A literature review on the redundancy of additional thyroid function tests in neonates of mothers with hypothyroidism.

AIM: Newborn thyroid screening tests are carried out during the first days after birth in many parts of the world. The aim of this review was to assess whether additional thyroid function tests of neonates born to mothers with hypothyroidism are necessary to diagnose newborns with congenital hypothyroidism (CH) missed by the usual screening test. METHODS: A search in PubMed and Google Scholar databases was conducted for pertinent studies, using relevant keywords. All studies that were published in any language from 1 January 2000 to 30 June 2023 were included. Observational cohort studies were included in the analysis, while case reports and studies not referring to neonates were excluded. RESULTS: Thirteen studies were identified comprising more than 4400 infants with CH. Studies with the larger study populations recommended against additional testing in healthy infants of hypothyroid mothers. Similar were the results of some smaller retrospective studies. Few studies identified in total 16 infants with CH that were missed on neonatal screening without, though, a definite causative link between the mother's and the infant's thyroid dysfunction. CONCLUSION: Based on available data, additional thyroid function tests seem redundant in identifying undiagnosed cases of CH. Larger studies are needed to reach a definite conclusion.

Pituitary gland height evaluated with magnetic resonance imaging in premature twins: the impact of growth and sex.

BACKGROUND: Pituitary gland height reflects secretory activity of the hypothalamo-pituitary axis. OBJECTIVE: To assess the cumulative impact of fetal growth and sex on pituitary gland height in premature twins, dissociated from prematurity. MATERIALS AND METHODS: A retrospective study was conducted, assessing the pituitary gland height in 63 pairs of preterm twins, measured from T1-weighted magnetic resonance imaging (MRI). Auxological parameters, including body weight, body length, and head circumference, at birth and at the time of MRI, were used as proxies for fetal and postnatal growth, respectively. The study population was divided into two groups, using corrected age at around term equivalent as the cutoff point. Statistical analysis was performed using mixed-effects linear regression models. RESULTS: When pituitary gland height was evaluated at around term equivalent, a greater pituitary gland height, suggesting a more immature hypothamo-pituitary axis, was associated with the twin exhibiting lower auxological data at birth. The same association was observed when body weight and length at MRI were used as covariants. In the group evaluated after term equivalent, a smaller pituitary gland height, suggesting a more mature hypothamo-pituitary axis, was associated with male sex. This difference was observed in twin pairs with higher average body weight at birth, and in babies exhibiting higher auxological data at MRI. CONCLUSION: After isolating the effect of prematurity, at around term equivalent, pituitary gland height reflects the cumulative impact of fetal growth on the hypothalamo-pituitary axis. Subsequently, pituitary gland height shows effects of sex and of fetal and postnatal growth.

Application of Advanced Molecular Methods to Study Early-Onset Neonatal Sepsis.

Early-onset sepsis (EOS) is a global health issue, considered one of the primary causes of neonatal mortality. Diagnosis of EOS is challenging because its clinical signs are nonspecific, and blood culture, which is the current gold-standard diagnostic tool, has low sensitivity. Commonly used biomarkers for sepsis diagnosis, including C-reactive protein, procalcitonin, and interleukin-6, lack specificity for infection. Due to the disadvantages of blood culture and other common biomarkers, ongoing efforts are directed towards identifying innovative molecular approaches to diagnose neonates at risk of sepsis. This review aims to gather knowledge and recent research on these emerging molecular methods. PCR-based techniques and unrestricted techniques based on 16S rRNA sequencing and 16S-23S rRNA gene interspace region sequencing offer several advantages. Despite their potential, these approaches are not able to replace blood cultures due to several limitations; however, they may prove valuable as complementary tests in neonatal sepsis diagnosis. Several microRNAs have been evaluated and have been proposed as diagnostic biomarkers in EOS. T2 magnetic resonance and bioinformatic analysis have proposed potential biomarkers of neonatal sepsis, though further studies are essential to validate these findings.

The role of serum vitamin 25(OH)D concentration in the Covid-19 pandemic in children.

The ongoing Coronavirus disease 19 (Covid-19) pandemic and associated mortality in children led to an effort to address risk factors and develop protective measures. Observational studies in adults showed that vitamin D deficiency is associated with Covid-19 severity. The aim of this review was to summarise data regarding the role of serum vitamin 25(OH)D concentration in the severity of Covid-19 and the associated multisystem inflammatory syndrome in children (MIS-C). Many studies noted lower concentrations of vitamin 25(OH)D in children with Covid-19 compared with healthy controls; however, studies that assessed vitamin 25(OH)D suboptimal concentrations as a risk factor for Covid-19 severity were scarce. There was no high-quality evidence that vitamin 25(OH)D concentrations are associated with Covid-19 severity. Similarly, for MIS-C, a few studies with a small number of patients found that vitamin D deficiency was associated with more severe MIS-C. Vitamin D has many immunomodulatory actions and is consumed in the immunomodulatory cells, especially in infections such as the Covid-19 which is associated with increased inflammation and cytokine storm. Therefore, decreased concentrations of plasma vitamin 25(OH)D have been proposed to be the result of vitamin use by immunomodulatory cells in severe Covid-19, rather than a predisposing factor. In conclusion, the available data cannot prove that vitamin D deficiency is a risk factor for severe Covid-19 disease. More studies, of prospective design, are needed to investigate the role of this marker independently of other risk factors.

Are the current feeding volumes adequate for the growth of very preterm neonates?

Postnatal growth failure, a common problem in very preterm neonates associated with adverse neurodevelopmental outcome, has recently been shown not to be inevitable. There is a wide discussion regarding feeding practices of very preterm neonates, specifically regarding feeding volumes and nutrients supply to avoid postnatal growth failure. Current guidelines recommend an energy intake of 115­140 kcal /kg per d with a considerably higher upper limit of 160 kcal/kg per d. The feeding volume corresponding to this energy supply is not higher than 200 ml/kg in most cases. From the other side, randomised and observational studies used higher feeding volumes, and these were associated with better weight gain and growth, while no complications were noted. Taking into account the above, nutritional practices should be individualised in each very and extremely preterm infant trying to reduce postnatal growth failure, pointing out that available data are inconclusive regarding the effect of high-volume feeds on growth. Large clinical trials are necessary to conclude in the best feeding practices of very preterm neonates.

Gaucher Disease Type 2 Manifested as Hemophagocytic Lymphohistiocytosis in a Neonate in the COVID-19 Era.

BACKGROUND: A term neonate presented with persistent severe thrombocytopenia, elevated liver enzymes, conjugated hyperbilirubinemia, hepatosplenomegaly, and mild hypotonia. OBSERVATIONS: A thorough workup for infections, congenital thrombocytopenias, and neonatal malignancies was negative. Because of increased anti-SARS-CoV-2 IgG antibodies after maternal COVID-19, multisystem inflammatory syndrome of neonates was considered and intravenous immunoglobulin was administered. The clinical condition of the neonate deteriorated and due to laboratory evidence of hyperinflammation, hemophagocytic lymphohistiocytosis was suspected, and treatment with etoposide and dexamethasone was initiated with temporary stabilization. Gaucher disease type 2 was eventually diagnosed. CONCLUSION: Gaucher disease can rarely present in neonates as hemophagocytic lymphohistiocytosis.

The trends for the "trend toward significance" in the pediatric literature.

Purpose This study is to examine whether the term "trend toward statistical significance" is used to describe statistically nonsignificant results in biomedical literature. We examined articles published in five high-impact pediatric journals, including The Lancet Child & Adolescent Health, The Journal of Pediatrics, Early Human Development, Frontiers in Pediatrics, and BMC Pediatrics to identify manuscripts where a "trend" was used to describe a statistically nonsignificant result, from January 2020 to December 2021, and, furthermore, for The Journal of Pediatrics, Early Human Development, and BMC Pediatrics from January 2010 to December 2011. We detected that a "trend toward significance" was used to describe a statistically nonsignificant result at least once in 146 articles (2.7%) during the period between 2020 and 2021 and in 97 articles (4.0%) during the period between 2010 and 2011. We found no significant difference in the proportion of published articles with inappropriate use of "trend" across journals belonging to the first quartile of impact compared to the second quartile or across journals publishing under the subscription model or open access policy compared to journals publishing solely under the open access policy, in any period. The overall proportion of the inappropriate use of "trend" declined significantly between 2010 and 2011 to 2020 and 2021 (p = 0.002, RR 0.66 95% CI 0.51-0.86). CONCLUSION: "Trend" statements were sporadically used to describe statistically nonsignificant results across pediatric literature. The inappropriate use of "trend" to describe almost significant differences could be misleading, and "trend" should be reserved only when a specific statistical test for trend has been performed, or in relation to appropriate scientific definitions. WHAT IS KNOWN: •Previously, researchers have reported inappropriate use of "trend" in articles across anaesthesia or major oncology journals. •In many cases, hypothesized results that are close but not lower than the statistical significance threshold are emphasized as "almost" significant. WHAT IS NEW: •"Trend" statements were sporadically used to describe statistically nonsignificant results across pediatric literature. •Inappropriate use of  "trend" was similar in journals with a subscription model compared to those having an open access policy and decreased within a 10-year period.

Is small for gestational age status independently correlated with body composition during childhood?

This study aims to examine if small for gestation age (SGA) status is correlated with alterations in body composition at prepuberty, independently of other factors, comparing SGA-born children with appropriate for gestational age (AGA)-born children. We examined anthropometrics, waist circumference, body mass index (BMI), six skinfold thickness, and body composition using the method of bioelectrical impedance in 636 children aged 7 to 10 years. We also considered age, gender, birth mode, mother's age, prepregnancy weight, weight gain during pregnancy, social status, parental BMI, type of feeding, and daily exercise. We examined 636 children at a mean age of 9 years: 106 SGA-born and 530 AGA-born children. SGA as compared to AGA-born children had a lower BMI z-score (0.26 ± 0.89 kg/cm2 vs 0.46 ± 0.84 kg/cm2, p < 0.050) and a lower lean mass, although that was not statistically significant (24.0 ± 6.6 kg vs 25.6 ± 6.4 kg, p < 0.100). SGA-born children presented no difference in waist circumference or fat mass in comparison to children born AGA. Logistic regression analysis revealed a strong independent negative association between SGA status and BMI (beta = - 2.33, OR = 0.70 p = 0.019) and SGA status and lean mass (beta = - 2.43, OR = 0.95 p = 0.010).  Conclusion: Our findings suggest that SGA-born children had a lower BMI as compared to AGA-born subjects, whereas SGA status was negatively associated with BMI and lean mass. What is Known: • Deviant birth weight for gestation has been associated with an increased risk of childhood adiposity. • Evidence remains scarce on whether small for gestational age status affects body composition and obesity later in childhood. What is New: • Among school-aged children, small for gestational age subjects had a lower body mass index as compared to appropriate for gestational age counterparts, whereas small for gestational age status was negatively associated with body mass index and lean mass. • A meticulous observation is needed during childhood in children born with deviant birth weight.

A systematic review and meta-analysis of the role of Doppler ultrasonography of the superior mesenteric artery in detecting neonates at risk of necrotizing enterocolitis.

The role of postnatal Doppler measurements of the superior mesenteric artery (SMA) in detecting neonates at risk of necrotizing enterocolitis (NEC) remains uncertain; therefore, we systematically reviewed and meta-analyzed the existing evidence regarding the usefulness of SMA Doppler measurements in detecting neonates at risk for NEC. We used the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, and we included studies which reported the following Doppler ultrasonography indices: peak systolic velocity, end-diastolic velocity, time average mean velocity, differential velocity, pulsatility index (PI) and resistive index. Eight studies were eligible for inclusion in the meta-analysis. Evidence suggested that, during the first postnatal day, neonates who developed NEC had a significantly higher peak systolic velocity (mean difference of 2.65 cm/s (95% confidence interval [CI] 1.23, 4.06, overall effect Z=3.66, P<0.001)), higher PI (mean difference of 1.52 (95% CI 0.00, 3.04, Z=1.96, P=0.05)) and higher resistive index (mean difference of 1.09 (95% CI 0.59, 1.60, Z=4.24, P<0.001)), compared to neonates who did not develop NEC. However, our findings do not support a strong association between the Doppler ultrasound indices and development of NEC at the time of disease onset. This meta-analysis suggests that first postnatal day SMA Doppler parameters, namely peak systolic velocity, PI and resistive index, are higher in neonates who develop NEC. On the other hand, the aforementioned indices are of uncertain significance once the diagnosis of NEC has been established.

Wolfram Syndrome 1: A Pediatrician's and Pediatric Endocrinologist's Perspective.

Wolfram syndrome 1 (WS1) is a rare autosomal recessive neurodegenerative disease caused by mutations in WFS1 and WFS2 genes that produce wolframin, a protein involved in endoplasmic reticulum calcium homeostasis and cellular apoptosis. Its main clinical features are diabetes insipidus (DI), early-onset non-autoimmune insulin-dependent diabetes mellitus (DM), gradual loss of vision due to optic atrophy (OA) and deafness (D), hence the acronym DIDMOAD. Several other features from different systems have been reported such as urinary tract, neurological, and psychiatric abnormalities. In addition, endocrine disorders that can appear during childhood and adolescence include primary gonadal atrophy and hypergonadotropic hypogonadism in males and menstrual cycle abnormalities in females. Further, anterior pituitary dysfunction with deficient GH and/or ACTH production have been described. Despite the lack of specific treatment for the disease and its poor life expectancy, early diagnosis and supportive care is important for timely identifying and adequately managing its progressive symptoms. The current narrative review focuses on the pathophysiology and the clinical features of the disease, with a special emphasis on its endocrine abnormalities that appear during childhood and adolescence. Further, therapeutic interventions that have been proven to be effective in the management of WS1 endocrine complications are discussed.

Structural and functional brain connectivity in moderate-late preterm infants with low-grade intraventricular hemorrhage.

PURPOSE: Brain functional connectivity (FC) changes and microstructural abnormalities are reported in infants born moderate and late preterm (MLPT). We evaluated the effect of low-grade (grades I, II) intraventricular hemorrhage (IVH) in MLPT babies on brain structural connectivity (SC) and FC. METHODS: Babies born MLPT between January 2014 and May 2017 underwent brain ultrasound (US) at 72 h and 7 days after birth, and MRI at around term equivalent. The MRI protocol comprised T1- and T2-weighted sequences, diffusion tensor imaging (DTI), and resting-state functional MRI (fMRI). SC and FC were assessed using graph analysis. RESULTS: Of 350 MLPT neonates, 15 showed low-grade IVH on US at 72 h, for which brain MRI was available in 10. These 10 infants, with mean gestational age (GA) 34.0 ± 0.8 weeks, comprised the study group, and 10 MLPT infants of mean GA 33.9 ± 1.1 weeks, with no abnormalities on brain US and MRI, were control subjects. All study subjects presented modularity, small world topology, and rich club organization for both SC and FC. The patients with low-grade IVH had lower FC rich club coefficient and lower SC betweenness centrality in the left frontoparietal operculum, and lower SC rich club coefficient in the right superior orbitofrontal cortex than the control subjects. CONCLUSIONS: Topological and functional properties of mature brain connectivity are present in MLPT infants. IVH in these infants was associated with structural and functional abnormalities in the left frontoparietal operculum and right orbitofrontal cortex, regions related to language and cognition.

A systematic review indicates an association between birth weight and body fat in childhood.

AIM: To summarise the existing evidence regarding the body fat of small or large for gestation subjects, evaluated from birth up to 18 years of age. METHODS: The PRISMA guidelines were adopted for the current systematic review, including studies having evaluated body fat with bioelectrical impedance analysis, air displacement plethysmography, dual-energy X-ray absorptiometry or magnetic resonance imaging. RESULTS: A total of 31 studies was included. The balance of evidence suggests that small for gestation infants have decreased fat mass at birth; postnatally they experience increased adiposity. In the long term, however, the evidence is inconclusive, since some studies suggest that foetal-restricted children with increased catch-up growth are at increased risk of fat accumulation, whereas other studies suggest a neutral or even negative association. Large for gestation infants have increased fat mass at birth, but in the long term, they have a lower body fat ratio, especially when they develop a catch-down growth. CONCLUSION: Some studies suggested that foetal-restricted children with increased catch-up growth are at increased risk of later adiposity, while other studies suggested a neutral or negative association. Given that the evidence is inconclusive, further studies are warranted. Large for gestation subjects have lower body fat when they develop catch-down growth.

A Novel εγδß-Thalassemia Deletion Associated with Severe Anemia at Birth and a ß-Thalassemia Intermedia Phenotype Later in Life in Three Generations of a Greek Family.

We describe a novel deletion causing heterozygous εγδß-thalassemia (εγδß-thal) across three generations of a Greek family. The Greek deletion is about 72 kb in length, spanning from the hypersensitive site 4 (HS4) in the locus control region (LCR) to the 3' end of the ß-globin gene, thus encompassing the entire ß-globin gene cluster. The deletion caused severe but transient neonatal anemia and a non transfusion-dependent chronic hemolytic anemia state later in life, resembling mild ß-thalassemia intermedia (ß-TI) rather than ß-thalassemia (ß-thal) trait, as had been previously reported. Apart from the presentation of clinical and laboratory characteristics, the challenges involving clinical management are also discussed.

Voiding urosonography and voiding cystourethrography in primary vesicoureteral reflux associated with mild prenatal hydronephrosis: a comparative study.

BACKGROUND: Contrast-enhanced harmonic voiding urosonography has been introduced as a sensitive, radiation-free imaging method for the diagnosis of vesicoureteric reflux. OBJECTIVE: To evaluate the occurrence/severity of vesicoureteric reflux in infants with mild prenatal hydronephrosis comparing voiding cystourethrography and voiding urosonography. MATERIALS AND METHODS: Sixty infants with prenatal hydronephrosis were studied (anteriοposterior pelvic diameter 5-9 mm on ultrasound [US] at gestational weeks 21-30). Postnatal US was performed within the first month of life, as well as voiding cystourethrography and contrast-enhanced voiding urosonography at 1.5-2.5 months at the same session. RESULTS: Vesicoureteric reflux was diagnosed on at least one modality in 19/60 (32%) infants, and more often on contrast-enhanced voiding urosonography (18/60, 30%) than on voiding cystourethrography (8/60, 13%), P=0.046. Among girls, reflux was more often seen on contrast-enhanced voiding urosonography (6/16, 38%) than on voiding cystourethrography (1/16, 6%), P=0.03. Vesicoureteric reflux missed by voiding cystourethrography was more severe (Grades I, II and III in one, nine and four kidney-ureter-units, respectively), compared with a single case missed by contrast-enhanced voiding urosonography (Grade I in one kidney-ureter-unit). CONCLUSION: In the absence of a reference standard, our results imply that voiding cystourethrography might underdiagnose reflux, and/or contrast-enhanced voiding urosonography may overdiagnose reflux.

Elevated 1-hour post-load plasma glucose identifies obese youth with abnormal glucose metabolism and an unfavourable inflammatory profile.

CONTEXT: Adults with plasma glucose levels at one hour (1h-GL) ≥8.6 mmol/L during an oral glucose tolerance test (OGTT) are at increased risk for type 2 diabetes mellitus and present an unfavourable cardiometabolic and inflammatory profile, but relevant data on children are scarce. OBJECTIVE: To investigate if elevated 1h-GL during OGTT in obese children and adolescents is associated with insulin resistance and specific pro-inflammatory biomarkers. RESEARCH DESIGN AND METHODS: The study group comprised 88 obese children who attended the Outpatient Pediatric Clinic of our Hospital between January and December 2016. Children were divided into two groups according to 1h-GL during an OGTT: group 1 (n = 57) consisted of those with 1h-GL <8.6 mmol/L and group 2 (n = 31) of those with 1h-GL ≥8.6 mmol/L. Arterial blood pressure, body mass index (BMI) and waist circumference (WC) z-scores were measured in all participants. Specific insulin resistance (IR) indices, that is HOMA-IR, Matsuda index and Cederholm insulin sensitivity index (ISI) were calculated. Further, pro-inflammatory biomarkers that have been correlated with obesity complications, namely adiponectin, leptin, visfatin and interleukin (IL)-6 together with lipid levels were measured in all participants. Logistic regression analysis was used. RESULTS: Children in group 2 had higher insulin (15.5 ± 6.4 vs 10.9 ± 4.8 µU/mL), HOMA-IR (3.41 ± 1.4 vs 2.34 ± 1.05) and lower Matsuda index [4.7 (3.1) vs 18.4 (17) median plus IQR] and Cederholm ISI (38 ± 6 vs 56 ± 11), than children in group 1 (all P < 0.001). They also had higher visfatin (15.4 ± 5.2 vs 10.1 ± 7 ng/mL), and IL-6 [12.5 (6.7) vs 4.8 (4.4) pg/mL], and lower adiponectin (5.9 ± 3.4 vs 11.8 ± 4.7 µg/mL) than children in group 1 (all P < 0.001). Logistic regression showed that these differences between the two groups were independent of age, sex, Tanner stage, BMI and WC z-scores. CONCLUSIONS: In obese children, 1h-GL ≥8.6 mmol/L during an OGTT is correlated with worsened IR, and an unfavourable metabolic and inflammatory profile. Thus, 1h-GL could be used as an additional marker to identify obese children and adolescents at increased risk of developing obesity complications.

Does idiopathic hypercalciuria affect bone metabolism during childhood? A prospective case-control study.

BACKGROUND: A limited number of studies have evaluated biochemical bone metabolism markers in children with idiopathic hypercalciuria, which in adults has been linked with osteopenia. Our aim was to investigate in children with idiopathic hypercalciuria biochemical markers of bone formation and resorption and the osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kB ligand (sRANKL) system which is involved in the osteoclastogenesis process. METHODS: A prospective study was conducted on 50 children with idiopathic hypercalciuria and 50 healthy age-, sex-, and Tanner stage-matched control subjects. Following the diagnosis, patients were requested to follow a 3-month dietary recommendation for idiopathic hypercalciuria. In patients, at diagnosis and at 3 months of follow-up, and in controls, bone-related hormones and serum/urine biochemical parameters were studied. The bone formation markers (total ALP and osteocalcin) and the bone resorption markers (ß-Crosslaps) and the OPG and sRANKL levels were determined. RESULTS: No differences were found in the bone formation markers or OPG and sRANKL between the children with idiopathic hypercalciuria and controls. The ß-Crosslaps and the ß-Crosslaps/osteocalcin ratio were higher in the patients at diagnosis than in controls (p = 0.019 and p = 0.029, respectively), with a trend to decrease after the 3-month dietary intervention. The initially increased 24-h urinary Ca in the patients decreased after the 3-month dietary intervention (p = 0.002). CONCLUSIONS: Children with idiopathic hypercalciuria had biochemical markers compatible with normal bone formation but increased bone resorption. After a 3-month dietary intervention, the trend observed towards decrease in the serum ß-Crosslaps may reflect a beneficial response.

Growth and function in childhood of a normal solitary kidney from birth or from early infancy.

BACKGROUND: Children with a solitary kidney (SK) have an increased long-term risk of hypertension, albuminuria and glomerulosclerosis. In this study, we assessed the early signs of impaired glomerular filtration in children with a SK from birth or from early infancy. METHODS: Renal growth and function at ages 4-15.5 years were studied in 38 children with SK and 40 matched control subjects in terms of accelerated growth. RESULTS: The systolic/diastolic blood pressure Z-scores (p = 0.01/<0.05) and the resistance index (RI) of the arcuate arteries (p = 0.05) were higher in the children with SK. Creatinine clearance and 24-h protein and albumin urinary excretion showed no difference. All but seven children with SK had 99mTc diethylene-triamine pentaacetic acid glomerular filtration rate values of >80 ml/min/1.73 m(2). An independent positive correlation was found between length of the follow-up time and 24-h albumin urinary excretion (ß = 0.54, p < 0.01). Accelerated postnatal growth was positively related with kidney volume (ß = 0.35, p < 0.05). CONCLUSIONS: Among our patient cohort, renal function was well preserved at ages 4-15.5 years in children who were born with a SK. However, both their higher blood pressure and RI and the correlation of 24-h albumin urinary excretion with length of follow-up time underline the need for monitoring to detect early signs of glomerular hyperfiltration and, if necessary, implement timely intervention. SK hypertrophy was found to be correlated with postnatal growth.

Recent Challenges in Diagnosis and Treatment of Invasive Candidiasis in Neonates.

Invasive Candida infections represent a significant cause of morbidity and mortality in the neonatal intensive care unit (NICU), particularly among preterm and low birth weight neonates. The nonspecific clinical presentation of invasive candidiasis, resembling that of bacterial sepsis with multiorgan involvement, makes the diagnosis challenging. Given the atypical clinical presentation and the potential detrimental effects of delayed treatment, empirical treatment is often initiated in cases with high clinical suspicion. This underscores the need to develop alternative laboratory methods other than cultures, which are known to have low sensitivity and a prolonged detection time, to optimize therapeutic strategies. Serum biomarkers, including mannan antigen/anti-mannan antibody and 1,3-ß-D-glucan (BDG), both components of the yeast cell wall, a nano-diagnostic method utilizing T2 magnetic resonance, and Candida DNA detection by PCR-based techniques have been investigated as adjuncts to body fluid cultures and have shown promising results in improving diagnostic efficacy and shortening detection time in neonatal populations. This review aims to provide an overview of the diagnostic tools and the current management strategies for invasive candidiasis in neonates. Timely and accurate diagnosis followed by targeted antifungal treatment can significantly improve the survival and outcome of neonates affected by Candida species.