Abstract
Late postnatal steroids are given to premature infants who cannot be weaned from ventilation because of the possible development of bronchopulmonary dysplasia (BPD). At that time, some infants still have a patent ductus arteriosus (PDA). In our experience, the use of betamethasone (BTM) seems to reduce the need for surgical/endovascular treatment of PDA. We evaluated herein the impact of oral BTM on PDA in extremely preterm infants with BPD. Extremely preterm infants (GA < 29 weeks) with PDA and treated with BTM to facilitate extubation/avoid reintubation were included in this retrospective, single-centre study. BTM was administered orally at 0.3 mg/kg/day for 3 days, 0.15 mg/kg/day the following 2 days, and 0.05 mg/kg/day on the last day. An echocardiography was performed before and after BTM treatment. The 51 infants included were born at a median [IQR] GA of 25.7 [25.0–26.7] weeks. At the time of BTM treatment (28 [26–30] days), 94.1% (48/51) were on invasive ventilation, and most (44/48, 91.7%) were extubated after BTM treatment. At that time, nearly all infants had a closed or non-haemodynamically significant PDA (50/51, 98.0%). None required surgical or endovascular treatment after BTM. Adverse effects included transient moderate hypertension (68.6%), transient hyperglycaemia (15.7%), and transient slowing of postnatal weight gain during BTM treatment.
Conclusion: In extremely preterm infants with a severe respiratory condition at 3 weeks of life, oral BTM treatment can help wean invasive ventilation and is associated with PDA closure. It could reduce the need for surgical or endovascular treatment that are associated with serious adverse effects.
Trial registration: Clinicaltrials.gov NCT05987202.
| What is Known: |
| • Patent ductus arteriosus and bronchopulmonary dysplasia are two most frequent complications of extreme prematurity. |
| • Betamethasone is one of the corticosteroids used to help wean invasive ventilation in infants at risk for bronchopulmonary dysplasia. |
| What is New: |
| • In extremely preterm infants still ventilated after 3 weeks of life and suffering from patent ductus arteriosus, treatment with oral betamethasone facilitated ventilatory weaning |
| • Oral betamethasone treatment was associated with patent ductus arteriosus closure in almost all infants. |
Keywords: Bronchopulmonary dysplasia, Prematurity, Patent ductus arteriosus, Corticosteroids, Ventilation
Introduction
Patent ductus arteriosus (PDA) affects 20 to 50% of infants born before a gestational age (GA) of 32 weeks and up to 60% before 29 weeks [1]. It is associated with increased mortality and morbidity: prolonged ventilatory support, pulmonary haemorrhage, necrotising enterocolitis (NEC), and intraventricular haemorrhage (IVH) [2]. Medical treatment (non-steroidal inflammatory drugs, paracetamol) results in PDA closure in 67.4% of preterm infants [3]. When medical treatment fails or is contraindicated, surgical or endovascular treatment may be considered. All of these treatments are associated with a risk of severe complications [3].
Bronchopulmonary dysplasia (BPD) affects 26.5% of preterm infants born between 24 and 29 weeks in Europe and 42.6% have severe BPD [4]. It is diagnosed from mild to severe according to ventilatory support and oxygen dependency at 28 days of life and 36 weeks corrected GA [5], but it can begin around 2 to 3 weeks of life and manifest as difficulty weaning the child from invasive ventilation [2, 6, 7]. Treatment with systemic steroids can be used when ventilatory weaning is impossible after the third week of life [6–8]. Steroids are used to facilitate extubation [6] or avoid reintubation due to the severity of BPD [9]. The main product used is dexamethasone (DXM), which reduces the risks of mortality and BPD, but has been associated with increased risk of impaired neurodevelopment.
Steroids could possibly have a direct effect on the PDA leading to closure through interference with prostaglandin synthesis [10] or a reduction sensitivity of the ductal muscle to prostaglandin E2 [11]. It has also been reported that postnatal DXM was associated with PDA closure [12–16]. However, due to long-term side effects of DXM, other products are used for the treatment of BPD, such as hydrocortisone and betamethasone (BTM). Hydrocortisone had no effect on the course of PDA when administered late (after 7 days of life) [17], but was associated with reduced incidence and need for surgical treatment of PDA [18, 19] when administered early. Concerning BTM, it has been reported in foetal rats that BTM induces ductal constriction [20]. Furthermore, infants born from mothers who received BTM antenatally had less frequently PDA than those born from untreated mothers [21, 22], and postnatally, BTM has a vasoconstrictor effect on the PDA [23] and could contribute to PDA closure. In our experience, the use of BTM seems to reduce the need for surgical/endovascular treatment of PDA. We therefore aimed to evaluate the impact of oral BTM on PDA closure in a population of extremely preterm infants at high risk for BPD.
Methods
Study design
Retrospective, single-centre study.
Population
All infants born < 29 weeks GA and hospitalised between 1 January 2018 and 31 December 2022 in the tertiary care unit of the Croix Rousse University Hospital (Lyon, France), were eligible if they met the following inclusion criteria: patent PDA and postnatal steroids treatment for invasive ventilation and/or non-invasive ventilation with prolonged oxygen dependence and/or hypercapnia.
Postnatal steroids
BTM treatment was given to infants with severe respiratory condition at 3 weeks of life (i.e. remaining on invasive ventilation) with the aim to wean them off ventilation, as well as those presenting high capnia (> 9 kPa) and/or FiO2 (> 0.4) under non-invasive ventilatory support with the aim to avoid reintubation. The use of BTM was based on previously published data from our unit, and consisted of 6 days of oral administration: 0.3 mg/kg/day for 3 days, 0.15 mg/kg/day the following 2 days, and 0.05 mg/kg/day on the last day [24]. In accordance with national recommendations, administration was initiated around the 21st day of life [6]. The treatment was indicated in infants with failure to wean invasive ventilation (failure of extubation or deventilation), infants with refractory hypoxia, and infants with non-invasive ventilation (NIV) to avoid re-intubation when there were significant hypercapnia (> 9 kPa) and hypoxia (FiO2 > 0.4).
Treatment of PDA
The first-line treatment of PDA was Ibuprofen. Paracetamol was used when there was a relative contraindication to ibuprofen (clinical bleeding, thrombocytopenia < 50,000 platelets/mm3, liver failure, diuresis < 1 ml/kg/hour over the last 12 h, uncontrolled sepsis, digestive intolerance).
Collected data
Data concerning pregnancy, delivery, infants at birth, and postnatal evolution were collected. BPD was considered as present when ventilatory support or oxygen therapy was needed at 36 weeks of postconceptional age (PCA) and severity was classified according to Jobe et al. [5]. Postnatal steroid treatment with BTM was also collected: duration of the course, number of courses, total cumulative dose.
To evaluate the effect of BTM treatment on respiratory support we collected information about respiratory status at the beginning and 24 h after the end of BTM treatment. For those on invasive ventilatory support BTM treatment was considered effective when they were extubated; for those on non-invasive ventilatory support, we collected capnia and FiO2 at the beginning and 24 h after the end of BTM treatment, and BTM was considered effective when FiO2 was reduced to < 0.3 and capnia was reduced < 8 kPa.
We evaluated adverse effects of BTM: systemic hypertension, hyperglycaemia, poor growth, late-onset sepsis (LOS), and NEC. LOS was considered present when infection was proven [25]. NEC was classified according to the modified Bell’s classification. We collected the interval between the end of BTM treatment and the occurrence of LOS as well as NEC. Systemic hypertension was considered present when mean blood pressure was > the 95th percentile for ≥ 48 h and treated if high blood pressure persisted for more than 96 h [26]. Hyperglycaemia was considered to be present when capillary blood glucose was ≥ 10 mmol/L or ≥ 8 mmol/L in the presence of glycosuria. In such cases, insulin was initiated. In infants already on insulin, this was increased if capillary blood glucose was ≥ 9 mmol/L. Weight gain was calculated the week before, during and the week after BTM treatment using the following equation: W2-W1/ ([W1 + W2]/2)/n), with n corresponding to the number of days between the measurement of body weight at day 1 (W1) and at the end (W2) of the treatment. Z-scores for body weight were calculated with reference to Fenton’s curves at the first and last day of BTM [27]. Delta z-scores for body weight between the beginning and 36 weeks PGA were calculated.
To evaluate the effect of BTM treatment on PDA, we collected data from echocardiography performed before and after BTM treatment, and PDA was classified according to McNamara et al. [28]. It was considered haemodynamically significant when the pulsatile transductal flow was maximum velocity < 2 m/s or continuous and at least one of the following criteria were present: ductal diameter > 1.5 mm, left atrium to aorta ratio > 1.5 (presence of signs of left volume overload), zero or negative diastolic perfusion in the systemic arteries (negative or zero diastole, resistivity index > 0.8) [28]. It was considered that BTM had a positive impact on the PDA when it was closed or hemodynamically insignificant after BTM treatment.
Statistical analysis
Results were expressed as numbers (percentage) for discrete variables and medians [interquartile range, IQR] for continuous variables. The Chi-squared test was used to compare qualitative variables, and the Wilcoxon test to compare quantitative variables. Statistical analyses were performed using the R Studio program version 4.2.1 (Inc., Boston, MA, US). P < 0.05 was considered statistically significant.
Ethics
The study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Institutional review board (Comité scientifique et éthique des Hospices Civils de Lyon, IRB: 00013204: n°23_178), the national data protection commission (CNIL) (n°23_5178) and registered on ClinicalTrials.gov (NCT05987202).
Results
Among the 467 extremely preterm infants admitted between January 2018 and December 2022, 25.7% (120/467) received BTM. Of these, 42.5% (51/120) presented with PDA and were included (Fig. 1); the PDA was hemodynamically significant in most infants (80.4%, 41/51).
Fig. 1.
Flow chart. BTM, betamethasone; PDA, patent ductus arteriosus
At birth, the median [IQR] GA was 25.7 [25.0–26.7] weeks and birth weight was 720 [640–798] g. Before BTM treatment administration, most infants received ibuprofen and/or paracetamol (88.2%, n = 45; of whom 14 [31.1%] received both ibuprofen and paracetamol). 17/51 received a single course of ibuprofen, 28/51 received two courses of ibuprofen, and 14/51 received a course of paracetamol, given the relative contraindications to ibuprofen.
Postnatal growth failure occurred in 22.0% (n = 11) of infants (Table 1).
Table 1.
Clinical characteristics of the 51 premature infants with bronchopulmonary dysplasia and patent ductus arteriosus treated with oral betamethasone
| Total population, N = 51 | |
|---|---|
| At birth | |
| Antenatal steroids (full course) | 38 (74.5) |
| Caesarean section | 33 (64.7) |
| Gestational age, weeks | 25.7 [25.0–26.7] |
| Birth weight, g | 720 [640–798] |
| Birth weight < 10th percentile | 9 (17.6) |
| Male sex | 25 (49.0) |
| Between birth and postnatal betamethasone treatment | |
| Invasive ventilation, days | 30.3 [25.0–35.7] |
| Conventional ventilation, days | 7.8 [4.7–10.5] |
| High-frequency oscillation, days | 22.8 [15.7–26.8] |
| Ibuprofen and/or paracetamol | 45 (88.2) |
| Ibuprofen (first course) | 17 (33.3) |
| Ibuprofen (second course) | 28 (54.9) |
| Paracetamol | 14 (27.4) |
| Diuretics | 39 (76.4) |
| At 36 weeks postconceptional age | |
| Body weight, g | 2328 [2080–2430] |
| Postnatal growth failure a | 11 (22.0) |
Data expressed as number (percentage) or median [interquartile range]
a Body weight < -1.28 SD (equivalent to 10th percentile) according to Fenton reference curves. One missing data
Immediately before BTM treatment, 94.1% (n = 48) of infants were on invasive ventilation. BTM was administered at a median 28 [26–30] days of life, and the median duration of treatment was 6 [6–9] days. At 24 h after completing BTM treatment, 91.7% (44/48) of infants were weaned from invasive ventilation. Among other infants, who remained on invasive ventilation (8.3%, 4/48; Table 2), one received a second course of BTM. All 3 infants on non-invasive ventilation at the beginning of BTM treatment, reduced their oxygen dependence and capnia (Table 2).
Table 2.
Postnatal course of premature infants with bronchopulmonary dysplasia and patent ductus arteriosus treated with oral betamethasone
| Total population, N = 51 | |
|---|---|
| Before betamethasone treatment | |
| Ventilatory support immediately before treatment | |
| Invasive ventilation | 48 (94.1) |
| Non-invasive ventilation | 3 (5.9) |
| Weight gain during 7 days before treatment, g/kg/day | 17.1 [11.3–22.7] |
| Betamethasone treatment | |
| Postnatal age, days | 28 [26–30] |
| Corrected gestational age, weeks | 29.8 [26.7–30.8] |
| Duration of betamethasone treatment, days | 6 [6–9] |
| Total cumulative dose of betamethasone (mg/kg) a | 1.38 [1.25–2.4] |
| Second or subsequent betamethasone treatment | 9 (17.6) |
| During betamethasone treatment | |
| Systemic hypertension during betamethasone treatment | 35 (68.6) |
| Hyperglycaemia requiring treatment | 8 (15.7) |
| Insulin treatment initiated | 5 (9.8) |
| Increase of pre-existing insulin | 3 (5.9) |
| Glycosuria | 6 (11.8) |
| Weight gain during betamethasone treatment, g/kg/day | 5.9 [-4.1–9.5] |
| After betamethasone treatment | |
| Respiratory status 24 h after BTM treatment | |
| In 48 infants on invasive ventilation at the time of BTM | |
| Weaned from invasive ventilation | 44 (91.7) |
| Still on invasive ventilation | 4 (8.3) |
| In 3 infants on non-invasive ventilation at the time of BTM | |
| Reduced FiO2 and capnia | 3 (100) |
| Secondary reopening of ductus arteriosus | 1 (2.0) |
| Ligature of PDA | 0 (0) |
| Late-onset sepsis | 5 (9.8) |
| Necrotising enterocolitis grade ≥ 2 | 5 (9.8) |
| Weight gain during 7 days after treatment, g/kg/day | 21.2 [17.7–27.3] |
| ΔZ-score for body weight between birth and 36 weeks, SD b | -0.58 [-0.96 – -0.16] |
Data expressed as number (percentage) or median [interquartile range]
a One missing data; b Three missing data
At the end of the first course of BTM, 98.0% (n = 50) of infants had a closed or a non-haemodynamically significant ductus arteriosus (Table 3). The percent reduction of PDA diameter between the start and the end of BTM treatment was significantly higher in infants with GA < 26 weeks at birth (100% [73.5–100]) than in infants born ≥ 26 weeks (47.7% [39.9–86.2], p = 0.015; Fig. 2A). The median total cumulative dose of BTM was not significantly different between infants whose PDA was closed (1.37 [1.26–2.43] mg/kg), those whose PDA became non-hemodynamically significant (1.36 mg/kg [1.25–1.57]), and in the 2 infants who experienced no change in their PDA (3.89 mg/kg [2.50–5.29], p = 0.147; Fig. 2B). PDA ligation was not necessary for any infant.
Table 3.
Patent ductus arteriosus status before and after betamethasone treatment in 51 preterm infants
| Before | After | ||||
|---|---|---|---|---|---|
| HS | NHS | CLOSED | NHS or CLOSED | ||
| HS | 41 | 1 | 19 | 21 | 40 |
| NHS | 10 | 0 | 1 | 9 | 10 |
| Total | 51 | 1 | 20 | 30 | 50 |
HS Haemodynamically significant
NHS Non-haemodynamically significant
Fig. 2.
Effect of betamethasone treatment in the 51 extremely premature infants. a. Reduction of the diameter of patent ductus arteriosus (PDA) in infants born < 26 or ≥ 26 weeks; significant difference between groups (p = 0.015). b. Evolution of PDA (closure, evolution from hemodynamically significant to non-hemodynamically significant, or absence of modification). Comparison based on total cumulative dose of betamethasone (in mg/kg). No significant difference between groups (p = 0.147). Data are presented as boxplots (median, interquartile range, and extreme values are shown)
Two-thirds (68.6%, n = 35) of infants had high blood pressure during BTM treatment, but none required anti-hypertensive treatment; 15.7% (n = 8) of infants experienced hyperglycaemia, requiring the initiation or increase of insulin treatment during oral BTM treatment. There were 5 (9.8%) infants who experienced LOS after BTM treatment, for 3 of whom this occurred > 2 weeks after BTM treatment; 5 infants experienced NEC (9.8%), for 2 of whom this occurred postoperatively following inguinal hernia repair. The median weight gain during BTM treatment was 5.9 [-4.1–9.5] g/kg/day; during the week before treatment this was 17.1 g/kg/day, during the week before treatment this was 21.2 g/kg/day. At 36 weeks corrected GA, 22% of infants had a body weight below the 10th percentile. The difference in Z-score for weight between birth and 36 weeks of corrected GA was -0.58 [-0.96– -0.16] (Table 2).
Discussion
In a population of extremely premature infants with PDA and treated with oral BTM to facilitate ventilatory weaning, this, as well as the closure of the PDA, was attained in almost all of the infants just after BTM treatment.
We observed that late BTM treatment had an impact on PDA course which has not been systematically reported in previous studies using late DXM or hydrocortisone. For instance, two retrospective studies in very small number of infants reported PDA closure after the late administration of high-dose intravenous DXM [12, 13]. However, in a randomized controlled study (DART trial) that included 70 infants there was no effect of late, low-dose, DXM on the frequency of PDA (34.3% vs. 42.9% in the placebo group, p = 0.46) [9]. Concerning hydrocortisone, in a large multicentre randomized trial that included 371 infants there was no significant effect of late, high-dose, hydrocortisone on the frequency of PDA (39.8% vs. 41.1%, p = 0.62) [17]. It is of note that this absence of effect of late postnatal steroid treatment is contrary to that reported for early treatment, as the frequency of PDA lower with DXM than placebo (10.6% vs.26.2%, p < 0.01 [14], 23% vs. 59%, p = 0.05 [15]), or hydrocortisone (36% vs. 73%, p = 0.01 [18]) even when this drug was used at a low dose in the PREMILOC study (PDA ligation: 15% vs. 21%, p = 0.03 [19]). The impact of late BTM treatment on PDA course observed in the present study could be due to differences in the product used or differences in the cumulative dose. Herein, the cumulative BTM dose was higher (1.38 mg/kg) than the BTM equivalent cumulative dose of DXM in the DART trial (DXM: 0.89 mg/kg, i.e. 0.89 mg/kg BTM equivalent) [9]. However, it was lower than the BTM equivalent hydrocortisone cumulative dose used in the randomized trial that evaluated hydrocortisone (72.5 mg/kg, i.e. 2.7 mg/kg BTM equivalent) [17], suggesting that the effect is unlikely to be related to the dose of steroids used. Concerning the effect of the product used, there is, to our knowledge, no published study has compared DXM, hydrocortisone and BTM to one another with regards to the effect on closing PDA. However, the effectiveness of BTM reported herein could be related to its contractile effect on the ductus arteriosus that has been reported in utero [29], as well as in vitro [22].
Other than the effect on PDA the present study, late oral BTM treatment administered during a short period, at low doses, helped to wean from invasive ventilation, reduce oxygen needs and hypercapnia in extremely preterm infants. Nearly all infants (91.7%) with invasive ventilatory support at the beginning of BTM treatment were weaned from ventilation 24 h after completing BTM treatment. This is a higher frequency of extubation than in randomized trials using DXM (60.0% 10 days after the beginning of DXM) [9] or hydrocortisone (66.3% 14 days after the beginning of hydrocortisone) [17]. Reduction of lung inflammation could improve respiratory function favouring closure of PDA, but data supporting this hypothesis are lacking, and it could be that the closure of the PDA is responsible for the improvement of the respiratory state.
In the present study there were few complications related to the administration of oral BTM. Transient systemic hypertension was present in a little over two-thirds of infants during the BTM treatment, but was moderate, not requiring initiation of anti-hypertensive treatment. Only one in ten infants developed hyperglycaemia treated by insulin treatment during the BTM course, which is close to that we reported in a previous study that included very premature infants treated by BTM (11%) [24]. Another important point is that postnatal DXM treatment is associated with impaired postnatal growth [30]. Herein, the weight gain (5.9 g/kg/day) treatment with BTM is lower than foetal growth (around 15 g/kg/day) [27], which could be explained by protein hypercatabolism induced by glucocorticoids. Nevertheless, the weight gain returned to a normal value quickly after the treatment and the difference in weight Z-score between birth and 36 weeks of corrected GA was low (-0.58 standard deviations, SD), corresponding to the expected value (maximum loss of -0.8 to -1 SD) [31]. Furthermore, the long-term effects of BTM on the neurodevelopment of premature infants was not investigated herein, but in a cohort of extremely premature infants treated with BTM we recently observed the absence of adverse effects on neurodevelopment at 2 years [32], although a randomized trial is needed to confirm this.
The results presented herein suggest that, when PDA is still hemodynamically significant in extremely preterm infants still requiring ventilatory support around 3 weeks of life, it could be beneficial to treat such patients with oral BTM before considering treatment with surgery or endovascular route, which are both associated with severe complications [3].
The present study has, however, certain limitations. Notably, its single-centre nature limited the number of eligible infants. Furthermore, the external validity of the results could be limited as they may not be reproducible with a different corticosteroid therapy protocol or a different management of invasive and non-invasive ventilation than that practiced in our neonatal unit. However, the observation of short-term hemodynamic and respiratory benefits, without major short-term adverse effects, suggest that it could be possible to evaluate oral BTM in the context of prospective studies in larger populations, with long-term follow-up. Another limitation could be the heterogeneity of our population as about 20% presented a non HSPDA. They were included as our main criteria for steroid treatment was developing bronchopulmonary dysplasia, preventing from progressing towards weaning from invasive ventilation or leading to reintubation. We did not exclude them as we hypothesized that, although PDA was non haemodunamiclly significant from an echocardiographic point of view, could represent an additional factor with a particular impact in this specific context.
In conclusion, the use of oral BTM in extremely premature infants with dependence on ventilatory support after 3 weeks of life can help wean invasive ventilation and is associated with PDA closure. Further large multicentre randomized studies could help to optimise the use of postnatal corticosteroid therapy and reduce the use of surgical or endovascular treatment which are associated with serious adverse effects.
Acknowledgements
The authors would like to thank Philip Robinson (Language editing service, Hospices Civils de Lyon) for help in manuscript preparation, as well as Fanny Joubert (Clinical Research Centre of Croix Rousse university hospital) for her administrative support.
Abbreviations
- BPD
Bronchopulmonary Dysplasia
- BTM
Betamethasone
- D
Day
- DXM
Dexamethasone
- FiO2
Fraction of inspired oxygen
- GA
Gestational Age
- IVH
Intraventricular Haemorrhage
- kPa
Kilo Pascal
- LOS
Late-Onset Sepsis
- NEC
Necrotising Enterocolitis
- NIV
Non-Invasive Ventilation
- PCA
Postconceptional Age
- PaCO2
Arterial carbon dioxide tension
- PDA
Patent Ductus Arteriosus
- SD
Standard Deviation
Authors’ Contributions
All authors contributed to the study conception and design, material preparation, data collection and analysis. The first draft of the manuscript was written by AR and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding
Open access funding provided by Hospices Civils de Lyon. The authors declare that no funds, grants, or other financial support were received.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Competing Interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Park J et al (2021) Patent ductus arteriosus treatment trends and associated morbidities in neonates. Sci Rep 11(1):10689. 10.1038/s41598-021-89868-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Benitz WE et al (2016) Patent ductus arteriosus in preterm infants. Pediatrics 137(1):e20153730. 10.1542/peds.2015-3730 [DOI] [PubMed] [Google Scholar]
- 3.Mitra S et al (2018) Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. JAMA 319(12):1221. 10.1001/jama.2018.1896 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Nuytten A et al (2020) Postnatal corticosteroids policy for very preterm infants and bronchopulmonary dysplasia. Neonatology 117(3):308–315. 10.1159/000507195 [DOI] [PubMed] [Google Scholar]
- 5.Jobe AH, Bancalari E (2001) Bronchopulmonary dysplasia. Am J Respir Crit Care Med 163(7):1723–1729. 10.1164/ajrccm.163.7.2011060 [DOI] [PubMed] [Google Scholar]
- 6.Jarreau P-H et al (2010) Utilisation de la corticothérapie postnatale chez le nouveau-né prématuré dans la prévention et le traitement de la dysplasie bronchopulmonaire: état des lieux et conduite à tenir. Arch Pédiatrie 17(10):1480–1487. 10.1016/j.arcped.2010.07.013 [DOI] [PubMed] [Google Scholar]
- 7.Cummings JJ, Pramanik AK, Committee on Fetus and Newborn (2022) Postnatal corticosteroids to prevent or treat chronic lung disease following preterm birth. Pediatrics 149(6):e2022057530. 10.1542/peds.2022-057530 [DOI] [PubMed] [Google Scholar]
- 8.Doyle LW, Cheong JL, Hay S, Manley BJ, Halliday HL (2021) Late (≥ 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev, 2021(11), 10.1002/14651858.CD001145.pub5. [DOI] [PMC free article] [PubMed]
- 9.Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB, and the DART Study Investigators (2006) Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized. Controlled Trial Pediatr 117(1):75–83. 10.1542/peds.2004-2843 [DOI] [PubMed] [Google Scholar]
- 10.Flower RJ, Blackwell GJ (1979) Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature 278(5703):456–459. 10.1038/278456a0 [DOI] [PubMed] [Google Scholar]
- 11.Clyman RI, Mauray F, Roman C, Rudolph AM, Heymann MA (1981) Glucocorticoids alter the sensitivity of the lamb ductus arteriosus to prostaglandin E2. J Pediatr 98(1):126–128. 10.1016/S0022-3476(81)80558-6 [DOI] [PubMed] [Google Scholar]
- 12.Heyman E, Ohlsson A, Shennan AT, Heilbut M, Coceani F (1990) Closure of patent ductus arteriosus after treatment with dexamethasone. Acta Paediatr 79(6–7):698–700. 10.1111/j.1651-2227.1990.tb11538.x [DOI] [PubMed] [Google Scholar]
- 13.Evans N (1994) Cardiovascular effects of dexamethasone in the preterm infant. Arch Dis Child Fetal Neonatal Ed 70(1):F25–F30. 10.1136/fn.70.1.F25 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Yeh TF et al (1997) Early postnatal dexamethasone therapy for the prevention of chronic lung disease in preterm infants with respiratory distress syndrome: a multicenter clinical trial. Pediatrics 100(4):e3. 10.1542/peds.100.4.e3 [DOI] [PubMed] [Google Scholar]
- 15.Morales P et al (1998) Effect of dexamethasone therapy on the neonatal ductus arteriosus. Pediatr Cardiol 19(3):225–229. 10.1007/s002469900290 [DOI] [PubMed] [Google Scholar]
- 16.Sehgal A, Nold MF, Roberts CT, Menahem S (2022) Cardiorespiratory adaptation to low-dose dexamethasone for lung disease in extremely preterm infants: a prospective echocardiographic study. J Physiol 600(19):4361–4373. 10.1113/JP282973 [DOI] [PubMed] [Google Scholar]
- 17.Onland W et al (2019) Effect of hydrocortisone therapy initiated 7 to 14 days after birth on mortality or bronchopulmonary dysplasia among very preterm infants receiving mechanical ventilation: a randomized clinical trial. JAMA 321(4):354. 10.1001/jama.2018.21443 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Peltoniemi O et al (2005) Pretreatment cortisol values may predict responses to hydrocortisone administration for the prevention of bronchopulmonary dysplasia in high-risk infants. J Pediatr 146(5):632–637. 10.1016/j.jpeds.2004.12.040 [DOI] [PubMed] [Google Scholar]
- 19.Baud O et al (2016) Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet 387(10030):1827–1836. 10.1016/S0140-6736(16)00202-6 [DOI] [PubMed] [Google Scholar]
- 20.Momma K, Takao A (1989) Increased constriction of the ductus arteriosus with combined administration of indomethacin and betamethasone in fetal rats. Pediatr Res 25(1):69–75. 10.1203/00006450-198901000-00016 [DOI] [PubMed] [Google Scholar]
- 21.Clyman RI et al (1981) Prenatal administration of betamethasone for prevention of patent ductus arteriosus. J Pediatr 98(1):123–126. 10.1016/S0022-3476(81)80557-4 [DOI] [PubMed] [Google Scholar]
- 22.Shelton EL et al (2018) Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data. Pediatr Res 84(3):458–465. 10.1038/s41390-018-0006-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Cambonie G, Mesnage R, Milési C, Pidoux O, Veyrac C, Picaud J-C (2008) Betamethasone impairs cerebral blood flow velocities in very premature infants with severe chronic lung disease. J Pediatr 152(1):270–275. 10.1016/j.jpeds.2007.07.007 [DOI] [PubMed] [Google Scholar]
- 24.Ben Said M, Hays S, Loys C, Coletto L, Godbert I, Picaud J (2013) Postnatal steroids in extremely low birth weight infants: betamethasone or hydrocortisone? Acta Paediatr 102(7):689–694. 10.1111/apa.12255 [DOI] [PubMed] [Google Scholar]
- 25.Leistner R, Piening B, Gastmeier P, Geffers C, Schwab F (2013) Nosocomial infections in very low birthweight infants in Germany: current data from the National Surveillance System NEO-KISS. Klin Pädiatr 225(2):75–80. 10.1055/s-0033-1334886 [DOI] [PubMed] [Google Scholar]
- 26.Alonzo CJ, Nagraj VP, Zschaebitz JV, Lake DE, Moorman JR, Spaeder MC (2020) Blood pressure ranges via non-invasive and invasive monitoring techniques in premature neonates using high resolution physiologic data. J Neonatal-Perinat Med 13(3):351–358. 10.3233/NPM-190260 [DOI] [PubMed] [Google Scholar]
- 27.Fenton TR, Anderson D, Groh-Wargo S, Hoyos A, Ehrenkranz RA, Senterre T (2018) An attempt to standardize the calculation of growth velocity of preterm infants—evaluation of practical bedside methods. J Pediatr 196:77–83. 10.1016/j.jpeds.2017.10.005 [DOI] [PubMed] [Google Scholar]
- 28.McNamara PJ, Sehgal A (2007) Towards rational management of the patent ductus arteriosus: the need for disease staging. Arch Dis Child Fetal Neonatal Ed 92(6):F424–F427. 10.1136/adc.2007.118117 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Wasserstrum N, Huhta JC, Mari G, Sharif DS, Willis R, Neal NK (1989) Betamethasone and the human fetal ductus arteriosus. Obstet Gynecol 74(6):897–900 [PubMed] [Google Scholar]
- 30.Buchiboyina AK et al (2021) Effect of cumulative dexamethasone dose in preterm infants on neurodevelopmental and growth outcomes: a Western Australia experience. Arch Dis Child Fetal Neonatal Ed 106(1):69–75. 10.1136/archdischild-2020-319147 [DOI] [PubMed] [Google Scholar]
- 31.Picaud J-C, Vincent M, Buffin R (2021) Human milk fortification for preterm infants: a review. Nutl Care Preterm Infants 122:225–47. 10.1159/000514744 [DOI] [PubMed] [Google Scholar]
- 32.Melan N, Pradat P, Godbert I, Pastor-Diez B, Basson E, Picaud J-C (2023) Neurodevelopment at 24 months corrected age in extremely preterm infants treated with dexamethasone alternatives during the late postnatal period: a cohort study. Eur J Pediatr 183(2):677–687. 10.1007/s00431-023-05319-z [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
No datasets were generated or analysed during the current study.