Cohort Of Newborns Research Articles

Bronchopulmonary dysplasia: Incidence and severity in premature infants born at high altitude

Bronchopulmonary dysplasia (BPD) is the most common cause of chronic lung disease in children born prematurely. There is little information about the epidemiology and severity of BPD places with high altitude. This study aimed to evaluate the frequency of BPD severity levels and the associated risk factors with severity in a cohort of preterm newborns ≤36weeks of gestational age born in Rionegro, Colombia MATERIALS AND METHODS: We carried out a retrospective analytical cohort of preterm newborns without major malformations from Rionegro, Colombia between 2011 and 2018 admitted to neonatal intensive unit at high altitude (2200 m above sea level). The main outcomes were the incidence and severity of BPD. The BPD incidence was 23.5% 95% (confidence interval [CI], 19.6-27.7). BPD was grade 1 in 69.9%, grade 2 in 15.5% and grade 3 in 14.5% of patients. After modeling regression analysis, the final variables associated with BPD severity levels were: sepsis (odds ratio [OR], 4.15; 95% CI, 1.33-12.96) and pulmonary hypertension (OR: 3.86; 95% CI, 1.30-11.4). The incidence of BPD was higher and similar to cities with higher altitudes. In our population, the variables associated with BPD severity levels were: sepsis and pulmonary hypertension. It is necessary to increase the awareness of risk factors, the effect of clinical practices, and early recognition of BPD to reduce morbidity in patients with this pathology.

Risk of large for gestational age births at early, full and late term in relation to pre-pregnancy body mass index: Mediation by gestational diabetes status.

Maternal pre-pregnancy body mass index (BMI) is strongly associated with infant birthweight and the risk differs in pregnancies complicated by gestational diabetes (GDM). To examine the risk of large for gestational age (LGA) (≥97th percentile) singleton births at early term, full term and late term in relation to maternal pre-pregnancy BMI status mediated through GDM. We analysed data from the 2018 U.S. National Vital Statistics Natality File restricted to singleton term births (N=3,229,783). In counterfactual models for causal inference, we estimated the total effect (TE), natural direct effect (NDE) and natural indirect effect (NIE) for the association of pre-pregnancy BMI with subcategories of LGA births at early, full and late term mediated through GDM, using log-binomial regression and adjusting for race/ethnicity, age, education, parity and infant sex. Proportion mediated was calculated on the risk difference scale and potential unmeasured confounders were assessed using the E-value. Overall, 6.4% of women had GDM, and there were 3.6% LGA singleton term births. The highest prevalence of GDM was among pre-gestational overweight/obesity that also had the highest rates of LGA births at term. The TE estimates for the risk of LGA births were the strongest across women with higher pre-pregnancy BMI compared to women with normal pre-pregnancy BMI. The NDE estimates were higher than the NIE estimates for overweight/obese BMI status. The proportion mediated, which answers the causal question to what extent the total effect of the association between pre-pregnancy BMI and LGA births is accounted for through GDM, was the highest (up to 16%) for early term births. Term singleton births make up the largest proportion in a cohort of newborns. While the percentage mediated through GDM was relatively small, health risks arising from pre-pregnancy overweight, and obesity can be substantial to both mothers and their offspring.

Severe Acute Complications of Sickle Cell Disease in Two Expert Referral Centers (UK and Italy): Natural History Studies Highlight Ongoing Unmet Need for Effective Disease Modifying or Curative Therapies

Severe Acute Complications of Sickle Cell Disease in Two Expert Referral Centers (UK and Italy): Natural History Studies Highlight Ongoing Unmet Need for Effective Disease Modifying or Curative Therapies

Prevalence and Factors Associated with Maternal Group B Streptococcus Colonization in Madagascar and Senegal.

Maternal group B Streptococcus (GBS) colonization is a major risk factor for neonatal GBS infection. However, data on GBS are scarce in low- and middle-income countries. Using sociodemographic data and vaginal swabs collected from an international cohort of mothers and newborns, this study aimed to estimate the prevalence of GBS colonization among pregnant women in Madagascar (n = 1,603) and Senegal (n = 616). The prevalence was 5.0% (95% CI, 3.9-6.1) and 16.1% (95% CI, 13.1-19.0) in Madagascar and Senegal, respectively. No factors among sociodemographic characteristics, living conditions, and obstetric history were found to be associated independently with GBS colonization in both countries. This community-based study provides one of the first estimates of maternal GBS colonization among pregnant women from Madagascar and Senegal.

Illness severity indicators in newborns by COVID-19 status in the United States, March-December 2020.

ObjectiveTo better understand COVID-19 in newborns, we compared in-hospital illness severity indicators by COVID-19 status during birth hospitalization.Study designIn a retrospective cohort of newborns born March–December 2020 in the Premier Healthcare Database Special COVID-19 Release, we classified COVID-19 status and severe illness indicators using ICD-CM-10 codes, laboratory data, and billing records. Illness severity indicators were compared by COVID-19 status, stratified by gestational age and race/ethnicity.ResultAmong 701,777 newborns, 209 had a COVID-19 diagnosis during the birth hospitalization. COVID-19 status differed significantly by race/ethnicity, gestational age, payor, and region. Late preterm/term newborns with COVID-19 had increased intensive care unit admission and sepsis risk; early preterm newborns with COVID-19 had increased risk for invasive ventilation. Risk for illness severity varied among racial/ethnic strata.ConclusionFrom March to December 2020, COVID-19 diagnosis in newborns was rare. More clinical data are needed to describe the risk profiles of newborns with COVID-19.

138 Fluid overload in newborns undergoing abdominal surgery

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Infants undergoing abdominal surgery, particularly those born preterm, are at risk of postoperative fluid overload and acute kidney injury due to immature cardiac and renal functions, which could contribute to increased morbidity and mortality. Objectives The purpose of this study was to evaluate the burden of fluid overload and acute kidney injury among newborns undergoing abdominal surgery and the association with adverse neonatal outcomes. Design/Methods Newborns who had undergone laparotomy from January 2017 to June 2019 admitted to a tertiary level Neonatal Intensive Care Unit were included in this retrospective cohort study. Fluid overload was assessed by the maximum percentage change in body weight and the difference between actual and prescribed fluid intake post-operatively. Acute kidney injury was defined as an increase in serum creatinine >1.5 times of baseline or >26 mmol/L, or oliguria (< 0 .5mL/kg/hr over 24-hour). Results There were 60 eligible infants with medians [IQR] gestational age (GA) and birth weight being 29 weeks [25–36] and 1240 grams [721–2871], respectively. Indications for laparotomy included small bowel obstruction (45%), necrotizing enterocolitis (23%), and large bowel obstruction (11.7%). In the first three post-operative days, 24/60 (40%) required inotropes, 5/59 (8.5%) had hyponatremia (<130 mmol/L), and 15/31(48.4%) developed hypoalbuminemia (<20 g/L). 52/60 (86.7%) infants had serum creatinine measured and 4 (6.7%) fulfilled our AKI criteria. The median of actual fluid intake was significantly higher than the prescribed fluid intake in the first 7 post-operative days (p<0.01) [Figure 1]. Medians [IQR] of maximum % change of body weight within the first 3- and 7-days post operation were 6 [3–13] and 11 [5 –17], respectively. While we did not identify any associations between post-operative fluid overload and mortality/bronchopulmonary dysplasia in this cohort, we found that every 1% increase in weight gain within the first 3 days post-operation were associated with an increase in 0.6 day of invasive ventilator support (p=0.012) [Figure 2]. Such correlation still exists after adjusting for GA (p=0.033). Conclusion In our cohort of newborns undergoing abdominal surgery, weight gain within the first three post-operative days was associated with an increase in duration of invasive ventilator support. Fluid overload does not seem to be associated with acute kidney injury. Careful attention to intra and early postoperative fluid balance may play an important role in optimizing outcomes of newborns undergoing abdominal surgery.

Ontogeny of plasma cytokine and chemokine concentrations across the first week of human life.

Introduction/background & aims:Early life is marked by distinct and rapidly evolving immunity and increased susceptibility to infection. The vulnerability of the newborn reflects development of a complex immune system in the face of rapidly changing demands during the transition to extra-uterine life. Cytokines and chemokines contribute to this dynamic immune signaling network and can be altered by many factors, such as infection. Newborns undergo dynamic changes important to health and disease, yet there is limited information regarding human neonatal plasma cytokine and chemokine concentrations over the first week of life. The few available studies are limited by small sample size, cross-sectional study design, or focus on perturbed host states like severe infection or prematurity. To characterize immune ontogeny among healthy full-term newborns, we assessed plasma cytokine and chemokine concentrations across the first week of life in a robust longitudinal cohort of healthy, full-term African newborns.Methods:We analyzed a subgroup of a cohort of healthy newborns at the Medical Research Council Unit in The Gambia (West Africa; N = 608). Peripheral blood plasma was collected from all study participants at birth (day of life (DOL) 0) and at one follow-up time point at DOL 1, 3, or 7. Plasma cytokine and chemokine concentrations were measured by bead-based cytokine multiplex assay. Unsupervised clustering was used to identify patterns in plasma cytokine and chemokine ontogeny during early life.Results:We observed an increase across the first week of life in plasma Th1 cytokines such as IFNγ and CXCL10 and a decrease in Th2 and anti-inflammatory cytokines such as IL-6 and IL-10, and chemokines such as CXCL8. In contrast, other cytokines and chemokines (e.g. IL-4 and CCL5, respectively) remained unchanged during the first week of life. This robust ontogenetic pattern did not appear to be affected by gestational age or sex.Conclusions:Ontogeny is a strong driver of newborn plasma-based levels of cytokines and chemokines throughout the first week of life with a rising IFNγ axis suggesting post-natal upregulation of host defense pathways. Our study will prove useful to the design and interpretation of future studies aimed at understanding the neonatal immune system during health and disease.

Predictive value of early amplitude integrated electroencephalogram (aEEG) in sleep related problems in children with perinatal hypoxic-ischemia (HIE)

BackgroundWhile great attention has been paid to motor and cognitive impairments in children with neonatal Hypoxic-Ischemic Encephalopathy (HIE), sleep related circadian rhythm problems, although commonly present, are often neglected. Subsequently, no early clinical indicators have been reported to correlate with sleep-related circadian dysfunction during development.MethodsIn this study, we first analyzed patterns of the amplitude integrated electroencephalogram (aEEG) in a cohort of newborns with various degrees of HIE. Next, during follow-ups, we collected information of sleep and circadian related problems in these patients and performed correlation analysis between aEEG parameters and different sleep/circadian disorders.ResultsA total of 101 neonates were included. Our results demonstrated that abnormal aEEG background pattern is significantly correlated with circadian rhythmic (r = 0.289, P = 0.01) and breathing issues during sleep (r = 0.237, P = 0.037). In contrast, the establishment of sleep–wake cycle (SWC) showed no correlation with sleep/circadian problems. Detailed analysis showed that summation of aEEG score, along with low base voltage (r = 0.272, P = 0.017 and r = -0.228, P = 0.048, respectively), correlates with sleep circadian problems. In contrast, background pattern (BP) score highly correlates with sleep breathing problem (r = 0.319, P = 0.004).ConclusionAbnormal neonatal aEEG pattern is correlated with circadian related sleep problems. Our study thus provides novel insights into predictive values of aEEG in sleep-related circadian problems in children with HIE.

Non-Nutritive Sweeteners in Human Amniotic Fluid and Cord Blood: Evidence of Transplacental Fetal Exposure.

This study aimed to investigate human fetal exposure to non-nutritive sweeteners (NNS) by analyzing amniotic fluid and umbilical cord blood. Concentrations of four NNS (acesulfame-potassium [ace-K], saccharin, steviol glucuronide, and sucralose) were measured in amniotic fluid (n = 13) and cord blood samples (n = 15) using liquid chromatography-mass spectrometry. Amniotic fluid samples were obtained for research purposes at the time of term elective cesarean birth or clinically indicated third trimester amnioreduction at Mercy Hospital for Women (Melbourne, Australia). All except four women were in the fasting state. Cord blood samples were obtained from an independent cohort of newborns whose mothers were enrolled in a separate clinical trial at the National Institutes of Health. Ten of 13 amniotic fluid samples contained at least one NNS (ace-K, saccharin, steviol glucuronide, and/or sucralose). Maximum amniotic fluid NNS concentrations of ace-K, saccharin, steviol glucuronide, and sucralose were 78.9, 55.9, 93.5, and 30.6 ng/mL, respectively. Ace-K and saccharin were present in 100% and 80% of the cord blood samples, with maximal concentrations of 6.5 and 2.7 ng/mL, respectively. Sucralose was not detected and steviol glucuronide was not measurable in any of the cord blood samples. Our results provide evidence of human transplacental transmission of NNS. Based on results predominantly obtained from rodent models, we speculate that NNS exposure may adversely influence the offsprings' metabolic health. Well-designed, prospective clinical trials are necessary to understand the impact of NNS intake during pregnancy on human development and long-term health. · NNS consumption during pregnancy has increased in recent years.. · Maternal NNS intake during pregnancy is associated with preterm birth and higher infant weight gain in epidemiologic studies.. · In rodents, in utero NNS exposure induces metabolic abnormalities in mothers and their offspring, alters offspring gut microbiota composition, and promotes sweet taste preference in adulthood.. · It is presently unknown whether and to what degree maternal NNS ingestion in humans leads to direct in utero exposure.. · This study provides the first evidence of in utero NNS exposure in humans and highlights the urgent need to investigate clinical consequences of early life NNS exposure on metabolism, weight, taste preference, and general health..

Umbilical Cord Erythroferrone Is Inversely Associated with Hepcidin, but Does Not Capture the Most Variability in Iron Status of Neonates Born to Teens Carrying Singletons and Women Carrying Multiples

BackgroundThe developing fetus requires adequate iron and produces its own hormones to regulate this process. Erythroferrone (ERFE) is a recently identified iron regulatory hormone, and normative data on ERFE concentrations and relations between iron status and other iron regulatory hormones at birth are needed. ObjectivesThe objective of this study was to characterize cord ERFE concentrations at birth and assess interrelations between ERFE, iron regulatory hormones, and iron status biomarkers in 2 cohorts of newborns at higher risk of neonatal anemia. MethodsUmbilical cord ERFE concentrations were measured in extant serum samples collected from neonates born to women carrying multiples (age: 21–43 y; n = 127) or teens (age: 14–19 y; n = 164). Relations between cord blood ERFE and other markers of iron status or erythropoiesis in cord blood were assessed by linear regression and mediation analysis. ResultsCord ERFE was detectable in all newborns delivered between 30 and 42 weeks of gestation, and mean concentration at birth was 0.73 ng/mL (95% CI: 0.63, 0.85 ng/mL). Cord ERFE was on average 0.25 ng/mL lower in newborns of black as opposed to white ancestry (P = 0.04). Cord ERFE was significantly associated with transferrin receptor (β: 1.17, P < 0.001), ferritin (β: −0.27, P < 0.01), and hemoglobin (Hb) (β: 0.04, P < 0.05). However, cord hepcidin and the hepcidin:erythropoietin (EPO) ratio captured the most variance in newborn iron and hematologic status (>25% of variance explained). ConclusionsNeonates born to teens and women carrying multiples were able to produce ERFE in response to neonatal cord iron status and erythropoietic demand. ERFE, however, did not capture significant variance in newborn iron or Hb concentrations. In these newborns, cord hepcidin and the hepcidin:EPO ratio explained the most variance in iron status indicators at birth.

Anticipating the long-term neurodevelopmental impact of the COVID-19 pandemic on newborns and infants: A call for research and preventive policy.

It is estimated that 116 million children were born worldwide in the first nine months of the COVID-19 pandemic. Given the critical importance of early life for neurodevelopment, and evidence suggesting that prenatal maternal stress and early childhood adversity negatively impact neurodevelopment, it is alarming that many pregnant women and new mothers are experiencing high levels of pandemic-related stress. Research and proactive mental health policy is needed to minimize the impact of the COVID-19 pandemic on the future mental health of a global cohort of newborns and infants.

Genetic-cellular epilepsy: Clues to diagnosing newborns with neonatal seizures

ObjectiveThe aim of this study was to analyse clinical characteristics of newborns with genetic-cellular epilepsy (GCE) to compare them to those of newborns with seizures with other aetiologies and elucidate clues to the diagnosis of GCE. MethodsThis retrospective single-centre study analysed data from an 8-year cohort of newborns with seizures from 2010-2017. Clinical, neurophysiological, laboratory, and imaging data and outcomes of children with GCE were compared to those of newborns with seizures with other aetiologies. ResultsA total of 112 newborns (N = 68; 61% boys) were included. Hypoxic-ischaemic encephalopathy (N = 42; 29%) was the most common seizure aetiology; GCE (with pathogenic variants KCNQ2, KCNQ3, SCN2A, TBC1D24, CHD2, and STXBP) was diagnosed in 9 (6%). The group of newborns with GCE significantly differed from the group with seizures with other aetiologies in terms of family history of epilepsy (p = 0.000), neonatal epileptic status (NES) (p = 0.007), normal imaging studies (p = 0.000), and outcomes (p = 0.034), but did not differ regarding the type and age of seizure onset, number of antiepileptic drugs administered, and EEG results.Positive family history of epilepsy (p = 0.027), presence of NES (p = 0.041), and normal imaging studies (p = 0.002) were most indicative of the diagnosis of GCE. Probability of GCE with this combination was 0.92. ConclusionIn a heterogenous group of newborns with seizures, a positive family history of epilepsy, presence of NES, and normal imaging studies were most indicative of the diagnosis of GCE.

Higher Concordance in Clinical Assessment versus Ultrasound to Estimate Fetal Weight when it compares with Birth Weight in Full-Term Newborns

Introduction: the aim of this trial was to estimate fetal weight by clinical and ultrasound methods and to compare with the weight at birth in full-term newborns. Methods: This is an epidemiological, observational, cross-sectional study of a cohort of healthy full-term newborns. The sample size was 102 neonates born at the Pablo Arturo Suarez Hospital, in Quito, Ecuador, from November 2019 to January 2020. Results: In full-term neonates, the estimate on ultrasound was 80.00%, while in the clinical assessment was 72.29%. The profile of newborn analyzed is man, mestizo, Ecuadorian, born in the highlands region, with a mean gestational age of 38.67 weeks and a mean birth weight of 3,023 grams, in whom it estimated the fetal weight through ultrasound and clinical assessment. The estimation of the absolute error in both methods analyzed was 2.43% to ultrasound and -4.65% to clinical assessment, and both showed moderate concordance, 78.2% to ultrasound, and 85.6% to clinical assessment. Multivariate analysis showed the neonates with modified weight by ultrasound are 13.44 times more likely to show altered weight at birth, while neonates with modified weight by the clinical assessment are 11.95 times more likely to show altered weight at birth. Conclusions: Accuracy in the clinical assessment was always higher than in the ultrasound method, especially in low weight newborns.

Validation of actigraphy in hospitalised newborn infants using video polysomnography

Actigraphy has been established as a reliable sleep assessment tool in adults; however, its utility in newborns remains unknown. Validation of actigraphy in newborns may provide a significant insight into the physiological and pathological acquisition process of mature diurnal sleep patterns and subsequent morbidities in both newborns and their mothers. Thus, the present study aimed to evaluate the accuracy of sleep-wake detection by overnight actigraphy in a cohort of newborns. Simultaneous recording of polysomnography and actigraphy data was performed in 40 newborns admitted to a tertiary neonatal intensive care unit (NICU). A mixed-effects logistic regression model to explain the sleep state identified by polysomnography was employed using the actigraphic activity score as a fixed independent variable and the individual newborn's identity as a random effect. To evaluate the usefulness of the actigraphic activity score as a surrogate marker of sleep, a receiver operating characteristic (ROC) curve analysis was performed using the variables that were used in the mixed-effects logistic regression model, and the area under the curve (AUC) was assessed. The results showed that polysomnography-determined sleep epochs were associated with a smaller activity index on actigraphy (odds ratio per 10 activity indices increase 0.81, 95% confidence interval [CI] 0.79-0.84). The AUC for the ROC curve was 0.87 (95% CI 0.87-0.88, range 0.54-0.99). An activity score of 124 showed the maximum overall accuracy (90.2%, 95% CI 87.7-92.1). Our present study suggests that sleep-wake states of NICU-hospitalised newborns can be precisely determined using actigraphy on the ankle.

Comparing the Predictivity of Human Placental Gene, microRNA, and CpG Methylation Signatures in Relation to Perinatal Outcomes.

Molecular signatures are being increasingly integrated into predictive biology applications. However, there are limited studies comparing the overall predictivity of transcriptomic versus epigenomic signatures in relation to perinatal outcomes. This study set out to evaluate mRNA and microRNA (miRNA) expression and cytosine-guanine dinucleotide (CpG) methylation signatures in human placental tissues and relate these to perinatal outcomes known to influence maternal/fetal health; namely, birth weight, placenta weight, placental damage, and placental inflammation. The following hypotheses were tested: (1) different molecular signatures will demonstrate varying levels of predictivity towards perinatal outcomes, and (2) these signatures will show disruptions from an example exposure (ie, cadmium) known to elicit perinatal toxicity. Multi-omic placental profiles from 390 infants in the Extremely Low Gestational Age Newborns cohort were used to develop molecular signatures that predict each perinatal outcome. Epigenomic signatures (ie, miRNA and CpG methylation) consistently demonstrated the highest levels of predictivity, with model performance metrics including R2 (predicted vs observed) values of 0.36-0.57 for continuous outcomes and balanced accuracy values of 0.49-0.77 for categorical outcomes. Top-ranking predictors included miRNAs involved in injury and inflammation. To demonstrate the utility of these predictive signatures in screening of potentially harmful exogenous insults, top-ranking miRNA predictors were analyzed in a separate pregnancy cohort and related to cadmium. Key predictive miRNAs demonstrated altered expression in association with cadmium exposure, including miR-210, known to impact placental cell growth, blood vessel development, and fetal weight. These findings inform future predictive biology applications, where additional benefit will be gained by including epigenetic markers.

Development of the genomic inflammatory index (GII) to assess key maternal antecedents associated with placental inflammation

IntroductionPlacental inflammation is associated with a variety of adverse health outcomes, including poor pregnancy outcomes as well as later in life health. The current clinical methodologies for evaluating placental histology for inflammation are limited in their sensitivity. The objective of this study was to develop a genomic inflammatory index (GII) that can be utilized as a biomarker to effectively quantify and evaluate placental inflammation. MethodsRNA-sequencing of n = 386 placentas from the Extremely Low Gestational Age Newborn (ELGAN) cohort was conducted. Transcriptional data for a biologically-targeted set of 14 genes, selected for their established role in pro-inflammatory signaling pathways, were aggregated to construct the GII. Multiple linear regression models were used to examine relationships between 47 perinatal factors and the GII. ResultsThe GII demonstrated a nine-fold difference across subjects and displayed positive trends with other indicators of placental inflammation. Significant differences in the GII were observed for race where women who self-identified as Black displayed higher levels of placental inflammation than those who self-identified as White women (p < 0.001). Additionally, married Black women showed reduced placental inflammation compared to those who were unmarried (beta value: 0.828, p-value: 0.032). Placentas from women who were treated with steroids during the delivery of the infant displayed higher GII levels than those who were not (p = 0.023). DiscussionOverall, the GII demonstrated an association between various perinatal factors and placental inflammation. It is anticipated that the GII will provide a novel genomics tool for quantifying placental inflammation, allowing for further investigation of causes, and ultimately the prevention, of inflammation in the placenta.

Cost effectiveness of typhoid vaccination in India

IntroductionWorld Health Organization has prequalified the use of typhoid conjugate vaccine (TCV) in children over six months of age in typhoid endemic countries. We assessed the cost-effectiveness of introducing TCV separately for urban and rural areas of India. MethodsA decision analytic model was developed, using a societal perspective, to compare long-term costs and outcomes (3% discount rate) in a new-born cohort of 100,000 children immunized with or without TCV. Three vaccination scenarios were modelled, assuming the protective efficacy of TCV to last for 5, 10 and 15 years following immunization. Incidence of typhoid infection estimated under ‘National Surveillance System for Enteric Fever’ (NSSEFI)’ was used. The prices of vaccine and cost of service delivery were included for vaccination arm. Both health system cost and out-of-pocket expenditures for treatment of typhoid illness and its complications was included. ResultsTCV introduction in urban areas would result in prevention of 17% to 36% typhoid cases and deaths. With exclusion of indirect costs, the incremental cost per QALY gained was ₹ 151,346 (54,730–307,975), ₹ 61,710 (−5250 to 163,283) and ₹ 45,188 (−17,069 to 141,093) for scenario 1, 2 and 3 respectively. While, with inclusion of indirect costs, all 3 scenarios were cost saving. Further, in rural areas, TCV is estimated to reduce the typhoid cases and deaths by 19% to 36%, with ICER (incremental cost per QALY gained) ranging from ₹ 2340 (1316–4370) to ₹ 3574 (2057 – 6691) thousand (inclusive of indirect costs) among the 3 vaccination scenarios. ConclusionFrom a societal perspective, introduction of TCV is a cost saving strategy in urban India. Further, due to low incidence of typhoid infection, introduction of TCV is not cost-effective in rural settings of India.

Prevalence of trochlear dysplasia in infants evaluated for developmental dysplasia of the hip.

PurposeThe purpose of this study was to define the incidence of trochlear dysplasia in an infant cohort being screened for developmental dysplasia of the hip (DDH).MethodsNewborns screened for DDH that were evaluated with ultrasound for the presence of trochlear dysplasia were retrospectively reviewed. The sulcus angle and trochlear depth were measured. Based on previous work, trochlear dysplasia was defined as a sulcus angle of > 159°. Our newborn cohort was then analyzed to identify potential risk factors for trochlear dysplasia.ResultsA total of 383 knees in 196 infants were studied. In total, 52% were referred for breech intrauterine positioning and 21% were ultimately diagnosed with DDH and had treatment initiated with a Pavlik harness. Of the entire cohort, 8% of knees were deemed to have trochlear dysplasia. Breech patients were found to have a flatter sulcus angle than those that were not breech (149.5° (sd 7.2°) versus 147.9° (sd 7.5°); p = 0.028). Similarly, a shallower trochlear depth was identified in breech patients versus non-breech patients (1.6 mm (sd 0.4) versus 1.8 mm (sd 0.4); p = 0.019). Those with trochlear dysplasia (as defined by sulcus angle > 159°) did show a smaller alpha angle (i.e. more dysplastic hip) as compared with those without trochlear dysplasia (59.2° (sd 10.2°) versus 65.9° (sd 7.5°); p < 0.001). Hips with DDH were 2.4-times more likely to have knees with trochlear dysplasia (95% confidence interval 1.1 to 5.3).ConclusionUltrasound screening of newborn knees reveals that trochlear dysplasia is relatively common in breech babies with DDH.Level of EvidenceIII

Study on the Clinical Significance of ACE2 and Its Age-Related Expression.

BackgroundACE2 plays a particular role in the changes in multiple organ functions. However, whether ACE2 expression differs at different ages and whether it plays a role in infection-related organ dysfunction remains unclear.MethodsFemale and male C57BL/6 mice in four different age groups were included in this study. Immunohistochemical and Western blot analyses were performed to evaluate ACE2 expression characteristics in lung tissues. At the same time, we detected the changes of ACE2 in human blood of different ages and evaluated its clinical significance in sepsis-associated organ dysfunction (SAOD).ResultsThis study indicated that ACE2 is expressed differently in mouse lung tissues at four different ages (P < 0.05). The peak expression distribution of ACE2 in lung tissues was in the newborn and middle-aged cohorts (P < 0.05). Infants younger than one year had a significantly higher concentration of ACE2 in serum and enhanced susceptibility compared with other ages (P < 0.05). Serum APTT, D-dimer, LDH, and PCT, as well as ACE2 in sepsis and SAOD groups, were statistically significant (P < 0.05) and were related to an increased risk of SAOD. There was a positive correlation between ACE2 and D-dimer (P < 0.05).ConclusionThe levels of ACE2 expression varied in different age groups. It tends to be higher in infants and young children. This result suggests that young children are more susceptible to infection. Moreover, a cutoff value for the ACE2 level >1551.15 pg/mL and D-dimer >984.5 U/L should be considered a warning sign of infection-associated organ dysfunction and guide the clinician in evaluating the patient’s multiple organ function.

Dxpr: an R package for generating analysis-ready data from electronic health records-diagnoses and procedures.

BackgroundEnriched electronic health records (EHRs) contain crucial information related to disease progression, and this information can help with decision-making in the health care field. Data analytics in health care is deemed as one of the essential processes that help accelerate the progress of clinical research. However, processing and analyzing EHR data are common bottlenecks in health care data analytics.MethodsThe dxpr R package provides mechanisms for integration, wrangling, and visualization of clinical data, including diagnosis and procedure records. First, the dxpr package helps users transform International Classification of Diseases (ICD) codes to a uniform format. After code format transformation, the dxpr package supports four strategies for grouping clinical diagnostic data. For clinical procedure data, two grouping methods can be chosen. After EHRs are integrated, users can employ a set of flexible built-in querying functions for dividing data into case and control groups by using specified criteria and splitting the data into before and after an event based on the record date. Subsequently, the structure of integrated long data can be converted into wide, analysis-ready data that are suitable for statistical analysis and visualization.ResultsWe conducted comorbidity data processes based on a cohort of newborns from Medical Information Mart for Intensive Care-III (n = 7,833) by using the dxpr package. We first defined patent ductus arteriosus (PDA) cases as patients who had at least one PDA diagnosis (ICD, Ninth Revision, Clinical Modification [ICD-9-CM] 7470*). Controls were defined as patients who never had PDA diagnosis. In total, 381 and 7,452 patients with and without PDA, respectively, were included in our study population. Then, we grouped the diagnoses into defined comorbidities. Finally, we observed a statistically significant difference in 8 of the 16 comorbidities among patients with and without PDA, including fluid and electrolyte disorders, valvular disease, and others.ConclusionsThis dxpr package helps clinical data analysts address the common bottleneck caused by clinical data characteristics such as heterogeneity and sparseness.