Publications by authors named "Janneke Dekker"

27 Publications

  • Page 1 of 1

Oxygen saturation and heart rate in healthy term and late preterm infants with delayed cord clamping.

Pediatr Res 2022 Jan 7. Epub 2022 Jan 7.

Neonatal Research Group, Health Research Institute and University and Polytechnic Hospital La Fe, Valencia, Spain.

Blood oxygen in the fetus is substantially lower than in the newborn infant. In the minutes after birth, arterial oxygen saturation rises from around 50-60% to 90-95%. Initial respiratory efforts generate negative trans-thoracic pressures that drive liquid from the airways into the lung interstitium facilitating lung aeration, blood oxygenation, and pulmonary artery vasodilatation. Consequently, intra- (foramen ovale) and extra-cardiac (ductus arteriosus) shunting changes and the sequential circulation switches to a parallel pulmonary and systemic circulation. Delaying cord clamping preserves blood flow through the ascending vena cava, thus increasing right and left ventricular preload. Recently published reference ranges have suggested that delayed cord clamping positively influenced the fetal-to-neonatal transition. Oxygen saturation in babies with delayed cord clamping plateaus significantly earlier to values of 85-90% than in babies with immediate cord clamping. Delayed cord clamping may also contribute to fewer episodes of brady-or-tachycardia in the first minutes after birth, but data from randomized trials are awaited. IMPACT: Delaying cord clamping during fetal to neonatal transition contributes to a significantly earlier plateauing of oxygen saturation and fewer episodes of brady-and/or-tachycardia in the first minutes after birth. We provide updated information regarding the changes in SpO and HR during postnatal adaptation of term and late preterm infants receiving delayed compared with immediate cord clamping. Nomograms in newborn infants with delayed cord clamping will provide valuable reference ranges to establish target SpO and HR in the first minutes after birth.
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http://dx.doi.org/10.1038/s41390-021-01805-yDOI Listing
January 2022

Feasibility and Effect of Physiological-Based CPAP in Preterm Infants at Birth.

Front Pediatr 2021 3;9:777614. Epub 2021 Dec 3.

Division of Neonatology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, Netherlands.

Preterm infants are commonly supported with 5-8 cmHO CPAP. However, animal studies demonstrate that high initial CPAP levels (12-15 cmHO) which are then reduced (termed physiological based (PB)-CPAP), improve lung aeration without adversely affecting cardiovascular function. We investigated the feasibility of PB-CPAP and the effect in preterm infants at birth. Preterm infants (24-30 weeks gestation) were randomized to PB-CPAP or 5-8 cmHO CPAP for the first 10 min after birth. PB-CPAP consisted of 15 cmHO CPAP that was decreased when infants were stabilized (heart rate ≥100 bpm, SpO ≥85%, FiO ≤ 0.4, spontaneous breathing) to 8 cmHO with steps of ~2/3 cmHO/min. Primary outcomes were feasibility and SpO in the first 5 min after birth. Secondary outcomes included physiological and breathing parameters and short-term neonatal outcomes. Planned enrollment was 42 infants. The trial was stopped after enrolling 31 infants due to a low inclusion rate and recent changes in the local resuscitation guideline that conflict with the study protocol. Measurements were available for analysis in 28 infants (PB-CPAP = 8, 5-8 cmHO = 20). Protocol deviations in the PB-CPAP group included one infant receiving 3 inflations with 15 cmHO PEEP and two infants in which CPAP levels were decreased faster than described in the study protocol. In the 5-8 cmHO CPAP group, three infants received 4, 10, and 12 cmHO CPAP. During evaluations, caregivers indicated that the current PB-CPAP protocol was difficult to execute. The SpO in the first 5 min after birth was not different [61 (49-70) vs. 64 (47-74), = 0.973]. However, infants receiving PB-CPAP achieved higher heart rates [121 (111-130) vs. 97 (82-119) bpm, = 0.016] and duration of mask ventilation was shorter [0:42 (0:34-2:22) vs. 2:58 (1:36-6:03) min, = 0.020]. Infants in the PB-CPAP group required 6:36 (5:49-11:03) min to stabilize, compared to 9:57 (6:58-15:06) min in the 5-8 cmH2O CPAP group ( = 0.256). There were no differences in short-term outcomes. Stabilization of preterm infants with PB-CPAP is feasible but tailoring CPAP appeared challenging. PB-CPAP did not lead to higher SpO but increased heart rate and shortened the duration of mask ventilation, which may reflect faster lung aeration.
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http://dx.doi.org/10.3389/fped.2021.777614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678466PMC
December 2021

Increased end-expiratory pressures improve lung function in near-term newborn rabbits with elevated airway liquid volume at birth.

J Appl Physiol (1985) 2021 09 5;131(3):997-1008. Epub 2021 Aug 5.

School of Physics and Astronomy, Monash University, Melbourne, Victoria, Australia.

Approximately 53% of near-term newborns admitted to intensive care experience respiratory distress. These newborns are commonly delivered by cesarean section and have elevated airway liquid volumes at birth, which can cause respiratory morbidity. We investigated the effect of providing respiratory support with a positive end-expiratory pressure (PEEP) of 8 cmHO on lung function in newborn rabbit kittens with elevated airway liquid volumes at birth. Near-term rabbits (30 days; term = 32 days) with airway liquid volumes that corresponded to vaginal delivery (∼7 mL/kg, control, = 11) or cesarean section [∼37 mL/kg; elevated liquid (EL), = 11] were mechanically ventilated (tidal volume = 8 mL/kg). The PEEP was changed after lung aeration from 0 to 8 to 0 cmHO (control, = 6; EL, = 6), and in a separate group of kittens, PEEP was changed after lung aeration from 8 to 0 to 8 cmHO (control, = 5; EL, = 5). Lung function (ventilator parameters, compliance, lung gas volumes, and distribution of gas within the lung) was evaluated using plethysmography and synchrotron-based phase-contrast X-ray imaging. EL kittens initially receiving 0 cmHO PEEP had reduced functional residual capacities and lung compliance, requiring higher inflation pressures to aerate the lung compared with control kittens. Commencing ventilation with 8 cmHO PEEP mitigated the adverse effects of EL, increasing lung compliance, functional residual capacity, and the uniformity and distribution of lung aeration, but did not normalize aeration of the distal airways. Respiratory support with PEEP supports lung function in near-term newborn rabbits with elevated airway liquid volumes at birth who are at a greater risk of suffering respiratory distress. Term babies born by cesarean section have elevated airway liquid volumes, which predisposes them to respiratory distress. Treatments targeting molecular mechanisms to clear lung liquid are ineffective for term newborn respiratory distress. We showed that respiratory support with an end-expiratory pressure supports lung function in near-term rabbits with elevated airway liquid volumes at birth. This study provides further physiological understanding of lung function in newborns with elevated airway liquid volumes at risk of respiratory distress.
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http://dx.doi.org/10.1152/japplphysiol.00918.2020DOI Listing
September 2021

The Effect of Initial Oxygen Exposure on Diaphragm Activity in Preterm Infants at Birth.

Front Pediatr 2021 9;9:640491. Epub 2021 Feb 9.

Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

The initial FiO that should be used for the stabilization of preterm infants in the delivery room (DR) is still a matter of debate as both hypoxia and hyperoxia should be prevented. A recent randomized controlled trial showed that preterm infants [gestational age (GA) < 30 weeks] stabilized with an initial high FiO (1.0) had a significantly higher breathing effort than infants stabilized with a low FiO (0.3). As the diaphragm is the main respiratory muscle in these infants, we aimed to describe the effects of the initial FiO on diaphragm activity. In a subgroup of infants from the original bi-center randomized controlled trial diaphragm activity was measured with transcutaneous electromyography of the diaphragm (dEMG), using three skin electrodes that were placed directly after birth. Diaphragm activity was compared in the first 5 min after birth. From the dEMG respiratory waveform several outcome measures were determined for comparison of the groups: average peak- and tonic inspiratory activity (dEMG and dEMG, respectively), inspiratory amplitude (dEMG), area under the curve (dEMG) and the respiratory rate (RR). Thirty-one infants were included in this subgroup, of which 29 could be analyzed [ = 15 (median GA 28.4 weeks) and = 14 (median GA 27.9 weeks) for the 100 and 30% oxygen group, respectively]. Tonic diaphragm activity was significantly higher in the high FiO-group (4.3 ± 2.1 μV vs. 2.9 ± 1.1 μV; = 0.047). The other dEMG-parameters (dEMG, dEMG, dEMG) showed consistently higher values in the high FiO group, but did not reach statistical significance. Average RR showed similar values in both groups (34 ± 9 vs. 32 ± 10 breaths/min for the high and low oxygen group, respectively). Preterm infants stabilized with an initial high FiO showed significantly more tonic diaphragm activity and an overall trend toward a higher level of diaphragm activity than those stabilized with an initial low FiO. These results confirm that a high initial FiO after birth stimulates breathing effort, which can be objectified with dEMG.
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http://dx.doi.org/10.3389/fped.2021.640491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899995PMC
February 2021

High-CPAP Does Not Impede Cardiovascular Changes at Birth in Preterm Sheep.

Front Pediatr 2020 22;8:584138. Epub 2021 Jan 22.

The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, Australia.

Continuous positive airway pressures (CPAP) used to assist preterm infants at birth are limited to 4-8 cmHO due to concerns that high-CPAP may cause pulmonary overexpansion and adversely affect the cardiovascular system. We investigated the effects of high-CPAP on pulmonary (PBF) and cerebral (CBF) blood flows and jugular vein pressure (JVP) after birth in preterm lambs. Preterm lambs instrumented with flow probes and catheters were delivered at 133/146 days gestation. Lambs received low-CPAP (LCPAP: 5 cmHO), high-CPAP (HCPAP: 15 cmHO) or dynamic HCPAP (15 decreasing to 8 cmHO at ~2 cmHO/min) for up to 30 min after birth. Mean PBF was lower in the LCPAP [median (Q1-Q3); 202 (48-277) mL/min, = 0.002] compared to HCPAP [315 (221-365) mL/min] and dynamic HCPAP [327 (269-376) mL/min] lambs. CBF was similar in LCPAP [65 (37-78) mL/min], HCPAP [73 (41-106) mL/min], and dynamic HCPAP [66 (52-81) mL/min, = 0.174] lambs. JVP was similar at CPAPs of 5 [8.0 (5.1-12.4) mmHg], 8 [9.4 (5.3-13.4) mmHg], and 15 cmHO [8.6 (6.9-10.5) mmHg, = 0.909]. Heart rate was lower in the LCPAP [134 (101-174) bpm; = 0.028] compared to the HCPAP [173 (139-205)] and dynamic HCPAP [188 (161-207) bpm] groups. Ventilation or additional caffeine was required in 5/6 LCPAP, 1/6 HCPAP, and 5/7 dynamic HCPAP lambs ( = 0.082), whereas 3/6 LCPAP, but no HCPAP lambs required intubation ( = 0.041), and 1/6 LCPAP, but no HCPAP lambs developed a pneumothorax ( = 0.632). High-CPAP did not impede the increase in PBF at birth and supported preterm lambs without affecting CBF and JVP.
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http://dx.doi.org/10.3389/fped.2020.584138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862825PMC
January 2021

Optimizing oxygenation of the preterm infant directly at birth: focus of future studies.

J Pediatr 2021 02 13;229:309. Epub 2020 Nov 13.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.

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http://dx.doi.org/10.1016/j.jpeds.2020.11.017DOI Listing
February 2021

Comparing the effect of two different interfaces on breathing of preterm infants at birth: A matched-pairs analysis.

Resuscitation 2020 12 17;157:60-66. Epub 2020 Oct 17.

Division of Neonatology, Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands.

Objective: Applying a face mask could provoke a trigeminocardiac reflex. We compared the effect of applying bi-nasal prongs with a face mask on breathing and heart rate of preterm infants at birth.

Methods: In a retrospective matched-pairs study of infants <32 weeks of gestation, the use of bi-nasal prongs for respiratory support at birth was compared to the use of a face mask. Infants who were initially breathing at birth and subsequently received respiratory support were matched for gestational age (±4 days), birth weight (±300 g), general anaesthesia and gender. Breathing, heart rate and other parameters were collected before and after interface application and in the first 5 min thereafter.

Results: In total, 130 infants were included (n = 65 bi-nasal prongs, n = 65 face mask) with a median (IQR) gestational age of 27 (25-28) vs 26 (25-28) weeks. The proportion of infants who stopped breathing after applying the interface was not different between the groups (bi-nasal prongs 43/65 (66%) vs face mask 46/65 (71%), p = 0.70). Positive pressure ventilation was given more often when bi-nasal prongs were used (55/65 (85%) vs 40/65 (62%), p < 0.001). Heart rate (101 (75-145) vs 110 (68-149) bpm, p = 0.496) and oxygen saturation (59% (48-87) vs 56% (35-84), p = 0.178) were similar in the first 5 min after an interface was applied in the infants who stopped breathing.

Conclusion: Apnoea and bradycardia occurred often after applying either bi-nasal prongs or a face mask on the face for respiratory support in preterm infants at birth.
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http://dx.doi.org/10.1016/j.resuscitation.2020.10.004DOI Listing
December 2020

High variability in nurses' tactile stimulation methods in response to apnoea of prematurity-A neonatal manikin study.

Acta Paediatr 2021 03 22;110(3):799-804. Epub 2020 Sep 22.

Division of Neonatology, Department of Paediatrics, Leiden University Medical Center, Leiden, the Netherlands.

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 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.
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http://dx.doi.org/10.1111/apa.15564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984214PMC
March 2021

Reflexes that impact spontaneous breathing of preterm infants at birth: a narrative review.

Arch Dis Child Fetal Neonatal Ed 2020 Nov 29;105(6):675-679. Epub 2020 Apr 29.

Neonatology, Leiden University Medical Center, Leiden, The Netherlands.

Some neural circuits within infants are not fully developed at birth, especially in preterm infants. Therefore, it is unclear whether reflexes that affect breathing may or may not be activated during the neonatal stabilisation at birth. Both sensory reflexes (eg, tactile stimulation) and non-invasive ventilation (NIV) can promote spontaneous breathing at birth, but the application of NIV can also compromise breathing by inducing facial reflexes that inhibit spontaneous breathing. Applying an interface could provoke the trigeminocardiac reflex (TCR) by stimulating the trigeminal nerve resulting in apnoea and a reduction in heart rate. Similarly, airflow within the nasopharynx can elicit the TCR and/or laryngeal chemoreflex (LCR), resulting in glottal closure and ineffective ventilation, whereas providing pressure via inflations could stimulate multiple receptors that affect breathing. Stimulating the fast adapting pulmonary receptors may activate Head's paradoxical reflex to stimulate spontaneous breathing. In contrast, stimulating the slow adapting pulmonary receptors or laryngeal receptors could induce the Hering-Breuer inflation reflex or LCR, respectively, and thereby inhibit spontaneous breathing. As clinicians are most often unaware that starting primary care might affect the breathing they intend to support, this narrative review summarises the currently available evidence on (vagally mediated) reflexes that might promote or inhibit spontaneous breathing at birth.
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http://dx.doi.org/10.1136/archdischild-2020-318915DOI Listing
November 2020

The Effect of Initial High vs. Low FiO on Breathing Effort in Preterm Infants at Birth: A Randomized Controlled Trial.

Front Pediatr 2019 12;7:504. Epub 2019 Dec 12.

Department of Neonatology, Leiden University Medical Center, Leiden, Netherlands.

Infants are currently stabilized at birth with initial low FiO which increases the risk of hypoxia and suppression of breathing in the first minutes after birth. We hypothesized that initiating stabilization at birth with a high O concentration, followed by titration, would improve breathing effort when compared to a low O concentration, followed by titration. In a bi-center randomized controlled trial, infants <30 weeks gestation were stabilized at birth with an initial O concentration of 30 or 100%, followed by oxygen titration. Primary outcome was minute volume of spontaneous breathing. We also assessed tidal volumes, mean inspiratory flow rate (MIFR) and respiratory rate with a respiratory function monitor in the first 5 min after birth, and evaluated the duration of mask ventilation in the first 10 min after birth. Pulse oximetry was used to measure heart rate and SpO values in the first 10 min. Hypoxemia was defined as SpO < 25th percentile and hyperoxemia as SpO >95%. 8-iso-prostaglandin F2α (8iPGF2α) was measured to assess oxidative stress in cord blood and 1 and 24 h after birth. Fifty-two infants were randomized and recordings were obtained in 44 infants (100% O-group: = 20, 30% O-group: = 24). Minute volumes were significantly higher in the 100% O-group (146.34 ± 112.68 mL/kg/min) compared to the 30% O-group (74.43 ± 52.19 mL/kg/min), = 0.014. Tidal volumes and MIFR were significantly higher in the 100% O-group, while the duration of mask ventilation given was significantly shorter. Oxygenation in the first 5 min after birth was significantly higher in infants in the 100% O-group [85 (64-93)%] compared to the 30% O-group [58 (46-67)%], < 0.001. The duration of hypoxemia was significantly shorter in the 100% O-group, while the duration of hyperoxemia was not different between groups. There was no difference in oxidative stress marker 8iPGF2α between the groups. Initiating stabilization of preterm infants at birth with 100% O led to higher breathing effort, improved oxygenation, and a shorter duration of mask ventilation as compared to 30% O, without increasing the risk for hyperoxia or oxidative stress. This study was registered in www.trialregister.nl, with registration number NTR6878.
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http://dx.doi.org/10.3389/fped.2019.00504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927294PMC
December 2019

Increasing Respiratory Effort With 100% Oxygen During Resuscitation of Preterm Rabbits at Birth.

Front Pediatr 2019 22;7:427. Epub 2019 Oct 22.

School of Physics and Astronomy, Monash University, Melbourne, VIC, Australia.

Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O may reduce the risk of hypoxia and increase respiratory effort at birth. Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% ( = 12) or 100% O ( = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O in kittens who started in 21% O, and remained at 100% O for kittens who started the experiment in 100% O. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Initially, kittens receiving 21% O had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O [median (IQR) respiratory rate: 16 (4-28) vs. 38 (29-46) bpm, = 0.001; variability in inter-breath interval: 33.3% (17.2-50.1%) vs. 27.5% (18.6-36.3%), = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O (11/12 vs. 1/8, = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O. FRC was not different between study groups at both timepoints. Initiating resuscitation with 100% O resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are mandatory to confirm the benefit of this approach in terms of oxygenation. In addition, the ability to avoid hyperoxia after initiation of resuscitation with 100% oxygen, using a titration protocol based on oxygen saturation, needs to be clarified.
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http://dx.doi.org/10.3389/fped.2019.00427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817611PMC
October 2019

Issues in cardiopulmonary transition at birth.

Semin Fetal Neonatal Med 2019 12 23;24(6):101033. Epub 2019 Sep 23.

Division of Neonatology, Department of Paediatrics, Leiden University Medical Centre, Leiden, the Netherlands.

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 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.
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http://dx.doi.org/10.1016/j.siny.2019.101033DOI Listing
December 2019

The effect of a face mask for respiratory support on breathing in preterm infants at birth.

Resuscitation 2019 11 12;144:178-184. Epub 2019 Sep 12.

Division of Neonatology, Department of Paediatrics, Leiden University Medical Centre, Leiden, Netherlands.

Objective: Applying a mask on the face for respiratory support could induce a trigeminocardiac reflex leading to apnoea and bradycardia. We have examined the effect of applying a face mask on breathing and heart rate in preterm infants at birth.

Methods: Resuscitation videos of infants ≤ 32 weeks gestation recorded from 2010 until 2018 at the Leiden University Medical Centre and the General University Hospital in Prague were reviewed. All infants received respiratory support via face mask. Breathing and heart rate were noted before and after application of the face mask and over the first 5 min.

Results: Recordings of 429 infants were included (median (IQR) gestational age of 28 (27-30) weeks). In 368/429 (86%) infants breathing was observed before application of the face mask and 197/368 (54%) of these infants stopped breathing following application of the face mask. Apnoea occurred at a median of 5 (3-17) seconds after application of the face mask with a duration of 28 (22-34) seconds of the first minute. In a logistic regression model, the occurrence of apnoea after face mask application was inversely associated with gestational age (OR = 1.424 (1.281-1.583), p < 0.001). Infants who stopped breathing had a significantly lower heart rate 82 (66-123) vs 134 (97-151) bpm, p < 0.001) and oxygen saturation (49% (33-59) vs 66% (50-82), p < 0.001) over the first minute after face mask application, compared to infants who continued breathing.

Conclusion: Applying a face mask for respiratory support affects breathing in a large proportion (54%) of preterm infants and this effect is gestational age dependent.
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http://dx.doi.org/10.1016/j.resuscitation.2019.08.043DOI Listing
November 2019

Stimulating and maintaining spontaneous breathing during transition of preterm infants.

Pediatr Res 2021 Oct 19;90(4):722-730. Epub 2019 Jun 19.

Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

Most preterm infants breathe at birth, but need additional respiratory support due to immaturity of the lung and respiratory control mechanisms. To avoid lung injury, the focus of respiratory support has shifted from invasive towards non-invasive ventilation. However, applying effective non-invasive ventilation is difficult due to mask leak and airway obstruction. The larynx has been overlooked as one of the causes for obstruction, preventing face mask ventilation from inflating the lung. The larynx remains mostly closed at birth, only opening briefly during a spontaneous breath. Stimulating and supporting spontaneous breathing could enhance the success of non-invasive ventilation by ensuring that the larynx remains open. Maintaining adequate spontaneous breathing and thereby reducing the need for invasive ventilation is not only important directly after birth, but also in the first hours after admission to the NICU. Respiratory distress syndrome is an important cause of respiratory failure. Traditionally, treatment of RDS required intubation and mechanical ventilation to administer exogenous surfactant. However, new ways have been implemented to administer surfactant and preserve spontaneous breathing while maintaining non-invasive support. In this narrative review we aim to describe interventions focused on stimulation and maintenance of spontaneous breathing of preterm infants in the first hours after birth.
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http://dx.doi.org/10.1038/s41390-019-0468-7DOI Listing
October 2021

High vs. Low Initial Oxygen to Improve the Breathing Effort of Preterm Infants at Birth: Study Protocol for a Randomized Controlled Trial.

Front Pediatr 2019 7;7:179. Epub 2019 May 7.

Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands.

Although most preterm infants breathe at birth, their respiratory drive is weak and supplemental oxygen is often needed to overcome hypoxia. This could in turn lead to hyperoxia. To reduce the risk of hyperoxia, currently an initial low oxygen concentration (21-30%) is recommended during stabilization at birth, accepting the risk of a hypoxic period. However, hypoxia inhibits respiratory drive in preterm infants. Starting with a higher level of oxygen could lead to a shorter duration of hypoxia by stimulating breathing effort of preterm infants, and combined with subsequent titration based on oxygen saturation, prolonged hyperoxia might be prevented. This multi-center randomized controlled trial will include 50 infants with a gestational age between 24 and 30 weeks. Eligible infants will be randomized to stabilization with an initial FiO of either 1.0 or 0.3 at birth. Hereafter, FiO will be titrated based on the oxygen saturation target range. In both groups, all other interventions during stabilization and thereafter will be similar. The primary outcome is respiratory effort in the first 5 min after birth expressed as average minute volume/kg. Secondary outcomes include inspired tidal volumes/kg, rate of rise to maximum tidal volume/kg, percentage of recruitment breaths with tidal volumes above 8 mL/kg, duration of hypoxia and hyperoxia and plasma levels of markers of oxidative stress (8-iso-prostaglandin F2α). Current resuscitation guidelines recommend oxygen titration if infants fail to achieve the 25th percentile of the SpO reference ranges. It has become clear that, using this approach, most preterm infants are at risk for hypoxia in the first 5 min after birth, which could suppress the breathing effort. In addition, for compromised preterm infants who need respiratory support at birth, higher SpO reference ranges in the first minutes after birth might be needed to prevent prolonged hypoxia. Enhancing breathing effort by achieving an adequate level of oxygenation could potentially lead to a lower incidence of intubation and mechanical ventilation in the delivery room, contributing to a lower risk on lung injury in high-risk preterm infants. Measuring 8-iso-prostaglandin F2α could lead to a reflection of the true amount of oxygen exposure in both study groups.
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http://dx.doi.org/10.3389/fped.2019.00179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514187PMC
May 2019

The Changing Landscape in Supporting Preterm Infants at Birth.

Neonatology 2019 11;115(4):392-397. Epub 2019 Apr 11.

Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

Noninvasive ventilation for preterm infants at birth has been recommended and universally adopted. The umbilical cord is often clamped immediately in order to provide the support the infant needs for stabilization. However, recent scientific data from experimental studies that involve animals in transition and human studies using physiological measurements at birth have increased awareness as to how little we know about how these interventions interact and integrate with the infant's changing physiology. It has become clear that in apneic infants the larynx is closed immediately after birth, which can completely negate the effect of noninvasive ventilation of the lung. For this reason, stimulating and supporting spontaneous breathing could enhance the success of noninvasive ventilation. Animal data also demonstrated that the large swings in blood pressure, blood flow, and oxygenation caused by immediate cord clamping can be avoided by postponing cord clamping until lung aeration has been established. In this review we will focus on these "game changers" that have the potential to completely change the approach used in stabilizing preterm infants at birth.
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http://dx.doi.org/10.1159/000497421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604262PMC
December 2019

Tactile stimulation in the delivery room: do we practice what we preach?

Arch Dis Child Fetal Neonatal Ed 2019 Nov 1;104(6):F661-F662. Epub 2019 Mar 1.

Department of Paediatrics, University of Oxford, Oxford, UK.

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http://dx.doi.org/10.1136/archdischild-2018-316344DOI Listing
November 2019

Comparison of Two Respiratory Support Strategies for Stabilization of Very Preterm Infants at Birth: A Matched-Pairs Analysis.

Front Pediatr 2019 29;7. Epub 2019 Jan 29.

Department of Paediatrics, Leiden University Medical Center, Leiden, Netherlands.

Respiratory support for stabilizing very preterm infants at birth varies between centers. We retrospectively compared two strategies that involved either increasing continuous positive airway pressures (CPAP), or increasing oxygen supplementation. Matched-pairs of infants (<28 weeks of gestation) were born either at the Leiden University Medical Center [low-pressure: CPAP 5-8 cmHO and/or positive pressure ventilation (PPV) and fraction of inspired oxygen (FiO) 0.3-1.0; = 27], or at the University Hospital of Cologne (high-pressure: CPAP 12-35 cmHO, no PPV and FiO 0.3-0.4; = 27). Respiratory support was initiated non-invasively via facemask at both units. Infants ( = 54) were matched between centers for gestational age and birth weight, to compare physiological and short-term clinical outcomes. In the low-pressure group, 20/27 (74%) infants received 1-2 sustained inflations (20, 25 cm HO) and 22/27 (81%) received PPV (1:19-3:01 min) using pressures of 25-27 cm HO. Within 3 min of birth [median (IQR)], mean airway pressures [12 (6-15) vs. 19 (16-23) cmHO, < 0.001] and FiO [0.30 (0.28-0.31) vs. 0.22 (0.21-0.30), < 0.001] were different in low- vs. high-pressure groups, respectively. SpO and heart rates were similar. After 3 min, higher FiO levels [0.62 (0.35-0.98) vs. 0.28 (0.22-0.38), = 0.005] produced higher SpO levels [77 (50-92) vs. 53 (42-69)%, < 0.001] in the low-pressure group, but SpO/FiO and heart rates were similar. While intubation rates during admission were significantly different (70 vs. 30%, = 0.013), pneumothorax rates (4 vs. 19%, = 0.125) and the occurrence of spontaneous intestinal perforations (0 vs. 15%, = 0.125) were similar between groups. Infants (<28 weeks) can be supported non-invasively at birth with either higher or lower pressures and while higher-pressure support may require less oxygen, it does not eliminate the need for oxygen supplementation. Future studies need to examine the effect of high pressures and pressure titration in the delivery room.
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http://dx.doi.org/10.3389/fped.2019.00003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362425PMC
January 2019

Sedation during minimal invasive surfactant therapy: a randomised controlled trial.

Arch Dis Child Fetal Neonatal Ed 2019 Jul 1;104(4):F378-F383. Epub 2018 Aug 1.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

Background And Aims: Although sedation for endotracheal intubation of infants is widely adopted, there is no consensus whether sedation should be used for minimal invasive surfactant therapy (MIST). We compared, in a randomised controlled setting, the level of stress and comfort of preterm infants during MIST with and without receiving low-dose sedation.

Methods: Infants between 26 and 36 weeks gestational age were randomised to receive either low-dose sedation (1 mg/kg propofol intravenous) or no premedication during MIST procedure. Standard comfort care was given in both groups, which consisted of administering sucrose in the cheek pouch of the infant and containment. Primary end point was the percentage of infants assessed to be comfortable during the procedure (COMFORTneo-score <14). Secondary parameters included complications of both the MIST procedure and low-dose sedation administration.

Results: In total, 78 infants were randomised and analysed, with a median (IQR) gestational age of 29 (28-32) weeks. The percentage of infants with a COMFORTneo score <14 during MIST was significantly higher in the sedated group (32/42 (76%) vs 8/36 (22%), p<0.001). The incidence of desaturation (SpO <85%) during the procedure was significantly higher in the sedated group (38/42 (91%) vs 25/36 (69%), p=0.023), and infants needed more often nasal intermittent mandatory ventilation during the procedure (39/42 (93%) vs 17/36 (47%), p<0.001). There were no differences in incidence of hypotension, bradycardia, intubation or pneumothoraxes.

Conclusion: Low-dose sedation increased comfort during MIST procedure in preterm infants, but the need for transient non-invasive ventilation was increased.

Trial Registration Number: NTR5010, pre-results.
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http://dx.doi.org/10.1136/archdischild-2018-315015DOI Listing
July 2019

Supporting breathing of preterm infants at birth: a narrative review.

Arch Dis Child Fetal Neonatal Ed 2019 Jan 26;104(1):F102-F107. Epub 2018 Jul 26.

Department of Paediatrics, Leiden University Medical Center, Leiden, Netherlands.

Most very preterm infants have difficulty aerating their lungs and require respiratory support at birth. Currently in clinical practice, non-invasive ventilation in the form of continuous positive airway pressure (CPAP) and positive pressure ventilation (PPV) is applied via facemask. As most very preterm infants breathe weakly and unnoticed at birth, PPV is often administered. PPV is, however, frequently ineffective due to pressure settings, mask leak and airway obstruction. Meanwhile, high positive inspiratory pressures and spontaneous breathing coinciding with inflations can generate high tidal volumes. Evidence from preclinical studies demonstrates that high tidal volumes can be injurious to the lungs and brains of premature newborns. To reduce the need for PPV in the delivery room, it should be considered to optimise spontaneous breathing with CPAP. CPAP is recommended in guidelines and commonly used in the delivery room after a period of PPV, but little data is available on the ideal CPAP strategy and CPAP delivering devices and interfaces used in the delivery room. This narrative review summarises the currently available evidence for why PPV can be inadequate at birth and what is known about different CPAP strategies, devices and interfaces used the delivery room.
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http://dx.doi.org/10.1136/archdischild-2018-314898DOI Listing
January 2019

Repetitive versus standard tactile stimulation of preterm infants at birth - A randomized controlled trial.

Resuscitation 2018 06 23;127:37-43. Epub 2018 Mar 23.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

Aim: To evaluate the direct effect of repetitive tactile stimulation on breathing effort of preterm infants at birth.

Methods: This randomized controlled trial compared the effect of repetitive stimulation on respiratory effort during the first 4 min after birth with standard stimulation based on clinical indication in preterm infants with a gestational age of 27-32 weeks. All details of the stimulation performed were noted. The main study parameter measured was respiratory minute volume, other study parameters assessed measures of respiratory effort; tidal volumes, rate of rise to maximum tidal volumes, percentage of recruitment breaths, and oxygenation of the infant.

Results: There was no significant difference in respiratory minute volume in the repetitive stimulation group when compared to the standard group. Oxygen saturation was significantly higher (87.6 ± 3.3% vs 81.7 ± 8.7%, p = .01) while the amount of FiO given during transport to the NICU was lower (28.2 (22.8-35.0)% vs 33.6 (29.4-44.1)%, p = .04). There was no significant difference in administration of positive pressure ventilation (52% vs 78%, p = .13), or the duration of ventilation (median (IQR) time 8 (0-118)s vs 35 (13-131)s, p = .23). Caregivers decided less often to administer caffeine in the delivery room to stimulate breathing in the repetitive stimulation group (10% vs 39%, p = .036).

Conclusion: Although the increase in respiratory effort during repetitive stimulation did not reach significance, oxygenation significantly improved with a lower level of FiO at transport to the NICU. Repetitive tactile stimulation could be of added value to improve breathing effort at birth.
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http://dx.doi.org/10.1016/j.resuscitation.2018.03.030DOI Listing
June 2018

Effect of Tactile Stimulation on Termination and Prevention of Apnea of Prematurity: A Systematic Review.

Front Pediatr 2018 2;6:45. Epub 2018 Mar 2.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands.

Apnea of prematurity (AOP) is one of the most common diagnoses in preterm infants. Severe and recurrent apneas are associated with cerebral injury and adverse neurodevelopmental outcome. Despite pharmacotherapy and respiratory support to prevent apneas, a proportion of infants continue to have apneas and often need tactile stimulation, mask, and bag ventilation and/or extra oxygen. The duration of the apnea and the concomitant hypoxia and bradycardia depends on the response time of the nurse. We systematically reviewed the literature with the aim of providing an overview of what is known about the effect of manual and mechanical tactile stimulation on AOP. Tactile stimulation, manual or mechanical, has been shown to shorten the duration of apnea, hypoxia, and or bradycardia or even prevent an apnea. Automated stimulation, using closed-loop pulsating or vibrating systems, has been shown to be effective in terminating apneas, but data are scarce. Several studies used continuous mechanical stimulation, with pulsating, vibrating, or oscillating stimuli, to prevent apneas, but the reported effect varied. More studies are needed to confirm whether automated stimulation using a closed loop is more effective than manual stimulation, how and where the automated stimulation should be performed and the potential side effects.
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http://dx.doi.org/10.3389/fped.2018.00045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840648PMC
March 2018

Elevated airway liquid volumes at birth: a potential cause of transient tachypnea of the newborn.

J Appl Physiol (1985) 2017 Nov 3;123(5):1204-1213. Epub 2017 Aug 3.

The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia;

Excessive liquid in airways and/or distal lung tissue may underpin the respiratory morbidity associated with transient tachypnea of the newborn (TTN). However, its effects on lung aeration and respiratory function following birth are unknown. We investigated the effect of elevated airway liquid volumes on newborn respiratory function. Near-term rabbit kittens (30 days gestation; term ~32 days) were delivered, had their lung liquid-drained, and either had no liquid replaced (control; = 7) or 30 ml/kg of liquid re-added to the airways [liquid added (LA); = 7]. Kittens were mechanically ventilated in a plethysmograph. Measures of chest and lung parameters, uniformity of lung aeration, and airway size were analyzed using phase contrast X-ray imaging. The maximum peak inflation pressure required to recruit a tidal volume of 8 ml/kg was significantly greater in LA compared with control kittens (35.0 ± 0.7 vs. 26.8 ± 0.4 cmHO, < 0.001). LA kittens required greater time to achieve lung aeration (106 ± 14 vs. 60 ± 6 inflations, = 0.03) and had expanded chest walls, as evidenced by an increased total chest area (32 ± 9%, < 0.0001), lung height (17 ± 6%, = 0.02), and curvature of the diaphragm (19 ± 8%, = 0.04). LA kittens had lower functional residual capacity during stepwise changes in positive end-expiratory pressures (5, 3, 0, and 5 cmH0). Elevated lung liquid volumes had marked adverse effects on lung structure and function in the immediate neonatal period and reduced the ability of the lung to aerate efficiently. We speculate that elevated airway liquid volumes may underlie the initial morbidity in near-term babies with TTN after birth. Transient tachypnea of the newborn reduces respiratory function in newborns and is thought to result due to elevated airway liquid volumes following birth. However, the effect of elevated airway liquid volumes on neonatal respiratory function is unknown. Using phase contrast X-ray imaging, we show that elevated airway liquid volumes have adverse effects on lung structure and function in the immediate newborn period, which may underlie the pathology of TTN in near-term babies after birth.
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http://dx.doi.org/10.1152/japplphysiol.00464.2017DOI Listing
November 2017

Tactile Stimulation to Stimulate Spontaneous Breathing during Stabilization of Preterm Infants at Birth: A Retrospective Analysis.

Front Pediatr 2017 3;5:61. Epub 2017 Apr 3.

Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands.

Background And Aims: Tactile maneuvers to stimulate breathing in preterm infants are recommended during the initial assessment at birth, but it is not known how often and how this is applied. We evaluated the occurrence and patterns of tactile stimulation during stabilization of preterm infants at birth.

Methods: Recordings of physiological parameters and videos of infants <32 weeks gestational age were retrospectively analyzed. Details of tactile stimulation during the first 7 min after birth (timing, duration, type, and indication) were noted.

Results: Stimulation was performed in 164/245 (67%) infants. The median (IQR) GA was 28 6/7 (27 2/7-30 1/7) weeks, birth weight 1,153 (880-1,385) g, Apgar score at 5 min was 8 (7-9), 140/245 (57%) infants were born after cesarean section, and 134/245 (55%) were male. There were no significant differences between the stimulated and the non-stimulated infants with regard to basic characteristics. In the stimulated infants, the first episode of stimulation was given at a median (IQR) of 114 (73-182) s after birth. Stimulation was repeated 3 (1-5) times, with a median (IQR) duration of 8 (4-16) s and a total duration of 32 (15-64) s. Modes of stimulation were: rubbing (68%) or flicking (2%) the soles of the feet, rubbing the back (12%), a combination (9%), or other (8%). In 67% of the stimulation episodes, a clear indication was noted (25% bradycardia, 57% apnea, 48% hypoxemia, 43% combination) and an effect was observed in 18% of these indicated stimulation episodes. A total effect of all stimulation episodes per infant remains unclear, but infants who did not receive stimulation were more often intubated in the delivery room (14/79 (18%) vs 12/164 (7%),  < 0.05).

Conclusion: There was a large variation in the use of tactile stimulation in preterm infants during stabilization at birth. In most cases, there was an indication for stimulation, but only in a small proportion an effect could be observed.
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http://dx.doi.org/10.3389/fped.2017.00061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377072PMC
April 2017

Caffeine to improve breathing effort of preterm infants at birth: a randomized controlled trial.

Pediatr Res 2017 Aug 17;82(2):290-296. Epub 2017 May 17.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

BackgroundCaffeine promotes spontaneous breathing by antagonizing adenosine. We assessed the direct effect of caffeine on respiratory effort in preterm infants at birth.MethodsThirty infants of 24-30 weeks of gestation were randomized for receiving caffeine directly after birth in the delivery room (caffeine DR group) or later in the neonatal intensive care unit (control group). Primary outcome was respiratory effort, expressed as minute volume, tidal volumes, respiratory rate, rate of rise to maximum tidal volume, and recruitment breaths at 7-9 min after birth.ResultsAfter correction for gestational age, minute volumes ((mean±SD; 189±74 vs. 162±70 ml/kg/min; P<0.05) and tidal volumes ((median (interquartile range (IQR)) 5.2 (3.9-6.4) vs. 4.4 (3.0-5.6) ml/kg) were significantly greater in the caffeine DR group. Although respiratory rates were similar ((mean±SD) 35±10 vs. 33±10), RoR increased significantly ((median (IQR) 14.3 (11.2-19.8) vs. 11.2 (7.9-15.2) ml/kg/s), and more recruitment breaths were observed (13 vs. 9%).ConclusionCaffeine increases respiratory effort in preterm infants at birth, but the effect on clinical outcomes needs further investigation.
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http://dx.doi.org/10.1038/pr.2017.45DOI Listing
August 2017

Sedation during Minimal Invasive Surfactant Therapy in Preterm Infants.

Neonatology 2016 24;109(4):308-13. Epub 2016 Feb 24.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

Background: There is no data available whether sedation should be given during minimally invasive surfactant therapy (MIST).

Objective: To compare the level of comfort of preterm infants receiving sedation versus no sedation for MIST.

Methods: A retrospective study of preterm infants receiving MIST was performed in Leiden University Medical Center in 2014. Sedation (propofol 1 mg/kg) was optional and left to the discretion of the caregiver. Standardized COMFORTneo scores were compared, and COMFORTneo <14 was considered comfortable. Basic characteristics and complications were noted.

Results: In 38 infants receiving MIST, 23 received propofol and 15 were not sedated. Mean (SD) gestational age [29 (2) vs. 29 (3) weeks] and birth weight [1,312 (483) vs. 1,469 (588) g] were not different. Median (IQR) COMFORTneo was not different between the groups before [11 (9-15) vs. 10 (8-12)] and after MIST [10 (8-12) vs. 9 (8-10)], but lower in the sedated group during MIST [12 (9-17) vs. 20 (15-23)] with more often COMFORTneo <14 (56 vs. 11%). Duration of MIST [2 (2-4) vs. 3 (2-7) min] and occurrence of bradycardia (13 vs. 33%) and hypotension (21 vs. 18%) were not different. Although not significant, intubation occurred more often in the sedated group (during MIST: 9 vs. 0%, <24 h after MIST: 26 vs. 13%). During MIST, oxygen saturation <80% lasted longer in the sedated group [3 (2-4) vs. 1 (0-2) min], and nasal intermittent positive pressure ventilation was applied more (100 vs. 33%).

Conclusions: Preterm infants receiving MIST were more comfortable when sedation was given, but needed ventilation more often. A randomized controlled trial is warranted to test whether the benefit of sedation outweighs the risks of complications.
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http://dx.doi.org/10.1159/000443823DOI Listing
November 2017

The effects of nurse prescribing: a systematic review.

Int J Nurs Stud 2014 Jul 16;51(7):1048-61. Epub 2013 Dec 16.

NIVEL, Netherlands Institute for Health Services Research, Utrecht, The Netherlands. Electronic address:

Background: In 2008, we conducted a systematic review on the effects of nurse prescribing using studies with a comparative design. In view of the growing number of countries that are introducing nurse prescribing and the fact that several studies into nurse prescribing have been conducted recently, there is a need for an updated review to reassess the available information on the effects of nurse prescribing when compared to physician prescribing.

Objective: To identify, appraise and synthesise the evidence on the effects of nurse prescribing when compared to physician prescribing on the quantity and types of medication prescribed and on patient outcomes.

Design: A systematic review.

Data Sources: In addition to the previous review, which covered the literature up to 2005, 11 literature databases and four websites were searched for relevant studies from January 2006 up to January 2012 without limitations as to language or country. Moreover, full-text copies of all studies included in the previous review were reviewed.

Review Methods: A three-stage inclusion process, consisting of an initial sifting, checking full-text papers for inclusion criteria and methodological assessment, was performed independently by two reviewers. Data on effects were synthesised using narrative and tabular methods.

Results: Thirty-five studies met the inclusion criteria. All but five studies had a high risk of bias. Nurses prescribe in comparable ways to physicians. They prescribe for equal numbers of patients and prescribe comparable types and doses of medicines. Studies comparing the total amount of medication prescribed by nurses and doctors show mixed results. There appear to be few differences between nurses and physicians in patient health outcomes: clinical parameters were the same or better for treatment by nurses, perceived quality of care was similar or better and patients treated by nurses were just as satisfied or more satisfied.

Conclusions: The effects of nurse prescribing on medication and patient outcomes seem positive when compared to physician prescribing. However, conclusions must remain tentative due to methodological weaknesses in this body of research. More randomised controlled designs in the field of nurse prescribing are required for definitive conclusions about the effects of nurse prescribing.
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http://dx.doi.org/10.1016/j.ijnurstu.2013.12.003DOI Listing
July 2014
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