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Background and Aim: Liver dysfunction with decreased antithrombin activity (AT) and/or thrombocytopenia is life-threatening in pregnant women. Whether AT is clinically useful for prediction of liver dysfunction remains unclear. Methods: A total of 541 women were registered prospectively at gestational week 34.7 (20.0 - 41.4) with available data on antenatal AT and platelet count (PLC). Results: Liver dysfunction defined as serum AST > 45 IU/L concomitant with lactate dehydrogenase (LDH) > 400 IU/L occurred in five women antenatally (≤ 2 weeks before delivery) and in 17 women postpartum (within 1 week postpartum). Median (5th - 95th) antenatal value was 85 (62 - 110)% for AT and 202 (118 - 315)×10^9/L for PLC in the 541 women, and was significantly lower in women with than without perinatal liver dysfunction; 75 (51 - 108) vs. 86 (62 - 110)% and 179 (56 - 244) vs. 203 (121 - 316)×10^9/L, respectively. Nineteen (86%) women with liver dysfunction showed AT ≤ 62% or thrombocytopenia (PLC ≤ 118×10^9/L) perinatally, but five lacked thrombocytopenia throughout the perinatal period. The best cut-off (AT, 77%; PLC, 139×10^9/L) suggested by receiver operating characteristic curve gave antenatal AT and PLC sensitivity of 59% and 41% with positive predictive value (PPV) of 8.6% and 14%, respectively, and combined use of AT and PLC improved sensitivity to 73% (16/22) with PPV of 9.2% for prediction of perinatal liver dysfunction. Conclusions: Reduced AT not accompanied by thrombocytopenia can precede liver dysfunction. Clinical introduction of AT may enhance safety of pregnant women.

Aims: This study was performed to determine the associations between serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) levels at mid-gestation with the risk of small for gestational age (SGA) neonates born at gestational week (GW) ≥ 36 in healthy women. Methods: PlGF and sFlt-1 concentrations were determined at GW 24-27 in 183 women with births at GW ≥ 36, but without gestational diabetes mellitus and hypertension. Results: Thirteen (7.1%) SGA neonates were born. Median (range) GW at blood sampling was similar between women with and without SGA (25 [24-25] and 24 [24-27], respectively, P = 0.671). Pre-pregnancy body mass index (BMI) and PlGF levels were significantly lower in women with than without SGA, while sFlt-1 levels and sFlt-1:PlGF ratio (sFlt-1/PlGF) did not differ significantly between the two groups. PlGF and sFlt-1/PlGF, but not BMI or sFlt-1, showed significant correlations with birthweight z-score; the correlation was positive for PlGF and negative for sFlt-1/PlGF. Women with PlGF level < 10th percentile and those with sFlt-1/PlGF level > 90th percentile showed significantly increased risk of SGA compared to those with respective counterpart characteristics; relative risk was 3.8 (95% CI, 1.3 - 11.3; 21% [4/19] vs. 5.5% [9/164]) for PlGF and 7.9 (3.0 - 20.8, 33.3% [6/18] vs. 4.2% [7/165]) for sFlt-1/PlGF. Conclusions: Maternal PlGF and sFlt-1/PlGF determined during GW 24-27 were associated with the risk of SGA born at GW ≥ 36, even in women with uncomplicated pregnancies.

Aim: Urine podocin mRNA expression and urine podocin : nephrin mRNA expression ratio (PNR) increase with increasing proteinuria during pregnancy complicated with pre-eclampsia (PE). This suggests that urine podocytes with reduced nephrin mRNA expression are abundant in pathological podocyturia. The aim of this study was therefore to determine post-partum changes in podocyturia and PNR in relation to proteinuria after pre-eclampsia (PE). Methods: A total of 137 peripartum urine specimens, consisting of 72 and 65 from 24 and 30 women with PE and normotensive control pregnancies (NCP), respectively, were studied. Determination of urine protein and creatinine concentration and quantitative analysis of podocyte-specific podocin and nephrin mRNA expression were carried out using reverse transcription-polymerase chain reaction in pelleted urine samples. Podocyturia was monitored via urine podocin mRNA expression. Podocyturia and proteinuria were normalized by urine creatinine concentration. Results: Podocyturia and urine PNR decreased with decreasing proteinuria as well as with increasing time after delivery in the urine from PE women. In physiological proteinuria (i.e. protein : creatinine ratio [P/Cr] 0.005-0.1 mg/mg), however, both podocyturia and PNR were significantly greater in the urine from PE women compared with NPC women, although P/Cr was similar between the groups (median, 0.037 mg/mg for PE vs 0.029 mg/mg for NCP). Conclusions: Podocyturia decreases with decreasing proteinuria in PE women after childbirth. In PE women, however, pathological podocyturia consisting of podocytes with decreased nephrin mRNA expression persisted even after proteinuria decreased to a level similar to that in NCP women.

Aim: Hyperfiltration is a cause of podocyturia and occurs physiologically in the kidney of pregnant women. Podocyturia is increased in preeclamptic pregnancies, but it is unclear whether there is also any increase in uncomplicated pregnancies. This study was performed to examine whether podocyturia and urine aquaporin 2 mRNA expression are increased in healthy pregnant women (PW) compared to healthy non-pregnant women (NPW). Methods: Eleven urines obtained from 11 NPW and longitudinal 76 urines from 40 PW with uncomplicated pregnancies (median number [range] of urine samples/person, 2 [1 - 3]) were studied. Determination of protein and creatinine concentrations and number of cells in urine other than blood cells, and quantitative analyses of the mRNA expression of aquaporin 2 (AQP2-mRNA), podocin (Pod-mRNA), and nephrin (Nep-mRNA) were performed using RT-PCR in pelleted urine samples. Podocyturia was monitored with urine Pod- and Nep-mRNA expression levels normalized relative to creatinine. Results: Urine cell density and urine AQP2-, Pod-, and Nep-mRNA expression normalized relative to creatinine were significantly higher in PW than NPW. The number of cells per milligram of creatinine was significantly positively correlated with expression of all three mRNAs with correlation coefficients (R-value) of 0.442, 0.481, and 0.561 for Pod-, Nep-, and AQP2-mRNA, respectively. AQP2-mRNA expression was strongly (R > 0.8) positively correlated with both Pod- and Nep-mRNA expression. Conclusion: Podocyturia monitored by Pod- and Nep-mRNA expression and urine cells expressing AQP2-mRNA were increased in uncomplicated pregnancies compared to healthy non-pregnant women. Urine cells expressing AQP2-mRNA increased with increasing podocyturia in healthy women.

Aim: This retrospective study was performed to determine the frequency of malformed infants born at a tertiary center in Hokkaido, Japan. The accuracy of prenatal diagnosis rates was also investigated. Methods: An observational study was performed using data of 1509 and 1743 newborn infants at a single center during two study periods, 2005-2009 (first) and 2010-2014 (second), respectively. Cases including minor anomalies (accessory auricle, nevus and fistula auris congenita) were not included. Results: In total, 274 and 569 malformations were identified in 191 and 337 newborn infants in the first and second study periods, respectively. The number of malformed infants increased significantly over time (13% [191/1509] vs 19% [337/1743], respectively; P < 0.001), mainly as a result of an increase in cases of congenital heart disease (CHD), from 59 to 141 (31% [59/191] vs 42% [141/337] of all malformed infants in the first and second periods, respectively). The overall accurate prenatal diagnosis rate improved over time from 47% (128/274) to 58% (329/569) because of significant improvements in accurate prenatal diagnosis of CHD subtypes (23% [16/70] vs 65% [151/232] in the first and second periods, respectively, P < 0.0001). Conclusions: The frequency of malformed newborns was higher in the tertiary center than in the general population. The increased number of cases with prenatal suspicion and diagnosis of CHD contributed to the increased frequency of malformed infants during the study period.

Marked fluid retention occurs in Ballantyne syndrome, but few reports are available on changes in cardiac morphology in this syndrome. A woman with generalized edema, dyspnea, fetal hydrops (skin edema and ascites), thickened placenta, and elevated plasma B-type natriuretic peptide level (344 pg/mL) was admitted to our hospital at gestational week (GW) 20^+3. Blood pressure remained within the normal range. However, acute increases in left atrial volume index, pulmonary artery systolic pressure, and hyperdynamic left ventricular function (as evidenced by increased left ventricular ejection fraction to 74% with cardiac index of 5.1 L/min/m2) occurred preceding fetal death at GW 21^+4 in the presence of increased inferior vena cava diameter (23 mm) and relatively low systemic vascular resistance of 752 dyn・s/cm5. These findings suggested life-threatening heart failure and required cesarean delivery at GW 21^+5 resulting in complete recovery. The placenta suggested cytomegalovirus infection.

Aim: Podocyte depletion in the kidney is associated with end-stage kidney disease (ESKD). Pre-eclampsia (PE) increases the risk of ESKD in later life. This study was performed to determine whether nephrinuria (soluble nephrin in the urine) is correlated with proteinuria and/or podocyturia (podocytes in the urine) in PE women. Methods: Eighty-three urine samples, consisting of 45 and 38 samples from 27 normotensive and nine PE women, respectively, underwent simultaneous determination of nephrin, protein, and creatinine concentrations in the urine supernatant and quantitative analysis of podocyte-specific protein mRNA expression. This included podocin (Pod-mRNA) and nephrin (Nep-mRNA), using real-time polymerase chain reaction in the pelleted urine. Nephrinuria and proteinuria were corrected by creatinine concentration. Pod- and Nep-mRNA expression levels were corrected by GAPDH. Results: Nephrinuria, proteinuria, Pod-mRNA expression, and Nep-mRNA expression all increased with advancing gestation in PE women, while not in normotensive women. The nephrinuria was strongly correlated with proteinuria (R = 0.901, P < 0.001), Pod-mRNA expression level (R = 0.824, P < 0.001), and Nep-mRNA expression level (R = 0.724, P < 0.001) in urine samples from PE women, while the nephrinuria was significantly correlated with proteinuria alone (R = 0.419, P < 0.005) in urine samples from normotensive women. Conclusion: Nephrinuria reflected well the degrees of proteinuria and podocyturia in PE women. This suggested that increased nephrinuria/proteinuria was associated with podocyte loss in the kidneys of PE women.

Background: Infant flow biphasic nasal continuous positive airway pressure (Bi-NCPAP) and regular NCPAP (Re-NCPAP) are equally useful with respect to the rate of successful weaning from mechanical ventilation. It remains unclear, however, whether Bi-NCPAP or Re-NCPAP is more effective for reducing apnea of prematurity (AOP). Methods: A multicenter randomized controlled study was conducted of 66 infants assigned to receive Bi-NCPAP and 66 assigned to receive Re-NCPAP for respiratory support after extubation. Primary outcome was the number of AOP events during the 48 h observation period after successful extubation, defined as no reintubation and no adverse events associated with the use of NCPAP during the observation period. The secondary outcome was successful extubation. Reintubation was at the discretion of the attending physician. Results: Baseline characteristics were similar between the two groups. The number of AOP events during the 48 h observation period was significantly lower in infants with Bi-NCPAP than in those with Re-NCPAP (5.2 ± 6.5 vs 10.3 ± 10.9 per infant, respectively; P = 0.002). The rate of successful extubation tended to be greater in those with Bi-NCPAP than in those with Re-NCPAP (92.4%, 61/66 vs 80.3%, 53/66, respectively; P = 0.074). Adverse events occurred in only one of 132 infants: erosive dermatitis developed on the nose after application of Re-NCPAP. The risk of reintubation did not differ significantly between the two groups (7.6%, 5/66 for Bi-NCPAP vs 18.2%, 12/66 for Re-NCPAP; P = 0.117). Conclusions: Bi-NCPAP was superior to Re-NCPAP for reduction of AOP following extubation.

Aim: Women with pre-eclampsia (PE), placenta previa (PP), placental abruption (PA), and placental mesenchymal dysplasia (PMD) have been described as having placental permeability dysfunction. This study was performed to determine whether occult fetomaternal hemorrhage (FMH) is common in women with such complications and in women with non-reassuring fetal status. Methods: Forty-one antenatal and 39 postnatal blood samples were obtained from 46 women, including 11 with placental permeability dysfunction (5, 3, 2, and 1 with PE, PP, PA, and PMD, respectively) and 35 controls without such complications. To estimate the amount of fetal red blood cells, flow cytometry was performed using the fetal cell count system with two antibodies against fetal hemoglobin and carbonic anhydrase and the β-γ system with two monoclonal antibodies against hemoglobin β-chain and hemoglobin γ-chain. A diagnosis of FMH was made when the fraction size of the isolated cell population on scatter plots expressing fetal hemoglobin alone or hemoglobin γ-chain alone accounted for ≥ 0.02% of the total cell population on scatter plots. Results: FMH was identified in five women, including one each with PE, PA, PP, PMD, and no complications. Thus, the prevalence rate of FMH was significantly higher in women with complications than in controls (36% [4/11] vs 2.9% [1/35], respectively, P = 0.009). The FMH occurrence rate did not differ between women with and without non-reassuring fetal status (7.7% [1/13] vs 12% [4/33], respectively, P = 1.000). Conclusion :The risk of fetal red blood cells trafficking into the maternal circulation may be increased in women complicated with PE, PA, PP, and PMD.

Figure S3. Absence of copy number alterations at the H19-IGF2 imprinted gene cluster in the placenta and cord blood samples of cases 1, 2, and 3. (PDF 395 kb)

Figure S1. Correlation plots for DNA methylation levels of H19-DMR and IGF2-DMRs in the placenta and cord blood samples of case/control set I and in the placenta samples of case/control set II. Figure S2. Methylation levels of 18 imprinted DMRs and LINE1 repetitive elements in the placentas of cases 1â 3 and controls determined by COBRA assays. (PDF 333 kb)

Aim: The aim of this study was to provide better counsel to pregnant women with suspected placental mesenchymal dysplasia (PMD) regarding the risks of preterm birth and intrauterine fetal death. Material and Methods: We reviewed the outcomes of 109 PMD pregnancies with gestational week (GW) ≥ 24 abstracted from 63 reports in the English-language published reports, including two cases that we encountered recently. The prospective risk of stillbirth at GW N was defined as the number of women with stillbirth at GW ≥ N divided by the number of women giving birth at GW ≥ N. Results: A total of 32 (29.4%) women experienced stillbirth at a median GW of 31 (range, 24-38). Preterm birth (GW < 37) occurred in 52 (67.5%) of the 77 live-born infants. Only 25 (22.9%) women had full-term (GW ≥ 37) live-born infants. The prospective risks of stillbirth were 29.4% (32/109), 27.5% (25/91), 20.9% (14/67) and 13.0% (6/46) for women who reached GW 24(+0), 28(+0), 32(+0) and 36(+0) respectively. Conclusion: As women with PMD are at markedly elevated risk of intrauterine fetal death, early admission to the hospital and intensive monitoring of fetal status should be considered, although whether this policy improves outcome has not been validated.

Aim: To determine intrapartum factors associated with neonatal encephalopathy leading to cerebral palsy (NE-CP). Methods: A total of 70 NE-CP patients who fulfilled study criteria (cephalic singleton pregnancy with attempted vaginal delivery [AVD] at gestational week [GW] ≥36; intrapartum occurrence of non-reassuring fetal status without apparent cause following reassuring fetal status on admission; and development of NE-CP) were compared with 210 AVD controls who had 1- and 5-min Apgar score ≥8 matched for GW, maternal parity, and use of uterotonics. Suboptimal care was defined as delayed reaction due to misinterpretation of fetal heart rate (FHR) tracing, or inappropriate trial of instrumental delivery (TOID). Successful and failed TOID were defined as vaginal and cesarean delivery after TOID, respectively. The 210 controls were assumed not to have had suboptimal care. Results: The rates of successful (34% vs 12%) and failed TOID (11% vs 0.0%), cesarean section (34% vs 14%), suboptimal care (57% vs 0.0%), pregnancy-induced hypertension (11% vs 2.4%), birthweight ≥3800 g (8.6% vs 1.9%), subgaleal hemorrhage (16% vs 0.0%) were significantly higher in NE-CP patients than in controls. Selection with the stepwise method and logistic regression analysis identified four independent risk factors for NE-CP: suboptimal intrapartum care (OR, 2.21; 95%CI: 1.99-2.47), cesarean section (OR, 1.19; 95%CI: 1.08-1.31), successful TOID (OR, 1.14; 95%CI: 1.03-1.25), and hypertension (OR, 1.20; 95%CI: 1.01-1.42). Conclusions: Training programs for improved interpretation of FHR tracing and appropriate TOID are required to prevent NE-CP among healthy and mature fetuses in Japan.

Aim To determine whether macrosomic infants with a birthweight of 4.0kg or more have increased risk of cerebral palsy associated with neonatal encephalopathy (Enc-CP). Methods A retrospective review of 132 singleton infants with Enc-CP fulfilling all of the following criteria: born at gestational week (GW) 37 or more (n=126) or weighing 2.5kg or more at birth (n=116) in or after January 2009 in Japan; no identifiable causes of cerebral palsy other than antenatal or intrapartum hypoxia; and exhibition of neonatal encephalopathy. National statistics of Japan were used to determine the numbers of infants according to birthweight categories. Results Of the 116 infants with a birthweight of 2.5kg or more, 46 (39.7%), 49 (42.2%), 17 (14.7%) and four (3.4%) infants had birthweights of 2.5-2.99, 3.0-3.49, 3.5-3.99 and 4.0kg or more, respectively. Corresponding figures among Japanese infants born in 2009-2011 were 42.8%, 45.4%, 10.9% and 0.90%, respectively. Infants with a birthweight of 4.0kg or more had a relative risk (95% confidence interval) of Enc-CP of 3.89 (1.52-9.95) compared to those with a birthweight of 2.5-2.99kg. Conclusion Japanese infants with a birthweight of 4.0kg or more have increased risk of Enc-CP.

As proposed criteria (Swansea criteria) for the diagnosis of acute fatty liver of pregnancy (AFLP) do not include antithrombin (AT) activity, diagnosis of AFLP may be delayed. The aim of this review is to underscore problems in the differential diagnosis of AFLP and the syndrome of hemolysis, elevated liver enzymes and low platelet counts (HELLP syndrome) and to facilitate prompt diagnosis of AFLP. Published works dealing with liver dysfunction in pregnancy, HELLP syndrome and AFLP were reviewed. AFLP and HELLP syndrome shared common clinical, laboratory, histological and genetic features, and differential diagnosis between them was often difficult. However, HELLP syndrome was likely to occur in patients with hypertension, but AFLP occurred often in the absence of hypertension. In addition, AFLP was exclusively associated with pregnancy-induced antithrombin deficiency (PIATD). Approximately 50% of patients with AFLP did not have thrombocytopenia at presentation. As the Swansea criteria for AFLP did not include PIATD, diagnosis of AFLP was delayed until manifestation of life-threatening complications; 60% of women were admitted to intensive care and 15% to a specialist liver unit. In conclusion, incorporation of AT activity of less than 65% into the diagnostic criteria for AFLP may facilitate suspicion and prompt diagnosis of AFLP, decrease uncertainty regarding the diagnosis of AFLP, and contribute to better investigation and understanding of the process leading to the development of liver dysfunction.

In a fetus with suspected heterotaxy syndrome, a decreased/absent baseline variability of fetal heart rate pattern developed at gestational week 36(+5) and continued for 5 days until birth at gestational week 37(+2), while repeat biophysical profile scorings with ultrasound were consistently unremarkable. This neonate weighing 2404 g with Apgar scores of 7 (1-min) and 8 (5-min) and umbilical arterial cord blood pH of 7.28 with base deficit of 3.9mmol/L, showed a heart rate of 120 b.p.m. for 3 h after birth, but subsequently developed sinus bradycardia (84 b.p.m.) unresponsive to crying. Isoproterenol initiated 9 h after birth was effective in the increase of heart rate to 120 b.p.m. in this neonate. Brain magnetic resonance imaging at 16 days of age was unremarkable. The decreased/absent baseline variability of fetal heart rate pattern was speculated to have been caused by sinus node dysfunction, and not by reduced fetal oxygenation in this case.

Aim: The aim of this study was to underscore problems associated with the dipstick test and determination of protein concentration alone in spot-urine (P-test) compared with spot-urine protein-to-creatinine ratio (P/Crtest) and to determine whether urine collection for 24-h test was complete. Material and Methods: Dipstick and P/Cr tests were performed simultaneously in 357 random spot-urine specimens from 145 pregnant women, including 35 with pre-eclampsia. Positive results were defined as 1+ on dipstick test, protein concentration 30 mg/dL on P-test, and P/Cr ratio 0.27 (mg/mg) on P/Cr test. Sixty-four 24-h urine tests (quantification of protein in urine collected during 24 h) were performed in 27 of the 145 women. We assumed that P/Cr ratio 0.27 predicted significant proteinuria (urinary protein 0.3 g/day). The 24-h urine collection was considered incomplete when urinary creatinine excretion was 25.0 mg/kg/day. Results: Forty-four percent (69/156) of specimens with a positive test result on dipstick test contained protein < 30 mg/dL. Dipstick test was positive for 25.7% (69/269) of specimens with protein < 30 mg/dL and for 28.8% (79/274) of specimens with P/Cr ratio < 0.27. P-test results were positive for 7.3% (20/274) and negative for 18.1% (15/83) of specimens with P/Cr ratio < 0.27 and 0.27, respectively. Incomplete 24-h urine collection occurred in 15.6% (10/64) of 24-h urine tests. Daily urinary creatinine excretion was 702–1397 mg, while creatinine concentration varied from 16 mg/dL to 475 mg/dL in spot-urine specimens. Conclusion: Dipstick test and P-test were likely to over- and underestimate risks of significant proteinuria, respectively. The 24-h urine collection was often incomplete.

Aims: To assess the usefulness of a new method for cesarean section (CS) that is comprised of a transverse incision into the uterine fundus, developed for women with placentas covering the entire anterior uterine wall, and introduced in September 2006. Methods: Review of medical records of 12 and 29 women who underwent CS by the new and conventional methods, respectively, for placenta previa, placenta accreta (accreta, increta, and percreta), or placenta widely covering the entire anterior uterine wall in which placenta accreta cannot be excluded between June 2003 and March 2011. Results: Placenta accreta (67% [8/12] vs. 10% [3/29], P = 0.0006) and cesarean hysterectomy (67% vs. 10%) were significantly more frequent in the group with the new compared with the conventional method. There were no significant differences between groups with the new and conventional methods in amount of blood loss (1732 ± 1067 vs. 1847 ± 1279 g, respectively), prevalence of blood loss > 3000 g (8.3% vs. 17%, respectively) or blood transfusion (92% vs. 72%, respectively), time required for cesarean hysterectomy (210 ± 58 vs. 195 ± 41 min), or neonatal conditions at birth. The amount of blood loss for cesarean hysterectomy was significantly less for the new than conventional method (1959 ± 1025 g vs. 4450 ± 1145 g, P = 0.041). Conclusions: The new method was superior to the conventional method with respect to reduction of blood loss during cesarean hysterectomy. However, careful observations are mandatory in women with preserved uterus with respect to a possible increased risk of uterine rupture in future pregnancies.

Background: Environmental pollution with radioiodine occurred after an accident at the Fukushima nuclear power plant (FNP) on March 11, 2011, in Japan. Whether environmental pollution with 131I can contaminate human breast milk has not been documented. Methods: 131I content was determined in 126 breast milk samples from 119 volunteer lactating women residing within 250 km of the FNP, between April 24 and May 31, 2011. The degree of environmental pollution was determined based on the data released by the Japanese government. Results: An 131I content (becquerels per kilogram, Bq/kg) of 210 in the tap water in Tokyo, which is located 230 km south of the FNP, on March 22 and of 3,500 in spinach sampled in a city located 140 km southwest of the FNP on March 19 decreased over time to < 21 on March 27 and 12 on April 26, respectively. Seven of 23 women who were tested in April secreted a detectable level of 131I in their breast milk. The concentrations of 131I (Bq/kg) in the breast milk of the 7 women were 2.3 (on month/day, 4/24), and 2.2, 2.3, 2.3, 3.0, 3.5 and 8.0 (4/25); the concentrations of 131I in the tap water available for these 7 women at the same time points were estimated to be

We present a case of short-rib polydactyly syndrome (SRP) type 3 in which accurate prenatal diagnosis was feasible using both ultrasonography and 3D-CT. SRPs encompass a heterogeneous group of lethal skeletal dysplasias. However, the phenotypes overlap with those of nonlethal skeletal dysplasias, i.e., Ellis-van Creveld syndrome and Jeune syndrome. As accurate prenatal diagnosis of SRPs is helpful for parents, we used 3D-CT in the early third trimester to examine a fetus suggested to have phenotypes of "short-rib dysplasia group" on ultrasonography. 3D-CT showed mild modification of the vertebral bodies, small ilia with horizontal acetabula and triangular partial ossification defects, and subtle metaphyseal irregularities of the femora. These CT findings and an extensive literature search regarding the phenotypes of various diseases categorized as "short-rib dysplasia group" led to a correct prenatal diagnosis of SRP type 3. This case exemplified the usefulness of 3D-CT for the precise prenatal diagnosis of skeletal dysplasias.

There has been only one case to date of pregnancy outcome after fundal transverse cesarean section (FTC). We report a pregnancy established after FTC. The FTC was performed at gestational week (GW) 24 in this patient’s first pregnancy, but the uteruswas preserved.Magnetic resonance imaging studies performed four times in her second pregnancy consistently showed part of the uterine fundus in which the muscle layer was interrupted. Concern regarding spontaneous uterine rupture in the absence of labor pains prompted us to interrupt her pregnancy at GW 31+5, delivering a premature, but otherwise healthy female infant, weighing 1832 g. The infant required transient intratracheal intubation for respiratory distress syndrome (for less than 1 h), but had an otherwise uneventful clinical course. Two cases, including ours, suggest that successful pregnancy outcome is feasible at least in some women with uterine scarring due to FTC.

BACKGROUND: Pregnancy-induced hypertension (PIH) is a common cause of perinatal mortality. It is believed to result from the interaction of several factors, including those related to the blood coagulation system. We performed genotyping and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to evaluate possible interactions of the PAI-1 polymorphisms with those of the angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3). \nMETHODS: An association study of PAI-1 polymorphism, and subgroup analyses of common variants of AGT and NOS3, among 128 patients with PIH and 376 healthy pregnant controls. \nRESULTS: No significant differences were found between the cases and controls in the frequencies of allele 4G or the 4G/4G genotype. In subgroup analyses, after adjustment for multiple comparison, a significant association with the AGT TT genotype was found among women with the PAI-1 4G/4G genotype, and an association with the NOS3 GA+AA genotype was found among women with the 5G/5G or 4G/5G genotypes. \nCONCLUSIONS: Our findings suggest that there are at least 2 pathways in the pathogenesis of severe PIH. However, with respect to early prediction and prevention of severe PIH, although the PAI-1 4G/4G genotype alone was not a risk factor for severe PIH, the fact that PAI-1 genotypes are associated with varying risks for severe PIH suggests that PAI-1 genotyping of pregnant women, in combination with other tests, may be useful in the development of individualized measures that may prevent severe PIH.

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.

Preeclampsia monitored by the amount of proteinuria usually does not show amelioration during pregnancy. A 37-year-old nulliparous woman was admitted to our hospital at gestational week (GW) 24-1/7 due to rapid weight gain (6.2 kg/4 weeks) and oligohydramnios. Hypertension (151/91 mmHg) appeared atGW25-0/7 and proteinuria not detected at GW 24-0/7 became significant (0.55 g/day) at GW 25-2/7. During the 2 successive weeks after administration of betamethasone at 12 mg twice and transabdominal amnioinfusion with 250 mL of Ringer’s acetate solution at GW 25-3/7, generalized edema, proteinuria and thrombocytopenia markedly improved: bodyweight, 78.0 to 69.0 kg; proteinuria, from 7.1 to 1.3 g/day; and platelet count, from 111 to 230 ¥ 109/L. However, intrauterine infection accompanied by non-reassuring fetal status necessitated emergency cesarean section at GW 28-3/7. Extraordinary bodyweight gain can herald the occurrence of preeclampsia and this weight gain together with signs of preeclampsia can ameliorate even during pregnancy, although its mechanism is unclear.

As the fibrinogen level decreases early in atonic bleeding, early administration of FFP may be important as an initial approach to treat atonic bleeding. Amniotic fluid embolism is classified into 2 types, conventional type and uterus-type., The Journal of Obstetrics and Gynaecology Research, 40(2), pp.336-337; 2014

To clarify the context of the gene-gene interrelationship in the manifestation of PIH, we analyzed Met235Thr variant of the angiotensinogen gene (AGT) and Glu298Asp variant of the endothelial nitric oxide synthase gene (NOS3) in terms of 4G/5G variant of the plasminogen activator inhibitor gene (PAI-1). One hundred forty-five Japanese patients with PIH were matched with 357 Japanese normal pregnant controls according to age and parity. Genotypings of variants of AGT, NOS3 and PAI-1 were carried out using PCR-RFLP methods after extraction of genomic DNA from 1.0 ml of whole blood samples. In 4G/4G of PAI-1, the frequency of T235 of AGT was higher in PIH (0.78) than in controls (0.56) (p, The 56th Annual Meeting of The American Society of Human Genetics