Early N-Terminal Pro B-Type Natriuretic Peptide (NTproBNP) Plasma Values and Associations with Patent Ductus Arteriosus Closure and Treatment-An Echocardiography Study of Extremely Preterm Infants.

The aim was to investigate the association of gestational age (GA), echocardiographic markers and levels of plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) with the closure rate of a haemodynamically significant patent ductus arteriosus (hsPDA). Ninety-eight Swedish extremely preterm infants, mean GA 25.7 weeks (standard deviation 1.3), born in 2012-2014, were assessed with echocardiography and for levels of NTproBNP. Thirty-three (34%) infants had spontaneous ductal closure within three weeks of age. Infants having spontaneous closure at seven days or less had significantly lower NTproBNP levels on day three, median 1810 ng/L (IQR 1760-6000 ng/L) compared with: infants closing spontaneously later, 10,900 ng/L (6120-19,200 ng/L); infants treated either with ibuprofen only, 14,600 ng/L (7740-28,100 ng/L); or surgery, 32,300 ng/L (29,100-35,000 ng/L). Infants receiving PDA surgery later had significantly higher NTproBNP values on day three than other infants. Day three NTproBNP cut-off values of 15,001-18,000 ng/L, predicted later PDA surgery, with an area under the curve in ROC analysis of 0.69 (0.54-0.83). In conclusion, the spontaneous PDA closure rate is relatively high in extremely preterm infants. Early NTproBNP levels can be used with GA in the management decisions of hsPDA.

Association between Neonatal Intakes and Hyperglycemia, and Left Heart and Aortic Dimensions at 6.5 Years of Age in Children Born Extremely Preterm.

Survivors of extremely preterm birth (gestational age < 27 weeks) have been reported to exhibit an altered cardiovascular phenotype in childhood. The mechanisms are unknown. We investigated associations between postnatal nutritional intakes and hyperglycemia, and left heart and aortic dimensions in children born extremely preterm. Postnatal nutritional data and echocardiographic dimensions at 6.5 years of age were extracted from a sub-cohort of the Extremely Preterm Infants in Sweden Study (EXPRESS; children born extremely preterm between 2004-2007, n = 171, mean (SD) birth weight = 784 (165) grams). Associations between macronutrient intakes or number of days with hyperglycemia (blood glucose > 8 mmol/L) in the neonatal period (exposure) and left heart and aortic dimensions at follow-up (outcome) were investigated. Neonatal protein intake was not associated with the outcomes, whereas higher lipid intake was significantly associated with larger aortic root diameter (B = 0.040, p = 0.009). Higher neonatal carbohydrate intake was associated with smaller aorta annulus diameter (B = -0.016, p = 0.008). Longer exposure to neonatal hyperglycemia was associated with increased thickness of the left ventricular posterior wall (B = 0.004, p = 0.008) and interventricular septum (B = 0.004, p = 0.010). The findings in this study indicate that postnatal nutrition and hyperglycemia may play a role in some but not all long-lasting developmental adaptations of the cardiovascular system in children born extremely preterm.

Right Heart Structure, Geometry and Function Assessed by Echocardiography in 6-Year-Old Children Born Extremely Preterm-A Population-Based Cohort Study.

Preterm birth has been associated with altered cardiac phenotype in adults. Our aim was to test the hypothesis that children surviving extremely preterm birth have important structural or functional changes of the right heart or pulmonary circulation. We also examined relations between birth size, gestational age, neonatal diagnoses of bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) with cardiac outcomes. We assessed a population-based cohort of children born in Sweden before 27 weeks of gestation with echocardiography at 6.5 years of age (n = 176). Each preterm child was matched to a healthy control child born at term. Children born preterm had significantly smaller right atria, right ventricles with smaller widths, higher relative wall thickness and higher estimated pulmonary vascular resistance (PVR) than controls. In preterm children, PVR and right ventricular myocardial performance index (RVmpi') were significantly higher in those with a PDA as neonates than in those without PDA, but no such associations were found with BPD. In conclusion, children born extremely preterm exhibit higher estimated PVR, altered right heart structure and function compared with children born at term.

Lung function and pulmonary vascular resistance are not associated in 6-year-old children born extremely preterm.

AIM: Children born preterm are at increased risk of reduced lung function. The aim was to test whether lung function was associated with pulmonary vascular resistance. METHODS: Participants were recruited from a population-based cohort born in 2004-2007. Lung function was assessed with spirometry after administration of a beta2-agonist. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1 ) were determined. Estimations of pulmonary vascular resistance, arterial dimensions, right ventricular wall thickness, sphericity, and systolic (TAPSE) and diastolic functions were performed with echocardiography. Adjusted regression analyses were used to study associations. RESULTS: Sixty-six children (33 boys) born at 22-26 weeks of gestational age (birthweights 460-1134 g) were assessed at a mean age of 6.7 years. Despite large variations in lung function with FVC z-scores ranging from -4.6 to +2.8, there were no associations between lung function and pulmonary arterial pressure, right ventricular structure or function. Children with higher FVC z-scores (r = .52, ß = .55 mm, P = .015) and higher FEV1 z-scores (r = .58, ß = .73 mm, P = .001) exhibited larger pulmonary arteries. CONCLUSION: In children born extremely preterm, lung function was not associated with pulmonary vascular resistance. Routine echocardiographic evaluation of extremely preterm children may not be indicated at age 6.5 years.

Postnatal nutritional intakes and hyperglycemia as determinants of blood pressure at 6.5 years of age in children born extremely preterm.

BACKGROUND: Adverse developmental programming by early-life exposures might account for higher blood pressure (BP) in children born extremely preterm. We assessed associations between nutrition, growth and hyperglycemia early in infancy, and BP at 6.5 years of age in children born extremely preterm. METHODS: Data regarding perinatal exposures including nutrition, growth and glycemia status were collected from the Extremely Preterm Infants in Sweden Study (EXPRESS), a population-based cohort including infants born <27 gestational weeks during 2004-2007. BP measurements were performed at 6.5 years of age in a sub-cohort of 171 children (35% of the surviving children). RESULTS: Higher mean daily protein intake (+1 g/kg/day) during postnatal weeks 1-8 was associated with 0.40 (±0.18) SD higher diastolic BP. Higher mean daily carbohydrate intake (+1 g/kg/day) during the same period was associated with 0.18 (±0.05) and 0.14 (±0.04) SD higher systolic and diastolic BP, respectively. No associations were found between infant growth (weight, length) and later BP. Hyperglycemia and its duration during postnatal weeks 1-4 were associated primarily with higher diastolic BP z-scores. CONCLUSIONS: These findings emphasize the importance of modifiable early-life exposures, such as nutrition and hyperglycemia, in determining long-term outcomes in children born extremely preterm.

The Preterm Heart in Childhood: Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable Births.

BACKGROUND: Preterm birth has been associated with increased risk of cardiovascular morbidity in adult life. We evaluated whether preterm birth is associated with deviating cardiac structure and function before school start. METHODS AND RESULTS: In total, 176 children aged 6 years and born extremely preterm (EXPT; gestational age of 22-26 weeks) and 134 children born at term (control [CTRL]) were studied. We used echocardiography to assess left heart dimensions, geometry, and functions. Recording and off-line analyses of echocardiographic images were performed by operators blinded to group belonging. Body size, blood pressure, and heart rate were also measured. Rates of family history of cardiovascular disease and sex distribution were similar in the EXPT and CTRL groups. Heart rate and systolic blood pressure did not differ, whereas diastolic blood pressure was slightly higher in EXPT than CTRL participants. After adjusting for body surface area, left ventricular length, width, and aortic valve annulus diameter were 3% to 5% smaller in EXPT than CTRL participants. Left ventricular longitudinal shortening and systolic tissue velocity were 7% to 11% lower, and transversal shortening fraction was 6% higher in EXPT than CTRL participants. The EXPT group also exhibited lower atrial emptying velocities than the CTRL group. Sex, fetal growth restriction, or a patent ductus arteriosus in the neonatal period did not contribute to cardiac dimensions or performance. CONCLUSIONS: Six-year-old children born extremely preterm exhibit a unique cardiac phenotype characterized by smaller left ventricles with altered systolic and diastolic functions than same-aged children born at term.

Blood Pressure in 6-Year-Old Children Born Extremely Preterm.

BACKGROUND: Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. METHODS AND RESULTS: We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (<27 gestational weeks; n=171) and in age- and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. CONCLUSIONS: Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.

Preterm arteries in childhood: dimensions, intima-media thickness, and elasticity of the aorta, coronaries, and carotids in 6-y-old children born extremely preterm.

BACKGROUND: Preterm birth increases risk for adult cardiovascular disease. We hypothesized that arteries in 6-y-old children born preterm are narrower, with thicker intima-media and stiffer than in peers born at term. METHODS: Children born extremely preterm (EXP, n = 176, birthweights: 348-1,161 g) and at term (CTRL, n = 174, birthweights: 2,430-4,315 g) were included. Using ultrasonography, we determined diameters of the coronaries (CA), common carotid arteries (CCA) and aorta, the carotid intima media thickness (cIMT), and the stiffness index of the CCA and aorta. RESULTS: Arteries were 5-10% narrower in EXP than in CTRL (P < 0.005) but after adjustment for body surface area, diameter differences diminished or disappeared. EXP-children born small for gestational age exhibited similar arterial dimensions as those born appropriate for date. The cIMT was 0.38 (SD = 0.04) mm and did not differ between groups. Carotid but not aortic stiffness was lower in EXP than in CTRL. CONCLUSION: In 6-y-old children born extremely preterm, conduit arteries are of similar or smaller size than in controls born at term, and they have no signs of accelerated intima media thickening or arterial stiffening. While these findings are reassuring for these children and their families, the causal pathways from preterm birth to adult cardiovascular disease remain unknown.

Childhood cardiac outcome after intrauterine laser treatment of twin-twin transfusion syndrome is favourable.

AIM: Intrauterine laser treatment is used to alleviate abnormal circulatory load and cardiac morbidity affecting foetuses with twin-twin transfusion syndrome (TTTS). We conducted this childhood follow-up study to fill the gap in knowledge about final cardiac outcomes after such interventions. METHODS: We investigated 19 TTTS pairs - 11 male and eight female - with a mean age of four and a half years (range 1.1-9.9) using 2D, blood flow and tissue Doppler, 3D and speckle tracking echocardiography, and compared them with 19 age-matched and gender-matched singletons. RESULTS: The only observed differences in cardiac structure or function between the donors and recipients were related to diastolic ventricular filling. Recipients had a lower left ventricular ratio of early and late diastolic filling compared with their donor cotwins [1.48(0.35) versus 1.66 (0.28), p < 0.05], but not compared with singleton controls. All observations, except one, were within the reference limits. Speckle tracking could not demonstrate any group differences in systolic ventricular function, besides marginally lower ventricular strain in the donors than controls. CONCLUSION: Double survivors of laser-treated TTTS showed only minor within-pair differences in diastolic cardiac function at childhood follow-up. Cardiac function in TTTS twins compared well to singleton controls, suggesting a favourable long-term outcome.

Progression to first-degree heart block in preschool children exposed in utero to maternal anti-SSA/Ro52 autoantibodies.

AIMS: To study the children exposed in utero to maternal anti-SSA/Ro52 antibodies in terms of impaired atrioventricular (AV) conduction or disturbed myocardial performance, and to investigate the ability of prenatal Doppler to predict conduction abnormalities during childhood. METHODS: Fifty-seven children exposed in utero to anti-SSA/Ro52 antibodies were grouped in accordance with (A) prolonged AV time intervals in utero by Doppler or (B) normal findings and examined by ECG, 24-hour ECG and echocardiography. RESULTS: PR interval on ECG was longer in group A (n = 16) compared with that of group B (n = 41), 140 ± 24 ms vs. 121 ± 13 ms (p < 0.01). Six cases of 1°Atrioventricular block (AVB) developed in group A, giving an estimated prevalence of 10.5%, (95% confidence interval; 4.4-22.2%), progressing from normal sinus rhythm at 1 month of age. Prenatal Doppler predicted development of 1°AVB at follow-up with a sensitivity of 100%, Positive predictive value (PPV) 37.5%, LR+ 5.1, and Negative predictive value (NPV) 100%. Children in group A had a slightly higher myocardial performance index in flow and tissue Doppler imaging recordings. CONCLUSIONS: Ten per cent of children exposed in utero to anti-SSA/Ro52, with a normal ECG at birth or 1 month of age, progressed to 1°AVB during preschool years. Cases at risk can be identified by prenatal Doppler echocardiography.