Automated electrochemiluminescence immunoassay for serum PlGF levels in women with singleton pregnancy at 9-13 weeks of gestation predicts preterm preeclampsia: a retrospective cohort study.

Our aims were to obtain the gestational-age-specific median of common logarithmic placental growth factor (PlGF) values in the first trimester in women with a singleton pregnancy in order to generate the gestational-age-specific multiple of the median (MoM) of log10PlGF at 9-13 weeks of gestation, to evaluate screening parameters of MoM of log10PlGF at 9-13 weeks of gestation to predict preterm preeclampsia (PE), and to construct an appropriate prediction model for preterm PE using minimum risk factors in multivariable logistic regression analyses in a retrospective sub-cohort study. Preterm PE occurred in 2.9% (20/700), and PE in 5.1% (36/700). Serum PlGF levels were measured using Elecsys PlGF®. MoMs of log10PlGF at 9-13 weeks of gestation in Japanese women with a singleton pregnancy followed a normal distribution. We determined the appropriate cut-off value of MoM of log10PlGF to predict preterm PE at around a10% false-positive rate (0.854). The MoM of log10PlGF < 0.854 yielded sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio (95% confidence interval [CI]), and negative likelihood ratio (95% CI) of 55.0%, 91.9%, 17.5%, 98.5%, 6.79 (4.22-10.91), and 0.49 (0.30-0.80), respectively. The combination of MoM of log10PlGF and presence of either chronic hypertension or history of PE/gestational hypertension (GH) yielded sensitivity and specificity of 80.0 and 85.7%, respectively, to predict preterm PE. In conclusion, the automated electrochemiluminescence immunoassay for serum PlGF levels in women with singleton pregnancy at 9-13 weeks of gestation may be useful to predict preterm PE.

Significant dependency of left atrial strain on left ventricular longitudinal motion.

BACKGROUND: The effects of left ventricular longitudinal function on the left atrial strain, including the left atrial reservoir function, have not been adequately quantified. METHODS: A total of 124 patients who underwent echocardiography were enrolled in this study. Left atrial strain analysis was performed using two-dimensional speckle tracking echocardiography, and the left atrial volume was derived using the modified Simpson's method. The peak left atrial strain (LAS) and left atrial expansion index (LAEI), as indices of left atrial reservoir function, were measured. The global longitudinal strain (GLS) and mitral annular plane systolic excursion (MAPSE), which are indices of contractile motion toward the left ventricular apex, were also measured. The correlation between LAS and candidate determinants, including left ventricular systolic longitudinal function, was evaluated, and multivariate regression analysis was performed. RESULTS: A significant correlation was found between LAS and left ventricular systolic longitudinal functions, GLS (r = 0.63, p < 0.001), and MAPSE (r = 0.65, p < 0.001). Two models, which were selected by multiple regression analyses for LAS, included GLS or MAPSE as independent determinants. GLS and MAPSE were also the strongest predictors, among other factors. CONCLUSION: LAS, when determined by evaluating the left atrial reservoir function, was significantly associated with left ventricular function, especially the systolic longitudinal function. Left ventricular function should be considered when assessing left atrial function by LAS.

Acute nicotine exposure blocks aromatase in the limbic brain of healthy women: A [11C]cetrozole PET study.

BACKGROUND: Of interest to women's mental health, a wealth of studies suggests sex differences in nicotine addiction and treatment response, but their psychoneuroendocrine underpinnings remain largely unknown. A pathway involving sex steroids could indeed be involved in the behavioural effects of nicotine, as it was found to inhibit aromatase in vitro and in vivo in rodents and non-human primates, respectively. Aromatase regulates the synthesis of oestrogens and, of relevance to addiction, is highly expressed in the limbic brain. METHODS: The present study sought to investigate in vivo aromatase availability in relation to exposure to nicotine in healthy women. Structural magnetic resonance imaging and two [11C]cetrozole positron emission tomography (PET) scans were performed to assess the availability of aromatase before and after administration of nicotine. Gonadal hormones and cotinine levels were measured. Given the region-specific expression of aromatase, a ROI-based approach was employed to assess changes in [11C]cetrozole non-displaceable binding potential. RESULTS: The highest availability of aromatase was found in the right and left thalamus. Upon nicotine exposure, [11C]cetrozole binding in the thalamus was acutely decreased bilaterally (Cohen's d = -0.99). In line, cotinine levels were negatively associated with aromatase availability in the thalamus, although as non-significant trend. CONCLUSIONS: These findings indicate acute blocking of aromatase availability by nicotine in the thalamic area. This suggests a new putative mechanism mediating the effects of nicotine on human behaviour, particularly relevant to sex differences in nicotine addiction.

Uterine contraction may not be an independent risk factor for spontaneous preterm birth before 35 weeks in women with cervical shortening.

OBJECTIVE: To compare the risk of spontaneous preterm birth (SPTB) before 35 weeks in symptomatic and asymptomatic women with cervical shortening at 16-34 weeks under mid-trimester universal screening of cervical length (CL). METHOD: Multicenter retrospective cohort study involving six secondary/tertiary perinatal centers was planned in 2016. Primary outcomes were SPTB before 35 weeks. In all, 407 women were analyzed using multivariable logistic regression analysis for predicting SPTB before 35 weeks while adjusting for presence/absence of uterine contraction, gestational weeks, vaginal bleeding, and CL classification (1-9, 10-14, 15-19, and 20-24 mm) at admission, the execution of cervical cerclage, and the presence/absence of past history of preterm delivery. RESULTS: SPTB before 35 weeks of pregnancy occurred in 14.5%. Presence of uterine contraction was not an independent risk factor for SPTB before 35 weeks (adjusted odds ratio [aOR] 1.22, 95% confidence interval [CI] 0.67-2.20). CL of 1-9 mm, CL of 10-14 mm, and vaginal bleeding at admission were independent risk factors for SPTB before 35 weeks (aOR 5.35, 95% CI 2.11-13.6; aOR 2.79, 95% CI 1.12-6.98; and aOR 2.37, 95% CI 1.12-5.10, respectively). CONCLUSION: In women with a cervical shortening at 16-34 weeks, presence of uterine contractions at admission may not be an independent risk factor for the occurrence of SPTB before 35 weeks.

LOX-1 deficiency increases ruptured abdominal aortic aneurysm via thinning of adventitial collagen.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a key mediator of inflammation and plays an important role in the pathogenesis of atherosclerosis. Conversely, LOX-1 deficiency has been shown to decrease inflammation and atherosclerosis, both of which have been proposed to contribute to abdominal aortic aneurysm (AAA) pathogenesis. However, the role of LOX-1 in AAA pathogenesis remains unknown. Here, we investigated the effects of Olr1 (which encodes LOX-1) deletion on angiotensin II (Ang II)-induced AAA in apolipoprotein E knockout (ApoE KO) mice to determine whether LOX-1 deficiency mitigates AAA development. To accomplish this, we used serial, non-invasive ultrasound assessment, which revealed that the incidence and expansion rate of AAA were similar regardless of Olr1 deletion. However, Olr1 deletion significantly increased severe AAAs, including ruptured AAAs resulting in death. Oil Red O staining of the harvested aortas showed that the extent of atheroma burden localized in aneurysmal lesions did not differ between LOX-1-deficient and control mice, suggesting that Olr1 deletion did not decrease atheroma burden in the aneurysmal wall. Further histopathological analysis revealed that aneurysmal lesions in LOX-1-deficient mice had fewer fibroblasts and myofibroblasts, as well as thinner adventitial collagen, although the degree of elastin fragmentation or disruption was similar between LOX-1-deficient and control mice. An in vitro study confirmed that the proliferation of adventitial fibroblasts collected from LOX-1-deficient mice was significantly attenuated despite Ang II stimulation. In conclusion, Olr1 deletion may not mitigate aneurysm development but rather increases the vulnerability of rupture by suppressing adventitial fibroblast proliferation and collagen synthesis.

Nonhyperemic Pressure Ratios-All the Same or Nuanced Differences?

Fractional flow reserve (FFR) has become the gold standard for invasively assessing the functional significance of coronary artery disease (CAD) to guide revascularization. The amount of evidence supporting the role of FFR in the cardiac catheterization laboratory is large and still growing. However, FFR uptake in the daily practice is limited by a variety of factors such as invasive instrumentation of the coronary artery that requires extra time and need for vasodilator medications for hyperemia. In this review, we describe the details of wire-based alternatives to FFR, providing insights as to their development, clinical evidence, and limitations.

O-ring-induced transverse aortic constriction (OTAC) is a new simple method to develop cardiac hypertrophy and heart failure in mice.

Suture-based transverse aortic constriction (TAC) in mice is one of the most frequently used experimental models for cardiac pressure overload-induced heart failure. However, the incidence of heart failure in the conventional TAC depends on the operator's skill. To optimize and simplify this method, we proposed O-ring-induced transverse aortic constriction (OTAC) in mice. C57BL/6J mice were subjected to OTAC, in which an o-ring was applied to the transverse aorta (between the brachiocephalic artery and the left common carotid artery) and tied with a triple knot. We used different inner diameters of o-rings were 0.50 and 0.45 mm. Pressure overload by OTAC promoted left ventricular (LV) hypertrophy. OTAC also increased lung weight, indicating severe pulmonary congestion. Echocardiographic findings revealed that both OTAC groups developed LV hypertrophy within one week after the procedure and gradually reduced LV fractional shortening. In addition, significant elevations in gene expression related to heart failure, LV hypertrophy, and LV fibrosis were observed in the LV of OTAC mice. We demonstrated the OTAC method, which is a simple and effective cardiac pressure overload method in mice. This method will efficiently help us understand heart failure (HF) mechanisms with reduced LV ejection fraction (HFrEF) and cardiac hypertrophy.

Neural correlates of beneficial effects of young plasma treatment in aged mice: PET-SPM analyses and neuro-behavioural/molecular biological studies.

PURPOSE: To investigate the in vivo neurofunctional changes and therapeutic effects of young blood plasma (YBP) in aged mice, as well as the molecular mechanisms underlying the therapeutic effects of YBP ex vivo and in vitro. METHODS: Aged C57/BL6 mice received systemic administrations of phosphate-buffered saline (PBS) or YBP twice a week, for 4 weeks. In vivo 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) under conscious state and cognitive behavioural tests were performed after 4-week treatment. In addition, an in vitro senescent model was established, and the expressions of key cognition-associated proteins and/or the alterations of key neuronal pathways were analysed in both brain tissues and cultured cells. RESULTS: Aged mice treated with YBP demonstrated higher glucose metabolism in the right hippocampus and bilateral somatosensory cortices, and lower glucose metabolism in the right bed nucleus of stria terminalis and left cerebellum. YBP treatment exerted beneficial effects on the spatial and long-term social recognition memory, and significantly increased the expressions of several cognition-related proteins and altered the key neuronal signalling pathways in the hippocampus and somatosensory cortex. Further in vitro studies suggested that YBP but not aged blood plasma significantly upregulated the expressions of several cognition-associated proteins. CONCLUSION: Our results highlight the role of the hippocampus and somatosensory cortex in YBP-induced beneficial effects on recognition memory in aged mice. 18F-FDG PET imaging under conscious state provides a new avenue for exploring the mechanisms underlying YBP treatment against age-related cognitive decline.

PET imaging of brain aromatase in humans and rhesus monkeys by 11C-labeled cetrozole analogs.

Aromatase is an estrogen synthetic enzyme that plays important roles in brain functions. To quantify aromatase expression in the brain by positron emission tomography (PET), we had previously developed [11C]cetrozole, which showed high specificity and affinity. To develop more efficient PET tracer(s) for aromatase imaging, we synthesized three analogs of cetrozole. We synthesized meta-cetrozole, nitro-cetrozole, and iso-cetrozole, and prepared the corresponding 11C-labeled tracers. The inhibitory activities of these three analogs toward aromatase were evaluated using marmoset placenta, and PET imaging of brain aromatase was performed using the 11C-labeled tracers in monkeys. The most promising analog in the monkey study, iso-cetrozole, was evaluated in the human PET study. The highest to lowest inhibitory activity of the analogs toward aromatase in the microsomal fraction from marmoset placenta was in the following order: iso-cetrozole, nitro-cetrozole, cetrozole, and meta-cetrozole. This order showed good agreement with the order of the binding potential (BP) of each 11C-labeled analog to aromatase in the rhesus monkey brain. A human PET study using [11C]iso-analog showed a similar distribution pattern of binding as that of [11C]cetrozole. The time-activity curves showed that elimination of [11C]iso-cetrozole from brain tissue was faster than that of 11C-cetrozole, indicating more rapid metabolism of [11C]iso-cetrozole. [11C]Cetrozole has preferable metabolic stability for brain aromatase imaging in humans, although [11C]iso-cetrozole might also be useful to measure aromatase level in living human brain because of its high binding potential.

Long-term outcome of fetus with ameliorated cystic hygroma.

OBJECTIVE: Cystic hygroma often ameliorates or disappears with pregnancy progression. Fetuses/neonates with amelioration, when without chromosomal or major structural abnormality, generally show a favorable outcome at birth. The present study was aimed to clarify the short/long-term outcomes of fetuses/neonates with the amelioration of cystic hygroma during pregnancy. MATERIAL AND METHODS: This was a retrospective observational study. We focused on fetuses with cystic hygroma managed in our institute between January 2006 and June 2019. The infants were followed by pediatricians (neonatologist, pediatric cardiologist, and pediatric neurologist) and pediatric outcomes were retrieved from the medical records up to 3 years old. RESULTS: One hundred and seven fetuses with cystic hygroma were included. Of the 107, cystic hygromas ameliorated in 31 fetuses (31/107: 29%). Of the 31, there were 26 livebirths. Half (n = 13) of the 26 fetuses had a good outcome, whereas the remaining half (n = 13) had abnormalities. Various abnormalities were detected in their infancies. A nuchal thickness (diameter of hygroma) of ≥5 mm was significantly correlated with abnormalities (P = 0.047). CONCLUSION: Physicians should pay attention to fetuses/neonates with ameliorated cystic hygroma. Of those, special attention should be paid to fetuses/neonates with a nuchal thickness at diagnosis ≥5 mm.

Importance of left ventricular contraction for left atrial reservoir function.

BACKGROUND: The determinants of left atrial (LA) reservoir function have not been clarified. METHODS: To elucidate the effect of left ventricular (LV) contraction on LA reservoir volume (ΔVLA), volume change due to mitral annular downward motion and aortic root anterior motion, which are related to LV contraction during systole, was calculated in 72 consecutive subjects [42 patients without any cardiac disease (control group), 13 patients with heart failure with reduced ejection fraction (HFrEF group) and 17 with preserved ejection fraction (HFpEF group)]. LA volume was calculated using the modified Simpson's method of bi-plane 2-D echocardiograms. ΔVLA was the difference between the maximum and minimum LA volumes. LA volume change according to mitral annular motion (ΔVMA) and aortic root motion (ΔVAR) were calculated by assuming an oval frustum and dented wedge, respectively. RESULTS: In the normal control group, ΔVAR + ΔVMA was 11.7 ml on average, correlating to ΔVLA (r = 0.55, p < 0.01), and the contribution rate to LA reservoir volume ((ΔVAR + ΔVMA)/ΔVLA) was 56% on average. In both, the HFrEF and HFpEF groups, ΔVAR, ΔVMA, and the contribution rate were significantly smaller than those in normal control group. Stroke volume correlated to ΔVAR and ΔVMA. The larger the maximum LA volume was, the smaller the contribution rate was. The smaller the rate was, the higher the systolic pulmonary artery pressure was. CONCLUSIONS: Both mitral annular motion and aortic root anterior motion, which are related to ventricular contraction, are important for the LA reservoir volume recruitment.

PET imaging of neural activity, ß-amyloid, and tau in normal brain aging.

Normal brain aging is commonly associated with neural activity alteration, ß-amyloid (Aß) deposition, and tau aggregation, driving a progressive cognitive decline in normal elderly individuals. Positron emission tomography (PET) with radiotracers targeting these age-related changes has been increasingly employed to clarify the sequence of their occurrence and the evolution of clinically cognitive deficits. Herein, we reviewed recent literature on PET-based imaging of normal human brain aging in terms of neural activity, Aß, and tau. Neural hypoactivity reflected by decreased glucose utilization with PET imaging has been predominately reported in the frontal, cingulate, and temporal lobes of the normal aging brain. Aß PET imaging uncovers the pathophysiological association of Aß deposition with cognitive aging, as well as the potential mechanisms. Tau-associated cognitive changes in normal aging are likely independent of but facilitated by Aß as indicated by tau and Aß PET imaging. Future longitudinal studies using multi-radiotracer PET imaging combined with other neuroimaging modalities, such as magnetic resonance imaging (MRI) morphometry, functional MRI, and magnetoencephalography, are essential to elucidate the neuropathological underpinnings and interactions in normal brain aging.

Low placental growth factor levels and high soluble endoglin levels at 26-31 weeks of gestation precede light placenta with and without relatively heavy infant, respectively: A retrospective cohort study.

AIM: Our aim was to examine whether serum levels of placental growth factor (PlGF) and soluble endoglin (sEng) at 19-25 and 26-31 weeks of gestation were associated with the occurrence of the 9-block categorization of placenta weight (PW) and fetal/placenta ratio (F/P ratio). METHODS: We performed a retrospective cohort study in 1391 women with singleton pregnancy. Serum levels of PlGF and sEng were measured by enzyme immunosorbent assay. A light placenta was defined as PW ZS < -1.28 SD. Based on the PW (light, normal, and heavy) and F/P ratio (relatively heavy, balanced growth, and relatively small), 9-block categorization were performed. Multivariable logistic regression analyses were performed. RESULTS: Low PlGF at 26-31 weeks was an independent risk factor for the birth of infants belonging to Block A (light placenta and relatively heavy infant), after adjusting for prepregnancy body mass index and serum levels of sEng. High sEng at 26-31 weeks was an independent risk factor for the birth of infants belonging to Block D (light placenta and balanced growth of infant), after adjusting for past history of either preeclampsia or gestational hypertension, high pulsatility index of uterine artery flow velocity waveforms in the second trimester, and serum level of PlGF. CONCLUSIONS: Low PlGF levels at 26-31 weeks of gestation may precede a light placenta and relatively heavy infant (Block A), and high sEng levels at 26-31 weeks of gestation may precede a light placenta and balanced growth of infant (Block D).

Impact of corporal punishment on victims' future violent behavior in extracurricular sports.

BACKGROUND: Over 500 cases of school-based corporal punishment (CP) are reported annually in Japan. A major feature of CP in Japanese schools is its high prevalence during extracurricular sports activities. OBJECTIVE: The purpose of this study was to examine the influence of having suffered a CP-related injury on victims' later use of CP in an athletics environment. PARTICIPANTS AND SETTING: Participants were 704 undergraduate students of a sports instructor training course who were recruited as volunteers during classes. METHODS: A questionnaire on past experiences of CP and later perpetration of CP was administered to the participants. It was found that 31.3% of the students had experienced CP and 2.3% had perpetrated CP on others. We conducted logistic regression analyses with CP as an objective dependent variable and gender, grade and past CP experience (elementary, junior high school, or high school) as explanatory variables. RESULTS: The results of the analysis revealed that having experienced CP had a significant relationship with the victims' perpetration of CP. Elementary school was the only life stage for which there was a significant correlation between having been a victim of CP and practicing it in the future. CONCLUSIONS: Many studies have explored the use of CP in families, while others have demonstrated that physical education students who received CP themselves are more likely to find CP an acceptable method of maintaining discipline. This is the first study that investigates whether students who experienced CP show a higher prevalence of CP perpetration. The findings indicate that experiencing CP in childhood is a risk factor for future use of CP. Proper care is required for children who have experienced CP at a young age.

Quantification of aromatase binding in the female human brain using [11 C]cetrozole positron emission tomography.

Aromatase, the enzyme that in the brain converts testosterone and androstenedione to estradiol and estrone, respectively, is a putative key factor in psychoneuroendocrinology. In vivo assessment of aromatase was performed to evaluate tracer kinetic models and optimal scan duration, for quantitative analysis of the aromatase positron emission tomography (PET) ligand [11 C]cetrozole. Anatomical magnetic resonance and 90-min dynamic [11 C]cetrozole PET-CT scans were performed on healthy women. Volume of interest (VOI)-based analyses with a plasma-input function were performed using the single-tissue and two-tissue (2TCM) reversible compartment models and plasma-input Logan analysis. Additionally, the simplified reference tissue model (SRTM), Logan reference tissue model (LRTM), and standardized uptake volume ratio model, with cerebellum as reference region, were evaluated. Parametric images were generated and regionally averaged voxel values were compared with VOI-based analyses of the reference tissue models. The optimal reference model was used for evaluation of a decreased scan duration. Differences between the plasma-input- and reference tissue-based methods and comparisons between scan durations were assessed by linear regression. The [11 C]cetrozole time-activity curves were best described by the 2TCM. SRTM nondisplaceable binding potential (BPND ), with cerebellum as reference region, can be used to estimate [11 C]cetrozole binding and generated robust and quantitatively accurate results for a reduced scan duration of 60 min. Receptor parametric mapping, a basis function implementation of SRTM, as well as LRTM, produced quantitatively accurate parametric images, showing BPND at the voxel level. As PET tracer, [11 C]cetrozole can be employed for relatively short brain scans to measure aromatase binding using a reference tissue-based approach.

Extremely high levels of multiple cytokines in the cord blood of neonates born to mothers with systemic autoimmune diseases.

Most infants born to mothers with autoimmune diseases are thought to be entirely healthy. However, the immunological conditions have not been examined thoroughly. Fourteen neonates born to mothers with systemic autoimmune diseases, namely systemic lupus erythematosus, mixed connective tissue disease, Sjögren's syndrome, rheumatoid arthritis, and systemic sclerosis, were included. Serum concentrations of 17 cytokines from the infants' umbilical artery (UA) and vein (UV) and from the mothers' peripheral blood were investigated by a bead array system. Cytokine expression in the placenta was investigated by immunohistochemical staining. The disease was controlled in all mothers, and none had chorioamnionitis. Hypercytokinemia was found in 11 neonates irrespective of their mothers' autoimmune diseases. In six neonates, serum cytokines were at extremely high levels. Four neonates were born by cesarean section because of a non-reassuring fetal status (NRFS) of unknown cause were all included in the hypercytokinemia group. However, all the subjects were discharged without any complications. The cytokine levels were almost the same between UA and UV, but the mothers' blood samples did not show elevation of serum cytokines. There were no differences in the expression of cytokines in the placenta among three patients with different serum cytokines levels. Hypercytokinemia frequently occurred and a cytokine storm state sometimes developed in neonates born to mothers with systemic autoimmune diseases. Growth restriction and NRFS may be related to hypercytokinemia in utero. It is plausible that the high level of cytokines in cord blood originate in neither the mother nor the placenta but in fetal immune tissues. It is important to investigate the immunological mechanisms, prevalence, and long-term influence of hypercytokinemia in a large sample size of neonates and mothers with systemic autoimmune diseases.

Deletion of interleukin-18 attenuates abdominal aortic aneurysm formation.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) is a common disease; however, its exact pathogenesis remains unknown, and no specific medical therapies are available. Interleukin (IL)-18 plays a crucial role in atherosclerotic plaque destabilization and is a strong predictor of cardiovascular death. Here, we investigated the role of IL-18 in AAA pathogenesis using an experimental mouse model. METHODS AND RESULTS: After infusion of angiotensin II (Ang II) for 4 weeks and ß-aminopropionitrile (BAPN) for 2 weeks, 58% of C57/6J wild-type (WT) mice developed AAA associated with enhanced expression of IL-18; however, disease incidence was significantly lower in IL-18-/- mice than in WT mice (p < 0.01), although no significant difference was found in systolic blood pressure between WT mice and IL-18-/- mice in this model. Additionally, IL-18 deletion significantly attenuated Ang II/BAPN-induced macrophage infiltration, macrophage polarization into inflammatory M1 phenotype, and matrix metalloproteinase (MMP) activation in abdominal aortas, which is associated with reduced expression of osteopontin (OPN). CONCLUSIONS: These findings indicate that IL-18 plays an important role in the development of AAA by enhancing OPN expression, macrophage recruitment, and MMP activation. Moreover, IL-18 represents a previously unrecognized therapeutic target for the prevention of AAA formation.

Temporary hypertension and white coat hypertension in the first trimester as risk factors for preeclampsia.

We compared the risk of preeclampsia (PE) among women with normal blood pressure (BP), high-normal BP, high BP, temporary hypertension (THT), white coat hypertension (WCH), and chronic hypertension (CH) in the first trimester. This was a retrospective cohort study involving 2858 pregnant women, who received regular maternal checkups at <12 weeks. BP levels were evaluated using the average of the second and third BP readings. When patients showed HT in the first trimester that later normalized during 14-19 weeks, we called this condition THT. BP levels were classified as normal BP, high-normal BP, high BP, THT, WCH, and CH. PE was defined as a new onset of HT after 20 weeks accompanied by either proteinuria or other organ dysfunctions. Gestational hypertension (GH) was defined as the new onset of HT after 20 weeks. The proportion of WCH in women with newly diagnosed HT was 47%. PE occurred in 1.3, 4.3, 8.1, 8.2, 14.3, and 25.0% of women with normal BP, high-normal BP, high BP, THT, WCH, and CH, respectively. GH occurred in 0.3, 1.8, 9.9, 2.0, and 28.6% of women with normal BP, high-normal BP, high BP, THT, and WCH, respectively. After adjusting for possible confounding variables, high-normal BP, high BP, THT, WCH, and CH were independent risk factors for PE vs. normal BP; in addition, high-normal BP, high BP/THT, and WCH were independent risk factors for GH vs. normal BP. In conclusion, THT and WCH in the first trimester were risk factors for PE, and WCH was a risk factor for GH.

Markedly higher sFlt-1/PlGF ratio in a woman with acute fatty liver of pregnancy compared with HELLP syndrome.

AIM: To compare serum levels of angiogenesis-related factors between 14 women with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome and a woman with acute fatty liver of pregnancy (AFLP). METHODS: Serum samples were collected in 2004-2008 and 2013-2016. The levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) were measured by an automated electrochemiluminescence immunoassay using Elecsys sFlt-1 and Elecsys PlGF. After logarithmic transformation, levels of sFlt-1, PlGF and the sFlt-1/PlGF ratio in a woman with AFLP were compared with those in women with HELLP syndrome, using the one-sample t-test. RESULTS: At 37 weeks of gestation, a patient was diagnosed with AFLP based on Swansea criteria (showing six features including elevated transaminases), and she also showed a duodenal ulcer with active bleeding, thrombocytopenia and hypertension. Her serum levels of sFlt-1 and sFlt-1/PlGF ratio were significantly higher than in those with HELLP syndrome (273 040 pg/mL vs 15 135 [mean], P < 0.001; 4236 vs 224, P < 0.001; respectively). However, her serum level of PlGF was not significantly different from those with HELLP syndrome. CONCLUSION: Serum levels of sFlt-1 and the sFlt-1/PlGF ratio, but not PlGF, in a woman with AFLP were markedly higher than those in women with HELLP syndrome. AFLP may be a different clinical entity from HELLP syndrome based on angiogenesis-related factors. Clinically, the sFlt-1/PlGF ratio may be used to rapidly distinguish AFLP from HELLP syndrome.