Quick Sequential Organ Failure Assessment: Modifications for Identifying Maternal Morbidity and Mortality in Obstetrical Patients.

OBJECTIVE: Screening tools, including the Systemic Inflammatory Response Syndrome (SIRS) criteria and Sequential Organ Failure Assessment (SOFA) criteria, have not been validated in the pregnant population. We aimed to determine if pregnancy-specific modifications to the quick SOFA (qSOFA) can improve prediction of severe maternal morbidity in pregnant women with serious infections. STUDY DESIGN: We performed a retrospective cohort study of pregnant patients with severe infections admitted to a single institution from January 1, 2011, through December 31, 2017. The primary outcome was severe maternal morbidity, defined as a composite of adverse maternal outcomes: intensive care unit (ICU) admission for >48 hours, need for invasive monitoring (central line or arterial line), intubation, pharmacologic hemodynamic support (intravenous vasopressors or inotropes), and/or maternal death. A logistic regression was then applied and the resulting predictors were analyzed individually and in combination with receiver operating characteristic (ROC) curves to modify qSOFA for pregnancy, that is, qSOFA-P. RESULTS: Analysis of 104 pregnant patients with severe infections found that the standard qSOFA did not accurately predict severe maternal morbidity (ROC area under the curve [AUC] = 0.54, p = 0.49, sensitivity = 0.38, and specificity = 0.70). Pregnancy-specific modifications or "qSOFA-P" (respiratory rate [RR] ≥ 35 breaths/minute and systolic blood pressure [SBP] ≤ 85 mm Hg) significantly improved prediction of severe maternal morbidity (AUC = 0.77, p < 0.001, sensitivity = 0.79, and specificity = 0.74). CONCLUSION: The standard qSOFA is a poor screening tool in the prediction of severe maternal morbidity in pregnant patients with infections. A pregnancy-specific screening system, qSOFA-P, improved prediction of severe maternal morbidity in pregnant women with severe infections. Further prospective and large multicenter studies are needed to validate this scoring system in pregnant women. KEY POINTS: · Validated scoring systems for evaluating pregnant patients with sepsis are needed.. · Modifications to existing systems may improve the evaluation of pregnant patients with sepsis.. · The qSOFA-P (RR ≥ 35 breaths/minute and SBP ≤ 85 mm Hg) includes modifications to qSOFA, and improves the detection of patients who would develop severe maternal morbidity...

Treponema pallidum infection predicts sexually transmitted viral infections (hepatitis B virus, herpes simplex virus-2, and human immunodeficiency virus) among pregnant women from rural areas of Mwanza region, Tanzania.

BACKGROUND: Sexually transmitted infections (STIs) is a global health problem with increased risk and morbidities during pregnancy. This study investigated the magnitude of viral STIs among pregnant women from three rural hospitals/clinics providing antenatal care in Mwanza region, Tanzania. METHODS: Between February and May 2018, a total of 499 pregnant women were enrolled and tested for Human immunodeficiency virus (HIV), Herpes simplex virus-2 (HSV-2), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) using rapid immunochromatographic tests and for syphilis using non-treponemal and treponemal antibody test. RESULTS: The median age of enrolled women was 25 (IQR: 22-31) years. Seventy eight (15.6, 95% CI: 12-18) of women tested had at least one sexually transmitted viral infection. Specific prevalence of HIV, HBV, HCV, HSV-2 IgG and HSV-2 IgM were found to be 25(5.0%), 29(5.8%), 2(0.4%), 188(37.7%) and 24(4.8%), respectively. The odds of having viral infection was significantly high among women with positive T. pallidum serostatus (adjusted odd ratio (aOR): 3.24, 95%CI; 1.2-85). By multivariable logistic regression analysis, history of STIs predicted HSV-2 IgM seropositivity (aOR: 3.70, 95%CI: 1.43-9.62) while parity (aOR: 1.23, 95%CI: 1.04-1.46) predicted HBV infection and syphilis positive results (aOR: 8.63, 95%CI: 2.81-26.45) predicted HIV infection. CONCLUSION: A significant proportion of pregnant women in rural areas of Mwanza region has at least one sexually transmitted viral infection which is independently predicted by positive T. pallidum serostatus. The strengthening and expansion of ANC screening package to include screening of STIs will ultimately reduce the viral STIs among pregnant women hence reduce associated morbidities and mortalities.

Maternal sepsis is an evolving challenge.

Despite major advances in the last century, particularly in high resource settings, maternal sepsis remains a common and potentially preventable cause of direct maternal death globally. A barrier to further progress has been the lack of consensus on the definition of maternal sepsis. Publications from two recent multidisciplinary consensus conferences, one on sepsis in the non-pregnant adult and the other on sepsis in the pregnant woman, concluded that the criteria for diagnosing sepsis should be clinically-based, applicable at the bedside, and should not be laboratory-based. Informed by reviews of the evidence, in 2017 WHO published a new definition of maternal sepsis based on the presence of suspected or confirmed infection. It also announced a Global Maternal and Neonatal Sepsis Initiative to identify the diagnostic criteria for the early identification, epidemiology, and disease classification of maternal sepsis. Standardizing the criteria for maternal sepsis optimizes clinical audit and research. It may facilitate the evaluation of the role of different clinical parameters and biomarkers in the diagnosis, earlier recognition and management of maternal infection and sepsis. Further work is required to develop an international consensus on the criteria for diagnosing maternal sepsis and any associated organ dysfunction.

Assessing the value of Western Cape Provincial Government health administrative data and electronic pharmacy records in ascertaining medicine use during pregnancy.

BACKGROUND: In African settings, where there is a high disease burden, there is a need to improve the science of documenting and analysing accurate information regarding medicine exposures in women immediately before and during pregnancy to assess the extent of use and safety in pregnant women and their unborn children. OBJECTIVES: To compare evidence of medicine use during pregnancy, as documented in paper-based clinical records (maternity case records (MCRs)) against electronic health information resources (Provincial Health Data Centre (PHDC)) and assess the level of concordance between the two as part of baseline investigations before piloting a provincial pregnancy exposure registry and birth defect surveillance system. The PHDC consolidates electronic clinical and pharmacy data. METHODS: A folder review of completed pregnancies between November 2013 and January 2016 was conducted on randomly selected MCRs from midwife-run obstetric units and a secondary maternity hospital in Cape Town, South Africa. Medication exposures in the MCR were captured and compared with a customised PHDC data extract. The type and timing of drug exposures were compared. Total exposures were compiled from all data sources. RESULTS: Two hundred and six MCRs from three facilities were sampled: 83 women had documented antiretroviral therapy (ART) exposure; all but 1 (1%) had been recorded in the PHDC extract. There was no evidence of ART use in the MCRs of 4 (5%) cases, despite evidence in the PHDC. There were imprecise drug names in the MCRs of 14 (17%) ART patients, discordant dates of onset between the MCRs and PHDC extracts in 10/83 (12%) and inaccurate medicine names and incorrect dates in 1 (1%) case each. Nine of 10 (90%) women who were administered antituberculosis medication were recorded in the PHDC extract. Ten of 21 (48%) isoniazid preventive therapy treatments appeared in the MCRs and PHDC; 9 (42%) in the PHDC only and 2 (10%) in the MCRs only. Half (n=18/36) of all antibiotic use was reflected only in the MCRs, while 13/36 (36%) appeared only in the PHDC extract. In the former cases, antibiotics used for treatment of sexually transmitted infections and urinary tract infections were dispensed from ward stock and not captured electronically. Antibiotics reflected only in the PHDC were either dispensed at a referral facility or before the first recorded antenatal clinic visit. Folic acid and iron were mostly documented in the MCR only (n=79/99 (80%) and n=107/128 (84%), respectively). However, analgesics and antihistamines more often appeared in the PHDC extract only (n=11/16 (73%) and n=5/5 (100%), respectively). CONCLUSIONS: The PHDC extract provided a better and more complete reflection of chronic drug exposures compared with the MCRs, especially when women sought care at facilities other than the antenatal care unit where they first attended, or when exposures occurred before the initial antenatal visit. The exception was antibiotics dispensed from ward stock to treat sexually transmitted and urinary tract infections.

Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy.

BACKGROUND: Prevention of reinfection and resurgence is an integral component of the goal to eradicate malaria. However, the adverse effects of malaria resurgences are not known. METHODS: We assessed the prevalence of Plasmodium falciparum infection among 1819 Mozambican women who delivered infants between 2003 and 2012. We used microscopic and histologic examination and a quantitative polymerase-chain-reaction (qPCR) assay, as well as flow-cytometric analysis of IgG antibody responses against two parasite lines. RESULTS: Positive qPCR tests for P. falciparum decreased from 33% in 2003 to 2% in 2010 and increased to 6% in 2012, with antimalarial IgG antibody responses mirroring these trends. Parasite densities in peripheral blood on qPCR assay were higher in 2010-2012 (geometric mean [±SD], 409±1569 genomes per microliter) than in 2003-2005 (44±169 genomes per microliter, P=0.02), as were parasite densities in placental blood on histologic assessment (50±39% of infected erythrocytes vs. 4±6%, P<0.001). The malaria-associated reduction in maternal hemoglobin levels was larger in 2010-2012 (10.1±1.8 g per deciliter in infected women vs. 10.9±1.7 g per deciliter in uninfected women; mean difference, -0.82 g per deciliter; 95% confidence interval [CI], -1.39 to -0.25) than in 2003-2005 (10.5±1.1 g per deciliter vs. 10.6±1.5 g per deciliter; difference, -0.12 g per deciliter; 95% CI, -0.67 to 0.43), as was the reduction in birth weight (2863±440 g in women with past or chronic infections vs. 3070±482 g in uninfected women in 2010-2012; mean difference, -164.5 g; 95% CI, -289.7 to -39.4; and 2994±487 g vs. 3117±455 g in 2003-2005; difference, -44.8 g; 95% CI, -139.1 to 49.5). CONCLUSIONS: Antimalarial antibodies were reduced and the adverse consequences of P. falciparum infections were increased in pregnant women after 5 years of a decline in the prevalence of malaria. (Funded by Malaria Eradication Scientific Alliance and others.).

Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission.

BACKGROUND: Pregnant HIV-infected women were screened for the development of HIV-1 drug resistance after implementation of a triple-antiretroviral transmission prophylaxis as recommended by the WHO in 2006. The study offered the opportunity to compare amplicon-based 454 ultra-deep sequencing (UDS) and allele-specific real-time PCR (ASPCR) for the detection of drug-resistant minor variants in the HIV-1 reverse transcriptase (RT). METHODS: Plasma samples from 34 Tanzanian women were previously analysed by ASPCR for key resistance mutations in the viral RT selected by AZT, 3TC, and NVP (K70R, K103N, Y181C, M184V, T215Y/F). In this study, the RT region of the same samples was investigated by amplicon-based UDS for resistance mutations using the 454 GS FLX System. RESULTS: Drug-resistant HIV-variants were identified in 69% (20/29) of women by UDS and in 45% (13/29) by ASPCR. The absolute number of resistance mutations identified by UDS was twice that identified by ASPCR (45 vs 24). By UDS 14 of 24 ASPCR-detected resistance mutations were identified at the same position. The overall concordance between UDS and ASPCR was 61.0% (25/41). The proportions of variants quantified by UDS were approximately 2-3 times lower than by ASPCR. Amplicon generation from samples with viral loads below 20,000 copies/ml failed more frequently by UDS compared to ASPCR (limit of detection = 650 copies/ml), resulting in missing or insufficient sequence coverage. CONCLUSIONS: Both methods can provide useful information about drug-resistant minor HIV-1 variants. ASPCR has a higher sensitivity than UDS, but is restricted to single resistance mutations. In contrast, UDS is limited by its requirement for high viral loads to achieve sufficient sequence coverage, but the sequence information reveals the complete resistance patterns within the genomic region analysed. Improvements to the UDS limit of detection are in progress, and UDS could then facilitate monitoring of drug-resistant minor variants in the HIV-1 quasispecies.

Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy

Background: Prevention of reinfection and resurgence is an integral component of the goal to eradicate malaria. However, the adverse effects of malaria resurgences are not known. Methods: We assessed the prevalence of Plasmodium falciparum infection among 1819 Mozambican women who delivered infants between 2003 and 2012. We used microscopic and histologic examination and a quantitative polymerase-chain-reaction (qPCR) assay, as well as flow-cytometric analysis of IgG antibody responses against two parasite lines. Results: Positive qPCR tests for P. falciparum decreased from 33% in 2003 to 2% in 2010 and increased to 6% in 2012, with antimalarial IgG antibody responses mirroring these trends. Parasite densities in peripheral blood on qPCR assay were higher in 2010-2012 (geometric mean [±SD], 409±1569 genomes per microliter) than in 2003-2005 (44±169 genomes per microliter, P=0.02), as were parasite densities in placental blood on histologic assessment (50±39% of infected erythrocytes vs. 4±6%, P<0.001). The malaria-associated reduction in maternal hemoglobin levels was larger in 2010-2012 (10.1±1.8 g per deciliter in infected women vs. 10.9±1.7 g per deciliter in uninfected women; mean difference, -0.82 g per deciliter; 95% confidence interval [CI], -1.39 to -0.25) than in 2003-2005 (10.5±1.1 g per deciliter vs. 10.6±1.5 g per deciliter; difference, -0.12 g per deciliter; 95% CI, -0.67 to 0.43), as was the reduction in birth weight (2863±440 g in women with past or chronic infections vs. 3070±482 g in uninfected women in 2010-2012; mean difference, -164.5 g; 95% CI, -289.7 to -39.4; and 2994±487 g vs. 3117±455 g in 2003-2005; difference, -44.8 g; 95% CI, -139.1 to 49.5). Conclusions: Antimalarial antibodies were reduced and the adverse consequences of P. falciparum infections were increased in pregnant women after 5 years of a decline in the prevalence of malaria. (Funded by Malaria Eradication Scientific Alliance and others).

Inconsistencies between recorded opportunistic infections and WHO HIV staging in western Kenya.

Opportunistic infections (OIs) are the main cause of morbidity and mortality among patients with HIV in developing countries. It is therefore critical that accurate diagnoses are made and that they are correctly recorded and managed. We reviewed 200 randomly selected records of clinical encounters with HIV infected pregnant women attending the ante-natal care (ANC) clinic in July 2012 at the Jaramogi Oginga Odinga Teaching and Referral Hospital in Kenya. None of the clients in WHO stage 4 and 2.8% of those in WHO stage 3 had a new OI diagnosis recorded during the clinical encounter. This data suggests current under-recording of OIs and the inconsistency between WHO staging and OI diagnosis. Structured methods such as SNOMED CT have the potential to improve complete and accurate recording of OIs which, in turn, enable automatedand accurate WHO staging.

Severe and critical cases of H1N1 influenza in pregnancy: a Chinese perspective.

CONTEXT: In 2009, an outbreak of A/H1N1 influenza spread worldwide. Following the start of winter in Liaoning province in China, the number of pregnant women infected with influenza increased significantly. Some of them developed respiratory failure and multiple organ failure. AIMS: The aim of this study was to determine the high-risk factors associated with the development of critical illness in the hospitalized pregnant women with A/H1N1 infection. SETTINGS AND DESIGN: This retrospective cohort study was carried out in the tertiary care obstetric department of a large general hospital. MATERIALS AND METHODS: The clinical data of H1N1 pregnant women hospitalized from November 2009 to January 2010 was reviewed. We classified these cases into severe and critical grades according to H1N1 influenza treatment guidelines. We selected maternal age, gestational age, and the time interval between symptom-onset and hospital admission as related factors of critical illness. STATISTICAL ANALYSIS: Logistic regression analyses to determine the relevance and importance of factors significantly associated with critical illness. RESULTS: Eighteen cases of H1N1 influenza pregnant women were admitted. Ten pregnant women were severe cases and eight pregnant women were critical cases. The maternal age (OR=0.979, 95% CI: 0.749~1.279)and the time interval between symptom-onset and hospital admission (OR=1.41, 95% CI: 0.917~2.169) were not found to be risk factors for critical cases. The significant risk factor associated with critical illness is gestational age (OR=53.726, 95% CI: 131.165~2477.918). The risk varied by weeks of gestation, with an odds ratio of 1.034 (95% CI: 0.968-1.106) during the first trimester, 9.667 (95% CI: 0.750-124.59) during the second trimester, and 87 (95% CI: 6.750-1121.39) during the third trimester. CONCLUSIONS: Gestational age is associated with the risk of developing critical infection. The risk increases with increasing weeks of gestation.

Perinatal sepsis.

Perinatal sepsis is one of the most challenging problems encountered in obstetric and intensive care. Sepsis is a clinical diagnosis and a serious pathologic process involving widespread release of inflammatory mediators that may lead to organ injury or rapid deterioration. Normal physiologic maternal adaptations in the intrapartal and early postpartal period may mask the subtle signs of sepsis. Attention to risk factors and early detection may improve outcome of the woman with perinatal sepsis.

The Stockholm classification of stillbirth.

OBJECTIVE: To design and validate a classification system for audit groups working with stillbirth. The classification includes well-defined primary and associated conditions related to fetal death. DESIGN: Descriptive. SETTING: All delivery wards in Stockholm. POPULATION: Stillbirths from 22 completed weeks in Stockholm, Sweden. METHODS: Parallel to audit work, the Stockholm stillbirth group has developed a classification of conditions related to stillbirth. The classification has been validated. MAIN OUTCOME MEASURE: The classification and the results of the validation are presented. RESULT: The classification with 17 groups identifying underlying conditions related to stillbirth (primary diagnoses) and associated factors which may have contributed to the death (associated diagnoses) is described. The conditions are subdivided into definite, probable and possible relation to the death. An evaluation of 382 cases of stillbirth during 2002-2005 resulted in 382 primary diagnoses and 132 associated diagnoses. The most common conditions identified were intrauterine growth restriction/placental insufficiency (23%), infection (19%), malformations/chromosomal abnormalities (12%). The 'unexplained' group together with the 'unknown' group comprised 18%. Validation was done by reclassification of 95 cases from 2005 by six investigators. The overall agreement regarding primary diagnosis was substantial (kappa=0.70). CONCLUSIONS: The Stockholm classification of stillbirth consists of 17 diagnostic groups allowing one primary diagnosis and if needed, associated diagnoses. Diagnoses are subdivided according to definite, probable and possible relation to stillbirth. Validation showed high degree of agreement regarding primary diagnosis. The classification can provide a useful tool for clinicians and audit groups when discussing cause and underlying conditions of fetal death.

Gérmenes patógenos más frecuentes encontrados en tracto genital de embarazadas en trabajo de parto, entre 35 y 40 semanas de gestación y sus complicaciones materno fetales atendidas en el Hospital Fernando Vélez Paiz: noviembre- diciembre 2007 / Pathogen most frequently found in genital tract of pregnant women in labor, between 35 and 40 weeks of pregnancy and its complications maternal fetal served at the Hospital Fernando Velez Paiz: November-December 2007

El presente estudio realizado, es descriptivo corte transversal, en el periodo de noviembre a diciembre del 2007, con un universo de 601, tomando una muestra por conveniencia de 106 personas que cumplia con los criterios de inclusión y exclusión, que acudieron en trabajo de parto al hospital Fernando Vélez Paíz. Se utilizo el programa estadístico para ciencias sociales (SPSS) 12.0 de Windows para el cálculo de frecuencias simples de las variables cuantitativas, tales como; promedio, desviación estándar. La asociación entre las variables cualitativas se determino a través de pruebas de significancia estadísticas de Chi cuadrado con su estimador Odds Ratio (OR), valor de p, con un intervalo de confianza del 95 por ciento. Se realizó un análisis multivariado de regresión logística para determinar el valor real de los factores y controlar los probables factores de confusión asociados al proceso de infección...

The relationship between prevention of mother to child transmission of HIV and stakeholder decision making in Uganda: implications for health policy.

OBJECTIVES: To explore a selection of stakeholders' use of evidence and other reasons in the relative ranking of the prevention of mother to child HIV transmission with nevirapine in a setting of extreme resource scarcity. DESIGN: Group interviews using nominal group technique with provision of evidence. SETTING: One rural and one urban district in Uganda. PARTICIPANTS: People living with HIV/AIDS, people from the general population, planners, health workers and people with hypertension. MAIN OUTCOME MEASURE: relative ranking of prevention of vertical HIV transmission with nevirapine compared to nine other interventions for different conditions and evaluation of participants' use of evidence in the ranking. RESULTS: In the overall final ranking, prevention of vertical HIV transmission with nevirapine was ranked as number five compared to the other eight conditions. Treatment for childhood diseases and highly active anti retroviral treatment (HAART) for HIV/AIDS were ranked higher. Group specific ranking followed the same pattern, although the people living with HIV-group ranked HAART consistently as number one. CONCLUSIONS: Stakeholders seem to rank prevention of vertical HIV transmission lower than treatment for malaria, pneumonia and diarrhoea. Policies considering prevention of vertical transmission of HIV should consider its implications. This study shows that stakeholders are open to considering evidence in assessing the relative priority of different interventions competing for scarce resources. More research is needed to develop methods that can involve representative stakeholders, including the public, in good and legitimate decisions on priorities.

Identification of diverse HIV type 1 subtypes and dual HIV type 1 infection in pregnant Ugandan women.

Vertical (mother-to-child) transmission accounts for the majority of pediatric HIV-1 infections. Many factors are involved in vertical transmission, however it is not clear which factors are most important for determining whether a mother will transmit HIV-1 to her infant. It has been suggested that HIV-1 subtype may influence vertical transmission and that subtype D viruses may be less likely to be transmitted in this setting. We analyzed HIV-1 gp120 V3 region sequences from the plasma of 20 pregnant Ugandan women of known transmission status who did not receive antiretroviral prophylaxis. V3 regions were cloned, sequenced, and subtyped by phylogenetic analysis. Among 11 women who transmitted HIV-1 to their infants, we detected subtypes A, C, D, and G. Two of the transmitters had dual infection with subtypes A and D. In addition, a third was infected with two distinct strains of subtype G viruses. HIV-1 subtype A and D viruses were found in 9 women who did not transmit the virus to their infants. This study reveals that pregnant Ugandan women harbor diverse HIV-1 subtypes, including women who transmit HIV-1 to their infants. Transmission of HIV-1 with subtype D V3 regions was confirmed in 4 of the 11 transmitters, including 2 who had dual infection with subtype A and D HIV-1.

Urinary tract infections in pregnancy.

Although pregnancy does not increase the prevalence of ASB in women, it does enhance the progression rate from asymptomatic to symptomatic disease. Furthermore, ASB is associated with preterm delivery. Given the fact that identification and eradication of ASB in pregnant women can lower the likelihood of pyelonephritis and prevent preterm delivery, every gravida should be systematically screened for ASB and appropriately treated. In the authors' opinion, a first-trimester urine culture remains the screening test of choice; reliance on symptoms to prompt screening is inadequate because the state of pregnancy can provoke frequency and nocturia. Multiple antibiotic regimens for ASB are safe during pregnancy and effective.

Genital herpes during pregnancy: inability to distinguish primary and recurrent infections clinically.

OBJECTIVE: To determine if the signs and symptoms of genital herpes in pregnancy accurately identify primary genital herpes infections using serologic testing for final classification. METHODS: Twenty-three women with clinical signs and symptoms suggestive of primary genital herpes infections in the second and third trimesters of pregnancy were subsequently cultured and tested serologically (for herpes simplex virus type 1 and herpes simplex virus type 2 antibodies) and classified as having true primary (no herpes simplex virus type 1 or type 2 antibodies), nonprimary (heterologous herpes simplex virus antibodies present), or recurrent (homologous antibodies present) infections. RESULTS: Only one of 23 women with clinical illnesses consistent with primary genital herpes virus simplex infections had serologically-verified primary infection. This primary infection was caused by herpes simplex virus type 1. Three women had nonprimary type 2 infections, and 19 women had recurrent infections. Among culture-proven recurrent infections, 12 were caused by herpes simplex virus type 2 and three by herpes simplex virus type 1. Only one infant was born preterm, and no clinically significant perinatal morbidity was observed. CONCLUSION: Correct classification of gestational genital herpes infections can be accomplished only when clinical evaluation is correlated with viral isolation and serologic testing using a type-specific assay. Severe first episodes of genital herpes infections among women in the second and third trimesters of pregnancy are not usually primary infections and are not commonly associated with perinatal morbidity.