Efficacy and safety of bivalent RSVpreF maternal vaccination to prevent RSV illness in Japanese infants: Subset analysis from the pivotal randomized phase 3 MATISSE trial.

BACKGROUND: Maternal vaccination with respiratory syncytial virus prefusion F vaccine (RSVpreF) is effective at preventing RSV-associated lower respiratory tract illness (LRTI) in newborns/infants. METHODS: This subgroup analysis from the global, phase 3, randomized, double-blind, placebo-controlled MATISSE (Maternal Immunization Study for Safety and Efficacy) trial evaluated participants enrolled in Japan. Pregnant women 24-36 weeks' gestation were randomized 1:1 to receive RSVpreF or placebo. Maternal safety endpoints included local reactions/systemic events within 7 days, adverse events (AEs) through 1 month, and serious AEs (SAEs) through 6 months after vaccination. In infants born to maternal participants, safety endpoints included specific birth outcomes, AEs through 1 month after birth, and SAEs and newly diagnosed chronic medical conditions through 12 or 24 months after birth. Vaccine efficacy in infants was assessed against RSV-positive, medically attended LRTI (RSV-MA-LRTI) and severe RSV-MA-LRTI through 180 days after birth. RESULTS: In Japan, 230 maternal participants received RSVpreF and 232 received placebo; 218 and 216 infants born to these mothers, respectively, were analyzed. Observed vaccine efficacy (95 % CIs) against infant RSV-MA-LRTI within 90 and 180 days after birth was 100.0 % (30.9, 100.0; RSVpreF, 0 cases; placebo, 7 cases) and 87.6 % (7.2, 99.7; RSVpreF, 1 case; placebo, 8 cases), respectively. Vaccine efficacy (95 % CIs) against severe RSV-MA-LRTI within 90 and 180 days was 100.0 % (-140.9, 100.0; RSVpreF, 0 cases; placebo, 3 cases) and 75.1 % (-151.5, 99.5; RSVpreF, 1 case; placebo, 4 cases), respectively. No safety concerns were identified. AE rates ≤1 month after vaccination/birth were similar in the RSVpreF (maternal, 16.1 %; infant, 48.6 %) and placebo (19.8 %; 50.5 %) groups. Preterm birth rates were also similar (RSVpreF, 3.2 %; placebo, 6.0 %). CONCLUSIONS: Safety and efficacy data in Japanese participants were consistent with overall MATISSE results, supporting the efficacy of maternal RSVpreF vaccination against severe MA-RSV-LRTI/MA-RSV-LRTI in infants, with no safety concerns. NCT04424316.

Impact of clinical practice guidelines for vacuum-assisted delivery on maternal and neonatal outcomes in Japan: A single-center observational study.

AIM: Practice guidelines for vacuum-assisted delivery in Japan were revised in 2014 to improve clinical safety. We aimed to determine the success rates of vacuum delivery before and after the release of the revised guidelines. METHODS: This retrospective observational study included singleton deliveries at term gestation. Success rate of vacuum delivery, duration of extraction, number of tractions and maternal and neonatal injuries were compared between 2011-2014 and 2015-2019. RESULTS: Vacuum extraction was attempted in 249 (15%) of 1657 deliveries. Duration of extraction was shorter in 2015-2019 (median, 3.0 min; interquartile range [IQR], 1.0-5.8 min) than in 2011-2014 (median, 4.0 min; IQR, 2.0-6.5 min; P = 0.0045). No significant differences were seen in success of vacuum extraction (98%), prolonged (>20 min) duration of extraction (1.5%) and repeated (>5 pulls) tractions (3.1%) in vacuum deliveries during 2011-2014, compared to success of vacuum extraction (94%), prolonged duration of extraction (1.6%) and repeated tractions (1.1%) in those during 2015-2019. Likewise, no significant differences were identified in maternal or neonatal injuries. CONCLUSION: Successful vacuum-assisted deliveries and shortened duration of extraction were still confirmed after guideline revision. However, because of consistent safe practice with vacuum delivery from before the revision, improvements in maternal and neonatal injuries were not observed.

Relationship between birth weight to placental weight ratio and major congenital anomalies in Japan.

Recent studies have indicated that birth weight to placental weight (BW/PW) ratio is related to perinatal outcomes, but the effect of congenital abnormalities on BW/PW ratio remains unclear. We performed this study to elucidate correlations between BW/PW ratio and congenital abnormalities. Subjects were 735 singleton infants born at 34-41 weeks of gestation admitted to our center between 2010 and 2016. Of these, 109 infants (15%) showed major congenital anomalies. Major congenital anomalies and subgroups were diagnosed according to European Surveillance of Congenital Anomalies criteria. The primary outcome was the association between BW/PW ratio and major congenital anomaly, and secondary outcomes were the distribution pattern of BW/PW ratio with major anomalies and by major anomaly subgroups in each categorization (<10th percentile, 10-90th percentile, or >90th percentile) of BW/PW ratio. BW/PW ratio was not associated (P = 0.20) with presence (adjusted mean BWPW ratio = 5.02, 95% confidence interval [CI] 4.87-5.18) or absence (adjusted mean BW/PW ratio = 4.91, 95%CI 4.85-4.97) of major anomalies, after adjusting for gestational age and sex. Proportions of infants with major anomalies according to BW/PW ratio categories were as follows: 12% in <10th percentile, 15% in 10-90th percentile, and 25% in >90th percentile of BW/PW ratio. Among major anomalies of the nervous system, congenital heart defects, and orofacial clefts, BW/PW ratio showed equally distributed trend across the three BW/PW ratio categories, but showed unequally distributed trend for anomalies of the digestive system, other anomalies/syndromes, or chromosomal abnormalities. BW/PW ratio was not associated with major congenital anomaly, and was distributed diffusely according to major anomaly subgroups. Major anomalies may tend to aggregate in the 90th percentile of the BW/PW ratio.

Maternal predictive factors for fetal congenital heart block in pregnant mothers positive for anti-SS-A antibodies.

OBJECTIVE: To determine the maternal predictive factors for fetal congenital heart block (CHB) in pregnancy in mothers positive for anti-SS-A antibodies. METHODS: The Research Team for Surveillance of Autoantibody-Exposed Fetuses and Treatment of Neonatal Lupus Erythematosus, the Research Program of the Japan Ministry of Health, Labor and Welfare, performed a national survey on pregnancy of mothers positive for anti-SS-A antibodies. We analyzed 635 pregnant mothers who tested positive for anti-SS-A antibodies before conception but had no previous history of fetal CHB. We performed univariate and multivariate analysis (models 1, 2, and 3 using different set of independent variables) investigated the relation between risk of fetal CHB and maternal clinical features. RESULTS: Of the 635 pregnant mothers, fetal CHB was detected in 16. Univariate analysis showed that fetal CHB associated with use of corticosteroids before conception (OR 3.72, p = 0.04), and negatively with use of corticosteroids (equivalent doses of prednisolone (PSL), at ≥10 mg/day) after conception before 16-week gestation (OR 0.17, p = 0.03). In multivariate analysis, model 1 identified the use of corticosteroids before conception (OR 4.28, p = 0.04) and high titer of anti-SS-A antibodies (OR 3.58, p = 0.02) as independent and significant risk factors, and model 3 identified use of corticosteroids (equivalent doses of PSL, at ≥10 mg/day) after conception before 16-week gestation as independent protective factor against the development of fetal CHB (OR 0.16, p = 0.03). Other maternal clinical features did not influence the development of fetal CHB. CONCLUSION: The results identified high titers of anti-SS-A antibodies and use of corticosteroids before conception as independent risk factors, and use of corticosteroids (equivalent doses of PSL, at ≥10 mg/day) after conception before 16-week gestation as an independent protective factor for fetal CHB.

Outcome of monochorionic twin pregnancies with moderate amniotic fluid discordance adjoining twin-twin transfusion syndrome.

OBJECTIVES: This study aimed to assess the perinatal outcome in monochorionic diamniotic (MD) twin pregnancies complicated by amniotic fluid discordance (AFD) adjoining twin-twin transfusion syndrome (TTTS). METHODS: An observational study of 84 consecutive MD twin pregnancies complicated by AFD that resembled TTTS was conducted. AFD adjoining TTTS was defined by a maximal vertical pocket of amniotic fluid ≤3 cm in one twin and ≥7 cm in the other excluding TTTS. The study population was divided into two groups, group 1 and group 2, according to positive and absent or reversed end-diastolic flow (AREDF) in the umbilical artery, respectively. RESULTS: Fifteen of the 35 (42.9%) group 1 cases and 30 of the 49 (61.2%) group 2 cases progressed to TTTS. The overall survival and intact survival rate in constant AFD that never progressed to TTTS in group 1 was 100% (40/40) and 90% (36/40), respectively. The overall survival and intact survival rate of constant AFD in group 2 with selective intrauterine growth restriction (sIUGR) was 54.2% (13/24) and 41.7% (10/24), respectively, and for those without sIUGR was 64.3% (9/14) and 57.1% (8/14), respectively. CONCLUSIONS: Constant AFD with AREDF in the umbilical artery represents an extremely high risk for adverse outcomes regardless of the presence of sIUGR.

Neurological outcomes in Chiari type II malformations and their correlation to morphological findings and fetal heart rate patterns: a retrospective study.

BACKGROUND: Correlations among Chiari type II malformation (CMII) morphological findings, the proportion of fetal heart rate patterns corresponding to the quiet phase (QP), and neurological outcomes have yet to be investigated. FINDINGS: The correlations among the morphological findings (i.e., the degree of ventriculomegaly, myelomeningocele levels, and degree of cerebellar herniation), proportion of time spent in QP, and developmental quotients (DQs) were analyzed in 22 children. The proportion of time spent in QP was compared between children with poor neurological outcomes (n = 9) and those with good outcomes (n = 13). Pearson's correlations and the Mann-Whitney U-test were used to assess for statistical significance; P < 0.05 was considered statistically significant. No significant differences were observed between the DQs and morphological findings, but the DQs and the proportion of time spent in QP were significantly correlated (r = 0.287, P = 0.01). The proportion of time spent in QP was significantly different between children with poor outcomes and those with good outcomes (median, 11% [range, 0-32%] vs. 28% [range, 2-55%]; P = 0.006). CONCLUSIONS: The proportion of fetal heart rate patterns corresponding to the QP might be a useful predictor of neurological outcomes in 2-year-old children with CMII.

Doppler sonographic evaluation of arteriovenous shunt flow in a fetus with dural sinus malformation.

Dural sinus malformation (DSM) is a rare congenital malformation characterized by a dilated dural sinus pouch. We present a case of prenatally diagnosed DSM and propose a parameter to predict poor fetal outcome. Detailed ultrasonography at 26 weeks of our patient showed an intracranial cyst in the left posterior fossa. Color Doppler study indicated an arteriovenous shunt within the cyst with increased blood flow velocity. Based on these findings, fetal DSM with arteriovenous shunt was diagnosed. Because of fetal hydrops with high-output cardiac failure and maternal pregnancy-induced hypertension, labor was induced at 32 weeks and resulted in stillbirth. In conclusion, based on the present case, we can deduce that color Doppler study is useful for prenatal diagnosis of DSM with arteriovenous shunt and that a high-flow velocity to the cystic lesion is a possible predictor of hydropic change in such fetuses.

The predictive value of anti-SS-A antibodies titration in pregnant women with fetal congenital heart block.

OBJECTIVE: Fetal congenital complete heart block (CHB) is irreversible and is associated with significant mortality and morbidity. Anti-SS-A antibodies in the maternal sera are involved in its pathogenesis; however, the predictive value of the antibody titer and its role in prediction of this complication are controversial. The aim of this study was to determine the predictive value of maternal anti-SS-A antibodies on the development of fetal CHB. METHODS: A retrospective chart review was performed for 189 cases of positive anti-SS-A antibodies determined by the double immunodiffusion (DID) method, and included 17 patients that developed fetal CHB. The relationship between the appearance of CHB and the anti-SS-A antibodies titer was examined. RESULTS: An anti-SS-A antibodies titer of 1:32 or higher was identified by analyzing the receiver-operating characteristics (area under curve 0.72) curve. An anti-SS-A antibodies titer of 32 or more times greater than the upper limit by DID was a risk factor for fetal CHB (odds ratio 27.77, 95% confidence interval (CI) 1.91-21.02, P < 0.05) in the multivariate analysis. Among 107 cases of anti-SS-A antibodies titers of 1:32 or higher, 65 patients (60.7%) were treated with oral steroids. Of these, four patients had CHB (6.2%). This rate of CHB was significantly lower (P < 0.01) than the rate in patients not treated with steroids. CONCLUSION: An anti-SS-A antibodies titer of 1:32 or higher in the maternal sera by DID was an independent risk factor for fetal CHB. In these patients, either antenatally administered prednisolone or betamethasone, was associated with a lower risk of fetal CHB.

Antenatally diagnosed congenital orbital teratoma in which rupture was associated with intrauterine fetal death.

We report a case of a fetus with a congenital orbital teratoma (COT), in which rupture of the tumor was associated with an intrauterine fetal demise. An ultrasound scan at 27 weeks' revealed a solid and cystic, complex mass in the orbital region with extensive vascularization suggestive of an orbital cystic teratoma. Magnetic resonance imaging (MRI) supported this diagnosis and clarified tumor localization. At 32 weeks', the patient presented with fetal demise and rupture of the mass was noted. Fetal COTs, like sacrococcygeal teratomas, carry the risk of rupture. MRI in utero is useful for evaluating the extent of disease.

Cervical length predicts placental adherence and massive hemorrhage in placenta previa.

AIM: To evaluate the relationship between cervical length (CL) and obstetrical outcome in women with placenta previa. MATERIAL AND METHODS: Eighty uncomplicated, singleton pregnancies with an antenatally diagnosed previa were categorized based on CL of over 30mm (n=60) or 30mm or less (n=20). A retrospective chart review was then performed for these cases to investigate the relationship between CL and maternal adverse outcomes. RESULTS: The mean CL was 38.5±5.4mm and 26.9±3.2mm and the mean gestational age at measurement was 29.2±2.7 and 28.5±2.7weeks of gestation for the longer and shorter CL groups, respectively. The median estimated blood loss at cesarean section (CS) was significantly higher in the shorter CL group (1302mL vs 2139mL, P=0.023) as was the percentage of patients with massive intraoperative hemorrhage (60.0 vs 18.3%, P=0.001). In the shorter versus longer CL patients, emergent CS before 37weeks (23.3 vs 50.0%, P=0.046) and the percentage of patients with placental adherence (6.7 vs 35.0%, P=0.004) were both significantly more frequent in the shorter CL group. The shorter CL was a risk factor both for massive estimated blood loss (≥2000mL) (odds ratio 6.34, 95% confidence interval 1.91-21.02, P≤0.01) and placental adherence (odds ratio 6.26, 95% confidence interval 1.23-31.87, P≤0.05) in the multivariate analysis. CONCLUSION: CL should be included in the assessment of a placenta previa given its relationship to emergent CS, cesarean hysterectomy, intraoperative blood loss and placental adherence.

Abnormal fetal movements, micrognathia and pulmonary hypoplasia: a case report. Abnormal fetal movements.

BACKGROUND: Micrognathia is a facial malformation characterized by mandibular hypoplasia and a small, receding chin that fails to maintain the tongue in a forward position. We previously reported a system of prenatal screening that we developed to identify fetuses with compromised central nervous system function by observing fetal behavior. In this paper we report the case of a preterm infant with micrognathia and pulmonary hypoplasia who presented abnormal fetal movements. CASE PRESENTATION: A 27-year-old Japanese primigravida at 33 weeks of gestation was referred to our hospital. Ultrasonographic examination revealed clinical polyhydramnios. Micrognathia was evident on midsagittal and 3 D scan. The lung area was less than the mean -2.0 standard deviations for the gestational age. The infant had mandibular hypoplasia and glossoptosis. After emergency cesarean delivery for non-reasuring fetal status, required immediate tracheostomy and cardiopulmonary resuscitation with mechanical ventilatory support. However, the infant's cardiopulmonary condition did not improve and she died 21 hours after birth. CONCLUSIONS: The findings of our ultrasound exam are suggestive of brain dysfunction. The observation of fetal behavior appears to be effective for the prediction of prognosis of cases with micrognathia.

Prenatal sonographic appearance of truncus arteriosus on wide-band Doppler imaging.

Persistent truncus arteriosus is an uncommon congenital cardiac anomaly. In most patients, this condition is not diagnosed prior to birth. We report a case in which this uncommon cardiac anomaly was diagnosed prenatally using wide-band Doppler imaging. When diagnosing fetal truncus arteriosus, sonologists should carefully search for the origin of the main pulmonary artery and for its 2 branches. Our experience suggests that wide-band Doppler imaging facilitates the prenatal diagnosis of truncus arteriosus.

Brain injury of the survivor diagnosed at 18 weeks of gestation after intrauterine demise of the co-twin: a case report.

Brain injury in a surviving fetus following the demise of a monochorionic co-twin has only rarely been reported in the first trimester or early second trimester; most documented cases were beyond 20 weeks of gestation.

Acute pancreatitis and cholecystitis associated with postpartum HELLP syndrome: a case and review.

We report a case of preeclampsia associated with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome and concomitant nonbiliary acute pancreatitis and cholecystitis in the first postpartum day. A thorough investigation ruled out known etiologies of both pancreatitis and cholecystitis. Following conservative treatment, the patient's HELLP syndrome, pancreatitis, and cholecystitis resolved on the third postpartum day. Preeclampsia is associated with microvascular abnormalities that may involve the splanchnic circulation. These abnormalities may cause not only HELLP syndrome but also pancreatitis and cholecystitis. Recognizing that ischemia can damage not only the liver but also the pancreas and gallbladder, could result in improvements in the diagnosis and management of pancreatitis in patients with preeclampsia.

Sudden fetal death associated with both duodenal atresia and umbilical cord ulcer: a case report and review.

We encountered one case of duodenal atresia complicated by massive intrauterine hemorrhage due to the perforation of an umbilical cord ulceration (UCU). UCU is an extremely rare complication in the perinatal period. Although the prenatal diagnosis of upper intestinal atresia has been established, little is known about the association between UCU and upper intestinal atresia. In this article, we report our case, review past articles, and discuss the underlying pathophysiological mechanisms of the cause of an UCU. Given the characteristic sites of upper intestinal atresia, we speculate that regurgitation of gastric or intestinal juice into the amniotic fluid could be responsible for the development of UCU. We also believe that close observation is required for patients who have upper intestinal atresia.