Samuel T. Bauer

Maternal sepsis mortality and morbidity during hospitalization for delivery: temporal trends and independent associations for severe sepsis.

BACKGROUND:Sepsis is currently the leading cause of direct maternal death in the United Kingdom. In this study, we aimed to determine frequency, temporal trends, and independent associations for severe sepsis during hospitalization for delivery in the United States. METHODS:Data were obtained from the Nationwide Inpatient Sample for the years 1998 through 2008. The presence of severe sepsis was identified by the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes. Logistic regression analysis was used to assess temporal trends for sepsis, severe sepsis, and sepsis-related death and also to identify independent associations of severe sepsis. RESULTS:Of an estimated 44,999,260 hospitalizations for delivery, sepsis complicated 1:3333 (95% confidence interval [CI], 1:3151–1:3540) deliveries, severe sepsis complicated 1:10,823 (95% CI, 1:10,000–1:11,792) deliveries, and sepsis-related death complicated 1:105,263 (95% CI, 1:83,333–1:131,579) deliveries. While the overall frequency of sepsis was stable(P = 0.95), the risk of severe sepsis and sepsis-related death increased during the study period, (P < 0.001) and (P = 0.02), respectively. Independent associations for severe sepsis, with an adjusted odds ratio and lower bound 95% CI higher than 3, include congestive heart failure, chronic liver disease, chronic renal disease, systemic lupus erythematous, and rescue cerclage placement. CONCLUSIONS:Maternal severe sepsis and sepsis-related deaths are increasing in the United States. Severe sepsis often occurs in the absence of a recognized risk factor and underscores the need for developing systems of care that increase sensitivity for disease detection across the entire population. Physicians should enhance surveillance in patients with congestive heart failure, chronic liver disease, chronic renal disease, and systemic lupus erythematous and institute early treatment when signs of sepsis are emerging.

Screening for partner violence during pregnancy

Objectives: An analysis of the international literature on partner violence provides insights for health care providers caring for women. Methods: The current literature on partner violence epidemiology, screening, and interventions was reviewed, focusing on pregnancy. Results: Adolescent girls and pregnant women are at highest risk for partner violence and homicide. Conclusion: Health care providers need to offer clinical screening and interventions to prevent consequences of partner violence, including homicide.

Maternal physiologic parameters in relationship to systemic inflammatory response syndrome criteria: a systematic review and meta-analysis.

OBJECTIVE: To establish the normal maternal range in healthy pregnant women for each component of the systemic inflammatory response syndrome (SIRS) criteria and compare these ranges with existing SIRS criteria. DATA SOURCES: PubMed, Embase, and ClinicalTrials.gov databases were searched to identify studies of healthy parturients from the first trimester through 12 weeks postpartum that reported maternal temperature, respiratory rate, PaCO2, heart rate, white blood cell count data, or a combination of these. METHODS OF STUDY SELECTION: Data were extracted from studies providing maternal values for components of SIRS criteria. The mean, standard deviation, and two standard deviations from the mean for all criteria parameters published in the literature were reported. TABULATION, INTEGRATION, AND RESULTS: Eighty-seven studies met inclusion criteria and included 8,834 patients and 15,237 data points: temperature (10 studies and 2,367 patients), respiratory rate (nine studies and 312 patients), PaCO2 (12 studies and 441 patients), heart rate (39 studies and 1,374 patients), and white blood cell count (23 studies and 4,553 patients). Overlap with SIRS criteria occurred in healthy pregnant women during the second trimester, third trimester, and labor for each of the SIRS criteria except temperature. Every mean value for PaCO2 during pregnancy (and up to 48 hours postpartum) was below 32 mm Hg. Two standard deviations above the mean for temperature, respiratory rate, and heart rate were 38.1°C, 25 breaths per minute, and 107 beats per minute, respectively. CONCLUSION: Current SIRS criteria often overlap with normal physiologic parameters during pregnancy and the immediate postpartum period; thus, alternative criteria must be developed to diagnose maternal sepsis.

Validation of metabolomic models for prediction of early-onset preeclampsia.

OBJECTIVE We sought to perform validation studies of previously published and newly derived first-trimester metabolomic algorithms for prediction of early preeclampsia (PE). STUDY DESIGN Nuclear magnetic resonance-based metabolomic analysis was performed on first-trimester serum in 50 women who subsequently developed early PE and in 108 first-trimester controls. Random stratification and allocation was used to divide cases into a discovery group (30 early PE and 65 controls) for generation of the biomarker model(s) and a validation group (20 early PE and 43 controls) to ensure an unbiased assessment of the predictive algorithms. Cross-validation testing on the different algorithms was performed to confirm their robustness before use. Metabolites, demographic features, clinical characteristics, and uterine Doppler pulsatility index data were evaluated. Area under the receiver operator characteristic curve (AUC), 95% confidence interval (CI), sensitivity, and specificity of the biomarker models were derived. RESULTS Validation testing found that the metabolite-only model had an AUC of 0.835 (95% CI, 0.769-0.941) with a 75% sensitivity and 74.4% specificity and for the metabolites plus uterine Doppler pulsatility index model it was 0.916 (95% CI, 0.836-0.996), 90%, and 88.4%, respectively. Predictive metabolites included arginine and 2-hydroxybutyrate, which are known to be involved in vascular dilation, and insulin resistance and impaired glucose regulation, respectively. CONCLUSION We found confirmatory evidence that first-trimester metabolomic biomarkers can predict future development of early PE.

The Zika virus and pregnancy: evidence, management, and prevention

Abstract Objective: To comprehensively review the available evidence and existing consensus reports and guidelines regarding the pregnancy and reproductive implications of the mosquito-transmitted Zika virus (ZIKV) infection. A primary focus was to provide pertinent information to aid clinicians in the management of pregnancies at risk for, exposed to, or with confirmed ZIKV infection. Method: An extensive literature review was performed using Pubmed. Practice guidelines and consensus reports were accessed from international, national, and professional organizations’ websites. The clinical articles for ZIKV infection testing varied from case reports to small epidemiologic studies. Results: A ZIKV epidemic has been declared in several countries in the Americas. Fifty-two travel-associated ZIKV infection cases have been reported throughout the USA (as of February 10, 2016). The consequences of congenital fetal/newborn ZIKV infection could potentially have devastating consequences including miscarriage, fetal death, and major anomalies such as microcephaly, brain and brain-stem defects, and long-term neurologic sequelae. While not definitive, current evidence suggests the existence of nonvector-borne transmission through sexual activity with an infected male partner. For women at risk for sexual transmission, condom use is advised, especially during pregnancy. Conclusion: While ZIKV infection appears to be a mild disease in the general population the potential consequences to the fetus and newborn could be profound. Management guidelines are currently evolving and will be significantly impacted as new evidence develops. It is therefore imperative that obstetric health-care providers keep abreast of this rapidly evolving information landscape that has so far characterized this outbreak.

Maternal Deaths Due to Sepsis in the State of Michigan, 1999–2006

OBJECTIVE: To identify maternal deaths due to sepsis in the state of Michigan, review the events leading to diagnosis, and evaluate treatment to identify areas for improvement. METHODS: A case series was collected for maternal deaths due to sepsis from a cohort of maternal deaths in the state of Michigan. The study period was 1999–2006 and included deaths during pregnancy and up to 42 days postpartum. Cases were identified using Maternal Mortality Surveillance records from the Michigan Department of Community Health. Each case was reviewed by all authors. RESULTS: Maternal sepsis was the cause of death in 15% (22/151) of pregnancy-related deaths. Of 22 deaths, 13 women presented to the hospital with sepsis, two developed sepsis during hospitalization, and seven developed sepsis at home without admission to the hospital for care. Review of available hospital records (n=15) revealed delays in initial appropriate antibiotic treatment occurred in 73% (11/15) of patients. Delay in escalation of care also occurred and was identified in 53% (8/15) of patients. CONCLUSION: Common elements in these deaths illustrate three key delays that may have contributed to the deaths: in recognition of sepsis, in administration of appropriate antibiotics, and in escalation of care. LEVEL OF EVIDENCE: III

Metabolomic determination of pathogenesis of late-onset preeclampsia

Abstract Objective: Our primary objective was to apply metabolomic pathway analysis of first trimester maternal serum to provide an insight into the pathogenesis of late-onset preeclampsia (late-PE) and thereby identify plausible therapeutic targets for PE. Methods: NMR-based metabolomics analysis was performed on 29 cases of late-PE and 55 unaffected controls. In order to achieve sufficient statistical power to perform the pathway analysis, these cases were combined with a group of previously analyzed specimens, 30 late-PE cases and 60 unaffected controls. Specimens from both groups of cases and controls were collected in the same clinical centers during the same time period. In addition, NMR analyses were performed in the same lab and using the same techniques. Results: We identified abnormalities in branch chain amino acids (valine, leucine and isoleucine) and propanoate, glycolysis, gluconeogenesis and ketone body metabolic pathways. The results suggest insulin resistance and metabolic syndrome, mitochondrial dysfunction and disturbance of energy metabolism, oxidative stress and lipid dysfunction in the pathogenesis of late PE and suggest a potential role for agents that reduce insulin resistance in PE. Conclusions: Branched chain amino acids are known markers of insulin resistance and strongly predict future diabetes development. The analysis provides independent evidence linking insulin resistance and late-PE and suggests a potentially important therapeutic role for pharmacologic agents that reduce insulin resistance for late-PE.

Zika Virus and Pregnancy

We thank our colleague for his interest in our recent publication. He has correctly identified the embryonic stage of our knowledge about the effects of the Zika Virus in pregnancy. Currently, the cause of this knowledge gap is the absence of robust data rather than lack of interest on the part of clinicians. It can be anticipated that in the next 2–3 years we will witness a dramatic increase in available information as governments and researchers mobilize to address this significant public health risk. We are optimistic that heath care personnel will be attentive to the new information that is generated as a result of this focus.

Maternal leukocytosis after antenatal corticosteroid administration: a systematic review and meta-analysis*

Abstract Although it is known that corticosteroid administration causes leukocytosis, the magnitude and length of time this leukocytosis persists is unknown during pregnancy. This study aimed to establish the expected range of maternal leukocytosis in healthy pregnant women at risk for preterm delivery after antenatal corticosteroid administration. PubMed, Embase and ClinicalTrials.gov were searched to identify the studies in healthy women at risk for preterm delivery without signs of clinical infection that reported white blood cell values preceding and after antenatal corticosteroid administration. The inverse variance weighting technique was used to calculate the weighted means and the standard deviation from the mean for each time period. Six studies met inclusion criteria and included 524 patients and 1406 observations. Mean ± standard deviation maternal white blood cell count values prior to antenatal corticosteroid administration and up to 24, 48, 72 and 96 hours after corticosteroid administration were 10.4 ± 2.4, 13.6 ± 3.6, 12.1 ± 3.0, 11.5 ± 2.9 and 11.1 ± 2.5 × 109/L, respectively. Leukocytosis in healthy, non-infected women is expected to peak 24 hours after antenatal corticosteroid administration and the magnitude of increase is small. Impact statement What is already known on this subject: While it is well known that administration of antenatal corticosteroids causes leukocytosis, it is currently unknown the magnitude and length of time the leukocytosis persists. What the results of this study add: This study establishes the expected range and the temporal progression and regression with antenatal corticosteroid administration in healthy pregnant women at risk for preterm delivery without clinical signs of infection. What the implications are of these findings for clinical practice and/or further research: Clinicians may wish to consider further investigation into the clinical cause, whether infectious or non-infectious, for absolute values and changes outside this range. Graphical Abstract