Risk factors for postpartum sepsis: a nested case-control study.

BACKGROUND: The Majority (99%) of maternal deaths occur in low and middle-income countries. The three most important causes of maternal deaths in these regions are postpartum hemorrhage, pre-eclampsia and puerperal sepsis. There are several diagnostic criteria used to identify sepsis and one of the commonly used criteria is systematic inflammatory response syndrome (SIRS). However, these criteria require laboratory investigations that may not be feasible in resource-constrained settings. Therefore, this study aimed to develop a model based on risk factors and clinical signs and symptoms that can identify sepsis early among postpartum women. METHODS: A case-control study was nested in an ongoing cohort of 4000 postpartum women who delivered or were admitted to the study hospital. According to standard criteria of SIRS, 100 women with sepsis (cases) and 498 women without sepsis (controls) were recruited from January to July 2017. Information related to the socio-demographic status, antenatal care and use of tobacco were obtained via interview while pregnancy and delivery related information, comorbid and clinical sign and symptoms were retrieved from the ongoing cohort. Multivariable logistic regression was performed and discriminative performance of the model was assessed using area under the curve (AUC) of the receiver operating characteristic (ROC). RESULTS: Multivariable analysis revealed that 1-4 antenatal visits (95% CI 0.01-0.62). , 3 or more vaginal examinations (95% CI 1.21-3.65), home delivery (95% CI 1.72-50.02), preterm delivery, diabetes in pregnancy (95% CI 1.93-20.23), lower abdominal pain (95% CI 1.15-3.42)) vaginal discharge (95% CI 2.97-20.21), SpO2 < 93% (95% CI 4.80-37.10) and blood glucose were significantly associated with sepsis. AUC was 0.84 (95% C.I 0.80-0.89) which indicated that risk factors and clinical sign and symptoms-based model has adequate ability to discriminate women with and without sepsis. CONCLUSION: This study developed a non-invasive tool that can identify postpartum women with sepsis as accurately as SIRS criteria with good discriminative ability. Once validated, this tool has the potential to be scaled up for community use by frontline health care workers.

A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery.

BACKGROUND: Surgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries. METHODS: We conducted a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low-resource countries. We randomly assigned patients to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics. The definition of pelvic infection was changed before the unblinding of the data; the original strict definition was two or more of the clinical features, without reference to the administration of antibiotics. RESULTS: We enrolled 3412 patients in Malawi, Pakistan, Tanzania, and Uganda. A total of 1705 patients were assigned to receive antibiotics and 1707 to receive placebo. The risk of pelvic infection was 4.1% (68 of 1676 pregnancies) in the antibiotics group and 5.3% (90 of 1684 pregnancies) in the placebo group (risk ratio, 0.77; 95% confidence interval [CI], 0.56 to 1.04; P = 0.09). Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) and 2.6% (44 of 1704 pregnancies), respectively (risk ratio, 0.60; 95% CI, 0.37 to 0.96). There were no significant between-group differences in adverse events. CONCLUSIONS: Antibiotic prophylaxis before miscarriage surgery did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. (Funded by the Medical Research Council and others; AIMS Current Controlled Trials number, ISRCTN97143849.).

Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.

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.

Prophylactic antibiotics to reduce pelvic infection in women having miscarriage surgery - The AIMS (Antibiotics in Miscarriage Surgery) trial: study protocol for a randomized controlled trial.

BACKGROUND: The estimated annual global burden of miscarriage is 33 million out of 210 million pregnancies. Many women undergoing miscarriage have surgery to remove pregnancy tissues, resulting in miscarriage surgery being one of the most common operations performed in hospitals in low-income countries. Infection is a serious consequence and can result in serious illness and death. In low-income settings, the infection rate following miscarriage surgery has been reported to be high. Good quality evidence on the use of prophylactic antibiotics for surgical miscarriage management is not available. Given that miscarriage surgery is common, and infective complications are frequent and serious, prophylactic antibiotics may offer a simple and affordable intervention to improve outcomes. METHODS: Eligible patients will be approached once the diagnosis of miscarriage has been made according to local practice. Once informed consent has been given, participants will be randomly allocated using a secure internet facility (1:1 ratio) to a single dose of oral doxycycline (400 mg) and metronidazole (400 mg) or placebo. Allocation will be concealed to both the patient and the healthcare providers. A total of 3400 women will be randomised, 1700 in each arm. The medication will be given approximately 2 hours before surgery, which will be provided according to local practice. The primary outcome is pelvic infection 2 weeks after surgery. Women will be invited to the hospital for a clinical assessment at 2 weeks. Secondary outcomes include overall antibiotic use, individual components of the primary outcome, death, hospital admission, unplanned consultations, blood transfusion, vomiting, diarrhoea, adverse events, anaphylaxis and allergy, duration of clinical symptoms, and days before return to usual activities. An economic evaluation will be performed to determine if prophylactic antibiotics are cost-effective. DISCUSSION: This trial will assess whether a single dose of doxycycline (400 mg) and metronidazole (400 mg) taken orally 2 hours before miscarriage surgery can reduce the incidence of pelvic infection in women up to 2 weeks after miscarriage surgery. TRIAL REGISTRATION: Registered with the ISRCTN (international standard randomised controlled trial number) registry: ISRCTN 97143849 . (Registered on April 17, 2013).

Frequent hypomethylation of PTGS2 gene promoter in human term placenta.

BACKGROUND: Gene expression profiles of several tumor suppressor genes are regulated by the methylation and demethylation of their promoters. Here, we aim to identify and quantify the methylation status of four tumor suppressor genes from placentas at term and compare them with the maternal white-blood-cells. METHODS: In order to achieve this objective, DNA enriched from twenty placentas at term and maternal white blood cells was bisulfite-converted and amplified using quantitative real-time methyl-light polymerase chain reaction for the four-genes studied (RASSF1A, APC, RAR-beta, and PTGS2). RESULTS: Among the four genes examined, RASSF1A, APC and RAR-beta promoter regions were hypermethylated in all the placental samples compared with maternal WBCs. Strikingly, PTGS2 was found to be hypomethylated in the placentas compared to the maternal cells. CONCLUSION: Since placental DNA represents fetal methylation profile and it is an established fact that there is certain amount of cell free circulating DNA in human plasma/serum, these data strongly suggest that hypermethylation of RASSF1A, APC and RAR-beta can be used as gender independent biomarkers to distinctly identify placental DNA in maternal blood. In addition, this is the first report which demonstrates hypomethylation of PTGS2 locus which may have important clinical implications e.g. placental abnormalities.

Validating MOSPA questionnaire for measuring physical activity in Pakistani women.

BACKGROUND: Precise measurements of activity at a population level are important for monitoring trends and evaluating health promotion strategies. Few studies have assessed the measurement of physical activity in developing countries. The aim of this study was to validate the MOSPA (Monica Optional Study of Physical Activity) questionnaire which was developed for the WHO-Monitoring trends and determinants of cardiovasculr disease (MONICA) study sites. METHODS: The MOSPA questionnaire assesses energy expendtiture (EE) related to physical activity (employment, household work, transportation, and leisure time) over a one year period. This questionnaire has been described in the manuscript as the long term (LT) questionnaire. An adapted short term (ST) 5 day questionnaire was developed to assess convergent validity. Questionnaire data were compared with physical activity EE estimates from a Caltrac accelerometer and with body composition measures (height, weight and bioelectrical impedance) in 50 women from the Aga Khan University (AKU) hospital antenatal clinics, Pakistan. Other forms of EE i.e. resting EE and thermic effect of food were not assessd in this study. RESULTS: Subjects were aged 26 +/- 3.8 years and were 16.1 +/- 6.7 weeks pregnant. Their average weight was 58.8 +/- 10.7 Kg. The average EE/day assessed by the Caltrac accelerometer, was 224 kcal and by MOSPA LT questionnaire it was 404 kcal. The questionnaires and Caltrac data were reasonably well correlated: r = 0.51 and r = 0.60 (P < 0.01) for LT and ST questionnaires respectively. Energy expenditure from questionnaire data was not correlated with body composition measures. CONCLUSION: The MOSPA questionnaire is useful in assessing physical activity levels in a sedentary population over a one year period.

Congenital vaginal obstructions: varied presentation and outcome.

Congenital obstructing lesions of vagina, hydrometrocolpos, and hematocolpos, present at a variable time during early childhood and adolescence to different medical and surgical specialties. Twenty-six cases presenting over an 18-years period (1987-2005) were divided into three groups; Group A: neonates (6), Group B: adolescents (18), and Group C: adults (2). Common presentations in neonates (Group A) were abdominal mass (5), neonatal sepsis (3), and respiratory distress (2); whereas abdominal pain (18), voiding dysfunctions (13), and backache (7) were prevalent in adolescents (Group B). Adults (Group C) presented with inability to consummate and infertility (2). Four patients received erroneous treatment; exploratory laparotomy (1) and appendectomy (3). Urinary symptoms and associated urinary abnormalities were present in more than 50% of cases, especially those with complex anomalies. Management included excision of imperforate hymen (16) and transverse vaginal septum (8) through perineal (20) and abdominoperineal approach (4). Patients with urogenital sinus (1) and cloacal malformation (1) had staged reconstruction at 2.5 years of age following preliminary vesicostomy and colostomy at birth. On follow up (range 1-15 years; mean 7) more than 60% patients have menstrual irregularity (11), endometriosis (5), and infertility (4). In conclusion, rarity and variable presentation of congenital vaginal obstructions can lead to delayed diagnosis and erroneous management. A high index of suspicion and cross-sectional imaging help in early diagnosis and associated renal anomalies. A comprehensive management is imperative to preserve the reproductive potentials, as significant proportion of patients may experience sexual difficulties, menstrual irregularity, and infertility.