Retinopathy of prematurity (ROP) is the most important cause of vision loss premature infants. With a continuous growth in this vulnerable population, the number of newborns at risk for severe,... Show moreRetinopathy of prematurity (ROP) is the most important cause of vision loss premature infants. With a continuous growth in this vulnerable population, the number of newborns at risk for severe, sight threatening ROP increases. In this thesis the results of the national Dutch inventory on risk factors, screening, treatment and sequelae of ROP are presented. The principal aims of the study were to determine characteristics of newborns who are at highest risk to develop severe ROP to assess quality of screening and treatment and to evaluate the national ROP guideline. Following these studies together with extensive cost-effectiveness analyses, the current Dutch ROP screening and treatment guideline was adapted and implemented in November 2023. The NEDROP 2 allowed for more stringent screening inclusion criteria, lowering the number of infants that need to undergo burdensome screening under the precondition that no severe ROP would be missed. Annually, this will lower the screening costs by nearly 60,000 euros. Show less
Objective To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of... Show moreObjective To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs).Methods Multicentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at <= 3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at >= 6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability.Results Neuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89 +/- 0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia.Conclusions Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis. Show less
Boer, A. de; Proost, L. de; Vries, M. de; Hogeveen, M.; Verweij, E.J.T.; Geurtzen, R. 2023
ObjectiveA shared decision-making (SDM) approach is recommended for prenatal decisions at the limit of viability, with a guiding role for parental values. People born extremely premature experience... Show moreObjectiveA shared decision-making (SDM) approach is recommended for prenatal decisions at the limit of viability, with a guiding role for parental values. People born extremely premature experience the consequences of the decision made, but information about their perspectives on prenatal decisions is lacking. Therefore, this study aims to describe their perspectives on what is important in decision-making at the limit of viability.DesignSemi-structured focus group discussions were conducted, recorded and transcribed verbatim. The data were independently analysed by two researchers in Atlas.ti.ResultsFour focus groups were conducted in the Netherlands, with five to six participants each, born between 240/7 and 300/7 weeks gestation in the period between 1965 and 2002. Considering their personal life experiences and how their extremely premature birth affected their families, the participants reflected on decision-making at the limit of viability. Various considerations were discussed and summarised into the following themes: anticipated parental regret, the wish to look at the baby directly after birth, to give the infant a chance at survival, quality of life, long-term outcomes for the infant and the family, and religious or spiritual considerations.ConclusionsInsights into the perspectives of adults born extremely premature deepened our understanding of values considered in decision-making at the limit of viability. Results point out the need for a more individualised prediction of the prognosis and more extensive information on the lifelong impact of an extremely premature birth on both the infant and the family. This could help future parents and healthcare professionals in value-laden decision-making. Show less
Halbmeijer, N.M.; Sonnaert, M.; Swarte, R.M.; Koopman-Esseboom, C.; Stuijvenberg, M. van; Tollenaer, S.M.D.; ... ; SToP-BPD Study Grp 2023
Objective To explore clinical effect modifiers of systemic hydrocortisone in ventilated very preterm infants for survival and neurodevelopmental outcome at 2 years' corrected age (CA).Design... Show moreObjective To explore clinical effect modifiers of systemic hydrocortisone in ventilated very preterm infants for survival and neurodevelopmental outcome at 2 years' corrected age (CA).Design Secondary analysis of a randomised placebo-controlled trial.Setting Dutch and Belgian neonatal intensive care units.Patients Infants born <30 weeks' gestational age (GA), ventilator-dependent in the second week of postnatal life.Intervention Infants were randomly assigned to systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190).Main outcome measures The composite of death or neurodevelopmental impairment (NDI) at 2 years' CA and its components. Candidate effect modifiers (GA, small for GA, respiratory index, sex, multiple births, risk of moderate/severe bronchopulmonary dysplasia or death) were analysed using regression models with interaction terms and subpopulation treatment effect pattern plots.Results The composite outcome was available in 356 (96.0%) of 371 patients (one consent withdrawn). For this outcome, treatment effect heterogeneity was seen across GA subgroups (<27 weeks: hydrocortisone (n=141) vs placebo (n=156), 54.6% vs 66.2%; OR 0.61 (95% CI 0.38 to 0.98); >= 27 weeks: hydrocortisone (n=30) vs placebo (n=31), 66.7% vs 45.2%; OR 2.43 (95% CI 0.86 to 6.85); p=0.02 for interaction). This effect was also found for the component death (<27 weeks: 20.1% vs 32.1%; OR 0.53 (95% CI 0.32 to 0.90); =27 weeks: 28.1% vs 16.1%; OR 2.04 (95% CI 0.60 to 6.95); p=0.049 for interaction) but not for the component NDI. No differential treatment effects were observed across other subgroups.Conclusion This secondary analysis suggests that in infants <27 weeks' GA, systemic hydrocortisone may improve the outcome death or NDI, mainly driven by itscomponent death. There was insufficient evidence for other selected candidate effect modifiers. Show less
Halbmeijer, N.M.; Onland, W.; Cools, F.; Swarte, R.M.; Heide-Jalving, M. van der; Dijk, P.; ... ; STOP-BPD Study Grp 2023
ObjectiveTo report the parent-reported behavioural outcomes of infants included in the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants study at 2 years' corrected... Show moreObjectiveTo report the parent-reported behavioural outcomes of infants included in the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants study at 2 years' corrected age (CA). DesignRandomised placebo-controlled trial. SettingDutch and Belgian neonatal intensive care units. PatientsInfants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life. InterventionInfants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). Main outcome measuresParent-reported behavioural outcomes at 2 years' CA assessed with the Child Behavior Checklist (CBCL 11/2-5). ResultsParents completed the CBCL of 183 (70% (183/262)) infants (hydrocortisone group, n=96; placebo group, n=87). Multiple imputation was used to account for missing data. Infants with critically elevated T-scores (>55) were found in 22.9%, 19.1% and 29.4% of infants for total, internalising and externalising problems, respectively; these scores were not significantly different between groups (mean difference -1.52 (95% CI -4.00 to 0.96), -2.40 (95% CI -4.99 to 0.20) and -0.81 (95% CI -3.40 to 1.77), respectively). In the subscales, we found a significantly lower T-score for anxiety problems in the hydrocortisone group (mean difference -1.26, 95% CI -2.41 to -0.12). ConclusionThis study found high rates of behaviour problems at 2 years' CA following very preterm birth, but these problems were not associated with hydrocortisone treatment initiated between 7 and 14 days after birth in ventilated preterm infants. Show less
Most preterm infants need respiratory support and extra oxygen during their admission to the neonatal intensive care. The amount of oxygen required can fluctuate a lot. Bedside staff frequently... Show moreMost preterm infants need respiratory support and extra oxygen during their admission to the neonatal intensive care. The amount of oxygen required can fluctuate a lot. Bedside staff frequently administer extra oxygen, and when the blood oxygen level is normalised, reduce this extra oxygen carefully. This is a delicate process, a fraction too much or a fraction too little may harm their underdeveloped organs.As one of the first, the LUMC has been titrating oxygen automatically since 2015. In this thesis we investigated the effect of this automatization and how preterm infants can profit from this technology. We found that automated oxygen titration reduced the duration of invasive ventilation, but outcome at two years of age was left unchanged. A new automated oxygen controller from 2018 led to even more improvement. Infants spent more time in the narrow therapeutic range, needed even less intensive respiratory support and developed less retinopathy – a disease of the retina which, when untreated, can lead to blindness.From this thesis we can conclude that there is a short-term benefit from automated oxygen titration and we are moving in the right direction. Further research is needed to make the most out of this technology. Show less
O'Donnell, C.P.F.; Dekker, J.; Rudiger, M.; Pas, A.B. te 2022
Despite increased amounts of research, most of the evidence that supports treatment of newborns in the delivery room is rated 'low' rather than 'high' quality. This assessment stems largely from a... Show moreDespite increased amounts of research, most of the evidence that supports treatment of newborns in the delivery room is rated 'low' rather than 'high' quality. This assessment stems largely from a lack of evidence from clinical trials. When trials have been performed, the evidence has often been downgraded due to enrolment of small or poorly representative samples, and for lack of blinding of caregivers and outcome assessors. Delivery room trials present particular challenges when obtaining consent, enrolling participants, taking measures to limit bias and identifying appropriate outcome measures. We hope our suggestions as to how future delivery room trials could be more pragmatic will inform the design of large studies that are necessary to allow clinical practice to evolve. Show less
Objective Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term... Show moreObjective Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term pulmonary and systemic effects of hydrocortisone initiated in the second week.Design Randomised placebo-controlled trial.Setting Dutch and Belgian neonatal intensive care units.Patients Infants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life.Intervention Infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190).Main outcome measures Data on extubation, ventilator settings, glucose levels, and blood pressure were recorded daily and analysed during the first 7 days of treatment using linear mixed-effects models.Results Infants in the hydrocortisone group (24.3%) failed extubation less often compared with placebo (38.6%, crude risk difference: -14.3% (95% CI: -23.4% to -4.8%)). The estimated difference in daily rate of change between hydrocortisone and placebo was -0.42 cmH(2)O (95% CI: -0.48 to -0.36) for mean airway pressure, -0.02 (95% CI: -0.02 to -0.01) for fraction of inspired oxygen, -0.37 (95% CI: -0.44 to -0.30) for respiratory index, 0.14 mmol/L (95% CI: 0.08 to 0.21) for blood glucose levels and 0.83 mm Hg (95% CI: 0.58 to 1.09) for mean blood pressure.Conclusions Systemic hydrocortisone initiated between 7 and 14 days after birth in ventilated preterm infants improves pulmonary condition, thereby facilitating weaning and extubation from invasive ventilation. The effects of hydrocortisone on blood glucose levels and blood pressure were mild and of limited clinical relevance. Show less
Haemolytic disease of the foetus and newborn (HDFN) is a condition in which the red blood cells of the foetus and the newborn child are destructed due to maternal alloantibodies. This can lead to... Show moreHaemolytic disease of the foetus and newborn (HDFN) is a condition in which the red blood cells of the foetus and the newborn child are destructed due to maternal alloantibodies. This can lead to anaemia already in early pregnancy. In case of severe anaemia, it can be necessary to perform one or more blood transfusions to the anaemic foetus, so called intrauterine transfusions (IUTs). This thesis evaluates the current therapy for HDFN and describes exogenous erythropoietin as potential new therapeutic agent to treat anaemia. It also gives starting points to individualise the treatment of these children in the future, as predictive values were identified for a more severe neonatal disease course. In addition to short-term outcomes measures after birth, the long-term effects of IUTs were also critically evaluated to optimise the treatment of HDFN. Show less
In this retrospective cohort study of the outcomes of infants born <32 week's gestation, moving from a traditional open bay neonatal unit to a new single-room unit was not associated with... Show moreIn this retrospective cohort study of the outcomes of infants born <32 week's gestation, moving from a traditional open bay neonatal unit to a new single-room unit was not associated with significant improvements in morbidity or mortality. Objective: In response to the increasing focus on family-centred care, neonatal intensive care unit (NICU) environments have gradually shifted towards the single-room design. However, the assumed benefits of this emerging design remain a subject of debate. Our goal was to evaluate the impact of single-room versus open-bay care on the risk of neonatal morbidity and mortality in preterm neonates. Design: Retrospective cohort study. Setting: Level III NICU. Patients: Neonates born Main outcome measures: Mortality and morbidities of a cohort of neonates admitted to a new, single-room unit (SRU) were compared with a historical cohort of neonates admitted to an open-bay unit (OBU). Group differences were evaluated and multivariable logistic regression analyses were performed. Results: Three-hundred and fifty-six and 343 neonates were admitted to the SRU and OBU, respectively. No difference in neonatal morbidities and mortality were observed between cohorts (bronchopulmonary dysplasia: OR 1.08, 95% CI 0.73 to 1.58, p=0.44; retinopathy of the prematurity stage >= 2: OR 1.36, 95% CI 0.84 to 2.22, p=0.10; intraventricular haemorrhage: OR 0.89, 95% CI 0.59 to 1.34, p=0.86; mortality: OR 1.55, 95% CI 0.75 to 3.20, p=0.28). In adjusted regression models, single-room care was independently associated with a decreased risk of symptomatic patent ductus arteriosus (adjusted OR 0.54, 95% CI 0.31 to 0.95). No independent association between single-room care and any of the other investigated outcomes was observed. Conclusions: Implementation of single-rooms in our NICU did not lead to a significant reduction in neonatal morbidity and mortality outcomes. Show less
Heuvel, J.F.M. van den; Hogeveen, M.; Holzik, M.L.; Heijst, A.F.J. van; Bekker, M.N.; Geurtzen, R. 2022
Background In case of extreme premature delivery at 24 weeks of gestation, both early intensive care and palliative comfort care for the neonate are considered treatment options. Prenatal... Show moreBackground In case of extreme premature delivery at 24 weeks of gestation, both early intensive care and palliative comfort care for the neonate are considered treatment options. Prenatal counseling, preferably using shared decision making, is needed to agree on the treatment option in case labor progresses. This article described the development of a digital decision aid (DA) to support pregnant women, partners and clinicians in prenatal counseling for imminent extreme premature labor. Methods This DA is developed following the International Patient Decision Aid Standards. The Dutch treatment guideline and the Dutch recommendations for prenatal counseling in extreme prematurity were used as basis. Development of the first prototype was done by expert clinicians and patients, further improvements were done after alpha testing with involved clinicians, patients and other experts (n = 12), and beta testing with non-involved clinicians and patients (n = 15). Results The final version includes information, probabilities and figures depending on users' preferences. Furthermore, it elicits patient values and provides guidance to aid parents and professionals in making a decision for either early intensive care or palliative comfort care in threatening extreme premature delivery. Conclusion A decision aid was developed to support prenatal counseling regarding the decision on early intensive care versus palliative comfort care in case of extreme premature delivery at 24 weeks gestation. It was well accepted by parents and healthcare professionals. Our multimedia, digital DA is openly available online to support prenatal counseling and personalized, shared decision-making in imminent extreme premature labor. Show less
In this thesis we have investigated spontaneous breathing as a possible driving force for placental transfusion and the implementation of PBCC in a clinical setting. Spontaneous breathing at birth,... Show moreIn this thesis we have investigated spontaneous breathing as a possible driving force for placental transfusion and the implementation of PBCC in a clinical setting. Spontaneous breathing at birth, and lung aeration, is pivotal to accomplish the increase in pulmonary blood flow and decrease in pulmonary vascular resistance needed for a successful transition to extra-uterine life. Indeed, we demonstrated spontaneous breathing to influence umbilical blood flow and to potentially create a preferential blood flow from the placenta towards the infant. Based on this thesis we have therefore concluded that spontaneous breathing is likely to be a driving force in placental transfusion. In addition, we investigated physiological-based cord clamping (PBCC). Experimental studies clearly demonstrated the beneficial physiological effects of PBCC and that lung aeration, with the subsequent increase in pulmonary blood flow, is vital for the success of this approach. The studies in this thesis demonstrate the proof of concept for performing PBCC in preterm infants in a clinical setting: that it is both possible and safe, and that a similar effect can be observed as in an experimental setting. We also demonstrated that resuscitation on the cord is at least as effective, while allowing longer and variable cord clamping times. Show less
Narayen, I.C.; Pas, A.B. te; Blom, N.A.; Akker-van Marle, M.E. van den 2019
Without a proper treatment, critical congenital heart defects (CCHD) lead to death in the first month of life. Timely diagnosis is pivotal for reducing morbidity and mortality. Pulse oximetry is... Show moreWithout a proper treatment, critical congenital heart defects (CCHD) lead to death in the first month of life. Timely diagnosis is pivotal for reducing morbidity and mortality. Pulse oximetry is used in many countries to screen newborns for CCHD. However, this screening has not been implemented in the Netherlands, because of the unique perinatal care system, with a high home birth rate and early discharge after hospital deliveries. This thesis describes research performed to assess the feasibility, accuracy, acceptability and costs of neonatal screening for CCHD with pulse oximetry in the Dutch perinatal care system. To do this, the protocol that is used in the United States and Scandinavia was adapted to fit the working scheme of community midwives. Show less
When providing oxygen therapy to a preterm infant, targeting SpO2 is essential for avoiding hypoxaemia and/or hyperoxaemia. However, this can be both difficult and challenging for nurses... Show moreWhen providing oxygen therapy to a preterm infant, targeting SpO2 is essential for avoiding hypoxaemia and/or hyperoxaemia. However, this can be both difficult and challenging for nurses working in a neonatal intensive care unit. The general aim of this thesis project was to assess the effect of changes in clinical practice regarding oxygen titration and compliance with respect to targeting SpO2 in preterm infants admitted to our NICU.The stepwise quality improvement project implemented in this thesis project improved compliance with respect to both targeting SpO2 and improving oxygen titration. This led to improved SpO2 distribution and decreases in both hypoxaemia and hyperoxaemia, as well as slight improvements in the handling of ABC events and oxygen titration following ABC. The introduction of training sessions, guidelines, and automated oxygen control increased awareness regarding the consequences of hypoxaemia and hyperoxaemia and led to increased efforts to prevent complications. Show less
The transition after birth represents one of the greatest physiologic challenges that humans encounter. Preterm infants often need respiratory support after birth. Little effort has been made to... Show moreThe transition after birth represents one of the greatest physiologic challenges that humans encounter. Preterm infants often need respiratory support after birth. Little effort has been made to determine the adequacy and efficacy of ventilation in the delivery room. The general aim of this thesis was to evaluate the adequacy and efficacy of neonatal resuscitation. This thesis comprises manikin studies and observational studies in the delivery room to evaluate and optimise current technique and the use of devices. Mask ventilation is difficult and mostly inefficient. It should be trained regularly with a focus on leak and airway obstruction. A respiratory function monitor is a useful device for feedback on mask technique during training and resuscitation in the delivery room. Spontaneous breathing, which is often missed, contributes to the stabilisation of infants after birth. When using a T-piece resuscitator a fixed gas flow rate is recommended. Caregivers often deviate from the guidelines and more time is needed for clinical evaluation of the infant. Future research and clinical practice should focus on training of optimal mask technique, establishing the efficacy of a respiratory function monitor in the delivery room, and the development of ventilation techniques that focus on the presence of breathing. Show less
Red blood cells (RBCs) are probably the most frequently used drug given to very preterm infants; more than 90% of infants with a birth weight <1000 grams receive one or more RBC transfusions.... Show moreRed blood cells (RBCs) are probably the most frequently used drug given to very preterm infants; more than 90% of infants with a birth weight <1000 grams receive one or more RBC transfusions. Except for reduction of the amount of blood drawn for laboratory tests and use of a single donor program, no measures have been shown to be an irrefutable safe way to reduce donor exposure. Preventative measures for anemia should be used to reduce the number of RBC transfusions needed. Alternatives for allogenic RBC transfusions, such as autologous RBC cord blood transfusion, should be further explored and implemented. A restrictive transfusion strategy does not seem harmful for the children in short term or long term outcome. Thrombocytopenia is also a frequently encountered problem in neonatal medicine with an increased risk for hemorrhage. Thrombocytopenia, irrespective of the severity, increases the incidence of intraventricular hemorrhage. A more restrictive platelet transfusion policy significantly reduces the number of infants receiving a platelet transfusion without a difference in occurrence of (severe) hemorrhage. We state that both for red blood cell and platelet transfusions in (premature) newborn infants, safe thresholds are still not established. Transfusions may have (late) detrimental effects. Safe thresholds for both erythrocytes and platelets need to be found by large prospective randomized trials focusing not only on the direct effects but also on the long-term effects. Show less
