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Dexamethasone is frequently prescribed for preterm infants to wean from respiratory support and/or to facilitate extubation. This pre-post intervention prospective study ascertained the impact on clinical (respiratory support) and echocardiographic parameters after dexamethasone therapy in preterm FGR infants compared to AGA infants. Echocardiography was performed within 24 hours before the start and after completion of 10-day therapy. Parameters assessed included those reflecting pulmonary vascular resistance and right ventricular output. Seventeen FGR infants (birth gestation and birthweight 25.2±1.1 weeks and 497±92g) were compared with 22 AGA infants (gestation and birthweight 24.5±0.8 and 663±100g). Baseline respiratory severity score (mean airway pressure x fractional inspired oxygen) was comparable between the groups, (median [interquartile range] FGR: 10 [6, 13] vs AGA: 8±2.8, P=0.08). Pre-dexamethasone parameters of pulmonary vascular resistance (FGR: 0.19±0.03 vs AGA 0.2±0.03, P=0.16) and right ventricular output (FGR: 171±20 vs 174±17 ml/kg/min, P=0.6) were statistically comparable. At post-dexamethasone assessments, the decrease in respiratory severity score was significantly greater in AGA infants, (median [interquartile range] FGR: 10 [6, 13] to 9 [2.6, 13.5], P=0.009 vs AGA: 8±2.8 to 3±1, P<0.0001). Improvement in measures of pulmonary vascular resistance (time to peak velocity/right ventricular ejection time) was greater in AGA infants (FGR: 0.19±0.03 to 0.2±0.03, P=0.13 vs AGA 0.2±0.03 to 0.25±0.03, P<0.0001). The improvement in right ventricular output was significantly greater in AGA infants (171±20 to 190±21, P=0.014 vs 174±17 to 203±22, P<0.0001). This highlights differential cardiorespiratory responsiveness to dexamethasone in extremely preterm FGR infants, which may reflect the in-utero maladaptive state.
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Chronic lung disease, also known as bronchopulmonary dysplasia, affects thousands of infants worldwide each year. The impact on resources is second only to bronchial asthma, with lung function affected well into adolescence. Diagnostic and therapeutic constructs have almost exclusively focused on pulmonary architecture (alveoli/airways) and pulmonary hypertension. Information on systemic hemodynamics indicates major artery thickness/stiffness, elevated systemic afterload, and/or primary left ventricular dysfunction may play a part in a subset of infants with severe neonatal-pediatric lung disease. Understanding the underlying principles with attendant effectors would aid in identifying the pathophysiological course where systemic afterload reduction with angiotensin-converting enzyme inhibitors could become the preferred treatment strategy over conventional pulmonary artery vasodilatation.NEW & NOTEWORTHY Extremely preterm infants are at a higher risk of developing severe bronchopulmonary dysplasia. In a subset of infants, diuretic and pulmonary vasodilator therapy is ineffective. Recent information points toward systemic hemodynamic disease (systemic arterial stiffness and left ventricular dysfunction) as a contributor via back-pressure changes. Mechanistic links include heightened renin angiotensin aldosterone system activity, inflammation, and oxygen toxicity. Angiotensin-converting enzyme inhibition may be operationally more suited compared with induced pulmonary artery vasodilatation.
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Displasia Broncopulmonar , Hemodinâmica , Humanos , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/metabolismo , Criança , Recém-Nascido , Lactente , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pulmão/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Animais , Sistema Renina-Angiotensina/efeitos dos fármacos , Rigidez Vascular , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/efeitos dos fármacos , Pré-EscolarRESUMO
Placental insufficiency is one of the major causes of fetal growth restriction (FGR), a significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. As well as the acute consequences of being born too small, affected offspring are at increased risk of cardiovascular disease, diabetes and other chronic diseases in later life. The placenta and heart develop concurrently, therefore placental maldevelopment and function in FGR may have profound effect on the growth and differentiation of many organ systems, including the heart. Hence, understanding the key molecular players that are synergistically linked in the development of the placenta and heart is critical. This review highlights the key growth factors, angiogenic molecules and transcription factors that are common causes of defective placental and cardiovascular development.
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Retardo do Crescimento Fetal , Placenta , Humanos , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/fisiopatologia , Gravidez , Feminino , Placenta/metabolismo , Insuficiência Placentária/metabolismo , Insuficiência Placentária/fisiopatologia , Animais , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/embriologia , Sistema Cardiovascular/fisiopatologia , Sistema Cardiovascular/crescimento & desenvolvimento , Peptídeos e Proteínas de Sinalização Intercelular/metabolismoRESUMO
OBJECTIVES: To evaluate whether kangaroo mother care (KMC) in preterm infants on non-invasive respiratory support improves indices of cardiorespiratory wellbeing. STUDY DESIGN: Prospective quasi-experimental observational study. SETTING: Tertiary perinatal neonatal unit. PATIENTS: 50 very preterm infants being managed with nasal continuous positive airway pressure. INTERVENTIONS: Continuous high-resolution preductal pulse-oximetry recordings using Masimo Radical-7 oximeter for 1 hour (incubator care) followed by 1 hour during KMC performed on the same day. MAIN OUTCOME MEASURES: Measures of cardiorespiratory stability (dips in oxygen saturations (SpO2)) of ≥5% less than baseline, % time spent with oxygen saturations <90%, SpO2 variability and heart rate fluctuation and incidence of bradycardias. RESULTS: The gestational age and birth weight of the cohort were 28.4±2.1 weeks and 1137±301 g, respectively. Dips in SpO2 of ≥5% less than baseline were significantly fewer with KMC, median (IQR) 24 (12 to 42) vs 13 (3 to 25), p=0.001. SpO2 variability (Delta 12 s and 2 s), (1.24±0.6 vs 0.9±0.4, p=0.005 and 4.1±1.7 vs 2.8±1.2, p<0.0001) and rapid resaturation and desaturation indices were significantly lower during KMC, compared with incubator care. Percentage time spent in oxygen saturations <90% was less with KMC (7.5% vs 2.7%, p=0.04). Mean heart rate was comparable although fluctuations in heart rate (rise by >8 bpm) were lower with KMC (43±22 vs 33±20, p=0.03). Seven (14%) infants had bradycardias during incubator care and none during KMC, p=0.012. CONCLUSIONS: KMC improves cardiorespiratory stability in ventilated preterm infants. Regular KMC has the potential to improve clinical outcomes in this vulnerable cohort.
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Extremely premature infants are at a higher risk of developing respiratory distress syndrome and circulatory impairments in the first few weeks of life. Administration of normal saline boluses to manage hypotension is a common practice in preterm infants. As a crystalloid, a substantial proportion might leak into the interstitium; most consequently the lungs in the preterm cohorts, putatively affecting ventilation. We downloaded and analyzed ventilator mechanics data in infants managed by conventional mechanical ventilation and administered normal saline bolus for clinical reasons. Data were downloaded for 30 min prebolus, 60 min during the bolus followed by 30 min postbolus. Sixteen infants (mean gestational age 25.2 ± 1 wk and birth weight 620 ± 60 g) were administered 10 mL/kg normal saline over 60 min. The most common clinical indication for saline was hypotension. No significant increase was noted in mean blood pressure after the saline bolus. A significant reduction in pulmonary compliance (mL/cmH2O/kg) was noted (0.43 ± 0.07 vs. 0.38 ± 0.07 vs. 0.33 ± 0.07, P = 0.003, ANOVA). This was accompanied by an elevation in the required peak inspiratory pressure to deliver set volume-guarantee (19 ± 2 vs. 22 ± 2 vs. 22 ± 3 mmHg, P < 0.0001, ANOVA), resulting in a higher respiratory severity score. Normal saline infusion therapy was associated with adverse pulmonary mechanics. Relevant pathophysiologic mechanisms might include translocation of fluid across pulmonary capillaries affected by low vascular tone and heightened permeability in extremes of prematurity, back-pressure effects from raised left atrial volume due to immature left-ventricular myocardium; complemented by the effect of cytokine release from positive pressure ventilation.NEW & NOTEWORTHY Administration of saline boluses is common in premature infants although hypovolemia is an uncommon underlying cause of hypotension. This crystalloid can redistribute into pulmonary interstitial space. In the presence of an immature myocardium and diastolic dysfunction, excess fluid can also be "edemagenic." This study on extremely premature infants (25 wk gestation) noted adverse influence on respiratory physiology after saline infusion. Clinicians need to choose judiciously and reconsider routine use of saline boluses in premature infants.
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Hipotensão , Síndrome do Desconforto Respiratório do Recém-Nascido , Lactente , Recém-Nascido , Humanos , Adulto Jovem , Adulto , Lactente Extremamente Prematuro , Soluções Cristaloides/uso terapêutico , Solução Salina/uso terapêutico , Respiração Artificial , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Mecânica RespiratóriaRESUMO
Hemodynamic changes accompanying the initial breaths at the time of birth are especially important for a smooth transition of fetal to neonatal circulation. Understanding the normal transitional physiology and the clinical impact of adverse adaptation is important for delineating pathology so as to guide physiologically relevant therapies. Disorders such as severe perinatal asphyxia, hemodynamically significant patent ductus arteriosus (and its surgical ligation) and utero-placental insufficiency underlying fetal growth restriction, can adversely affect left ventricular (LV) function. The left ventricle is the predominant chamber involved in systemic perfusion during postnatal life. Cardiac output is closely linked to afterload; the latter is determined by arterial properties such as stiffness and compliance. This article outlines normal transition in term and preterm infants. It also highlights the adverse impact of three not uncommon neonatal disorders on LV function. Perinatal asphyxia leads to a reduced LV output, superior vena cava and coronary artery blood flow and an increase in the troponin level. Multiple haemodynamic changes are observed in the premature infant with a large patent ductus arteriosus. They need careful analysis to determine when ligation should proceed. Ligation itself generally results in a dramatic increase in afterload which may lead to a reduction in LV contractility and the need for ionotropic support. Fetal growth restricted infants have a higher systolic pressure, a somewhat hypertrophied heart arising from an increased arterial wall thickness/stiffness and systemic peripheral resistance. Point of care ultrasound (POCUS) helps differentiate normal transition and that resulting from neonatal disorders. It may be increasingly utilized in guiding management.
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Fetal growth restriction (FGR) increases the risk cardiovascular disease (CVD) in adulthood. Placental insufficiency and subsequent chronic fetal hypoxemia are causal factors for FGR, leading to a redistribution of blood flow that prioritizes vital organs. Subclinical signs of cardiovascular dysfunction are evident in growth-restricted neonates; however, the mechanisms programming for CVD in adulthood remain unknown. This study aimed to determine the potential mechanisms underlying structural and functional changes within the heart and essential (carotid) and nonessential (femoral) vascular beds in growth-restricted lambs. Placental insufficiency was surgically induced in ewes at 89 days gestational age (dGA, term = 148dGA). Three age groups were investigated: fetal (126dGA), newborn (24 h after preterm birth), and 4-wk-old lambs. In vivo and histological assessments of cardiovascular indices were undertaken. Resistance femoral artery function was assessed via in vitro wire myography and blockade of key vasoactive pathways including nitric oxide, prostanoids, and endothelium-dependent hyperpolarization. All lambs were normotensive throughout the first 4 wk of life. Overall, the FGR cohort had more globular hearts compared with controls (P = 0.0374). A progressive decline in endothelium-dependent vasodilation was demonstrated in FGR lambs compared with controls. Further investigation revealed that impairment of the prostanoid pathway may drive this reduction in vasodilatory capacity. Clinical indicators of CVD were not observed in our FGR lambs. However, subclinical signs of cardiovascular dysfunction were present in our FGR offspring. This study provides insight into potential mechanisms, such as the prostanoid pathway, that may warrant therapeutic interventions to improve cardiovascular development in growth-restricted newborns.NEW & NOTEWORTHY Our findings provide novel insight into the potential mechanisms that program for cardiovascular dysfunction in growth-restricted neonates as our growth-restricted lambs exhibited a progressive decline in endothelium-dependent vasodilation in the femoral artery between birth and 4 wk of age. Subsequent analyses indicated that this reduction in vasodilatory capacity is likely to be mediated by the prostanoid pathway and prostanoids could be a potential target for therapeutic interventions for fetal growth restriction (FGR).
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Doenças Cardiovasculares , Insuficiência Placentária , Nascimento Prematuro , Ovinos , Animais , Gravidez , Feminino , Recém-Nascido , Humanos , Retardo do Crescimento Fetal , Placenta/irrigação sanguínea , Carneiro Doméstico , ProstaglandinasRESUMO
Growth-restricted neonates have worse outcomes after perinatal asphyxia, with more severe metabolic acidosis than appropriately grown neonates. The cardiovascular physiology associated with fetal growth restriction (FGR) may alter their response to asphyxia. However, research on asphyxia in FGR is limited. Here we compared cardiovascular hemodynamics in preterm FGR and control lambs during mild perinatal asphyxia. We induced FGR in one twin at 89 days gestation (term 148 days), while the other served as a control. At 126 days gestation, lambs were instrumented to allow arterial blood pressure and regional blood flow recording, and then mild perinatal asphyxia was induced by umbilical cord clamping, and resuscitation followed neonatal guidelines. FGR lambs maintained carotid blood flow (CBF) for 7 min, while control lambs rapidly decreased CBF (P < 0.05). Fewer growth-restricted lambs needed chest compressions for return of spontaneous circulation (ROSC) (17 vs. 83%, P = 0.02). The extent of blood pressure overshoot after ROSC was similar, but it took longer for MAP to return to baseline in FGR lambs (18.83 ± 0.00 vs. 47.67 ± 0.00 min, P = 0.003). Growth-restricted lambs had higher CBF after ROSC (P < 0.05) and displayed CBF overshoot, unlike control lambs (P < 0.03). In conclusion, preterm growth-restricted lambs show resilience during perinatal asphyxia based on prolonged CBF maintenance and reduced need for chest compressions during resuscitation. However, CBF overshoot after ROSC may increase the risk of cerebrovascular injury in FGR.NEW & NOTEWORTHY Preterm growth-restricted lambs maintain carotid blood flow for longer than control lambs during asphyxia and have a lower requirement for chest compressions than control lambs during resuscitation. Preterm growth-restricted, but not control, lambs displayed an overshoot in carotid blood flow following return of spontaneous circulation.
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Asfixia Neonatal , Asfixia , Gravidez , Feminino , Animais , Ovinos , Asfixia/complicações , Animais Recém-Nascidos , Carneiro Doméstico , Asfixia Neonatal/complicações , Asfixia Neonatal/terapia , Hemodinâmica/fisiologiaRESUMO
Epidemiologists have long documented a higher risk of adult-onset cardiovascular diseases (CVDs) such as stroke, hypertension, and coronary artery disease, as well as mortality from circulatory causes in low birth-weight cohorts (poor in utero substrate supply). Utero-placental insufficiency and in utero hypoxemic state-induced alterations in arterial structure and compliance are important initiating factors for adult-onset hypertension. The mechanistic links between fetal growth restriction and CVD include decreased arterial wall elastin-to-collagen ratio, endothelial dysfunction, and heightened renin-angiotensin-aldosterone system (RAAS). Systemic arterial thickness on fetal ultrasound and vascular changes in placental histopathology in growth restricted cohorts indicate fetal/developmental origins of adult-onset circulatory diseases. Similar findings of impaired arterial compliance have been noticed across age groups (neonates through to adults). Such changes augment what occurs as "normal arterial aging," resulting in accelerated arterial aging. Data from animal models suggest that hypoxemia-associated vascular adaptations enacted in utero are region specific, reflecting long-term vascular pathology. In this review, we explore the influence of birthweight and prematurity on blood pressure and arterial stiffness, demonstrating impaired arterial dynamics in growth-restricted cohorts across age groups, explain how early arterial aging influences adult-onset CVDs, describe pathophysiology data from experimental models and finally, discuss interventions which may influence aging by way of altering various cellular and molecular mechanisms of arterial aging. Age-appropriate interventions which have noted efficacy include prolonged breastfeeding and high polyunsaturated fatty acids dietary intake. Targeting the RAAS seems a promising approach. New data indicate activation of sirtuin 1 and maternal resveratrol may have beneficial effects.
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Doenças Cardiovasculares , Hipertensão , Humanos , Animais , Feminino , Gravidez , Doenças Cardiovasculares/etiologia , Placenta , Artérias , Retardo do Crescimento Fetal , EnvelhecimentoRESUMO
Bronchopulmonary dysplasia (BPD) is the most common sequela of prematurity. Although multifactorial in etiology, there is increasing evidence that fetal growth restriction (FGR) and antenatal exposure of the fetus to inflammation play important roles in the postnatal pathophysiology of BPD. Recent studies have focused on disrupted angiogenesis and its influence on alveolarization. Although there are multiple mechanistic links, inflammation is known to be a key driver of this disruption, affecting pulmonary arterial circulation. Although postnatal corticosteroids are commonly used in extremely premature infants to treat inflammation, aimed at obviating the need for intubation and mechanical ventilation or to facilitate extubation, the use of dexamethasone has not reduced the incidence of BPD. Here, we summarize current knowledge on alternative anti-inflammatory treatment options, which have shown promising outcomes either preclinically or clinically. These include supplementation with vitamins C and E (antioxidants), ω-3 polyunsaturated fatty acids, pentoxifylline, anti-inflammatory cytokines of the IL (interleukin)-1 family, namely IL-1 receptor antagonist and IL-37, and the beneficial properties of breast milk. Evaluating these alternative treatments, either individually or as combination therapies in randomized controlled trials stands to immensely benefit the clinical outlook, particularly regarding BPD, for extremely premature infants.
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Displasia Broncopulmonar , Glucocorticoides , Recém-Nascido , Lactente , Feminino , Gravidez , Humanos , Dexametasona/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/etiologia , Inflamação/tratamento farmacológico , Inflamação/complicaçõesRESUMO
Tachypnoea in the newborn is common. It may arise from the many causes of the respiratory distress syndrome such as hyaline membrane disease, transient tachypnoea of the newborn, meconium aspiration etc. Congenital heart disease rarely presents with early tachypnoea on day one or two, in contrast to the early presentation of cyanosis, unless there is "pump" (ventricular) failure such as may occur in a cardiomyopathy/myocarditis, or as a result of severe obstruction to either ventricle. Space-occupying lesions within the chest, for example from a diaphragmatic hernia or a congenital cystic adenomatoid malformation, may present with early tachypnoea, as can a metabolic cause resulting in acidosis. The aim of this paper, however, is to focus on infants where the tachypnoea persists or develops beyond the newborn period, at times with minimal signs but occasionally with serious underlying pathology. They include causes that may have originated in the newborn but then persist; for example, arising from pulmonary hypoplasia or polycythemia. Many congenital cardiac abnormalities, particularly those causing left sided obstructive lesions, or those due to an increasing left to right shunt from large communications between the systemic and pulmonary circulations, need be considered. Respiratory causes, for example arising from aspiration, primary ciliary dyskinesia, cystic fibrosis, or interstitial lung disease, may lead to ongoing tachypnoea. Infective causes such as bronchiolitis or infantile wheeze generally are readily recognisable. Finally, there are a few infants who present with persistent tachypnoea over the first few weeks/months of their life who remain well and have normal investigations with the tachypnoea gradually resolving. How should one approach infants with persistent tachypnoea?
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BACKGROUND: Paracetamol is commonly used for analgesia and patent ductus arteriosus (PDA) treatment in preterm infants. We aimed to evaluate early neurodevelopmental outcomes of extreme preterm infants exposed to paracetamol during their neonatal admission. METHODS: This retrospective cohort study included surviving infants born at <29 weeks gestation, or with a birth weight of <1000 grams. Neurodevelopmental outcomes studied were early cerebral palsy (CP) or high risk of CP diagnosis, Hammersmith Infant Neurological Examination (HINE) score and Prechtl General Movement Assessment (GMA) at 3-4 months corrected age. RESULTS: Two hundred and forty-two infants were included, of which 123 were exposed to paracetamol. After adjusting for birth weight, sex and chronic lung disease, there were no significant associations between paracetamol exposure and early CP or high risk of CP diagnosis (aOR 1.46, 95% CI 0.61, 3.5), abnormal or absent GMA (aOR 0.82, 95% CI 0.37, 1.79) or HINE score (adjusted ß -0.19, 95% CI -2.39, 2.01). Subgroup analysis stratifying paracetamol exposure into <180 mg/kg or ≥180 mg/kg cumulative dose found that neither had significant effects on outcomes. CONCLUSIONS: In this cohort of extreme preterm infants, no significant association was found between exposure to paracetamol during the neonatal admission and adverse early neurodevelopment. IMPACT: Paracetamol is commonly used in the neonatal period for analgesia and patent ductus arteriosus treatment in preterm infants, although prenatal paracetamol use has been associated with adverse neurodevelopmental outcomes. Exposure to paracetamol during the neonatal admission was not associated with adverse early neurodevelopment at 3-4 months corrected age in this cohort of extreme preterm infants. The findings from this observational study is consistent with the small body of literature supporting the lack of association between neonatal paracetamol exposure and adverse neurodevelopmental outcomes in preterm infants.
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Permeabilidade do Canal Arterial , Síndrome da Persistência do Padrão de Circulação Fetal , Lactente , Gravidez , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Acetaminofen/efeitos adversos , Permeabilidade do Canal Arterial/tratamento farmacológico , Peso ao Nascer , Estudos Retrospectivos , Ibuprofeno/efeitos adversosRESUMO
Preterm birth is defined as delivery at <37 weeks of gestational age (GA) and exposes 15 million infants worldwide to serious early life diseases. Lowering the age of viability to 22 weeks GA entailed provision of intensive care to a greater number of extremely premature infants. Moreover, improved survival, especially at extremes of prematurity, comes with a rising incidence of early life diseases with short- and long-term sequelae. The transition from fetal to neonatal circulation is a substantial and complex physiologic adaptation, which normally happens rapidly and in an orderly sequence. Maternal chorioamnionitis or fetal growth restriction (FGR) are two common causes of preterm birth that are associated with impaired circulatory transition. Among many cytokines contributing to the pathogenesis of chorioamnionitis-related perinatal inflammatory diseases, the potent pro-inflammatory interleukin (IL)-1 has been shown to play a central role. The effects of utero-placental insufficiency-related FGR and in-utero hypoxia may also be mediated, in part, via the inflammatory cascade. In preclinical studies, blocking such inflammation, early and effectively, holds great promise for improving the transition of circulation. In this mini-review, we outline the mechanistic pathways leading to abnormalities in transitional circulation in chorioamnionitis and FGR. In addition, we explore the therapeutic potential of targeting IL-1 and its influence on perinatal transition in the context of chorioamnionitis and FGR.
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Compared to preterm appropriate for gestational age (AGA) fetuses, fetuses with fetal growth restriction (FGR) have earlier visualisation of coronary artery blood flow (CABF) but impaired cardiac function. This dichotomy remains uncharacterised during postnatal life. This study compared CABF and cardiac function in preterm FGR infants, against AGA infants during the postnatal period. FGR was defined as birthweight < 10th centile for gestation and sex with absent/reversed antenatal umbilical artery Doppler. Diastolic CABF was measured in the left anterior descending coronary artery. Twenty-eight FGR infants were compared with 26 AGA infants (gestation and birthweight, 29.7 ± 1.3 vs 29.9 ± 1 weeks, P = 0.6 and 918 ± 174 vs 1398 ± 263g, P < 0.001, respectively). Echocardiography was performed in the second week of life. FGR infants had higher CABF (velocity time integral, 2.4 ± 0.9 vs 1.6 ± 0.8 cm, P = 0.002). Diastolic function was impaired (↑ trans-mitral E/A ratio in FGR infants; 0.84 ± 0.05 vs 0.79 ± 0.03, P = 0.0002) while the systolic function was also affected (mean velocity of circumferential fibre shortening [mVCFc], 1.9 ± 0.3 vs 2.7 ± 0.5 circ/s, P < 0.001). Indexing CABF to cardiac function noted significant differences between the groups (CABF: E/A [FGR vs AGA], 2.9 ± 1.1 vs 2.1 ± 1, P = 0.01 and CABF: mVCFc [FGR vs AGA], 1.3 ± 0.5 vs 0.6 ± 0.3, P < 0.001). Diastolic blood pressure (BP) was significantly higher, and CABF to diastolic BP ratio trended higher in FGR infants (30 ± 2 vs 25 ± 3 mmHg, P < 0.001 and 0.08 ± 0.03 vs 0.06 ± 0.03, P = 0.059, respectively). Greater CABF in FGR infants did not translate into better cardiac function. This dichotomy may be a persistent response to fetal hypoxaemia (fetal programming) and/or reflection of altered cardiac architecture.
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Feto , Recém-Nascido Prematuro , Recém-Nascido , Lactente , Feminino , Humanos , Gravidez , Peso ao Nascer , Idade Gestacional , Retardo do Crescimento Fetal/diagnóstico , PerfusãoRESUMO
Bronchopulmonary dysplasia (BPD) is the most common respiratory sequela of prematurity, and infants born with fetal growth restriction (FGR) are disproportionately represented in BPD statistics, as factors which affect somatic growth may also affect pulmonary growth. Effects of in-utero hypoxia underlying FGR on lung parenchymal architecture predisposing to BPD are well documented, but the pulmonary vascular constructs are not well appreciated. Disruption of angiogenesis during critical periods of lung growth impairs alveolarization, contributing to BPD pathogenesis. Pulmonary artery thickness/stiffness has been noted in FGR in the initial postnatal weeks, and also in well-grown infants with established BPD. The lack of waveform cushioning by the major arteries exposes the pulmonary resistance vessels to higher pulsatile stress, thereby accelerating microvascular disease. Reactive oxygen species, increased sympathetic activity and endothelial dysfunction are common mediators in FGR and BPD; each putative targets for prevention and/or therapeutics using interleukin (IL)-1 receptor antagonist (IL-1Ra), melatonin or inhibition of renin-angiotensin-aldosterone system. While BPD is the archetypal respiratory disease of infancy, effects of FGR on pulmonary function are long-term, extending well into childhood. This narrative links FGR in very/extremely preterm infants with BPD through the vascular affliction as a mechanistic and potentially, therapeutic pathway. Our objectives were to depict the burden of disease for FGR and BPD amongst preterm infants, portray vascular involvement in the placenta in FGR and BPD cohorts, provide high resolution vascular ultrasound information in both cohorts with a view to address therapeutic relevance, and lastly, link this information with paediatric age-group lung diseases.
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Displasia Broncopulmonar , Doenças do Recém-Nascido , Lactente , Gravidez , Feminino , Recém-Nascido , Humanos , Criança , Retardo do Crescimento Fetal , Pulmão , Lactente Extremamente PrematuroRESUMO
The cardiovascular impact of dexamethasone (Dex) is not well understood. Most data are obtained from a 6 week, high-dose regimen, and are limited to findings of hypertension and cardiac hypertrophy. The present study ascertained the impact of low-dose Dex on cardiac indices when administered to extremely preterm infants for lung disease. A pre-post intervention prospective echocardiographic (Echo) study was undertaken, with cardiac assessments performed before and within 24 h after completion of first course of therapy (10 day regimen, cumulative 0.89 mg kg-1 ). Thirty infants with a gestational age of 24.6 ± 1.1 weeks and birthweight of 612 ± 125 g, respectively, were studied. The age at Dex administration was 20 ± 9 days. Fractional inspired oxygen decreased from 0.7 ± 0.23 to 0.35 ± 0.14 (P < 0.001). Patent ductus arteriosus was noted in 20 infants at Echo1. At Echo2, the ductal diameter decreased from 2.16 ± 0.8 to 1.1 ± 0.8 mm (P = 0.0003), with complete closure in 7/20 (35%). A reduction in left pulmonary artery end-diastolic velocity was noted (17 ± 12 to 9 ± 10 cm s-1 , P < 0.001). Pulmonary vascular resistance decreased (increased time to peak velocity/right ventricular ejection time, 0.2 ± 0.03 to 0.23 ± 0.03, P = 0.0001) and right ventricular systolic performance improved (tricuspid annular plane systolic excursion, 4.9 ± 0.8 to 5.5 ± 0.9 mm, P = 0.02). No significant changes in fractional shortening and left ventricular mass were noted. A significant increase in blood pressure was noted. As a percentage of pre-treatment baseline, the mean increase for systolic blood pressure was 20.3% (95% confidence interval = 14-26) on day 2 (P = 0.008). Low-dose Dex influenced cardiovascular parameters related to pulmonary circulation. KEY POINTS: Corticosteroid therapy is frequently used in preterm infants who are dependent on ventilator support. Echocardiographic studies in infants administered a 6 week course of steroids have noted left ventricular hypertrophy, outlet obstruction and hypertension, but no information is available on right heart indices. The cardiopulmonary effects of the current, significantly lesser cumulative dose (10 day regimen, commonly described as 'DART') have not been evaluated. The present study noted a significant influence on ductal and pulmonary circulation indices. Left heart architecture and function was maintained, whereas a significant but transient increase in blood pressure was noted.