Interatrial Communications: Prevalence and Subtypes in 12,385 Newborns-a Copenhagen Baby Heart Study.

The prevalence of interatrial communications in newborns, i.e., patent foramen ovale or atrial septal defect, was previously reported to be between 24 and 92%, but the area has been impeded by lack of a universal classification method. A recently published novel echocardiographic diagnostic algorithm for systematic classification of interatrial communications had inter-and intraobserver agreements superior to standard expert assessment. This study aimed to determine the prevalence of subtypes of interatrial communications on transthoracic echocardiography in newborns. Echocardiograms of newborns aged 0-30 days were prospectively collected in the population-based cohort study Copenhagen Baby Heart Study in 2017-2018 and analyzed according to the new diagnostic algorithm, classifying interatrial communications into three subtypes of patent foramen ovale and three subtypes of atrial septal defects. Echocardiograms from 15,801 newborns were analyzed; 3416 (21.6%) were excluded due to suboptimal image quality or severe structural heart disease (n = 3), leaving 12,385 newborns (aged 12 [interquartile range 8; 15] days, 48.2% female) included in the study. An interatrial communication was detected in 9766 (78.9%) newborns. According to the algorithm, 9029 (72.9%) had a patent foramen ovale, while 737 (6.0%) fulfilled criteria for an atrial septal defect, further divided into subtypes. An interatrial communication was seen on echocardiography in almost 80% of newborns aged 0-30 days. Patent foramen ovale was 12 times more frequent than atrial septal defects. The observed prevalence of atrial septal defects was higher than previously reported. Follow up studies could distinguish which interatrial communications require follow-up or intervention. ClinicalTrial.gov, NCT02753348, posted April 27, 2016, [ https://classic.clinicaltrials.gov/ct2/show/NCT02753348 ].

Significance of lipids, lipoproteins, and apolipoproteins during the first 14-16 months of life.

BACKGROUND AND AIMS: The aims of this study were to investigate lipid parameters during the first 14-16 months of life, to identify influential factors, and to test whether high concentrations at birth predict high concentrations at 2- and 14-16 months. METHODS: The Copenhagen Baby Heart Study, including 13,354 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n = 444), 2 months (n = 364), and 14-16 months (n = 168), was used. RESULTS: Concentrations of lipids, lipoproteins, and apolipoproteins in umbilical cord blood samples correlated highly with venous blood samples from newborns. Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and lipoprotein(a) increased stepwise from birth to 2 months to 14-16 months. Linear mixed models showed that concentrations of LDL cholesterol, non-HDL cholesterol, and lipoprotein(a) above the 80th percentile at birth were associated with significantly higher concentrations at 2 and 14-16 months. Finally, lipid concentrations differed according to sex, gestational age, birth weight, breastfeeding, and parental lipid concentrations. CONCLUSIONS: Lipid parameters changed during the first 14-16 months of life, and sex, gestational age, birth weight, breastfeeding, and high parental concentrations influenced concentrations. Children with high concentrations of atherogenic lipid traits at birth had higher concentrations at 2 and 14-16 months. These findings increase our knowledge of how lipid traits develop over the first 14-16 months of life and may help in deciding the optimal child age for universal familial hypercholesterolaemia screening.

Normative Echocardiographic Left Ventricular Parameters and Reference Intervals in Infants.

BACKGROUND: In pediatric echocardiography, reference intervals are required to distinguish normal variation from pathology. Left ventricular (LV) parameters are particularly important predictors of clinical outcome. However, data from healthy newborns are limited, and current reference intervals provide an inadequate approximation of normal reference ranges. OBJECTIVES: Normative reference intervals and z-scores for 2-dimensional echocardiographic measurements of LV structure and function based on a large group of healthy newborns were developed. METHODS: The study population included 13,454 healthy newborns from the Copenhagen Baby Heart Study who were born at term to healthy mothers, had an echocardiogram performed within 30 days of birth, and did not have congenital heart disease. To develop normative reference intervals, this study modeled 10 LV parameters as a function of body surface area through joint modeling of 4 statistical components. RESULTS: Infants in the study population (48.5% were female) had a median body surface area of 0.23 m2 (IQR: 0.22-0.25 m2) and median age of 12.0 days (IQR: 8.0-15.0 days) at examination. All normative reference intervals performed well in both sexes without stratification on infant sex. In contrast, creation of separate reference models for infants examined at <7 days of age and those examined at 7-30 days of age was necessary to optimize the performance of the reference intervals. CONCLUSIONS: This study provides normative reference intervals and z-scores for 10 clinical, widely used echocardiographic measures of LV structure and function based on a large cohort of newborns. These results provide highly needed reference material for clinical application by pediatric cardiologists.

Red blood cell parameters in early childhood: a prospective cohort study.

OBJECTIVES: Red blood cell parameters are frequently used biomarkers when assessing clinical status in newborns and in early childhood. Cell counts, amounts, and concentrations of these parameters change through gestation and after birth. Robust age-specific reference intervals are needed to optimize clinical decision making. METHODS: The Copenhagen Baby Heart Study (CBHS) and the COMPARE study are prospective cohort studies including red blood cell parameters from 7,938 umbilical cord blood samples and 295 parallel venous blood samples from newborns with follow-up at two and at 14-16 months after birth. RESULTS: For venous blood at birth, reference intervals for hemoglobin, erythrocytes, and hematocrit were 145-224 g/L, 4.1-6.4 × 1012/L, and 0.44-0.64, respectively. Hemoglobin, erythrocytes, and hematocrit were lower at birth in children delivered by prelabor cesarean section compared to vaginal delivery. Conversion algorithms based on term newborns were: venous hemoglobin=(umbilical cord hemoglobin-86.4)/0.39; venous erythrocytes=(umbilical cord erythrocytes-2.20)/0.44; and venous hematocrit=(umbilical cord hematocrit-0.24)/0.45. CONCLUSIONS: This study presents new reference intervals for red blood cell parameters in early childhood, describes the impact of delivery mode, and provide exact functions for converting umbilical cord to venous blood measurements for term newborns. These findings may improve clinical decision making within neonatology and infancy and enhance our clinical understanding of red blood cell parameters for health and diseases in early life.

Prevalence of Left Ventricular Noncompaction in Newborns.

BACKGROUND: Left ventricular noncompaction (LVNC) is characterized by excessive trabeculations of the LV and may be associated with reduced systolic function or severe adverse outcomes. Several aspects remain to be elucidated; there is controversy to whether LVNC cardiomyopathy is a distinct cardiomyopathy caused by failure of the spongy fetal myocardium to condense during fetal development or acquired later in life as a morphological trait associated with other types of cardiomyopathy; the prevalence in unselected populations is unknown and the distinction between normal variation and pathology remains to be defined. In this study, we aimed to determine the prevalence of LVNC and the association to LV systolic function in a large, population-based cohort of neonates. In addition, we assessed the normal ratio of noncompact to compact (NC:C) myocardium in 150 healthy neonates. METHODS: Echocardiographic data were prospectively collected in the population study Copenhagen Baby Heart Study. The ratio of NC:C was measured in 12 ventricular segments. LVNC was defined as NC:C ≥2 in at least one segment. Neonates with LVNC were matched 1:10 to controls on sex, gestational age, and weight and age at the examination day. RESULTS: In total, 25 590 neonates (52% males, median age 11 [interquartile range, 7-15] days) underwent echocardiography. Among 21 133 with satisfactory visualization of ventricular segments, we identified a prevalence of LVNC of 0.076% (95% CI, 0.047-0.123). LV ejection fraction was lower in neonates with LVNC compared with matched controls (median 49.5 versus 59.0%; P<0.0001). In neonates with otherwise healthy hearts, the median NC:C ratio ranged from 0.0 to 0.7 and the 99th percentiles from 1.0 to 1.9 for each of the 12 segments. CONCLUSIONS: The prevalence of LVNC based on neonatal echocardiography was 0.076%. LVNC was associated with lower LV systolic function. The findings in normal newborns support the cutoff NC:C ≥2 as an appropriate diagnostic criterion. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02753348.

Maternal Hypertensive Disorders of Pregnancy and Cardiac Structure and Function in the Newborn.

Background: Maternal hypertensive disorders of pregnancy (HDPs) are strongly associated with offspring congenital heart defects. Objectives: This study assessed whether infants exposed to maternal HDPs were also more likely to have subtle cardiac structural and functional abnormalities than unexposed infants. Methods: We used regression analyses to compare: 1) left ventricular parameters from conventional echocardiography performed in infants from the Copenhagen Baby Heart Study born to mothers with preeclampsia, gestational hypertension (GH), or no HDP; and 2) advanced echocardiographic parameters for 545 term infants born to mothers with preeclampsia and 545 matched infants not exposed to HDPs. Results: Compared with infants unexposed to HDPs (n = 17,384), infants exposed to preeclampsia (n = 754) had a thicker interventricular septum in end-diastole (adjusted mean difference [± SD] 0.05 [±0.02] mm; P = 0.004), thicker left ventricular posterior wall (0.04 [±0.02] mm; P = 0.009), larger left ventricular internal diameter (0.12 [±0.06] mm; P = 0.04), and larger left ventricular volume (0.21 [±0.10] mL; P = 0.03). Systolic function changes included increased fractional shortening (0.36% [±0.14%]; P = 0.01) and stroke volume (0.18 [±0.07] mL; P = 0.006), whereas diastolic function changes included lower transmitral early peak inflow velocity (-1.76 [±0.49] mL; P = 0.0003), lower mitral annulus lateral wall a' (-0.21 [±0.09] cm/s; P = 0.02), and smaller lateral E/e' (-1.06 [±0.38] cm/s; P = 0.005). Conversely, there was little evidence of any association between maternal GH (n = 469) and offspring left ventricular parameters. Conclusions: Maternal preeclampsia, but not GH, was associated with subtle newborn cardiac morphological and functional alterations, including thickening of the left ventricular myocardium and altered systolic and diastolic function.