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1.
PLoS One ; 17(2): e0263451, 2022.
Article in English | MEDLINE | ID: mdl-35180230

ABSTRACT

Congenital Malaria (CM) is an underestimated and under-researched problem in Colombia, despite its severe clinical, epidemiological, economic, and public health consequences. The objective was to determine the general frequency of CM, the specific frequency of CM by diagnostic test and plasmodial species, and identify its associated factors. A retrospective study was carried out using the records of 567 newborns. qPCR and Thick Blood Smear (TBS) were performed. The frequency of infection was determined with a 95% confidence interval. Associated factors were identified by non-parametric tests and odds ratios; the confusion was controlled with a logistic regression model. All cases corresponded to submicroscopic CM (negative with TBS and positive with PCR), and the frequency was 12.2% (95%CI = 9.4-14.9). The detection was statistically higher in the umbilical cord with 16,2% (95%CI = 12.4-19.9) versus peripheral blood of the newborn with 2.2% (95%CI = 0.7-4.9). CM was statistically higher in newborn whose mothers had malaria in the last year, gestational and placental malaria. The median birth weight in newborn infected with CM was lower compared to the one of healthy neonates. Because the control program in Colombia is based on TBS, it must be improved with the inclusion of other tests that allow the detection of submicroscopic CM. In addition, the program has other limitations such as do not have specific actions for pregnant women and have a passive surveillance system. These difficulties do not allow to show the magnitude of CM, its consequences on neonatal and infant health, constituting a serious problem of health injustice.


Subject(s)
Infant, Newborn, Diseases/epidemiology , Malaria, Falciparum/epidemiology , Malaria, Vivax/epidemiology , Plasmodium falciparum/genetics , Plasmodium vivax/genetics , Pregnancy Complications, Parasitic/epidemiology , Adolescent , Adult , Birth Weight , Colombia/epidemiology , Cross-Sectional Studies , Female , Humans , Infant, Low Birth Weight , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/parasitology , Malaria, Falciparum/blood , Malaria, Falciparum/parasitology , Malaria, Vivax/blood , Malaria, Vivax/parasitology , Polymerase Chain Reaction/methods , Pregnancy , Pregnancy Complications, Parasitic/blood , Pregnancy Complications, Parasitic/parasitology , Retrospective Studies , Umbilical Cord/parasitology , Young Adult
2.
Article in English | MEDLINE | ID: mdl-35032892

ABSTRACT

A sensitive and accurate hydrophilic interaction liquid chromatography - tandem mass spectrometry method (HILIC-MS/MS) was developed and validated for the determination of phenylephrine concentration in Dried Blood Spot (DBS) samples from preterm infants, after ocular administration of an ophthalmic solution with phenylephrine. Sample preparation involved the extraction of the analyte from an 85 µL DBS sample with methanol - acetonitrile (50:50, v/v). Chromatographic separation was achieved on an ACQUITY UPLC BEH AMIDE column, under isocratic conditions within a 5 min run. Detection was achieved with a triple quadrupole MS applying electrospray ionization in positive mode. The method was fully validated and proved precise and accurate with in a linear range of 0.59-3.53 ng/ml in blood. The method was developed to provide insights on the level of exposure of infant population to phenylephrine after ocular administration.


Subject(s)
Chromatography, High Pressure Liquid/methods , Dried Blood Spot Testing/methods , Eye Diseases, Hereditary/diagnosis , Infant, Newborn, Diseases/diagnosis , Infant, Premature/blood , Mydriasis/diagnosis , Mydriatics/blood , Phenylephrine/blood , Tandem Mass Spectrometry/methods , Eye Diseases, Hereditary/blood , Female , Humans , Infant , Infant, Newborn , Infant, Newborn, Diseases/blood , Male , Mydriasis/blood , Mydriatics/administration & dosage , Ophthalmic Solutions , Phenylephrine/administration & dosage
3.
J Pediatr Hematol Oncol ; 44(1): e84-e90, 2022 01 01.
Article in English | MEDLINE | ID: mdl-33735151

ABSTRACT

Carboxyhemoglobin (COHb) is an index of endogenous carbon monoxide formation during the hem degradation process and could be used to confirm hemolysis in neonates. The influence of other clinical factors on COHb values in neonates has not been fully investigated. We aimed to evaluate the influence of hemolysis, sepsis, respiratory distress, and postnatal age on COHb values. We retrospectively analyzed COHb measurements determined with a carbon monoxide-oximeter in 4 groups of term neonates: A-sepsis, B-respiratory distress, C-hemolysis, and D-healthy neonates. The mean COHb values were 1.41% (SD: 0.26), 1.32% (SD: 0.27), 2.5% (SD: 0.69), and 1.27% (SD: 0.19) (P<0.001) in groups A (n=8), B (n=37), C (n=16), and D (n=76), respectively. COHb in group C was significantly higher than in the other groups. There was a negative correlation between postnatal age and COHb in healthy neonates. A cut-off level of 1.7% had 93% (95% confidence interval [CI]: 89%-97%) sensitivity and 94% (95% CI: 90%-98%) specificity for diagnosis of hemolysis. COHb values were higher during the first days of life. We found that COHb levels in neonates with hemolysis were significantly higher and that the influence of sepsis and respiratory distress on COHb values was insignificant.


Subject(s)
Carbon Monoxide/blood , Carboxyhemoglobin/metabolism , Hemolysis , Infant, Newborn, Diseases/blood , Respiratory Distress Syndrome/blood , Sepsis/blood , Humans , Infant, Newborn , Oximetry , Retrospective Studies
4.
Clin Biochem ; 100: 48-54, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34852256

ABSTRACT

OBJECTIVE: Alkaline phosphatase (ALP) is a ubiquitous enzyme in humans that can be used for diagnosing childhood diseases. Infants have the highest rapid growth rate and are susceptible to metabolic bone diseases. In infants, ALP activities exhibit significant month-wise variations, and authoritative standards are lacking. The present study aimed to provide a reference for the diagnosis of diseases related to abnormal ALP activities in infants. METHODS: This study included 24,618 samples collected from infants aged 0-12 months from three medical centers in Chongqing, China. Samples of infants diagnosed with diseases that may affect ALP activity have been exclude. ALP activity was analyzed using an automatic biochemical analyzer. A percentile curve for ALP activity in male and female infants was constructed using MATLAB, and the skewness-median-coefficient of variation method was employed for curve fitting. RESULTS: ALP activity in male and female infants peaked at 0-4 months; the peak appeared at 1-2 months and declined gradually thereafter. After 4-5 months of age, the ALP activities declined further, with the lowest values observed at 11-12 months of age. A comparison between the data from this study and a those from a published German study indicates that Chinese infants exhibited peak ALP activity later and subsequent decline greater than German infants. CONCLUSIONS: A percentile curve was constructed for month-wise ALP activity in male and female infants, which could provide a reference for diagnosing diseases related to abnormal ALP activity in infants.


Subject(s)
Alkaline Phosphatase/blood , Bone Diseases, Metabolic/blood , Infant, Newborn, Diseases/blood , China , Female , Humans , Infant , Infant, Newborn , Male , Sex Factors
5.
Ginekol Pol ; 92(11): 818-821, 2021.
Article in English | MEDLINE | ID: mdl-34907520

ABSTRACT

The influence of the blood group on the occurrence and severity of diseases has aroused the curiosity of scientists for many years. The AB0 group system is the best known and described blood group system. It is also the only system whose antibodies are constantly present in the blood serum. The most common blood type in Poland, according to data provided by Honorary blood donation and blood therapy, is group A Rh+ (plus), while the least common is group AB Rh- (minus). In studies of pregnant women scientists discovered the influence of blood type in the development of preeclampsia, gestational diabetes, the risk of preterm labor, and even COVID-19 infection. The impact of the mothers' blood group also affects the birth weight of newborns, as well as the development of hemolytic disease of the newborn due to the heterospecificity of AB0. The influence of the blood group on the increased risk of developing certain diseases and complications of the neonatal period has also been proven. Therefore, it seems important to study blood groups of pregnant women and newborns of different nationalities, correlate the results with available reports and use this knowledge in everyday clinical practice. This will help to increase the speed of detection of diseases in pregnancy and neonatal period. It will also facilitate the management of the patient depending on their blood group.


Subject(s)
Blood Group Antigens , COVID-19 , Infant, Newborn, Diseases/blood , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Poland/epidemiology , Pregnancy , SARS-CoV-2
6.
Nat Commun ; 12(1): 7288, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34911947

ABSTRACT

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.


Subject(s)
Gastrointestinal Microbiome , Infant, Newborn, Diseases/prevention & control , Rotavirus Infections/microbiology , Rotavirus Infections/prevention & control , Rotavirus Vaccines/administration & dosage , Rotavirus/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Female , Humans , Immunity, Maternally-Acquired , Immunoglobulin A/blood , Immunoglobulin A/immunology , India , Infant , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/microbiology , Infant, Newborn, Diseases/virology , Malawi , Male , Milk, Human/chemistry , Milk, Human/immunology , Pregnancy , Prospective Studies , Rotavirus/genetics , Rotavirus/physiology , Rotavirus Infections/blood , Rotavirus Infections/virology , Rotavirus Vaccines/immunology , United Kingdom , Vaccine Efficacy , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology , Virus Shedding
7.
Hypertens Pregnancy ; 40(4): 336-345, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34697981

ABSTRACT

Objective:To compare the effect of comorbidities on the phenotype and outcomes of preeclampsia.Methods: A matched retrospective cohort study of women delivering at a tertiary maternity center following a diagnosis of preeclampsia. We collected data on signs and symptoms, biochemical markers, and maternal and perinatal outcomes.Results:We studied 474 women; 158 women with and 316 without comorbidities. Compared to women without comorbidities, women with comorbidities delivered earlier. They suffered fewer maternal but more neonatal complications.Conclusion: Women with comorbidities receive earlier intervention than women without comorbidities, which may lead to fewer maternal complications but worse neonatal outcomes.


Subject(s)
Angiogenic Proteins/blood , Biomarkers/blood , Hypertension/epidemiology , Infant, Newborn, Diseases/epidemiology , Pre-Eclampsia/diagnosis , Pregnancy Complications/diagnosis , Adult , Angiogenic Proteins/analysis , Biomarkers/analysis , Comorbidity , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/blood , Phenotype , Pre-Eclampsia/blood , Pre-Eclampsia/epidemiology , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/epidemiology , Pregnancy Outcome/epidemiology , Retrospective Studies
8.
Front Endocrinol (Lausanne) ; 12: 690648, 2021.
Article in English | MEDLINE | ID: mdl-34267729

ABSTRACT

The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the in utero environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of ZNF696 was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted P < 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of ZNF696 in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.


Subject(s)
Blood Glucose/analysis , DNA Methylation , Diabetes, Gestational/genetics , Hypoglycemia/genetics , Infant, Newborn, Diseases/genetics , Adult , Alleles , Diabetes, Gestational/blood , Female , Gene Frequency , Humans , Hypoglycemia/blood , Infant, Newborn , Infant, Newborn, Diseases/blood , Middle Aged , Pregnancy
9.
Sci Rep ; 11(1): 13777, 2021 07 02.
Article in English | MEDLINE | ID: mdl-34215818

ABSTRACT

Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are two of the most common emergencies of the gastrointestinal tract in preterm infants with very low birth weight (VLBW, birth weight < 1500 g). Identification of risk factors among these children is crucial for earlier diagnosis and prompt intervention. In this study, we investigated a relationship between ABO blood groups and the risk for surgical NEC/FIP. We genotyped the ABO locus (rs8176746 and rs8176719) in VLBW infants enrolled in a prospective, population-based cohort study of the German Neonatal Network (GNN). Of the 10,257 VLBW infants, 441 (4.3%) had surgical NEC/FIP. In univariate analyses, the blood group AB was more prevalent in VLBW infants with surgical NEC/FIP compared to non-AB blood groups (OR 1.51, 95% CI 1.07-2.13, p = 0.017; absolute risk difference 2.01%, 95% CI 0.06-3.96%). The association between blood group AB and surgical NEC/FIP was observed in a multivariable logistic regression model (OR of 1.58, 95% CI 1.10-2.26, p = 0.013) as well. In summary, our study suggests that the risk of surgical NEC and FIP is higher in patients with blood group AB and lower in those having non-AB blood groups.


Subject(s)
ABO Blood-Group System/blood , Enterocolitis, Necrotizing/epidemiology , Infant, Newborn, Diseases/epidemiology , Infant, Premature, Diseases/epidemiology , Intestinal Perforation/epidemiology , Child, Preschool , Enterocolitis, Necrotizing/blood , Enterocolitis, Necrotizing/pathology , Enterocolitis, Necrotizing/surgery , Female , Fetal Diseases/blood , Fetal Diseases/pathology , Fetal Diseases/surgery , Gestational Age , Humans , Infant , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/pathology , Infant, Newborn, Diseases/surgery , Infant, Premature/blood , Infant, Premature, Diseases/pathology , Infant, Premature, Diseases/surgery , Infant, Very Low Birth Weight , Intestinal Perforation/blood , Intestinal Perforation/pathology , Intestinal Perforation/surgery , Male , Risk Factors
10.
Biomed Res Int ; 2021: 6638622, 2021.
Article in English | MEDLINE | ID: mdl-34307663

ABSTRACT

INTRODUCTION: As the clinical manifestation of neonatal infection is nonspecific and characterised by varied clinical features, it is highly problematic to establish an early diagnosis. Recently, hopes have been raised by the new acute-phase protein-pentraxin 3 (PTX3). PTX3 belongs to the family of long pentraxins, which is synthesized in numerous cells like endothelial cells, macrophages, and monocytes infiltrating sites of inflammation. Material and Methods. In our research, we have enrolled 29 newborns with infection as the study group and 47 healthy ones as the control group, as well as their mothers. The C-reactive protein (CRP), procalcitonin (PCT), and PTX3 levels were determined in venous blood samples from all investigated neonates and their mothers. Moreover, PTX3 concentrations were assessed in the umbilical cord. RESULTS: There were statistically significant differences in PTX3 levels between healthy and sick newborns both in the umbilical cord (p = 0.02) and venous blood (p = 0.01). The highest PTX3 concentrations were observed in children with infection in the presence of premature rupture of membranes (PROM). PTX3 concentrations in this group were significantly higher compared to those in healthy children without PROM. We observed elevated PCT levels in newborns with infection. No differences in CRP levels in 12 hours of life were noticed between the investigated groups. A comparison of ROC curves for PTX3 and PCT concentrations revealed similar sensitivity and specificity in the prediction of infection in neonates. CONCLUSIONS: Serum PTX3 is an important and specific biomarker of early infection. It is already elevated in the umbilical cord, so measuring PTX3 concentration might be useful in the early prediction of infection in newborns.


Subject(s)
C-Reactive Protein/metabolism , Early Diagnosis , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/diagnosis , Infections/blood , Infections/diagnosis , Serum Amyloid P-Component/metabolism , Adult , Biomarkers/blood , Case-Control Studies , Female , Fetal Blood/metabolism , Humans , Infant, Newborn , Male , Procalcitonin/blood , ROC Curve , Statistics, Nonparametric , Young Adult
11.
BMC Infect Dis ; 21(1): 386, 2021 Apr 26.
Article in English | MEDLINE | ID: mdl-33902487

ABSTRACT

BACKGROUND: Congenital cytomegalovirus disease (cCMV) is common and can be fatal or cause severe sequelae. Circulating strains of cytomegalovirus carry a high number of variable or disrupted genes. One of these is UL146, a highly diverse gene with 14 distinct genotypes encoding a CXC-chemokine involved in viral dissemination. UL146 genotypes 5 and 6 lack the conserved ELR motif, potentially affecting strain virulence. Here, we investigate whether UL146 genotypes 5 and 6 were associated with congenital CMV infection. METHODS: Viral DNA was extracted and UL146 sequenced from 116 neonatal dried blood spots (DBS) stored in the Danish National Biobank since 1982 and linked to registered cCMV cases through a personal identifier. These sequences were compared to UL146 control sequences obtained from CMV DNA extracted from 83 urine samples from children with suspected bacterial urinary tract infections. RESULTS: Three non-ELR UL146 genotypes (5 and 6) were observed among the cases (2.6%) and two were observed among the controls (2.4%; P > 0.99). Additionally, no significant association with cCMV was found for the other 12 genotypes in a post-hoc analysis, although genotype 8 showed a tendency to be more frequent among cases with 12 observations against three (P = 0.10). All fourteen genotypes were found to have little intra-genotype variation. Viral load, gender, and sample age were not found to be associated with any particular UL146 genotype. CONCLUSIONS: No particular UL146 genotype was associated with cCMV in this nationwide retrospective case-control study. Associations between CMV disease and disrupted or polymorph CMV genes among immunosuppressed people living with HIV/AIDS and transplant recipients should be investigated in future studies.


Subject(s)
Chemokines, CXC/chemistry , Chemokines, CXC/genetics , Cytomegalovirus Infections/epidemiology , Cytomegalovirus/genetics , Genotype , Infant, Newborn, Diseases/epidemiology , Viral Proteins/chemistry , Viral Proteins/genetics , Amino Acid Motifs , Amino Acid Sequence , Base Sequence , Case-Control Studies , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/urine , Cytomegalovirus Infections/virology , DNA, Viral/blood , DNA, Viral/genetics , Denmark/epidemiology , Female , Humans , Infant , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/urine , Infant, Newborn, Diseases/virology , Male , Polymorphism, Genetic , Retrospective Studies , Viral Load
12.
Ned Tijdschr Geneeskd ; 1652021 03 04.
Article in Dutch | MEDLINE | ID: mdl-33720562

ABSTRACT

OBJECTIVE: Evaluate the effectiveness and safety of application of oral glucose to neonates with an increased risk of neonatal hypoglycaemia. BACKGROUND: Neonatal hypoglycaemia is a common problem in neonates with potential permanent neurological damage. Recent studies show that the use of oral glucose to prevent and treat neonatal hypoglycaemia leads to a decrease in intravenous glucose administration and fewer clinical admissions. However, oral glucose administration is still rarely used. In 2019 Isala hospital implemented the use of oral glucose in neonates with an increased risk of neonatal hypoglycaemia. METHOD: Retrospective evaluation study in Isala hospital between November 1, 2018 and December 31. Neonates with one of the following risk factors for neonatal hypoglycaemia: prematurity (gestational age between 34+0-37+0), maternal diabetes requiring medication, asphyxia with an Apgar score <7 at five minutes and/or a birthweight <2500 grams. The frequency of glucose infusions, the lowest glucose value and the type of food were compared between neonates treated before and after the use of oral glucose. RESULTS: The number of glucose infusions decreased after introduction of oral glucose (14.0% versus 5.9%, -8.1% [-14.1, -2.1]). The lowest measured glucose value (2.2 mmol/l versus 2.5 mmol/l, 0.3 mmol/l [0.15, 0.47]) was significantly higher after introduction of oral glucose. Mild complications (vomiting and food refusal) occurred in 3.8% of neonates receiving oral glucose, all without clinical consequence. CONCLUSION: The use of oral glucose administration in neonates with an increased risk of hypoglycaemia reduces the number of intravenous glucose by half and is safe to use.


Subject(s)
Administration, Oral , Glucose/administration & dosage , Hypoglycemia/drug therapy , Infant, Newborn, Diseases/drug therapy , Adult , Asphyxia/complications , Blood Glucose/metabolism , Diabetes, Gestational , Female , Fetal Diseases/etiology , Gestational Age , Glucose/therapeutic use , Hospitals , Humans , Hypoglycemia/blood , Hypoglycemia/etiology , Hypoglycemia/prevention & control , Infant, Low Birth Weight , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/etiology , Infant, Newborn, Diseases/prevention & control , Infant, Premature , Infusions, Intravenous , Netherlands , Pregnancy , Retrospective Studies , Risk Factors , Safety , Treatment Outcome
13.
Pediatr Surg Int ; 37(7): 881-886, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33779823

ABSTRACT

PURPOSE: The role of hypoalbuminemia and raised C-reactive protein (CRP) levels in predicting critical prognosis has been described extensively in adult literature. However, there are limited studies in pediatrics, particularly neonates. The CRP/albumin (CRP/ALB) ratio is often associated with higher mortality, organ failure and prolonged hospital stay. We hypothesized that the serum CRP/ALB ratio has a prognostic value in predicting surgery and mortality in neonates with necrotizing enterocolitis (NEC). METHODS: Retrospective review of all neonates with clinical and radiological evidence of non-perforated NEC that were treated in a tertiary-level referral hospital between 2009 and 2018. General patient demographics, laboratory parameters and outcomes were recorded. Receiver operating characteristics analysis was performed to evaluated optimal cut-offs and area under the curve (AUC) with 95% confidence intervals (CI). RESULTS: A total of 191 neonates were identified. Of these, 103 (53.9%) were born at ≤ 28 weeks of gestation and 101 (52.9%) had a birth weight of ≤ 1000 g. Eighty-four (44.0%) patients underwent surgical intervention for NEC. The overall survival rate was 161/191 (84.3%). A CRP/ALB ratio of ≥ 3 on day 2 of NEC diagnosis was associated with a statistically significant higher likelihood for surgery [AUC 0.71 (95% CI 0.63-0.79); p < 0.0001] and mortality [AUC 0.66 (95% CI 0.54-0.77); p = 0.0150], respectively. CONCLUSIONS: A CRP/ALB ratio of ≥ 3 on day 2 is indicative of a critical pathway in neonates with radiologically confirmed, non-perforated NEC. This could be used as an additional criterion to guide parental counselling in NEC for surgical intervention and mortality.


Subject(s)
C-Reactive Protein/metabolism , Enterocolitis, Necrotizing/blood , Infant, Newborn, Diseases/blood , Serum Albumin/metabolism , Biomarkers/blood , Birth Weight , Enterocolitis, Necrotizing/mortality , Enterocolitis, Necrotizing/surgery , Female , Humans , Infant , Infant Mortality/trends , Infant, Newborn , Infant, Newborn, Diseases/mortality , Infant, Newborn, Diseases/surgery , Malaysia/epidemiology , Male , Prognosis , ROC Curve , Retrospective Studies , Survival Rate/trends
14.
Int J Hematol ; 113(6): 945-949, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33569741

ABSTRACT

Neonatal alloimmune thrombocytopenia (NAIT) arises from fetomaternal platelet incompatibility that results in transplacental passage of maternal antibodies mostly against fetal human platelet antigens (HPA), whereas NAIT due to anti-human leukocyte antigen (HLA) antibodies is extremely rare. Here, we report a case of Down syndrome (DS) with NAIT that was attributed to HLA antibodies. A boy with DS was delivered at 36 weeks' gestation. His platelet count declined to 13.0 × 109/L, suggestive of NAIT rather than other conditions, including transient abnormal myelopoiesis. Random platelet concentrates and intravenous immunoglobulin administration resolved the thrombocytopenia without clinical complications. Immunoserological investigations detected anti-HLA, but no anti-HPA antibodies in samples from the patient and the mother. HLA typing and cross-matching indicated that anti-HLA antibodies to paternal HLA A31 and B61, which had probably been induced during a prior pregnancy, led to NAIT in this case. Although it is a rare condition, healthcare providers should consider NAIT due to HLA antibodies and be vigilant for subsequent cases in DS.


Subject(s)
Autoantibodies/blood , Down Syndrome/blood , HLA-A Antigens/blood , HLA-B Antigens/blood , Infant, Newborn, Diseases/blood , Purpura, Thrombocytopenic, Idiopathic/blood , Adult , Female , Humans , Infant, Newborn , Male , Purpura, Thrombocytopenic, Idiopathic/congenital
15.
Br J Haematol ; 192(4): 778-784, 2021 02.
Article in English | MEDLINE | ID: mdl-33529380

ABSTRACT

Neonatal alloimmune neutropenia (NAIN) is caused by maternal alloimmunisation to fetal human neutrophil antigens (HNAs). This study investigated maternal HNA/HLA alloantibodies involved with NAIN and identified the frequency of NAIN in Brazilian neonates. Neonatal neutropenia (neutrophil count < 1.5 × 109 /L) was investigated in samples from 10,000 unselected neonates, resulting in 88 neutropenic newborns (NBs) and their 83 mothers. Genotyping was performed by PCR-SSP (HNA-1/-4) and PCR-RFLP (HNA-3/-5). Serologic studies were performed by GAT (granulocyte agglutination test), Flow-WIFT (white blood cells immunofluorescence test) and LABScreen-Multi-HNA-Kit (OneLambda®) (LSM). Neonatal neutropenia was identified in 88/10,000 (0·9%) NBs. Genotyping revealed 60·2% maternal-fetal HNA incompatibilities (31·8% for HNA-1; 14·8% for HNA-3; 15·9% for HNA-4; 21·6% for HNA-5). Serologic studies revealed 37·3% of mothers with positive results with at least one technique. The detected anti-HNA specificities were confirmed in eight positive cases related to HNA-1/-3 systems. In cases with maternal-fetal HNA-4/-5 incompatibility, no specific neutrophil alloantibodies were found but anti-HLA I/II were present. Anti-HNA-2 was not identified. This is a large Brazilian study which involved the investigation of antibodies against all five HNA systems in neutropenia cases and showed a frequency of NAIN in 8/10,000 neonates. Among the HNA antibodies identified, we highlight the anti-HNA-1d and anti-HNA-3b, antibodies unusual in alloimmunised women, and rarely related to NAIN cases.


Subject(s)
Infant, Newborn, Diseases/diagnosis , Neutropenia/diagnosis , Brazil/epidemiology , Female , Genotype , Humans , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/epidemiology , Infant, Newborn, Diseases/genetics , Isoantibodies/blood , Isoantibodies/genetics , Isoantibodies/immunology , Leukocyte Count , Male , Neutropenia/blood , Neutropenia/epidemiology , Neutropenia/genetics , Neutrophils/immunology
16.
J Mol Diagn ; 23(4): 389-398, 2021 04.
Article in English | MEDLINE | ID: mdl-33387697

ABSTRACT

Vertical transmission of Trypanosomacruzi is the cause of congenital Chagas disease, a re-emerging infectious disease that affects endemic and nonendemic regions alike. An early diagnosis is crucial because prompt treatment achieves a high cure rate, precluding evolution to symptomatic chronic Chagas disease. However, early diagnosis involves low-sensitive parasitologic assays, making necessary serologic confirmation after 9 months of life. With the aim of implementing early diagnostic strategies suitable for minimally equipped laboratories, a T. cruzi-loop-mediated isothermal amplification (LAMP) prototype was coupled with an automated DNA-extraction device repurposed from a three-dimensional printer (PrintrLab). The whole process takes <3 hours to yield a result, with an analytical sensitivity of 0.1 to 2 parasite equivalents per milliliter, depending on the T. cruzi strain. Twenty-five blood samples from neonates born to seropositive mothers were tested blindly. In comparison to quantitative real-time PCR, the PrintrLab-LAMP dual strategy showed high agreement, while both molecular-based methodologies yielded optimal sensitivity and specificity with respect to microscopy-based diagnosis of congenital Chagas disease. PrintrLab-LAMP detected all 10 congenitally transmitted T. cruzi infections, showing promise for point-of-care early diagnosis of congenital Chagas disease.


Subject(s)
Chagas Disease/diagnosis , Chagas Disease/transmission , DNA, Protozoan/genetics , DNA, Protozoan/isolation & purification , Endemic Diseases , Infant, Newborn, Diseases/diagnosis , Infectious Disease Transmission, Vertical , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Point-of-Care Systems , Trypanosoma cruzi/genetics , Bolivia/epidemiology , Chagas Disease/epidemiology , Chagas Disease/parasitology , DNA, Protozoan/blood , Diagnostic Tests, Routine/methods , Early Diagnosis , Female , Humans , Infant , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/epidemiology , Infant, Newborn, Diseases/parasitology , Real-Time Polymerase Chain Reaction/methods , Sensitivity and Specificity
17.
Eur Rev Med Pharmacol Sci ; 25(1): 215-221, 2021 01.
Article in English | MEDLINE | ID: mdl-33506910

ABSTRACT

OBJECTIVE: To investigate the clinical efficacy of combination of mouse nerve growth factor (NGF) and nimodipine in the treatment of neonatal intracranial hemorrhage (NICH) and its effect on plasma platelet-activating factor (PAF), C-type natriuretic peptide (CNP), matrix metalloproteinase-2 (MMP-2), and neurological function. PATIENTS AND METHODS: A total of 90 infants with severe ICH admitted to our hospital from December 2016 to December 2018 were enrolled for retrospective study. According to different treatment schemes, they were assigned into 2 groups: group A (n=40) treated with mouse NGF plus nimodipine; group B (n=50) treated with nimodipine. The recovery time, serum indexes (PAF, MMP-2, CNP), neurological function (neonatal behavioral neurological assessment (NBNA) score), complications, and total effective rate of patients were recorded, and the satisfaction degree of family members was statistically analyzed. RESULTS: Patients in group A showed shorter recovery time, down-regulated PAF and MMP-2, evidently up-regulated CNP, and significantly increased NBNA score after one/two weeks of treatment, as well as fewer complications, higher total effective rate and higher satisfaction of family members. CONCLUSIONS: To sum up, the combination of mouse NGF and nimodipine achieves good clinical efficacy in NICH, which down-regulates plasma PAF and MMP-2, up-regulates CNP, and improves neurological function. Therefore, it is suitable for clinical promotion.


Subject(s)
Infant, Newborn, Diseases/drug therapy , Intracranial Hemorrhages/drug therapy , Nerve Growth Factor/pharmacology , Nimodipine/pharmacology , Animals , Humans , Infant, Newborn , Infant, Newborn, Diseases/blood , Injections, Intramuscular , Intracranial Hemorrhages/blood , Matrix Metalloproteinase 2/blood , Matrix Metalloproteinase 2/metabolism , Mice , Natriuretic Peptide, C-Type/blood , Natriuretic Peptide, C-Type/metabolism , Nerve Growth Factor/administration & dosage , Nimodipine/administration & dosage , Platelet Activating Factor/metabolism , Retrospective Studies
18.
Am J Perinatol ; 38(S 01): e21-e25, 2021 08.
Article in English | MEDLINE | ID: mdl-32120421

ABSTRACT

OBJECTIVE: This study examined patterns of care after birth in newborns treated with therapeutic hypothermia to identify remediable causes for the poorer outcomes observed in outborn infants. STUDY DESIGN: This was a secondary analysis of 150 newborns (68 outborn) prospectively enrolled at our center in the Vermont Oxford Neonatal Encephalopathy Registry from January 2008 to October 2016. RESULTS: The 5-minute Apgar's score and cord pH value did not differ, but cord blood gases were obtained far less frequently in outborns (p = 0.002). Outborns needed more chest compressions (p = 0.01) and epinephrine (p = 0.04), and had more brain injury on neuroimaging (p = 0.05). Outborns took longer to reach target hypothermia temperature (p < 0.0001). CONCLUSION: The lack of cord gas values and longer time to reach target temperature observed in the outborns are two observed differences in care that can be potentially remedied by providing education and resources at delivering hospitals in rapid identification of hypothermia candidates, though further research is needed to define the effects of such measures. Possible solutions are also discussed here.


Subject(s)
Hypothermia, Induced , Hypoxia-Ischemia, Brain/therapy , Patient Transfer , Apgar Score , Body Temperature , California , Fetal Blood/chemistry , Humans , Hypoxia-Ischemia, Brain/blood , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/therapy , Intensive Care Units, Neonatal , Prospective Studies , Registries , Secondary Care Centers , Time-to-Treatment
19.
Pediatr Res ; 89(5): 1087-1093, 2021 04.
Article in English | MEDLINE | ID: mdl-32601461

ABSTRACT

Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants and is a leading cause of morbidity and mortality in infants born between 23 and 28 weeks of gestation. Fifty to 95% of all infants with NEC develop thrombocytopenia (platelet counts <150 × 109/L) within 24-72 h of receiving this diagnosis. In many patients, thrombocytopenia is severe and is treated with one or more platelet transfusions. However, the underlying mechanism(s) and biological implications of NEC-related thrombocytopenia remain unclear. This review presents current evidence from human and animal studies on the clinical features and mechanisms of platelet depletion in NEC. Anecdotal clinical experience is combined with evidence from laboratory studies and from an extensive literature search in databases PubMed, EMBASE, and Scopus and the electronic archives of abstracts presented at the annual meetings of the Pediatric Academic Societies. To avoid bias in identification of existing studies, key words were short-listed prior to the actual search both from anecdotal experience and from PubMed's Medical Subject Heading (MeSH) thesaurus. IMPACT: Fifty to 95% of infants with necrotizing enterocolitis (NEC) develop idiopathic thrombocytopenia (platelet counts <150 × 109/L) within 24-72 h of disease onset. Early clinical trials suggest that moderate thrombocytopenia may be protective in human NEC, although further work is needed to fully understand this relationship. We have developed a neonatal murine model of NEC-related thrombocytopenia, where enteral administration of an immunological stimulant, trinitrobenzene sulfonate, on postnatal day 10 induces an acute necrotizing ileocolitis resembling human NEC. In this murine model, thrombocytopenia is seen at 15-18 h due to platelet consumption and mild-moderate thrombocytopenia is protective.


Subject(s)
Blood Platelets/physiology , Enterocolitis, Necrotizing/blood , Thrombocytopenia/etiology , Animals , Blood Platelets/drug effects , Enterocolitis, Necrotizing/complications , Humans , Infant, Newborn , Infant, Newborn, Diseases/blood , Mice , Platelet Activation , Platelet Transfusion , Thrombin/pharmacology , Thrombocytopenia/therapy
20.
J Stroke Cerebrovasc Dis ; 30(3): 105553, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33360521

ABSTRACT

OBJECTIVE: This study is to investigate the role of microRNA (miR)-30b in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonates. METHODS: Totally 26 cases of neonatal HIE were included in this study. The protein expression levels of CD26P and PAI-1 were detected with ELISA. Serum levels of miR-30b and PAI-1 mRNA was measured by quantitative real-time PCR. Human brain microvascular endothelial cells (HBMECs) were cultured under hypoxic condition, and the intracellular expression levels of miR-30b and PAI-1 were evaluated. Dual-luciferase reporter assay was performed to confirm the interaction between miR-30b and PAI-1. RESULTS: Compared with the control group, both the mRNA and protein expression levels of PAI-1 in the serum were up-regulated in the neonates with HIE, together with up-regulated serum CD26P levels. However, the serum expression level of miR-30b was down-regulated in neonatal HIE. In hypoxia-induced HBMECs, the mRNA and protein expression levels of PAI-1 were significantly up-regulated, while the miR-30b expression level was significantly down-regulated. Dual-luciferase reporter assay showed that PAI-1 was the direct target of miR-30b. CONCLUSION: Neonatal HIE is accompanied with abnormal platelet activation, significantly up-regulated serum PAI-1 expression levels, and down-regulated miR-30b expression. MiR-30b might regulate the disease pathogenesis and immune responses via modulating PAI-1.


Subject(s)
Brain/blood supply , Endothelial Cells/metabolism , Hypoxia-Ischemia, Brain/blood , Infant, Newborn, Diseases/blood , MicroRNAs/blood , Biomarkers/blood , Case-Control Studies , Cell Hypoxia , Cells, Cultured , Female , Gene Expression Regulation , Humans , Hypoxia-Ischemia, Brain/genetics , Infant, Newborn , Infant, Newborn, Diseases/genetics , Male , MicroRNAs/genetics , P-Selectin/blood , Plasminogen Activator Inhibitor 1/blood , Plasminogen Activator Inhibitor 1/genetics
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