Doctor of Philosophy, Kobe University (2012)
Doctor of Medicine, Kobe University (2004)
Monochorionic diamniotic (MD) twins with selective intrauterine growth restriction (sIUGR) have known associations with cardiac complications. However, the cardiac load of dichorionic diamniotic (DD) twins with sIUGR (DD-sIUGR) remains unclear. N-terminal pro-brain natriuretic peptide (NT-pro BNP) is a convenient marker of cardiac dysfunction in neonates, and is elevated in MD twins with sIUGR (MD-sIUGR). However, there are no reports assessing serum NT-pro BNP levels in DD-sIUGR. Here, we aimed to clarify serum NT-pro BNP levels at birth in DD-sIUGR, and to compare them with those of MD-sIUGR. Forty-one DD twin pairs admitted to our center between October 2007 and January 2013 were enrolled in this study and separated into two groups: nine twins with sIUGR (DD-sIUGR group) and 32 twins without sIUGR (DD without sIUGR group). Sixteen MD twins with sIUGR (MD-sIUGR group) served as positive controls. Serum NT-pro BNP levels at birth in DD-sIUGR [median 2,115 pg/ml (range, 443-6,590 pg/ml)] were significantly higher than in DD without sIUGR [1,080 pg/ml (range, 313-3,470 pg/ml); p=0.001], and significantly lower than in MD twins with sIUGR [4,520 pg/ml (range, 529-62,400 pg/ml); p=0.04]. Serum NT-pro BNP levels between larger and smaller DD co-twins were significantly correlated (r = 0.582; p<0.0001). In conclusion, serum NT-pro BNP levels at birth in DD twins with sIUGR were higher than those without, and lower than in MD twins with sIUGR.
View details for PubMedID 24598275
Our objective was to correlate vascular endothelial growth factor (VEGF) genetic polymorphisms with the risk of bronchopulmonary dysplasia (BPD) development in premature newborns. Fifty-five newborns with BPD (BPD: median gestational age [GA]: 27 weeks, birthweight [BW]: 786 g) and 42 newborns without BPD (non-BPD: median GA: 29 weeks, BW: 1,165 g), who were born at <32 weeks gestational age and were admitted to Kobe University Hospital, were included. BPD was defined as oxygen dependency at 36 weeks postmenstrual age. Genomic DNA was extracted from the umbilical cord, cord blood, or buccal mucosa. Six VEGF genotypes (-1498T > C, -1154G > A, -634C > G, -7C > T, 936C > T, and 1612G > A) were determined by DNA sequencing. Clinical characteristics, and allele and genotype frequencies of VEGF in the BPD and non-BPD groups were analyzed. G allele frequencies in -634C > G of the BPD group were significantly higher than in the non-BPD group (66.4% vs. 50%, P = 0.02). -634C > G genotype distributions differed significantly between the BPD and non-BPD groups (BPD: CC 7%/CG 53%/GG 40%; non-BPD: CC 24%/CG 52%/GG 24%; P = 0.04). Multivariate logistic regression showed that duration of ventilation, VEGF-634G > C G alleles, and male gender were independent risk factors for BPD. In conclusion, polymorphism VEGF -634C > G may influence the risk of BPD.
View details for DOI 10.1038/srep04459
View details for PubMedID 24662923
View details for DOI 10.4172/2167-0897.1000124
We report a monochorionic diamniotic twin pair born at 29 weeks of gestation in which both twins developed severe retinopathy of prematurity (ROP) with retinal detachment. The pregnancy was terminated due to reversal of donor-recipient phenotypes in possible TTTS. Both twins had unstable cardiopulmonary status during the first week, and developed chronic lung disease. The larger twin, born at 1372 g, developed stage 4a ROP in both eyes, and the smaller twin, born at 1168 g, developed stage 4a ROP in the left eye. Genetic analysis of NDP, FZD4, LRP5, TSPAN12 genes revealed no mutations; however, VEGF gene polymorphism analysis showed heterozygous carrier state of the VEGF 936T allele in both twins, which is a risk factor for threshold ROP in Japanese newborn infants. We speculate the synergistic effects of unstable perinatal cardiopulmonary status and genetic predisposition due to VEGF 936C>T polymorphism caused the development of severe ROP with retinal detachment.
View details for DOI 10.1111/j.1442-200X.2012.03690.x
View details for Web of Science ID 000320620100031
View details for PubMedID 23782366
Serum unbound bilirubin (UB) is a measure of bilirubin not bound to albumin, and has been reported to be better than total bilirubin level at identifying infants at risk of developing bilirubin-induced neurotoxicity, including auditory abnormalities. A detailed treatment strategy for newborns with high serum UB has not been established. The aim of this study was to assess auditory outcomes in newborns with serum UB ≥1.00 μg/dL who were treated according to a novel treatment protocol.A prospective clinical study was conducted in newborns weighing >1500 g with serum UB ≥1.00 μg/dL who were admitted to Kobe University Hospital and Kakogawa Municipal Hospital, Japan from 2006 to 2011. Enrolled newborns were treated as follows: (i) if serum UB was 1.00-1.50 μg/dL, phototherapy and infusion were given with or without albumin or immunoglobulin therapy; and (ii) if serum UB was >1.50 μg/dL, exchange transfusion was performed immediately. Auditory brainstem responses were evaluated at the time of discharge.A total of 89 Japanese newborns with UB ≥1.00 μg/dL were enrolled at a median age of 4 days. Of these, 85 had UB 1.00-1.50 μg/dL and four had UB >1.50 μg/dL. After being treated according to the protocol, no newborns were diagnosed with auditory brainstem response abnormalities.The present treatment protocol for Japanese newborns with serum UB ≥1.00 μg/dL may be useful for the prevention of bilirubin-induced auditory abnormalities.
View details for DOI 10.1111/j.1442-200X.2012.03726.x
View details for Web of Science ID 000315094100012
View details for PubMedID 22978498
Twin-to-twin transfusion syndrome (TTTS) affects 15% of monochorionic diamniotic (MD) twin pregnancies, and is associated with adverse perinatal outcome. Recently, fetoscopic laser photocoagulation (FLP) has been widely accepted as the most definitive therapy to treat TTTS. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a powerful diagnostic marker of cardiac dysfunction in neonates, and is elevated in MD twins with TTTS. However, there are no reports assessing the effect of FLP on neonatal cardiac overload in TTTS by measuring the serum NT-proBNP levels at birth. Here, we aimed to compare serum NT-proBNP levels at birth in MD twins with TTTS treated with FLP or not. Twelve MD twin pairs with TTTS admitted to our center between October 2007 and September 2012 were enrolled in this study. The MD twin pairs were separated into two groups: seven twins (12 newborn infants) with FLP (FLP group) and five twins (nine newborn infants) without FLP (non-FLP group). Gestational age, birthweight, and Apgar scores were significantly higher in the FLP group than that in the non-FLP group. Serum NT-proBNP levels at birth were significantly lower in the FLP group than in the non-FLP group [1425 pg/ml (range, 466-9560) vs. 29900 pg/ml (range, 7300-77900), respectively; p=0.0003]. The serum NT-proBNP levels of larger and smaller co-twins were significantly correlated with each other (r=0.750; p=0.026). In conclusion, serum NT-proBNP levels at birth are lower in MD twins with TTTS after FLP treatment than in those without FLP.
View details for PubMedID 23756660
Objective:To compare serum N-terminal pro-brain natriuretic peptide levels at birth between monochorionic diamniotic twins with and without selective intrauterine growth restriction.Study Design:Blood samples were collected from 73 monochorionic diamniotic twins without twin-to-twin transfusion syndrome. Two groups were studied on the basis of fetal ultrasonographic findings: 16 twins with and 57 twins without selective intrauterine growth restriction. Selective intrauterine growth restriction was defined as an estimated fetal weight below the 10th percentile in one twin at 18 to 26 weeks of gestation. Serum N-terminal pro-brain natriuretic peptide levels were measured.Result:Serum N-terminal pro-brain natriuretic peptide levels in monochorionic diamniotic twins with selective intrauterine growth restriction were significantly higher than in those without selective intrauterine growth restriction. Selective intrauterine growth restriction was independently associated with increased N-terminal pro-brain natriuretic peptide levels.Conclusion:N-terminal pro-brain natriuretic peptide levels at birth are elevated in monochorionic diamniotic twins with selective intrauterine growth restriction.Journal of Perinatology advance online publication, 26 September 2013; doi:10.1038/jp.2013.119.
View details for DOI 10.1038/jp.2013.119
View details for PubMedID 24071906
To assess renin, aldosterone, human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) levels in cord blood from monochorionic diamniotic (MD) twins with a birthweight (BW) discordance that do not satisfy the criteria of twin-to-twin transfusion syndrome (TTTS).Cord blood samples were obtained from 28 MD twins without TTTS. They were divided into two groups on the basis of BW discordance as follows: large (>7.5%) and small (7.5%). Cord blood renin, aldosterone, hANP and BNP levels were measured.Renin levels in MD twins with a large BW discordance were significantly higher than those in MD twins with a small BW discordance, with no significant differences in aldosterone, hANP and BNP levels. A significant correlation was found between renin levels and BW discordance.Renin is activated in MD twins with a BW discordance of >7.5%, even in non-TTTS.
View details for DOI 10.1038/jp.2011.136
View details for Web of Science ID 000305916200007
View details for PubMedID 21941232
The American Academy of Pediatrics guidelines recommend that the total bilirubin (TB)/albumin (Alb) ratio (B/A ratio), instead of serum concentration of unbound bilirubin (UB), can be used with TB for determining treatment modality for jaundiced newborns ≥ 35 weeks of gestation. It is unknown, however, whether the B/A ratio is actually correlated with serum UB.Four hundred and ninety-seven serum samples were obtained from 209 newborns ≥ 35 weeks of gestation, who were admitted to Kobe University Hospital. Serum UB concentration was measured using the glucose oxidase-peroxidase method. Serum TB and Alb concentrations were measured on spectrophotometry. B/A ratios were calculated and were linearly compared with serum UB. Furthermore, the accuracy of the B/A ratio was evaluated.The B/A ratio was significantly correlated with serum UB concentration. A serum UB concentration of 0.6 µg/dL was in agreement with a B/A ratio of 0.5. For comparison of the number of newborns who had serum UB concentrations ≥ or <0.6 µg/dL and B/A ratios ≥ or <0.5, we found the following characteristics: the concordance rate between serum UB concentrations and the B/A ratio was 94%, sensitivity was 51%, and specificity was 99%.The B/A ratio is significantly correlated with serum UB concentration in newborns ≥ 35 weeks of gestation. The B/A ratio, however, is underestimated when serum UB concentrations are >0.6 µg/dL.
View details for DOI 10.1111/j.1442-200X.2011.03457.x
View details for Web of Science ID 000300671100015
View details for PubMedID 21883690
Free bilirubin concentration (B(f)) is an index for identifying newborns at risk for developing bilirubin-induced neurotoxicity. It has been suggested that B(f) measured by a single peroxidase concentration (B(f-single)) does not equal the equilibrium concentration of B(f), which is confirmed by B(f) at two different peroxidase concentrations (B(f-two)). However, the differences between B(f-single) and B(f-two) are unknown in the serum of term or late-preterm newborn infants. Furthermore, to apply B(f-single) with savings on time and cost to the clinical setting, it is very important for us to clarify the differences between B(f-single) and B(f-two).Forty serum samples were obtained from 21 term or late-preterm newborns who were admitted at Kobe University Hospital. Using a peroxidase method, B(f-single) was measured at one peroxidase concentration, and B(f-two) was determined at two different peroxidase concentrations (the manufacturer's recommended peroxidase concentration and half the manufacturer's recommended peroxidase concentration). To clarify the relationship between B(f-single) and peroxidase concentrations, B(f-single) was measured at five different concentrations of peroxidase reagent. Intra-day and inter-day analyses were performed to assess the precision of B(f-single) and B(f-two).1/B(f-single) increased as peroxidase concentration increased. B(f-single) was significantly lower than B(f-two) (B(f-single): 0.50 microg/dL [0.13 - 1.22 microg/dL] versus B(f-two): 0.59 microg/dL [0.15 - 1.76 microg/dL], p < 0.001), but B(f-single) was significantly correlated with B(f-two) (r = 0.953, p < 0.0001). Intra-day analysis showed that the CV was 9.7% for B(f-two) and 3.3% for B(f-single), and the inter-day CV was 12.4% for B(f-two) and 3.2% for B(f-single).Although B(f-single) and B(f-two) are not identical, B(f-single) is significantly correlated with B(f-two) and it is more precise than B(f-two) in term or late-preterm newborns.
View details for Web of Science ID 000305711100018
View details for PubMedID 22783582
The serum concentration of unbound bilirubin (UB), which is bilirubin not bound to albumin (Alb), is a better index than total bilirubin concentration (TB) for identifying infants at risk for developing bilirubin neurotoxicity. The degree to which the hypoalbuminemia following abdominal surgery in jaundiced newborns affects bilirubin binding is unknown.To determine whether lower Alb occurring in newborns undergoing abdominal surgery shortly after birth results in significantly higher UB in serum versus nonsurgical patients at comparable serum TB.A matched case-control study was conducted with term and late-preterm newborns. The surgery group included 15 newborns who underwent abdominal operation within 3 days after birth. Clinical and laboratory data (serum UB, TB, and Alb concentrations, UB/TB ratio, and binding constant) in the surgery group were collected and compared with those of 30 control newborns who did not undergo abdominal surgery (control group).Serum UB and the UB/TB ratio in the surgery group were significantly higher than those in the control group (p < 0.02, p < 0.001, respectively), whereas there were no significant differences in serum TB and binding constant between the groups. Serum Alb concentrations in the surgery group were significantly lower than those in the control group (p < 0.001). When pre- and postoperative serum Alb concentrations were compared, there was a significant decrease from 3.4 to 2.7 g/dl (p < 0.001).Our study suggests that hypoalbuminemia following abdominal surgery causes a higher serum UB at comparable serum TB in newborns.
View details for DOI 10.1159/000314893
View details for Web of Science ID 000284159600006
View details for PubMedID 20881436
We report the intact surviving case of a newborn with a birth weight of 412 g delivered from an active systemic lupus erythematosus (SLE) mother with antiphospholipid syndrome. A review of the literature revealed that our infant is the lowest surviving birth weight in newborns from SLE mothers to date.
View details for DOI 10.3109/14767050903414492
View details for Web of Science ID 000282080400017
View details for PubMedID 20476875