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.

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.

Clinical chorioamnionitis criteria are not sufficient for predicting intra-amniotic infection.

AIM: To evaluate the diagnostic performance of three conventional clinical chorioamnionitis criteria; including Gibbs, Lencki, and suspected triple I; for the prediction of intra-amniotic infection. METHODS: A retrospective cohort study was conducted using data from three perinatal centers from 2014 to 2018. Patients with preterm labor or premature prelabor rupture of membranes between 22 and 33 weeks of gestation and those who underwent transabdominal amniocentesis to detect intra-amniotic infection were selected. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms, including genital mycoplasmas, plus low glucose level or leukocytosis in amniotic fluid. Sensitivity, specificity, and positive and negative likelihood ratios were calculated to determine the diagnostic performance of each criterion in predicting intra-amniotic infection. RESULTS: Of 99 pregnant women who met the study inclusion criteria, 13 (13.1%) had intra-amniotic infection confirmed by amniocentesis and 86 (86.9%) had no intra-amniotic infection. Maternal characteristics were not significantly different between groups, except for the higher incidence of preterm, prelabor rupture of membranes in pregnant women with intra-amniotic infection (53.8 versus 14%, p < .01). The incidences of clinical chorioamnionitis in the non-IAI and IAI groups were 1 of 86 (1.2%), 1 of 86 (1.2%), 0 of 86 (0%) and 2 of 13 (15.4%), 2 of 13 (15.4%), 2 of 13 (15.4%) according to Gibbs, Lenki, and suspected triple I criteria, respectively. The specificity of the three criteria ranged from 98.8 to 100%; however, the sensitivity was low (15.4%). The positive likelihood ratio was significant for three criteria from 13.2 (95% confidence interval [CI], 1.29-135) to infinite. However, the negative likelihood ratio was not low enough and not significant for the three criteria (0.85 [95% CI, 0.67-1.07] to 0.86 [95% CI, 0.68-1.08]). CONCLUSION: The conventional clinical chorioamnionitis criteria are not sensitive for the prediction of intra-amniotic infection in pregnant women with preterm labor and/or preterm prelabor rupture of membranes.

Multiple cardiac rhabdomyomas not associated with tuberous sclerosis in a dizygotic twins: a case report.

BACKGROUND: Rhabdomyomas comprise the majority of cardiac tumors in fetuses and are found in association with tuberous sclerosis complex. More than 90% of fetuses and neonates with multiple cardiac rhabdomyomas have signs of tuberous sclerosis complex. However, solitary cardiac rhabdomyoma cases are largely unrelated to tuberous sclerosis complex. Here, we report a case involving multiple cardiac rhabdomyomas not associated with tuberous sclerosis complex in a dizygotic twin. CASE PRESENTATION: A 36-year-old Japanese woman was diagnosed with a dizygotic twin pregnancy in the first trimester. Consistent with dizygosity, the fetal sex was discordant (male and female). At 27 weeks of gestation, hydrops and multiple echogenic cardiac masses were noted in the male baby, with the largest mass measuring 34 × 30 mm. The female fetus appeared normal. The cardiac masses enlarged gradually with the progression of the hydrops. At 32 weeks of gestation, intrauterine death of the male fetus was confirmed. The next day, autopsy of the male fetus was performed after cesarean section. Three well-demarcated white-tan-colored nodules were formed in the ventricular walls and interventricular septum, with the largest nodule (40 × 30 mm) in the left ventricular wall. Histologically, these lesions were diagnosed as rhabdomyomas. CONCLUSIONS: We encountered a case involving multiple cardiac rhabdomyomas arising in one of dizygotic twin fetuses. Unlike most reported cases of multiple cardiac rhabdomyomas, this case was not accompanied by tuberous sclerosis complex. To the best of our knowledge, this is the first case report of multiple cardiac rhabdomyomas that developed in only one of dizygotic twins in the English literature.

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.

Plasmapheresis for the Treatment of Anti-M Alloimmunization in Pregnancy.

Intrauterine transfusion is the standard antenatal treatment for a fetus with severe anemia. Plasmapheresis is an alternative treatment for cases with a history of severe hemolytic disease of the fetus and newborns at less than 20 weeks of gestation. There is only one previous report of plasmapheresis for the anti-M alloimmunization in pregnancy, and we report here on the successful treatment of plasmapheresis for anti-M alloimmunization. A woman with a history of intrauterine fetal death at 24 weeks of gestation due to severe fetal anemia caused by anti-M alloimmunization received plasmapheresis once or twice a week from 14 weeks of gestation onward. An intrauterine blood transfusion was conducted at 28 weeks, and a cesarean section was performed at 31 weeks. The infant had anemia and jaundice but was discharged at day 46. Plasmapheresis may delay the development of fetal anemia and reduce the risk of early and repeat intrauterine transfusion in cases of anti-M alloimmunization in pregnancy.

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.

Leaner Women with Impaired Insulin Secretion Accounts for about 40% of Gestational Diabetes Mellitus in Japan.

AIM: To identify the involvement of leanness and impaired insulin secretion with Japanese gestational diabetes mellitus (GDM). METHOD: A cross-sectional study was conducted comprising 219 at-risk pregnant women who underwent a 75g glucose tolerance test at a single institute in Tokyo, Japan. We identified GDM and normal glucose tolerance (NGT). The cut-off value of the homeostasis model assessment insulin resistance (HOMA-IR) for detecting GDM was determined. The GDM group was divided into subgroups according to insulin resistance based on the cut-off value of HOMA-IR. We compared the prepregnancy body mass index (BMI) and homeostasis model assessment of ß-cell function (HOMA-ß) between the group comprising low insulin resistance (LIR) and the group comprising high insulin resistance (HIR). RESULTS: Seventy GDM cases and 149 NGT cases were identified. By using receiver operating characteristic curve analysis, the HOMA-IR cut-off value was determined to be 1.41. Twenty-five GDM cases (36%) were classified as LIR and forty-five GDM cases (64%) were classified as HIR. The background including indications for having 75gOGTT and the gestational age having 75gOGTT did not differ between groups. The BMI of the LIR group was significantly lower than that of the HIR group (20.9±2.8 vs. 24.4 ± 5.5, p<0.01), and the HOMA-ß of the LIR group was significantly lower than that of the HIR group (95.5±30.3 vs. 146.0±70.1, p<0.01). A positive linear correlation was found between BMI and HOMA-ß in cases of GDM (r=0.27, p=0.02). CONCLUSION: Leanness with impaired insulin secretion is deeply involved in Japanese gestational diabetes mellitus.

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.

A case of mirror syndrome caused by hydrops fetalis after fetoscopic laser photocoagulation.

Fetoscopic laser photocoagulation (FLP) of placental anastomoses is a well-established procedure for twin-to-twin transfusion syndrome that improves fetal outcome with rare maternal complications. However, fetal hydrops can develop even after FLP, and mirror syndrome can occur, indicating that both the fetal and maternal courses should be monitored after FLP.

Influence of maternal obesity on fetal growth at different periods of pregnancies with normal glucose tolerance.

AIM: We aimed to examine the influence of maternal obesity on fetal growth in utero at different periods of pregnancies with normal glucose tolerance. METHODS: A retrospective cohort study on 356 pregnant women with normal glucose tolerance was conducted. The women were categorized by pre-pregnancy body mass index (BMI) as obese (OB; BMI ≥ 25.0 kg/m2 ) or non-obese (n-OB). Z-scores of the fetal abdominal circumference (AC) and the rate of fetal macrosomia (AC ≥ 90th percentile) at 19, 30, and 36 gestational weeks (GW) were compared between the two groups. Maternal demographics (age, parity, height, pre-pregnancy BMI, history of prior large-for-gestational-age delivery) were compared between the pregnancies with and without fetal macrosomia at each gestational age. Multiple logistic regression analysis was performed to determine the independent risk factors for fetal macrosomia. RESULTS: Birthweights of the neonates were significantly higher in the OB group. Z-scores of the fetal AC were significantly higher in the OB group at 30 and 36 GW, while no significant difference was found at 19 GW. The rates of fetal macrosomia in the OB group were also higher at 30 and 36 GW, while maternal obesity was not associated with fetal macrosomia at 19 GW. Pre-pregnancy BMI was detected as the independent predictor of fetal macrosomia at 30 GW (odds ratio, 1.19 [95% CI]) and 36 GW (odds ratio, 1.13 [95% CI]). CONCLUSION: Maternal pre-pregnancy obesity has a promoting effect on fetal growth from the third trimester through birth.

Increased maternal insulin resistance promotes placental growth and decreases placental efficiency in pregnancies with obesity and gestational diabetes mellitus.

AIM: Homeostasis model assessment for insulin resistance (HOMA-IR) was measured during pregnancy to analyze placental weight and efficiency in relation to maternal insulin resistance. METHODS: A retrospective study of 510 pregnant women (130 with gestational diabetes mellitus [GDM], 380 with normal glucose tolerance) was conducted. We reviewed the patients' demographic data (age, parity, pre-pregnancy body mass index [BMI]) and perinatal outcomes (birth weight, placental weight, BMI at delivery, maternal weight gain, HOMA-IR). The birth weight to placental weight (B/P) ratio was calculated for placental efficiency. The subjects were categorized by BMI at delivery, and maternal, neonatal and placental characteristics were compared between the groups to investigate the determinants of placental weight and B/P ratios. RESULTS: Obesity was significantly associated with heavier placental weight and lower B/P ratios. The presence of GDM did not affect placental weight, whereas the B/P ratios in women with GDM were significantly lower than in women with normal glucose tolerance. HOMA-IR was positively correlated with placental weight (ρ = 0.217, P < 0.001) and negatively with B/P ratio (ρ = -0.181, P < 0.001). CONCLUSIONS: Increased maternal insulin resistance promoted placental growth and inhibited placental efficiency. Maternal insulin resistance may be one of the pathophysiological conditions responsible for altered placental size and function in pregnancies with obesity and GDM.

Women with Subclinical Hypothyroidism Are at Low Risk of Poor Pregnancy Outcome in Japan.

Maternal subclinical hypothyroidism may be associated with adverse pregnancy outcomes, although not consistently across regions. Here, we sought to determine the effect of elevated thyroid-stimulating hormone (TSH) on pregnancy outcomes in Japanese women without known medical complications. TSH was determined by dried blood spots at 8-20 weeks of gestation, and 3.0-10.0 µU/mL of TSH was considered as elevated TSH (eTSH). A retrospective study involving 167 cases of eTSH was conducted. Five hundred and seventy eight of controls with normal TSH and without thyroid antibodies were selected. We compared a composite adverse maternal outcome comprised of spontaneous abortion, premature delivery, gestational diabetes mellitus (GDM), placental abruption, and pregnancy-induced hypertension, as well as composite adverse neonatal outcome including stillbirths, heavy for date, light for date, and a low Apgar score (< 7) at 5 minutes between two groups. The incidence of GDM was significantly higher in eTSH (p < 0.01); however, composite adverse maternal and neonatal outcome did not differ between groups (p = 0.19 and p = 0.50, respectively). Although 27 out of 167 cases in eTSH have antibodies, composite adverse outcome did not differ between eTSH with antibodies and controls (p = 0.64 and p = 0.50, respectively). Additionally, composite adverse maternal and neonatal outcome did not differ between the group larger than the median of TSH in eTSH (n = 81) and controls (p = 0.43 and p = 0.98, respectively). Thus, elevated TSH is not associated with overall adverse pregnancy outcomes in women without known medical complications.

Maternal Morbidity in Women with Placenta Previa Managed with Prediction of Morbidly Adherent Placenta by Ultrasonography.

Objective. To determine maternal morbidity in women with placenta previa managed with prediction of morbidly adherent placenta (MAP) by ultrasonography. Methods. A retrospective cohort study was undertaken comprising forty-one women who had placenta previa with or without risk factors for MAP. Women who had all three findings (bladder line interruption, placental lacunae, and absence of the retroplacental clear zone) were regarded as high suspicion for MAP and underwent cesarean section followed by hysterectomy. We attempted placental removal for women having two findings or less. Results. Among 28 women with risk, nine with high suspicion underwent hysterectomy and were diagnosed with MAP. Three of 19 women with two findings or less eventually underwent hysterectomy and were diagnosed with MAP. The sensitivity and positive predictive value for the detection of MAP were 64% and 100%. The pathological severity of MAP was significantly correlated with the cumulative number of findings. There were no cases of MAP among 13 women without risk. There was no difference of blood loss between women with high suspicion and those without risk (2186 ± 1438 ml versus 1656 ± 848 ml, resp.; p = 0.34). Conclusion. Management with prediction of MAP by ultrasonography is useful for obtaining permissible morbidity.

Prediction of spontaneous preterm delivery in asymptomatic twin pregnancies using cervical length and granulocyte elastase.

OBJECTIVE: The purpose of this study was to evaluate sonographic cervical length (CL) and granulocyte elastase (GE) in cervical secretion as predictors of preterm delivery in asymptomatic twin pregnancies. MATERIALS AND METHODS: This study prospectively enrolled asymptomatic twin pregnancies with CL < 25 mm at 22-29 weeks of gestation. All women were hospitalized for preterm labor, and the cervical secretion was obtained for GE testing on admission. The results of CL measurement and GE testing were reviewed, and the relationship between each variables and preterm delivery prior to 34 weeks of gestation was assessed. RESULTS: Overall, we included 54 women with twin pregnancies, of which 12 (22.2%) had preterm deliveries prior to 34 weeks of gestation. A CL of <20 mm was significantly associated with preterm delivery with an odds ratio of 4.88 (95% confidence limit, 1.15-20.73). GE was not an independent predictive marker for preterm delivery. We also performed a subgroup analysis on the combination of CL and GE for predicting preterm delivery. Among the patients with GE(-), CL < 20 mm markedly increased the risk of preterm delivery with an odds ratio of 10.89 (95% confidence limit, 1.40-77.10). CL was not associated with preterm delivery among those with GE(+). Those with negative GE and shorter CL demonstrated the shortest duration of pregnancy after admission. CONCLUSION: The combination of sonographic CL and GE of cervical secretion is useful to predict the risk of preterm delivery in asymptomatic twin pregnancies.

Circadian Variation in the Onset of Placental Abruption.

Objective. To determine circadian variation in the onset of placental abruption. Methods. A retrospective study involving 115 placental abruptions, divided into four subgroups based on initial symptoms comprising abdominal pain, vaginal bleeding, both abdominal pain and bleeding, or other symptoms. The time of the initial symptom was considered the disease onset. We analyzed the frequency of disease onset and adverse perinatal outcome including perinatal death relative to the daily four 6-hour intervals. Results. Abdominal pain displayed significant circadian variation regarding the period of onset with higher levels from 0:00 AM to 6:00 AM (65%) compared with 0:00 PM to 6:00 PM (24%, p < 0.01). Vaginal bleeding did not display significant circadian variation (p = 0.45). Adverse perinatal outcome showed significant circadian variation with a higher occurrence of perinatal death from 0:00 AM to 6:00 AM (35%) compared with 0:00 PM to 6:00 PM (0%, p < 0.01). After adjustment using variables of abdominal pain and time period, both variables significantly affected perinatal death (odds ratio: 13.0 and 2.2, resp.). The risk of adverse perinatal outcome increased significantly when abdominal pain occurred, except for the period 0:00 PM to 6:00 PM (OR, 9.5). Conclusion. Placental abruption beginning with abdominal pain has circadian variation.

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.

Branched-chain amino acids regulate insulin-like growth factor-binding protein 1 (IGFBP1) production by decidua and influence trophoblast migration through IGFBP1.

STUDY QUESTION: Do branched-chain amino acids (BCAAs) influence the migration of human extravillous trophoblast (EVT) cells through changes in insulin-like growth factor-binding protein 1 (IGFBP1) production in decidual cells? STUDY FINDING: Decidua-derived IGFBP1 had a stimulating effect on migration of EVT. WHAT IS KNOWN ALREADY: IGFBP1 is abundantly secreted from human decidual cells and influences trophoblast migration in human placenta of early pregnancy. In hepatic cells, the expression of IGFBP1 is influenced by nutritional status and BCAAs regulate IGFBP1 production. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: This is a laboratory-based study using human decidual cells and trophoblast cells isolated from placental tissue of early pregnancy (n = 50) and grown as primary cultures. Production of IGFBP1 from decidual cells was examined by enzyme-linked immunosorbent assay and immunoblotting after incubation with or without BCAAs. EVT migration was evaluated using the media conditioned by decidual cells. The effect of conditioned media on phosphorylation of focal adhesion kinase (FAK) in EVT was also analyzed by immunoblotting. The same experiments were repeated in the presence of RGD peptide, which inhibits IGFBP1 binding to α5ß1 integrin. An EVT migration assay and the immunoblotting of phosphorylated FAK were also conducted with exogenous IGFBP1. The effect of the conditioned media on cytotrophoblast cell number was also assessed using WST-1 in a cell proliferation assay. MAIN RESULTS AND THE ROLE OF CHANCE: Deprivation of BCAAs on decidual cells significantly suppressed IGFBP1 secretion (P < 0.05, versus BCAA+). Exogenous IGFBP1-stimulated EVT migration (P < 0.05) and phosphorylation of FAK (P < 0.05), and the RGD peptide inhibited these effects. EVT migration and phosphorylation of FAK were stimulated by the conditioned media, presumably by IGFBP1 in the media. RGD treatment abrogated the stimulating effects of conditioned media. The conditioned media deprived of BCAAs had suppressive effects on EVT migration (P < 0.05, versus BCAA+) and phosphorylation of FAK (P < 0.05, versus BCAA+). The conditioned media did not affect number of cytotrophoblast cells. LIMITATIONS, REASONS FOR CAUTION: The conclusions are based on in vitro experiments with human decidual cells and trophoblast cells isolated from placental tissue of early pregnancy, and we were unable to ascertain whether these mechanisms actually operate in vivo. We investigated the effect of decidua-derived IGFBP1 on EVT migration, however, we cannot completely rule out the possibility that endogenous IGF could also influence cell migration. WIDER IMPLICATIONS OF FINDINGS: Interruption of the BCAA supply to uterine decidual cells in early pregnancy may suppress EVT migration through reduced IGFBP1 secretion, which may be one of the pathophysiological conditions responsible for pre-eclampsia. LARGE SCALE DATA: None. STUDY FUNDING/ AND COMPETING INTERESTS: All funds were obtained through Kyorin University School of Medicine. The authors have no conflict of interest to declare.

Preterm labor and neonatal sepsis caused by intrauterine Helicobacter cinaedi infection.

Helicobacter cinaedi is a rare pathogen but known to cause bacteremia, cellulitis and enterocolitis. Recently, cases of involving various organs are increasingly reported such as endocarditis, meningitis, and kidney cyst infection. We report a case of intrauterine H. cinaedi infection leading preterm birth and neonatal sepsis. A 29-year-old pregnant women who was no underlying disease hospitalized due to threatened preterm labor at 22 weeks of gestation. Clinical findings showed uterine tenderness, fever, leukocytosis and elevated C-reactive protein. H. cinaedi was isolated from amniotic fluid obtained by transabdominal amniocentesis. We diagnosed as intrauterine H. cinaedi infection and administered intravenous ampicillin followed by oxytocin to terminate pregnancy. A live 446 g male infant was delivered. The patient was no signs of infection throughout postpartum course and discharged on post-delivery day 5. The neonate was admitted in neonatal intensive care unit and administered ampicillin and amikacin. H. cinaedi was isolated from umbilical cord blood culture. He has no signs of infection on day 5 but died from uncontrollable hyperglycemia and ketoacidosis on 15 days of age. H. cinaedi can cause intrauterine infection during pregnancy and lead preterm labor and neonatal sepsis.