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BACKGROUND In Japan, 44.3% of neonates are delivered in private clinics without an attending pediatrician. Obstetricians in the clinics must resuscitate asphyxiated neonates in unstable condition, such as respiratory failure, and they are frequently transferred to tertiary perinatal medical centers. There has been no study comparing the physiological status and prognosis of neonates transported by ambulance with those transported by helicopter. METHODS Medical and transport records were used to compare the physiological status of neonates transported to Kagoshima City Hospital by land and those transported by air between January 1, 2013, and December 31, 2017. RESULTS Data from 425 neonates transferred by land and 143 by air were analyzed. There were no significant differences between the two groups in mean gestational age, mean birthweight, fetal blood pH, Apgar score, or the Score for Neonatal Acute Physiology with Perinatal Extension-II (SNAPPE-II) on arrival to the tertiary center (16.3 ± 15.4 [95% confidence interval (CI): 13.2-17.7] vs 16.4 ± 15.4 [95% CI: 13.9-19.0], respectively; P = 0.999); both groups had SNAPPE-II score 10-19, indicating no difference in mortality risk. The times to starting first aid and to admission to the intensive care unit were significantly reduced in neonates transported by air than by land. In subgroup analysis of patients of a gestational age ≤28 weeks, all cases of severe intraventricular hemorrhage (IVH) were observed in the land transportation group. CONCLUSIONS Neonatal transportation by air is as safe as land transportation, and time to first aid and intensive care are significantly reduced by transportation by air than by land. Air transport could also contribute to the prevention of IVH in neonatal transportation.

AIM Periventricular leukomalacia (PVL) is an important cause of cerebral palsy in premature infants, and cystic PVL is the most serious form of the disease. The risk factors for cystic PVL in singleton fetuses at a gestational age of

Introduction: We aimed to evaluate the risk factors for mortality and neurodevelopmental impairment (NDI) among infants of 22–23 weeks’ gestational age, which currently remain unclear. Methods: This retrospective case-control study included 104 infants delivered at 22–23 weeks’ gestation at Kagoshima City Hospital from 2006 to 2015. We compared 65 and 34 cases of survival to discharge and postnatal in-hospital death (5 excluded), respectively, and 26 and 35 cases with and without NDI, respectively, using maternal, prenatal, and postnatal records. A high rate of survivors’ follow-up (61/65) was achieved in this study. Results: The survival rate was 75.0% (21/28) and 62.0% (44/71) among infants born at 22 and 23 weeks’ gestation, respectively. Infants who died weighed less (525.5 vs. 578 g, p = 0.04) and their intrauterine growth retardation (IUGR) rate (p = 0.02). Mortality was associated with an increased incidence of bradycardia on fetal heart rate monitoring (11.8 vs. 1.5%, p = 0.046), periventricular hemorrhagic infarction (PVHI; 32.4 vs. 6.2%, p = 0.001), necrotizing enterocolitis (NEC, surgery or drain tube; 14.7 vs. 0.0%, p = 0.004), and tension pneumothorax (29.4 vs. 6.2%, p = 0.004). There were significant differences in the proportion of PVHI (15.4 vs. 0%, p = 0.03) between infants with and without NDI. Conclusions: IUGR, bradycardia, PVHI, NEC, and tension pneumothorax were associated with neonatal mortality among infants born at 22–23 weeks’ gestation. NDI at 36–42 months’ chronological age was associated with PVHI.

We conducted a questionnaire survey on the current obstetric management of preterm labor (PL) and preterm premature rupture of the membranes (pPROM). The questionnaire covered approximately a third of all preterm deliveries and nearly half of the preterm deliveries before 32 gestational weeks. The diagnostic criterion for PL was either painful uterine contractions or cervical dilatation. Tocolytic agents were primarily used as long-term maintenance therapy. Intrauterine infection was clinically diagnosed at most responding institutions. Amniocentesis was performed for PL or pPROM at only a small number (10%) of institutions. Prenatal steroids were administered for PL or pPROM, if indicated, at approximately 40-60% of responding institutions. Prophylactic antibiotics to maintain pregnancy were administered for pPROM at approximately 90% and for PL at approximately 20% of institutions. Maintenance therapy with a tocolytic agent was used for pPROM at approximately 90% of institutions.

Aim Recent reports have shown lower levels of Clostridium and higher levels of Lactobacillales in the intestinal microbiota in preterm birth patients compared to term birth patients. However, the influence of probiotics on perinatal status has not been elucidated. The aim of our study was to evaluate the effects of probiotics on perinatal outcomes. Methods We retrospectively evaluated the effects of oral probiotics on perinatal outcome in patients at high risk of preterm birth. Probiotics containing Streptococcus faecalis, Clostridium butyricum and Bacillus mesentericus were administered for prophylaxis of bacterial vaginosis or treatment of constipation starting at 12.5 ± 4.1 weeks until delivery. Patients not administered probiotics were defined as the non-probiotics group. Between these two groups, perinatal outcomes including gestational age at birth, birth weight, chorioamnionitis or funisitis and preterm birth before 32 weeks were compared. In addition, multivariate regression analyses were performed to evaluate factors influencing preterm birth before 32 weeks, chorioamnionitis/funisitis and normal vaginal flora. Results The probiotics group showed longer gestation, higher birth weight, lower rates of chorioamnionitis and higher rates of normal vaginal flora compared to the non-probiotics group. Multivariate regression analysis showed that probiotics significantly suppressed preterm birth before 32 weeks and tended to suppress chorioamnionitis/funisitis. The adjusted odds ratios (95% confidence interval) for preterm birth before 32 weeks and chorioamnionitis/funisitis were 0.05 (0.01–0.71) and 0.07 (0.01–1.03), respectively. Conclusions Oral probiotics containing Clostridium had a significant effect on the prevention of preterm birth before 32 weeks of gestation.

AIMS Magnesium sulfate has neuroprotective effects in preterm infants. Whether other antepartum treatments interfere with the neuroprotective actions is not well known. This study aims to explore the impacts of antenatal administration of Magnesium sulfate or beta-2 adrenergic agonists as tocolytic agents on the developing brain in premature infants. METHODS This is a retrospective cohort study in four tertiary perinatal centers in Japan. We collected data of pregnant women and infants born between 28 and 36 weeks for tocolytic agents, gestational age, sex, antenatal corticosteroid, fetal growth restriction, pathological chorioamnionitis, low umbilical arterial pH values (

Preterm labor may be induced by infection pathways, including ascending infection, hematogenous transplacental infection, and transovarial disseminated infection. Causative bacteria may originate from the vagina, intestinal tract, or oral cavity; however, approximately 90% of cases involve an ascending infection from the vagina, and the presence of abnormal microbiota in the vagina is a major cause of preterm labor. Conversely, in recent years, researchers have alluded that abnormal microbiota in the gut causes a pro-inflammatory state, which could contribute to preterm labor. The administration of probiotics to improve this state and thereby prevent preterm labor is being studied; however, at this time, although probiotics can normalize vaginal microbiota, there is no clear evidence that they can prevent preterm labor. To clarify the therapeutic effects of probiotics in preventing preterm labor, a randomized controlled trial is required, wherein the type of bacteria administered, starting time, administration duration, and treatment subjects are taken into account.

Background There have been few reports regarding outcomes after extracorporeal membrane oxygenation (ECMO) in newborn Japanese infants. Methods A review of 61 neonates with ECMO through January 1995 at a single center was performed. ECMO was used in neonates with oxygenation index > 20 after conventional treatments. Background factors, such as etiology, vascular access mode (veno–venous [VV] or veno–arterial [VA]), number of days with ECMO, and early ECMO (within 24 hours after birth), were analyzed in relation to outcome with respect to survival to hospital discharge (SHD). Results SHD was achieved in 35 (57%) infants, while the remaining 26 died during the hospital stay. Gestational age at birth was significantly higher and number of days with ECMO was significantly lower in SHD infants compared to those with adverse outcome (median, 4.0 vs. 5.5 days, respectively, P = 0.008). The SHD rate was significantly higher for those with VV than VA (78% [18/23] vs. 45% [17/38], respectively, P = 0.016), and for those with than without early ECMO (72% [28/39] vs. 32% [7/22], respectively, P = 0.003). The SHD rate was relatively high in neonates with meconium aspiration syndrome (MAS) (86% [12/14]), persistent pulmonary hypertension (PPHN) associated with hypoxic ischemic encephalopathy (HIE) (75% [6/8]), and emphysema (80% [4/5]). Stepwise logistic regression analysis identified two independent risk factors for SHD including early ECMO (OR [95%CI], 9.63 [2.47 – 37.6]) and ECMO length < 8 days (8.05 [1.94 – 33.5]). Conclusions Neonates having early ECMO and those with ECMO duration less than 8 days may have benefited from ECMO with respect to SHD. This article is protected by copyright. All rights reserved.

Uhl anomaly is an extremely rare condition, and herein, we present a case of prenatally diagnosed Uhl anomaly to illustrate the associated echocardiographic features. Fetal echocardiography at 26 weeks indicated an enlarged right ventricle, severe tricuspid and pulmonary regurgitation, and ruptured ventricular septal aneurysm, resulting in a circular shunt. At 36 weeks, based on the presence of a thin ventricular wall and absence of apical trabeculation, a diagnosis of Uhl anomaly was made. The neonate, delivered by cesarean section, underwent main pulmonary artery ligation to eliminate the circular shunt immediately after birth. Moreover, he underwent ductus arteriosus ligation and received a pulmonary artery to aorta shunt for progressive lung congestion. He is currently well and awaiting a staged Fontan operation involving a bidirectional Glenn procedure. Understanding and accurate prenatal diagnoses of Uhl anomaly may help in parental counseling, planning appropriate perinatal care, and increasing the chances of survival.

Aim To clarify perinatal outcomes of monoamniotic (MM) twin pregnancies. Material and Methods MM twins delivered in seven tertiary perinatal centers during the last decade were retrospectively evaluated. All pregnant women were scheduled to begin inpatient management at around 24 weeks of gestation and undergo a planned cesarean section beyond 32 weeks. Pregnancy outcomes, prevalence of fetal death and cord entanglement, perinatal mortality and neuromorbidity rate at discharge were examined. Results The study group comprised 38 MM twin pregnancies (76 fetuses). Cord entanglement was confirmed in 88% (30/34) of women, and fetal deaths occurred in nine women (eight were both fetal deaths, and one was single fetal death). The cord entanglement accounted for 65% (11/17) of the fetal deaths. The median gestational age at delivery was 31+3 weeks, but that for viable infants was 32+3 weeks; the median birth weight was 1642 g, the perinatal mortality rate was 2% (1/60), and the neuromorbidity rate was 8% (5/50). The overall survival rate was 75% (57/76). Conclusion Perinatal outcomes in our study were relatively good irrespective of high frequency of cord entanglement. Close fetal monitoring may allow MM twin pregnancies to extend gestational age, which may contribute to reduce both fetal death and neonatal morbidity by immaturity, although the best delivery weeks remained undetermined.

Aim: To evaluate the methods of screening and prenatal diagnosis of vasa previa. Material and Methods: We reviewed cases of vasa previa in our hospital between January 2002 and December 2007. During this period, we visualized the site of cord insertion using transabdominal ultrasonography and observed the internal os using gray-scale transvaginal ultrasonography. A diagnosis of vasa previa was confirmed by transvaginal color Doppler imaging. Results: We encountered 10 cases of vasa previa among 5131 deliveries. All cases had one or more known risk factors. In all of the four cases that underwent screening in the second trimester (i.e. between 20 and 25 weeks of gestation), the diagnosis was correct. Routine ultrasonography detected in only three of the other six cases of vasa previa that were referred to our hospital after 26 weeks of gestation. Of the other three cases referred after 26 weeks of gestation, in two cases vasa previa was detected by detailed examination using color Doppler transvaginal ultrasonography after fetal heart rate monitoring detected the presence of non-reassuring fetal status; in the remaining case, we were unable to make an antenatal diagnosis. Non-reassuring fetal status was seen on fetal heart rate monitoring in four of the five detected cases complicated by preterm labor. Conclusion: We consider that the best timing of antenatal screening for vasa previa is the second trimester. Non-reassuring fetal heart rate pattern without other possible causes warrants detailed examination of vasa previa.

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.

Our purpose was to evaluate the clinical validity of electronic fetal heart rate monitoring to detect fetal acidemia and to evaluate the prevalence of cerebral palsy in unselected low-risk pregnancies.We selected two secondary and two tertiary level institutions in which 10,030 infants were born. Among them, 5546 of the pregnancies were low-risk pregnancies by antepartum evaluation. The fetal heart rate patterns were interpreted according to the guidelines of the National Institute of Child Health and Human Development. The correlations between the fetal heart rate pattern and umbilical blood gases and the fetal heart rate pattern and cerebral palsy were studied. Spastic cerebral palsy was diagnosed ator =1 year by pediatric neurologists. Statistics included unpaired t test, contingency table with chi(2) and Fisher tests, and one-way analysis of variance with Bonferroni/Dunn test.On the basis of the severity of decelerations, frequency of decelerations, and decreased variability, umbilical pH, and Po(2) level were decreased accordingly, and incidence of pH7.1 was increased. Sensitivity and false-positive rate of nonreassuring fetal heart rate patterns for fetal acidemia were 63% and 89%. There were nine cerebral palsy cases: six of the cases were preexisting asphyxia before monitoring was initiated, two of the cases were cytomegaloviral infections, and one of the cases was a maternal amniotic fluid embolism.In low-risk pregnancies, intrapartum fetal heart rate monitoring was useful to detect fetal acidemia. Cerebral palsy caused by intrapartum asphyxia was restricted to unavoidable accidents under continuous fetal heart rate monitoring.

In fetal sheep, we found that the augmentation of cardiac contractility by beta-adrenergic receptor (beta-AR) stimulation was reduced after exposure to long-term hypoxia. However, cyclic adenosine monophosphate (cAMP) production after beta-AR stimulation was higher in long-term hypoxic fetal sheep than in normoxic ones. Therefore, we studied the potential role of changes in myocardial protein kinase A (PKA) activity and troponin I (TnI) isoforms in fetal and nonpregnant sheep exposed to approximately 112 days of hypoxia at high altitude (3820 m).Resting and maximally stimulated (by cAMP) PKA activity was measured by phosphorylation of the artificial peptide, Kemptide. Specificity was confirmed by inhibition with PKI, a specific PKA inhibitor. For TnI isoforms, sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to resolve the proteins. We used monoclonal anti-cardiac TnI antibody (clone C5), which also cross-reacted with slow skeletal muscle TnI, to identify TnI isoforms.For the fetal hearts, resting PKA activity was significantly higher in the high-altitude group than the control group, but total PKA activity was not different between the normoxic and hypoxic groups. In the adult hearts, no significant difference was observed in either resting or total PKA activity between normoxic and hypoxic groups. For both the fetal and adult sheep, the predominant TnI was the cardiac isoform, and hypoxic exposure produced no change in the TnI isoform composition.Neither a reduction in PKA activity nor a change in TnI isoforms could explain the reduction in beta-receptor augmentation of cardiac contractility in fetal sheep exposed to long-term hypoxia.

We studied the effect of long-term, high-altitude hypoxia on cardiac myosin, actin, and troponin T (TnT) isoforms and Ca2+ and Mg2+-activated myofibrillar adenosine triphosphatase (ATPase) activities in fetal and adult sheep. We exposed pregnant (beginning at day 30 of gestation) and nonpregnant sheep to high altitude (3820 m) for 110 days. Myosin, actin, and TnT isoforms were analyzed by Western analysis. In purified myofibrillar preparations, Ca2+ and Mg2+-ATPase activities were measured by the appearance of inorganic phosphate after the addition of NaATP and various concentrations of either calcium or magnesium to the reaction mixture. We found no change in myosin, actin, or TnT isoform composition after exposure to long-term hypoxia in either fetal or adult sheep. However, Mg2+-activated myofibrillar ATPase activity decreased significantly in the right ventricle of both fetus and adult after hypoxic exposure. There was also a significant maturational increase in both Ca2+ and Mg2+-ATPase activity in control animals. The decrease in Mg2+-activated myofibrillar ATPase activity might affect the decrease in cardiac contractility previously noted in the right ventricle of fetal sheep after exposure to long-term hypoxia. Likewise, the increase in Ca2+ and Mg2+-activated ATPase activities from the fetus to adult could partially explain the previously found maturational increase in cardiac contractility.

We measured fetal plasma concentrations of epinephrine, norepinephrine, and vasopressin during acute hypoxemia in goats and tested whether hypermagnesemia altered these endocrine responses.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.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.Magnesium sulfate had no effect on fetal plasma concentrations of vasopressin, epinephrine, and norepinephrine during acute hypoxemia.

Our objective was to test if tight glycemic control versus loose glycemic control in gestational diabetic patients and a gestational age of32 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 at32 weeks and kept so until delivery (group 1) and32 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 at32 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.

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.

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.

Our purpose was to investigate the relationship between the birth weights and 24-h urinary C-peptide in infants of diabetic mothers.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-value0.05. 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.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.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.

To determine if fetal heart rate (FHR) decelerations periodically occur with uterine contractures during 6 hours' induced hypoxemia in goats.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.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.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.

Aims To determine whether treating mild gestational diabetes mellitus (GDM) is associated with improvement of pregnancy outcomes in Japan. Methods In a multi-institutional retrospective study, we examined pregnant women meeting the criteria for mild GDM (i.e., only one abnormal value [OAV] for 75-g OGTT; fasting glucose ≥100 mg/dL, 1-h postprandial glucose ≥180 mg/dL, and 2-h postprandial glucose ≥150 mg/dL), receiving either routine prenatal care (non-treatment group) or dietary intervention alone or dietary intervention with self-monitoring of blood glucose and/or insulin therapy, if necessary (treatment group). Pregnancy outcomes were compared between these groups. Results Data from 893 eligible women were collected from 30 institutions. Participants included 542 untreated and 351 treated women. Although there were no significant differences in baseline clinical characteristics or maternal and perinatal outcomes between these groups, the incidence of large-for-gestational-age (LGA) infants was lower in the treatment group ( P = 0.07). Multiple logistic regression analysis (MLRA) revealed that pre-pregnancy BMI and gestational weight gain were associated with LGA infants, while 75-g OGTT results were unrelated to LGA. When overweight and obese women were the subjects, the number of LGA infants was significantly lower in the intervention than in the control group, and gestational weight gain was significantly lower in the treatment than in the control group. MLRA showed that intervention was significantly related to a lower incidence of LGA infants. Conclusions Our study suggests that maternal BMI impacts fetal growth and that treatment for overweight or obese mothers with OAV is associated with a lower frequency of LGA infants.

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 1 st 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.

To clarify perinatal outcomes of monoamniotic (MM) twin pregnancies.MM twins delivered in seven tertiary perinatal centers during the last decade were retrospectively evaluated. All pregnant women were scheduled to begin inpatient management at around 24 weeks of gestation and undergo a planned cesarean section beyond 32 weeks. Pregnancy outcomes, prevalence of fetal death and cord entanglement, perinatal mortality and neuromorbidity rate at discharge were examined.The study group comprised 38 MM twin pregnancies (76 fetuses). Cord entanglement was confirmed in 88% (30/34) of women, and fetal deaths occurred in nine women (eight were both fetal deaths, and one was single fetal death). The cord entanglement accounted for 65% (11/17) of the fetal deaths. The median gestational age at delivery was 31⁺³ weeks, but that for viable infants was 32⁺³ weeks; the median birth weight was 1642 g, the perinatal mortality rate was 2% (1/60), and the neuromorbidity rate was 8% (5/50). The overall survival rate was 75% (57/76).Perinatal outcomes in our study were relatively good irrespective of high frequency of cord entanglement. Close fetal monitoring may allow MM twin pregnancies to extend gestational age, which may contribute to reduce both fetal death and neonatal morbidity by immaturity, although the best delivery weeks remained undetermined.

Although several studies have examined fetal cardiac responses to acute hypoxemia, relatively little is known of the response to prolonged hypoxemia. To determine the effects of long-term hypoxemia on ovine fetal cardiac function, we measured right (QRV) and left ventricular outputs (QLV) and determined the effects of increasing preload (ventricular function curve) and afterload (arterial pressure sensitivity curve) on the left ventricle. Six days after fetal surgical instrumentation with catheters and electromagnetic flow probes (approximately 123 days gestation), we administered N2 into the maternal trachea for 14 days to reduce maternal PO2 to approximately 55 Torr (hypoxemic group, Hyp, n = 6). Normoxic animals were used as controls (Cont, n = 6). With the onset of hypoxemia, fetal arterial PO2 was reduced from approximately 27 to approximately 18 Torr. Fetal heart rate in Hyp fetuses decreased approximately 22% on day 14 compared with Cont (P < 0.05). Mean arterial pressure in the Hyp group was higher than that of Cont but not significantly so. Right and left atrial pressures were not affected by hypoxemia. QRV in Hyp fetuses was maintained on day 1 but decreased significantly by day 3 (approximately 19%) and further decreased on days 7 (approximately 28%) and 14 (approximately 34%). QLV was not depressed until day 7 (approximately 20%), with a further decrease on day 14 (approximately 38%). In association with the decreased QLV the plateau of the ventricular function curve in Hyp fetuses was depressed significantly on days 7 and 14. In contrast, the slope of the arterial pressure sensitivity curve in the Hyp group did not differ from Cont.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the methods of screening and prenatal diagnosis of vasa previa.We reviewed cases of vasa previa in our hospital between January 2002 and December 2007. During this period, we visualized the site of cord insertion using transabdominal ultrasonography and observed the internal os using gray-scale transvaginal ultrasonography. A diagnosis of vasa previa was confirmed by transvaginal color Doppler imaging.We encountered 10 cases of vasa previa among 5131 deliveries. All cases had one or more known risk factors. In all of the four cases that underwent screening in the second trimester (i.e. between 20 and 25 weeks of gestation), the diagnosis was correct. Routine ultrasonography detected in only three of the other six cases of vasa previa that were referred to our hospital after 26 weeks of gestation. Of the other three cases referred after 26 weeks of gestation, in two cases vasa previa was detected by detailed examination using color Doppler transvaginal ultrasonography after fetal heart rate monitoring detected the presence of non-reassuring fetal status; in the remaining case, we were unable to make an antenatal diagnosis. Non-reassuring fetal status was seen on fetal heart rate monitoring in four of the five detected cases complicated by preterm labor.We consider that the best timing of antenatal screening for vasa previa is the second trimester. Non-reassuring fetal heart rate pattern without other possible causes warrants detailed examination of vasa previa.

Objective: We sought to determine the effects of long-term hypoxemia on fetal cardiac output and flow distribution. Study Design: We exposed six pregnant sheep to high altitude (3820 m) hypoxia from 30 to 135 days' gestation (term 146 days). Ten to 14 days after surgery we determined fetal cardiac output and organ blood flows by means of the radiolabeled microsphere technique during a baseline period and also during an additional 30-minute period of more severe added acute hypoxemia. Results: Baseline maternal arterial Po 2 was 60.7 ± 1.7 torr and fell to 35.1 ± 3.0 torr during the added acute hypoxemia. Fetal arterial Po 2 decreased from 18.5 ± 1.1 to 11.4 ± 1.5 torr during added acute hypoxemia. Baseline fetal cardiac output was 351 ± 55 ml/min/kg, which was significantly lower than previously reported values in low-altitude fetuses. Blood flow to critical organs such as the heart and brain was maintained at levels found in low-altitude fetuses, but flow to the carcass was significantly lower (−49%) than the mean value reported in the literature for low-altitude fetuses. Oxygen delivery was also maintained at normal levels to the brain and heart but was reduced in the kidneys (−31%), gastrointestinal tract (51%), and carcass (−58%). During added acute hypoxemia cardiac output did not change significantly; however, blood flow to the brain, heart, and adrenal glands increased 112%, 135%, and 156% ( p Conclusion: We conclude that during long-term hypoxemia redistribution of fetal cardiac output is maintained favoring the brain and heart.

To test the hypothesis that long-term hypoxemia affects fetal cardiac function, we measured right (RVO) and left (LVO) ventricular output by electromagnetic flow probes. We also determined their responses to increased preload (ventricular function curve, VFC) and afterload (arterial sensitivity curve, ASC). We exposed seven pregnant ewes to high altitude (3,820 m) from 30 to 120 days gestation, at which time surgery was performed. Thereafter, maternal arterial PO2 was maintained at approximately 60 Torr by N2 administration. Fetal arterial PO2 was significantly reduced in the hypoxemic fetuses (Hyp, n = 7) compared with that of control (Con, n = 9) (19.3 +/- 0.8 vs. 23.3 +/- 0.5 Torr, P less than 0.01). Mean arterial pressures in the Hyp group were elevated (52.0 +/- 1.2 vs. 44.4 +/- 1.7 mmHg, P less than 0.01) and fetal heart rate showed minimal change. Catecholamine concentrations in the Hyp group tended to be higher than the Con group, but not significantly so. For Con and Hyp, RVO equaled 275.7 +/- 9.1 vs. 183.1 +/- 10.1 (P less than 0.01), LVO equaled 165.7 +/- 16.9 vs. 141.6 +/- 16.5 (NS), and combined ventricular output (CVO) equaled 441.1 +/- 22.9 vs. 334.9 +/- 28.3 ml.min-1.kg-1 (P less than 0.05). For the LV there were no significant differences of the VFC between the Con and Hyp groups. However, the right VFC in the Hyp was significantly shifted downward. Concerning afterload, in the RV the slope of the ASC of Con was steeper than that of Hyp (-3.00 +/- 0.05 vs. -0.84 +/- 0.11 ml.ml.min-1.g-1.mmHg-1, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aim: This retrospective study was performed to reveal the natural history of cytomegalovirus (CMV) infected fetuses during the perinatal period and to find prenatal findings associated with poor outcomes. Methods: 33 neonates with CMV infection, born after 30 weeks of gestation, were registered from a total of 12 414 infants between 1995 and 2003. Maternal and neonatal medical records were reviewed regarding fetal growth; abdominal signs including ascites and hepatosplenomegaly; cerebral signs including ventriculomegaly, microcephaly, and calcification; and fetal heart rate monitoring, for signs which may have been detected by the standard obstetric ultrasonography. Univariate and multivariate analyses were performed to test for any associations between these manifestations and poor outcomes such as death and neurological damages. Results: Among the 33 infants, 6 died, 10 developed neurological damage including cerebral palsy (n = 8), epilepsy (n = 5), and hearing difficulties (n = 5), and the remaining 17 were normal. After adjusting for ganciclovir treatment and gender, death was 40-fold more likely associated with infants having abdominal signs (OR 40, 95%CI 4.6–930) than those without abdominal signs. Similarly, poor outcomes (death or neurological damage) were more likely associated with infants having either abdominal or cerebral signs (OR 39, 95%CI 3.8–1323). Fetal growth restriction and non-reassuring fetal heart rate patterns were not significantly associated with poor outcomes. Conclusion: The absence of abdominal signs guarantees the infant's survival. The presence of abdominal or cerebral signs is associated with poor outcomes, suggesting that these fetuses are possible candidates to receive in-utero therapy of congenital CMV infection.

We evaluated an association of nonreassuring fetal heart rate (FHR) patterns and subsequent cerebral palsy (CP) in pregnancies with intrauterine bacterial infection. Among 10,030 infants born during 1995 to 2000, 139 were complicated with acute intrauterine bacterial infection in labor. The FHR patterns 2 hours immediately before delivery were interpreted according to the guidelines of the National Institute of Child Health and Human Development. The correlations between the FHR patterns and umbilical blood gases, as well as FHR patterns and CP were studied. Statistics included unpaired t test, contingency table with chi (2) and Fisher test, and one-way analysis of variance with Bonferroni/Dunn test. Fifteen infants (11%) developed CP at 2 years or older. Nonreassuring FHR patterns including recurrent late deceleration, severe variable deceleration, and prolonged deceleration occurred in 24% of pregnancies with intrauterine infection. Incidence of CP was not different according to the FHR deceleration patterns or umbilical pH values. Multiple logistic regression analysis revealed that fetal tachycardia (OR, 11; 95% CI, 1.8 to 67) and lower gestational age (< 34 weeks; OR, 9.4; 95% CI, 0.96 to 93) was associated with CP in intrauterine infection. Nonreassuring FHR patterns were increased in intrauterine infection. CP occurred more frequently and was associated with tachycardia and lower gestational age, but not with FHR deceleration patterns or acidemia, suggesting different pathophysiology from acute hypoxia-ischemia.

Threatened premature labor (TPL) often results in preterm birth (PB). The aim of the present study was to evaluate the associations of periodontal and general health conditions with TPL and PB in relation to serum cytokine levels and the composition of subgingival plaque.Eighty-eight women were enrolled in the study. Systemic conditions were assessed, and subgingival plaque samples obtained for bacterial analysis. Periodontal examinations included assessments of plaque, gingivitis, clinical attachment level, probing depth, and bleeding on probing. Serum cytokine levels also were analyzed. Gestational age at delivery was recorded, and the mothers were divided into a TPL or non-TPL group, and into a non-TPL-TB (term birth), non-TPL-PB, TPL-TB, or TPL-PB group, accordingly.Forty subjects were classified as TPL and 18 as TPL-PB. There were significant differences between the TPL and non-TPL subjects in several of the systemic and periodontal parameters and serum cytokine levels. Significant differences were observed between the TPL-TB and TPL-PB groups in the percentage of Tannerella forsythensis (Tf, formerly Bacteroides forsythus), and the serum interleukin (IL)-8 and IL-1beta levels. Significant negative correlations between the gestational age at delivery and several periodontal parameters and serum IL-8 and IL-1beta levels, and significant positive correlations between periodontal status and serum IL-8 and IL-1beta levels, were observed.The TPL women revealed worsened periodontal conditions and elevated serum IL-8 and IL-1beta levels compared to the non-TPL women. The elevated levels of serum IL-8 and IL-1beta could have affected the maintenance of the proper uterine-fetus relationship, resulting in premature uterine contractions.

Introduction: Regarding its pathogenesis, discordant development in early gestation, as well as vascular anastomoses between twins are postulated to be required for the establishment of the twin-reversed arterial perfusion (TRAP) sequence. However, first trimester findings associated with this complication have not yet been reported. Case: A discordant monochorionic twin was revealed upon examination of a 24-year-old primigravida at 11 weeks’ gestation. Cystic masses were identified on the back of the smaller twin, later followed by the appearance of skin edema and pericardial effusion, indicating cardiac failure. Subsequently, despite diagnosis of fetal demise at 15 weeks the lower body was shown to have further developed and the heartbeats appeared again, resulting in an acardia anceps or hemicardia. No remarkable change was observed in the larger normal twin. Conclusion: This occurrence was considered consistent with the current hypothesis regarding the pathogenesis of the acardiac anomaly. First trimester discordancy in a monochorionic twin gestation is considered to represent an early manifestation of TRAP sequence.

We studied the effect of long-term, high-altitude hypoxia on cardiac myosin, actin, and troponin T (TnT) isoforms and Ca(2+)- and Mg(2+)-activated myofibrillar adenosine triphosphatase (ATPase) activities in fetal and adult sheep.We exposed pregnant (beginning at day 30 of gestation) and nonpregnant sheep to high altitude (3820 m) for 110 days. Myosin, actin, and TnT isoforms were analyzed by Western analysis. In purified myofibrillar preparations, Ca(2+)(-) and Mg(2+)-ATPase activities were measured by the appearance of inorganic phosphate after the addition of NaATP and various concentrations of either calcium or magnesium to the reaction mixture.We found no change in myosin, actin, or TnT isoform composition after exposure to long-term hypoxia in either fetal or adult sheep. However, Mg(2+)-activated myofibrillar ATPase activity decreased significantly in the right ventricle of both fetus and adult after hypoxic exposure. There was also a significant maturational increase in both Ca(2+)- and Mg(2+)-ATPase activity in control animals.The decrease in Mg(2+)-activated myofibrillar ATPase activity might affect the decrease in cardiac contractility previously noted in the right ventricle of fetal sheep after exposure to long-term hypoxia. Likewise, the increase in Ca(2+)- and Mg(2+)-activated ATPase activities from the fetus to adult could partially explain the previously found maturational increase in cardiac contractility.

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

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.

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.

The effects of magnesium sulfate on fetal heart rate (FHR) response during acute hypoxemia in goats were investigated.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.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.Magnesium sulfate masks FHR-slowing responses during acute hypoxemia in fetal goats.