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Prof. Dr. med. Sven Schulzke

Department of Clinical Research
Profiles & Affiliations

Neonatal Respiratory Disease Research Group

Our research includes methodological, physiological and clinical studies of neonatal/infant lung function and autonomic instability of preterm infants, diagnosis and treatment of chronic lung disease of infancy, optimising mechanical ventilation, and clinical trials and meta-analyses of trials in neonates.

A major research topic is understanding, diagnosing and preventing effects of autonomic instability and structural immaturity of the lung in preterm infants. This group is closely collaborating with researchers from the Paediatric Pneumology Research Group and the Neuropediatrics Research Group at UKBB.

Selected Publications

Kaempfen, Siree, Hug, Mareike, Sanchez, Carlos, Delgado-Eckert, Edgar, & Schulzke, Sven M. (2025). Heart Rate Variability Does Not Predict Recurrence of Apnoea of Prematurity After Ceasing Caffeine Therapy: A Prospective Cohort Study. Acta Paediatrica, International Journal of Paediatrics, 114(6), 1371–1378. https://doi.org/10.1111/apa.17579

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Zannin, Emanuela, Rigotti, Camilla, Schulzke, Sven M., Sindelar, Richard, Werther, Tobias, Lavizzari, Anna, Neumann, Roland P., Wallström, Linda, Mosca, Fabio, Ventura, Maria Luisa, Dellacà, Raffaele L., & Veneroni, Chiara. (2025). Early respiratory system reactance predicts respiratory outcomes in preterm infants: a retrospective, multicentre study [Journal-article]. European Respiratory Journal, 65(1), 2400246. https://doi.org/10.1183/13993003.00246-2024

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Neumann, Roland P., Gerull, Roland, Hasler, Pascal W., Wellmann, Sven, & Schulzke, Sven M. (2024). Vasoactive peptides as biomarkers for the prediction of retinopathy of prematurity [Journal-article]. Pediatric Research, 95(7), 1868–1874. https://doi.org/10.1038/s41390-024-03091-w

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Neumann RP, Gerull R, Zannin E, Fouzas S, & Schulzke SM. (2022). Volumetric Capnography at 36 Weeks Postmenstrual Age and Bronchopulmonary Dysplasia in Very Preterm Infants. Journal of Pediatrics, 241, 97–102. https://doi.org/10.1016/j.jpeds.2021.10.019

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Selected Projects & Collaborations

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RELIEF-Trial: Restricted versus liberal fluid intake for prevention of bronchopulmonary dysplasia - a cluster-randomised multiple period cross-over trial

Research Project  | 1 Project Members

20% der Frühgeborenen in der Schweiz, die mehr als 10 Wochen zu früh zur Welt kommen, entwickeln eine chronische Lungenerkrankung, die langfristig auch Wachstum und Gehirnentwicklung beeinflussen kann. Das passiert hauptsächlich, weil Sauerstoff und Beatmung, welche die Kinder zum Überleben brauchen, auch ihre sehr empfindlichen Lungen angreifen. Da die kleinen Blutgefässe in der Lunge von Frühgeborenen aufgrund der Unreife noch undicht sind, hat auch die Flüssigkeitsmenge einen Einfluss darauf.


Warum könnte Flüssigkeitseinschränkung helfen 

Niemand weiss, wieviel Flüssigkeit kleine Frühgeborene exakt brauchen. Bei Flüssigkeitseinschränkung läuft vermutlich weniger Wasser in die Lunge. Dadurch brauchen die Kinder wohl weniger Sauerstoff und Beatmung, seltener Medikamente und haben damit weniger Nebenwirkungen. Bei Flüssigkeitseinschränkung muss man die Milch stärker anreichern, damit Frühgeborene genug Nährstoffe bekommen, z.B. ausreichend Eiweiss, Kalorien und Salze, was die Verdauung erschweren kann.


Studienziel

Wir möchten herausfinden, ob Frühgeborene weniger häufig eine chronische Lungenerkrankung bekommen, wenn man ihnen weniger Flüssigkeit statt mehr Flüssigkeit gibt. 


Wo wird die Studie gemacht

Alle neun Spitäler in der Schweiz, die kleine Frühgeborene behandeln, nehmen an dieser Studie teil.


Was wird in der Studie gemacht

Wir werden die Flüssigkeitsmenge von Frühgeborenen über 30 Monate hinweg alle 6 Monate abwechselnd leicht senken bzw. erhöhen. Sie wird aber immer im Rahmen üblicher Mengen in Schweizer Spitälern sein. Wir werden Sorge tragen, dass die Kinder immer ihre erforderlichen Nährstoffe erhalten.


Was wird untersucht

Die teilnehmenden Spitäler zählen, wie viele Frühgeborene während der Studienzeit eine chronische Lungenerkrankung bekommen. Sie messen Wachstum, Dauer des Spitalaufenthalts, ob Medikamente für chronische Lungenerkrankung nötig waren und allfällige Nebenwirkungen auftraten. 12 und 24 Monate nach Spitalaustritt werden die Eltern nach Atemproblemen, Entwicklung der Kinder, Notfallbehandlungen oder Spitaleinweisungen befragt. Dann wird berechnet, ob die anfängliche Flüssigkeitsmenge einen Einfluss auf diese Probleme hat.


Wem nützt diese Studie

Die Studienteilnehmer werden selbst keinen direkten Nutzen haben. Frühgeborene, die nach Studienende zur Welt kommen, haben einen Nutzen, weil man dann eher weiss, wieviel Flüssigkeit sie brauchen, um die chronische Lungenerkrankung zu vermeiden.


Wie wurden Eltern und Öffentlichkeit in die Studie eingebunden

Eltern von Frühgeborenen sind schon seit der Vorbereitung an dieser Studie beteiligt. Sie haben geholfen zu messen was für Familien wirklich von Bedeutung ist und Dokumente so zu schreiben, dass sie gut verständlich sind.


Wie werden die Studienergebnisse öffentlich gemacht

Die Ergebnisse dieser Studie werden auf Internetseiten der Studie und der Elternvereinigungen, in wissenschaftlichen Zeitschriften, sowie in sozialen und allgemeinen Medien veröffentlicht werden.

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Predictive value of heart rate variability on cardiorespiratory events of preterm infants routinely immunised in the hospital

Research Project  | 2 Project Members

Preterm birth is a major challenge of health care systems across the globe, affecting about 10% of all infants born worldwide, resulting in almost 13 million preterm births per year. The autonomic nervous system of preterm infants is characterized by instability of heart rate and breathing, requiring continuous monitoring of vital signs over several months and long-term respiratory support. Cardiorespiratory events due to this instability, summarised under the term 'apnoea of prematurity' (AOP), affect at least 80% of very preterm infants born before 32 weeks of gestation. AOP may lead to severe hypoxaemia requiring immediate resuscitation and recent data show that repetitive episodes of AOP increase the risk of post-discharge death and long-term neurodevelopmental impairment. Most importantly, severity and frequency of AOP may drastically increase upon challenging the autonomic system by routine immunisation. It is, however, very important to provide timely immunisation and establish early immunity against typical vaccine-preventable diseases in preterm infants as they are particularly vulnerable to complications arising from those diseases. Current recommendations are to initially immunise preterm infants in the hospital under continuous monitoring of vital signs if the treating physician considers an infant to be at risk of post-immunisation AOP. However, there are no objective criteria to predict post-immunisation AOP. Although the first immunisation of very preterm infants typically takes place in the hospital under continuous monitoring of vital signs, immunisations of infants at risk of AOP are often delayed due to fear of AOP or may be initiated in non-intensive care settings (normal wards) where adequate respiratory support cannot be provided but may be needed due to post-immunisation AOP. Also, due to an international trend of early discharge home of preterm infants, immunisations may be arranged in the rooms of the family paediatrician without further monitoring of vital signs and no specific knowledge of the individual risk of post-immunisation AOP. Thus, developing of new biomarkers and objective criteria to better understand and assess the risk of post-immunisation AOP is urgently needed. We recently developed a systematic quality control algorithm for assessing heart rate variability data in a standardised manner and demonstrated that the sample entropy (SampEn) of interbeat intervals, a parameter of heart rate variability derived from nonlinear time series analysis, predicts cardiorespiratory stability in preterm infants. SampEn reflects the regularity of heart rate and the presence of spikes in a given time series of heart beats and has been validated to be a reliable predictor of incipient events such as sepsis. SampEn of heart rate can be obtained non-invasively from electrocardiogram monitors, which are routinely used to monitor preterm infants immunised in the hospital. We aim to evaluate whether real-time calculation of SampEn at a) 32 and 36 weeks corrected age, b) upon primary routine immunisation in the hospital, c) at discharge from the hospital after initial prematurity-related hospital stay, and d) on readmission for immunisation in the hospital based on previous post-immunisation AOP or referral of the family paediatrician has prognostic utility for the risk of post-immunisation AOP in very preterm infants. We will further assess whether immunisation itself initiates a step response in SampEn and compare SampEn values from preterm infants to those of term healthy infants to study maturational effects. The biomarker SampEn provides a unique opportunity to objectively prognosticate autonomic stability with the goal of optimising risk stratification and establishing timely immunisation in preterm infants. Such real-time display of SampEn thus could become a valuable tool to better understand autonomic regulation in preterm infants and guide physicians in providing an optimal level of care for immunisation based on personalised risk assessment in order to provide an adequate setting and staffing. This approach combines both novel scientific aspects on prognostic value of nonlinear time series analysis and pragmatic utility of SampEn for decision-making on within hospital risk-stratification and necessity of readmission for immunisation.

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Impact of early maturation, immunisation and caffeine on control of breathing in preterm infants with and without chronic lung disease

Research Project  | 1 Project Members

This study aims to provide further insight into the early maturation of respiratory control in infants born preterm. In addition, quanitification of breathing regulation in preterm infants with and without chronic lung disease using new analytical techniques may give improved insight into the impact that CLDI has upon this process. Examination of the impact of two common interventions known to affect respiratory control (i.e. caffeine administration and immunisation) may provide a mechanism for quantifying control impairments in infants affected by CLDI. Early identification of those infants most at risk for abnormal control may prove useful in assessing the necessity for ongoing clinical monitoring during the pre- and post-discharge care of infants born preterm.

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Physiological deadspace measurements in ventilated preterm infants

Research Project  | 1 Project Members

Should ventilator target tidal volumes be adjusted for gestational age? Authors: Roland Neumann, roland.neumann@health.wa.gov.au1, Alexander Larcombe, alexanderl@ichr.uwa.edu.au2, Graham Hall, graham.hall@health.wa.gov.au2,3, J. Jane Pillow, jpillow@meddent.uwa.edu.au4, Sven Schulzke, sven.schulzke@health.wa.gov.au1,4. Author Affiliations: 1King Edward Memorial Hospital and 2Telethon Institute for Child Health Research Perth, Australia; 3School of Paediatrics and Child Health and 4School of Women s and Infants Health, University of Western Australia, Perth, Australia. Background: Preterm infants are susceptible to volutrauma, but lung volumes capacities may vary. The relationship between gestation and the alveolar deadspace and tidal volumes is unknown. Aims: To measure Vd,MM on day 1 of life in ventilated very preterm infants. We hypothesized that after adjusting for set target tidal volume on the ventilator ( volume guarantee ) and respiratory rate, the ratio of alveolar to total tidal volume (Valv/VT) increases with gestational age at birth. Methods: 120 s of tidal breathing was recorded from unsedated, sleeping preterm infants (n=43; gestation 23-31 w, mean (SD) birth weight 1.1 (0.4) kg, postnatal age 14.3 (7.2) h) receiving patient-triggered ventilation (Babylog 8000 plus, Draeger Medical, Luebeck, Germany) using a mainstream ultrasonic flowmeter (Spiroson Exhalyzer D, Ecomedics AG, CH). Airway deadspace was calculated from the molar mass signal (Vd,MM). Alveolar volume (Valv) was calculated as VT Vd,MM. Arterial blood gases were obtained immediately after lung function testing. Multiple linear regression was used to analyse outcomes. Results: Mean (SD) values for Vd,MM, VT, and Valv/VT were 2.51 (0.61) mL/kg, 6.57 (1.54) mL/kg, and 0.62 (0.06) respectively. Mean (SD) arterial PaCO2 was 42.9 (5.8) mmHg. Valv/VT was positively associated with gestational age (R2 = 0.26, p = 0.012) after adjusting for set volume guarantee (range 3.8-5.1 mL/kg) and respiratory rate. Conclusions: In ventilated very preterm infants, Valv/VT on day 1 increases with gestational age. Ventilator target tidal volumes should be adjusted for maturity as well as body size at birth to avoid potential alveolar overdistension.