Time of day is a critical factor for most biological functions, but concepts from the field of chronobiology have yet to be fully translated to clinical practice. Circadian rhythms, generated ...internally and synchronised to the external environment, promote function and support survival in almost every living species. Fetal circadian rhythms can be observed in utero from 30weeks gestation, coupled to the maternal rhythm, but synchronise to the external environment only after birth. Important cues for synchronisation include the light/dark cycle, the timing of feeding, and exposure to melatonin in breast milk. Disruption to these cues may occur during admission to the neonatal intensive care unit. This can impair the development of circadian rhythms, and influence survival and function in the neonatal period, with a potential to impact health and well-being throughout adult life. Here we outline the rationale and evidence to support a chronobiological approach to neonatal care.
Bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants and often complicated by pulmonary hypertension (PH), leading to substantial morbidity and mortality. Sildenafil is ...often used to treat PH and improve symptoms in this condition, even though evidence of safety and effectiveness is scarce. The aim of this study was to perform a systematic review and meta-analysis about the effectiveness and safety of chronic use of sildenafil in preterm infants with BPD-associated PH. Data sources were PubMed, EMBASE, and Medline. Studies reporting the effectiveness of sildenafil therapy in BPD-associated PH in newborns and infants were included. All-cause mortality, improvement in PH, improvement in respiratory scores, and adverse events were extracted. Five studies were included, yielding a total of 101 patients with 94.2 patient-years of total follow-up. The pooled mortality rate was 29.7%/year (95% confidence interval CI = 6.8–52.7). Estimated pulmonary arterial pressure improved > 20% in 69.3% (95% CI = 56.8–81.8) of patients within 1–6 months. Respiratory scores improved in 15.0% (95% CI = 0.0–30.4) of patients within 2–7 days. There were no serious adverse events during sildenafil therapy. This systematic review shows that in the treatment of BPD-associated PH in preterm infants, sildenafil may be associated with improvement in PAP and respiratory scores. However, there is no clear evidence of its effect on mortality rates. Considering BPD as a complex disease with variable expression patterns, these results support the need for a prospective registry and standardized approach.
We present a case of a 38+1 weeks pregnant patient (G1P0) with a proven COVID-19 infection, who was planned for induction of labour because of pre-existent hypertension, systemic lupus erythematosus, ...respiratory problem of coughing and mild dyspnoea without fever during the COVID-19 pandemic in March 2020. To estimate the risk of vertical transmission of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) during labour and delivery, we collected oropharyngeal, vaginal, urinary, placental and neonatal PCRs for SARS-CoV-2 during the period of admission. All PCRs, except for the oropharyngeal, were negative and vertical transmission was not observed. Labour and delivery were uncomplicated and the patient and neonate were discharged the next day. We give a short overview of the known literature about SARS-CoV-2-related infection during pregnancy, delivery and outcome of the neonate.
Sedation to preterm neonates receiving less invasive surfactant administration (LISA) for respiratory distress syndrome is controversial.
Systematic review and meta-analysis of randomized controlled ...trials (RCTs) and observational studies (OS) to evaluate the effect of sedative drugs for LISA on respiratory outcomes and adverse effects.
One RCT (78 neonates) and two OS (519 neonates) were analyzed in pairwise meta-analysis and 30 studies (2164 neonates) in proportion-based meta-analysis. Sedative drugs might not affect the duration of the procedure RCT: mean difference (MD) (95% CI); -11 (-90; 67) s; OS: MD 95% CI: -60 (-178; 58) s; low certainty of evidence (CoE). Evidence for success at the first attempt and rescue intubation was uncertain (very low CoE). The risk of nasal intermittent positive pressure ventilation RCT: 1.97 (1.38-2.81); OS: RR, 95% CI: 2.96 (1.46; 6.00), low CoE, desaturation RCT: RR, 95% CI: 1.30 (1.03; 1.65), low CoE, and apnea OS: RR, 95% CI: 3.13 (1.35; 7.24), very low CoE might be increased with sedation. Bradycardia, hypotension, and mechanical ventilation were comparable between groups (low CoE).
Use of sedative drugs for LISA temporarily affects the newborn's breathing. Further trials are warranted to explore the use of sedation for LISA.
The effect of sedative drugs (analgesics, sedatives, anesthetics) compared to the effect of no-sedation for LISA in preterm infants with RDS is underexplored. This systematic review and meta-analysis assesses the impact of sedative drugs compared to no-sedation for LISA on short-term pulmonary outcomes and potential adverse events. Sedative drugs for LISA temporarily affect the newborn's breathing (desaturation, apnea) and increase the need for nasal intermittent positive pressure ventilation. For most outcomes, certainty of evidence is low/very low.
Abstract only
Background
Pulmonary vein stenosis (PVS) can occur as a result of a congenital anomaly or as a complication of radiofrequency ablation in treatment of atrial fibrillation. PVS impairs ...outflow to the left atrium, which produces a passive pressure increase in consecutively the pulmonary veins, capillaries and pulmonary arteries, ultimately leading to pulmonary hypertension (PH).
PH, defined as a chronic elevation of pulmonary artery pressure >25 mmHg, is characterized by remodeling of the pulmonary arterioles, that produces a further increase in pulmonary vascular resistance, thereby sustaining a vicious cycle of elevations in pressure, resistance and vascular remodeling. The resultant progressive increase in right ventricular (RV) after load leads to an impaired exercise capacity and eventually results in overt right heart failure and death.
Here we test the hypothesis that vasoconstriction and vascular remodeling in PH is a result of decreased production of the vasodilator and anti‐proliferative factor nitric‐oxide (NO).
Methods
Swine either underwent non‐restrictive banding of the confluent of both inferior pulmonary veins (PVB group n=7), or sham operation (SH group n=6). Four weeks after surgery, all animals were chronically instrumented to longitudinally assess hemodynamics at rest and during exercise for an additional 8 weeks (week 5–12). To determine whether the contribution of endogenous NO‐production in regulation of pulmonary vascular resistance was reduced, the NO‐synthase inhibitor Nω‐nitro‐L‐arginine (NLA) was administered, and hemodynamic responses to exercise were re‐assessed. At sacrifice, the heart was excised to assess RV hypertrophy.
Results
PVB swine developed a gradual elevation of mean pulmonary artery pressure (mPAP) compared to SH group 41±7 vs 19±4 mmHg (p<0.01) and increased total pulmonary vascular resistance index (tPVRi) of 250±62 vs 105±15 mmHg·L
−1
·min·kg (p<0.01). Both PVB and SH groups showed similar increase in pulmonary resistance and pressure after NO‐synthase inhibition with NLA at rest and during exercise, indicating preserved NO‐production in banded swine. Interestingly, NO‐synthase inhibition improved oxygenation in exercising PVB swine, as arterial pO
2
was significantly increased by NLA (
Figure
). Right ventricular hypertrophy was evident from the increased RV/LV ratio of 0.59±0.03 vs 0.44±0.01 g/g, and the RV/Bodyweight ratio of 1.74±0.11 vs 1.29±0.06 g/kg (both p<0.01).
Conclusion
Banded swine gradually developed pulmonary hypertension which eventually resulted in RV hypertrophy. At this stage of the disease, increased pulmonary artery pressure and resistance are not due to NO‐deficiency. Interestingly, the observed improvement of oxygenation upon NO‐synthase inhibition suggests that at this stage, maintaining low RV after load has priority over optimal oxygenation, possibly in an attempt to prevent excessive RV hypertrophy.
Support or Funding Information
CVON2012‐08 (PHAEDRA), Sophia Foundation S13‐12
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