Cook Cervical Ripening Balloon for placenta accreta spectrum disorders with placenta previa: a novel approach to uterus preserving.

PURPOSE: To evaluate the efficacy of intrauterine inflated Cook Cervical Ripening Balloon (ICRB) in postpartum hemorrhage (PPH) management and fertility preserving for placenta accreta spectrum disorders with placenta previa (previa PAS). METHODS: At a tertiary referral center, 74 patients suffering with previa PAS were entered into this retrospective cohort study from January, 2016 to December, 2020, and were confirmed intraoperatively that abnormal invasive placenta reaches the cervical internal ostium and the upper part of the cervical canal. In control group (n = 39), the combination of infrarenal abdominal aorta balloon occlusion (IAABO) and longitudinal parallel compression suture to lower uterine segment were performed. In study group (n = 35), in addition to the aforementioned surgical techniques, ICRB was implemented at the cervical internal ostium and the outside of the cervix simultaneously. RESULTS: Use of ICRB significantly reduced the rate of peripartum hysterectomy (2.9% vs 30.4%, p = 0.001), and associated with a reduction in surgical time and duration of IAABO (mean 172.7 min vs 206.6 min, p = 0.017; median 30 min vs 40 min, p < 0.001). Use of ICRB significantly reduced the estimated amount of blood loss (median 2500 ml vs 4000 ml, p < 0.001), amounts of packed red blood cells and fresh-frozen plasma transfusion (median 6 U vs 13.5 U, p < 0.001; median 450 ml vs 1200 ml, p < 0.001), postoperative hospital stay and the incidence of oligomenorrhea postoperatively (median 5 days vs 6 days, p = 0.009; 13.8% vs 61.1% p = 0.001). No significant difference was observed between both the groups regarding the use of cryo and PLT, injury of urinary system, relaparotomy, admission to the ICU, postpartum hematocele in uterine cavity, and postoperative complications (including incidence rate of DVT, incidence rate of femoral thrombosis, puerperal morbidity, intrauterine infection, surgical site infection, and deep tissue infection). CONCLUSION: ICRB was a simple, effective procedure for PPH management and fertility preserving in some previa PAS cases in which abnormal invasive placenta reaches the cervical internal ostium and the upper part of the cervical canal, in tandem with IAABO and compression suture.

HC diet inhibited testosterone synthesis by activating endoplasmic reticulum stress in testicular Leydig cells.

Emerging epidemiological studies indicate that hypercholesterolaemia is a risk factor for testosterone deficiency. However, the underlying mechanism is unclear. Testicular Leydig cells are the primary source of testosterone in males. To identify the effect and mechanism of cholesterol overload on Leydig cell function, rats were fed with a HC (HC) diet to induce hypercholesterolaemia. During the 16-week feeding period, serum testosterone levels were reduced in a time-dependent manner in rats fed the HC diet. Accordingly, these steroidogenic enzymes within the Leydig cells, including steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage cytochrome P450 (P450scc) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD), were down-regulated. Notably, the HC-fed rats showed evident endoplasmic reticulum (ER) stress in the testis, including a dilated ER as an evident pathological change in the Leydig cell ultrastructure, up-regulated ER stress biomarker (binding immunoglobulin protein) levels and activation of the activating transcription factor 6 (ATF6)-related unfolded protein response pathway. Further analysis showed that when 4-phenyl butyric acid (4-PBA) was used to block ER stress in HC-fed rats for 8 weeks, the testosterone deficiency was significantly alleviated. Our findings suggested that high dietary cholesterol intake affected serum testosterone levels by down-regulating steroidogenic enzymes and that activated ER stress might serve as the underlying mechanism.

Invasive placenta previa: Placental bulge with distorted uterine outline and uterine serosal hypervascularity at 1.5T MRI - useful features for differentiating placenta percreta from placenta accreta.

OBJECTIVES: To characterise MRI features of invasive placenta previa and to identify specific features for differentiating placenta percreta (PP) from placenta accreta (PA). METHODS: Forty-five women with PP and 93 women with PA who underwent 1.5T placental MRI were included. Two radiologists independently evaluated the MRI features of invasive placenta previa, including our novel type of placental bulge (i.e. placental bulge type-II, characterized by placental bulge with distorted uterine outline). Pearson's chi-squared or Fisher's two-sided exact test was performed to compare the MRI features between PP and PA. Logistic stepwise regression analysis and the area under the receiver operating characteristic curve (AUC) were performed to select the optimal features for differentiating PP from PA. RESULTS: Significant differences were found in nine MRI features between women with PP and those with PA (P <0.05). Placental bulge type-II and uterine serosal hypervascularity were independently associated with PP (odds ratio = 48.618, P < 0.001; odds ratio = 4.165, P = 0.018 respectively), and the combination of the two MRI features to distinguish PP from PA yielded an AUC of 0.92 for its predictive performance. CONCLUSION: Placental bulge type-II and uterine serosal hypervascularity are useful MRI features for differentiating PP from PA. KEY POINTS: • Placental bulge type-II demonstrated the strongest independent association with PP. • Uterine serosal hypervascularity is a useful feature for differentiating PP from PA. • MRI features associated with abnormal vessels increase the risk of massive haemorrhage.

Association of maternal serum lipids at late gestation with the risk of neonatal macrosomia in women without diabetes mellitus.

BACKGROUND: Macrosomia is a serious public health problem worldwide due to its increasing prevalence and adverse influences on maternal and neonatal outcomes. Maternal dyslipidemia exerts potential and adverse impacts on pregnant women and newborns. However, the association between maternal serum lipids and the risk of macrosomia has not yet been clearly elucidated. We explored the association between the maternal lipids profile at late gestation and the risk of having macrosomia among women without diabetes mellitus (DM). METHODS: The medical records of 5407 pregnant women giving birth to single live babies at term were retrospectively analyzed. Subjects with DM, hypertension, thyroid disorders and fetal malformation were excluded. Maternal fasting serum lipids were measured during late pregnancy. Logistic regression analysis was used to analyze the variables associated with the risk of macrosomia. RESULTS: Maternal serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were related to macrosomia; each 1 mmol/L increase in TG resulted in a 27% increase in macrosomia risk, while each 1 mmol/L increase in HDL-C level resulted in a 37% decrease in macrosomia risk, even after adjusting for potential confounders. Notably, the risk of macrosomia increased progressively with increased maternal serum TG levels and decreased HDL-C levels. Compared with women with serum TG levels < 2.5 mmol/L, women with TG levels greater than 3.92 mmol/L had an approximately 2.8-fold increased risk of macrosomia. Compared with women with serum HDL-C levels above 2.23 mmol/L, women with HDL-C levels of less than 1.62 mmol/L had a 1.9-fold increased risk of giving birth to an infan with macrosomia. In addition, a higher risk of macrosomia was observed in women with simultaneous hypertriglyceridemia and low serum HDL-C levels (odds ratio [OR] 2.400, 95% confidence interval [CI]: 1.760-3.274) compared to those with hypertriglyceridemia or low serum HDL-C alone (OR 2.074, 95% CI: 1.609-2.673 and OR 1.363, 95% CI: 1.028-1.809, respectively). CONCLUSIONS: Maternal serum TG levels and HDL-C levels at late gestation are independent predictors of macrosomia in women without DM.

Retrospective analysis: Conservative treatment of placenta increta with methotrexate.

AIM: To evaluate the efficacy of conservative treatment with methotrexate against placenta increta by two different routes of administration through retrospective analysis. METHODS: A total of 54 women diagnosed with placenta increta after vaginal delivery were enrolled in this retrospective study. The participants accepted conservative management with methotrexate through either intravenous injection or local multi-point injection under ultrasound guidance. The treatment was considered effective if no hysterectomy was mandatory during the follow-up period. RESULTS: Out of the 54 cases, 21 patients were treated with methotrexate intravenously (group 1), and 33 patients received local multi-point injection to the placenta increta under ultrasound guidance (group 2). No maternal death occurred. In group 1, 10 patients expelled the placentas spontaneously, 7 patients underwent uterine curettage and 4 patients underwent hysterectomy for uncontrollable post-partum hemorrhage and infection. In group 2, 25 patients expelled placentas spontaneously and 8 patients underwent uterine curettage with no incidence of hysterectomy. The success rate in group 1 and group 2 was 17/21 and 33/33, respectively. The average time of the spontaneous placenta expulsion was 79.13 ± 29.87 days in group 1 and 42.42 ± 31.83 days in group 2. CONCLUSION: Local multi-point methotrexate injection under ultrasound guidance is a better alternative for patients with placenta increta, especially for preserving fertility.

SIMVASTATIN DECREASES SEX HORMONE LEVELS IN MALE RATS.

OBJECTIVE: Statins can inhibit therate-limiting enzyme hydroxymethyl glutaric acid-coenzyme A reductase to reduce cholesterol biosynthesis, and they are used frequently in the clinic. Cholesterol is also a precursor for sex hormones. However, it is not clear whether statins can affect sex hormone levels. The aim of this study was to investigate the effect of long-term use of statins on sex hormone levels in vivo. METHODS: Forty male Sprague-Dawley rats were randomly divided into four groups. Three simvastatin groups were administered different doses of simvastatin intragastrically daily (4, 8, or 16 mg/kg/day, n = 10). The control group was administered vehicle intragastrically daily (n = 10). The serum lipid spectrum and testosterone, estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured before (0 weeks) and after 20 and 40 weeks of simvastatin administration. RESULTS: In the control group, there were no statistically significant differences between lipid levels, liver function, or sex hormone levels before and after intragastric administration. Compared with the previous intragastric administration group, there was no obvious change in liver function with different doses of simvastatin. However, serum levels of total cholesterol, low-density-lipoprotein cholesterol, triglycerides, testosterone, estradiol, and progesterone were markedly decreased in a dose- and time-dependent manner. By contrast, the levels of FSH and LH were significantly higher, showing feedback regulation. CONCLUSION: Long-term simvastatin intake reduces serum testosterone, estradiol, and progesterone levels in male rats. ABBREVIATIONS: HMG-CoA = hydroxymethyl glutaric acid CoA LDL = low-density lipoprotein LDL-C = low-density-lipoprotein cholesterol FSH = follicle-stimulating hormone LH = luteinizing hormone.

LDL in patients with subclinical hypothyroidism shows increased lipid peroxidation.

BACKGROUND: Population-based studies have demonstrated that subclinical hypothyroidism (SCH) is an independent risk factor for atherosclerosis (OR = 1.9). However, this connection cannot be entirely explained by dyslipidemia accompanied by SCH. Lipid peroxidation also plays an important role in the development of atherosclerosis. In this study, we aimed to evaluate oxidative stress in SCH patients, as measured according to concentrations of hydroxy-octadecadienoic acids (HODEs) and hydroxy-eicosatetraenoic acids (HETEs) in both plasma and low density lipoproteins (LDL). SUBJECTS AND METHODS: The concentrations of HODEs and HETEs in both LDL and plasma were examined in euthyroid (n = 10), mild SCH (4.5 ≤ TSH < 10 mU/L, n = 10), and significant SCH (TSH ≥ 10 mU/L, n = 10) subjects, using a liquid chromatograph-electrospray ionization- mass spectrometer. Then, we explored the relationship among LDL oxidation, TSH levels, and carotid intima-media thickness (IMT), a biomarker of subclinical atherosclerosis. RESULTS: Serum LDL-C levels and mean-IMT in the significant SCH group were higher than in the euthyroid group (p < 0.05). The HODE and HETE concentrations clearly increased in the significant SCH patients compared with the euthyroid subjects, but there was no difference between the mild SCH and euthyroid groups. Among all subjects, linear and significant positive correlations were identified between TSH and mean-IMT after adjustment for confounding factors (r = 0.480, p = 0.018). Both 9-HODE (r = 0.376, p = 0.041) and 13-HODE (r = 0.447, p = 0.013) in LDL were linearly and positively correlated with TSH. The concentrations of HODEs (both 9-HODE and 13-HODE) in LDL were much higher in the thickened IMT group than in the normal IMT group (p = .017 and 0.015, respectively). HODEs in LDL were also positively associated with mean-IMT. CONCLUSIONS: Our findings showed that lipid peroxidation was higher in the significant SCH patients than in the euthyroid subjects, which suggested that qualitative as well as quantitative changes in serum lipids resulting from SCH may add to atherosclerosis risk.

Hsa-miRNA-125b may induce apoptosis of HTR8/SVneo cells by targeting MCL1.

MiR-125b regulates the kinds of cells that undergo apoptosis physiologically and pathologically. However, whether miR-125b affects the apoptotic behavior of trophoblasts and the underlying molecular regulatory mechanisms remains unclear. This study investigated the effect of miR-125b on apoptosis of HTR-8/SVneo cells in vitro. Constructed wild-type reporter vector (Wt-3'UTR) or mutated type reporter vector (Mut-3'UTR) reporter plasmids were transiently transfected into 293 T cells along with miR-125b mimics or a negative control. The luciferase reporter assay was used to validate whether the predicted MCL1 gene is a direct target of miR-125b. The HTR8/SVneo cells were transfected with miR-125 mimics, inhibitors, or a scramble control. Real-time polymerase chain reaction and western blotting were used to analyze mRNA and protein expression of the target gene MCL1. Flow cytometry was used to determine the effects on apoptosis. The luciferase activity assay validated the ability of miR-125b to specifically attenuate MCL1 transcription in the 293 T cell line, suggesting that MCL1 is a direct target of miR-125b. After transfection by miR-125b, relative expression and translation of the target gene MCL1 mRNA were repressed in HTR-8/SVneo cells. Trophoblast cells were induced to undergo apoptosis by overexpressing miR-125b in the HTR-8/SVneo cell line. In conclusion, MiR-125b may induced apoptosis of HTR8/SVneo cells by targeting MCL1. Our findings suggest that miR-125b may play a pivotal role in the pathophysiology of placentation.

Maternal hyperuricemia superimposed on maternal hypertension aggravates the risk of small-for-gestational-age fetus.

AIMS: Small-for-gestational-age (SGA) fetus is an important public health issue because of its high mortality and long-term effects on health. Maternal hyperuricemia is associated with diverse adverse pregnant outcomes and neonatal disturbance. We aimed to evaluate whether maternal hyper-uric acid (HUA) is associated with the risk of SGA fetus and to explore whether it can modify the association between maternal hyper-blood pressure (HBP) and SGA fetus. MATERIALS AND METHODS: We performed a population-based cross-section retrospective study, a total of 6715 pregnant females were recruited. Multiple logistic regression analysis was performed to identify risk factors significantly correlated with SGA fetus, and then studied the effect of maternal HUA on the association between maternal HBP and SGA fetus. KEY FINDINGS: We collected 537 SGA fetuses among 6715 pregnant females. Maternal HUA was an independent risk factor for SGA delivery (odds ratio (OR), 2.737; 95% confidence interval (CI), 2.110-3.551). A dose-response association between maternal uric acid and SGA delivery was found among normotensive and hypertensive group. Compared with those whose uric acid was lower than 270 µmo/L with normal-blood pressure (NBP), the risk for SGA delivery in those whose uric acid was higher than 370 µmo/L with stage 2 or 3 hypertension increased 12.695-fold. SIGNIFICANCE: Our results suggest that maternal HUA could increase the risk of neonatal SGA, and maternal HUA could be superimposed upon pre-existing maternal HBP and increase the risk for SGA fetus.

Downregulation of MicroRNA-125a in Placenta Accreta Spectrum Disorders Contributes Antiapoptosis of Implantation Site Intermediate Trophoblasts by Targeting MCL1.

The typical hallmark of placenta accreta spectrum (PAS) disorders is increased implantation site intermediate trophoblast (ISIT) cell numbers. However, the extent of trophoblast proliferation and apoptosis have not been found to differ from those of normal placentation. MicroRNA-125a (miR-125a) induces apoptosis in colon cancer cell by targeting myeloid cell leukemia-1 gene (MCL1). We aimed to investigate the influence of miR-125a on ISIT cells in PAS disorders in 15 patients (self-paired trials) with placenta previa and PAS disorders. Expression of miR-125a and MCL1 were measured in villous trophoblasts and basal plate myometrial fibers from creta site and adjacent noncreta tissues by real-time quantitative polymerase chain reaction, and expression of the MCL1 protein was assayed by Western blotting. Flow-cytometry was used to examine the effect of miR-125a overexpression on apoptosis in vitro in HTR-8/SVneo cells, and luciferase activity assays was used to confirm miR-125a targeting of MCL1. In vivo, the expression levels of miR-125a was significantly lower in creta versus noncreta tissues, and the expression of MCL1 was upregulated; moreover, immunohistochemistry showed that the increased ISIT cells in the creta were positive for MCL1 protein. MCL1 was downregulated in the miR-125a-overexpressing HTR-8/SVneo cells in vitro, and overexpression of miR-125a-induced apoptosis in the HTR-8/SVneo trophoblast line. Finally, luciferase activity assays confirmed that miR-125a directly target the 3' untranslated region of MCL1 in the 293T cell line. In conclusion, downregulation of MCL1-targeting miR-125a exerts an antiapoptotic effect on ISIT cells in PAS disorders.

Aspirin Ameliorates Preeclampsia Induced by a Peroxisome Proliferator-Activated Receptor Antagonist.

Reduced expression of peroxisome proliferator-activated receptor γ (PPARγ) in the placenta was found in women with severe preeclampsia. Aspirin is currently used as the only recommended intervention in pregnancies for prevention of preeclampsia. In this study, we aimed to investigate whether aspirin could attenuate PPARγ inhibitor (T0070907)-induced preeclampsia and its impact on expression of PPARγ. Sixty Sprague-Dawley rats were used and treated with different doses of aspirin (0, 1, and 1.5 mg/kg) in presence or absence of PPARγ antagonist, T0070907. We found that mean arterial blood pressure was significantly reduced by aspirin treatment in T0070907-exposed rats. T0070907 exposure also led to significant decrease in fetal weight and increase in placental weights. However, 1.5 mg/kg of aspirin reversed these effects of T0070907. Additionally, aspirin also reversed T0070907-induced changes in the levels of thromboxane B2, vascular endothelial growth factor, soluble fms-like tyrosine kinase, and matrix metalloproteinase 2 in both maternal blood and placental tissue. The increased messenger RNA and protein levels of Cox1 and Cox2 induced by T0070907 were markedly reduced by aspirin treatment. Importantly, T0070907 repressed both transcriptional and translational levels of PPARγ, which were reversed by aspirin. In conclusion, this study suggests that aspirin prevented the occurrence of preeclampsia, which is possibly through enhancing both transcriptional and translational levels of PPARγ.

Unsatisfactory Glucose Management and Adverse Pregnancy Outcomes of Gestational Diabetes Mellitus in the Real World of Clinical Practice: A Retrospective Study.

BACKGROUND: Facing the increasing prevalence of gestational diabetes mellitus (GDM), this study aimed to evaluate the management of GDM and its association with adverse pregnancy outcomes. METHODS: The data of 996 inpatients with GDM who terminated pregnancies in our hospital from January 2011 to December 2015 were collected. Treatments during pregnancy and the last hospital admission before delivery were analyzed. Pregnancy outcomes of the GDM patients were compared with 996 nondiabetic subjects matched by delivery year and gestational age. The association between fasting plasma glucose (FPG) and adverse pregnancy outcomes was examined by logistic regression analyses. RESULTS: The average prevalence of GDM over the 5 years was 4.4% (1330/30,191). Within the GDM patients, 42.8% (426/996) received dietary intervention, whereas 19.1% (190/996) received insulin treatment. Adverse outcomes were more likely to occur in patients with unsatisfactory control of blood glucose such as respiratory distress syndrome (RDS, χ2 = 13.373, P < 0.01). Elevated FPG was identified as an independent risk factor for premature birth (odds ratio [OR] = 1.460, P < 0.001), neonatal care unit admission (OR = 1.284, P < 0.001), RDS (OR = 1.322, P = 0.001), and stillbirth (OR = 1.427, P < 0.001). CONCLUSIONS: Management of GDM in the real world of clinical practice was unsatisfactory, which might have contributed to adverse pregnancy outcomes.

[Clinical study of selective multifetal pregnancy reduction in second trimester].

OBJECTIVE: To investigate the operative indication, timing, method, selective standards of feticided fetus and the number of reduced fetuses of selective multifetal pregnancy reduction in second trimester, and the pregnancy outcome of multifetal pregnancy by this operation. METHODS: Trans-abdominal selective multifetal pregnancy reductions in 37 cases of multiple pregnancy (twins 6 cases, triplets 21 cases, quadruplets 8 cases, and quintuplets 2 cases) during 12(+1) - 25 weeks were performed under ultrasound guidance. The fetus to be reduced was injected potassium chloride (KCl) intracardiacally until the fetal heartbeat stopped gradually. Totally 46 fetuses were reduced. Periodic prenatal examination and monitoring of coagulation function were carried out after the procedure. The pregnancy complications and pregnancy outcome of all cases were recorded. RESULTS: (1) The successful ratio of reduction was 100% (46/46 fetuses) and the successful pregnancy ratio was 88.9% (24/27). (2)Among all the 37 cases, fifteen delivered after 36 weeks, seven delivered in 32 - 36 weeks, three delivered in 28 - 32 weeks, two aborted after feticide, and ten cases were in pregnancy at the time of this study. The mean gestational age of all was (34.9 +/- 4.1) weeks, and the delivery ratio after 28 weeks was 92.6% (25/27). (3) The mean birth weight of singletons was (3014 +/- 640) g, and of twins was (2557 +/- 573) g. The neonates of three triplets all died except for in one case two fetuses were alive. (4) Except in two cases after reducing one fetus of monoamniotic twins, another one died within 24 hours, the remaining fetuses were all alive. (5) Pre-eclampsia occurred in three cases. None of the cases had blood coagulation disturbances. CONCLUSION: (1) Selective multifetal pregnancy reduction in second trimester can feticide the abnormal fetus objectively or reduce the fetal number effectively. It is a safe procedure to decrease the complications of multifetal pregnancy and increase the birth weight. (2) If the intention is reducing the fetal number, we choose the fetus who lies in the fundus uteri and reduce the multifetal pregnancy to twins. (3) It is advised to aviod performing the procedure during vaginal bleeding. We reduce fetus after vaginal bleeding stops for one or more weeks. (4) Selective second-trimester multifetal pregnancy reduction will not result in the disturbance of blood coagulation and the death of remaining fetus. The incidence of pre-eclampsia is decreased after multifetal pregnancy reduction.

Downregulation of miR-29a/b/c in placenta accreta inhibits apoptosis of implantation site intermediate trophoblast cells by targeting MCL1.

OBJECTIVE: Placenta accreta is defined as abnormal adhesion of placental villi to the uterine myometrium. Although this condition has become more common as a result of the increasing rate of cesarean sections, the underlying causative mechanism(s) remain elusive. Because microRNA-29a/b/c (miR-29a/b/c) have been shown to play important roles in placental development, this study evaluated the roles of these microRNAs in placenta accreta. METHODS: Expression of miR-29a/b/c and myeloid cell leukemia-1 (MCL1) were quantified in patient tissues and HTR8/SVneo trophoblast cells using the real-time quantitative polymerase chain reaction. Western blotting was used to analyze expression of the MCL1 protein in HTR8/SVneo trophoblast cells with altered expression of miR-29a/b/c. To determine their role in apoptosis, miR-29a/b/c were overexpressed in HTR-8/SVneo cells, and levels of apoptosis were analyzed by flow cytometry. Luciferase activity assays were used to determine whether MCL1 is a target gene of miR-29a/b/c. RESULTS: Expression of miR-29a/b/c was significantly lower in creta sites compared to noncreta sites (p = 0.018, 0.041, and 0.022, respectively), but expression of MCL1 was upregulated in creta sites (p = 0.039). MCL1 expression was significantly downregulated in HTR-8/SVneo cells overexpressing miR-29a/b/c (p = 0.002, 0.008, and 0.013, respectively). Luciferase activity assays revealed that miR-29a/b/c directly target the 3' untranslated region of MCL1 in 293T cells. Over-expression of miR-29a/b/c induced apoptosis in the HTR-8/SVneo trophoblast cell line. Moreover, histopathological evaluation revealed that the number of implantation site intermediate trophoblast (ISIT) cells was increased in creta sites and that these cells were positive for MCL1. CONCLUSIONS: Our results demonstrate that in placenta accreta, miR-29a/b/c inhibits apoptosis of ISIT cells by targeting MCL1. These findings provide new insights into the pathogenesis of placenta accreta.

Some severe maternal diseases might be caused by fetal-versus-maternal disease (FVMD).

Pregnancy-related disease is a common challenging clinical problem. From our review and clinical experience, we hypothesize that many severe pregnancy-related complications might be caused by a fetal-versus-maternal disease (FVMD), based on the fact that maternal disease is related to immunity and that fetal cells are present in maternal blood. Fetus is a semi-antigen and can be considered as a tumor or graft. The pathophysiology of FVMD must be complex. We speculate it to be a three-step process: impaired maternal immunological function, fetal T-cell activation and injury of target organs. More experiments and research will be needed to prove our hypothesis.