Bladder Temperature During Neonatal Targeted Temperature Management: A Case Report.

BACKGROUND: Neonatal encephalopathy is a clinical condition of altered neurological function in the first days of life. Targeted temperature management (TTM) is a validated approach to mitigate neurologic sequelae. Current literature suggests using rectal or esophageal site to assess temperature during TTM, but few studies focused on the best and the less invasive site to evaluate the temperature. This case report describes the performance of the bladder temperature monitoring during TTM. CLINICAL FINDINGS: A female newborn was born at 39 weeks' gestational age plus 4 days. At delivery, the newborn was in cardiorespiratory arrest. PRIMARY DIAGNOSIS: After performing cardiopulmonary resuscitation and neurological examination, a hypoxic-ischemic encephalopathy was diagnosed. INTERVENTIONS: After about 2 hours from birth, the newborn underwent TTM. OUTCOMES: A total of 4642 measurements of rectal temperature and 4520 measurements of bladder temperature were collected. Agreement between the 2 sites was statistically significant with a mean difference of 0.064°C ± 0.219 (95% confidence interval, -0.364 to 0.494); F = 47.044; and P value of less than .001. Furthermore, difference between rectal and bladder sites was not influenced by patient's urine output ( F = 0.092, P = .762). PRACTICE RECOMMENDATIONS: Bladder temperature seems to have a good reliability and not to be inferior to the other assessment site currently used. Using bladder catheter with temperature sensor could reduce the number of devices, ensure safer stabilization, and decrease treatment downtime.

Lower insulin sensitivity remains a feature of children born very preterm.

BACKGROUND: The first report of children born very preterm (<32 weeks of gestation) having insulin resistance was made 16 years ago. However, neonatal care has improved since. Thus, we aimed to assess whether children born very preterm still have lower insulin sensitivity than term controls. METHODS: Participants were prepubertal children aged 5 to 11 years born very preterm (<32 weeks of gestation; n = 51; 61% boys) or at term (37-41 weeks; n = 50; 62% boys). Frequently sampled intravenous glucose tolerance tests were performed, and insulin sensitivity was calculated using Bergman's minimal model. Additional clinical assessments included anthropometry, body composition using whole-body dual-energy X-ray absorptiometry scans, clinic blood pressure, and 24-hour ambulatory blood pressure monitoring. RESULTS: Children born very preterm were 0.69 standard deviation score (SDS) lighter (P < .001), 0.53 SDS shorter (P = .003), and had body mass index 0.57 SDS lower (P = .003) than children born at term. Notably, children born very preterm had insulin sensitivity that was 25% lower than term controls (9.4 vs 12.6 × 10-4 minutes-1 ·[mU/L]; P = .001). Other parameters of glucose metabolism, including fasting insulin levels, were similar in the two groups. The awake systolic blood pressure (from 24-hour monitoring) tended to be 3.1 mm Hg higher on average in children born very preterm (P = .054), while the clinic systolic blood pressure was 5.4 mm Hg higher (P = .002). CONCLUSIONS: Lower insulin sensitivity remains a feature of children born very preterm, despite improvements in neonatal intensive care. As reported in our original study, our findings suggest the defect in insulin action in prepubertal children born very pretermis primarily peripheral and not hepatic.

Idiopathic short stature and growth hormone sensitivity in prepubertal children.

OBJECTIVE: We compared growth hormone sensitivity to an insulin-like growth factor I (IGF-I) generation test in children with idiopathic short stature (ISS) and of normal stature (NS) across the birthweight range. METHODS: Forty-six prepubertal children (~7.1 years) born at term were studied: ISS (n = 23; 74% boys) and NS (n = 23; 57% boys). Children underwent a modified IGF-I generation test with recombinant human growth hormone (rhGH; 0.05 mg/kg/d) over four consecutive days. Hormonal concentrations were measured at baseline and day 5. RESULTS: Children with idiopathic short stature were 1.90 SDS lighter (P < 0.0001) but had 4.5% more body fat (P = 0.0007) than NS children. Overall, decreasing birthweight SDS across the normal range (-1.9 to +1.5 SDS) was associated with lower percentage IGF-I response to rhGH stimulation in univariable (r = 0.45; P = 0.002) and multivariable models (ß = 24.6; P = 0.006). Plasma IGF-I concentrations rose in both groups with rhGH stimulation (P < 0.0001). GHBP levels (P = 0.002) were suppressed in ISS children (-19%; P = 0.029) but increased among NS children (+18%; P = 0.028), with contrasting responses also observed for leptin and IGFBP-1. Further, the increase in insulin concentrations in response to rhGH stimulation was ~3-fold greater in NS children (142% vs 50%; P = 0.006). CONCLUSIONS: A progressive decrease in birthweight SDS was associated with a reduction in GH sensitivity in both NS and ISS children. Thus, the lower IGF-I response to rhGH stimulation in association with decreasing birthweight indicates that the ISS children at the lower end of the birthweight spectrum may have partial GH resistance, which may contribute to their poorer growth.

Partial remission in type 1 diabetes and associated factors: Analysis based on the insulin dose-adjusted hemoglobin A1c in children and adolescents from a regional diabetes center, Auckland, New Zealand.

BACKGROUND: Partial remission (PREM) by the insulin dose-adjusted HbA1c (IDAA1c) method has not been evaluated for the combined associations of ethnicity and socioeconomic status in children and adolescents with type 1 diabetes (T1D). OBJECTIVE: To investigate prevalence and predictors of PREM defined by IDAA1c. METHODS: Six hundred fourteen of 678 children (aged <15 years) with new-onset T1D (2000-2013) from a regional pediatric diabetes service (Auckland, New Zealand). RESULTS: Overall rate of PREM at 3 months was 42.4%, and lower in Maori/Pacific children (28.6%; P = .006) and those of other ethnicities (28.8%; P = .030) compared with New Zealand Europeans (50.4%). Comparing the most and least deprived socioeconomic quintiles, the odds of PREM were lower among the most deprived (adjusted odds ratio [aOR] 0.44; P = .019). Lower rates of PREM were seen in children aged 0 to 4.9 years (23.8%) and 10 to 14 years (40.9%) than in children aged 5 to 9.9 years (57.4%; P < .05). Further predictors of lower rates of PREM were ketoacidosis at diagnosis (aOR 0.54 with DKA; P = .002) and diabetes duration (aOR 0.84 per month; P < .0001). Patient's sex, body mass index standard deviation score, or autoantibodies were not associated with PREM. PREM at 3 months was associated with lower HbA1c over 18 months compared with children not in PREM (65.0 vs 71.3 mmol/mol; P < .0001), independent of ketoacidosis. CONCLUSIONS: This study on a regional cohort of youth with T1D showed social and ethnic disparities in rates of PREM defined by IDAA1c. Further research into reducing ketoacidosis rates at diagnosis and addressing factors associated with lower rates of PREM in non-European children are important health priorities.

Nulliparity is associated with subtle adverse metabolic outcomes in overweight/obese mothers and their offspring.

BACKGROUND: We aimed to evaluate metabolic outcomes in overweight/obese nulliparous and multiparous women and their offspring. STUDY DESIGN: Seventy-two overweight and obese women who participated in a randomized controlled trial of exercise in pregnancy were included in the study, comparing 18 nulliparous and 54 multiparous women and their singleton offspring. Women were assessed at 19 and 36 weeks of gestation. Fetal growth was measured using standard obstetric ultrasound techniques. Cord blood was collected at birth. Maternal and offspring body composition was assessed using DXA ~2 weeks after delivery. RESULTS: Nulliparous women had higher HbA1c in the third trimester of pregnancy than multiparous women (5.48% vs 5.29%; P=.002) and were more insulin-resistant based on the surrogate marker sex hormone-binding globulin (354 vs 408 nmol/L; P=.047). Nulliparous women also had higher levels of the inflammatory marker tumour necrosis factor-alpha (4.74 vs 3.62 pg/mL; P=.025). At birth, the offspring of nulliparous women were on average 340 g (P=.013) and 0.69 standard deviation scores (P=.026) lighter than those born of multiparous women. Cord blood data showed lower insulin-like growth factor-II (P=.026) and higher IGF binding protein-1 (P=.002) levels in the offspring of nulliparous women. In addition, a less favourable metabolic profile was observed in the offspring of nulliparous women, as indicated by higher triglyceride (P<.001) and interleukin-6 (P=.039) concentrations. CONCLUSIONS: Infants born of nulliparous overweight and obese women appear to be exposed to a less favourable metabolic environment in utero, with evidence of subtle adverse metabolic outcomes at birth compared to infants of overweight/obese multiparous women.

Being born large for gestational age is associated with earlier pubertal take-off and longer growth duration: a longitudinal study.

AIM: Perinatal factors seem to influence the onset of puberty, but there is limited information on the potential effect of large size at birth on pubertal growth. This study evaluated pubertal growth in children born large for gestational age (LGA) compared to children born appropriate for gestational age (AGA). METHODS: Longitudinal growth data collected from 70 children - 40 AGA and 30 LGA - were analysed. The ages at take-off, peak height velocity, final height and pubertal growth spurts were calculated using the Preece-Baines model I. RESULTS: Large for gestational age children showed an earlier age at take-off compared to AGA children (10.1 ± 1.2 versus 11.0 ± 1.4 years, p = 0.007), whereas the age at peak height velocity and at final height was similar. LGA children showed a longer growth spurt duration (2.5 ± 1 versus 1.5 ± 1.2 years, p < 0.001) and total pubertal duration (5.3 ± 1.2 versus 4.6 ± 1.2 years, p = 0.036) than AGA children. Results were similar when stratified by sex. CONCLUSION: Being born LGA was associated with an earlier pubertal take-off and longer growth duration. These unique findings, due to the lack of studies on pubertal growth patterns in LGA children, might lead the way to novel research and a different approach to LGA children at the onset of pubertal growth.

Spectrum of phenotypic anomalies in four families with deletion of the SHOX enhancer region.

BACKGROUND: SHOX alterations have been reported in 67% of patients affected by Léri-Weill dyschondrosteosis (LWD), with a larger prevalence of gene deletions than point mutations. It has been recently demonstrated that these deletions can involve the SHOX enhancer region, rather that the coding region, with variable phenotype of the affected patients.Here, we report a SHOX gene analysis carried out by MLPA in 14 LWD patients from 4 families with variable phenotype. CASE PRESENTATION: All patients presented a SHOX enhancer deletion. In particular, a patient with a severe bilateral Madelung deformity without short stature showed a homozygous alteration identical to the recently described 47.5 kb PAR1 deletion. Moreover, we identified, for the first time, in three related patients with a severe bilateral Madelung deformity, a smaller deletion than the 47.5 kb PAR1 deletion encompassing the same enhancer region (ECR1/CNE7). CONCLUSIONS: Data reported in this study provide new information about the spectrum of phenotypic alterations showed by LWD patients with different deletions of the SHOX enhancer region.

Parents' Participation in Care during Neonatal Intensive Care Unit Stay in COVID-19 Era: An Observational Study.

BACKGROUND: Parents play a crucial role in the care of infants during their stay in the neonatal intensive care unit (NICU). Recent studies have reported a decrease in parental participation due to the coronavirus disease (COVID-19) pandemic, which has led to restricted access policies in hospitals. The aim of this study was to describe the barriers to good parental participation during their stay in the neonatal intensive care unit in the COVID-19 era. METHODS: This was a quantitative, observational study. RESULTS: A total of 270 parents participated in this study. Mothers' participation in care was higher than that of fathers (p = 0.017). Parents who lived at the birth of their first child reported a better level of participation in care compared to those who lived at the birth of their second-born (p = 0.005). Parents of extremely preterm neonates reported a lower interaction with their infants than parents of term newborns (p < 0.001). CONCLUSIONS: Some disadvantaged categories reported lower scores for cultural and linguistic minorities, parents of multiple children, and fathers. The COVID-19 pandemic has made several family-centred care activities impossible, with a higher impact on those who benefited most of these facilities. This study was prospectively approved by the IRB-CRRM of the University "G. d'Annunzio" Chieti-Pescara on 23 January 2024 (approval number CRRM: 2023_12_07_01).

Weight loss in obese prepubertal children: the influence of insulin resistance.

BACKGROUND: Insulin resistance (IR), a link of paramount importance between obesity and cardiovascular/metabolic complications, seems to be implicated in weight changes. OBJECTIVE: To determine whether IR could influence weight status during a 1-year intervention program in obese prepubertal children. METHODS: Forty-four children with IR (IR group) and 42 children without IR (NIR group) were enrolled. Body mass index standard deviation score (BMI-SDS), waist circumference (WC), and homeostasis model assessment (HOMA-IR) were evaluated. RESULTS: NIR children showed a significant reduction of BMI-SDS and WC at final assessment (p = 0.009 and p = 0.001, respectively), whereas IR children presented unchanged values. HOMA-IR decreased after intervention in the NIR group (p = 0.0008), but was exacerbated in IR children (p = 0.004). A positive and significant association between HOMA-IR at baseline and BMI at follow-up was found (B ± SE = 0.87 ± 0.24, p = 0.001). HOMA-IR at baseline was also significantly associated with WC at follow-up (B ± SE = 2.12 ± 0.69, p = 0.003). CONCLUSIONS: IR seems to influence adiposity changes in obese prepubertal children. Further longitudinal studies are needed to verify the relationship between IR and weight loss during childhood.

Birth size, growth trajectory and later cardio-metabolic risk.

There is increasing evidence of a strong association between intrauterine growth and subsequent development of chronic disease in adult life. Birth size and growth trajectory have been demonstrated to have an impact on cardio-metabolic health, both in childhood and adult life. Hence, careful observation of the children's growth pattern, starting from the intrauterine period and the first years of life, should be emphasized to detect the possible onset of cardio-metabolic sequelae. This allows to intervene on them as soon as they are detected, first of all through lifestyle interventions, whose efficacy seems to be higher when they are started early. Recent papers suggest that prematurity may constitute an independent risk factor for the development of cardiovascular disease and metabolic syndrome, regardless of birth weight. The purpose of the present review is to examine and summarize the available knowledge about the dynamic association between intrauterine and postnatal growth and cardio-metabolic risk, from childhood to adulthood.

Neonatal diagnosis of circumferential skin creases.

BACKGROUND: Circumferential skin creases is a rare and heterogeneous disorder characterized by multiple and redundant skin folds, which can present as an isolated feature or in association with other phenotypic anomalies. Here, we report the case of a newborn who immediately captured our attention because of his phenotype. CASE: A male Caucasian infant was born at 39 weeks and 4 days of gestational age with an instrumental delivery, after a pregnancy characterized by threat of preterm birth at 32 weeks. Fetal ultrasounds were reported to be normal. The patient was the first child of non-consanguineous parents. Anthropometry at birth: weight 3.590 kg (0.57 SDS); length 53 cm (1.73 SDS); cranial circumference 35.5 cm (0.83 SDS). Clinical examination soon after birth revealed multiple, asymmetric and deep skin folds involving forearms, legs and lower eyelids (right > left). These folds seemed not to cause any physical discomfort. In addition, hypertrichosis, micrognathia, low-set ears and a thin, down-turned border of upper lip were observed. Cardio-respiratory, abdominal and neurological examination was unremarkable. There was no family history of similar appearance or other physical abnormalities. Given the clinical picture, an array-CGH was performed, which was normal. A genetic counseling was requested and Circumferential Skin Creases disorder was diagnosed based on the typical cutaneous involvement and, given the absence of other clinical signs, it was supposed a benign evolution, with skin folds tending to disappear over time. In addition, the baby's DNA was requested for a targeted genetic analysis, which resulted negative. CONCLUSIONS: This clinical case underlines the need of performing a detailed neonatal physical examination in order to realize a timely diagnostic approach. Our patient presented with multiple skin folds, facial dysmorphism but normal systemic and neurological examination. Anyways, since Circumferential Skin Creases may be associated with later neurological symptoms, a regular reevaluation is recommended.

Perinatal diagnosis of congenital urogenital sinus abnormality.

Anomalies of the urogenital sinus, which is a transient feature of the early human embryological development, are rare birth defects. Urogenital sinus abnormalities commonly present as pelvic masses, hydrometrocolpos, or ambiguous genitalia and most commonly occur within the context of congenital adrenal hyperplasia. Anomalies of the urogenital sinus requires surgical repair. We experienced a case of a female newborn with congenital urogenital sinus abnormality in which the early diagnosis helped us to prevent complications by decompressing the vagina soon after birth. Antibiotic prophylaxis was sufficient to avoid infections and to decompress the genitourinary system, thus allowing a deferred elective surgery to correct the sinus.

The possible role of esRAGE and sRAGE in the natural history of diabetic nephropathy in childhood.

The advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p = 0.003 and p = 0.001) and pubertal (p = 0.002 and p = 0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p = 0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume (p = 0.0004, r = -0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy.

High Prevalence of Cardiometabolic Comorbidities Among Children and Adolescents With Severe Obesity From a Large Metropolitan Centre (Hangzhou, China).

Objective: This study aimed to describe the clinical characteristics of children and adolescents with obesity, and the prevalence of cardiometabolic comorbidities over 10 years in this population from a large metropolitan centre in China. Methods: This was a cross-sectional study (2008-2017) of patients aged <18 years with obesity [body mass index (BMI) ≥ 95th percentile for age and sex] enrolled at the Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine (Hangzhou, Zhejiang Province). Clinical assessments included anthropometry, blood pressure, liver ultrasound, lipid profile, oral glucose tolerance test, and uric acid. For examination of outcomes, our study cohort was stratified by sex and age bands (<10 vs. ≥10 years), with the study period also split into two strata (2008-2012 and 2013-2017). Results: A total of 2,916 patients (1,954 boys and 962 girls) were assessed at a mean age of 10.5 years. Patients almost invariably presented severe obesity (median BMI SDS = 2.98; Q1 = 2.60, Q3 = 3.39). Obesity-related comorbidities were common among boys and girls, including type 2 diabetes mellitus (2.6% and 3.6%, respectively), abnormal glycaemia (33.6% and 35.5%, respectively), hypertension (33.9% and 32.0%, respectively), dyslipidaemia (35.2% and 39.6%, respectively), hyperuricaemia (16.2% and 8.3%, respectively), acanthosis nigricans (71.9% and 64.0%, respectively), abnormal liver function (66.9% and 47.0%, respectively), and non-alcoholic fatty liver disease (NAFLD) (63.8% and 45.1%, respectively); 38.7% of boys and 44.4% of girls aged ≥10 years had metabolic syndrome. Notably, the incidence of many cardiometabolic comorbidities was in 2013-2017 compared to 2008-2012. For example, rates of hypertension among boys aged <10 years and aged ≥10 years rose from 28.4% and 26.5% to 48.0% and 35.8%, respectively, and in girls from 20.3% and 20.8% to 41.7% and 39.6%, respectively. In 2013-2017, 9.5% of girls in the older group had metabolic syndrome compared to 2.2% in 2008-2013. Conclusions: We observed a high incidence of obesity-related cardiometabolic comorbidities among Chinese children and adolescents with severe obesity over 10 years. It was particularly concerning that rates of several comorbidities rose markedly over the study period, highlighting the need to address the obesity epidemic early in life (in China and elsewhere) to prevent the development of obesity-related comorbidities and, subsequently, of overt disease.

Severe Hypercapnia Requiring 48-h Whole-Body Hypothermia in an Infant with Acute Bronchiolitis.

Bronchiolitis is a clinical syndrome involving the lower respiratory tract of infants and young children. The majority of patients recover using adequate hydration and oxygen (O2) therapy, while a small number of patients require ventilatory assistance. Beyond these therapeutical approaches, there are no available strategies for patients that do not improve. Hypothermia is a measure used to prevent neonatal hypoxic-ischemic encephalopathy by preventing carbon dioxide (CO2) production and subsequent tissue damage. Other medical applications of hypothermia have been proposed, such as in acute respiratory failure and necrotizing colitis. Case report: We report the case of a 50-day-old girl hospitalized with severe bronchiolitis caused by respiratory syncytial virus. On admission, the girl presented severe hypercapnic respiratory failure, requiring intubation and ventilatory support with conventional and non-conventional systems. However, the patient's general conditions worsened with elevated O2 demand, thus whole-body hypothermia was attempted and performed for 48 h, with a gradual improvement in the respiratory function. No adverse effects were detected. Conclusions: Whole-body hypothermia could have a critical role as a rescue treatment in infants affected by severe hypercapnic respiratory failure, at the expense of few and rare side effects (bradycardia, coagulopathy, hyperglycemia). Notably, beyond reducing CO2 production, whole-body hypothermia might have an impact in restoring lung function in newborns using bronchiolitis refractory to maximal medical therapy and invasive ventilation.

Molecular Characterization by Whole-Genome Sequencing of Clinical and Environmental Serratia marcescens Strains Isolated during an Outbreak in a Neonatal Intensive Care Unit (NICU).

The whole-genome sequencing (WGS) of eighteen S. marcescens clinical strains isolated from 18 newborns hospitalized in the Neonatal Intensive Care Unit (NICU) at Pescara Public Hospital, Italy, was compared with that of S. marcescens isolated from cradles surfaces in the same ward. The identical antibiotic resistance genes (ARGs) and virulence factors were found in both clinical and environmental S. marcescens strains. The aac(6')-Ic, tetA(41), blaSRT-3, adeFGH, rsmA, and PBP3 (D350N) genes were identified in all strains. The SRT-3 enzyme, which exhibited 10 amino acid substitutions with respect to SST-1, the constitutive AmpC ß-lactamase in S. marcescens, was partially purified and tested against some ß-lactams. It showed a good activity against cefazolin. Both clinical and environmental S. marcescens strains exhibited susceptibility to all antibiotics tested, with the exception of amoxicillin/clavulanate.

Neonatal diagnosis of Marcus Gunn jaw-winking syndrome.

This report highlights the importance for neonatologists/pediatricians of considering Marcus Gunn jaw-winking syndrome among differential diagnoses of ptosis. A detailed clinical assessment is crucial to promptly recognize and appropriately manage it.

The associations between maternal BMI and gestational weight gain and health outcomes in offspring at age 1 and 7 years.

In secondary analyses of a randomised controlled trial of exercise during pregnancy, we examined associations between mid-pregnancy maternal body mass index (BMI) and excessive gestational weight gain (GWG) with offspring health. Follow-up data were available on 57 mother-child pairs at 1-year and 52 pairs at 7-year follow-ups. Clinical assessments included body composition and fasting blood tests. At age 1 year, increased maternal BMI in mid-gestation was associated with greater weight standard deviation scores (SDS) in the offspring (p = 0.035), with no observed associations for excessive GWG. At age 7 years, greater maternal BMI was associated with increased weight SDS (p < 0.001), BMI SDS (p = 0.005), and total body fat percentage (p = 0.037) in their children. Irrespective of maternal BMI, children born to mothers with excessive GWG had greater abdominal adiposity (p = 0.043) and less favourable lipid profile (lower HDL-C and higher triglycerides). At 7 years, maternal BMI and excessive GWG had compounded adverse associations with offspring adiposity. Compared to offspring of mothers with overweight/obesity plus excessive GWG, children of normal-weight mothers with adequate and excessive GWG were 0.97 and 0.64 SDS lighter (p = 0.002 and p = 0.014, respectively), and 0.98 and 0.63 SDS leaner (p = 0.001 and p = 0.014, respectively). Both greater maternal BMI in mid-pregnancy and excessive GWG were independently associated with increased adiposity in offspring at 7 years.