Predictive factors for vaginal delivery by induction of labor in uncomplicated pregnancies at 40-41 gestational weeks: A Japanese prospective single-center cohort study.

AIM: We investigated cervical parameters predictive of vaginal delivery in elective labor induction among women at 40-41 gestational weeks. METHODS: This Japanese prospective single-center cohort study was conducted between July 2019 and June 2020. We enrolled women with an uncomplicated singleton pregnancy who underwent labor induction at 40-41 gestational weeks. We analyzed background characteristics and cervical parameters, including Bishop score, cervical length, posterior cervical angle, and changes in cervical parameters before and after cervical dilatation. The endpoint was the rate of vaginal delivery. RESULTS: Of 142 eligible participants, all 24 multiparous women underwent vaginal delivery. Among the nulliparous women (n = 118), the following categories showed significantly higher rates of vaginal delivery: Bishop scores of ≥6 before and after dilatation, compared with Bishop score <6 (adjusted prevalence ratio (aPR) [95% confidence interval (CI)]; 1.58 [1.17-2.13] and 1.56 [1.13-2.14], respectively) and cervical length of <10 and 10-20 mm before dilation, compared with cervical length of >30 mm (aPR [95% CI]; 1.47 [1.00-2.15] and 2.13 [1.42-3.18], respectively). The posterior cervical angle and other background characteristics showed no significant associations. Furthermore, women with cervical lengths of ≥20 mm before and <20 mm after dilatation showed a higher rate of vaginal delivery, compared to cervical length of ≥20 mm even after dilatation (aPR [95% CI]; 1.95 [1.19-3.20]). CONCLUSIONS: High Bishop score, short cervical length, and changes in cervical length with dilatation are potential independent predictors of vaginal delivery following elective labor induction in nulliparous women at 40-41 gestational weeks.

Predictive factors for successful external cephalic version with regional anesthesia.

AIM: We aimed to investigate predictive factors of successful external cephalic version (ECV) using regional anesthesia. METHODS: In this retrospective study, we included women who underwent ECV at our center from 2010 to 2022. The procedure had been conducted using regional anesthesia and the administration of intravenous ritodrine hydrochloride. The primary outcome was the success of ECV, which was defined as the rotation from a non-cephalic to a cephalic presentation. Primary exposures were maternal demographic factors and ultrasound findings at ECV. To determine predictive factors, we conducted a logistic regression analysis. RESULTS: Of 622 pregnant women who underwent ECV, missing data on any variables (n = 14) were excluded and the remaining 608 were analyzed. The success rate during the study period was 76.3%. Multiparous women had significantly higher success rates than primiparous women (adjusted odds ratio [OR]: 2.06 [95% confidence interval (CI): 1.31-3.25]). Women with a maximum vertical pocket (MVP) of <4 cm had significantly lower success rates than those with 4 cm < MVP ≤6 cm (OR: 0.56 [95% CI: 0.37-0.86]). The non-anterior placental location was associated with higher success rates than the anterior placental location (OR: 1.46 [95% CI: 1.00-2.17]). CONCLUSIONS: Multiparity, MVP >4 cm, and non-anterior placental locations were associated with successful ECV. These three factors could be useful for patient selection for successful ECV.

A pregnant woman with thymoma-associated pure red cell aplasia.

BACKGROUND: Pure red cell aplasia (PRCA) is a hematological disorder characterized by anemia with severe reticulocytopenia caused by a marked reduction in erythroid precursors in the bone marrow. PRCA is known to be associated with pregnancy, but thymoma-associated PRCA during pregnancy is very rare, and its successful management has not been reported. CASE PRESENTATION: A 37-year-old primiparous woman with severe anemia was referred to our center at 27 weeks' gestation. She was diagnosed with PRCA based on bone aspiration findings at 33 weeks' gestation. Magnetic resonance imaging (MRI) revealed an anterior mediastinal mass 4 cm in size suspected of being thymoma. She was therefore diagnosed with thymoma-associated PRCA during pregnancy. Surgery for thymoma was planned after delivery, since the imaging findings were suggestive of early-stage thymoma (Masaoka stage I or II). With transfusion of a total 3,360 ml of red blood cells (RBCs) during pregnancy, the patient gave birth to a baby girl weighing 2,548 g at 40 weeks' gestation. The baby showed transient congenital cutaneous candidiasis. The placental pathology revealed subamniotic inflammation with a fungal structure. Treatment with topical anti-fungal cream immediately ameliorated the baby's skin lesion. Maternal anemia did not improve after delivery; however, the thymoma did not increase in size. At five months after delivery, the mother underwent thymectomy with oral cyclosporine A. A pathological examination revealed Masaoka stage II-a thymoma. She completely had recovered from anemia at six months after surgery. Cyclosporine A treatment was discontinued three years after surgery. Remission has been sustained for four years since surgery. CONCLUSIONS: A very rare case of thymoma-associated PRCA during pregnancy was diagnosed without any subjective symptoms and was expectantly managed, resulting in a good prognosis. Although bone marrow aspiration during pregnancy is an invasive test, it is important to confirm the diagnosis. Conservative management with blood transfusion was possible for early-stage thymoma-associated PRCA during pregnancy. Active surveys, including MRI, for PRCA during pregnancy led to the detection of thymoma at an early stage and the achievement of a preferable pregnancy outcome.

Pregnant women's opinions toward prenatal pretest genetic counseling in Japan.

In-person models of genetic counseling (GC) have been the common method in Japan for pregnant women to receive GC. However, recent increases in the number of pregnant women considering undergoing prenatal testing have made it challenging to retain individualized in-person care. To explore pregnant women's opinions toward pretest GC models and the ideal time duration, a self-administered questionnaire survey was conducted for women at their first prenatal visit. A total of 114 valid respondents (93.4%) were included in the analyses. Of these, 80.7% of women preferred in-person GC, followed by classroom (9.6%), group (3.5%), and telegenetic-based GC (2.6%). Women with experience in undergoing prenatal testing significantly did not prefer in-person GC (p = 0.05). Sixty-two women (54.4%) preferred a duration of 15-29 min for pretest GC sessions, followed by 30-59 min (28.9%) and <15 min (14.9%). Women's preference of ≥30 min in length was significantly associated with anhedonia, singleton pregnancies, acquaintance with people with trisomy 21, and awareness of prenatal testing. Women who were unaware of the need for agreement with the partner for prenatal testing and who did not know the average life expectancy of a trisomy 21 patient significantly preferred <15 min in length over other durations. While the majority of women preferred in-person GC for <30 min, their preferences varied by their background characteristics, experiences, attitudes, and knowledge. These findings will help establish a prenatal GC system offering a choice of GC models in Japan; however, further large-scale studies are needed to confirm these findings.

Spontaneously conceived heterotopic pregnancy with abdominal pregnancy implanted on the vesicouterine pouch: A case report and literature review.

We report the case of a 36-year-old woman with spontaneously conceived heterotopic pregnancy with abdominal pregnancy. She visited the hospital at 5 weeks and 4 days of gestation and transvaginal ultrasonography revealed a normal intrauterine pregnancy. Two days later, she was urgently transported to the hospital due to extreme abdominal pain. Emergent laparotomy was performed to investigate the cause of massive intraperitoneal bleeding, which was confirmed to have been due to an abdominal pregnancy that implanted on the vesicouterine pouch. The hematic mass, including chorionic villi, was successfully removed from the peritoneum. The subsequent course of the intrauterine pregnancy was uneventful and a healthy baby was born at term. To the best of our knowledge, this is an extremely rare case report of a spontaneously conceived heterotopic abdominal pregnancy, in which the intrauterine pregnancy showed a successful outcome despite the collapse of the abdominal pregnancy at a very early stage.

Delivery mode and maternal and neonatal outcomes of combined spinal-epidural analgesia compared with no analgesia in spontaneous labor: A single-center observational study in Japan.

AIM: We aimed to assess the outcomes of combined spinal-epidural (CSE) analgesia compared with no analgesia in spontaneous labor. METHODS: We performed a retrospective cohort study of deliveries between 2008 and 2014 comparing two groups based on the use of CSE analgesia in both nulliparous and multiparous women. Adjusted odds ratios (aOR) were calculated using logistic regression analysis. RESULTS: Among 5247 (3334 nulliparous, 1913 multiparous) singleton deliveries, 3041 (2045, 996, respectively) patients received CSE analgesia and 2206 (1289, 917, respectively) had no analgesia. CSE analgesia was associated with increased risk of oxytocin augmentation (P < 0.01), prolonged duration of labor (P < 0.01), instrumental delivery (aOR, 3.35; 95% confidence interval (CI), 2.69-4.19 for nulliparous and aOR, 2.13; 95% CI, 1.32-3.53 for multiparous women), blood loss volume during vaginal delivery (P < 0.01), meconium-stained amniotic fluid (aOR, 1.23; 95% CI, 1.02-1.51 and aOR, 1.39; 95% CI, 1.01-1.93) and Apgar score less than 7 at 1 min (aOR, 1.85; 95% CI, 1.28-2.74 and aOR, 2.65; 95% CI, 1.35-5.61) in both nulliparous and multiparous women, respectively, and umbilical arterial blood gas pH less than 7.15 (aOR, 2.69; 95% CI, 1.35-5.75) and umbilical arterial blood gas pH less than 7.10 (aOR, 3.69; 95% CI, 1.11-16.69) in multiparous women. There was no significant difference in incidence of cesarean delivery or Apgar score less than 7 at 5 min. CONCLUSION: We observed several increased risks in obstetric and neonatal outcomes among pregnant women who received CSE analgesia during labor. Preparations for these risks are needed when administering CSE analgesia during labor.

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.

The effects of gestational transient thyrotoxicosis on the perinatal outcomes: a case-control study.

PURPOSE: To study the effects of gestational transient thyrotoxicosis (GTT) on pregnancy outcomes. METHODS: This case-control study retrospectively analyzed 7976 women with singleton pregnancies whose thyroid function was measured before 16 weeks of gestation and who delivered at ≥22 weeks of pregnancy. GTT was defined as hyperthyroidism (free thyroxine [FT4] level: ≥95th percentile) in the early pregnancy, which normalized in mid-pregnancy without thyroid-stimulating hormone receptor antibodies. Using data extracted from electronic records, we examined the association between GTT and the pregnancy outcomes (preterm delivery, gestational age at delivery, pregnancy induced hypertension (PIH), preeclampsia, placental abruption, caesarian section, birth weight, low birth weight, Apgar score, cord pH, stillbirth at gestational week ≥22, and neonatal death). We classified the cases into quartiles according to their FT4 values during the early pregnancy and investigated the association with the gestational age at delivery. RESULTS: Two hundred and eight cases of GTT and 6317 cases with normal thyroid assessments were reviewed. GTT was associated with hyperemesis gravidarum, but not with stillbirth, preterm delivery, PIH, preeclampsia, placental abruption, or low birth weight. The gestation period was shorter in patients with GTT than in those with a normal thyroid function (38.69 ± 1.79 vs. 39.07 ± 1.64 weeks, p < 0.01). Higher FT4 levels during the early pregnancy were associated with earlier delivery (p = 0.02). CONCLUSIONS: GTT was associated with a lower gestational age at delivery but not with adverse pregnancy outcomes. There was a negative correlation between the FT4 values in the early pregnancy and the gestational period.

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.

Strict management of a pregnant patient with giant coronary artery aneurysm due to Kawasaki disease.

Coronary artery aneurysms (CAA) may occur in Kawasaki disease (KD). Patients with giant CAA (diameter >8 mm), in particular, have higher risk of myocardial infarction. Previous reports have demonstrated the necessity of anticoagulation therapy in such cases. The management of patients with KD complicated by giant CAA later in life, however, remains controversial. Here, we describe the strict management in the case of a 28-year-old pregnant Japanese woman with KD with giant CAA (diameter, 11 mm). Instead of warfarin, the patient was given low-dose aspirin and i.v. unfractionated heparin during pregnancy to prevent thrombosis in the giant CAA. At 38 weeks of gestation, she had spontaneous delivery of a healthy baby. No thrombotic or bleeding complications were observed. The strict anticoagulation therapy resulted in successful pregnancy and delivery without any adverse events.

Usefulness of ultrasonography and MRI for diagnosis of fetal pulmonary agenesis: case report and review of the literature.

A pregnant Japanese female was referred to our hospital due to intrauterine fetal growth restriction. A prenatal diagnosis of right pulmonary agenesis could be made using ultrasonography and fetal magnetic resonance imaging, and a Caesarian section was performed at 34 weeks of gestation. The infant developed a respiratory disorder immediately, received systemic management in the neonatal intensive care unit (NICU), and was discharged at age of 103 days without any severe sequelae.

Labor risk factors for fetal heart rate abnormality after combined spinal-epidural analgesia.

OBJECTIVE: To explore the association between obstetric factors or outcomes and fetal heart rate (FHR) abnormalities after combined spinal-epidural analgesia (CSEA). METHODS: Women with singleton term deliveries who received CSEA at our institution between January 1 and December 31, 2017, were analyzed using medical records. We performed a logistic regression analysis to compare factors and outcomes between cases with and without new FHR abnormalities within 1 h after CSEA. RESULTS: Of the 393 women, 163 showed the new occurrence of FHR abnormality after CSEA. Rupture of the membrane (odds ratio [OR] 2.49; 95% confidence interval [CI] 1.52-4.09; P < 0.01) and dilatation of the cervix (OR 1.24; 95% CI 1.07-1.44; P < 0.01) were significantly associated with FHR abnormalities. There were significant differences in FHR abnormality rates between women with cervical dilatation of 2 cm or less and 3 cm or more (OR 2.20; 95% CI 1.01-4.81; P = 0.047) and 6 cm or less and 7 cm or more (OR 2.46; 95% CI 1.01-6.01; P = 0.048). FHR abnormalities were not significantly associated with cesarean delivery during labor, instrumental delivery, APGAR score below 7 at 1 or 5 min, or umbilical arterial blood gas pH less than 7.2. CONCLUSION: Rupture of the membrane and an advanced dilated cervix were risk factors for FHR abnormality when CSEA was initiated.

Association of Isolated Hypothyroxinemia and Subclinical Hypothyroidism With Birthweight: A Cohort Study in Japan.

Context: Isolated hypothyroxinemia (low maternal free thyroxine [FT4] in the absence of thyroid-stimulating hormone [TSH] elevation) and subclinical hypothyroidism (high TSH in the absence of FT4 elevation) during early pregnancy are common. However, there are limited data regarding pregnancy outcomes, particularly their association with birthweight. Objective: We assessed the association between isolated hypothyroxinemia and subclinical hypothyroidism during the first trimester and birthweight. Methods: Analyses were conducted using a database of pregnant women (n = 1105; median age, 35 years) who delivered at the National Center for Child Health and Development, a tertiary hospital in Tokyo. The primary outcomes included the rates of small for gestational age (SGA), large for gestational age (LGA), and low birth weight. Results: Of the 1105 pregnant women, 981 were classified into the euthyroidism group, 25 into the isolated hypothyroxinemia group, and 26 into the subclinical hypothyroidism group during the first trimester. The prevalence of SGA was significantly higher in isolated hypothyroxinemia and subclinical hypothyroidism groups than the euthyroidism group (28.0% and 19.2%, respectively, vs 5.7%; P < .01). The odds ratio with 95% CI for SGA was 12.51 (4.41-35.53) for isolated hypothyroxinemia and 4.44 (1.57-12.56) for subclinical hypothyroidism in a multivariable adjustment model. Isolated hypothyroxinemia and subclinical hypothyroidism were not significantly associated with LGA and low birth weight. Conclusion: Pregnant women with isolated hypothyroxinemia and subclinical hypothyroidism in the first trimester have an increased likelihood of SGA. Screening and careful perinatal checkups for isolated hypothyroxinemia and subclinical hypothyroidism may help identify pregnant women at high risk for SGA.

Pertussis, diphtheria, and tetanus antibodies seroprevalence in pregnant women and neonates, as a preliminary data for introduction of preconception or prenatal DTaP vaccination among Japanese society.

An increasing number of countries have been introducing acellular pertussis vaccination during pregnancy for the prevention of neonatal pertussis. In response to the fact that infantile pertussis cases of 0-5 months age groups remained unchanged despite the universal vaccination program, prenatal pertussis vaccination has been a rising issue in Japan. Hence, we investigated the seroprevalence of pertussis, diphtheria, and tetanus antibodies in Japanese pregnant women and neonates, and evaluated the necessity of diphtheria-tetanus-acellular pertussis (DTaP) vaccination during the preconception or prenatal period. Maternal PT-IgG (EIA) and FHA-IgG (EIA) for the first trimester, within 1 week after delivery, and cord blood were collected, along with colostrum pertussis-IgA (ELISA), diphtheria-IgG (EIA), tetanus-IgG (EIA), and blood samples from the first trimester. The maternal seroprevalence of PT-IgG and FHA-IgG was 69 % and 75 %, respectively. All tested participants were positive for diphtheria-IgG and tetanus-IgG (100 %). First trimester PT-IgG/FHA-IgG antibody titers were significantly associated with cord blood PT-IgG/FHA-IgG titers (P < 0.001). We found that pertussis seroprevalence among pregnant Japanese women was approximately 70 %. The antibody seropositivity rate of pertussis was lower than that of diphtheria and tetanus. Fetal acquired passive immunity against pertussis is higher when the level of maternal antibody in the first trimester is sufficient. At least 30 % of study population did not reach to the threshold value to provide sufficient pertussis immunity for the neonates and themselves. The acellular pertussis vaccine (DTaP) approved in Japan lacks safety information for pregnancy, hence, a solution for prompt administration of prenatal acellular pertussis vaccination might be introducing DTaP in the preconception period.

Ultrasonographic assessment of fetal thyroid in Japan: thyroid circumference and distal femoral and proximal tibial ossification.

PURPOSE: The present study established a nomogram of fetal thyroid circumference (FTC) and the appearance timing of fetal distal femoral and proximal tibial ossification to assess fetal thyroid function in Japan. METHODS: Between April 2015 and July 2019, normal pregnant women at our hospital were recruited for the study. FTC was measured by the automatic ellipse outline and plotted against gestational age (GA). Fetal distal femoral and proximal tibial ossification measurements were obtained with standard electronic calipers from outer-to-outer margins (> 1 mm as the presence of ossification). RESULTS: A total of 199 pregnant women were examined. FTC increased logarithmically to GA. A nomogram of FTC was expressed by a logarithmic formula: [Formula: see text]. The respective 5-95th percentiles of FTC at each GA were 20.2-36.2 mm at 22 weeks, 25.0-44.8 mm at 26 weeks, 29.2-52.3 mm at 30 weeks, and 32.9-59.0 mm at 34 weeks. The fetal distal femoral epiphysis was not visualized before 30 weeks, but was visualized in 100% of fetuses after 35 weeks of gestation. The fetal proximal tibial epiphysis was not visualized before 33 weeks, but was visualized in 73.7% of fetuses at 37 weeks of gestation. CONCLUSION: We generated a GA-dependent FTC nomogram for Japanese fetuses. We also confirmed the appearance timing of fetal distal femoral and proximal tibial ossification to assess bone maturation. These assessments may be very useful for evaluating fetal thyroid function in Japan.

A CASE OF FAMILIAL NONAUTOIMMUNE HYPERTHYROIDISM DURING PREGNANCY.

OBJECTIVE: Familial nonautoimmune hyperthyroidism (FNAH) is a rare disease. To date there are few, if any, reports of pregnancies in women with FNAH. Our objective here is to present such a case. METHODS: Free thyroxine (free T4), free triiodothyronine (free T3), thyroid-stimulating hormone (TSH), and antibodies related to the thyroid were measured. Fetal thyroid function indicators including thyroid volume and ossification were checked using ultrasound. Thyroid-stimulating hormone receptor (TSHR) gene analyses were performed. RESULTS: The patient was a 30-year-old woman with no past medical history. She was introduced to our hospital in the fifth gestational week for pregnancy care because her family history revealed that her mother had nonautoimmune hyperthyroidism with a TSHR-activating germ-line mutation (Asn406Ser). The serum free T4 was 1.88 ng/dL (normal, 0.62 to 1.19 ng/dL), free T3 was 3.27 pg/mL (normal, 2.55 to 3.88 pg/mL), TSH was 0.02 µIU/mL (normal, 0.007 to 3.619 µIU/mL), and TSHR was negative which were considered to be consistent with mild primary hyperthyroidism. Serum free T4, free T3, and TSH concentrations were monitored every 4 to 6 weeks with a peak free T4 of 2.23 ng/dL noted at gestational week 9. The patient had no signs related to hyperthyroidism throughout pregnancy. The patient delivered a 3,518 g girl at 40 weeks of gestation. Genetic analysis of her TSHR gene showed heterozygous Asn406Ser mutation. The offspring did not show any signs of prenatal hyperthyroidism, and thyroid function at day 6 after delivery revealed a free T4 of 2.41 ng/dL (normal, 1.83 to 2.91 ng/dL) and a TSH of 3.55 µIU/mL (normal, 0.51 to 4.57 µIU/mL). CONCLUSION: Women with FNAH and mild thyrotoxicosis prior to pregnancy may have continuous hyperthyroidism with additional change due to the series of human chorionic gonadotropin secretion during pregnancy.

Establishment of an immortalized human extravillous trophoblast cell line by retroviral infection of E6/E7/hTERT and its transcriptional profile during hypoxia and reoxygenation.

Investigation into the function of human trophoblasts has been largely restricted by a lack of suitable cell models. We aimed to produce normal human trophoblast cell lines with a long lifespan and to provide an ideal in vitro cell model. Primary human trophoblast cells were derived from a placenta that had undergone elective abortion at the 7th week of gestation. The cells were immortalized by infection with retroviral expression vectors containing the type 16 human papillomaviruses E6 and E7 in combination with human telomerase reverse transcriptase (hTERT). Characterization of the cell line was performed by immunocytochemistry using a panel of antibodies, Western blotting, real-time RT-PCR, an invasion assay, gelatin zymography, karyotype analysis and a nude mouse assay. Gene expression profiles under hypoxia (1% O2, 1 h) and subsequent reoxygenation (20% O2, 6 h) were analyzed using cDNA microarray. Immunocytochemistry revealed an extravillous trophoblastic phenotype by positive staining for hCGbeta, cytokeratin 7, HLA-G and CD9. A transwell insert invasion assay showed the invasiveness of this cell line and gelatin zymography detected the secretion of MMP-2 and MMP-9. Karyotype analysis exhibited an almost normal chromosomal number which ranged from 46 to 48 and the cells showed no tumorigenecity in a nude mouse assay. Forty-three genes showing reversible up- or down-regulation during hypoxia were detected using an oligonucleotide array. This newly immortalized cell line, HChEpC1b, is a useful model for the study of extravillous trophoblast function.

Priming of peripheral monocytes with prolactin (PRL) sensitizes IFN-gamma-mediated indoleamine 2,3-dioxygenase (IDO) expression without affecting IFN-gamma signaling.

Prolactin (PRL) was originally identified by its ability to stimulate mammary development and lactation, and its essential roles other than lactation have recently been implicated in female reproduction. However, little is known about PRL-mediated events in pregnancy. The tryptophan catabolism enzyme indoleamine 2,3-dioxygenase (IDO) is interferon-gamma (IFN-gamma)-inducible and has recently become a focus for maternal-fetal tolerance for successful pregnancy. Based on recognition that PRL is one of the up-regulated hormones in pregnancy, in a previous study we have shown that PRL induces IDO expression in monocytes in cooperation with a suboptimal concentration of IFN-gamma. Here, we demonstrate that PRL sensitizes monocytes to induce IDO expression in response to low doses of IFN-gamma without affecting the typical IFN-gamma signaling events, such as STAT1 phosphorylation and IRF-1 induction. In addition, IDO induction in these cell cultures was observed only after 24 h pre-exposure to PRL. These results indicate a priming effect of PRL on monocytes that occurs before IFN-gamma signaling and increases their sensitivity to IFN-gamma for IDO induction, rather than a synergistic effect of PRL and IFN-gamma on IDO induction. These results offer new insights into the roles of PRL in female reproduction, as well as provide a better understanding as to how IDO expression is regulated and achieved in pregnancy.

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.