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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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.
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.
•Pregnant women without or with fetal growth restriction (FGR) were enrolled.•Placental oxygenation was assessed with blood oxygen level-dependent (BOLD) MRI.•PeakΔR2* of BOLD MRI were decreased in the FGR group.•Low peakΔR2* values may reflect placental dysfunction.
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.
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.
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.
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% O
2
), hyperoxia (10 L O
2
/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.
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).
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.
During the coronavirus disease (COVID-19) pandemic, caesarean section (CS) has been the preferred deliver method for pregnant women with COVID-19 in order to limit the use of hospital beds and ...prevent morbidity among healthcare workers.BACKGROUNDDuring the coronavirus disease (COVID-19) pandemic, caesarean section (CS) has been the preferred deliver method for pregnant women with COVID-19 in order to limit the use of hospital beds and prevent morbidity among healthcare workers.To evaluate delivery methods used during the COVID-19 pandemic as well as the rates of adverse events and healthcare worker morbidity associated with caesarean deliveries.METHODSTo evaluate delivery methods used during the COVID-19 pandemic as well as the rates of adverse events and healthcare worker morbidity associated with caesarean deliveries.We investigated maternal and neonatal backgrounds, delivery methods, indications and complication rates among pregnant women with COVID-19 from December 2020 to August 2022 in Mie Prefecture, Japan. The predominant mutation period was classified as the pre-Delta, Delta and Omicron epoch.METHODSWe investigated maternal and neonatal backgrounds, delivery methods, indications and complication rates among pregnant women with COVID-19 from December 2020 to August 2022 in Mie Prefecture, Japan. The predominant mutation period was classified as the pre-Delta, Delta and Omicron epoch.Of the 1291 pregnant women with COVID-19, 59 delivered; 23 had a vaginal delivery and 36 underwent CS. Thirteen underwent CS with no medical indications other than mild COVID-19, all during the Omicron epoch. Neonatal complications occurred significantly more often in CS than in vaginal delivery. COVID-19 in healthcare workers was not attributable to the delivery process.RESULTSOf the 1291 pregnant women with COVID-19, 59 delivered; 23 had a vaginal delivery and 36 underwent CS. Thirteen underwent CS with no medical indications other than mild COVID-19, all during the Omicron epoch. Neonatal complications occurred significantly more often in CS than in vaginal delivery. COVID-19 in healthcare workers was not attributable to the delivery process.The number of CS with no medical indications and neonatal complications related to CS increased during the COVID-19 pandemic. Although this study included centres that performed vaginal deliveries during COVID-19, there were no cases of COVID-19 in healthcare workers. It is possible that the number of CS and neonatal complications could have been reduced by establishing a system for vaginal delivery in pregnant women with recent-onset COVID-19, given that there were no cases of COVID-19 among the healthcare workers included in the study.CONCLUSIONThe number of CS with no medical indications and neonatal complications related to CS increased during the COVID-19 pandemic. Although this study included centres that performed vaginal deliveries during COVID-19, there were no cases of COVID-19 in healthcare workers. It is possible that the number of CS and neonatal complications could have been reduced by establishing a system for vaginal delivery in pregnant women with recent-onset COVID-19, given that there were no cases of COVID-19 among the healthcare workers included in the study.
Selective fetal growth restriction (sFGR) is a condition of twin pregnancy in which the development of one fetus is restricted, despite normal growth of the other fetus. A method of intrauterine ...therapy for sFGR does not currently exist. The only treatment for sFGR is to terminate the pregnancy before the FGR worsens. In twin pregnancies, maternal and intrauterine environments are common in both fetuses, thus a placental factor is considered the cause of FGR in fetuses. Tadalafil is a phosphodiesterase (PDE)-5 inhibitor that induces an increase in uterine blood flow by dilatation of blood vessels in cases of FGR with placental dysfunction, which improves FGR.
The aim of this study was to investigate the safety and maximum tolerated dose (MTD) of tadalafil administered for twin pregnancy (diamniotic-monochorionic twin or diamniotic-dichorionic twin).
In this phase I, open-label, dose-escalation trial, sequential patient cohorts (3 + 3 dose-escalation design) for twin pregnancy received tadalafil (20 or 40 mg/d) as a single dose by oral administration from the day they were diagnosed with sFGR, defined as estimated fetal weight (EFW) < 3% tiles, that is, −1.8 SD the mean EFW for gestational age (GA) to unacceptable toxicity or the day of delivery. This study evaluated the safety of maternally administered tadalafil for sFGR, examining maternal, fetal, and neonatal adverse events. Maternal adverse events were graded on the basis of the Common Terminology Criteria for Adverse Events v4.0.
Six women with sFGR who were pregnant with twins were treated with tadalafil. There were no severe adverse events in either cohort, although the most common (≥3 patients) drug-related adverse events were headache and heart failure. The MTD of tadalafil among Japanese patients was 40 mg.
Tadalafil has a manageable safety profile up to an MTD of 40 mg/d.
Purpose: To investigate the accuracy of computer analysis and its features to be used as a fu fetal heart rate (FHR) interpretation method in clinical settings.
Methods: The Trium CTG Online® was ...used as the computer analysis software. Twenty-six cases of intrapartum FHR tracings (total time, 6900 min) were randomly selected from third-trimester pregnancies. Three obstetricians blinded to the patients' clinical information traced the decelerations, variability, and baseline cardiotocogram (CTG) data. Three obstetrician observer individually interpreted the data and only the waveforms they interpreted were adopted. The agreement between the deceleration and baseline, variability, and level of five-tier system was estimated. Weighted kappa (κ) statistics were used to assess reliability.
Results: Based on the observers and Trium's classification, κ was 0.78 and the strength of agreement level was substantial. The obstetricians and Trium mostly agreed on the variability and baseline data. However, κ of each deceleration was approximately 0.65 (0.63-0.66), with substantial strength of agreement.
Conclusion: Based on the obstetricians and Trium's interpretation, the latter was found to be excellent for FHR interpretation. However, it was difficult for Trium to interpret specific waveform patterns. Therefore, clinical staff should understand these characteristics to more sensitively evaluate the fetal well-being.
We have demonstrated that tadalafil facilitates fetal growth in mice with L-NG-nitroarginine methyl ester (L-NAME)-induced preeclampsia (PE) with fetal growth restriction (FGR). Tadalafil is a ...selective phosphodiesterase 5 inhibitor that dilates the maternal blood sinuses in the placenta, thereby facilitating the growth of the fetus. The purpose of this study was to investigate the effects of tadalafil treatment for PE and FGR on the developing brain in FGR offspring using an L-NAME-induced mouse model of PE with FGR. A control group of dams received carboxymethylcellulose (CMC). L-NAME-treated groups received L-NAME dissolved in CMC from 11 days post coitum (d.p.c.). The L-NAME-treated dams were divided into two subgroups 14 d.p.c. One subgroup continued to receive L-NAME. The other subgroup received L-NAME with tadalafil suspended in CMC. Tadalafil treatment for PE with FGR reduced the expression of hypoxia-inducible factor-2α in the placenta and in the brain of the FGR fetus. Moreover, tadalafil treatment in utero shows improved synaptogenesis and myelination in FGR offspring on postnatal day 15 (P15) and P30. These results suggest that tadalafil treatment for PE with FGR not only facilitates fetal growth, but also has neuroprotective effects on the developing brain of FGR offspring through modulating prenatal hypoxic conditions.