Naoki Masaoka

Blood pressure and urine output during the first 120 h of life in infants born at less than 29 weeks’ gestation related to umbilical cord milking

Objective: To investigate the effects of umbilical cord milking on cardiopulmonary adaptation in very low birth weight infants. Patients and methods: This study was the secondary analysis of a randomised control study of the effect of umbilical cord milking in premature infants. Forty singleton infants born between 24 and 28 weeks’ gestation were randomly assigned to groups in which the umbilical cord was clamped either immediately after birth (control group, n = 20) or after umbilical cord milking (milked group, n = 20). Blood pressure, heart rate, urine output, fluid intake, and ventilatory index values in both groups were measured during the first 120 h after birth. Results: There were no significant differences in gestational age or birth weight between the two groups. The initial haemoglobin value was higher in the milked group (mean (SD) 16.5 (1.4) g/dl in the milked vs 14.1 (1.6) g/dl in the control; p<0.01). During the first 12 h, blood pressure was significantly higher in the milked group. Urine output in the milked group was higher than that in the control group during the first 72 h. There were no significant differences in heart rate, water intake, or ventilatory index values between the groups. Conclusion: Umbilical cord milking may facilitate early stabilisation of both blood pressure and urine output in very low birth weight infants.

Transplacental effects of allopurinol on suppression of oxygen free radical production in chronically instrumented fetal lamb brains during intermittent umbilical cord occlusion

Objective. To evaluate the transplacental effect of allopurinol, which acts as a xanthine oxidase inhibitor and free radical scavenger, on inhibiting the production of superoxides during intermittent partial umbilical cord occlusion. Methods. Using four chronically instrumented fetal lambs, ewes received 400 mg allopurinol over a period of two hours. Concentrations of allopurinol and oxypurinol in blood samples from mothers and fetuses and fetal brain microdialysis perfusate were measured by HPLC. In another three cases the production of superoxide during intermittent umbilical cord occlusion was studied by measurement of chemiluminescence in perfusate before and after administration of Allopurinol. Results. (i) Allopurinol concentration in mothers had reached equilibrium by 30 min after starting administration and maintained a concentration about 6 μg/ml. Allopurinol concentration in fetuses increased gradually and reached 2.25 ± 0.54 μg/ml at 120 min; (ii) Oxypurinol concentration in both mothers and fetuses increased during administration of allopurinol; (iii) Concentrations of allopurinol and oxypurinol in the perfusates reached 0.32 ± 0.12 μg/ml, 0.53 ± 0.22 μg/ml at 120min respectively; and (iv) Administration of allopurinol significantly suppressed superoxide production during intermittent partial umbilical cord occlusion. Conclusion. These results demonstrated a good transfer of allopurinol from mother to fetus and suggested the possibility of intrauterine treatment to inhibit fetal brain damage resulting from increased oxygen free radicals.

Nitric Oxide and Endothelin 1 during Postnatal Life

Nitric oxide (NO) is a potent vasodilator produced by endothelial cells. Endothelin 1 (ET-1), another agent made by endothelial cells, is the most potent vasoconstrictor known to date. Endogenous NO and ET-1 may play a part in the normal physiological pulmonary vascular changes during the postnatal period. However, the changes of NO and ET-1 in healthy neonates have not been defined. We determined serum NO metabolites, i.e., nitrites and nitrates, and plasma ET-1 in 19 healthy neonates at birth (cord blood) and at ages 5 and 30 days. The sums of serum nitrite and nitrate (NOx) levels were 27.5 +/- 12.8, 53.8 +/- 14.2, and 38.3 +/- 13.2 mumol/l at birth, age 5 days, and age 30 days, respectively. The plasma ET-1 concentrations were 3.9 +/- 1.6, 1.1 +/- 0.2, and 1.1 +/- 0.2 x 10(6) mumol/l at birth, age 5 days, and age 30 days, respectively. These changes in healthy neonates suggest the presence of active physiological roles for NO and ET-1 in circulatory adaptation to extra-uterine life.

Kinetics of serum S100B in newborns with intracranial lesions

Background: The purpose of the present study was to evaluate the usefulness of serum S100B as a clinical marker of intracranial lesions in newborns.

Effect of magnesium sulfate treatment on neonatal bone abnormalities.

OBJECTIVE It has been reported that neonatal bone abnormalities occur as a result of long-term intravenous magnesium administration (MgSO4) to pregnant women. The purpose of this retrospective study was to evaluate the frequency of such abnormalities and the clinical background of both mothers and neonates. PATIENTS AND METHODS We reviewed maternal (114 cases) and neonatal (139 cases) charts from all pregnant women who received intravenous MgSO4 administration for preterm labor and preeclampsia between June 1, 1992, and May 31, 1994. All chest X-ray films were obtained within 48 h after birth and reviewed by a doctor who was unaware of the clinical data. Radiolucent transverse metaphyseal bands of the proximal humerus were considered as abnormal. The subjects were divided into affected (group 1 and 1a) and unaffected (group 2 and 2a) groups. Neonates born to pregnant women given no MgSO4 at the same period, were considered as control. RESULTS The total number of bone abnormalities in the offspring of mothers receiving MgSO4 amounted to 13 (11.4%). Group 1 consisted of 13 cases and group 2 of 101 cases. In the control group bone abnormalities were not observed (p < 0.05). Significant differences were found between groups 1 and 2 in the gestational ages at the start of MgSO4 administration and at delivery, and in the total duration of administration and doses of MgSO4. Also, cases of multiple pregnancy and pregnancy complicated with impaired glucose tolerance were more prevalent in group 1. According to the results obtained from 139 neonates, cases showing low Apgar and high magnesium score and those receiving respiratory support were more noticeable in group 1a (15 cases). CONCLUSIONS The gestational ages and the total doses of MgSO4 in pregnant women were the main factors related to the onset of neonatal bone abnormalities, but other factors also have a possible bearing on the condition. In addition, the cases with onset of bone abnormality seemed to be associated with symptoms attributable to hypermagnesemia of neonates.

Very low-density lipoprotein in the cord blood of preterm neonates.

Human fetuses have markedly low levels of serum lipids and a unique lipoprotein profile with respect to quality, with low-density lipoprotein (LDL)-like particle as the dominant cholesterol carrier. However, little is known about triglyceride (TG) distribution. In addition, lipid metabolism is important in lung development, with indications that TG from very low-density lipoprotein (VLDL) is essential for surfactant synthesis. We investigated TG distribution in preterm neonate cord blood and the relationship of VLDL-TG levels with respiratory distress syndrome (RDS). The study included 103 appropriate-for-gestational-age neonates (61 males). We performed serum lipoprotein analyses in cord blood by high-performance liquid chromatography with gel permeation columns. Term neonates had low cord blood TG concentrations distributed equally to the LDL and VLDL fractions. However, preterm neonates had even lower TG concentrations, with VLDL as the dominant carrier. The LDL-TG and high-density lipoprotein-TG concentrations in cord blood increased gradually with gestational age, but cord blood VLDL-TG concentrations increased dramatically from 32 to 34 weeks of gestational age. Neonates with RDS exhibited no RDS-specific lipoprotein profile; however, most were born before the timing of the dramatic VLDL-TG increase. Our results suggest that 34 weeks of gestation is a critical period for TG metabolism, indicating the need for evaluation of the lipid nutritional state in preterm neonates.

Changes in Purine Metabolism and Production of Oxygen Free Radicals by Intermittent Partial Umbilical Cord Occlusion in Chronically Instrumented Fetal Lambs

Objective: Undetected umbilical‐cord compression has been suggested to be implicated in unexplained fetal brain damage. We tested the hypothesis that the generation of oxygen‐free radicals (OFRs) during intermittent partial umbilical cord occlusion might play a causal role in antenatal CNS injury.

Fetal Blood Values by Percutaneous Umbilical Blood Sampling

Cordocentesis was performed, and fetal blood was sampled in 81 of 93 attempted procedures. In 45 fetuses, who proved to be normal later by normal pregnancy outcome, hematological analyses and blood chemistries were performed. The results showed an increase in total white blood cell count, red blood cell, hemoglobin, hematocrit and platelet count, while the mean corpuscular volume and mean corpuscular hemoglobin decreased during gestation. Total protein and albumin concentrations increased during pregnancy. These results provide information for the diagnosis of fetal hematological disorders, and assist in making decisions for possible fetal therapy in utero.

Rhabdomyolysis caused by tocolytic therapy with oral ritodrine hydrochloride in a pregnant woman with placenta previa

Oral‐ritodrine‐hydrochloride‐induced rhabdomyolysis is rare. We report a case of oral‐ritodrine‐hydrochloride‐induced rhabdomyolysis in a pregnant woman with placenta previa without neuromuscular disorders. The patient was a 30‐year‐old, Japanese primigravida woman, who became pregnant spontaneously. At 23 gestational weeks, she was diagnosed as having placenta previa and prophylactic oral ritodrine hydrochloride (15 mg/day) was initiated. At 29 1/7 gestational weeks, she was referred to our hospital for perinatal management of placenta previa. Two days thereafter, vaginal bleeding accompanied by frequent uterine contractions occurred and she was admitted. On admission, laboratory tests revealed an abnormal increase of blood creatine kinase (CK) value of 7200 IU/L. CK‐MB isoenzyme was 208 IU/L. Aspartate transaminase (163 IU/L), alanine transaminase (74 IU/L) and lactate dehydrogenase (536 IU/L) levels were also increased. The patient started to complain of extreme muscle pain in her upper and lower limbs and general weakness. The next day, laboratory tests revealed a tremendous increase of blood CK level of 87 300 IU/L, a blood myoglobin level of 11 200 ng/mL, and a urinary myoglobin level of 615 ng/mL. An emergency cesarean section was carried out. After delivery, the laboratory data improved gradually with the CK levels at 107 IU/L. If patients complain of muscular symptoms following oral ritodrine hydrochloride use, physicians should consider rhabdomyolysis.

The effects of sivelestat sodium hydrate on uterine contraction and the concentration of maternal and fetal blood cytokines in a sheep model of intra-amniotic infection induced by lipopolysaccharide.

Objective. To evaluate the effects of a neutrophil elastase inhibitor, sivelestat sodium hydrate, in a sheep model of intra-amniotic infection(IAI) induced by lipopolysaccharide (LPS) injected into the intra-amniotic compartment. Methods. We examined 15 chronically instrumented ewes, the ewes were assigned randomly as group A (five ewes) administered an antibiotic after LPS administration, group B (five ewes) administered a neutrophil elastase inhibitor (0.2 mg/kg/h) with an antibiotic after LPS administration, and group C (five ewes) a sham operation group. Uterine contraction was evaluated by fetal tracheal pressure and concentrations of PGE2, IL-6, IL-8, TNF-α in maternal and fetal blood before and after LPS administration were measured chronologically. Results. (1) All ewes of group A delivered within 72 h, but only one ewe of group B delivered. Uterine contraction of group B was suppressed about 60% in comparison with group A. (2) Maternal blood concentrations of PGE2, IL-6, IL-8, and TNF-α level of group A increased chronologically and when compared with groups B and C the increase was significantly higher. (3) There were no significant changes in the fetal blood cytokines in any of the three groups. Conclusion. Administration of neutrophil elastase inhibitor might suggest a useful strategy to prevent premature delivery resulting from intrauterine infection.