Molecular and cellular pediatrics最新文献

{"title":"Current skin care practices in very low birth weight infants in German Neonatal Intensive Care Units - results from a cross-sectional survey.","authors":"Janina Marissen, Regina Thoma, Christoph Härtel","doi":"10.1186/s40348-026-00237-0","DOIUrl":"10.1186/s40348-026-00237-0","url":null,"abstract":"<p><strong>Background: </strong>The skin is the largest epithelial organ and a critical barrier. However, in preterm infants, particularly very low birth weight infants (VLBWI, < 1500 g), it is immature and highly susceptible to injury and infection. Despite growing awareness of neonatal skin care, evidence-based guidelines for this vulnerable population are lacking. This study aimed to provide an overview of current skin care practices in German Neonatal Intensive Care units (NICUs) and compare them with other European centers.</p><p><strong>Methods: </strong>A cross-sectional, web-based survey was distributed to German level III NICUs (n = 70) and selected European centers (n = 10) in May 2025. The questionnaire comprised 20 items covering skin risk assessment and skin care routines, bathing, skin antisepsis, and perceived challenges. Responses were analyzed descriptively.</p><p><strong>Results: </strong>The overall response rate was 73.8% (n = 59). Responses were analyzed from 48 German NICUs and eight European centers. Among German centers, only 14.6% (n = 7) reported applying skin risk assessment tools, and 16.7% (n = 8) reported standardized skin care protocols. A dexpanthenol-containing cream was the most commonly used skin care product. Use of other products varied greatly, while 39.6% of German centers (n = 19) reported using no skin care products at all. Bathing was practiced in 77.1% of NICUs (n = 37), with frequency and use of additives varying. Octenidine 0.1% and its combinations were the main products for skin antisepsis. Major challenges perceived by neonatologists included high skin vulnerability (87.5%), issues with adhesives (72.9%), risk of infection (64.5%), and limited or unclear evidence in skin care of VLBWI (54.2%). Criteria for product selection included clinical evidence (60.4%), practical experience (60.4%), and hygiene regulations (54.2%). Comparison with reports from the other European countries revealed both notable similarities and considerable variations in practices across the international context.</p><p><strong>Conclusion: </strong>Skin care practices for VLBWI in German and European NICUs vary widely, with limited use of standardized protocols or risk assessment tools. High skin vulnerability, issues with adhesives and infection risk remain the main challenges. These findings underscore the urgent need for evidence-based guidelines to optimize skin care in this high-risk population.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-truncating variants in APBA1 in minors with severe, early-onset obesity: implications for genetic testing.","authors":"Joanna Lerner, Abubakar Moawia, Stefanie Zorn, Simone Kloker, Margit Klehr-Martinelli, Kay Winner, Denisa Penfold, Thomas M K Völkl, Miriam Krausnick, Reiner Siebert, Martin Wabitsch","doi":"10.1186/s40348-026-00235-2","DOIUrl":"10.1186/s40348-026-00235-2","url":null,"abstract":"<p><p>BACKGROUND: Severe, early-onset obesity is a monogenic disorder in a subset of patients. Recently, rare protein-truncating variants (PTVs) in BSN and APBA1 have been implicated as monogenic causes of obesity. Truncating variants in these two genes have been associated with adult-onset monogenic obesity. Here, we aimed to investigate the occurrence of rare PTVs in APBA1 and BSN in minors with severe obesity manifesting in early childhood or adolescence. METHODS: Previously obtained exome data of 209 children and adolescents (0–18 years) with severe obesity manifesting in early childhood or adolescence genetically tested at the Ulm University Medical Center between April 2022 and May 2024 were mined for rare PTVs in APBA1 (NM_ 001163.4; NP_ NP_001154.2) and BSN (NM_003458.4; NP_003449.2). In all patients, monoallelic, and in the case of autosomal-recessive inheritance, biallelic likely pathogenic and pathogenic variants in well-known obesity-associated genes were excluded. Clinical re-evaluation was performed in two identified cases with rare potentially protein-truncating variants in APBA1. RESULTS: The first patient (male, 15 years) presented with a BMI of 33.7 kg/m2 (BMI z-score: 2.7) after nine years of excessive weight gain despite life-style interventions. He had a body fat percentage of 49.5% and showed hyperphagia. The patient displayed impaired expressive language development, dyslexia and an IQ of 84. His mother also had obesity and dyslexia while his father and younger sister were unaffected. We identified the heterozygous, likely pathogenic variant APBA1:c.814C > T;p.(Gln272*) in the index patient and his mother. The second patient (male, 6 years) presented with a BMI of 30.0 kg/m2 (BMI z-score: 3.8), a body fat percentage of 43.6% and hyperphagia. The child had upslanting palpebral fissures and showed impaired expressive language development. Both parents of the boy were affected by severe obesity and underwent bariatric surgery. We identified the heterozygous variant of unknown significance APBA1:c.2442 + 3A > C predicted to impair proper splicing in the index patient and his mother. CONCLUSION: We conclude that rare potentially protein-truncating variants in APBA1 are also found in some minors with early-onset and severe obesity. Therefore, those variants might not be restricted to adult-onset disease. We therefore propose to include APBA1 in diagnostic genetic testing for monogenic obesity in minors and adults. </p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient neonatal diabetes mellitus as an early diagnostic clue to HNF1B-related disease - two case reports and a literature review.","authors":"Marcin Kołbuc, Paweł Bednarek, Rafał Motyka, Tomasz Jarmoliński, Marzena Michalak-Kloc, Bodo B Beck, Małgorzata Urbańska-Kosińska, Marcin Zaniew","doi":"10.1186/s40348-026-00234-3","DOIUrl":"10.1186/s40348-026-00234-3","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic variants in the HNF1B gene cause a multi system disorder encompassing organ abnormalities-primarily affecting the kidneys and pancreas-as well as metabolic disturbances, collectively referred to as HNF1B-related disease. While maturity-onset diabetes of the young type 5 is a well-recognized manifestation, neonatal diabetes mellitus (NDM) associated with HNF1B is exceedingly rare, and has only been reported in patients harboring single nucleotide variants.</p><p><strong>Case presentation: </strong>We describe two unrelated female children presenting with transient NDM caused by a complete HNF1B gene deletion. Both developed hyperglycemia within the first days of life requiring short-term insulin therapy, followed by spontaneous normalization of glycemia. However, their subsequent phenotypes diverged significantly. The first patient exhibited bilateral renal dysplasia while maintaining normal neurodevelopment. In contrast, the second patient developed later-onset cystic kidney disease, neurodevelopmental delay, and dysmorphic features, consistent with a broader 17q12 deletion syndrome spectrum. Although, in both cases, kidney abnormalities and extra-renal features (NDM, hypomagnesemia, hyperuricemia) were observed, both patients experienced a delay in diagnosis. On follow-up, serial oral glucose tolerance tests (OGTT), HbA1c assessments, and glucagon stimulation tests to date demonstrated preserved β-cell function, with the exception of hyperglycemia in 30-60 min of the extended OGTT in one patient.</p><p><strong>Conclusions: </strong>These two cases represent the first report of transient NDM due to HNF1B deletion. Our findings broaden the molecular and clinical spectrum of HNF1B-related diabetes, and emphasize the importance of considering HNF1B defects in children with transient neonatal hyperglycemia.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnoses of double heterozygous NF1 variants and dual RASopathy.","authors":"Daniela Angelova-Toshkina, Denny Schanze, Pia Vaassen, Michael C Frühwald, Thorsten Rosenbaum, Martin Zenker, Michaela Kuhlen","doi":"10.1186/s40348-026-00225-4","DOIUrl":"10.1186/s40348-026-00225-4","url":null,"abstract":"<p><p>Genetic testing in neurofibromatosis type 1 (NF1) occasionally reveals two heterozygous NF1 variants in the same individual. Correct interpretation hinges on allelic phasing, elucidation of somatic second hits in lesions, and distinction from bona fide dual RASopathy diagnoses. We provide a focused, critical review of the primary literature on (i) cis doublets in NF1, (ii) purported germline trans configurations—particularly in spinal neurofibromatosis, (iii) biallelic somatic inactivation of NF1 in café-au-lait macules, tumors, and juvenile myelomonocytic leukemia, and (iv) confirmed cases of dual RASopathy. We also include an index patient with two heterozygous NF1 variants to illustrate clinical challenges. Phase-proven cis doublets are rare, often closely spaced, and generally accompany classic NF1 without reproducible phenotype escalation. Claims of germline trans NF1 pathogenic variants weaken on reappraisal: second alleles reported in spinal neurofibromatosis typically do not meet current pathogenicity standards, while Nf1−/− mouse embryonic lethality underscores the biological implausibility of constitutive biallelic loss. In contrast, biallelic somatic NF1 inactivation is pervasive across NF1 lesions, including café-au-lait macules, plexiform and cutaneous neurofibromas, and juvenile myelomonocytic leukemia, due to mitotic recombination (copy-neutral loss-of-heterozygosity), microdeletions, or a second variant. Confirmed dual RASopathy diagnoses (most often NF1 plus PTPN11) are rare and produce blended systemic phenotypes. Interpretation of double NF1 findings should prioritize independent American College of Medical Genetics and Genomics/Association for Molecular Pathology classification of each variant, rigorous phasing (segregation/RNA/allele-specific methods), and tumor-focused analysis where applicable. Our index case and synthesis support a practical workflow that clarifies counseling and helps avoid over-calling dual pathogenicity.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic variability in female individuals with the NAA10 missense variants p.(L126R), p.(L126V), or p.(F128L) leading to NAA10-related syndrome.","authors":"Anja Bühler, Katharina Aigner-Radakovics, Federica Diofano, Elaine Marchi, Karolina Weinmann-Emhardt, Amina Paquay, Stephanie V Lilja, Bernhard Rosensteiner, Randie Harpell, Ewelina Bernard, Steffen Just, Reginald E Bittner, Gholson J Lyon, Monika Kustermann","doi":"10.1186/s40348-026-00230-7","DOIUrl":"10.1186/s40348-026-00230-7","url":null,"abstract":"<p><p>BACKGROUND: NAA10-related syndrome is an exceptionally rare X-linked disorder caused by variants in the N-alpha-acetyltransferase 10 (NAA10) gene. Despite its role in acetylating nearly half of the human proteome, establishing genotype-phenotype correlations remains challenging due to the limited number of documented cases and the extremely broad phenotypic spectrum. METHODS: We performed exome sequencing and clinical phenotyping of three female patients. To investigate the pathogenic mechanisms without interference from endogenous protein, we generated the first viable NAA10 knockout (ΔNAA10) cell line using CRISPR/Cas9 in the 8-MG-BA glioblastoma line. This null-background model allowed for the analysis of GFP-tagged patient variants, specifically focusing on colocalization with the auxiliary subunit NAA15. RESULTS: Our study expands the global landscape of NAA10-related diseases—now totaling 145 individuals with 46 pathogenic variants—by describing three females with de novo NAA10 variants clustering closely within the N-acetyltransferase domain: p.(L126R), p.(L126V), and p.(F128L). The first patient exhibits severe global developmental delay, neuroimaging anomalies, and congenital cardiac defects and remains non-verbal. The second patient experiences developmental delays, particularly in motor skills and language. The third patient also presents with severe global developmental delay with significant motor impairments and remains non-verbal. Localization studies in the ΔNAA10 cells revealed that while the p.L126V variant maintained near-wild-type protein stability and colocalization with NAA15, the bulky p.L126R and disruptive p.F128L substitutions severely impaired NatA complex formation and altered cellular distribution. This study expands the known clinical landscape by detailing the phenotypic spectrum of three female patients, including two entirely novel cases described here for the first time. We aimed to explore how specific variants in the catalytic domain affect protein stability and NatA complex formation, helping to explain the diverse clinical manifestations observed in affected females. CONCLUSION: This study highlights the broad phenotypic spectrum of NAA10-related syndrome and demonstrates that clinical severity is driven by the specific amino acid substitution rather than the position alone. With 145 cases now identified globally, the need for precision modeling is critical. Our novel ΔNAA10 cell line proves to be a robust tool for linking specific biochemical defects to clinical phenotypes, potentially offering new insights into this complex syndrome. </p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of azacitidine and trametinib against leptomeningeal melanosis associated with congenital melanocytic nevus syndrome.","authors":"Lina Raljević, Katalin Komlosi, Ursula Feige, Matthias Eckenweiler, Silke Lassmann, Haroun Bel Hadj Jrad, Martin Werner, Judith Fischer, Cristina Has, Tobias Feuchtinger, Markus Uhl, Charlotte M Niemeyer, Simone Hettmer","doi":"10.1186/s40348-026-00233-4","DOIUrl":"10.1186/s40348-026-00233-4","url":null,"abstract":"<p><p>BACKGROUND: Congenital melanocytic nevus syndrome is a disorder characterized by postzygotic, mosaic NRAS Proto-Oncogene, GTPase mutations. Clinical manifestations include melanotic skin lesions and, optionally, central nervous system melanosis typically noted during early infancy. Affected individuals have an increased risk of developing malignant melanomas at an early age. CASE: We report a child with neurocutaneous melanosis due to this syndrome, who had innumerable nevi at birth and diffuse leptomeningeal thickening. He developed increased intracranial pressure at 4 weeks of age. The nucleoside analogue azacitidine and the Mitogen-Activated Protein Kinase, Kinase inhibitor trametinib were started at 6 weeks of age resulting in rapid reduction of leptomeningeal thickening. At 53 months of age, the patient still takes trametinib and has met all developmental milestones. There has been no evidence of melanoma, and he exhibits minimal residual leptomeningeal changes. CONCLUSION: To our best knowledge, this is the first child with this syndrome who has undergone successful therapy to reduce leptomeningeal thickening. </p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The conundrum in diagnosing Maturity-Onset Diabetes of the Young (MODY) in a large German pedigree with early-onset diabetes and a novel HNF1A variant.","authors":"Eleni Z Giannopoulou, Abubakar Moawia, Josef Högel, Joanna Lerner, Stefanie Zorn, Christian Denzer, Reiner Siebert, Martin Wabitsch","doi":"10.1186/s40348-026-00229-0","DOIUrl":"10.1186/s40348-026-00229-0","url":null,"abstract":"<p><p>BACKGROUND: Genetic screening for maturity-onset diabetes of the young (MODY) involves sequencing of the coding regions of known disease-associated genes. We describe the complex and challenging diagnostic journey of a patient with early-onset diabetes with a novel, intronic HNF1A variant likely affecting a branching site. CASE PRESENTATION: The patient was diagnosed with diabetes at the age of 10 years after incidental hyperglycemia (HbA1c 8.1%, C-peptide 3.0 μg/dl), without polyuria, polydipsia, or weight loss. Type 1 diabetes associated autoantibodies were negative, but the patient had a strong family history of early-onset diabetes (classified as type 1 or type 2 diabetes). Initial genetic testing for HNF4A, GCK, HNF1A, and HNF1B coding regions (including exon/intron boundaries ± 20 bp) and MLPA were negative. Sulfonylureas provided good glycemic control until age 16, when insulin was added. At age 18, an expanded targeted next-generation sequencing (NGS) panel for MODY was also negative. At age 24, whole-exome-sequencing via NGS and additional analysis was conducted, focusing on synonymous and intronic variants, and revealed a heterozygous HNF1A variant (c.327-28A > G;p.?) in the patient and four affected relatives. The variant co-segregated with diabetes, and was predicted to affect splicing via branching site disruption, suggesting pathogenicity. CONCLUSION: In summary, this case highlights the importance of a comprehensive diagnostic approach that combines clinical, biochemical, and extended genetic evaluation. When MODY is strongly suspected despite negative targeted testing, broader sequencing—including intronic and regulatory regions—should be pursued. Accurate variant interpretation remains essential to prevent misclassification and to optimize diagnosis, treatment, and understanding of the genetic complexity of monogenic diabetes. </p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective screening for congenital cytomegalovirus infection in the Survey of Neonates in Pomerania shows very low disease burden.","authors":"Jan Baier, Chiara Konrad, Maximilian Groffmann, Till Ittermann, Heike Allenberg, Maria Asmus, Friedrich Ihler, Chia-Jung Busch, Kathrin Lehmann, Karsten Becker, Anja Lange, Matthias Heckmann","doi":"10.1186/s40348-026-00231-6","DOIUrl":"10.1186/s40348-026-00231-6","url":null,"abstract":"<p><p>BACKGROUND: Congenital cytomegalovirus (cCMV) infection is considered one of the most common infectious pathologies in neonates, showing a wide range of clinical manifestations, ranging from completely asymptomatic to critically ill newborns. Primary infection during the first trimester of pregnancy carries the highest risk of severe fetal involvement. However, the majority of infected fetuses show an asymptomatic or mild course of disease. The most common long-term sequela is sensorineural hearing loss, which is detected in only about 50% of affected children during newborn hearing screenings. Furthermore, epidemiological data on disease burden remain limited and show considerable variability. The aim of this study was to investigate the prevalence of cCMV and its associated disease burden at follow-up, particular sensorineural hearing loss, in a population-based birth cohort. RESULTS: We conducted a retrospective analysis for cCMV in n = 1995 newborns using urine and plasma biosamples from the second baseline cohort of the Survey of Neonates in Pomerania (SNiP-II). Four participants (prevalence rate 0.2%) were tested positive. Two of these cases had already been identified shortly after birth, having been screened for cCMV due to clinical suspicion. The seroprevalence of IgG antibodies among pregnant women was 47.6%. For follow-up, the patient database of our Department of Otolaryngology, Head and Neck Surgery (ENT) was reviewed for hearing pathologies in all children born during the SNiP-II recruitment period (2013–2017). Twelve out of n = 1138 SNiP-II participants (1.1%) showed confirmed sensorineural hearing loss (SNHL), none of which were associated with cCMV. A complete clinical follow-up of the cCMV-positive cases revealed no sequelae related to the infection. CONCLUSIONS: By using a population-based retrospective analysis approach, we demonstrated a very low prevalence and disease burden of cCMV in our region. Our data supports the current guideline recommendations of a risk factor-based screening strategy. </p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors and outcomes of delayed completion of the hexavalent 3 + 1 immunisation series in German preterm infants - an observational study.","authors":"Hannah Kraft, Marie-Theres Dammann, Kathrin Hanke, Michael Zemlin, Janina Soler Wenglein, Jule Rohde, Désirée Lasserre, Alexander Humberg, Claudia Roll, Christoph Härtel, Jan Rupp, Folke Brinkmann, Sabine Pirr, Reinhard Jensen, Rainer Odendahl, Peter Ahrens, Christine Silwedel, Johannes Liese, Wolfgang Göpel, Egbert Herting, Guido Stichtenoth, Ingmar Fortmann","doi":"10.1186/s40348-026-00228-1","DOIUrl":"10.1186/s40348-026-00228-1","url":null,"abstract":"<p><p>BACKGROUND: Although very low birthweight infants (VLBWI, birthweight < 1500 g) are at increased risk of infectious diseases, they frequently receive primary vaccinations with the hexavalent vaccine (DTaP-IPV-Hib-HepB) later than recommended. Detailed data on the adherence to the hexavalent 3 + 1 immunisation schedule (at 2, 3, 4 and 11 months of age) in German VLBWI are scarce. OBJECTIVE: This study evaluated the timeliness of the primary hexavalent vaccination series among VLBWI from the German Neonatal Network (GNN) and aimed at identifying risk factors and outcomes associated with delayed series completion. STUDY DESIGN AND METHODS: As part of the multicentre, population-based GNN, N = 3,394 VLBWI born between 2009 and 2016 underwent a follow-up examination at 6 years of age, including documentation of vaccination certificates. Uni- and multivariate analyses were performed to evaluate the timely completion of the 3 + 1 schedule for hexavalent immunisation and to examine risk factors and outcomes associated with delays. RESULTS: Despite a high overall hexavalent vaccination coverage of more than 97% by six years of age, only 3.3% (n = 108) of VLBWI received the hexavalent booster at the recommended age of 11 months, and 41.6% (n = 1,373) had completed the primary vaccination series by 15 months of age. Progressive delays were observed across subsequent doses, with the lowest schedule-adherent coverage recorded for the booster dose. A timely first hexavalent vaccination (OR 0.61; 95% CI 0.52–0.72) was protective against delayed series completion, while bronchopulmonary dysplasia (BPD) was associated with a delay of the booster beyond 15 months of age (OR 1.31; 95% CI 1.07–1.61). Timely series completion was associated with decreased risk of incomplete vaccine protection at daycare entry (OR 0.09; 95% CI 0.07–0.14) and a lower rate of parent-reported pertussis within the first 6 years of life (OR 0.47; 95% CI 0.24–0.90). CONCLUSION: Our data demonstrate significant delays in the primary vaccination series which were most pronounced at the booster dose and particularly affects the most susceptible infants, i.e., VLBWI with BPD. However, vulnerable preterm infants would benefit greatly from timely vaccinations to ensure optimal protection by the time they are increasingly exposed to infectious pathogens, as for instance upon entry into childcare settings. </p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rapid review of genetic association studies of parent-of-origin effects and fetal growth.","authors":"Esther Joo Won Kang, Andrew Thomas Dewan","doi":"10.1186/s40348-026-00224-5","DOIUrl":"10.1186/s40348-026-00224-5","url":null,"abstract":"<p><p>BACKGROUND: Genetic factors contribute, in part, to fetal growth restriction (FGR), a developmental condition of disrupted fetal development associated with serious health consequences. Among these factors, variants that display parent-of-origin effects (POE) may play a significant role in the variation of human fetal growth. MAIN BODY: We conducted a synthesis of the available evidence on genetic associations between POE variants and fetal growth traits, aiming to summarize identified variants and compare study designs. Literature searches were performed on the Ovid research platform using the bibliographic databases MEDLINE and Embase, identifying 17 genetic association studies that reported 38 study-wide significant POE variants associated with one or more fetal growth trait(s). Candidate gene approaches were dominant among the studies identified (n = 13), but the application of genome-wide association studies (GWAS) continues to expand as computational phasing and POE determination methods have advanced. While genetic association studies are useful for identifying POE variants, low replication of findings among independent studies remains a major hindrance to validation. Birth weight was the most common measure of fetal growth among our identified studies (n = 15). Further research is needed on alternative measures of fetal growth. Additionally, most of the studies were conducted in sample populations of White European ancestry (n = 9), indicating a gap in research among more diverse populations. CONCLUSION: Genetic association studies have provided evidence that POE variants contribute to fetal growth variation, encouraging further investigations into the genetic regulation and biological mechanisms underlying fetal growth. </p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}