Isolated gestational proteinuria preceding the diagnosis of preeclampsia : an observational study

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

A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands

Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived growth factor and a critical regulator of fetal organ development in mice and humans. Using a single-cell RNA sequencing (RNA-seq) atlas of salivary gland (SG) and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse, we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5) but, after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNA-seq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos population express the hall- marks of ancient ionocyte signature Forkhead box i1 and 2 (Foxi1, Foxi2), Achaete-scute homolog 3 (Ascl3), and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized SG ionocytes located in ducts and important for the ionic modification of saliva. In addition, they maintain FGF10-dependent gland homeostasis via communication with FGFR2bpos ductal and myoepithelial cells

Echocardiography findings in a case with Ballantyne syndrome

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

Quantification of eight benzodiazepines in human breastmilk and plasma by liquid-liquid extraction and liquid-chromatography tandem mass spectrometry : Application to evaluation of alprazolam transfer into breastmilk.

Breastfeeding is strongly encouraged for infant and maternal health. Benzodiazepines (BZDs) are widely prescribed drugs for symptoms, such as anxiety and insomnia, which many women could experience during the postpartum period. However, limited information is currently available to evaluate the transfer of different BZDs into breastmilk. In order to assess the proprieties of this medication during breastfeeding, robust and sensitive analytical methods to quantify BZDs are required. For this purpose, we developed a method for quantification of BZDs, including alprazolam, bromazepam, clonazepam, clotiazepam, etizolam, flunitrazepam, lorazepam, and CM7116 (a metabolite of ethyl loflazepate), in human breastmilk and plasma using liquid chromatography/tandem mass spectrometry (LC/MS/MS). Sample preparation was performed by a simple liquid-liquid extraction (LLE) with ethyl acetate. For sample preparation of CM7116, the pretreatment process to completely obtain the metabolite was added before the LLE step. The BZDs were separated by a C column using a gradient elution of acetonitrile in aqueous ammonium acetate solution, and were detected in the positive ion electrospray mode with multiple reaction monitoring (MRM). Lower limits of quantification (LLOQs) in breastmilk ranged from 0.25 to 0.5 ng/mL, and those in plasma ranged from 0.5 to 1.0 ng/mL. The intra-day and inter-day precision, and accuracy of data were assessed and found to be acceptable. The developed method was successfully applied to measure the concentration of alprazolam in breastmilk and plasma, which were donated by a lactating woman who had been regularly treated with alprazolam. Milk to plasma (M/P) ratios were calculated as 0.52 (before oral administration) and 0.49 (2 h after administration) 3 days after delivery. The M/P ratio 1 month after delivery was calculated as 0.41 (2 h after administration). We estimated that the relative infant dose (RID) values of alprazolam ranged from 3.11 to 4.61%

Long-term persistent fetomaternal hemorrhage

Key Clinical Message: It is not clear that how long the affected fetuses can tolerate fetomaternal hemorrhage (FMH). Incidental serial measurements of the fetal peak systolic velocity of the middle cerebral artery and the retrospective analysis of stocked blood available incidentally indicated that our patient had suffered from FMH for at least 2 weeks prior to delivery

Protein S deficiency present in a pregnant woman with dyspnea, abdominal pains, restlessness, agitation and hypofibrinogenemia

Key Clinical Message: Hypofibrinogenemia is rare in pulmonary thromboembolism. A pregnant woman with dyspnea, abdominal pain, restlessness, agitation and protein S deficiency exhibited normal blood oxygenation and high D-dimer (370 mu g/mL) and undetectable fibrinogen levels in the blood. The pathogenesis responsible for present findings may have some features similar to amniotic fluid embolism

Essential thrombocythemia as a risk factor for stillbirth

Introduction: The risk of abortion is known to be high in women with essential thrombocythemia (ET). However, a few studies have focused on the risk of stillbirth among fetuses reaching gestational age compatible with life. Methods: Review of medical charts of pregnant women with ET who received cares at a single center between January 2003 and June 2013 and the English literature in which more than 20 pregnancies with ET were dealt with regarding outcomes. Outcomes were classified into three categories: spontaneous abortion or preterm delivery before GW 24, stillbirth at and after GW 24, and live birth (LB). Japan national statistics was used to estimate the risk of stillbirth among women with GW 22 or more. Results: In all nine pregnancies in four women with ET at our hospital, two miscarriages, one stillbirth (intrauterine death at GW 35), and six LBs occurred. There were six reports in the English literature in which a total of 374 pregnancy outcomes were described: 110 miscarriages (29%), 14 stillbirths (3.7% of all 374 pregnancies and 5.3% of 264 pregnancies with GW >= 24), and 250 LBs (67%) occurred. Japan national statistics between 1995 and 2011 indicated that the risk of stillbirth was less than 0.50% among women with GW >= 22. Conclusions: The risk of still birth was extremely high among women with ET. More intensified monitoring of fetal wellbeing may be required to improve outcome of pregnancy complicated with ET. (C) 2013 Elsevier Ltd. All rights reserved

Anemia in a neonate with placental mesenchymal dysplasia

Causes of intrauterine fetal death (IUFD) are uncertain in most placental mesenchymal dysplasia (PMD) cases. Our case showed high α-fetoprotein levels in the maternal circulation, markedly dilated subchorionic vessels, and neonatal hemoglobin concentration of 8.4 g/dL, suggesting that fetal anemia may explain some adverse outcomes in PMD pregnancies

Association between nephrinuria, podocyturia, and proteinuria in women with pre-eclampsia

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