Immunological disease activity parameters at conception are risk factors for preterm birth and low birth weight in patients with systemic lupus erythematosus.

OBJECTIVE: This study aimed to identify which disease activity parameters may be risk factors for preterm birth (PB) and low birth weight (LBW) in patients with systemic lupus erythematosus (SLE). We also analyzed the extent to which these parameters affected PB and LBW. METHODS: We collected the SLE Disease Activity Index (SLEDAI), the rate of lupus low disease activity state (LLDAS) attainment, complement levels, and the titer of anti-double stranded DNA (dsDNA) antibody as disease activity parameters. We retrospectively analyzed the associations of these parameters with PB and LBW. RESULTS: Sixty pregnancies were included in this study. C3 levels and anti-dsDNA antibody titers at conception were strongly associated with PB (p = 0.03 and p = 0.01, respectively), whereas C3 and CH50 levels were associated with LBW (p = 0.02 and p = 0.03, respectively). A logistic regression analysis showed that the cutoff values of C3 and anti-dsDNA antibody for PB were 62.0 mg/dl and 5.4 IU/ml, respectively. The cutoff values of C3 and CH50 for LBW were 87.0 mg/dl and 41.8 U/ml, respectively. The risk of PB or LBW was increased when divided by the cutoff value, and the combination of these cutoff values showed a significantly higher risk of PB and LBW (p = 0.01 and p < 0.01, respectively). CONCLUSIONS: PB and LBW are strongly associated with disease activity parameters in patients with SLE. Therefore, strictly monitoring and controlling these disease activity parameters, with or without clinical manifestation, is important for women who want to become mothers.

[Promotion of Equal Access to Medical Services for Children, Adolescent and Young Adult(CAYA)Cancer Patients with Reproductive Problems-A Nationwide Expansion of the Regional Oncofertility Network in Japan].

OBJECTIVES: Fertility preservation is important for Children, Adolescent and Young Adult(CAYA)cancer patients. Although a regional oncofertility network was established in Japan in 2012, regional inequality persists. This study was aimed at expanding the oncofertility network throughout Japan. METHODS: Oncologists, reproductive medicine specialists, and administrative officials from 24 regions, currently without a regional oncofertility network, conferred to discuss problems and strategies for network expansion. RESULTS: Regional oncofertility networks had already been established in 4 of 24 regions. Consultation and support and a collaboration system between facilities and individual doctors were found in 13 and 14 regions, respectively. Regarding which organization should lead the network operation, the regions(number)chose the prefecture (10), prefectural cancer centers(10), and OB/GYN department of hospitals specializing in cancer treatment(9). Obstacles to establishing a regional oncofertility network were the lack of manpower(21), budget(19), know-how(16), and specialists( 12). DISCUSSION: CAYA cancer patients need equal access to oncofertility networks, and a public support system is essential for preserving the fertility of cancer patients. We should organize a oncofertility network in association with prefectural administration. Medical staff training and supply of materials using the Oncofertility Consortium Japan system are required to promote the oncofertility network throughout Japan.

Twin fetal facial expressions at 30-33+6 weeks of gestation.

Objective To assess the characteristics of twin fetal facial expressions at 30-33 + 6 weeks of gestation using four-dimensional (4D) ultrasound to clarify twin fetal brain development and maturation. Methods Frequencies of seven fetal facial expressions were studied using 4D ultrasound for 15 minutes in 30 singleton pregnancies and 18 twin pregnancies [four monochorionic diamniotic (MD) and 14 dichorionic diamniotic (DD) twins] at 30-33 + 6 weeks of gestation. Comparison of the frequency in each facial expression was performed between singleton and twin fetuses. Results Mouthing was the most frequent facial expression at 30-33 + 6 weeks of gestation, followed by blinking in twin and singleton fetuses. Both facial expressions were significantly more frequent than other expressions (P < 0.05). The frequencies of mouthing and scowling in twin fetuses were significantly lower than those in singleton fetuses, but there were no significant differences in the frequencies of the five other facial expressions between the fetal groups. Conclusion Our results suggest that restricted twin fetal behavior before 20 weeks of gestation may still affect the frequencies of twin facial expressions early in the third trimester of pregnancy. Moreover, the frequencies of facial expressions in twins are different from those of singleton fetuses.

Neurological development may be accelerated in growth-restricted fetuses: a 4D ultrasound study.

Objective To assess whether neurological maturation and development are accelerated in fetal growth restriction (FGR) in utero using four-dimensional (4D) ultrasound. Methods The facial expressions of 50 appropriate-for-gestational-age (AGA) and 34 FGR fetuses aged between 28 and 35 gestational weeks were assessed using 4D ultrasound. Subsequently, they were differentiated into two gestational age groups (19 aged 28-31 weeks and 31 aged 32-35 weeks in AGA, and 15 aged 28-31 weeks and 19 aged 32-35 weeks in FGR). Fifteen-minute recordings were made, and the frequencies of seven facial expressions during that time were examined. Correlation analysis was conducted to assess the changing number of significant correlations with advancing gestation in each group. Results Out of 21 combinations of facial expressions at 28-31 and 32-35 gestational weeks in AGA fetuses, there was only three significant correlations. Similarly, only one was noted out of 21 combinations at 28-31 gestational weeks, but there were seven significant correlations in FGR fetuses at 32-35 weeks (P=0.018). However, there was no significant difference in the number of correlations of facial expressions between AGA (3/21) and FGR (7/21) fetuses at 32-35 weeks of gestation (P=0.147). Conclusion Our results suggest that the number of significant correlations of fetal facial expressions in FGR fetuses increases more compared with that in AGA fetuses at 32-35 weeks of gestation. Due to the acceleration of neurological maturation and development in FGR fetuses, the control of facial expressions by the brain may be more evident compared with AGA fetuses at 32-35 weeks of gestation. However, the data and their interpretation in the present study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size are needed to obtain strong or additional evidence.

Change in fetal behavior in response to vibroacoustic stimulation.

Objective To assess fetal behavioral changes in response to vibroacoustic stimulation (VAS) in normal singleton pregnancies using four-dimensional (4D) ultrasound. Methods Ten types of fetal movements and facial expressions in 68 healthy pregnant women between 24 and 40 weeks were studied using 4D ultrasound for 3 min before and after 3-s VAS. The frequencies of mouthing, yawning, tongue expulsion, back arch, jerky arm movement, startle movement, smiling, scowling, hand-to-face movement, and blinking were evaluated. The fetuses were subdivided into four gestational age groups (24-27, 28-31, 32-35, and ≥36 weeks). Comparison of the frequencies of the fetal behaviors before and after the stimulation in each gestational age group was conducted to detect the response to stimulation with advancing gestation. Results There were no significant differences in the frequency of each fetal behavior before and after VAS at 24-27, 28-31, and 32-35 weeks of gestation. However, the frequencies of blinking and startle movements were significantly higher after VAS in the 36-40 gestational age group (P < 0.05). Conclusion The age of 36 weeks of gestation might represent an advanced stage of brain and central nervous system development and maturation as the response to stimuli is prominent at this age compared with earlier gestation.

Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy.

AIM: To assess the effect of psychotropic drugs on fetal behavior using four-dimensional (4D) ultrasound in the third trimester of pregnancy. METHODS: Fetal behavior was assessed using Kurjak's antenatal neurodevelopmental test (KANET) using 4D ultrasound between 28 and 36 weeks of gestation. Thirty healthy (control group) and 10 psychotropic-drug-administered pregnant (case group) women were studied. The total value of the KANET score and values of each parameter (eight parameters) were compared between the two groups. RESULTS: The total KANET score was normal (except for one fetus in the case group: total score of 9) in both groups, and there was no significant difference in the total KANET score. When individual KANET parameters were compared, no significant differences were noted in any of the eight parameters. CONCLUSION: Our results showed that there is no difference in fetal behavior between fetuses of normal pregnant women and those of psychotropic-drug-administered pregnant women in the third trimester of pregnancy. These results suggest that psychotropic drugs may not affect fetal behavioral development in utero. However, the data and their interpretation in the present study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size are needed to assess the effect of psychotropic drugs on fetal neurobehavior during pregnancy.

Characteristic findings of high-grade cervical intraepithelial neoplasia or more on magnifying endoscopy with narrow band imaging.

BACKGROUND: Colposcopy, which is a standard modality for diagnosing cervical intraepithelial neoplasia (CIN), can have limited accuracy owing to poor visibility. Flexible magnifying endoscopy with narrow band imaging (ME-NBI) has excellent diagnostic accuracy for early gastrointestinal neoplasms and is expected to be highly useful for CIN diagnosis. This study aimed to determine the characteristic findings and evaluate the diagnostic ability of ME-NBI for lesions ≥ CIN 3. METHODS: A well-designed prospective diagnostic case series conducted at multiple tertiary-care centers. A total of 24 patients who underwent cervical conization with a preoperative diagnosis of high-grade squamous cell intraepithelial lesions (HSILs) or lesions ≥ CIN 3 were enrolled. Prior to conization, still images and video of ME-NBI were captured to investigate the cervical lesions. The images were reviewed based on histological examination of the resected specimens. RESULTS: The NBI-ME images revealed the following abnormal findings: (1) light white epithelium (l-WE), (2) heavy white epithelium (h-WE), and (3) atypical intra-epithelial papillary capillary loop (IPCL). Pathological examination of the resected specimens confirmed cervical lesions ≥ CIN 3 in 21 patients. The ME-NBI findings were classified into four groups: l-WE, l-WE with atypical IPCL, h-WE, and h-WE with atypical IPCL, at rates of 0, 23.8, 9.5, and 66.7%, respectively. Additionally, all 3 patients with micro-invasive carcinoma showed a strong irregularity of IPCLs. CONCLUSION: The lesions ≥ CIN 3 demonstrated characteristic ME-NBI findings of h-WE alone, or l-/h-WE with atypical micro-vessels. This study indicates that ME-NBI may have novel value for CIN diagnosis.

Ultrasound study of fetal movements in singleton and twin pregnancies at 12-19 weeks.

Objective To evaluate fetal behavioral differences between singleton and twin fetuses before 20 weeks of gestation using four-dimensional (4D) ultrasound. Methods 4D ultrasound was used to examine fetal movements in 58 singleton and 48 twin normal fetuses at 12-19 weeks. The frequencies of eight fetal movements were assessed through 15-min recordings. The fetuses were divided into two gestational age groups (12-13 and 14-19 weeks) to evaluate the changes with advancing gestation in twin versus singleton fetuses. Results Arm and general movements were the most frequent movements in singleton fetuses, whereas only general movement was significantly more frequent than the other seven fetal movements in twin fetuses at 12-13 weeks. At 14-19 weeks, frequencies of arm and leg movements were significantly higher than those of the other six movements in singleton fetuses, while only arm movement was significantly more frequent than the other fetal movements in twin fetuses. Comparisons of fetal movements between singleton and twin fetuses revealed that only arm movement showed a significant difference at 12-13 weeks, while the frequencies of all movements in singleton fetuses were significantly higher than those in twin fetuses at 14-19 weeks. Conclusion Our results suggest that the limitation of available space and crowding of twin fetuses with advancing gestation may have a marked impact on twin fetal movements compared with singleton fetuses, even in the first half of pregnancy. Further studies are needed to assess whether decreased fetal movements in twin pregnancy can affect fetal and neonatal development and maturation before and after birth.

Prediction of postnatal developmental disabilities using the antenatal fetal neurodevelopmental test: KANET assessment.

Objective To assess the usefulness of the antenatal fetal neurodevelopmental test for the prediction of postnatal developmental disabilities. Methods Fetal behavior was assessed with Kurjak's antenatal neurodevelopmental test (KANET) using four-dimensional ultrasound between 28 and 38 weeks of gestation. A score range of 0-5 was characterized as abnormal, from 6 to 9 was considered borderline, and 10-16 was normal. After birth, follow-up was conducted for at least 2 years in all fetuses. Results There were 337 normal (95.47%) and 16 borderline (4.53%) cases among the 353 cases studied, whereas there was no abnormal case. Five cases with postnatal developmental disabilities (one case of Werdig-Hoffmann disease diagnosed just after delivery, one case of autism spectrum disorder diagnosed at 24 months, one case of Ullrich congenital muscular dystrophy diagnosed at 9 months and two cases of developmental disorders diagnosed at age 3 and 18 months) were noted among the 337 normal cases (1.48%), whereas three cases with developmental disabilities (one case of motor development delay diagnosed at 6 months, one case of Duchenne muscular dystrophy diagnosed at 18 months and one case of autism spectrum disorder diagnosed at age 30 months) were found among the 16 borderline cases (18.75%). There was a significant difference in the prevalence of postnatal developmental disabilities between the normal and borderline KANET groups (P<0.001). Conclusion Our results suggest that the KANET assessment may be a useful diagnostic modality for the prediction of postnatal developmental disabilities.

HDLive Silhouette Inversion Mode in Diagnosis of Complete Hydatidiform Mole.

We present our experience of using the HDLive silhouette inversion mode to assess complete hydatidiform mole early in pregnancy. The HDLive silhouette inversion mode clearly depicted the number, size, and spatial position of molar vesicles, compared with conventional two-dimensional sonography or the HDLive inversion mode. Moreover, spatial relationships among molar vesicles, intrauterine anechoic fluid collection, and the uterine wall enabled the clear localization of the lesion. This technique provides new insights, and has the potential to supplement conventional two-dimensional sonography in the diagnosis of complete hydatidiform mole.

4D ultrasound study of fetal movement early in the second trimester of pregnancy.

AIM: To assess the frequency of fetal movement and reproducibility of fetal movement counting in normal singleton pregnancies early in the second trimester using four-dimensional (4D) ultrasound. METHODS: Twenty-nine singleton pregnancies were studied for 15 min employing 4D ultrasound at 14-16 (19 cases) and 17-19 (10 cases) weeks of gestation. The frequencies of eight fetal movements (head anteflexion, head retroflexion, body rotation, hand to face movement, general movement, isolated arm movement, isolated leg movement and mouthing movement) were evaluated. RESULTS: The most frequent fetal movements were isolated arm movements at 14-16 and 17-19 weeks' gestation. There was a significant difference only in the frequency of mouthing movement between 14-16 and 17-19 weeks' gestation (P<0.05). All fetal movements showed intra- and inter-class correlation coefficients greater than 0.87, with good intra- and inter-observer agreements. CONCLUSION: The difference in the frequency of mouthing movement at 14-16 and 17-19 weeks' gestation may be due to increasing fetal swallowing because of the increasing amniotic fluid early in the second trimester of pregnancy. To the best of our knowledge, this is the first study on the reproducibility assessment of fetal movement counting using 4D ultrasound. However, the data and their interpretation in the present study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size are needed to assess the reproducibility of fetal movement counting using 4D ultrasound.

Antenatal diagnosis of idiopathic dilatation of pulmonary artery with 3D power doppler imaging.

We present a case of antenatal diagnosis of idiopathic dilatation of the pulmonary artery by three-dimensional power Doppler imaging (HDliveFlow with silhouette mode). Two-dimensional sonography clearly demonstrated a 10.4-mm-diameter fetal pulmonary artery (PA), whereas the aorta (Ao) diameter was 5.04 mm. HDliveFlow clearly demonstrated the spatial relationships and different sizes of PA and Ao. The PA size returned to normal (8.0 mm) on the 11th day after birth (Ao: 9.0 mm). HDliveFlow may be an adjunctive tool to two-dimensional sonography to diagnose abnormalities of fetal great vessels. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:121-123, 2017.

Immunoreactivity of glucose transporter 8 is localized in the epithelial cells of the choroid plexus and in ependymal cells.

High fructose intake is known to be associated with increased plasma triglyceride concentration, impaired glucose tolerance, insulin resistance, and high blood pressure. In addition, excess fructose intake is also thought to be a risk factor for dementia. Previous immunohistochemical studies have shown the presence of glucose transporter 5 (GLUT5), a major transporter of fructose, in the epithelial cells of the choroid plexus and ependymal cells in the brains of humans, rats, and mice, while GLUT2, a minor transporter of fructose, was localized in the ependymal cells of rat brain. In this study, immunoreactivity for the fructose transporter GLUT8 was observed in the cytoplasm of the epithelial cells in the choroid plexus and in the ependymal cells of the brains of humans and mice. These structures were not immunoreactive for GLUT7, GLUT11, and GLUT12. Our findings support the hypothesis of the transport of intravascular fructose through the epithelial cells of the choroid plexus and the ependymal cells.

Three-Dimensional Color/Power Doppler Sonography and HD live Silhouette Mode for Diagnosis of Molar Pregnancy.

We present our experience of using new 3-dimensional color/power Doppler sonography (HDliveFlow; GE Healthcare Japan, Tokyo, Japan) with the HD live silhouette mode for diagnosing complete molar pregnancy in the first trimester and differentiating it from missed abortion with hydropic degeneration. In the case of a complete mole, color Doppler sonography showed numerous vesicles without blood vessels, whereas HDliveFlow with the HD live silhouette mode clearly depicted these vesicles forming a mass with the clear demarcation of its edges and showed no blood flow inside the mass. In contrast to the hydropic abortion, which appeared as some vesicles with many blood vessels around them on color Doppler sonography, HDliveFlow with the HD live silhouette mode showed some vesicles embedded within the abundant blood vessels. The spatial relationship between the vesicles and surrounding highly vascularized uterus could be shown on HDliveFlow with the HD live silhouette mode. This technique might be beneficial as an additional diagnostic tool along with conventional color/power Doppler sonography, and it facilitates the early discrimination of these cases in the first trimester of pregnancy.

Is yolk sac tumor related to the pathophysiology of low birthweight?

An 8-year-old Japanese girl was admitted with an ovarian yolk sac tumor. Regarding birth history, the patient had been delivered by cesarean section at 25 weeks of gestation with a birthweight of 711g. She had required neonatal intensive care including oxygenation, various medications, and tests. After surgery and chemotherapy, there was no recurrence for 2 years, at the time of writing. Yolk sac tumor, which is a malignant germ cell tumor, is rare in children. Although the cause and risk factors are unclear, it has been reported that malignant germ cell tumors in childhood have been associated with pathophysiology at birth. Given that premature infants are more likely to survive due to advances in perinatal care, it is expected that such cases will increase in the near future. We suggest that children born prematurely require careful follow up.

Does ethnicity have an effect on fetal behavior? A comparison of Asian and Caucasian populations.

AIM: This study aimed to evaluate the ethnic difference in fetal behavior between Asian and Caucasian populations. METHODS: Fetal behavior was assesed by Kurjak's antenatal neurodevelopmental test (KANET) using four-dimensional (4D) ultrasound between 28 and 38 weeks of gestation. Eighty-nine Japanese (representative of Asians) and seventy-eight Croatian (representative of Caucasians) pregnant women were studied. The total value of KANET score and values of each parameter (eight parameters) were compared. RESULTS: The total KANET score was normal in both populations, but there was a significant difference in total KANET scores between Japanese (median, 14; range, 10-16) and Croatian fetuses (median, 12; range, 10-15) (P<0.0001). When individual KANET parameters were compared, we found significant differences in four fetal movements (isolated head anteflexion, isolated eye blinking, facial alteration or mouth opening, and isolated leg movement). No significant differences were noted in the four other parameters (cranial suture and head circumference, isolated hand movement or hand to face movements, fingers movements, and gestalt of general movements). CONCLUSION: Our results suggest that ethnicity should be considered when evaluating fetal behavior, especially during assessment of fetal facial expressions. Although there was a difference in the total KANET score between Japanese and Croatian populations, all the scores in both groups were within normal range. Our results indicate that ethnical differences in fetal behaviour do not affect the total KANET score, but close follow-up should be continued in some borderline cases.

HDlive rendering image of adnexal tumors: preliminary report.

BACKGROUND: Our objective is to present our first experience of adnexal tumors reconstructed employing the HDlive rendering mode. METHODS: Seven adnexal tumors (one case each of chocolate cyst, benign cystic teratoma, serous cystadenofibroma, and torsion of the hydrosalpinx, and three cases of ovarian cancer) were studied using the HDlive rendering mode. RESULTS: In the case of the chocolate cyst, the smooth inner wall with numerous tiny projections was clearly identified. In the case of benign cystic teratoma, a smooth hair ball inside the cyst was evident. In the case of the serous cystadenofibroma, a smooth, solid projection and relatively smooth septum were noted. In the three cases of ovarian cancer, numerous irregular papillae and irregular, thick septae were depicted. In the case of the bilateral hydrosalpinx with torsion of the right tube, different fluid contents were recognized. CONCLUSION: The HDlive rendering mode provides anatomically realistic features such as macroscopic specimens for physicians and pathologists due to the complete depiction of the inner surface of the adnexal tumors.

Immunohistochemical localization of HCA1 receptor in placenta in presence of fetal growth restriction.

INTRODUCTION: Glucose metabolism produces lactate and hydrogen ions in an anaerobic environment. Fetuses with intrauterine growth restriction are considered to become progressively lactacidemic as well as hypoxic. Roles of lactate in the placenta in the presence of fetal growth restriction (FGR) remain to be clarified. METHODS: Immunohistochemical localization of lactate-related substances, such as a receptor for lactate (hydroxy-carboxylic acid 1 receptor (HCA1 receptor/GPR81)), monocarboxylate transporters (MCTs) for lactate, lactate dehydrogenases (LDHs), and proteins expressed in syncytiotrophoblasts or cytotrophoblasts was examined in placentas of appropriate weight for gestational age (AGA) fetus and those showing FGR. RESULTS: Immunoreactivity for the HCA1 receptor was present in the cytoplasm of some trophoblasts, predominantly localized to their basal (fetus-facing) side, and was frequently colocalized with that for E-cadherin or serine peptidase inhibitor, Kunitz type 1 (SPINT1), a marker protein of cytotrophoblasts. Immunoreactivity for MCT1 and MCT4 was present on the basal and the microvillous (maternal-facing) membranes of trophoblasts in both groups, respectively. Clear immunoreactivity for LDHA and LDHB was also observed in the cytoplasm of trophoblasts, mainly localized to their basal side. However, there were no significant differences in immunohistochemically stained areas of lactate-related substances between AGA and late-onset FGR groups. On the other hand, there were correlations between coefficients of the presence of chorioamnionitis and the values of LDHB and E-cadherin. DISCUSSION: Immunohistochemical localization of the HCA1 receptor was predominantly observed in the cytoplasm located on the basal side of trophoblasts, suggesting a role of lactate in human placental development, including syncytialization.