast the expected rates on MMR and 95% confidence intervals (95% CI). In Chile, following World Health Organization suggestions, maternal deaths aggravated by SARS-CoV-2 are assigned to code O98.5 (non-respiratory infectious indirect) accompanied by code U07.1 or U07.2, depending on confirmation of the presence or absence of the virus. ITS analysis revealed that the SARS-CoV-2 outbreak impacted the MMR due to indirect causes, with a greater increase in indirect nonrespiratory causes than respiratory causes. The ARIMA forecast was consistent with ITS, showing that the expected MMR for indirect causes (3.44 in 2020 and 1.55 in 2021) was substantially lower than the observed rates (9.65 in 2020 and 7.46/100.000 LBs in 2021). For nonrespiratory indirect causes, the observed values of the MMR for 2020 (8.77/100.000 LBs) and 2021 (7.46/100.000 LBs) were double the predicted values of 4.02 (95% CI: 0.44-7.61) and 3.83 (95% CI: -0.12-7.79), respectively. A lower effect was observed on direct obstetrical deaths. During 2020-2021, there was a rise in the MMR in Chile attributable to SARS-CoV-2. The pandemic contributed to an escalation in the MMR due to indirect causes, particularly nonrespiratory and infectious causes. MMR due to direct obstetric causes were less affected. This suggests that the pandemic disproportionately affected maternal health by exacerbating conditions unrelated to pregnancy, childbirth, or postpartum, more than those directly linked to obstetric complications.

Impact of emerging virus pandemics on cause-specific maternal mortality time series: a population-based natural experiment using national vital statistics, Argentina 1980-2017.

Background: Emerging pandemic viruses may have multiple deleterious effects on maternal health. This study examines the effects of a pandemic influenza virus on cause-specific maternal mortality time series, using Argentinian vital statistics. Methods: We conducted a population-based natural experiment from national vital records of maternal deaths between 1980 and 2017. Joinpoint regression models were used to model time series of the maternal mortality ratio (MMR). The sensitivity of the registry to detect the effects of the pandemic H1N1 2009 influenza virus on cause-specific MMR was analysed using a panel of parallel interrupted time series (ITS). Findings: Over this 38-year study, the MMR decreased by 58·6% (69·5 to 28·8 deaths/100,000 live births), transitioning from direct obstetric causes (67·0 to 21·1/100,000 live births; 68·4% decrease) to indirect causes (2·6 to 7·7/100,000 live births; 196·2% increase). The regression analysis showed an average reduction of -2·2%/year (95% CI: -2·9 to -1·4) with 2 join points in the total trend (1998 and 2009). Parallel ITS analyses revealed the pandemic H1N1 virus had an increasing effect on mortality from the respiratory system- and sepsis-related complications (level change 4·7 and 1·6/100,000 live births respectively), reversing after the outbreak. No effect was found on MMR from hypertensive disorders, haemorrhage, abortive outcomes, other direct obstetric causes, and indirect non-respiratory comorbidities. Interpretation: The Argentinian maternal death registry appears sensitive to detect different effects of emerging infectious epidemics on maternal health. In a population-based natural experiment, pandemic H1N1 virus impacted maternal mortality almost exclusively from the respiratory system- and sepsis-related complications. Funding: Supported by FISAR www.fisarchile.org.

A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients.

Desmopressin (dDAVP) is a well-known peptide analog of the antidiuretic hormone vasopressin, used to prevent excessive bleeding during surgical procedures. dDAVP increases hemostatic mediators, such as the von Willebrand factor (vWF), recently considered a key element in resistance to metastasis. Studies in mouse models and veterinary trials in dogs with locally-advanced mammary tumors demonstrated that high doses of perioperative dDAVP inhibited lymph node and early blood-borne metastasis and significantly prolonged survival. We conducted a phase II dose-escalation trial in patients with breast cancer, administering a lyophilized formulation of dDAVP by intravenous infusion in saline, 30-60 min before and 24 h after surgical resection. Primary endpoints were safety and tolerability, as well as selection of the best dose for cancer surgery. Secondary endpoints included surgical bleeding, plasma levels of vWF, and circulating tumor cells (CTCs) as measured by quantitative PCR of cytokeratin-19 transcripts. Only 2 of a total of 20 patients experienced reversible adverse events, including hyponatremia (grade 4) and hypersensitivity reaction (grade 2). Reactions were adequately managed by slowing the infusion rate. A reduced intraoperative bleeding was noted with increasing doses of dDAVP. Treatment was associated with higher vWF plasma levels and a postoperative drop in CTC counts. At the highest dose level evaluated (2 µg/kg) dDAVP appeared safe when administered in two slow infusions of 1 µg/kg, before and after surgery. Clinical trials to establish the effectiveness of adjunctive perioperative dDAVP therapy are warranted. This trial is registered on www.clinicaltrials.gov (NCT01606072).