National Institute Of Child Health Research Articles

Personalized lung care: Bronchopulmonary dysplasia risk prediction tool tailored for neonates born in resource-limited settings.

Predicting bronchopulmonary dysplasia (BPD) to assess the risk-benefit of therapy is necessary considering the side effects of medications. We developed and validated an instrument for predicting BPD and compared it with an instrument currently used for neonates born in a Brazilian hospital. This was a retrospective cohort study of patients born between 2016 and 2020 with a gestational age (GA) between 23 and 30 weeks. Predictive equations were elaborated using methods of component variable selection collected on the 14th day of life; 70% of the sample was randomly selected for the construction of risk prediction equations and the remaining 30% for their validation, application, and comparison with the National Institute of Child Health and Human Development (NICHD) instrument. The sensitivity, specificity, and predictive values of the equations were calculated. The equation that used variables with p < 5% in Fisher's exact test presented the best results: specificity of 98% and positive predictive value of 93% and could be used for BPD prediction of all small-for-gestational-age (SGA) infants. The NICHD calculator applied to our population had a specificity of 93% and a positive predictive value of 75% and could not be applied to extremely SGA infants. Our tool can predict the risk of BPD on the 14th day of life, has higher specificity and positive predictive value to our population than the NICHD instrument, and can be suitable for SGA infants. The results must be confirmed by applying it to other populations to validate our tool.

Spectrum of respiratory distress and outcome in neonates admitted in National Institute of Child Health, Karachi, Pakistan.

Objective: To find out the spectrum of respiratory distress and outcome in neonates admitted to Neonatal Intensive care unit (NICU) of National Institute of Child Health (NICH), Karachi, Pakistan. Study Design: Cross-sectional study. Setting: NICU of NICH, Karachi, Pakistan. Period: June 2022 to May 2023. Methods: We analyzed 148 neonates of either gender presenting with respiratory distress. At the time of enrollment, demographic and clinical information was noted in all neonates along with detailed maternal history. Relevant laboratory and radiological studies were performed. Final outcomes were recorded in terms of discharged, expired or referred. Results: In a total of 148 neonates, 96 (64.9%) were boys. The mean age was 4.04±5.65 days. Tachypnea, nasal flaring, intercostal recession, subcostal recession, grunting, and cyanosis 148 (100%), 146 (98.6%), 138 (93.2%), 133 (89.9%), 97 (65.5%), and 83 (56.1%) were the most frequent clinical presentations among neonates with respiratory distress. The most frequent causes behind respiratory distress were noted to be respiratory distress syndrome, sepsis, and meconium staining of labour in 31 (20.9%), 25 (16.9%), and 24 (16.2%) neonates. Mortality was observed in 21 (14.2%) neonates. Significant association of neonates presenting with congenital pneumonia (p=0.048), or congenital anomalies (p&lt;0.001) were found to with poor outcomes. Mechanical ventilation was found to have significant relationship with poor outcomes (p&lt;0.001). Conclusion: Tachypnea, Nasal flaring, intercostal and subcostal recessions, grunting, and cyanosis were the primary clinical presentations among the neonates with respiratory distress. Congenital pneumonia, and congenital anomalies emerged as key predictors of poor outcomes.

Spectrum of skeletal dysplasia in short stature children in tertiary care hospital.

Objective: To evaluate the spectrum of skeletal dysplasia in short stature children at National Institute of Child Health (NICH), Pakistan. Study Design: Case Series study. Setting: Department of Endocrinology, NICH, Karachi, Pakistan. Period: January 2022 to November 2023. Methods: Short statured (height &lt; -2.0 SD) children of either gender aged between 1 month up to 16 years and diagnosed with skeletal dysplasia were analyzed. At the time enrollment, gender, age, anthropometric measures, antenatal history, and family history were noted. Complete skeletal survey was performed. Results: In a total of 131 short statured children with skeletal dysplasia, 77 (58.8%) were male. The mean and median age were 5.54±4.33 and 5.0 (1.5-8) years. Consanguinity was reported in 85 (64.9%) cases whereas siblings were affected among 9 (6.9%) cases. The most frequent presenting complaints and clinical features were joint pain, facial dysmorphism, movement limitations, and infections, reported by 67 (51.1%), 67 (51.1%), 65 (49.6%), and 63 (48.1%) children respectively. Mucopolysaccharidosis (29.0%), achondrodysplasia (13.7%), and osteogenesis imperfecta (10.7%) were the most common types of skeletal dysplasia. Conclusion: Mucopolysaccharidosis, achondrodysplasia, and osteogenesis imperfecta were the most frequent types of skeletal dysplasia. The most frequent presenting complaints and clinical features were joint pain, facial dysmorphism, movement limitations, and infections. The high prevalence of consanguinity and familial history emphasizes a probable genetic basis for skeletal dysplasia.

Pediatric arterial ischemic stroke; Risk factors, clinical presentation and short-term outcome of patients presenting at a tertiary care hospital.

Objective: To determine the risk factors, clinical presentation and short term outcome in children presenting with arterial ischemic stroke at a tertiary care hospital. Study Design: Prospective Observational study. Setting: Medical Units of National Institute of Child Health, Karachi, Pakistan. Period: November 2022 October 2023. Methods: Children of either gender aged between 1 month to 12 years and admitted with the diagnosis of pediatric arterial ischemic stroke during the study duration were analyzed. Detailed medical and neurological examinations were performed. Routine work up and laboratory investigations were done. Modified Rankin Scale (MRS) scores at the time of enrollment, discharge and after 3 month follow-up were recorded. Results: In a total of 35 children, 21 (60.0%) were boys the mean age was 6.89±3.63 years. The most frequent presenting clinical features were focal neurological deficits noted in 29 (82.9%) children whereas fever, and fits were reported in 26 (74.3%), and 22 (62.9%) children, respectively. Right hemiplegia was observed in 15 (42.9%) children. Stroke was secondary to moyamoya 8 (22.9%), infections in 6 (17.1%) children. Mortality was reported among 3 (8.6%) children while 3 others lost during the follow ups. Comparison of mean mRS scores at the time of admission, discharge and after 3 months showed significant reduction (p&lt;0.001). Conclusion: Focal neurological deficits were the predominant clinical features, with a significant incidence of associated fever and seizures. Moyamoya and infections emerged as primary causative factors. Despite a mortality rate of 8.6%, there was an overall improvement in outcomes, as evidenced by a significant reduction in Modified Rankin Scale scores at admission, discharge, and after three months.

PECARN prediction rules for CT imaging of children presenting to the emergency department with blunt abdominal or minor head trauma: a multicentre prospective validation study

The intra-abdominal injury and traumatic brain injury prediction rules derived by the Pediatric Emergency Care Applied Research Network (PECARN) were designed to reduce inappropriate use of CT in children with abdominal and head trauma, respectively. We aimed to validate these prediction rules for children presenting to emergency departments with blunt abdominal or minor head trauma. For this prospective validation study, we enrolled children and adolescents younger than 18 years presenting to six emergency departments in Sacramento (CA), Dallas (TX), Houston (TX), San Diego (CA), Los Angeles (CA), and Oakland (CA), USA between Dec 27, 2016, and Sept 1, 2021. We excluded patients who were pregnant or had pre-existing neurological disorders preventing examination, penetrating trauma, injuries more than 24 h before arrival, CT or MRI before transfer, or high suspicion of non-accidental trauma. Children presenting with blunt abdominal trauma were enrolled into an abdominal trauma cohort, and children with minor head trauma were enrolled into one of two age-segregated minor head trauma cohorts (younger than 2 years vs aged 2 years and older). Enrolled children were clinically examined in the emergency department, and CT scans were obtained at the attending clinician's discretion. All enrolled children were evaluated against the variables of the pertinent PECARN prediction rule before CT results were seen. The primary outcome of interest in the abdominal trauma cohort was intra-abdominal injury undergoing acute intervention (therapeutic laparotomy, angiographic embolisation, blood transfusion, intravenous fluid for ≥2 days for pancreatic or gastrointestinal injuries, or death from intra-abdominal injury). In the age-segregated minor head trauma cohorts, the primary outcome of interest was clinically important traumatic brain injury (neurosurgery, intubation for >24 h for traumatic brain injury, or hospital admission ≥2 nights for ongoing symptoms and CT-confirmed traumatic brain injury; or death from traumatic brain injury). 7542 children with blunt abdominal trauma and 19 999 children with minor head trauma were enrolled. The intra-abdominal injury rule had a sensitivity of 100·0% (95% CI 98·0-100·0; correct test for 145 of 145 patients with intra-abdominal injury undergoing acute intervention) and a negative predictive value (NPV) of 100·0% (95% CI 99·9-100·0; correct test for 3488 of 3488 patients without intra-abdominal injuries undergoing acute intervention). The traumatic brain injury rule for children younger than 2 years had a sensitivity of 100·0% (93·1-100·0; 42 of 42) for clinically important traumatic brain injuries and an NPV of 100·0%; 99·9-100·0; 2940 of 2940), whereas the traumatic brain injury rule for children aged 2 years and older had a sensitivity of 98·8% (95·8-99·9; 168 of 170) and an NPV of 100·0% (99·9-100·0; 6015 of 6017). The two children who were misclassified by the traumatic brain injury rule were admitted to hospital for observation but did not need neurosurgery. The PECARN intra-abdominal injury and traumatic brain injury rules were validated with a high degree of accuracy. Their implementation in paediatric emergency departments can therefore be considered a safe strategy to minimise inappropriate CT use in children needing high-quality care for abdominal or head trauma. The Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Identification of bacterial determinants of tuberculosis infection and treatment outcomes: a phenogenomic analysis of clinical strains.

Bacterial diversity could contribute to the diversity of tuberculosis infection and treatment outcomes observed clinically, but the biological basis of this association is poorly understood. The aim of this study was to identify associations between phenogenomic variation in Mycobacterium tuberculosis and tuberculosis clinical features. We developed a high-throughput platform to define phenotype-genotype relationships in M tuberculosis clinical isolates, which we tested on a set of 158 drug-sensitive M tuberculosis strains sampled from a large tuberculosis clinical study in Ho Chi Minh City, Viet Nam. We tagged the strains with unique genetic barcodes in multiplicate, allowing us to pool the strains for in-vitro competitive fitness assays across 16 host-relevant antibiotic and metabolic conditions. Relative fitness was quantified by deep sequencing, enumerating output barcode read counts relative to input normalised values. We performed a genome-wide association study to identify phylogenetically linked and monogenic mutations associated with the in-vitro fitness phenotypes. These genetic determinants were further associated with relevant clinical outcomes (cavitary disease and treatment failure) by calculating odds ratios (ORs) with binomial logistic regressions. We also assessed the population-level transmission of strains associated with cavitary disease and treatment failure using terminal branch length analysis of the phylogenetic data. M tuberculosis clinical strains had diverse growth characteristics in host-like metabolic and drug conditions. These fitness phenotypes were highly heritable, and we identified monogenic and phylogenetically linked variants associated with the fitness phenotypes. These data enabled us to define two genetic features that were associated with clinical outcomes. First, mutations in Rv1339, a phosphodiesterase, which were associated with slow growth in glycerol, were further associated with treatment failure (OR 5·34, 95% CI 1·21-23·58, p=0·027). Second, we identified a phenotypically distinct slow-growing subclade of lineage 1 strains (L1.1.1.1) that was associated with cavitary disease (OR 2·49, 1·11-5·59, p=0·027) and treatment failure (OR 4·76, 1·53-14·78, p=0·0069), and which had shorter terminal branch lengths on the phylogenetic tree, suggesting increased transmission. Slow growth under various antibiotic and metabolic conditions served as in-vitro intermediate phenotypes underlying the association between M tuberculosis monogenic and phylogenetically linked mutations and outcomes such as cavitary disease, treatment failure, and transmission potential. These data suggest that Mtuberculosis growth regulation is an adaptive advantage for bacterial success in human populations, at least in some circumstances. These data further suggest markers for the underlying bacterial processes that contribute to these clinical outcomes. National Health and Medical Research Council/A∗STAR, National Institutes of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the Wellcome Trust Fellowship in Public Health and Tropical Medicine.

Similar rates of denial in NICHD and control interviews with alleged child abuse victims in the Netherlands

AbstractPurposeIn the current study, we investigated whether denial and avoidance rates differed statistically significantly based on the interview protocol used.MethodWe examined 38 National Institute of Child Health and Human Development (NICHD) interview transcripts, and 30 control transcripts from interviews from an earlier study (Applied Cognitive Psychology, 2022, 36, 7) conducted with alleged child victims of abuse at Dutch child protection services.ResultsWe detected 57 denial and 282 avoidance statements across the 68 interviews. No statistically significant differences emerged between (1) the proportion of denials using NICHD (42%, n = 16/38) and control interviews (30%, n = 9/30), and (2) the average number of denial statements between NICHD (M = 0.84) and control interviews (M = 0.83). Furthermore, denials (and avoidances) were not more or less likely to occur in response to certain types of questions, even though the majority of denials in our sample occurred in response to option‐posing questions (60%, n = 34/57). Denials did occur statistically significantly less often within the first half of the individual interviews in NICHD than in control interviews.ConclusionsOur findings call attention to the difficulties child protection services face in investigative interviews with alleged child victims.

Incidence and Predictors of Bronchopulmonary Dysplasia Development and Severity Among Preterm Infants Born at 32 Weeks of Gestation or Less.

Background As the most common chronic lung disease (CLD) related to premature birth, bronchopulmonary dysplasia (BPD) is associated with long-term lung disease along with cardiovascular and neurodevelopmental disorders. However, data on the incidence and predictors of BPD in Qatar are lacking. Objectives In this study, we aimed to determine the incidence of BPD among infants born at ≤ 32 weeks gestational age (GA) at our neonatal unit, and identify risk factors for the development of BPD and moderate-severe BPD. Methods This was a retrospective observational cohort study conducted at a single site: a level-III neonatal intensive care unit (NICU) in Qatar. We included 1539 neonates born at ≤ 32 weeks of gestation with birth weights of ≤ 1500 grams who were admitted to the NICU between 2017 and 2020. Univariate and multivariate logistic regression analyses were performed to identify potential factors and predictors and their possible associations with the development of BPD and moderate-severe BPD. We also applied BPD classifications to determine the variability in the incidence of BPD in our cohort according to various definitions (2001 National Institute of Child Health and Human Development (NICHD) Diagnostic Criteria, 2016 Revisions of NICHD Criteria, and 2019 Neonatal Research Network Jensen Grading). Results A total of 451 infants (29.3%) had BPD (BPD group) while 1088 (70.7%) did not (non-BPD group), and the overall incidence of BPD was 29.3%. The most relevant risk factors associated with a higher risk of developing BPD identified in the multivariate logistic regression analysis were appropriate weight for gestational age (adjusted OR (aOR) 3.67, 95%CI 2.02-6.67, P < 0.001), presence of patent ductus arteriosus (PDA) (aOR 2.61, 95%CI 1.86-3.66, P < 0.001), late-onset sepsis (aOR 2.16; 95%CI 1.29-3.62; P = 0.003), and use of invasive ventilation (aOR 1.90; 95%CI 1.35-2.69; P < 0.001). The most relevant independent risk factors associated with a higher risk for developing moderate-severe BDP were postnatal steroids (aOR 7.12, 95%CI 3.77-13.44, P < 0.001), use of inhaled nitric oxide (aOR 3.65, 95%CI 1.48-9.01, P = 0.005), use of invasive ventilation (aOR 2.13, 95%CI 1.13-4.00, P = 0.019), late-onset sepsis (aOR 2.07, 95%CI 1.10-3.91, P = 0.025), and male sex (aOR 2.04, 95%CI 1.24-3.36, P = 0.005). The difference in the distribution of BPD severity across the three different definitions of NICHD was significant (P < 0.001). Conclusion The results of this study showed that the incidence of BPD remained high in infants born at ≤ 32 weeks of gestational age and birth weight <1500 g with appropriate weight for gestational age. The presence of PDA at birth or first echocardiography, late-onset sepsis, and use of invasive ventilation were significant risk factors for the incidence of BPD. The identification of risk factors will contribute to the implementation of lung-protective strategies for at-risk infants who may benefit from potential preventive therapy.

Frequency of hospital acquired malnutrition at a tertiary care pediatric hospital.

Objective: To determine the frequency of hospital acquired malnutrition in hospitalized pediatric population. Design: Cross-sectional study. Setting: Department of Pediatrics, National Institute of Child Health, Karachi, Pakistan. Period: January 2023 to June 2023. Methods: The inclusion criteria were children (irrespective of gender) aged between 1 and 12 years who were admitted for at least 48 hours. Weight of the children was measured daily from the time of admission to discharge. The hospital-acquired malnutrition rate was determined by dividing the patients with decreased weight-for-height (WFH) or body mass index (BMI) z-scores by total samples, then multiplying by 100. Results: In a total of 367 children, the mean age was 6.4±2.8 years whereas 203 (55.4%) children were boys. Hospital stays ranged from 2 to 19 days, with a mean of 18±6.9 days. At the time of discharge, the mean weight to be 17.6±6.53 kg, indicating a mean weight drop of 1.3±1.14 kg from admission to discharge. Weight reduction during hospitalization was observed in all age groups, with the highest percentage observed in children aged 2 to 5 years (77.7%) and the lowest in those aged 1 to 2 years (38.9%). Significant changes were observed in both WFH z-scores (mean difference -1.06, ± 1.69, p&lt;0.001) for children under 60 months and BMI z-scores (mean difference -1.07, ± 4.63, p=0.023) for children over 60 months from admission to discharge. Conclusion: Hospital acquired malnutrition is common among pediatric patients and deteriorates when a child is hospitalized without attention to adequate nutritional support. Weight loss shows direct correlation with duration of hospitalization.

CHARACTERISTICS AND PATTERNS OF PSYCHIATRIC ILLNESS AMONG CHILDREN AND ADOLESCENTS AT A TERTIARY CARE HOSPITAL IN KARACHI PAKISTAN

Objective To assess the patterns of psychiatric illness among children and adolescents presented at psychiatric clinic of a public sector teaching hospital in Karachi, Pakistan. Study Design A cross sectional study Place and Duration of the study The study was conducted at the Child and Adolescent Psychiatry outpatient clinic of the National Institute of Child Health (NICH) in Karachi, during February 2019 to October 2019. Methodology Using consecutive, non-probability sampling, all male and female participants, age less than 18 were recruited from the study setting. Data collection was done using a pre-designed semi-structured proforma. The data was analyzed using descriptive statistics. Results A total of 250 pediatric patients visiting the psychiatric clinic were enrolled in this study. These included 161 (64.4%) males and 89 (35.6%) females. Mean age was 9.55 ±3.374 years. 31 (12.4%) patients reported directly to the psychiatry clinic while 160 (64%) patients were referred from pediatric medicine clinics. The remaining 59 (23.6%) patients were referred from adult psychiatry clinics. 126 (50.4%) were diagnosed to have stress and related disorders, 85 (34%) patients were diagnosed with neurodevelopmental disorders. About 5 (2%) patients were diagnosed with psychotic and mood disorders, 34 (13.6%) were diagnosed with other nonspecific disorders. Conclusion The study reveals a male predominance among children and adolescents at a public sector hospital, with a high referral rate from pediatricians. The diverse mental health issues include stress, neurodevelopmental, and other diagnoses, highlighting the need for deeper investigation and targeted clinical attention.  

The impact of ovarian stimulation on the human endometrial microenvironment.

How does ovarian stimulation (OS), which is used to mature multiple oocytes for ART procedures, impact the principal cellular compartments and transcriptome of the human endometrium in the periovulatory and mid-secretory phases? During the mid-secretory window of implantation, OS alters the abundance of endometrial immune cells, whereas during the periovulatory period, OS substantially changes the endometrial transcriptome and impacts both endometrial glandular and immune cells. Pregnancies conceived in an OS cycle are at risk of complications reflective of abnormal placentation and placental function. OS can alter endometrial gene expression and immune cell populations. How OS impacts the glandular, stromal, immune, and vascular compartments of the endometrium, in the periovulatory period as compared to the window of implantation, is unknown. This prospective cohort study carried out between 2020 and 2022 included 25 subjects undergoing OS and 25 subjects in natural menstrual cycles. Endometrial biopsies were performed in the proliferative, periovulatory, and mid-secretory phases. Blood samples were processed to determine serum estradiol and progesterone levels. Both the endometrial transcriptome and the principal cellular compartments of the endometrium, including glands, stroma, immune, and vasculature, were evaluated by examining endometrial dating, differential gene expression, protein expression, cell populations, and the three-dimensional structure in endometrial tissue. Mann-Whitney U tests, unpaired t-tests or one-way ANOVA and pairwise multiple comparison tests were used to statistically evaluate differences. In the periovulatory period, OS induced high levels of differential gene expression, glandular-stromal dyssynchrony, and an increase in both glandular epithelial volume and the frequency of endometrial monocytes/macrophages. In the window of implantation during the mid-secretory phase, OS induced changes in endometrial immune cells, with a greater frequency of B cells and a lower frequency of CD4 effector T cells. The data underlying this article have been uploaded to the Genome Expression Omnibus/National Center for Biotechnology Information with accession number GSE220044. A limited number of subjects were included in this study, although the subjects within each group, natural cycle or OS, were homogenous in their clinical characteristics. The number of subjects utilized was sufficient to identify significant differences; however, with a larger number of subjects and additional power, we may detect additional differences. Another limitation of the study is that proliferative phase biopsies were collected in natural cycles, but not in OS cycles. Given that the OS cycle subjects did not have known endometrial factor infertility, and the comparisons involved subjects who had a similar and robust response to stimulation, the findings are generalizable to women with a normal response to OS. OS substantially altered the periovulatory phase endometrium, with fewer transcriptomic and cell type-specific changes in the mid-secretory phase. Our findings show that after OS, the endometrial microenvironment in the window of implantation possesses many more similarities to that of a natural cycle than does the periovulatory endometrium. Further investigation of the immune compartment and the functional significance of this cellular compartment under OS conditions is warranted. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases (R01AI148695 to A.M.B. and N.C.D.), Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD109152 to R.A.), and the March of Dimes (5-FY20-209 to R.A.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or March of Dimes. All authors declare no conflict of interest.

Comparison of Growth Outcomes Between Human Milk-Fed Preterm Infants on Standard Versus Adjustable Fortification Protocols.

Background: Human milk (HM) is usually fortified using standard fortification (STD) to improve nutrition of preterm infants. However, the protein component may still be insufficient. HM could be further fortified with additional protein to improve STD. Objective: The primary objective was to compare changes in body weight (g/day, g/kg/day), length, and head circumference (mm/day) between preterm neonates fed HM with STD and those fed HM with adjustable fortification (ADJ). Methods: This study was a prospective, single-blinded, randomized controlled study in preterm infants of gestational age <32 weeks and weighing ≤1,800 g, admitted to the neonatal unit of the Queen Sirikit National Institute of Child Health. Once the infants received full HM feed with STD at 24 kcal/oz, they were randomized to either continue with STD or with ADJ group by adding additional protein to the STD and making further protein adjustments based on the blood urea nitrogen levels. Results: Thirty preterm infants completed the study and were randomized into two groups of 15 each. The baseline characteristics, total fluid, and energy intake were similar. Compared with the STD group, infants in the ADJ group exhibited significantly greater weight gain (36.46 ± 6.09 vs. 25.78 ± 8.81 g/day; p = 0.001) and greater length gain (1.93 ± 0.57 vs. 1.12 ± 0.64 mm/day; p = 0.001). Protein intake significantly correlated with both weight (r = 0.632, p < 0.001) and length gain (r = 0.577, p = 0.001); however, no correlation was found between energy intake, volume intake, and growth outcomes. Conclusion: Preterm infants fed with ADJ had significantly higher weight and length gains than those fed with STD, suggesting that additional protein intake may play an important role in growth.

Establishing age and gender-specific serum creatinine reference ranges for Thai pediatric population.

Accurate assessment of kidney function in children requires age and gender-specific reference ranges for serum creatinine. Traditional reference values, often derived from adult populations and different ethnic backgrounds, may not be suitable for children. This study aims to establish specific reference ranges for serum creatinine in the Thai pediatric population, addressing the gap in localized and age-appropriate diagnostic criteria. This retrospective study analyzed serum creatinine levels from Thai children aged newborn to 18 years, collected from the Laboratory Information System of the Queen Sirikit National Institute of Child Health from January 2017 to December 2021. The Bhattacharya method was employed to establish reference ranges, considering different age groups and genders. The study compared these newly established reference values with international studies, including those of Schlebusch H., Pottel H., and Chuang GT., to validate their relevance and accuracy. A total of 27,642 data entries (15,396 males and 12,246 females) were analyzed. The study established distinct reference ranges for serum creatinine, which varied significantly across different age groups and between genders. These ranges were found to gradually increase with age from 2 months to 18 years. The study also highlighted notable differences in reference values when compared with other ethnic populations. The study successfully establishes tailored reference ranges for serum creatinine in Thai children, providing a valuable tool for more accurate diagnosis and monitoring of kidney health in this demographic. This initiative marks a significant advancement in pediatric nephrology in Thailand and suggests a need for continuous refinement of these ranges and further research in this area.

Reflections on the Multicenter Randomized Trial of Treatment for Mild Gestational Diabetes.

After the 2006 hyperglycemia and adverse pregnancy outcomes study, which confirmed the relationship between maternal glycemia and pregnancy outcomes, the debate remained on whether treatment benefited gestational diabetes mellitus (GDM). Nonetheless, practitioners continued to universally screen for and treat women identified as GDM. To assess the benefits and harms of screening and treatment of GDM, the National Institute of Child Health and Human Development Maternal and Fetal Medicine Unit Network designed and conducted a well-designed randomized controlled trial in women with mild GDM. The trial established that treatment of GDM resulted in a significant reduction in several important perinatal and maternal outcomes.

Social Determinants of Health and Redirection of Care for Infants Born Extremely Preterm

Redirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding. To examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm. This is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks' gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic). The primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks' gestation, death and neurodevelopmental impairment at 22 to 26 months' corrected age. Of the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type. For infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.

The long and winding road: Pathways from basic research to implementation and evaluation.

In this article, we celebrate Dante Cicchetti's extensive contributions to the discipline of developmental psychopathology. In his seminal article, he articulated why developmental psychopathology was imperative to create research portfolios that could inform the causes, consequences, and trajectories for adults often initiated by early lived experiences (Cicchetti, 1984). In this three-part article, we share our transdisciplinary efforts to use developmental psychopathology as a foundational theory from which to develop, implement, and evaluate interventions for populations who experienced early adversity or who were at risk for child abuse and neglect. After describing interventions conducted at Mt. Hope Family Center that spanned over three decades, we highlight the criticality of disseminating results and address policy implications of this work. We conclude by discussing future directions to facilitate work in developmental psychopathology. Currently, one of three national National Institute of Child Health and Human Development-funded child abuse and neglect centers, we look forward to continuing to build upon Dante's efforts to disseminate this important work to improve society for our children, our nation's often most vulnerable and forgotten citizens.

Safety of low weight gain or weight loss in pregnancies with class 1, 2, and 3 obesity: a population-based cohort study

There are concerns that current gestational weight gain recommendations for women with obesity are too high and that guidelines should differ on the basis of severity of obesity. In this study we investigated the safety of gestational weight gain below current recommendations or weight loss in pregnancies with obesity, and evaluated whether separate guidelines are needed for different obesity classes. In this population-based cohort study, we used electronic medical records from the Stockholm-Gotland Perinatal Cohort study to identify pregnancies with obesity (early pregnancy BMI before 14 weeks' gestation ≥30 kg/m2) among singleton pregnancies that delivered between Jan 1, 2008, and Dec 31, 2015. The pregnancy records were linked with Swedish national health-care register data up to Dec 31, 2019. Gestational weight gain was calculated as the last measured weight before or at delivery minus early pregnancy weight (at <14 weeks' gestation), and standardised for gestational age into z-scores. We used Poisson regression to assess the association of gestational weight gain z-score with a composite outcome of: stillbirth, infant death, large for gestational age and small for gestational age at birth, preterm birth, unplanned caesarean delivery, gestational diabetes, pre-eclampsia, excess postpartum weight retention, and new-onset longer-term maternal cardiometabolic disease after pregnancy, weighted to account for event severity. We calculated rate ratios (RRs) for our composite adverse outcome along the weight gain z-score continuum, compared with a reference of the current lower limit for gestational weight gain recommended by the US Institute of Medicine (IOM; 5 kg at term). RRs were adjusted for confounding factors (maternal age, height, parity, early pregnancy BMI, early pregnancy smoking status, prepregnancy cardiovascular disease or diabetes, education, cohabitation status, and Nordic country of birth). Our cohort comprised 15 760 pregnancies with obesity, followed up for a median of 7·9 years (IQR 5·8-9·4). 11 667 (74·0%) pregnancies had class 1 obesity, 3160 (20·1%) had class 2 obesity, and 933 (5·9%) had class 3 obesity. Among these pregnancies, 1623 (13·9%), 786 (24·9%), and 310 (33·2%), respectively, had weight gain during pregnancy below the lower limit of the IOM recommendation (5 kg). In pregnancies with class 1 or 2 obesity, gestational weight gain values below the lower limit of the IOM recommendation or weight loss did not increase risk of the adverse composite outcome (eg, at weight gain z-score -2·4, corresponding to 0 kg at 40 weeks: adjusted RR 0·97 [95% CI 0·89-1·06] in obesity class 1 and 0·96 [0·86-1·08] in obesity class 2). In pregnancies with class 3 obesity, weight gain values below the IOM limit or weight loss were associated with reduced risk of the adverse composite outcome (eg, adjusted RR 0·81 [0·71-0·89] at weight gain z-score -2·4, or 0 kg). Our findings support calls to lower or remove the lower limit of current IOM recommendations for pregnant women with obesity, and suggest that separate guidelines for class 3 obesity might be warranted. Karolinska Institutet and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Classes and predictors of reversal in male patients with congenital hypogonadotropic hypogonadism: a cross-sectional study of six international referral centres

Although some male patients with congenital hypogonadotropic hypogonadism (CHH) undergo spontaneous reversal following treatment, predictors of reversal remain elusive. We aimed to assemble the largest cohort of male patients with CHH reversal to date and identify distinct classes of reversal. This multicentre cross-sectional study was conducted in six international CHH referral centres in Brazil, Finland, France, Italy, the UK, and the USA. Adult men with CHH (ie, absent or incomplete spontaneous puberty by age 18 years, low serum testosterone concentrations, and no identifiable cause of hypothalamic-pituitary-gonadal [HPG] axis dysfunction) were eligible for inclusion. CHH reversal was defined as spontaneous recovery of HPG axis function off treatment. Centres provided common data elements on patient phenotype, clinical assessment, and genetics using a structured, harmonised data collection form developed by COST Action BM1105. Latent class mixture modelling (LCMM) was applied to establish whether at least two distinct classes of reversal could be identified and differentially predicted, and results were compared with a cohort of patients without CHH reversal to identify potential predictors of reversal. The primary outcome was the presence of at least two distinct classes of reversal. A total of 87 male patients with CHH reversal and 108 without CHH reversal were included in the analyses. LCMM identified two distinct reversal classes (75 [86%] in class 1 and 12 [14%] in class 2) on the basis of mean testicular volume, micropenis, and serum follicle-stimulating hormone (FSH) concentration. Classification probabilities were robust (0·998 for class 1 and 0·838 for class 2) and modelling uncertainty was low (entropy 0·90). Compared with class 1, patients in class 2 had significantly larger testicular volume (p<0·0001), no micropenis, and higher serum FSH concentrations (p=0·041), consistent with the Pasqualini syndrome (fertile eunuch) subtype of CHH. Patients without CHH reversal were more likely to have anosmia (p=0·016), cryptorchidism (p=0·0012), complete absence of puberty (testicular volume <4 cm³; p=0·0016), and two or more rare genetic variants (ie, oligogenicity; p=0·0001). Among patients who underwent genetic testing, no patients (of 75) with CHH reversal had a rare pathogenic ANOS1 variant compared with ten (11%) of 95 patients without CHH reversal. Individuals with CHH reversal had a significantly higher rate of rare variants in GNRHR than did those without reversal (nine [12%] of 75 vs three [3%] of 95; p=0·025). Applying LCMM to a large cohort of male patients with CHH reversal uncovered two distinct classes of reversal. Genetic investigation combined with careful clinical phenotyping could help surveillance of reversal after withdrawing treatment, representing the first tailored management approach for male patients with this rare endocrine disorder. National Institutes of Health National Center for Advancing Translational Sciences; Ministry of Health, Rome, Italy; Ministry of University, Rome, Italy; National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development; and the Josiah Macy Jr Foundation. For the Italian translation of the abstract see Supplementary Materials section.

The Impact of Preoperative Pain on Outcomes After Vaginal Reconstructive Surgery and Perioperative Pelvic Floor Muscle Training

ABSTRACT In the United States, around 9 million women are affected by pelvic pain due to conditions such as interstitial cystitis/bladder syndrome, fibromyalgia, pelvic floor myalgias, chronic opioid use, or irritable bowel syndrome. Treatment options for concurrent pelvic floor disorders and pelvic pain can prove challenging due to the overall desire to avoid exacerbating overall pain while optimizing pelvic floor symptoms. The primary aim of this study was to compare both perioperative pelvic muscle training and vaginal reconstructive surgery among women who experienced or lacked preoperative pain and to inform better approaches to management of women with preoperative pain. The study was a secondary analysis of the Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) randomized clinical trial, as performed via the Pelvic Floor Disorders network. The main study's design was a 2 × 2 randomized factorial design with a surgical intervention and a perioperative behavioral intervention. The Eunice Kennedy Shriver National Institute of Child Health and Development data and specimen hub provided the data for this study. Included were 374 women undergoing surgery for both stress urinary incontinence and stage 2–4 pelvic organ prolapse from 2008 to 2013. All participants underwent vaginal prolapse repair and midurethral sling, and were randomized to either perioperative pelvic muscle therapy or usual care. The Pain scale, the Pelvic Floor Impact Questionnaire, the Pelvic Floor Distress Inventory, and the Patient Global Impression of Improvement were all completed by patients at baseline and repeated through month 24. The OPTIMAL trial had a primary outcome of surgical success as defined by anatomical success, but the primary outcome of this secondary analysis was a change in pain scale scores over 24 months after surgery. Three hundred seventy-four women participated in the original trial, with 368 in this secondary analysis. One hundred nine of the 368 women reported preoperative pain. Women with pelvic pain were more likely to be Hispanic, but there were no differences in surgical procedures performed, hospital stay, complications (ie, bladder injury, suture exposure, etc), or estimated blood loss in women with and without pelvic pain. Women with preoperative pain experienced greater pain at all time points, but also exhibited greater pain improvement at 24 months after surgery. Women with preoperative pain had worse baseline pelvic floor symptoms than those without pain. Although women with pain and women without pain had improvements in distress symptoms measured with the Pelvic Floor Distress Inventory, women with pain saw a greater improvement after surgery. All distress subscales improved significantly more in women with pain than women without pain. One additional interesting finding was that women randomized to sacrospinous suspension and pelvic muscle therapy had greater improvements in postoperative pain than those randomized to usual care. Notably, rates of surgical anatomic success and extent of Patient Global Impression of Improvement were not different between women with and without pain. Strengths of the study include its design as a secondary analysis of a large prospective multicenter randomized controlled trial. A substantial proportion of participants reported at least moderate pain at baseline but were not selected based on preoperative pain. Women in the trial were randomized to types of vaginal reconstructive surgery and pelvic muscle training, which allowed the authors to draw conclusions in categories of physical therapy treatments and surgeries for women with and without preoperative pain. Limitations of the study include a lack of preoperative pain data, pain diagnoses, and participant medications in the OPTIMAL trial. Furthermore, the study used no validated pain scale and was limited by OPTIMAL trial data collection intervals. Thankfully, data collected at numerous points over 24 months in some regard accounted for pain symptoms over time. The study found that, for patients with preoperative pain, significant improvement in pelvic floor symptoms and pain takes place after vaginal reconstructive surgery. Similar postoperative improvement rates were found. In addition, perioperative pelvic floor muscle training may be beneficial for patients with planned sacrospinous ligament fixation.

Viral DNAemia and DNA Virus Seropositivity and Mortality in Pediatric Sepsis

Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with sepsis. To assess the association of the presence of viral DNA with sepsis-related mortality in a large multicenter study. This cohort study compares pediatric patients with and without plasma cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), human herpesvirus 6 (HHV-6), parvovirus B19 (B19V), BK polyomavirus (BKPyV), human adenovirus (HAdV), and torque teno virus (TTV) DNAemia detected by quantitative real-time polymerase chain reaction or plasma IgG antibodies to CMV, EBV, HSV-1, or HHV-6. A total of 401 patients younger than 18 years with severe sepsis were enrolled from 9 pediatric intensive care units (PICUs) in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Data were collected from 2015 to 2018. Samples were assayed from 2019 to 2022. Data were analyzed from 2022 to 2023. Death while in the PICU. Among the 401 patients included in the analysis, the median age was 6 (IQR, 1-12) years, and 222 (55.4%) were male. One hundred fifty-four patients (38.4%) were previously healthy, 108 (26.9%) were immunocompromised, and 225 (56.1%) had documented infection(s) at enrollment. Forty-four patients (11.0%) died in the PICU. Viral DNAemia with at least 1 virus (excluding TTV) was detected in 191 patients (47.6%) overall, 63 of 108 patients (58.3%) who were immunocompromised, and 128 of 293 (43.7%) who were not immunocompromised at sepsis onset. After adjustment for age, Pediatric Risk of Mortality score, previously healthy status, and immunocompromised status at sepsis onset, CMV (adjusted odds ratio [AOR], 3.01 [95% CI, 1.36-6.45]; P = .007), HAdV (AOR, 3.50 [95% CI, 1.46-8.09]; P = .006), BKPyV (AOR. 3.02 [95% CI, 1.17-7.34]; P = .02), and HHV-6 (AOR, 2.62 [95% CI, 1.31-5.20]; P = .007) DNAemia were each associated with increased mortality. Two or more viruses were detected in 78 patients (19.5%), with mortality among 12 of 32 (37.5%) who were immunocompromised and 9 of 46 (19.6%) who were not immunocompromised at sepsis onset. Herpesvirus seropositivity was common (HSV-1, 82 of 246 [33.3%]; CMV, 107 of 254 [42.1%]; EBV, 152 of 251 [60.6%]; HHV-6, 253 if 257 [98.4%]). After additional adjustment for receipt of blood products in the PICU, EBV seropositivity was associated with increased mortality (AOR, 6.10 [95% CI, 1.00-118.61]; P = .049). The findings of this cohort study suggest that DNAemia for CMV, HAdV, BKPyV, and HHV-6 and EBV seropositivity were independently associated with increased sepsis mortality. Further investigation of the underlying biology of these viral DNA infections in children with sepsis is warranted to determine whether they only reflect mortality risk or contribute to mortality.