Treatment of Symptomatic Focal Hepatic Hemangioma with Propranolol in Neonates: Is It Efficient?

Hepatic hemangiomas (HH) - classified into congenital hepatic hemangiomas (CHH) or infantile hepatic hemangiomas (IHH) - are benign vascular tumors that are mainly asymptomatic, but may cause clinical problems that require treatment. While focal, multifocal, and diffuse IHH are responsive to propranolol treatment, CHH is mainly focal and thought to be resistant to treatment with propranolol. The clinical and imaging distinctions between CHH and IHH in cases of focal lesions can be challenging, while histopathological distinction is mostly lacking in the clinical setting. We report 4 neonatal symptomatic cases of focal HH treated with propranolol, with partial or complete resolution of the tumor, and the positive hemodynamic effect of propranolol in one case. We believe that although clear differentiation cannot be achieved between CHH and IHH without histopathological examination in cases of focal HH in neonates, propranolol treatment should be attempted in symptomatic cases since its benefits outweigh the possible small risk of side effects of propranolol.

Postnatal treatment for children with fetal and neonatal alloimmune thrombocytopenia: a multicentre, retrospective, cohort study.

BACKGROUND: Children affected by fetal and neonatal alloimmune thrombocytopenia (FNAIT) are at risk of severe intracranial haemorrhage. Management in the postnatal period is based on sparse evidence. We aimed to describe the contemporary management and outcomes of patients with FNAIT in high-income countries. METHODS: In this multicentre, retrospective, cohort study, we set up a web-based registry for the collection of deidentified data on the management and course of neonates with FNAIT. Eight centres from seven countries (Australia, Norway, Slovenia, Spain, Sweden, the Netherlands, and the USA) participated. Eligibility criteria comprised neonates with FNAIT being liveborn between Jan 1, 2010, and Jan 1, 2020; anti-human platelet antigen (HPA) alloantibodies in maternal serum; confirmed maternal and fetal HPA incompatibility; and bleeding detected at antenatal ultrasound, neonatal thrombocytopenia (<150 × 109 platelets per L), or both in the current or previous pregnancy. Clinical data were retrieved from local medical records of the first neonatal admission and entered in the registry. The key outcome was the type of postnatal treatment given to neonates with FNAIT. Other outcomes were daily median platelet counts in the first week of life, median platelet count increment after first unmatched versus first matched transfusions, and the proportion of neonates with mild or severe bleeding. FINDINGS: 408 liveborn neonates with FNAIT were entered into the FNAIT registry, of whom 389 from Australia (n=74), Norway (n=56), Slovenia (n=19), Spain (n=55), Sweden (n=31), the Netherlands (n=138), and the USA (n=16) were included in our analyses. The median follow-up was 5 days (IQR 2-9). More neonates were male (241 [64%] of 379) than female (138 [36%]). Severe thrombocytopenia (platelet count <50 × 109 platelets per L) was reported in 283 (74%) of 380 neonates, and extreme thrombocytopenia (<10 × 109 platelets per L) was reported in 92 (24%) neonates. Postnatal platelet count nadir was higher in the no-treatment group than in all other groups. 163 (42%) of 389 neonates with FNAIT received no postnatal treatment. 207 (53%) neonates received platelet transfusions, which were either HPA-unmatched (88 [43%] of 207), HPA-matched (84 [41%]), or a combination of both (35 [17%]). The proportion of neonates who received HPA-matched platelet transfusions varied between countries, ranging from 0% (Slovenia) to 63% (35 of 56 neonates; Norway). Postnatal intravenous immunoglobulin treatment was given to 110 (28%) of 389 neonates (alone [n=19] or in combination with platelet transfusions [n=91]), with the proportion receiving it ranging from 12% (17 of 138 neonates; the Netherlands) to 63% (ten of 16 neonates; the USA) across countries. The median platelet increment was 59 × 109 platelets per L (IQR 35-94) after HPA-unmatched platelet transfusions and 98 × 109 platelets per L (67-134) after HPA-matched platelet transfusions (p<0·0001). Severe bleeding was diagnosed in 23 (6%) of 389 liveborn neonates, with one having a severe pulmonary haemorrhage and 22 having severe intracranial haemorrhages. Mild bleeding was diagnosed in 186 (48%) neonates. INTERPRETATION: Postnatal management of FNAIT varies greatly between international centres, highlighting the absence of consensus on optimal treatments. Our data suggest that HPA-matched transfusions lead to a larger median platelet count increment than HPA-unmatched transfusions, but whether HPA matching is also associated with a reduced risk of bleeding remains unknown. FUNDING: Sanquin.

Clinical Factors Influencing Endogenous Carbon Monoxide Production and Carboxyhemoglobin Levels in Neonates.

Carboxyhemoglobin (COHb) is an index of endogenous carbon monoxide formation during the hem degradation process and could be used to confirm hemolysis in neonates. The influence of other clinical factors on COHb values in neonates has not been fully investigated. We aimed to evaluate the influence of hemolysis, sepsis, respiratory distress, and postnatal age on COHb values. We retrospectively analyzed COHb measurements determined with a carbon monoxide-oximeter in 4 groups of term neonates: A-sepsis, B-respiratory distress, C-hemolysis, and D-healthy neonates. The mean COHb values were 1.41% (SD: 0.26), 1.32% (SD: 0.27), 2.5% (SD: 0.69), and 1.27% (SD: 0.19) (P<0.001) in groups A (n=8), B (n=37), C (n=16), and D (n=76), respectively. COHb in group C was significantly higher than in the other groups. There was a negative correlation between postnatal age and COHb in healthy neonates. A cut-off level of 1.7% had 93% (95% confidence interval [CI]: 89%-97%) sensitivity and 94% (95% CI: 90%-98%) specificity for diagnosis of hemolysis. COHb values were higher during the first days of life. We found that COHb levels in neonates with hemolysis were significantly higher and that the influence of sepsis and respiratory distress on COHb values was insignificant.

Genomic and phenotypic characterisation of invasive neonatal and colonising group B Streptococcus isolates from Slovenia, 2001-2018.

BACKGROUND: Group B Streptococcus (GBS) is the leading cause of invasive neonatal disease in the industrialized world. We aimed to genomically and phenotypically characterise invasive GBS isolates in Slovenia from 2001 to 2018 and contemporary colonising GBS isolates from screening cultures in 2018. METHODS: GBS isolates from 101 patients (invasive isolates) and 70 pregnant women (colonising isolates) were analysed. Basic clinical characteristics of the patients were collected from medical records. Antimicrobial susceptibility and phenotypic capsular serotype were determined. Whole-genome sequencing was performed to assign multilocus sequence types (STs), clonal complexes (CCs), pathogenicity/virulence factors, including capsular genotypes, and genome-based phylogeny. RESULTS: Among invasive neonatal disease patients, 42.6% (n = 43) were females, 41.5% (n = 39/94) were from preterm deliveries (< 37 weeks gestation), and 41.6% (n = 42) had early-onset disease (EOD). All isolates were susceptible to benzylpenicillin with low minimum inhibitory concentrations (MICs; ≤0.125 mg/L). Overall, 7 serotypes were identified (Ia, Ib, II-V and VIII); serotype III being the most prevalent (59.6%). Twenty-eight MLST STs were detected that clustered into 6 CCs. CC-17 was the most common CC overall (53.2%), as well as among invasive (67.3%) and non-invasive (32.9%) isolates (p < 0.001). CC-17 was more common among patients with late-onset disease (LOD) (81.4%) compared to EOD (47.6%) (p < 0.001). The prevalence of other CCs was 12.9% (CC-23), 11.1% (CC-12), 10.5% (CC-1), 8.2% (CC-19), and 1.8% (CC-498). Of all isolates, 2.3% were singletons. CONCLUSIONS: A high prevalence of hypervirulent CC-17 isolates, with low genomic diversity and characteristic profile of pathogenicity/virulence factors, was detected among invasive neonatal and colonising GBS isolates from pregnant women in Slovenia. This is the first genomic characterisation of GBS isolates in Slovenia and provides valuable microbiological and genomic baseline data regarding the invasive and colonising GBS population nationally. Continuous genomic surveillance of GBS infections is crucial to analyse the impact of IND prevention strategies on the population structure of GBS locally, nationally, and internationally.

Neonatal Cyanosis Due to Hemoglobin Variant: Hb F-Sarajevo.

Neonatal cyanosis is rarely due to hemoglobin variants with low oxygen affinity. We describe the clinical course and results of molecular genetic analysis of a boy who presented after birth with severe cyanosis. Arterial blood-gas analysis demonstrated a pronounced shift of the oxygen-hemoglobin dissociation curve to the right and molecular genetic analysis revealed a γ-globin variant, Hb F-Sarajevo. The patient presented is the second reported case of neonatal cyanosis due to this mutation, which was first described in 2012 by Zimmermann-Baer and coauthors. With the introduction of universal screening for congenital heart disease, the finding of low oxygen saturation will uncover more neonates with hemoglobinopathies with low oxygen affinity.

The role of carboxyhemoglobin measured with CO-oximetry in the detection of hemolysis in newborns with ABO alloimmunization.

OBJECTIVES: To evaluate carboxyhemoglobin (COHb) values measured with a CO-oximeter (Roche-cobas b 221) in jaundiced newborns with or without hemolysis and healthy controls in order to assess whether COHb measurement determined with a CO-oximeter could be used as an indicator of hemolysis in newborns with ABO alloimmunization. METHODS: A total of 86 term newborn infants were prospectively studied. The study cohort consisted of three subgroups: 18 infants with ABO HDN, 21 infants with hyperbilirubinemia without hemolytic disease who required phototherapy, and 47 healthy controls. The COHb, bilirubin, and Hb levels were measured. RESULTS: The three subgroups did not differ significantly with respect to birth weight, gestational age, gender, Apgar score, or mode of delivery. The ABO HDN infants had significantly higher COHb values than the healthy controls (median 2.4% versus 1.3%, p < 0.0005) and the group with hyperbilirubinemia without hemolytic disease (median 2.4% versus 1.3%, p < 0.0005), although the infants with hyperbilirubinemia without hemolytic disease did not have significantly higher COHb values compared with the healthy controls. The cut-off value of 1.7% COHb had 72% sensitivity and 97% specificity for confirming hemolysis in ABO alloimmunization. CONCLUSIONS: Our data show that COHb values determined with CO-oximeters are higher in newborns with hemolysis than in those without hemolysis. COHb measured with CO-oximeters could be used to confirm hemolysis in infants with ABO alloimmunization.

Head growth in infants with infantile spasms may be temporarily reduced.

Epileptic activity, as a component of epileptic encephalopathies, can interfere with brain growth and development. Infantile spasms as a syndrome represent such epileptic activity during the period of spasms and hypsarrhythmia. The rate of head growth in infants with infantile spasms during the period of spasms has not been studied previously. A retrospective study of head growth in 38 infants with infantile spasms and no other cause of abnormal head growth is presented. Mental outcome was assessed at follow-up. The mean head circumference of infants with infantile spasms was not significantly smaller than in the normal population, but the proportion of head circumference below the tenth percentile in the infantile spasms group was higher (27%). Head circumference below the tenth percentile in the fourth and fifth month after the onset of infantile spasms was significantly associated with later mental retardation (P = 0.004). There was no correlation with specific treatment of infantile spasms. Transiently diminished head growth in infants with infantile spasms coincides temporally with the onset of infantile spasms and "catches up" during remission of infantile spasms in favorable cases. This pattern can reflect the negative influence of epileptic activity on brain growth during the sensitive period. Head circumference can provide a reliable predictive value of mental outcome in children with infantile spasms.