Evaluating congenital syphilis in a reverse sequence testing environment.

OBJECTIVES: To examine the effect of maternal reverse-sequence (RS) syphilis screening on management of infants at risk for congenital syphilis (CS) using a standardized approach. STUDY DESIGN: A retrospective study from 2011 to 2014 at an academic medical center using RS testing, involving chemiluminescent immunoassay (CIA), rapid plasma  reagin (RPR), and fluorescent treponemal antibody-absorption (FTA-ABS) assays for syphilis. Clinical management and outcomes of infants born to mothers with discordant (CIA+/RPR-/FTA+) serology were compared with national or internal guidelines. RESULTS: Sixty-three infants were classified as discordant (n = 21), presumed false positive (CIA+/RPR-/FTA-; n = 16), or true positive (CIA+/RPR+; n = 26) based on maternal serology. Only 24% of cases in the discordant group underwent recommended full evaluation. None of the evaluated infants in the discordant group (n = 8) were diagnosed with CS. CONCLUSIONS: Management of infants with discordant maternal RS serology remained reliant on clinical judgment. In our high-risk population, RS testing did not identify additional cases of CS.

Differentiating Streptococcus pseudoporcinus from GBS: could this have implications in pregnancy?

BACKGROUND: Streptococcus agalactiae (GBS) is a common pathogen known to cause neonatal and maternal infectious morbidity. Streptococcus pseudoporcinus (S pseudoporcinus) is a separate, recently identified ß-hemolytic gram-positive coccus that can cause false-positive results on standard GBS agglutination testing assays. OBJECTIVE: To determine the prevalence and clinical implications of Streptococcus pseudoporcinus colonization in pregnancy. MATERIALS AND METHODS: This is a 2-year retrospective cohort study comparing pregnant women colonized with GBS to those colonized with S. pseudoporcinus. A proteomics method of identification, namely, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, was used to distinguish between S. pseudoporcinus and GBS colonization. Antibiotic susceptibility testing was carried out on all specimens. Maternal and neonatal chart reviews were conducted to identify predictors of S. pseudoporcinus colonization and to compare maternal and neonatal outcomes. RESULTS: S. pseudoporcinus colonization occurred in 1.6% of all pregnancies. A total of 2.5% of all GBS-positive results by agglutination assay were false positive, instead reflecting S. pseudoporcinus colonization. Clindamycin resistance among S. pseudoporcinus isolates is uncommon. S. pseudoporcinus colonization in pregnancy is independently associated with African American race, tobacco use, and body mass index ≥35. Preterm premature rupture of membranes or spontaneous preterm birth was more common in patients colonized with S. pseudoporcinus. CONCLUSION: Although the prevalence of S. pseudoporcinus colonization is low, it primarily occurs in African American women and is associated with preterm premature rupture of membranes or spontaneous preterm birth when compared to individuals colonized with GBS.

Methyl mercury, but not inorganic mercury, associated with higher blood pressure during pregnancy.

Prior studies addressing associations between mercury and blood pressure have produced inconsistent findings; some of this may result from measuring total instead of speciated mercury. This cross-sectional study of 263 pregnant women assessed total mercury, speciated mercury, selenium, and n-3 polyunsaturated fatty acids in umbilical cord blood and blood pressure during labor and delivery. Models with a) total mercury or b) methyl and inorganic mercury were evaluated. Regression models adjusted for maternal age, race/ethnicity, prepregnancy body mass index, neighborhood income, parity, smoking, n-3 fatty acids and selenium. Geometric mean total, methyl, and inorganic mercury concentrations were 1.40µg/L (95% confidence interval: 1.29, 1.52); 0.95µg/L (0.84, 1.07); and 0.13µg/L (0.10, 0.17), respectively. Elevated systolic BP, diastolic BP, and pulse pressure were found, respectively, in 11.4%, 6.8%, and 19.8% of mothers. In adjusted multivariable models, a one-tertile increase of methyl mercury was associated with 2.83mmHg (0.17, 5.50) higher systolic blood pressure and 2.99mmHg (0.91, 5.08) higher pulse pressure. In the same models, an increase of one tertile of inorganic mercury was associated with -1.18mmHg (-3.72, 1.35) lower systolic blood pressure and -2.51mmHg (-4.49, -0.53) lower pulse pressure. No associations were observed with diastolic pressure. There was a non-significant trend of higher total mercury with higher systolic blood pressure. We observed a significant association of higher methyl mercury with higher systolic and pulse pressure, yet higher inorganic mercury was significantly associated with lower pulse pressure. These results should be confirmed with larger, longitudinal studies.

Prenatal exposure to tobacco smoke leads to increased mitochondrial DNA content in umbilical cord serum associated to reduced gestational age.

We investigated if prenatal exposures to tobacco smoke lead to changes in mitochondrial DNA content (mtDNA) in cord serum and adversely affect newborns' health. Umbilical cord serum cotinine levels were used to determine in utero exposure to smoking. Cord serum mtDNA was measured by quantitative polymerase chain reaction analysis of the genes coding for cytochrome c oxidase1 (MT-CO1) and cytochrome c oxidase2 (MT-CO2). Log transformed levels of mtDNA coding for MT-CO1 and MT-CO2 were significantly higher among infants of active smokers with higher serum level of cotinine (p < 0.05) and inversely associated with gestational age (p = 0.08; p = 0.02). Structural equation modeling results confirmed a positive association between cotinine and MT-CO1 and2 (p < 0.01) and inverse associations with gestational age (p = 0.02) and IGF-1 (p < 0.01). We identified a dose-dependent increase in the level of MT-CO1 and MT-CO2 associated to increased cord serum cotinine and decreased gestational age.

A Model for the Departmental Quality Management Infrastructure Within an Academic Health System.

As quality improvement and patient safety come to play a larger role in health care, academic medical centers and health systems are poised to take a leadership role in addressing these issues. Academic medical centers can leverage their large integrated footprint and have the ability to innovate in this field. However, a robust quality management infrastructure is needed to support these efforts. In this context, quality and safety are often described at the executive level and at the unit level. Yet, the role of individual departments, which are often the dominant functional unit within a hospital, in realizing health system quality and safety goals has not been addressed. Developing a departmental quality management infrastructure is challenging because departments are diverse in composition, size, resources, and needs.In this article, the authors describe the model of departmental quality management infrastructure that has been implemented at the Johns Hopkins Hospital. This model leverages the fractal approach, linking departments horizontally to support peer and organizational learning and connecting departments vertically to support accountability to the hospital, health system, and board of trustees. This model also provides both structure and flexibility to meet individual departmental needs, recognizing that independence and interdependence are needed for large academic medical centers. The authors describe the structure, function, and support system for this model as well as the practical and essential steps for its implementation. They also provide examples of its early success.

A home calendar and recall method of last menstrual period for estimating gestational age in rural Bangladesh: a validation study.

BACKGROUND: The best method of gestational age assessment is by ultrasound in the first trimester; however, this method is impractical in large field trials in rural areas. Our objective was to assess the validity of gestational age estimated from prospectively collected date of last menstrual period (LMP) using crown-rump length (CRL) measured in early pregnancy by ultrasound. METHODS: As part of a large, cluster-randomized, controlled trial in rural Bangladesh, we collected dates of LMP by recall and as marked on a calendar every 5 weeks in women likely to become pregnant. Among those with a urine-test confirmed pregnancy, a subset with gestational age of <15 weeks (n = 353) were enrolled for ultrasound follow-up to measure CRL. We compared interview-assessed LMP with CRL gestational age estimates and classification of preterm, term, and post-term births. RESULTS: LMP-based gestational age was higher than CRL by a mean (SD) of 2.8 (10.7) days; differences varied by maternal education and preterm birth (P < 0.05). Lin's concordance correlation coefficient was good at ultrasound [0.63 (95 % CI 0.56, 0.69)] and at birth [0.77 (95 % CI 0.73, 0.81)]. Validity of classifying preterm birth was high but post-term was lower, with specificity of 96 and 89 % and sensitivity of 86 and 67 %, respectively. Results were similar by parity. CONCLUSIONS: Prospectively collected LMP provided a valid estimate of gestational age and preterm birth in a rural, low-income setting and may be a suitable alternative to ultrasound in programmatic settings and large field trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT00860470.

The influence of atopy and asthma on immune responses in inner-city adults.

Asthma in the inner-city population is usually atopic in nature, and is associated with significant morbidity and mortality. However, the underlying immune abnormalities that underlie asthma in urban adults have not been well defined. We investigated the influence of atopy and asthma on cytokine responses of inner-city adult women to define immune abnormalities associated with asthma and atopy. Blood samples were collected from 509 of 606 inner-city women enrolled in the Urban Environment and Childhood Asthma (URECA) study. We tested for associations between atopy and asthma status and cytokine responses in peripheral blood mononuclear cells incubated ex vivo with a panel of innate and adaptive immune stimulants. Atopic subjects had heightened Th2 cytokine responses (IL-4, IL-5, IL-13) to cockroach and dust mite antigens, tetanus toxoid, and phytohemagglutinin (P < 0.05 for all). Differences in cytokine responses were greatest in response to stimulation with cockroach and dust mite. In a multivariate analysis, atopy was broadly related to increased Th2-like responses to all antigens and PHA, while asthma was only weakly related to mitogen-induced IL-4 and IL-5 responses. There were few asthma or allergy-related differences in responses to innate stimuli, including IFN-α and IFN-γ responses. In this inner-city adult female population, atopy is associated with enhanced Th2 responses to allergens and other stimuli, and there was little or no additional signal attributable to asthma. In particular, these data indicate that altered systemic interferon and innate immune responses are not associated with allergies and/or asthma in inner-city women.

DNA methylation of cord blood cell types: Applications for mixed cell birth studies.

Epigenome-wide association studies of disease widely use DNA methylation measured in blood as a surrogate tissue. Cell proportions can vary between people and confound associations of exposure or outcome. An adequate reference panel for estimating cell proportions from adult whole blood for DNA methylation studies is available, but an analogous cord blood cell reference panel is not yet available. Cord blood has unique cell types and the epigenetic signatures of standard cell types may not be consistent throughout the life course. Using magnetic bead sorting, we isolated cord blood cell types (nucleated red blood cells, granulocytes, monocytes, natural killer cells, B cells, CD4(+)T cells, and CD8(+)T cells) from 17 live births at Johns Hopkins Hospital. We confirmed enrichment of the cell types using fluorescence assisted cell sorting and ran DNA from the separated cell types on the Illumina Infinium HumanMethylation450 BeadChip array. After filtering, the final analysis was on 104 samples at 429,794 probes. We compared cell type specific signatures in cord to each other and methylation at 49.2% of CpG sites on the array differed by cell type (F-test P < 10(-8)). Differences between nucleated red blood cells and the remainder of the cell types were most pronounced (36.9% of CpG sites at P < 10(-8)) and 99.5% of these sites were hypomethylated relative to the other cell types. We also compared the mean-centered sorted cord profiles to the available adult reference panel and observed high correlation between the overlapping cell types for granulocytes and monocytes (both r=0.74), and poor correlation for CD8(+)T cells and NK cells (both r=0.08). We further provide an algorithm for estimating cell proportions in cord blood using the newly developed cord reference panel, which estimates biologically plausible cell proportions in whole cord blood samples.

Postdischarge surveillance for infection following cesarean section: A prospective cohort study comparing methodologies.

OBJECTIVE: To assess how enhanced postdischarge telephone follow-up calls would improve case finding for surgical site infection (SSI) surveillance after cesarean section. METHODS: We conducted a prospective cohort study of all patients who delivered by cesarean section between April 22 and August 22, 2010. In addition to our routine surveillance, using clinical databases and electronic patient records, we also made follow-up calls to the patients at 7, 14, and 30 days postoperation. A standard questionnaire with questions about symptoms of SSI, health-seeking behaviors, and treatment received was administered. Descriptive statistics and univariate analysis were performed to assess the effect of the enhanced surveillance. RESULTS: One hundred ninety-three patients underwent cesarean section during this study period. Standard surveillance identified 14 infections with telephone follow-ups identifying an additional 5 infections. Using the call as a gold standard, the sensitivity of the standard methodology to capture SSI was 73.3%. The duration of the calls ranged from 1 to 5 minutes and were well received by the patients. CONCLUSIONS: Results suggest that follow-up telephone calls to patients following cesarean section identifies 26.3% of the total SSIs. Enhanced surveillance can provide more informed data to enhance performance and avoid underestimation of rates.

Cord Blood Methylmercury and Fetal Growth Outcomes in Baltimore Newborns: Potential Confounding and Effect Modification by Omega-3 Fatty Acids, Selenium, and Sex.

BACKGROUND: Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions. OBJECTIVE: Our objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex. METHODS: This cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004-2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg). RESULTS: Geometric mean cord blood MeHg was 0.94 µg/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, ßln(MeHg) = -0.045 (g/cm(3)) × 100 (95% CI: -0.084, -0.005). There was no evidence of a MeHg × sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg × n-3 HUFAs interaction with birth length [among low n-3 HUFAs, ßln(MeHg) = 0.40 cm, 95% CI: -0.02, 0.81; among high n-3 HUFAs, ßln(MeHg) = -0.15, 95% CI: -0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, ßln(MeHg) = 0.01 cm, 95% CI: -0.27, 0.29; among high n-3 HUFAs, ßln(MeHg) = -0.37, 95% CI: -0.63, -0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, ßln(MeHg) without these variables was -16.8 g (95% CI: -75.0, 41.3) versus -29.7 (95% CI: -93.9, 34.6) with all covariates. Corresponding values for ponderal index were -0.030 (g/cm(3)) × 100 (95% CI: -0.065, 0.005) and -0.045 (95% CI: -0.084, -0005). CONCLUSION: We observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies.

Recognition of Streptococcus pseudoporcinus Colonization in Women as a Consequence of Using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Group B Streptococcus Identification.

During a 14-month period of using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for group B streptococcus (GBS) identification, we recovered 32 (1%) Streptococcus pseudoporcinus isolates from 3,276 GBS screening cultures from female genital sources (25 isolates from pregnant women and 7 from nonpregnant women). An additional two S. pseudoporcinus isolates were identified from a urine culture and a posthysterectomy wound culture. These isolates were found to cross-react with three different GBS antigen agglutination kits, PathoDx (Remel) (93%), Prolex (Pro-Lab Diagnostics) (38%), and Streptex (Remel) (53%). New approaches to bacterial identification in routine clinical microbiology laboratories may affect the prevalence of S. pseudoporcinus.

Obstetric Surgical Site Infections: 2 Grams Compared With 3 Grams of Cefazolin in Morbidly Obese Women.

OBJECTIVE: To estimate whether morbidly obese gravid patients were less likely to develop a surgical site infection after receiving a higher dose of preoperative prophylactic antibiotics. METHODS: A retrospective cohort study of morbidly obese pregnant women undergoing cesarean delivery was conducted at two tertiary care centers from 2008 to 2013. Exposure was defined as receiving 2 g compared with 3 g cefazolin preoperatively. Disease was defined by diagnosis of a surgical site infection using Centers for Disease Control and Prevention criteria. We estimated a sample size of 141 patients in each group for a 67% reduction (15% to 5%) in risk for a surgical site infection. RESULTS: There were 335 women included in the cohort with a median absolute weight of 310 (interquartile range 299-333) pounds. Forty-four (13.1%) women were diagnosed with a surgical site infection. There was no difference in surgical site infection among those women who received 2 g compared with 3 g cefazolin (13.1% [23/175] compared with 13.1% [21/160]; P=.996). Labor (crude odds ratio [OR] 2.31, 95% confidence interval [CI] 1.21-4.40), internal labor monitoring (OR 2.78, 1.45-5.31), blood loss greater than 1,500 mL (OR 2.15, 1.09-5.78), and staple closure (OR 2.2, 1.15-4.21) were associated with a surgical site infection among the entire cohort. After multivariable analysis, blood loss greater than 1,500 mL (adjusted OR 3.32, 1.32-8.37) and staple closure (adjusted OR 2.45, 1.19-5.02) remained associated with an increased risk for a surgical site infection, whereas 3 g cefazolin still was not associated with reduced risk for a surgical site infection (adjusted OR 1.33, 0.64-2.74). CONCLUSION: In our multicenter retrospective cohort study, preoperative 3 g cefazolin prophylaxis administered to morbidly obese gravid patients did not reduce surgical site infections. LEVEL OF EVIDENCE: III.

Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns.

BACKGROUND: Human exposure to the widespread environmental contaminant mercury is a known risk factor for common diseases such as cancer, cardiovascular disease and neurological disorders through poorly characterized mechanisms. Evidence suggests mercury exposure may alter DNA methylation levels, but to date, the effects in early life on a genome-wide scale have not been investigated. METHODS: A study sample of 141 newborns was recruited in Baltimore, MD, USA and total mercury and methylmercury were measured in cord blood samples. We quantified genome-wide DNA methylation data using CHARM 2.0, an array-based method, and used region-finding analyses to identify concentration-associated differentially methylated regions (DMRs). To test for replication of these identified DMRs in the pilot, or Vanguard, phase of the National Children's Study (NCS), we compared bisulfite-pyrosequenced DNA at candidate regions from 85 whole cord blood samples with matched first trimester maternal mercury concentration measures. RESULTS: Total mercury concentration was associated with methylation at DMRs inside ANGPT2 and near PRPF18 genes [false discovery rate (FDR) < 0.05], as well as DMRs near FOXD2 and within TCEANC2 (FDR< 0.1) genes. Methylmercury concentration was associated with an overlapping DMR within TCEANC2 (FDR< 0.05). In NCS replication analyses, methylation levels at three of four cytosine-guanine DNA dinucleotides (CpG sites) within the TCEANC2 DMR were associated with total mercury concentration (P < 0.05), and this association was diminished after adjusting for estimated cell proportions. CONCLUSIONS: Evidence for an association between mercury and DNA methylation at the TCEANC2 region was found, which may represent a mercury-associated shift in cord blood cell composition or a change in methylation within blood cell types. Further confirmatory studies are needed.

Elucidating the molecular basis of adverse health effects from exposure to anthropogenic polyfluorinated compounds using toxicoproteomic approaches.

Linear, short-chain polyfluorinated and perfluorinated alkyl compounds, often referred to as PFCs, have been in worldwide use as surfactants and polymer precursors for decades, and environmental dispersal of these highly persistent compounds represents a public health threat. Whereas ubiquitous low-level exposure to these compounds has been demonstrated in human populations from around the world, the exact mechanisms of toxicity and their toxic potency remain subject to investigation and scientific dispute. As with other environmental exposures, a major hurdle for gaining a better understanding of their human health impacts is the limited utility of cell culture and animal models serving as convenient, yet imperfect proxies to human physiology and disease. The present communication provides a brief overview of the current understanding of potential health effects of PFC exposure and examines how new toxicoproteomic methodologies can provide insight into the molecular mechanism of PFC exposure. Furthermore, we showcase an exemplary data set to illustrate how toxicoproteomic, population-wide studies might overcome limitations of animal models to more fully understand the metabolism and effects of PFCs and other environmental stressors where it matters most, in human populations experiencing real-world, chronic, low-level exposures.

A potential method to lower risk for surgical site infection during cesarean birth.

It's common practice to use a preparation containing chlorhexidine to prepare the surgical site before cesarean birth. We observed an interaction between ultrasound gel, used for electronic fetal heart monitoring before birth, and chlorhexidine. This interaction creates the potential for surgical site infection. Using isopropyl alcohol to thoroughly remove all gel before application of chlorhexidine was associated with reduced rates of postsurgical infection at our institution.

Diagnostic accuracy of fetal heart rate monitoring in the identification of neonatal encephalopathy.

OBJECTIVE: To estimate the diagnostic accuracy of electronic fetal heart rate abnormalities in the identification of neonates with encephalopathy treated with whole-body hypothermia. METHODS: Between January 1, 2007, and July 1, 2013, there were 39 neonates born at two hospitals within our system treated with whole-body hypothermia within 6 hours of birth. Neurologically normal control neonates were matched to each case by gestational age and mode of delivery in a two-to-one fashion. The last hour of electronic fetal heart rate monitoring before delivery was evaluated by three obstetricians blinded to outcome. RESULTS: The differences in tracing category were not significantly different (neonates in the case group 10.3% I, 76.9% II, 12.8% III; neonates in the control group 9.0% I, 89.7% II, 1.3% III; P=.18). Bivariate analysis showed neonates in the case group had significantly increased late decelerations, total deceleration area 30 (debt 30) and 60 minutes (debt 60) before delivery and were more likely to be nonreactive. Multivariable logistic regression showed neonates in the case group had a significant decrease in early decelerations (P=.03) and a significant increase in debt 30 (.01) and debt 60 (P=.005). The area under the receiver operating characteristic curve, sensitivity, and specificity were 0.72, 23.1%, and 94.9% for early decelerations; 0.66, 33.3%, and 87.2% for debt 30, and 0.68, 35.9%, and 89.7% for debt 60, respectively. CONCLUSION: Abnormalities during the last hour of fetal heart rate monitoring before delivery are poorly predictive of neonatal hypoxic-ischemic encephalopathy qualifying for whole-body hypothermia treatment within 6 hours of birth. LEVEL OF EVIEDENCE: II.

Decreasing cesarean section surgical site infection: an ongoing comprehensive quality improvement program.

This report illustrates how the "plan-do-study-act" method of continuous quality improvement can be effective in reducing surgical site infection after cesarean delivery.