Tine Brink Henriksen

Aim: In many countries, all newborns undergo a routine clinical newborn examination before discharge. Key aim of this examination is to detect conditions for which early treatment may improve outcomes. This study aimed to describe variation in the timing, content, professional responsibility and follow‐up arrangements for routine clinical newborn examination in Norway, Denmark and Sweden. Methods: April to September 2024, we distributed a survey to Norwegian paediatricians and to representatives of maternity and paediatric departments in Denmark and Sweden. Results: We analysed responses from 45 hospitals: Norway ( N = 20), Denmark ( N = 12) and Sweden ( N = 13). In Norway and Sweden, a more comprehensive examination was generally performed by paediatricians within 72 h after birth. In Denmark, midwives typically performed a simplified examination within 12 h, with paediatric assessment when indicated. Examination content was broadly similar in Norway and Sweden but differed in Denmark. All participating hospitals reported routine pulse oximetry screening, but cardiac auscultation and follow‐up of heart murmurs differed. Conclusion: The organisation of routine clinical newborn examination differs across Scandinavia. These differences in care pathways may influence resource use and clinical decision making. Whether they translate into differences in neonatal morbidity or mortality remains unknown.

Autism has prenatal origins, yet diagnosis typically occurs years after behavioural signs emerge. Umbilical cord blood (UCB) provides a unique window into the perinatal molecular environment, but large-scale studies examining molecular signatures associated with subsequent autism diagnosis remain limited. Here, we performed metabolomic and proteomic profiling of UCB in a nested case-control study within the Danish National Birth Cohort. Among 70,292 pregnancies, we identified 465 mother–child dyads with childhood autism (ICD-10 F84.0) and 465 neurotypical (NT) controls. UCB samples were available from 398 autistic and 394 NT children, which were divided into two largely orthogonal participant sets to enable initial profiling and subsequent confirmation of key pathway findings. Participant set 1 (258 autism, 263 NT controls) underwent multi-modal omics profiling, including untargeted metabolomics, a targeted metabolite panel, and discovery proteomics, while participant set 2 (140 autism, 131 NT controls) underwent discovery proteomics and targeted steroid metabolomics. Metabolomics revealed differences in fatty acid, phospholipid, and steroid profiles between autistic and NT children. A reduced steroid signature emerged in participant set 1, characterized by a significantly lower aggregate steroid score in autistic children compared with NT children (P = 0.00517). In participant set 2, targeted steroid analysis confirmed reduced concentrations of the neuroactive steroid allopregnanolone (P = 0.0279), and pregnenolone (P = 0.0300), with modest discrimination between autistic and NT children (AUROC = 0.64, 95% CI 0.59–0.67). Proteomic analyses independently identified convergent alterations in complement signalling and extracellular matrix signalling across both participant subsets. These findings identify a reproducible perinatal steroid signature associated with later autism diagnosis, and implicate disrupted steroidogenesis alongside immune and extracellular matrix signalling in autism biology. These molecular signatures may support prognostic biomarker development and earlier identification of children with autism.

Prematurity is a major risk factor for invasive Group B Streptococcus (iGBS) disease in infancy. Whether gestational age (GA) modifies the association between GBS genomic characteristics and postnatal age at disease onset remains unclear. We analyze isolates from infants with iGBS disease in Denmark between 2000 and 2023 using whole-genome sequencing to identify clonal complexes and genes encoding alpha-like surface proteins and capsular serotypes. Isolates are classified into clones based on shared genomic characteristics.Among 510 infants, 356 (70%) are term, 66 (13%) moderate preterm, and 88 (17%) very preterm. Approximately half of term and moderate preterm infants develop iGBS during days 1–3 of life, compared with 9% of very preterm infants. GBS clone distributions differ by GA and postnatal age, particularly for disease onset at 4–89 days. Term and moderate preterm infants are predominantly infected with CC17/Rib/III (71%), whereas very preterm infants show greater clonal diversity, with a lower prevalence of CC17/Rib/III (31%) and higher prevalences of CC23/Alp1/Ia (27%) and CC12/AlphaC/Ib-II (19%). These findings show that GA modifies associations between GBS genomic characteristics and postnatal age at disease onset, highlighting the importance of GA- and postnatal age-stratified GBS surveillance to inform preventive strategies and maternal vaccine implementation.

Purpose: To examine the accuracy of the diagnoses of early-onset neonatal infection in the Danish National Patient Register. Patients and Methods: All Danish neonates born after 35 weeks of gestation with an ICD10 diagnosis of sepsis or meningitis within the first week of life between 2010 and 2018 were identified. To examine the validity of the diagnoses, medical records were reviewed for 500 neonates diagnosed with sepsis and all 63 neonates diagnosed with meningitis. Proven infection was defined by bacterial pathogens identified from blood or cerebrospinal fluid. Probable sepsis was defined as at least 5 days of antibiotic treatment, two clinical signs of infection, and one abnormal blood biomarker. Probable meningitis was defined as at least 14 days of antibiotics, neurological affection, and cerebrospinal fluid analysis consistent with meningitis. Positive predictive values (PPVs) with 95% CI were estimated using the proven definition of infection as well as the criteria for either proven or probable infection. Results: The PPV for sepsis diagnoses using the proven definition was 0.04 (0.02, 0.06), while the PPV using both the proven and probable definition was 0.52 (0.45, 0.58). Sepsis diagnoses with a specified pathogen showed the highest PPV for proven sepsis at 0.36 (0.29, 0.43) and for proven or probable sepsis at 0.65 (0.58, 0.72). The PPV for meningitis diagnoses using the proven definition was 0.24 (0.13, 0.37), while the PPV using both the proven and probable definition was 0.38 (0.25, 0.52). Conclusion: We found a poor validity for the ICD10 diagnoses of early-onset neonatal infection in the Danish National Patient Register. This highlights that the diagnoses should be used cautiously in future research and surveillance and emphasises the need for supporting information on microbiological samples. Additionally, this highlights the importance of establishing a consensus definition of neonatal sepsis to improve diagnostic accuracy.