Caesarean Section of Multifetal Pregnancy.

Planned caesarean delivery (CD) did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity in twin pregnancy between 32 0/7 and 38 6/7 weeks of gestation, with the first twin in the vertex presentation. As prevalence rises for the second twin, emergency CD is necessary for delivery of the second twin after vaginal delivery of the first twin. Waiting after 38 weeks' gestation essentially requires close fetal and maternal surveillance to identify if those pregnancies may benefit to extend a gestational period. It is important to construct a system in which an emergency CD can be performed anytime. The caesarean section does not change in even multifetal pregnancy. Each step after laparotomy has few tips: (1) because the uterus strongly leans to the right, image the uterine rotation. To avoid thick vessels on the uterine lateral wall, perform long U -shaped incision using a scissor. 2) Ensure not to rupture the membrane of the second twin before delivery of the first twin. (3) Check the presentation of the second twin before rupture of that fetus's membrane. The second twin tends to change the presentation. If the upper uterine segment will clamp down and entrap the second twin, a vertical uterine incision is performed without hesitation. Women with multifetal pregnancy are at increased risk of postpartum hemorrhage (PPH). Mainly PPH is caused by uterine atony. Oxytocin should be prepared before starting the CD. All bleeding may not be recognized in the operation field. Do not lose the timing of blood transfusion.

Synergistic effects of tumor necrosis factor-α and insulin-like growth factor-I on survival of human trophoblast-derived BeWo cell line.

OBJECTIVE: Trophoblast survival is regulated by cytokines and growth factors. While the pharmacological levels (10-100 ng/mL) of tumor necrosis factor (TNF)- α affect trophoblasts survival in vitro, the effects of the physiological levels (1-10 pg/mL) of TNF-α remain unknown. We investigated the effects of the physiological levels of TNF-α on proliferation and apoptosis of human trophoblast cells by using BeWo cells. Insulin-like growth factor (IGF)-I is also a potent regulator of trophoblast survival and has been known to exert synergistic effects with other hormones. The interaction of IGF-I and TNF-α on BeWo cells survival was also examined. METHODS: After incubating BeWo under the presence of TNF-α (10-105 pg/mL) and IGF-I (102 ng/mL), we assessed cell number by WST-1 assay and cell proliferation by BrdU uptake assay and immunocytochemistry with anti-Ki67 antibody. Apoptosis was evaluated by TUNEL assay and caspase-3, 8 activity assays. RESULTS: Under the presence of IGF-I, cell number, BrdU uptake, and Ki-67 expression of BeWo were dose-dependently enhanced by low TNF-α (10-102 pg/mL), while no such effects were detected without IGF-I. Higher levels of TNF-α (104-105 pg/mL) showed inhibiting effects on cell number and cell proliferation. The number of TUNEL positive cells were decreased and caspase activities were suppressed by lower levels (10-102 pg/mL) of TNF-α and IGF-I independently. Higher levels of TNF-α (104-105 pg/mL) showed promoting effects on apoptosis irrespective of IGF-I. CONCLUSION: The physiological levels of TNF-α and IGF-I had synergetic effects on enhancing cell proliferation and also independently inhibited apoptosis of Bewo cells.

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.

Non-essential and branched-chain amino acids differentially regulate insulin-like growth factor binding protein-1 production and phosphorylation in HepG2 cells.

Deprivation of branched-chain amino acids (BCAAs) induces insulin-like growth factor binding protein-1 (IGFBP-1) production in HepG2 cells, while the role of non-essential amino acids (NEAAs) remains unknown. We investigated changes in IGFBP-1 production and phosphorylation induced by NEAAs and also examined its significance on IGF-I activity in HepG2 cells. We demonstrated that decreased BCAAs and increased NEAAs stimulated phosphorylated IGFBP-1 secretion. We also revealed that decreased BCAA-to-NEAA ratios enhanced phosphorylated IGFBP-1 secretion, while changes in the total amount of amino acids (AAs) had no effect. Phosphorylation of IGF-I receptor ß-subunits mediated by exogenous IGF-I in HepG2 cells was inhibited by decreased BCAAs, increased NEAAs, and decreased BCAA-to-NEAA ratios, while the total amount of AAs had no effect. In addition to BCAAs, NEAAs are also responsible for the regulation of IGFBP-1 secretion and phosphorylation in HepG2 cells. Moreover, the balance of BCAAs and NEAAs regulated IGFBP-1 secretion and phosphorylation.

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.

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.

Intrapartum group B Streptococcus screening using real-time polymerase chain reaction in Japanese population.

OBJECTIVE: The objective of this study was to analyze the diagnostic accuracy of a commercial real-time polymerase chain reaction (PCR) assay for group B streptococcus (GBS) colonization status and to compare results of the intrapartum PCR with the antepartum conventional GBS culture in Japanese pregnant women. METHODS: This prospective observational study enrolled Japanese pregnant women at 35-37 weeks' gestation. Paired recto-vaginal swabs were obtained for PCR and conventional culture, both at 35-37 weeks' gestation and at admission for delivery. Performance of PCR was analyzed by comparing with the culture results. Furthermore, using the intrapartum culture results as the gold standard, the test of both the antepartum culture and the intrapartum PCR were characterized. RESULTS: We prospectively enrolled 79 pregnant women at 35-37 weeks' gestation, and the intrapartum results were obtained from 73 of those women. The sensitivity of PCR was 86.2%, and concordance rate with the conventional culture was 96.7% overall. Compared with the intrapartum culture, the sensitivity and the specificity of the intrapartum PCR were 83.3% and 98.4%, respectively, while the sensitivity and the specificity of the antepartum culture were 100.0% and 95.1%. CONCLUSIONS: The intrapartum real-time PCR assay for GBS screening has the accuracy similar to the antepartum conventional culture method.

Prenatal diagnosis of Klippel-Trenaunay-Weber syndrome with Kasabach-Merritt syndrome in utero.

Klippel-Trenaunay-Weber syndrome (KTWS), a congenital disease characterized by cutaneous hemangiomas, soft tissue and bone hypertrophy, and occasionally arteriovenous malformations, is extremely rare and its natural history in utero is unknown. We present a prenatally diagnosed case of KTWS complicated with Kasabach-Merritt syndrome in utero and fetal hydrops from acute anemia. The fetus was diagnosed with KTWS at 24 weeks of gestation based on the ultrasound findings of hemangiomas and unilateral hypertrophy of the lower extremity. Acute enlargement of the hemangiomas and the appearance of new retroperitoneal hemangiomas were detected at 27 weeks, along with skin edema and cardiomegaly. Doppler examination showed elevated peak systolic velocity in the middle cerebral artery, indicating acute fetal anemia. We believe the fetus's condition was complicated with Kasabach-Merritt syndrome in utero, which caused acute hemolytic anemia leading to high-output cardiac failure and fetal hydrops.

Antepartum reversible cerebral vasoconstriction syndrome with pre-eclampsia and reversible posterior leukoencephalopathy.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headache and diffuse segmental constriction of the cerebral arteries that resolves spontaneously within a few months. Pregnancy is one of the precipitating factors of RCVS and most of the reported cases occurred in the post-partum period. We report a case of RCVS that occurred in a pregnant women with pre-eclampsia during her antepartum period. A 34-year-old woman in full-term pregnancy presented with a severe and acute headache. Magnetic resonance angiography (MRA) showed multiple segmental constrictions of the cerebral arteries. Magnetic resonance imaging revealed a high-intensity lesion in the left occipital lobe, consistent with reversible posterior leukoencephalopathy syndrome, on fluid attenuated inversion recovery sequences. The case was also complicated by severe pre-eclampsia and the patient underwent emergency cesarean section. Although her symptoms resolved rapidly, MRA revealed new lesions of arterial constriction 4 days after onset. The vasoconstriction completely resolved on MRA after 10 days and the patient was discharged without neurological sequelae.

Prenatal diagnosis of umbilical artery thrombosis.

Umbilical artery thrombosis (UAT) is rare and few prenatally diagnosed cases have been reported. We describe 2 cases of fetal growth restriction prenatally diagnosed as UAT by ultrasound examination. In each case the cross section of the umbilical cord showed one normal artery and a small echogenic area which was suspected as an occluded thrombotic artery and they were surrounded by a highly curving 'C-shaped' vein. UAT was confirmed by histological examinations after deliveries in both cases. The characteristic ultrasound finding of the umbilical vessel, which is the so-called 'orange grabbed sign', enables the prenatal diagnosis of UAT and it is valuable with respect to perinatal fetal management because UAT is associated with increased perinatal morbidity and mortality.