Safety and dose-finding trial of tadalafil administered for fetus in labor: A phase I clinical study.

AIM: This study aimed to investigate the safety and efficacy of tadalafil in protecting the fetus from hypoxic stress caused by repeated labor pains during delivery and preventing fetal hypoxic-ischemic encephalopathy. METHODS: The study used a three-case cohort approach. Three patients were administered 10 mg tadalafil and monitored for serious adverse events. In the absence of serious tadalafil-associated adverse events as assessed by the Safety Evaluation Committee, three new patients were added to the study and treated with 20 mg/dose. The blood levels of tadalafil were recorded before and after 2, 4, 8, and 12 h of administration and 2 h after delivery. RESULTS: A total of seven patients were enrolled, and after excluding one patient who delivered before 37 weeks, tadalafil was administered to six patients. Maternal adverse events were considered acceptable from the maternal perspective, with grade 1 headache, anorexia, and myalgia and no obstetrical complications after delivery at both doses. No serious neonatal adverse events were associated with tadalafil. Tadalafil blood levels remained stable at both doses. In addition, the level of soluble fms-like tyrosine kinase-1 did not alter, while that of the placental growth factor differed significantly before and after tadalafil administration. CONCLUSIONS: The study confirmed the safety of tadalafil administration during delivery for both mothers and newborns. The stable tadalafil blood levels confirmed the efficacy of the tested administration regime at 12 h interval. These findings would assist in conducting phase II trials to further verify the optimal dose and safety of tadalafil.

Two-dimensional phase-contrast MRI reveals changes in uterine arterial blood flow in pregnant women administered tadalafil for fetal growth restriction.

INTRODUCTION: We aimed to examine the effect of uterine arterial (UtA) blood flow changes after tadalafil treatment for fetal growth restriction (FGR) using two-dimensional (2D) phase-contrast magnetic resonance imaging (PC-MRI). METHODS: We recruited 14 pregnant women with FGR aged 20-44 years, at ≥20 weeks' gestation, between May 2019 and July 2020. They underwent 2D PC-MRI for UtA blood flow measurement 3 days (interquartile range: 2-4) after diagnosis. This group (FGR group) was compared with 14 gestational age (GA)-matched healthy pregnant women (control group). Six patients in the FGR group received treatment with tadalafil administered at 20 mg twice daily after the first MRI until delivery. They underwent a second MRI a week later. RESULTS: The median total UtA blood/body surface area was 420 mL/min/m2 (290-494) in the FGR group and 547 mL/min/m2 (433-681) in the control group (p = 0.01). Percent increase in blood flow were significantly different between the FGR cases treated with tadalafil and control at 15.8 % (14.3-21.3) and 4.2 % (3.6-8.7), respectively (p = 0.03). DISCUSSION: UtA blood flow in pregnant women with FGR was significantly lower than that in healthy pregnant women. Tadalafil is expected to improve UtA blood flow, thereby improving placental function in pregnant patients with FGR.

Accurate evaluation of the progress of delivery with transperineal ultrasound may improve vaginal delivery: a single-center retrospective study.

Although digital examination of the cervix is the standard method used worldwide for evaluating the progress of delivery, it is subjective. Transperineal ultrasound (TPU) is combined with digital evaluation for accurate assessment of fetal descent and rotation of the advanced part of the fetus. This retrospective study aimed to clarify the impact of introducing TPU on perinatal outcomes at Mie University Hospital. We analyzed singleton pregnant women who underwent delivery management at our hospital between April 2020 and March 2021. Perinatal outcomes were compared between patients who used TPU (TPU+ group) and those who did not (TPU- group). The angle of progression and head direction were measured. The rate of vaginal delivery was significantly increased (90.9% vs. 71.6%; P = 0.0017), and the second stage of labor was significantly prolonged in the TPU+ group (148.1 vs. 75.8 min; P < 0.0001). A significant difference was observed in termination in the latent phase between the TPU+ group [3/8 (37.5%) cases] and TPU- group [20/25 (80.0%) cases] (P = 0.036). The rate of vaginal delivery can be increased through accurate evaluation of the progress of delivery with TPU.

COVID-19 during pregnancy could potentially affect placental function.

OBJECTIVE: COVID-19 is an ongoing pandemic and has been extensively studied. However, the effects of COVID-19 during pregnancy, particularly on placental function, have not been verified. In this study, we used blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate whether COVID-19 incidence during pregnancy has any lasting effects with respect to placental oxygenation. METHODS: This is a case-control study, in which eight cases of singleton pregnancies before 30 weeks gestation with COVID-19 mothers were included. Placental oxygenation was evaluated using BOLD-MRI after 32 weeks of gestation. BOLD-MRI was consecutively performed under normoxia (21% O2), hyperoxia (100% O2), and normoxia for 4 min each. Individual placental time-activity curves were evaluated to calculate the peak score (peakΔR2*) and the time from the start of maternal oxygen administration to the time of peakΔR2* (time to peakΔR2*). Eighteen COVID-19-free normal pregnancies from a previous study were used as the control group. RESULTS: No significant differences were found between the two groups regarding maternal background, number of days of delivery, birth weight, and placental weight. The parameter peakΔR2* was significantly decreased in the COVID-19 group (8 ± 3 vs. 5 ± 1, p < .001); however, there was no significant difference in time to peakΔR2* (458 ± 74 s vs. 471 ± 33 s, p = .644). CONCLUSIONS: In this study, BOLD-MRI was used to evaluate placental oxygenation during pregnancy in COVID-19-affected patients. COVID-19 during pregnancy decreased placental oxygenation even post-illness, but had no effect on fetal growth; further investigation of the possible effects of COVID-19 on the fetus and mother is warranted.

The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep.

Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies have examined the effects of gram-negative bacterial inflammation on the developing brain, although gram-positive bacterial infections are a major contributor to adverse outcomes. Killed Su-strain group 3 A streptococcus pyogenes (Picibanil, OK-432) is being used for pleurodesis in fetal hydrothorax/chylothorax. We therefore examined the neural and cardiovascular effects of clinically relevant intra-plural infusions of Picibanil. Chronically instrumented preterm (0.7 gestation) fetal sheep received an intra-pleural injection of low-dose (0.1 mg, n = 8) or high-dose (1 mg, n = 8) Picibanil or saline-vehicle (n = 8). Fetal brains were collected for histology one-week after injection. Picibanil exposure was associated with sustained diffuse white matter inflammation and loss of immature and mature oligodendrocytes and subcortical neurons, and associated loss of EEG power. These neural effects were not dose-dependent. Picibanil was also associated with acute changes in heart rate and attenuation of the maturational increase in mean arterial pressure. Even a single exposure to a low-dose gram-positive bacterial-mediated inflammation during the antenatal period is associated with prolonged changes in vascular and neural function.

Prevention of fetal brain injury in category II tracings.

INTRODUCTION: With category II fetal heart rate tracings, the preferred timing of interventions to prevent fetal hypoxic brain damage while limiting operative interventions remains unclear. We aimed to estimate fetal extracellular base deficit (BDecf ) during labor with category II tracings to quantify the timing of potential interventions to prevent severe fetal metabolic acidemia. MATERIAL AND METHODS: A longitudinal study was conducted using the database of the Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy, including infants with severe cerebral palsy born at ≥34 weeks' gestation between 2009 and 2014. Cases included those presumed to have an intrapartum onset of hypoxic-ischemic insult based on the fetal heart rate pattern evolution from reassuring to an abnormal pattern during delivery, in association with category II tracings marked by recurrent decelerations and an umbilical arterial BDecf ≥ 12 mEq/L. BDecf changes during labor were estimated based on stages of labor and the frequency/severity of fetal heart rate decelerations using the algorithm of Ross and Gala. The times from the onset of recurrent decelerations to BDecf 8 and 12 mEq/L (Decels-to-BD8, Decels-to-BD12) and to delivery were determined. Cases were divided into two groups (rapid and slow progression) based upon the rate of progression of acidosis from onset of decelerations to BDecf 12 mEq/L, determined by a finite-mixture model. RESULTS: The median Decels-to-BD8 (28 vs. 144 min, p < 0.01) and Decels-to-BD12 (46 vs. 177 min, p < 0.01) times were significantly shorter in the rapid vs slow progression. In rapid progression cases, physicians' decisions to deliver the fetus occurred at ~BDecf 8 mEq/L, whereas the "decisions" did not occur until BDecf reached 12 mEq/L in slow progression cases. CONCLUSIONS: Fetal BDecf reached 12 mEq/L within 1 h of recurrent fetal heart rate decelerations in the rapid progression group and within 3 h in the slow progression group. These findings suggest that cases with category II tracings marked by recurrent decelerations (i.e., slow progression) may benefit from operative intervention if persisting for longer than 2 h. In contrast, cases with sudden bradycardia (i.e., rapid progression) represent a challenge to prevent severe acidosis and hypoxic brain injury due to the limited time opportunity for emergent delivery.

Evaluation of fetal acidemia during delivery using the conventional 5-tier classification and Rainbow systems.

The association between prepartum time-series fetal heart rate pattern changes and cord blood gas data at delivery was examined using the conventional 5-tier classification and the Rainbow system for 229 female patients who delivered vaginally. They were classified into three groups based on the results of umbilical cord blood gas analysis at delivery. The fetal heart rate pattern classifications were based on analysis of measurement taken at 10-min intervals, beginning at 120 min pre-delivery. The relationship between fetal heart rate pattern classification and cord blood pH at delivery changed over time. The 5-tier classification at each interval increased before delivery in the Mild and Severe groups compared with the Normal group. No significant differences were observed between acidemia groups. The Rainbow classification showed a significant differences between the acidemia groups at each interval, particularly during the prepartum period. A relationship between classification and outcome was evident before delivery for both the 5-tier classification and Rainbow system.

Efficacy of a portable interface pressure sensor for robotic surgery in preventing compartment syndrome.

BACKGROUND/OBJECTIVE: This study determines whether the use of a portable interface pressure sensor (Palm Q) for robotic surgery could prevent compartment syndrome. METHODS: In the present single center, non-trial observational study, patients diagnosed with gynecological diseases between April 2015 and August 2020 treated with laparoscopic or robotic surgery were enrolled. We assessed 256 cases involving surgery performed in the lithotomy position with an operative time >4 h. The Palm Q device was placed preoperatively on both sides of the patients' lower legs. The pressure was measured every 30 min preoperatively and intraoperatively and adjusted to ≤30 mmHg. If the pressure reached ≥30 mmHg, the operation was stopped, the patient was repositioned, the leg position was released, the pressure was reduced to ≤30 mmHg, and the procedure was resumed. We compared the maximum creatine kinase levels of the Palm Q and non-Palm Q groups. We also analyzed the correlation between the patients' symptoms postoperatively (shoulder and leg pain) and compartment syndrome. RESULTS: Our data showed that immediate postoperative creatine kinase levels predict compartment syndrome. Propensity score matching of the 256 enrolled patients resulted in 92 cases (46 per group), balanced for age, body mass index, and lifestyle disease. Creatine kinase levels differed significantly between the Palm Q and non-Palm Q groups (p = 0.041). None of the patients in the Palm Q group experienced well-leg compartment syndrome complications. CONCLUSION: Palm Q can potentially help to prevent perioperative compartment syndrome.

Fetal Biometric Assessment and Infant Developmental Prognosis of the Tadalafil Treatment for Fetal Growth Restriction.

Background and Objectives: Tadalafil is expected to treat fetal growth restriction (FGR), a risk factor for stillbirth and neonatal morbidity. This study aimed to evaluate the fetal biometric growth pattern of fetuses with FGR treated with tadalafil by ultrasonographic assessment. Materials and Methods: This was a retrospective study. Fifty fetuses diagnosed with FGR and treated by maternal administration of tadalafil and ten controls who received conventional treatment at Mie University Hospital from 2015 to 2019 were assessed. Fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) at the start of treatment and at two weeks and four weeks of treatment were mainly assessed by ultrasound examination. The Wilcoxon signed-rank test was used to assess the measures. The Kyoto Scale of Psychological Development (KSPD) was used to assess the developmental prognosis on tadalafil-treated children at 1.5 years of corrected age (CA) and 3 years old. Results: The median gestational age at the start of treatment was 30 and 31 weeks in the tadalafil and control groups, respectively, and the median gestational age at delivery was 37 weeks in both groups. The Z-score of HC was significantly increased at 4 weeks of treatment (p = 0.005), and the umbilical artery resistance index was significantly decreased (p = 0.049), while no significant difference was observed in the control group. The number of cases with an abnormal score of less than 70 on the KSPD test was 19% for P-M, 8% for C-A, 19% for L-S, and 11% for total area at 1.5 years CA. At 3 years old, the respective scores were 16%, 21%, 16%, and 16%. Conclusions: Tadalafil treatment for FGR may maintain fetal HC growth and infants' neuro-developmental prognosis.

Comparative study of the usefulness of risk score assessment in the early stages of COVID-19 affected pregnancies: Omicron variant versus previous variants.

AIM: To evaluate the utility of the risk score in assessing the current status and prognosis of COVID-19 in pregnancy. METHODS: Seventy-seven cases affected before the Omicron variant epidemic and 50 pregnant cases affected by the Omicron variant were included. The risk score consists of maternal background, current condition, and examination findings. We determined the risk score in the early stages of disease onset. RESULTS: There were no significant differences in the maternal or gestational ages between the groups. The risk score was significantly lower in the After-Group patients (those affected during the Omicron epoch), while 14.3% of the Before-Group patients (those affected during the pre-Delta and Delta epochs), experienced a worsening of disease after the visit to the center, whereas none of the After-Group patients did. The Before Group's frequency of risk score items was higher among the two groups for "fever for ≥48 h," "mild pneumonia image," and "blood tests," whereas "disease onset 14 days after the second vaccination" was increased in After Group. The blood test parameters for platelet count, C-reactive protein, and D-dimer levels were not significantly different between the groups. CONCLUSIONS: The risk score system appeared superior in detecting deteriorating cases. There were no cases of post-illness deterioration in the After-Group, suggesting that cases of the Omicron variant in pregnancy may have had a less severe course compared to that of previous variants. However, there was no significant difference between the groups in terms of a specific blood test evaluation, suggesting the need for a combined evaluation of cases affected during pregnancy.

Safety and efficacy of levonorgestrel-releasing intrauterine device in the treatment of atypical endometrial hyperplasia and early endometrial cancer.

AIM: To investigate the recurrence rate, live-birth rate, and treatment outcomes of levonorgestrel-releasing intrauterine device (LNG-IUD) for the management of atypical endometrial hyperplasia (AEH) or Grade-1 endometrial cancer (EC) in patients who desire fertility-sparing treatment and those seeking conservative treatment without fertility preservation. METHODS: We prospectively enrolled nine patients from a single institution between April 2009 and September 2013 who were followed up for 60 months after LNG-IUD insertion. RESULTS: The median patient age was 35 (range: 29-39) years. The overall recurrence rate was 56% (5/9). The median interval between removal of the LNG-IUD and recurrence was 20.5 (range: 2-30) months. Three of the nine patients had Grade-1 EC, and six had AEH. The response rates to the LNG-IUD in patients with Grade-1 EC and AEH were 66% and 100%, respectively. Four patients (three with AEH, one with Grade-1 EC) experienced recurrence 6 months after MPA treatment and all 4 (100%) had complete response. Eight patients desired fertility preservation, of which 37% (3/8) conceived after receiving fertility treatment and 25% (2/8) had a live birth; the remaining three had previously received MPA for 6 months and had a recurrence; of these, 1 had a live birth. CONCLUSION: LNG-IUD is effective for the management of AEH and EC in young patients who desire fertility-sparing treatment, including those ineligible for MPA owing to the presence of comorbidities and those with recurrence after MPA treatment (6-month treatment), and patients seeking conservative treatment without fertility preservation.

Does Vaginal Cuff Creation and Avoidance of a Uterine Manipulator Improve the Prognosis of Total Laparoscopic Radical Hysterectomy for Early Cervical Cancer? A Retrospective Multicenter Study.

Our goal was to compare the treatment outcomes of open-abdominal radical hysterectomy (O-RH) and total laparoscopic hysterectomy (TLRH) with vaginal cuff creation and without using a uterine manipulator in stage IB1-B2 (tumor size < 4 cm) cervical cancer cases. In this retrospective multicenter analysis, 94 cervical cancer stage IB1-B2 patients who underwent O-RH or TLRH in six hospitals in Japan between September 2016 and July 2020 were included; 36 patients underwent TLRH. Propensity score matching was performed because the tumor diameter was large, and positive cases of lymph node metastases were included in the O-RH group due to selection bias. The primary endpoint was progression-free survival (PFS) and recurrence sites of TLRH and O-RH. PFS and OS (overall survival) were not significant in both the TLRH (n = 27) and O-RH (n = 27) groups; none required conversion to laparotomy. The maximum tumor size was <2 and ≥2 cm in 12 (44.4%) and 15 (55.6%) patients, respectively, in both groups. Reportedly, the TLRH group had lesser bleeding than the O-RH group (p < 0.001). Median follow-up was 33.5 (2−65) and 41.5 (6−75) months in the TLRH and O-RH groups, respectively. PFS and OS were not significantly different between the two groups (TLRH: 92.6%, O-RH: 92.6%; log-rank p = 0.985 and 97.2%, 100%; p = 0.317, respectively). The prognosis of early cervical cancer was not significantly different between TLRH and O-RH. Tumor spillage was prevented by creating a vaginal cuff and avoiding the use of a uterine manipulator. Therefore, TLRH might be considered efficient.

Relationship between Edinburg Postnatal Depression Scale (EPDS) Scores in the Early Postpartum Period and Related Stress Coping Characteristics.

Despite postpartum depression being a common mental health problem, there is no screening method for it. The only risk assessment used is the Edinburgh Postnatal Depression Scale (EPDS). We investigated the relationship between Brief Scale for Coping Profile (BSCP) subscales performed during pregnancy and EPDS scores. We recruited 353 women with normal pregnancies (160 primiparas, and 193 multiparas) and performed BSCP at 26 weeks of gestation. The EPDS was first performed within one week after delivery (T1), and then after one month (T2). Spearman's correlation coefficients were calculated for the BSCP and EPDS for the whole and primi/multipara groups. Multiple regression analysis was performed with the EPDS T2 scores as the dependent variable. The EPDS scores were higher in the primipara group compared to the multipara (p < 0.001), and the EPDS T1 scores were higher than the overall T2 score (p < 0.001). In the multiple regression analysis, EPDS T1 and the "seeking help for solution" subscale were selected as significant explanatory variables when analyzed in the whole group; EPDS T1 and "active solution" for the primiparas; and EPDS T1, "changing mood", and "seeking help for solution" for the multiparas. The BSCP can be used as a screening tool for postpartum depression during pregnancy.

Evaluation of the tolerability of monoclonal antibody therapy for pregnant patients with COVID-19.

AIM: To evaluate the tolerability of casirivimab and imdevimab (CAS/IMB) therapy in pregnant women with COVID-19 in Japan and its impact on the neonate and process of delivery. METHODS: Eight cases of pregnancy complicated by COVID-19 and requiring hospitalization during the delta variant epidemic were included. Gestational age, initial symptoms, pregnancy complications and outcome, severity of illness, blood test findings at the time of treatment initiation and on days 3-5 after administration, body temperature at administration, and 8, 24, and 48 h post-administration, delivery outcome, and neonatal findings were recorded. Ten pregnant women who required hospitalization at the same time and did not receive CAS/IMB were used as controls. RESULTS: Of the eight cases, seven were mild, and one case was of moderate severity. Body temperature in the CAS/IMB group was significantly higher at 8 h post-administration than that at the time of administration. However, body temperature significantly reduced at 24 and 48 h post-administration in the CAS/IMB group compared with that in the control group. There were no apparent adverse events after CAS/IMB administration. CONCLUSIONS: Maternal administration of CAS/IMB was safe. Although it was difficult to evaluate the improvement in disease by blood test findings, the fever improved within 24 h, which suggests rapid improvement in patient condition.

Evaluation of placental oxygenation in fetal growth restriction using blood oxygen level-dependent magnetic resonance imaging.

INTRODUCTION: Abnormalities in placental function can lead to fetal growth restriction (FGR), but there is no consensus on their evaluation. Using blood oxygen level-dependent magnetic resonance imaging (BOLD MRI), we compared placental oxygenation between FGR cases and previously reported normal pregnancies. METHODS: Eight singleton pregnant women (>32 weeks of gestation) diagnosed with fetal growth failure during pregnancy were recruited. BOLD MRI was consecutively performed under normoxia (21% O2), hyperoxia (100% O2), and normoxia for 4 min each. Each placental time-activity curve was evaluated to calculate the peak score (peakΔR2*) and the time from the start of maternal oxygen administration to the time of peakΔR2* (time to peakΔR2*). In six of the eight FGR cases, placental FGR-related pathological findings were evaluated after delivery. RESULTS: The parameter peakΔR2* was significantly decreased in the FGR group (8 ± 3 vs 6 ± 1, p < 0.001), but there was no significant difference in time to peakΔR2* (458 ± 74 s vs 468 ± 57 s, p = 0.750). The findings in the six FGR cases assessed for placental pathologies included chorangiosis in two cases, avascular chorions in two cases, placental infarction in two cases, and syncytial knot formation in one case. DISCUSSION: The peakΔR2* values were lower in the FGR group than in the normal pregnancy group. This suggests that oxygenation of the placenta is decreased in the FGR group compared to the normal group, and this may be related to FGR. Placental pathology also revealed findings possibly related to FGR, suggesting that low peakΔR2* values in the FGR group may reflect placental dysfunction.

Appropriate Method of Administering Vasopressors for Maternal Hypotension Associated with Combined Spinal Epidural Anesthesia in Elective Cesarean Section: Impact on Postnatal Respiratory Support for Newborns.

Background and Objectives: Vasopressors are used for treating maternal hypotension. However, the appropriate administration method and effects on newborns have not been reported. We evaluated maternal blood pressure fluctuation and neonatal findings in patients who received continuous vasopressor administration during elective cesarean sections and those who received bolus vasopressor administration upon onset of hypotension. Materials and Methods: We retrospectively analyzed the data of 220 patients scheduled for elective cesarean delivery under spinal anesthesia at Mie University Hospital between April 2017 and March 2021. The patients were classified according to the method of vasopressor administration. Maternal information, intraoperative maternal blood pressure fluctuation, and neonatal findings were examined. A multiple regression analysis was performed for the administration of postpartum neonatal respiratory support using maternal background information and other variables related to blood pressure changes as independent variables. Results: The Continuous group and the Bolus group were composed of 98 and 122 patients, respectively. No difference was observed in maternal background information between the groups. Significant changes were noted in several blood pressure parameters between both groups. As for neonatal parameters, newborns of Bolus group patients had lower pO2, 1 min and 5 min Apgar scores, and required more respiratory support than those of Continuous group patients. In the multiple regression analysis, the groups and maternal post-anesthesia diastolic blood pressure variability were considered explanatory variables. Conclusions: Maternal hypotension and the need for neonatal respiratory support associated with anesthesia administration in elective cesarean section may be improved by continuous vasopressor administration upon induction of combined spinal-epidural anesthesia.

Fetal heart rate variability is a biomarker of rapid but not progressive exacerbation of inflammation in preterm fetal sheep.

Perinatal infection/inflammation can trigger preterm birth and contribute to neurodevelopmental disability. There are currently no sensitive, specific methods to identify perinatal infection. We investigated the utility of time, frequency and non-linear measures of fetal heart rate (FHR) variability (FHRV) to identify either progressive or more rapid inflammation. Chronically instrumented preterm fetal sheep were randomly assigned to one of three different 5d continuous i.v. infusions: 1) control (saline infusions; n = 10), 2) progressive lipopolysaccharide (LPS; 200 ng/kg over 24 h, doubled every 24 h for 5d, n = 8), or 3) acute-on-chronic LPS (100 ng/kg over 24 h then 250 ng/kg/24 h for 4d plus 1 µg boluses at 48, 72, and 96 h, n = 9). Both LPS protocols triggered transient increases in multiple measures of FHRV at the onset of infusions. No FHRV or physiological changes occurred from 12 h after starting progressive LPS infusions. LPS boluses during the acute-on-chronic protocol triggered transient hypotension, tachycardia and an initial increase in multiple time and frequency domain measures of FHRV, with an asymmetric FHR pattern of predominant decelerations. Following resolution of hypotension after the second and third LPS boluses, all frequencies of FHRV became suppressed. These data suggest that FHRV may be a useful biomarker of rapid but not progressive preterm infection/inflammation.

Evaluation of placental oxygenation index using blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) during normal late pregnancy.

AIM: Noninvasive blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) has recently been used to evaluate placental oxygenation. However, this method still has unresolved problems, such as long testing times and lack of normal values set. In the present study, we used a shorter protocol in BOLD-MRI and established normal values for placental oxygenation in late pregnancy. METHODS: We recruited 18 healthy singleton pregnant women (>32 weeks of gestation) who had a normal body size before pregnancy and a normal course of pregnancy. They underwent BOLD-MRI with three consecutive 4-min periods of different oxygenation: normoxia (21% O2), hyperoxia (10 L O2/min), and then normoxia. Placental time-activity curves were presented as signal intensity change relative to baseline (ΔR2*). The time from starting maternal oxygen administration to peak ΔR2*. To assess the relationship between peak ΔR2* values and placenta-related parameters and fetal development, the correlation between peak ΔR2*, placental weight, and neonatal birth weight was evaluated using Spearman's rank correlation test. RESULTS: In all cases, the BOLD signal was elevated by maternal oxygen administration, with the peak resolving within 4 min after the end of oxygen administration. Peak ΔR2* and time to peak ΔR2* during oxygenation were 7.99 ± 2.58, and 458.1 ± 73.9 s, respectively. There was a significant correlation between peak ΔR2* and neonatal birth weight (percentile) (r = 0.537, p = .022), and between placental weight and neonatal birth weight (r = 0.769, p < .01). CONCLUSIONS: In all cases, the BOLD signal increased with maternal hyperoxia using this protocol. So, 4 min observation following maternal oxygen administration is sufficient for peak ΔR2* evaluation. These reference values set in this study may be one of the indicators of BOLD signal changes in normal pregnancies after 32 weeks of gestation.