National Institute Of Child Health Research Articles

VENOUS THROMBOEMBOLISM AND ITS OUTCOME IN PEDIATRIC PATIENTS AT A TER-TIARY CARE HOSPITAL OF KARACHI

Venous thromboembolism (VTE) was once considered a rare finding in pediatric population but it has been increasing with recent advances in medical care and technology to diagnose it. This study was conducted to determine the clinical presentation, associated factors and outcome of VTE in hospitalized children in a tertiary care children hospital of Karachi. This descriptive cross sectional study was conducted at National Institute of Child Health, Karachi from December 2020 to January 2022. All patients hospitalized with VTE or who were diagnosed to have DVT while at hospital were included in study. Demographic characteristics, clinical presentation, medical history and laboratory workup was recorded in a semi-structured proforma. Patients were managed by treating physicians as per hospital protocol. Treatment details were recorded along with outcome. A Total of 36 children were diagnosed with VTE. Nine (25%) patients were admitted with clinical features suggestive of DVT while remaining 27 (75%) developed DVT during hospital stay. Median hospital stay of those who developed DVT at hospital was 15 days (IQR 10-30days). Infectious etiology (n=21, 58.3%) was the most common admitting diagnosis followed by central nervous system disorders (n=4, 11.1%). Common clinical features among VTE children were fever, seizures and edema of limbs. Prolonged hospital stay with immobilization and central venous catheterization particularly due to infectious etiology are common factors among children who develop VTE and such patients need to be considered for VTE prophylaxis and treatment.

Bone Mineral Density in Children with Congenital Adrenal Hyperplasia

Background: C Treatment in all forms of CAH includes lifelong replacement of steroids. Steroids have an impact on bone health in multiple ways and are known to cause osteoporosis when given in high doses or for a longer duration. Objective: To evaluate bone mineral density (BMD), using dual-energy X-ray absorptiometry (DEXA) scan in children with CAH taking long-term steroids presenting in the pediatric endocrinology ward of National Institute of Child Health, (NICH) Karachi, Pakistan. Materials and Methods: This cross-sectional study was performed at the Department of Pediatric Endocrinology, National Institute of Child Health, Karachi from October 2021 to July 2022. A total of 47 diagnosed cases of CAH taking steroids for more than 5 years were enrolled. Assessment of BMD was done using a DEXA scan. Lumbar spine BMD was done and Z-score was modified for height for age z-score. The dose of steroids and duration was calculated. Results: Out of 47 patients, low BMD was observed in 8 (17.02%) patients. Individuals with low BMD had significantly higher median duration, (p=0.017), dose (p=0.003), and median alkaline phosphate level (p=0.036),) but low median BMD value (p=0.009) and z score (p<0.001) than normal BMD individuals. Although median bone age (p=0.009) was appropriate for chronologic age in low BMD patients. A moderate negative significant correlation was observed between z score and age (rho=-0.319, p=0.029), z-score and duration of steroid treatment (rho=-0.364, p=0.012), z score and alkaline phosphate (rho=-0.466, p=0.001), z score and bone age (rho=-0.378, p=0.009). Conclusion: Low BMD was observed in 17% of children on the DEXA scan. Moreover, these individuals had significantly higher median average duration and dose of hydrocortisone.

Clinical and etiological profile of Complicated Urinary Tract Infection in Children: A health facility-based cross-sectional study

Background: Urinary tract infection (UTI) is known to be the most frequent bacterial infection in the paediatric population. Objective: To determine the clinical profile and etiology of complicated urinary tract infection (UTI) in children. Methods: This cross-sectional study was done at the Department of Nephrology and Neonatology, National Institute of Child Health, Karachi from 1st January 2022 to 30th June 2022. In 241 children of either gender, (male and female) aged up to 15 years having structural or functional anomalies of the kidney and urinary tract or recurrent infection due to underlying kidney or urinary tract abnormalities were enrolled. Demographic and clinical characteristics along with laboratory parameters and etiological agents of complicated UTI were noted. Ultrasonography examination and dimercaptosuccinic acid (DMSA) renal scan (where indicated) were performed. Results: Of 241 children, 179 (74.3%) were male. The mean age was 3.08±3.63 years. Capillary refill time was prolonged in 78 (32.4%) children. Fever/chills, nausea/vomiting, urinary urgency, and dehydration were the most frequently noted clinical presentations reported in 232 (96.2%), 109 (45.2%), 91 (37.8%), and 89 (36.9%) children respectively. Ultrasonography findings were evident of bilateral moderative hydronephrosis in 60 (24.9%) children. E. coli followed by Pseudomonas and Klebsiella species were the most commonly found etiological agents noted in 98 (40.7%), 50 (20.7%), and 40 (16.6%) children respectively. Conclusion: The majority of the children with complicated UTIs were male. Fever/chills, nausea/vomiting, urinary urgency, and dehydration were the most frequently noted clinical presentations. The most commonly observed ultrasonography findings were bilateral moderative hydronephrosis

Comparison of Body Composition Bio Electrical Impedance Analysis of Type-1 Diabetes vs. Non-Diabetes in Children and Adolescent

Background: Analyzing the body composition of children and adolescents with diabetes is becoming more and more popular. For managing weight changes that may emerge from treatment and evaluating treatment response, it is essential to comprehend the body composition of diabetic children. Objective: To compare body composition by Bioelectrical Impedance Analysis (BIA) among T1DM versus healthy children and adolescents in Pakistan. Methods: This comparative cross-sectional study was performed during Jan-March, 2023. Type 1 diabetic children and adolescents were enrolled from the pediatric endocrinology outpatient clinic of the National Institute of Child Health whereas healthy children and adolescents were enrolled from a nearby school to the hospital location. Evaluation of anthropometry indices and bioelectrical impedance analysis was performed after obtaining the consent of parents. Results: A total of 100 subjects were enrolled in the study, 50 each in the diabetic and healthy group. The mean age of participants was 10.4 ± 2.4 years. The majority of study subjects were females (61%). The mean duration of T1DM was 4.7 ± 0.8 years. Height (127.4 ± 11.7 versus 139.5 ± 15, p<0.001), Waist-hip ratio (0.8 ± 0.1 versus 0.7± 0.3, p=0.037) and resistance (686.2 ± 90.7 versus 651.1 ± 96.6, p=0.002) were significantly higher among T1DM group than healthy group. Percentage of muscle mass (45.1 ± 8.2 versus 50.3 ± 7.6, p=0.008), body cell mass (47.1 ± 3.8 versus 50.6 ± 4.5, p=0.045), reactance (56.3 ± 9.8 versus 62.4 ± 4.2, p=0.017) and phase angle (4.3 ± 0.9 versus 5.7 ± 0.6, p=0.012) were significantly lower in T1DM patients than healthy individuals. Conclusion: BIA analysis showed that body composition parameters and body functional status were lower among T1DM children and adolescents than in the healthy group in terms of resistance, reactance, and phase angle.

Intrapartum electronic fetal monitoring and perinatal outcomes: Analysis of components of fetal heart rate pattern

Aim: The aim of this study was to assess the components of cardiotocography (CTG) during labor to identify the variables associated with the risk of adverse perinatal outcomes and to ascertain the mode of delivery in these women. Materials and Methods: This prospective observational study included 191 women at term with singleton pregnancy in labor. The CTG findings including baseline heart rate, accelerations, beat-to-beat variability, and type and severity of decelerations were noted as per the International Federation of Gynecology and Obstetrics classification and grouped into Category II or III patterns as per the National Institute of Child Health and Human Development classification. Low APGAR score, cord PH <7, neonatal intensive care unit admission, respiratory distress, and hypoxic-ischemic encephalopathy were considered adverse neonatal outcomes. Results: Persistent fetal tachycardia, poor beat-to-beat variability, and severe variable deceleration showed a significant association with adverse neonatal outcome and delivery by cesarean section (P < 0.05). Adverse neonatal outcomes were noted in 4.2% of babies and 40.9% of babies born to mothers whose CTG was categorized as II and III patterns, respectively (P < 0.001). Birth by cesarean section was significantly different between those with Category II and Category III patterns, 33.7% and 65.4%, respectively (P < 0.01). Conclusion: Reduction in the beat-to-beat variability and presence of severe variable decelerations are independent risks for adverse neonatal outcomes, irrespective of the category of CTG pattern. Category III fetal heart rate pattern shows a significant association with adverse outcomes and risk of cesarean delivery. Grading the Category II patterns may help in identifying variables that are truly associated with acidemia and further research into this is recommended.

Cardiovascular Compromise in Pediatrics in the Times of COVID-19: SARS-CoV-2 Infection and Kawasaki Disease

Introduction: The pandemic caused by the new SARS-CoV-2 virus has reported an increase in morbidity and mortality worldwide during the years 2020 to 2022. Many pediatric infections have been reported as mild. The cardiovascular complications due to COVID-19 described in the literature are mainly in adults, however, reports in the pediatric population have been less frequent. Objective: To describe the clinical characteristics and evolution of patients treated in two centers with cardio-pediatric care services who presented cardiovascular involvement during the COVID-19 pandemic related to the presence of SARS-CoV-2 infection and Kawasaki disease (KD). Materials and Methods: Through a descriptive, retrospective study, the medical records, electrocardiographic and echocardiographic studies were reviewed in both groups of patients between May 2020 and May 2022 at the National Institute of Child Health and Alberto Sabogal Hospital. None of the cases had a history of previous structural heart disease. Results: The patients studied were 31 in total, with 21 cases of COVID-19 (SARS-CoV-2 infection) and 10 of KD. The female sex predominated, with an average age of 6.2 years (COVID-19) and 2.9 years (Kawasaki). In the echocardiogram, mild pericardial effusion was the most common finding. Coronary alterations were found in 60% of patients with KD and in only 18% of COVID-19 cases. We found 15 patients who met the criteria for the so-called multisystem syndrome (MIS-C) among COVID-19 cases, 5 of them with hemodynamic compromise. Conclusion: During the COVID-19 pandemic, the clinical picture in both groups: SARS-CoV-2 infection and KD presented some similar characteristics, mainly in relation to coronary involvement (greater involvement in KD), and in the evolution, a greater hemodynamic compromise was evidenced in cases of SARS-CoV-2 infection but without associated mortality.

Sensitivity and Specificity of C-Reactive Protein Against Blood Culture in Patients with Neonatal Sepsis - A Hospital-Based Study

Background: Neonatal septicemia is one of the primary causes of disease and death in low-income countries which makes early diagnosis an important factor to prevent microbial resistance and initiate antibiotic therapy. C-reactive protein is an essential biological indicator that might play an important role in the early detection of neonatal sepsis. Objective: The present study was conducted to determine the sensitivity and specificity of CRP against blood culture in the identification of neonatal sepsis. Methods: This study was carried out on 416 neonates identified with sepsis at the NICU and SICU of the National Institute of Child Health, Karachi, Pakistan for a span of 06 months from April 2022 to September 2022. The first blood sample for the evaluation of CRP and blood culture was drawn at the time of admission. The second sample of CRP and blood culture was drawn 72 hours after the first blood collection. The sensitivity and specificity of CRP were calculated on both occasions. Results: Of the total 416 neonates, 165(39.6 %) patients’ blood culture was positive and in 273 (65.9%) patients CRP was positive. The validation study of CRP in the diagnosis of neonatal septicemia reported sensitivity, specificity, positive predictive value, and negative predictive value to be 87.1%, 45.9%, 52.6%, and 83.7% 72 hours after the admission in comparison to 80.6%, 44.2%, 48.7%, and 77.6% at the time of admission. Conclusion: The high specificity and sensitivity of CRP against blood culture make it an important diagnostic modality that might play a helpful role in the diagnosis of neonatal sepsis.

Clinical Manifestations and Etiology of Liver Abscess in Children in Tertiary Care Hospital

Background: The liver is a major metabolic organ with a dual blood supply, hence vulnerable to infection. The liver abscess (LA) is a space-occupying lesion in the liver parenchyma filled with pus caused by bacteria, parasites, or fungus. Objective: To determine the clinical manifestations and etiology of liver abscess among children presenting at a tertiary care hospital. Methodology: This descriptive cross-sectional study was conducted at the medical department of the National Institute of Child Health, Karachi, Pakistan from July 2022 to December 2022. A total of 147 children of either gender aged below 12 years with liver abscesses were analyzed. At the time of enrollment, demographic features, clinical features, characteristics, and etiological agents of LA. The cause of the liver abscess was confirmed by pus culture, blood culture, and indirect haemagglutination assay (IHA). Aspiration was performed among cases who had LA&gt;5cm and liquefication of abscess. Results: Of a total of 147 children with LA, 96 (65.3%) were boys. The mean age was 7.08±2.61 years. Socioeconomic status of 112 (76.2%) children was poor. In terms of frequency of presenting features/complaints, pyrexia (100%) and abdominal pain (98.6%) were the most commonly found whereas hepatomegaly (98%) and right hypochondrium tenderness (97.3%) were the commonest signs. The right hepatic lobe was involved in 120 (81.6%) LA cases and the majority of LA were solitary (93.2%). The size of the liver in 57 (38.8%) LA cases was between 3-6 cm while 93 (63.3%) cases were aspirated. The etiological diagnosis revealed that bacterial involvement was found in 36 (24.5%) LA cases while amoebic presence was noted in 75 (51.0%) cases. No cases of fungal involvement were found. Conclusion: A predominance of male gender and low socioeconomic status was found among children with LA presenting at a tertiary care hospital in Karachi, Pakistan. The most frequent presenting complaints were pyrexia and abdominal pain. Amoebic presence was the most common etiologic agent behind LA.

Frequency of Functional Gastrointestinal Disorders in Children with Recurrent Abdominal Pain

Background: Functional gastrointestinal disorders (FGIDs) are common disorders characterized by chronic or recurrent gastrointestinal (GI) symptoms, not related to structural or biochemical abnormalities Objective: To determine the frequency of FGIDs in children with complaints of recurrent abdominal pain. Methods: This cross-sectional study was done at the outpatient department of pediatrics, National Institute of Child Health, Karachi, Pakistan from October 2022 to March 2023. Children of either gender aged 1-12 years with complaints of recurrent abdominal pain were analyzed. Socio-demographic characteristics along with presenting complaints and types of FGIDs were noted. Results: In a total of 188 children, the mean age was 7.22±1.96 years while 107 (56.9%) children were boys. The mean duration of symptoms was 2.7±1.8 months. The most frequent presenting complaints were pain during bowel movement, nausea, and epigastric pain reported by 88 (46.8%), 75 (39.9%), and 64 (34.0%) children respectively. Frequency distribution of functional GI disorders revealed that functional abdominal pain was the commonest noted in 72 (38.3%) children while irritable bowel syndrome (IBS) and functional dyspepsia were found among 38 (20.2%) and 37 (19.7%) children respectively. Stratification of functional GI disorders showed a statistically significant relationship (p&lt;0.001) concerning presenting complaints. Conclusion: Among children with FGIDs, the most frequent presenting complaints were pain during bowel movement, nausea, and epigastric pain. Functional abdominal pain, IBS, and functional dyspepsia were the most frequent types of FGIDs.

Rhabdomyolysis in Children Under Treatment for Diabetic Ketoacidosis at National Institute of Child Health

Objectives: To determine the frequency of rhabdomyolysis in children under treatment for Diabetic Ketoacidosis (DKA) at National Institute of Child Health (NICH). Materials and Methods: Total 100 patients who were suffering from DKA were enrolled. Blood and urine samples were collected from of each child in aseptic conditions in sterilized container and sent for base line labs, urine ketone and serum creatinine kinase (CK) levels. All the demographic details and duration of diabetes mellitus and DKA and its treatment were recorded on a predesigned data collection proforma. Results: Out of 100 patients, 43 were male and 57 were female with mean age of 9.79±3.26 years. Seventy percent of the patients were aged 7.1-14 years, followed by 25.0% patients were aged 1-7 years and only 5.0% patients were aged of 14.1-18 years. The Mean duration of DM and DKA were 3.89±2.75 years and 9.72±4.65 hours respectively. Mean RBS, Urea and Creatinine level were 404.9± 99.1, 35.70±27.5 mg/dl and 0.73±0.75 mg/dl respectively. Mean hemoglobin and WBC level were 13.61±14.3 g/l and 16.33±11.8 respectively. The mean Na level was 137.79±5.64 mmol/l, mean K level was 4.01±0.89 mmol/l, mean Phosphorus level was 27.6±42.0 mg/dl and mean Cl level was 106.8±6.3 mmol/l. The mean PH was found 7.1±6.49 and mean Bicarbonate was 7.56±3.01 mmol/l. Fifty two percent patients were treated for more than 24 hours and 48.0% patients were treated for less than 24 hours. 7% patients under treatment for DKA were suffered from Rhabdomyolysis and expiry was 5%. Practical implication: In this study we find out that there is very little chance of causing rhabdomyolysis under treatment for DKA but we should take precautionary measures to prevent its progression towards its complications i.e., renal failure and cardiac Arrest which can lead to mortality. This study will lead a positive role in early cure of the DKA patients to avoid further complication. Conclusion: It is concluded that in DKA patients Rhabdomyolysis is of clinical concern because it can result in significant morbidity and mortality by causing Acute Renal failure, DIC, Cardiac Arrest, Arrythmias, significant electrolyte imbalance, but there is very little chance of causing rhabdomyolysis under treatment for DKA in our setup and it too can be avoided by early and aggressive treatment of DKA. Keywords: Rhabdomyolysis, Diabetic Ketoacidosis, Children, Hemoglobin , Creatinine

Acute Kidney Injury in Patients with Diabetic Ketoacidosis at National Institute of Child Health

Objectives: To determine the frequency of acute kidney injury (AKI) in patients with diabetic Ketoacidosis at National Institute of Child Health (NICH). Materials and Methods: Totally 80 patients who were enrolled. Demographics data were noted. Five ml venous blood sample and urine sample were collected from of each child in aseptic conditions in sterilized container and sent to laboratory of the hospital for random blood sugar (RBS), serum urea, serum creatinine, serum electrolytes (Na, K, Ph,) complete blood count (CBC, hemoglobin (Hb), white blood cells (WBC), platelets count, arterial blood gas (ABG), and ketones. All were drawn at the time of admission and after 24 hours. All children were catheterized at time of admission to monitor urine output which is part of DKA protocol and was recorded at 6, 12, 24 hours. AKI were labelled according to KDIGO classification as stage I, II, III depending upon rise in serum creatinine from baseline or according to urine output at 6, 12, 24 hours. All the demographic details and duration of diabetes mellitus and DKA and its treatment were recorded on a predesigned data collection proforma. Results: Out of 80 patients, 44.3% were male and 55.7% were female with mean age of 9.63± 3.34 years. 67% of the patients were aged 7.1-14 years, followed by 27% patients were aged 1-7 years and only 5.7% patients were aged of 14.1-18 years. The mean Duration of hospital stay was 6.88±1.45 days. The Mean Hb and WBCs, and Platelets level were 12.13±1.9 g/l, 16.37±7.97 and 348836.3±140355.4 respectively. The mean PH of all the enrolled patients was found 7.08±0.14 and mean Bicarbonate was 7.54±3.37mmol/L. The mean RBS at admission time and after 24-hour treatment were 403.7±95.42 mg/dl and 266.7±65.1 mg/dl respectively. The mean Serum Urea at admission time and after 24-hour treatment were 36.6±28.9 mg/dl and 36.9±23.5 mg/dl respectively. And the mean serum creatinine (mg/dl) at admission time and after 24-hour treatment were 0.75±0.58 and 0.76±0.55 mg/dl respectively. The mean electrolytes (Na, K, Ph) at admission time and after 24 hours were 138.4±7.0 mmol/l and 139.1±4.0 mmol/l, 4.0±0.83 mg/dl and 4.88±4.83 mg/dl, 19.2±30.7 mg/dl and 16.1±22.0 mg/dl respectively. Frequency of AKI was 31.8% and patients needed for peritoneal dialysis were 3.4%. Practical implication: In our study it was find out that AKI is a common complication in patients with Diabetic ketoacidosis. So this study will help the clinical practioner to also treat the patients for acute kidney injury that will provide early recovery from all the symptom of acute kidney injury. Conclusion: AKI is a common complication in children who are admitted for DKA and clinical practitioner should take precautionary parameter to avoid such complication. Keywords: Acute Kidney Injury, Diabetic Ketoacidosis, Children, DM, DM Type-1, child health, Frequency, NICH

Imaging Characteristics of Retinoblastoma: A Single Tertiary Care Center Experience from Pakistan

Background: Retinoblastoma is a rare tumor of eye in the pediatric population. It is seen in every 15000-18000 births with no gender or racial predilection. Retinoblastoma can have a variable presentation ranging from leukocoria to a mass in the eye. Aim: To provide physicians a snapshot of different modes of presentation. This study employs the data from computed tomography (CT) and magnetic resonance imaging (MRI) and analyzing it for frequency of different presentations from a radiological point of view. Methods: This was a retrospective cross-sectional study carried out at the National Institute of Child Health (NICH) which is the largest tertiary care pediatric center in Karachi, Pakistan. Records of children from 1 month to 16 years who were diagnosed with retinoblastoma between March 2021 to March 2022 were accessed from the database and assessed. The collected data was then analyzed on SPSS 26. Results: The most frequent presentation noted was leukocoria followed by vision loss, swelling, pain and redness. Calcification was the most frequently reported feature in CT scan whereas retroglobular involvement was mostly seen in MRI scans. Chi square showed a statistically significant correlation between age at presentation with presenting symptoms (p=0.04) and sellar involvement (p=0.00). Additionally, statically significant association was seen between family history and laterality in our study. Conclusion: MRI is the recommended modality due to its sensitivity and superior soft-tissue resolution. CT scan is superior to MRI in detecting calcifications. In developing countries due to a lack of proper facilities and awareness, there is a disparity in the prognosis and presentation of retinoblastoma. Bilateral tumors are most commonly heritable and patients presenting with tumors in both eyes are recommended a through genetic workup. Keywords: Retinoblastoma, ocular tumor, leukocoria, red eye, Magnetic resonance imaging, computed tomography

Predicting 2-year neurodevelopmental outcomes in extremely preterm infants using graphical network and machine learning approaches

Infants born extremely preterm (<28 weeks' gestation) are at high risk of neurodevelopmental impairment (NDI) with 50% of survivors showing moderate or severe NDI when at 2 years of age. We sought to develop novel models by which to predict neurodevelopmental outcomes, hypothesizing that combining baseline characteristics at birth with medical care and environmental exposures would produce the most accurate model. Using a prospective database of 692 infants from the Preterm Epo Neuroprotection (PENUT) Trial, which was carried out between December 2013 and September 2016, we developed three predictive algorithms of increasing complexity using a Bayesian Additive Regression Trees (BART) machine learning approach to predict both NDI and continuous Bayley Scales of Infant and Toddler Development 3rd ed subscales at 2 year follow-up using: 1) the 5 variables used in the National Institute of Child Health and Human Development (NICHD) Extremely Preterm Birth Outcomes Tool, 2) 21 variables associated with outcomes in extremely preterm (EP) infants, and 3) a hypothesis-free approach using 133 potential variables available for infants in the PENUT database. The NICHD 5-variable model predicted 3-4% of the variance in the Bayley subscale scores, and predicted NDI with an area under the receiver operator curve (AUROC, 95% CI) of 0.62 (0.56-0.69). Accuracy increased to 12-20% of variance explained and an AUROC of 0.77 (0.72-0.83) when using the 21 pre-selected clinical variables. Hypothesis-free variable selection using BART resulted in models that explained 20-31% of Bayley subscale scores and AUROC of 0.87 (0.83-0.91) for severe NDI, with good calibration across the range of outcome predictions. However, even with the most accurate models, the average prediction error for the Bayley subscale predictions was around 14-15 points, leading to wide prediction intervals. Higher total transfusion volume was the most important predictor of severe NDI and lower Bayley scores across all subscales. While the machine learning BART approach meaningfully improved predictive accuracy above a widely used prediction tool (NICHD) as well as a model utilizing NDI-associated clinical characteristics, the average error remained approximately 1 standard deviation on either side of the true value. Although dichotomous NDI prediction using BART was more accurate than has been previously reported, and certain clinical variables such as transfusion exposure were meaningfully predictive of outcomes, our results emphasize the fact that the field is still not able to accurately predict the results of complex long-term assessments such as Bayley subscales in infants born EP even when using rich datasets and advanced analytic methods. This highlights the ongoing need for long-term follow-up of all EP infants. Supported by the National Institute of Neurological Disorders and StrokeU01NS077953 and U01NS077955.

Neonatal and Obstetric Provider Perceptions and Management at 22 Weeks' Gestation.

Active treatment for periviable infants may be influenced by neonatal and obstetric provider perceptions of prognosis. The two aims of this study are to (1) quantify prognostic discordance between provider and data-driven survival estimates and (2) evaluate if prognostic discordance is associated with the threshold probability of survival at which neonatal providers recommend active treatment or obstetric providers recommend antenatal corticosteroids. Provider survival estimates and threshold probabilities of survival for active treatment and antenatal steroid use were obtained from a case-based survey for an infant or pregnancy at 22 weeks' gestation that was administered at two Atlanta hospitals. Data-driven survival estimates, including ranges, were acquired through the National Institute of Child Health and Human Development Extremely Preterm Birth Outcomes Tool. Prognostic discordance was calculated as the difference between a provider and data-driven estimates and classified as pessimistic (provider estimate below data-driven estimate range), accurate (within range), or optimistic (above range). The association between prognostic discordance and the threshold probability of survival was evaluated using nonparametric tests. We had 137 neonatal respondents (51% response rate) and 57 obstetric responses (23% response rate). The overall median prognostic discordance was 1.5% (interquartile range: 17, 13) and 52 (27%) of all respondents were pessimistic, 100 (52%) were accurate, and 42 (22%) were optimistic. The survival threshold above which neonatal and obstetric providers recommended active treatment or antenatal corticosteroids was 30% (20-45%) and 10% (0-20%), respectively. Thresholds did not significantly differ among the three prognostic discordance groups (p = 0.45 for neonatal and p = 0.53 for obstetric providers). There was also no significant correlation between the magnitude of prognostic discordance and thresholds. Prognostic discordance exists among both neonatal and obstetric providers. However, this discordance is not associated with the threshold probability of survival at which providers recommend active treatment or antenatal corticosteroids at 22 weeks' gestation. · Prognostic discordance at 22 weeks' gestation exists for neonatal and obstetric providers.. · Prognostic discordance is not associated with survival thresholds for neonatal active treatment.. · Prognostic discordance is not associated with survival thresholds for the use of antenatal corticosteroids..

Increasing access to justice for children: A brief report on the Brazilian Sign Language version of the NICHD protocol

Children with disabilities are abused, including sexually abused, at higher rates than their non-disabled counterparts. To ensure access to justice for all child victims of violence, child protection systems must have adequate protocols and training to support each child, including those who are hard of hearing or deaf. One important modification is ensuring that investigative interview protocols, such as the National Institute of Child Health and Human Development investigative interview protocol (NICHD), are adapted to provide hard of hearing children with the interview’s full benefits. The current report presents an innovative effort to develop a culturally-sensitive translation of the NICHD from Brazilian Portuguese to Brazilian Sign Language (LIBRAS) and an accompanying training on the NICHD for translators (NICHD-LIBRAS). The NICHD-LIBRAS was translated by a three-step process. In Step 1, the Brazilian NICHD was translated by a certified LIBRAS translator into morphemes. In Step 2, the authors used a modulation format to detect discrepancies between the original protocol and the translated language. Finally, in Step 3, the protocol was recorded into a video format, back-translated by a certified LIBRAS interpreter, and posted on YouTube. The tool is publicly available for Brazilian professionals and for researchers to test its efficacy and feasibility. The current brief report aims to encourage future efforts to adapt investigative interview protocols for children with disabilities and to advance access to justice for children from diverse contexts.

Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer's disease: a cross-sectional study

Important insights into the early pathogenesis of Alzheimer's disease can be provided by studies of autosomal dominant Alzheimer's disease and Down syndrome. However, it is unclear whether the timing and spatial distribution of amyloid accumulation differs between people with autosomal dominant Alzheimer's disease and those with Down syndrome. We aimed to directly compare amyloid changes between these two groups of people. In this cross-sectional study, we included participants (aged ≥25 years) with Down syndrome and sibling controls who had MRI and amyloid PET scans in the first data release (January, 2020) of the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study. We also included carriers of autosomal dominant Alzheimer's disease genetic mutations and non-carrier familial controls who were within a similar age range to ABC-DS participants (25-73 years) and had MRI and amyloid PET scans at the time of a data freeze (December, 2020) of the Dominantly Inherited Alzheimer Network (DIAN) study. Controls from the two studies were combined into a single group. All DIAN study participants had genetic testing to determine PSEN1, PSEN2, or APP mutation status. APOE genotype was determined from blood samples. CSF samples were collected in a subset of ABC-DS and DIAN participants and the ratio of amyloid β42 (Aβ42) to Aβ40 (Aβ42/40) was measured to evaluate its Spearman's correlation with amyloid PET. Global PET amyloid burden was compared with regards to cognitive status, APOE ɛ4 status, sex, age, and estimated years to symptom onset. We further analysed amyloid PET deposition by autosomal dominant mutation type. We also assessed regional patterns of amyloid accumulation by estimated number of years to symptom onset. Within a subset of participants the relationship between amyloid PET and CSF Aβ42/40 was evaluated. 192 individuals with Down syndrome and 33 sibling controls from the ABC-DS study and 265 carriers of autosomal dominant Alzheimer's disease mutations and 169 non-carrier familial controls from the DIAN study were included in our analyses. PET amyloid centiloid and CSF Aβ42/40 were negatively correlated in carriers of autosomal dominant Alzheimer's disease mutations (n=216; r=-0·565; p<0·0001) and in people with Down syndrome (n=32; r=-0·801; p<0·0001). There was no difference in global PET amyloid burden between asymptomatic people with Down syndrome (mean 18·80 centiloids [SD 28·33]) versus asymptomatic mutation carriers (24·61 centiloids [30·27]; p=0·11) and between symptomatic people with Down syndrome (77·25 centiloids [41·76]) versus symptomatic mutation carriers (69·15 centiloids [51·10]; p=0·34). APOE ɛ4 status and sex had no effect on global amyloid PET deposition. Amyloid deposition was elevated significantly earlier in mutation carriers than in participants with Down syndrome (estimated years to symptom onset -23·0 vs -17·5; p=0·0002). PSEN1 mutations primarily drove this difference. Early amyloid accumulation occurred in striatal and cortical regions for both mutation carriers (n=265) and people with Down syndrome (n=128). Although mutation carriers had widespread amyloid accumulation in all cortical regions, the medial occipital regions were spared in people with Down syndrome. Despite minor differences, amyloid PET changes were similar between people with autosomal dominant Alzheimer's disease versus Down syndrome and strongly supported early amyloid dysregulation in individuals with Down syndrome. Individuals with Down syndrome aged at least 35 years might benefit from early intervention and warrant future inclusion in clinical trials, particularly given the relatively high incidence of Down syndrome. The National Institute on Aging, Riney and Brennan Funds, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the German Center for Neurodegenerative Diseases, and the Japan Agency for Medical Research and Development.

Association between marked fetal heart rate variability and neonatal acidosis: A prospective cohort study.

To assess the association between marked variability in fetal heart rate (FHR) and neonatal acidosis. Bicentric prospective cohort study. From January 2019 to December 2019, in two French tertiary care maternity units. Women in labour at ≥37 weeks of gestation, with continuous FHR monitoring until delivery and with the availability of umbilical arterial pH. Women with intrauterine fetal death or medical termination, multiple pregnancies, non-cephalic presentation or planned caesarean delivery were excluded. The exposure was marked variability in FHR in the 60 minutes before delivery, defined as a variability greater than 25 beats per minute, with a minimum duration of 1minute. To assess the association between marked variability and neonatal acidosis, we used multivariable modified Poisson regression modelling. We then conducted subgroup analyses according to the US National Institute of Child Health and Human Development (NICHD) category of the associated fetal heart rate. Neonatal acidosis, defined as an umbilical artery pH of ≤7.10. Among the 4394 women included, 177 (4%) had marked variability in fetal heart rate in the 60 minutes before delivery. Acidosis occurred in 6.0% (265/4394) of the neonates. In the multivariable analysis, marked variability was significantly associated with neonatal acidosis (aRR2.30, 95%CI 1.53-3.44). In subgroup analyses, the association between marked variability and neonatal acidosis remained significant in NICHD category-I and category-II groups. Marked variability was associated with a twofold increased risk of neonatal acidosis.

Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm

Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm. To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months' corrected age. This cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks' gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers. Culture-confirmed LOM. Incidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021). Among 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 (P < .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 (P < .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P < .001) and among those with culture-confirmed LOS (23%-79%, P < .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus, 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection. In this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.

Self-regulation linking the quality of early parent-child relationship to adolescents' obesity risk and food consumption.

The quality of parent-child relationships has been examined as a contributor to children's healthy behaviours and weight outcomes, but the mechanisms accounting for associations remain understudied. This study examined whether the quality of early parent-child relationship is associated with adolescent obesity risk and whether self-regulation and (un)healthful food consumption mediate these associations. Employing structural equation modelling, two theory-driven models were examined using a large sample (N=1237) drawn from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. Indicators of the quality of parent-child relationship included assessments of child attachment security and observational assessments of maternal sensitivity (15, 24, and 36 months). Self-regulation at 54 months was assessed using behavioural and computerized tasks and, at ages 11-12 and 15 years, using parental ratings of self-control. Food consumption was self-reported at age 11-12. Height and weight measures in early/middle childhood and adolescence were used to compute BMI z-scores. No direct associations between the quality of parent-child relationship and adolescent obesity risk were found in either model. Instead, child self-regulation was found to mediate the associations between the quality of parent-child relationship and both unhealthy food consumption and higher adolescent BMI status. The findings highlight how the nature of parent-child relationships impacts developing regulatory processes in children which, in turn, have implications for obesity-related behaviours and outcomes. Interventions to reduce childhood obesity should consider self-regulation skills across multiple domains, and early parenting practices that foster these capacities.

Assessment of validity and utility of a bronchopulmonary dysplasia outcome estimator.

To assess the validity and utility of the bronchopulmonary dysplasia (BPD) outcome estimator developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). This retrospective study correlated the BPD and mortality outcomes of 23-28-week prematurely born infants with those predicted by the 2022 NICHD BPD outcome estimator. In addition, evidence-based recommended postnatal steroid administration using risk predictions by the BPD estimator was compared with actual postnatal steroid use. Among the 223 infants enrolled in the study, 139 did not develop BPD, 64 babies developed BPD, and 20 babies died. BPD estimator predicted outcomes correctly in 74% of cases who did not develop BPD, 48% of cases with Grade 1 BPD, and 35% of deaths. Only 6% of cases with Grade 2 BPD and none of the babies with Grade 3 BPD were identified correctly. The predicted and actual steroid use for BPD prevention/treatment were 37.2% and 29.6%, respectively (p = 0.18). The BPD estimator had a sensitivity of 72.7%, specificity of 77.7%, positive predictive value of 57.8%, and negative predictive value of 87.1% to predict actual postnatal steroid use. In this cohort, the 2022 NICHD BPD estimator underestimated probabilities for babies who did not develop BPD, may overestimate probabilities for babies who develop BPD and had low sensitivity to predict mortality. In addition, the application of the BPD estimator may result in an overestimation of postnatal steroid use.