Outcomes following liver transplantation in young infants: Data from the SPLIT registry.

Liver transplantation (LT) in young patients is being performed with greater frequency. We hypothesized that objective analysis of pre-, intra-, and postoperative events would help understand contributors to successful outcomes and guide transplant decision processes. We queried SPLIT registry for pediatric transplants between 2011 and 2018. Outcomes were compared for age groups: 0-<3, 3-<6, 6-<12 months, and 1-<3 years (Groups A, B, C, D respectively) and by weight categories: <5, 5-10, >10 kg; 1033 patients were available for analysis. Cholestatic disease and fulminant failure were highest in group A and those <5 kg; and biliary atresia in group C (72.8%). Group A had significantly higher life support dependence (34.6%; P < .001), listing as United Network for Organ Sharing status 1a/1b (70.4%; P < .001), and shortest wait times (P < .001). The median (interquartile range) for international normalized ratio and bilirubin were highest in group A (3.0 [2.1-3.9] and 16.7 [6.8-29.7] mg/dL) and those <5 kg (2.6 [1.8-3.4] and 13.5 [3.0-28.4] mg/dL). A pediatric end -stage liver disease score ≥40, postoperative hospital stays, rejection, and nonanastomotic biliary strictures were highest in group A with lowest survival at 93.1%. Infants 0 to <3 months and those <5 kg need more intensive care with lower survival and higher complications. Importantly, potential LT before reaching status 1a/1b and aggressive postoperative management may positively influence their outcomes.

Impact of Personal Protective Equipment on the Performance of Emergency Pediatric Tasks.

OBJECTIVES: Personal protective equipment (PPE) is worn by health care providers (HCPs) to protect against hazardous exposures. Studies of HCPs performing critical resuscitation tasks in PPE have yielded mixed results and have not evaluated performance in care of children. We evaluated the impacts of PPE on timeliness or success of emergency procedures performed by pediatric HCPs. METHODS: This prospective study was conducted at 2 tertiary children's hospitals. For session 1, HCPs (medical doctors and registered nurses) wore normal attire; for session 2, they wore full-shroud PPE garb with 2 glove types: Ebola level or chemical. During each session, they performed clinical tasks on a patient simulator: intubation, bag-valve mask ventilation, venous catheter (IV) placement, push-pull fluid bolus, and defibrillation. Differences in completion time per task were compared. RESULTS: There were no significant differences in medical doctor completion time across sessions. For registered nurses, there was a significant difference between baseline and PPE sessions for both defibrillation and IV placement tasks. Registered nurses were faster to defibrillate in Ebola PPE and slower when wearing chemical PPE (median difference, -3.5 vs 2 seconds, respectively; P < 0.01). Registered nurse IV placement took longer in Ebola and chemical PPE (5.5 vs 42 seconds, respectively; P < 0.01). After the PPE session, participants were significantly less likely to indicate that full-body PPE interfered with procedures, was claustrophobic, or slowed them down. CONCLUSIONS: Personal protective equipment did not affect procedure timeliness or success on a simulated child, with the exception of IV placement. Further study is needed to investigate PPE's impact on procedures performed in a clinical care context.

Validation and human factor analysis study of an infant weight estimation device.

BACKGROUND: Weight is critical for the medical management of infants; however, scales can be unavailable or inaccessible in some practice settings. We recently developed and validated a robust infant weight estimation method based on chest circumference (CC) and head circumference (HC). This study was designed to determine the human factors (HF) experience with, and predictive performance of, an infant weight estimation device that implements this method. METHODS: Prospective, multi-center, observational, masked study of 486 preterm and term infants (0-90 days) assessed by 15 raters. Raters measured the infant using calibrated scales/measures and masked versions of the device. Raters also evaluated critical tasks associated with device use. Mean error (ME) and mean percentage error (MPE) were used to assess predictive performance. RESULT: Among 486 infants enrolled (36.8 ± 4.0 weeks gestational age, 31.5 ± 28.6 days postnatal age), predicted weight correlated highly with actual weight (r = 0.97, ME: - 69 ± 257 g, MPE: - 1.3 ± 6.9%). Predicted weight was within 10 and 15% of actual weight in 86 and 99%, of infants. HF errors were low, 0.1-0.8% depending on task. In all cases raters were confident or very confident in their measurements. CONCLUSION: The device was statistically equivalent to the method on which it was based and approximated weight with acceptable variance from the true weight. HF data suggest the device is easy to use. This device can be used to estimate weight in infants when calibrated scales are impractical or unavailable.

Birth defects in Taiwan: A 10-year nationwide population-based, cohort study.

BACKGROUND/PURPOSE: Birth defects (BDs) are main causes of mortality and disability in infants and children. The aims of this study were to analyze the prevalence, types and risk factors of BDs in Taiwan. METHODS: Data of all births (including live and stillbirths), types, characteristics, and associated risk factors of BDs were obtained from the National Birth Registry and National Health Insurance Research Data base in Taiwan between 2005 and 2014. Birth defects were coded according to International Classification of Diseases 9th Revision-Clinical Modification codes 740-759. RESULTS: A total of 55,299 infants were diagnosed as having BDs among 2,033,004 births. The prevalence of BDs was 271.66 per 10,000 births. The prevalence of BDs did not change significantly between 2005 and 2014, there was a higher birth rate and lower BDs in 2012 (year of dragon) in Taiwan. The most common type of BDs was cardiovascular abnormalities, and ventricular septal defect was the most common disease. Extreme maternal age (<18 years or ≧30 years), preterm, and low birth weight were associated with BDs. Maternal diseases associated with BDs included hypertension, cardiovascular diseases, renal diseases, genitourinary infections, anemia, mental disorders, and diabetes mellitus. CONCLUSION: The prevalence of BDs was 271.66 per 10,000 births. The most common types of BDs were cardiovascular abnormalities. If we can reduce maternal chronic diseases, we will decrease the prevalence of BDs.

Impact of Personal Protective Equipment on Pediatric Cardiopulmonary Resuscitation Performance: A Controlled Trial.

OBJECTIVES: This study aimed to determine whether personal protective equipment (PPE) results in deterioration in chest compression (CC) quality and greater fatigue for administering health care providers (HCPs). METHODS: In this multicenter study, HCPs completed 2 sessions. In session 1 (baseline), HCPs wore normal attire; in session 2, HCPs donned full PPE. During each session, they performed 5 minutes of uninterrupted CCs on a child manikin. Chest compression rate, depth, and release velocity were reported in ten 30-second epochs. Change in CC parameters and self-reported fatigue were measured between the start and 2- and 5-minute epochs. RESULTS: We enrolled 108 HCPs (prehospital and in-hospital providers). The median CC rate did not change significantly between epochs 1 and 10 during baseline sessions. Median CC depth and release velocity decreased for 5 minutes with PPE. There were no significant differences in CC parameters between baseline and PPE sessions in any provider group. Median fatigue scores during baseline sessions were 2 (at start), 4 (at 2 minutes), and 6 (at 5 minutes). There was a significantly higher median fatigue score between 0 and 5 minutes in both study sessions and in all groups. Fatigue scores were significantly higher for providers wearing PPE compared with baseline specifically among prehospital providers. CONCLUSIONS: During a clinically appropriate 2-minute period, neither CC quality nor self-reported fatigue worsened to a significant degree in providers wearing PPE. Our data suggest that Pediatric Basic Life Support recommendations for CC providers to switch every 2 minutes need not be altered with PPE use.

Mortality After Bereavement: The Role of Cardiovascular Disease and Depression.

OBJECTIVES: Late-life bereavement is associated with an increased risk of mortality. This study assesses the associations among bereavement, cardiovascular disease (CVD), and depressive symptoms on mortality in older men and women. METHODS: We examined data from the Cardiovascular Health Study, a prospective population-based cohort study of older adults. We compared mortality in those who became bereaved from 1989 to 1999 (n = 593) to an age- and sex-matched sample of individuals who remained married (n = 593). Cox regression was used to examine the association between bereavement and 3-year all-cause mortality and whether or not the association differed by sex, presence of CVD, or postbereavement depressive symptoms. RESULTS: One hundred ninety-nine (16.8%) individuals died. There was no association of bereavement with mortality (hazard ratio [HR] = 0.98 [0.74-1.30]). However, there were significant interaction effects of bereavement with participant sex (p < .001) and CVD (p = .010). Bereavement decreased the risk of mortality in women (HR = 0.67 [0.46-0.97]) and increased the risk of mortality in men (HR = 1.77 [1.14-2.75]). Within sex, the association of bereavement with mortality differed according to CVD status. The reduced risk of mortality associated with bereavement in women was only observed in women with CVD, and the increased risk in men was only observed in men without CVD. High levels of depressive symptoms attenuated the relation between bereavement and mortality in men without CVD. CONCLUSIONS: The relation between bereavement and mortality was different in men and women and varied by CVD status. Bereavement decreased mortality in women with CVD and increased mortality in men without CVD.

Psychiatric Disorders and Weight Change in a Prospective Study of Bariatric Surgery Patients: A 3-Year Follow-Up.

OBJECTIVES: To document changes in Axis I psychiatric disorders after bariatric surgery and examine their relationship with postsurgery weight loss. METHODS: As part of a three-site substudy of the Longitudinal Assessment of Bariatric Surgery Research Consortium, 199 patients completed the Structured Clinical Interview for DSM-IV before Roux-en-Y gastric bypass or laparoscopic adjustable gastric band. At 2 or 3 years after surgery, 165 (83%) patients completed a follow-up assessment (presurgery median body mass index = 44.8 kg/m, median age = 46 years, 92.7% white, 81.1% female). Linear-mixed modeling was used to test change in prevalence of psychiatric disorders over time, report remission and incidence, and examine associations between psychiatric disorders and weight loss. RESULTS: Compared with status presurgery, the prevalence of any Axis I psychiatric disorder was significantly lower at 2 and 3 years after surgery (30.2% versus 16.8% [p = .003] and 18.4% [p = .012], respectively). Adjusting for site, age, sex, race, presurgery body mass index, and surgical procedure, presurgery mood, anxiety, eating or substance use disorders (lifetime or current) were not related to weight change, nor were postsurgery mood or anxiety disorders (p for all > .05). However, having a postsurgery eating disorder was independently associated with less weight loss at 2 or 3 years (ß = 6.7%, p = .035). CONCLUSIONS: Bariatric surgery was associated with decreases in psychiatric disorders through 3 years after surgery. Postsurgical eating disorders were associated with less weight loss after surgery, adding to the literature suggesting that disordered eating after surgery is related to suboptimal weight loss.

Objectively-measured sedentary time and cardiometabolic health in adults with severe obesity.

It is unknown whether sedentary behavior is independently associated with the cardiometabolic health of adults with severe obesity. Additionally, there is debate regarding how best to derive meaningful indices of sedentary time (ST) from activity monitor data. A convenience sample of adults with severe obesity (N=927; 79% female, median age 45y, median body mass index (BMI) 46kg/m(2)) completed a research assessment at one of ten US hospitals in 2006-2009 prior to bariatric surgery. Cardiometabolic health was assessed via physical measures, fasting blood samples and medication use. Indices of ST were derived from StepWatch™ activity monitor data with minimum bout durations of 1min, 10min and 30min. Cross-sectional associations were examined. Median (25th, 75th percentile) ST was 9.3h/d (8.1, 10.5) in ≥1min bouts, 6.5h/d (5.2, 8.0) in ≥10min bouts, or 3.2h/d (2.1, 4.5) in ≥30min bouts. Associations with ST were generally strongest with the ≥10min bout duration. Independent of moderate-to-vigorous intensity physical activity, BMI and other potential confounders, 1h/day ST in ≥10min bouts was associated with higher odds of diabetes by 15% (95%CI: 1.05-1.26), metabolic syndrome by 12% (95%CI: 1.01-1.24) and elevated blood pressure by 14% (95%CI: 1.02-1.26), and was associated with 1.4cm (95%CI: 0.9-1.9) larger waist circumference. Findings indicate the importance of considering ST as a distinct health risk among adults with severe obesity, and suggest a 10min minimum duration may be preferable to 1min or 30min for establishing ST from activity monitor data.

Change in Pain and Physical Function Following Bariatric Surgery for Severe Obesity.

IMPORTANCE: The variability and durability of improvements in pain and physical function following Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB) are not well described. OBJECTIVES: To report changes in pain and physical function in the first 3 years following bariatric surgery, and to identify factors associated with improvement. DESIGN, SETTING, AND PARTICIPANTS: The Longitudinal Assessment of Bariatric Surgery-2 is an observational cohort study at 10 US hospitals. Adults with severe obesity undergoing bariatric surgery were recruited between February 2005 and February 2009. Research assessments were conducted prior to surgery and annually thereafter. Three-year follow-up through October 2012 is reported. EXPOSURES: Bariatric surgery as clinical care. MAIN OUTCOMES AND MEASURES: Primary outcomes were clinically meaningful presurgery to postsurgery improvements in pain and function using scores from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) (ie, improvement of ≥5 points on the norm-based score [range, 0-100]) and 400-meter walk time (ie, improvement of ≥24 seconds) using established thresholds. The secondary outcome was clinically meaningful improvement using the Western Ontario McMaster Osteoarthritis Index (ie, improvement of ≥9.7 pain points and ≥9.3 function points on the transformed score [range, 0-100]). RESULTS: Of 2458 participants, 2221 completed baseline and follow-up assessments (1743 [78.5%] were women; median age was 47 years; median body mass index [BMI] was 45.9; 70.4% underwent RYGB; 25.0% underwent LAGB). At year 1, clinically meaningful improvements were shown in 57.6% (95% CI, 55.3%-59.9%) of participants for bodily pain, 76.5% (95% CI, 74.6%-78.5%) for physical function, and 59.5% (95% CI, 56.4%-62.7%) for walk time. Additionally, among participants with severe knee or disability (633), or hip pain or disability (500) at baseline, approximately three-fourths experienced joint-specific improvements in knee pain (77.1% [95% CI, 73.5%-80.7%]) and in hip function (79.2% [95% CI, 75.3%-83.1%]). Between year 1 and year 3, rates of improvement significantly decreased to 48.6% (95% CI, 46.0%-51.1%) for bodily pain and to 70.2% (95% CI, 67.8%-72.5%) for physical function, but improvement rates for walk time, knee and hip pain, and knee and hip function did not (P for all ≥.05). Younger age, male sex, higher income, lower BMI, and fewer depressive symptoms presurgery; no diabetes and no venous edema with ulcerations postsurgery (either no history or remission); and presurgery-to-postsurgery reductions in weight and depressive symptoms were associated with presurgery-to-postsurgery improvements in multiple outcomes at years 1, 2, and 3. CONCLUSIONS AND RELEVANCE: Among a cohort of participants with severe obesity undergoing bariatric surgery, a large percentage experienced improvement, compared with baseline, in pain, physical function, and walk time over 3 years, but the percentage with improvement in pain and physical function decreased between year 1 and year 3. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00465829.

Factors Associated with Post-Traumatic Symptoms in Mothers of Preterm Infants.

OBJECTIVES: Symptoms of post-traumatic distress in mothers of preterm infants have been a subject of mental health research. The aim of this study was to assess the prevalence of and risk factors associated with such symptoms in mothers of preterm infants in Taiwan. METHODS: This was a cross-sectional study performed between January 1, 2010 and June 30, 2011. One hundred and two mothers of preterm infants born at less than 37 weeks gestation and with a subsequent neonatal intensive care unit (NICU) stay between 2005 and 2009 were recruited. Participants completed a demographic questionnaire, the Impact of Event Scale-Revised (IES-R), the Center for Epidemiologic Studies Depression Scale (CES-D) and the neuroticism subscale of the Maudsley Personality Inventory (MPI). The preterm infants' data were taken from medical records. RESULTS: The prevalence of symptoms of distress was 25.5% (26/102) in the participants. These symptoms were associated with previous miscarriages, preterm premature rupture of membranes, neurotic personality and depression. CONCLUSIONS: The experience of preterm birth and NICU hospitalization can be traumatic to mothers. Early support for mothers during the preterm infants' NICU stay and transition to home care are recommended.

Electroencephalography and transcranial Doppler ultrasonography in neonatal citrullinemia.

The authors present a case of citrullinemia with a genotype of argininosuccinate synthetase (ASS1), c.380 G>A (p.R127Q)/c.380 G>A (p.R127Q), in two alleles. A 3-day-old female infant presented with status epilepticus and coma. Laboratory data showed hyperammonemia and marked lactic acidosis in the blood and cerebrospinal fluid; electroencephalography showed severely suppressed cerebral activity and focal paroxysmal volleys of slow and sharp waves (< 1Hz) over the left hemisphere. Real-time transcranial Doppler ultrasonography showed a brain edema and high peaked systolic and low diastolic flows in basal, anterior, and middle cerebral arteries; however, immediately after a blood exchange transfusion, systolic flows were lower and diastolic flows were higher. The resistance indices were significantly different (means: 0.58 vs. 0.37; p=0.01). The patient was placed on diet therapy. After six blood exchange transfusions and peritoneal dialysis, her neurologic examination results and serum ammonia and lactate values were normal. The authors found that electroencephalography and transcranial Doppler ultrasonography were useful for the diagnosis and follow-up treatment of neonatal citrullinemia.

Neurodevelopment Outcomes in Very-Low-Birth-Weight Infants with Metabolic Bone Disease at 2 Years of Age.

Metabolic bone disease (MBD) predominantly affects preterm infants, particularly very-low-birth-weight (VLBW) infants weighing <1500 g. However, there are limited reports on MBD and neurodevelopmental outcomes. This study aimed to analyze the risk factors for MBD and understand its impact on neurodevelopmental outcomes at 2 years of corrected age. Overall, 749 VLBW infants weighing <1350 g at birth were enrolled. Exclusion criteria were major congenital abnormalities, chromosomal abnormalities, and loss of follow-up on the Bayley Scales of Infant Development, Third Edition (BSID-III) test at 24 months of corrected age. Infants were retrospectively assessed by a trained case manager using the BSID-III test at 6, 12, and 24 months old. Infants were categorized as with or without MBD according to radiographic signs. Of those enrolled, 97 VLBW infants were diagnosed with MBD, compared to 362 VLBW infants without MBD. The proportion of infants that completed three follow-ups was 86%. At the assessment at 2 years of age, infants with MBD had lower and more significant differences in motor, language, and cognitive composites. MBD is associated with poor neurodevelopmental outcomes in cognitive, motor, and language composites for VLBW infants at 24 months of corrected age.

Effectiveness of corticosteroids and epinephrine use in neonates for the first extubation attempt: A retrospective study.

BACKGROUND: This study aimed to analyze the use of corticosteroids and epinephrine in neonates for the first extubation attempt and compared clinical characteristics of infants with successful and failed extubation events. METHODS: This was a retrospective cohort study conducted at a single level III neonatal intensive care unit in Taiwan. The study included 215 infants born between 2020 and 2021 who had been intubated for more than 48 h before their first extubation attempt. We compared perinatal and peri-extubation characteristics and outcomes between the two groups. Successful extubation was defined as freedom from invasive ventilatory support 72 h after extubation. The relationship between corticosteroids, local epinephrine, and successful extubation was determined using multivariate logistic regression analysis. RESULTS: In the univariate analysis, the failed extubation group received a significantly higher proportion of intravenous dexamethasone (p = 0.006) than the successful extubation group. Furthermore, the failed extubation group had a longer duration of nebulized epinephrine (p = 0.034) and more episodes of local application of epinephrine to the superior larynx (p = 0.003) than the successful extubation group. Multivariate analysis revealed that the absence of lung atelectasis, tachycardia 72 h after extubation, and lower post-extubation PCO2 were the key factors associated with successful extubation. CONCLUSIONS: There were trends toward systemic dexamethasone, local application of epinephrine to the superior larynx, and longer duration of nebulized epinephrine in the reintubation group. However, corticosteroid or local epinephrine use was not significantly associated with successful extubation. Lung atelectasis, elevated levels of carbon dioxide, and tachycardia were identified as risk factors for extubation failure.

Application of Physiologically Based Pharmacokinetic Modeling to Characterize the Effects of Age and Obesity on the Disposition of Levetiracetam in the Pediatric Population.

BACKGROUND: Levetiracetam is an antiseizure medication used for several seizure types in adults and children aged 1 month and older; however, due to a lack of data, pharmacokinetic (PK) variability of levetiracetam is not adequately characterized in certain populations, particularly neonates, children younger than 2 years of age, and children older than 2 years of age with obesity. OBJECTIVE: This study aimed to address the gap by leveraging PK data from two prospective standard-of-care pediatric trials (n = 88) covering an age range from 1 month to 19 years, including those with obesity (64%), and applying a physiologically based PK (PBPK) modeling framework. METHODS: A published PBPK model of levetiracetam for children aged 2 years and older was extended to pediatric patients younger than 2 years of age and patients older than 2 years of age with obesity by accounting for the obesity and age-related changes in PK using PK-Sim® software. The prospective pediatric data, along with the literature data for neonates and children younger than 2 years of age, were used to evaluate the extended PBPK models. RESULTS: Overall, 82.4% of data fell within the 90% interval of model-predicted concentrations, with an average fold error within twofold of the accepted criteria. PBPK modeling revealed that children with obesity had lower weight-normalized clearances (0.053 L/h/kg) on average than children without obesity (0.063 L/h/kg). The effect of maturation was well-characterized, resulting in comparable PBPK-simulated, weight-normalized clearances for neonates and children younger than 2 years of age reported from the literature. CONCLUSIONS: PBPK modeling simulations revealed that the current US FDA-labeled pediatric dosing regimen listed in the prescribing information can produce the required exposure of levetiracetam in these target populations with dose adjustments for children with obesity aged 4 years to younger than 16 years.

Reducing Medication Errors in Children's Hospitals.

OBJECTIVES: Knowledge of the prevalence and characteristics of medication errors in pediatric and neonatal patients is limited. This study aimed to evaluate the incidence and medication error characteristics in a pediatric hospital over 5 years and to determine whether serial error prevention programs to optimize a computerized physician order entry (CPOE) system reduce error incidence. METHODS: We retrospectively reviewed medication errors documented between January 2015 and December 2019. RESULTS: A total of 2,591,596 prescriptions were checked, and 255 errors were identified. Wrong dose prescriptions constituted the most common errors (56.9%). Medications with the highest rate of errors were antibiotics/antiviral drugs (36.9%). Oral route medications comprised the highest portion (60.8%), followed by intravenous ones (28.6%). The most common stage for medication errors was physician ordering (93.3%). Junior residents were responsible for most errors (45.9%). Most errors occurred in the pediatric ward (53.7%). In total, 221 (86.7%) errors were near misses. Only 4 errors (1.6%) were considered significant and required active monitoring or intervention. Type of error, stage of error, staff composition, and severity level of errors were significantly related to the number of errors in different years. There was a statistically significant decrease in errors per 100,000 prescriptions across different years after optimizing the CPOE system. CONCLUSIONS: The incidence of medication errors decreased with extensive use of the CPOE system. Continuous application of the CPOE optimization program can effectively reduce medication errors. Further incorporation of pediatric-specific decision-making and support tools and error prevention measures into CPOE systems is needed.

Maternal diabetes mellitus and birth defects in Taiwan: A 5-year nationwide population-based cohort study.

BACKGROUND: Birth defects (BDs) are the main causes of mortality and disability in infants and children. Associations between maternal diabetes mellitus (DM), including gestational DM (GDM) and pregestational DM (type 1 or type 2), and the risk of BDs have been reported. This study aims to determine the relationship between maternal DM and BDs and to investigate whether reducing the incidence of DM can decrease the incidence of BDs. METHODS: We identified all births in Taiwan from the National Birth Defects Surveillance Program between January 1, 2010, and December 31, 2014. Information on the infants' characteristics (sex, gestational age, and birth weight) and mothers' characteristics (age, parity, and associated diseases, including DM) were obtained from the National Birth Registry and National Health Insurance Research Database (NHIRD) in Taiwan. BDs were coded according to the International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) codes 740-759. RESULTS: Multiple logistic regression analysis with adjusted odds ratio (aOR) and 95% confidence interval (95% CI) for all BDs showed that the aOR (95% CI) was 1.002 (0.965-1.041), and the p -value was 0.9139 in the GDM group. In the type 1 DM group, the aOR (95% CI) was 1.748 (1.110-2.754), and the p -value was 0.016. In the type 2 DM group, the aOR (95%CI) was 1.175 (1.005-1.375), 1.331 (1.196-1.482), and 1.391 (1.216-1.592), and the p -value was 0.0437, <0.0001, and <0.0001 for the duration of mothers with type 2 DM <2, 2 to 5, >5 years, respectively. CONCLUSION: Mothers with pregestational DM (type 1 or type 2) increase the incidence of BD. Appropriate maternal glycemic control may achieve good pregnancy and perinatal outcomes.

Pharmacokinetics and Proposed Dosing of Levetiracetam in Children With Obesity.

OBJECTIVE: Characterize levetiracetam pharmacokinetics (PK) in children with obesity to inform dosing. METHODS: Children 2 to <21 years old receiving standard of care oral levetiracetam across two opportunistic studies provided blood samples. Levetiracetam plasma PK data were analyzed with a nonlinear mixed-effects modeling approach. Indirect measures for body size and covariates were tested for model inclusion. Individual empirical Bayesian estimates using the final model parameters were compared by obesity status. Monte Carlo simulation using total body weight was performed in children with normal estimated glomerular filtration rate to identify dosing for children with obesity that resulted in comparable exposures to normal weight adults and children after receiving label dosing. RESULTS: The population PK model was developed from 341 plasma concentrations from 169 children. A 1-compartment model best fit the data with fat-free mass as a significant covariate. Compared with children with normal weight, children with obesity had significantly lower body weight-normalized clearance (median [range], 4.77 [1.49-10.44] and 3.71 [0.86-13.55] L/h/70 kg, respectively). After label dosing with the oral formulation in children with obesity 4 to <16 years old, maximum and minimum steady-state concentrations were higher (25% and 41%, respectively [oral solution] and 27% and 19%, respectively [tablet]) compared with children with normal weight. Comparable exposures between children with and without obesity were achieved with weight-tiered dosing regimens of <75 kg or ≥75 kg. CONCLUSIONS: Weight-tiered dosing for levetiracetam oral solution and tablets for children with obesity 4 to <16 years old results in more comparable exposures to children of normal weight.

A MID1 gene mutation in a patient with Opitz G/BBB syndrome that altered the 3D structure of SPRY domain.

Mutations in the MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder that affects development of midline structures and comprises hypertelorism, cleft lip/palate, hypospadias, and laryngo-tracheo-esophageal abnormalities, and, at times, neurological, anal, and cardiac defects. MID1 gene abnormalities include missense, nonsense, and splicing mutations, small insertions, small deletions, and complex rearrangements. Here, we present a patient with Opitz G/BBB syndrome and a unique MID1 gene point mutation c.1703T

Nine genes that may contribute to partial trisomy (6)(p22→pter) and unique presentation of persistent hyperplastic primary vitreous with retinal detachment.

We report on a newborn girl with facial anomalies, a congenital heart defect, severe pre- and postnatal growth retardation, feeding problems, and persistent hyperplastic primary vitreous. Cytogenetic analysis by high resolution GTG banding showed extra chromosomal material on the short arm of one chromosome 1 of the patient, but neither parent. SKY and CGH analysis demonstrated that the patient had a de novo 46,XX, der(1)t(1;6)(p36.3; p22). Compared with previously reported cases of partial trisomy 6p22 syndrome, this patient exhibited a unique condition for this syndrome: persistent hyperplastic primary vitreous (PHPV) with retinal detachment. The human genome database was searched for candidate genes and we propose the following nine genes located in the 6p22→6pter region for their potential contribution to the phenotype of partial trisomy 6p22→pter and persistent hyperplastic primary vitreous (PHPV) with retinal detachment: Forkhead box Q1 (FOXQ1), FOXF2, FOXC1, NRN1, EDN1, ATXN1, DEK oncogene, E2F3, and NRNS1.

Study of leptin levels and gene polymorphisms in patients with central precocious puberty.

INTRODUCTION: Three single-nucleotide polymorphisms (SNPs) in the leptin (LEP) or leptin receptor (LEPR) genes were assessed for their association with central precocious puberty (CPP). RESULTS: The control group with the A/G SNP at LEPR 223 or A/G SNP at LEPR 109 exhibited significantly higher peak luteinizing hormone (LH) levels. The leptin level in the CPP group was significantly higher than that in the control group, but SNPs in either LEP or LEPR gene could not explain this observation. DISCUSSION: In conclusion, SNPs at LEPR 223 and LEPR 109 were significantly associated with higher levels of LH in girls without CPP, but none of the genotypes at these SNPs were significantly associated with CPP. METHODS: The SNP genotypes of LEP (polymorphism at promoter at nt-2548) and LEPR (223A/G, 109A/G) of 219 healthy girls and 249 girls diagnosed with CPP were compared. Allele frequencies in SNPs were compared with anthropometric measures, circulating leptin, hormones (estradiol, follicle-stimulating hormone, and LH), and lipid concentrations for CPP risk.