Cause Of Infant Mortality Research Articles

Lessons from Real Life Experience: Importance of In-House Sequencing and Smart Ratio-Based Real-Time PCR Outperform Multiplex Ligation-Dependent Probe Amplification in Prenatal Diagnosis for Spinal Muscular Atrophy: Bench to Bedside Diagnosis.

Spinal muscular atrophy (SMA) is a rare, recessively inherited neurodegenerative disorder caused by the presence of pathogenic variants in the SMN gene. As it is the leading inherited cause of infant mortality, identification of SMN gene pathogenic variant carriers is important for diagnostic purposes with effective genetic counseling. Multiple ligation probe analysis (MLPA), a probe-based method, is considered as the gold standard for SMA carrier analysis. However, MLPA might give false-negative results in cases with variations in the probe-binding regions. Here, we present a case born to consanguineous SMA carrier parents. Prenatal diagnosis with MLPA failed to detect the compound heterozygous mutant state of the proband and she was born unfortunately with SMA phenotype. Further analysis with a real-time polymerase chain reaction kit was able to detect the compound heterozygous state of the patient and was confirmed with targeted next-generation sequencing technology.

THE EFFECT OF LOW BIRTH WEIGHT (LBW) ON NEONATAL DEATH IN GORONTALO CITY

Indonesia is a developing country with high maternal and infant mortality rates. One of the causes of infant mortality in Indonesia is the incidence of Low Birth Weight (LBW) of 38.85%. The number of neonatal deaths in Gorontalo City between 2018 - 2021 is 83 cases. The novelty of this research is the effect of LBW on neonatal death. This study aims to see the impact of LBW on neonatal mortality in Gorontalo City after controlling for maternal risk factors in the form of a history of complications and the frequency of ANC. The research design used was analytic with a case-control approach. The sample in this study consisted of 30 cases and 60 controls. The results of the survey show that from the effects of bivariate analysis, the history of complications variable has an Odds Ratio Crude value of 55 and an Odds Ratio Adjusted of 13 and the Mantel-Haenszel test value: p-value α (0.000 0.05). In contrast, Antenatal Care has an Odds Ratio Crude value of 28 and Odds Ratio Adjusted by 17 and the value of the Mantel-Haenszel test: p-value α (0.000 0.05). The Odds Ratio value for LBW is 20 with a p-value α (0.000 0.05). This study concludes that LBW has a 20 times risk of neonatal death (95% CI = 6.506 – 61.485)

Role of Fetal Cardiac MRI in Assessment of Congenital Heart Diseases in Comparison to Fetal Echocardiography

Introduction •Abnormalities of the cardiovascular system are the most common congenital diseases in the fetus and the first cause of infant mortality (Johnson et al. 2014). •Without a doubt, Echocardiography is the method of choice to visualize the fetal cardiac cardiovascular abnormalities. Unlike fetal echocardiography imaging, cardiovascular magnetic resonance (CMR) is relatively unaected by maternal and fetal conditions such as maternal obesity, uterine myoma, twins, oligohydramnios, fetal position and rib calcification, which particularly impair sonographic visualization of the fetal heart (Donofrio et al. 2014; Wielandner et al. 2013). •Fetal cardiac MR imaging is a novel MRI technique which can provide valuable information that could add to the prenatal diagnosis and evaluation of cardiac and most of extra-cardiac anomalies. The evaluation of pre-natal congenital cardiac anomalies is important for postnatal management. Aim of the work To highlight the advantage of MRI over fetal echocardiography in assessment of fetal congenital cardiac anomalies. Methods and material Twenty-six feti with suspected or diagnosed congenital cardiac anomalies. All cases underwent detailed history taking, fetal echocardiography and fetal cardiac MR. Study is approved by the ethics review board of Ain Shams University Hospital. Fetal echocardiography was done according to standard protocol and performed by suitable curvilinear probe. Then MRI of the fetal heart was done with uterine SURVEY_BFFE (balanced fast field echo), Black blood single shot -BH, white blood Cine, sBFFE_RLT DYN 3D(real time 3Ddynamic). Images were acquired in the transverse, four-chamber, shortaxis, coronal and oblique sagittal views. Findings of fetal echocardiography were compared with that of cardiac MRI. Results •Regarding the diagnostic performance of prenatal Echo and fetal cardiac MRI showed significant moderate agreement between the two modalities in the detection of different congenital cardiac anomalies, Kappa test: 0.500; p-value 0.021*. •Qualitative analysis: All cardiac structures were delineable by echocardiography and cardiac MRI. There was full agreement(κ = 1) between fetal echocardiography and cardiac MRI in evaluating the cardiac situs(24normal,1 levocardia, 1 ectopia cordis), aorta (20normal, 3 hypoplastic aorta,1 aortic stenosis,1 rt. Sided aortic arch and 1 small sized aorta), transverse cardiac diameter (22 normal, 4 cardiomegaly), foramen ovale (25 normal, 1 large single atrium), Good agreement was found between echocardiography and cardiac MRI for detection of position of the cardiac apex (23 normal, 2 dextrocardia and 1 mesocardia) •Fetal MRI had a significant role in detection of additional extracardiac anomalies in 13 cases. Conclusion fetal cardiac MR imaging as an adjunct to fetal echocardiography may provide valuable information that could add to the prenatal diagnosis and evaluation of cardiac and most of extra cardiac anomalies.

Handle with Care: A Narrative Review of Infant Safe Sleep Practices across Clinical Guidelines and Social Media to Reduce SIDS.

Sudden Infant Death Syndrome (SIDS) is a leading cause of infant mortality across the United States and the world. There are multiple environmental and behavioral determinants of sudden infant death which are modifiable risk factors and potential targets for intervention. In this increasingly digital era, health education and communication on SIDS have taken many forms, which extend to social media. Current published studies on coverage of infant safe sleep practices are scant and were published well before the newly revised guidelines of the American Academy of Pediatrics that review ways to prevent infant sleep-related deaths based on evidence-based SIDS-reduction measures. In this Perspective: Review of a Pediatric Field, the current state of published knowledge and coverage on a range of infant safe sleep considerations across social media are reviewed. We delineate gaps in the knowledge and practice as well as the central differences between the 2016 and 2022 AAP Safe Sleep guidelines. We also present recommendations for further research and practice which support coverage of future content on the revised guidelines across social media as the basis to present the most up-to-date and evidence-based information for reducing sudden infant death from sleep-related causes. Tapping into the potential of social media as a learning modality in health promotion also contributes towards the larger goal of the World Health Organization, United Nations International Children's Emergency Fund (UNICEF), and Healthy People 2030 to reduce infant mortality on both global and national levels.

Congenital heart disease in the resolving polyclinic of children’s cardiology at the Hospital del Niño “Dr. Ovidio Aliaga Uría” at 3.650 masl

Introduction: Congenital malformations are the leading cause of early neonatal mortality and the second leading cause of infant mortality. Among them, congenital heart diseases are the main cause of mortality in the early neonatal period. Material and methods: A prospective cross-sectional study was conducted at the "Dr. Ovidio Aliaga Uría" Children's Hospital in La Paz, Bolivia, at an altitude of 3,650 masl. A pediatric cardiology outpatient clinic was set up to examine 42 children, recording clinical data, physical examination, and color Doppler echocardiography. Results: The most frequent reason for referral was a heart murmur. In 52.38% (n=22) of the evaluated patients, congenital heart disease was present, with ventricular septal defects being the most common at 40.91% (n=9), followed by atrial septal defects at 18.18% (n=4), persistent foramen ovale at 13.64% (n=3), and patent ductus arteriosus at 9.09% (n=2) of patients. Discussion: There are very few studies in populations living at altitudes above 3,000 masl. Our study shows a high percentage of children with cardiac defects, which may be attributed to accurate diagnosis at referral or possibly a higher incidence of cardiac malformations in the studied population. Conclusion: the most common cardiac defect was ventricular septal defect, as described in populations living at sea level.

Reclassification of the Etiology of Infant Mortality With Whole-Genome Sequencing

ABSTRACT Infant mortality rates are quite high even in developed countries; in the United States, infant deaths occur approximately 1 in 200 live births. The leading cause of infant mortality is congenital malformation or chromosomal abnormality, which cause roughly 20% of infant deaths, followed by other causes such as pregnancy complications, preterm birth or low birth weight, and sudden infant death syndrome. Improvements in treatments for certain conditions such as pregnancy complications or prematurity have previously resulted in a reduction in mortality due to these causes. Although the same may be true of congenital malformations or chromosomal abnormalities, the relationship between these factors and infant mortality has not been closely examined. Previous studies have largely been retrospective in nature and varied greatly among method and records used, perpetuating inaccuracies and imprecision. This study aimed to clarify and add to previous literature by examining the relationship between single-locus genetic disease (Mendelian genetic disease) and overall infant mortality. This study applied diagnostic whole-genome sequencing (WGS) to infants in intensive care to diagnose diseases of unknown etiology in a single hospital system between 2015 and 2020. The study was retrospective and included review of medical records and death certificates, as well as results from WGS. Where possible, WGS information was obtained on living infants and their parents, and where that was not possible, it was obtained postmortem. Death certificates and causes of death were also examined and compared with WGS results. In the final sample, 112 infants who died underwent WGS either premortem or postmortem. WGS identified genetic diseases in 46 (41%) of these infants. Of the genetic diseases identified, 83% had previous evidence supporting an association with childhood mortality, and evidence was gathered from previous literature that could improve outcomes for 30%. Death certificate comparisons showed that of 45 infants where WGS showed underlying genetic disease, 62% were not reported on the certificate or attributed to the cause of death. In addition to the 112 infants who died, the study population included 434 infants who survived and also had WGS performed. No significant differences were found between the groups in sex, race, or ethnicity. Types of genetic disease varied between infants who died and those who survived, with only 4% being found in both. Certain diseases were more likely to occur in infants who survived, and others were more likely to occur in infants who died. Specific etiology had some prognostic value, positively predicting either death or survival. These results indicate that first, after examination of WGS in comparison with death certificates, genetic diseases are chronically underreported. In addition, WGS showed that etiology of leading causes of infant mortality could be fundamentally different than previously thought. WGS is also not currently a widespread treatment, and although steps are being taken to make it more widely accessible, there are still many changes that need to be made. This study is limited by its small size, and may have limited generalizability to other patient populations. Future research should characterize the optimal breadth of WGS testing and implementation, as well as the potential for WGS to reduce infant mortality by identifying treatable disorders.

Awareness of sudden infant death syndrome and its associated risk factors among Saudi mothers attending well-baby clinics at PHC, PSMMC, Riyadh, Saudi Arabia: A cross-sectional study.

Sudden infant death syndrome (SIDS) is a leading cause of infant mortality all over the world. Mortality due to SIDS can be averted by educating families and caretakers about safe practices for putting infants to sleep. However, the knowledge, attitude, and practices of mothers while putting the infant to sleep is a gray areas in literature. The objectives of the study were to measure the knowledge and awareness about SIDS and its associated risk factors practiced among Saudi mothers attending well-baby clinics in Saudi Arabia to develop appropriate educational program-based interventions for safe practices of infant care. This cross-sectional study was carried out among 385 mothers attending well-baby clinics of primary health care (PHC) and prince sultan military medical city (PSMMC) in Riyadh Saudi Arabia. Information was captured on sociodemographic characteristics, the health status of mothers and infants, knowledge, attitude, and practice followed by mothers while putting infants to sleep. From a total number of 385 responses, 350 participants were eventually included in the final sample due to the incompletion of the questionnaire of 350 mothers; only 26% (n = 93) mothers had heard of SIDS. However, 259 mothers were willing to attend the awareness session. Only 94 mothers had knowledge as well as practicing the correct behavior of putting the infant to sleep on the back referred to as "good behavior concordant pairs." Similarly, other good practices include not co-sharing a bed with the infant, removing pillows, blankets, and other wedged objects, using a pacifier, breastfeeding the infant during sleep, not using multiple quilts, not covering the infant's head with a quilt, not using a head cap. The number of good behavior concordant pairs (in green) were 124, 38, 56, 98, 18, 117, and 68 respectively. The rate of knowledge and practice for good behavior regarding SIDS was low among Saudi mothers in Riyadh Saudi Arabia. SIDS-related deaths can be averted by improving the understanding of SIDS risk reduction practices among mothers by using health promotion strategies.

Smartphone-Based Video Antenatal Preterm Birth Education

Preterm birth is a leading cause of infant mortality and child morbidity. Preterm birth is not always unexpected, yet standard prenatal care does not offer anticipatory education to parents at risk of delivering preterm, which leaves parents unprepared to make health care choices during the pregnancy that can improve survival and decrease morbidity in case of preterm birth. To evaluate the effect of the Preemie Prep for Parents (P3) program on maternal knowledge of preterm birth, preparation for decision-making, and anxiety. Recruitment for this randomized clinical trial conducted at a US academic medical center took place from February 3, 2020, to April 12, 2021. A total of 120 pregnant persons with a risk factor for preterm birth were enrolled between 16 and 21 weeks' gestational age and followed up through pregnancy completion. Starting at 18 weeks' gestational age, P3 program participants received links delivered via text message to 51 gestational age-specific short animated videos. Control participants received links to patient education webpages from the American College of Obstetricians and Gynecologists. At 25 weeks' gestation, scores on the Parent Prematurity Knowledge Questionnaire (scored as percent correct), Preparation for Decision Making Scale (scored 0-100), and Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety computerized adaptive test. Analysis was based on an intention to treat. A total of 120 pregnant participants (mean [SD] age, 32.5 [4.9] years) were included in the study; 60 participants were randomized to each group. Participants in the P3 group scored higher than those in the control group on knowledge of long-term outcomes at 25 weeks (88.5% vs 73.2%; estimated difference, 15.3 percentage points; 95% CI, 8.3-22.5 percentage points; P < .001). Participants in the P3 group reported being significantly more prepared than did participants in the control group for neonatal resuscitation decision-making at 25 weeks (Preparation for Decision Making Scale score, 76.0 vs 52.3; difference, 23.7; 95% CI, 14.1-33.2). There was no difference between the P3 group and the control group in anxiety at 25 weeks (mean [SE] PROMIS Anxiety scores, 53.8 [1.1] vs 54.0 [1.1]; difference, -0.1; 95% CI, -3.2 to 2.9). In this randomized clinical trial, pregnant persons randomly assigned to the P3 program had more knowledge of core competencies and were more prepared to make decisions that affect maternal and infant health, without experiencing worse anxiety. Mobile antenatal preterm birth education may provide a unique benefit to parents with preterm birth risk factors. ClinicalTrials.gov Identifier: NCT04093492.

The third pandemic: The respiratory syncytial virus landscape and specific considerations for the allergist/immunologist.

Background: Since its initial identification in 1956, respiratory syncytial virus (RSV) has been the second most common cause of mortality in infants <6 months of age and a major cause of morbidity and mortality associated with lower respiratory tract infection (LRTI) in older adults (ages >60 years) worldwide. Of particular interest to the allergist/immunologist is a growing body of evidence that suggests an association between LRTI caused by RSV in infants with later-life development of asthma, wheezing, or impaired lung function in adults. Efforts to develop a RSV vaccine have been thwarted for >70 years by the occurrence of enhanced respiratory disease (ERD), an adverse RSV vaccine reaction, in the 1960s, in which more-severe illness occurred on natural infection after vaccination of infants who were RSV naive and with a formalin-inactivated RSV vaccine. Recent advances in knowledge of the structural biology of the RSV surface fusion glycoprotein, however, have revolutionized RSV vaccine development for preventive interventions and have offered, at last, the hope of an effective and safe vaccine for the prevention of RSV disease. Objective: The purpose of this report was to examine the current evidence that supports the epidemiology, disease manifestations, molecular biology, treatments, and new vaccine development of RSV vaccines. Results: The host-immune response to RSV infection is carried out by two distinct but overlapping universes of mucosal and systemic immune systems in which a balanced set of B- and T-cell responses are involved in protective immunity that includes the mucosal immune system in which immunoglobulin A (IgA) prevails and the systemic immune system in which IgG neutralizing antibody predominates. The key to developing an effective vaccine is now thought to be linked to the availability of a stabilized prefusion F protein in the immunizing vaccine, which can perform a dual function of a balanced mucosal and/or systemic immune response as well as an effective antibody specifically directed to critical epitopes on the requisite prefusion F protein. Conclusion: The unfortunate manifestation of RSV ERD that occurred in the 1960s has led to a better understanding of the structural biology of the RSV surface fusion glycoprotein and has provided a basis for the development of more effective and safer RSV vaccines and monoclonal antibody preparations for immunoprophylaxis of the dread effects of RSV disease. There are now a large number of clinical trials in progress that are evaluating these products, which include recombinant vector, subunit, particle-based, live-attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. This article gives an overview of the many aspects of RSV disease and development of virus (RSV) vaccines of particular interest to the allergist/immunologist.

Factors Associated With an Increased Risk of Facial Malformations.

Background Facial anomalies comprise a significant component of birth defects, with oral clefts being the second most common entity in this group. All organ systems within the body can be affected by congenital anomalies, mostly affecting the musculoskeletal system. Birth defects are among the leading causes of infant mortality and morbidity around the world. Objectives To find the factors associated with an increased risk of facial malformations so that steps for improving preventive measures can be taken. Methodology This was a cross-sectional study in which the data were collected from the files of infants admitted to the pediatric department. Data regarding the type of congenital anomaly, maternal investigations done during pregnancy, maternal history of medication, diabetes, hypertension, radiation exposure, smoking, and alcohol history, and family history of congenital anomalies was collected from the files of neonates and from the pediatrician. In the case of unanswered questions, the parent was contacted after 10 days with their consent. Results Of the sample size of 259 children (males: 132; females: 127), 68 (26%) had a cleft lip, 69 (27%) had a cleft palate, 110 (42%) had both cleft lip and palate, five (2%) had a cleft lip with nasal deformity, five (2%) had a cleft lip and palate with nasal deformity, and two (1%) had hypertelorism. Eight percent of neonates with craniofacial malformations had a family history of congenital malformations; 80.7% of neonates had a history of parental consanguinity; and 19.3% were unrelated. In regard to the mothers, 41.3% of the mothers had diabetes, 4% had hypertension, 4% had both gestational diabetes and hypertension, and 55% had neither of these diseases. Of the 55% of mothers with neither disease, 75% were married to their cousins, while 25% were not married within the family. Practical implications This study, highlighting the major factors contributing to the incidence of congenital facial malformations, will educate the community and establish awareness among the younger generation of the top causes of anomalies, therefore making a huge impact on increasing efforts to reduce the prevalence of congenital anomalies. Conclusion Defects of both the cleft lip and palate had the highest prevalence of facial malformations among study subjects (110 patients (42%)). Parental consanguinity is one of the leading factors associated with an increased risk of facial malformations.

A Novel Peptide Prevents Enterotoxin- and Inflammation-Induced Intestinal Fluid Secretion by Stimulating Sodium-Hydrogen Exchanger 3 Activity

Acute diarrheal diseases are the second most common cause of infant mortality in developing countries. This is contributed to by lack of effective drug therapy that shortens the duration or lessens the volume of diarrhea. The epithelial brush border sodium (Na+)/hydrogen (H+) exchanger 3 (NHE3) accounts for a major component of intestinal Na+ absorption and is inhibited in most diarrheas. Because increased intestinal Na+ absorption can rehydrate patients with diarrhea, NHE3 has been suggested as a potential druggable target for drug therapy for diarrhea. A peptide (sodium-hydrogen exchanger 3 stimulatory peptide [N3SP]) was synthesized to mimic the part of the NHE3 C-terminus that forms a multiprotein complex that inhibits NHE3 activity. The effect of N3SP on NHE3 activity was evaluated in NHE3-transfected fibroblasts null for other plasma membrane NHEs, a human colon cancer cell line that models intestinal absorptive enterocytes (Caco-2/BBe), human enteroids, and mouse intestine invitro and invivo. N3SP was delivered into cells via a hydrophobic fluorescent maleimide or nanoparticles. N3SP uptake stimulated NHE3 activity at nmol/L concentrations under basal conditions and partially reversed the reduced NHE3 activity caused by elevated adenosine 3',5'-cyclic monophosphate, guanosine 3',5'-cyclic monophosphate, and Ca2+ in cell lines and in invitro mouse intestine. N3SP also stimulated intestinal fluid absorption in the mouse small intestine invivo and prevented cholera toxin-, Escherichia coli heat-stable enterotoxin-, and cluster of differentiation 3 inflammation-induced fluid secretion in a live mouse intestinal loop model. These findings suggest pharmacologic stimulation of NHE3 activity as an efficacious approach for the treatment of moderate/severe diarrheal diseases.

Implementation of Rapid Genome Sequencing for Critically Ill Infants With Complex Congenital Heart Disease.

Rapid genome sequencing (rGS) has been shown to improve care of critically ill infants. Congenital heart disease (CHD) is a leading cause of infant mortality and is often caused by genetic disorders, yet the utility of rGS has not been prospectively studied in this population. We conducted a prospective evaluation of rGS to improve the care of infants with complex CHD in our cardiac neonatal intensive care unit. In a cohort of 48 infants with complex CHD, rGS diagnosed 14 genetic disorders in 13 (27%) individuals and led to changes in clinical management in 8 (62%) cases with diagnostic results. These included 2 cases in whom genetic diagnoses helped avert intensive, futile interventions before cardiac neonatal intensive care unit discharge, and 3 cases in whom eye disease was diagnosed and treated in early childhood. Our study provides the first prospective evaluation of rGS for infants with complex CHD to our knowledge. We found that rGS diagnosed genetic disorders in 27% of cases and led to changes in management in 62% of cases with diagnostic results. Our model of care depended on coordination between neonatologists, cardiologists, surgeons, geneticists, and genetic counselors. These findings highlight the important role of rGS in CHD and demonstrate the need for expanded study of how to implement this resource to a broader population of infants with CHD.

Genomic newborn screening for rare diseases.

Rare diseases are a leading cause of infant mortality and lifelong disability. To improve outcomes, timely diagnosis and effective treatments are needed. Genomic sequencing has transformed the traditional diagnostic process, providing rapid, accurate and cost-effective genetic diagnoses to many. Incorporating genomic sequencing into newborn screening programmes at the population scale holds the promise of substantially expanding the early detection of treatable rare diseases, with stored genomic data potentially benefitting health over a lifetime and supporting further research. As several large-scale newborn genomic screening projects launch internationally, we review the challenges and opportunities presented, particularly the need to generate evidence of benefit and to address the ethical, legal and psychosocial issues that genomic newborn screening raises.

Predictors of adverse short-term outcomes in late preterm infants

BackgroundInfants born between 34 weeks and 36 weeks and 6 days of gestation are defined as late preterm infants (LPIs), and they account for approximately 74% of all premature births. Preterm birth (PB) remains the leading cause of infant mortality and morbidity worldwide.AimTo analyse short-term morbidity and mortality and identify predictors of adverse outcomes in late preterm infants.Patients and methodsIn this retrospective study, we evaluated adverse short-term outcomes of LPIs admitted to the Intensive Care Unit (ICU), Clinic for Children’s Diseases, University Clinical Center Tuzla, between 01.01.2020 and 31.12.2022. The analysed data included sex, gestational age, parity, birth weight, Apgar score (i.e., assessment of vitality at birth in the first and fifth minutes after birth), and length of hospitalization in NICU, as well as short-term outcome data. Maternal risk factors we observed were: age of mother, parity, maternal morbidity during pregnancy, complications and treatment during pregnancy. LPIs with major anatomic malformations were excluded from the study. Logistic regression analysis was used to identify risk factors for neonatal morbidity among LPIs.ResultsWe analysed data from 154 late preterm newborns, most of whom were male (60%), delivered by caesarean Sect. (68.2%) and from nulliparous mothers (63.6%). Respiratory complications were the most common outcome among all subgroups, followed by CNS morbidity, infections and jaundice requiring phototherapy. The rate of almost all of the complications in the late-preterm group decreased as gestational age increased from 34 to 36 weeks. Birth weight (OR: 1,2; 95% CI: 0,9 − 2,3; p = 0,0313) and male sex (OR: 2,5; 95% CI: 1,1–5,4; p = 0,0204) were significantly and independently associated with an increased risk for respiratory morbidity, and gestational weeks and male sex were associated with infectious morbidity. None of the risk factors analysed herein were predictors of CNS morbidity in LPIs.ConclusionA younger gestational age at birth is associated with a greater risk of short-term complications among LPIs, thus highlighting the need for increased knowledge about the epidemiology of these late preterm births. Understanding the risks of late preterm birth is critical to optimizing clinical decision-making, enhancing the cost-effectiveness of endeavours to delay delivery during the late preterm period, and reducing neonatal morbidity.

In Vitro Modeling as a Tool for Testing Therapeutics for Spinal Muscular Atrophy and IGHMBP2-Related Disorders.

Spinal Muscular Atrophy (SMA) is the leading genetic cause of infant mortality. The most common form of SMA is caused by mutations in the SMN1 gene, located on 5q (SMA). On the other hand, mutations in IGHMBP2 lead to a large disease spectrum with no clear genotype-phenotype correlation, which includes Spinal Muscular Atrophy with Muscular Distress type 1 (SMARD1), an extremely rare form of SMA, and Charcot-Marie-Tooth 2S (CMT2S). We optimized a patient-derived in vitro model system that allows us to expand research on disease pathogenesis and gene function, as well as test the response to the AAV gene therapies we have translated to the clinic. We generated and characterized induced neurons (iN) from SMA and SMARD1/CMT2S patient cell lines. After establishing the lines, we treated the generated neurons with AAV9-mediated gene therapy (AAV9.SMN (Zolgensma) for SMA and AAV9.IGHMBP2 for IGHMBP2 disorders (NCT05152823)) to evaluate the response to treatment. The iNs of both diseases show a characteristic short neurite length and defects in neuronal conversion, which have been reported in the literature before with iPSC modeling. SMA iNs respond to treatment with AAV9.SMN in vitro, showing a partial rescue of the morphology phenotype. For SMARD1/CMT2S iNs, we were able to observe an improvement in the neurite length of neurons after the restoration of IGHMBP2 in all disease cell lines, albeit to a variable extent, with some lines showing better responses to treatment than others. Moreover, this protocol allowed us to classify a variant of uncertain significance on IGHMBP2 on a suspected SMARD1/CMT2S patient. This study will further the understanding of SMA, and SMARD1/CMT2S disease in particular, in the context of variable patient mutations, and might further the development of new treatments, which are urgently needed.

Risk factors characterisation for CHD: a case-control study in Bogota and Cali, Colombia, 2002-2020.

CHDs correspond to 28% of all congenital anomalies, being the leading cause of infant mortality in the first year of life. Thus, it is essential to explore risk factors for CHDs presentation, allowing the detection of probable cases within a population. We identified newborns with CHDs within a cohort from the Program for the Prevention and Monitoring of Congenital Defects in Bogota and Cali, 2002-2020. Cases were classified as isolated, complex isolated, polymalformed, and syndromic. Variables were analysed by comparing case and control averages with Student's t test using a 95% confidence level. Prevalence obtained was 19.36 per 10 000 live births; non-specified CHD, ventricular septal defect, and atrial septal defect were the most prevalent. As risk factors were found: paternal and maternal age above 45 years, pregestational diabetes, mother's body mass index above 25, low educational level, and socio-economic status. As protective factors: folic acid consumption within the first trimester and pregestational period. Different risk and protective factors associated with the presentation of CHDs have been described. We consider that public health strategies should be aimed to reduce risk factors exposure. Also, improving diagnosis and prognosis by having a close monitoring on high-risk patients.

Immunomodulation of cytokine signalling at feto-maternal interface by microRNA-223 and −150–5p in infection-associated spontaneous preterm birth

Spontaneous preterm birth (sPTB) is a global health concern and it is the most prevalent cause of infant mortality and morbidity with occurrence rate of 5 – 18% worldwide. Studies suggest infection and infection-driven activation of inflammatory responses are the potential risk factors for sPTB. MicroRNAs (miRNAs) are thought to control the expression of several immune genes, making them crucial components of the intricate immune regulatory network and the dysregulation of miRNAs in placenta has been associated to several pregnancy-related complications. However, studies on possible role of miRNAs in immunomodulation of cytokine signalling in infection-associated sPTB are scarce. Present study aimed to investigate expression/ correlation of a few circulating miRNAs (miR-223, −150-5p, −185-5p, −191-5p), miRNA target genes and associated cytokines in sPTB women found infected with Chlamydia trachomatis/ Mycoplasma hominis/ Ureaplasma urealyticum. Non-heparinized blood and placental sample were collected from 140 sPTB and 140 term women visiting Safdarjung hospital, New Delhi (India) for conducting PCR and RT-PCR for pathogen detection and miRNA/ target gene/ cytokine expression, respectively. Common target genes of differentially expressed miRNAs were obtained from databases. The correlation between select target genes/ cytokines and serum miRNAs was determined by Spearman’s rank correlation. 43 sPTB were infected with either pathogen and a significant upregulation of serum miRNAs was observed. However, miR-223 and 150–5p showed maximum fold-change (4.78 and 5.58, respectively) in PTB versus control group. IL-6ST, TGF-β R3 and MMP-14 were important target genes among 454 common targets, whereas, IL-6 and TGF-β were associated cytokines. miR-223 and 150–5p showed significant negative correlation with IL-6ST/ IL-6/ MMP-14 and positive correlation with TGF-β R3/ TGF-β. A significant positive correlation was found between IL-6ST and IL-6, TGF-β R3 and TGF-β. However, miR-185–5p and 191–5p were not significantly correlated. Although post-transcriptional validation is required, yet on the basis of mRNA findings, the study concludes that miR-223 and 150–5p are apparently of clinical importance in regulation of inflammatory processes during infection-associated sPTB.

Pneumonia detection with QCSA network on chest X-ray

Worldwide, pneumonia is the leading cause of infant mortality. Experienced radiologists use chest X-rays to diagnose pneumonia and other respiratory diseases. The diagnostic procedure's complexity causes radiologists to disagree with the decision. Early diagnosis is the only feasible strategy for mitigating the disease's impact on the patent. Computer-aided diagnostics improve the accuracy of diagnosis. Recent studies established that Quaternion neural networks classify and predict better than real-valued neural networks, especially when dealing with multi-dimensional or multi-channel input. The attention mechanism has been derived from the human brain's visual and cognitive ability in which it focuses on some portion of the image and ignores the rest portion of the image. The attention mechanism maximizes the usage of the image's relevant aspects, hence boosting classification accuracy. In the current work, we propose a QCSA network (Quaternion Channel-Spatial Attention Network) by combining the spatial and channel attention mechanism with Quaternion residual network to classify chest X-Ray images for Pneumonia detection. We used a Kaggle X-ray dataset. The suggested architecture achieved 94.53% accuracy and 0.89 AUC. We have also shown that performance improves by integrating the attention mechanism in QCNN. Our results indicate that our approach to detecting pneumonia is promising.

P49: Are We Timely Detecting Congenital Heart Defects in Bogotá and Cali (Colombia)?

Background: Congenital heart defects (CHD) are the main cause of infant mortality. Properly attending CHD demands strategies to improve prenatal diagnosis, planning birth on adequate hospitals, assure timely clinical care for complex cases, and guarantee follow-up and health care access for patients lifelong. Accordingly, Colombian normativity dictates that all pregnant women must have at least a first and second trimester screening with fetal heart examination, 7 to 10 prenatal control visits, and psychological support and information on voluntary termination. The aim of this study was to characterize demographics and prenatal care of expectant mothers of pediatric patients with a confirmed CHD diagnosis. Methods: This study was prospective and observational with an incidental sampling of 134 CHD patients treated at Fundación Cardioinfantil (Bogotá), Hospital Universitario San Ignacio (Bogotá), and Clinica Imbanaco (Cali) in Colombia. Women, after consent, were interviewed about demographics, prenatal care, pre and postnatal diagnosis, and children clinical evolution. We analyzed CHD according to their complexity (simple, moderate or complex) and clinical presentation (isolated, multiple anomalies or syndromes). Data were collected using the REDCap tool, descriptive statistics were calculated using Excel. Variables were expressed as mean (range). Results: 43% of all CDH were prenatally detected (66% of complex CHD were only detected postnatally). Mothers were young (mean age 28.1 years, DE 6.2), 82.1% had completed high school, 71.6% had low-income and 82.1% lived in urban areas with the father. Only 3% had twin pregnancies and 19% had chronic comorbidities (hypertensive disorders, diabetes, or hypothyroidism). On average, mothers had 6.8 prenatal control visits (DE 2.6) and 4.6 ultrasound scans (DE 2.5). As for the proper moment for ultrasound scans, only 61.1% of first-trimester scans and 58.9% of second-trimester scans were on time according to normative. 41% of women did not have psychological support, and 49% did not receive information on voluntary termination. About labor, 45% were spontaneous and 55% cesarian deliveries. Regarding babies (50.7% females), 24.0% were small for gestational age and 25.4% were born before 37 weeks. Most babies had an isolated CHD (15% simple, 76% complex), 5% had multiple anomalies, and 5% syndromes. Comparing prenatal diagnosis (ultrasound scans) and postnatal diagnosis, only in 22% of cases we found a complete agreement, and in 56% CDH was not reported on the ultrasound exams. Conclusion: Ultrasonography is a useful tool to detect CHD, but improving early detection requires better and timely access, especially for complex cases. Colombian normative for prenatal care is not working as expected. Delfos program is funded by Minciencias (Contract No.120484267276).

Completeness and Accuracy of Immunization Status and Smoking Habits Associated with the Incidence of Acute Respiratory Infections in Toddlers in the Kaliasin Health Center Working Area

ARI is the leading cause of infectious disease morbidity and mortality in the world. Nearly four million people die from ARI every year. According to WHO in 2016, the morbidity and mortality rate of ARI is quite high, especially in toddlers. ARI is the number one cause of infant mortality in Indonesia. South Lampung Regency ranks first in the number of ARI cases in children under five every year. The purpose of this study was to determine the factors associated with the incidence of ARI in toddlers. This study is a quantitative study with Cross Sectional design with a population of 2,578 toddlers and a sample of 126 toddlers. The sampling technique used was purposive sampling using univariate and bivariate analysis tests using Chi Square. Toddlers who experience ARI 39.7%, toddlers who have complete immunization status 62.7%, toddlers who have completeness and accuracy of immunization status 27.0% and who have smoking habits 57.9%. There is a relationship between completeness of immunization (p-value = 0.000) with OR 4.450 (CI 2.057-9.624), completeness and accuracy of immunization (p-value = 0.000) with OR 5.553 (CI 1.976-15.607) and smoking habits (p-value = 0.000) with OR 9.419 (CI 3.747-23.677) with the incidence of ARI in toddlers. It is expected that health workers can increase promotive and preventive efforts to the community in the form of counseling or socialization to provide knowledge related to ARI disease