Aim: Neonatal intensive care unit (NICU) nurses provide tactile stimulation to terminate apnoea in preterm infants, but guidelines recommending specific methods are lacking. In this study, we... Show moreAim: Neonatal intensive care unit (NICU) nurses provide tactile stimulation to terminate apnoea in preterm infants, but guidelines recommending specific methods are lacking. In this study, we evaluated current methods of tactile stimulation performed by NICU nurses.Methods: Nurses were asked to demonstrate and explain their methods of tactile stimulation on a manikin, using an apnoea scenario. All nurses demonstrated their methods three times in succession, with the manikin positioned either prone, supine or lateral. Finally, the nurses were asked how they decided on the methods of tactile stimulation used. The stimulation methods were logged in chronological order by describing both the technique and the location. The nurses' explanations were transcribed and categorised.Results: In total, 47 nurses demonstrated their methods of stimulation on the manikin. Overall, 57 different combinations of technique and location were identified. While most nurses (40/47, 85%) indicated they learned how to stimulate during their training, 15/40 (38%) of them had adjusted their methods over time. The remaining 7/47 (15%) stated that their stimulation methods were self-developed.Conclusion: Tactile stimulation performed by NICU nurses to terminate apnoea was highly variable in both technique and location, and these methods were based on either prior training or intuition. Show less
Boer, M.C. den; Martherus, T.; Houtlosser, M.; Root, L.; Witlox, R.S.G.M.; Pas, A.B. te 2020
Video and physiological parameter recording of neonatal stabilization was implemented at the Neonatal Intensive Care Unit (NICU) of the Leiden University Medical Center. In order to improve... Show moreVideo and physiological parameter recording of neonatal stabilization was implemented at the Neonatal Intensive Care Unit (NICU) of the Leiden University Medical Center. In order to improve documentation and the quality of care provided during neonatal transition, we implemented weekly plenary audits reviewing recordings of neonatal stabilization in 2014. In audits, provided care is reviewed, discussing, among others, mask technique, compliance to the prevailing local guideline, and clinical decision making and alternative treatment options. In this perspective, we argue that auditing neonatal stabilization is a valuable tool to improve patient safety and the quality of care provided during neonatal stabilization. We, therefore, report lessons learned and areas for improvement that could be identified and addressed during audits conducted at our NICU. Important areas for improvement were guideline compliance, documentation, the usage of medical devices, the conduct of delivery room studies, and clinical decision making. By reporting our experiences, we hope to encourage other NICUs to also implement regular audit meetings, fitting to their improvement needs. Show less
Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs... Show moreCongenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs into the chest. Pulmonary hypertension is a major contributor to both mortality and morbidity, however, treatment modalities are limited. Novel prenatal and postnatal interventions, such as fetal surgery and medical treatments, are currently under investigation. Until now, the perinatal stabilisation period immediately after birth has been relatively overlooked, although optimising support in these early stages may be vital in improving outcomes. Moreover, physiological parameters obtained from the perinatal stabilisation period could serve as early predictors of adverse outcomes, thereby facilitating both prevention and early treatment of these conditions. In this review, we focus on the perinatal stabilisation period by discussing the current delivery room guidelines in infants born with CDH, the physiological changes occurring during the fetal-to-neonatal transition in CDH, novel delivery room strategies and early predictors of adverse outcomes. The combination of improvements in the perinatal stabilisation period and early prediction of adverse outcomes may mitigate the need for specific postnatal management strategies. Show less
Simma, B.; Walter, S.; Konstantelos, D.; Vonderen, J. van; Pas, A.B. te; Rudiger, M.; Kuster, H. 2020
Objective To assess delivery room management of infants born preterm at 4 Level III perinatal centers in 3 European countries.Study design This was a prospective, multicenter observational study.... Show moreObjective To assess delivery room management of infants born preterm at 4 Level III perinatal centers in 3 European countries.Study design This was a prospective, multicenter observational study. Management at birth was video-recorded and evaluated (Interact version 9.6.1; Mangold-International, Arnstorf, Germany). Data were analyzed and compared within and between centers.Results The infants (n = 138) differed significantly with respect to the median (25%, 75%) birth weight (grams) (Center A: 1200 [700, 1550]; Center B: 990 [719, 1240]; Center C: 1174 [835, 1435]; Center D: 1323 [971, 1515] [B vs A, C, D: P < .05]), gestational week (Center A: 28.4 [26.3, 30.0]; Center B: 27.9 [26.7, 29.6]; Center C: 29.3 [26.4, 31.0]; Center D: 30.3 [28.0, 31.9]), Apgar scores, rates of cesarean delivery, and time spent in the delivery room. Management differed significantly for frequency and drying time, rates of electrocardiographic monitoring, suctioning or stimulation, and for fundamental interventions such as time for achieving a reliable peripheral oxygen saturation signal (seconds) (Center A: 97.6 +/- 79.3; Center B: 65.1 +/- 116.2; Center C: 97.1 +/- 67.0; Center D: 114.4 +/- 140.5; B vs A, C, D: P < .001) and time for intubation (seconds) (Center A: 48.7 +/- 4.2; Center B: 49.0 +/- 30.7; Center C: 69.1 +/- 37.9; Center D: 65.1 +/- 23.8; B vs D, P < .025). Mean procedural times did not meet guideline recommendations. The sequence of interventions was similar at all centers.Conclusions The Video Apgar Study showed great variability in and between 4 neonatal centers in Europe. The study also showed it is difficult to adhere to published guidelines for recommended times for important, basic measures such as peripheral oxygen saturation measurements and intubation. Show less
Simma, B.; Walter, S.; Konstantelos, D.; Vonderen, J. van; Pas, A.B. te; Rudiger, M.; Kuster, H. 2020
ObjectiveTo assess delivery room management of infants born preterm at 4 Level III perinatal centers in 3 European countries.Study designThis was a prospective, multicenter observational study.... Show moreObjectiveTo assess delivery room management of infants born preterm at 4 Level III perinatal centers in 3 European countries.Study designThis was a prospective, multicenter observational study. Management at birth was video-recorded and evaluated (Interact version 9.6.1; Mangold-International, Arnstorf, Germany). Data were analyzed and compared within and between centers.ResultsThe infants (n = 138) differed significantly with respect to the median (25%, 75%) birth weight (grams) (Center A: 1200 [700, 1550]; Center B: 990 [719, 1240]; Center C: 1174 [835, 1435]; Center D: 1323 [971, 1515] [B vs A, C, D: P < .05]), gestational week (Center A: 28.4 [26.3, 30.0]; Center B: 27.9 [26.7, 29.6]; Center C: 29.3 [26.4, 31.0]; Center D: 30.3 [28.0, 31.9]), Apgar scores, rates of cesarean delivery, and time spent in the delivery room. Management differed significantly for frequency and drying time, rates of electrocardiographic monitoring, suctioning or stimulation, and for fundamental interventions such as time for achieving a reliable peripheral oxygen saturation signal (seconds) (Center A: 97.6 ± 79.3; Center B: 65.1 ± 116.2; Center C: 97.1 ± 67.0; Center D: 114.4 ± 140.5; B vs A, C, D: P < .001) and time for intubation (seconds) (Center A: 48.7 ± 4.2; Center B: 49.0 ± 30.7; Center C: 69.1 ±37.9; Center D: 65.1 ± 23.8; B vs D, P < .025). Mean procedural times did not meet guideline recommendations. The sequence of interventions was similar at all centers.ConclusionsThe Video Apgar Study showed great variability in and between 4 neonatal centers in Europe. The study also showed it is difficult to adhere to published guidelines for recommended times for important, basic measures such as peripheral oxygen saturation measurements and intubation. Show less
Martherus, T.; Hoed, A. den; Cramer, S.J.E.; Tan, R.N.G.B.; Hooper, S.B.; Pas, A.B. te 2020
Objective To assess leakage caused by the Pedi-Cap.Methods Bench test I: Pedi-Caps were connected between the Neopuff and a test lung and placed underwater to detect the leak. Bench test II: the... Show moreObjective To assess leakage caused by the Pedi-Cap.Methods Bench test I: Pedi-Caps were connected between the Neopuff and a test lung and placed underwater to detect the leak. Bench test II: the disposable Avea VarFlex Flow Transducer measured the leak. Retrospective analysis: recordings of intubations in the delivery room were analysed.Results The (rippled) male end of the Pedi-Cap is the origin of the leak. In bench test I, 32% of the Pedi-Caps caused inevitable extensive leaks and 34% caused leaks that diminished after sealing the end. In bench test II (n=44) and the retrospective analysis (n=17), the flow transducer measured 22% (18-60) and 39% (8-82) leakage, respectively. Leakage decreased after removal of the Pedi-Cap (before vs after; 17% (7-75) vs 4% (2-10), p=0.004).Conclusion The Pedi-Cap causes the leak which can compromise respiratory support. We recommend to remove the Pedi-Cap directly after change of colour and to be cautious when using the device as evaluation tool. Show less
Background Umbilical venous catheters (UVCs) are associated with thrombus formation. Most studies on thrombosis in infants with UVCs focus on only one part of the route, and none assessed a control... Show moreBackground Umbilical venous catheters (UVCs) are associated with thrombus formation. Most studies on thrombosis in infants with UVCs focus on only one part of the route, and none assessed a control group of infants without UVCs.Objective To determine the incidence and location of thrombi in infants after umbilical catheterisation and compare this with a control group of infants without umbilical catheters.Design Prospective observational study with serial ultrasonography of the UVC route from the umbilico-portal confluence to the heart. Ultrasonography was performed until day 14 after catheterisation in cases and day 14 after birth in controls.Results Thrombi in the UVC route were detected in 75% (30/40) of infants with UVCs in the study group, whereas no thrombi were detected in the control group of infants without UVCs (0/20) (p<0.001). Six thrombi (20%) were located in the right atrium. Most of these were also partly present in the ductus venosus. Six thrombi (20%) were located in the ductus venosus only, and in 12 infants (40%), the thrombus was at least partly located in the umbilico-portal confluence. Thrombi persisted after UVC removal in 25/30 cases. Two infants with thrombotic events were treated with low-molecular-weight heparin and resolution was found. In the other 23 infants managed expectantly, 2 died due to necrotising enterocolitis, 1 was lost to follow-up and in 20 spontaneous regression was seen.Conclusions Thrombotic events occur frequently in infants after umbilical catheterisation. Most thrombi were asymptomatic and regressed spontaneously with expectant management. Routine screening for thrombi in UVCs is therefore not advised. Show less
Boer, M.C. den; Houtlosser, M.; Foglia, E.E.; Lopriore, E.; Vries, M.C. de; Engberts, D.P.; Pas, A.B. te 2020
Objective To gain insight into neonatal care providers' perceptions of deferred consent for delivery room (DR) studies in actual scenarios.Methods We conducted semistructured interviews with 46... Show moreObjective To gain insight into neonatal care providers' perceptions of deferred consent for delivery room (DR) studies in actual scenarios.Methods We conducted semistructured interviews with 46 neonatal intensive care unit (NICU) staff members of the Leiden University Medical Center (the Netherlands) and the Hospital of the University of Pennsylvania (USA). At the time interviews were conducted, both NICUs conducted the same DR studies, but differed in their consent approaches. Interviews were audio-recorded, transcribed and analysed using the qualitative data analysis software Atlas.ti V.7.0.Results Although providers reported to regard the prospective consent approach as the most preferable consent approach, they acknowledged that a deferred consent approach is needed for high-quality DR management. However, providers reported concerns about parental autonomy, approaching parents for consent and ethical review of study protocols that include a deferred consent approach. Providers furthermore differed in perceived appropriateness of a deferred consent approach for the studies that were being conducted at their NICUs. Providers with first-hand experience with deferred consent reported positive experiences that they attributed to appropriate communication and timing of approaching parents for consent.Conclusion Insight into providers' perceptions of deferred consent for DR studies in actual scenarios suggests that a deferred consent approach is considered acceptable, but that actual usage of the approach for DR studies can be improved on. Show less
Mank, A.; Carrasco, C.C.; Thio, M.; Clotet, J.; Pauws, S.C.; DeKoninck, P.; Pas, A.B. te 2020
Objective To assess the predictive value of tidal volume (Vt) of spontaneous breaths at birth in infants with congenital diaphragmatic hernia (CDH).Design Prospective study.Setting Tertiary... Show moreObjective To assess the predictive value of tidal volume (Vt) of spontaneous breaths at birth in infants with congenital diaphragmatic hernia (CDH).Design Prospective study.Setting Tertiary neonatal intensive care unit.Patients Thirty infants with antenatally diagnosed CDH born at Hospital Sant Joan de Deu in Barcelona from September 2013 to September 2015.Interventions Spontaneous breaths and inflations given in the first 10 min after intubation at birth were recorded using respiratory function monitor. Only expired Vt of uninterrupted spontaneous breaths was included for analysis. Receiver operating characteristics (ROC) analysis was performed and the area under the curve (AUC) was estimated to assess the predictive accuracy of Vt.Main outcome measures Mortality before hospital discharge and chronic lung disease (CLD) at day 28 of life.Results There were 1.233 uninterrupted spontaneous breaths measured, and the overall mean Vt was 2.8 +/- 2.1 mL/kg. A lower Vt was found in infants who died (n=14) compared with survivors (n=16) (1.7 +/- 1.6 vs 3.7 +/- 2.1 mL/kg; p=0.008). Vt was lower in infants who died during admission or had CLD (n=20) compared with survivors without CLD (n=10) (2.0 +/- 1.7 vs 4.3 +/- 2.2 mL/kg; p=0.004). ROC analysis showed that Vt <= 2.2 mL/kg predicted mortality with 79% sensitivity and 81% specificity (AUC=0.77, p=0.013). Vt <= 3.4 mL/kg was a good predictor of death or CLD (AUC=0.80, p=0.008) with 85% sensitivity and 70% specificity.Conclusion Vt of spontaneous breaths measured immediately after birth is associated with mortality and CLD. Vt seems to be a reliable predictor but is not an independent predictor after adjustment for observed/expected lung to head ratio and liver position. Show less
IMPORTANCE Most preterm infants require respiratory support to establish lung aeration after birth. Intermittent positive pressure ventilation and continuous positive airway pressure are standard... Show moreIMPORTANCE Most preterm infants require respiratory support to establish lung aeration after birth. Intermittent positive pressure ventilation and continuous positive airway pressure are standard therapies. An initial sustained inflation (inflation time >5 seconds) is a widely practiced alternative strategy.OBJECTIVE To conduct a systematic review and meta-analysis of sustained inflation vs intermittent positive pressure ventilation and continuous positive airway pressure for the prevention of hospital mortality and morbidity for preterm infants.DATA SOURCES MEDLINE (through PubMed), Embase, the Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials were searched through June 24, 2019.STUDY SELECTION Randomized clinical trials of preterm infants born at less than 37 weeks' gestation that compared sustained inflation (inflation time >5 seconds) vs standard resuscitation with either intermittent positive pressure ventilation or continuous positive airway pressure were included. Studies including other cointerventions were excluded.DATA EXTRACTION AND SYNTHESIS Two reviewers assessed the risk of bias of included studies. Meta-analysis of pooled outcome data used a fixed-effects model specific to rarer events. Subgroups were based on gestational age and study design (rescue vs prophylactic sustained inflation).MAIN OUTCOMES AND MEASURES Death before hospital discharge.RESULTS Nine studies recruiting 1406 infants met inclusion criteria. Death before hospital discharge occurred in 85 of 736 infants (11.5%) treated with sustained inflation and 62 of 670 infants (9.3%) who received standard therapy for a risk difference of 3.6%(95% CI, -0.7% to 7.9%). Although analysis of the primary outcome identified important heterogeneity based on gestational age subgroups, the 95% CI for the risk difference included 0 for each individual gestational age subgroup. There was no difference in the primary outcome between subgroups based on study design. Sustained inflation was associated with increased risk of death in the first 2 days after birth (risk difference, 3.1%; 95% CI, 0.9%-5.3%). No differences in the risk of other secondary outcomes were identified. The quality-of-evidence assessment was low owing to risk of bias and imprecision.CONCLUSIONS AND RELEVANCE There was no difference in the risk of the primary outcome of death before hospital discharge, and there was no evidence of efficacy for sustained inflation to prevent secondary outcomes. These findings do not support the routine use of sustained inflation for preterm infants after birth. Show less
Knol, R.; Brouwer, E.; Akker, T. van den; DeKoninck, P.; Geloven, N. van; Polglase, G.R.; ... ; Pas, A.B. te 2020
Aim: To test whether stabilising very preterm infants while performing physiological-based cord clamping (PBCC) is at least as effective as the standard approach of time-based delayed cord clamping... Show moreAim: To test whether stabilising very preterm infants while performing physiological-based cord clamping (PBCC) is at least as effective as the standard approach of time-based delayed cord clamping (DCC).Methods: A randomised controlled non-inferiority study was performed in two centres from May until November 2018, including preterm infants born below 32 weeks of gestational age. Infants were allocated to PBCC or standard DCC. Infants receiving PBCC were stabilised on a purpose-built resuscitation table with an intact umbilical cord. The cord was clamped when the infant had regular spontaneous breathing, heart rate >= 100 bpm and SpO(2) 90% while using FiO(2) 0.40. In infants receiving DCC, the cord was clamped at 30 60 seconds after birth before they were transferred to the standard resuscitation table for further treatment and stabilisation. Primary outcome was time to reach respiratory stability.Results: Thirty-seven infants (mean gestational age 29+0 weeks) were included. Mean cord clamping time was 5:49 +/- 2:37 min in the PBCC (n = 20) and 1:02 +/- 0:30 min in the DCC group (n = 17). Infants receiving PBCC needed less time to reach respiratory stability (PBCC 5:54 +/- 2:27 min; DCC 7:07 +/- 2:54 min; mean difference corrected for gestational age 1:19 min, 95 degrees 6 CI [3:04 0:27]), showing non-inferiority with the pre-defined limit of 1:15 min. No significant differences between the groups were found for maternal blood loss, postpartum haemorrhage, infant temperature at admission or short-term neonatal outcomes.Conclusion: Stabilisation of very preterm infants with physiological-based cord clamping is at least as effective as with standard DCC. Show less
Objective: The aim of this study was to evaluate the differences in leukocyte counts at birth between donors and recipients with twin-twin transfusion syndrome (TTTS) or twin anemia-polycythemia... Show moreObjective: The aim of this study was to evaluate the differences in leukocyte counts at birth between donors and recipients with twin-twin transfusion syndrome (TTTS) or twin anemia-polycythemia sequence (TAPS). Methods: We performed a retrospective cohort study in monochorionic twin pairs with TTTS or TAPS. TTTS and TAPS cases treated with fetoscopic laser surgery were excluded. Primary outcome was the difference in leukocyte levels at birth between donor and recipient twins and the presence of leukopenia (defined as leukocyte count <4 x 10(9)/L). Secondary outcomes included early-onset sepsis, necrotizing enterocolitis, use of antibiotics during admission, and neonatal mortality. Results: We included 99 twins pairs, of which 61 twin pairs were affected by TAPS and 38 twin pairs by TTTS. The mean leukocyte count at birth in donors and recipients was 7.5 x 10(9)/L versus 7.4 x 10(9)/L (p = 0.936), respectively. Leukopenia was significantly more common in donor twins compared to recipient twins (7.1% [7/99] vs. 0% [0/99], p = 0.016). Of the 7 donors with leukopenia, 6 were affected by TAPS and 1 by TTTS. Overall, donors were more often affected by early-onset sepsis than recipients, 23.7% (23/97) versus 13% (13.7/95) (p = 0.049), respectively. Conclusions: Leukocyte counts at birth in twins with TTTS or TAPS are similar between donors and recipients, but TAPS donors are at an increased risk of leukopenia. Overall, TTTS and TAPS donors seem to be at an increased risk of early-onset neonatal sepsis compared to recipient twins. Show less
Introduction During delayed umbilical cord clamping, the factors underpinning placental transfusion remain unknown. We hypothesised that reductions in thoracic pressure during inspiration would... Show moreIntroduction During delayed umbilical cord clamping, the factors underpinning placental transfusion remain unknown. We hypothesised that reductions in thoracic pressure during inspiration would enhance placental transfusion in spontaneously breathing preterm lambs.Objective Investigate the effect of spontaneous breathing on umbilical venous flow and body weight in preterm lambs.Methods Pregnant sheep were instrumented at 132-133 days gestational age to measure fetal common umbilical venous, pulmonary and cerebral blood flows as well as arterial and intrapleural (IP) pressures. At delivery, doxapram and caffeine were administered to promote breathing. Lamb body weights were measured continuously and breathing was assessed by IP pressure changes.Results In 6 lambs, 491 out of 1117 breaths were analysed for change in body weight. Weight increased in 46.6% and decreased in 47.5% of breaths. An overall mean increase of 0.02 +/- 2.5 g per breath was calculated, and no net placental transfusion was observed prior to cord clamping (median difference in body weight 52.3 [-54.9-166.1] g, p=0.418). Umbilical venous (UV) flow transiently decreased with each inspiration, and in some cases ceased, before UV flow normalised during expiration. The reduction in UV flow was positively correlated with the standardised reduction in (IP) pressure, increasing by 109 mL/min for every SD reduction in IP pressure. Thus, the reduction in UV flow was closely related to inspiratory depth.Conclusions Spontaneous breathing had no net effect on body weight in preterm lambs at birth. UV blood flow decreased as inspiratory effort increased, possibly due to constriction of the inferior vena cava caused by diaphragmatic contraction, as previously observed in human fetuses. Show less
Background and objectives Necrotizing enterocolitis (NEC) is a common and often severe gastrointestinal emergency in newborn infants. While usually affecting (very) premature infants, an... Show moreBackground and objectives Necrotizing enterocolitis (NEC) is a common and often severe gastrointestinal emergency in newborn infants. While usually affecting (very) premature infants, an association between NEC and haemolytic disease of the foetus and newborn (HDFN) has been suggested. HDFN may be an additional risk factor to develop NEC. The objective of this study was to evaluate the occurrence of NEC in infants affected with moderate to severe HDFN in a large single centre cohort as compared to a broad population of infants without HDFN. Materials and methods Retrospective cohort study of medical records of neonates with and without HDFN, with a gestational age at birth >= 30 weeks and <= 38 weeks, and admitted to the Leiden University Medical Center between January 2000 and December 2016. Results A total of 3284 patient records of infants born in the study period were reviewed and 317 cases of HDFN were identified. The incidence of NEC was significantly higher among infants with HDFN compared to infants without HDFN: 4/317 affected infants (1 center dot 3%) vs. 11/2967 affected infants (0 center dot 4%, relative risk 3 center dot 40, 95% confidence interval: 1 center dot 09-10 center dot 63). Conclusions We observed a higher incidence of NEC in an overall late preterm to near term population of infants with moderate to severe HDFN, compared to infants born without HDFN. The clinician taking care of an HDFN-affected infant should be cautious of this higher risk. Show less
Dekker, J.; Martherus, T.; Lopriore, E.; Giera, M.; McGillick, E.V.; Hutten, J.; ... ; Pas, A.B. te 2019
The transition from fetal to newborn life involves a complex series of physiological events that commences with lung aeration, which is thought to involve 3 mechanisms. Two mechanisms occur during... Show moreThe transition from fetal to newborn life involves a complex series of physiological events that commences with lung aeration, which is thought to involve 3 mechanisms. Two mechanisms occur during labour, Na+ reabsorption and fetal postural changes, and one occurs after birth due to pressure gradients generated by inspiration. However, only one of these mechanisms, fetal postural changes, involves the loss of liquid from the respiratory system. Both other mechanisms involve liquid being reabsorbed from the airways into lung tissue. While this stimulates an increase in pulmonary blood flow (PBF), in large quantities this liquid can adversely affect postnatal respiratory function. The increase in PBF (i) facilitates the onset of pulmonary gas exchange and (ii) allows pulmonary venous return to take over the role of providing preload for the left ventricle, a role played by umbilical venous return during fetal life. Thus, aerating the lung and increasing PBF before umbilical cord clamping (known as physiological based cord clamping), can avoid the loss of preload and reduction in cardiac output that normally accompanies immediate cord clamping. Show less
