Anie Lapointe

Background: Postnatal corticosteroids (CS) improve respiratory outcomes in preterm infants, but effects on growth and neurodevelopment remain incompletely understood. Methods: This third instalment of a narrative review series builds on physiologic principles to examine systemic CS consequences. Main Findings: We explore the interplay between growth restriction, hypoxia, and neurodevelopmental vulnerability, discussing brain imaging, metabolic disruptions, and HPA axis suppression. Conclusion: This review advocates for a holistic, physiology-informed approach to optimize outcomes by integrating nutritional vulnerability with cardiorespiratory status.

Postnatal corticosteroids are frequently administered to extremely preterm infants to support respiratory management, yet their effects on the immature cardiovascular system are complex and underexplored. As the second installment in a series on physiology-informed steroid use, this narrative review focuses on the cardiovascular consequences of systemic corticosteroid therapy in preterm neonates. We examine how corticosteroids influence key aspects of cardiovascular physiology, including ductal closure, systemic and pulmonary vascular resistance, myocardial remodeling, and autonomic regulation. Attention is given to the hemodynamic transition of early postnatal life and how steroid exposure may interact with patency of the ductus arteriosus and vascular development. The potential for corticosteroids to contribute to reactive myocardial hypertrophy, systemic hypertension, and pulmonary hypertension is also reviewed in the context of both short- and long-term outcomes. Emerging diagnostic and monitoring tools are discussed for their potential to guide individualized therapy. These include targeted neonatal echocardiography (TnECHO) to assess cardiac function and structure, electrocardiography (ECG) for rhythm and conduction abnormalities, heart rate variability analysis for autonomic function, and circulating biomarkers to evaluate myocardial stress and inflammation. Together, these tools may inform tailored steroid timing and dosing, especially in the research context, while monitoring for signs of cardiovascular side effects in real time. By synthesizing mechanistic insights with evolving clinical evidence, this review highlights the need for a more nuanced understanding of how corticosteroids affect the developing cardiovascular system. It underscores the importance of integrating cardiovascular monitoring into routine care to optimize therapeutic benefit while minimizing unintended harm. Alongside companion reviews addressing respiratory and growth impacts, this installment contributes to a broader framework for individualized, physiology-driven steroid use in extremely preterm infants.

Extremely preterm infants often require prolonged respiratory support due to lung immaturity and inflammation, placing them at high risk of lung injury and development of bronchopulmonary dysplasia (BPD). In many of these infants, systemic postnatal corticosteroids are used to reduce lung inflammation, facilitate mechanical ventilation (MV) weaning and extubation, and improve short-term pulmonary outcomes. However, despite decades of clinical use, substantial variation persists in timing, choice of agent and dosing. These inconsistencies reflect a lack of strong evidence and a limited understanding of the systemic and organ-specific effects of therapy for a highly heterogenous population usually exposed to this medication. This narrative review addresses these gaps by integrating current knowledge of the inflammatory and respiratory effects of postnatal corticosteroids in extremely preterm infants. We explore how corticosteroids modulate pulmonary inflammation, their effects on lung development, and how they affect key clinical outcomes such as extubation success and BPD severity. We also examine evolving approaches to corticosteroid administration and dosing, highlighting the importance of individualized strategies informed by developmental and disease-specific considerations. Comparative data from randomized controlled trials are reviewed, including the efficacy and side-effect profiles of commonly used regimens. Current evidence supports judicious use of late low-dose dexamethasone, while early prophylaxis with inhaled or intratracheal steroids remains experimental and is not routinely advised. In line with a physiology-driven approach, we also discuss emerging domain-specific monitoring tools that may enhance patient selection and optimize timing of intervention. By synthesizing mechanistic insights with clinical evidence, this review supports a more nuanced, individualized approach to postnatal corticosteroid therapy in extremely preterm infants, balancing therapeutic benefits with potential systemic trade-offs.

The management of patent ductus arteriosus (PDA) in premature infants remains a significant debate in neonatology. Interventions aimed at accelerating ductal closure, often using nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen, are common practice. However, recent evidence increasingly challenges this approach. Pharmacological agents for PDA closure demonstrate limited efficacy and carry significant risks of systemic toxicity, affecting renal, gastrointestinal, vascular, and pulmonary systems. Multiple recent randomized controlled trials (RCTs) and meta-analyses have largely failed to demonstrate that early active treatment improves crucial clinical outcomes such as mortality, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), or necrotizing enterocolitis (NEC). Some studies even suggest potential harm, particularly an increased risk of BPD and mortality in vulnerable extremely preterm infants. Procedural closure methods (surgical ligation, transcatheter techniques), while achieving anatomical closure, also pose significant risks and lack evidence of improved clinical outcomes. Given the high rates of spontaneous PDA closure, especially in extremely preterm infants, and the lack of proven benefit alongside potential harm from interventions, a paradigm shift towards expectant or conservative management is gaining support. This approach emphasizes supportive care, minimizing interventions, and may be complemented by the judicious use of postnatal corticosteroids in selected infants with significant lung disease, which might indirectly facilitate ductal closure by addressing underlying inflammation.

Chronic pulmonary hypertension (cPH) associated with bronchopulmonary dysplasia (BPD) is a major contributor to morbidity and mortality in extremely preterm infants. Despite improvements in neonatal care, the burden of BPD and its pulmonary vascular complications remains significant. Early detection and standardized management of cPH are essential to improve outcomes. Echocardiography plays a central role in screening and guiding treatment, particularly in high-risk infants requiring respiratory support at or beyond 36 weeks postmenstrual age. The Targeted Neonatal Echocardiography—Quebec (TnECHO-Qc) collaborative has developed a province-wide screening and management algorithm for cPH in preterm infants with BPD. This initiative outlines a stepwise approach to echocardiographic evaluation, including specific criteria for identifying elevated pulmonary arterial pressures, grading severity, and scheduling follow-up based on clinical and imaging findings. Additional management elements encompass biomarker use, respiratory and nutritional optimization, and consideration of airway anomalies, reflux, and aspiration. Pharmacologic therapies, including inhaled nitric oxide and pulmonary vasodilators, are considered for moderate to severe cPH with a pre-capillary component (“pulmonary arterial hypertension”) after stabilization of ventilation and oxygenation, and guided by echocardiography follow-up. This collaborative initiative establishes a standardized, multidisciplinary framework to enable timely recognition and individualized management of chronic pulmonary hypertension (cPH) in preterm infants. The primary goal is to reduce adverse outcomes and support long-term health, with the effectiveness of the framework to be evaluated through longitudinal outcome assessments.

Objective: To evaluate sildenafil’s effects on cardiac function and hemodynamic stability in neonates with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). Study Design: Two phase Ib trials (SANE-01/02; NCT02812433, NCT04169191) enrolled neonates with MRI-confirmed brain injury receiving sildenafil (n=20) or placebo (n=4) enterally (2.0–3.0 mg/kg q12h × 14 doses). Targeted echocardiography, speckle-tracking, and biomarkers were measured on days 2–10. Results: Sildenafil improved left and right ventricular outputs (p=0.02; p<0.001), decreased pulmonary hypertension markers (p=0.001), and enhanced ventricular strain (p<0.001 for LV; p=0.02 for RV). Inotropic support and lactate levels declined, and cardiac biomarkers improved. Improvements were greatest during TH. Conclusion: Sildenafil was well tolerated and improved cardiovascular function, supporting its potential as an adjunctive therapy in HIE.

Objective To assess the association between day-2 cardiac function and brain injury in neonates with HIE undergoing therapeutic hypothermia. Study design A prospective single-center study (2016–2021) including neonates ≥36 weeks gestation with moderate to severe HIE treated with TH. Brain injuries were evaluated using MRI and a validated scoring system, and logistic regression identified cardiovascular predictors. Results Among 55 neonates, 33 (60%) had brain injuries. Day-2 ventricular dysfunction was found in 16 (29%). Neonates with brain injuries had higher gestational age, more severe aEEG patterns, and higher Sarnat scores. Significant predictors of brain injury included higher gestational age, severe initial aEEG patterns, and increased left ventricular strain. No significant differences were observed in standard echocardiography measurements. Conclusion Severe initial aEEG patterns and increased left ventricular strain, rather than day-2 cardiac dysfunction, were more predictive of brain injury in HIE neonates. Early assessments may further clarify the role of hemodynamics.

Pulmonary hemorrhage (PH) is a life-threatening complication predominantly affecting preterm infants, particularly those with very low birth weight (VLBW) and fetal growth restriction (FGR). Typically occurring within the first 72 h of life, PH is characterized by acute respiratory deterioration and significant morbidity and mortality. This review synthesizes current evidence on the multifactorial pathogenesis of PH, highlighting the roles of immature pulmonary vasculature, surfactant-induced hemodynamic shifts, and left ventricular diastolic dysfunction. Key risk factors include respiratory distress syndrome (RDS), hemodynamically significant patent ductus arteriosus (hsPDA), sepsis, coagulopathies, and genetic predispositions. Diagnostic approaches incorporate clinical signs, chest imaging, lung ultrasound, and echocardiography. Management strategies are multifaceted and include ventilatory support—particularly high-frequency oscillatory ventilation (HFOV)—surfactant re-administration, blood product transfusion, and targeted hemostatic agents. Emerging therapies such as recombinant activated factor VII and antifibrinolytics show promise but require further investigation. Preventive measures like antenatal corticosteroids and early indomethacin prophylaxis may reduce incidence, particularly in high-risk populations. Despite advancements in neonatal care, PH remains a major contributor to neonatal mortality and long-term neurodevelopmental impairment. Future research should focus on individualized risk stratification, early diagnostic tools, and optimized treatment protocols to improve outcomes. Multidisciplinary collaboration and innovation are essential to advancing care for this vulnerable population.

Pulmonary hemorrhage (PH) is a life-threatening complication predominantly affecting preterm infants, particularly those with very low birth weight (VLBW) and fetal growth restriction (FGR). Typically occurring within the first 72 hours of life, PH is characterized by acute respiratory deterioration and significant morbidity and mortality. This review synthesizes current evidence on the multifactorial pathogenesis of PH, highlighting the roles of immature pulmonary vasculature, surfactant-induced hemodynamic shifts, and left ventricular diastolic dysfunction. Key risk factors include respiratory distress syndrome (RDS), hemodynamically significant patent ductus arteriosus (hsPDA), sepsis, coagulopathies, and genetic predispositions. Diagnostic approaches incorporate clinical signs, chest imaging, lung ultrasound, and echocardiography. Management strategies are multifaceted and include ventilatory support—particularly high-frequency oscillatory ventilation (HFOV)—surfactant re-administration, blood product transfusion, and targeted hemostatic agents. Emerging therapies such as recombinant activated factor VII and antifibrinolytics show promise but require further investigation. Preventive measures like antenatal corticosteroids and early indomethacin prophylaxis may reduce incidence, particularly in high-risk populations. Despite advancements in neonatal care, PH remains a major contributor to neonatal mortality and long-term neurodevelopmental impairment. Future research should focus on individualized risk stratification, early diagnostic tools, and optimized treatment protocols to improve outcomes. Multidisciplinary collaboration and innovation are essential to advancing care for this vulnerable population.

Objective Study the association between cardiac biomarkers and echocardiography parameters of ventricular performance in neonates with neonatal encephalopathy (NE). Methods Prospective observational study (2016–2021) of neonates undergoing therapeutic hypothermia (TH). Neonates with brain injury had repeated echocardiography and biomarkers measurements on day of life (DOL) 2, 3, 4, and 10. Pearson correlation and generalized linear mixed effect models were used to account for repeated measurements. Receiver operating characteristic curves were constructed to assess sensitivity/specificity. Results 56 neonates had 128 measurements. Creatine Kinase (CK) and cardiac troponin-I (CTn-I) were associated with right ventricular (RV) function. A CK of 1961 U/L and a CTn-I of 91 ng/L identified low Tricuspid Annular Plane Systolic Excursion (<7 mm) with sensitivities of 93% and 79%, and specificities of 55% and 74%, respectively. Conclusions Elevated CK and CTn-I were associated with decreased RV performance. Trending these markers can be used to suspect altered RV function and may flag optimal timing for evaluation(s) by echocardiography during TH.