Infant Morbidity Research Articles

Disorders of Coagulation in the Newborn.

The coagulation system in newborns varies from that of children and adults, with many circulating hemostatic factors being lower in the newborn. Infants are also susceptible to diseases and conditions in the pregnant person affecting their coagulation system, which can make it difficult to rapidly identify the cause behind coagulopathy in a neonate. Coagulation disorders can result in high levels of infant morbidity and mortality, which makes early diagnosis and prompt treatment critical. This review outlines the clinical characteristics, diagnosis and management, epidemiology, and etiologies of both common and uncommon congenital and acquired forms of neonatal coagulopathy.

COMPARISON OF PLGF LEVELS, AMONG SMALL FOR GESTATIONAL AGE AND APPROPRIATE FOR GESTATIONAL AGE MOTHERS

Objective. Early detection of small for gestational age fetuses can prevent infant morbidity and mortality. The objective of this study was to compare the levels of Placental Growth Factor among small for gestational age with appropriate for gestational age mothers and to identify the predictive value of PlGF in detecting pregnancies with Intra uterine growth retardation in local population. Design. Quasi experimental (comparative cross-sectional) study. Place & duration of study. Gynecological department of Ayub Medical complex, Abbottabad from August 2021 to January 2022. Methodology. The studied population included total 68 mothers in last trimester with 34 in each group, i.e. appropriate for gestational age and small for gestational age. Fetal size was estimated either by clinical examination (symphysis fundal height) or estimated fetal weight by ultrasound examination. Sociodemographic along with reproductive history were recorded and blood samples analyzed for PlGF difference in both groups. Results. The median age of mothers was 32.5 years. The PlGF in small for gestational age was observed in the below normal concentration (mean value = 126.7 pg/mL) while it was observed in normal ranges in appropriate for gestational age mothers (mean value = 24.2 pg/ml) with P-value (<0.001). Conclusion. Mothers with small for gestational age were having significantly lower placental growth factor levels compared to mothers with appropriate for gestational age.

Cardiogenic Necrotizing Enterocolitis in Infants with Congenital Heart Disease: A Systematic Review and Meta-analysis.

Necrotizing enterocolitis (NEC) is a known cause of morbidity and mortality in infants with congenital heart disease (CHD), but reports about the burden of cardiogenic NEC frequently conflict. To synthesize the extant literature on the incidence, risk factors, and prognosis of NEC in patients with CHD. Medline, Cochrane, and EMBASE were searched from 1946 through 2023 for studies of NEC in infants 0-12months of age with CHD. Risk of bias was assessed with validated tools for incidence and risk factors. Pooled estimates were meta-analyzed by risk of bias or synthesized without meta-analysis. Eighty-six studies with a total of 67,924 participants were included. The incidence of cardiogenic NEC was 7.1% (95% CI 4.7-10.5%) in term infants and 13.0% (10.2-16.5%) in low birthweight preterm infants. NEC required surgery in 0.8% (0.5-1.1%) of term and 2.7% (2.0-3.7%) of premature infants, respectively. Only gestational age and birth weight were consistently associated with risk of NEC. Restricting pooled estimates to studies of moderate or low risk of bias significantly reduced the number of studies included. Necrotizing enterocolitis is a common cause of morbidity in infants with CHD, but additional research is needed to determine which infants are at highest risk of developing NEC and would benefit most from a change in management. This systematic review and meta-analysis was conducted according to a prespecified protocol registered at the Prospective Register of Systematic Reviews (CRD42021282114).

Di-(2-ethylhexyl) Phthalate Exposure Induces Developmental Toxicity in the Mouse Fetal Heart via Mitochondrial Dysfunction.

Congenital heart disease (CHD) is a major cause of infant mortality and morbidity, with growing interest in the role of environmental factors in its etiology. Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, has been implicated in the development of CHD. This study aimed to investigate the effects of DEHP exposure on fetal heart development in mice. Pregnant mice exposed to DEHP exhibited increased fetal malformations, decreased fetal weight, and reduced crown-rump length.f Transcriptomic analysis revealed the downregulation of genes involved in aerobic respiration and mitochondrial ATP synthesis. Functional assays demonstrated reduced mitochondrial respiration, decreased ATP production, elevated reactive oxygen species levels, and lowered mitochondrial membrane potential in DEHP-exposed fetal cardiomyocytes. These findings underscore the detrimental effects of DEHP on fetal cardiac health and provide insights into the molecular mechanisms underlying DEHP-induced CHD. Understanding these mechanisms is crucial for developing preventive strategies against environmental toxicants that affect fetal cardiac development.

Prevalence of unplanned first pregnancy and socioeconomic factors in Benin: a cross-sectional and analytical study

BackgroundEarly or unplanned pregnancy is an obstacle to the well-being of adolescent girls, especially as early motherhood has health and social consequences on the young mother and the newborn. This...

Implementation Strategies Used to Reduce UEs in the Neonatal Intensive Care Unit.

Unplanned extubation (UE) is the premature or unintended removal of an artificial airway and can cause worse patient outcomes. Study objectives were to describe implementation strategies used to reduce UE in the Hospital for Sick Children neonatal ICU (NICU) and their influence on UE rates, and contributing factors and patient characteristics of infants who had an UE, and compare them between the biological sexes. We hypothesized that the boys would experience more UEs and worse outcomes compared to the girls. The single-center retrospective cohort study included all infants who experienced UE (2007-2019). Outcomes consisted of implementation reduction strategies developed by using the plan-do-study-act quality-improvement methodology and UE characteristics, including patient (eg, sex, length of stay) and unplanned extubation situation characteristics (eg, events and/or procedures, repeats). Five plan-do-study-act cycles were implemented. Analyses included text summaries of all strategies, and quantitative descriptive and comparative statistics. UE per 100 ventilator days decreased from 3.46 to 0.14. Key success factors included setting achievable goals; ensuring that strategies were evaluated and amended; maintaining consistency over the long-term; incorporating strategies in the NICU; having institutional support and validation; and having good communication. There were 302 UE in 257 infants, 141 boys (55%), average ± SD gestational age of 31 ± 6 weeks, and 31 (12%) had 45 repeated UEs. The only significant difference between the biological sexes was that more boys (129 [92%]) versus girls (94 [83%]) received the Hospital for Sick Children NICU endotracheal tube taping protocol (P = .030). The incidence of UE occurred in a 2-peaked pattern, highest for those < 32 weeks and ≥ 32 weeks of gestational age. Infants < 32 weeks of gestational age and with repeated UE had longer durations of invasive mechanical ventilation and length of stay. For infants <32 versus => 32 weeks gestational age, the median (interquartile range) duration of mechanical ventilation was 38 (16-77) d versus 6 (3-13) d and hospital length of stay 61 (30-100) d versus 16 (10-41) d. For infants with repeated versus no repeated unplanned extubations, duration of mechanical ventilation was 69 (26-125) d versus 13 (4-52) d and hospital length of stay 90 (39-137) d versus 32 (12-75) d. Detailed well-planned UE reduction strategies significantly reduced the rate of UEs with key factors of success identified. UE characteristics and infant morbidity did not differ between the biological sexes. Infants < 32 weeks of gestational age and with repeated UE had a longer duration of mechanical ventilation and length of stay.

Effectiveness of psychoeducation interventions for pregnant women with gestational diabetes mellitus: an integrative review

BackgroundGestational diabetes mellitus occurs in approximately 15–17% of pregnant women worldwide and causes high mortality and morbidity for mothers and infants. Pregnant women who are newly diagnosed with gestational diabetes mellitus experience higher levels of stress and anxiety than pregnant women without this condition. Thus, it is important to identify effective interventions to help pregnant women cope with the additional stress and anxiety associated with pregnancy-related complications.AimThis integrative review aimed to synthesise evidence on the effects of educational interventions for pregnant women with gestational diabetes mellitus regarding knowledge, self-efficacy, self-care behaviour, anxiety, depression, and birth outcomes.MethodsAn integrative review of articles published between 2009 and 2024, written in English and Arabic. The review followed the Whittemore and Knafl’s 5-stage process framework.ResultsFrom the 922 abstracts identified using search terms, 16 articles were eligible for this review. Psychoeducational interventions were provided for (1) informational support: information about gestational diabetes mellitus, diabetes mellitus, blood glucose monitoring, exercise management, diet management, and stress; (2) motivational support: setting individual goals, enhancing health behaviours, and motivational messages; (3) emotional support: expression of feelings, enforcement of self-management, and sharing of experiences; and (4) relaxation techniques: breathing exercises, meditation, and mindfulness. In this review, only two studies entirely focused on reducing stress and anxiety through cognitive-behavioural stress management training and mindfulness training. The effects of the interventions on self-efficacy, knowledge, depression, anxiety, and birthing outcomes were inconsistent due to variations in intervention designs and duration. However, consistent positive outcomes were found in self-care behaviours.ConclusionThis integrative review found informational and motivational support were frequently used by pregnant women. In contrast, emotional support and relaxation techniques were rarely used. Psychoeducational interventions may enhance self-care behaviours, improve self-efficacy, and reduce stress and depression for women with gestational diabetes mellitus. Nurses and midwives play an essential role in providing holistic care through comprehensive psychoeducational interventions for pregnant women.

Vaccine decision-making among pregnant women: a protocol for a cross-sectional mixed-method study in Brazil, Ghana, Kenya and Pakistan

Maternal immunization is a critical strategy to prevent both maternal and infant morbidity and mortality from several infectious diseases. When the first COVID-19 vaccines became available during the pandemic, there was mixed messaging and confusion amongst the broader public and among those associated with health care systems about the recommendations for COVID-19 vaccinations in pregnancy in many countries. A multi-country, mixed-methods study is being undertaken to describe how vaccine decision-making occurs amongst pregnant and postpartum women, with a focus on COVID-19 vaccines. The study is being conducted in Brazil, Ghana, Kenya, and Pakistan. In each country, participants are being recruited from either 2 or 3 maternity hospitals and/or clinics that represent a diverse population in terms of socio-economic and urban/rural status. Data collection includes cross-sectional surveys in pregnant women and semi-structured in-depth interviews with both pregnant and postpartum women. The instruments were designed to identify attitudinal, behavioral, and social correlates of vaccine uptake during and after pregnancy, including the decision-making process related to COVID-19 vaccines, and constructs such as risk perception, self-efficacy, vaccine intentions, and social norms. The aim is to recruit 400 participants for the survey and 50 for the interviews in each country. Qualitative data will be analyzed using a grounded theory approach. Quantitative data will be analyzed using descriptive statistics, latent variable analysis, and prediction modelling. Both the quantitative and qualitative data will be used to explore differences in attitudes and behaviors around maternal immunization across pregnancy trimesters and the postpartum period among and within countries. Each country has planned dissemination activities to share the study findings with relevant stakeholders in the communities from which the data is collected and to conduct country-specific secondary analyses.

Preeclampsia Risk in Bali, Indonesia: The Role of Maternal Body Mass Index (BMI) and Gestational Weight Gain (GWG)

Background: Preeclampsia, a hypertensive disorder of pregnancy, significantly contributes to maternal and infant mortality and morbidity globally, including in Indonesia. Pre-pregnancy obesity and excessive gestational weight gain (GWG) are established risk factors for preeclampsia. This study investigated the association between pre-pregnancy body mass index (BMI) and GWG with the incidence of preeclampsia in Bali, Indonesia. Methods: A case-control study was conducted at a Maternal Hospital in Bali, Indonesia, from May 2023 to May 2024. The study included 429 pregnant women: 143 with preeclampsia (cases) and 286 without (controls). Data were collected from medical records. BMI was categorized using Asia-Pacific criteria, and GWG was assessed based on the 2009 Institute of Medicine (IOM) guidelines. Logistic regression analysis was performed to determine the associations, adjusting for maternal age, education, and occupation. Results: Obesity class II (BMI ≥ 30 kg/m²) and obesity class I (BMI 25.0-29.9 kg/m²) were significantly associated with an increased risk of preeclampsia, with adjusted odds ratios (AOR) of 2.90 (95% CI: 1.19-7.08) and 2.78 (95% CI: 1.60-4.81), respectively, compared to women with normal weight. Excessive GWG was also significantly associated with preeclampsia (AOR 2.53; 95% CI: 1.48-4.33) compared to adequate GWG. Conclusion: Maternal obesity and excessive GWG are significant risk factors for preeclampsia in Bali, Indonesia. These findings underscore the importance of pre-pregnancy counseling and interventions to manage weight and promote healthy GWG to reduce the burden of preeclampsia.

Maternal and infant outcomes in women with sickle cell disease: a matched cohort study

ObjectiveWomen with sickle cell disease (SCD) have adverse maternal and infant outcomes. Our aim was to determine whether the outcomes of SCD mothers and their infants differed from African or...

New Strides in Prevention of Malaria during Pregnancy Present Multitudinous Opportunities.

Pregnant women are at a higher risk of developing complications from malaria, a mosquito-borne disease caused by Plasmodium parasites, resulting in considerable maternal and infant morbidity and mortality. Malaria in pregnancy causes unfavorable and life-threatening outcomes for both the mother and fetus not limited to maternal anemia, hypoglycaemia, cerebral malaria, pulmonary edema, and puerperal sepsis. WHO recommends wide-ranging strategies for this detrimental but preventable disease; however, numerous challenges persist in ensuring high uptake of preventive therapies, effective usage of insecticide-treated bed nets, and early initiation and optimal antenatal care coverage for pregnant women. This work distils recent global advances in preventive strategies for malaria in pregnancy. We discuss three mainstay interventions by WHO, viz. intermittent preventive treatment of malaria in pregnancy (IPTp), utilization and outcomes of insecticide-treated bed nets (ITNs), and headways in malaria case management using therapeutic drugs. We cover multitudinous facets of antenatal care, WHO-advised community-based delivery of IPTp (c-IPTp), intermittent screening and treatment for malaria in pregnancy (ISTp), a malaria vaccine for pregnant women, and auxiliary factors that are crucial for improving prevention outcomes. Despite the reduction in malaria globally, malaria in pregnancy remains a prevalent issue in endemic areas, which warrants strengthening of preventative strategies. This work attempts to consolidate pivotal observations of the prevention of malaria during pregnancy by highlighting key advances, priority areas, new opportunities, research gaps, and challenges that need to be addressed to ensure improved outcomes in pregnant women infected with malaria.

O PRÉ NATAL FRENTE A MORBIMORTALIDADE MATERNO INFANTIL

This study addresses the critical importance of prenatal care in reducing maternal and infant morbidity and mortality, highlighting the significance of early adherence by pregnant women to these services. Through a literature review, it was possible to identify complications associated with non-adherence to prenatal care, such as premature births, low birth weight, and the prevalence of gestational complications that can be mitigated with adequate and timely care. Among the effective strategies for the recruitment and retention of pregnant women, the role of nurses was emphasized as fundamental, utilizing techniques that include health education, the use of information technology, and interdisciplinary practices. Programs such as Rede Cegonha were also mentioned, highlighting their contribution to strengthening prenatal care, childbirth, and postpartum support. The study underscores the need for efficient public policies and ongoing research to improve prenatal services, ensuring that all pregnant women have access to effective and humane care, guaranteeing a healthy pregnancy and a safe childbirth. This work emphasizes the urgency of integrated and evidence-based approaches in prenatal care, aiming for significant improvements in maternal and infant health.

Early prediction of mortality and morbidities in VLBW preterm neonates using machine learning.

Predicting mortality and specific morbidities before they occur may allow for interventions that may improve health trajectories. Integrating key maternal and postnatal infant variables in the first 2 weeks of age into machine learning (ML) algorithms will reliably predict survival and specific morbidities in VLBW preterm infants. ML algorithms were developed to integrate 47 features for predicting mortality, bronchopulmonary dysplasia (BPD), neonatal sepsis, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and retinopathy of prematurity (ROP). A retrospective cohort (n = 3341) was used to train and validate the models with a repeated 10-fold cross-validation strategy. These models were then tested on a separate cohort (n = 447) to evaluate the final model performance. Among the seven ML algorithms employed, tree-based ensemble models, specifically Random Forest (RF) and XGBoost, had the best performance metrics. The area under the receiver operating characteristic curve (AUROC) of sepsis with or without meningitis (0.73), NEC (0.73), BPD (0.71), and mortality (0.74) exceeded 0.7, while the area under Precision-Recall curve (AUPRC) for all outcomes was greater than the prevalence, demonstrating effective risk stratification in VLBW preterm infants. Our study demonstrates the potential of predictive analytics leveraging ML techniques in advancing precision medicine. Reliable prediction of adverse outcomes before they occur has the potential to institute interventions and possibly improve health trajectories in VLBW preterm infants. We used machine learning to develop and test predictive models for mortality and five major morbidities in VLBW preterm infants. Individualized prediction of outcomes and individualized interventions will advance Precision Medicine in Neonatology.

Relationship between platelet count and severity of neonatal respiratory distress syndrome

BackgroundNeonatal respiratory distress syndrome (NRDS) is a primary cause of morbidity and mortality in premature infants. Platelets have a unique role in lung repair and remodeling. This study aimed to determine the relationship between platelet count and NRDS severity.MethodsThe study included 234 newborns diagnosed with NRDS from January 2019 to August 2023. This study employed two methods of grouping: the first based on platelet count, dividing participants into thrombocytopenia (platelet count < 150 × 109/L, n = 50) and non-thrombocytopenia groups (platelet count ≥ 150 × 109/L, n = 184), and the second based on the severity of NRDS, categorizing them into severe (n = 24) and mild-moderate (n = 210) groups. Within the first grouping method, the thrombocytopenia group was further subdivided into moderate-severe group (platelet count < 100 × 109/L, n = 4) and mild group (platelet count was between 100.0 × 109/L and 150.0 × 109/L, n = 46). This study aimed to analyze the clinical characteristics of NRDS with thrombocytopenia, explore the correlation between platelet count and clinical indicators of NRDS. Binary Logistic regression analysis was employed to identify independent risk factors for thrombocytopenia in NRDS.ResultsA higher proportion of newborns in the severe group exhibited thrombocytopenia (severe group = 41.7%, mild-moderate group = 19.0%). Hospital stay, ventilation time, oxygen therapy duration were longer in the thrombocytopenia group compared to the non-thrombocytopenia group. Hospital stay, ventilation time, oxygen therapy duration, chest radiography score, and C-reactive protein (CRP) levels were inversely associated with platelet count. Conversely, Apgar scores at 1 and 5 min, gestational age, and birth weight showed positive correlations with platelet count. Point-biserail correlation showed that thrombocytopenia was more likely to occur in newborns whose mothers had gestational hypertension, and the lower platelet count, the more severe NRDS. Oxygen therapy duration, birth weight < 1500 g, gestational hypertension and CRP levels emerged as independent risk factors for thrombocytopenia in NRDS. All differences were statistically significant (p all < 0.05).ConclusionNRDS accompanied by thrombocytopenia indicates a more severe condition and poorer clinical outcomes. It is hypothesized that NRDS with thrombocytopenia involves a complex multifactorial etiology, including severe lung inflammation.

Impact of the method of delivery and feeding practice on the gut microbiome of infants in the postnatal period

BACKGROUND: The increasing frequency of cesarean sections and artificial feeding creates a predisposition to allergic diseases, obesity, and diabetes mellitus. Pathogenesis of these involves changes in the gut microbiome of infants. AIM: The aim of this study was to evaluate the impact of the method of delivery and feeding practice on the gut microbiome of infants. MATERIALS AND METHODS: This study included 103 infants aged 4-6 weeks (group 1: 39 infants born vaginally and breastfed; group 2: 10 infants born vaginally and formula-fed; group 3: 31 infants born by caesarean section and breastfed; group 4: 23 infants born by caesarean section and formula-fed), each of whom had stool collected for 16S ribosomal RNA gene sequencing. RESULTS: We found differences in the relative abundance of Akkermansia spp. [34.07 (29.29–38.85)% in group 4 and 0.01 (0.01–0.02)% in group 1; p = 0.011], Bifidobacterium spp. [30.68 (21.65–39.41)% in group 1 and 17.08 (9.86–21.68)% in group 4, (p = 0.002); 31.46 (24,30–52.97)% in group 3 and 17.08 (9.86–21.68)% in group 4 (p = 0.001)], and Enterococcus spp. [4.69 (1.01–8.59)% in group 3 and 0.58 (0.12–1.87)% in group 1 (p = 0.003); 4.29 (2.07–6.96)% in group 4 and 0.58 (0.12–1.87)% in group 1 (p = 0.001)]. The coefficient of correlation adaptometry was maximum for groups of infants who were breastfed. Analysis of the morbidity of infants in the first year of life revealed differences in the incidence of acute respiratory viral infections between infants in groups 1 and 4 (17.9 and 78.3%, respectively; p = 0.0064), as well as groups 3 and 4 (32.2 and 78.3%, respectively; p = 0.018). CONCLUSIONS: The relative abundance of Bifidobacterium spp. depends on feeding practice to a greater extent than on the method of delivery. The method of delivery affects the relative abundance of opportunistic bacteria such as Enterococcus spp. Correlation analysis demonstrated the role of breastfeeding as a mechanism for “learning” and maturing the immune system of children.

Evaluate the Knowledge about the WHO- Recommended Antenatal Visits among Antenatal Mothers in the Outpatient Department

One of the most crucial aspects of the World Health Organization's family welfare program in India is the promotion of maternal and child health. ANC is the care given to women during pregnancy to ensure that both the mother and the kid remain healthy. Reducing infant and mother mortality and morbidity as well as promoting, protecting, and preventing maternal and perinatal health are beneficial for the long-term growth and development of the nation. Sadly, a lot of women in underdeveloped nations do not get this kind of care.  Objectives: Assess the knowledge of WHO recommended ANC visit among pregnant women..  Methodology:  Research Approach: Qualitative study,  Research Design: Descriptive study,  Population: Antenatal mothers Antenatal mothers who are attending OPD.  Sample Size: The sample size consider of 30 antenatal mothers.  Sample Technique: Non probability sampling convenient sampling techniques adopted in this study.  Result: This study had given some clues that majority 22 (74%) of them had moderate knowledge. 6 (20%) of them had inadequate knowledge, 2(7%) of them had adequate knowledge about antenatal mothers.  Conclusion: This study experiences helped the investigator to spell out some recommendations and develop a self- instructional module so as to improve the knowledge about antenatal mothers.

Prevalence and Predictors of Fear of Childbirth Among the Pregnant Women Attending a Tertiary Care Hospital in Imphal-East District Manipur, North-East India: A Cross-Sectional Study

Background: Fear of childbirth (FOC) is a feeling of uncertainty and anxiousness before, during or after delivery which may increase the risk of various physical problems and mental disorders thereby affecting maternal and infant morbidity and mortality. Objectives: To estimate the prevalence of fear of childbirth and to determine its associated factors among pregnant women. Methodology: A hospital-based cross-sectional study was conducted among pregnant women attending ante-natal clinic of a tertiary-care hospital in Imphal-East District of Manipur. A 30-item questionnaire was used for data collection. Descriptive statistics, univariate and multivariate logistic regression analysis were performed to test for association taking all variables with p &lt; 0.2 for model building for the adjusted analysis. A p value &lt;0.05 was taken as level of significance. Ethical approval was obtained from the Institutional Ethics Committee. Results: Out of 431 participants, fear of childbirth was seen in 36%. Increasing age of the respondent (AOR: 0.877) and residing in urban area (AOR: 0.548) showed a protective effect but respondents having past history of abortion (AOR: 2.054) and being in the third trimester of pregnancy (AOR: 1.964) were found to have an increased risk of having ‘Fear of childbirth’ (p&lt;0.005). Conclusions: Overall, 155 (36%) of women had fear of childbirth. It is important that healthcare professionals to be aware of fear of childbirth and ensure that pregnant women receive adequate health education, counselling during regular ANC checkups.

Principles of resuscitation for infants with severe bronchopulmonary dysplasia

Severe bronchopulmonary dysplasia (sBPD) requiring invasive mechanical ventilation is a heterogeneous disease process that contributes to morbidity and mortality in infants. As the most common lung disease of prematurity, sBPD has a multitude of overlapping cardiac, airway, pulmonary vascular, and infectious phenotypic presentations that progress through four different phases of care. Premature infants with sBPD are at a high risk of acute decompensation and subsequent cardiopulmonary arrest. A comprehensive determination of the complex phenotypes that contribute to the clinical presentation will help clinicians decipher the phase of care, identify cardiopulmonary compromise earlier and guide targeted therapeutic intervention during acute episodes of deterioration. The approach to resuscitation of premature infants with sBPD undergoing an acute decompensation differs from general neonatal and pediatric resuscitation practices. This review summarizes the phenotypes of sBPD, the phases of care, the common triggers of acute exacerbations, and the principles of resuscitation of a deteriorating infant with sBPD. We offer a framework for sBPD resuscitation with a focus on prevention, assessment, and post-resuscitative care.

The Analysis Study of Effects of Probiotics, Prebiotics, Lactoferrin and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Comprehensive Systematic Review

The Analysis Study of Effects of Probiotics, Prebiotics, Lactoferrin and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Comprehensive Systematic Review

Evaluation of A Non-Nucleoside Inhibitor of the RSV RNA-Dependent RNA Polymerase in Translatable Animals Models

Respiratory Syncytial Virus (RSV) causes severe respiratory infections and concomitant disease resulting in significant morbidity and mortality in infants, elderly, and immunocompromised adults. Vaccines, monoclonal antibodies, and small molecule antivirals are now either available, or in development, to prevent and treat RSV infections. Although, rodent and non-rodent preclinical animal models have been used to evaluate these emerging agents there is still a need to improve our understanding of the pharmacokinetic (PK)-pharmacodynamic (PD) relationships, within and between animal models to enable better design of human challenge studies and clinical trials. Herein, we report a PKPD evaluation of MRK-1, a novel small molecule non-nucleoside inhibitor of the RSV L polymerase protein, in the semi-permissive cotton rat and African green monkey models of RSV infection. These studies demonstrate a strong relationship between in vitro activity, in vivo drug exposure, and pharmacodynamic efficacy as well as revealing limitations of the cotton rat RSV model. Additionally, we report unexpected horizontal transmission of human RSV between co-housed African green monkeys, as well as a lack of drug specific resistant mutant generation. Taken together these studies further our understanding of these semi-permissive animal models and offer the potential for expansion of their preclinical utility in evaluating novel RSV therapeutic agents.