Magnesium sulphate and perinatal mortality and morbidity in very-low-birthweight infants born between 24 and 32 weeks of gestation in Japan.

OBJECTIVE: Maternal exposure to magnesium sulphate has a neuroprotective effect in premature infants. This study aimed to examine this neuroprotective effect and the dose-response relationship in very-low-birthweight infants born between 24 and 32 weeks of gestation. STUDY DESIGN: A retrospective cohort study compared the rates of mortality and brain damage between three groups: no magnesium sulphate, low-dose (<50g) magnesium sulphate and high-dose (≥50g) magnesium sulphate. RESULTS: Japanese maternal and neonatal databases were linked using six key parameters from 2003 to 2007. Of 298,514 deliveries, 9101 were very-low-birthweight infants. Among these, full matching was possible for 5562 infants. Of the fully-matched infants, 3763 were born between 24 and 32 weeks of gestation, and 1813 (48%) were followed-up beyond 18 months. A multivariate analysis of the data, including gestational age, sex, fetal growth restriction, antenatal steroids and low pH (<7.1), showed that the low-dose group had no beneficial effects in terms of a reduction in mortality or incidence of brain damage (cerebral palsy or mental retardation). The high-dose group showed a significantly higher mortality rate [odds ratio (OR) 1.9, 95% confidence interval (CI) 1.2-2.9]. A stratified subgroup analysis of infants born between 28 and 32 weeks of gestation showed that survivors in the low-dose group had significantly lower rates of cerebral palsy (OR 0.4, 95% CI 0.2-0.98) and brain damage (OR 0.2, 95% CI 0.1-0.9), while the high-dose group did not show any significant changes. CONCLUSION: This study found that antepartum exposure to magnesium sulphate did not reduce the infant mortality rate or influence neurological outcomes. However, among infants born between 28 and 32 weeks of gestation, rates of cerebral palsy and brain damage were found to be significantly lower among survivors in the low-dose group.

Comparison of pregnancy outcomes between women with gestational diabetes and overt diabetes first diagnosed in pregnancy: a retrospective multi-institutional study in Japan.

AIMS: To determine differences in pregnancy outcomes including diabetic complications, maternal and perinatal complications between gestational diabetes mellitus and overt diabetes in pregnancy in Japan. METHODS: A multi-institutional retrospective study compared pregnancy outcomes between gestational diabetes mellitus and overt diabetes in pregnancy. We examined pregnant women who met the former criteria for gestational diabetes mellitus and received dietary intervention with self-monitoring of blood glucose with or without insulin. Overt diabetes in pregnancy was defined as ≥2 abnormal values on 75-g oral glucose tolerance test, fasting glucose ≥126 mg/dl (7.0 mmol/l) and 2-h postprandial glucose ≥200 mg/dl (11.1 mmol/l), or glycated hemoglobin levels ≥6.5% (48 mmol/mol). RESULTS: Data were collected on 1267 women with gestational diabetes and 348 with overt diabetes in pregnancy. Pregestational body mass index was higher (26.2 ± 6.1 vs. 24.9 ± 5.7 kg, P<0.05) and gestational age at delivery was earlier (37.8 ± 2.5 weeks vs. 38.1 ± 2.1 weeks, P<0.05) in overt diabetes than in gestational diabetes. Glycated hemoglobin (6.8 ± 1.1% [51 mmol/mol] vs. 5.8 ± 0.5% [40 mmol/mol], P<0.05) and glucose on 75-g oral glucose tolerance test and prevalence of retinopathy (1.2% vs. 0%, P<0.05) and pregnancy-induced hypertension (10.1% vs. 6.1%, P<0.05) were higher in overt diabetes than in gestational diabetes. Pregnancy-induced hypertension was associated with pregestational body mass index, gestational weight gain, chronic hypertension, and nulliparity but not with 75-g oral glucose tolerance test. CONCLUSIONS: Overt diabetes in pregnancy is significantly associated with maternal complications such as retinopathy and pregnancy-induced hypertension.

An amino-terminal fragment of hemokinin-1 has an inhibitory effect on pruritic processing in rats.

Hemokinin-1 (HK-1) is a peptide encoded by the preprotachykinin gene, TAC-4, and shares the hydrophobic carboxyl-terminal (C-terminal) region common to mammalian tachykinin peptides, such as substance P (SP). It is generally believed that C-terminal fragments of SP elicit an excitatory effect, while pretreatment with amino-terminal (N-terminal) fragments of SP inhibits the function of SP; however, there is no available information on HK-1. Therefore, to clarify the characteristics of C-terminal and N-terminal fragments of HK-1, HK-1 was divided into HK-1 (1-5) as the N-terminal fragment and HK-1 (6-11) as the C-terminal fragment based on the similarity of amino acids between HK-1 and SP. Intrathecal administration of HK-1 (6-11) induced scratching behavior similar to HK-1, while HK-1 (1-5) hardly induced scratching. Pretreatment with HK-1 (1-5), however, attenuated scratching induced by HK-1 and SP, whereas pretreatment with SP (1-5) attenuated SP-induced scratching, but not HK-1. Furthermore, intrathecal administration of HK-1 (1-5) and SP (1-5) markedly attenuated the induction of flinching and enhancement of c-Fos expression in the spinal cord following the intradermal administration of formalin, a noxious stimulant, while pretreatment with HK-1 (1-5), but not SP (1-5), markedly attenuated the induction of scratching behavior by subcutaneous administration of pruritic agents, such as serotonin or histamine. Taken together, these findings indicate that HK-1 (1-5) suppresses pruritic and nociceptive processing, while SP (1-5) suppresses nociceptive processing. Therefore, it is suggested that HK-1 (1-5) may be a useful tool for revealing pruritic processing and HK-1 may play a crucial role in pruritic processing.

Maternal IgG avidity, IgM and ultrasound abnormalities: combined method to detect congenital cytomegalovirus infection with sequelae.

OBJECTIVE: We used maternal immunoglobulin M (IgM), immunoglobulin G (IgG) avidity index (AI) and fetal ultrasonography (US) to effectively detect a congenital cytomegalovirus-infected fetus that would suffer neurological sequelae after birth. STUDY DESIGN: The detecting method was prospectively adapted to 1163 unselected pregnant women. IgM, IgG and IgG-AI were measured at the first prenatal examination (10.8±2.2 weeks of gestation). Advanced US was performed for the IgM-positive women at our center. The urine of 1163 neonates was examined via PCR. All infected neonates were followed for neurological development. RESULT: Most women (83.3%) were seropositive. Among them, 40 (4.1%) were IgM positive. Nine of forty (22.5%) had low AI, of which one showed abnormal US and suffered severe sequelae. The remaining eight had a normal US; however, one infant had hearing impairment. There were another three infected infants with normal development. Their mothers' serological results were: IgM positive with high AI (n=1); IgG positive; IgM negative with high AI (n=1); and both IgG and IgM negative (n=1). CONCLUSION: This method enabled us to detect infected fetuses having severe sequelae. However, the problem remains of detecting infected fetuses that only have a hearing impairment.

Associations of intrauterine growth restriction with placental pathological factors, maternal factors and fetal factors; clinicopathological findings of 257 Japanese cases.

Intrauterine growth restriction (IUGR) is the leading cause of fetal mortality and morbidity. As an etiology, each of placental findings, maternal factors and fetal factors has been reported to be associated with IUGR, although a comprehensive approach to examine all of these parameters as a cause of IUGR has not been reported. In the present study, therefore, we comprehensively examined the placental findings and maternal and fetal factors in the cases of IUGR (n=257, mean maternal age, 30 years; gestational weeks, 34 weeks) and normal growth pregnancies (n=258, mean maternal age, 30 years; gestational weeks, 33 weeks), and determined risk factors for IUGR. The prevalence of pregnancy hypertension (PHT) (19% vs. 8%, P<0.01), smoking habit (3% vs. 0.7%, P<0.05) and fetal anomaly (3.5% vs. 0.8%, P<0.05) were higher in IUGR cases than normal growth pregnancies. Pathologically, the prevalence of infarction (33% vs. 14%, P<0.05), fetal vessel thrombosis (22% vs. 6%, P<0.001) and chronic villitis (11% vs. 3%, P<0.001) were higher in IUGR cases than those in normal growth pregnancies. A multivariable regression analysis revealed that maternal factors (PHT), fetal factors (anomaly), and placental findings (infarction, fetal vessel thrombosis, and chronic villitis) are independently associated with increased risk of IUGR (all P<0.01).

Characteristics of the spin-trapping reaction of a free radical derived from AAPH: further development of the ORAC-ESR assay.

The characteristics of the spin-trapping reaction in the oxygen radical absorbance capacity (ORAC)-electron spin resonance (ESR) assay were examined, focusing on the kind of spin traps. 2,2-Azobis(2-amidinopropane) dihydrochloride (AAPH) was used as a free radical initiator. The spin adducts of the AAPH-derived free radical were assigned as those of the alkoxyl radical, RO· (R=H(2)N(HN)C-C(CH(3))(2)). Among the spin traps tested, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), 5,5-dimethyl-4-phenyl-1-pyrroline N-oxide (4PDMPO), 5-(2,2-dimethyl-1,3-propoxycyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO), and 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO) were applicable to the ORAC-ESR assay. Optimal formation of spin-trapped radical adduct was observed with 1 mM AAPH, 10 mM spin trap, and 5 s UV irradiation. The calibration curve (the Stern-Volmer's plot) for each spin trap showed good linearity, and their slopes, k (SB)/k (ST), were estimated to be 87.7±2.3, 267±15, 228±9, and 213±16 for DMPO, 4PDMPO, CYPMPO, and DEPMPO, respectively. Though the k (SB)/k (ST) values for selected biosubstances varied with various spin traps, their ratios to Trolox (the relative ORAC values) were almost the same for all spin traps tested. The ORAC-ESR assay also had a very good reproducibility. The ORAC-ESR assay was conducted under stoichiometric experimental conditions. The present results demonstrate the superiority of the ORAC-ESR assay.

Estimation of physiologic ability and surgical stress (E-PASS) for a surgical audit in elective digestive surgery.

BACKGROUND: This study was undertaken to establish an equation to estimate mortality with the use of the prediction scoring system designated as the Estimation of Physiologic Ability and Surgical Stress (E-PASS), and to evaluate the system's usefulness in defining quality of care by comparing it with the Physiologic and Operative Severity Score for the enUmeration for Mortality and morbidity (POSSUM) and Portsmouth-possum (P-POSSUM) scoring systems previously generated for surgical audit. METHODS: Patients (n=5212; group A) who underwent elective gastrointestinal surgery were analyzed to establish equations for estimated 30-day and in-hospital mortality rates. The usefulness of E-PASS was evaluated in another series of 1934 patients (group B) who underwent elective digestive surgery in 6 national hospitals. The ratio of observed to estimated mortality rates (OE ratio) of each hospital was defined as a measure of quality. RESULTS: In group A, 30-day and in-hospital mortality rates increased as the Comprehensive Risk Score (CRS) increased, providing equations for estimated mortality rates. There was an excellent correlation between the estimated and observed mortality rates in individual diseases: R=0.958, N=6, P=.0027 for in-hospital mortality; R=0.937, N=6, P=.0059 for 30-day mortality. In all patients of group B, the E-PASS system estimated the 30-day mortality rates by 0.63-fold (linear analysis), whereas the POSSUM score was 11.0-fold (exponential analysis). The E-PASS system estimated the in-hospital mortality rates by 1.2-fold (linear analysis), whereas the P-POSSUM score was 4.5-fold (linear analysis). The OE ratios for 30-day mortality among the 6 hospitals defined by E-PASS correlated well with those defined by POSSUM: R=0.996, N=6, P<.0001. Similarly, the OE ratios for in-hospital mortality defined by E-PASS were also highly correlated with those defined by P-POSSUM:(R=0.929, N=6, P=.0075. CONCLUSIONS: The E-PASS scoring system may be useful in defining surgical quality and may be more accurate than existing systems in evaluating elective digestive surgery.

Insulin-meal interval and short-term glucose fluctuation in tightly controlled gestational diabetes mellitus.

OBJECTIVE: To study the effect of two insulin-meal intervals on short-term glucose fluctuations in tightly controlled gestational diabetes mellitus (GDM). METHODS: We performed a prospective and paired study in 11 Japanese GDM women requiring insulin for good glycemic control during the third trimester. The women were subjected to test two insulin-meal intervals: 15 min and 30 min. Both regimens were examined in each patient in random order, 2 days apart. Blood glucose was measured by an automated glucose monitor every 2 min. Short-term glucose fluctuations of the two observations were analyzed by two-way ANOVA for repeated measurements with a post hoc t test (p < 0.05). Data were expressed as mean +/- SD. RESULTS: Daily glucose profiles of the two groups showed that their glycemic controls on the days of observation were good and that the two glucose profile curves were superimposable. A transient decrease in glucose (nadir 62 +/- 6 mg/dl) was observed at 6-10 min of meal ingestion in the 30-min regimen, which was significantly different from the glucose fluctuations during the 15-min regimen. The 2-h postprandial glucose levels were similar in both experiments. CONCLUSIONS: In women with tightly controlled GDM during the third trimester, insulin-meal intervals of 15 min are beneficial when compared with 30-min intervals, in that they avoid preprandial hypoglycemia without increasing 2-h postprandial hyperglycemia.

Evaluation of an Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system to predict postoperative risk: a multicenter prospective study.

We previously reported generating a scoring system termed E-PASS that predicted postsurgical risk. This study was undertaken to evaluate the usefulness of this system. A consecutive series of 902 patients who underwent elective gastrointestinal operations in six national hospitals in Japan were prospectively assessed for a comprehensive risk score (CRS) of the E-PASS, which was compared with their postoperative course. The postoperative morbidity rates linearly increased as the CRS increased. The postoperative mortality rate was only 0.13%, when the CRS was below 0.5; however, it increased to 9.7% when the CRS ranged from 0.5 to <1.0, and to 26.9% when the CRS was > or =1.0. The CRS correlated significantly with the severity of postoperative complications (rs = 0.527, P < 0.0001) and the costs of hospital stay (rs = 0.810, P < 0.0001). When the CRS-adjusted mortality rate at the CRS of > or =0.5 was compared among the hospitals, it was related to the hospital volume of operations, being 44.2% at the volume of <100 cases per year, 20.6% at the range of 100-199 cases, and 8.6% at the volume of > or =200 cases. These results suggest that E-PASS may be useful for predicting postsurgical risk, estimating medical expense, and comparing surgical quality.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (6)--Six-month repeated oral dose toxicity study in dogs].

A six-month repeated oral dose toxicity study of Cefmatilen hydrochloride hydrate (S-1090) at dose levels of 40, 100 and 250 mg potency/kg/day was conducted in male and female beagle dogs. No toxicologically significant changes were observed in general conditions of all animals. Reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were observed in all treated groups. Plasma irons showed a tendency to increase in the males and females of the 250 mg potency/kg group. However, as no changes suggesting anemia or hepatic injury were observed in this group, the change of plasma iron was considered to have no toxicological significance. No toxicologically significant changes were observed in other examination items. The plasma S-1090 concentrations increased in a manner less than dose-proportional. Based on the above results, the NOAEL of S-1090 was assessed to be 250 mg potency/kg/day.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (5)--Six-month repeated oral dose toxicity study and supplement study in rats].

Cefmatilen hydrochloride hydrate (S-1090) was orally administered to rats at dose levels of 100, 300 and 1000 mg potency/kg once daily for 6 months. All the S-1090 treated groups showed soft feces, reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet), abdominal distention, increased food and water consumption, lower urine pH, and a decrease of white blood cells counts (except for males of the 100 mg potency/kg group). One male in the 300 mg potency/kg group showed mucous feces and marked decrease in body weight, and diet in the middle stage of the administration period. In necropsy of the survivors of all treated groups, marked cecal enlargement was noted. No remarkable changes were observed in the other examination items. From the early stage of the withdrawal period, animals in the 1000 mg potency/kg group showed again soft or mucous feces and a marked decrease in body weight. Of these animals, one male died and another male was sacrificed in a moribund state at about 2 weeks of the withdrawal period. Enterocolitis was observed in these cases. Almost all animals recovered within 3 weeks of withdrawal. A supplemental study of the 6-month toxicity study was conducted to examine the mechanisms of enterocolitis and the changes observable in the 100 or 300 mg potency/kg groups after drug withdrawal. As a reference, cefdinir (CFDN), an oral cephem antibiotic the same as S-1090, was added in the 1000 mg potency/kg group. No deaths occurred in any groups. Decreased intestinal flora were noted in all the groups treated with S-1090 or CFDN at the end of the dosing period. At 2 weeks of the withdrawal period, C. difficile and its D-1 toxin in the cecal contents were highly detected in the S-1090 300 and 1000 mg potency/kg groups and CFDN group. Inflammatory changes in the cecum and colon were observed in these groups. At 4 weeks of the withdrawal period, intestinal flora in the S-1090 groups almost returned to the condition before dosing, but those in the CFDN group were retained highly. Cecal D-1 toxin in the CFDN group was positive and higher than in the S-1090 groups. It was thus considered that the critical condition with enterocolitis resulted from C. difficile, which proliferated more rapidly than the other bacteria and D-1 toxin produced by this bacteria in the withdrawal period. Above changes were commonly observed in the CFDN group. The NOAEL of S-1090 was assessed to be 100 mg potency/kg/day which induced no enteritis.

Long-term magnesium sulfate treatment as protection against hypoxic-ischemic brain injury in seven-day-old rats.

OBJECTIVE: Our purpose was to study the effects of long-term treatment with magnesium sulfate on hypoxic-ischemic brain damage in newborn rats. STUDY DESIGN: Seven-day-old rat pups (n = 120) were exposed to unilateral carotid artery ligation and 2 hours of hypoxia (8% oxygen in 92% nitrogen). Neuronal loss was evaluated in 4 groups. The loading dose group (n = 25) received a bolus injection of 270 mg/kg magnesium sulfate intraperitoneally. The maintenance group (n = 26) received 3 days of continuous infusion of magnesium sulfate with a micro-osmotic pump at a rate of 72 mg/kg per hour. The loading dose-plus-maintenance group (n = 23) received both. The control group (n = 46) did not receive magnesium. Seven days after the injury the pups were killed and the brains were removed for analysis. Severity of neuronal loss was evaluated in the cerebral cortex and hippocampus and compared among groups by chi2 test. RESULTS: Cyst formation resulting from necrosis was significantly decreased in the maintenance group (15%) and loading dose-plus-maintenance group (9%) but not in the loading dose group (52%) relative to the control group (46%). Severity of neuronal loss in the cerebral cortex and the hippocampus was also significantly improved in the maintenance group and the loading dose-plus-maintenance group but not in the loading dose group. Mortality rates were not different among the groups. Magnesium ion concentrations at 24 hours were significantly decreased from the preinfusion value of 0.49 +/- 0.01 mmol/L in the control group (0.34 +/- 0.03 mmol/L) but remained within normal ranges in the maintenance group (0.46 +/- 0.02 mmol/L with a pump infusing 72 mg/kg per hour and 0.56 +/- 0.05 mmol/L with a pump infusing 24 mg/kg hour). There was an inverse relationship between the maintenance dose and neuronal loss but not between the maintenance dose and mortality rate. CONCLUSION: Long-term magnesium administration had neuroprotective effects against hypoxia-ischemia in newborn rats.

Fetal cardiovascular function during prolonged magnesium sulfate tocolysis.

The purpose of this study was to evaluate the fetal cardiovascular function during prolonged magnesium sulfate tocolysis. We performed a fetal ultrasonographic examination in 15 patients (Mg group) during magnesium sulfate tocolysis for the treatment of preterm labor. The maternal serum magnesium concentration was 5.7 +/- 0.5 mg/dl at the time of the examination. Sixteen fetuses in normal pregnancies at similar gestational ages were used as the control group. The fetal heart rate and the middle cerebral artery pulsatility index in the Mg group were lower than in the control group (p < 0.01). Fractional shortening (FS) of the right ventricle in the Mg group was lower (p < 0.01), while FS of the left ventricle was higher (p < 0.01) than in the controls. The calculated blood flow through the tricuspid orifice in the Mg group was lower than in the control group (p < 0.01). In contrast, the blood flow through the mitral orifice in the Mg group was higher than in the control group (p < 0.01). In conclusion, in spite of the fact that the right ventricular function is depressed, the fetus maintains its cardiac output during prolonged hypermagnesemia by increasing its left ventricular function. These results indicate the different fetal intracardiac and peripheral circulation, especially in the brain, from normal fetuses.

Magnesium sulfate and fetal plasma concentrations of epinephrine, norepinephrine, and vasopressin in response to acute hypoxemia in goats.

OBJECTIVE: We measured fetal plasma concentrations of epinephrine, norepinephrine, and vasopressin during acute hypoxemia in goats and tested whether hypermagnesemia altered these endocrine responses. METHODS: Five chronically catheterized goat fetuses at 124-129 days' gestation were used. After 4 hours of infusion (magnesium or vehicle as controls), 30 minutes of hypoxemia was induced by infusing nitrogen gas through a maternal tracheal catheter. Fetal plasma concentrations of epinephrine, norepinephrine, and vasopressin were measured before and during hypoxemia. Both magnesium sulfate and vehicle infusions were performed in each animal. Repeated-measures analysis of variance (ANOVA) and two-way ANOVA with post hoc test were used to determine statistical significance. RESULTS: During hypoxemia, fetal PO(2) decreased significantly from 30 to 14 mmHg with no significant changes in fetal pH or PCO(2) in both groups. Fetal heart rate was reduced significantly by hypoxemia, but to a lesser extent in the magnesium group (change in decrease in fetal heart rate: 41 beats per minute [bpm] in controls versus 26 bpm with magnesium). Mean blood pressure did not change significantly during hypoxemia in both groups. Fetal plasma concentrations of epinephrine, norepinephrine, and vasopressin significantly increased from the prehypoxemic values both with magnesium and in controls. There were no significant differences in these hormone concentrations between magnesium and the controls. CONCLUSION: Magnesium sulfate had no effect on fetal plasma concentrations of vasopressin, epinephrine, and norepinephrine during acute hypoxemia.

Antepartum evaluation of monochorionic diamniotic (MD) twins; MD-twin score: a new scoring method for perinatal outcome.

OBJECTIVE: Our purpose was to establish a new scoring method to survey monochorionic diamniotic (MD) twins during antepartum periods. STUDY DESIGN: A retrospective study was performed regarding MD twins delivered between January 1992 and July 1996. Maternal and neonatal records were assessed for the following 5 perinatal variables; birth-weight discordance, amniotic-fluid discordance, hydrops fetalis, umbilical-cord insertion, and fetal-heart-rate monitoring. Each variable was coded as normal or abnormal and then assigned an arbitrary weight of 0 if normal and 1 if abnormal, yielding a range of scores from 0 (all normal) to 5 (all abnormal). The relationships between individual variables and their combinations and the outcome of pregnancy was determined. A poor pregnancy outcome consisted of intrauterine death, neonatal death, or neurological sequelae of at least one twin. The 5-variable combination was termed as the MD-twin score. A chi-square test and logistic regression analysis were used to determine statistical significance. RESULTS: There were 59 MD pregnancies, of which 13 pregnancies resulted in a poor outcome. The single variable that most likely contributed to a poor outcome was amniotic-fluid discordance. All 35 pregnancies with an MD-twin score of < or = 2 had a good outcome. There were 14 pregnancies with a score of 3, and 21% of them had a poor outcome. All of the pregnancies with a score of > or = 4 had a poor outcome. When we chose the MD-twin score of 3 as the critical point for a poor outcome, the likelihood ratio statistics became the highest of any single variable or any combination of variables. CONCLUSION: The MD-twin score predicted poor outcomes better than did any single variable or combination of variables.

Causes of maternal mortality in Japan.

CONTEXT: Japan's maternal mortality rate is higher than that of other developed countries. OBJECTIVES: To identify causes of maternal mortality in Japan, examine attributes of treating facilities associated with maternal mortality, and assess the preventability of such deaths. DESIGN AND SETTING: Cross-sectional study of maternal deaths occurring in Japan between January 1, 1991, and December 31, 1992. SUBJECTS: Of 230 women who died while pregnant or within 42 days of being pregnant, 197 died in a hospital and had medical records available, 22 died outside of a medical facility, and 11 did not have records available. MAIN OUTCOME MEASURES: Maternal mortality rates per 100,000 live births by cause (identified by death certificate review and information from treating physicians or coroners); resources and staffing patterns of facilities where deaths occurred; and preventability of death, as determined by a 42-member panel of medical specialists. RESULTS: Overall maternal mortality was 9.5 per 100,000 births. Hemorrhage was the most common cause of death, occurring in 86 (39%) of 219 women. Seventy-two (37%) of 197 deaths occurring in facilities were deemed preventable and another 32 (16%) possibly preventable. Among deaths that occurred in a medical facility with an obstetrician on duty, the highest rate of preventable deaths (4.09/100,000 live births) occurred in facilities with 1 obstetrician. Among the 72 preventable deaths, 49 were attributed to 1 physician functioning as the obstetrician and anesthetist. While the unpreventable maternal death rate was highest in referral facilities, the preventable maternal death rate was 14 times lower in referral facilities than in transferring facilities. CONCLUSIONS: Inadequate obstetric services are associated with maternal mortality in Japan. Reducing single-obstetrician only delivery patterns and establishing regional 24-hour inpatient obstetrics facilities for high-risk cases may reduce maternal mortality in Japan. JAMA. 2000;283:2661-2667.

Early glycemic control reduces large-for-gestational-age infants in 250 Japanese gestational diabetes pregnancies.

Our objective was to test if tight glycemic control versus loose glycemic control in gestational diabetic patients and a gestational age of < 32 weeks influence fetal growth, fetal distress, and neonatal complication. We performed a retrospective study with 250 gestational diabetes mellitus in Japanese women. Two groups were categorized according to the timing at which good maternal glycemic control was attained at < 32 weeks and kept so until delivery (group 1) and > 32 weeks or never until delivery (group 2). In these two groups, neonatal growth (large-for-gestational age: LGA; appropriate- : AGA; and small- : SGA), neonatal complications (hypoglycemia, jaundice, polycythemia, and cumulative incidence), and incidence of fetal distress were compared. The chi2 test, unpaired t test, one-way analysis of variance (ANOVA) and multiple logistic regression analyses were used for statistical analyses. Maternal age, height, prepregnancy body mass index (BMI), gestational age at delivery were not different between the groups. In group 2 (> 32 weeks), LGA, macrosomia (> 4 kg), neonatal hypoglycemia was significantly increased compared with those in group 1. Incidence of SGA, fetal distress, and neonatal jaundice were not different between the groups. Multiple logistic regression analysis for LGA showed significant relation to timing of maternal glycemic control. We concluded that good glycemic control should be attained at < 32 weeks and maintained until delivery to reduce LGA infants and neonatal hypoglycemia in gestational diabetes mellitus. This management did not appear to decrease SGA infants or fetal distress.

Intracranial haemorrhage as a cause of maternal mortality during 1991-1992 in Japan: a report of the Confidential Inquiry into Maternal Deaths Research Group in Japan.

OBJECTIVE: To determine the causes of maternal deaths by intracranial haemorrhage in Japan. DESIGN: Retrospective analysis of records relating to maternal deaths in 1991 and 1992. SAMPLES: Two hundred and thirty maternal deaths, including 25 cases of primary intracranial haemorrhage and two cases with secondary bleeding. METHODS: Attending doctors were interviewed and completed a 600-item data collection instrument for each maternal death. An expert committee reviewed the data for each death to determine whether the maternal deaths could have been prevented. MAIN OUTCOME MEASURES: Preventability of maternal death from intracranial haemorrhage treated in obstetric and emergency services in Japan. RESULTS: Half of the primary intracranial haemorrhages occurred during pregnancy, 20% during labour, and 30% in the postnatal period. Neurosurgeons considered that there were only three women in whom surgical drainage was indicated. The committee determined that there was only one maternal death which had a > or = 70% of being prevented. After detailed discussion of each case, 60% of the women (15/25) may have been saved by earlier and more intensive medical intervention. CONCLUSIONS: These findings suggest that detailed history taking and early diagnosis of intracranial haemorrhage would be helpful. Regionalisation of obstetric emergency systems are necessary to reduce maternal deaths in Japan due to intracranial haemorrhage.

[Comparison of the effect of rapid infusion of lactated and that of acetated Ringer's solutions on maternal and fetal metabolism and acid-base balance].

The maternal and neonatal metabolism and acid-base balance were investigated in 20 parturients undergoing combined spinal and epidural anesthesia for cesarean delivery. Patients received intravenous infusion at a rate of either 25 ml.kg-1.h-1 of lactated (LR group, n = 10) or acetated (AR group, n = 10) Ringer's solution before anesthesia, to prevent hypotension during anesthesia. We obtained venous blood samples as follows; maternal control before anesthesia, maternal sample A after the infusion, umbilical sample B, and neonatal pedal sample C 5 h after birth, and determined lactate, pyruvate, bicarbonate, and base excess concentrations, and pH in each sample. In sample A, the lactate level was significantly higher and base excess level was significantly lower in the LR group than in the AR group. The pH of sample A and B was significantly higher in the AR group than in the LR group. However, no differences in all parameters of sample C between the two groups were observed. These results demonstrated that acetated Ringer's solution is better than lactated Ringer's solution in rapid infusion before cesarean section because of the correction of neonatal lactic acidosis.

[Clinicobacteriological studies on the nine cases with upper genital tract Mycoplasma hominis infection].

Clinicobacteriological characteristics of nine cases isolated Mycoplasma hominis from the genital tract were studied, and the following results were obtained: elevation of IgG antibodies to M. hominis was measured by ELISA in all cases, but in the MI method only one case showed an elevation of metabolic inhibitory antibody. Convalescent sera from seven patients showed additional and high density bands which were not recognized by acute phase sera in immunoblotting. It was thought that in two patients M. hominis was a causal bacteria for pelvic inflammatory disease (PID). In three cases, it was suggested that M. hominis was related to a premature delivery and idiopathic labor. As infectious symptoms, two patients had body temperatures of more than 38 degrees C but other cases showed 37-37.8 degrees C. Though all cases showed an elevation of CRP, six elevations were slight. As a medication beta-lactam agents were administrated, but their efficacy was not recognized. Furthermore, two patients showed spontaneous recovery in spite of improper antimicrobial agents administration or drainage combined with antimicrobial agents. From the above results. It was thought that M. hominis played a causative role in upper genital tract infection.