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AimThe purpose of this study was to assess the prevalence of strabismus and nystagmus and to analyse associated factors in preterm and full-term infants in adulthood.MethodsThe Gutenberg Prematurity Eye Study is a retrospective cohort study with a prospective ophthalmological examination of participants born preterm and full-term (aged 18–52 years). Perinatal data were carefully assessed for risk factors and comprehensive ophthalmological examinations were conducted. The association between strabismus and nystagmus was assessed by analysing 16 different perinatal and actual risk factors in multivariable analysis. Participants were grouped into full-term controls (gestational age (GA) at birth ≥37 weeks), preterm participants without retinopathy of prematurity (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).ResultsIn total, 892 eyes of 450 preterm and full-term individuals (mean age: 28.6 years, SD: ± 8.6 years, 251 females) were included. Strabismus was observed in 2.1% (3/140), 6.6% (9/137), 17.4% (16/92), 11.1% (2/18), 27.1% (13/48) and 60% (9/15) of participants and nystagmus in 0.7% (1/140), 1.5% (2/137), 4.3% (4/92), 5.6% (1/18), 10.4% (5/48) and 26.7% (4/15) of participants in the respective groups. In the multivariable regression model, strabismus was associated with GA (OR=0.90; p=0.046), anisometropia ≥1.5 diopter (OR=3.87; p=0.003), hypermetropia ≥2 diopter (OR=9.89; p<0.001) and astigmatism ≥1.5 diopter (OR=2.73; p=0.017). Esotropia was more frequent than exotropia and hypermetropia/hypometropia. Most strabismus cases occurred within the first 10 years of life. The strongest predictor associated with nystagmus was perinatal adverse events (OR=15.8; p=0.002).ConclusionLow GA and refraction of the eye are independent risk factors for strabismus, which typically occurs in the first 10 years of life. Perinatal adverse events are the most important factors for the presence of nystagmus in adulthood.

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&lt; 0.001) with GA, birth weight, ROP, ROP treatment, and perinatal adverse events and was poorer in both ROP groups. Visual acuity of &lt;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.

Background/aimsTo evaluate whether anterior segment anatomy and axial length are associated with prematurity and perinatal factors in adults.MethodsThe 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.ResultsThe 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).ConclusionOur 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.

Supplemental Digital Content is Available in the Text.This study investigated the long-term effects of prematurity on macular morphology in adulthood indicating that fetal origins affect foveal shape, resulting in foveal hypoplasia potentially affecting the visual acuity in later life.

Hintergrund: Frühgeburtlichkeit und das Auftreten der Frühgeborenenretinopathie (ROP) erhöhen das Risiko für das Auftreten von amblyogenen Risikofaktoren in der Kindheit und Jugend. Ziel der Arbeit: Das Ziel der vorliegenden Studie war die Beschreibung der augenärztlichen Versorgung und der Augenerkrankungen ehemaliger früh- und reifgeborener Personen im Erwachsenenalter. Material und Methoden: Die Gutenberg Prematurity Eye Study (GPES) ist eine retrospektive Kohortenstudie mit einer prospektiven augenärztlichen Untersuchung von ehemaligen früh- und reifgeborenen Personen, geboren zwischen 1969 und 2002 (aktuelles Alter 18 bis 52 Jahre). Alle Teilnehmenden wurden hinsichtlich amblyogener Parameter wie z. B. dem Vorliegen eines Strabismus und von Refraktionsfehlern untersucht. Die Teilnehmenden wurden gruppiert in Personen mit normalem Gestationsalter (GA) ≥ 37 (Kontrollgruppe), Frühgeborene ohne ROP mit GA 33–36 (Gruppe 2), GA 29–32 (Gruppe 3), GA ≤ 28 Wochen (Gruppe 4) und solche mit ROP ohne Behandlung (Gruppe 5) und mit ROP mit Behandlung (Gruppe 6). Es wurde von allen Teilnehmenden erhoben, wie oft sie innerhalb der letzten 12 Monate bei einer augenärztlichen Untersuchung gewesen sind. Ergebnisse: Insgesamt wurden die Daten von 140 reifgeborenen und 310 frühgeborenen Erwachsenen in die vorliegende Studie eingeschlossen. Ein Strabismus lag bei 2,1 % (3/140), 6,6 % (9/137), 17,4 % (16/92), 11,1 % (2/18), 27,1 % (13/48) und 60 % (9/15) in den jeweiligen Gruppen 1 bis 6 vor. Der Anteil an Probanden mit augenärztlicher Untersuchung innerhalb der letzten 12 Monate war in den Gruppen der extrem Frühgeborenen mit und ohne ROP im Vergleich zur Kontrollgruppe am höchsten. Insgesamt waren 33,3 % (1/3) der Reifgeborenen und 57,1 % (28/49) der Frühgeborenen mit Strabismus und 0 % (0/3) der Reifgeborenen und 46,9 % (15/32) der Frühgeborenen mit Amblyopie innerhalb der letzten 12 Monate bei einer augenärztlichen Untersuchung. Diskussion: Extrem frühgeborene Personen mit und ohne postnatale ROP zeigten die höchste Rate an Augenerkrankungen sowie die höchste Rate an augenärztlichen Kontrolluntersuchungen innerhalb der letzten 12 Monate. Dies deutet darauf hin, dass extrem frühgeborene Personen insbesondere mit postnataler ROP insgesamt lebenslang häufigere augenärztliche Kontrolluntersuchungen wahrnehmen.

ObjectiveTo assess incidence and burden of neonatal herpes simplex virus (HSV) infections and to explore possible transmission routes.MethodsA 2-year prospective nationwide surveillance study performed in 2017 and 2018. All German paediatric departments (n=464 in 2017, n=441 in 2018) were contacted on a monthly basis to report potential cases of neonatal HSV infections. Infants with a postnatal age of ≤60 days and a positive HSV PCR or HSV culture from skin, mucous membrane, vesicles or conjunctival smear, blood or cerebrospinal fluid were included in the study.Results37 cases were analysed. 29 patients who exhibited no or only mild clinical symptoms were discharged home without organ damage or neurological abnormalities. Four patients showed significant neurological impairment, one patient required liver transplantation and two patients died during in-patient treatment. The 2-year incidence of neonatal HSV infections was 2.35 per 100 000 live births (95% CI 1.69 to 3.02) and disease-specific mortality was 0.13 per 100 000 live births (95% CI 0.04 to 0.21). Data on possible transmission routes were available in 23 cases. In 20 cases, an orofacial HSV infection was present in one or more family members. An active maternal genital HSV infection was reported in 3 cases.ConclusionNeonatal HSV infections are rare in Germany. Most infants have a benign clinical course, but some infants are severely affected. Postnatal HSV exposure may account for a considerable number of neonatal HSV infections.

ObjectiveClosed-loop automatic control (CLAC) of the fractional inspired oxygen (FiO2) improved oxygen administration to preterm infants on respiratory support. We investigated whether a revised CLAC algorithm (CLACfast, ≤2 FiO2adjustments/min), compared with routine manual control (RMConly), increased the proportion of time with arterial haemoglobin oxygen saturation measured by pulse oximetry within prespecified target ranges (Target%) while not being inferior to the original algorithm (CLACslow: ≤0.3 FiO2adjustments/min).DesignUnblinded randomised controlled crossover study comparing three modes of FiO2control in random order for 8 hours each: RMC supported by CLACfastwas compared with RMConlyand RMC supported by CLACslow. A computer-generated list of random numbers using a block size of six was used for the allocation sequence.SettingTwo German tertiary university neonatal intensive care units.PatientsOf 23 randomised patients, 19 were analysed (mean±SD gestational age 27±2 weeks; age at randomisation 24±10 days) on non-invasive (n=18) or invasive (n=1) respiratory support at FiO2>0.21.Main outcome measureTarget%.ResultsMean±SD [95% CI] Target% was 68%±11% [65% to 71%] for CLACfastversus 65%±11% [61% to 68%] for CLACslowversus 58%±11% [55% to 62%] for RMConly. Prespecified hypothesis tests of: (A) superiority of CLACfastversus RMConlyand (B) non-inferiority of CLACfastversus CLACslowwith margin of 5% yielded one-sided p values of <0.001 for both comparisons.ConclusionsThis revised and faster CLAC algorithm was still superior to routine care in infants on respiratory support and not inferior to a previously tested slower algorithm.Trial registration numberNCT03163108.

Background:Modified expression of nitric oxide synthases (NOSs) and an imbalance between the pro-oxidative and the antioxidative system accompany endothelial dysfunction, the first stage of atherosclerosis. Humans born small (SGA) or large (LGA) for gestational age are at higher risk of developing atherosclerosis later in life than humans born appropriate for gestational age (AGA). We hypothesized that indicators of endothelial dysfunction could be detectable at birth. The purpose of this study was to find out whether the expression patterns of NO synthases (endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS)), pro-oxidative enzymes (components of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, NADPH oxidase 1 (NOX1), NOX2, NOX4, p22phox, and p47phox), and antioxidative enzymes (superoxide dismutase 1–3 (SOD1–3), glutathione peroxidase 1 (GPX1), and catalase) in umbilical arteries differ among SGA, LGA, and AGA newborns.Methods:Thirty-six umbilical cords were obtained from healthy, normal, full-term SGA, AGA, and LGA newborns. The umbilical arteries were dissected and homogenized. mRNA expression was analyzed with quantitative real-time PCR. Western blotting was performed to determine protein expression.Results:mRNA and protein expression of NO synthases, pro-oxidative enzymes, and antioxidative enzymes did not differ in the umbilical arteries from newborns of the three groups.Conclusion:Indicators of endothelial dysfunction in terms of differences in enzyme expression in SGA or LGA newborns vs. AGA newborns were not present at birth.

In a previous study, human umbilical vein preparations constricted at Po2values above the physiologic intrauterine Po2range and dilated at hypoxia. Denudation of the endothelium reversed the hypoxic vasodilatation only, suggesting the release of a nonendothelial vasoconstrictor. We therefore hypothesized that norepinephrine from adrenergic nerve terminals could be responsible for the observed constricting effects. We measured intracellular membrane potential and isometric tension of human umbilical vein strips with and without functional adrenergic denervation by 6-OH-dopamine during variation of Po2. With Po2increasing from 5 to 104 mm Hg, intact preparations depolarized of from -58.6 ± 1.1 mV (SEM) to -53.3 ± 1.0 mV (p < 0.001) and isometric tension increased from 0.673 ± 0.037 g to 0.825 ± 0.044 g (p < 0.02). Intact preparations pretreated with 6-OH-dopamine depolarized from -58.0 ± 0.5 mV to -55.8 ± 0.6 mV (p < 0.01), and isometric tension increased from 0.598 ± 0.040 g to 0.661 ± 0.018 g (p < 0.02). At Po2values above the physiologic intrauterine umbilical venous Po2range, membrane potential and isometric tension were significantly lower in preparations with 6-OH-dopamine pretreatment compared with matched controls (p < 0.05). Denudation of the endothelium reversed the hypoxic hyperpolarization and vasodilatation observed in intact preparations. However, membrane potential and isometric tension were not different between endothelium-denuded preparations with and without 6-OH-dopamine pretreatment. We conclude that locally released norepinephrine contributes to the depolarization and vasoconstriction of the human umbilical vein at hyperoxia but does not antagonize the endothelium-dependent vasodilation at hypoxia.

There is a lack of knowledge concerning the frequency and significance of respiratory viral infections that occur in the neonatal intensive care unit. In the present study, all neonates with suspected nosocomial bacterial sepsis were screened for a panel of respiratory viruses. Respiratory viral infections were detected in 10 of these cases. This was comparable with the frequency of a blood-culture–proven sepsis.