Yukari Yada

Cytokine profiles of seventeen cytokines, growth factors and chemokines in cord blood and its relation to perinatal clinical findings.

Few papers have investigated the cytokine profiles of multiple cytokines in cord blood. We obtained cord blood samples from 224 infants admitted to our neonatal intensive care unit. Cytokine profiles of 17 cytokines were investigated using cytometric bead array technology. We found a wide variety of cytokines of various levels which ranged from 0.59pg/ml (in Interleukin (IL)-4) to 222.0pg/ml (in macrophage inflammatory protein-1beta. Pro-inflammatory cytokines were highly correlated with each other and with granulocyte-colony stimulating factor and IL-8. On the contrary, IL-5, IL-13, and IL-17 did not show any significant correlation with other cytokines. Several maternal factors were strongly related to several cytokines in cord blood. IL-6, IL-8 and monocyte chemotactic protein-1 were closely related to certain neonatal diseases in preterm neonates. Some cytokines may be regulated independently of each other, while others appear to work as a network affecting physiological and pathological conditions in the fetus.

Prolonged maternal magnesium administration and bone metabolism in neonates

BACKGROUND Magnesium sulfate (MgSO(4)) has been used as a tocolytic agent in cases of refractory preterm labor. Prolonged maternal administration of MgSO(4) may induce bone demineralization in the neonate. However, the effects of MgSO(4) on serum biochemistry related to bone metabolism in neonates remain unclear. AIM To assess the effects of prolonged maternal administration of MgSO(4) on fetuses and neonates. STUDY DESIGN This retrospective case-control study examined 167 neonates. Cases comprised 58 neonates whose mothers had received intravenous MgSO(4) administration for >5 days. Neonatal serum levels of magnesium (Mg), calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) were reviewed. We also investigated whether subject neonates showed appearance of osteopenia at the metaphyseal lines on radiography at birth. RESULTS Mean serum Mg and P levels were significantly higher, and Ca levels were significantly lower, in cases than in controls at birth. Mean serum ALP level was 1188.5IU/l in cases, significantly higher than that in controls at birth. Bone abnormalities were noted on radiography in 2 subjects. By 3 weeks old, serum ALP levels did not differ significantly between cases and controls. Logistic regression analysis revealed maternal administration of MgSO(4) and multiple pregnancies were significantly related to serum ALP level in neonates at birth. CONCLUSION Prolonged maternal administration of MgSO(4) significantly affects neonatal serum biochemistry related to bone metabolism. Potential long-term adverse effects on neonates and how Mg affects fetal bone metabolism in utero need to be investigated in future studies.

Utility of a Doppler-derived index combining systolic and diastolic performance (Tei index) for detecting hypoxic cardiac damage in newborns

Abstract The purpose of this study was to assess cardiac function of newborns with mild asphyxia by a Doppler-derived index combining systolic and diastolic performance (Tei index). We studied 20 preterm infants with mild asphyxia. A control group consisted of 20 gestational age-matched preterm infants without asphyxia. Echocardiograms were performed during the fourth and seventh days after birth. Peak velocities of an early filling wave (E) and an atrial contraction wave (A) were measured from the mitral inflow velocity profile and the ratio of peak E to A was calculated. Ejection time was measured from the left ventricular outflow Doppler signal. The sum of isovolumetric times was obtained by subtracting the ejection time from the interval between cessation and onset of mitral inflow. The index was the sum of isovolumetric times divided by ejection time. Ejection fraction was also calculated. The ratio of peak E to A and ejection fraction were the same in both groups. The myocardial performance index in patients with asphyxia was higher than that in patients without asphyxia. We concluded that patients with mild asphyxia have a mild cardiac dysfunction and this change can be detected by a myocardial performance index.

The risk of birth defects in dichorionic twins conceived by assisted reproductive technology

The purpose of this study was to examine whether dichorionic twins conceived by assisted reproductive technology (ART; intracytoplasmic sperm injection [ICSI], in vitro fertilization [IVF], gamete-intrafallopian tube transfer [GIFT]) have a higher risk of birth defects compared to dichorionic twins conceived naturally. We reviewed the medical records of 406 mothers with dichorionic twin pregnancies, who received continuous antenatal care from < or = 20 weeks of gestation and gave birth to infants after > or = 24 weeks of gestation in our institute. Birth defects were diagnosed at the time of hospital discharge according to the International Classification of Diseases, 10th Revision. Occurrence of birth defects was compared between twins conceived by ART and those conceived naturally using logistic regression analysis. Overall, 51 of 812 infants (51/812 = 6.2%) had birth defects. The incidence of birth defects in ART-conceived twins was significantly higher than that of naturally conceived twins with an odds ratio of 6.9 (95% confidence interval [CI] 2.1, 22.5), 3.7 (95% CI 1.2, 12.0), and 4.3 (95% CI 1.4, 14.3) for ICSI, IVF, and GIFT, respectively. The higher frequency of birth defects in ART-conceived twins was still significant after adjusting for higher maternal age in the ART group, with an adjusted odds ratio of 6.7 (95% CI 2.1, 21.9), 3.6 (95% CI 1.1, 11.5), and 3.7 (95% CI 1.2-11.8) for ICSI, IVF, and GIFT, respectively. Dichorionic twins conceived by ART, compared to dichorionic twins conceived naturally, had a much higher risk for birth defects diagnosed at hospital discharge.

Certain type of chronic lung disease of newborns is associated with Ureaplasma urealyticum infection in utero.

Background: Recent studies of chronic lung disease (CLD) of newborns emphasize the contribution of antenatal infection. However, the association of Ureaplasma urealyticum infection and CLD has been controversial. The purpose of the present paper was to determine whether U. urealyticum is associated with chorioamnionitis (CAM) and a certain type of CLD.

Selective excretion of anti-inflammatory cytokine interleukin-10 in a superantigen-inducing neonatal infectious disease.

Neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED) is an emerging neonatal infectious disease caused by TSS toxin-1 (TSST-1). Although NTED and TSS are caused by the same superantigenic exotoxin, NTED is less severe than TSS. The mechanism of this reduced severity in NTED has not been elucidated. Thirteen patients with NTED were enrolled in the study. We investigated serum cytokine profile using a cytometric bead array system with a cytokine panel. Expression of Vbeta2 and CD45RO in CD4(+) T cells was investigated in mononuclear cells by using flowcytometry. Ten patients with other bacterial infections and eight patients without any infections were also enrolled as control groups. The mean serum level of IL-10 was 1209.9 pg/mL in patients with NTED at the time of admission into the study. The other inhibitory cytokine, IL-4, exhibited a minimum level. The high level of IL-10 rapidly decreased within 3-9 days of the onset of NTED. The cytokine profile of NTED, with its high IL-10 level, was clearly different from that of the other bacterial infections. The increased level of IL-10 seems to be related to the reduced severity of NTED. Th2 shift is not thought to be the cause of this IL-10 excretion.

Gut hormone profiles in preterm and term infants during the first 2 months of life.

Abstract Aim: To investigate changes of gut hormones in term and preterm infants in the first 2 months after birth, as the role and relationships of gut hormones in premature infants has not been well elucidated. Methods: In 29 preterm and five term infants, fasting serum concentrations of leptin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide, insulin, amylin, and ghrelin were measured using a bead array system. Results: Serum leptin concentration soon after birth showed a positive correlation with gestational week in all infants (r=0.623, p<0.01). Serum leptin level rapidly decreased in all infants. In preterm infants, serum GLP-1 levels at birth showed negative correlations with gestational week (r=–0.447, p=0.02). Serum GIP, GLP-1, and PYY levels increased after birth and were persistently high until 10 weeks of life. Conclusion: Serum concentrations of different gut hormones changed postnatally in their specific ways in preterm infants.

Irregular peak‐to‐peak intervals between ascending aortic flows during fetal ventricular tachycardia in long QT syndrome

After delivery, MR imaging revealed that the cyst was located in the left cerebral hemisphere and that there was a solid area in the medial portion of the cyst (Figure 2i–k), suggestive of a cystic CPP. Immediate placement of an Ommaya cerebrospinal fluid reservoir was performed for repeated aspiration of the cyst contents and on the 33rd day after delivery a left parietal craniotomy was performed. Intraoperative findings revealed that the cyst was located in the left cerebral hemisphere, with a papillary tumor situated on the cyst wall, connected to the choroid plexus. Pathological examination confirmed the diagnosis of cystic CPP. The infant’s postoperative course was unremarkable and he was discharged on the 73rd day after delivery without further neurological sequelae. Cystic CPP forming in the cerebral hemisphere is extremely rare, with only two cases reported previously in the literature1–5. CPP is isodense to hyperdense on computed tomography and shows homogeneous enhancement following contrast administration. Cystic CPP manifests as a cystic tumor with or without a mural nodule2,5. If present, the nodule demonstrates enhancement after contrast medium injection6. Prenatally, CPP presents on ultrasound examination as a highly echogenic mass located in one lateral ventricle, adjacent to normal choroid plexus; these findings are necessary for the correct diagnosis7. Tomita et al. reported that in cystic CPP of the cerebral hemispheres the solid part appears in the medial portion5. In our case, ultrasonographic examination detected a medially located solid part with increased echogenicity, similar to that of choroid plexus. This is the first reported case of a confirmed extraventricular intracerebral cystic CPP that showed a marked increase in tumor size prenatally. Cystic CPP should be considered in the differential diagnoses when a cyst with a hyperechogenic solid part is detected in the cerebral hemisphere.

Developmental outcome of very low birth weight twins conceived by assisted reproduction techniques.

Objective:To evaluate the differences in developmental outcomes between very low birth weight twins conceived by assisted reproduction techniques and those conceived spontaneously.Study design:Twenty-two sets of very low birth weight twins were evaluated by the Kyoto Scale for Psychological Development at 36 months of corrected age. Total developmental quotient and developmental quotient (DQ) for three subscales, posture-motor, cognition-adaptation and language-social, were evaluated.Results:Twins conceived with medical assistance demonstrated a higher incidence of total DQ below 85 with lower DQ for cognition-adaptation and language-social skills than spontaneously conceived twins, whereas the quotient for posture-motor skills in medically assisted twins was comparable to that of spontaneously conceived twins.Conclusion:At 3 years of age very low birth weight twins conceived by assisted reproduction techniques demonstrated lower cognitive and language skills than twins conceived naturally.

Hemophagocytic lymphohistiocytosis in a newborn infant born to a mother with Sjögren syndrome antibodies.

We encountered a neonatal patient with hemophagocytic lymphohistiocytosis (HLH) whose mother was positive for anti-Ro/SSA and anti-La/SSB antibodies. Complete atrioventricular block was found in a male patient at 29 weeks of gestation. The patient was born at 40 weeks of gestation. He showed severe circulatory disturbance at 22 h after the birth, and he also had elevated serum levels of aspartate aminotransferase (1027 IU l−1), alanine aminotransferase (121 IU l−1), lactic dehydrogenase (3490 IU l−1), ferritin (9769.7 ng ml−1) and soluble interleukin-2 (IL-2) receptor (3230 U ml−1). We could not find any known HLH genetic abnormality in the patient, but he fulfilled seven of the eight criteria for HLH. Serum levels of IL-6 and IL-8 had been already elevated in his cord blood, and serum levels of granulocyte-macrophage colony-stimulating factor and IL-8 were significantly increased on the second day of life. His symptoms regressed with the administration of hydrocortisone. We presumed that transplacental transfer of maternal antibodies could be related to the occurrence of HLH.