IgE to cross-reactive carbohydrate determinants (CCD) in childhood: Prevalence, risk factors, putative origins.

BACKGROUND: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. METHODS: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA). RESULTS: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. CONCLUSIONS: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction.

Impact of preterm birth on the onset of panic disorder in later life - Results from the Gutenberg Prematurity Study (GPS).

BACKGROUND: The present study aimed to investigate whether prematurity and perinatal stress exert long-term effects on the onset of panic disorder in later life. METHODS: From 40,189 adults born in Germany between 1969 and 2002, a study cohort (n = 427) stratified by gestational age (GA) (extremely preterm: GA < 29 weeks; very preterm: GA 29-32 weeks; moderately preterm: GA 33-36 weeks; and full-term GA ≥ 37 weeks) was selected (age 28.5 ± 8.7 years). Multivariable logistic regression analyses were conducted to investigate associations between gestational age at birth and panic disorder adjusting for age, gender, socioeconomic status, and perinatal factors. RESULTS: The prevalence of panic disorder was roughly equal in moderate to very preterm and full-term birth groups at 1.9%-3.8%. However, this rate significantly increased to 14.3% in the extreme preterm category (GA <2 9: 14.3 %, p = 0.002). In multivariable analyses, female gender and GA were independently associated with panic disorder. Adjusting for age, gender and socioeconomic status, panic disorder was associated with lower GA at birth (OR = 1.12 per week (CI95%: 1.01-1.26, p = 0.037). Whereas adjustment for nutrition status or indicators of perinatal stress had no effect, correction for the length of postnatal ICU-stay eliminated the association between preterm birth and later panic disorder. LIMITATIONS: Limitations include the small number of cases and the reliance on questionnaires to assess mental status. CONCLUSIONS: Prematurity likely increases the risk of panic disorder later in life, and the subsequent postnatal ICU-stay appears to be of critical importance. However, due to strong collinearity and other associated factors with preterm births, it remains unclear which is the primary determinant.

A Complex Intervention to Prevent Medication-Related Hospital Admissions.

BACKGROUND: Children are often treated off-label and are at a disadvantage in pharmacotherapy. The aim of this study was to implement and evaluate a quality assurance measure (PaedPharm) for pediatric pharmacotherapy whose purpose is to reduce medication-related hospitalizations among children and adolescents. METHODS: PaedPharm consisted of the digital pediatric drug information system PaedAMIS, pediatric pharmaceutical quality circles (PaedZirk), and an adverse drug event (ADE) reporting system (PaedReport). The intervention was implemented in a cluster-randomized trial (DRKS 00013924) in 12 regions, with a pediatric and adolescent medicine clinic in each and a total of 152 surrounding private practitioners, in 6 sequences over 8 quarters. In addition to the proportion of ADE-related hospital admissions (primary endpoint), comprehensive process evaluation included other endpoints such as coverage, user acceptance, and relevance to practice. RESULTS: 41 829 inpatient admissions were recorded, of which 5101 were patients of physicians who participated in our study. 4.1% of admissions were ADE-related under control conditions, and 3.1% under intervention conditions (95% CI: [2.3; 5.9] and [1.8; 4.5], respectively). A model-based comparison yielded an intervention effect of 0.73 (population-based odds ratio; [0.39; 1.37]; p = 0.33). PaedAMIS achieved moderate user acceptance and PaedZirk achieved high user acceptance. CONCLUSION: The introduction of PaedPharm was associated with a decrease in medication-related hospitalizations that did not reach statistical significance. The process evaluation revealed broad acceptance of the intervention in outpatient pediatrics and adolescent medicine.

Vaccination Intention Following Receipt of Vaccine Information Through Interactive Simulation vs Text Among COVID-19 Vaccine-Hesitant Adults During the Omicron Wave in Germany.

Conclusions and Relevance: In this cross-sectional study, vaccine-hesitant adults presented with an interactive risk ratio simulation were more likely to show positive change in COVID-19 vaccination intention and benefit-to-harm assessment than those presented with a conventional text-based information format. These findings suggest that the interactive risk communication format can be an important tool in addressing vaccination hesitancy and fostering public trust. Design, Setting, and Participants: Cross-sectional study conducted online with 1255 COVID-19 vaccine-hesitant adult residents of Germany in April and May 2022, surveyed using a probability-based internet panel maintained by respondi, a research and analytics firm. Participants were randomized to 1 of 2 presentations on the benefits and adverse events associated with vaccination. Exposure: Participants were randomized to a text-based description vs an interactive simulation presenting age-adjusted absolute risks of infection, hospitalization, ICU admission, and death after exposure to coronavirus in vaccinated vs unvaccinated individuals relative to the possible adverse effects as well as additional (population-level) benefits of COVID-19 vaccination. Importance: Hesitancy toward COVID-19 vaccination is a major factor in stagnating uptake rates and in the risk of health care systems becoming overwhelmed. Main Outcomes and Measures: Absolute change in respondents' COVID-19 vaccination intention category and benefit-to-harm assessment category. Objective: To compare an interactive risk ratio simulation (intervention) with a conventional text-based risk information format (control) and analyze change in participants' COVID-19 vaccination intention and benefit-to-harm assessment. Results: Participants were 1255 COVID-19 vaccine-hesitant residents of Germany (660 women [52.6%]; mean [SD] age, 43.6 [13.5] years). A total of 651 participants received a text-based description, and 604 participants received an interactive simulation. Relative to the text-based format, the simulation was associated with greater likelihood of positive change in vaccination intentions (19.5% vs 15.3%, respectively; absolute difference, 4.2%; adjusted odds ratio [aOR], 1.45; 95% CI, 1.07-1.96; P = .01) and benefit-to-harm assessments (32.6% vs 18.0%; absolute difference, 14.6%; aOR, 2.14; 95% CI, 1.64-2.80; P < .001). Both formats were also associated with some negative change. However, the net advantage (positive - negative change) of the interactive simulation over the text-based format was 5.3 percentage points for vaccination intention (9.8% vs 4.5%) and 18.3 percentage points for benefit-to-harm assessment (25.3% vs 7.0%). Positive change in vaccination intention (but not in benefit-to-harm assessment) was associated with some demographic characteristics and attitudes to COVID-19 vaccination; negative changes were not.

Ocular geometry in adults born extremely, very and moderately preterm with and without retinopathy of prematurity: results from the Gutenberg Prematurity Eye Study.

BACKGROUND/AIMS: To evaluate whether anterior segment anatomy and axial length are associated with prematurity and perinatal factors in adults. METHODS: The Gutenberg Prematurity Eye Study examined adults born preterm and term aged 18-52 years. All participants underwent a prospective ophthalmic examination (optical biometry via a LenStar 900, Haag-Streit) in Germany. The associations between gestational age (GA), birth weight (BW) and BW percentile, retinopathy of prematurity (ROP) occurrence, ROP treatment and other perinatal factors with the main outcome measures were evaluated by univariate and multivariable linear regression analyses. Main outcome measures were corneal radius, white-to-white distance, anterior chamber depth, lens thickness and axial length. RESULTS: The study involved 861 eyes of 438 preterm and full-term individuals (aged 28.6±8.7 years, 245 females,). After adjustment for age and gender, a steeper corneal radius was associated with lower GA (B=0.02; p<0.001) and a lower BW percentile (B=0.003; p<0.001). A smaller white-to-white distance was linked to lower GA (B=0.02; p<0.001), a lower BW percentile (B=0.004; p<0.001) and postnatal ROP occurrence (B=-0.26; p<0.001). Decreased axial length was associated with lower GA at birth (B=0.05; p=0.002) and pre-eclampsia (B=-0.34; p=0.015). ROP-treated eyes had a shallower anterior chamber depth (B=-0.63; p=0.001) and increased lens thickness (B=0.64, p<0.001). CONCLUSION: Our analyses in adults demonstrate that the corneal morphology is influenced by GA and BW percentile, while the anterior chamber depth and lens thickness are affected by ROP treatment, namely laser therapy and cryotherapy. The present study highlights that perinatal factors lead to lifelong sequelae of ocular shape.

Visual acuity, amblyopia, and vision-related quality of life in preterm adults with and without ROP: results from the Gutenberg prematurity eye study.

OBJECTIVES: This study investigated the effects of prematurity and ROP on visual acuity and VRQoL in adults (18-52 years). METHODS: The Gutenberg Prematurity Eye Study is a retrospective cohort study with a prospective ophthalmologic examination. Preterm and full-term participants at an age from 18 to 52 years were included. Distant corrected visual acuity (DCVA) and VRQoL were assessed in participants (892 eyes of 450 individuals aged 28.6 ± 8.6 years, 251 females) grouped into full-term controls (gestational age [GA] at birth ≥37 weeks), preterm participants without ROP and GA 33-36 weeks (group 2), GA 29-32 weeks (group 3), GA ≤ 28 weeks (group 4), non-treated ROP (group 5) and treated ROP (group 6). Main outcome measures were distant corrected visual acuity (DCVA), VRQoL and prevalence of amblyopia. RESULTS: The DCVA of the better eye correlated (p < 0.001) with GA, birth weight, ROP, ROP treatment, and perinatal adverse events and was poorer in both ROP groups. Visual acuity of <20/200 in the better eye was observed in two participants (4.2%) in the ROP group and one person (6.7%) in the treated ROP group. The prevalence of amblyopia increased in the ROP groups. Compared to full-term controls, visual functioning VRQoL scores were lower in preterm individuals independent of ROP while socioemotional VRQoL scores were only lower in the treated ROP group. CONCLUSION: Participants with postnatal ROP and its treatment showed decreased visual acuity and VRQol in adulthood, with amblyopia occurring more frequently in more preterm participants with ROP.

A lower birth weight percentile is associated with central corneal thickness thinning: Results from the Gutenberg Prematurity Eye Study (GPES).

PURPOSE: Prematurity, prenatal growth restriction, and retinopathy of prematurity (ROP) are associated with altered ocular geometry, such as a steeper corneal shape in childhood, but it is unclear whether perinatal history affects corneal thickness development, so this study investigated whether corneal thickness in adulthood is affected by perinatal history. MARTERIALS AND METHODS: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. The corneal thickness was measured by Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany), and the relationship between perinatal parameters respective birth weight percentile and corneal thickness at different locations was assessed using uni- and multivariable linear regression models. Covariates included age, sex, mean corneal radius, white-to-white distance, gestational age, birth weight percentile, ROP occurrence, and treatment. The main outcome measures were corneal thickness at the apex, the pupil center, and the corneal periphery. RESULTS: The corneal thickness was measured in 390 participants (754 eyes, mean age 29.7+/-8.7 years, 224 females). In multivariable analyses, a lower birth weight percentile was associated with a lower corneal thickness at the apex (B = 0.20, p = 0.003) and the pupil (B = 0.19, p = 0.007). These effects diminished towards the corneal periphery and were not observed beyond the 4-mm diameter circle around the thinnest corneal position. Neither gestational age, ROP occurrence, or ROP treatment affected the corneal thickness. CONCLUSION: A lower birth weight percentile in subjects born preterm as a proxy for restricted fetal growth is associated with corneal thickness thinning in adults aged 18 to 52 years, indicating that corneal thickness development, particularly in the corneal center, may originate in the fetal stage.

A singleplex IgE test to a mixture of molecules from multiple airborne allergen sources: Innovating in vitro screening of respiratory allergies.

BACKGROUND: In vitro immunoglobulin E (IgE) tests can be better standardized if based on molecules rather than extracts. However, singleplex screening tests for respiratory or food allergies are still based on extracts only. TARGET: To validate a novel singleplex IgE screening test for respiratory allergies, based on a mix of major allergenic molecules Der p 1, Der p 2, Fel d 1, Can f 1, Can f 2, Can f 3, Can f 5, Bet v 1, Phl p 1, and Art v 1 (Molecular SX01, NOVEOS, HYCOR, USA), and requiring only four microliters (µl) of serum. METHODS: We examined six subsets of sera from participants of the German Multicenter Allergy Study (MAS) birth cohort enrolling 1314 newborns during 1990: (1) monosensitized (n = 58); (2) polysensitized (n = 24); (3) nonsensitized, with total IgE levels above (n = 24) or (4) below (n = 24) 300 kU/L; (5) sensitized to milk and/or egg but not to airborne allergens (n = 24); and (6) sera of children aged ≤5 years at their earliest IgE monosensitization to airborne allergens (n = 41). Sera were analyzed with the novel molecular SX01 test (NOVEOS) and with three categories of comparators: ImmunoCAP Phadiatop SX01, extracts, and molecules of D. pteronyssinus, cat, dog, grass, and birch. Sensitivity, specificity, positive and negative predictive values were calculated. Quantitative interrelationships were determined using Spearman's rank-order correlation coefficient and Bland-Altmann plots. RESULTS: The molecular SX01 test predicted the outcome of IgE tests based on molecules, extracts, or Phadiatop in 188 (96.4%), 171 (87.7%), and 171 (87.7%) of the 195 sera, respectively. Accordingly, sensitivity was 93.5%, 89.0%, and 82.4%, whereas specificity was 100%, 97.6%, and 96.1% when compared with molecular, extract, and Phadiatop tests, respectively. Inconsistent outcomes were largely confined to sera with IgE-Ab levels around the cutoff value of 0.35 kU/L, except for 5/195 (2.5%) sera, containing high levels of IgE to Phl p 5 and/or Alt a 1 only. IgE levels measured by the molecular SX01 test and with IgE tests to molecules, extracts, and Phadiatop were highly correlated (rho 0.90; p < .001), (rho 0.87, p < .001), (rho 0.84, p < .001), respectively. The novel molecular SX01 test detected IgE-Ab in 27/28 (sensitivity 96.4%) of the sera of preschool children at their earliest IgE sensitization to the same molecules. DISCUSSION: Our study validates the prototype of a novel category of IgE test, based on molecular mixes. The test's rather good precision and accuracy in early screening IgE sensitization to airborne allergens in German children may be further improved by adding a few other molecules, such as Phl p 5 and Alt a 1.

Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice.

Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency in functional phenylalanine hydroxylase (PAH), resulting in accumulation of phenylalanine (Phe) in patients' blood and organs. Affected patients encounter severe developmental delay, neurological deficits, and behavioral abnormalities when not treated. Early diagnosis and treatment are extremely important; newborn screening programs have been implemented in most countries to ensure early identification of patients with PKU. Despite available treatment options, several challenges remain: life-long adherence to a strict diet, approval of some medications for adults only, and lack of response to these therapies in a subpopulation of patients. Therefore, there is an urgent need for treatment alternatives. An mRNA-based approach tested in PKU mice showed a fast reduction in the accumulation of Phe in serum, liver and brain, the most significant organ affected. Repeated injections of LNP-formulated mouse PAH mRNA rescued PKU mice from the disease phenotype for a prolonged period of time. An mRNA-based approach could improve the quality of life tremendously in PKU patients of all ages by replacing standard-of-care treatments.

Intravenous ferric carboxymaltose for the management of iron deficiency and iron deficiency anaemia in children and adolescents: a review.

Iron deficiency is the primary cause of anaemia worldwide and is particularly common among children and adolescents. Intravenous (IV) iron therapy is recommended for paediatric patients with certain comorbidities or if oral iron treatment has been unsuccessful. IV ferric carboxymaltose (FCM) has recently been approved by the US Food and Drug Administration for use in children aged > 1 year. This narrative review provides an overview of the available publications on the efficacy and safety of IV FCM in children and adolescents. A literature search using PubMed and Embase yielded 153 publications; 33 contained clinical data or reports on clinical experience relating to IV FCM in subjects < 18 years of age and were included in the review. No prospective, randomised controlled studies on the topic were found. Most publications were retrospective studies or case reports and included patients with various underlying conditions or patients with inflammatory bowel disease. Efficacy data were included in 27/33 publications and improvements in anaemia, and/or iron status parameters were reported in 26 of them. Safety data were included in 25/33 publications and were in line with the adverse events described in the prescribing information. CONCLUSION: The available publications indicate that IV FCM, a nanomedicine with a unique and distinctive therapeutic profile, is an effective and generally well-tolerated treatment for iron deficiency or iron deficiency anaemia in children and adolescents. Despite the wealth of retrospective evidence, prospective, randomised controlled trials in the paediatric setting are still necessary. WHAT IS KNOWN: • Iron deficiency and iron deficiency anaemia are usually managed using oral iron therapy, but intravenous iron therapy is recommended for certain paediatric patients. • Intravenous ferric carboxymaltose (FCM) has recently been approved in the US for use in children aged > 1 year. WHAT IS NEW: • Despite evidence that FCM is effective and generally well tolerated in children and adolescents, so far, only retrospective studies, non-randomised uncontrolled prospective studies, or case reports have been published in full. • There is a strong need for prospective, randomised controlled trials on FCM in the paediatric setting.

mRNA-based therapy proves superior to the standard of care for treating hereditary tyrosinemia 1 in a mouse model.

Hereditary tyrosinemia type 1 is an inborn error of amino acid metabolism characterized by deficiency of fumarylacetoacetate hydrolase (FAH). Only limited treatment options (e.g., oral nitisinone) are available. Patients must adhere to a strict diet and face a life-long risk of complications, including liver cancer and progressive neurocognitive decline. There is a tremendous need for innovative therapies that standardize metabolite levels and promise normal development. Here, we describe an mRNA-based therapeutic approach that rescues Fah-deficient mice, a well-established tyrosinemia model. Repeated intravenous or intramuscular administration of lipid nanoparticle-formulated human FAH mRNA resulted in FAH protein synthesis in deficient mouse livers, stabilized body weight, normalized pathologic increases in metabolites after nitisinone withdrawal, and prevented early death. Dose reduction and extended injection intervals proved therapeutically effective. These results provide proof of concept for an mRNA-based therapeutic approach to treating hereditary tyrosinemia type 1 that is superior to the standard of care.

The role of preterm birth, retinopathy of prematurity and perinatal factors on corneal aberrations in adulthood: Results from the Gutenberg prematurity eye study.

INTRODUCTION: Prematurity and retinopathy of prematurity (ROP) are associated with altered corneal shape and reduced visual acuity in childhood, but their long-term effects on corneal shape in later life are still unclear. This study evaluated whether prematurity and related perinatal factors are associated with corneal aberrations in adulthood. METHODS: The Gutenberg Prematurity Eye Study (GPES) is a cohort study using Scheimpflug imaging of the cornea. Associations were assessed between corneal Zernike aberrations and gestational age (GA), birth weight (BW), BW percentile, ROP occurrence, ROP treatment and other perinatal factors using univariate and multivariable linear regression analyses. RESULTS: This study involved 444 eyes of 256 individuals born preterm (aged 28.1 ± 8.4 years, 146 females) and 231 eyes of 132 individuals born full-term (aged 29.8 ± 8.9 years, 77 females). Multivariable analyses revealed an association between corneal higher-order aberrations and lower birth weight percentile (B = -0.001, p < 0.001) as well as ROP treatment (B = 0.120, p = 0.03). Corneal lower-order aberrations were also associated with lower birth weight percentile (B = -0.004; p = 0.001) and ROP treatment (B = 0.838, p = 0.01) but not with ROP occurrence. Increased corneal aberrations were correlated with lower visual acuity and the spherical equivalent refractive error. CONCLUSIONS: Perinatal factors, particularly low birth weight percentile and ROP treatment lead to a more irregular corneal shape in adulthood, thereby reducing optical image quality and potentially contributing to reduced visual acuity and altered refractive error.

RETINAL THICKNESS AND FOVEAL HYPOPLASIA IN ADULTS BORN PRETERM WITH AND WITHOUT RETINOPATHY OF PREMATURITY: The Gutenberg Prematurity Eye Study.

PURPOSE: This study analyses whether prematurity, retinopathy of prematurity (ROP), and associated factors lead to altered foveal shape in adulthood and whether these alterations are associated with visual acuity. METHODS: The Gutenberg Prematurity Eye Study is a German cohort study with a prospective ophthalmologic examination (participants aged 18-52 years) of individuals born preterm and full-term that were examined with spectral domain optical coherence tomography. Participants were grouped according to gestational age (GA) and postnatal ROP status. Multivariable linear regression analyses for foveolar retinal thickness, foveal hypoplasia, and posterior vitreous status were performed. RESULTS: A total of 755 eyes of 414 preterm and full-term individuals were included (aged 28.6 ± 8.6 years, 233 female individuals). Central foveal retinal thickness increased as GA decreased. The prevalence of foveal hypoplasia was 2% (control group), 9% (GA 33-36), 18% (GA 29-32), 48% (GA ≤28), 50% (ROP without treatment), and 82% of eyes (with ROP requiring treatment). In multivariable analyses, central foveal thickness was independently associated with GA and advanced stages of ROP requiring treatment while foveal hypoplasia was only associated with GA. Posterior vitreous was more frequently visible as partially detached in full-term than in preterm individuals. Lower distant-corrected visual acuity correlated with increased foveolar thickness (rho = 0.08; P = 0.03) and with foveal hypoplasia (rho = 0.15, P < 0.001). CONCLUSION: Our findings indicate that there are fetal origins affecting foveal shape, resulting in foveal hypoplasia potentially affecting the visual acuity in adulthood.

Peripapillary Retinal Nerve Fiber Layer Thickness in Adults Born Extremely, Very, and Moderately Preterm With and Without Retinopathy of Prematurity: Results From the Gutenberg Prematurity Eye Study (GPES).

PURPOSE: This study investigated whether prematurity and associated factors or prenatal growth restriction have long-term effects on the peripapillary retinal nerve fiber layer (pRNFL) in adulthood. DESIGN: Retrospective cohort study. METHODS: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. Selected individuals born term and preterm (age 18-52 years) were examined with spectral-domain optical coherence tomography (SD-OCT) in adulthood, and perinatal medical charts were reviewed. The pRNFL thickness was measured using SD-OCT. Univariate and multivariable linear regression analyses were conducted to investigate associations between pRNFL and gestational age (GA; categorical), birth weight percentile (categorical), retinopathy of prematurity (ROP) occurrence, and treatment and other perinatal parameters with adjustment for age, sex, and spherical equivalent. RESULTS: In total, 766 eyes of 406 preterm and full-term individuals were included (mean age 28.4 ± 8.6 years, 228 females). After adjustment for age, sex, and spherical equivalent, global pRNFL thinning was associated with moderate (GA = 33-36 wk, ß = -4.68, P < .001), very (GA = 29-32 wk, ß = -5.72, P < .001), and extreme (GA ≤ 28 wk, ß = -8.69, P < .001) prematurity but not with low birth weight percentile (<25th percentile, P = .9) and ROP occurrence (P = .9) in multivariable analysis. ROP treatment was associated with increased pRNFL in the temporal sector (P = .002). Maternal smoking during pregnancy showed an association with pRNFL thinning (P = .07). CONCLUSION: Our data indicate that the more preterm individuals are born the more pRNFL thinning occurs, whereas prenatal growth restriction and postnatal occurrence of ROP show less effects on pRNFL thickness. Furthermore, individuals with severe ROP with treatment but not lower ROP stages without treatment showed an increased temporal pRNFL thickness.

Der p 23-specific IgE response throughout childhood and its association with allergic disease: A birth cohort study.

BACKGROUND: The Dermatophagoides pteronyssinus molecule Der p 23 is a major allergen whose clinical relevance has been shown in cross-sectional studies. We longitudinally analysed the trajectory of Der p 23-specific IgE antibody (sIgE) levels throughout childhood and youth, their early-life determinants and their clinical relevance for allergic rhinitis and asthma. METHODS: We obtained sera and clinical data of 191 participants of the German Multicentre Allergy Study, a prospective birth cohort. Serum samples from birth to 20 years of age with sIgE reactivity to Der p 23 in a customised semiquantitative microarray were newly analysed with a singleplex quantitative assay. Early mite exposure was assessed by measuring the average content of Der p 1 in house dust at 6 and 18 months. RESULTS: Der p 23-sIgE levels were detected at least once in 97/191 participants (51%). Prevalence of Der p 23 sensitisation and mean sIgE levels increased until age 10 years, plateaued until age 13 years and were lowest at age 20 years. Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were more prevalent in Der p 23-sensitised children, including those with monomolecular but persistent sensitisation (11/97, 11%). A higher exposure to mites in infancy and occurrence of AD before 5 years of age preceded the onset of Der p 23 sensitisation, which in turn preceded a higher incidence of asthma. CONCLUSIONS: Der p 23 sensitisation peaks in late childhood and then decreases. It is preceded by early mite exposure and AD. Asthma and AR can occur in patients persistently sensitised to Der p 23 as the only mite allergen, suggesting the inclusion of molecular testing of Der p 23-sIgE for subjects with clinical suspicion of HDM allergy but without sIgE to other major D.pt. allergens.

Dry Eye Parameters and Lid Geometry in Adults Born Extremely, Very, and Moderately Preterm with and without ROP: Results from the Gutenberg Prematurity Eye Study.

Background/Aims: This study aimed to analyze the effects of perinatal history on tear film properties and lid geometry in adults born preterm. Methods: The Gutenberg Prematurity Eye Study (GPES) is a German prospective examination of adults born preterm and term aged 18 to 52 years with Keratograph® 5M and Schirmer test I. Main outcome measures were first non-invasive tear film break-up time (F-NITBUT), bulbar redness (BR), Schirmer test, and nasal palpebral angle measurement. The associations with gestational age (GA), birth weight (BW), and BW percentile, retinopathy of prematurity (ROP), ROP treatment, and other perinatal factors were evaluated using regression analyses. Results: 489 eyes of 255 preterm and 277 eyes of 139 full-term individuals (aged 28.6 +/− 8.8 years, 220 females) were included. Of these, 33 participants (56 eyes) had a history of spontaneously regressed ROP and 9 participants (16 eyes) had a history of ROP treatment. After adjustment for age and sex, lower F-NITBUT (<20 s) was associated with ROP treatment (OR = 4.42; p = 0.025). Lower GA correlated with increased bulbar redness (B = −0.02; p = 0.011) and increased length of wetting in the Schirmer test (B = −0.69; p = 0.003). Furthermore, low GA was associated with narrowing of the nasal palpebral angle (B = 0.22; p = 0.011) adjusted for age and sex, but not when considering ROP in the multivariable model. Conclusion: Our analyses indicate that perinatal history affects ocular surface properties, tear production and lid geometry in adults born term and preterm. This might indicate that affected persons have a predisposition to diseases of the corneal surface such as the dry eye disease.

Optic Nerve Head Morphology in Adults Born Extreme, Very, and Moderate Preterm With and Without Retinopathy of Prematurity: Results From the Gutenberg Prematurity Eye Study.

PURPOSE: This study aimed to investigate associations of prematurity and associated factors with optic disc morphology in adulthood as long-term effects. DESIGN: Retrospective cohort study. METHODS: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination of adults (age 18-52 years) in Germany. In every participant, photography of optic discs was performed with a nonmydriatic fundus camera, and optic disc measurements were done manually. The vertical cup-to-disc ratio (VCDR), optic disc area, and torted and tilted discs were assessed and exploratively compared between individuals with retinopathy of prematurity (ROP) with treatment, an ROP group without treatment and groups of individuals of different gestational ages (GAs) without ROP (GA ≤ 28 weeks, GA 29-32 weeks, GA 33-36 weeks, and GA ≥ 37 weeks [control group]). RESULTS: The present analysis included 743 eyes of 393 individuals born preterm and full-term (aged 28.4 ± 8.6 years, 223 females). The VCDR was significantly larger in subjects with a GA ≤28 weeks without ROP compared to the full-term control group (GA ≥37 weeks) (P = .002). Subjects with ROP without treatment also had a larger VCDR (P = .001), whereas those with ROP treatment showed a smaller VCDR than the full-term control group (P = .02). In addition, individuals with ROP treatment were more likely to have a torted disc than the full-term control group (P = .006). CONCLUSION: The present study provides evidence that individuals born extremely preterm have increased VCDR in adulthood. Furthermore, these results indicate that fetal origins affect optic disc morphology until adulthood, which might predispose the affected individual to degenerative optic nerve head diseases or being incorrectly diagnosed to glaucoma.