Antenatal Administration of Betamethasone Contributes to Intimal Thickening of the Rat Ductus Arteriosus.

BACKGROUND: Antenatal betamethasone (BMZ) is a standard therapy for reducing respiratory distress syndrome in preterm infants. Recently, some reports have indicated that BMZ promotes ductus arteriosus (DA) closure. DA closure requires morphological remodeling; that is, intimal thickening (IT) formation; however, the role of BMZ in IT formation has not yet been reported. Methods and Results: First, DNA microarray analysis using smooth muscle cells (SMCs) of rat preterm DA on gestational day 20 (pDASMCs) stimulated with BMZ was performed. Among 58,717 probe sets, ADP-ribosyltransferase 3 (Art3) was markedly increased by BMZ stimulation. Quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed the BMZ-induced increase of Art3 in pDASMCs, but not in aortic SMCs. Immunocytochemistry showed that BMZ stimulation increased lamellipodia formation. BMZ significantly increased total paxillin protein expression and the ratio of phosphorylated to total paxillin. A scratch assay demonstrated that BMZ stimulation promoted pDASMC migration, which was attenuated byArt3-targeted siRNAs transfection. pDASMC proliferation was not promoted by BMZ, which was analyzed by a 5'-bromo-2'-deoxyuridine (BrdU) assay. Whether BMZ increased IT formation in vivo was examined. BMZ or saline was administered intravenously to maternal rats on gestational days 18 and 19, and DA tissues were obtained on gestational day 20. The ratio of IT to tunica media was significantly higher in the BMZ-treated group. CONCLUSIONS: These data suggest that antenatal BMZ administration promotes DA IT through Art3-mediated DASMC migration.

Glutamate Promotes Contraction of the Rat Ductus Arteriosus.

BACKGROUND: Extremely preterm infants frequently have patent ductus arteriosus (PDA). Recent recommendations include immediately beginning amino acid supplementation in extremely preterm infants. However, the effect of amino acids on closure of the ductus arteriosus (DA) remains unknown.Methods and Results:Aminogram results in human neonates at day 2 revealed that the plasma glutamate concentration was significantly lower in extremely preterm infants (<28 weeks' gestation) with PDA than in those without PDA and relatively mature preterm infants (28-29 weeks gestation). To investigate the effect of glutamate on DA closure, glutamate receptor expression in fetal rats was examined and it was found that the glutamate inotropic receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type subunit 1 (GluR1), mRNA was highly expressed in the DA compared to the aorta on gestational day 19 (preterm) and gestational day 21 (term). GluR1 proteins were co-localized with tyrosine hydroxylase-positive autonomic nerve terminals in the rat and human DA. Intraperitoneal administration of glutamate increased noradrenaline production in the rat DA. A whole-body freezing method demonstrated that glutamate administration induced DA contraction in both preterm (gestational day 20) and term rat fetuses. Glutamate-induced DA contraction was attenuated by the calcium-sensitive GluR receptor antagonist, NASPM, or the adrenergic receptor α1 blocker, prazosin. CONCLUSIONS: These data suggest that glutamate induces DA contraction through GluR-mediated noradrenaline production. Supplementation of glutamate might help to prevent PDA in extremely preterm infants. (Circ J 2016; 80: 2388-2396).

Relationship Between Short Umbilical Cord Length and Adverse Pregnancy Outcomes.

To investigate how umbilical cord length relates to pregnancy outcomes, we retrospectively analyzed data from 89,042 deliveries recorded in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System. We included term deliveries in which vaginal birth was attempted. Umbilical cord length was categorized into four groups: less than the first percentile, from the first percentile to less than the 10th percentile, from the 10th percentile to less than 25th percentile, and from the 25th percentile to less than the 75th percentile, which constituted the control group. Cord lengths of 33, 43, 48, 63 cm corresponded to the first, 10th, 25th, and 75th percentile values of the cord length distribution, respectively. Statistically significant differences were observed in the rate of unplanned cesarean delivery for all three short cord groups compared to control. There was a higher odds ratio for unplanned cesarean delivery as the umbilical cord became shorter.

Immune response to Haemophilus influenzae type b conjugate vaccine in preterm infants.

BACKGROUND: Haemophilus influenzae type b (Hib) vaccine became available for use in Japan in December 2008. The aim of the present study was to evaluate the immunogenicity of Hib vaccine in Japanese preterm infants. METHODS: Serum samples were obtained from 54 preterm infants before the first vaccination and 1 month after the third. Anti-polyribosylribitol phosphate (PRP) antibodies were measured using an enzyme-linked immunosorbent assay method. Antibody positivity was defined as levels >1 µg/mL. RESULTS: Of the 54 preterm infants, 46 (85.2%) achieved antibody levels >1 µg/mL. This compares with the 92.4% reported in full-term infants. The antibody seroconversion rate of infants starting vaccination at 2 months of age was close to being significantly lower than when vaccination was started at 3 months of age (P= 0.060). In addition, the percentage of infants achieving a positive response in the group with a history of antenatal steroid exposure was significantly higher than in those not exposed (P= 0.046). Thus, risk factors for lower Hib antibody concentrations after three doses of vaccine were age at first vaccination and lack of use of antenatal steroids. CONCLUSIONS: There is a possibility that perinatal factors and the environment unique to preterm infants are related to their lower antibody positivity rates compared to full-term infants. It may therefore be preferable to modify the proposed immunization schedule.

Urinary ß2-microglobulin in very preterm neonates with chorioamnionitis.

It is important to identify premature infants with prenatal inflammation as it contributes to short- and long-term complications. Our object was to study how prenatal inflammation affects the urinary ß(2)-microglobulin (ß(2)-MG) level. Preterm neonates were divided based on the presence of chorioamnionitis (CAM) into the CAM (n = 100) and non-CAM groups (n = 117). These were further subdivided into five groups each: 30 preterm neonates of 23-26; 42 neonates of 27-28; 54 neonates of 29-30; 51 neonates of 31-32; and 40 neonates of 33-34 weeks' gestation. The urinary ß(2)-MG level within 48 h of birth was significantly higher in the CAM group than in the non-CAM group among the neonates of 23-26 weeks' gestation (18.3 ± 6.9 vs 10.0 ± 5.6 × 10(4) µg/gCr, p = 0.0018) and the neonates of 27-28 weeks' gestation (16.2 ± 10.8 vs 8.8 ± 3.3 × 10(4) µg/gCr, p = 0.0101). However, there was no difference in urinary ß(2)-MG level between the CAM and the non-CAM group among the neonates ≥ 29 weeks 'gestation. Moreover, the elevated urinary ß(2)-MG level in the neonates ≤ 28 weeks ' gestation with CAM had disappeared by 1 week after birth. The reasons for the increase in urinary ß(2)-MG level within 48 h of birth in very preterm neonates (≤ 28 weeks' gestation) with CAM are believed to be not only prematurity, but also prenatal inflammation. It is suggested that the urinary ß(2)-MG level during the early postnatal period can identify prenatal inflammation.

Early discharge from a neonatal intensive care unit and rates of readmission.

BACKGROUND: Increasing admissions to neonatal intensive care units (NICUs) demand early discharge from the units. Our hospital aims to early discharge patients who meet the following requirements: they are able to regulate body temperature; neither apnea nor bradycardia is observed; and bodyweight increases with lactation. We studied the real state of this strategy. METHODS: We looked at postmenstrual age, bodyweight, complication at the time of discharge and the readmission rate in 609 patients with gestational age of less than 34 weeks, who were discharged from our NICU between January 2000 and March 2008. RESULTS: The postmenstrual age and bodyweight at discharge decreased with the increase of gestational age. This tendency was stronger in cases with gestational age of less than 26 weeks. A comparison was made between two patient groups with a gestational age of less than 26 weeks and with the age of 26 weeks or longer. Many patients with a gestational age of less than 26 weeks suffered frequently from complications and were on home oxygen therapy. The readmission rates within 3 months and 1 year of NICU discharge were 10.4% and 26.9% in patients with gestational age between 22 and 25 weeks, respectively, while those rates were 2.8% and 7.4% in patients with gestational weeks of 26 to 34, respectively. CONCLUSION: The postmenstrual age and bodyweight at NICU discharge decreased in inverse proportion to gestational age, especially less than 26 weeks. Our requirements for early discharge were verified by the readmission rate in this investigation.

Severity of chorioamnionitis and neonatal outcome.

AIM: The aim of this study is to elucidate whether the stage of chorioamnionitis is or is not associated with the development of neonatal diseases. MATERIAL & METHODS: We reviewed the neonatal intensive care unit discharge files and placental pathology reports of 302 preterm infants. The presence of various stages of chorioamnionitis as well as absence of an association with chorioamnionitis (non-chorioamnionitis) were compared among neonatal diseases. RESULTS: Preterm infants were grouped according to three stages of chorioamnionitis or the absence of an association with chorioamnionitis. Gestational age differed significantly between these groups. Before controlling for gestational age, the chorioamnionitis stage was significantly higher among infants with chronic lung disease, retinopathy of prematurity and intraventricular hemorrhage than in infants without these diseases. On the other hand, the chorioamnionitis stage was lower in infants with respiratory distress syndrome than without. After controlling for gestational age, the stage of chorioamnionitis was significantly lower in infants with respiratory distress syndrome than in infants without respiratory distress syndrome, whereas, significant differences were not detected between the presence and absence of chronic lung disease, retinopathy of prematurity and intraventricular hemorrhage. Furthermore, gestational age was a significant risk factor for chronic lung disease, respiratory distress syndrome, retinopathy of prematurity and intraventricular hemorrhage. CONCLUSIONS: We found no significant differences in stages of chorioamnionitis between infants with and without neonatal diseases except for respiratory distress syndrome. A significant inverse relationship was observed between the stage of chorioamnionitis and development of respiratory distress syndrome.

Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

BACKGROUND: It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. METHODS: The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. RESULTS: The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. CONCLUSION: Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

Efficacy of expectant management of severe preeclampsia and preeclampsia superimposed on chronic hypertension before 34 weeks gestation.

OBJECTIVES: To investigate the effect of chronic hypertension on expectant management for preeclampsia (PE). STUDY DESIGN: Pregnant women who were diagnosed with severe PE before 34 weeks of gestation between 2005 and 2016 and managed at a tertiary center were the subjects of the study. Mothers were classified into two groups: a severe superimposed PE (SSP) group and a severe PE (SP) group. We compared the groups in terms of perinatal outcomes. MAIN OUTCOME MEASURES: Pregnancy prolongation from the diagnosis of severe PE to delivery. RESULTS: The SSP group included 30 women whereas the SP group included 79 women. Expectant management could be performed in 24 subjects (80.0%) in the SSP group and 49 (62.0%) in the SP group (P = 0.110). Gestational age at diagnosis of PE (P = 0.016) and gestational age at delivery (P = 0.031) were significantly lower in the SSP group than in the SP group. There were no significant differences between the groups in terms of pregnancy prolongation (SSP, 8.5 days versus SP, 6.0 days; P = 0.25) or maternal and neonatal complications. CONCLUSIONS: Compared to severe PE, severe PE superimposed on chronic hypertension does not increase the prevalence of maternal complications, and an equivalent pregnancy prolongation was obtained. Expectant management was possible in severe superimposed PE on chronic hypertension, as it was in severe PE.

Clinical significance of low result of 1-h 50-g glucose-challenge test in pregnant women.

OBJECTIVE: The objective of this study is to examine the effect of low-glucose value on the 1-h 50-g glucose challenge test (GCT) on neonatal body weight in low-risk Asian singleton pregnant women. METHOD: We retrospectively analyzed women who delivered a singleton neonate at term at a tertiary center and underwent GCT at 24-28 weeks of gestation between June 2001 and June 2015. The low GCT group was defined as <75 mg/dL and 75-139 mg/dL were control. We compared these two groups of maternal characteristics, small for gestational age neonate (SGA), large for gestational age neonate (LGA), low-birth weight, and macrosomia. The χ2 test, Fisher's exact test, and Student's t test were used. RESULTS: There were 313 low GCT groups and 4611 control. The low GCT group were younger, had lower prepregnancy body weight, higher stature, and lower prepregnancy body mass index (BMI). After adjusting these variables, the low GCT group had a lower rate of LGA and a higher rate of SGA. Neonatal body weight is more influenced by maternal physique than by low GCT result (standardized coefficient (ß); GCT 0.071, height 0.188, prepregnancy BMI 0.143). CONCLUSIONS: Neonatal body weight was only slightly influenced by low GCT result, but markedly influenced by maternal physique, such as height and prepregnancy BMI.

Placenta Accreta following Hysteroscopic Lysis of Adhesions Caused by Asherman's Syndrome: A Case Report and Literature Review.

Asherman's syndrome is defined as partial or complete obstruction of the uterine cavity primarily caused by intrauterine procedures and infections. Hysteroscopic adhesiolysis is commonly used to treat Asherman's syndrome. Although the frequency of placenta accreta is known to increase with pregnancy after hysteroscopic adhesiolysis, precise data remain unknown. We report a case of placenta accreta following hysteroscopic lysis of adhesions caused by Asherman's syndrome and IVF treatment and review the literature on placenta accreta following hysteroscopic adhesiolysis. It is necessary to consider placenta accreta as a complication of pregnancies after hysteroscopic adhesiolysis for Asherman's syndrome, particularly in those conceived using IVF.

Safety and efficacy of DTaP-IPV vaccine use in healthcare workers for prevention of pertussis.

Pertussis can be fatal for infants. The best way to prevent infant pertussis is to promote adult immunization. However, Tdap has not been licensed in Japan, so we investigated the effect and safety of the DTaP-IPV vaccine instead. The study examined 154 pediatric healthcare workers. Participants without effective levels of antibodies against pertussis toxin were given DTaP-IPV, reduced to 0.2 mL. In total, 48 of the 154 participants (31.2%) were seronegative for pertussis toxin. After vaccination of the seronegative participants, 40 of the 41 measured (97.5%) had acquired an effective response, and all 35 of those tested maintained a protective antibody level ten months after vaccination. Redness was observed in 14 of the 41 (34.1%) and soreness in 19 (46.3%). This study demonstrated that vaccination with reduced 0.2 mL DTaP-IPV successfully provided effective immunity. At least ten months after vaccination, all subjects maintained an adequate level of antibodies.

Incidence and pregnancy outcomes of superimposed preeclampsia with or without proteinuria among women with chronic hypertension.

OBJECTIVE: To investigate the incidence and pregnancy outcomes of superimposed preeclampsia (PE) with or without proteinuria among women with chronic hypertension. METHODS: This retrospective study included 142 women with essential hypertension diagnosed at ⩽20weeks of gestation, managed at a tertiary center. They were divided into three groups (non-PE, PE with proteinuria, and PE without proteinuria) to compare pregnancy outcomes. The non-PE group was further divided into two subgroups (controlled and uncontrolled hypertension). RESULTS: There were 87 women in the non-PE group, 47 in the PE with proteinuria group, and 8 in the PE without proteinuria group. Median gestational age at delivery was 38.7weeks in the non-PE group, 30.4 in the PE with proteinuria group, and 28.4 in the PE without proteinuria group. In three of the women in the PE without proteinuria group, the diagnostic criteria were fulfilled by liver involvement (complicated by thrombocytopenia in one woman). The remaining five women had uteroplacental dysfunction. The 87 women in the non-PE group were divided into a controlled hypertension subgroup of 75 women and uncontrolled hypertension subgroup of 12. The median gestational age at delivery was 39.1weeks in the controlled HT subgroup and 34.1weeks in the uncontrolled hypertension subgroup. The pregnancy outcomes were significantly poorer in the latter group. CONCLUSION: Pregnancy outcomes were unfavorable in both the PE without proteinuria and PE with proteinuria groups. Women with non-PE uncontrolled hypertension also had poor pregnancy outcomes, although their outcomes were better than those of women with PE.

Emergent Uterine Arterial Embolization Using N-Butyl Cyanoacrylate in Postpartum Hemorrhage with Disseminated Intravascular Coagulation.

Although it is widely accepted that uterine artery embolization (UAE) is an effective therapeutic strategy for postpartum hemorrhage (PPH), no consensus has been reached regarding the efficacy of UAE in patients with PPH with disseminated intravascular coagulation (DIC). This single-center retrospective cohort study included patients treated with UAE using NBCA for PPH between 2010 and 2015. The patients were divided into DIC and non-DIC groups, according to the obstetrical DIC score and the overt DIC diagnostic criteria issued by the International Society of Thrombosis and Haemostasis (ISTH), and their clinical outcomes were compared. There were 28 patients treated with UAE using NBCA. Complete hemostasis was achieved by UAE in 19 of 28 patients. In eight of nine patients with unsuccessful hemostasis, surgical hemostatic interventions were performed after UAE, and hemostasis was achieved in seven patients. UAE using NBCA showed no significant intergroup differences in complete hemostasis according to the presence or absence of DIC based on obstetrical DIC score (70% versus 62.5%, P = 1.000) or ISTH DIC score (54.5% versus 76.5%, P = 0.409). UAE using NBCA may be a useful first-choice treatment for PPH with DIC.

A monochorionic diamniotic twin pregnancy requiring termination due to maternal anemia caused by bleeding from chronic abruption.

In patients with bloody amniotic fluid, expectant management for chronic abruption is difficult and should not be applied except after a 48-h waiting period required for administration of steroids.

Preterm premature rupture of membrane after polypectomy using an Endoloop polydioxanone suture II(™).

Polypectomy using an Endoloop PDS II (™) during pregnancy can be responsible for miscarriage and preterm delivery. Cervical polyps should not be removed in pregnant women except in cases where a malignancy is suspected.

Spontaneous reduction of an incarcerated gravid uterus in the third trimester.

An incarcerated gravid uterus is an uncommon complication of pregnancy. On rare occasions, an incarcerated gravid uterus resolves spontaneously even in the third trimester of pregnancy. Severe abdominal pain might be caused by spontaneous reduction and should be considered as a possible cause.

Decreased serum osmolality promotes ductus arteriosus constriction.

AIMS: At birth, dynamic changes occur in serum components and haemodynamics, such as closure of the ductus arteriosus (DA). A previous study demonstrated that, in full-term human neonates, serum osmolality decreased transiently after birth, but recovered over the next few days. However, the significance of this transient decrease in osmolality has never been addressed. The objective of the present study was to examine the role of changes in serum osmolality after birth in DA closure. METHODS AND RESULTS: We found that rats exhibited a similar transient hypoosmolality after birth. Hypotonic stimulation induced constriction of DA rings and increased Ca(2+) transient in DA smooth muscle cells, but not in the aorta. The hypoosmotic sensor transient receptor potential melastatin 3 (TRPM3) was highly expressed in the rat DA, and TRPM3 silencing abolished the Ca(2+) response to hypoosmolality. Pregnenolone sulfate stimulation of TRPM3 induced rat DA constriction ex vivo and in vivo. Furthermore, hypertonic fluid injection impaired rat DA closure. In humans, neonatal serum hypoosmolality was observed in relatively mature preterm infants (≥28 weeks). In extremely preterm infants (<28 weeks), however, this hypoosmolality was absent. Instead, a rapid increase in osmolality occurred thereafter. Such an increase was greater, in particular, among patent DA (PDA) patients. CONCLUSIONS: A transient decrease in serum osmolality may promote DA closure during the first few days of life. Adjusting serum osmolality to proper levels might help to prevent the onset of PDA, improving the therapeutic outcome in extremely preterm infants.

Soluble tumor necrosis factor receptor-I in preterm infants with chorioamnionitis.

AIM: The aim of our study was (i) to determine whether chorioamnionitis (CAM) is associated with an elevated soluble tumor necrosis factor receptor I (sTNFR-I) level and (ii) to examine the time course of the concentration of sTNFR-I in preterm infants after birth. METHODS: We measured sTNFR-I levels in the cord blood of 112 preterm infants (gestational age < or =34 weeks), and those in peripheral blood of 30 preterm infants on days 7, 14, 21 and 28. RESULTS: The median value for the sTNFR-I was significantly elevated in 33 infants with CAM at stage 3 (4618 pg/mL) compared with the 52 infants without CAM (2866 pg/mL), or the 13 infants with CAM at stage 1 (3638 pg/mL) and the 14 infants at stage 2 (3242 pg/mL). The severity of CAM is an independent factor for the elevation of cord blood sTNFR-I. The sTNFR-I level on day 0 was significantly higher in eight infants with CAM at stage 3 than in the 22 infants without CAM or with CAM at stage 1 and 2; however there were no significant differences on days 7, 14, 21 and 28. The serum level of sTNFR-I showed a significant gradual decline with time. CONCLUSIONS: We suggest that there is an association between elevated sTNFR-I levels in cord blood and maternal CAM, and this elevation may reflect the fetal inflammation. However the elevation of sTNFR-I could not persist postnatally for a long time.