Role of fibroblast growth factor-23 as an early marker of metabolic bone disease of prematurity.

PURPOSE: Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients. METHODS: A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05. RESULTS: In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation. CONCLUSIONS: MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.

Assessment of inflammatory biomarkers to identify surgical/death necrotizing enterocolitis in preterm infants without pneumoperitoneum.

BACKGROUND: Necrotizing enterocolitis (NEC) is a life-threatening disease that affects premature infants. However, the role of inflammatory biomarkers in identifying surgical/death NEC without pneumoperitoneum remains elusive. PURPOSE: We aimed to verify the value of platelet-to-lymphocyte ratio (PLR) and the combination of white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil lymphocyte ratio (NLR), PLR, C reactive protein (CRP) and procalcitonin (PCT) in predicting the severity of NEC, and to construct a model to differ surgically NEC from non-surgically NEC. METHODS: A retrospective analysis was performed on 191 premature infants with NEC. Based on the inclusion and exclusion criteria, 90 infants with Stage II and IIIA NEC were enrolled in this study, including surgical/death NEC (n = 38) and medical NEC (n = 52). The values of inflammatory biomarkers were collected within 24 h of onset. RESULTS: The univariate analysis revealed that the values of WBC (p = 0.040), ANC (p = 0.048), PLR (p = 0.009), CRP (p = 0.016) and PCT (p < 0.01) in surgical/death NEC cohort were significantly higher than medical NEC cohort. Binary multivariate logistic regression analysis indicates that ANC, PLR, CRP, and PCT are capable of distinguishing infants with surgical/death NEC, and the AUC of the regression equation was 0.79 (95% CI 0.64-0.89; sensitivity 0.63; specificity 0.88), suggesting the equation has a good discrimination. IMPLICATIONS FOR PRACTICE AND RESEARCH: Elevated PLR is associated with severe inflammation in surgical/death NEC patients. The prediction modelling of combination of ANC, PLR, CRP and PCT can differentiate surgical/death NEC from infants with medical NEC, which may improve risk awareness and facilitate effective communication between nurses and clinicians. However, multicentre research is needed to verify these findings for better clinical management of NEC.

[Extremely preterm infants with severe intraventricular hemorrhage: neurological evolution and long term and educational status]. / Niños muy prematuros con hemorragia intraventricular extensa: evolución neurológica y escolaridad a largo plazo.

Extensive intraventricular hemorrhage (IVH) in very preterm newborns (VPNB) is associated with mortality and severe long-term neurological sequelae. OBJECTIVES: To know the most frequent neurological pathologies associated with extensive IVH, to determine the functional outcomes of mobility in the motor area and intellectual capacity in the cognitive area, to analyze the association between both areas and to know the schooling achieved. PATIENTS AND METHOD: Descriptive and longitudinal study in VPNB with extensive IVH born between 2001 and 2014. They underwent protocolized neurological follow-up until school age. The functional outcomes in mobility and intellectual capacity were categorized into 4 levels: level 1 corresponds to good functionality and autonomy; level 2, functionality that allows independence, with support in some tasks; level 3 requires constant external support; and level 4 where there is total dependence. The association was analyzed using Chi-square and Cramer's V coefficient. RESULTS: 74 children completed the follow-up; the most frequent associated neurological pathologies were neurodevelopmental disorders, hypertensive hydrocephalus, and epilepsy. Independent mobility (normal or with limitations) reached 74.4% while 24.3% used wheelchairs. 51.3% was categorized as normal to borderline intellectual range, 12.2% as mild intellectual disability (ID), 17.6% as moderate ID, and 19.9% as severe to profound ID. There was a strong statistical association between functional levels of mobility and intellectual capacity (p < 0.000 and V = 0.62). Schooling was proportional to intellectual capacity: 56.8% attended regular schools, 27.0% attended special schools, and 16.2% had no schooling. CONCLUSIONS: 2/3 VPNB with extensive IVH showed positive functional outcomes, from normal to mild limitations that allow an almost autonomous life; in 1/3 the outcomes were unfavorable in mobility and cognitive performance, and there was a strong statistical correlation between both areas studied. Schooling was consistent with the intellectual level.

European survey showed wide variations in diagnostic procedures and management strategies for metabolic bone disease of prematurity in 22 countries.

AIM: The aim of this study was to evaluate the clinical relevance, diagnostic procedures and treatment strategies for metabolic bone disease in preterm infants across Europe. METHODS: An e-survey was distributed by email to 545 neonatal units in 38 European countries between July and October 2021. The protocol was based on the Checklist for Reporting Results of Internet E-Surveys. RESULTS: In total, 76 neonatal units (14%) from 22 European countries (58%) completed the e-survey. In the 12 months prior to the survey, 29% of 76 units reported at least one symptomatic case of fracture associated with metabolic bone disease of prematurity, and 18% of 76 units reported at least one case of craniofacial deformity. Most centres followed local guidelines for diagnosis (77% of 73 units) and treatment (63% of 72 units). Alkaline phosphatase was the blood marker most used for treatment indication (81% of 72 units), and phosphate supplementation was the treatment most used (82% of 71 units). CONCLUSION: Metabolic bone disease of prematurity remains clinically relevant. Wide variations in diagnostic procedures and management strategies were observed in European neonatal units. Evidence-based consensus guidelines appear urgently needed to reduce the number of symptomatic cases.

Risk factors for acute kidney injury in very-low birth weight newborns: a systematic review with meta-analysis.

This study aims to analyze the main risk factors for acute kidney injury in the subgroup of very-low birth weight newborns, using the diagnosing criteria of the Kidney Disease Improving Global Outcomes (KDIGO) or the Acute Kidney Injury Network (AKIN). A systematic review of the literature was performed on the EMBASE® and PubMed® platforms. Studies that evaluated the risk factors for developing AKI in VLBW newborns were included. For the meta-analysis, we only included the risk factors that were associated with AKI in the univariate analysis of at least two studies. After an initial screening, abstract readings, and full-text readings, 10 articles were included in the systematic review and 9 in the meta-analysis. The incidence of AKI varied from 11.6 to 55.8%. All the studies have performed multivariate analysis, and the risk factors that appeared most were PDA and hemodynamic instability (use of inotropes or hypotension), sepsis, and invasive mechanical ventilation. After the meta-analysis, only cesarian delivery did not show an increased risk of AKI, all the other variables remained as important risk factors. Moreover, in our meta-analysis, we found a pooled increased risk of death in newborns with AKI almost 7 times.  Conclusion: AKI in VLBW has several risk factors and must be seen as a multifactorial disease. The most common risk factors were PDA, hemodynamic instability, sepsis, and invasive mechanical ventilation. What is known: • Acute kidney injury is associated with worst outcomes in all ages. It´s prevention can help diminish mortality. What is new: • A synthesis of the main risk factors associated with AKI in very low birth weight newborns.

Analysis of similarities and differences between transient symptomatic zinc deficiency and acrodermatitis enteropathica in children: a case report of a Chinese Yi-ethnic infant.

BACKGROUND: Transient symptomatic zinc deficiency (TSZD), an acquired type of zinc deficiency, is a rare, but probably underrecognized disease, extremely in breastfed premature with low birthweight infants. Its clinical manefestations are similar to Acrodermatitis enteropathica (AE), which is a genetic zinc absorption disorder caused by SLC39A4 gene mutations. This gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family. The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. TSZD is often misdiagnosed as AE because of their extremely similar manefestations, characterized by a typical rash. Therefore, the differention between them is still a clinical challenging. CASE PRESENTATION: Here, we present a case of TSZD in a 4 month and 23 days female Chinese Yi-ethnic premature with AE-like skin lesions, mainly presenting periorificial, perianal and perineal crusted, eroded, erythemato-squamous eruption. Laboratory examination showed the patient's blood zinc level was significantly decreased. Further sequencing of the SLC39A4 gene showed no mutation in the infant and her parents. Skin lesions significantly improved after 6 days of initial zinc supplementation (3 mg/kg/d), and maintenance treatment with 1 mg/kg/day of zinc was discontinued after 8 months without recurrence. CONCLUSIONS: The clinical manifestations of TSZD and AE are extremely similar, leading to a high rate of clinical misdiagnosis. While genetic analysis of the SLC39A4 gene is a reliable method for differentiating TSZD from AE. It is recommended that SLC39A4 gene test should be performed as far as possible in children with AE-like rash.

New and old lessons from a devastating case of neonatal E coli meningitis.

BACKGROUND: Neonatal Escherichia coli (E coli) meningitis results in significant morbidity and mortality. We present a case of a premature infant with extensive central nervous system (CNS) injury from recurrent E coli infection and the non-traditional methods necessary to identify and clear the infection. CASE PRESENTATION: The infant was transferred to our institution's pediatric intensive care unit (PICU) after recurrence of E coli CNS infection requiring neurosurgical intervention. He had been treated for early onset sepsis (EOS) with ampicillin and gentamicin for 10 days followed by rapid development of ampicillin-resistant E coli septic shock and meningitis after discontinuation of antibiotics. Sterility of the CNS was not confirmed at the end of 21 days of cefepime therapy and was subsequently followed by recurrent ampicillin-resistant E coli septic shock and CNS infection. Despite 6 weeks of appropriate therapy with sterility of CSF by traditional methods, he suffered from intractable seizures with worsening hydrocephalus. Transferred to our institution, he underwent endoscopic 3rd ventriculostomy with cyst fenestration revealing purulent fluid and significant pleocytosis. An additional 3 weeks of systemic and intraventricular antibiotics with cefepime and tobramycin were given but a significant CNS neutrophil-predominant pleocytosis persisted (average of ∼ 21,000 cells/mm3). Repeated gram stains, cultures, polymerase chain reaction (PCR) testing, and metagenomic next generation sequencing (NGS) testing of CSF were negative for pathogens but acridine orange stain (AO) revealed numerous intact rod-shaped bacteria. After the addition of ciprofloxacin, sterility and resolution of CSF pleocytosis was finally achieved. CONCLUSION: Neonatal E coli meningitis is a well-known entity but unlike other bacterial infections, it has not proven amenable to shorter, more narrow-spectrum antibiotic courses or limiting invasive procedures such as lumbar punctures. Further, microbiologic techniques to determine CSF sterility suffer from poorly understood limitations leading to premature discontinuation of antibiotics risking further neurologic damage in vulnerable hosts.

Necrotizing enterocolitis in premature infants at different gestation ages.

OBJECTIVE: Aim: To compare X-ray signs in different gestational and body weight groups of patients with NEC. PATIENTS AND METHODS: Materials and Methods: We conducted a retrospective study, enrolling 52 preterm newborns with symptoms of NEC regardless of onset time, who underwent treatment at Neonatal Intensive Care Units in Municipal Non-commercial enterprise "City Children Hospital №2", Odesa. The patients were split into 3 clinical groups: very preterm newborns (VPN), moderately preterm newborns (MPN), and moderately preterm newborns with intrauterine growth restriction (MPN+IUGR). RESULTS: Results: In the VPN group NEC was diagnosed at stage II (58,82±12,30) % and III (41,18±12,30) % by Bell MJ, р>0,05. In the group MPN+IUGR, NEC stage II (33,33±14,21) % and stage III (66,66 ±14,21) %, р>0,05, were equally observed. In the MPN group, NEC was diagnosed at stage I (41,67±10,28) % and II (58,33±10,28) %, р>0,05, without prevalence of any. Also only localized forms were observed. In VPN, we observed localized forms in most cases, while diffuse forms were diagnosed in (11,76±8,05) % cases, р<0,05. In the MPN+IUGR group, we found diffuse form of the NEC in half of the cases - (50,00±15,08) %. In the VPN and MPN+IUGR groups, NEC developed at 13,23±0,39 and 14,33±1,19 days, respectively. However, in MPN without IUGR, NEC developed at 17,75±0,55 days, significantly later than in the MPN+IUGR group, р<0,05. CONCLUSION: Conclusions: We have described distinct features of NEC in MPN with IUGR. Compared to MPN without IUGR, NEC had more severe course and earlier manifestation in such neonates.

Receptor-interacting protein kinase-3 (RIPK3): a new biomarker for necrotising enterocolitis in preterm infants.

OBJECTIVE: This study aimed to evaluate the role of receptor-interacting protein kinase-3 (RIPK3) in the diagnosis, estimation of disease severity, and prognosis of premature infants with necrotising enterocolitis (NEC). METHODS: RIPK3, lactic acid (LA), and C-reactive protein (CRP) levels were measured in the peripheral blood of 108 premature infants between 2019 and 2023, including 24 with stage II NEC, 18 with stage III NEC and 66 controls. Diagnostic values of the indicators for NEC were evaluated via receiver operating characteristic (ROC) curve analysis. RESULTS: Plasma RIPK3 and LA levels upon NEC suspicion in neonates with stage III NEC were 32.37 ± 16.20 ng/mL. The ROC curve for the combination of RIPK3, LA, CRP for NEC diagnosis were 0.925. The time to full enteral feeding (FEFt) after recovery from NEC was different between two expression groups of plasma RIPK3 (RIPK3 < 20.06 ng/mL and RIPK3 ≥ 20.06 ng/mL). CONCLUSION: Plasma RIPK3 can be used as a promising marker for the diagnosis and estimation of disease severity of premature infants with NEC and for the guidance on proper feeding strategies after recovery from NEC.

Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Infants Born Extremely Preterm.

OBJECTIVE: The objective of this study was to examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks of gestational age) on vs off invasive mechanical ventilation. STUDY DESIGN: This is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in 5 level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean gestational age: 26.4 weeks, SD 1.71). Monitoring data were available and analyzed for 719 infants (47 512 patient-days); of whom, 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72 hours after birth and ≥5-day antibiotics). RESULTS: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer events with oxygen saturation <80% (IH80) and more bradycardia events before sepsis. IH events were associated with higher sepsis risk but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model including postmenstrual age, cardiorespiratory variables (apnea, periodic breathing, IH80, and bradycardia), and ventilator status predicted sepsis with an area under the receiver operator characteristic curve of 0.783. CONCLUSION: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.

Pulse oximetry signal loss during hypoxic episodes in preterm infants receiving automated oxygen control.

The aim of this study was to analyze signal loss (SL) resulting from low signal quality of pulse oximetry-derived hemoglobin oxygen saturation (SpO2) measurements during prolonged hypoxemic episodes (pHE) in very preterm infants receiving automatic oxygen control (AOC). We did a post hoc analysis of a randomized crossover study of AOC, programmed to set FiO2 to "back-up FiO2" during SL. In 24 preterm infants (median (interquartile range)) gestational age 25.3 (24.6 to 25.6) weeks, recording time 12.7 h (12.2 to 13.6 h) per infant, we identified 76 pHEs (median duration 119 s (86 to 180 s)). In 50 (66%) pHEs, SL occurred for a median duration of 51 s (33 to 85 s) and at a median frequency of 2 (1 to 2) SL-periods per pHE. SpO2 before and after SL was similar (82% (76 to 88%) vs 82% (76 to 87%), p = 0.3)).  Conclusion: SL is common during pHE and must hence be considered in AOC-algorithm designs. Administering a "backup FiO2" (which reflects FiO2-requirements during normoxemia) during SL may prolong pHE with SL.  Trial registration: The study was registered at www. CLINICALTRIALS: gov under the registration no. NCT03785899. WHAT IS KNOWN: • Previous studies examined SpO2 signal loss (SL) during routine manual oxygen control being rare, but pronounced in lower SpO2 states. • Oxygen titration during SL is unlikely to be beneficial as SpO2 may recover to a normoxic range. WHAT IS NEW: • Periods of low signal quality of SpO2 are common during pHEs and while supported with automated oxygen control (SPOC), FiO2 is set to a back-up value reflecting FiO2 requirements during normoxemia in response to SL, although SpO2 remained below target until signal recovery. • FiO2 overshoots following pHEs were rare during AOC and occurred with a delayed onset; therefore, increased FiO2 during SL does not necessarily lead to overshoots.

A novel useful marker in the early discrimination of transient hyperthyrotropinemia/hypothyroxinemia and congenital hypothyroidism in preterm infants: thyroid-stimulating hormone/free thyroxine ratio.

OBJECTIVES: Transient hyperthyrotropinemia/transient hypothyroxinaemia and congenital hypothyroidism (CH) have completely different treatment and clinical outcomes. However, a powerful, highly sensitive and cost-effective marker for the differentiation of these clinical entities in the early postnatal period is not available. Therefore, we aimed to test the potential, early predictive, diagnostic power of the thyroid-stimulating hormone (TSH)/free thyroxine (fT4) ratio for differentiation of the two clinical entities in the early period of life. METHODS: TSH and fT4 levels were recorded on the postnatal day 7 of premature infants<32 weeks of gestational age. TSH/fT4 ratio was calculated. The significance degree of TSH/fT4 ratio was analyzed for the differentiation of transient hyperthyrotropinemia or transient hypothyroxinaemia and CH. RESULTS: The study included 1,204 preterm infants<32 weeks of gestational age. Of the 1,204 infants, 978 (81.2 %) had normal thyroid function. Eighty-eight infants (7.3 %) were diagnosed with CH and 138 (11.5 %) with transient hyperthyrotropinemia or transient hypothyroxinemia. Initial TSH/fT4 ratio>4.8 was found to be an early diagnostic warning sign with high power in favor of transient hyperthyrotropinemia or transient hypothyroxinemia (AUC value: 0.947) and TSH/fT4 ratio>12.5 (AUC value: 0.999) was found to be an early diagnostic warning sign with high power in favor of CH (p=0.0001). CONCLUSIONS: We found for the first time that the TSH/fT4 ratio can be used for the early differentiation of transient hyperthyrotropinemia/transient hypothyroxinaemia and CH in preterm infants without additional cost and with high power.

Urinary tract infections in very premature neonates: the definition dilemma.

BACKGROUND AND OBJECTIVES: Data on urinary tract infections (UTIs) in very preterm neonates (VPTNs) are scarce. We aimed to (i) describe the characteristics of UTIs in VPTNs and (ii) compare the diagnostic practices of neonatal clinicians to established pediatric guidelines. METHODS: All VPTNs (<29 weeks GA) with a suspected UTI at the CHU Sainte-Justine neonatal intensive care unit from January 1, 2014, and December 31, 2019, were included and divided into two definition categories: Possible UTI, and Definite UTI. RESULTS: Most episodes were Possible UTI (87%). Symptoms of UTIs and pathogens varied based on the definition category. A positive urinalysis was obtained in 25%. Possible UTI episodes grew 2 organisms in 62% of cases and <50,000 CFU/mL in 62% of cases. CONCLUSION: Characteristics of UTIs in VPTNs vary based on the definition category and case definitions used by clinicians differ from that of established pediatric guidelines.

Machine learning-based analysis for prediction of surgical necrotizing enterocolitis in very low birth weight infants using perinatal factors: a nationwide cohort study.

Early prediction of surgical necrotizing enterocolitis (sNEC) in preterm infants is important. However, owing to the complexity of the disease, identifying infants with NEC at a high risk for surgical intervention is difficult. We developed a machine learning (ML) algorithm to predict sNEC using perinatal factors obtained from the national cohort registry of very low birth weight (VLBW) infants. Data were collected from the medical records of 16,385 VLBW infants registered in the Korean Neonatal Network (KNN). Infants who underwent surgical intervention were identified with sNEC, and infants who received medical treatment, with medical NEC (mNEC). We used 38 variables, including maternal, prenatal, and postnatal factors that were obtained within 1 week of birth, for training. A total of 1085 patients had NEC (654 with sNEC and 431 with mNEC). VLBW infants showed a higher incidence of sNEC at a lower gestational age (GA) (p < 0.001). Our proposed ensemble model showed an area under the receiver operating characteristic curve of 0.721 for sNEC prediction.    Conclusion: Proposed ensemble model may help predict which infants with NEC are likely to develop sNEC. Through early prediction and prompt intervention, prognosis of sNEC may be improved. What is Known: • Machine learning (ML)-based techniques have been employed in NEC research for prediction, diagnosis, and prognosis, with promising outcomes. • While most studies have utilized abdominal radiographs and clinical manifestations of NEC as data sources, and have demonstrated their usefulness, they may prove weak in terms of early prediction. What is New: • We analyzed the perinatal factors of VLBW infants acquired within 7 days of birth and used ML-based analysis to identify which infants with NEC are vulnerable to clinical deterioration and at high risk for surgical intervention using nationwide cohort data.

Screening for functional gastrointestinal disorders in preterm infants up to 12 months of corrected age: a prospective cohort study.

Functional gastrointestinal disorders (FGIDs) are characterized by a variety of symptoms that are frequently age-dependent, chronic, or recurrent and are not explained by structural or biochemical abnormalities. There are studies in the literature reporting different results regarding the relationship between prematurity and FGIDs. The main objective of this study was to compare the frequency of FGIDs between preterm and term infants. The secondary objective was to evaluate whether there was any association between neonatal characteristics and development of FGIDs. A multicenter prospective cohort study that included preterm infants born before 37 weeks of gestation and healthy term infants was carried out. At 1, 2, 4, 6, 9, and 12 months of age, infants were assessed for the presence of FGIDs using the Rome IV criteria. In preterm infants, an additional follow-up visit was made at 12 months corrected age. 134 preterm and 104 term infants were enrolled in the study. Infantile colic, rumination syndrome, functional constipation, and infant dyschezia were more common in preterm infants. Incidence of other FGIDs (infant regurgitation, functional diarrhea and cyclic vomiting syndrome) were similar among preterm and term infants. Preterm infants who are exclusively breastfeed in the first 6 months of life have a lower incidence of infantile colic (18.8% vs 52.1%, p = 0.025). In terms of chronological age, FGIDs symptoms started later in preterm infants; this difference was statistically significant for infantile colic and regurgitation (median age 2 months vs 1 month, p < 0.001).   Conclusions: Preterm infants have a higher prevalence of FGIDs compared with term controls. Therefore, especially if they have gastrointestinal complaints, they should be screened for FGIDs. Possibly due to maturational differences, the time of occurrence of FGIDs may differ in preterm infants. Infantile colic incidence decreases with exclusive breastfeeding. What is Known: • The functional gastrointestinal disorders are a very common in infancy. • Data on preterm infants with FGIDs are currently very limited. What is New: • Preterm infants have a higher incidence of infantile colic, rumination syndrome, functional constipation and infant dyschezia when compared to term infants. • Preterm infants who are exclusively breastfed during the first 6 months of life experience a lower incidence of infantile colic.

Screening for Delayed Thyroid Stimulation Hormone Rise and Atypical Congenital Hypothyroidism in Infants Born Very Preterm and Infants with Very Low Birth Weight.

OBJECTIVE: To determine among infants born very preterm (VPT) or with very low birth weight (VLBW) the incidence of alterations in thyroid function and associated comorbidities; the incidence of atypical congenital hypothyroidism (CH) requiring thyroxine therapy; and reference ranges for rescreening at 1 month of age. STUDY DESIGN: A retrospective review of infants born VPT or with VLBW and admitted to UC Irvine Medical Center between January 1, 2012, and December 31, 2020. Repeat thyroid screening was obtained at 1 month of life (+10 days). Infants with thyroid-stimulating hormone (TSH) >5 µIU/mL or free thyroxine <0.8 ng/dL underwent follow-up testing and endocrinology consultation. Initial newborn screening (NBS) and repeat thyroid screening data were collected via chart review. Demographic data and short-term outcomes were abstracted from the California Perinatal Quality Care Collaborative database. RESULTS: In total, 430 patients were included; 64 of 429 patients (14.9%) had TSH >5 µIU/mL and 20 of 421 patients (4.8%) had free thyroxine <0.8 ng/dL. Logistic regression analysis identified small for gestational age (P = .044), patent ductus arteriosus (P = .013), and late-onset sepsis (P = .026) as risk factors associated with delayed TSH rise. Atypical CH requiring treatment through neonatal intensive care unit discharge was diagnosed in 6 patients (incidence of 1.4%); none were identified by NBS. The 90th percentile TSH for infants with extremely low birth weight (<1000 g) was 7.2 µIU/mL, and the 95th percentile for those with birth weight of 1000-1500 g was 6.1 µIU/mL; using these cutoff values identified all infants diagnosed with atypical CH with 100% sensitivity and 90%-95% specificity. CONCLUSIONS: Abnormal thyroid function is common in infants born preterm. Those infants, including some with atypical CH, are missed by NBS. We recommend repeat thyroid screening with TSH at 1 month of age in infants born VPT or infants with VLBW to identify CH that may require therapy.

Electrical Cardiometry during transition and short-term outcome in very preterm infants: a prospective observational study.

The purpose of this study is to evaluate the association of Electrical Cardiometry (EC)-derived cardiac output indexed to weight (CO) and its changes during the first 48 h in relation to adverse short-term outcome in very preterm infants. In this prospective observational study of preterm infants < 32 weeks gestational age (GA), the combined adverse outcome was defined as mortality or abnormal cranial ultrasound (any grade intracranial hemorrhage (ICH) or periventricular leukomalacia) within the first 2 weeks postnatally. Logistic regression models were used to investigate the association between median CO and outcome and mixed-effects models for the time trajectory of CO. In the absence of device-specific thresholds for low or high CO, no thresholds were used in our analysis. Fifty-three infants (median (IQR) GA 29.0 (25.4-30.6) weeks, birthweight 1020 (745-1505) g) were included in the analysis. Median CO was 241 (197-275) mL/kg/min for the adverse outcome and 198 (175-227) mL/kg/min for normal outcome (odds ratio (OR) (95% confidence interval (95% CI)), 1.01 (1.00 to 1.03); p = 0.028). After adjustment for GA, the difference was not significant (adjusted OR (95% CI), 1.01 (0.99 to 1.02); p = 0.373). CO trajectory did not differ by outcome (p = 0.352). A post hoc analysis revealed an association between CO time trajectory and ICH ≥ grade 2.          Conclusions: EC-derived CO estimates within 48 h postnatally were not independently associated with brain injury (any grade) or mortality in the first 14 days of life. CO time trajectory was found to be associated with ICH ≥ grade 2. What is Known: • Bioreactance-derived cardiac output indexed to bodyweight (CO) in the transitional period has been associated with adverse short-term outcome in preterm infants. What is New: • Electrical Cardiometry (EC)-derived CO measurements in very preterm infants during the transitional period are not independently associated with adverse outcome (death or ultrasound detected brain damage) within 2 weeks postnatally. • In the first 48 h EC-derived CO increases over time and is higher in extremely preterm infants compared to very preterm and differs from previously reported bioreactance-derived CO values.