Nationwide status of progestogen treatment to prevent spontaneous preterm birth: A questionnaire survey for childbirth healthcare facilities in Japan.

AIM: This study aimed to investigate the current status of progestogen treatment for pregnant women at a high risk for preterm birth (PTB) in childbirth healthcare facilities in Japan. METHODS: A web-based nationwide questionnaire survey regarding progestogen use for prevention of PTB was conducted among childbirth healthcare facilities from 2019 to 2021. RESULTS: Valid responses were obtained from 528 facilities (25.2% of those surveyed), including 155 tertiary perinatal facilities (making up 92.3% of all tertiary perinatal care facilities). In the survey period, progestogen treatment was implemented in 207 facilities (39.2%) for PTB prevention. Regarding types of progestogens, 17α-hydroxyprogesterone caproate was used in 170 facilities (82.1%), with a low dose (125 mg/week) administered in 62.9% of the facilities to comply with the regulations of the national health insurance system, although 250 mg/week is considered the best dose. Vaginal progesterone was used in 36 facilities (17.4%), although the cost of vaginal progesterone was not covered by health insurance. Of the facilities not administering progestogen treatment, approximately 40% expressed that vaginal progesterone would be their first choice for PTB prevention in daily practice if it would be covered by health insurance in the future. CONCLUSIONS: Due to the current regulations of the Japanese health insurance system, 17α-hydroxyprogesterone caproate, rather than vaginal progesterone, was mainly used for PTB prevention. Despite global evidence supporting vaginal progesterone as the approach with the highest efficacy, only a limited number of facilities have utilized it due to the current drug use regulations in Japan.

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.

Development and application of a large-scale disaster preparedness system in the perinatal field.

OBJECTIVE: To introduce the Perinatal Early Assessment and Communication system for Emergencies (PEACE), a dedicated internet-based system for sharing maternal and newborn health information during large-scale disaster. METHODS: PEACE was developed by the Japan Society of Obstetrics and Gynecology (JSOG) to enable internet-based sharing of maternal and newborn support information between facilities and rescue teams in disaster areas. PEACE input rates during prefecture-scale disasters and in disaster drills were surveyed for two facility categories: centers for perinatal medical care (CPMs) and combined clinics + regional general hospitals. RESULTS: The PEACE input rate was 60%-100% (mean 86%) for CPMs and 5%-86% (mean 47%) among clinics + regional general hospitals. After encouraging PEACE input from JSOG, the Japan Association of Obstetricians and Gynecologists (JAOG), and the disaster response departments of prefectural governments, input rates increased significantly from 74% to 98% in CPMs (P = 0.018) and from 14% to 80% in clinics + regional general hospitals (P = 0.020). CONCLUSION: JSOG has established the first national system for sharing health information of pregnant women and newborns for use during disasters. The cooperation of prefectures and experience during disaster drills were critical to improving PEACE input rates.

Fetal heart rate evolution and brain imaging findings in preterm infants with severe cerebral palsy.

BACKGROUND: Cerebral palsy is more common among preterm infants than among full-term infants. Although there is still no clear evidence that fetal heart rate monitoring effectively reduces cerebral palsy incidence, it is helpful to estimate the timing of brain injury leading to cerebral palsy and the causal relationship with delivery based on the fetal heart rate evolution patterns. Understanding the relationship between the timing and the type of brain injury can help to identify preventive measures in obstetrical care. OBJECTIVE: This study aimed to examine the relationship between the timing of insults and the type of brain injury in preterm infants with severe cerebral palsy. STUDY DESIGN: This longitudinal study was based on a nationwide database for cerebral palsy. The data of infants with severe cerebral palsy (equivalent to levels 3-5 of the Gross Motor Function Classification System-Expanded and Revised), born between 2009 and 2014 at 28 to 33 weeks of gestation, were included. The intrapartum fetal heart rate evolution patterns were evaluated by 3 obstetricians blinded to clinical information other than gestational age at birth, and these were categorized after agreement by at least 2 of the 3 reviewers into (1) continuous bradycardia, (2) persistently nonreassuring (prenatal onset), (3) reassuring-prolonged deceleration, (4) Hon's pattern (intrapartum onset), (5) persistently reassuring (pre- or postnatal onset), and (6) unclassified. Infant brain magnetic resonance imaging findings at term-equivalent age were assessed by a pediatric neurologist blinded to the background details, except for gestational age at birth and corrected age at image acquisition, and these were categorized as (1) basal ganglia-thalamus, (2) white matter, (3) watershed cortex or subcortex, (4) stroke, (5) normal, and (6) unclassified based on the predominant site involved. The risk factors for the basal ganglia-thalamus group were compared with those of the combined white matter and watershed injuries group. RESULTS: Among 1593 infants with severe cerebral palsy, 231 were born at 28 to 33 weeks of gestation, and 140 met the eligibility criteria. Fetal heart rate evolution patterns were categorized as bradycardia (17% [24]); persistently nonreassuring (40% [56]); reassuring-prolonged deceleration (7% [10]); reassuring-Hon (6% [8]); persistently reassuring (7% [10]); and unclassified (23% [32]). Cerebral palsy was presumed to have an antenatal onset in 57% of infants and to have been caused by intrapartum insult in 13% of infants. Magnetic resonance imaging showed that 34% (n=48) of infants developed basal ganglia-thalamus-dominant brain injury. Of the remaining 92 infants, 43% (60) showed white matter injuries, 1% (1) showed watershed injuries, 4% (5) showed stroke, 1% (1) had normal findings, and 18% (25) had unclassified findings. Infants with continuous bradycardia (adjusted odds ratio, 1033.06; 95% confidence interval, 15.49-68,879.92) and persistently nonreassuring fetal heart rate patterns (61.20; 2.09-1793.12) had a significantly increased risk for basal ganglia-thalamus injury. CONCLUSION: Severe cerebral palsy was presumed to have an antenatal onset in 57% of infants and to have been caused by intrapartum insult in only 13% of infants born at 28 to 33 weeks of gestation. Although the white matter-watershed injury was predominant in the study populations, severe acute hypoxia-ischemia may be an important prenatal etiology of severe cerebral palsy in preterm infants.

Uterine contraction may not be an independent risk factor for spontaneous preterm birth before 35 weeks in women with cervical shortening.

OBJECTIVE: To compare the risk of spontaneous preterm birth (SPTB) before 35 weeks in symptomatic and asymptomatic women with cervical shortening at 16-34 weeks under mid-trimester universal screening of cervical length (CL). METHOD: Multicenter retrospective cohort study involving six secondary/tertiary perinatal centers was planned in 2016. Primary outcomes were SPTB before 35 weeks. In all, 407 women were analyzed using multivariable logistic regression analysis for predicting SPTB before 35 weeks while adjusting for presence/absence of uterine contraction, gestational weeks, vaginal bleeding, and CL classification (1-9, 10-14, 15-19, and 20-24 mm) at admission, the execution of cervical cerclage, and the presence/absence of past history of preterm delivery. RESULTS: SPTB before 35 weeks of pregnancy occurred in 14.5%. Presence of uterine contraction was not an independent risk factor for SPTB before 35 weeks (adjusted odds ratio [aOR] 1.22, 95% confidence interval [CI] 0.67-2.20). CL of 1-9 mm, CL of 10-14 mm, and vaginal bleeding at admission were independent risk factors for SPTB before 35 weeks (aOR 5.35, 95% CI 2.11-13.6; aOR 2.79, 95% CI 1.12-6.98; and aOR 2.37, 95% CI 1.12-5.10, respectively). CONCLUSION: In women with a cervical shortening at 16-34 weeks, presence of uterine contractions at admission may not be an independent risk factor for the occurrence of SPTB before 35 weeks.

Effects of External Radiation Exposure on Perinatal Outcomes in Pregnant Women After the Fukushima Daiichi Nuclear Power Plant Accident: the Fukushima Health Management Survey.

BACKGROUND: This study aimed to investigate the effects of maternal exposure to external radiation on perinatal outcomes among women who experienced the Fukushima Daiichi Nuclear Disaster (FDND) using the Fukushima Health Management Survey (FHMS). METHODS: Data from the Pregnancy and Birth Survey and Basic Survey in the FHMS were combined to analyze external maternal radiation exposure following the FDND, and the relationship between radiation dose and perinatal outcomes was analyzed using binomial logistic regression analysis. Missing dose data were supplemented using multiple imputation. RESULTS: A total of 6,875 individuals responded to the survey. Congenital anomalies occurred in 2.9% of patients, low birth weight (LBW) in 7.6%, small for gestation age (SGA; <10th percentile) in 8.9%, and preterm birth in 4.1%. The median maternal external radiation dose was 0.5 mSv (maximum, 5.2 mSv). Doses were classified as follows: <1 mSv (reference), 1 to <2 mSv, and ≥2 mSv. For congenital anomalies, the crude odds ratio for 1 to <2 mSv was 0.81 (95% confidence interval [CI], 0.56-1.17) (no participants with congenital anomaly were exposed to ≥2 mSv). At 1 to <2 mSv and ≥2 mSv, the respective adjusted odds ratios were 0.91 (95% CI, 0.71-1.18) and 1.21 (95% CI, 0.53-2.79) for LBW, 1.14 (95% CI, 0.92-1.42) and 0.84 (95% CI, 0.30-2.37) for SGA, and 0.91 (95% CI, 0.65-1.29) and 1.05 (95% CI, 0.22-4.87) for preterm birth. CONCLUSION: External radiation dose due to the FDND was not associated with congenital anomalies, LBW, SGA, or preterm birth.

The Effects of the Great East Japan Earthquake on Perinatal Outcomes: Results of the Pregnancy and Birth Survey in the Fukushima Health Management Survey.

There are limited studies on the long-term effects of natural/environmental disasters, especially nuclear disasters, on obstetric outcomes. This study aimed to review the results of perinatal outcomes immediately after the Great East Japan Earthquake (GEJE) and the Fukushima Daiichi Nuclear Power Plant accident, as well as their long-term trends over 8 years, in the Fukushima Health Management Survey. The annual population-based Pregnancy and Birth Survey is conducted as part of the Fukushima Health Management Survey. The Fukushima Prefecture government launched it to assess the health conditions of pregnant women and their neonates after the GEJE. The self-reported questionnaire was sent to 115,976 pregnant women by mail from January 2012, with 58,344 women responding to the questionnaire (50.3% response rate). Pregnancy complications, such as gestational hypertension, respiratory diseases, and mental disorders, increased in some women who were pregnant at the time of the earthquake and immediately after the earthquake. However, the direct effects on newborns, such as preterm birth, low birth weight, and congenital anomalies, were not immediately clear after the earthquake. Although there were significant differences in the occurrence of preterm birth and low birth weight among the districts, there was no change in the occurrences of preterm birth, low birth weight, or anomalies in newborns in Fukushima Prefecture from the fiscal year 2011 to the fiscal year 2018. Therefore, the long-term effects of the post-disaster radiation accident on perinatal outcomes are considered to be very small.

Does a cervical pessary reduce the rate of preterm birth in women with a short cervix?

OBJECTIVES: To evaluate neonatal outcomes after the use of a cervical pessary in Japanese women with short cervical length (CL) less than 25 mm. METHODS: This multicenter study involved women with singleton pregnancies between 20 and 29+6 gestational weeks and a CL of less than 25 mm. The primary outcome was preterm birth (PTB) before 34 weeks of gestation. This study was registered in the Japan Registry of Clinical Trials (JRCT: jRCTs042180102). RESULTS: Two hundred pregnant women were enrolled; 114 in the pessary group and 86 in the expectant management group as controls. In the pessary group, all 114 neonates were investigated for perinatal outcomes, and 112 pregnant women were investigated for primary, and secondary outcomes. In the control group, 86 pregnant women were investigated for primary and secondary outcomes and 86 neonates were investigated for neonatal outcomes. There were no significant differences in PTB in ≤34, ≤37, and ≤28 weeks of gestation or in preterm rupture of membranes (PROM) ≤34 weeks between the groups. The gestational weeks at birth and birth weight were significantly higher in the pessary group. Regression analysis demonstrated that the CL decreased without a pessary, whereas the shortening rate was suppressed during the intervention. No significant differences were observed in adverse neonatal outcomes, chorioamnionitis, or preterm PROM. CONCLUSIONS: The cervical pessary effectively reduced CL shortening during pregnancy resulting in an average increased gestational age, however, did not reduced the rates of preterm birth.

Fetal heart rate evolution patterns in cerebral palsy associated with umbilical cord complications: a nationwide study.

BACKGROUND: The aim of the present study was to clarify fetal heart rate (FHR) evolution patterns in infants with cerebral palsy (CP) according to different types of umbilical cord complications. METHODS: This case-control study included children born: with a birth weight ≥2000 g, at gestational age ≥33 weeks, with disability due to CP, and between 2009 and 2014. Obstetric characteristics and FHR patterns were compared among patients with CP associated with (126 cases) and without (594 controls) umbilical cord complications. RESULTS: There were 32 umbilical cord prolapse cases and 94 cases with coexistent antenatal umbilical cord complications. Compared with the control group, the persistent non-reassuring pattern was more frequent in cases with coexistent antenatal umbilical cord complications (p = 0.012). A reassuring FHR pattern was observed on admission, but resulted in prolonged deceleration, especially during the first stage of labor, and was significantly identified in 69% of cases with umbilical cord prolapse and 35% of cases with antenatal cord complications, compared to 17% of control cases (p < 0.001). CONCLUSION: Hypercoiled cord and abnormal placental umbilical cord insertion, may be associated with CP due to acute hypoxic-ischemic injury as well as sub-acute or chronic adverse events during pregnancy, while umbilical cord prolapse may be characterized by acute hypoxic-ischemic injury during delivery.

Correlation between fetal heart rate evolution patterns and magnetic resonance imaging findings in severe cerebral palsy: A longitudinal study.

OBJECTIVE: To investigate the association between hypoxic-ischaemic insult timing and brain injury type in infants with severe cerebral palsy (CP). DESIGN: Longitudinal study. SETTING: Database of the Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy. SAMPLE: Infants with severe CP born at ≥34 weeks of gestation. METHODS: The intrapartum fetal heart rate (FHR) strips were categorised as continuous bradycardia; persistently non-reassuring (NR-NR); reassuring-prolonged deceleration (R-PD); Hon's pattern (R-Hon); persistently reassuring (R-R); and unclassified. The brain magnetic resonance imaging (MRI) scans were categorised based on the predominant site involved: basal ganglia-thalamus (BGT); white matter (WM); watershed (WS); stroke; normal; and unclassified. MAIN OUTCOME MEASURES: Manifestations of the brain MRI types and the association between FHR evolution pattern and MRI type were analysed. RESULTS: Among 672 eligible infants, 76% had BGT-dominant injury, 5.4% WM, 1.2% WS, 1.6% stroke, 1.9% normal, and 14% unclassified. Placental abruption and small-for-gestational age were associated with an increased (adjusted odds ratio [aOR] 8.02) and decreased (aOR 0.38) risk of BGT injury, respectively. The majority of infants had BGT injury in most FHR groups (bradycardia, 97%; NR-NR, 75%; R-PD, 90%; R-Hon, 76%; and R-R, 45%). The risk profiles in case of BGT in the NR-NR group were similar to those in the R-PD and R-Hon groups. CONCLUSION: BGT-dominant brain damage accounted for three-fourths of the cases of CP in term or near-term infants, even in prenatal onset cases. Hypoxic-ischaemic insult has a major impact on CP development during the antenatal period. TWEETABLE ABSTRACT: Basal ganglia-thalamus injury constitutes 76% of severe cerebral palsy cases, predominant even in antenatal-onset cases.

Effects of prophylactic vaginal progesterone administration on mild cervical shortening (TROPICAL study): a multicenter, double-blind, randomized trial.

Vaginal progesterone reduces the preterm birth frequency among high-risk women with a cervical length ≤25 mm at midtrimester. However, the strategy may promote no substantial reduction in overall preterm birth rates, because such high-risk women are only approximately 2% of all pregnant women, which restrict the number of participants. Our purpose was to determine whether prophylactic vaginal progesterone administration can preserve cervical length and reduce preterm birth rates among women with mild cervical shortening.This multicenter, parallel-arm, double-blind, randomized, placebo-controlled trial involved vaginal progesterone administration (200 mg daily from 16 to 33 weeks of gestation) among asymptomatic women with a singleton pregnancy and a sonographic cervical length of 25 to <30 mm between 16 and 23 weeks of gestation. The primary and secondary endpoints were cervical shortening rates at 34 weeks of gestation and preterm birth rates, respectively. The trial was registered at the University Hospital Medical Information Network (UMIN000013518) in Japan.Between April 2014 and March 2018, 119 women were randomly assigned to the progesterone group (n = 59) and the placebo group (n = 60). No significant differences in the frequency of women with a cervical length ≥20 mm at 34 weeks of gestation were observed between both groups. All preterm births occurred after 34 weeks of gestation, except for one patient in the placebo group. The progesterone group had a lower rate of preterm birth before 37 weeks than the placebo group (3.4% vs. 15.0%, respectively; p < .05).Despite having no effect on preserving cervical length, prophylactic vaginal progesterone administration reduced preterm birth frequency among women with mild cervical shortening. Our results are suggesting that women with mild cervical shortening are at risk for late preterm birth and the need for expanding progesterone treatment indications to include not only high-risk but also low-risk populations.

New device with force sensors for laparoscopic liver resection - investigation of grip force and histological damage.

INTRODUCTION: As the benefits of minimally invasive surgery are recognized, the rate of laparoscopic liver resection (LLR) is rapidly increasing. Liver tissue is fragile compared to tissue of the stomach and colon. In endoscopic and robotic surgery, sufficient tactile sensation is yet to be obtained. Therefore, it is necessary to measure and indicate the grip force of forceps during surgery. We developed a new device consisting of force sensors and investigated its grip force and the resulting histological damage to liver tissue. MATERIAL AND METHODS: We measured the grip force generated during laparoscopic surgery in pigs using the forceps with pressure sensors developed by us. Throughout the hepatectomy, we measured the grip force generated by the forceps in real time. We investigated the histological damage to the liver caused by using the forceps with different grip forces. RESULTS: The subject produced a mean grip force of 1.75 N during the procedures. The maximum grip force was 3.38 N. By grasping the tissues of the liver with forceps, bleeding and destruction of the hepatic lobules were observed in a manner dependent on increasing grip force. CONCLUSION: The new device is necessary for preventing liver damage in laparoscopic hepatic resection.

Obstetric factors associated with uterine rupture in mothers who deliver infants with cerebral palsy.

Objective: The aim of the present study was to clarify the obstetric factors associated with uterine rupture in mothers who deliver infants with cerebral palsy (CP) in Japan.Methods: This retrospective case-cohort study reviewed the obstetric characteristics and clinical courses of mothers who experienced uterine rupture and compared those who delivered an infant with CP (cases) with those who delivered an infant without CP (cohort). Data were obtained from the Japan Obstetric Compensation System for CP database (27 cases) and the perinatal database of the Japan Society of Obstetrics and Gynecology (312 cohorts). The subjects included live singleton infants delivered between 2009 and 2014 with a birth weight ≥2000 g and gestation ≥33 weeks.Results: Augmentation was performed 33% in cases and 8% in cohorts (p < .001). The amount of bleeding during surgery was 1819 g in cases and 1096 g in cohorts (p < .001). Length of gestational weeks and neonatal birth weight were significantly higher and Apgar scores and umbilical arterial pH were lower in cases compared to cohorts (p < .001). In cases with CP, 11 cases of uterine rupture involved scarred uteruses. Seven were trial of labor after a previous cesarean. On one hand, 16 cases occurred in unscarred uteruses. Five of the uterine fundal pressure maneuvers and four of tachysystole due to excessive augmentation were reported in association with uterine rupture.Conclusion: Two-third of the relevant obstetric factors for CP associated with uterine rupture were iatrogenic. At least, to reduce CP resulting from delivery-related uterine rupture, reckless delivery management should be avoided.

Risk factors for cerebral palsy in neonates due to placental abruption.

AIM: This study aimed to identify risk factors for the onset of cerebral palsy (CP) in neonates due to placental abruption and investigate their characteristics. METHODS: A retrospective case-control study was conducted using a nationwide registry from Japan. The study population included pregnant women (n = 122) who delivered an infant with CP between 2009 and 2015, where placental abruption was identified as the single cause of CP. The control group consisted of pregnant women with placental abruption, who delivered an infant without CP and were managed from 2013 to 2014. They were randomly identified from the prenatal database of the Japan Society of Obstetrics and Gynecology (JSOG-DB; n = 1214). Risk factors were investigated using multivariate analysis. RESULTS: Alcohol consumption (3.38, 2.01-5.68) (odds ratio, 95% confidence interval), smoking during pregnancy (3.50, 1.32-9.25), number of deliveries (1.28, 1.05-1.56), polyhydramnios (5.60, 1.37-22.6), oral administration of ritodrine hydrochloride (2.09, 1.22-3.57) and hypertensive disorders in pregnancy (2.25, 1.27-4.07) were significant risk factors. In contrast, intravenous administration of oxytocin (odds ratio, 95% confidence interval: 0.22, 0.09-0.58) and magnesium sulfate (0.122, 0.02-0.89) attenuated risk. CONCLUSION: Alcohol consumption, smoking during pregnancy, number of deliveries, polyhydramnios, oral administration of ritodrine hydrochloride and hypertensive disorders in pregnancy were identified as risk factors for CP following placental abruption. Regarding alcohol consumption and smoking during pregnancy, the results suggest the importance of educational activities targeting pregnant women to increase their awareness of placental abruption.

Weekend and off-hour effects on the incidence of cerebral palsy: contribution of consolidated perinatal care.

OBJECTIVE: This study estimated the effects of weekend and off-hour childbirth and the size of perinatal medical care center on the incidence of cerebral palsy. METHODS: The cases were all children with severe cerebral palsy born in Japan from 2009 to 2012 whose data were stored at the Japan Obstetric Compensation System for Cerebral Palsy database, a nationally representative database. The inclusion criteria were the following: neonates born between January 2009 and December 2012 who had a birth weight of at least 2000 g and gestational age of at least 33 weeks and who had severe disability resulting from cerebral palsy independent of congenital causes or factors during the neonatal period or thereafter. Study participants were restricted to singletons and controls without report of death, scheduled cesarean section, or ambulance transportation. The controls were newborns, randomly selected by year and type of delivery (normal spontaneous delivery without cesarean section and emergency cesarean section) using a 1:10 case to control ratio sampled from the nationwide Japan Society of Obstetrics and Gynecology database. RESULTS: A total of 90 cerebral palsy cases and 900 controls having normal spontaneous delivery without cesarean section were selected, as were 92 cerebral palsy cases and 920 controls with emergent cesarean section. A significantly higher risk for cerebral palsy was found among cases that underwent emergent cesarean section on weekends (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.06-2.81) and during the night shift (OR 2.29, 95% CI 1.30-4.02). No significant risk was found among normal spontaneous deliveries on weekends (OR 1.63, 95% CI 0.97-2.73) or during the quasi-night shift (OR 1.26, 95% CI 0.70-2.27). Regional perinatal care centers showed significantly higher risk for cerebral palsy in both emergent cesarean section (OR 2.35, 95% CI 1.47-3.77) and normal spontaneous delivery (OR 2.92, 95% CI 1.76-4.84). CONCLUSION: Labor on weekends, during the night shift, and at regional perinatal medical care centers was associated with significantly elevated risk for cerebral palsy in emergency cesarean section.

Fetal heart rate pattern in term or near-term cerebral palsy: a nationwide cohort study.

BACKGROUND: It is crucial to interpret fetal heart rate patterns with a focus on the pattern evolution during labor to estimate the relationship between cerebral palsy and delivery. However, nationwide data are not available. OBJECTIVE: The aim of our study was to demonstrate the features of fetal heart rate pattern evolution and estimate the timing of fetal brain injury during labor in cerebral palsy cases. STUDY DESIGN: In this longitudinal study, 1069 consecutive intrapartum fetal heart rate strips from infants with severe cerebral palsy at or beyond 34 weeks of gestation, were analyzed. They were categorized as follows: (1) continuous bradycardia (Bradycardia), (2) persistently nonreassuring, (3) reassuring-prolonged deceleration, (4) Hon's pattern, and (5) persistently reassuring. The clinical factors underlying cerebral palsy in each group were assessed. RESULTS: Hypoxic brain injury during labor (those in the reassuring-prolonged deceleration and Hon's pattern groups) accounted for 31.5% of severe cerebral palsy cases and at least 30% of those developed during the antenatal period. Of the 1069 cases, 7.86% were classified as continuous bradycardia (n=84), 21.7% as persistently nonreassuring (n=232), 15.6% as reassuring-prolonged deceleration (n=167), 15.9% as Hon's pattern (n=170), 19.8% as persistently reassuring (n=212), and 19.1% were unclassified (n=204). The overall interobserver agreement was moderate (kappa 0.59). Placental abruption was the most common cause (31.9%) of cerebral palsy, accounting for almost 90% of cases in the continuous bradycardia group (64 of 73). Among the cases in the Hon's pattern group (n=67), umbilical cord abnormalities were the most common clinical factor for cerebral palsy development (29.9%), followed by placental abruption (20.9%), and inappropriate operative vaginal delivery (13.4%). CONCLUSION: Intrapartum hypoxic brain injury accounted for approximately 30% of severe cerebral palsy cases, whereas a substantial proportion of the cases were suspected to have either a prenatal or postnatal onset. Up to 16% of cerebral palsy cases may be preventable by placing a greater focus on the earlier changes seen in the Hon's fetal heart rate progression.

Randomized trial of the efficacy of intravaginal ulinastatin administration for the prevention of preterm birth in women with a singleton pregnancy and both cervical shortening and inflammation of lower genital tract.

AIM: To assess the preventive effect on preterm birth of intravaginal ulinastatin (urinary trypsin inhibitor; UTI) administration during the mid-trimester in women with singleton pregnancy and both cervical shortening and lower genital infections. METHODS: Pregnant women with a short cervical length < 25 mm between 16 and 26 weeks of gestation and who had been diagnosed with a lower genital infection were randomly assigned for intravaginal UTI administration or placebo. All of the women were screened for infection or inflammation of the lower genital tract, and women with negative results were excluded. RESULTS: Of the 92 patients with a short cervical length who were assessed for eligibility for this study, 86 singleton patients were enrolled. All patients were randomized to one of two treatment groups: patients administered UTI (n = 35) and placebo (n = 35). There were no differences between the two groups in the incidence of preterm delivery before 28, 30, 32, 34 and 37 weeks of gestation and in perinatal outcomes. CONCLUSION: For women diagnosed with a short cervical length < 25 mm) between 16 and 26 weeks of gestation and lower genital infection, who were at risk of preterm birth, administration of transvaginal UTI with vaginal irrigation showed no apparent benefit. Future research on the efficacy of UTI should evaluate modified modes of UTI application.

Valproate-Induced Polycystic Ovary Syndrome in a Girl with Epilepsy: A Case Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common ovulatory disorder that can be induced by sodium valproate (VPA). PATIENT: We report a case of PCOS that developed in a 15-year-old girl with idiopathic epilepsy after she took VPA. VPA administration stopped her seizures, but it also led to weight gain and amenorrhea, and the patient was diagnosed with PCOS on the basis of diagnostic imaging and serological examination results. Cessation of VPA administration led to reduced weight gain and restored menstruation. CONCLUSIONS: The risk of PCOS developing in patients with epilepsy is known to be high, and the association of VPA with PCOS is well established, so if physicians feel this is the best drug to prescribe for female patients with epilepsy, they should carefully monitor the patients' weight and menstruation, and immediately perform ovarian imaging and hormonal examinations if any abnormalities are observed.

Cervical Dilatation Curves of Spontaneous Deliveries in Pregnant Japanese Females.

Background: Although cervical dilatation curves are crucial for appropriate management of labor progression, abnormal labor progression and obstetric interventions were included in previous and widely-used cervical dilatation curves. We aimed to describe the cervical dilatation curves of normal labor progression in pregnant Japanese females without abnormal labor progression and obstetric interventions. Methods: We completed retrospective obstetric record reviews on 3172 pregnant Japanese females (parity = 0, n = 1047; parity = 1, n = 1083; parity ≥ 2, n = 1042), aged 20 to 39 years old at delivery, with pregravid body mass indices of less than 30. All patients underwent spontaneous deliveries with term, singleton, cephalic and live newborns of appropriate-for-gestational age birthweight, without adverse neonatal outcomes. We characterized labor progression patterns by examining the relationship between elapsed times from the full dilatation and cervical dilatation stages, and labor durations by examining the distribution of time intervals from one cervical dilatation stage, to the next, and ultimately to the full dilatation. Results: Fastest cervical changes occurred at 6 cm (primiparas) and 5 cm (multiparas) of dilatation. The 95%tile of labor progression took over 3 hours to progress from 6 cm to 7 cm (primiparas), and over 2 hours to progress from 5 cm to 6 cm (multiparas). The 5%tile of traverse time to the full dilatation, during the active phase, was less than 1 hour (primiparas) and 0.5 hours (multiparas). At the end of the active phase, no deceleration phase was observed. Conclusions: Active labor may not start until 5 cm of dilatation. At the beginning of the active phase, cervical dilatation was slower than previously described. These results may reduce opportunities for obstetric interventions during labor progression.

Relevant obstetric factors associated with fetal heart rate monitoring for cerebral palsy in pregnant women with hypertensive disorder of pregnancy.

AIM: The study identifies the relevant obstetric factors associated with fetal heart rate (FHR) monitoring for cerebral palsy (CP) in pregnant women with hypertensive disorders of pregnancy (HDP). METHODS: The subjects were neonates with CP (birth weight ≥ 2000 g, gestational age ≥ 33 weeks) who were approved for compensation for CP by the Operating Organization of the Japan Obstetric Compensation System between 2009 and 2012. After selection of women with antepartum HDP, obstetric characteristics associated with FHR monitoring were analyzed. RESULTS: The subjects included 33 neonates with CP whose mothers suffered from HDP during pregnancy and 450 neonates whose mothers did not develop HDP. The rates of placental abruption (48.5% vs. 20%; P < 0.001) and light-for-gestational age (12.1% vs. 2.2%; P = 0.011) were significantly higher in women with HDP than in those without HDP. Regarding FHR pattern analysis, fetal bradycardia was observed on admission to hospital in 94% of women with placental abruption. In women without placental abruption, FHR was likely to indicate a favorable pattern on admission, but became worse with the progression of labor. CONCLUSION: This is first study to clinically demonstrate FHR patterns in CP cases in association with HDP. Although antepartum CP is undetectable, pregnant women with HDP should be placed under strict observation and management to minimize fetal hypoxic conditions during labor.