Masahiko Nakata

The outcome and prognostic factors of twin-twin transfusion syndrome following fetoscopic laser surgery.

To evaluate the outcome and preoperative risks of twin–twin transfusion syndrome (TTTS) following fetoscopic laser surgery (FLS).

Prenatal Influence of Ischemia-Hypoxia-Induced Intrauterine Growth Retardation on Brain Development and Behavioral Activity in Rats

The effects of intrauterine growth retardation (IUGR) on brain histological or functional development were examined in rats. IUGR was induced by ligating the bilateral uterine arteries at day 17 of pregnancy. On day 22 of pregnancy, cesarean section was performed, and pups with a birth weight of <2 SD of the mean birth weight of control pups were regarded as IUGR rats. Morphological changes of the brain were studied by Nissl’s staining at different timepoints during prenatal and postnatal periods. For behavioral study, an open-field test was performed at 5, 7 and 10 weeks after birth. Histological studies showed the migration disorder of the neurons in the cerebral cortex from embryonic day 17 to postnatal day (PD) 49. The open-field test revealed locomotor disturbance at PD49 in male IUGR rats, but not in female IUGR rats or control rats. It is concluded that IUGR due to antenatal ischemia-hypoxia causes morphological changes in the central nervous system, and induces behavioral impairment, particularly in male rats.

Perinatal Outcome of Monochorionic Twins with Selective Intrauterine Growth Restriction and Different Types of Umbilical Artery Doppler under Expectant Management

Objectives: To evaluate the prognosis of monochorionic twins with selective intrauterine growth restriction (sIUGR), classified according to the type of umbilical artery Doppler, under expectant management. Methods: The outcome of 81 cases with isolated sIUGR was evaluated according to a classification based on umbilical artery (UA) Doppler diastolic flow in the IUGR twin (I: present, II: constantly absent/reverse, III: intermittently absent/reverse). Selective feticide was not considered due to legal constraints. Perinatal outcomes included perinatal death and neurological outcome at 6 months of age. Results: From 81 cases with the diagnosis of sIUGR, twin-twin transfusion was diagnosed in 18 cases. This left 63 cases, of which 23 were classified as type I (36.5%), 27 as type II (42.9%) and 13 as type III (20.6%). Intrauterine death occurred in 4.3% (1), 29.6% (8) and 15.4% (2) among IUGR twins, and 4.3% (1), 22.2% (6) and 0.0% (0) among larger twins. Neonatal death occurred in 0.0% (0), 18.5% (5) and 0.0% (0) among IUGR twins, and 0.0% (0), 11.1% (3) and 23.0% (3) among larger twins. Neurological abnormalities at 6 months were found in 4.3% (1), 14.8% (4) and 23.1% (3) in smaller twins and 0.0% (0), 11.1% (3) and 38.5% (5) in larger twins, respectively. Intact survival at 6 months was recorded in 91% (21), 37% (10) and 61% (8) in smaller twins and 95% (22), 55% (15) and 38% (5) in larger twins, respectively. Conclusion: The outcome in monochorionic twins with sIUGR and abnormal umbilical artery Doppler is poor under expectant management. Normal Doppler seems to be associated with a good prognosis.

Ultrasound assessment of venous blood flow before and after laser therapy: approach to understanding the pathophysiology of twin–twin transfusion syndrome

To estimate direction and volume of blood exchange between the donor twin and recipient twin by ultrasound assessment of blood flow in the umbilical vein before and after selective laser photocoagulation of communicating vessels (SLPCV) for twin–twin transfusion syndrome (TTTS).

Ultrasound predictors of mortality in monochorionic twins with selective intrauterine growth restriction

The aim of this study was to evaluate the use of ultrasound assessment to predict risk of mortality in expectantly managed monochorionic twin fetuses with selective intrauterine growth restriction (sIUGR).

Current status of pregnancy-related maternal mortality in Japan: a report from the Maternal Death Exploratory Committee in Japan.

Objective To clarify the problems related to maternal deaths in Japan, including the diseases themselves, causes, treatments and the hospital or regional systems. Design Descriptive study. Setting Maternal death registration system established by the Japan Association of Obstetricians and Gynecologists (JAOG). Participants Women who died during pregnancy or within a year after delivery, from 2010 to 2014, throughout Japan (N=213). Main outcome measures The preventability and problems in each maternal death. Results Maternal deaths were frequently caused by obstetric haemorrhage (23%), brain disease (16%), amniotic fluid embolism (12%), cardiovascular disease (8%) and pulmonary disease (8%). The Committee considered that it was impossible to prevent death in 51% of the cases, whereas they considered prevention in 26%, 15% and 7% of the cases to be slightly, moderately and highly possible, respectively. It was difficult to prevent maternal deaths due to amniotic fluid embolism and brain disease. In contrast, half of the deaths due to obstetric haemorrhage were considered preventable, because the peak duration between the initial symptoms and initial cardiopulmonary arrest was 1–3 h. Conclusions A range of measures, including individual education and the construction of good relationships among regional hospitals, should be established in the near future, to improve primary care for patients with maternal haemorrhage and to save the lives of mothers in Japan.

The Doppler cerebroplacental ratio predicts non‐reassuring fetal status in intrauterine growth restricted fetuses at term

Aim:  To investigate whether cerebroplacental ratio (CPR) can be a useful marker to predict non‐reassuring fetal status (NRFS) in small for gestational age (SGA) infants at term.

Ultrasound Assessment prior to Laser Photocoagulation for Twin-Twin Transfusion Syndrome for Predicting Intrauterine Fetal Demise after Surgery in Japanese Patients

Objective: To evaluate the use of ultrasound before selective laser photocoagulation of communicating vessels (SLPCV) for twin–twin transfusion syndrome in predicting intrauterine fetal demise (IUFD). Methods: Fifty-five patients underwent SLPCV in Japan. Fetal biometry and Doppler studies of the umbilical artery, ductus venosus, and umbilical vein were performed prior to SLPCV. The visualization of the bladder and hydrops was recorded. Association between the parameters and IUFD was analyzed using multiple logistic regression analysis. The study was approved by the Institutional Review Board and patients gave their informed consent. Results: The IUFD incidence was 25.5% (14/55) in the donors and 12.7% (7/55) in the recipients. Twelve donors and 4 recipients of them ended in unexplainable IUFD. In the analysis of 53 donors, absent or reversed end-diastolic flow of umbilical artery (UAAREDF) was only associated with IUFD (p = 0.016). No parameters could predict IUFD in 52 recipients. Conclusions: UAAREDF may be useful for predicting IUFD of the donor after SLPCV.

NF‐κB activation in peripheral blood mononuclear cells in neonatal asphyxia

Neonatal asphyxia results in hypoxic–ischaemic encephalopathy. Previous studies have demonstrated that brain hypoxia and ischaemia lead to the production of proinflammatory cytokines, including tumour necrosis factor‐α (TNF‐α), interleukin‐1 (IL‐1) and IL‐6. Transcription factor NF‐κB is essential for the expression of these cytokines. We examined whether or not NF‐κB is activated in peripheral mononuclear cells (PBMC) in neonatal asphyxia by flow cytometry. In addition, we examined the relationship between NF‐κB activation in PBMC and the neurological prognosis. Flow cytometry analysis demonstrated that the level of NF‐κB activation in CD14+ monocytes/macrophages of the patients with asphyxia who had neurological sequelae was significantly higher than in the controls, and in the patients with asphyxia who survived (31·7 ± 7·2%versus 2·5 ± 0·9%, P = 0·008, and versus 1·6 ± 1·4%, P = 0·014, respectively). Our findings suggest that NF‐κB activation in peripheral blood CD14+ monocytes/macrophages in neonatal asphyxia is important for predicting the subsequent neurological sequelae.

MMP-9 and TIMP-1 in the cord blood of premature infants developing BPD.

We investigated matrix metalloproteinase‐9 (MMP‐9) and tissue inhibitor of metalloproteinase 1 (TIMP‐1) levels in the cord blood of 29 premature infants who were <30 weeks gestation. One, 8, and 14 infants developed severe, moderate and mild bronchopulmonary dysplasia (BPD), respectively, and 6 did not. MMP‐9 and TIMP‐1 levels in the cord blood were determined by ELISA. MMP‐9/TIMP‐1 ratios in the cord blood of infants who developed severe or moderate BPD (n = 9) were significantly higher than those who developed mild BPD or did not develop BPD (n = 20; P = 0.015). Multivariate linear regressions demonstrated that MMP‐9 levels and MMP‐9/TIMP‐1 ratios in the cord blood of the premature infants correlated with the oxygen supplementation period (r = 0.58, P = 0.003 and r = 0.41, P = 0.030, respectively). The MMP‐9 levels and MMP‐9/TIMP‐1 ratios correlated with the severity of maternal chorioamnionitis (both trend P = 0.006).