Emi H. Kato

Maternal serum and amniotic fluid bisphenol A concentrations in the early second trimester

To assess human exposure to bisphenol A (BPA) over a 10-year period, BPA concentrations in maternal serum (MS) and amniotic fluid (AF) obtained at early second trimester were determined. ELISA was used to measure BPA in 200 MS/AF pairs in women carrying fetuses with normal karyotypes (Group I) and in 48 pairs with abnormal karyotypes (Group II). In Group I, BPA concentrations in AF (median: 0.26 ng/ml) were lower (P<0.01) than in MS (2.24 ng/ml). Over a 10-year period, yearly BPA concentrations in MS decreased from 5.62 to 0.99 ng/ml (P<0.001). Eight of the Group I AF samples had relatively high concentrations of BPA (2.80-5.62 ng/ml). In Group II, BPA concentrations in AF (0 ng/ml) were lower (P<0.01) than in MS (2.97 ng/ml). MS BPA concentrations in Group II were higher (P<0.01) than in Group I.

Pre-conceptional Natural Killer Cell Activity and Percentage as Predictors of Biochemical Pregnancy and Spontaneous Abortion with Normal Chromosome Karyotype

Problem: The aim of the present study was to determine whether pre‐conceptional natural killer (NK) cell activity and percentage are predictive of subsequent spontaneous abortion in women with recurrent spontaneous abortion (RSA).

High NK Cell Activity in Early Pregnancy Correlates with Subsequent Abortion with Normal Chromosomes in Women with Recurrent Abortion

PROBLEM: The aim of this study was to assess the role of natural killer (NK) cells in pregnant women with a history of recurrent spontaneous abortion (RSA). 
METHOD OF STUDY: Consecutive 66 pregnant women with a history of RSA were prospectively assessed for peripheral NK cell activity, percentage of the NK cell subsets, and subsequent pregnancy outcome. 
RESULTS: NK cell activity in women with subsequent live birth (group I) at 4–5 gestational weeks (GW) (mean±SD, 32.5±12.3%) significantly decreased at 6–7 GW (28.1±12.1%) and at 8–9 GW (28.0±11.8%). NK cell activity in women with subsequent abortion with normal chromosomes (group II) at 6–7 GW (41.2±19.0%) was significantly higher than that in group I women, while NK cell activity at 6–7 GW in women with subsequent abortion with abnormal chromosomes (group III) was the same as the level in group I women. 
CONCLUSIONS: High NK cell activity at 6–7 GW correlates with subsequent abortion with normal chromosomes.

Antiphospholipid antibodies increase the risk of pregnancy-induced hypertension and adverse pregnancy outcomes

Antiphospholipid antibody (aPL) is associated with thromboembolism. There is scant evidence of a relationship between the aPL profile and serious adverse pregnancy outcome. The aim of this study was to assess whether aPL measurements during early pregnancy were useful in predicting a serious adverse pregnancy outcome. In this prospective study, we measured aPLs, including lupus anticoagulant (LA), IgG, IgM, IgA anticardiolipin antibody (aCL), IgG, IgM phosphatidylserine-dependent antiprothrombin antibody, and IgG kininogen-dependent antiphosphatidylethanolamine antibody (aPE) during the first trimester in a consecutive series of 1155 women. The 99 th percentile cut-off values in each aPL were determined using samples from 105 women who did not exhibit any pregnancy morbidity. We assessed the predictive risk of a serious adverse pregnancy outcome adjusted for confounding factors. We found that IgG aCL was associated with developing pregnancy-induced hypertension (PIH) (odds ratio 11.4, 95% CI 2.7-48); IgG aPE with PIH (8.3, 2.4-29), severe PIH (20.4, 4.5-91), and premature delivery (PD) (12.7, 3.1-50); and LA with PD (11.0, 2.8-44) and low birth weight (8.0, 2.1-31). The combinations of IgG aPE plus IgG aCL (17.5, 4.7-66.7) or IgG aPE plus LA (22.2, 5.4-909) measurements predicted severe PIH with 30.8% sensitivity and 99.2% specificity. We conclude that aPL measurements during early pregnancy may be useful in predicting adverse pregnancy outcome.

Intravenous Immunoglobulin Treatment in Women with Recurrent Abortions: Increased Cytokine Levels and Reduced Th1/ Th2 Lymphocyte Ratio in Peripheral Blood

PROBLEM:  The aim of this study was to investigate changes in peripheral blood Th1/Th2 cytokine levels and lymphocyte ratios after massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology.

Massive Intravenous Immunoglobulin Treatment in Women with Four or More Recurrent Spontaneous Abortions of Unexplained Etiology: Down-Regulation of NK Cell Activity and Subsets

PROBLEM: The aims of this study were to investigate the efficacy of massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology, and to investigate changes in peripheral natural killer (NK) cell activity and subsets.
 METHOD OF STUDY: MIVIg treatment was performed in 18 pregnancies from 15 women with 4 or more consecutive RSA of unexplained etiology. NK cell activity and subsets were assessed in 8 of the pregnancies.
 RESULTS: 14 pregnancies resulted in live births and 4 resulted in abortions with chromosome abnormality. The pre‐infusion NK cell activity (mean±SD, 40.9±17.0%) at 4.4±0.5 weeks of gestation (GW) decreased to 15.0±7.9% at post‐infusion status (5.4±0.5 GW). Pre‐infusion percentages of CD56+CD16− cells (3.5±2.1%) and CD56+CD16− cells (16.8±8.8%) decreased to 3.0±2.2% and 11.1±6.9%, respectively, after MIVIg treatment.
 CONCLUSIONS: MIVIg treatment was effective in all 14 pregnancies from RSA women of unexplained etiology, excluding 4 abortions with chromosome abnormality. Peripheral NK cell activity and subsets were suppressed by MIVIg treatment.

A1166C variant of angiotensin II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene

AbstractHypertension in pregnancy (HP) is a multifactorial disease manifested due to a complex combination of environmental factors and several predisposing genes including factors in the renin angiotensin system. The aim of this study was to assess the association between the A1166C variant of the angiotensin II type 1 receptor (AT1) gene and severe HP. We carried out association studies and multivariate analyses including other candidate causal factors of HP such as the M235T variant of the angiotensinogen (AGT) gene, prepregnancy body mass index (BMI), and family history of hypertension in Japanese subjects. One hundred and fourteen patients with severe HP and 291 normal pregnancy controls were genotyped. Among primiparous subjects, the frequency of “AC+CC genotype of AT1” was significantly higher in severe HP than in the controls. A multivariate analysis with “AC+CC genotype of AT1” and “TT genotype of AGT” revealed that these were independently associated with primiparous severe HP. However, when “family history of hypertension” and “prepregnancy BMI ≥25” were added as factors examined in the multivariate analysis, only “TT genotype of AGT” and “family history of hypertension” were found to be independent potent factors. The present results suggest that the C1166 allele of the AT1 gene may be concerned with the predisposition to essential hypertension independently of the T235 allele of the AGT gene.

Fetal treatment of congenital heart block ascribed to anti-SSA antibody: case reports with observation of cardiohemodynamics and review of the literature.

Yamada H, Kato EH, Ebina Y, Moriwaki M, Yamamoto R, Furuta I and Fujimoto S. Fetal treatment of congenital heart block ascribed to anti‐SSA antibody: case reports with observation of cardiohemodynamics and review of the literature. AJRI 1999; 42:226–232

Postpartum thyroid dysfunction in women with normal thyroid function during pregnancy.

The aim of this study was to establish the risk of postpartum thyroid dysfunction (PPTD) in women who had normal thyroid function during pregnancy and no history of thyroid disease.

Management of Pregnancy with Congenital Antithrombin III Deficiency: Two Case Reports and a Review of the Literature

Women with antithrombin (AT) III deficiency are prone to pregnancy‐associated venous thromboembolism. We report 2 cases with genetically confirmed ATIII deficiency, one with a mutation in exon 3A and the other with an exon 4 deletion, in whom the pregnancies were successfully managed with prophylactic therapies for thrombosis. A 35‐year‐old pregnant woman was treated with intravenous infusions of ATIII concentrate alone, and the other 22‐year‐old pregnant woman was mainly treated with subcutaneous injections of heparin and oral low‐dose aspirin therapy. Both pregnancies resulted in vaginal deliveries of healthy neonates. The literature concerning prophylactic therapies for thrombosis in ATIII deficiency‐complicated pregnancy is reviewed, and the clinical problems, including the adverse effects of the therapies, are discussed.