ABSTRACT
Thousands of genetic variants in protein-coding genes have been linked to disease. However, the functional impact of most variants is unknown as they occur within intrinsically disordered protein regions that have poorly defined functions1-3. Intrinsically disordered regions can mediate phase separation and the formation of biomolecular condensates, such as the nucleolus4,5. This suggests that mutations in disordered proteins may alter condensate properties and function6-8. Here we show that a subset of disease-associated variants in disordered regions alter phase separation, cause mispartitioning into the nucleolus and disrupt nucleolar function. We discover de novo frameshift variants in HMGB1 that cause brachyphalangy, polydactyly and tibial aplasia syndrome, a rare complex malformation syndrome. The frameshifts replace the intrinsically disordered acidic tail of HMGB1 with an arginine-rich basic tail. The mutant tail alters HMGB1 phase separation, enhances its partitioning into the nucleolus and causes nucleolar dysfunction. We built a catalogue of more than 200,000 variants in disordered carboxy-terminal tails and identified more than 600 frameshifts that create arginine-rich basic tails in transcription factors and other proteins. For 12 out of the 13 disease-associated variants tested, the mutation enhanced partitioning into the nucleolus, and several variants altered rRNA biogenesis. These data identify the cause of a rare complex syndrome and suggest that a large number of genetic variants may dysregulate nucleoli and other biomolecular condensates in humans.
Subject(s)
Cell Nucleolus , HMGB1 Protein , Humans , Arginine/genetics , Arginine/metabolism , Cell Nucleolus/genetics , Cell Nucleolus/metabolism , Cell Nucleolus/pathology , HMGB1 Protein/chemistry , HMGB1 Protein/genetics , HMGB1 Protein/metabolism , Intrinsically Disordered Proteins/chemistry , Intrinsically Disordered Proteins/genetics , Intrinsically Disordered Proteins/metabolism , Syndrome , Frameshift Mutation , Phase TransitionABSTRACT
BACKGROUND: Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects of TNF blockade on short- and long-term immune responses after repeated vaccination remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated and sialylated Fc glycans, whilst long-term IgG Abs have low levels of galactosylation and sialylation and are most likely generated by long-lived plasma cells (PCs) derived primarily from the germinal center (GC) response. Thus, IgG Fc glycosylation patterns may be applicable to distinguish short- and long-term vaccine responses after repeated vaccination under the influence of anti-TNF treatment. METHODS: We used COVID-19 vaccination as a model to investigate vaccine-induced IgG subclass levels and Fc glycosylation patterns, B cell subsets, and effector functions of short- and long-term Ab responses after up to three vaccinations in patients on anti-TNF or other immunosuppressive treatments and in healthy individuals. Using TriNetX, a global healthcare database, we determined the risk of SARS-CoV-2 breakthrough infections in vaccinated patients treated with anti-TNF or other immunosuppressive drugs. RESULTS: Anti-TNF treatment reduced the long-term abundance of all anti-S IgG subclasses with low levels of galactosylation and sialylation. Re-activation of potential memory B cells initially generated highly galactosylated and sialylated IgG antibodies, which were progressively reduced after each booster dose in anti-TNF-treated patients, especially in the elderly. The reduced short- and long-term IgG (1) levels in anti-TNF-treated patients correlated with diminished functional activity and an increased risk for the development of COVID-19. CONCLUSIONS: The data suggest that anti-TNF treatment reduces both GC-dependent long-lived PCs and GC-dependent memory B cell-derived short-lived PCs, hence both the long- and short-term IgG subclass responses, respectively, after repeated vaccination. We propose that anti-TNF therapy, especially in the elderly, reduces the benefit of booster vaccination.
ABSTRACT
The analysis of CRONOS data for this article presents the infection prevalence among parturients and subsequent changes in obstetric management over time in Germany. 2,184 women with peripartum SARS-CoV-2 infection (<14d before birth) were included. Monthly period prevalence was calculated using the number of affected women on the CRONOS registry relative to total monthly births in each hospital from March 2020 to May 2022 and compared to RKI data. Trends related to changes in obstetric management were calculated based on severity of illness. By June 2021, the obstetric population shows a discretely higher infection prevalence compared to the general population, falling below the RKI reported prevalence by October 2021. The overall rate of iatrogenic deliveries remains unchanged over time (p-value for trend=0.779). During wave 1 to 4, deliveries due to SARS-CoV-2 infection rose among moderately to severely ill women (p-value for trend 0.0000) and was increased compared to moderately ill women (p=0.001). We showed that comprehensive screening provides timely information on infection prevalence. Recruitment fatigue caused by higher clinician workload due to increased admissions and more cases with severe illness probably caused reduced prevalence reporting. Changes in obstetric management were related to COVID-19 symptom severity. A comprehensive national perinatal registry is needed to examine other areas of perinatal care in Germany.
Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Pregnancy , Humans , Female , COVID-19/epidemiology , SARS-CoV-2 , Prevalence , Peripartum Period , Pandemics , Routinely Collected Health Data , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiologyABSTRACT
SARS-CoV-2 infection and COVID-19 disease are thought to have an impact on breastfeeding rate - besides other known peripartal issues. Data of the national CRONOS registry regarding breastfeeding behavior in 6,746 women was analyzed regarding the time window between maternal SARS-CoV-2 infection and time of delivery. In addition, other influencing factors like the predominant viral variant, maternal disease severity, and gestational age at delivery were taken into account. Our data suggest that within the variables analyzed, in the case of acute maternal infection (<14 days before birth), breastfeeding behavior improved with increasing gestational age at birth (p<0.0001), with less severe maternal illness (p<0.0001) and as the pandemic progressed with less virulent viral variants (p=0.01). When adjusting for COVID-19-associated and non-associated factors, rooming-in remains the most important factor positively influencing breastfeeding behavior. With regards to the benefits for mother and infants from breastfeeding, a separation of mother and child even in case of infectious settings should be avoided.
Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Infant , Infant, Newborn , Child , Female , Humans , Pregnancy , Breast Feeding , Pandemics , SARS-CoV-2 , Mothers , Pregnancy Complications, Infectious/epidemiologyABSTRACT
The humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients with chronic inflammatory disease (CID) declines more rapidly with tumor necrosis factor-α (TNF-α) inhibition. Furthermore, the efficacy of current vaccines against Omicron variants of concern (VOC) including BA.2 is limited. Alterations within immune cell populations, changes in IgG affinity, and the ability to neutralize a pre-VOC strain and the BA.2 virus were investigated in these at-risk patients. Serum levels of anti-SARS-CoV-2 IgG, IgG avidity, and neutralizing antibodies (NA) were determined in anti-TNF-α patients (n = 10) and controls (n = 24 healthy individuals; n = 12 patients under other disease-modifying antirheumatic drugs, oDMARD) before and after the second and third vaccination by ELISA, immunoblot and live virus neutralization assay. SARS-CoV-2-specific B- and T cell subsets were analysed by multicolor flow cytometry. Six months after the second vaccination, anti-SARS-CoV-2 IgG levels, IgG avidity and anti-pre-VOC NA titres were significantly reduced in anti-TNF-α recipients compared to controls (healthy individuals: avidity: p ≤ 0.0001; NA: p = 0.0347; oDMARDs: avidity: p = 0.0012; NA: p = 0.0293). The number of plasma cells was increased in anti-TNF-α patients (Healthy individuals: p = 0.0344; oDMARDs: p = 0.0254), while the absolute number of SARS-CoV-2-specific plasma cells 7 days after 2nd vaccination were comparable. Even after a third vaccination, these patients had lower anti-BA.2 NA titres compared to both other groups. We show a reduced SARS-CoV-2 neutralizing capacity in patients under TNF-α blockade. In this cohort, the plasma cell response appears to be less specific and shows stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were enhanced.
Subject(s)
AIDS Vaccines , Antirheumatic Agents , COVID-19 , Influenza Vaccines , Papillomavirus Vaccines , Respiratory Syncytial Virus Vaccines , SAIDS Vaccines , Antibodies, Neutralizing , Antibodies, Viral , BCG Vaccine , COVID-19/prevention & control , Diphtheria-Tetanus Vaccine , Diphtheria-Tetanus-Pertussis Vaccine , Humans , Immunity , Immunoglobulin G , Measles-Mumps-Rubella Vaccine , SARS-CoV-2 , Tumor Necrosis Factor Inhibitors , Tumor Necrosis Factor-alpha , VaccinationABSTRACT
BACKGROUND: Medical simulation training requires realistic simulators with high fidelity. This prospective multi-center study investigated anatomic precision, physiologic characteristics, and fidelity of four commercially available very low birth weight infant simulators. METHODS: We measured airway angles and distances in the simulators Premature AirwayPaul (SIMCharacters), Premature Anne (Laerdal Medical), Premie HAL S2209 (Gaumard), and Preterm Baby (Lifecast Body Simulation) using computer tomography and compared these to human cadavers of premature stillbirths. The simulators' physiologic characteristics were tested, and highly experienced experts rated their physical and functional fidelity. RESULTS: The airway angles corresponded to those of the reference cadavers in three simulators. The nasal inlet to glottis distance and the mouth aperture to glottis distance were only accurate in one simulator. All simulators had airway resistances up to 20 times higher and compliances up to 19 times lower than published reference values. Fifty-six highly experienced experts gave three simulators (Premature AirwayPaul: 5.1 ± 1.0, Premature Anne 4.9 ± 1.1, Preterm Baby 5.0 ± 1.0) good overall ratings and one simulator (Premie HAL S2209: 2.8 ± 1.0) an unfavorable rating. CONCLUSION: The simulator physiology deviated significantly from preterm infants' reference values concerning resistance and compliance, potentially promoting a wrong ventilation technique. IMPACT: Very low birth weight infant simulators showed physiological properties far deviating from corresponding patient reference values. Only ventilation with very high peak pressure achieved tidal volumes in the simulators, as aimed at in very low birth weight infants, potentially promoting a wrong ventilation technique. Compared to very low birth weight infant cadavers, most tested simulators accurately reproduced the anatomic angular relationships, but their airway dimensions were relatively too large for the represented body. The more professional experience the experts had, the lower they rated the very low birth weight infant simulators.
Subject(s)
Infant, Premature , Simulation Training , Cadaver , Humans , Infant , Infant, Newborn , Infant, Very Low Birth Weight , Prospective Studies , Simulation Training/methodsABSTRACT
In orally fed preterm infants, poor weight gain may be linked to low fecal pancreatic elastase-1 (FPE-1) activity, indicative of exocrine pancreatic insufficiency. The objective of this study was the retrospective assessment of the effect of exogenous digestive enzyme replacement by gavage in preterm infants with growth failure and low FPE-1 (<200 µg/g). We analyzed weight gain relative to baseline and caloric intake during 14-day periods before and after institution of digestive enzyme replacement containing 6000 U lipase and 240 U protease kg-1 d-1. Among 46 of 132 preterm infants < 1250g birth weight surviving to at least 14 days in whom FPE-1 was determined, 38 infants had low FPE-1 (< 200 µg/g), and 33 infants received exogenous digestive enzyme replacement. Average daily weight gain significantly increased from 14.4 [range 2.6-22.4] g kg-1 d-1 to 17.4 [8.4-29.0] g kg-1 d-1 (P = 0.001), as did weight gain per kcal, from 0.08 [0.02-0.13] g kcal-1 d-1 to 0.11 [0.05-0.18] g kcal-1 d-1.Conclusion: In preterm infants with signs and symptoms of exocrine pancreatic insufficiency, exogenous digestive enzyme replacement is associated with improved growth. What is Known: ⢠Very preterm infants on full enteral nutrition may display growth failure linked to transient poor exocrine pancreatic function. ⢠Porcine pancreatic enzymes covered with an acid-resistant coating are too large to pass the internal diameter of most gavage tubes used in very preterm infants. What is New: ⢠Administration of a liquid formulation of acid-resistant microbial digestive enzymes in preterm infants with growth failure and low fecal pancreatic elastase-1 values was associated with improved weight gain. ⢠Response to exogenous digestive enzyme replacement was associated with the prior extent of growth failure.
Subject(s)
Exocrine Pancreatic Insufficiency , Infant, Premature , Animals , Enteral Nutrition , Exocrine Pancreatic Insufficiency/drug therapy , Humans , Infant , Infant, Newborn , Infant, Very Low Birth Weight , Retrospective Studies , SwineABSTRACT
BACKGROUND: The extensive use of antibiotics is reflected by an increasing prevalence of infections with multidrug-resistant bacteria, including third-generation cephalosporin-resistant bacteria (3GCRB). For neonatal intensive care units screening and enhanced barrier precautions are recommended to control the spread of multidrug-resistant Gram-negative bacteria, while evidence for efficacy of barrier precautions remains scarce in a non-outbreak setting. OBJECTIVE: To determine the impact of a screening program for maternal 3GCRB colonization and the effects of contact precautions and cohort nursing, concerning the risk of neonatal late-onset sepsis (LOS) and antibiotic use rates (AURs). STUDY DESIGN: In a retrospective matched-pair cohort study, data of neonates exposed to maternal 3GCRB colonization were compared with findings in non-exposed neonates. RESULTS: Of 3,144 neonates admitted, 184 neonates born to 3GCRB-positive mothers were eligible. Among them, 37 (20%) became 3GCRB positive during hospital stay. 3GCRB-exposed infants had a lower rate of LOS (6.5 vs. 14.1%, p=0.03) and lower AURs in that time period compared to controls (mean 0.009 vs. 0.025, p=0.006). When started within the first 72h after birth, days of therapy with meropenem were significantly lower in non-exposed vs. 3GCRB-exposed infants (mean 0.13 vs. 0.42; p=0.002). No invasive infections with 3GCRB occurred. CONCLUSIONS: Neonates of 3GCRB-positive mothers do not have an increased a priori risk for invasive 3GCRB infection and may benefit from enhanced contact precautions measures. HINTERGRUND: Der zunehmende Einsatz von Antibiotika führt zu einem Anstieg von Infektionen mit multiresistenten Erregern wie z. B. Drittgeneration Cephalosporin-resistenten Bakterien (3GCRB). Empfehlungen zu Screening- und Kohortierungsmaßnahmen auf neonatologischen Intensivstationen zielen auf die Prävention von horizontaler Transmission und invasiven Infektionen ab. Für Nicht-Ausbruchssituationen ist die Evidenz für Hygienemaßnahmen und Screeningprogrammen unzureichend. ZIEL: Evaluation eines Screening für mütterliche 3GCRB-Besiedlung mit nachfolgender Isolation bzw. Kohortenpflege des Neugeborenen (NG) unter Bezug auf das Risiko einer Late-Onset-Sepsis (LOS) und die Anzahl der Antibiotika-Tage (AUR). STUDIENDESIGN: In einer retrospektiven Fall-Kontroll-Kohortenstudie wurden Daten von NG mit maternaler 3GCRB-Besiedelung im Vergleich zu einer Kontrollgruppe mit unauffälligem Screening analysiert. ERGEBNISSE: In einer Kohorte von 3144 NG fanden sich 184 NG von 3GCRB-besiedelten Müttern. Bei 37 (20%) wurde im Verlauf eine Besiedelung mit 3GCRB nachgewiesen. In der Gruppe der 3GCRB-exponierten NG kam es seltener zu einer LOS (6,5 vs. 14,1%, p=0,03). Zwischen dem 4. Lebenstag und der Entlassung hatten 3GCRB-exponierte NG eine niedrigere AUR (Mittelwert 0,009 vs. 0,025, p=0,006) als die Kontrollgruppe. Die Behandlungstage mit Meropenem (Start in den ersten 3 Lebenstagen), war in der Kontrollgruppe signifikant geringer als in der 3GCRB-exponierten Gruppe (Mittelwert 0,13 vs. 0,43 Tage; p=0,002). In beiden Gruppen trat keine invasive Infektion mit 3GCRB auf. SCHLUSSFOLGERUNG: Neugeborene, deren Mütter 3GCRB besiedelt sind, haben kein erhöhtes a priori Risiko für eine invasive Infektion mit 3GCRB Erregern und profitieren wahrscheinlich von erweiterten Kohortierungs- und Isolationsmaßnahmen.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cephalosporins/pharmacology , Drug Resistance, Bacterial , Sepsis/drug therapy , Bacteria/drug effects , Humans , Incidence , Infant, Newborn , Retrospective StudiesABSTRACT
The novel coronavirus SARS-CoV-2 has developed into a pandemic, yet still has many unknowns. The modalities of transmission, different symptoms and manifestations as well as concomitant circumstances of the disease are insufficiently characterized. Especially patient groups in special situations like pregnant women and newborns have to be considered separately. The current knowledge about pregnancy, labor and the first days of life is characterized by particular uncertainty due to the scarce data available. However, there is currently no evidence of significant unfavorable maternal and perinatal outcome. Many pregnant women with SARS-CoV-2 infection remain asymptomatic. The possibility of vertical transmission to the child cannot be excluded with certainty. However, indications of vertical transmission were detected only in individual cases. Newborn infections are also rather rare, unspecific and usually mild, with respiratory symptoms dominating. In this article, the data available to date are examined in order to provide better information, advice and treatment for pregnant women and newborns with SARS-CoV-2 and to provide suggestions for future research.
Subject(s)
Coronavirus Infections/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Pandemics , Perinatal Care , Pneumonia, Viral/prevention & control , Pregnancy Complications, Infectious/virology , Betacoronavirus , COVID-19 , Child , Coronavirus Infections/epidemiology , Female , Humans , Infant, Newborn , Pneumonia, Viral/epidemiology , Pregnancy , SARS-CoV-2ABSTRACT
Gordon syndrome or distal arthrogryposis type 3 is a rare autosomal dominant disorder characterized by contractures of upper and lower limbs. It is distinguishable from other forms of distal arthrogryposis by cleft palate and short stature. Recently, Gordon syndrome has been associated to heterozygous mutations in the piezo-type mechanosensitive ion channel component 2 gene (PIEZO2). Different mutations of this gene also cause distal arthrogryposis type 5 and Marden-Walker syndrome. Dysfunction of this ion channel provides pleiotropic effects on joints, ocular muscles, and bone development. Here, we present a family with three affected individuals exhibiting multiple contractures (metacarpo-phalangeal and interphalangeal joints as well as elbow, shoulder, knee, and ankle joints), clubfeet, short stature, bifid uvula/cleft palate, and a distinct facial phenotype including ptosis. In addition, mild intellectual disability and delay in psychomotor development are obvious. The multigenerational phenotypic spectrum of Gordon syndrome is present in the 37-year-old father, his 4-year-old son and a male neonate showing typical signs of arthrogryposis in the prenatal ultrasound examination already seen at 13 week of gestation. In all affected family members, we identified the PIEZO2 mutation c.8057G>A (p.Arg2686His) by Sanger sequencing. Our analysis indicated that mild delay in psychomotor development and intellectual disability could be part of the phenotypic spectrum of Gordon syndrome. © 2016 Wiley Periodicals, Inc.
Subject(s)
Arthrogryposis/diagnosis , Arthrogryposis/genetics , Cleft Palate/diagnosis , Cleft Palate/genetics , Clubfoot/diagnosis , Clubfoot/genetics , Genetic Association Studies , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/genetics , Ion Channels/genetics , Mutation , Adult , Alleles , Amino Acid Substitution , Child, Preschool , Codon , Comparative Genomic Hybridization , DNA Mutational Analysis , Exons , Facies , Genotype , Humans , Infant, Newborn , Male , Pedigree , Phenotype , Ultrasonography, PrenatalABSTRACT
UNLABELLED: Despite high-dose vitamin A supplementation of very low birth weight infants (VLBW, <1500 g), their vitamin A status does not improve substantially. Unknown is the impact of urinary retinol excretion on the serum retinol concentration in these infants. Therefore, the effect of high-dose vitamin A supplementation on the urinary vitamin A excretion in VLBW infants was investigated. Sixty-three VLBW infants were treated with vitamin A (5000 IU intramuscular, 3 times/week for 4 weeks); 38 untreated infants were classified as control group. On days 3 and 28 of life, retinol, retinol-binding protein 4 (RBP4), glomerular filtration rate, proteinuria, and Tamm-Horsfall protein were quantified in urine. On day 3 of life, substantial retinol and RBP4 losses were found in both groups, which significantly decreased until day 28. Notwithstanding, the retinol excretion was higher (P < 0.01) under vitamin A supplementation as compared to infants of the control group. On day 28 of life, the urinary retinol concentrations were predictive for serum retinol concentrations in the vitamin A treated (P < 0.01), but not in the control group (P = 0.570). CONCLUSION: High urinary retinol excretion may limit the vitamin A supplementation efficacy in VLBW infants. Advanced age and thus postnatal kidney maturation seems to be an important contributor in the prevention of urinary retinol losses.
Subject(s)
Infant, Very Low Birth Weight/urine , Retinol-Binding Proteins/urine , Vitamin A/administration & dosage , Vitamins/administration & dosage , Dietary Supplements , Glomerular Filtration Rate , Humans , Infant, Newborn , Proteinuria , Regression Analysis , Vitamin A/urine , Vitamins/urineABSTRACT
Fetal cardiac tumors are a rare finding in prenatal ultrasonography. Most of them are rhabdomyoma, which are thought to be pathognomonic for tuberous sclerosis complex. We present an infant with prenatally diagnosed cardiac rhabdomyoma (CR), who was found to suffer from Beckwith-Wiedemann syndrome (BWS). This congenital overgrowth syndrome is characterized by macrosomia, macroglossia, omphalocele, hypoglycemia, and hemihypertrophy. BWS patients have an increased risk for formation of benign and malignant tumors, typically intra-abdominally located, but, to the best of our knowledge, fetal CRs have not been reported before. BWS must be added to the list of differential diagnoses and to the prenatal counseling of the parents in cases of prenatal detection of CR.
Subject(s)
Beckwith-Wiedemann Syndrome/complications , Fetal Diseases/diagnostic imaging , Fetal Heart/diagnostic imaging , Heart Neoplasms/diagnostic imaging , Rhabdomyoma/diagnostic imaging , Ultrasonography, Prenatal/methods , Adolescent , Diagnosis, Differential , Female , Heart Neoplasms/complications , Heart Neoplasms/embryology , Humans , Male , Pregnancy , Rhabdomyoma/complications , Rhabdomyoma/embryologyABSTRACT
INTRODUCTION: The management of a pregnancy in a bicornuate uterus is particularly challenging. A bicornuate uterus is a rare occurrence and a twin pregnancy in a bicornuate uterus even more rare. These pregnancies call for intensive diagnostic investigation and interdisciplinary care. CASE PRESENTATION: We report on a 27-year-old European woman patient (gravida I, para 0) with a simultaneous pregnancy in each cavity of a bicornuate bicollis uterus after embryo transfer. The condition was confirmed by hysteroscopy and laparoscopy. Several unsuccessful in vitro fertilization (IVF) attempts had been performed earlier before embryo transfer in each cornus. After a physiological course of pregnancy with differential screening at 12 + 6 weeks and 22 + 0 weeks of gestation, the patient presented with therapy-resistant contractions at 27 + 2 weeks. This culminated in the uncomplicated spontaneous delivery of the leading fetus and delayed spontaneous delivery of the second fetus. DISCUSSION: Only 16 cases of twin pregnancy in a bicornuate unicollis uterus have been reported worldwide and only 6 in a bicornuate bicollis uterus. The principal risks in such pregnancies are preterm labor, intrauterine growth restriction, malpresentation and preeclampsia. These typical risk factors of a twin pregnancy are greatly potentiated in the above mentioned setting. CONCLUSION: A twin pregnancy in the presence of a uterine malformation is rare and difficult to manage. These rare cases must be collected and reported in order to work out algorithms of monitoring and therapy as well as issue appropriate recommendations for their management.
Subject(s)
Bicornuate Uterus , Pregnancy , Female , Infant, Newborn , Humans , Adult , Pregnancy, Twin , Uterus/diagnostic imaging , Uterus/abnormalities , Twins , HysteroscopyABSTRACT
Introduction Awareness of SARS-CoV-2 infection in pregnant women and the potential risk for infection of their neonates is increasing. The aim of this study was to examine the immune status of affected women and evaluate the dynamics of placental antibody transfer. Materials and Methods The study included 176 women with SARS-CoV-2 infection during pregnancy who delivered between April 2020 and December 2021 at eight obstetric maternity sites. Demographic data, maternal and neonatal characteristics were summarized. Antibody testing for IgA and IgG in maternal blood sera and umbilical cord samples was evaluated and IgG transfer ratios were calculated. Values were related to the time of infection during pregnancy and birth. Results The percentage of IgG positive women increased from 29.0% (95% CI 23.8â-â37.8) at presentation with a positive PCR test result to 75.7% (95% CI 71.6â-â79.8), the percentage of IgG positive umbilical cord blood samples increased from 17.1% (95% CI 13.0â-â21.3) to 76.4% (95% CI 72.2â-â80.7) at more than six weeks after infection. Regression lines differed significantly between maternal and fetal IgG responses (p < 0.0001). Newborns react with a latency of about one week; umbilical cord blood antibody concentrations are highly correlated with maternal concentration levels (ρ = 0.8042; p < 0.0001). IgG transplacental transfer ratios were dependent on infection-to-birth interval. Two of the umbilical cord blood samples tested positive for IgA. Conclusions These findings confirm vertical SARS-CoV-2 transmission is rare; however, antibodies are transferred to the fetus soon after infection during pregnancy. Since transplacental antibody transfer might have a protective value for neonatal immunization this information may be helpful when counseling affected women.
ABSTRACT
BACKGROUND: Milk curd obstruction as a cause of intestinal obstruction has been known since 1959, but has nearly disappeared. However, in recent years it has experienced a revival in small premature infants. OBJECTIVE: The aim of this study was to evaluate the clinical characteristics of milk curd obstruction (lactobezoar) in preterm infants. METHODS: Data of preterm infants with milk curd obstruction cared for at a large tertiary neonatal intensive care unit between 2012 and 2016 were retrieved from the electronic registry and paper records. RESULTS: A total of 10 infants (2 girls, 8 boys) were identified: the median birth weight was 595 g (range 270-922), gestational age was 24.4 weeks (23.4-27.0), weight-for-gestational age percentile was 16 (0-62), and age at diagnosis was 28 days (16-64). Five infants (50%) were small for gestational age. All neonates had received fortified human milk (added protein 2.0 g/100 mL, range 0-2.8; added calcium 2,400 µmol/100 mL, range 0-6 844; added phosphate 2,400 µmol/100 mL, range 0-5,178). Seven neonates underwent surgery, and 2 infants died. Hyperechoic masses in extended bowel loops, visualised by abdominal ultrasound, and pale/acholic faeces were hallmarks of milk curd obstruction. CONCLUSIONS: In this study, milk curd obstruction occurred exclusively in infants with a birth weight < 1,000 g (2.2%) and < 28 weeks' gestational age (2.4%). Male and small for gestational age infants appeared to be at increased risk. Paying attention to the colour of the faeces of infants at risk might help to diagnose milk curd obstruction at an early stage.
Subject(s)
Food, Fortified/adverse effects , Intestinal Obstruction/etiology , Milk, Human , Perinatal Death/etiology , Birth Weight , Female , Gestational Age , Humans , Infant, Extremely Low Birth Weight , Infant, Extremely Premature , Infant, Newborn , Intestinal Obstruction/diagnosis , Intestinal Obstruction/surgery , MaleSubject(s)
COVID-19 , Pregnancy Complications, Infectious , Premature Birth , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Outcome Assessment, Health Care , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome/epidemiology , SARS-CoV-2ABSTRACT
BACKGROUND: The relative dose response (RDR) test, which quantifies the increase in serum retinol after vitamin A administration, is a qualitative measure of liver vitamin A stores. Particularly in preterm infants, the feasibility of the RDR test involving blood is critically dependent on small sample volumes. OBJECTIVES: This study aimed to assess whether the RDR calculated with retinol-binding protein 4 (RBP4) might be a substitute for the classical retinol-based RDR test for assessing vitamin A status in very preterm infants. METHODS: This study included preterm infants with a birth weight below 1,500 g (n = 63, median birth weight 985 g, median gestational age 27.4 weeks) who were treated with 5,000 IU retinyl palmitate intramuscularly 3 times a week for 4 weeks. On day 3 (first vitamin A injection) and day 28 of life (last vitamin A injection), the RDR was calculated and compared using serum retinol and RBP4 concentrations. RESULTS: The concentrations of retinol (p < 0.001) and RBP4 (p < 0.01) increased significantly from day 3 to day 28. On day 3, the median (IQR) retinol-RDR was 27% (8.4-42.5) and the median RBP4-RDR was 8.4% (-3.4 to 27.9), compared to 7.5% (-10.6 to 20.8) and -0.61% (-19.7 to 15.3) on day 28. The results for retinol-RDR and RBP4-RDR revealed no significant correlation. The agreement between retinol-RDR and RBP4-RDR was poor (day 3: Cohen's κ = 0.12; day 28: Cohen's κ = 0.18). CONCLUSION: The RDR test based on circulating RBP4 is unlikely to reflect the hepatic vitamin A status in preterm infants.