Heart rate variability is depressed in the early transitional period for newborns with complex congenital heart disease
- 作者列表："Mulkey, Sarah B.","Govindan, Rathinaswamy","Metzler, Marina","Swisher, Christopher B.","Hitchings, Laura","Wang, Yunfei","Baker, Robin","Larry Maxwell, G.","Krishnan, Anita","Plessis, Adre J.
Purpose To compare early changes in autonomic nervous system (ANS) tone between newborns with complex congenital heart disease (CHD) and newborns without CHD. Methods We performed a case–control study of heart rate variability (HRV) in newborns with complex CHD [transposition of the great arteries (TGA) or hypoplastic left heart syndrome (HLHS)] and low-risk control newborns without CHD. Cases with CHD were admitted following birth to a pediatric cardiac intensive care unit and had archived continuous ECG data. Control infants were prospectively enrolled at birth. ECG data in cases and controls were analyzed for HRV in the time and frequency domains at 24 h of age. We analyzed the following HRV metrics: alpha short ( α _s), alpha long ( α _L), root mean square short and long (RMS_s and RMS_L), low-frequency (LF) power, normalized LF (nLF), high-frequency (HF) power, and normalized HF (nHF). We used ANOVA to compare HRV metrics between groups and to control for medication exposures. Results HRV data from 57 infants with CHD (TGA, n = 33 and HLHS, n = 24) and from 29 controls were analyzed. The HRV metrics α _S, RMS_L, LF, and nLF were significantly lower in infants with CHD than in the controls. Due to the effect of normalization, nHF was higher in CHD infants ( P < 0.0001), although absolute HF was lower ( P = 0.0461). After adjusting for medications, α _S and nLF remained lower and nHF higher in newborns with CHD ( P < 0.0005). Conclusions Infants with complex CHD have depressed autonomic balance in the early postnatal period, which may complicate the fetal–neonatal transition.
目的比较复杂先天性心脏病 (CHD) 新生儿与非 CHD 新生儿早期自主神经系统 (ANS) 张力的变化。方法: 我们对复杂 CHD (大动脉转位 (TGA) 或左心发育不良综合征 (HLHS)) 新生儿进行了心率变异性 (HRV) 的病例对照研究。和无 CHD 的低风险控制新生儿。CHD 病例出生后入住小儿心脏重症监护病房，并存档连续心电图数据。出生时前瞻性入组对照婴儿。分析病例组和对照组 24 h 时的 HRV 时域和频域数据。我们分析了以下 HRV 指标: α 短 (α _ s) 、 α 长 (α _ L) 、均方根短和长 (RMS_s 和 RMS_L),低频 (LF) 功率、归一化 LF (nLF) 、高频 (HF) 功率和归一化 HF (nHF)。我们使用 ANOVA 比较组间 HRV 指标，并控制药物暴露。结果分析了 57 例 CHD 婴儿 (TGA，n = 33，HLHS，n = 24) 和 29 例对照组的 HRV 数据。CHD 婴儿的 HRV 指标 α _ S 、 RMS_L 、 LF 和 nLF 均显著低于对照组。由于正常化的影响，CHD 婴儿的 nHF 较高 (P <0.0001)，但绝对 HF 较低 (P = 0.0461)。校正药物治疗后，CHD 新生儿的 α _ S 和 nLF 仍较低，nHF 较高 (p <0.0005)。结论复杂 CHD 患儿在出生后早期存在自主神经平衡低下，可使胎儿-新生儿转变复杂化。
METHODS:BACKGROUND:Preterm birth is a risk factor for elevated blood pressure in childhood and the development of hypertension and cardiometabolic disease in adulthood; however, mechanisms for the development of both are poorly understood. Rapid weight gain early in childhood may serve as a driver directly and indirectly through cortisol levels found to be elevated in early childhood in individuals born preterm. OBJECTIVES:The objective of this pilot study was to examine the effect sizes of the relationships between weight gain and blood pressure in toddlers born very preterm. A secondary aim was to note any mediating effect of cortisol on the relationships between weight gain and blood pressure. METHODS:A cross-sectional design with a convenience sample of 36 toddlers who were born very preterm was used to examine the relationships between postnatal weight gain, cortisol, and blood pressure at follow-up. RESULTS:Many of the participants experienced rapid weight gain in the first 12 months of life. Mean systolic and diastolic readings were 94 and 56.6, respectively. Diastolic blood pressure readings were obtained from 23 participants and the majority were elevated. Weight gain was associated with diastolic blood pressure with a medium effect size. A mediating role with cortisol was not supported.Although findings need to be validated in a larger sample, the blood pressure elevations in this sample were alarming. If readings continue to amplify as these children age, the fact that elevations are already present during the toddler period could indicate more significant cardiovascular disease in adulthood for this population. Rapid weight gain in early life may be a driver for elevated blood pressure even during early childhood in individuals born preterm.
METHODS:This article presents a case series of n = 21 models of fetal cardiovascular anatomies obtained from post mortem microfocus computed tomography (micro-CT) data. The case series includes a broad range of diagnoses (e.g., tetralogy of Fallot, hypoplastic left heart syndrome, dextrocardia, double outlet right ventricle, atrio-ventricular septal defect) and cases also had a range of associated extra-cardiac malformations (e.g., VACTERL syndrome, central nervous system anomalies, renal anomalies). All cases were successfully reconstructed from the microfocus computed tomography data, demonstrating the feasibility of the technique and of the protocols, including in-house printing with a desktop 3D printer (Form2, Formlabs). All models were printed in 1:1 scale as well as with the 5-fold magnification, to provide insight into the intra-cardiac structures. Possible uses of the models include education and training.
METHODS:Abstract Background Congenital heart disease (CHD) affects ~ 1% of live births and is the most common birth defect. Although the genetic contribution to the CHD has been long suspected, it has only been well established recently. De novo variants are estimated to contribute to approximately 8% of sporadic CHD. Methods CHD is genetically heterogeneous, making pathway enrichment analysis an effective approach to explore and statistically validate CHD-associated genes. In this study, we performed novel gene and pathway enrichment analyses of high-impact de novo variants in the recently published whole-exome sequencing (WES) data generated from a cohort of CHD 2645 parent-offspring trios to identify new CHD-causing candidate genes and mutations. We performed rigorous variant- and gene-level filtrations to identify potentially damaging variants, followed by enrichment analyses and gene prioritization. Results Our analyses revealed 23 novel genes that are likely to cause CHD, including HSP90AA1, ROCK2, IQGAP1, and CHD4, and sharing biological functions, pathways, molecular interactions, and properties with known CHD-causing genes. Conclusions Ultimately, these findings suggest novel genes that are likely to be contributing to CHD pathogenesis.