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Among the physiological changes occurring during pregnancy, the benefits of morning sickness, which is likely mediated by human chorionic gonadotropin (HCG) and induces serum ketone production, are unclear. We investigated the relationship between serum levels of ketone bodies and HCG in the first, second, and third trimesters and neonatal body shape (i.e., birth weight, length, head circumference, and chest circumference) in 245 pregnant women. Serum levels of 3-hydroxybutyric acid peaked in late-stage compared with early stage pregnancy (27.8 [5.0−821] vs. 42.2 [5.0−1420] µmol/L, median [range], p < 0.001). However, serum levels of ketone bodies and HCG did not correlate with neonatal body shape. When weight loss during pregnancy was used as an index of morning sickness, a higher pre-pregnancy body mass index was associated with greater weight loss. This study is the first to show that serum ketone body levels are maximal in the third trimester of pregnancy. As the elevation of serum ketone bodies in the third trimester is a physiological change, high serum levels of ketone bodies may be beneficial for mothers and children. One of the possible biological benefits of morning sickness is the prevention of diseases that have an increased incidence due to weight gain during pregnancy.

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It is undetermined which blood variables related to iron storage during the first trimester of pregnancy could efficiently predict anemia occurring during the third trimester. Red blood cell count (RBC), hemoglobin concentration, hematocrit, ferritin, iron, and total iron binding capacity (TIBC) were assessed longitudinally during the first, second, and third trimesters of 231 healthy Japanese women. None of the patients had anemia in the first trimester and none used iron supplementation before the second trimester blood test. Anemia was defined as hemoglobin (Hb) < 11 g/dL for the first trimester and Hb < 10.0 g/dL for the third trimester. Forty-seven (20%) women developed anemia in the third trimester. The first trimester RBC, Hb, hematocrit, and ferritin levels were significantly lower in women with third-trimester anemia than those without anemia. The first trimester hemoglobin level exhibited a greater area under the curve of the receiver operating characteristic curve for prediction of the third trimester anemia than other blood variables; the optimal cut-off (12.6 g/dL) of hemoglobin yielded a sensitivity of 83% (39/47). First trimester hemoglobin levels were significantly better predictors of anemia during the third trimester than the indices of iron storage, including serum iron, ferritin, and TIBC levels.

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INTRODUCTION: The mortality due to uterine cervical cancer has been gradually increasing in women under 40 years of age (U40) in Japan. We investigated the effect of high-risk human papillomavirus (HR-HPV) on U40 subjects without any overt cytological abnormalities. MATERIALS AND METHODS: We retrospectively examined the clinical data, including the findings of a cobas 4800 HPV test that was approved in Japan in 2013 to triage women with atypical squamous cells of undetermined significance (ASC-US) and a histological examination in 589 Japanese women. RESULTS: The overall prevalence rate of HR-HPV was 34.5%. Biopsy-confirmed cervical intraepithelial neoplasia (CIN) 2, or worse (CIN2+) was identified in 45.1% (23/51) of HR-HPV-positive women with ASC-US, who underwent colposcopy immediately. The mean period from the HPV test to the diagnosis of CIN2+ was 3.7 months. CIN2+ was more common (69.6%) in U40 patients. The rates of single or multiple infections of HPV-16, HPV-18, and 12 other HR-HPV (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) in CIN2+ U40 patients were 31.3%, 0%, and 81.3%, respectively. The relative risk for CIN 2+ among U40 women with HPV-16 was not significantly different from that of the patients with infection of any of the 12 other HR-HPVs. CONCLUSION: The results of this study suggest that the 12 other HR-HPVs have a potential to generate high-grade cervical lesions among young women, and the examination rate of colposcopy should be increased.

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The present report describes a case of laparoscopic posterior pelvic exenteration of a primary adenocarcinoma of the rectovaginal septum (PARS) without associated endometriosis. A 49-year-old woman was admitted to hospital for rectal bleeding. Imaging studies showed a 7-cm solid tumor located in the rectovaginal septum, presenting with invasion to the posterior aspect of the uterine cervix and the anterior rectal wall. The patient received laparoscopic posterior exenteration and rectosigmoid anastomosis followed by chemotherapy. There were no intra- or post-operative complications. Histopathological examination of the neoplastic tissue revealed moderate to severe cytological atypia with bizarre multinucleated cells and prominent mitotic figures. Histopathologically, R0 resection was achieved. No endometriotic lesions were confirmed in the primary tumor or other removed tissues. Immunohistochemistry showed positive staining for cytokeratin (CK)7, cancer antigen 125, vimentin, estrogen receptor and p53, but negative staining for CK20, progesterone receptor, p40 and thyroid transcription factor 1. Based on these findings and on the location of the tumor, the neoplasm was diagnosed as PARS without associated endometriosis, which may have arisen from metaplasia of the embryological Müllerian-duct remnants.

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AIM: The aim of this study was to determine whether women with pregnancy-induced antithrombin deficiency (PIATD) had higher risk of liver dysfunction in the absence of thrombocytopenia. METHODS: We carried out a retrospective observational study at five centers in all 129 women with incidentally found PIATD among 5249 maternities and 129 control women without PIATD matched for number of fetuses and gestational week at delivery. PIATD was diagnosed in women with antenatal antithrombin (AT) activities of ≤75% followed by a further decrease to ≤65% peripartum. Liver dysfunction was defined as serum aspartate aminotransferase >  45 IU/L concomitant with lactate dehydrogenase >  400 IU/L. Thrombocytopenia was defined as platelet count < 120 × 109 /L. RESULTS: Thrombocytopenia (22% [28/129] vs 5.4% [7/129], P =  0.0001) and liver dysfunction (16% [20/129] vs 0.0% [0/129], P =  0.0000) occurred significantly more often in PIATD than in control women. Of the 20 women with liver dysfunction, 15 (75%) had PIATD, but not thrombocytopenia. Thus, even in the absence of thrombocytopenia, liver dysfunction occurred significantly more often in PIATD than in control women (15% [15/101] vs 0.0% [0/122], respectively, P =  0.0000). The relative risk (95% confidence interval) of liver dysfunction was 28.6 (1.64-500) for women with AT activity of 60-65% and 52.4 (3.17-865) for women with AT activity of <60%, compared to women with AT activity ≥66%. CONCLUSION: PIATD can occur in the absence of thrombocytopenia and PIATD women had higher risk of liver dysfunction even in the absence of thrombocytopenia.

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INTRODUCTION: It is unclear whether hysterotomy closure techniques can affect niche development. Therefore, this study aimed to analyze the effect of single-layer and double-layer interrupted closures of hysterotomy incisions during primary cesarean section on the formation of uterine niches. MATERIAL AND METHODS: A prospective cohort study of women undergoing primary cesarean section was performed between June 2011 and July 2014. Saline contrast sonohysterography was used to measure the niche depth and residual myometrium. The ratio of the niche depth to the sum of the niche depth and residual myometrium thickness (niche ratio) was calculated. RESULTS: Niches were identified in 14/58 (24.1%) women with single-layer sutures and 55/209 (26.3%) women with double-layer sutures (p = 0.74). Single-layer closure was associated with more than a five-fold increase in the odds of a niche ratio ≥0.4 (odds ratio 5.59; 95% CI 1.71-18.28). CONCLUSION: Single-layer closure may be associated with an increased risk of larger niches (niche ratio ≥0.4), although it may not increase the overall frequency of niche formation.

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INTRODUCTION: Some pregnant women develop significant proteinuria in the absence of hypertension. However, clinical significance of isolated gestational proteinuria (IGP) is not well understood. This study aimed to determine the prevalence of IGP in singleton pregnancies and the proportion of women with IGP who subsequently developed preeclampsia (IGP-PE) among all PE cases. MATERIAL AND METHODS: This was an observational study of 6819 women with singleton pregnancies at 12 centers, including 938 women with at least once determination of protein-to-creatinine ratio (P/Cr). Significant proteinuria in pregnancy (SPIP) was defined as P/Cr (mg/mg) level >0.27. IGP was defined as SPIP in the absence of hypertension. Gestational hypertension (GH) preceding preeclampsia (GH-PE) was defined as preeclampsia (PE) in which GH preceded SPIP. Simultaneous PE (S-PE) was defined as PE in which both SPIP and hypertension occurred simultaneously. RESULTS: IGP and PE were diagnosed in 130 (1.9%) and 158 (2.3%) of 6819 women, respectively. Of 130 women with IGP, 32 (25%) progressed to PE and accounted for 20% of all women with PE. Hence, women with IGP had a relative risk of 13.1 (95% CI; 9.2-18.5) for developing PE compared with those without IGP [25% (32/130) vs. 1.9% (126/6689)]. At diagnosis of SPIP, P/Cr levels already exceeded 1.0 more often in women with S-PE than in those with IGP-PE [67% (33/49) vs. 44% (14/32), respectively, p = 0.031]. CONCLUSIONS: IGP is a risk factor for PE, and IGP-PE accounts for a considerable proportion (20%) of all PE.

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BACKGROUND: The dipstick test is widely used as a primary screening test for detection of significant proteinuria in pregnancy (SPIP). However, it often shows a false positive test result. This study was performed to determine which pregnant women should be recommended to undergo determination of urinary protein-to-creatinine ratio (mg/mg, P/Cr test) after dipstick test for confirmation of SPIP. METHODS: This was a multicenter, prospective, and observational study of 2212 urine specimens from 1033 pregnant women who underwent simultaneous dipstick and P/Cr tests in the same spot urine samples at least once. SPIP was defined as P/Cr > 0.27. Preeclampsia was diagnosed in women with both hypertension and SPIP. RESULTS: Preeclampsia, hypertension alone, and SPIP alone developed in 202 (20 %), 73 (7.1 %), and 120 (12 %) women, respectively. Creatinine concentration [Cr] varied greatly, ranging from 8.1 to 831 mg/dL in the 2212 urine samples. Rate of positive dipstick test results increased with increasing [Cr], while SPIP prevalence rate was lower in urine samples with higher [Cr], yielding higher false positive rates in samples with higher [Cr]. Postpartum urine samples had significantly lower [Cr] compared to those obtained antepartum (60 [8.7-297] vs. 100 [10-401] mg/dL, respectively). At the first P/Cr test among women with similar dipstick test results, the risk of having SPIP was consistently and significantly higher for hypertensive women than for normotensive women at any dipstick test result: 18 % (14/77) vs. 3.2 % (8/251), 47 % (26/55) vs. 8.7 % (37/425), 91 % (82/90) vs. 59 % (44/75) for negative/equivocal, 1+, and ≥ 2+ test results, respectively. The risk of SPIP was 16 % (9/55) for normotensive women when two successive antenatal urine samples showed a dipstick test result of 1 + . CONCLUSIONS: For prediction of SPIP, the dipstick test was more likely to show a false positive result in concentrated urine samples with higher [Cr]. Hypertensive women with ≥ 1+ as well as normotensive women with ≥ 2+ on dipstick test should be advised to undergo the P/Cr test.

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Preeclamptic twin pregnancy with larger gestational weight gain (GWG) is suggested to have a higher risk of peripartum cardiomyopathy (PPCM). This was true in a 5-year experience at a single center. A primiparous woman with twins and prepregnancy weight of 51.0 kg exhibited hypertension at gestational week (GW) 32(-6/7) and GWG of 18.3 kg (6.0 kg and 2.9 kg during the last four weeks and one week of gestation, resp.) concomitant with generalized edema, gave birth at GW 34(-4/7), developed proteinuria, cough, and dyspnea postpartum, and was diagnosed with preeclampsia and PPCM showing left ventricular ejection fraction of 34% and plasma BNP level of 1530 pg/mL. This was the only case of PPCM among 101 (12 with preeclampsia) and 3266 women with twin and singleton pregnancies, respectively. Thus, PPCM occurred significantly more often in women with preeclamptic twin pregnancies than in women with singleton pregnancies (8.3% [1/12] versus 0.0% [0/3266], P = 0.0355). This patient showed the greatest weight gain of 6.0 kg during the last four weeks of gestation and the greatest weight loss of 19.2 kg during one month postpartum among 90 women with twin deliveries at GW ≥ 32.

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OBJECTIVE: To examine the pathophysiology of reductions in antithrombin (AT) activity during pregnancy and to better characterize the laboratory features of pregnant women with severely depressed AT activity. METHODS: Laboratory variables for blood samples obtained within 5 d prior to delivery were compared among three women groups with severely depressed (<45%, n = 6), modestly depressed (45-69%, n = 10), and normal AT activity levels (>70%, n = 134). RESULTS: Pregnancy-induced hypertension was present in 16.7% (1/6), 30.0% (3/10), and 9.0% (12/134) of the women with the above-mentioned AT activities, respectively. The AT activities were significantly and negatively correlated with the D-dimer, urate, and creatinine levels. The D-dimer level was significantly and negatively correlated with the fibrinogen level. Women with AT activity <45% exhibited markedly elevated levels of hemoglobin and liver enzymes and a significantly lower level of fibrinogen than the other women groups, while the platelet count did not differ among the three groups. CONCLUSIONS: Enhanced thrombin generation was involved in the decrease in AT activity. AT activity can decrease in the absence of thrombocytopenia. The liver dysfunction that was seen in cases with severely depressed AT activity may have resulted from impairments in liver perfusion caused by microthromboses generated as a result of the relative lack of AT and/or the shortage of circulating plasma in women with reduced AT activities.

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AIM: To examine the incidence of umbilical cord presentation, including cord prolapse (UCP) and cord descent (UCD), after the use of a trans-cervical balloon catheter (TCBC), such as a Foley catheter and a metreurynter, for the induction of labor (IOL). METHODS: A retrospective medical chart review was conducted, focusing on the occurrence of UCP and UCD in 800 women who underwent IOL with a TCBC at five hospitals during the study period (2008-2009 for two hospitals and 2006-2009 for three hospitals). The five hospitals had a total of 8245 deliveries during the study period. UCP and UCD were defined as the descent of the umbilical cord in advance of the presenting fetal part in the presence and absence of rupture of fetal membranes, respectively. RESULTS: The frequency of IOL using a TCBC with 70-250 mL of saline varied among the five hospitals from 4.9% to 18.8% (mean ± SD, 10.7 ± 5.0%). UCP and UCD occurred in two and four women, respectively, with the frequency of cord presentation varying among the hospitals from 0.0% to 1.8% (mean ± SD, 0.9 ± 0.9%); the cord presentation was significantly more likely to occur when 180-250 mL of saline was used, compared with when 70-150 mL of saline was used (8.2% [5/61] vs 0.15% [1/662], P < 0.0001). A change in the presenting fetal body part also occurred in 0.5% (4/800) of the women. CONCLUSION: The use of a TCBC with 180-250 mL of saline increases the risk of cord presentation.

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We report a 32-year-old woman (1-gravid, 1-para) with a vesicular lesion in her uterus that was pointed out on ultrasound at 8 weeks' gestation. Amniocentesis at 15 weeks' gestation showed a normal female karyotype, 46XX. As the pregnancy advanced, the mole-like lesion became relatively reduced. Throughout gestation, the maternal human chorionic gonadotropin level was normal, but the serum alpha fetoprotein level rose as her pregnancy progressed. Her fetus did not exhibit any remarkable anomalies. The patient visited our hospital complaining of a diminished feeling of fetal movements at 36 weeks 5 days' gestation, and intrauterine fetal death (IUFD) was confirmed. She delivered a 2336-g female without any definite anomalies. A pathological examination led to a diagnosis of placental mesenchymal dysplasia, and androgenetic/biparental mosaicism in the placenta was identified using p57kip2 immunohistochemical staining. And it also revealed that the rupture of the cirsoid chorionic vessels had led to IUFD.

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The impact of cytomegalovirus (CMV) infection of the genital tract during pregnancy on adverse pregnancy outcomes is not understood fully. A real-time PCR assay was used to determine vaginal shedding of CMV in 993 healthy pregnant Japanese women and the results were compared with the outcome of pregnancy. CMV DNA was detected in 76 (7.7%) of the women. The outcome of pregnancy could be determined finally in 848 women, of whom 60 (7.1%) were CMV positive. The carriers of CMV had an increased miscarriage rate (RR 6.96, 95% CI 2.04-23.84, P < 0.01). These findings suggest that latent genital tract CMV infection predisposes to adverse pregnancy outcomes.

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To examine the association between colonization by two newly classified species of genital ureaplasmas (Ureaplasma parvum and U. urealyticum) in early pregnancy and subsequent late abortion or preterm birth at <34 weeks of gestation, four species of genital mycoplasmas--Mycoplasma genitalium, M. hominis, U. parvum, and U. urealyticum--as well as Chlamydia trachomatis and Neisseria gonorrhoeae were examined by PCR-based methods in a prospective cohort study of 877 women with singleton pregnancies at <11 weeks of gestation. Antibiotics were used only in cases in which C. trachomatis and/or N. gonorrhoeae was detected. Multivariate logistic-regression analysis was used to assess independent risk factors after taking maternal low body weight and past history of preterm birth into account. M. genitalium, M. hominis, U. parvum, U. urealyticum, C. trachomatis, and N. gonorrhoeae were detected in 0.8%, 11.2%, 52.0%, 8.7%, 3.2%, and 0.1% of these 877 women, respectively. Twenty-one (2.4%) women experienced late abortion or preterm birth at <34 weeks of gestation. Three factors-detection of U. parvum in the vagina (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.1 to 8.5); use of antibiotics, such as penicillin and cefatrizine, for incidental inflammatory complications before 22 weeks of gestation (OR, 4.2; 95% CI, 1.6 to 10.0); and past history of preterm birth (OR, 10.4; 95% CI, 2.7 to 40.5)-were independently associated with late abortion and preterm birth. In conclusion, vaginal colonization with U. parvum, but not U. urealyticum, is associated with late abortion or early preterm birth.

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It is possible that women with triplet pregnancies are more likely to exhibit pregnancy-induced antithrombin deficiency, gestational thrombocytopenia, and perinatal elevation in serum aspartate aminotransferase (AST) than women with twin pregnancies. We retrospectively reviewed changes in antithrombin activity, platelet count, and blood chemistry in 23 twin and seven triplet pregnancies in which the mothers received antenatal care and gave birth in our hospital during 1999 and 2001. Both antithrombin activity and platelet counts gradually decreased until delivery, then promptly increased after delivery in both twin and triplet pregnancies. A significantly larger number of women developed gestational thrombocytopenia of < 100 x 10 (9)/L (43% [three of seven] versus 4.3% [one of 23]; p < 0.01) and pregnancy-induced antithrombin deficiency of < 60% of normal activity (57% [four of seven] versus 17% [four of 23]; p < 0.05) in triplet than in twin pregnancies. Eight women with pregnancy-induced antithrombin deficiency, including three women with gestational thrombocytopenia, were significantly more likely to develop perinatal elevations of AST, lactate dehydrogenase, serum creatinine, fibrin/fibrinogen degradation products, and D-dimer than were those without pregnancy-induced antithrombin deficiency. These findings suggest that women with triplet pregnancies are at an increased risk of the HELLP syndrome and acute fatty liver of pregnancy compared with women with twin pregnancies.

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Two cases with a large cystic mass within the placenta are reported. By ultrasonography, it was found that both women had a subchorionic hypoechoic lesion (11.0 x 4.8 x 4.0 cm and 6.6 x 3.7 x 2.2 cm, respectively) at 24 and 35 weeks of gestation, respectively. In both cases, turbulent blood flow generated by a pulsatile jet flow (pulse rate; 40 to 60 beats per minute) into the cystic lesion seen on real-time imaging and lesions being low intensity on T1-weighted and isointensity on T2-weighted magnetic resonance image suggested that they contained fresh maternal blood. In both cases, the sonolucency of the lesions did not change until cesarean deliveries of females, both of whom were small-for-gestational-age infants (1940 g at 37 weeks and 2195 g at 37 weeks, respectively). Biochemical analysis of the fluid in the cystic lesion sampled during the cesarean section in the latter case confirmed that the fluid had originated from the maternal blood. These lesions histologically corresponded to large avillous areas surrounded by normal villi. Thus, a huge placental lake was diagnosed in both cases.

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PROBLEM: Enhanced secretion of type-2 T-helper (Th2) cytokine is a characteristic feature in normal physiological pregnancy. A study has demonstrated defective production of interleukine-4 (IL-4) and other Th2 cytokine in women with recurrent pregnancy loss (RPL). Several studies have suggested that IL-4 variable number of tandem repeat (VNTR) gene polymorphism is probably associated with different IL-4 production. METHODS OF STUDY: The IL-4 VNTR genotypes were assessed in 109 Japanese women with RPL and 210 ethnically matched women experiencing at least one live birth and no spontaneous abortion. RESULTS: No significant differences in IL-4 VNTR genotype frequencies were found between the RPL and the control [B1B1 genotype (reference); B1/B2 and B2/B2 genotypes, odds ratio, 0.91; 95% confidence interval, 0.58-1.45]. CONCLUSION: The present study suggests that the IL-4 VNTR allele is not a major genetic regulator in RPL.

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Hypochondroplasia is an autosomal dominant skeletal dysplasia expressing postnatal onset of short stature with mild rhizomelic shortening of the limbs. This manifestation leads to restricted prenatal diagnosis of the disorder. We report here on a sporadic case of a hypochondroplastic baby, whose prenatal sonographic measurements were serially recorded from 19 weeks of gestation. Mild shortening of the limbs became manifest after 26 weeks of gestation. Biparietal diameter was within the normal range throughout gestation. Both parents were of average stature. A tentative diagnosis of a nonlethal short-limb skeletal dysplasia was made. At birth, the clinical manifestations of the neonate were not characteristic, but the radiographic features raised the possibility of hypochondroplasia. Molecular analyses revealed a C to G mutation at nucleotide 1659 of the fibroblast growth factor receptor 3 (FGFR3) gene, a common mutation in hypochondroplasia.

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Intrauterine fetal growth restriction is a multifactorial disorder, and its aetiology includes both environmental and genetic components. We aimed to investigate whether maternal genetic polymorphisms of metabolic enzymes affects fetal growth and pregnancy duration. Genomic DNA was obtained from 134 women who experienced singleton deliveries beyond 24 weeks of gestation. Maternal age, birth weight, gestational age at birth and frequencies of fetal growth restriction, prematurity and pregnancy-induced hypertension were compared among genotypic subgroups of cytochrome p450 (CYP) and glutathione S-transferase (GST) genes. The polymorphisms of CYP1A1 (MspI), CYP17 (MspAI) and GSTP1 (BsmAI) genotypes, and the presence or absence of GSTM1 and GSTT1 genes were analysed by PCR-based methods. The frequency of fetal growth restriction (<10th percentile/<-1.5 SD; 22.7%/11.4%) in 44 women who were homozygous for the A1 allele (A1A1) of CYP17 was significantly higher than that (7.8%/2.2%) in 90 women who carried the A2 allele (A1A2/A2A2) of CYP17 (P < 0.05), with an odds ratio =3.41 (95% confidence interval = 1.18-9.84). The gestational age at birth (mean +/- SD, 37.5 +/- 3.1 weeks) in 67 women with GSTM1 null genotype was significantly lower than that (38.5 +/- 2.4 weeks) in 67 women who carried GSTM1 (P < 0.05). The polymorphism of CYP17 that encodes the cytochrome p450c17alpha enzyme might be associated with the pathophysiology underlying fetal growth restriction.

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OBJECTIVE: The aim of this study was to elucidate the clinical characteristics of uterine leiomyomas having abnormal chromosome karyotype. STUDY DESIGN: A total of 394 myomas were obtained from 213 patients for cytogenetic analysis. The size (number of nodules=144), histopathology (n=302), and gonadotropin-releasing hormone analogue (GnRHa)-response (n=58) were investigated in relation to chromosome karyotype in myomas. RESULTS: 302 myomas from 166 patients were successfully karyotyped. A total of 21 myomas from 21 patients showed abnormal chromosome karyotype. The high frequencies of involved chromosomes 12, 14, 1, 7 were observed. The diameters of myomas with abnormal karyotype were significantly larger than those of myomas with normal karyotype. The frequency of the degeneration in myomas with abnormal karyotype was significantly higher than that with normal karyotype. The reduction rate in size of myomas by GnRHa treatments did not differ between the two types (karyotype normal versus abnormal) of nodules. CONCLUSIONS: Chromosomally abnormal myomas were larger in diameter and showed a higher frequency of degeneration, suggesting that the cytogenetic background in uterine leiomyoma affects a tumor's growth potential.

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