Clinical features and pregnancy outcome in antiphospholipid syndrome patients with history of severe pregnancy complications.

Abstract Objective. To clarify the clinical significance of antiphospholipid antibody (aPL) profile in patients with obstetric antiphospholipid syndrome (APS). Methods. Clinical records of 13 pregnant patients (15 pregnancies) with obstetrical APS were reviewed over 10 years. Patients who met the Sapporo Criteria fully were studied, whereas those with only early pregnancy loss were excluded. In addition to classical aPL: lupus anticoagulant (LA), anticardiolipin antibody (aCL), and anti-ß2-glycoprotein I (aß2GPI); phosphatidylserine-dependent anti-prothrombin antibody (aPS/PT) and kininogen-dependent anti-phosphatidylethanolamine antibody (aPE) were also examined in each case. Results. Cases were divided into two groups according to patient response to standard treatment: good and poor outcome groups. All cases with poor outcome presented LA, with IgG aß2GPI and IgG aPS/PT were also frequently observed. IgG aPE did not correlate with pregnancy outcome. Conclusion. aPL profile may predict pregnancy outcome in patients with this subset of obstetric APS.

Is in vitro fertilization associated with preeclampsia? A propensity score matched study.

BACKGROUND: Although an increased risk of preeclampsia in pregnancies conceived by in vitro fertilization (IVF) has been reported, it remains unknown whether IVF is associated with preeclampsia. In the present study, we sought to investigate whether IVF is associated with preeclampsia in pregnant women using propensity score matching analysis. METHODS: This study included 3,084 pregnant women who visited the National Center for Child Health and Development before 20 weeks of gestation without hypertension or renal disease and delivered a singleton after 22 weeks of gestation between 2009 and 2011. Of the 3084 patients, 474 (15.4%) conceived by IVF (IVF group) and 2,610 (84.6%) conceived without IVF (non-IVF group). The propensity score for receiving IVF was estimated using multiple logistic regression with 27 maternal and paternal variables. This model yielded a c-statistic of 0.852, indicating a strong ability to differentiate between those conceiving with and without IVF. The association between IVF and onset of preeclampsia was assessed by the propensity matched sample (pair of N = 474). RESULTS: There were 46 preeclampsia cases (1.5%) in the total study population, with a higher proportion of cases in the IVF group (15 cases, 3.2%) than the non-IVF group (31 cases, 1.2%). Before propensity score matching, the IVF group was 2.72 (95% confidence intervals [CI]: 1.46-5.08) times more likely to have preeclampsia when unadjusted, and 2.32 (95% CI: 1.08-4.99) times more likely to have preeclampsia when adjusted for maternal and paternal variables by logistic regression. After propensity score matching, the IVF group did not show a significantly greater association with preeclampsia compared to the non-IVF group (odds ratio: 2.50, 95% CI: 0.49-12.89), although point estimates showed a positive direction. CONCLUSIONS: Propensity score matching analysis revealed that the association between IVF and preeclampsia became weaker than when conventional adjustments are made in multivariate logistic regression analysis, suggesting that the association between IVF and preeclampsia might be confounded by residual unmeasured factors.

Changes in cytomegalovirus seroprevalence in pregnant Japanese women-a 10-year single center study.

BACKGROUND: Human cytomegalovirus (CMV) causes congenital infections during pregnancy, and seroepidemiological data are important for estimating the risk of infection. However, only a few reports of CMV seroprevalence exist for pregnant Japanese women. OBJECTIVES: The purpose of this study was to assess CMV seroprevalence in pregnant Japanese women. STUDY DESIGN: This cross-sectional study involved pregnant Japanese women who delivered from 2003 to 2012 at our hospital (n=15,616). Among these women, 14,099 (90.3%) underwent tests for the presence of CMV IgG. Those with an equivocal test result were excluded (n=195) from this analysis, leaving a study sample of 13,904 Japanese pregnant women. The prevalence of CMV IgG was also assessed by calendar year, age, and parity. RESULTS: The overall CMV IgG prevalence rate was 66.0%. CMV IgG prevalence significantly decreased over the course of 10 years from 2003 to 2012 (from 69.9% in 2003 to 65.2% in 2012) (p<0.001). Adjusted odds ratios for CMV IgG positivity in women aged <25, 25-30, 35-40, and >40 years were 1.66 (95%CI: 1.25-2.20), 1.20 (95%CI: 1.07-1.35), 1.16 (95%CI: 1.07-1.26), and 1.44 (95%CI: 1.28-1.62), respectively, compared to women aged 30-35 years. Adjusted odds ratios for CMV IgG positivity for a parity of 1, 2, and ≥3 were 1.14 (95%CI: 1.06-1.23), 1.52 (95%CI: 1.32-1.77), and 2.54 (95%CI: 2.69-3.84), respectively, compared to nulliparous women. CONCLUSION: We found that 34% of pregnant Japanese women were susceptible to CMV infection. Calendar year, maternal age, and parity were significantly associated with changes in CMV seroprevalence among this population.

Prediction of gestational diabetes mellitus by soluble (pro)renin receptor during the first trimester.

CONTEXT: There are currently no factors that have been shown to predict gestational diabetes mellitus (GDM) during early pregnancy. The soluble (pro)renin receptor [s(P)RR] may contribute to the development of GDM. OBJECTIVE: The objective of the study was to determine whether plasma s(P)RR concentrations during early pregnancy are associated with the development of GDM later in pregnancy. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted at a referral birth center. Pregnant women who first visited our hospital during the first trimester (<14 weeks of gestation) between 2010 and 2011 were enrolled. Inclusion criteria included singleton pregnancy and the absence of preexisting diabetes mellitus. A total of 716 women participated in this study. MAIN OUTCOME MEASURE: The association of plasma s(P)RR concentrations with the onset of GDM later in pregnancy was measured. RESULTS: Among 716 participants, 44 (6.1%) had GDM and 672 (93.9%) did not. There were 176 participants in the first plasma s(P)RR concentration quartile (Q1: < 25.8 ng/mL), 179 in the second (Q2: 25.8-30.2 ng/mL), 181 in the third (Q3: 30.2-34.2 ng/mL), and 180 in the fourth (Q4: > 34.2 ng/mL). GDM distribution was 7 (4.0%) in Q1, 5 (2.8%) in Q2, 13 (7.2%) in Q3, and 19 (10.6%) in Q4. A multivariate model adjusted for baseline characteristics, medical complications, and gestational characteristics revealed that the risk of developing GDM among women in Q4 compared with Q1 was 2.90 (95% confidence interval 1.11-7.49). CONCLUSION: Increased s(P)RR concentrations during the first trimester may predict the development of GDM later in pregnancy.

Association between soluble (Pro)renin receptor concentration in cord blood and small for gestational age birth: a cross-sectional study.

OBJECTIVE: The (pro)renin receptor [(P)RR] has been recognized as a multifunctional receptor. The purpose of this study was to assess the association between plasma soluble (P)RR [s(P)RR] concentration in human cord blood (i.e., neonatal blood at birth) and small for gestational age (SGA) birth. METHODS: Participants were women with a singleton pregnancy who delivered at the National Center for Child Health and Development between January 2010 and December 2011. Inclusion criteria were availability of maternal pre-pregnancy and paternal body mass index, and the absence of structural anomalies in neonates. s(P)RR concentration in cord blood was measured in 621 neonates. The 621 pairs of mothers and neonates were categorized into four groups based on quartiles of s(P)RR concentrations in cord blood. SGA was defined as a birth weight below the 10(th) percentile for gestational age. Logistic regression analysis was performed to assess the association between cord plasma s(P)RR concentration (quartiles) and incidence of SGA births. RESULTS: Among 621 neonates, 55 (8.9%) were diagnosed as SGA (SGA group) and 566 (91.1%) were not (non-SGA group). Average s(P)RR concentration in cord blood was 66.1±12.6 ng/ml (mean±standard deviation). There were 155 pairs in the first plasma s(P)RR concentration quartile (Q1: <58.2 ng/ml), 153 pairs in the second quartile (Q2: 58.2-65.1 ng/ml), 157 pairs in the third quartile (Q3: 65.1-73.1 ng/ml) and 156 pairs in the fourth quartile (Q4: >73.1 ng/ml). The distribution of SGA births was 18 (11.6%) in Q1, 14 (9.2%) in Q2, 16 (10.2%) in Q3 and 7 (4.5%) in Q4, respectively. The odds ratio of SGA births was 0.24 (95% confidence interval: 0.08-0.71) for the fourth quartile compared to the first quartile in multivariate models. The P-value for trend was also significant (P = 0.020). CONCLUSION: High s(P)RR concentration is associated with a lower SGA birth likelihood.

Changes in the prevalence of the measles, rubella, varicella-zoster, and mumps virus antibody titers in Japanese pregnant women.

In the present study, immunity against infectious diseases, which are capable of influencing both the mother and fetus during pregnancy and the infant in the postnatal period, were assessed in pregnant women to elucidate the necessity of vaccination during the childbearing age. It was determined that there was a trend of increases in the proportion of patients that had low antibody titers observed at a young age. Overall, after adjusting for age, low antibody titers of measles (≤ 4 via the neutralization test [NT]), rubella (≤ 16 via the hemagglutination inhibition [HI]), and varicella and mumps (plus minus or negative on the enzyme-linked immunosorbent assay [EIA]) indicated that the rates of necessity for vaccination against measles, rubella, varicella, and mumps were 27.6%, 16.1%, 3.9%, and 23.8%, respectively. In Japan, acquired immunity for measles, rubella, and mumps was dependent on vaccination, whereas acquired immunity for varicella was dependent on natural infection. We recommend that women be vaccinated after delivery, as these vaccines are live, and thereby, are contraindicated during pregnancy.

Soluble (pro)renin receptor and blood pressure during pregnancy: a prospective cohort study.

The renin-angiotensin system is believed to influence blood pressure (BP) during pregnancy, but the associations between BP during pregnancy and the soluble form of the (pro)renin receptor (s[P]RR), a new component of the tissue renin-angiotensin system, remain undetermined. In this prospective cohort study of 437 pregnant women with normal BP (systolic <140 mm Hg and diastolic <90 mm Hg) during early pregnancy (<16 weeks of gestation) regression analysis was performed to examine the associations between plasma s(P)RR concentrations and BP in 3 gestational stages (20-24, 28-32, and 36-40 weeks of gestation) and logistic regression analysis to evaluate the incidence of preeclampsia. Plasma s(P)RR concentrations at early, middle (16-28 weeks), and late pregnancy (>28 weeks) and at delivery averaged 29.7 ± 10.0, 31.3 ± 12.0, 39.2 ± 8.9, and 40.4 ± 10.2 ng/mL (mean ± SD), respectively. A 1-ng/mL increase in plasma s(P)RR concentration in early pregnancy predicted systolic/diastolic BP elevation in the later 3 gestational stages: 0.11 (95% CI, 0.014-0.20)/0.093 (0.027-0.16) mm Hg for 20 to 24 weeks, 0.11 (0.029-0.19)/0.088 (0.027-0.15) mm Hg for 28 to 32 weeks, and 0.16 (0.058-0.26)/0.12 (0.043-0.19]) mm Hg for 36 to 40 weeks, respectively. Plasma s(P)RR concentrations in middle and late pregnancy were not associated with BP. Adjusted models revealed that women with plasma s(P)RR concentrations above the 75th percentile at delivery had a significantly increased risk of preeclampsia (odds ratio, 22.5 [95% CI, 1.8-279.9]). In conclusion, high circulating levels of s(P)RR at early pregnancy predicted a subsequent elevation in BP, and high concentrations at delivery were significantly associated with preeclampsia.

Early-onset group B streptococcal disease following culture-based screening in Japan: a single center study.

AIM: We investigated trends in early-onset group B streptococcal disease (EOD) after the introduction of culture-based screening in Japan. MATERIAL AND METHODS: A retrospective cohort study examined EOD trends in 9506 pregnancies and 10 715 neonates at our center from 2002 to 2009. RESULTS: EOD occurred in four neonates (4/7332: 0.55/1000 live births). The EOD incidence among infants born to women positive for GBS by screening was 0.90 cases per 1000 live births (1/1107). In contrast, the EOD incidence among infants negative by GBS screening was 0.48 cases per 1000 live births (3/6225). Thus, of the four affected neonates, three had mothers who tested negative on antepartum GBS screening. Two neonates had symptoms of infection during labor and intrapartum antibiotic agents were administered. The other two neonates received no antibiotics because deliveries were uneventful and they were negative on GBS screening. CONCLUSION: The incidence of EOD is 0.90 cases per 1000 live births among GBS-positive women and 0.48 cases per 1000 live births among GBS-negative women. The results of our study implied that EOD can develop regardless of GBS screening and intrapartum clinical course, although the method of sample collection, indications for antibiotic prophylaxis, and the antibiotics regimen should be considered.

Successful pregnancy in a patient suffering from recurrent mid-trimester miscarriage with C9 deficiency after receiving cervical cerclage followed by clindamycin and progesterone: a case report.

Complement component 9 (C9) deficiency is relatively common, especially in Japan. Here we present the case of a 27-year-old Japanese woman whose obstetric history involved three mid-trimester miscarriages (at 22 weeks', 18 weeks' and 21 weeks' gestation) and one early spontaneous miscarriage. Her fifth pregnancy was successfully managed by cervical cerclage at 13 weeks' gestation, followed by clindamycin administration (600 mg/day for 7 days) and progesterone injections (250 mg/week). She gave birth to a healthy 3326-g male infant at 40 weeks and 1 day gestation after natural onset of labor. After delivery, the serum complement components were analyzed. C9 protein and activity were undetectable in the patient's serum. We suggest that an immunologic disorder such as C9 deficiency should be considered as a potential complication of undiagnosed recurrent miscarriages.

Increased rate of cesarean section in primiparous women aged 40 years or more: a single-center study in Japan.

PURPOSE: To investigate perinatal outcomes in late primiparous women aged 35-39 and ≥40 years. Our main research question: "Was the rate of cesarean section similar between these 2 groups of advanced maternal age?" METHODS: Primiparous women aged ≥35 years, who delivered in our center between April 2004 and March 2007, were enrolled in this study. They were divided into two groups: women aged 35-39 years and those aged ≥40 years. Antenatal complications, deliveries, and neonatal outcomes were analyzed. Fetal abnormalities, abortions, and multiple gestations were excluded. RESULTS: We assessed 752 cases (35-39 years, 610 cases; ≥40 years, 142 cases). Incidence of cesarean section (CS) was significantly higher in pregnant women aged ≥40 years (P < 0.01). The CS rate amounted to 50.0% of all deliveries in this age group. Among patients with labor deliveries, the CS rate was also significantly higher in the older age group (P < 0.05). With regard to indication for CS with labor deliveries, the rate of non-progressive labor/dystocia was 19.4% in primiparous women aged ≥40 years and 11.0% in those aged 35-39 years, respectively (P < 0.05). In contrast, the rates of antenatal complications were not different between the two groups, except for gestational diabetes or leiomyoma. No significant differences between the two groups could be found for neonatal outcomes such as birth weight, Apgar score, and admission to neonatal intensive care unit. CONCLUSIONS: CS rate was 50.0% in primiparous women aged ≥40 years. In addition, CS caused by dystocia was almost twice as frequent in primiparous women aged ≥40 years as in women aged 35-39 years. Among late pregnancies, primiparous women aged 40 years and older had higher risk of CS.

Efficacy of double vaccination with the 2009 pandemic influenza A (H1N1) vaccine during pregnancy.

OBJECTIVE: To evaluate the efficacy of double vaccination with the 2009 pandemic influenza A (H1N1) vaccine during pregnancy. METHODS: A study of the 2009 H1N1 vaccine was conducted in 128 pregnant women, who were between 8 and 32 weeks of gestation in October 2009, to monitor the immune response to vaccination and the change in antibody positivity rate and to assess the immune response. Furthermore, the study aimed to assess the changes in these parameters after the first and second vaccination, monitor the maintenance of antibody titers in maternal blood, assess antibody transfer to umbilical cord blood, and evaluate the vaccine. RESULTS: The antibody positivity rate increased from 7.2% before vaccination to 89.5% after the second vaccination. The vaccine was efficacious, producing a sufficient immune response in 90% of patients, regardless of the stage of gestation. The antibody titers were maintained until delivery, and were higher in umbilical cord blood at delivery than in maternal blood. Although the second vaccination increased the antibody titers in 27% of patients, and the antibody titers in maternal and umbilical cord blood at delivery tended to be higher in the double vaccination group than in the single, the differences were not statistically significant. CONCLUSION: Single vaccination induces sufficient immune response and transfer of immunity to the fetus in pregnant women with no pre-existing antibodies. LEVEL OF EVIDENCE: III.

Five-year study assessing the feasibility and safety of autologous blood transfusion in pregnant Japanese women.

AIM: To assess the feasibility and safety of autologous blood donation during pregnancy in Japanese women. MATERIAL AND METHODS: We enrolled patients who were either at high risk for massive blood loss during delivery or had blood that was difficult to match for transfusion between March 2005 and February 2010. After delivery, we reviewed hospital records of these patients to collect data on blood donation procedures, obstetric outcome and blood transfusions received. RESULTS: We enrolled 314 patients during the study period and performed 809 blood donations. The median volume of donated blood was 1200 mL (range, 400-2000 mL). Vasovagal reflex as an adverse donor reaction occurred in 10 of the 314 patients (3.2%) during 11 of the 809 donations (1.4%). There were no cases of non-reassuring fetal heart rate patterns during blood donations. Twenty-five (7.8%) of the 322 neonates were admitted to the neonatal intensive care unit. All 322 infants were healthy 1 month after delivery. Among 314 patients, autologous blood re-transfusion was performed for 56 (17.8%) and homologous blood transfusion was performed concurrently for 5 (1.6%). Placenta previa was the indication with the highest re-transfusion rate (42.4%). All re-transfusions were performed without side-effects. CONCLUSION: Autologous blood donation is feasible and safe for pregnant women and their infants. Although indications of autologous blood donation are controversial, it should be considered for cases of placenta previa.

Acquisition of anti-Diego b antibodies possibly resulting from feto-maternal hemorrhage during pregnancy.

Anti-Diego b (Di(b) ) antibodies, rare antibodies against red blood cell antigens, can cause severe hemolysis. We report a patient who most likely acquired anti-Di(b) antibodies during pregnancy. The patient was a 39-year-old Japanese woman who delivered by cesarean section at 38 weeks of gestation. She required a second operation to treat re-bleeding of the surgical scar, but it was difficult to schedule this surgery because we could not obtain enough blood for transfusion due to the presence of anti-Di(b) antibodies. These antibodies were likely acquired during pregnancy; she did not have irregular antibodies at 11 weeks of gestation. We speculate that she became sensitized to fetal blood due to feto-maternal hemorrhage. The infant had no hemolytic conditions. Testing for the presence of irregular antibodies should be performed during late stages of pregnancy as well as early stages.

Prediction of pregnancy-induced hypertension by a shift of blood pressure class according to the JSH 2009 guidelines.

Elevated blood pressure (BP) at early or mid pregnancy is a known risk factor for pregnancy-induced hypertension (PIH). However, the association between BP changes during the first half of pregnancy and subsequent PIH development is unknown. We used changes in maternal BP between 16 and 20 weeks of gestation to evaluate the risk of PIH. A total of 976 pregnant women with BP estimations recorded before 16 weeks and at 20 weeks of gestation participated in this study. BPs were classified by the Japanese Society of Hypertension 2009 Hypertension Treatment Guidelines (JSH 2009). There was a significant trend for future PIH in women whose JSH 2009 BP class increased between 16 and 20 weeks of gestation, and the risk of PIH was highest among women whose BP was Class IV Hypertension (systolic BP≥140 mm Hg and/or diastolic BP≥90 mm Hg). The risk of PIH increased in women whose BPs shifted from Classes I Optimal (systolic BP<120 mm Hg and diastolic BP<80 mm Hg) and II Normal (systolic BP 120-129 mm Hg and/or diastolic BP 80-84 mm Hg) before 16 weeks to Class III High-Normal (systolic BP 130-139 mm Hg and/or diastolic BP 85-89 mm Hg) at 20 weeks of gestation. These shifts in BP class were significantly correlated with the risk of PIH after adjustments for variables (P-value for trend <0.05). Within JSH 2009 Classes I, II and III, a shift in BP from a low to a high class between 16 and 20 weeks of gestation predicts the subsequent development of PIH.

[Influenza vaccination safety during pregnancy].

Increased morbidity and mortality in pregnant women were reported following three major historical influenza pandemics. To prevent influenza infection during pregnancy, the Centers for Disease Control (CDC) and the American College of Obstetricians and Gynecologists (ACOG) recommend that all pregnant women and those intending to get pregnant during the influenza season be vaccinated. In 2004, they advised expanding vaccination guidelines from the second and third trimester to all three trimesters. We evaluated the safety of influenza vaccination during pregnancy in 182 subjects from 2007-2009. No adverse events were seen in pregnancy or fetal medical condition regardless of the pregnancy stage at which vaccine was administered.

Sinusoidal heart rate patterns as a manifestation of massive fetomaternal hemorrhage in a monochorionic-diamniotic twin pregnancy: a case report.

OBJECTIVE: A case of fetomaternal hemorrhage (FMH) in monochorionic twins is reported. METHOD: Case report. RESULT: The patient felt a decrease in fetal movements at 32 gestational weeks. Cardiotocography showed sinusoidal heart rate patterns in both fetuses. The fetal hemoglobin level in maternal blood was 6.6% (normal 0.0-1.0%). Since the patient was diagnosed with massive FMH, cesarean section was performed and both babies delivered to receive neonatal treatment. Severe anemia was apparent in both infants, based on red blood cell count, hemoglobin concentration, and hematocrit of 86 x 10 and 85 x 10(4)/mm(3) (normal 376-456 x 10(4)/mm(3)), 3.1 g/dl each (normal 10.9-13.5 g/dl), and 10.7 and 10.4% (normal 32.2-41.2%), respectively. Severe anemia may develop in both fetuses following massive FMH in monochorionic twins. As such, if abnormal circulation is detected in 1 monochorionic twin, the other fetus will also require special attention.

Intra-Abdominal Bleeding during Pregnancy, Preterm Delivery, and Placental Polyp in a Long-Term Survivor of Neuroblastoma: A Case Report.

Background. There are few reports of pregnancies in long-term survivors of pelvic neuroblastoma. Case. A 30-year-old Japanese woman with a history of pelvic neuroblastoma in her childhood, which was treated with surgical resection, chemotherapy, and radiation. Her pregnancy continued with conservative management, but she delivered a 510 g female infant at 23 weeks of gestation due to sudden onset of labor pain. She also had a placental polyp and developed massive postpartum bleeding. Conclusion. Cancer treatment, especially radiation therapy, in childhood may cause adverse outcomes during pregnancy in long-term survivors of neuroblastoma.

Relationship of Th1/Th2 cell balance with the immune response to influenza vaccine during pregnancy.

To determine the optimal timing for influenza vaccination in pregnant women, we measured alterations in the types 1 and 2 T helper cell (Th1/Th2) balance during pregnancy, monitored specific immunity to inoculated antigens after vaccination with inactivated influenza vaccine, evaluated the relevance of the Th1/Th2 ratio and immune responses to the vaccination, monitored the maintenance of high antibody titers until delivery and measured the transplacental antibody transfer rate. No significant alterations of the Th1/Th2 balance were noted in the 65% of pregnant women among whom the Th1/Th2 ratio was lower than 9.9% in the first trimester. In those groups with a ratio higher than 10% in the first trimester, there was a tendency for the ratio to decrease as gestation advanced. The efficiency of immunization was not influenced by the Th1/Th2 status or by the stage of gestation. The antibody titer decreased steadily with time from 1 month after vaccination to the time of delivery. Conversely, the transfer rate of antibodies from maternal to fetal blood at the time of delivery increased with the duration of gestation after vaccination. Nevertheless, the antibody titers in both maternal and fetal blood were sufficient to afford protection against infection. Thus, efficient influenza vaccination can be undertaken at any stage of pregnancy.

[Case of external cephalic version under combined spinal-epidural anesthesia followed by vaginal delivery].

For a parturient with breech presentation, an external cephalic version is sometimes done to enable vaginal delivery. Usually external cephalic version has been done without anesthesiologist's management. However there have been several reports indicating a benefit of anesthesia for external cephalic version. We report successful case of external cephalic version under combined spinal-epidural anesthesia followed by vaginal delivery.