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Objective: This study was performed to evaluate the application of fetal middle cerebral artery peak systolic velocity (MCA-PSV) for prediction of newborn anemia with umbilical cord blood hemoglobin concentration at birth (UCB-Hb) < 10.0 g/dL among infants born at gestational week (GW) ≥ 36 to unselected women., Materials and Methods: We reviewed the medical charts of 699 women giving birth to singleton infants at GW ≥ 36 with available data on MCA-PSV measured at GW ≥ 25 at the discretion of the attending physician. Multiple of the median (MoM) MCA-PSV (MCA-PSV MoM) > 1.5 was defined as a positive MCA-PSV test result., Results: The MCA-PSV test was applied 2309 times (313 and 1996 times during second and third trimesters, respectively) in 699 women. The results were positive in 4.4% (102/2309) of tests and at least once in 9.9% (69/699) of women. Anemic infants were born to one (1.4%) and six (1.0%) of 69 and 630 women with and without at least one positive test result, respectively. MoM determined 4, 3, and 2 weeks before birth showed significant weak negative correlations with UCB-Hb at birth (correlation coefficient: 0.298-0.325)., Conclusions: Among unselected women giving birth at or near term, the MCA-PSV test was unsatisfactory for prediction of newborn anemia in this retrospective observational study., (Copyright © 2019. Published by Elsevier B.V.)

Although the effects of prenatal passive smoking on birth weight have been reported, the effects of metabolic gene polymorphisms on passive smoking have not been studied. Therefore, we investigated the effects of maternal passive smoking and metabolic gene polymorphisms on child growth up to 3years of age using cotinine as a biomarker. We included 1356 Japanese participants in a prospective cohort between 2003 and 2007 (cotinine levels at the third trimester≤0.21ng/mL and 0.22 to 11.48ng/mL for non-passive and passive smokers, respectively), and measured child outcomes such as weight, length, head circumference, and Kaup index. Additionally, we analyzed cytochrome P450 1A1 (CYP1A1), epoxide hydrolase 1 (EPHX1), and two N-acetyltransferase 2 (NAT2) genotypes using real-time polymerase chain reaction methods. Associations were investigated using multiple regression models. Kaup index gain from birth up to 3years of age was significantly smaller in children born to passive smokers than in those born to non-passive smokers (-0.34kg/m 2 ; 95% confidence interval: -0.67, -0.01). Maternal CYP1A1 genotype was not associated with prenatal passive smoking and Kaup index gain, but was significantly associated with prenatal passive smoking and head circumference gain from birth up to 3years of age (-0.75cm; 95% confidence interval: -1.39, -0.12). Thus, this study suggests that prenatal passive smoking may have potent effects on postnatal growth from birth up to 3years of age. Moreover, children with maternal CYP1A1 genotype may be more susceptible to the effects of prenatal passive smoking., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: This study was performed to determine how often Japanese women diagnosed as normoglycemic on first-trimester 75-g glucose tolerance test (75gGTT) later develop gestational diabetes mellitus (GDM)., Material and Methods: Sixty-two women with random plasma glucose (PG) level ≥ 105 mg/dL during the first trimester and subsequent first-trimester diagnosis of normoglycemia with 75gGTT underwent 50-g glucose challenge test (50gGCT) during the second trimester. Twenty-one with a positive 50gGCT result (60-m PG ≥ 140 mg/dL) underwent second-trimester 75gGTT. First-trimester random PG levels and 75gGTT results were compared between 21 and 41 women with positive and negative 50gGCT results, respectively. Changes in immunoreactive insulin (IRI) associated with 75gGTT were determined simultaneously., Results: All 21 women with a positive 50gGCT result showed normoglycemia on second-trimester 75gGTT. Thus, none of the 62 women developed GDM. Insulin resistance increased significantly in the 21 women with 75gGTT during the first and second trimesters, as indicated by increases in homeostasis model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment for β-cell function (HOMA-β) with no significant changes in preload or afterload PG levels. Neither random PG levels (116 ± 12 vs. 116 ± 12 mg/dL, respectively) nor 75gGTT results (86 ± 6 vs. 84 ± 5 mg/dL for 0-minute [0-m] PG level, 130 ± 28 vs. 131 ± 25 mg/dL for 60-m PG, and 111 ± 19 vs. 118 ± 18 mg/dL for 120-m PG, respectively) during the first trimester differed significantly between the 41 and 21 women with negative and positive second-trimester 50gGCT results, respectively., Conclusion: Although insulin resistance increased in the second trimester, risk of developing GDM was < 1/62 among Japanese women in whom hyperglycemia was excluded with first-trimester GTT., (Copyright © 2016. Published by Elsevier B.V.)

Background: It was recently suggested that platelet reactivity is reduced in early pregnancy. This study was performed to determine whether the citrated whole blood from 33 pregnant women in their first trimester showed spontaneous platelet aggregation and whether it differed in extent from that of 11 non-pregnant women., Methods: The platelet count and number of platelet aggregates (PA) were serially determined in the same citrated whole blood specimens at 15, 30, 45, 60, 75, and 90min after blood sampling using a hematology analyzer., Results: The number of PA increased significantly at 30min and thereafter in both groups, but was consistently lower for pregnant than non-pregnant women over the 90-min observation period. The platelet count decreased significantly in a time-dependent manner in both groups, but was significantly lower at 30 and 90min for non-pregnant than pregnant women. The number of PA showed a significant positive correlation with net decrease in platelet count for both pregnant and non-pregnant women. PA counts were also significantly positively correlated with the mean platelet volume., Conclusion: Platelet reactivity monitored by the increase in number of PA and the fall in platelet count was reduced in early pregnancy compared with non-pregnant healthy controls., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Fetomaternal hemorrhage (FMH) can cause severe morbidity. However, perinatal risk factors for long-term poor outcome due to FMH have not been extensively studied., Aims: To determine which FMH infants are likely to have neurological sequelae., Study Design: A single-center retrospective observational study. Perinatal factors, including demographic characteristics, Kleihauer-Betke test, blood gas analysis, and neonatal blood hemoglobin concentration ([Hb]), were analyzed in association with long-term outcomes., Subjects: All 18 neonates referred to a Neonatal Intensive Care Unit of Kagoshima City Hospital and diagnosed with FMH during a 15-year study period. All had a neonatal [Hb] <7.5g/dL and 15 of 17 neonates tested had Kleihauer-Betke test result >4.0%., Outcome Measures: Poor long-term outcome was defined as any of the following determined at 12 month old or more: cerebral palsy, mental retardation, attention deficit/hyperactivity disorder, and epilepsy., Results: Nine of the 18 neonates exhibited poor outcomes. Among demographic characteristics and blood variables compared between two groups with poor and favorable outcomes, significant differences were observed in [Hb] (3.6±1.4 vs. 5.4±1.1g/dL, P=0.01), pH (7.09±0.11 vs. 7.25±0.13, P=0.02) and base deficits (17.5±5.4 vs. 10.4±6.0mmol/L, P=0.02) in neonatal blood, and a number of infants with [Hb]≤4.5g/dL (78%[7/9] vs. 22%[2/9], P=0.03), respectively. The base deficit in neonatal arterial blood increased significantly with decreasing neonatal [Hb]., Conclusions: Severe anemia causing severe base deficit is associated with neurological sequelae in FMH infants., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To investigate whether planning of pregnancy in women with epilepsy affects seizure control during pregnancy and to compare the maternal and neonatal outcomes in planned and unplanned pregnancies., Methods: This was a retrospective cohort study of 153 pregnant women with epilepsy who were treated at the University of Tsukuba Hospital and Hokkaido University Hospital between 2003 and 2011. Twenty-one pregnancies were excluded due to insufficient data. Data of patients followed by neurologists during their planned pregnancies (planned-pregnancy group, n=51) were compared to those of patients referred to neurologists after conception for managing epilepsy during pregnancy (unplanned-pregnancy group, n=81). The treatment profile for epilepsy, seizure control, and maternal and neonatal outcomes in both groups were compared using Chi-square test or Fisher's exact test and Mann-Whitney U test., Results: Compared to the unplanned-pregnancy group, the planned-pregnancy group showed a significantly greater proportion of patients receiving monotherapy with antiepileptic drugs (80% vs. 61%: planned vs. unplanned, P=0.049) and those not requiring valproic acid (77% vs. 56%, P=0.031). Furthermore, the frequency of epileptic seizures (16% vs. 35%, P=0.018) and changes in antiepileptic drugs (24% vs. 41%, P=0.042) were significantly lower in the planned-pregnancy group than in the unplanned-pregnancy group. No significant intergroup differences were noted in the obstetric complications and neonatal outcomes, including congenital malformations., Conclusion: For women with epilepsy, planning of pregnancy is associated with good seizure control during pregnancy and less fetal exposure to antiepileptic drugs., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the association of the N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP) levels with plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in singleton pregnancies., Design: Serum NT-proBNP levels, PRA and PAC were determined in 215 blood specimens from 139 women with singleton pregnancies, including 34 and 105 women who did and did not develop hypertensive disorders in pregnancy, respectively. Twenty-five blood specimens were obtained from 25 women who later developed hypertension (systolic BP⩾140mmHg and/or diastolic BP⩾90mmHg), but were normotensive at the time of blood sampling., Results: The serum NT-proBNP levels [pg/ml, median (range), 32 (5-142)] did not change in normotensive women, but increased significantly to 97 (23-436) after the development of hypertension (D/H). The PRA [ng/ml/h, median (range), 7.1 (1-20)] did not change in normotensive women, but decreased significantly to 1.9 (1-16) after D/H. PAC (pg/ml) increased significantly from 397 (94-1750) to 667 (123-2010) between the 2nd and 3rd trimesters in normotensive women. However, as PAC of hypertensive women did not change significantly before and after D/H, PAC [293 (116-1720)] after D/H was significantly lower than that [667 (123-2010)] of the 3rd trimester in the normotensive women. The serum levels of NT-proBNP were significantly and negatively correlated with both PRA and PAC., Conclusions: The renin-angiotensin-aldosterone system is suppressed in pregnant women with cardiac conditions associated with higher NT-proBNP levels., (Copyright © 2013 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To assess adverse fetal outcomes and short-term prognoses of infants exposed to oseltamivir or zanamivir in utero during pandemic (H1N1) 2009 in Japan., Study Design: Case series study. We asked the 2611 obstetric facilities in Japan that are members of the Japan Society of Obstetrics and Gynecology to participate, and data were provided from 157 facilities. We evaluated the numbers of pregnancy complications and neonatal abnormalities., Results: We evaluated 624 infants born to 619 women given oseltamivir and 50 infants born to 50 women given zanamivir. Of patients given oseltamivir before gestational week 22, 3 experienced miscarriage and 1 experienced induced abortion. The overall rate of congenital malformations was 2.1% (14/670). In infants exposed during the first trimester, the rate of malformations was 1.3% (2/156) with oseltamivir and 0.0% (0/15) with zanamivir, although in infants exposed during the second and third trimesters, this rate was 2.6% (12/464) with oseltamivir and 0.0% (0/35) with zanamivir. Increased rates of miscarriage in women given antiviral drugs before gestational week 22 (0.9% [3/322]), preterm delivery in women given antiviral drugs before gestational week 37 (5.5% [33/600]), stillbirth (0% [0/670]), neonatal death (0.15% [1/670]), birthweight <2500 g (8.7% [58/670]), small-for-gestational-age infants (8.4% [56/670]), necrotizing enterocolitis (0.0%), intraventricular hemorrhage (0.0%), seizures (0.15% [1/670]), and other transient abnormalities in the neonatal period (4.3% [29/670]) were not observed in those exposed to antiviral drugs before the corresponding episodes or complications., Conclusion: Short-term prognoses of infants exposed to oseltamivir or zanamivir in utero were not adversely affected., (Copyright © 2013 Mosby, Inc. All rights reserved.)

We performed a retrospective review of medical charts regarding blood d-dimer levels determined cross-sectionally by the latex agglutination assay in 1952 samples from 1185 women to determine changes in d-dimer levels according to the stage of pregnancy. Three of 17 women in whom further investigations were performed were found to have clinical venous thromboembolism (VTE). The median and 95th percentile values of d-dimer (μg/mL) in the 1182 women without clinical VTE, 0.54 and 2.41 at gestational week (GW) 4-13, increased gradually to 1.22 and 5.03 at GW 14-27, 1.81 and 6.18 at GW 28-35, and 2.13 and 5.85 at GW 36-42, respectively. A total of nine women (0.76%), including three women with clinical VTE, exhibited a d-dimer level >14.0μg/mL, which was well above the 99th percentile for any stage of pregnancy. Thus, 3 (33%) of the nine with a d-dimer level >14μg/mL developed clinical VTE, while none of the remaining 1176 women with a d-dimer level ⩽14μg/mL developed clinical VTE. Although further prospective studies are required, our results suggested that there is a certain cut-off d-dimer value that would allow us to differentiate between pregnant women with and without clinical VTE., (Copyright © 2013 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To determine how urine dipstick test, edema, and/or excessive weight gain (EWG, defined as ⩾500g/week) at antenatal visits predict significant proteinuria (defined as a protein-to-creatinine ratio [P/Cr, mg/mg] ⩾0.27) and preeclampsia., Methods: Data from 3279 antenatal visits between 30 and 36weeks of gestation were studied in 783 women with singleton pregnancies. In 24 preeclamptic pregnancies, data from 89 antenatal visits at and before diagnosis of preeclampsia were used. Spot P/Cr was determined in women with repeated positive dipstick test results in two successive antenatal visits or in those with a positive dipstick test result tested in the presence of hypertension., Results: Proteinuria on dipstick test, edema, and EWG appeared often in both women with and without preeclampsia; 66.7% vs. 27.7%, 83.3% vs. 44.1%, and 91.7% vs. 81.6%, respectively. However, repeated positive dipstick test results in two successive antenatal visits yielded sensitivity of 45.5%, specificity of 95.2%, and positive and negative predictive values of 30.0% and 97.4%, respectively, for detection of significant proteinuria and corresponding figures of 33.3%, 94.1%, 14.0%, and 98.0% for prediction of preeclampsia., Conclusion: Repeated positive dipstick test results in two successive antenatal visits warrant a need for a confirmation test of significant proteinuria., (Copyright © 2013 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Complete automation of high-performance liquid chromatography (HPLC) for determination of hemoglobin F (%Hb F) and hemoglobin A1c (%Hb A1c) levels has made this procedure available in many clinical laboratories. However, the physiological changes in %Hb F during pregnancy and the effects of physiological and supraphysiological levels of %Hb A1c on measurement of %Hb F have not been studied extensively., Methods: Simultaneous determination of %Hb F and %Hb A1c was conducted in 490 blood samples obtained before (n=21), during the 1st (n=150), 2nd (n=116), and 3rd (n=192) trimesters of pregnancy, and postpartum (n=11) from 357 women, including 60 women with hyperglycemia but unaffected by clinical fetomaternal hemorrhage, by HPLC., Results: Mean (SD) Hb F levels were 0.71% (0.25%) before pregnancy. The value of 0.82% (0.47%) during the 1st trimester decreased significantly to 0.66% (0.35%) during the 2nd trimester and to 0.58% (0.38%) during the 3rd trimester. The level was 0.62% (0.31%) approximately one year after delivery. Thus, %Hb F was highest during the 1st trimester of pregnancy. The effects of varied %Hb A1c levels on %Hb F measurements were clinically negligible., Conclusions: The data presented in this work may be used as reference intervals of %Hb F determined with HPLC during pregnancy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Twin pregnancy differs considerably from singleton pregnancy in many aspects and it is unknown how serum NT-proBNP level behaves in women with twin pregnancies. Serum NT-proBNP levels were determined longitudinally at gestational weeks (GW) 24 and 35 in normotensive women with 13 twin and 99 singleton pregnancies. The effects of maternal demographic characteristics on NT-proBNP levels were also analyzed. The serum NT-proBNP levels (pg/ml) in twin pregnancies, which were not different from those in singleton pregnancies at 24 GW (26±15 vs. 40±27, respectively, P=0.0718), increased significantly (P=0.0038) and were significantly higher than those in singleton pregnancies at 35 GW (72±49 vs. 34±24, P<0.0001). In the analysis including women with singleton pregnancies, the serum levels of NT-proBNP at 35 GW were significantly inversely correlated with pre-pregnancy body mass index (BMI, kg/m(2)) and were significantly higher in nulliparous than multiparous women. Thus, women with twin pregnancy were likely to exhibit an increase in serum NT-proBNP levels in the late stage of pregnancy, especially in lean and nulliparous women. The relative greater blood volume expansion occurring in twin than in singleton pregnancies was considered to be responsible for this phenomenon., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Although abruptio placentae causes hypoxia in the infant and thus leading to cerebral palsy (CP), its incidence and clinical features at a nationwide level have not been demonstrated., Aims: To determine the proportion of abruptio placentae among antenatal and intrapartum causative factors leading to cerebral palsy (CP) and clinical features of such abruptio placentae., Study Design: A review was conducted in 107 infants with CP in whom CP was determined to be due to antenatal and or intrapartum hypoxic conditions by the Japan Council for Quality Health Care until April 2012., Results: Abruptio placenta was responsible for 28 (26%) of the 107 CP infants, and was the single leading causative factor of CP. Of these 28 women, 22 (79%) exhibited non-reassuring fetal status on admission to obstetric facilities at 36.2 ± 2.6 weeks of gestation and had neonates with umbilical cord arterial blood pH (base excess) of 6.728 ± 0.164 (-25 ± 5.4 mmol/L). In these 22 women, strong abdominal pain and/or profuse vaginal bleeding occurred 159 ± 99 min prior to admission to an obstetric facility, and the interval until delivery after admission was 47 ± 31 min. Hypertension or isolated proteinuria preceded clinical events in one (4.5%) and five (23%) of these 22 women, respectively., Conclusions: Abruptio placentae was responsible for CP in one quarter of all cases determined to be due to antenatal and/or intrapartum hypoxic conditions in Japan. New strategies to shorten the interval until admission to an obstetric facility after onset of symptoms are urgently needed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Recent studies indicate that insulin resistance resulting from altered post-receptor signaling is associated with polycystic ovary syndrome (PCOS). We hypothesized that insulin receptor substrate-1 (IRS-1) Gly972Arg polymorphism and/or ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Lys121Gln polymorphism predisposes women to PCOS and that these polymorphisms also affect anthropometric variables, glucose metabolism and androgen synthesis. To test those ideas, we studied the genotypes, indexes of insulin resistance, and hormone profiles in 123 Japanese women with PCOS and 380 healthy Japanese controls. We found that there were significantly more IRS-1 972Arg carriers among the PCOS patients than among the healthy controls (10.6% vs. 4.8%, p=0.029), which is consistent with our finding that women carrying the IRS-1 972Arg allele had a significantly increased risk of developing PCOS (odds ratio: 3.31, 95% confidence interval: 1.49-7.35). By contrast, the ENPP1 Lys121Arg polymorphism was distributed equally among PCOS patients and controls. In addition, neither of these polymorphisms studied affected the anthropometric variables, metabolic parameters or androgen levels of women with PCOS. We conclude that the IRS-1 Gly972Arg polymorphism is associated with PCOS in the Japanese population.

Adenomyomectomy is a treatment option to preserve fertility and reduce symptoms associated with adenomyosis. Although this procedure is reasonably expected to increase the risk of uterine rupture during pregnancy, reports on this issue are scarce. We recently encountered a 33-year-old nulliparous woman with a twin pregnancy who experienced a spontaneous uterine rupture at 30 weeks' gestation. This patient was the first to conceive after undergoing laparoscopic adenomyomectomy at our institution. Her pregnancy was established with in vitro fertilization-embryo transfer 12 months after laparoscopic adenomyomectomy. The uterine rupture was heralded by a sudden onset of severe abdominal pain while she was receiving intravenous ritodrine. This case reinforces that pregnancy after adenomyomectomy should be closely monitored with respect to uterine rupture.