Short- and Long-Term Outcomes of Extremely Preterm Infants in Japan According to Outborn/Inborn Birth Status.

OBJECTIVES: Outborn (born outside tertiary centers) infants, especially extremely preterm infants, are at an increased risk of mortality and morbidity in comparison to inborn (born in tertiary centers) infants. Extremely preterm infants require not only skilled neonatal healthcare providers but also highly specialized equipment and environment surroundings. Maternal transport at an appropriate timing must be done to avoid the delivery of extremely preterm infants in a facility without the necessary capabilities. Cases of unexpected deliveries at birth centers or level I maternity hospitals need to be attended emergently. We compared the differences in short- and long-term outcomes between outborn and inborn infants to improve our regional perinatal system. DESIGN: Retrospective cohort study. SETTING: Neonatal Research Network of Japan database. PATIENTS: Extremely preterm infants (gestational age between 22 + 0 and 27 + 6 wk) in the Neonatal Research Network of Japan database between 2003 and 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 12,164 extremely preterm infants, who were divided into outborn (n = 785, 6.5%) and inborn (n = 11,379, 93.5%) groups, were analyzed. Significant differences were observed in demographic and clinical factors between the two groups. Outborn infants had higher short-term odds of severe intraventricular hemorrhage (adjusted odds ratio, 1.49; 95% CI, 1.11-2.00; p < 0.01), necrotizing enterocolitis (adjusted odds ratio, 1.49; 95% CI, 1.11-2.00; p < 0.01), and focal intestinal perforation (adjusted odds ratio, 1.58; 95% CI, 1.09-2.30; p = 0.02). There were no significant differences in long-term outcomes between the two groups, except in the rate of cognitive impairment (adjusted odds ratio, 1.49; 95% CI, 1.01-2.20; p = 0.04). CONCLUSIONS: The frequency of severe intraventricular hemorrhage, necrotizing enterocolitis or focal intestinal perforation, and cognitive impairment was significantly higher in outborn infants. Thus, outborn/inborn birth status may play a role in short- and long-term outcomes of extremely preterm infants. However, more data and evaluation of improvement in the current perinatal environment are needed.

Formation of Micrometer Scale Metal Structures on Glass by Selective Electroless Plating on Photopatterned Titanium and Copper Containing Films.

A procedure for formation of catalytic SiO2 substrate adhesive layer patterns and selective electrochemical metal deposition on the catalyst images was investigated. A photoreactive solution containing a diazonaphthoquinone sulfonate ester and Ti and Cu complexes was developed to deposit Cu catalyst-TiO2 adhesive layer latent images on glass. Sub-micrometer/micrometer scale positive tone photoactive TiCu complex film patterns were formed using a conventional photolithography technique. The Cu ions in 40-50 nm thick Ti and Cu oxide layers formed by pyrolysis of the TiCu complex films were reduced, residual Cu displaced with Pd then the porous Ti oxide structure filled and plated with Cu by selective electroless then electrolytic plating. Annealing the Cu plating filled TiO2 layers on glass resulted in formation of a smooth Ti3+/Cu1+ oxide interface that enabled formation of 20 µm thick Cu deposits on glass substrate with up to 1 kN/m adhesion strength. The adhesion strength was attributed to chemical bonding of Ti3+ and Cu1+ oxides to the glass and Ti4+ oxide to the Cu plating that was formed upon annealing the Cu filled TiO2 interlayer. Furthermore, a dip coating procedure was adapted that allowed copper film deposition on the entire surface of a 300 µm thick glass substrate with 50 µm in diameter holes enabling formation of electrically conductive through glass substrate interconnects.

Impact of chorioamnionitis on short- and long-term outcomes in very low birth weight preterm infants: the Neonatal Research Network Japan.

OBJECTIVE: To evaluate the short- and long-term outcomes among very low birth weight (VLBW) preterm infants after histologic chorioamnionitis (HCA). METHODS: We performed a retrospective analysis of 5849 single infants (birth weight <1500 g) born at a gestational age between 22 + 0 and 33 + 6 weeks. Clinical data were obtained from the Neonatal Research Network Japan between 2003 and 2007. Multivariable logistic regression analyses were performed to assess the effect of HCA on short- and long-term outcome. RESULTS: According to logistic regression analysis, HCA was associated with lower incidence of respiratory distress syndrome (odds ratio [OR] = 0.54; p < 0.001), increased chronic lung disease (OR = 1.68; p < 0.001) and sepsis (OR = 1.71; p < 0.001) and as a short-term outcomes. There was no significant association with intraventricular hemorrhage (OR = 1.11; p = 0.33), periventricular leukomalacia (OR = 1.07; p = .070) and death before discharge (OR = 0.97; p = 0.084). HCA was associated with increased home oxygen therapy (OR = 3.09; p < 0.001), but not with cerebral palsy (CP; OR = 0.91; p = 0.63), develop quotient < 70 (OR = 1.27; p = 0.17), visual impairment (OR = 1.08; p = 0.77), severe hearing impairment (OR = 1.28; p = 0.62) and death (OR = 0.98; p = 0.91) before three years of age. CONCLUSIONS: In this retrospective population-based study in Japan, HCA was not a risk factor for death, neurodevelopmental impairment and CP in VLBW three-year-old preterm infants.

Long-term outcomes of antenatal corticosteroids treatment in very preterm infants after chorioamnionitis.

PURPOSE: To evaluate the effect of antenatal corticosteroids (AC) therapy on short- and long-term outcomes among very low birth weight preterm infants after histologic chorioamnionitis (HCA). METHODS: We performed a retrospective analysis of 5240 single very low birth weight (VLBW) infants born at 22 + 0 and 33 + 6 weeks of gestation between 2003 and 2007, who registered to the Neonatal Research Network Japan. The effects of AC therapy on mortality, neurodevelopmental outcomes at 3 years of age and neonatal morbidities were analyzed in the groups with or without HCA using logistic regression analysis. RESULTS: In the study subjects, 840 were with HCA, 2734 were without HCA, and 1666 were excluded without data for HCA. AC therapy was significantly associated with decreasing mortality before 3 years of age; [0.52 (0.32-0.86)], [odds ratio (95 % confidence intervals]. There were no differences between the two groups regarding neurodevelopmental outcomes, including cerebral palsy [0.90 (0.41-1.99)], development quotient <70 [0.93 (0.48-1.81)], visual impairment [0.46 (0.04-5.18)], and severe hearing impairment [4.00 (0.30-53.4)] in the group with HCA as well as without HCA. Regarding neonatal morbidities, AC therapy was associated with a lower incidence of respiratory distress syndrome [0.67 (0.50-0.91)], sepsis [0.62 (0.41-0.94)], late-onset adrenal insufficiency [0.62 (0.39-0.98)] and an increased incidence of chronic lung disease [1.62 (1.18-2.24)] in the group with HCA. In the group without HCA, AC therapy was associated with decreasing respiratory distress syndrome [0.60 (0.43-0.84)] and increasing chronic lung disease [1.34 (1.11-1.62)]. CONCLUSION: AC therapy is significantly associated with reduced mortality before 3 years of age in VLBW infants with HCA, but not with neurodevelopmental outcomes, which was same as the results found in infants without HCA. AC therapy is recommended for women with suspected chorioamnionitis, as well as those without chorioamnionitis.

The Effects of Antenatal Corticosteroids on Short- and Long-Term Outcomes in Small-for-Gestational-Age Infants.

AIM: To evaluate the effect of antenatal corticosteroids (ANS) on short- and long-term outcomes in small-for-gestational age (SGA) infants. METHODS: A retrospective database analysis was performed. A total of 1,931 single infants (birth weight <1,500 g) born at a gestational age between 22 weeks and 33 weeks 6 days who were determined to be SGA registered in the Neonatal Research Network Database in Japan between 2003 and 2007 were evaluated for short-term outcome and long-term outcome. RESULTS: ANS was administered to a total of 719 infants (37%) in the short-term outcome evaluation group and 344 infants (36%) in the long-term outcome evaluation group. There were no significant differences between the ANS group and the no-ANS group for primary short-term outcome (adjusted odds ratio (OR) 0.73; 95% confidence interval (CI) 0.45-1.20; P-value 0.22) or primary long-term outcome (adjusted OR 0.69; 95% CI 0.40-1.17; P-value 0.17). CONCLUSIONS: Our results show that ANS does not affect short- or long-term outcome in SGA infants when the birth weight is less than 1500 g. This study strongly suggests that administration of ANS resulted in few benefits for preterm FGR fetuses.

Cesarean delivery and perinatal mortality rates in Japan, 2007-2011.

OBJECTIVE: Cesarean delivery (CD) rates are increasing dramatically in developed countries. In this study, we examined the relationship between CD rates and perinatal mortality (PM) rates in all 47 prefectures in Japan. METHODS: The CD rates were derived from a national obstetrics facility survey conducted by the Japan Association of Obstetricians and Gynecologists (JAOG), which included 94.1% of all childbirths in Japan during the 5-year period from 2007 to 2011. The PM rates were based on vital statistics during the same period. RESULTS: During the 5-year period from 2007 to 2011, the CD rates compiled for the 47 prefectures in Japan increased significantly in each successive year, whereas PM rates decreased significantly in each successive year. However, no statistically significant correlation between CD and PM rates was detected. CONCLUSION: There is a lack of evidence for a significant correlation between recently increasing CD rates and decreasing PM rates in Japan.

The effects of antenatal corticosteroids therapy on very preterm infants after chorioamnionitis.

PURPOSE: To evaluate the effectiveness of antenatal corticosteroids (AC) therapy on outcomes of very low birthweight infants with histologic chorioamnionitis. METHODS: We performed a retrospective analysis of 10,935 single infants born at a gestational age between 22 + 0 and 33 + 6 weeks and birth weight <1,500 g. Clinical data were obtained from the Neonatal Research Network that included the tertiary neonatal intensive care units throughout Japan between 2003 and 2008. RESULTS: Data of 7,896 infants were available for the period 2003-2008 and were included in the analysis. According to logistic regression analysis, AC were significantly associated with reduced mortality [odds ratio (OR) = 0.50; p < 0.001], lower incidence of respiratory distress syndrome (OR = 0.72; p < 0.001), neonatal seizure (OR = 0.65; p = 0.003) and intraventricular hemorrhage (OR = 0.68; p = 0.001) in cases after histologic chorioamnionitis compared with the cases had no AC therapy (n = 3,271 vs. 4,625). Antenatal corticosteroids were significantly associated with reduced mortality [odds ratio (OR) = 0.60; p < 0.001] among the cases without histologic chorioamnionitis. CONCLUSION: In the retrospective population-based study in Japan, AC exposure was significantly associated with a lower rate of death and neurological morbidity in cases with histologic chorioamnionitis. These outcome data in Japan will be important for further improvement of antenatal practice and care.

Management of eclampsia and stroke during pregnancy.

To establish the etiologies and therapeutic strategies for the treatment of eclampsia and stroke during pregnancy, we performed a questionnaire-based study of stroke during pregnancy in Aichi prefecture (2005-2009). This study revealed the following findings: 66% of deliveries were managed in primary medical institutions, 40% of eclampsia episodes and 31% of strokes occurred at primary medical institutions, and 19% of strokes occurred at home. Home-onset strokes displayed a mortality rate of 40%. Using the results of this questionnaire, we investigated cases of eclampsia and/or stroke during pregnancy and revealed important issues regarding their management. In pregnant women with eclampsia or stroke, accurate antihypertensive and anticonvulsive treatment are necessary. Discriminating between eclampsia and stroke during labor is difficult. However, when facial or arm muscle weakness or a facial deficit is detected, stroke should be strongly suspected. Brain computed tomography can usually detect most cases of hemorrhagic stroke. When a stroke is detected, collaborative treatment with a neurosurgeon should be started as soon as possible. If stroke is suspected at a primary medical institution, rapid maternal transport to an intensive medical institution is necessary. In patients whose blood pressure is greater than 180/120 mmHg, the use of MgSO4 to decrease the risk of convulsions and reduce blood pressure is recommended. These findings might aid the development of therapeutic strategies for pregnant women with eclampsia or stroke.

Validation of the prediction model for success of vaginal birth after cesarean delivery in Japanese women.

AIM: To validate a previously developed prediction model for vaginal birth after cesarean (VBAC) using a Japanese cohort. METHODS: We performed a cohort study of all term pregnant women with a vertex position, singleton gestation, and one prior low transverse cesarean delivery attempting a trial of labor between April 1985 and March 2010. Variables necessary for the prediction of successful VBAC were maternal age, pre-pregnancy body mass index, ethnicity, prior vaginal delivery, prior VBAC, and indication for prior cesarean delivery. They were extracted from medical records and put into the formula that calculates an individual woman's predicted VBAC success rate. The predicted rates were then partitioned into deciles and compared with the actual VBAC rates. The predictive ability of the model was assessed with a receiver operating characteristic and the area under the curve (AUC) was determined. RESULTS: Seven hundred and twenty-five women who met the inclusion criteria had complete data available, of which 664 (91.6%) had VBAC. The predicted probability of VBAC, as calculated by the regression equation, was significantly higher in those who had a successful trial of labor (median 80.1%, interquartile range 71.5-88.7) than those who did not (median 69.4%, interquartile range 59.9-78.9, P<0.001). The predictive model had AUC of 0.80, which was comparative to the originally described one. When the predicted rates were each deciles of over 70%, the actual success rates were more than 90%. CONCLUSION: The previously published prediction model for VBAC developed in the USA is also available to Japanese women.

Aggressive intervention of previable preterm premature rupture of membranes.

OBJECTIVE: To assess the neonatal and maternal outcomes of pregnancy complicated by previable preterm premature rupture of membranes (PPROM). DESIGN: Retrospective study. SETTING: Tertiary referral hospital. Sample. Forty-five women having aggressive intervention with antibiotics, amnioinfusion, cerclage and tocolysis. METHODS: The hospital database between July 2001 and December 2009 was reviewed for women with singleton fetuses and PPROM before 23(+0) weeks of gestation. We analysed maternal and neonatal characteristics. MAIN OUTCOME MEASURES: Neonatal survival without major morbidity. RESULTS: Thirty-eight infants were delivered alive and seven were stillborn. Ten infants died in the neonatal intensive care unit and one in the labor ward. Twenty-seven live-born infants survived to discharge from hospital. The survival rate of pregnancies with aggressive management was 60% (27 of 45); that of live-born infants was 71.1% (27 of 38). The median gestational age at PPROM and at delivery were significantly lower in the non-surviving group than the surviving group. Thirty-seven women (82.2%) had an amniotic neutrophil elastase level >0.15 µg/mL. Only four women (8.9%) developed clinical chorioamnionitis. Overall, 90.7% of the women showed histological evidence of chorioamnionitis. Eighty-three per cent of the surviving children had bronchopulmonary dysplasia. Nine infants had serious sequelae at a corrected age of one and a half years. Maternal complications were uncommon. CONCLUSIONS: An aggressive treatment protocol for women with previable PPROM resulted in a high neonatal survival rate. Neonatal survival was associated with higher gestational age at delivery and with more frequent use of antenatal corticosteroids. The prognosis is still bad in PPROM before 22(+0) weeks of gestation.

Observation on validity of the five-tier system for fetal heart rate pattern interpretation proposed by Japan Society of Obstetricians and Gynecologists.

OBJECTIVE: To evaluate the five-tier classification of fetal heart rate (FHR) tracings recently proposed by Japan Society of Obstetricians and Gynecologists (JSOG). METHODS: The database between January and June 2009 was reviewed for women in active labor at ?36 + 0 gestational weeks, with singleton fetuses in cephalic presentation and with umbilical artery blood gas analyses. Continuous FHR tracings were assessed according to the five-tier classification proposed by JSOG, where level 1 is normal, level 2 is subnormal and levels 3?5 are abnormal patterns. RESULTS: A total of 341 parturient women were eligible for this study protocol. The median (range) of the levels in the first and the second stage of labor were 1 (1-4) and 2 (1-4), respectively (p < 0.001). Both pH and base excess of umbilical artery decreased with higher levels of FHR tracings interpretation (p < 0.01). Interventions resulting in delivery were more necessary in the first stage of labor than in the second stage of labor in cases of levels 3 and more. CONCLUSIONS: Five-tier system for FHR tracing interpretation proposed by JSOG intercorrelates with the fetal acid-base balance well. Categorization of FHR tracings by uniform diagnostic criteria will be useful to standardize therapeutic strategy by sharing common perception among obstetrical staff.

Invasive group A streptococcal infection in pregnancy.

We conducted a literature review of 55 pregnancies with symptomatic Group A streptococcus (Streptococcus pyogenes) infection reported in English (20 cases), French (2 cases) and Japanese (33 cases) to seek ways of improving prognosis. Multiparous women (83% [39/47]) in the third trimester (90% [47/52]) were prone to infection from winter to spring (75% [21/28]). Onset was heralded by flu-like symptoms, such as high fever (94% [46/49]), with upper respiratory (40% [22/55]) and/or gastrointestinal symptoms (49% [27/55]). Characteristic findings were early onset of shock (91% [50/55]) and infection-induced strong uterine contraction (73% [40/55]) suggestive of placental abruption. The clinical course was too acute and severe to rescue the mother (58% [32/55] died) and/or infant (66% [39/59] died). However, outcome has improved over the last decade, with rescue of 68% (15/22) of the mothers since 2000, and early use of antibiotics (71% [22/31] survived) and use of intravenous immunoglobulin (91% [10/11] survived) were associated with favourable outcome. Early use of antibiotics and intravenous immunoglobulin may improve outcome of pregnant women suffering from flu-like symptoms, shock and strong uterine contractions suggestive of placental abruption.

Fetal intraventricular bleeding possibly due to maternal vitamin K deficiency.

We report a rare case of fetal intraventricular bleeding possibly due to maternal vitamin K deficiency. A 20-year-old woman was admitted to our hospital due to impending premature delivery and loss of dietary intake at 28 weeks of gestation. Her blood examination showed metabolic alkalosis, prolonged prothrombin time, and extremely high level of plasma des-gamma-carboxyprothrombin (protein induced by vitamin K absence, PIVKA-II). Intraventricular hemorrhage was demonstrated by ultrasonography 6 days after admission. She delivered a 2,288-gram girl infant at 40 weeks of gestation. Cranial computerized tomography and magnetic resonance images obtained postnatally demonstrated a reduced cerebral parenchyma adjacent to the interior side of the right lateral ventricle and the deficit of left cerebellum. The infant's head control was insufficient and central impaired hearing was noted at 6 months of life.

[Diagnostic accuracy and time-course change of cervical intraepithelial neoplasia].

We investigated the results of cervical cytology, pathology of colposcopic biopsy and surgical specimen among 765 women suspected to have cervical intraepithelial neoplasia (CIN). Significantly more patients with cervical cytology class III b than class III a were diagnosed in CIN grade 3 on colposcopic biopsy. The concordance rate of colposcopic biopsy and surgical specimen was 79.8%, but we preoperatively diagnosed CIN grade 3 or more at 96.1% with colposcopic biopsy. In time course observation, CIN regressed in 26.3% of all patients, progressed in 19.3% and did not change in 54.4%. Many patients of CIN grade 2 progressed to grade 3 in two years. Significantly more patients of CIN grade 1 or 2 with cervical cytology class III b progressed than with class III a (p<0.05).

[Complication with paraaortic lymphadenectomy in gynecological cancer patients].

Although paraaortic lymphadenectomy is one of the standard treatments for gynecological cancer in Japan, it is very invasive so one must examine its safety for patients. Paraaortic lymphadenectomy was performed in 215. Two hundred and fifteen gynecologic cancer patients at our hospital between January 1991 and August 2005. We evaluated operation time, estimated blood loss and the incidence of operative injury, wound complication, and postoperative ileus. It was revealed that the mean operation time was 364 minutes and the estimated blood loss was increased at the operation around the vena cava or renal vein. After we adopted Kocher's technique, the mean blood loss was decreased. The incidence of postoperative ileus was 13.3%, but almost all of the patients were cured within seven days without surgical treatment. The incidence of wound complication was within 10%.

Placenta previa increta/percreta in Japan: a retrospective study of ultrasound findings, management and clinical course.

AIM: Placenta accreta is an abnormally firm attachment of placental villi to the uterine wall, which may cause postpartum hemorrhage resulting in maternal morbidity and mortality. The purpose of the present study was to clarify the incidence, clinical background and prognosis of placenta previa increta/percreta treated with different modalities in Japan. METHODS: Medical records of cases with placenta previa increta/percreta in eight tertiary centers between January 1994 and December 2004 were reviewed. Placenta accreta without actual invasion into the myometrium confirmed by pathology was not included in placenta increta/percreta. Details of obstetric history, maternal background, ultrasonographical findings, the course of delivery, subsequent complications and management were noted. RESULTS: Among the total of 59,008 deliveries, 45,261 were by the vaginal route (76.7%) and 13 747 by cesarean section (23.3%). In this study, 408 cases were diagnosed as placenta previa (0.69%), 18 of these being placenta increta and 5 placenta percreta. Only 1.1% of cases of placenta previa without prior cesarean section were increta/percreta, in contrast to 37% of placenta previa after prior cesarean sections. Mean intraoperation blood loss was 3630 +/- 2216 g (increta) and 12,140 +/- 8343 g (percreta). One patient with placenta previa percreta died of hemorrhage. Stepwise treatment (cesarean section without separation of the placenta, arterial embolization and hysterectomy) was applied for 4 cases, which had the least blood loss. CONCLUSIONS: Placenta previa increta/percreta is a life-threatening disease. Patients who undergo hysterectomy after uterine arterial embolization demonstrate reduced intraoperation blood loss, and this treatment should be incorporated to reduce maternal morbidity.

Would omitting the assessment of heart rate be harmful to initial neonatal care?

OBJECTIVE: To test the hypothesis that counting heart rate is dispensable and other components of the Apgar score are satisfactory to evaluate the physical condition of infants shortly after birth in routine deliveries. METHODS: The database of the Japanese Red Cross Nagoya First Hospital was reviewed for newborn infants whose Apgar scores were marked by trained neonatologists attending delivery. RESULTS: The scores of respiratory effort, muscle tone, and reflex irritability increased parallel to Apgar scores. Heart rate gained higher marks even in lower Apgar scores, whereas color demonstrated lower marks even in higher Apgar scores. Correlation coefficients were higher among respiratory effort, muscle tone, and reflex irritability. In contrast, both heart rate and color exhibited lower correlation coefficients against other components and total Apgar scores. High correlation coefficients were shown between the sum of the four components other than heart rate and the total score. CONCLUSIONS: Heart rate and color play more independent roles in the Apgar score. Heart rate seems to be dispensable and the other components of the Apgar score are satisfactory to evaluate the physical condition of infants shortly after birth, and hence, counting heart rate may be omitted in routine deliveries when a newborn infant is apparently well.

Life-threatening septic shock in a pregnant woman with ileus.

Septic shock during pregnancy is very rare but has high mortality. We report a case of septic shock in a pregnant woman with ileus, showing that severe ileus in a pregnant woman could be attributed to life-threatening septic shock and that we should give special attention to a nosocomial infection.

Impact of subclinical chorioamnionitis on maternal and neonatal outcomes.

BACKGROUND: Chorioamnionitis is considered to be one of the main causes of preterm labor and has been associated with an adverse perinatal outcome in preterm infants. The controversy about the benefits/risks of delaying labor is a critical issue concerning the management of chorioamnionitis. METHODS: The database between July 2001 and March 2006 was reviewed for women with singleton pregnancies between 22 and 28 weeks of gestation and with chorioamnionitis diagnosed on admission by amniotic fluid neutrophil elastase level. Women were classified according to the severity of chorioamnionitis (group A, amniotic fluid neutrophil elastase level of 0.15-1 microg/ml; B, 1-10 microg/ml; and C, > or = 10 microg/ml). During expectant management, serum C-reactive protein levels monitored the remission and aggravation of chorioamnionitis. Following deliveries, placentas were examined for histologic chorioamnionitis. RESULTS: One hundred women were enrolled (group A, 38; B, 34; C, 28). The latency period until delivery was significantly longer in group A than in groups B and C. C-reactive protein levels just before delivery were higher than those on admission in 61% of the overall cases. Histologic chorioamnionitis and funisitis were manifested in 90.4% and 65.5%, respectively. Intrauterine fetal demise (4 cases) and neonatal and postneonatal deaths during admission (10 cases) were observed. Bronchopulmonary dysplasia was the most common major morbidity noted in groups B and C. CONCLUSION: Chorioamnionitis could be controlled but is hard to cure. Higher levels of amniotic fluid neutrophil elastase are associated with a shorter interval from admission to delivery in women with subclinical chorioamnionitis.