A poor long-term neurological prognosis is associated with abnormal cord insertion in severe growth-restricted fetuses.

OBJECTIVE: To clarify and compare if the neurological outcomes of fetal growth restriction (FGR) cases with abnormal cord insertion (CI) are associated with a higher risk of a poor neurological outcome in subjects aged 3 years or less versus those with normal CI. METHODS: A multicenter retrospective cohort study was conducted among patients with a birth weight lower than the 3rd percentile, based on the standard reference values for Japanese subjects after 22 weeks' gestation, who were treated at a consortium of nine perinatal centers in Japan between June 2005 and March 2011. Patients whose birth weights were less than the 3rd percentile and whose neurological outcomes from birth to 3 years of age could be checked from their medical records were analyzed. The relationship between abnormal CI and neurological outcomes was analyzed. Univariate and multivariate models of multivariate logistic regression were employed to estimate the raw and odds ratio (OR) with 95% confidence intervals comparing marginal (MCI) and velamentous cord insertion (VCI) to normal CI. RESULTS: Among 365 neonates, 63 cases of MCI and 14 cases of VCI were observed. After excluding 24 cases with neonatal or infant death from the total FGR population, the assessment of the outcomes of the infants aged 3 years or younger showed the following rates of neurological complications: 7.3% (n=25) for cerebral palsy, 8.8% (n=30) for developmental disorders, 16.7% (n=57) for small-for-gestational-age short stature (SGA), 0.6% (n=2) for impaired hearing, 0.9% (n=3) for epilepsy, 1.2% (n=4). The ORs (95% confidence intervals) based on multivariate analysis were as follows: cerebral palsy=10.1 (2.4-41.5) in the VCI group and 4.3 (1.6-11.9) in the MCI group, developmental disorders=6.7 (1.7-26) in the VCI group and 3.9 (1.1-14.2) in the single umbilical artery (SUA) group, 5.1 (1.4-18.7) for birth weight <1000 g and 2.8 (1.2-6.7) for placental weight <200 g. CONCLUSIONS: The present results indicate that growth-restricted fetuses diagnosed with a birth weight below the 3rd percentile exhibiting abnormal umbilical CI are at a high risk for poor neurological outcomes, including cerebral palsy and/or developmental disorders.

Significance of oligohydramnios in preterm small-for-gestational-age infants for outcome at 18 months of age.

AIM: The aim of this study was to evaluate the association between oligohydramnios and other perinatal factors in preterm small-for-gestational-age (SGA) infants who had cerebral palsy at 18 months of age or who had died before this age. METHODS: This retrospective study included 320 infants with birthweights < 3rd percentile delivered between 22 and 33 complete weeks of gestation. We evaluated the incidence of CP at 18 months of age and of death before this age. The significant risk factors, including oligohydramnios, of CP or death of preterm SGA infants were evaluated by logistic regression analysis. RESULTS: The incidence of CP or death was 47/320 (14.7%), consisting of 24/320 (7.5%) cases of CP and 23/320 (7.2%) cases of death. Oligohydramnios (adjusted odds ratio, 2.18; 95% confidence interval, 1.07-4.45) and gestational age (adjusted odds ratio, 0.76; 95% confidence interval, 0.66-0.87) were independently correlated with outcome. CONCLUSION: The incidence of adverse outcomes was approximately 15% in preterm SGA infants. SGA infants born with oligohydramnios may be at increased risk for CP or death compared to those with normal amniotic volume.

Incidences of Feto-Fetal Transfusion Syndrome and Perinatal Outcomes in Triplet Gestations with Monochorionic Placentation.

INTRODUCTION: This study aimed to determine the incidences of feto-fetal transfusion syndrome (FFTS) and perinatal outcomes in triplet gestations with monochorionic placentation. MATERIALS AND METHODS: In this retrospective cohort study, we evaluated the incidences of FFTS and perinatal outcomes at 28 days of age in cases of triplet gestations with monochorionic placentation who visited our centers before 16 weeks of gestation and delivered over a period of 11 years. RESULTS: In 41 triplet gestations (17 monochorionic triamniotic, 22 dichorionic triamniotic, 1 dichorionic diamniotic, and 1 monochorionic monoamniotic), the incidence of FFTS was 17.1%, and the median gestational age at FFTS diagnosis was 19 weeks. In 123 triplets, the incidences of fetal death and neonatal death at 28 days of age were 8.1 and 0.9%, respectively. None of the surviving infants had grade 3 or 4 intraventricular hemorrhage, while cystic periventricular leukomalacia occurred in 6 of 113 infants (5.3%). The incidence of poor outcomes (death or any major neurological complication at 28 days of age) was 13.8%. DISCUSSION: Seventeen percent of triplet pregnancies with monochorionic placentation developed FFTS, and 14% had a poor outcome. Therefore, triplet gestations with monochorionic placentation should be followed carefully.

Prenatal risk stratification of severe small-for-gestational-age infants: a Japanese multicenter study.

OBJECTIVE: To establish a prenatal prognostic classification of severe small-for-gestational-age (SGA) infants based on gestational age and fetal findings. METHODS: A retrospective cohort study of 366 singleton infants (birth weight <3rd percentile) delivered between 22 and 34 weeks' gestation at nine tertiary perinatal centers. A decision tree model was developed for the prediction of death or severe morbidity. RESULTS: There were 35 infants with poor outcome. Prematurity was the most powerful factor in those born before 27.9 weeks' gestation, while oligohydramnios was the most powerful factor in those born at 27.9 weeks or after. The rate of poor outcome in infants born before 25.1 weeks, between 25.1 and 27.9 weeks, at 27.9 weeks or after with oligohydramnios, at 27.9 weeks or after without oligohydramnios, was 53.9%, 18.2%, 13.6% and 3.2%, respectively. CONCLUSIONS: Risk stratification based on gestation of 25 weeks, 28 weeks and oligohydramnios may aid in prognosis of severe SGA infants.

Factors affecting maternal serum magnesium levels during long-term magnesium sulfate tocolysis in singleton and twin pregnancy.

AIM: Our aim was to determine factors that affect maternal serum magnesium (Mg) levels, to help ensure the safety and efficacy of long-term magnesium sulfate (MgSO4 ) therapy for threatened preterm labor in singleton and twin pregnancies. MATERIAL AND METHODS: We retrospectively and arbitrarily studied 100 patients (singleton pregnancy, n = 65; twin pregnancy, n = 35) who received i.v. MgSO4 for >48 h for tocolysis of threatened preterm labor. We used multiple regression analysis to investigate the functional relations between the candidate factors and maternal serum Mg levels. RESULTS: MgSO4 was administered as a loading dose of 3 g for 1 h followed by a maintenance dose of 1.0-2.0 g/h. There were no maternal severe adverse events related to the elevated Mg levels in any of the subjects. The results of multiple regression analysis revealed that total dose of MgSO4 for 24 h before blood collection (g/day), total serum protein level (g/dL), serum total calcium level (mg/dL), serum creatinine level (mg/dL) and maternal bodyweight (kg) significantly affected maternal serum Mg levels in both singleton and twin pregnancies (all P-values were < 0.001). Gestational age (weeks) and period of MgSO4 administration (days) at blood collection had no significant effect in singleton or twin pregnancies. CONCLUSION: Our study statistically shows that dose of MgSO4 , total serum protein level, serum total calcium level, serum creatinine level and maternal bodyweight are key factors to achieving safe and effective long-term tocolysis with MgSO4 in not only singleton but also twin pregnancies.

Perinatal outcome and clinical features of monochorionic monoamniotic twin gestation.

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

Transfection of antisense chorionic gonadotropin beta gene into choriocarcinoma cells suppresses the cell proliferation and induces apoptosis.

CONTEXT: Choriocarcinoma cells not only synthesize human chorionic gonadotropin (hCG), but also express LH/CG receptors on the cell membrane. This suggests that the hCG and LH/CG receptors may play a role in regulating the biological function of choriocarcinoma cells in an autocrine/paracrine manner. OBJECTIVE AND METHODS: The objective of this study was to ascertain whether the inhibition of CGbeta gene expression in choriocarcinoma cells affects their proliferation and apoptosis. Expression vector bearing antisense CGbeta gene was transfected into the choriocarcinoma cell line, JAr. CGbeta protein synthesis was monitored by Western immunoblot, and CGbeta mRNA expression was determined by RT-PCR. Cell proliferation was assessed by 3-[4,5-dimethlthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay and nuclear incorporation of 5-bromo-2'-deoxyuridine, and the apoptosis-positive rate was assessed by terminal deoxynucleotidyltransferase-mediated deoxy-UTP nick end labeling analysis and nuclear staining with Hoechst 32258. RESULTS: JAr cells transfected with antisense CGbeta gene (JAr-aCGbeta cells) showed a significant decrease in hCG production and cell proliferation compared with untransfected and mock-transfected cells. The apoptosis-positive rate of the JAr-aCGbeta cells significantly increased compared with that of the controls. LH/CG receptor expression in JAr-aCGbeta cells decreased compared with that in controls. By contrast, supplementation of exogenous hCG significantly increased the LH/CG receptor expression and viability of JAr-aCGbeta cells. CONCLUSIONS: These results suggest that hCG, through its binding to the LH/CG receptor, may augment proliferation and inhibit apoptosis in choriocarcinoma JAr cells, and that the introduction of an antisense gene may be a potential approach to the inhibition of choriocarcinoma cell growth.

Prenatal evaluation of bidirectional epignathus: comparison of ultrasonography and magnetic resonance imaging.

Epignathus is an unusual, benign, congenital teratoma of the hard palate. Most of these teratomas are unidirectional and protrude through the mouth. Hence, the prognosis depends on the size of the tumor and degree of face distortion and airway obstruction. Occasionally, intracranial extension of the tumor is present, involving and destroying the brain tissue, resulting in a poor prognosis. The authors describe 2 cases of bidirectional epignathus, showing the different findings on ultrasonography and magnetic resonance imaging.