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Background: Patent ductus arteriosus (PDA) ligation has been associated with adverse outcome. Insufficient adjustment for postnatal, pre-ligation confounders prevents differentiating between association and confounding by indication.

Objective: To determine association between PDA ligation and outcome in Swiss extremely preterms after adjusting for pre-ligation confounders.

Design/Methods: Population-based, retrospective cohort study of infants born below 28 weeks gestation between 2012-2016, excluding infants with major malformations. 5 units performed PDA ligation ≤10% ("low" group) and 4 units >10% ("high" group). Outcomes were compared using 1:1 propensity score matching within the sub-cohort of treated infants. Matching was achieved based on case-mix as well as on comorbidities occurring pre-ligation: IVH grades 3-4, NEC, sepsis, BPD.

Results: PDA ligation occurred in 6% of 575 infants in the "low" group and 18% of 567 infants in the "high" group. In the “low” group, 57% infants were medically treated for PDA and in the “high” group 55%. Figure 1 reveals outcome after PDA ligation in the "low" versus the "high" group. Figure 2 reveals the outcome after PDA ligation vs. medical treatment, after restricting the dataset to infants surviving at least to day 10 to avoid survival bias: most ligated patients were recruited when survival was stable (Figure 3).

Conclusions: Extremely preterms treated in units performing fewer PDA ligations had lower odds for adverse outcome at hospital discharge. Infants with PDA ligation had higher odds for adverse outcome after propensity score matching for case-mix and pre-ligation confounders. These results may guide a revision of PDA ligation practice in Switzerland.

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Background: Although indomethacin and ibuprofen are standard treatments for hemodynamically significant patent ductus arteriosus (hsPDA), they are associated with renal impairment and gastrointestinal complications. We have previously reported the safety and feasibility of intravenous paracetamol administration for hsPDA closure in indomethacin- or ibuprofen-resistant preterm infants or in preterm infants for whom the use of these agents was contraindicated. There have been few reports that measured the plasma paracetamol concentrations in preterm infants after intravenous paracetamol administration for treating hsPDA.

Methods: Paracetamol (15 mg/kg every 6 h for 3 days) was administered to preterm infants with hsPDA who were resistant to indomethacin or ibuprofen or to those for whom these agents were contraindicated. Plasma paracetamol concentrations, serum aminotransferases and creatinine concentrations, and urine outputs were measured. The Rumack–Matthew nomogram was used to interpret paracetamol concentrations to assess potential hepatotoxicity.

Results: Paracetamol was administered to 16 preterm infants. hsPDA closure or narrowing was observed in 14 infants, with the need for surgical closure totally avoided in 7 cases. In 3 infants, elevated serum creatinine concentrations (1.62, 2.90, and 2.47 mg/dL, respectively) and high plasma paracetamol concentrations (41.0, 26.4, and 116.7 μg/mL, respectively) were observed. Although these were above the high-risk line on the Rumack–Matthew nomogram, no paracetamol-related side effects or adverse events were reported.

Conclusion: Intravenous paracetamol administration was effective for hsPDA. However, in patients with impaired renal function, plasma paracetamol concentrations were above the high-risk line for potential hepatotoxicity. Therefore, further pharmacokinetic studies and long-term follow-up are needed for safety assessment.

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Background & Aims: Our group demonstrated that a PDA severity score (PDAsc) on postnatal day 2 predicts chronic lung disease or death (CLD/Death). We hypothesise that in preterm infants at high risk of developing CLD/Death based on a PDAsc, early treatment with Ibuprofen compared with placebo will result in a reduction in CLD/Death.

Methods: This was a randomised two arm pilot study of 60 infants <29 weeks’ gestation. Infants with a high PDAsc (≥5.0) at 36–48 hours of age were randomised to receive either Ibuprofen or Placebo intravenously. The primary outcome was CLD/Death. Analysis was performed on an intention to treat basis. A post hoc analysis compared successful PDA closure in the Ibuprofen Group to infants who maintained ductal patency in the Placebo Group.

Results: Thirty infants were assigned Ibuprofen and 30 received placebo. There was no difference in the primary outcome (Table). Post hoc analysis revealed lower rates of the primary outcome and chronic lung disease in infants in the Ibuprofen arm (Table). Thirteen infants with a PDAsc <5.0 were also followed. The Figure illustrates the progression of echocardiography markers in the groups (Figure).

Conclusion: In the primary analysis, treatment with Ibuprofen did not result in a reduction in the rate of the primary outcome or its components. Future RCTs should focus on comparing early shunt elimination with prolonged exposure to the ductal shunt. Early shunt elimination in preterm infants with a PDA changes underlying physiology and may reduce respiratory morbidity when compared to infants with prolonged shunt exposure.

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Introduction. It has been shown that blood concentrations of NT-proBNP may be useful in identifying preterm infants at risk of haemodynamically significant patent ductus arteriosus (hsPDA) and its complications.

The aim of the study was to assess predictive value of serum NT-proBNP levels for early PDA closure in very preterm newborns.

Methods. 52 infants <32 weeks’ gestation aged <72 hours with PDA diameter >1.5 mm were involved into a randomised study. 27 (52%) of them were treated with ibuprofen or paracetamol starting within the first 3 days of life. Expectant management was applied to 25 (48%) infants. All patients underwent planned echocardiographic (daily) and two serum NT-proBNP measurements at median (IQR) ages of 2 (1-2) and 8 (8-9) days.

Results. The groups were similar in terms of birth weight, gestational age, prevalence of perinatal risk factors, incidence of hsPDA, and early neonatal morbidity. Primary ductus closure occurred in 24 (89%) treated infants and in 21 (84%) infants managed expectantly. Initial concentrations of NT-proBNP were not different between the groups. By the 8^th day median NT-proBNP values in both groups significantly decreased but remained similar. NT-proBNP serum concentrations on the second day of life could reliably predict ductus closure within the first 10 days after birth in treated babies (the AUC was significant 0.81 [95% CI: 0.58–0.99]) but not in infants who were managed expectantly.

Conclusions. Serum NT-proBNP concentrations on the second day of life could reliably predict early PDA closure in treated but not in expectantly managed very preterm infants.

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Background. Patent ductus arteriosus (PDA) treatment remains controversial. Modeling on the predictive capacity of spontaneous closure would help in decision making process.

Aim. To design a predictive model of early spontaneus closure of PDA.

Methods: Infants <29 weeks of gestational age (GA) were scanned for PDA (screening) between 18-72 h of postnatal age (PNA) and then serially, if indicated. PDA treatment was decided according to Echo and clinical parameters. A PDA score (range= 0-18) was retrospectively applied (Sehgal et al 2013, modified). The association between Echo and perinatal variables with early spontaneus closure was examined.

Results: Among 87 eligible infants (median GA=27 weeks and PNA at screening=42 h), 24 were excluded due to contraindication of treatment leading to 63 infants for analyses. Of them, 42 infants had conservative management (screening score 4) and 21 received ibuprofen treatment at PNA 69h (screening score=8; treatment score=12). Among them, 7 infants were treated at screening and 14 after serial scans. GA, birth weight and cord pH were associated with early spontaneus closure; while advanced resuscitation, absent/reverse diastolic velocity in descending aorta and screening score were associated with ibuprofen treatment. Screening score predicted no early spontaneus closure with a cut-off value=6.5 (AUC=0.87, sensitivity=76.2%, specificity=78.6%). Multiple regression analysis showed that the best predictive model of early spontaneus PDA closure followed the equation:

[log(p/1-p) = 34.235-1.420*GA+0.533*screening PDA score].

Conclusion. The best predictive model of early spontaneus PDA closure included GA and PDA score at screening. This model may help clinicians in decision making for PDA treatment.

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Background: Most neonatal units reserve PDA ligation for ventilator dependent babies.

Objectives:

1.Compare outcomes between early and late (>28days) ligation groups.

2. Clinical and demographic factors predicting early extubation (≤ 7days) after ligation.

Methods: Retrospective review of preterm babies who underwent PDA ligation between 2009-2019. Decision for ligation was based on clinical and echocardiogram features.

Results: A total of 133 babies were ligated with mean gestational age (± standard deviation) and birth weight of 25±1.6 weeks and 757±211 grams respectively. Median age (Inter-quartile range) for ligation was 32 days (25-42) with median duration of hospital stay 113.5 days (99-136). 11 babies died before discharge. There is no difference in demographics between two groups. Both groups had similar clinical outcomes including Bayley’s score at 2 years. Numbers of babies with severe bronchopulmonary dysplasia (BPD) were lower in early group (63% vs 81%, p =0.02). With regression analysis, only age at ligation was positively associated with severe BPD with odds ratio of 1.1 (1.0-1.1). Early ligation had marginally less duration of hospital stay (median 110 vs 114) [adjusted Hazard ratio: 0.98 (0.97 to 0.99)]. With regression analysis, early extubation as the dependent outcome and birth gestational age, birth weight and age at ligation as independent factors, none of the factors were significant.

Conclusion: If early extubation is the primary reason for PDA ligation, timing of ligation did not make any difference. Similar long-term outcomes in both early and late ligation groups except the babies with severe BPD were less in early ligation group.

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Background & Aims: Infants born to mothers with gestational diabetes mellitus (GDM) have impaired myocardial performance and are at risk of pulmonary hypertension (PH). Myocardial deformation and left ventricular (LV) rotational mechanics remain relatively unexplored in this population. We aimed to assess LV and right ventricular (RV) function in GDM infants and compare them to healthy controls.

Methods: We studied 40 infants with maternal GDM and 40 infants of healthy mothers. Three echocardiograms were carried out over the first 3 days after birth to measure LV and RV function using speckle tracking echocardiography (STE), LV rotational mechanics and pulmonary vascular resistance. GDM infants were further assessed based on maternal insulin need.

Results: GDM infants had a lower gestation at birth and a thicker septal wall, a higher LV eccentricity index (indicating septal bowing) and a higher PAATi (indicating higher pulmonary vascular resistance) (Table 1). GDM infants had lower LV strain, systolic and early diastolic strain rates, lower RV strain and early diastolic strain rates (Figure 1). By day 3, GDM infants had higher twist, torsion and higher LV twist and untwist rates (Figure 2). GDM status was an independent predictor of LV and RV function and pulmonary vascular resistance (p=<0.01).

Conclusion: GDM results in important changes in LV and RV function and pulmonary vascular resistance. LV diastolic dysfunction may explain the increase in PVR and the resulting decrease in RV function. LV twist increase in GDM infant may be a compensatory mechanism for the lower longitudinal function in this cohort.