FOVEAL AVASCULAR ZONE IN ADULTS BORN PRETERM WITH AND WITHOUT RETINOPATHY OF PREMATURITY: Results From The Gutenberg Prematurity Eye Study.

PURPOSE: To examine potential changes in the foveal avascular zone (FAZ) during adulthood due to prematurity and retinopathy of prematurity (ROP), as assessed by measurements of the FAZ area and circularity. METHODS: The Gutenberg Prematurity Eye Study is a retrospective German cohort study with a prospective ophthalmologic examination of adults aged 18 years to 52 years, born either preterm or full-term, using spectral-domain optical coherence tomography angiography. Participants were categorized into groups based on gestational age and postnatal ROP status. The study conducted multivariable linear regression analyses to explore associations with the FAZ. RESULTS: The study cohort comprised 380 right eyes from individuals born both preterm and full-term, with an average age of 28.4 years ± 8.6 years, including 214 women. The FAZ area decreased as gestational age decreased: FAZ was 0.28 mm 2 ± 0.12 mm 2 in the control group, 0.21 ± 0.10 mm 2 at GA 33 weeks to 36 weeks, 0.18 mm 2 ± 0.10 mm 2 at GA 29 weeks to 32 weeks, 0.11 mm 2 ± 0.10 mm 2 at GA ≤28 weeks, 0.11 mm 2 ± 0.10 mm 2 in ROP without treatment, and 0.11 mm 2 ± 0.10 mm 2 in those requiring ROP treatment. In the multivariable analyses, smaller FAZ was independently associated with gestational age ( P < 0.05), increased foveal retinal thickness ( P < 0.05), and foveal hypoplasia ( P < 0.05). Moreover, no association was seen between visual acuity and FAZ. CONCLUSION: The main perinatal factor associated with a smaller FAZ in this German cohort is preterm birth, while ROP, ROP treatment, or other perinatal factors do not affect FAZ observed in adulthood. A smaller FAZ shape in preterm individuals might be an indicator of foveal hypoplasia.

Attitudes and values towards decisions at the margin of viability among expectant mothers at risk for preterm birth.

AIM: To explore how expectant mothers at risk for preterm birth would like to be involved in decision-making at the margin of viability and what they would base their decisions on. METHODS: This cross-sectional observational study included a mixed-methods post-hoc analysis alongside a previously reported randomised clinical trial. Expectant mothers between 280/7 and 366/7 weeks' gestation who were hospitalised for risk of preterm birth responded to written case vignettes of an impending preterm birth at the margin of viability. Participants responded to closed and open-ended questions that were theoretically coded for attitudes and values towards shared decision-making. RESULTS: Sixty-four expectant mothers were included in the analysis, 36 provided written perspectives. Decision-making was perceived as an enormous burden and a potential source of guilt and regret. Weighing personal values in terms of 'fighting for the baby' and 'quality of life' were used to inform the decision-making process. Explicitly stating that any decision is a good decision, empowerment through co-constructing shared decisions rather than simply presenting choices, sharing the clinicians' personal views, and honest, and empathetic counselling were perceived as supportive. CONCLUSION: Mothers at risk for preterm birth provided specific insights into their decision-making patterns that may be helpful to clinicians.

European survey showed wide variations in diagnostic procedures and management strategies for metabolic bone disease of prematurity in 22 countries.

AIM: The aim of this study was to evaluate the clinical relevance, diagnostic procedures and treatment strategies for metabolic bone disease in preterm infants across Europe. METHODS: An e-survey was distributed by email to 545 neonatal units in 38 European countries between July and October 2021. The protocol was based on the Checklist for Reporting Results of Internet E-Surveys. RESULTS: In total, 76 neonatal units (14%) from 22 European countries (58%) completed the e-survey. In the 12 months prior to the survey, 29% of 76 units reported at least one symptomatic case of fracture associated with metabolic bone disease of prematurity, and 18% of 76 units reported at least one case of craniofacial deformity. Most centres followed local guidelines for diagnosis (77% of 73 units) and treatment (63% of 72 units). Alkaline phosphatase was the blood marker most used for treatment indication (81% of 72 units), and phosphate supplementation was the treatment most used (82% of 71 units). CONCLUSION: Metabolic bone disease of prematurity remains clinically relevant. Wide variations in diagnostic procedures and management strategies were observed in European neonatal units. Evidence-based consensus guidelines appear urgently needed to reduce the number of symptomatic cases.

Ophthalmologic Care of Former Preterm and Full-Term Infants during Their Childhood and Adolescence - A Retrospective View of Their Parents. / Augenärztliche Versorgung früh- und reifgeborener Personen in deren Kindheit und Jugend ­ eine retrospektive Sicht der Eltern.

BACKGROUND: The aim of the present study was to evaluate the ophthalmologic care in childhood and adolescence of infants born preterm and full-term from the retrospective point of view of their parents. METHODOLOGY: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination of persons born preterm and full-term between 1969 and 2002 (now aged 18 to 52 years), and asks their parents about the ophthalmologic care received by their children in childhood and adolescence from their retrospective perspective. Participants and their parents were grouped into those with normal gestational age (GA) ≥ 37 (control group), preterm born infants without retinopathy of prematurity (ROP) and gestational age (GA) 33 - 36 (group 2), GA 29 - 32 (group 3), GA ≤ 28 weeks (group 4), and those with ROP without treatment (group 5) and with ROP with treatment (group 6). Parents of participants were interviewed about the ophthalmic care received by their children. RESULTS: In total, data from 57 full-term and 131 preterm infants and their parents were included in the present study. The parents of the participants reported that ophthalmologic examination had taken place until 6 years of age in the respective groups 1 to 6 in 22/57 (38.6%), 33/58 (56.9%), 22/38 (57.9%), 3/6 (50%), 19/21 (90.5%), and 7/8 (87.5%). Overall, between 83% and 100% of parents in the different groups reported that ophthalmologic care had been adequate. A change of ophthalmologist due to dissatisfaction with treatment was reported by a total of 4/57 (7%), 9/58 (15.5%), 8/38 (21.1%), 1/6 (16.7%), 1/21 (4.8%) and 2/8 (25%) in the respective groups. DISCUSSION: The present study demonstrates adequate satisfaction and good treatment regarding ophthalmologic care of former preterm children from the parents' perspective. Especially parents of children with ROP rated the treatment positively.

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.

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.

A single center experience in 90 cases with nonimmune hydrops fetalis: diagnostic categories ‒ mostly aneuploidy and still often idiopathic.

OBJECTIVES: The prognosis of nonimmune hydrops fetalis (NIHF) is still poor with a high mortality and morbidity rate despite progress in perinatal care. This study was designed to investigate etiology and outcome of NIHF. METHODS: A retrospective review of 90 NIHF cases from 2007 to 2019 was conducted at University Medical Center of the Johannes Gutenberg University, Mainz, Germany. Demographics, genetic results, prenatal and postnatal outcomes including one year survival as well as autopsy data were extracted. Etiology of hydrops was classified using 13 previously established categories. In 4 patients observed between 2016 and 2019, we used a next-generation-sequencing (NGS) panel for genetic evaluation. RESULTS: Ninety NIHF cases were identified, with a median gestational age (GA) at diagnosis of 14 weeks. There were 25 live-born infants with a median GA of 34 weeks at birth, 15 patients survived to one year. There was aneuploidy in more than one third of the cases. All 90 cases were subclassified into etiologic categories with chromosomal 35, idiopathic 15, syndromic 11, cardiovascular 9, inborn errors of metabolism 6, lymphatic dysplasia 3, thoracic 3, infections 3, gastrointestinal 3 and hematologic 2. The NGS panel was used in 4 cases and 4 diagnoses were made. CONCLUSIONS: In 90 cases with NIHF we identified an aneuploidy in more than one third of the cases. Improved techniques, such as possibly specific genetic analysis, could reduce the high rate of unexplained cases of NIHF.

Mutations in PRDM15 Are a Novel Cause of Galloway-Mowat Syndrome.

BACKGROUND: Galloway-Mowat syndrome (GAMOS) is characterized by neurodevelopmental defects and a progressive nephropathy, which typically manifests as steroid-resistant nephrotic syndrome. The prognosis of GAMOS is poor, and the majority of children progress to renal failure. The discovery of monogenic causes of GAMOS has uncovered molecular pathways involved in the pathogenesis of disease. METHODS: Homozygosity mapping, whole-exome sequencing, and linkage analysis were used to identify mutations in four families with a GAMOS-like phenotype, and high-throughput PCR technology was applied to 91 individuals with GAMOS and 816 individuals with isolated nephrotic syndrome. In vitro and in vivo studies determined the functional significance of the mutations identified. RESULTS: Three biallelic variants of the transcriptional regulator PRDM15 were detected in six families with proteinuric kidney disease. Four families with a variant in the protein's zinc-finger (ZNF) domain have additional GAMOS-like features, including brain anomalies, cardiac defects, and skeletal defects. All variants destabilize the PRDM15 protein, and the ZNF variant additionally interferes with transcriptional activation. Morpholino oligonucleotide-mediated knockdown of Prdm15 in Xenopus embryos disrupted pronephric development. Human wild-type PRDM15 RNA rescued the disruption, but the three PRDM15 variants did not. Finally, CRISPR-mediated knockout of PRDM15 in human podocytes led to dysregulation of several renal developmental genes. CONCLUSIONS: Variants in PRDM15 can cause either isolated nephrotic syndrome or a GAMOS-type syndrome on an allelic basis. PRDM15 regulates multiple developmental kidney genes, and is likely to play an essential role in renal development in humans.

[Comparison of the Accuracy of the Measurement of Fetal Hemoglobin by Blood Gas Analysis and by Laboratory Gold Standard: a Prospective Diagnostic Study]. / Prospektiver Vergleich der Genauigkeit der Messung des fetalen Hämoglobins mittels Blutgasanalyse mit dem Goldstandard bei früh- und reifgeborenen Neugeborenen.

BACKGROUND: In neonatologic clinical practice and research the percentage of fetal hemoglobin (HbF) of total hemoglobin can be of interest. Blood gas analyzers offer the measurement of HbF. However, it is not known if results are accurate enough to apply in clinical decision-making or scientific questions. In this prospective diagnostic study, we examined the accuracy of HbF measurement by a blood gas analyzer. METHODS: On a neonatal intensive care and neonatal ward, the percentage of HbF was measured using both the laboratory gold standard (HbFlab, reference method) and the blood gas analyzer (HbFgas) (ABL 800 Flex, Radiometer). Agreement of HbFlab and HbFgas was assessed by the Bland-Altman method including bias and limits of agreement and by calculation of the root mean square error (RMSE). RESULTS: Thirty-five measurements in 23 term and preterm infants with a median body weight of 2190 g (min-max 967-3800 g) and a median postmenstrual age of 36+1 weeks (min-max 29+6-43+2) were performed. The Bland-Altman diagram for the measurement of HbF(gas) versus HbF(lab) shows an overestimation of HbF by the blood gas analyzer (bias 9.3%, limits of agreement 1 to 17.6%). RMSE was 10.2%; 45.7% of HbFgas measurements were >10% out of range from HbFlab. There was no influence of age, body temperature or oxygen saturation on the bias (p=0,132; p=0,194; p=0,970), but bias increased with increasing HbFlab (Pearson correlation r=0,426; p=0,011). CONCLUSION: The measurement of HbF in term and preterm infants by a blood gas analyzer lacked sufficient agreement with that of the reference method to recommend this application for clinical decision-making or scientific purposes.

[Results of the hypothermia registry of the University Hospital Dresden from 2010-2017. Application of hypothermia therapy in newborns in Germany]. / Ergebnisse des Hypothermienetzwerks des Universitätsklinikums Dresden von 2010­2017. Entwicklung der Hypothermietherapie bei Neugeborenen in Deutschland.

INTRODUCTION: Therapeutic hypothermia (TH) improves the outcome in newborns with hypoxic-ischemic encephalopathy (HIE) and should be used in case of perinatal asphyxia and signs of moderate/severe HIE. MATERIAL/METHODS: Frequency of HIE and the application of TH were extracted from the neonatal survey, a registry that collects data from all German hospitals, and from the hypothermia registry, established in 2010. The latter was also used to analyze short-term outcomes of the newborns. RESULTS: Between 2010 and 2017, 106 of Germany's 213 perinatal centers joined the registry. Response rates varied between 22 and 60%. The registry recorded 164 (IQR 115-224) TH cases per year in newborns with HIE. In the neonatal survey, 517 (382-664) TH and 543 (432-581) HIE cases were reported. Since 2014 there have been more cases of TH than HIE. After TH, 10.4% (8-13%) of the newborns died, 81% (78-82%) of the newborns were discharged home, 3.6% (3-5%) to a rehabilitation facility, and 5.4% (5-7%) transferred to another clinic. 89% (87-89%) were on complete oral feedings. DISCUSSION: After the introduction of TH in the clinical routine, the number of treated newborns increased continuously. Currently, the number of TH is higher than the number of children with HIE, which is difficult to explain, as the presence of a moderate or severe HIE is a mandatory requirement for TH. The data from the hypothermia registry showed no significant changes in mortality or neurological outcome over time.

[Kagami-Ogata Syndrome: An Anomaly of the Ribs as a Pathognomonic Feature for the Clinical Diagnosis of an (epi)Genetic Syndrome]. / Das Kagami-Ogata-Syndrom: Eine Rippenanomalie als pathognomonisches Korrelat für die klinische Diagnose eines (epi)genetischen Syndroms.

Within 4 years (2014-2017), we genetically diagnosed 2 newborns with Kagami-Ogata syndrome (OMIM #608149). As fetuses they exhibited prenatal polyhydramnios and in 1 case hepatomegaly. After birth, the newborns suffered from respiratory distress. Typical phenotypic features, such as muscular hypotonia, a protruding philtrum, full cheeks and a depressed nasal bridge, were present. Chest X-rays revealed coat-hanger ribs and a bell-shaped thorax, suggestive of the entity. Kagami-Ogata syndrome is caused by an aberrant gene expression of chromosome 14 and was first described in 1991. Possible causes are paternal uniparental disomy of chromosome 14, epimutations and microdeletions. Approximately 70 cases have been reported in the literature, with 34 comprising the original cohort of M. Kagami and T. Ogata. The incidence of the disease is unknown. Patients often manifest a developmental delay and an intellectual disability, although in the meantime cases with milder clinical courses have been described. In the cohort of Kagami and Ogata 3 patients developed hepatoblastoma, which is a common feature in another imprinting disorder, namely the Beckwith-Wiedemann syndrome. Therefore, hepatoblastoma should be considered in follow-up examinations.

Weaning Premature Infants from Nasal Continuous Positive Airway Pressure - Current Practice and Scientific Evidence.

Objective In the past decade, a number of trials have been conducted to determine the optimal strategy of weaning premature infants from nasal continuous airway pressure (nCPAP). However, a paucity of information exists on how weaning is actually performed in clinical routine. Aim of this study was to investigate the current practice of weaning premature infants from nCPAP in Germany. Methods An online survey was performed in German tertiary care neonatal units. Results All 160 German tertiary care units were contacted. Replies were retrieved from 85/160 (53%) units, of which 83/160 (52%) completed the questionnaire. 66/83 (80%) respondents indicated to wean without the use of formal written policies. In 44/83 (53%) units weaning decisions are made jointly between physicians and nurses, whereas physicians are the sole decision makers in 33/83 (40%) as are nurses in 6/83 (7%) units. Many units use more than one weaning strategy. 81/83 units (98%) gradually reduce nCPAP pressure as the initial step in the weaning process. 9/83 (11%) units stop nCPAP at standard criteria [CICADA (CeasIng nCpap At standarD criteriA) method] and 58/83 (70%) units use a cycling nCPAP on/off strategy. 52/83 (63%) of the responding units use nasal high flow at least at some point during the weaning process, either as a gradual weaning method or during nCPAP breaks. Conclusion Weaning strategies from nCPAP vary widely in German tertiary care neonatal units. It appears that evidence is still insufficient to promote a distinct weaning strategy which in turn highlights the urgent need for further adequately powered clinical trials.

Viral Infections in Neonates with Suspected Late-Onset Bacterial Sepsis-A Prospective Cohort Study.

Objective The aim of our study was to evaluate the occurrence of viral infections in infants with suspected late-onset bacterial sepsis in a neonatal intensive care unit. Methods In a prospective study, infants with suspected late-onset bacterial sepsis underwent viral testing alongside routine blood culture sampling. Using a multiplex reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay, nasopharyngeal aspirates were analyzed for adenovirus, respiratory syncytial virus (RSV), influenza virus A and B, H1N1 virus, parainfluenza virus 1 to 4, metapneumovirus, coronavirus, and picornavirus. Stools were examined for adenovirus, rotavirus, norovirus, and enterovirus. Results Between August 2010 and March 2014, data of 88 infants with 137 episodes of suspected late-onset bacterial sepsis were analyzed. Six infants were diagnosed with a respiratory viral infection (2 × RSV, 4 × picornavirus). Blood culture-proven bacterial sepsis was detected in 15 infants. Neither viral-bacterial coinfections nor polymerase chain reaction positive stool samples were found. Conclusion Respiratory viruses can be detected in a considerable number of neonates with suspected late-onset bacterial sepsis. In contrast, gastrointestinal viral or enterovirus infections appear uncommon in such cases.

Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C.

OBJECTIVE: Congenital sodium diarrhoea (CSD) refers to a form of secretory diarrhoea with intrauterine onset and high faecal losses of sodium without congenital malformations. The molecular basis for CSD remains unknown. We clinically characterised a cohort of infants with CSD and set out to identify disease-causing mutations by genome-wide genetic testing. DESIGN: We performed whole-exome sequencing and chromosomal microarray analyses in 4 unrelated patients, followed by confirmatory Sanger sequencing of the likely disease-causing mutations in patients and in their family members, followed by functional studies. RESULTS: We identified novel de novo missense mutations in GUCY2C, the gene encoding receptor guanylate cyclase C (GC-C) in 4 patients with CSD. One patient developed severe, early-onset IBD and chronic arthritis at 4 years of age. GC-C is an intestinal brush border membrane-bound guanylate cyclase, which functions as receptor for guanylin, uroguanylin and Escherichia coli heat-stable enterotoxin. Mutations in GUCY2C were present in different intracellular domains of GC-C, and were activating mutations that enhanced intracellular cyclic guanosine monophosphate accumulation in a ligand-independent and ligand-stimulated manner, following heterologous expression in HEK293T cells. CONCLUSIONS: Dominant gain-of-function GUCY2C mutations lead to elevated intracellular cyclic guanosine monophosphate levels and could explain the chronic diarrhoea as a result of decreased intestinal sodium and water absorption and increased chloride secretion. Thus, mutations in GUCY2C indicate a role for this receptor in the pathogenesis of sporadic CSD.

Key features and clinical variability of COG6-CDG.

The conserved oligomeric Golgi (COG) complex consists of eight subunits and plays a crucial role in Golgi trafficking and positioning of glycosylation enzymes. Mutations in all COG subunits, except subunit 3, have been detected in patients with congenital disorders of glycosylation (CDG) of variable severity. So far, 3 families with a total of 10 individuals with biallelic COG6 mutations have been described, showing a broad clinical spectrum. Here we present 7 additional patients with 4 novel COG6 mutations. In spite of clinical variability, we delineate the core features of COG6-CDG i.e. liver involvement (9/10), microcephaly (8/10), developmental disability (8/10), recurrent infections (7/10), early lethality (6/10), and hypohidrosis predisposing for hyperthermia (6/10) and hyperkeratosis (4/10) as ectodermal signs. Regarding all COG6-related disorders a genotype-phenotype correlation can be discerned ranging from deep intronic mutations found in Shaheen syndrome as the mildest form to loss-of-function mutations leading to early lethal CDG phenotypes. A comparison with other COG deficiencies suggests ectodermal changes to be a hallmark of COG6-related disorders. Our findings aid clinical differentiation of this complex group of disorders and imply subtle functional differences between the COG complex subunits.

Ocular geometry in adults born small, appropriate or large for gestational age at term.

PURPOSE: Intrauterine growth restriction leading to a birth weight (BW) which is too low for gestational age (GA) is a known risk factor for various altered organ morphologies and dysfunction in later life. This study aimed to determine for the first time the effects of being small (SGA) or large for gestational age (LGA) on the ocular geometry of adults born at term. METHODS: All participants were examined with optical biometry (LenStar 900, Haag Streit) to compare the corneal curvature, white-to-white distance, anterior chamber depth, lens thickness and axial length between former moderate (BW percentile 3rd to <10th) and severe (BW <3rd percentile) SGA, controls (BW 10th-90th percentile) and former moderate (BW >90th to 97th percentile) and severe (BW >97th percentile) LGA. Multivariable linear regression was used to analyse associations with GA, BW percentile categories, placental insufficiency, preeclampsia and breastfeeding after adjustment for age and sex. RESULTS: In total, 589 eyes of 296 individuals born at term (aged 30.0 ± 9.4 years, 156 females) were examined, including 40 severe SGA, 38 moderate SGA, 140 with normal BW, 38 moderate LGA and 40 severe LGA. There was an association between a steeper corneal curvature with moderate (B = -0.201; p < 0.001) and severe SGA (B = -0.199; p < 0.001), with extreme SGA associated with smaller white-to-white (B = -0.263; p = 0.001) and a shorter axial length (B = -0.524; p = 0.031). CONCLUSIONS: Severe and moderate prenatal growth restriction in adults born at term leads to an altered ocular geometry, namely a steepening of the cornea and a smaller corneal diameter.

Optimistic vs Pessimistic Message Framing in Communicating Prognosis to Parents of Very Preterm Infants: The COPE Randomized Clinical Trial.

Importance: In the neonatal intensive care unit, there is a lack of understanding about how best to communicate the prognosis of a serious complication to parents. Objective: To examine parental preferences and the effects of optimistic vs pessimistic message framing when providing prognostic information about a serious complication. Design, Setting, and Participants: This crossover randomized clinical trial was conducted at a single German university medical center between June and October 2021. Eligible participants were parents of surviving preterm infants with a birth weight under 1500 g. Data were analyzed between October 2021 and August 2022. Interventions: Alternating exposure to 2 scripted video vignettes showing a standardized conversation between a neonatologist and parents, portrayed by professional actors, about the prognosis of a hypothetical very preterm infant with severe intraventricular hemorrhage. The video vignettes differed in the framing of identical numerical outcome estimates as either probability of survival and probability of nonimpairment (optimistic framing) or a risk of death and impaired survival (pessimistic framing). Main Outcomes and Measures: The primary outcome was preference odds (ratio of preference for optimistic vs pessimistic framing). Secondary outcomes included state anxiety, perceptions of communication, and recall of numerical estimates. Results: Of 220 enrolled parents (142 [64.5%] mothers; mean [SD] age: mothers, 39.1 [5.6] years; fathers, 42.7 [6.9] years), 196 (89.1%) preferred optimistic and 24 (10.1%) preferred pessimistic framing (preference odds, 11.0; 95% CI, 6.28-19.10; P < .001). Preference for optimistic framing was more pronounced when presented second than when presented first (preference odds, 5.41; 95% CI, 1.77-16.48; P = .003). State anxiety scores were similar in both groups at baseline (mean difference, -0.34; -1.18 to 0.49; P = .42) and increased equally after the first video (mean difference, -0.55; 95% CI, -1.79 to 0.69; P = .39). After the second video, state anxiety scores decreased when optimistic framing followed pessimistic framing but remained unchanged when pessimistic framing followed optimistic framing (mean difference, 2.15; 95% CI, 0.91 to 3.39; P < .001). With optimistic framing, participants recalled numerical estimates more accurately for survival (odds ratio, 4.00; 95% CI, 1.64-9.79; P = .002) but not for impairment (odds ratio, 1.50; 95% CI, 0.85-2.63; P = .16). Conclusions and Relevance: When given prognostic information about a serious complication, parents of very preterm infants may prefer optimistic framing. Optimistic framing may lead to more realistic expectations for survival, but not for impairment. Trial Registration: German Clinical Trials Register (DRKS): DRKS00024466.

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.

Fetal Growth Restriction Leads to an Enlarged Cup-to-Disc Ratio in Adults Born at Full Term.

PURPOSE: This study explores associations between fetal growth restriction or excessive fetal growth, along with perinatal factors on the optic nerve head morphology in adulthood. DESIGN: Retrospective cohort study. METHODS: This retrospective cohort study involved a prospective ophthalmological examination of individuals born at full term (with a gestational age of ≥37 weeks) from 1969 to 2002. Each participant underwent nonmydriatic fundus camera photography to capture images of the optic discs, followed by manual measurements. The vertical cup-to-disc ratio (VCDR) and optic disc area were examined and analyzed in relation to the baby's birth weight relative to the gestational age. These categories included those with former moderate (birth weight percentile between the 3rd and <10th), severe SGA (below the third percentile), normal (AGA, 10th-90th percentile), and moderately (birth weight >90th-97th percentile) and severely (birth weight >97th percentile) large for gestational age (LGA) adults within the age range of 18 to 52 years. RESULTS: Overall, 535 eyes of 280 individuals (age 29.7 ± 9.2 years, 144 females) born at full term were included. Multivariable analysis showed a significant association between a larger VCDR and the severe SGA group (B = 0.05, 95% CI 0.01-0.10; P = .02). In the univariable model, placental insufficiency was associated with VCDR (B = 0.10, 95% CI 0.01-0.19; P = .03). Other perinatal factors did not demonstrate an association with VCDR. Furthermore, there was an indication of an association suggesting a smaller optic disc area in individuals born moderately SGA at full term (B = -0.17, 95% CI -0.33 to -0.001; P = .05). CONCLUSIONS: This study provides evidence that individuals born at-term with severe SGA have an increased VCDR, suggesting that fetal growth restriction has a lasting impact on optic disc morphology independent of prematurity throughout adulthood.