In many preterm infants, the ductus arteriosus remains patent beyond the first few days of life. This prolonged patency is associated with numerous adverse outcomes, but the extent to which these adverse outcomes are attributable to the hemodynamic consequences of ductal patency, if at all, has not been established. Different treatment strategies have failed to improve short-term outcomes, with a paucity of data on the correct diagnostic and pathophysiological assessment of the patent ductus arteriosus (PDA) in association with long-term outcomes. Echocardiography is the selected method of choice for detecting a PDA, assessing the impact on the preterm circulation and monitoring treatment response. PDA in a preterm infant can result in pulmonary overcirculation and systemic hypoperfusion, Therefore, echocardiographic assessment should include evaluation of PDA characteristics, indices of pulmonary overcirculation with left heart loading conditions, and indices of systemic hypoperfusion. In this review, we provide an evidence-based overview of the current and emerging ultrasound measurements available to identify and monitor a PDA in the preterm infant. We offer indications and limitations for using Neonatologist Performed Echocardiography to optimize the management of a neonate with a PDA.

Oral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS) has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1) MTS and one oral finding and polydactyly, or 2) MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes severe hypoplasia of the cerebellar vermis, hypoplastic and dysplastic cerebellar hemispheres, marked enlargement of the posterior fossa, increased retrocerebellar collection of cerebrospinal fluid, abnormal brainstem, and frequently supratentorial abnormalities that occasionally include characteristic hypothalamic hamartomas. Additionally, two new JSRD neuroimaging findings (ascending superior cerebellar peduncles and fused thalami) have been identified. Tongue hamartomas, additional frenula, upper lip notch, and mesoaxial polydactyly are specific findings in OFD VI, while cleft lip/palate and other types of polydactyly of hands and feet are not specific. Involvement of other organs may include ocular findings, particularly colobomas. The majority of the patients have absent motor development and profound cognitive impairment. In OFD VI, normal cognitive functions are possible, but exceptional. Sequencing of known JSRD genes in most patients failed to detect pathogenetic mutations, therefore the genetic basis of OFD VI remains unknown. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD VI are significantly worse, suggesting a correlation with the more severe neuroimaging findings. Based on the literature and this study we suggest as diagnostic criteria for OFD VI: MTS and one or more of the following: 1) tongue hamartoma(s) and/or additional frenula and/or upper lip notch; 2) mesoaxial polydactyly of one or more hands or feet; 3) hypothalamic hamartoma.

Neonatal heart failure (HF) is a progressive disease caused by cardiovascular and non-cardiovascular abnormalities. The most common cause of neonatal HF is structural congenital heart disease, while neonatal cardiomyopathy represents the most common cause of HF in infants with a structurally normal heart. Neonatal cardiomyopathy is a group of diseases manifesting with various morphological and functional phenotypes that affect the heart muscle and alter cardiac performance at, or soon after birth. The clinical presentation of neonates with cardiomyopathy is varied, as are the possible causes of the condition and the severity of disease presentation. Echocardiography is the selected method of choice for diagnostic evaluation, follow-up and analysis of treatment results for cardiomyopathies in neonates. Advances in neonatal echocardiography now permit a more comprehensive assessment of cardiac performance that could not be previously achieved with conventional imaging. In this review, we discuss the current and emerging echocardiographic techniques that aid in the correct diagnostic and pathophysiological assessment of some of the most common etiologies of HF that occur in neonates with a structurally normal heart and acquired cardiomyopathy and we provide recommendations for using these techniques to optimize the management of neonate with HF.

The current diagnosis of Congenital Heart Disease (CHD) in neonates relies on echocardiography. Its limited availability requires alternative screening procedures to prioritise newborns awaiting ultrasound. The routine screening for CHD is performed using a multidimensional clinical examination including (but not limited to) auscultation and pulse oximetry. While auscultation might be subjective with some heart abnormalities not always audible it increases the ability to detect heart defects. This work aims at developing an objective clinical decision support tool based on machine learning (ML) to facilitate differentiation of sounds with signatures of Patent Ductus Arteriosus (PDA)/CHDs, in clinical settings. The heart sounds are pre-processed and segmented, followed by feature extraction. The features are fed into a boosted decision tree classifier to estimate the probability of PDA or CHDs. Several mechanisms to combine information from different auscultation points, as well as consecutive sound cycles, are presented. The system is evaluated on a large clinical dataset of heart sounds from 265 term and late-preterm newborns recorded within the first six days of life. The developed system reaches an area under the curve (AUC) of 78% at detecting CHD and 77% at detecting PDA. The obtained results for PDA detection compare favourably with the level of accuracy achieved by an experienced neonatologist when assessed on the same cohort.

Objective: Closed-loop automatic control (CLAC) of the fractional inspired oxygen (FiO₂) improved oxygen administration to preterm infants on respiratory support. We investigated whether a revised CLAC algorithm (CLAC_fast, ≤2 FiO₂adjustments/min), compared with routine manual control (RMC_only), increased the proportion of time with arterial haemoglobin oxygen saturation measured by pulse oximetry within prespecified target ranges (Target%) while not being inferior to the original algorithm (CLAC_slow: ≤0.3 FiO₂adjustments/min).Design: Unblinded randomised controlled crossover study comparing three modes of FiO₂control in random order for 8 hours each: RMC supported by CLAC_fastwas compared with RMC_onlyand RMC supported by CLAC_slow. A computer-generated list of random numbers using a block size of six was used for the allocation sequence.Setting: Two German tertiary university neonatal intensive care units.Patients: Of 23 randomised patients, 19 were analysed (mean±SD gestational age 27±2 weeks; age at randomisation 24±10 days) on non-invasive (n=18) or invasive (n=1) respiratory support at FiO₂>0.21.Main outcome measure: Target%.Results: Mean±SD [95% CI] Target% was 68%±11% [65% to 71%] for CLAC_fastversus 65%±11% [61% to 68%] for CLAC_slowversus 58%±11% [55% to 62%] for RMC_only. Prespecified hypothesis tests of: (A) superiority of CLAC_fastversus RMC_onlyand (B) non-inferiority of CLAC_fastversus CLAC_slowwith margin of 5% yielded one-sided p values of <0.001 for both comparisons.Conclusions: This revised and faster CLAC algorithm was still superior to routine care in infants on respiratory support and not inferior to a previously tested slower algorithm.Trial registration number: NCT03163108.

The hemodynamically relevant patent ductus arteriosus in preterm infants is not well defined. Different clinical and echocardiographic parameters are used and the diagnostic accuracy is unknown because of the lack of a gold standard definition. Our study evaluates the inter-observer repeatability of echocardiographic and Doppler-ultrasound parameters. This prospective observational study included 19 very low birth weight preterm infants (median [interquartile range]: gestational age 28.0 (28.0–29.0) weeks, birth weight 1130 (905–1321) g, postnatal age at measurement 8.7 (4.8–23.5) d) with a clinical suspicion of ductal patency in whom 27 repeated echocardiographic and Doppler-ultrasound examinations were performed within 30 min by 2 of 3 independent observers (54 measurements overall). The repeatability index (=2 times the standard deviation of the differences/mean of all measurements) according to Bland and Altman was used to assess repeatability of different parameters. The repeatability indices of the echocardiographic parameters (left Atrium-to-Aortic root-ratio, diameter of the patent ductus arteriosus at its narrowest part, the left-ventricular-preejection-period-to-ejection-time-ratio and the ratio of the velocity time integrals in the large vessels were 16, 21, 23 and 26 % respectively. The repeatability indices of Doppler-ultrasound measurements (resistance index in celiac artery and anterior cerebral artery) were 11 and 14 %, respectively. The inter-observer repeatability of all echocardiographic parameters was poor compared to that of resistance indices in peripheral vessels. Therefore, interventions for ductal patency should be indicated based on averaged repeated rather than single measurements, especially when measured values are close to their cut-off value - both in clinical routine and for study purposes.