Differential postnatal cardiovascular course of donor-recipient twins and associated pathophysiology-a cohort study.American journal of physiology. Heart and circulatory physiology • October 25, 2024
Eugene Ting, Mark Teoh, Arvind Sehgal
Fetal echocardiography in twin-to-twin transfusion pregnancies treated with photocoagulation noted impaired cardiac function. Systematic information about cardiac structure or function and arterial distensibility after birth is not available. This study evaluated cardiovascular function and arterial dynamic properties in survivors of twin-to-twin transfusion syndrome (TTTS). Eleven pairs of donor-recipient twins were compared with each other and with 20 singletons of comparable gestational age. The twin cohort was born at 31.5 ± 2 wk gestational age; birthweights of donors-recipients were comparable (donors: 1,358 ± 421 g vs. recipients: 1,617 ± 460 g, P = 0.2). Significant intertwin differences were noted for cardiac function parameters. Recipients had greater septal thickness (donors: 2.3 ± 0.15 vs. recipients: 2.7 ± 0.36 mm, P = 0.01) and globularity [lower sphericity index (donors: 1.76 ± 0.1 vs. recipients: 1.62 ± 0.12, P = 0.009)]. They also had lower cardiac function [tricuspid annular plane systolic excursion (donors: 4.6 ± 0.5 vs. recipients: 4.1 ± 0.4 mm, P = 0.02) and right ventricular fractional area change (donors: 30 ± 1 vs. recipients: 27.7 ± 1.3%, P = 0.0001)]. Compared with singletons, differences were statistically more significant for recipients. Arterial distensibility however was more affected in donors [higher arterial wall stiffness index (donors: 2.5 ± 0.2 vs. recipients: 2.2 ± 0.2, P = 0.008) and lower pulsatile diameter (donors: 51 ± 5 vs. recipients: 63 ± 10 µm, P < 0.0001)]. Compared with singletons, the differences were statistically more significant for donors. Evaluation in the neonatal period noted that cardiac function and arterial distensibility are affected in TTTS twins. These cohorts will benefit from close postnatal follow-up for the evolution of cardiac and arterial impairments.NEW & NOTEWORTHY Evaluation for fetuses with twin-to-twin transfusion syndrome noted impaired cardiac function in recipients. Systematic data after birth are lacking. We noted greater ventricular dilatation, globularity, and hypertrophied interventricular septum in the recipient. Right ventricular contractility was reduced; differences between recipients-singletons had greater statistical significance compared with donors-singletons. The aorta had greater stiffness and lower distensibility in donors compared with recipients; the differences for arterial indices were statistically more significant with donors-singletons.
Diagnostic and therapeutic precision in cardiovascular diseases in the neonatal intensive care.Journal Of Perinatology : Official Journal Of The California Perinatal Association • February 18, 2025
Arvind Sehgal, Matthew Buckingham, Rachael Hyland, Patrick Mcnamara
While patent ductus arteriosus, pulmonary hypertension, and systemic hypotension are key medical issues amongst neonates, there are other common biological conditions which present with distinct physiological diagnostic and therapeutic challenges. This review focuses on such hemodynamic considerations in cardiomyopathy accompanying infants of diabetic mothers, twin-to-twin transfusion syndrome, and left heart pathology in infants with severe chronic lung disease. It details the pathophysiological mechanisms, diagnostic approaches, and therapeutic strategies essential for optimizing cardiovascular stability in this fragile cohort. A regimented, protocol-driven approach may lead to an increased risk of unintended treatment side effects in patients where diagnostic precision is low. This review provides a rational basis of the management of hemodynamic instability, at the same time laying out knowledge gaps and considerations for future research.
Proteinuria in preterm neonates: influence of fetal growth restriction.Journal Of Perinatology : Official Journal Of The California Perinatal Association • September 18, 2024
Arvind Sehgal, Criona Levins, Emma Yeomans, Zhong Lu, David Metz
Objective: To compare proteinuria in preterm neonates with fetal growth restriction-small for gestational age (FGR-SGA) against equally preterm but appropriate for gestational age (AGA) neonates.
Methods: Prospective, observational cohort study.
Results: Eighteen FGR-SGA neonates were compared with 18 AGA neonates (gestation; 29 ± 1 vs 29 ± 2 weeks, P = 0.8). Urine total protein (median [interquartile range]) in FGR-SGA was higher 370 [323, 573] vs 255 [193, 453] mg/L in AGA, P = 0.017 at first assessment (week one) and 565 [445, 743] vs 225 [135, 458] mg/L, P = 0.0011 at second assessment (week four). Urine protein creatinine ratio was 393 [250, 445] in FGR-SGA vs 227 [163, 367] mg/mmol in AGA, P = 0.029 at first assessment and 444 [368, 699] vs 240 [199, 411] mg/mmol, P = 0.0014 at second assessment. Mean blood pressure was higher in FGR-SGA group & directly correlated with proteinuria.
Conclusions: Increased proteinuria in FGR-SGA suggests reduced nephron endowment and hyper-filtration.
Vascular responsiveness to low-dose dexamethasone in extremely premature infants: negative influence of fetal growth restriction.American Journal Of Physiology. Heart And Circulatory Physiology • July 19, 2024
Arvind Sehgal, Marcel Nold, Calum Roberts, Samuel Menahem
Dexamethasone is frequently prescribed for preterm infants to wean from respiratory support and/or to facilitate extubation. This pre-/postintervention prospective study ascertained the impact on clinical (respiratory support) and echocardiographic parameters after dexamethasone therapy in preterm fetal growth restriction (FGR) infants compared with appropriate for gestational age (AGA) infants. Echocardiography was performed within 24 h 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 birth weight, 25.2 ± 1.1 wk and 497 ± 92 g, respectively) were compared with 22 AGA infants (gestation and birth weight, 24.5 ± 0.8 and 663 ± 100 g, respectively). Baseline respiratory severity score (mean airway pressure × 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 the 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 (ratio of time to peak velocity to 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.NEW & NOTEWORTHY Dexamethasone (DEX) is frequently used in preterm infants dependent on ventilator support. Differences in vascular structure and function that may have developed prenatally arising from the chronic intrauterine hypoxemia in FGR infants may adversely affect responsiveness. The clinical efficacy of DEX was significantly less in FGR (birth weight < 10th centile) infants, compared with appropriate for gestational age (AGA) infants. Echocardiography showed significantly less improvement in pulmonary vascular resistance in FGR, compared with AGA infants.
Systemic hemodynamics and pediatric lung disease: mechanistic links and therapeutic relevance.American Journal Of Physiology. Heart And Circulatory Physiology • July 05, 2024
Arvind Sehgal, Andrew South, Samuel Menahem
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.
