Effect of ß-lactam antibiotics on the gut microbiota of term neonates.

ß-Lactam antibiotics are a class of antibiotics commonly used to treat bacterial infections. However, the effects of ß-lactam antibiotics on term neonatal intestinal flora have not been fully elucidated. Hospitalized full-term newborns receiving ß-lactam antibiotics formed the antibiotic group (n = 67), while those without antibiotic treatment comprised the non-antibiotic group (n = 47). A healthy group included healthy full-term newborns (n = 16). Stool samples were collected for 16 S rDNA sequencing to analyze gut microbiota variations. Further investigation was carried out within the ß-lactam antibiotic group, exploring the effects of antibiotic use on the newborns' gut microbiota in relation to the duration and type of antibiotic administration, delivery method, and feeding practices. The antibiotic group exhibited significant difference of microbial community composition compared to the other groups. Genera like Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas were enriched, while Escherichia-Shigella, Clostridium sensu stricto 1, Bifidobacterium, and Parabacteroides were reduced. Klebsiella negatively correlated with Escherichia-Shigella, positively with Enterobacter, while Escherichia-Shigella negatively correlated with Enterococcus and Streptococcus. Regardless of neonatal age, ß-lactam antibiotics induced an elevated abundance of Klebsiella and Enterococcus. The impact on gut microbiota varied with the duration and type of antibiotic (cefotaxime or ampicillin/sulbactam). Compared to vaginal delivery, cesarean delivery after ß-lactam treatment heightened the abundance of Klebsiella, Enterobacteriaceae_Unclassified, Lactobacillales_Unclassified, and Pectobacterium. Feeding patterns minimally influenced ß-lactam-induced alterations. In conclusion, ß-lactam antibiotic treatment for neonatal pneumonia and sepsis markedly disrupted intestinal microbiota, favoring Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas. The impact of ß-lactam varied by duration, type, and delivery method, emphasizing heightened disruptions post-cesarean delivery.

Influencing factors for surgical treatment in neonatal necrotizing enterocolitis: a systematic review and meta-analysis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a complex disease characterized by gastrointestinal inflammation and is one of the most common gastrointestinal emergencies in neonates. Mild to moderate cases of NEC require medical treatment, whereas severe cases necessitate surgical intervention. However, evidence for surgical indications is limited and largely dependent on the surgeon's experience, leading to variability in outcomes. The primary aim of this study is to identify the risk factors for surgical intervention in neonatal NEC, which will aid in predicting the optimal timing for surgical intervention. METHODS: A literature search was conducted in PubMed, Embase, and Web of Science databases for case-control studies exploring risk factors for NEC requiring surgical intervention. The search was completed on June 16, 2024, and data analysis was performed using R Studio 4.3.2. RESULTS: 18 studies were included, comprising 1,104 cases in the surgery group and 1,686 in the medical treatment group. The meta-analysis indicated that high C-reactive protein (CRP) levels [OR = 1.42, 95% CI (1.01, 1.99)], lower gestational age [OR = 0.52, 95% CI (0.3, 0.91)], sepsis [OR = 2.94, 95% CI (1.87, 4.60)], coagulation disorder [OR = 3.45, 95% CI (1.81, 6.58)], lack of enteral feeding [OR = 3.18, 95% CI (1.37, 7.35)], and hyponatremia [OR = 1.22, 95% CI (1.07, 1.39)] are significant risk factors for surgical treatment in neonatal NEC. CONCLUSIONS: High CRP levels, coagulation disorders, sepsis, lower gestational age, lack of enteral feeding, and hyponatremia are significant risk factors for surgical intervention in neonatal NEC. These findings have potential clinical significance for predicting surgical risk.

The diagnostic value of salivary C-reactive protein in neonatal infections: a meta-analysis.

PURPOSE: C-reactive protein (CRP), as an acute phase protein, is a sensitive indicator of neonatal bacterial infection. Some recent studies have shown that there is a correlation between CRP levels in serum and saliva, and using saliva to detect CRP levels is expected to be an ideal and non-invasive method to predict neonatal infection. The purpose of this Meta-analysis was to evaluate the diagnostic value of salivary CRP for neonatal infection. METHODS: We searched PubMed, Embase, Web of Science, and Scopus databases in October 2023 and included observational studies that examined salivary CRP in newborns with bacterial infections. Data was extracted regarding the methodology, participant characteristics, and outcome measures. RESULTS: Nine articles were included, with a total of 696 newborns. Salivary CRP levels are significantly higher in neonates with infections compared to non-infected group (SMD = 0.58, 95%CI [0.40-0.76], P < 0.001). The accuracy for salivary CRP to predict serum CRP abnormality is high (sensitivity 86%, specificity 88%, area under the curve = 0.94). CONCLUSIONS: Our meta-analysis suggested that salivary CRP can be used as an alternative biomarker to serum CRP for detecting neonatal infection.

Ceftriaxone-induced severe hemolytic anemia, renal calculi, and cholecystolithiasis in a 3-year-old child: a case report and literature review.

Ceftriaxone is widely used in pediatric outpatient care for its efficacy against respiratory and digestive system infections, yet its increasing association with severe immune hemolytic reactions requires heightened vigilance from pediatricians. This report details a rare and severe case of ceftriaxone-induced severe immune hemolytic anemia (IHA), hemolytic crisis, myocardial injury, liver injury, renal calculi, and cholecystolithiasis in a previously healthy 3-year-old child. The child, treated for bronchitis, experienced sudden pallor, limb stiffness, and altered consciousness following the fifth day of ceftriaxone infusion, with hemoglobin (Hb) levels precipitously dropping to 21 g/L. Immediate cessation of ceftriaxone and the administration of oxygen therapy, blood transfusion, intravenous immunoglobulin (IVIG), and corticosteroids led to a gradual recovery. Despite initial improvements, the patient's condition necessitated extensive hospital care due to complications including myocardial injury, liver injury, renal calculi, and cholecystolithiasis. After a 12-day hospital stay and a 3-month follow-up, the child showed complete normalization of Hb and liver function and resolution of calculi. In children, ceftriaxone infusion may trigger severe, potentially fatal, hemolytic reactions. Pediatricians must promptly recognize symptoms such as pallor, limb stiffness, and unresponsiveness, indicative of ceftriaxone-induced severe IHA, and immediately discontinue the drug. Effective management includes timely blood transfusion, respiratory support, IVIG administration, and corticosteroids when necessary, along with rigorous vital signs monitoring. Continued vigilance is imperative, even after cessation of ceftriaxone, to promptly address any residual adverse effects.

Comparison of Different Treatments of Persistent Pulmonary Hypertension of the Newborn: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening disease. Despite being considered the gold standard treatment scheme, inhaled nitric oxide (iNO) is not readily available in settings with limited resources. Therefore, in recent years, research on related drugs is being actively pursued. Herein, we aimed to use random-effects network meta-analysis to evaluate the efficacy and associated mortality of different PPHN therapies. DATA SOURCES: We electronically searched the PubMed, Embase, and Cochrane Library for data up to January 27, 2023. STUDY SELECTION: Randomized controlled trials involving neonates with PPHN assessing efficacy and mortality of various treatments. DATA EXTRACTION: Details of study population, treatments, and outcomes were extracted. DATA SYNTHESIS: Direct pairwise comparisons and a network meta-analysis was performed under random effects. The ranking probability was further assessed based on the surface under the cumulative ranking curve (SUCRA). We analyzed 23 randomized clinical trials involving 902 newborns with PPHN. Sixteen different treatment strategies were compared with each other and conventional therapy (CON). A median concentration of 10-20 parts per million (ppm) iNO (MNO) coupled with sildenafil orally administered at a dose of 1-3 mg/kg/dose every 6-8 hours (OSID) demonstrated the best efficacy (MNO + OSID vs. CON: odds ratio [OR] = 27.53, 95% CI, 2.36-321.75; SUCRA = 0.818, ranking first; moderate quality). OSID combined with milrinone administered IV also performed well in terms of efficacy (OSID + milrinone vs. CON: OR = 25.13, 95% CI = 1.67-377.78; SUCRA = 0.811, ranking second; low quality) and mortality reduction (CON vs. OSID + milrinone: OR = 25.13, 95% CI = 1.67-377.78; SUCRA = 0.786, ranking last; low quality). CONCLUSIONS: MNO + OSID is the most effective PPHN treatment. If iNO is not available, OSID + milrinone is preferred.

RDmaster: A novel phenotype-oriented dialogue system supporting differential diagnosis of rare disease.

BACKGROUND: Clinicians often lack the necessary expertise to differentially diagnose multiple underlying rare diseases (RDs) due to their complex and overlapping clinical features, leading to misdiagnoses and delayed treatments. The aim of this study is to develop a novel electronic differential diagnostic support system for RDs. METHOD: Through integrating two Bayesian diagnostic methods, a candidate list was generated with enhance clinical interpretability for the further Q&A based differential diagnosis (DDX). To achieve an efficient Q&A dialogue strategy, we introduce a novel metric named the adaptive information gain and Gini index (AIGGI) to evaluate the expected gain of interrogated phenotypes within real-time diagnostic states. RESULTS: This DDX tool called RDmaster has been implemented as a web-based platform (http://rdmaster.nbscn.org/). A diagnostic trial involving 238 published RD patients revealed that RDmaster outperformed existing RD diagnostic tools, as well as ChatGPT, and was shown to enhance the diagnostic accuracy through its Q&A system. CONCLUSIONS: The RDmaster offers an effective multi-omics differential diagnostic technique and outperforms existing tools and popular large language models, particularly enhancing differential diagnosis in collecting diagnostically beneficial phenotypes.

Neutrophil extracellular traps in adult diseases and neonatal bacterial infectious diseases: A review.

Neutrophils, the most abundant type of white blood cells, are pivotal in fighting bacterial infections due to their immunological and anti-infection capabilities. In recent years, scientists have discovered a novel mechanism known as neutrophil extracellular traps, which are fibrous networks primarily released by neutrophils that combat bacterial infections. There is a growing interest in studying NETs and their role in human infectious diseases, particularly in neonates susceptible to bacterial infections. NETs and their components have been found in various samples from neonatal-infected patients, providing a new route for early diagnosis of neonatal infectious diseases. This paper aims to summarize the studies on NETs in adult diseases and mainly discuss NETs in neonatal sepsis, necrotizing enterocolitis, and purulent meningitis, to provide scientific evidence for early monitoring, diagnosis, and treatment of neonatal infections.

Comparison of Different Adjuvant Therapies for Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: Neonatal hypoxic-ischemic encephalopathy is a major cause of perinatal death and neurodevelopmental impairment (NDI). Hypothermia (HT) is the standard of care; however, additional neuroprotective agents are required to improve prognosis. The authors searched for all drugs in combination with HT and compared their effects using a network meta-analysis. METHODS: The authors searched PubMed, Embase, and Cochrane Library until September 24, 2022 for articles assessing mortality, NDI, seizures, and abnormal brain imaging findings in neonates with hypoxic-ischemic encephalopathy. Direct pairwise comparisons and a network meta-analysis was performed under random effects. RESULTS: Thirteen randomized clinical trials enroled 902 newborns treated with six combination therapies: erythropoietin magnesium sulfate, melatonin (MT), topiramate, xenon, and darbepoetin alfa. The results of all comparisons were not statistically significant, except for NDI, HT vs. MT+HT: odds ratio = 6.67, 95% confidence interval = 1.14-38.83; however, the overall evidence quality was low for the small sample size. CONCLUSIONS: Currently, no combination therapy can reduce mortality, seizures, or abnormal brain imaging findings in neonatal hypoxic-ischemic encephalopathy. According to low quality evidence, HT combined with MT may reduce NDI.

Larotrectinib treatment for infantile fibrosarcoma in newborns: a case report and literature review.

Infantile fibrosarcoma (IFS) is a rare tumor in childhood characterized by a single, localized, painless mass that grows rapidly but has a relatively indolent biological behavior and a favorable prognosis. Eighty-five percent of infantile fibrosarcomas are associated with t (12;15) (p13;25) chromosomal translocation resulting in ETV6-NTRK3 gene fusion, which provides the target for targeted therapy. Here, we report a case of IFS in a newborn with a mass in the left lower extremity confirmed by imaging, histopathological examination, tissue FISH testing, and high-throughput sequencing to detect gene rearrangement. Based on gene fusion targeted drug testing results, the patient was treated with standard doses of larotrectinib, resulting in significant mass shrinkage with no adverse effects, demonstrating the treatment effect of targeted therapy. This case provides a reference for using larotrectinib in newborns with IFS.

Long noncoding RNA signatures in intrauterine infection/inflammation-induced lung injury: an integrative bioinformatics study.

BACKGROUND: Intrauterine infection/inflammation can result in fetal and neonatal lung injury. However, the biological mechanisms of intrauterine infection/inflammation on fetal and neonatal lung injury and development are poorly known. To date, there are no reliable biomarkers for improving intrauterine infection/inflammation-induced lung injury. METHODS: An animal model of intrauterine infection/inflammation-induced lung injury was established with pregnant Sprague-Dawley rats inoculated with Escherichia coli suspension. The intrauterine inflammatory status was assessed through the histological examination of the placenta and uterus. A serial of histological examinations of the fetal and neonatal rats lung tissues were performed. The fetal and neonatal rat lung tissues were harvested for next generation sequencing at embryonic day 17 and postnatal day 3, respectively. Differentially expressed mRNAs and lncRNAs were identified by conducting high-throughput sequencing technique. The target genes of identified differentially expressed lncRNAs were analyzed. Homology analyses for important differentially expressed lncRNAs were performed. RESULTS: The histopathological results showed inflammatory infiltration, impaired alveolar vesicular structure, less alveolar numbers, and thickened alveolar septa in fetal and neonatal rat lung tissues. Transmission electron micrographs revealed inflammatory cellular swelling associated with diffuse alveolar damage and less surfactant-storing lamellar bodies in alveolar epithelial type II cells. As compared with the control group, there were 432 differentially expressed lncRNAs at embryonic day 17 and 125 differentially expressed lncRNAs at postnatal day 3 in the intrauterine infection group. The distribution, expression level, and function of these lncRNAs were shown in the rat genome. LncRNA TCONS_00009865, lncRNA TCONS_00030049, lncRNA TCONS_00081686, lncRNA TCONS_00091647, lncRNA TCONS_00175309, lncRNA TCONS_00255085, lncRNA TCONS_00277162, and lncRNA TCONS_00157962 may play an important role in intrauterine infection/inflammation-induced lung injury. Fifty homologous sequences in Homo sapiens were also identified. CONCLUSIONS: This study provides genome-wide identification of novel lncRNAs which may serve as potential diagnostic biomarkers and therapeutic targets for intrauterine infection/inflammation-induced lung injury.

Role of gut-brain axis in neurodevelopmental impairment of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a common gastrointestinal disease of preterm infants with high morbidity and mortality. In survivors of NEC, one of the leading causes of long-term morbidity is the development of severe neurocognitive injury. The exact pathogenesis of neurodevelopmental delay in NEC remains unknown, but microbiota is considered to have dramatic effects on the development and function of the host brain via the gut-brain axis. In this review, we discuss the characteristics of microbiota of NEC, the impaired neurological outcomes, and the role of the complex interplay between the intestinal microbiota and brain to influence neurodevelopment in NEC. The increasing knowledge of microbial-host interactions has the potential to generate novel therapies for manipulating brain development in the future.

Brain Damage in the Preterm Infant: Clinical Aspects and Recent Progress in the Prevention and Treatment.

Although the prevalence of brain injury and related neurodevelopmental disabilities resulting from preterm birth are major public health concerns, there are no definite neuroprotective strategies to prevent or reduce brain injury. The pattern of brain injury seen in preterm infants has evolved into more subtle lesions that are still essential to diagnose regarding neurodevelopmental outcomes. There is no specific effective method for the treatment of premature infant brain injury, and the focus of clinical treatment is still on prevention. Prevention of this injury requires insight into the pathogenesis, but many gaps exist in our understanding of how neonatal treatment procedures and medications impact cerebral hemodynamics and preterm brain injury. Many studies provide evidence about the prevention of premature infant brain injury, which is related to some drugs (such as erythropoietin, melatonin, mesenchymal stem cells, etc.). However, there are still some controversies about the quality of research and the effectiveness of therapy. This review aims to recapitulate the results of preclinical studies and provide an update on the latest developments around etiological pathways, prevention, and treatment.

Modulation of PC1/3 activity by a rare double-site homozygous mutation.

Objectives: Preprotein convertase 1/3 deficiency is a rare autosomal recessive disorder in which patients present with malabsorptive diarrhea and a series of symptoms of endocrine disorders such as polydipsia, reactive hypoglycemia, growth hormone deficiency, hypothyroidism, adrenal insufficiency, and early onset obesity. In its essence, pituitary hormone deficiency is caused by insufficient cleavage of pituitary prohormones. Here, we describe a female child with a rare double-site homozygous mutation in PCSK1 (Proprotein convertase subtilisin/kexin-type 1) gene, and thereby intend to investigate the relationship between these novel mutation sites and changes in protein synthesis and function. Methods: We tested this patient's blood and urine fecal indicators of infection, blood electrolytes, and relevant endocrine hormone levels in the laboratory. Next Generation Sequencing was applied to screen the patient's DNA. Western Blot was performed to evaluate the mutant protein's expression. The enzymatic activity was measured as the rate of cleavage of a synthetic fluorogenic substrate in a specific solution. Results: We found that this patient presented shortly after birth with uncorrectable diarrhea and symptoms of metabolic acidosis with hypothyroidism. Next Generation Sequencing revealed that a rare double-site homozygous missense mutation, c.763G > A (p.G255R) and c.758C > T (p.S253L), were detected in exon 7 of PCSK1 (Proprotein convertase subtilisin/kexin-type 1) gene on chromosome 5 of the patient. Western blotting revealed that there was no significant decrease in protein synthesis levels in the mutant phenotype compared to the wild type. Compared with WT type, the proteins expressed by the mutations showed a significant decrease in the enzyme activity towards the fluorescent substrates. However, neither the single site mutation p.S253L or p.G255R, nor the double-site mutation of both, all showed no significant differences from each other. Conclusions: These two missense mutations have not been reported before, and it is even rarer to find homozygous variation of two sites in one patient. This study identifies two novel mutations for the first time and further investigates the changes in protein synthesis and enzyme activity, providing a new pathway to continue to explore the pathogenesis of diseases associated with the function of PC1/3.

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OBJECTIVES: To investigate the level of 25 hydroxyvitamin D [25(OH)D] in late preterm infants and the effect of vitamin D3 supplementation on the neurobehavioral development of infants and young children. METHODS: In this prospective study, 161 late preterm infants who were admitted from June 2017 to June 2020 were enrolled. According to the level of 25(OH)D in umbilical cord blood, they were divided into three groups: sufficiency group (n=52), insufficiency group (n=53), and deficiency group (n=56). Each group was further divided into subgroup A (vitamin D3 800 IU/d) and subgroup B (individualized vitamin D3 supplementation) using a random number table. The levels of 25(OH)D were measured at 3 months after birth and at the corrected ages of 10 months and 18 months. The neurobehavioral development levels were determined by the Gesell Developmental Scale at the corrected ages of 10 months and 18 months. RESULTS: Within 24 hours and 3 months after birth, the insufficiency group and the deficiency group had a significantly lower level of 25(OH)D than the sufficiency group (P<0.05), and the insufficiency group had a significantly higher level of 25(OH)D than the deficiency group (P<0.05). In the deficiency group, subgroup B had a significantly higher level of 25(OH)D than subgroup A (P<0.05) at 3 months after birth. At the corrected ages of 10 months and 18 months, the insufficiency and deficiency groups had significantly lower scores of five functional areas of the Gesell Development Scale than the sufficiency group (P<0.05). Compared with the insufficiency group, the deficiency group had a significantly lower score of language at the corrected age of 10 months and a significantly lower score of gross motor at the corrected age of 18 months (P<0.05). Compared with subgroup A of the deficiency group, subgroup B had a significantly higher score of adaptive ability at the corrected age of 10 months and significantly higher scores of adaptive ability and response ability at the corrected age of 18 months (P<0.05). CONCLUSIONS: There is a significant difference in the level of 25(OH)D in umbilical cord blood in late preterm infants. Individualized vitamin D supplementation appears to be more effective for the treatment of vitamin D deficiency. Vitamin D level at birth and in early infancy has certain influence on neurobehavioral development.

Profound Hypothermia Concomitant With Severe Coagulation Dysfunction and Leukopenia in a Preterm Infant: A Case Report and Literature Review.

BACKGROUND: Neonatal hypothermia is common around the world; however, profound hypothermia is a very rare-but life-threatening-event. CLINICAL FINDINGS: This was a very rare case involving a 15-day old preterm infant diagnosed with profound hypothermia (rectal temperature, 27°C) concomitant with severe coagulation dysfunction and leukopenia on admission. PRIMARY DIAGNOSIS: Profound hypothermia together with severe coagulopathy, leukopenia, late-onset sepsis, and pneumonia. INTERVENTIONS: The patient was rewarmed slowly, with a rectal temperature rising at a rate of 0.5°C/h < R < 1°C/h. Vital signs were closely monitored. Coagulation factors were supplemented by intravenous infusion of fresh frozen plasma. Supportive treatment with intravenous infusion of immunoglobulin was provided, and antibiotics were used empirically. Nil per os and intravenous rehydration were also implemented. OUTCOMES: The condition of the preterm infant gradually improved and was successfully discharged. PRACTICE RECOMMENDATIONS: Profound hypothermia is very rare in preterm infants. However, once it occurs, it may be concomitant with severe coagulopathy and leukopenia. Successful management involves slow rewarming, prompt supplementation of coagulation factors, empirical antibiotics, and supportive treatment.

Impact of the COVID-19 pandemic on infectious disease hospitalizations of neonates at a tertiary academic hospital: a cross-sectional study.

BACKGROUND: To investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on hospitalizations for neonatal infectious diseases. METHODS: We analyzed data for neonatal inpatients admitted at a tertiary academic hospital with a principal diagnosis of an infectious disease during January 2015 to December 2020. We compared hospitalizations in 2020 (COVID-19 cohort), corresponding with the impact of COVID-19 pandemic and associated containment measures, and the comparable 2015 to 2019 (pre-COVID-19 cohort). RESULTS: 14,468 cases admitted for neonatal infectious diseases were included in our study, with 1201 cases in the COVID-19 cohort and 13,267 cases in the pre-COVID-19 cohort. The leading causes of hospitalizations for neonatal infectious diseases remain being respiratory tract infections (median ratio = 0.461, 95% CI 0.335-0.551), sepsis (median ratio = 0.292, 95% CI 0.263-0.361), gastric intestinal infections (median ratio = 0.095, 95% CI 0.078-0.118) and dermatologic infections (median ratio = 0.058, 95% CI 0.047-0.083). The seasonality of neonatal infectious disease hospitalizations could be obviously observed, with the total number and the overall rate of hospitalizations for neonatal infectious diseases in the first and fourth quarters greater than that of hospitalizations for neonatal infectious diseases in the second and third quarters in each year (1362.67 ± 360.54 vs 1048.67 ± 279.23, P = 0.001; 8176/20020 vs 6292/19369, P < 0.001, respectively). Both the numbers and the proportions of hospitalizations for neonatal infectious diseases in different quarters of the COVID-19 cohort significantly decreased as compared with those forecasted with the data from the pre-COVID-19 cohort: the numbers per quarter (300.25 ± 57.33 vs 546.64 ± 100.43, P-value = 0.006), the first quarter (0.34 vs 0.40, P = 0.002), the second quarter (0.24 vs 0.30, P = 0.001), the third quarter (0.24 vs 0.28, P = 0.024), and the fourth quarter (0.29 vs 0.35, P = 0.003). CONCLUSIONS: Despite the outbreak of the COVID-19 pandemic, the leading causes of hospitalizations for neonatal infectious diseases remain unchanged. The seasonality of neonatal infectious disease hospitalizations could be obviously observed. The numbers as well as the overall rates of hospitalizations for neonatal infectious diseases in the COVID-19 cohort dramatically declined with the impact of the COVID-19 pandemic and its mitigation measures.

Severe neonatal anemia affected by massive fetomaternal hemorrhage: a single-center retrospective observational study.

OBJECTIVES: Massive fetomaternal hemorrhage (FMH) is a rare but sometimes life-threatening event, and surviving neonates may suffer major neurological complications. Severe neonatal anemia (SNA) affected by massive FMH is less reported in the literature. This study aims to explore the clinical characteristics, laboratory diagnoses, treatments and outcomes of SNA affected by massive FMH. METHODS: Data were collected retrospectively from the hospital's electronic medical record system. All neonates born in the hospital and admitted to the neonatal unit diagnosed as SNA affected by massive FMH from 1 January 2013 to 31 June 2017 were included. RESULTS: A total of 8 cases of SNA affected by FMH were identified among 6825 neonates admitted to the neonatal unit. They all presented with pallor but without hydrops at birth. Median gestational age and birthweight were 375/7 (360/7‒401/7) weeks and 2,625 (2300‒3050) g, respectively. Median hemoglobin level was 39.5 (25‒53) g/L at birth and 109.5 (94-127) g/L at discharge. Median maternal serum alpha-fetoprotein (AFP) was 3958.5 (1606‒14,330) ng/mL, which was significantly increased. Three out of eight cases manifested as antenatal decreased fetal movement. Only 1 with the lowest initial hemoglobin 25 g/L manifested as characteristic sinusoidal fetal heart rate tracing and suffered severe neonatal asphyxia and hypovolemic shock. Having experienced resuscitation, he was admitted to the neonatal unit and received twice transfusion of cross-matched red blood cells there. Another case with the initial hemoglobin 45 g/L received positive pressure ventilation and once transfusion. All cases were successfully discharged with a median hospital stay of 8 (5-12) days. Follow-up was available for 6 (75%) of 8 neonates (age range 13 months to 50 months), and all infants were observed to be in good condition with normal neurological status. In our series of eight cases, there were no neonatal deaths. CONCLUSION: This study strengthens the idea that maternal AFP testing is valuable to confirm massive fetomaternal hemorrhage. Surviving neonates of massive FMH might have a good outcome despite severe anemia at birth.

Familial hemophagocytic lymphohistiocytosis in a neonate: Case report and literature review.

RATIONALE: Familial hemophagocytic lymphohistiocytosis (FHL) is a potentially fatal disease that rarely presents in the neonatal period. Timely diagnosis is a key challenge owing to the atypical clinical manifestations. Here, we describe a case of FHL type 3 with disease onset in the early neonatal period and review the relevant literature. Our findings may provide insights into the diagnosis and treatment of this rare disease. PATIENT CONCERNS: A 6-day-old male neonate presented with fever, hepatosplenomegaly, cytopenia, hyperferritinemia, hypofibrinogenemia, hemophagocytosis, and hypertriglyceridemia. DIAGNOSIS: Considering the clinical picture (prolonged fever, progressive hepatosplenomegaly, high triglycerides, low fibrinogen, and high ferritin), along with abnormal natural killer-cell activity, combining sequence analysis of genomic DNA results (compound heterozygous mutations of UNC13D), the patient was finally diagnosed with FHL type 3 (FHL3). INTERVENTIONS: The patient was initially treated with HLH-1994 protocol and subsequently switched to an oral regimen of ruxolitinib due to incomplete remission of the disease. OUTCOMES: The trend of change in weekly cytokine levels, neutrophil counts, hemoglobin, and platelet counts indicated that the complete remission was not achieved after the treatment of HLH-1994 protocol. The platelet counts fluctuated within the normal range after oral administration of ruxolitinib. But soon after, the patient did not respond to treatment and eventually died of respiratory failure. LESSON: Timely diagnosis of FHL is challenging. This case report illustrates that thrombocytopenia can be the first clinical sign of FHL with neonatal onset. Genetic testing, detection of cytokines, and flow cytometry should be performed as soon as possible to confirm the diagnosis. Given the high morbidity and mortality of FHL, pediatricians should have a high suspicion index for this disease.