Noriyoshi Watanabe

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.

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.

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. J. Med. Virol. 81:1923–1928, 2009.

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.

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

Prenatal diagnosis of chondrodysplasia punctata tibia–metacarpal type using multidetector CT and three-dimensional reconstruction

We report a case of chondrodysplasia punctata tibia–metacarpal type (CDP-TM) that was diagnosed prenatally using multidetector CT (MDCT) with three-dimensional (3-D) CT reconstructions. Prenatal US had shown severe thoracic hypoplasia and rhizomelic shortening of the limbs, raising the suspicion of thanatophoric dysplasia. However, MDCT showed punctate calcifications in the epiphyseal cartilage of the humeri and femora, carpal bones, and paravertebral region. On 3-D CT, the tibiae were much shorter than the fibulae, the humeri were very short and bowed, and severe platyspondyly was evident. These findings led to the diagnosis of CDP-TM. The diagnosis was confirmed on postnatal radiographs. Prenatal MDCT with 3-D images may make a useful contribution to prenatal diagnosis in selected fetuses with severe skeletal dysplasia.

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 10th 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.

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-β2-glycoprotein I (aβ2GPI); 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 aβ2GPI 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.

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.

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.