A quasi-randomized controlled trial of Ninjin'yoeito for the treatment of postpartum anemia and the prevention of postpartum depression.

AIM: To study the effect of Ninjin'yoeito (NYT) on postpartum anemia and on the development of postpartum depression (PPD). METHODS: In this prospective, single-center, open-label, quasi-randomized controlled trial, patients with anemia 1-2 days postdelivery were randomized to receive either NYT or an oral iron preparation for 4 weeks. The primary endpoint was the hemoglobin (Hb) level. Secondary endpoints were fatigue (assessed by the numerical rating scale [NRS]) and prevalence of postpartum depressive symptoms, as defined by an Edinburgh postnatal depression scale (EPDS) score ≥9. Hb levels and fatigue were measured before, and 4 weeks after, treatment and the EPDS was measured 4 weeks posttreatment. RESULTS: Of 1066 participants (NYT group: 532, iron group: 534) 1061 (NYT group: 529, iron group: 532) underwent full analysis. The Hb level increased significantly in both groups (p < 0.001), and there were no significant differences between the groups in terms of the change in Hb levels (NYT: 2.4 ± 0.8 g/dL vs. iron: 2.5 ± 0.7 g/dL, p = 0.098). Fatigue decreased significantly in the NYT group (p < 0.001) but did not change in the iron group, and the difference was significant (p < 0.001). There was a significant difference between the two groups in terms of the prevalence of postpartum depressive symptoms (NYT: 5.7% vs. iron: 9.4%, odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.36-0.93). CONCLUSION: The results suggest that NYT improves postpartum anemia and fatigue, and may be able to prevent the development of PPD.

Plasma antithrombin levels correlate with albumin and total protein in gestational hypertension and preeclampsia.

OBJECTIVE: To analyze the antithrombin-III (AT-III) activity in the plasma in relation to the serum albumin and total protein in preeclampsia and gestational hypertension. STUDY DESIGN: The medical records of 139 patients who were diagnosed with gestational hypertension (n=33) and preeclampsia (n=106) were reviewed, and the relationships between the activity of AT-III and serum albumin or total protein were evaluated. MAIN OUTCOME MEASURES: The plasma AT-III activity in gestational hypertension and preeclampsia was correlated with the serum albumin and TP levels. RESULTS: There were significant correlations between AT-III activity and albumin in gestational hypertension (r=0.504, p=0.003) and preeclampsia (r=0.343, p=0.003). There were also significant correlations between AT-III activity and TP in gestational hypertension (r=0.619, p=0.001) and preeclampsia (r=0.366, p=0.001). Regression coefficients between AT-III and albumin and between AT-III and TP in gestational hypertension (23.7 and 14.0, respectively) were significantly steeper than those in preeclampsia (14.6 and 9.6, respectively). CONCLUSIONS: The plasma AT-III activity in gestational hypertension and preeclampsia was correlated with the serum albumin and TP levels. This suggests that AT-III activity is more likely to decrease in gestational hypertension than in preeclampsia.

Survival rate of extremely low birth weight infants and its risk factors: case-control study in Japan.

Aim. To clarify the effect of perinatal events on the survival of ELBW infants in Japan. Methods. 1,713 ELBW infants, from 92,630 live births in 2001 and 2002, born at 22-36 weeks of gestation were registered. Case was defined as death at discharge. The relevant variables were compared between the cases (n = 366) and the controls (n = 1,347). Results. The total survival rate was 78.6%. There was a significant difference between the survival rate in cesarean and vaginal delivery at 24-31 weeks of gestation. Cesarean delivery in infants with a birth weight >400 g was significantly advantageous to the survival rate of ELBW infants than vaginal delivery. The significant contributing factors were gestational age at delivery (OR: 0.97), Apgar score at 5 min (0.56), antenatal steroid (0.41), and birth weight (0.996). Nonvertex presentation (1.81), vaginal delivery (1.56), and placental abruption (2.50) were found to be significantly associated with neonatal death. Conclusions. Cesarean section might be advantageous for survival in ELBW infants over 24 gestational weeks or 400 grams of birth weight. Nonvertex presentation, vaginal delivery, and placental abruption could be significant risk factors for survival of ELBW infants.

Prediction of fetal acidemia in placental abruption.

BACKGROUND: To determine the major predictive factors for fetal acidemia in placental abruption. METHODS: A retrospective review of pregnancies with placental abruption was performed using a logistic regression model. Fetal acidemia was defined as a pH of less than 7.0 in umbilical artery. The severe abruption score, which was derived from a linear discriminant function, was calculated to determine the probability of fetal acidemia. RESULTS: Fetal acidemia was seen in 43 survivors (43/222, 19%). A logistic regression model showed bradycardia (OR (odds ratio) 50.34, 95% CI 11.07-228.93), and late decelerations (OR 15.13, 3.05-74.97), but not abnormal ultrasonographic findings were to be associated with the occurrence of fetal acidemia. The severe abruption score was calculated for the occurrence of fetal acidemia, using 6 items including vaginal bleeding, gestational age, abdominal pain, abnormal ultrasonographic finding, late decelerations, and bradycardia. CONCLUSIONS: An abnormal FHR pattern, especially bradycardia is the most significant risk factor in placental abruption predicting fetal acidemia, regardless of the presence of abnormal ultrasonographic findings or gestational age.

Ritodrine Should Be Carefully Administered during Antenatal Glucocorticoid Therapy Even in Nondiabetic Pregnancies.

Aim. Antenatal glucocorticoid therapy (AGT) has been commonly used recently. However, this therapy has severe harmful effects such as maternal hyperglycemia. In Japan, ritodrine hydrochloride has been used as a tocolytic agent. In this study, we performed retrospective casecontrol study to clarify whether concomitant use of ritodrine and glucocorticoid was safe to pregnant women without diabetes mellitus. Methods. We reviewed the computerized records of pregnant women with pregestational diabetes (n = 9) and nondiabetes (n = 45) who gave birth at our hospital between 2002 and 2011. Cases and controls received AGT. Blood glucose after the therapy was analyzed, and additional volume of insulin was compared to that before the therapy. Results. From this study, 30 units of insulin were necessary when performing AGT in diabetic pregnant women. And also, an increase in blood glucose of 40 mg/dL was seen after the therapy even in nondiabetic pregnant women. Blood glucose increased significantly in the group that also received ritodrine, and it was shown that the number of pregnant women who might develop ketoacidosis might increase 11-fold. Conclusions. Ritodrine should be carefully administered during antenatal glucocorticoid therapy. It may be necessary to adequately monitor blood glucose, when performing the therapy, even in nondiabetic pregnant women.

Umbilical artery pH may be a possible confounder for neonatal adverse outcomes in preterm infants exposed to antenatal magnesium.

OBJECTIVES: To determine the normal range of ionized magnesium (IMg) levels in cord blood during preterm gestation and to investigate whether antenatal Mg administration affects neonatal intraventricular hemorrhage (IVH) or patent ductus arteriosus (PDA). METHODS: In this retrospective case-control study, we reviewed 118 pregnant women with antenatal Mg administration and their infants after they gave birth at one tertiary care center between January 2006 and December 2010. Thirty-seven cases with IVH and/or PDA were compared to 81 controls by multiple logistic regression analysis. The normal range of IMg levels was determined by another 79 subjects without any tocolytic agents and possible confounders. Perinatal and neonatal characteristics were then compared between three groups divided by the IMg levels in cord serum. RESULTS: The normal range of IMg levels in cord blood was determined to be 0.47 ± 0.07 mmol/L, regardless of gestational weeks. IMg level in cord serum could not be a risk factor for IVH or PDA. Elevation of IMg level in cord blood resulted in an increased incidence of IVH and a decreased incidence of PDA, but not significantly. IMg level in cord blood was inversely correlated with umbilical artery pH (p = 0.067). CONCLUSIONS: There was no significant relationship between the IMg levels in cord serum and neonatal IVH and PDA. Umbilical artery pH may be a possible confounder.

Risk factors associated with preterm delivery in women with cardiac disease.

BACKGROUND: The purpose of this study was to identify clinical characteristics of preterm delivery at less than 37 weeks of gestation (PD37G) and prenatal events associated with preterm delivery at less than 35 weeks of gestation (PD35G) in women with cardiac disease (WCD). METHODS: A case-control study was conducted of 599 pregnancies in 479 single pregnant women with congenital or acquired cardiac lesions or cardiac arrhythmias. The relevant variables were compared between women who had PD35G (n=37) and the controls (n=562). Cardiac dysfunction was defined as the appearance of clinical symptoms of heart failure, abnormal electrocardiogram, or cardiac ultrasonography. RESULTS: PD37G occurred in 77 cases (12.9%). The spontaneous and indicated preterm delivery was 26 (33.8%) and 51 (66.2%) cases, respectively. The presence of cardiac dysfunction [odds ratio (OR) 21.82, 95% confidence interval (CI) 8.3-57.49], New York Heart Association class II (OR 3.96, 95% CI 1.05-14.93), cardiomyopathy (OR 7.74, 95% CI 1.69-35.45) and pregnancy-induced hypertension (PIH) (OR 3.15, 95% CI 1.37-7.24) was significantly associated with an increased risk of PD35G. No maternal death was seen within one year after delivery. CONCLUSIONS: Although pregnancy and delivery are generally safe in WCD, it is necessary to be aware of the risk factors of cardiac dysfunction, cardiomyopathy, and PIH from the aspect of PD35G.

Levels of soluble endothelial selectin in umbilical cord serum are influenced by gestational age and histological chorioamnionitis, but not by pre-eclampsia.

AIMS: The aim of this study was to examine the factors that influence soluble endothelial selectin (sE-selectin) levels in umbilical cord serum. MATERIALS AND METHODS: sE-selectin levels in umbilical cord serum were measured in 144 patients using enzyme-linked immunosorbent assay. We examined the association of sE-selectin levels with gestational age, pre-eclampsia (PE), histological chorioamnionitis (HCAM), preterm premature rupture of membranes, magnesium sulfate use, birthweight, and placental weight. RESULTS: A significant positive correlation was observed between sE-selectin levels and gestational age in the patients who had neither PE nor HCAM (r = 0.559, P < 0.0001). This statistically positive correlation persisted in patients with PE without HCAM (n = 25, r = 0.644, P < 0.001), but not in patients with HCAM without PE (n = 58, r = 0.102, P = 0.448). In matched gestational age analysis, sE-selectin levels were increased in the presence of HCAM (P = 0.0006), but were not influenced by the presence of PE (P = 0.127), preterm premature rupture of membranes (P = 0.352) or magnesium sulfate use (P = 0.337). CONCLUSION: sE-selectin levels in umbilical cord serum were positively correlated with gestational weeks. sE-selectin levels in umbilical cord serum were higher in mothers with HCAM but not with PE, when compared with gestational-age-matched controls.

Short- and long-term outcomes in babies born after antenatal magnesium treatment.

AIM: To identify the prenatal events associated with adverse outcome in babies born at less than 32 weeks' gestation, including antenatal magnesium sulfate treatment. METHODS: A case-control study was performed to examine the effect of long-term tocolysis with MgSO4. Long-term neonatal and infantile adverse outcomes were defined as one of the following: intraventricular hemorrhage, periventricular leukomalacia, cerebral palsy and infantile death. RESULTS: Data were analyzed for 425 cases (236 who received magnesium sulfate and 189 control cases who did not). Perinatal deaths included 13 cases that had received magnesium (5.5%) and 17 control cases (9.0%). Long-term neonatal and infantile adverse outcomes were noted in 80 cases. The factor associated with an increased risk of combined adverse outcome after adjustment for confounding effects was the administration of corticosteroids (adjusted odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.81), but not magnesium sulfate (OR 0.82, 95% CI 0.48-1.40). In the subgroup that also received ritodrine (n = 315), magnesium sulfate was given to 195 cases. In this group, the factor associated with an increased risk of combined adverse outcome (n = 64) after adjustment for the confounding effects was also corticosteroids (adjusted OR 0.25, 95% CI 0.13-0.49), but magnesium sulfate was not associated with an increase in risk (OR 0.64, 95% CI 0.34-1.22). CONCLUSIONS: Long-term tocolysis with magnesium sulfate is not a significant factor related to the occurrence of neonatal and infantile adverse outcomes. Further study is needed to clarify the dose-response effect of magnesium sulfate.

Case of asymptomatic portal vein thrombosis after cesarean delivery.

We report a case of acute portal vein thrombosis (PVT) after a cesarean delivery. The patient was admitted for treatment of severe pre-eclampsia. On the second day after cesarean delivery, the elevations of aspartic aminotransferase and alanine aminotransferase were observed. Thereafter, acute PVT was diagnosed with ultrasonography. Although early anticoagulant therapy seems to be effective in the treatment of acute PVT, close observation must be made due to the risk of bleeding.

T cell activation in abnormal perinatal events.

The aim of this study was to determine the percentage of CD45RO(+) T cells in umbilical cord blood from neonates born at less than 37 weeks of gestation. Fifty-nine patients were enrolled in this study, including 49 with preterm and 10 with term deliveries. Preterm deliveries were divided into two categories; spontaneous (Group A, n= 31) and indicated (Group B, n= 18). Perinatal infection was categorized as C-CAM, H-CAM and neonatal infection. The percentage of CD45RO(+) T cells in the umbilical cord was assessed using flow cytometry. IL-6 was measured using ELISA. In Group A, the percentage of CD45RO(+) T cells and concentrations of IL-6 in patients with perinatal infection (n= 18) were significantly higher than in those without perinatal infection (n= 13). A significant correlation between percentage of CD45RO(+) T cells and IL-6 concentrations was observed in the cord blood (r= 0.62, P= 0.001). In Group B, pink-tinged amniotic fluid was observed in seven cases. In these cases, an increase in the percentage of CD45RO(+) T cells (>10%) was noted. In the cases without perinatal infection, which included all those delivered at term (n= 32), no correlation was observed between the percentage of CD45RO(+) T cells and gestational age at delivery (r=-0.139, P= 0.448). We concluded that a high percentage of CD45RO(+) cord blood T cells is observed not only in perinatal infection, but also in the presence of abnormal perinatal events such as maternal bleeding in preterm gestation.

Assessment of the usefulness of antithrombin-III in the management of disseminated intravascular coagulation in obstetrically Ill patients.

OBJECTIVE: The aim of this study was to analyze the antithrombin-III (AT-III) activity in the serum in relation to other laboratory findings, including the serum albumin, total protein (TP), and uric acid (UA), and to assess the recovery of the AT-III activity in the serum after its administration in obstetrically ill patients. PATIENTS AND METHODS: The medical records of 27 patients who were diagnosed to have disseminated intravascular coagulation (DIC) based on the obstetric DIC scores were reviewed and the relationships between the activity of AT-III in the serum and other laboratory findings were evaluated. The effect of administration of AT-III on the recovery of AT-III activity in the serum was also evaluated. RESULTS: All the patients survived without any sequelae. The mean obstetric DIC score was 11.1 ± 3.1 (range 8-19) and the mean blood loss during the first 24 hours was 3798 ± 3,435 mL (range 480-16 208 mL). There was a significant correlation between the serum AT-III activity before the treatment and the serum albumin (r = .67, P = .001) and TP (r = .59, P = .021), but not serum UA. Seven patients required over 3000 IU of AT-III concentrate to obtain an increase in the serum AT-III activity to over 70%. The UA level in this group was significantly higher than that in the remaining patients. CONCLUSION: The serum AT-III activity was correlated with the serum albumin level before the start of treatment. Therefore, measurement of the serum albumin level before and during treatment is helpful.

The importance of low blood urea nitrogen levels in pregnant patients undergoing hemodialysis to optimize birth weight and gestational age.

Most published reports indicate that intensified hemodialysis results in better pregnancy outcomes. Here we studied clinical characteristics and the outcomes of 28 pregnant women receiving hemodialysis. We found an association between maternal blood data and birth weight, and gestational age and outcomes. There were 18 surviving infants who were followed up for one year. In the others there were 4 spontaneous abortions, 1 stillbirth, 3 neonatal deaths and 2 deaths after birth. Analysis of blood chemistry for 20 pregnancies from 12 weeks of gestation until delivery showed that the average hemoglobin level was significantly higher in the group that successfully delivered than in the unsuccessful group. There were significant negative relationships between the blood urea nitrogen (BUN) level and the birth weight or gestational age in the latter cohort. A birth weight equal to or greater than 1500 g or a gestational age equal to or exceeding 32 weeks corresponded to BUN levels of 48-49 mg/dl or less. Whether the low BUN is the direct cause of the improved outcome remains to be examined.

Clinical features of fetal growth restriction complicated later by preeclampsia.

OBJECTIVE: To assess the maternal and perinatal outcome of preeclampsia with fetal growth restriction (FGR) and to assess the risk factors of FGR complicated later by preeclampsia. SUBJECTS AND METHODS: A cohort of women with preeclampsia and/or FGR (n = 306) were retrospectively reviewed. First, the maternal and perinatal outcome were compared between preeclampsia with FGR (n = 37) and preeclampsia without FGR (n = 96). Second, the clinical findings of FGR followed later by preeclampsia (n = 24) were compared to FGR without preeclampsia (n = 149). RESULTS: The incidence of severe hypertension and critical maternal complications in women with preeclampsia with FGR was significantly higher than in those with preeclampsia without FGR. In women diagnosed with FGR, 13.8% (24/173) developed preeclampsia later. In this group, FGR was diagnosed at 28.8 gestational weeks, which was then complicated by preeclampsia at a mean of 32.6 gestational weeks, and delivered at 33.3 gestational weeks. The diagnosis of FGR was earlier and the incidence of proteinuria at entry was more common in women with FGR complicated later by preeclampsia than in those with FGR without preeclampsia (45.8% vs 4.7%; P < 0.001). CONCLUSIONS: Preeclampsia with FGR is severe condition which can possibly adversely affect the maternal condition. About 15% of all mothers diagnosed with FGR developed preeclampsia afterwards; therefore, those with FGR are considered to be candidates for close monitoring for the clinical manifestation of preeclampsia, and those with early-onset FGR with proteinuria may represent a high-risk group for preeclampsia.

Prognosis in cervical insufficiency at less than 32 weeks of gestation.

OBJECTIVE: To identify prenatal events associated with adverse outcome in babies at less than 32 weeks of gestation in cases of cervical insufficiency and preterm labor (PTL)/premature rupture of the membranes (PROM). STUDY DESIGN: A case-control study was performed using a logistic regression model at 17 tertiary hospitals in Japan. Adverse outcome was defined as neonatal death or abnormal cerebral ultrasound scans (intraventricular hemorrhage [IVH] and periventricular leukomalacia [PVL]) prior to discharge from hospital. RESULTS: Data were analyzed for 307 cases (74 for cervical insufficiency and 233 for PTL/PROM). Neonatal death and IVH/PVL were noted in 25 and 29 cases, respectively. A significant association of cervical insufficiency (odds ratio (OR) 1.32, 95% confidence interval (CI) 1.02-1.68), gestational age at delivery (<26 weeks) (OR 4.64, 95% CI 1.73-12.44), and Apgar score <7 at 5 min (OR 3.3, 95% CI 1.42-7.64) with combined neonatal death or IVH and PVL was found in a logistic regression model that controlled for in utero transportation, gestational age on admission, clinical chorioamnionitis, and histopathologic chorioamnionitis. CONCLUSION: Cervical insufficiency is a significant factor related to the occurrence of adverse outcome.