Minipuberty in Male Full-term Neonates Appropriate and Small for Gestational Age and in Preterm Babies: Data from a Single Centre

Objective: The postnatal activation of the hypothalamic-pituitary-gonadal (HPG) axis is usually known as "minipuberty". There are still open questions about its biological function and significance depending on sex, gestational age (GA) and birth weight (BW) with few available longitudinal data. Methods: A single-centre, longitudinal study to quantify urinary follicle stimulating hormone (uFSH), luteinizing hormone (uLH) and testosterone (uTs) in male neonates. Neonates were enrolled and stratified into three subgroups: full-term boys appropriate for GA (FT AGA); FT boys with BW ≤3rd centile [FT small for gestational age (SGA)]; and preterm (PT) boys ≤33 weeks of GA. Urinary hormones were correlated to simultaneous auxological parameters, linear growth and external genitalia at scheduled time-points. Results: Forty-six boys were recruited, with subgroup sizes FT AGA n=23, FT SGA n=11 and PT n=12. PT boys display a pulsatile pattern of urinary gonadotropins (uGns) with higher levels of uLH and a gradual increase of uTs. Testicular descent started from 29-32 weeks with the peak of uTs. During the first 12-months post-term age (PTA), FT AGA boys displayed a better linear growth (p<0.05). PT showed higher uGns levels until 3-months PTA. PT babies had higher uLH levels than FT AGA, with a peak at 7 and 30 days, during the first 90 days of life (p<0.001) and higher uTs levels. Correlation analysis between penile growth of all neonates and uTs was significant (p=0.04) but not within subgroups. Conclusion: This study investigated postnatal HPG axis activation in term and PT infants. Minipuberty may involve an early window of opportunity to evaluate the functionality of the HPG axis. Further studies with a long-term follow-up are needed with a special focus on possible consequences of GA and BW.

Perinatal and postnatal exposure to phthalates and early neurodevelopment at 6 months in healthy infants born at term.

Background: Phthalates are non-persistent chemicals largely used as plasticizers and considered ubiquitous pollutants with endocrine disrupting activity. The exposure during sensible temporal windows as pregnancy and early childhood, may influence physiological neurodevelopment. Aims and Scope: The aim of this study is to analyze the relationship between the urinary levels of phthalate metabolites in newborn and infants and the global development measured by the Griffiths Scales of Children Development (GSCD) at six months. Methods: Longitudinal cohort study in healthy Italian term newborn and their mothers from birth to the first 6 months of life. Urine samples were collected at respectively 0 (T0), 3 (T3), 6 (T6) months, and around the delivery for mothers. Urine samples were analyzed for a total of 7 major phthalate metabolites of 5 of the most commonly used phthalates. At six months of age a global child development assessment using the third edition of the Griffith Scales of Child Development (GSCD III) was performed in 104 participants. Results: In a total of 387 urine samples, the seven metabolites analyzed appeared widespread and were detected in most of the urine samples collected at any time of sampling (66-100%). At six months most of the Developmental Quotients (DQs) falls in average range, except for the subscale B, which presents a DQ median score of 87 (85-95). Adjusted linear regressions between DQs and urinary phthalate metabolite concentrations in mothers at T0 and in infants at T0, T3 and T6 identified several negative associations both for infants' and mothers especially for DEHP and MBzP. Moreover, once stratified by children's sex, negative associations were found in boys while positive in girls. Conclusions: Phthalates exposure is widespread, especially for not regulated compounds. Urinary phthalate metabolites were found to be associated to GSCD III scores, showing inverse association with higher phthalate levels related to lower development scores. Our data suggested differences related to the child's sex.

Late-Onset Sepsis Mortality among Preterm Infants: Beyond Time to First Antibiotics.

Objective: To investigate the impact of timing, in vitro activity and appropriateness of empirical antimicrobials on the outcome of late-onset sepsis among preterm very low birth weight infants that are at high risk of developing meningitis. Study design: This retrospective study included 83 LOS episodes in 73 very low birth weight infants born at ≤32 weeks' gestation with positive blood and/or cerebrospinal fluid culture or polymerase chain reaction at >72 h of age. To define the appropriateness of empirical antimicrobials we considered both their in vitro activity and their ideal delivery through the blood-brain barrier when meningitis was confirmed or not ruled out through a lumbar puncture. The primary outcome was sepsis-related mortality. The secondary outcome was the development of brain lesions. Timing, in vitro activity and appropriateness of empirical antimicrobials, were compared between fatal and non-fatal episodes. Uni- and multi-variable analyses were carried out for the primary outcome. Results: Time to antibiotics and in vitro activity of empirical antimicrobials were similar between fatal and non-fatal cases. By contrast, empirical antimicrobials were appropriate in a lower proportion of fatal episodes of late-onset sepsis (4/17, 24%) compared to non-fatal episodes (39/66, 59%). After adjusting for Gram-negative vs. Gram-positive pathogen and for other supportive measures (time to volume administration), inappropriate empirical antimicrobials remained associated with mortality (aOR, 10.3; 95% CI, 1.4-76.8, p = 0.023), while timing to first antibiotics was not (aOR 0.9; 95% CI, 0.7-1.2, p = 0.408; AUC = 0.88). The association between appropriate antimicrobials and brain sequelae was also significant (p = 0.024). Conclusions: The risk of sepsis-related mortality and brain sequelae in preterm very low birth weight infants is significantly associated with the appropriateness (rather than the timing and the in vitro activity) of empirical antimicrobials. Until meningitis is ruled out through lumbar puncture, septic very low birth weight infants at high risk of mortality should receive empiric antimicrobials with high delivery through the blood-brain barrier.

The Kids Are Alright (?). Infants' Development and COVID-19 Pandemic: A Cross-Sectional Study.

Objectives: The study aimed to assess and compare the global development in six-month-old infants before and during the pandemic restrictive social distancing measures. Methods: This cross-sectional nested study involved infants assessed through the Griffiths Scales of Child Development (GSCD) between September 2019 and April 2021. Infants were classified in a pre-COVID or a COVID group, considering the evaluation date and the restrictive measures in place. GSCD subscales and General Development Scores (GDS) were calculated and compared. Results: One hundred and four healthy term-born infants were evaluated. GDS in the COVID group (n:70; median: 94; IQR: 90-100) appeared significantly lower than in the pre-COVID group (n:34; median: 98; IQR: 97-103; p < 0.001). Language and personal-social-emotional subareas scores appeared the most affected. A decreasing trend of GDS along with the severity of restriction was observed. Conclusion: A reduction in infant development scores was observed during pandemic social distancing. Further studies are needed to systematize these findings and to address effective public health policies for infants and families during long-term forced isolation periods.

Neonatal septic shock, a focus on first line interventions.

Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis is challenging, since neonatal septic shock may overlap with the physiological changes occurring at birth. The outcome of septic shock depends on a prompt recognition of symptoms and a strict adherence to cardiopulmonary resuscitation guidelines. Fluid administration plays a major role in the initial management of septic shock. If there is no response to volume filling, inotropes must be infused within one hour of onset (dopamine, dobutamine, adrenaline). Life-threatening infections require immediate and aggressive empiric use of antimicrobials. In the pediatric age, delay in antibiotic initiation for treating septic shock is associated with poor outcome and increased risk of mortality. There is a gap regarding first line interventions in neonatal septic shock. This review addresses initial interventions in the treatment of neonatal septic shock and discusses currently available evidences., These interventions may allow to improve the outcome if they are promptly carried out.

Clinical Presentation of Celiac Disease and Diagnosis Accuracy in a Single-Center European Pediatric Cohort over 10 Years.

(1) Background: Changes in the clinical presentation of celiac disease (CD) in children have been reported. The guidelines of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) allow esophagogastroduodenoscopy (EGD) with biopsies to be avoided under specific circumstances. We aimed to assess the clinical picture of pediatric CD patients at diagnosis and to validate ESPGHAN non-biopsy criteria. (2) Methods: Patients with suspected CD or undergoing screening from 2004 to 2014 at the University Hospital in Modena, Italy were enrolled. The accuracy of ESPGHAN non-biopsy criteria and modified versions were assessed. (3) Results: In total, 410 patients were enrolled, of whom 403 were considered for analysis. Of the patients considered, 45 were asymptomatic and diagnosed with CD (11.2%) while 358 patients (88.2%) were symptomatic, of whom 295 were diagnosed with CD. Among symptomatic CD patients, 57 (19.3%) had gastrointestinal symptoms, 98 (33%) had atypical symptoms and 140 (47.4%) had both. No difference was found for the presence of gastrointestinal symptoms at different ages. The non-biopsy ESPGHAN criteria yielded an accuracy of 59.4% with a positive predictive value (PPV) of 100%; 173 out of 308 EGD (56.2%) could have been avoided. The modified 7× and 5× upper limit of normal cut-offs for IgA anti tissue-transglutaminase reached 60.7% and 64.3% of EGD avoided, respectively. (4) Conclusions: Over 10 years, late age at diagnosis and increased rates of atypical CD presentation were found. ESPGHAN non-biopsy criteria are accurate for CD diagnosis and allow half of unneeded EGD to be avoided. Modified versions allowed sparing a greater number of EGD.

Perinatal Exposure to Phthalates: From Endocrine to Neurodevelopment Effects.

Phthalates, as other endocrine disrupting chemicals (EDCs), may alter the homeostasis and the action of hormones and signaling molecules, causing adverse health outcomes. This is true especially for infants, who are both more exposed and sensitive to their effects. Phthalates are particularly harmful when the exposure occurs during certain critical temporal windows of the development, such as the prenatal and the early postnatal phases. Phthalates may also interfere with the neuroendocrine systems (e.g., thyroid hormone signaling or metabolism), causing disruption of neuronal differentiation and maturation, increasing the risk of behavioral and cognitive disorders (ADHD and autistic behaviors, reduced mental, psychomotor, and IQ development, and emotional problems). Despite more studies being needed to better understand the role of these substances, plenty of evidence suggests the impact of phthalates on the neuroendocrine system development and function. This review aims to update the knowledge on the neuroendocrine consequences of neonatal and perinatal exposure to phthalates.

Treatment of chronic infected post-oncological wounds with a dermal matrix: two case studies.

The reconstruction of complex wounds in patients with comorbidities in the lower extremities is a challenging problem for surgeons. Skin grafting is frequently used to cover large skin defects, but it has several limits, including unwanted outcomes resulting from scars, poor elasticity and limitations in joint movement due to contractures. Locoregional flaps, particularly in the lower limbs, have limited application due to the size of the defect. Tissue engineering of the skin has offered major improvements in the coverage of large defects. Dermal matrix can be applied in order to generate a new dermis that allows good re-epithelialisation or skin grafting at a later stage. The reconstruction of large lower limb defects is more complicated in the case of chronic wounds showing no tendency to heal due to chronic infection. For all surgeons, it is very important to prevent the formation of a biofilm or manage it when it is already established before undertaking surgical procedures that involve a dermal matrix. We report our reconstruction strategy of chronic infected neoplastic ulcers of the lower extremities with a dermal matrix and our postoperative dressing protocol.