40 years neonatology

Over the last decades neonatology and pediatric intensive care medicine made significant advancements, probably more than most other medical specialties, which have substantially improved the survival rates of preterm infants born at increasingly younger developmental ages and enhanced long-term clinical outcomes.

It is difficult to objectively rank these achievements in terms of biomedical importance and their significance for population health. Having had the honor of heading a thriving academic Division of Neonatology for more than 22 years (1 May 1992–1 October 2014) enables me to shine the light on a personal selection of notable accomplishments of medical care and research in the field of modern neonatology, contributed in part by this Division of Neonatology at the Department of Pediatrics of the Medical University Vienna, Austria.

Before presenting these achievements, enabled by substantial progress in research and technology, against the background of the steady decrease of perinatal and neonatal mortality in Austria over the past decades (Fig. 1), I would like to commence by quoting David M. Cutler [1]: “The technology of birth: is it worth it?”

“We evaluate the costs and benefits of increased medical spending for low-birthweight infants. Lifetime spending on low-birthweight babies increased by roughly $ 40,000 per birth between 1950 and 1990. The health improvements resulting from this have been substantial. Infant mortality rates fell by 72% over this time period, largely due to improved care for premature births. Considering both length and quality of life, we estimate the rate of return for care of low-birthweight infants at over 500%. Although prenatal care and influenza shots are more cost-effective than neonatal care, it is significantly more cost-effective than other recent innovations, such as coronary artery bypass surgery, treatment of severe hypertension, or routine Pap smears for women aged 20 to 74. We conclude that the answer to the question posed in this paper is a resounding yes.” [1].

The development of neonatal intensive care units (NICUs) equipped with advanced monitoring and therapeutic technologies had an enormous impact on survival rates and outcomes of critically ill newborns. The NICUs facilitate early detection and intervention for various health complications, ensuring timely treatment and reducing the risk of long-term negative outcomes particularly of premature infants but also of term newborns with congenital or acquired illnesses or malformations The establishment and continuous improvement of NICUs rests on a number of substantial cornerstones of technological advancements, which importantly include the discovery of “continuous positive airway pressure (CPAP)” as non-invasive method for treating respiratory distress syndrome (RDS) and preventing the need for mechanical ventilation. This concept, which was first introduced by George Gregory, a pioneer of modern neonatology in 1971 [2], revolutionized the treatment of premature infants with respiratory failure.

Further continuous improvements in technology and modes of mechanical ventilatory support have made intensive care treatment safer and more effective. Of great importance in this context was the recognition of oxygen as a potential harmful drug for brain, eyes, lungs and other tissues during treatment when hypoxic or hyperoxic insults were not prevented [3‐10].

In a next step for improving clinical outcomes after premature birth and neonatal morbidities I had the opportunity to initiate the regionalization concept of neonatal intensive care for Vienna. This unique approach included the categorization of NICUs into different levels (level I–level IV) based on the intensity of care they can provide, with level IV NICUs being constructed and equipped for treating the most complex cases, including surgical interventions.

A major goal of the concept was to transport women at risk for developing ill neonates prior to delivery to specialized perinatal care centers instead of transporting newborns with life-threatening conditions after birth. This development has been crucial in further enhancing the options for providing timely and appropriate care for severely sick and high-risk infants.

Increased awareness of the importance of neurodevelopmental care, including strategies to support brain development and minimize stress in the NICU environment, has led to improved long-term outcomes and quality of life for premature infants. This specialized care involves a combination of evidence-based strategies tailored to the unique needs of each infant, with a primary focus on promoting a nurturing and developmentally supportive environment. Key components include minimizing exposure to excessive light and noise, providing gentle handling and skin-to-skin contact through kangaroo care, promoting breastfeeding or appropriate nutritional support, and implementing developmental positioning to support motor development and reduce the risk of musculoskeletal issues [46‐56].

Further developments have led to the inclusion of comprehensive follow-up visits, ensuring continued support for infants’ optimal brain and behavioral development. In 1994 we introduced follow-up visits in our institution, involving multidisciplinary teams comprising neonatologists, developmental specialists, physical therapists and other healthcare professionals to monitor infants’ growth and neurodevelopmental progress through standardized developmental screening and assessments tools. As such, these follow-up visits serve as critical opportunities to monitor infants’ progress, to promptly address developmental delays or concerns and tailor interventions and support services accordingly. Maintaining a continuum of care from the NICU to outpatient settings allows improvement of long-term outcomes and promoting the most beneficial development of preterm and high-risk infants beyond the neonatal period.

Prenatal, i.e., intrauterine and early as well as late onset postnatal infections and septicemia, remain a major cause of mortality and morbidity rates among premature infants despite the use of modern anti-infective therapy. Especially extremely preterm infants and ill infants requiring intensive care invasive treatment are prone to systemic infections compromising multiple organs, due to their immature immune defense system. Infections can occur through various routes, including vertical transmission from the mother, hospital-acquired infections or community exposure. The consequences of infection in premature infants can be severe, ranging from systemic inflammatory response syndrome (SIRS) to sepsis, meningitis, pneumonia, and necrotizing enterocolitis (NEC). These conditions not only pose immediate threats to life but also increase the risk of long-term neurodevelopmental impairments, such as cerebral palsy, cognitive deficits, and sensory impairments.

Consequently, infection control was the major target of our interventions since the early 1970s until today when neonatal care was rapidly advancing and premature and LBWI of decreasing gestational ages, nowadays down to 22/23 weeks, survived without or with minor neurological sequelae. Members of our department were involved in a large number of clinical, laboratory, molecular and immunological studies in this area [63, 67‐82].

Austria and France were the first European countries to introduce, and are still, the only countries with a nationwide prenatal serological toxoplasmosis screening program. In Austria it began in 1974 in response to the high incidence of 7.8 infected infants per 1000 live births [83, 84]. In 1992 we introduced an Austrian Register for Toxoplasma Infection in pregnancy for determining the actual incidence of primary gestational infections with Toxoplasma gondii and congenital toxoplasmosis. Annually, 8.5 per 10,000 women acquired Toxoplasma infection during pregnancy, and 1.0 per 10,000 infants had congenital Toxoplasma infection (13% mean transmission rate) We showed that women treated according to the Austrian scheme had a sixfold, decrease in the maternal-fetal transmission rate compared to untreated women.

We also showed that the screening program is economically justified.

We introduced for all newborns of infected mothers a routine follow-up program until age 12 months including 3‑monthly serological tests using the Sabin-Feldmann dye (still the gold standard test), brain ultrasound scans, ophthalmologic examinations, psychological testing of cognitive and other developmental skills.

If the parasite had already reached the fetal compartment, only medications which are able to cross the placenta barrier can be effective [85‐105].

This nationwide program for congenital metabolic and endocrinologic disorders was introduced in 1966 by Otto Thalhammer as the so-called Vienna test program for the early detection of phenylketonuria [106]. It constitutes a critical public health initiative aimed at identifying infants at risk of certain inherited conditions early in life, allowing for timely intervention and treatment. This program typically involves the collection of blood samples from newborns shortly after birth, which are then analyzed for various metabolic and endocrine disorders. Over time, the Austrian initiative evolved by expanding the screening panel from phenylketonuria (PKU) and galactosemia to congenital hypothyroidism, biotinidase deficiency, cystic fibrosis, and congenital adrenal hyperplasia. In 2002, the introduction of tandem mass spectrometry (MS/MS) substantially increased the number of detectable inborn errors of metabolism and now includes disorders of fatty acid oxidation, organic acidurias and various disorders of amino acid metabolism and recently (one of the first in Europe): spinal muscular atrophy (SMA) and severe congenital immune deficiencies (SCID). Early detection through newborn screening enables the timely recommendation of appropriate interventions, such as dietary modifications, hormone replacement therapy, gene therapy or other medical interventions, before symptoms manifest, thus preventing serious complications and mitigating the long-term impact of these conditions on the infant’s health and development [107‐109].

The VONN is an internet-based quality improvement collaborative.

Its mission is: “To improve the quality, safety and value of care for newborn infants and their families through a coordinated program of data-driven quality improvement, education and research” (https://​public.​vtoxford.​org/​).

We realized early that treatment according to international quality standards and continuous quality improvement is of upmost importance for providing neonatal medicine in its highest standard. Internal quality control through review of hospital statistics is limited because of the small number of patients per center. Thus, evaluation of different clinical management strategies is nearly impossible unless individual center results are continuously assessed and monitored in a standardized way and compared with international standards. For this reason, our center for high-risk neonates decided to participate in the VONN, the biggest and most comprehensive neonatal database worldwide. In 1994 we were the first European (and non-US) center to become a member of the VONN [5]. Meanwhile, 1400 centers worldwide have joined. The reporting tools give centers the necessary data and benchmarks to make meaningful improvements. Since 1994 we continue each year to participate and contribute to this excellent and important quality control system. Our example was later followed by almost all national and European international centers treating high-risk neonates mainly VLBWI.

Over the past four decades, advancements in research and technology have allowed a transformative development of neonatal medicine. Survival rates without increased morbidity for very premature infants with gestational ages reaching to what we consider nowadays the border of viability have constantly increased.

Prenatal care has evolved to include routine screening, risk assessments and interventions aimed at identifying and managing conditions that predispose mothers to preterm labor or fetal complications. The Austrian social and healthcare system has allowed improvements in the national organization and administration of prenatal, perinatal and postnatal care systems to reduce risk factors associated with neonatal mortality and improve long-term outcomes of affected infants.

In my professional life as a neonatologist in Austria I have had the possibility to support and to shape some of these developments in my position as Head of the Division of Neonatology at the Medical University of Vienna.

Current state-of-the-art medical technologies and staffed by skilled healthcare professionals, now provides round-the-clock monitoring, specialized therapies, and developmental support. Moreover, past ongoing research endeavors with our contributions have deepened our understanding of the intricate mechanisms underlying the most severe and complex neonatal morbidities, such as those associated with metabolic complications, respiratory and hematologic pathologies and their comorbidities and associated adverse consequences, which have and are continuing to pave the way for new targeted interventions and preventive strategies.

Despite these remarkable advancements, challenges persist, including the persistent rates of prematurity, socioeconomic disparities in neonatal outcomes, and the long-term consequences of preterm birth on neurodevelopment and overall population health. Equally important and challenging for clinicians and nursing staff are the various ethical and cultural issues always apparent in neonatal intensive care units. In my view and as stated by others [110], senior and junior staff should concede for themselves more space for reflecting and perhaps changing ethical attitudes including communication strategies with parents.

As we look ahead, it is imperative to build upon the progress made, harnessing the power of science and technology to further improve the survival and quality of life for preterm infants in Austria and worldwide. At the same time, neonatology must continue to prioritize ethical reflection and education, fostering a culture of integrity, interdisciplinary collaboration, and the development of guidelines and protocols that uphold ethical standards while addressing the evolving needs and complexities of neonatal medicine.