Fetal heart rate patterns complicated by chorioamnionitis and subsequent cerebral palsy in Japan.

AIM: This retrospective study was performed to investigate whether certain fetal heart rate patterns were associated with subsequent cerebral palsy (CP) in infants with chorioamnionitis at or near term. METHODS: We used cases registered by the Japan Obstetric Compensation System for CP, which is a nationwide population-based database. Among them, 133 infants with chorioamnionitis who were born at ≥34 weeks of gestation were enrolled. All infants underwent magnetic resonance imaging (MRI), and all fetal heart rate charts had been interpreted according to the National Institute of Child Health and Human Development criteria, focusing on antepartum and immediately before delivery. RESULTS: The incidence of CP after chorioamnionitis at ≥34 weeks of gestation was 0.3 per 10 000 in Japan. Between the clinical (24%) and subclinical groups (76%), the incidence of abnormal fetal heart rate patterns did not differ. According to the MRI classification, 88% of the infants with CP showed hypoxic-ischemic encephalopathy. Half of the infants with CP experienced terminal bradycardia, leading to severe acidosis and exclusively to hypoxic-ischemic encephalopathy. In another half, who did not experience bradycardia, 80% had moderate acidosis (pH 7.00-7.20) resulting in hypoxic-ischemic encephalopathy, and the remaining 20% showed non-acidosis resulting in brain damage other than hypoxic-ischemic encephalopathy. The fetal heart rate patterns before the terminal bradycardia showed that the incidence rates of late deceleration or decreased variability were high (>60%). CONCLUSION: Fifty percent of pregnant women with chorioamnionitis-related CP had terminal bradycardia that exclusively resulted in hypoxic-ischemic encephalopathy.

Effects of sturgeon fillet intake on top-ranked Japanese female long-distance runners.

AIMS: The aim of this study is to investigate whether consumption of sturgeon fillets reduces the oxidative stress marker urinary 8-hydroxy-2'-deoxyguanosine (8OHdG) in top-ranked Japanese female long-distance runners. METHODS: In a before-and-after study, nine professional long-distance female athletes ate 100 g/day of sturgeon fillets for 2 weeks. Urinalysis (8OHdG, an oxidative stress marker, and creatinine), blood tests (fatty acids and 25-hydroxyvitamin D [25OHD]), exercise intensity, subjective fatigue, muscle elasticity, muscle mass, body fat mass, and nutritional intake using image-based dietary assessment (IBDA) were compared before, immediately after, and 1 month after the intervention. RESULTS: Consumption of sturgeon fillets suppressed 8OHdG (p < 0.05) in the increased exercise intensity female athletes. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and 25OHD levels in blood increased from before to immediately after and 1 month after the intervention (p < 0.05). IBDA showed that intake of n-3 fatty acid increased after and one month after the intervention, whereas DHA, imidazole dipeptide and vitamin D intake increased after the intervention (p < 0.05) and then decreased after 1 month (p < 0.05). There were no significant changes in subjective fatigue, muscle elasticity, muscle mass, and body fat. CONCLUSIONS: The results suggest that eating sturgeon fillets during intense training may increase blood levels of EPA, DHA, and 25OHD, which may suppress urinary oxidative stress (8OHdG) in top-ranked Japanese long-distance runners.

Histological severity of maternal and fetal inflammation is correlated with the prevalence of maternal clinical signs.

AIM: To evaluate whether there is a stepwise increase in the prevalence of maternal clinical signs according to the severity of histological inflammation in the chorioamniotic membranes, placenta, and umbilical cord in preterm deliveries. METHODS: This retrospective study, conducted between January 2007 and May 2017, included patients with preterm delivery between 22 and 33 weeks. The histological findings of maternal/fetal inflammatory responses were staged and graded according to the Amsterdam Placental Workshop Group consensus statement. Correlations between the histological severity of maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and clinical signs were evaluated using the Cochran-Armitage trend test. RESULTS: A total of 138 patients were included. The stage and grade of the maternal inflammatory response were correlated with earlier gestational weeks at delivery and lighter birth weight. The prevalence of clinical chorioamnionitis was significantly correlated with a higher stage and grade of the maternal inflammatory response (Gibbs/Lencki criteria: 15.8%/15.8% in Stage 3, 16.3%/14% in Grade 2). No significant correlations were observed between gestational weeks at delivery and birth weight and stage/grade of fetal inflammatory response. The prevalence of clinical chorioamnionitis was significantly correlated with higher stage and grade of fetal inflammatory response (Gibbs/Lencki criteria: 25%/25% in Stage 3 and 29.4%/29.4% in Grade 2). CONCLUSION: Correlations exist between the severity of histological maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and positive maternal clinical signs in preterm deliveries. However, the prevalence of clinical chorioamnionitis was 20%-30% even in the most severe fetal inflammatory responses.

Cerclage in surgically shortened uterine cervix and pregnancy outcome: A retrospective comparison between the abdominal and vaginal procedures.

BACKGROUND: Cerclage for uterine cervical incompetence can be performed by the transabdominal or transvaginal approach. Transabdominal cerclage (TAC) is indicated for women with a short cervix or a cervical laceration who are inapplicable to transvaginal cerclage (TVC). The larger the volume of tissue removed in cervical conization, the greater the rate of miscarriage or preterm delivery in the subsequent pregnancy. AIMS: The aim of this study was to compare TAC and TVC in post-cervical conization pregnancies. METHODS: A retrospective, two-group, comparative study was conducted involving subjects who underwent cervical cerclage (TAC, n = 14; TVC, n = 18) following cervical conization and who were cared for at the University of Miyazaki Hospital between 2008 and 2020. We compared study subject characteristics and outcomes between the two groups. Primary outcome was incidence of preterm labor <37 weeks of gestation between the two groups. RESULTS: The preoperative median cervical length was significantly shorter in the TAC group (20.0 mm) than in the TVC group (31.0 mm; p < 0.01). Preoperative vaginal discharge cultures positive for Gardnerella showed a tendency to be greater in the TAC group (p = 0.073). There was no significant difference in the preterm delivery rate < 37 weeks of gestation between TAC (1/14, 7.1%) and TVC (6/18, 33.3%) groups, p = 0.10. Noninferiority test using multiple regression analysis showed that TAC is not inferior to TVC regarding gestational age at delivery, even though cervical length of TAC was significantly shorter. CONCLUSION: Women who were inapplicable to TVC due to a short cervix still achieved an equivalent outcome with TAC.

Association between fetal vascular malperfusion and gestational diabetes.

AIM: Diabetes mellitus (DM) is a major complication in pregnancy. Placental lesions with DM remain unclear and controversial. Recently, the terms of placental pathological findings, such as maternal and fetal vascular malperfusions (MVM and FVM, respectively) were introduced by the Amsterdam Placental Workshop Group Consensus Statement (APWGCS). FVM cases were classified as the partial obstruction type (global FVM) and the complete obstruction type (segmental FVM). The aim of this study was to clarify the pathological characteristics of the placenta with pregestational DM/gestational DM; GDM according to APWGCS. METHODS: We studied the placentas of 182 DM women (27 pregestational DM and 155 GDM) and control placentas of 460 women without DM during 2011-2018. We excluded cases of intrauterine fetal death or multiple pregnancies. We reviewed microscopical findings including, MVM, FVM, chorioamnionitis with the slides according to the APWGCS. RESULTS: Microscopically, the incidence of FVM was significantly higher in GDM patients than control (17% vs. 10%, p = 0.0138), but not significant in pregestational DM (11%, p = 0.7410). Segmental FVM (complete obstruction) was significantly more observed in GDM than control group (5% vs. 0.4%, p = 0.0013). Segmental FVM in GDM showed high incidence of light-for-dates infant (three of seven cases, 43%, p = 0.0288). In addition, several segmental FVM findings (villous stromal-vascular karyorrhexis and stem vessel occlusion) were frequently noted in 2 or 3 points positive of 75 g oral glucose tolerance test than 1 point positive GDM. CONCLUSION: Our placental findings suggest disorder of carbohydrate metabolism might affect the fetal vascular damage, especially complete fetal vascular obstruction.

Feasibility of a mobile cardiotocogram device for fetal heart rate self-monitoring in low-risk singleton pregnant women.

AIM: This study aimed to clarify the feasibility of a mobile cardiotocogram (CTG) device for self-monitoring fetal heart rate (FHR) in low-risk singleton pregnant women. METHODS: This study was conducted at six university hospitals and seven maternity clinics in Japan. Using a mobile cardiotocogram device (iCTG, Melody International Ltd., Kagawa, Japan), participants of more than 34 gestational weeks measured the FHR by themselves at least once a week until hospitalization for delivery. We evaluated the acquisition rate of evaluable FHR recordings and the frequency of abnormal FHR patterns according to the CTG classification system of the Japan Society of Obstetrics and Gynecology (JSOG). The participants also underwent a questionnaire survey after delivery to evaluate their satisfaction level of self-monitoring FHR using the mobile CTG device. RESULTS: A total of 1278 FHR recordings from 101 women were analyzed. Among them, 1276 (99.8%) were readable for more than 10 min continuously, and the median percentage of the total readable period in each recording was 98.9% (range, 51.4-100). According to the JSOG classification system, 1245 (97.6%), 9 (0.7%), 18 (1.4%), and four (0.3%) FHR patterns were classified as levels 1, 2, 3, and 4, respectively. The questionnaire survey revealed high participant satisfaction with FHR self-monitoring using the iCTG. CONCLUSION: The mobile CTG device is a feasible tool for self-monitoring FHR, with a high participant satisfaction level.

Tissue factor expression and tumor-infiltrating T lymphocytes in ovarian carcinomas and their association with venous thromboembolism.

Ovarian cancer is a known risk factor of venous thromboembolism (VTE). Thrombogenic factor expression and lymphocytic infiltrate have been reported in endometriosis and ovarian cancers. We reviewed 30 cases of ovarian carcinomas (high grade serous carcinoma, 10; endometrioid carcinoma, 10; clear cell carcinoma (CCC), 10) and 16 endometriotic lesions. We immunohistochemically investigated the expressions of tissue factor (TF), podoplanin, P-selectin, and number of CD4 and CD8 positive lymphocytes in cancer tissue and endometriotic lesions, along with their relationship with VTE. The expression of TF was higher in CCC. The TF expression and the number of CD8 positive cells were higher in cancer tissues with VTE than in those without VTE. The podoplanin or P-selectin expression did not differ among histological types or between cases with and without VTE. Our results demonstrated a high TF expression and intraepithelial CD8 cells in CCC, which were associated with VTE. The results suggest that infiltrating lymphocytes may affect TF expression that, in turn, influences VTE.

A case of facial cellulitis caused by group B streptococcus in an extremely low birthweight infant.

Group B streptococcus (GBS) is an important pathogen that causes neonatal sepsis and meningitis, which have high mortality and morbidity. Cellulitis is a rare presentation of late-onset neonatal GBS infection. We report the case of an extremely low birthweight infant with facial cellulitis caused by late-onset GBS infection. A 590-g male neonate was delivered by Cesarean section at 23 gestational weeks due to intrauterine GBS infection. Although he was effectively treated with 2 weeks of antimicrobial therapy for early-onset GBS sepsis, he subsequently developed facial and submandibular cellulitis caused by GBS at 44 days of age. He was treated with debridement and antibiotic therapy, and after 2 months his facial involvement had improved, but cosmetic issues remained. Neonatal GBS infection requires a prompt sepsis workup followed by the initiation of empiric antibiotic therapy. Additionally, lifesaving surgical debridement is sometimes necessary for cellulitis, even in premature infants.

Intrapartum fetal heart rate patterns and perinatal outcome in chorioamnionitis at or beyond 34 weeks of gestation.

AIM: To investigate intrapartum fetal heart rate (FHR) patterns in women with chorioamnionitis at or beyond 34 weeks of gestation in relation to neonatal outcome and to compare clinical and subclinical chorioamnionitis. METHODS: A retrospective questionnaire survey on deliveries during 2015 was conducted by the Perinatology Committee of the Japan Society of Obstetrics and Gynecology from 2016 to 2018. A total of 498 singleton births complicated by chorioamnionitis delivered at ≥34 weeks of gestation without major congenital malformations were included. The subjects were divided into clinical and subclinical chorioamnionitis groups based on Lencki's criteria. Poor perinatal outcome was defined as death or brain damage. We analyzed clinical features, FHR patterns in the last 2 h before delivery, gestational age, birthweight, Apgar score, umbilical arterial blood gas analysis, and infant's outcome. RESULTS: Incidence of chorioamnionitis at ≥34 weeks of gestation was 0.59% (522/87827). Clinical and subclinical chorioamnionitis comprised 240 and 258 cases, respectively. Abnormal FHR patterns (late deceleration or decreased baseline variability) were significantly associated with poor perinatal outcome. Combined late deceleration and decreased variability showed low positive predictive value (12.8%) and high negative predictive value (99.5%), and was significantly associated with long-term poor outcome in clinical chorioamnionitis only (odds ratio: 29.4, p < 0.01). Poor perinatal outcome showed no significant difference between the clinical and subclinical chorioamnionitis groups. CONCLUSIONS: Combined late deceleration and decreased variability could predict poor perinatal outcome in clinical chorioamnionitis. Poor perinatal outcome occurred in infants born to mothers with clinical and subclinical chorioamnionitis.

Delayed rhythm formation of normal-structured, growth-restricted fetuses using fetal heart rate monitoring patterns.

AIMS: Growth-restricted fetuses have delayed rhythm formation in utero. The awake-sleep cycle of fetal heart rate pattern is thought to represent fetal rhythm. We aimed to study if the emergence of rhythm formation on fetal heart rate pattern delays in fetal growth restriction compared to appropriate-for-date fetuses. METHODS: This was a retrospective cohort study including 75, normal-structured, singleton fetuses. Of them, 21 were fetal growth restriction and the remaining 54 were appropriate-for-date infants. We examined timing of emergence of rhythm formation on fetal heart rate pattern comparing between fetal growth restriction and appropriate-for-date fetuses after adjusting possible confounding factors as outcome measures. RESULTS: Rhythm formation was significantly delayed in fetal growth restriction (<10th percentile) compared to the appropriate-for-date subgroups (10-30, 30-50, 50-70 and 70-90th percentile) by 1-2 weeks. After adjusting confounding factors, growth restriction was the only independent variable to delay fetal rhythm formation. One infant for each group had neurodevelopmental disorder and the incidence did not reach statistically significant. CONCLUSION: Based on fetal heart rate pattern analysis, growth-restricted fetuses show 1-2 weeks delay in rhythm formation compared to appropriate-for-date fetuses.

Impact of tocolysis-intent magnesium sulfate and beta-adrenergic agonists on perinatal brain damage in infants born between 28-36 weeks' gestation.

AIMS: Magnesium sulfate has neuroprotective effects in preterm infants. Whether other antepartum treatments interfere with the neuroprotective actions is not well known. This study aims to explore the impacts of antenatal administration of Magnesium sulfate or beta-2 adrenergic agonists as tocolytic agents on the developing brain in premature infants. METHODS: This is a retrospective cohort study in four tertiary perinatal centers in Japan. We collected data of pregnant women and infants born between 28 and 36 weeks for tocolytic agents, gestational age, sex, antenatal corticosteroid, fetal growth restriction, pathological chorioamnionitis, low umbilical arterial pH values (<7.1), multiple pregnancy, mode of delivery and institutions after excluding clinical chorioamnionitis, non-reassuring fetal status or major anomalies. Tocolytic agents were categorized into four groups: no-tocolysis, magnesium sulfate, beta-2 adrenergic agonists and the combination of them. We conducted multiple comparisons with multivariate analyses using generalized linear regression models to compare the prevalence of a poor perinatal outcome defined as infant's death, brain damage, particularly cerebral palsy and developmental delay. RESULTS: Among 1083 infants, 39% were no-tocolysis, 47% were magnesium sulfate, 41% were beta-2 adrenergic agonists and 27% were combination group, including the duplication. The incidence of poor perinatal outcome was decreased by magnesium sulfate (OR 0.27, 95% CI 0.10-0.72), but not changed significantly by beta-2 adrenergic agonists (OR 1.28, 95% CI 0.63-2.59) or the combination group (OR 2.24, 95% CI 0.67-7.54), compared with the no-tocolysis. CONCLUSION: The combination therapy for tocolysis with beta-2 adrenergic agonists diminished the magnesium sulfate neuroprotective action after adjusting for covariables.

Characteristics and influence of Mycoplasma/Ureaplasma cultures in amniotic fluid on perinatal outcomes.

AIM: To investigate the effects of Mycoplasma/Ureaplasma cultured in amniotic fluid on perinatal characteristics in preterm delivery between 22 and 33 weeks of gestation. METHODS: The study was conducted in a tertiary perinatal center and involved 38 pregnant women who had undergone amniocentesis to evaluate intrauterine infection due to preterm labor or premature rupture of membranes. The subjects were divided into three groups based on the culture results: negative (Negative Group, n = 24), positive for Mycoplasma/Ureaplasma (M/U Group, n = 6), and positive for other pathogens (Other Pathogens Group, n = 8). One-way analysis of variance was used to compare the three groups. RESULTS: The incidence of histological chorioamnionitis and neonatal sepsis was significantly different among the three groups (the Negative Group and the Other Pathogens Group, P < 0.01; the M/U Group and the Other Pathogens Group, P = 0.03). In the M/U Group, no infants had sepsis, severe intraventricular hemorrhage, cystic periventricular leukomalacia, or poor neurological outcomes, but one infant developed bronchopulmonary dysplasia and needed home oxygen treatment. Although one died of gastrorrhexis, the remaining five patients had normal brain magnetic resonance imaging findings and developed normally. CONCLUSION: The presence of Mycoplasma/Ureaplasma isolated from amniotic fluid did not cause neonatal sepsis or poor prognosis. In some infants, there was no histological chorioamnionitis in the placenta. These pathogens thus seem to be less invasive than any other microbes with respect to perinatal outcomes.

Impact of summer heat stress on the thermal environment of bovine female genital tract.

Summer heat stress (HS) is associated with a reduction in conception rate, increase in services per conception, and early embryonic death. However, the impact of summer HS on the thermal environment of different regions of the bovine female genital tract remains unknown. This study aimed to elucidate the effect of summer HS on the thermal environment of different regions of the genital tract in the cow. Three non-pregnant Japanese Black cows were investigated using a specially designed digital thermometer to record the temperatures of the rectum (RT), vagina (VT), cervix (CT), uterine body (UBT), and uterine horns (UHT) on days 0, 1, 2, 3, and 8 of the estrous cycle (day 0 = heat) in February (winter), May (spring), and August (summer). During the experiment, the temperature humidity index (THI) was recorded. THI during summer was higher (P Ë‚ 0.001) than in winter and spring (78.45 ± 0.32 vs. 60.26 ± 1.20 and 68.51 ± 0.80, respectively) and was higher than the alert THI indicating HS (i.e., THI > 73). Consequently, the VT, CT, UBT, and UHT were elevated during summer HS (P < 0.05) in comparison to winter and spring. THI was positively correlated (P < 0.01) with RT, VT, CT, UBT, and UHT. Linear regression revealed that VT, CT, UBT, and UHT increased by 0.05 °C per unit of THI. VT was more highly correlated than RT with THI and with the temperature of other regions of genital tract. HS induced increases in the temperatures of different regions of the female genital tract. The relationship between THI and VT could be incorporated into a mathematical model to predict the thermal load of HS on different regions of the female genital tract.

The Presence of Thyroid Peroxidase Antibody Is Associated with Lower Placental Weight in Maternal Thyroid Dysfunction.

Thyroid dysfunction (TD) is caused by thyroid peroxidase (TPO) antibody, as seen in Hashimoto's disease. TD is a common problem of reproductive age and may impair fetal development. Here, we determined the effect of TPO antibody on perinatal outcomes in Japanese women with TD before conception. A retrospective study involving cases of maternal TD with term singleton birth was conducted. The subjects with TD were divided into two groups according to the presence (n = 22) or absence (n = 20) of TPO antibody. The control groups matched for age, parity, and gestational weeks were selected for TPO antibody-positive (n = 44) and -negative TD subjects (n = 40), respectively. Using the standard curve of Japanese placental weight, the frequency of placental weight less than the 50th percentile (small placenta) was examined. Placental weight was lower among TPO antibody-positive TD subjects, compared with TPO antibody-negative TD subjects (p < 0.01). However, other outcomes were similar between the groups. Importantly, compared with control mothers, placental weight was significantly lower (p < 0.01), birth weight tended to be lower (p = 0.07), and the incidence of gestational diabetes mellitus was higher (p = 0.02) among TPO antibody-positive subjects. There was no significant difference in placental weight between TPO antibody-negative subjects and controls. The frequency of small placenta was significantly higher in TPO antibody-positive subjects (odds ratio: 16.7) even when considering diabetes and pregnancy induced hypertension. Thus, the presence of TPO antibody is associated with lower placental weight among Japanese women having TD.

Manual removal of placenta in women having unpredictable adherent placenta.

AIM: Our aim is to provide expected outcomes for undergoing manual removal of placenta (MROP) following vaginal delivery in women having an unpredictable adherent placenta (AP). METHODS: The data were obtained from four hospitals in Miyazaki Prefecture, Japan. We used propensity score-matched (1:1) analysis to match women who underwent MROP with women who did not undergo MROP (control). Total blood loss and hemorrhagic rate used as a ratio of women who reached a certain amount of blood loss were compared. Subgroup analysis was undertaken and was dependent on the presence of AP. We found the cut-off value of blood loss for detecting AP. RESULTS: Thirty-seven MROP cases were identified. Total blood loss and hemorrhagic rate differed significantly between MROP cases and controls; 95% of controls had blood loss of 1000 mL or less, whereas for the MROP cases, it was 14%. Fourteen MROP cases were diagnosed with AP. The hemorrhagic rate differed significantly between MROP cases with and without AP (n = 19); 79% of MROP cases without AP had blood loss of 2000 mL or less, whereas for the MROP cases with AP, it was 7%. There were seven incidents of hysterectomy and two of arterial embolization in MROP cases with AP. Through receiver operating characteristic curve analysis, 2035 mL of blood loss was determined to be the optimal cut-off value for detecting AP. CONCLUSION: The incidence of unpredictable AP in MROP cases was as high as 38%. The morbidity of MROP cases with unpredictable AP was severe. MROP should be prohibited in the absence of appropriate hemostatic preparations.

Oral diatrizoate acid for meconium-related ileus in extremely preterm infants.

BACKGROUND: Intestinal disorders are common in very low-birthweight infants. The purpose of this study was to evaluate the impact of prophylactic oral Gastrografin® (diatrizoate acid) on meconium-related ileus (MRI) in extremely preterm infants. METHODS: This was a retrospective case-control study of infants born extremely preterm at <28 weeks of gestation and treated with diatrizoate acid (prophylactic group) or not (control group) in the periods 2007-2014 and 2000-2009, respectively. In the 2007-2014 period, 120 infants received prophylactic diatrizoate acid solution. From the 165 infants in the control group, we selected 120 infants matched for gestational age. Cases of death before 72 h of life or congenital abnormalities were excluded. Intestinal disorders, time until full enteral feeding, duration of hospital stay, mortality rate, and neurodevelopmental outcome were compared. RESULTS: MRI occurred in six infants in the control group and in none of the infants in the prophylactic group (P = 0.039). Median time until full enteral feeding was 25 versus 22 days (P < 0.01), hospital stay was 142 versus 126 days (P < 0.01), and mortality rate for infants aged 24-27 weeks was 8.2% versus 0% (P = 0.021), respectively. CONCLUSIONS: Prophylactic oral diatrizoate acid reduced MRI in extremely preterm infants without side-effects and decreased the mortality rate of infants born at 24-27 weeks, and is thus beneficial in extremely preterm infants.

Annual Report of the Perinatology Committee, Japan Society of Obstetrics and Gynecology, 2016: Overall report on a comprehensive retrospective study of obstetric management of preterm labor and preterm premature rupture of the membranes.

We conducted a questionnaire survey on the current obstetric management of preterm labor (PL) and preterm premature rupture of the membranes (pPROM). The questionnaire covered approximately a third of all preterm deliveries and nearly half of the preterm deliveries before 32 gestational weeks. The diagnostic criterion for PL was either painful uterine contractions or cervical dilatation. Tocolytic agents were primarily used as long-term maintenance therapy. Intrauterine infection was clinically diagnosed at most responding institutions. Amniocentesis was performed for PL or pPROM at only a small number (10%) of institutions. Prenatal steroids were administered for PL or pPROM, if indicated, at approximately 40-60% of responding institutions. Prophylactic antibiotics to maintain pregnancy were administered for pPROM at approximately 90% and for PL at approximately 20% of institutions. Maintenance therapy with a tocolytic agent was used for pPROM at approximately 90% of institutions.

Prenatal diagnosis of premature chromatid separation/mosaic variegated aneuploidy (PCS/MVA) syndrome.

Premature chromatid separation/mosaic variegated aneuploidy (PCS/MVA) syndrome is a rare genetic disorder. In this case report, we describe the prenatal diagnosis of PCS/MVA syndrome in a 24-year-old, gravida 1, para 1, woman who was referred to us in her second trimester due to fetal growth restriction and extreme microcephaly (-5.0 standard deviations). Amniocentesis and chromosomal analysis confirmed PCS in 80% of cultured fetal cells. PCS findings were positive in 9% of paternal cells and 11% of maternal cells, indicative that both were PCS carriers. Genetic analysis confirmed that the fetus carried a combined heterozygote of maternal G > A point mutation of the promoter area of the BUB1B gene and a paternal Alu sequence insertion between intron 8 and exon 9 of the BUB1B gene. As PCS/MVA syndrome is associated with the development of various malignancies in early life, prenatal diagnosis is important for effective planning of post-natal care.

Maternal immunoglobulin G avidity as a diagnostic tool to identify pregnant women at risk of congenital cytomegalovirus infection.

BACKGROUND: The immunoglobulin (Ig) G avidity index (AI) is useful to detect primary cytomegalovirus (CMV) infection. However, because IgG matures with time, this index is not useful to detect a primary infection, unless measured at an appropriate time. OBJECTIVES: We aimed to clarify the difference between using IgG AI and IgM positivity according to the stage of pregnancy to identify congenital CMV infection risk. STUDY DESIGN: We collected the serum samples from 1115 pregnant women who underwent maternal screening for primary infection (n = 956) and were referred to our hospital because of CMV IgM positivity (n = 155) or had abnormal fetal ultrasonography findings (n = 4). The same sera samples were used to measure CMV IgM, IgG, and IgG AI. An IgG AI of <35% was defined as low. Neonatal urine collected within 5 days after birth was examined by polymerase chain reaction to confirm congenital infection. RESULTS: Fourteen mothers gave birth to infected neonates. The sensitivity, specificity, and negative predictive values of the low IgG AI group with IgM-positive samples to discriminate between women with congenital infection at ≤14 weeks of gestation were 83.3, 83.8, and 99.1, respectively, which were higher than those of other subjects. Uni- and multivariate analyses revealed that IgM positivity and low IgG AI were independent variables associated with congenital infection at any stage of pregnancy, except low IgG AI at ≥15 weeks of gestation. CONCLUSION: Low IgG AI with IgM positivity at ≤14 weeks of gestation was a good indicator of congenital infection, which should prove useful in obstetric practice.

Antithrombin improves the maternal and neonatal outcomes but not the angiogenic factors in extremely growth-restricted fetuses at <28 weeks of gestation.

AIMS: Severe preterm fetal growth restriction (FGR) remote from term is problematic. We aimed to investigate the effect of maternally-administered antithrombin on maternal and neonatal outcomes. A prospective, one-arm, pilot study was performed in 14 women with severe FGR (≤5th centile) at <28 weeks of gestation, without hypertensive disorders. Maternal plasma concentrations of soluble Feline McDonough Sarcoma (FMS)-like trypsin kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured and categorized into three groups: group 1; low sFlt-1 and high PlGF, group 2; moderate sFlt-1 and low PlGF, and group 3; high sFlt-1 and low PlGF. Antithrombin was administered for 3 days. The incidence of perinatal mortality, infant morbidity, and the period of pregnancy prolongation were compared. RESULTS: In group 1 (n=4), their pregnancies were extended for longer periods and the maternal and infant outcomes were good. The prolongation periods were shorter in groups 2 (n=3) and 3 (n=7), which resulted in poor maternal [severe preeclampsia or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome] and infant outcomes. CONCLUSIONS: The evaluation of the maternal sFlt-1 and PlGF at 21-27 weeks of gestation is useful in the managements of severe FGR. Antithrombin treatment could prolong the pregnancies with low sFlt-1 and high PlGF without negatively affecting maternal or fetal health.