Integrating Implementation Science with Quality Improvement to Improve Perinatal Outcomes.

Implementation science is an interdisciplinary field that seeks to contribute generalizable knowledge that can improve the translation of clinical evidence in routine care. To promote the integration of implementation science approaches with health care quality improvement, the authors offer a framework that links the Model for Improvement with implementation strategies and methods. Perinatal quality improvement teams can leverage the robust frameworks of implementation science to diagnose implementation barriers, select implementation strategies, and assess the strategies' contribution to improving care. Partnerships between implementation scientists and quality improvement teams could accelerate efforts by both groups to achieve measurable improvements in care.

A Novel Mobile Health Tool for Home-Based Identification of Neonatal Illness in Uganda: Formative Usability Study.

BACKGROUND: While early identification of neonatal illness can impact neonatal mortality rates and reduce the burden of treatment, identifying subtle clinical signs and symptoms of possible severe illness is especially challenging in neonates. The World Health Organization and the United Nations Children's Fund developed the Integrated Management of Neonatal Childhood Illness guidelines, an evidence-based tool highlighting seven danger signs to assess neonatal health. Currently, many mothers in low-resource settings rely on home visits from community health workers (CHWs) to determine if their baby is sick. However, CHWs visit infrequently, and illness is often detected too late to impact survival. Thus, delays in illness identification pose a significant barrier to providing expedient and effective care. Neonatal Monitoring (NeMo), a novel neonatal assessment tool, seeks to increase the frequency of neonatal screening by task-shifting identification of neonatal danger signs from CHWs to mothers. OBJECTIVE: This study aimed to explore the usability and acceptability of the NeMo system among target users and volunteer CHWs by assessing ease of use and learnability. METHODS: Simulated device use and semistructured interviews were conducted with 32 women in the Iganga-Mayuge districts in eastern Uganda to evaluate the usability of the NeMo system, which involves a smartphone app paired with a low cost, wearable band to aid in identification of neonatal illness. Two versions of the app were evaluated using a mixed methods approach, and version II of the app contained modifications based on observations of the first cohort's use of the system. During the posed scenario simulations, participants were offered limited guidance from the study team in order to probe the intuitiveness of the NeMo system. The ability to complete a set of tasks with the system was tested and recorded for each participant and closed- and open-ended questions were used to elicit user feedback. Additionally, focus groups with 12 CHWs were conducted to lend additional context and insight to the usability and feasibility assessment. RESULTS: A total of 13/22 subjects (59%) using app version I and 9/10 subjects (90%) using app version II were able to use the phone and app with no difficulty, despite varying levels of smartphone experience. Following modifications to the app's audio instructions in version II, participants' ability to accurately answer qualitative questions concerning neonatal danger signs improved by at least 200% for each qualitative danger sign. All participants agreed they would trust and use the NeMo system to assess the health of their babies. Furthermore, CHWs emphasized the importance of community sensitization towards the system to encourage its adoption and regular use, as well as the decision to seek care based on its recommendations. CONCLUSIONS: The NeMo system is an intuitive platform for neonatal assessment in a home setting and was found to be acceptable to women in rural Uganda.

Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: a matched case-control study.

BACKGROUND: Reducing death due to neonatal sepsis is a global health priority, however there are limited tools to facilitate early recognition and treatment. We hypothesized that measuring circulating biomarkers of endothelial function and integrity (i.e. Angiopoietin-Tie2 axis) would identify young infants with sepsis and predict their clinical outcome. METHODS: We conducted a matched case-control (1:3) study of 98 young infants aged 0-59 days of life presenting to a referral hospital in Bangladesh with suspected sepsis. Plasma levels of Ang-1, Ang-2, sICAM-1, and sVCAM-1 concentrations were measured at admission. The primary outcome was mortality (n = 18); the secondary outcome was bacteremia (n = 10). RESULTS: Ang-2 concentrations at presentation were higher among infants who subsequently died of sepsis compared to survivors (aOR 2.50, p = 0.024). Compared to surviving control infants, the Ang-2:Ang-1 ratio was higher among infants who died (aOR 2.29, p = 0.016) and in infants with bacteremia (aOR 5.72, p = 0.041), and there was an increased odds of death across Ang-2:Ang-1 ratio tertiles (aOR 4.82, p = 0.013). CONCLUSIONS: This study provides new evidence linking the Angiopoietin-Tie2 pathway with mortality and bacteremia in young infants with suspected sepsis. If validated in additional studies, markers of the angiopoietin-Tie2 axis may have clinical utility in risk stratification of infants with suspected sepsis.

Effect of Maternal Obesity on Maternal-Fetal Transfer of Preoperative Cefazolin at Cesarean Section.

OBJECTIVES: American Congress of Obstetricians and Gynecologists recommends a single dose of antibiotic prophylaxis before all cesarean sections (C/S). This recommendation is based on pharmacokinetic studies that include only non-obese patients. We sought to evaluate 1) cefazolin plasma concentrations among obese and non-obese patients after administration of a 2-g cefazolin dose for prevention of surgical wound infections, and 2) whether cefazolin concentration in fetal circulation may be protective against pathogens that cause early onset neonatal sepsis. METHODS: Maternal and fetal cefazolin plasma concentrations were compared between obese (body mass index [BMI] ≥ 30 kg/m2) and non-obese (BMI < 25 kg/m2) healthy, term pregnant women undergoing scheduled C/S. Liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods were used for quantification of total and free cefazolin concentrations in maternal blood (MB) and umbilical cord blood (UCB). RESULTS: Eight women were screened and consented. There was no difference between groups in MB total and free cefazolin concentrations. All MB samples had total and free cefazolin concentrations greater than the minimum inhibitory concentration 90 (MIC90) for Group B Streptococcus (GBS), Staphylococcus aureus, and Escherichia coli. All UCB samples had total and free cefazolin concentrations greater than MIC90 for GBS and S aureus, even when administered as briefly as 18 minutes before delivery. A lower concentration of total cefazolin was detected in UCB of neonates of obese women compared to non-obese women (p > 0.05). CONCLUSIONS: Administration of 2 g of cefazolin to women undergoing scheduled C/S might be an adequate prophylactic dose for surgical wound infection in both non-obese and obese patients; and cefazolin concentration in fetal circulation may be protective against GBS and S aureus.

Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy.

BACKGROUND: There are no definitive markers to aid in diagnosis of neonatal encephalopathy (NE). The purpose of our study was (1) to identify and evaluate the utility of neuronal nitric oxide synthase (NOS1) in umbilical cord blood as a NE biomarker and (2) to identify the source of NOS1 in umbilical cord blood. METHODS: This was a nested case-control study of neonates >35 weeks of gestation. ELISA for NOS1 in umbilical cord blood was performed. Sources of NOS1 in umbilical cord were investigated by immunohistochemistry, western blot, ELISA, and quantitative PCR. Furthermore, umbilical cords of full-term neonates were subjected to 1% hypoxia ex vivo. RESULTS: NOS1 was present in umbilical cord blood and increased in NE cases compared with controls. NOS1 was expressed in endothelial cells of the umbilical cord vein, but not in artery or blood cells. In ex vivo experiments, hypoxia was associated with increased levels of NOS1 in venous endothelial cells of the umbilical cord as well as in ex vivo culture medium. CONCLUSION: This is the first study to investigate an early marker of NE. NOS1 is elevated with hypoxia, and further studies are needed to investigate it as a valuable tool for early diagnosis of neonatal brain injury.

Antibiotic Therapy for Chorioamnionitis to Reduce the Global Burden of Associated Disease.

Chorioamnionitis is associated with significant maternal and neonatal morbidity and mortality throughout the world. In developed countries, great progress has been made to minimize the impact of chorioamnionitis, through timely diagnosis and appropriate treatment. In the global setting, where many women deliver outside the healthcare facilities, this diagnosis is frequently overlooked and not properly treated. In addition to its impact on maternal health, a significant proportion of neonatal morbidity and mortality can be prevented by both recognition and access to readily available treatment. With the increasing focus on saving the most vulnerable members of society, we echo the need for providing parturient women with suspected chorioamnionitis universal access to appropriate therapy. We describe known effective antibiotic therapies for chorioamnionitis and provide an overview of additional potential antimicrobial treatments that might be effectively implemented in areas with limited access to care.

Early skin-to-skin contact for healthy full-term infants after vaginal and caesarean delivery: a qualitative study on clinician perspectives.

AIMS AND OBJECTIVES: This study aims to provide insight into key factors from a clinician's perspective that influence uninterrupted early skin-to-skin contact after vaginal and caesarean delivery of healthy full-term infants. BACKGROUND: Early skin-to-skin contact of healthy full-term infants ideally begins immediately after birth and continues for the first hour or the first breastfeed as recommended by the Baby Friendly Hospital Initiative. However, adoption of early skin-to-skin contact is low in many settings and the barriers that hinder its universal use are not well understood. DESIGN: An exploratory qualitative research design using semi-structured interviews. METHODS: Eleven clinicians were interviewed, including five registered nurses and one medical doctor from the obstetrics and gynaecology unit as well as four registered nurses and one medical doctor from the neonatal intensive care unit. Core topics that were discussed included perceptions on early skin-to-skin contact and facilitating factors and barriers to early skin-to-skin contact after vaginal and caesarean delivery. Interview sessions were recorded, transcribed and analysed using a thematic analysis approach. A coding framework was developed from which subthemes emerged. The overall themes were adopted from Lee et al.'s thematic framework to categorise factors into institutional, familial-level and implementation factors. FINDINGS: Critical institutional factors included inadequate staffing and education of clinicians on early skin-to-skin contact. On a familial level, parental education and motivation were identified as important factors. Barriers to implementation included the absence of a clinical algorithm and unclear definitions for eligible mothers and infants. CONCLUSIONS: Various facilitating factors and barriers to early skin-to-skin contact of healthy full-term infants born via vaginal and caesarean delivery were identified. RELEVANCE TO CLINICAL PRACTICE: Addressing these factors can help to provide a better understanding of clinician perspectives on early skin-to-skin contact and help guide its implementation as standard of care for healthy full-term infants.

Population-based Incidence and Etiology of Community-acquired Neonatal Viral Infections in Bangladesh: A Community-based and Hospital-based Surveillance Study.

BACKGROUND: The etiology of >90% of cases of suspected neonatal infection remains unknown. We conducted community-based surveillance in conjunction with hospital-based surveillance in a rural region in Bangladesh from June 2006 to September 2007 to assess the incidence and etiology of community-acquired viral infections among neonates. METHODS: Community health workers (CHWs) assessed neonates at home on days 0, 2, 5 and 8 after birth and referred cases of suspected illness to the hospital (CHW surveillance). Among neonates with clinically suspected upper respiratory tract infection (URTI), pneumonia, sepsis and/or meningitis, virus identification studies were conducted on nasal wash, cerebrospinal fluid and/or blood specimens. In the hospital-based surveillance, similar screening was conducted among all neonates (referred by CHWs and self-referred) who were admitted to the hospital. RESULTS: CHW surveillance found an incidence rate of 15.6 neonatal viral infections per 1000 live births with 30% of infections identified on the day of birth. Among neonates with suspected sepsis, a viral etiology was identified in 36% of cases, with enterovirus accounting for two-thirds of those infections. Respiratory syncytial virus was the most common etiologic agent among those with viral pneumonia (91%) and URTI (68%). There was a low incidence (1.2%) of influenza in this rural population. CONCLUSION: Viral infections are commonly associated with acute newborn illness, even in the early neonatal period. The estimated incidence was 5-fold greater than reported previously for bacterial infections. Low-cost preventive measures for neonatal viral infections are urgently needed.

Prenatal cerebellar hemorrhage: fetal and postnatal neuroimaging findings and postnatal outcome.

BACKGROUND: Despite significant progress in fetal neuroimaging techniques, only a few well-documented examples of prenatal cerebellar hemorrhages are available in the literature. In the majority of these individuals, the diagnosis of prenatal cerebellar hemorrhages led to termination of pregnancy or death occurred in utero; data about postnatal outcome of children with prenatal diagnosis of cerebellar hemorrhages are scant. We describe fetal and postnatal neuroimaging findings and the neurodevelopmental outcome of a child with a large cerebellar hemorrhage that occurred at approximately 27 weeks' gestation. METHOD: Data about neurological features and neurodevelopmental outcome were collected from the clinical history and follow-up examination. All pre- and postnatal MRI data were qualitatively evaluated for infra- and supratentorial abnormalities. RESULTS: Fetal MRI at 27 weeks' gestation showed a T1-hyperintense and T2-hypointense lesion within the cerebellum suggestive of bilateral cerebellar hemorrhages with extension into the adjacent subarachnoid, subdural, and intraventricular spaces. The prenatal cerebellar hemorrhage was possibly related to maternal sepsis. Postnatal MRI showed encephalomalacic changes involving the vermis and both cerebellar hemispheres. Neurodevelopmental follow-up at 15 months of age was concerning for global developmental delay and significant right esotropia. CONCLUSION: This child illustrates (1) the role of prenatal neuroimaging in the diagnosis of fetal cerebellar hemorrhages, (2) the significance of cerebellar involvement for neurodevelopment, and (3) the importance of the collection of postnatal outcome data in children with prenatal diagnosis of cerebellar hemorrhage.

Current management and long-term outcomes following chorioamnionitis.

Chorioamnionitis is the process of active infection within the amniotic cavity that induces an inflammatory response. A wide variety of pathologic organisms can cause chorioamnionitis. Prompt diagnosis and timely treatment with broad-spectrum antibiotics can help avert the significant short-term and long-term consequences that may result. This review aims to summarize the up-to-date diagnosis criteria, treatment protocols, and long-term sequelae of missed diagnoses or poorly treated disease. It also calls for future studies that aim to better understand the mechanism of disease and to develop better detection and intervention methods to prevent the significant associated morbidity.

Newborn care practices in rural Bangladesh: Implications for the adaptation of kangaroo mother care for community-based interventions.

Bangladesh has one of the world's highest rates of low birth weight along with prevalent traditional care practices that leave newborns highly vulnerable to hypothermia, infection, and early death. We conducted formative research to explore existing newborn care practices in rural Bangladesh with an emphasis on thermal protection, and to identify potential facilitators, barriers, and recommendations for the community level delivery of kangaroo mother care (CKMC). Forty in-depth interviews and 14 focus group discussions were conducted between September and December 2012. Participants included pregnant women and mothers, husbands, maternal and paternal grandmothers, traditional birth attendants, village doctors, traditional healers, pharmacy men, religious leaders, community leaders, and formal healthcare providers. Audio recordings were transcribed and translated into English, and the textual data were analyzed using the Framework Approach. We find that harmful newborn care practices, such as delayed wrapping and early initiation of bathing, are changing as more biomedical advice from formal healthcare providers is reaching the community through word-of-mouth and television campaigns. While the goal of CKMC was relatively easily understood and accepted by many of the participants, logistical and to a lesser extent ideological barriers exist that may keep the practice from being adopted easily. Women feel a sense of inevitable responsibility for household duties despite the desire to provide the best care for their new babies. Our findings showed that participants appreciated CKMC as an appropriate treatment method for ill babies, but were less accepting of it as a protective method of caring for seemingly healthy newborns during the first few days of life. Participants highlighted the necessity of receiving help from family members and witnessing other women performing CKMC with positive outcomes if they are to adopt the behavior themselves. Focusing intervention messages on building a supportive environment for CKMC practice will be critical for the intervention's success.

Perinatal biomarkers in prematurity: early identification of neurologic injury.

Over the past few decades, biomarkers have become increasingly utilized as non-invasive tools in the early diagnosis and management of various clinical conditions. In perinatal medicine, the improved survival of extremely premature infants who are at high risk for adverse neurologic outcomes has increased the demand for the discovery of biomarkers in detecting and predicting the prognosis of infants with neonatal brain injury. By enabling the clinician to recognize potential brain damage early, biomarkers could allow clinicians to intervene at the early stages of disease, and to monitor the efficacy of those interventions. This review will first examine the potential perinatal biomarkers for neurologic complications of prematurity, specifically, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL) and posthemorrhagic hydrocephalus (PHH). It will also evaluate knowledge gained from animal models regarding the pathogenesis of perinatal brain injury in prematurity.

Amniotic fluid exhibits an innate inhibitory activity against HIV type 1 replication in vitro.

Indirect evidence suggests that amniotic fluid (AF) may play a role in the pathogenesis of in utero HIV-1 transmission. The purpose of this study was to evaluate the potential innate inhibitory role of AF on HIV replication, which may contribute to protection of the fetus against intrauterine transmission. AF was collected from term HIV-1-negative women undergoing scheduled cesarean section. The inhibitory effect of AF against HIV-1(BA-L) replication was tested in vitro with or without the addition of protease inhibitor cocktail (PIC) in PHA-stimulated PBMC cultures. Quantitative measurement of human neutrophil peptides 1-3 (HNP1-3) was performed on all AF samples, using an ELISA assay. AF exhibited a dose-dependent inhibitory activity against HIV-1(BA-L) replication, with all samples (n=12) reaching significant inhibitory effect using 50% AF. In vitro, this activity decreased over time, but was able to be sustained with the addition of PIC. The HNP1-3 concentration in AF samples (n=12) ranged from undetectable (<41 pg/ml, n=3) to >250,000 pg/ml with a median of 5,146 pg/ml. AF exhibited a significant and dose-dependent innate inhibitory activity against HIV-1 replication, which was present in all AF samples tested. This effect was prolonged in the presence of PIC, suggesting that the inhibitory factor was in the cell-free protein fraction. The HNP1-3 concentration in AF was in the subinhibitory range for HIV with no correlation between its concentration and the HIV-1 inhibitory activity. These data show the presence of a significant innate inhibitory activity against HIV in AF.

Matched sibling donor haematopoietic stem cell transplantation in Fanconi anaemia: an update of the Cincinnati Children's experience.

Our results for 18 patients undergoing matched sibling donor stem cell transplant for Fanconi anaemia at Cincinnati Children's Hospital Medical Center were published in 1994. The present report updates our results in 35 consecutive patients. Thirty patients transplanted for marrow aplasia received cyclophosphamide 5 mg/kg for 4 d and 400 cGy thoraco-abdominal irradiation. Five patients with clones involving chromosome 7, myelodysplastic syndrome or leukaemia received a more aggressive regimen with total body irradiation. Horse antithymocyte globulin was administered in the pretransplant period to promote engraftment and in the post-transplant period for additional graft-versus-host disease (GVHD) prophylaxis. The median age at bone marrow transplantation was 7.6 years. Median day of engraftment was day +12 (range 9-49), eight patients developed acute GVHD and four chronic GVHD, one limited and three extensive. Twenty-nine of 35 patients (89% actuarial survival at 10 years) had survived with a median follow up of 10.2 years; two children had developed secondary malignancy. All surviving patients had normal blood counts with full donor engraftment. These data indicate excellent long-term outcomes and serve as a reference for newer radiation-free preparative regimes that may reduce the risk of late secondary malignancy.

The effect of pre-pregnancy body mass index and gestational weight gain on pregnancy outcomes in urban care settings in Urmia-Iran.

BACKGROUND: Nutritional status of women has been considered an important prognostic indicator of pregnancy outcomes. Few studies have evaluated patterns of weight gain and pre-pregnancy body mass index in developing regions where malnutrition and poor weight gain as well as maternal obesity have significant influences on the pregnancy outcome. This study aims to show effect of pregnancy body mass index and the corresponding gestational weight gain on the outcome of pregnancy. METHODS: On a prospective cross sectional study, two hundred and seventy women from urban areas of Northwest Iran were recruited for participation during their first eight weeks of pregnancy. Body mass index (BMI) was categorized and gestational weight gain was divided into two groups of normal and abnormal based on recommendations of Institute of Medicine (IOM) published in 1990. Chi square and one way ANOVA were used in the univariate analysis of the association between weight gain and corresponding adverse outcomes including cesarean, preterm labor and low neonatal birth weight. Adjusted odds ratios for adverse outcomes were determined by multiple logistic regression models, while controlling for the following factors: maternal age, parity, and education. RESULTS: Both pre-pregnancy BMI < 19 and abnormal weight gain during pregnancy were found to be associated with low neonatal birth weight defined as < 2500 g. Abnormal weight gain, during pregnancy was not related to an increased risk of preterm labor or cesarean delivery but it was highly associated with low birth weight (LBW)(P < 0.05). CONCLUSION: Low pre-pregnancy BMI is an established risk factor for LBW. Abnormal gestational weight gain may further complicate the pregnancy as an additional risk factor for neonatal LBW. All women, regardless of their pre-pregnancy BMI may be at risk for abnormal weight gain and hence low birth weight. Pre-pregnancy and gestation nutritional assessments remain significant part of all prenatal visits.