Clinical and Bacteriologic Characteristics of Six Cases of Bifidobacterium breve Bacteremia Due to Probiotic Administration in the Neonatal Intensive Care Unit.

BACKGROUND: Bifidobacterium breve is widely used as a probiotic in preterm infants and children with congenital surgical conditions, however, some cases of probiotics-induced bacteremia have been reported recently. OBJECTIVES: To examine the clinical and bacteriologic features of Bifidobacterium breve bacteremia caused by a probiotic (BBG-01) in term and preterm infants. METHODS: We included 298 patients who were admitted to the neonatal intensive care unit of Miyagi Children's Hospital and were given BBG-01 as a probiotic within the period June 2014 to February 2019. We experienced six cases of B. breve bacteremia and assessed their features retrospectively. RESULTS: The incidence rate of B. breve bacteremia in our hospital was 2% (6/298), higher than reported previously. The median age at onset, corrected age, and weight of the patients was 8 days (range: 5-27 days), 35 weeks (range: 26-39 weeks), and 1,940 g (range: 369-2734 g), respectively. The bacteremia triggers were gastrointestinal perforations in two cases, food protein-induced enterocolitis syndrome in two cases, adhesive ileus in one case, ileal volvulus in one case, and aspiration pneumonia following esophageal atresia repair in one case. B. breve was detected on blood cultures after a median of 5 days 13 hours (range: 4 days 18 hours-9 days 13 hours). No patient demonstrated serious symptoms, such as septic shock. All patients received antibiotics and recovered without any sequelae. CONCLUSIONS: Ileus and intestinal mucosal damage, such as enteritis, can cause B. breve bacteremia. The incidence of B. breve bacteremia may be higher than reported previously and detection via culture may require a longer time than typically needed for more common bacteria. It is associated with a good prognosis.

Head titubation and irritability as early symptoms of Joubert syndrome with a homozygous NPHP1 variant.

BACKGROUND: Joubert syndrome is an autosomal recessive or X-linked genetic disease with a cerebellar vermis defect or hypoplasia, hypotonia, ocular dyskinesia, and mental retardation. In neonates, respiratory problems such as apnea and tachypnea are notable. CASE REPORT: We report a patient Joubert syndrome with a homozygous NPHP1 variant, who had head titubation with irritability, including exaggerated jitteriness and a marked Morrow reflex appeared soon after birth without neonatal respiratory problems. These symptoms decreased gradually and disappeared until 1 year. CONCLUSION: Irritability with head titubation may be an early clinical clue for the clinician to suspect Joubert syndrome.

Diagnostic Specificity of Cerebral Magnetic Resonance Imaging for Punctate White Matter Lesion Assessment in a Preterm Sheep Fetus Model.

Recent studies, using magnetic resonance imaging (MRI) to assess white matter injury in preterm brains, increasingly recognize punctate white matter lesions (PWML) as the primary lesion type. There are some papers showing the relationship between the size and number of PWML and the prognosis of infants. However, the histopathological features are still unknown. In this study, we experimentally induced periventricular leukomalacia (PVL) in a sheep fetus model, aiming to find whether MRI can visualize necrotic foci (small incipient lesions of PVL) as PWML. Three antenatal insults were employed to induce PVL in preterm fetuses at gestational day 101-117: (i) hypoxia under intrauterine inflammation, (ii) restriction of artificial placental blood flow, and (iii) restriction of artificial placental blood flow after exposure to intrauterine inflammation. MRI was performed 3-5 days after the insults, and standard histological studies of the PVL validated its findings. Of the 89 necrotic foci detected in histological samples from nine fetuses with PVL, 78 were visualized as PWML. Four of the lesions detected as abnormal findings on MRI could not be histologically detected as corresponding abnormal findings. The diagnostic sensitivity and positive predictive values of histologic focal necrosis visualized as PWML were 0.92 and 0.95, respectively. The four lesions were excluded from these analyses. These data suggest that MRI can visualize PVL necrotic foci as PWML 3-5 days after the injury induction. PWML can spontaneously become obscure with time after birth, so their accurate diagnosis in the acute phase can prevent overlooking mild PVL.

A novel PHOX2B gene mutation in an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease.

Congenital central hypoventilation syndrome is a disorder of respiratory control caused by mutations in the paired-like homeobox 2B gene. Mutations in the paired-like homeobox 2B gene are also responsible for Hirschsprung's disease. Variant Hirschsprung's disease is a rarer disorder that does not meet the diagnostic criteria of Hirschsprung's disease, although severe functional bowel obstruction persists. We present a case of an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease. A male infant who was diagnosed to have fetal growth restriction and polyhydramnios was delivered by emergency cesarean section at 30 weeks and 3 days of gestational age due to non-reassuring fetal status. The birth weight was 979 g, and intensive care was started immediately following delivery. The patient exhibited refractory apnea and was diagnosed with congenital central hypoventilation syndrome by genetic testing of the paired-like homeobox 2B gene. The patient also exhibited refractory functional bowel obstruction and was diagnosed to have variant Hirschsprung's disease through pathological examination of his intestinal specimens. The patient grew slowly but surely with intensive care including mechanical ventilation and parenteral nutrition. However, the patient repeatedly suffered from sepsis and died of fungemia at 197 days of age. This is the first congenital central hypoventilation syndrome case that was accompanied with variant Hirschsprung's disease, and the paired-like homeobox 2B mutation detected in this case (NM_003924.3: c.441G > C; p.(Gln147His)) is novel. This case suggests that the paired-like homeobox 2B mutation causes not only congenital central hypoventilation syndrome and Hirschsprung's disease, but also variant Hirschsprung's disease in humans. It also highlights the extreme difficulty in treating premature infants with severe and prolonged functional bowel obstruction.