Influenza 2014-2015 among pregnant Japanese women: primiparous vs multiparous women.

This study was performed to determine whether multiparous pregnant women are prone to influenza. A questionnaire survey was conducted at 19 centres located throughout Japan, targeting all 6,694 postpartum women within 7 days after birth before leaving the hospital. All women gave birth during the study period between March 1, 2015, and July 31, 2015. Data regarding vaccination and influenza infection in or after October 2014, age, previous experience of childbirth, and number and ages of cohabitants were collected. Seventy-eight percent (n = 51,97) of women given questionnaires responded. Of these, 2,661 (51 %) and 364 (7.0 %) women reported having been vaccinated and having contracted influenza respectively. Multiparous women had a higher risk of influenza regardless of vaccination status (8.9 % [121/1362] vs 5.7 % [74/1299], relative risk [95 % confidence interval], 1.80 [1.36 to 2.38] for vaccinated and 9.3 % [112/1198] vs 4.3 % [57/1328], 2.18 [1.60 to 2.97] for unvaccinated women) compared to primiparous women. The risk of influenza increased with increasing number of cohabitants: 4.8 % (100/2089), 7.5 %, (121/1618), 9.0 %, (71/785), and 10.4 % (58/557) for women with 1, 2, 3, and ≥4 cohabitants respectively. Family size is a risk factor for influenza infection in pregnancy.

Amniotic fluid embolism: a comparison between patients who survived and those who died.

This study aimed to investigate comparative clinical courses for a series of women with amniotic fluid embolism (AFE) and to assess factors associated with patient survival. Clinical courses of nine patients with AFE in a single tertiary centre were reviewed. AFE was diagnosed when a woman presented with typical clinical symptoms accompanied by abnormal laboratory tests (including abnormal coagulation) or at autopsy when fetal debris was found in the maternal pulmonary arteries. Five patients survived and four died. The first clinical manifestations of AFE were variable; dyspnoea was noted in only four patients. Other signs were state of shock, abdominal pain and uterine atony. The mean +/- SD interval between the onset of clinical manifestations and treatment was significantly shorter for survivors (48.0 +/- 36.3 min) than for non-survivors (137.5 +/- 49.7 min). The number of failed organs was significantly fewer for the survivors compared with the non-survivors. AFE was accompanied by a wide variety of clinical manifestations, but early diagnosis and treatment appeared to be the most critical factors associated with survival.

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.

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.

Intrauterine infection, magnesium sulfate exposure and cerebral palsy in infants born between 26 and 30 weeks of gestation.

OBJECTIVE: To identify prenatal events associated with cerebral palsy (CP) in infants born between 26 and 30 weeks of gestation. STUDY DESIGN: Case (n=22)-control (n=170) study was performed using a logistic regression model. RESULTS: Significant association of intrauterine infection with increased risk of CP was found in a logistic regression model that controlled for abnormal FHR patterns, placental infection, fetal acidosis at birth (umbilical artery pH<7. 1), and low Apgar score (<7) (odds ratio (OR) 5.47, 95% confidence interval (CI) 1.46-20.4). Magnesium sulfate exposure was associated with decreased risk (OR 0.13, CI 0.03-0.66) after exclusion of premature rupture of the membranes and abruptio placentae. In the magnesium exposure group, cases were infants born less than 28 weeks of gestation (3/21 vs. 0/61, P=0.015). CONCLUSION: In this case-control study, both intrauterine infection and magnesium sulfate exposure were significant factors related to the occurrence of cerebral palsy.

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.

Neonatal 24-hour urinary C-peptide and birth weight in infants of diabetic mothers.

OBJECTIVE: Our purpose was to investigate the relationship between the birth weights and 24-h urinary C-peptide in infants of diabetic mothers. METHODS: Sixty pregnancies with gestational diabetes mellitus (DM) were enrolled. Neonatal urine was collected for the first and second 24 h for measuring C-peptide. Birth weights were classified into 3 categories according to the Japanese standard curves; heavy-for-date (HFD), appropriate-for-date (AFD), and light-for-date (LFD). Unpaired t-test was used for comparison of 24-h urinary C-peptide in the 3 birth weight categories, with P-value <0.05. There were 7 HFD, 47 AFD, and 6 LFD infants. Birth weight averaged 3.9+/-0.7, 3.0+/-0.4, and 2.3+/-0.3 kg, respectively. RESULTS: Insulin concentrations of the umbilical artery were significantly higher in HFD than in AFD, and significantly higher in AFD than in LFD (49.5+/-45.1, 16.8+/-15.2, and 6.3+/-6.1 microU/ml). During the first 24 h, urinary C-peptide was significantly higher in HFD than in AFD (2.73+/-1.52 vs. 0.76+/-0.81 microg/day), and significantly higher in AFD than in LFD (0.27+/-0.27). On the second day, there was no longer statistical significance. CONCLUSIONS: Measurement of 24-h urinary C-peptide revealed that, among infants of diabetic mothers, HFD infants continue to secrete more insulin than AFD and LFD infants for the first 24 h.

Hemangioma of the umbilical cord: stenotic change of the umbilical vessels.

We report a rare case of an umbilical cord hemangioma diagnosed by ultrasound at 16 weeks of gestation. The umbilical cord consisted of a hemangioma nodule and pseudocysts near the placental insertion, a large gelatin-like swelling adjacent to the nodule on its fetal side, and a short normal part extending to the navel. At 17 weeks of gestation, this condition resulted in the intrauterine death of the fetus. Microscopically, there were communications between the capillary of the hemangioma and the umbilical vessels, verifying the origin of the tumor. Moreover, the umbilical vein and one of the arteries changed stenotically due to the intravascular proliferation of the hemangioma. These findings indicate the possibility of a pathological association between the umbilical cord hemangioma and fetal demise due to impaired umbilical circulation.

Echocardiographic findings of pulmonary atresia or critical pulmonary stenosis and intact ventricular septum in utero.

BACKGROUND: Neonates with right ventricular outflow obstruction and intact ventricular septum show serious hemodynamic problems, such as severe hypoxemia, congestive heart failure due to massive tricuspid regurgitation, respiratory distress related to huge pulmonary hypoplasia or ventricular dysfunction due to right ventricle-coronary communication. Recent advances in fetal diagnosis include many cases of in utero diagnosis of pulmonary atresia or critical pulmonary stenosis and intact ventricular septum. METHOD: Among the fetuses examined from April 1994 to March 1998, five fetuses were found with pulmonary atresia (PA) or critical pulmonary stenosis (CPS). Fetal echocardiograms were reviewed to elucidate the accuracy of fetal information and the efficacy of fetal diagnosis in the perinatal management of patient with CPS or PA and intact ventricular septum. RESULTS: The five cases were divided into two groups: two with a very small right ventricle (group 1) and three with a tripartite right ventricle (group 2). Fetal cardiomegaly and right atrial dilatation were prominent in group 2, whereas cardiac sizes were normal in group 1. Serial fetal examination in one group 2 fetus revealed developing right ventricular hypertrophy in utero. All group 2 cases showed massive tricuspid regurgitation (TR). Estimated right ventricular pressures from TR always exceeded the systemic blood pressures of gestational age-matched neonates. Reversed flow through the ductus arteriosus was recorded in both groups and ductus-dependent pulmonary circulation after birth was anticipated. Patency of both tricuspid and pulmonary valves was difficult to recognize in utero, as was right ventricle-coronary artery communication. Four of the five cases were maternally transported and survived palliative and/or definitive intervention. One fetus with chromosomal abnormality was observed without intervention during infancy and received palliative surgery when she was two years old. CONCLUSION: Fetal hemodynamic information was useful for making decisions not only after birth, but also in utero, and may eventually result in improving the prognosis of babies with PA/CPS. Serial observation of the fetuses with PA/CPS may also suggest the possible pathogenesis of PA/CPS in utero.

Periodic fetal heart rate decelerations during 6 hours' hypoxemia induced in goats.

OBJECTIVE: To determine if fetal heart rate (FHR) decelerations periodically occur with uterine contractures during 6 hours' induced hypoxemia in goats. METHODS: In five chronically catheterized goat fetuses at 125-130 days' gestation, incidence of FHR decelerations was compared between 6 hours' control time and 6 hours' induced hypoxemia with two-way ANOVA and Duncan's multiple range test. Three other fetuses were used as controls for circadian rhythm. RESULTS: Fetal PaO2 was significantly decreased from 26.1 to 16.3 mmHg without acidemia. During hypoxemia, 42 decelerations were induced along with 5 initial decelerations during the acute phase hypoxemia. Incidence of decelerations increased significantly from 0.07 +/- 0.15 per hour in 6-hour controls to 1.40 +/- 0.28 per hour during 6 hours' induced hypoxemia. Short-term variability and long-term variability of the 42 decelerations were significantly increased. These variabilities were also increased during the 5 initial decelerations. Frequency of uterine contractures did not change during hypoxemia. There was an observable association of FHR decelerations with uterine contractures during hypoxemia. CONCLUSION: Fetal heart rate decelerations occurred periodically in association with uterine contractures during induced 6 hours' hypoxemia, which were characterized by slow onset and recovery with increases in variability.

Fetal glioblastoma: rapid growth during the third trimester.

We present a case of fetal glioblastoma which appeared after 28 weeks' gestation. The first ultrasonographic finding was an enlarged fetal head with right shifted falx cerebri at 31 weeks' gestation. At 33 weeks, a large and high echogenic mass in the left hemisphere and right enlarged ventricle was identified. Magnetic resonance imaging showed that the tumor was localized in the left hemisphere and a margin of the tumor was defined. Because fetal well-being judging from biophysical parameters was good and we considered that the tumor was resectable, a male fetus weighing 2,670 g was delivered at 34 weeks' gestation by cesarean section. However, he was inoperable due to consumptive coagulopathy and rapid growth of the tumor, and died on the 41st day of life.

Effects of 4 hours magnesium sulfate infusion on fetal heart rate variability and reactivity in a goat model.

Effects of magnesium sulfate were investigated on fetal heart rate (FHR) baseline, variability, and reactivity in goats. Six chronically catheterized fetuses of Japanese Saanen goat at 125 to 130 days' gestation (term = 147 days) were used. Magnesium sulfate was directly infused to the fetuses. Short-term variability and long-term variability were obtained according to Huey et al. The baseline, reactivity, short-term variability and long-term variability of the FHR were compared between those receiving magnesium sulfate infusions and those receiving vehicle infusions without magnesium sulfate for 4 hr. Two-way analysis of variance (ANOVA) and Duncan's multiple range test was applied for statistical significance. Four hours magnesium sulfate infusion significantly increased fetal plasma concentration of magnesium from 2.4-6.6 mg/dL, without significant changes in fetal respiratory gases and pH values. The baseline FHR was significantly decreased by magnesium infusion compared with that receiving vehicle infusion. The incidence of acceleration, short-term variability, and long-term variability during the fourth hour of magnesium infusion was also significantly decreased compared to a controlled infusion. The time spent by high amplitude phase of short-term variability and that of long-term variability were also significantly reduced. Significant correlation was obtained between the magnesium concentration and incidence of acceleration at fourth hour of magnesium infusion. Four hours infusion of magnesium sulfate significantly decreases baseline FHR, short-term variability, long-term variability, and reactivity in fetal goats at 0.85 gestation.

Effects of magnesium sulfate on the fetal heart rate response during acute hypoxemia in goats.

OBJECTIVE: The effects of magnesium sulfate on fetal heart rate (FHR) response during acute hypoxemia in goats were investigated. METHODS: The FHR responses due to hypoxemia during magnesium sulfate infusion (Mg study) were compared with those during vehicle infusion (controls) in six chronically instrumented goat fetuses at 125-130 days' gestation. RESULTS: Four-hour infusions of magnesium sulfate significantly increased fetal plasma concentrations of magnesium from 2.3 to 6.5 mg/dL. During the hypoxemic period, the fetal arterial oxygen pressure was significantly decreased from 29.0 +/- 2.5 to 14.6 +/- 2.6 torr in the controls, and from 28.9 +/- 3.9 to 13.7 +/- 4.7 torr during the Mg study. Neither arterial carbon dioxide pressure nor pH was significantly altered. In the controls, FHR was significantly decreased by hypoxemia, accompanied by increases in variability. In the Mg study, FHR was not significantly decreased by hypoxemia. Acute hypoxemia also increased the FHR variability during magnesium infusion, which was significantly reduced compared with those in the control population. CONCLUSION: Magnesium sulfate masks FHR-slowing responses during acute hypoxemia in fetal goats.

Vasopressin and catecholamine responses to 24-hour, steady-state hypoxemia in fetal goats.

The purpose of the present study was to determine the effect of prolonged hypoxemia without acidemia on fetal stress hormones. Twenty-four-hour hypoxemia was conducted in nine chronically catheterized pregnant goats to determine fetal plasma concentrations of arginine vasopressin (AVP), epinephrine (E), and norepinephrine (NE). Nine experiments were performed. Six resulted in nonacidemic, steady-state hypoxemia, and three incidentally resulted in hypoxemia with progressive acidemia. In steady-state hypoxemia, fetal PO2 decreased significantly from 28.1 +/- 2.4 Torr to 18.8 +/- 2.5 Torr, fetal PCO2 also decreased significantly by about 5 Torr, and pH values did not change significantly. Fetal plasma concentrations of AVP, E, and NE were significantly increased at 1 h of hypoxemia. As hypoxemia continued, AVP returned to control level by 24 h, while E and NE remained elevated throughout the hypoxemic period. In the three experiments with progressive acidemia, AVP, E, and NE increased further as fetal acidosis progressed. We conclude that fetal AVP acts as a shorter-term stress hormone than E and NE in steady-state hypoxemia. This adaptive response is present without progressive acidosis. We also conclude that accompanying acidemia is a more potent stimulus for AVP, E, and NE than isolated hypoxemia during longer-term studies.

[Retinopathy and perinatal outcome in diabetic pregnancy].

Sixty patients with diabetes mellitus (DM) antedated pregnancy were enrolled; seven had proliferative retinopathy, 13 had simple retinopathy, and 40 were intact. Diet and/or insulin was prescribed to adjust their glucose control at fasting to < 100 mg/dl, as well as at 2 hours postprandial to < 120 mg/dl. Glycohemoglobin (Hemoglobin A1c) levels ranged between 5.4% and 6.4% in the third trimester in three groups. Incidences of pregnancy complications (toxemia, hydramnios, urinary tract infection and cesarean section) and neonatal complications (low Apgar score, hypoglycemia, jaundice, polycythemia, respiratory distress syndrome and anomaly) did not differ significantly with the grade of retinopathy. Compared with the intact group, the duration of DM was significantly longer in the retinopathy groups and the incidence of fetal distress was significantly higher in the proliferative retinopathy group. In ten of 60 patients (16.7%) the grade of retinopathy progressed during pregnancy. In four patients photocoagulation was performed for neovascularization, and proved to be effective. There was a tendency for those whose retinopathy progressed to the proliferative stage during pregnancy to have larger decreases in glycohemoglobin and for their retinopathy to worsen after delivery. With tight maternal glucose control and intensive fetal surveillance, we obtained good perinatal outcome in pregnancies with diabetic retinopathy, as compared to diabetic pregnancy without diabetic microangiopathy. Careful and frequent monitoring of retinal changes should be required during pregnancy and the postpartum period.

[Recent advances in ovarian cancer chemotherapy from the survival standpoint].

The following consensus has been reached over the last two decades from clinical research: 1) Single nonplatinum agents or nonplatinum combinations have failed to demonstrate a significantly longer median survival. 2) Platinum combinations are generally better than single-agent platinum when platinum is used at the same dose. 3) Cisplatin-based chemotherapy produced a substantial clinical improvement as indicated by increased response rate duration of response and time to progression, but the overall effect on survival has been modest. The higher doses of cisplatin, ranging from 12.5 to 50 mg/sm/week, have demonstrated a general trend for prolonged median survival. But a more escalated dose of platinum supported by PBSCT is an investigational setting to ensure the advantage for overall survival in the near future. This consensus has been achieved from analysis of clinical trials in Europe and the United States for ovarian cancer chemotherapy, but only a few Japanese clinical trials have showed a similar tendency in the manner of retrospective studies. Six cycles of chemotherapy of cisplatin/cyclophosphamide or carboplatin/cyclophosphamide have become the standard and yield clinical response rates of approximately 60-70% and 5-year survival of 15-25 percent for advanced ovarian cancer. Taxol is thought to be the next promising candidate for cisplatin combination and secondary chemotherapy for ovarian cancer. It augurs to improve the overall survival. We look forward to early use of taxol in Japan at the clinical level.

Effects of isoproterenol on the cardiovascular system of fetal sheep exposed to long-term high-altitude hypoxemia.

We exposed fetuses to high-altitude (3,820 m) hypoxemia from 30 to 130 days gestation, when we measured fetal heart rate, right and left ventricular outputs with electromagnetic flow probes, and arterial blood pressure during an isoproterenol dose-response infusion. We also measured the distribution of cardiac output with radiolabeled microspheres during the maximal isoproterenol dose. Baseline fetal arterial blood pressure was higher in long-term hypoxemic fetuses (50.1 +/- 1.3 vs. 43.4 +/- 1.0 mmHg) but fell during the isoproterenol infusion to 41.3 +/- 1.4 and 37.5 +/- 1.4 mmHg, respectively, at the highest dose. Heart rate was the same in both groups and did not differ during isoproterenol infusion. Baseline fetal cardiac output was lower in the hypoxemic group (339 +/- 18 vs. 436 +/- 19 ml.min-1.kg-1) due mainly to a reduction in right ventricular output. During the isoproterenol infusion, right ventricular output increased to the same extent in both hypoxemic and normoxic fetuses (approximately 35%); however, left ventricular output increased only approximately 15% in the hypoxemic group compared with approximately 40% in the normoxic group. The percent change in individual organ blood flows during isoproterenol infusion in the hypoxemic groups was not significantly different from the normoxic group. All of the mechanisms that might be responsible for the differential response of the fetal left and right ventricles to long-term hypoxia are not understood and need further exploration.

Cerebral magnetic resonance angiographic findings in severe preeclampsia.

OBJECTIVE: The purpose of our study was to investigate the cerebral pathophysiology of severe preeclampsia using the noninvasive method of magnetic resonance angiography. STUDY DESIGN: We studied cerebral magnetic resonance angiography findings in 9 severely preeclamptic patients. RESULTS: Magnetic resonance angiographies were abnormal on first scanning within 48 h postpartum, followed by normal findings on repeat scanning during the 1st postpartum month in 6 patients. The most common abnormality was vascular narrowing of anterior cerebral artery and basilar artery. Three of these 6 patients complained of headaches and/or visual disturbances. CONCLUSION: This study shows that cerebral artery vasospasm is seen in some severe preeclamptic patients.