Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model
No open license is recorded for this paper. Reuse terms are set by the publisher.
Open Access
Free full text on PubMed Central (PMC6206915)
Abstract
Background
Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care.
Methods
A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration.
Results
Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08).
Conclusions
The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.
Balachandran S et al., 2026·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To assess the impact of the COVID-19 pandemic on reproductive outcomes in patients with recurrent pregnancy loss (RPL) and the influence of material and social deprivation on these outcomes.
This retrospective cohort study included RPL patients seen at a specialized clinic between March 1, 2018, and February 28, 2022. Patients were categorized into two groups based on care period: pre-pandemic (March 1, 2018-February 29, 2020) and pandemic (March 1, 2020-February 28, 2022). Cumulative probabilities of birth were estimated using the cumulative incidence function within a competing risk framework, treating pregnancy loss as a competing event. Fine and Gray regression models calculated sub-distribution hazard ratio (sHR) of birth.
544 patients were included in the study, with 255 in the pre-pandemic group and 289 in the pandemic group. Individuals in the pandemic group were less likely to achieve pregnancy than those in the pre-pandemic group (relative risk = 0.50, 95% confidence interval [CI] 0.39 - 0.66). Among those who conceived, the cumulative probability of live birth was 0.77 in both groups. Relative to individuals residing in high-social deprivation neighborhoods, those living in moderately deprived areas had higher sub-distribution hazards of live birth (adjusted sHR = 1.97, 95% CI 1.25 - 3.10; P = 0.003).
Within specialized RPL care and a universal maternity care system, pregnancy rates were lower during the first two years of the COVID-19 pandemic. However, among those who conceived, the probability of achieving a live birth remained similar between the pre-pandemic and pandemic periods.
Eckler R et al., 2025·PloS one·Free full text on PubMed Central
To investigate the impact of the COVID-19 pandemic's onset on clinical and demographic characteristics, pregnancy complications, and monthly conception rates resulting in births through spontaneous conceptions and in-vitro fertilization (IVF) in British Columbia (BC), Canada.
This retrospective population-based cohort study examined individuals who gave birth (both live births and stillbirths) in BC between June 1, 2010, and March 31, 2021, with estimated conception dates from January 1, 2010 to June 30, 2020. Data were obtained from the BC Perinatal Data Registry. Two groups were identified based on the estimated conception date: the pre-pandemic conception group (conception from January-1-2010 to February-29-2020) and the pandemic conception group (conception from March-1-2020 to June-30-2020). A time series forecasting method (ARIMA) was employed to observe trends in conception rates during the study period.
304,244 individuals with pregnancies resulting in live births or stillbirths during the study period were evaluated. A total of 429,843 such conceptions were included in the study: 417,753 (97.2%) occurring before the onset of the pandemic and 12,090 (2.8%) in the pandemic period. In June 2020, conceptions resulting in births decreased by 26.6% compared with June 2019. Trends in conceptions resulting in live births were similar, with a conception rate of 235.2 per 100,000 women of reproductive age in June 2020, compared with the expected rate of 305.0 per 100,000. In March 2020, 0.5% of conceptions that resulted in births ended in stillbirths, compared to 1.7% in March 2019. IVF conceptions ending in births declined during the pandemic, dropping to 2.5 and 2.8 per 100,000 in March and April 2020, respectively, compared with the expected 13.1 per 100,000. However, by June 2020, these rates began to recover toward the expected levels. Rates of gestational diabetes mellites (GDM), gestational hypertension (GHTN), and postpartum intensive care unit (ICU) admissions were similar before and during the COVID-19 pandemic.
During the challenging period of the COVID-19 pandemic in BC, couples may have chosen to delay conception. Rates of conceptions resulting in stillbirths remained relatively unchanged. IVF conception rates were impacted by the suspension of elective procedures. Preterm birth rates slightly exceeded expected levels but remained within normal fluctuations, and small increases in GDM and GHTN prevalence were also observed.
Recurrent Pregnancy Loss · Immune and Thrombophilia Factors
Balachandran S et al., 2025·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC·Free to read
To investigate the impact of the COVID-19 pandemic on the care received by patients with recurrent pregnancy loss (RPL) in British Columbia, Canada. To explore the differential impact of socioeconomic status on health care utilization outcomes during the COVID-19 pandemic for patients with RPL.
This is a retrospective cohort study of patients from an RPL clinic located within a tertiary referral centre. Patients were divided into 2 groups based on the date of their initial visit to the clinic: (1) pre-pandemic group (March 1, 2018-February 28, 2020) and (2) pandemic group (March 1, 2020-February 28, 2022). Data were sourced from the RPL Clinic Database and Population Data BC. Outcomes assessed included visit trends, immediate pandemic impact, and socioeconomic effects.
Demographic and clinical characteristics were not significantly different between study groups, except for increased referral rates to fertility clinics by the RPL clinic during the COVID-19 pandemic (4.90% vs. 9.50%). The mean number of visits per patient was comparable between pre-pandemic (3.50 ± 2.00) and during the pandemic (3.40 ± 3.40). However, monthly initial visits were lower during the pandemic (12.50 ± 3.10) compared with pre-pandemic (14.40 ± 4.83). Telehealth was rare in the pre-pandemic period and increased dramatically during the pandemic, with virtual visits reaching up to 64% of total and 94% of initial visits. The pandemic's onset caused immediate drops in total (38.80%) and initial visits (51.70%). Health care utilization was higher among those with less material deprivation, whereas contrasting effects were observed in those with less social deprivation.
The COVID-19 pandemic impacted the care received by patients with RPL within a tertiary care centre. There was a shift in how services were provided to patients, uniquely impacting specific populations within the community.
Bedaiwy MA et al., 2025·Gynecologic and obstetric investigation
Accessory and cavitated uterine masses (ACUM) are rare Mullerian anomalies, defined as an isolated accessory cavitated mass lined with endometrial epithelium.
This article explores ACUM lesions from two aspects and integrates a case report of a successful laparoscopic-assisted intervention for ACUM in a 24-year-old woman with refractory dysmenorrhea with a review of current literature on laparoscopic surgical techniques. Unique to this case was the process of undergoing targeted genetic sequencing via the Find ITTM Panel Version 3.4 on the ACUM, looking for mutations in KRAS, PIK3CA, and FGFR2. A process that was inspired by recent reports that indicate that even normal endometrium can harbor cancer-associated mutations.
A comprehensive search of Ovid MEDLINE and Embase was performed. Studies were selected if they explored laparoscopic surgery's impact on ACUM patients' outcomes related to fertility, menorrhagia, or dysmenorrhea. Risk of bias assessment was performed using the JBI Critical Appraisal Checklist.
From 160 articles identified, 25 full-text articles were analyzed with a total of 75 unique patients discussed. Dysmenorrhea was present in 100% of cases (n = 75/75), and laparoscopic resection improved patient symptoms in 84% (n = 63/75) of cases. The mass excised in the case was positive for somatic missense mutations in RET (R813W) and HRAS (G12S) genes, identified at low variant allele frequencies.
These results demonstrated that laparoscopic surgical approaches are effective and frequently the first surgical approach chosen for the treatment of ACUM, but that techniques to treat these conditions are not standardized. This case is the first to demonstrate mutations in ACUM, suggesting a potential role for cancer-associated somatic mutations in their genesis. Future developments in this area may include sending more of these samples for genetic analysis, improving our understanding of how these lesions are formed, while also working to standardize how they are removed.
Research Methods › Measurement and Statistics › Instrument Development and Validation
Beth A Payne, Helen Ryan, Jeffrey Bone, Alice B Aarvold, J Mark Ansermino, Mary Bowen, J Guilherme Cecatti, Cynthia Chazotte, Tim Crozier, Anne-Cornélie J M de Pont, Oktay Demirkiran, Tao Duan, Marlot Kallen, Wessel Ganzevoort, Michael Geary, Dena Goffman, Jennifer A Hutcheon, Stephen E Lapinsky, Isam Lataifeh, Jing Li, Sarka Liskonova, Emily M Hamel, Colm O'Herlihy, Ben W J Mol, P Gareth R Seaward, Ramzy Tadros, Turkan Togal, Rahat Qureshi, U Vivian Ukah, Daniela Vasquez, Euan Wallace, Vivian Zhou, Keith R Walley, P von Dadelszen
Elizabeth Payne, B Payne, H Ryan, Jeff Bone, J Bone, A Aarvold, M Bowen, C Chazotte, Timothy Crozier, T Crozier, A Pont, O Demirkiran, T Duan, M Kallen, W Ganzevoort, Mike Geary, M Geary, D Goffman, Jen Hutcheon, Jenny Hutcheon, J Hutcheon, Steve Lapinsky, S Lapinsky, I Lataifeh, J Li, S Liskonova, E Hamel, C O'Herlihy, Benjamin Mol, B Mol, R Tadros, T Togal, R Qureshi, D Vasquez, E Wallace, V Zhou, K Walley
PMID 30373675 30373675 DOI 10.1186/s13054-018-2215-6 10.1186/s13054-018-2215-6 Payne et al. 2018, Payne 2018