Biochemical surveillance versus clinical observation of term infants born after prolonged rupture of membranes - A quality assurance initiative.

AIM: To examine whether biochemical surveillance vs clinical observation of term infants with prolonged rupture of membranes as a risk factor for early-onset sepsis is associated with differences in patient trajectories in maternity and neonatal intensive care units. METHODS: A retrospective study of live-born infants with gestational age ≥ 37 + 0 weeks born after prolonged rupture of membranes (≥24 h) in four Norwegian hospitals 2017-2019. Two hospitals used biochemical surveillance, and two used predominantly clinical observation to identify early-onset sepsis cases. RESULTS: The biochemical surveillance hospitals had more C-reactive protein measurements (p < 0.001), neonatal intensive care unit admissions (p < 0.001) and antibiotic treatment (p < 0.001). Hospitals using predominantly clinical observation initiated antibiotic treatment earlier in infants with suspected early-onset sepsis (p = 0.04) but not in infants fulfilling early-onset sepsis diagnostic criteria (p = 0.09). There was no difference in antibiotic treatment duration (p = 0.59), fraction of infants fulfilling early-onset sepsis diagnostic criteria (p = 0.49) or length of hospitalisation (p = 0.30), and no early-onset sepsis-related adverse outcomes. CONCLUSION: The biochemical surveillance hospitals had more C-reactive protein measurements, but there was no difference in antibiotic treatment duration, early-onset sepsis cases, length of hospitalisation or adverse outcomes. Personnel resources needed for clinical surveillance should be weighed against the limitation of potentially painful procedures.

A young woman with a transfusion-related pregnancy complication. / En ung kvinne med transfusjonsutløst svangerskapskomplikasjon.

BACKGROUND: Individuals with the K0 phenotype are extremely rare. They may develop anti-Ku antibodies, which react with all antigens of the Kell blood group system, thereby leading to haemolytic transfusion reactions and haemolytic disease of the fetus and newborn. CASE PRESENTATION: A primigravida who was transfused with one unit of red blood cells due to iron deficiency anaemia developed anti-Ku antibodies. The pregnancy was closely monitored by ultrasound and antibody titres. Maternal autologous blood collection was performed twice during the last trimester as back-up in case of maternal peripartum bleeding, and a few frozen K0 red blood cell units were provided in case of severe fetal anaemia. At gestational week 36+6, labour was induced due to increasing antibody titres and high blood velocities in the fetal middle cerebral artery during systole. The woman was delivered vaginally without need for transfusion. The infant was diagnosed with haemolytic disease of the fetus and newborn and treated with phototherapy, repeated infusions of intravenous immunoglobulin and iron supplements until normalisation of haemoglobin at three months of age. INTERPRETATION: Iron deficiency anaemia should be treated primarily with iron supplementation before considering blood transfusions, which pose the risk of developing alloantibodies that can cause transfusion complications and haemolytic disease of the fetus and newborn.

Novel mutations in the gene encoding ATP binding cassette protein member A3 (ABCA3) resulting in fatal neonatal lung disease.

AIM: To investigate whether intractable respiratory distress syndrome in three Norwegian term infants was due to mutations in the ABCA3 gene. METHODS: The genes encoding SP-B (SFTPB), SP-C (SFTPC), and ABCA3 (ABCA3) were sequenced from the parents of one infant and two unrelated infants with fatal neonatal lung disease. Lung tissue was examined by histology, immunohistochemistry and electron microscopy. RESULTS: Novel ABCA3 mutations were identified in each family. One patient had a phenotype differing from previous descriptions of this disease with an initial uneventful period. The diagnosis was established 19 years after death by analysing DNA material from the parents, with an ABCA3 mutation identified on one allele in each parent. The other two infants had more typical clinical courses with the onset of respiratory symptoms immediately after birth. ABCA3 mutations were identified on both alleles from these two infants, and electron microscopy of alveolar type 2 cells demonstrated abnormal lamellar body formation characteristic of this disorder. CONCLUSION: ABCA3 mutations were the basis for lung disease in all three patients. Children with lung disease due to ABCA3 deficiency may not have symptoms at birth. The finding of five novel mutations indicates allelic heterogeneity for ABCA3 mutations within the Norwegian population.

Albumin mixed with meconium attenuates pulmonary dysfunction in a newborn piglet model with meconium aspiration.

We hypothesized that lipids and bile acids in meconium may induce pulmonary insufficiency in newborns. Because albumin may bind these components we studied the effect of albumin on meconium-induced lung injury in piglets. We measured concentration of FFA in the meconium (110 mg dry weight/mL) and added albumin to provide a molar FFA to albumin ratio of 1:1. Newborn piglets, 0-2 d of age, artificially ventilated and exposed to hypoxemia by ventilation with 8% O2, were randomized to group A receiving meconium (n = 12) or group B receiving meconium + albumin (n = 12), 3 mL/kg intratracheally. The animals were reoxygenated for 8 h. Reoxygenation was started when mean blood pressure was <20 mm Hg or base excess was <-20 mM. Pulmonary function was assessed in parallel with pulmonary hemodynamics. From the start of reoxygenation and the next 8 h we found a significant difference (by ANOVA) between the two groups in oxygenation index (p = 0.005), with an increase from 1.6 +/- 0.2 to 6.1 +/- 6.8 (p = 0.04) in the meconium group and from 1.8 +/- 0.3 to 3.1 +/- 3.1 (NS) in meconium + albumin group. There were also significant differences (by ANOVA) between the groups in favor of the treatment group concerning need of inspired fraction of O2, mean airway pressure, dynamic compliance of the respiratory system, time constant, ventilation index, and pulmonary vascular resistance. In conclusion, albumin given concurrently with meconium significantly reduced detrimental effects of meconium aspiration in the lungs of newborn piglets.

Comparison of pulmonary and inflammatory effects of lipid- and water-soluble components in meconium in newborn piglets.

To understand the pathogenesis of meconium aspiration syndrome, we compared the pulmonary and inflammatory effects of the water and lipid extracts of human meconium instilled into the lungs of newborn piglets. The piglets were artificially ventilated, made hypoxemic, and randomized into three groups. At start of reoxygenation, 3 ml/kg of one of the following mixtures was instilled intratracheally: (1) meconium (n = 12); (2) water extract of meconium (n = 12), and (3) lipid extract of meconium (n = 12). During 8 h of reoxygenation, hemodynamics, pulmonary gas exchange, lung mechanics, and interleukin-8 concentrations in tracheobronchial aspirates were monitored. Oxygenation index (p = 0.04) and mean airway pressure (p = 0.04) increased more in the lipid extract group than in the water extract group. Dynamic compliance and mean arterial blood pressure decreased (p < 0.05) in the meconium and lipid extract groups, but not in the water extract group. At 8 h of reoxygenation, the interleukin-8 concentration in the tracheobronchial aspirates was three times higher in the lipid extract group as compared with the water extract group (110 +/- 102 vs. 37 +/- 27 pg/ml; p = 0.02). In conclusion, pulmonary dysfunction in meconium aspiration syndrome is caused by both the water- and lipid-soluble fractions of meconium, with stronger inflammatory and more detrimental effects promoted by the lipid extract than the water extract.

Intratracheal albumin reduces interleukin-8 in tracheobronchial aspirates in piglets after meconium aspiration.

Meconium aspiration induces pulmonary inflammation and reduces surfactant function. We hypothesized that albumin mixed with meconium attenuates pulmonary inflammation and improves surfactant function after meconium aspiration. We measured the concentration of free fatty acids (FFA) in the meconium (110 mg dry weight/mL) and added albumin to provide a molar FFA:albumin ratio of 1:1. Newborn piglets, 0-2 day of age, artificially ventilated and exposed to hypoxemia by ventilation with 8% O2, were randomized to group A receiving meconium (n = 12), or group B receiving meconium + albumin (n = 12), 3 ml/kg intratracheally. The animals were reoxygenated for 8 h. Reoxygenation was started when mean arterial blood pressure was < 20 mm Hg or base excess was < -20 mmol/L. During 8 h of reoxygenation the interleukin-8 concentrations in tracheobronchial aspirates increased 5-fold more in the meconium vs. the meconium + albumin groups (93 +/- 56 vs. 18 +/- 4 pg/mL, p < 0.005). There were no differences between the groups for tumor necrosis factor alpha in tracheobronchial aspirates, recruitment of inflammatory cells in the airspaces or surfactant function in bronchoalveolar lavage fluid. In conclusion, albumin significantly decreased interleukin-8 concentrations in tracheobronchial aspirates after meconium aspiration.