Macular Curvature in Adults Born Preterm With and Without ROP: Results from the Gutenberg Prematurity Eye Study.

Purpose: This study investigated the effects of prematurity and retinopathy of prematurity (ROP) as well as the associations of the ocular geometry with macular curvature in adults. Methods: The Gutenberg Prematurity Eye Study is a retrospective cohort study of preterm and full-term participants aged 18 to 52 years with a prospective ophthalmologic examination. The main outcome measure was the macular curvature in the central foveal optical coherence tomography (OCT) scan and its associations with gestational age (GA), birth weight and birth weight percentile, ROP occurrence, ROP treatment, and other perinatal factors were evaluated in univariable and multivariable linear regression analyses. Furthermore, a second model assessed the association of ocular geometry with macular curvature. Results: In the present study, 550 eyes of 284 adults born preterm and 277 eyes of 139 adults born full-term were examined (aged = 28.7 ± 8.7 years, 240 female subjects). In multivariable analyses for perinatal parameters, ROP treatment (B = -52.44, P = 0.023) and maternal smoking during pregnancy (B = 26.41, P = 0.019) showed an association with macular curvature. Regarding ocular geometric parameters, posterior segment length (B = 9.07, P < 0.001) and subfoveal choroidal thickness (B = -0.26, P < 0.001) were associated with macular curvature, central corneal thickness, anterior chamber depth, lens thickness, and foveal retinal thickness were not associated. Conclusions: Adults treated for ROP had relatively more negative curvature values compared to the full-term group, indicating a macular protrusion toward the vitreous cave. A thicker subfoveal choroidal thickness was associated with a flatter macular curvature, whereas a longer posterior segment length was associated with a steeper macular curvature indicating the characteristics of the myopic elongation of the eye.

Video versus direct laryngoscopy to improve the success rate of nasotracheal intubations in the neonatal intensive care setting: a randomised controlled trial.

OBJECTIVE: To assess whether video laryngoscopy (VL) for tracheal intubation of neonates results in a higher first-attempt success rate and fewer adverse tracheal intubation-associated events (TIAEs) when compared with direct laryngoscopy (DL). DESIGN: Single-centre, parallel group, randomised controlled trial. SETTING: University Medical Centre Mainz, Germany. PATIENTS: Neonates <440/7 weeks postmenstrual age in whom tracheal intubation was indicated either in the delivery room or in the neonatal intensive care unit. INTERVENTION: Intubation encounters were randomly assigned to either VL or DL at first attempt. PRIMARY OUTCOME: First-attempt success rate during tracheal intubation. RESULTS: Of 121 intubation encounters assessed for eligibility, 32 (26.4%) were either not randomised (acute emergencies (n=9), clinicians' preference for either VL (n=8) or DL (n=2)) or excluded from the analysis (declined parental consent (n=13)). Eighty-nine intubation encounters (41 in the VL and 48 in the DL group) in 63 patients were analysed. First-attempt success rate was 48.8% (20/41) in the VL group compared with 43.8% (21/48) in the DL group (OR 1.22, 95% CI 0.51 to 2.88).The frequency of adverse TIAEs was 43.9% (18/41) and 47.9% (23/48) in the VL and DL group, respectively (OR 0.85, 95% CI 0.37 to 1.97). Oesophageal intubation with concomitant desaturation never occurred in the VL group but in 18.8% (9/48) of intubation encounters in the DL group. CONCLUSION: This study provides effect sizes for first-attempt success rates and frequency of TIAEs with VL compared with DL in the neonatal emergency setting. This study was underpowered to detect small but clinically important differences between the two techniques. The results of this study may be useful in planning future trials.

[Changes in neonatal care : Implications for ophthalmological care]. / Wandel der neonatologischen Versorgung : Implikationen für die augenärztliche Versorgung.

BACKGROUND: Preterm infants are at risk of characteristic, sometimes life-threatening diseases and development of deficits related to immaturity. In the field of ophthalmology, retinopathy of prematurity (ROP) and vision impairment reflect structural and functional disturbances in this large group of patients. In high income countries, more and more very immature preterm infants survive into adolescence and adulthood. OBJECTIVE: To characterize the impact of an increasing number of surviving individuals born preterm on the provision of ophthalmological care in Germany. MATERIAL AND METHODS: A literature search and analysis of key figures and quality indicators published in national health registers were carried out. RESULTS: Currently, about 60,000 preterm infants are born in Germany every year. Of these, approximately 3600 extremely immature preterm infants with a gestational age < 28 weeks are treated with a curative approach on neonatal units. The survival rate is around 80%. A rise in the proportion of infants suffering from severe ROP has not been observed in recent years in Germany. The incidences of other structural and functional visual impairments vary between 3% and 25% in high income countries. CONCLUSION: The incidence of ROP apparently has not increased in Germany. However, specific peculiarities of the structure and function of the visual system of individuals born preterm have to be taken into account. Approximately 70,000 outpatient check-ups of infants and toddlers, who require both, ophthalmological and developmental neurological expertise, are estimated for Germany each year.

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.

Foveal and Peripapillary Choroidal Thickness in Adults Born Extremely, Very, and Moderately Preterm With and Without ROP-Results From the Gutenberg Prematurity Eye Study.

Purpose: The present study investigated the long-lasting effect of prematurity, prenatal growth restriction, and associated factors on foveal and peripapillary choroidal thickness in adulthood. Methods: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. Foveal and peripapillary choroidal thicknesses were measured at different sectors using spectral-domain optical coherence tomography. Multivariable linear regression analyses were performed to determine associations among gestational age, birth weight percentile, retinopathy of prematurity (ROP) occurrence and treatment, and other perinatal factors, such as maternal smoking and others with foveal and global peripapillary choroidal thickness. Results: A total of 735 eyes of 408 study participants were included (age = 28.4 ± 8.6 years, 229 women). Multivariable regression analyses revealed that foveal choroidal thinning was associated with maternal smoking during pregnancy (B = -38.1, 95% confidence interval [CI] = -65.5 to -10.7, P = 0.006), whereas other perinatal factors revealed no association. Global peripapillary choroidal thinning showed a trend to a lower birth weight percentile (B = 0.22, 95% CI = -0.01 to 0.45, P = 0.057). No correlation was observed between foveal and peripapillary choroidal thicknesses with visual acuity. Conclusions: This study indicates that maternal cigarette smoking during pregnancy has adverse long-lasting effects on choroidal development in the fovea and low birth weight percentile as a surrogate marker for adverse perinatal growth might be linked with peripapillary choroidal thinning whereas prematurity showed no long-term effects. Translational Relevance: Altered choroidal layer development caused by perinatal influence factors might be a risk factor for reduced visual function and predispose affected individuals to eye diseases in later life.

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.

[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.

Rapid detection by hydrops panel of Noonan syndrome with PTPN11 mutation (p.Thr73Ile) and persistent thrombocytopenia.

BACKGROUND: Nonimmune hydrops fetalis (NIHF) is still a challenging diagnosis. The differential diagnosis is extensive and the success of identifying a cause depends on the thoroughness of efforts to establish a diagnosis. For the early diagnosis of NIHF, a virtual gene panel diagnostic tool was developed. The female premature baby in question was delivered via emergency cesarean at 30 + 1 weeks of gestational age (GA) due to rapidly developing NIHF to a healthy mother. The family history was noncontributory. METHODS: DNA of the family was extracted and sequenced by the virtual hydrops panel with whole-exome sequencing. RESULTS: The hydrops panel revealed Noonan syndrome (NS) with a germline mutation in PTPN11 c.218C>T (p.Thr73Ile). CONCLUSION: The diagnosis of our patient was rapidly confirmed by the hydrops panel. The variant of c.218C>T (p.Thr73Ile) has not yet been described in literature relating to NIHF. Only a few case reports of this variant are known. This particular mutation is associated with Noonan syndrome, congenital heart defect and persistent thrombocytopenia. Few reveal juvenile myelomonocytic leukemia.

[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.

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.

What If the Prenatal Diagnosis of a Lethal Anomaly Turns Out to Be Wrong?

Advances in prenatal diagnosis create a unique set of clinical ethics dilemmas. Doctors routinely obtain genetic screening, radiologic images, and biophysical profiling. These allow more accurate diagnosis and prognosis than has ever before been possible. However, they also reveal a wider range of disease manifestations than were apparent when prenatal diagnosis was less sophisticated. Sometimes, the best estimates of prognosis turn out to be wrong. The infant's symptoms may be less severe or more severe than anticipated based on prenatal assessment. We present a case in which a prenatal diagnosis was made of severe osteogenesis imperfecta, leading to a decision to induce delivery at 31 weeks. On postnatal evaluation, the infant's disease did not appear to be as bad as had been anticipated. We discuss the ethical implications of such diagnostic and prognostic errors.

Digoxin-like immunoreactive substance in nonoliguric hyperkalemia of the premature infant.

Nonoliguric hyperkalemia of premature infants probably results from a transient inhibition of membrane-bound Na+/K+-ATPase during the first 24 h after birth. We hypothesized that the endogenous digitalis-like activity of the serum of premature infants, which inhibits the Na+/K+-ATPase, triggered hyperkalemia. Serum concentrations of potassium ([K+]) and of the digoxin-like immunoreactive substance ([DLIS]) were measured during the first 24 h after birth in 60 infants including 30 infants <30 gestational weeks. Contrary to our hypothesis, there was a negative linear correlation between [DLIS] at birth and [K+] 24 h after birth (r2 = 0.24, p < 0.002). 24 h after birth there was no correlation between [DLIS] and [K+]. Thus, a major role of DLIS in nonoliguric hyperkalemia could not be established.

Pulmonary re-occurrence of post-transplant lymphoproliferative disease with hypogammaglobulinaemia.

UNLABELLED: We report the case of a 12-year-old boy, who developed Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disease (PTLD) 7 years after renal transplantation. He responded well to the reduced immunosuppressive therapy and treatment with ganciclovir. Two years later he developed severe pneumonia and hypogammaglobulinaemia related to EBV infection exacerbation. An X-ray film revealed persistent pneumonia in the right lung. Lung biopsy showed a large, diffuse EBV-associated B-cell lymphoma. This constellation suggested re-occurrence of the primary PTLD. CONCLUSION: We present a case of recurring Epstein-Barr virus-associated post-transplant lymphoproliferative disease with a remarkably late onset in addition to hypogammaglobulinaemia.