Severe Phenotype With RECQL4 Syndrome: A Report of Two Cases.

Baller-Gerold syndrome (BGS, OMIM: 218600), RAPADILINO syndrome (OMIM 266280), and Rothmund-Thomson syndrome (RTS, OMIM 266280), which are caused in some cases by RECQL4 pathogenic variants, show autosomal recessive inheritance. Some refer to them collectively as RECQL4 syndromes. Most cases have been reported during infancy and childhood periods. However, there have been no reports of phenotypes resulting in a lethal course in the perinatal period. We identified two fetuses with biallelic RECQL4 pathogenic variants during the perinatal period. The two fetuses with RECQL4 syndrome showed structural abnormalities, including severely hypoplastic forearms and lower legs. One fetus also had severe pulmonary hypoplasia. One case resulted in neonatal death because of respiratory failure, and the other was artificially terminated during pregnancy. The RECQL4 pathogenic variants were identified by exome sequencing followed by Sanger sequencing. The biallelic RECQL4 pathogenic variants can induce a lethal skeletal disorder.

Confined placental mosaicism with trisomy 13 complicated by severe preeclampsia: A case report and literature review.

A 31-year-old primiparous woman underwent non-invasive prenatal testing. The result was trisomy 13 (T13) positive. The chromosome 13 t-statistics (Z-score) was significantly high. The result of amniocentesis was normal karyotype (46,XX). Detailed ultrasound showed no fetal structural abnormalities. We suspected T13 confined placental mosaicism (CPM) and observed the course naturally. From the late second trimester, severe fetal growth restriction manifested followed by proteinuria and hypertension, diagnosing her with preeclampsia (PE). At 35 + 5 weeks, emergent cesarean section was required, yielding a 1480 g female infant. We sampled five locations of chorionic villi in the placenta. T13 cells dominated cells with normal karyotypes in all parts and the rate of trisomic cells ranged from 57% to 96%, which were generally high rate. None developed PE in reported T13 CPM cases and this is the first case of PE. The dominancy of T13 cells can be associated with PE development.

Isolation of pure primary term human cytotrophoblasts and their differentiation into syncytiotrophoblast-like cells as an ex vivo model of the human placenta.

The placenta plays a fundamental role in fetal growth and maintenance of pregnancy. Its cellular components include a large multinucleated syncytiotrophoblast (STB) and its progenitor, cytotrophoblasts (CTBs), both of which perform vital functions in the human placenta. Primary cytotrophoblasts isolated from term human placentas that spontaneously fuse and differentiate into syncytiotrophoblast-like cells in vitro have been utilized to investigate the functions of the syncytiotrophoblast and placenta with multiple modifications. Although recent advances have enabled the use of trophoblast stem cell-derived organoids as a model for villous trophoblasts, primary CTBs offer several advantages, including spontaneous differentiation, easy access to materials (from term-delivered human placentas), and simple methodology. Here, we present a precise step-by-step process for isolating pure CTBs from term human placenta based on previously reported placenta digestion, density centrifugation, and CTB purification using anti-HLA-A, B, C antibody. Subsequently, we provide a method to improve CTB viability and differentiation into STB-like cells using epidermal growth factor (EGF) and a ROCK inhibitor (Y-27632) that ensures long-term and stable cultures without altering their proliferation. Because these cells can grow on standard tissue culture plates, this model can be easily utilized for various placental investigations, including innate immune responses, drug resistance, and STB metabolism. Employing this approach considerably enhances our understanding of placental functions, which are key to maternal and offspring health.

Two-year outcomes of intravitreal brolucizumab for neovascular age-related macular degeneration: treat, extend, and stop-protocol.

PURPOSE: To investigate the real-world 2-year treatment outcomes of intravitreal brolucizumab (IVBr) for neovascular age-related macular degeneration (nAMD). METHODS: This multicenter, prospective, and interventional study included 53 eyes treated with brolucizumab from October 2020 to August 2021 at 3 institutions. A modified treat-and-extend (TAE) regimen with predefined discontinuation criteria was used. The mTAE regimen was discontinued if patients responded positively and achieved a treatment interval of 16 weeks twice with no sign of recurrence. The number of patients discontinuing TAE and the visual and anatomic changes at 1 and 2 years after the first IVBr were evaluated. RESULTS: Thirty-eight eyes from 38 patients (71%) completed the 2-year observation period and 7 eyes from 7 patients experienced intraocular inflammation (IOI). Of these 38 patients, 18 (47%) could discontinue the TAE at a median [interquartile range] of 13.1 [12.9-16.8] months after the first IVBr. Best-corrected visual acuity, central subfield retinal thickness, and central choroidal thickness were significantly improved compared with baseline at both 1 and 2 years after the first IVBr (all P < 0.001). An extension study revealed a 1-year recurrence rate of 5.6% (standard deviation, 5.4%) after TAE discontinuation. CONCLUSIONS: While IOI is a concern with brolucizumab, careful observation allows discontinuing the TAE regimen in patients treated with IVBr. Moreover, brolucizumab may reduce the risk of recurrence after treatment interruption. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry ( http://www.umin.ac.jp/ ; R000050688 UMIN 000044374).

Association between adenomyosis and placenta accreta and mediation effect of assisted reproductive technology on the association: A nationwide observational study.

OBJECTIVES: To investigate the association between adenomyosis and placenta accreta spectrum (PAS) and to evaluate the effect of assisted reproductive technology (ART) in mediating this association. METHODS: We retrieved data for singleton women from the Japanese nationwide perinatal registry between 2013 and 2019, excluding women with a history of adenomyomectomy. To investigate the association between adenomyosis and PAS among women, we used a multivariable logistic regression model with multiple imputation for missing data. We evaluated mediation effect of ART including in vitro fertilization and intracytoplasmic sperm injection on the association between adenomyosis and PAS using causal mediation analysis based on the counterfactual approach. RESULTS: Of 1 500 173 pregnant women, 1539 (0.10%) had adenomyosis. The number receiving ART was 489/1539 (31.8%) and 117 482/1 498 634 (7.8%) in women with and without adenomyosis, respectively. The proportion of women who developed PAS was 21/1539 (1.4%) in women with adenomyosis and 7530/1 498 634 (0.5%) in women without adenomyosis. Adenomyosis was significantly associated with PAS (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.26-3.00; P = 0.002). Mediation analysis showed that OR of the total effect of adenomyosis on PAS was 1.98 (95% CI 1.13-3.04), OR of natural indirect effect (effect explained by ART) was 1.15 (95% CI 1.01-1.41), and OR of natural direct effect (effect unexplained by ART) was 1.72 (95% CI 0.86-2.82). The proportion mediated (natural indirect effect/total effect) was 26.5%. Adenomyosis was also significantly associated with PAS without previa (OR 1.96; 95% CI 1.23-3.13, P = 0.005). CONCLUSION: Adenomyosis was significantly associated with PAS. ART mediated 26.5% of the association between adenomyosis and PAS.

One-year visual and anatomical outcomes of intravitreal faricimab injection for neovascular age-related macular degeneration after prior brolucizumab treatment.

This single-center retrospective cohort study analyzed the 1-year real-world treatment outcomes of 63 consecutive eyes (of 60 patients) with neovascular age-related macular degeneration (nAMD) that were switched from intravitreal brolucizumab (IVBr) to intravitreal faricimab (IVF) and managed on a treat-and-extend regimen with discontinuation criteria. After the switch, patients opted to continue IVF, to switch back to IVBr, or receive photodynamic therapy (PDT). Thirty-eight patients continued IVF, 16 patients were switched back to IVBr, 2 patients received PDT, and 4 patients paused treatment. Best-corrected visual acuity (BCVA), central subfield thickness (CST), subfoveal choroidal thickness (sf-CT), and injection intervals were compared immediately before and 1 year after the initial IVF. Whereas there was no change in BCVA and CST; 0 [- 0.0969 to 0.125, P = 0.58], - 1.5 [- 27.8 to 13.5, P = 0.11] µm, respectively, sf-CT decreased significantly; - 19.5 [- 45.5 to 7.75, P = 0.015] µm. The patients switched back showed no significant change in sf-CT. The injection interval extended significantly in the IVF continuation and the switch-back group (2.0 and 3.0 weeks, respectively; [P = 0.0007 and 0.0078]) in eyes with a pre-switching interval of less than 12 weeks. Faricimab shows promise as a safe and effective alternative to brolucizumab for treating nAMD.

A novel variant in IFT122 associated with a severe phenotype of cranioectodermal dysplasia.

A 27-year-old multiparous woman conceived her fetus naturally. Early second-trimester ultrasound showed short extremities with systemic subcutaneous edema. The pregnancy was artificially terminated at 19 weeks of gestation because of the abnormalities based on the parents' wishes. The parents desired whole-exome sequencing to detect a causative gene using the umbilical cord and the parents' saliva. Compound heterozygous variants (NC_000003.11(NM_052989.3):c.230 T > G/NC_000003.11(NM_052985.4):c.1178A > T) were identified. We described a fetus with a novel compound heterozygous variant in IFT122. The phenotype of this case was severer than of other types of cranioectodermal dysplasia.

Prediction of antenatal bleeding and preterm deliveries using placental magnetic resonance imaging in patients with placenta previa.

PURPOSE: This study aimed to clarify associations between subacute hematoma on placental magnetic resonance imaging (MRI), antenatal bleeding, and preterm deliveries in patients with placenta previa (PP) without placenta accreta spectrum (PAS). MATERIALS AND METHODS: This retrospective study investigated 78 consecutive patients with PP (median age, 34.5 years; interquartile range [IQR], 31-37 years) who underwent placental MRI in the third trimester. Patients with PAS detected intraoperatively or pathologically were excluded. Two radiologists evaluated the presence of subacute hematomas and their locations on placental MRI. We examined associations between presence of subacute hematoma and antenatal bleeding, emergency cesarean section (CS), hysterectomy, gestational age (GA) at delivery, birth weight, and amount of blood loss at CS. We also examined the association between perinatal outcome and subacute hematoma location: marginal, retro-placental, or intra-placental. Inter-observer agreement for the detection of subacute hematoma was calculated using kappa analysis. RESULTS: Subacute hematomas were identified on MRI in 39 of the 78 patients (50.0%). Antenatal bleeding and emergency CS were more prevalent in patients with subacute hematoma on MRI (20 patients [51.3%] and 18 patients [46.2%], respectively) than in patients without (7 patients [17.9%], Fisher's exact test, p = 0.004 and 7 patients [17.9%], p = 0.014, respectively). GA at delivery was significantly lower in patients with subacute hematoma (median 36w3d, IQR 35w4d-37w1d) than in patients without (median 37w1d, IQR 36w4d-37w2d; Mann-Whitney test: p = 0.048). Marginal hematoma was significantly associated with antenatal bleeding and emergency CS. Inter-observer agreement for the presence of subacute hematoma was moderate (κ = 0.573). CONCLUSION: Subacute hematoma on placental MRI was associated with antenatal bleeding, emergency CS and shorter GA at delivery in patients with PP. Marginal hematoma was also associated with antenatal bleeding and emergency CS. Placental MRI appears useful for predicting antenatal bleeding and preterm delivery in patients with PP.

Clinical relevance of reversible cerebral vasoconstriction syndrome in pregnant women with posterior reversible encephalopathy syndrome: review of case reports in Japan.

We systematically reviewed case reports of posterior reversible encephalopathy syndrome (PRES), and investigated the characteristics of PRES in pregnant Japanese women and the clinical relevance of reversible cerebral vasoconstriction syndrome (RCVS) in pregnant women with PRES. Articles were collected using the PubMed/Medline and Ichushi-Web databases. This review was ultimately conducted on 121 articles (162 patients). The clinical characteristics of PRES, individual sites of PRES lesions, edema types, and clinical characteristics of RCVS in PRES cases were examined. The most common individual site of PRES lesion was the occipital lobe (83.3%), followed by the basal ganglia, parietal lobe, frontal lobe, brain stem, cerebellum, temporal lobe, thalamus, and splenium corpus callosum (47.5, 42.6, 24.7, 16.1, 9.3, 5.6, 4.3, and 0.0%, respectively). Edema types in 79 cases with PRES were mainly the vasogenic edema type (91.1%), with very few cases of the cytotoxic edema type (3.8%) and mixed type (5.1%). Among 25 PRES cases with RCVS, RCVS was not strongly suspected in 17 (68.0%) before magnetic resonance angiography. RCVS was observed at the same time as PRES in 13 cases (approximately 50%), and between days 1 and 14 after the onset of PRES in the other 12. These results suggest that the basal ganglia is a frequent site of PRES lesions in pregnant women. RCVS may occur at or after the onset of PRES, even if there are no symptoms to suggest RCVS.

Association between earthquakes and perinatal outcomes: A systematic review and meta-analysis.

BACKGROUND: Evidence for the association between earthquakes and adverse perinatal outcomes is limited. OBJECTIVES: To evaluate the association between earthquakes and perinatal outcomes including preterm birth and low birth weight. SEARCH STRATEGY: We searched studies using MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Platform Search Portal, and ClinicalTrials.gov on February 9, 2023. SELECTION CRITERIA: We included before-and-after studies that evaluated the associations between earthquakes and perinatal outcomes in women living in affected areas. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data. We calculated the pooled odds ratio (OR) with the random-effects model. We analyzed outcomes in subgroups of Asians and others. We evaluated the certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation system. MAIN RESULTS: We included 2 607 405 women in 13 studies. Earthquakes may not increase preterm birth (nine studies, 1 761 760 participants: OR 1.10, 95% confidence interval [CI] 0.98-1.24, low certainty of evidence) or low birth weight (seven studies, 1 753 891 participants: OR 1.10, 95% CI 0.94-1.28, low certainty of evidence). Subgroup analyses showed that earthquakes may be associated with an increase of preterm birth among populations in Asia (OR 1.44, 95% CI 1.07-1.95), but this was not evident in others (OR 0.93, 95% CI 0.83-1.05). CONCLUSIONS: Perinatal outcomes might not change after earthquakes. Further research on the association between earthquakes and perinatal outcomes, combined with an assessment of the characteristics of the region, is needed.

BeWo exomeres are enriched for bioactive extracellular placenta-specific C19MC miRNAs.

Extracellular vesicles (EVs), including exosomes, are carriers of extracellular microRNAs (miRNAs). Exomeres, non-vesicular extracellular nanoparticles (NVEPs), are novel extracellular cargo carriers. However, little is known of the characteristics of placental trophoblast-derived exomeres. In this study, we characterized trophoblast-derived exomeres and investigated the cell-cell communication of placenta-specific miRNAs carried by those exomeres using an in vitro model system (BeWo trophoblasts and Jurkat T cells). BeWo exomeres (∼ 40 nm diameter) had pilling-like nanoparticle structures, which were distinct from cup-shaped exosomes (∼ 90-110 nm diameter). BeWo cells secreted more exomeres than exosomes. Exomeres were positive for AGO2 but negative for exosome markers (CD63, CD9, CD81, FLOT1, and TSG101). The levels of placenta-specific miRNAs in exomeres were significantly higher than in exosomes. In a cell-cell communication analysis using a placenta-specific miRNA, BeWo exomeres delivered significantly more miR-517a-3p to recipient Jurkat cells compared with exosomes. Moreover, exomere-miR-517a-3p significantly reduced the expression of PRKG1 in miR-517a-3p-inhibitor (-) Jurkat cells compared with miR-517a-3p-inhibitor (+) cells, suggesting that miR-517a-3p inhibition reversed the exomere-miR-517a-3p-mediated repression of PRKG1 expression in recipient cells. Therefore, BeWo trophoblast exomeres are enriched with bioactive extracellular placenta-specific miRNAs, which were formerly considered to be carried by exosomes. Our findings provide insight into trophoblast-derived NVEPs.

Unfavorable switching of skewed X chromosome inactivation leads to Menkes disease in a female infant.

Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, and female carriers are usually asymptomatic. We describe a 7-month-old female patient with severe intellectual disability, epilepsy, and low levels of serum copper and ceruloplasmin. While heterozygous deletion of exons 16 and 17 of the ATP7A gene was detected in the proband, her mother, and her grandmother, only the proband suffered from Menkes disease clinically. Intriguingly, X chromosome inactivation (XCI) analysis demonstrated that the grandmother and the mother showed skewing of XCI toward the allele with the ATP7A deletion and that the proband had extremely skewed XCI toward the normal allele, resulting in exclusive expression of the pathogenic ATP7A mRNA transcripts. Expression bias analysis and recombination mapping of the X chromosome by the combination of whole genome and RNA sequencing demonstrated that meiotic recombination occurred at Xp21-p22 and Xq26-q28. Assuming that a genetic factor on the X chromosome enhanced or suppressed XCI of its allele, the factor must be on either of the two distal regions derived from her grandfather. Although we were unable to fully uncover the molecular mechanism, we concluded that unfavorable switching of skewed XCI caused Menkes disease in the proband.

Cytoplasmic and nuclear DROSHA in human villous trophoblasts.

In villous trophoblasts, DROSHA is a key ribonuclease III enzyme that processes pri-microRNAs (pri-miRNAs) into pre-miRNAs at the placenta-specific, chromosome 19 miRNA cluster (C19MC) locus. However, little is known of its other functions. We performed formaldehyde crosslinking, immunoprecipitation, and sequencing (fCLIP-seq) analysis of terminal chorionic villi to identify DROSHA-binding RNAs in villous trophoblasts. In villous trophoblasts, DROSHA predominantly generated placenta-specific C19MC pre-miRNAs, including antiviral C19MC pre-miRNAs. The fCLIP-seq analysis also identified non-miRNA transcripts with hairpin structures potentially capable of binding to DROSHA (e.g., SNORD100 and VTRNA1-1). Moreover, in vivo immunohistochemical analysis revealed DROSHA in the cytoplasm of villous trophoblasts. DROSHA was abundant in the cytoplasm of villous trophoblasts, particularly in the apical region of syncytiotrophoblast, in the full-term placenta. Furthermore, in BeWo trophoblasts infected with Sindbis virus (SINV), DROSHA translocated to the cytoplasm and recognized the genomic RNA of SINV. Therefore, in trophoblasts, DROSHA not only regulates RNA metabolism, including the biogenesis of placenta-specific miRNAs, but also recognizes viral RNAs. After SINV infection, BeWo DROSHA-binding VTRNA1-1 was significantly upregulated, and cellular VTRNA1-1 was significantly downregulated, suggesting that DROSHA soaks up VTRNA1-1 in response to viral infection. These results suggest that the DROSHA-mediated recognition of RNAs defends against viral infection in villous trophoblasts. Our data provide insight into the antiviral functions of DROSHA in villous trophoblasts of the human placenta.

One-year outcome of brolucizumab for neovascular age-related macular degeneration in Japanese patients.

A new anti-vascular endothelial growth factor agent, brolucizumab, was approved by the United States Food and Drug Administration in 2019. We evaluated whether brolucizumab reduces the treatment burden of neovascular age-related macular degeneration (nAMD) after switching by examining 1-year treatment outcomes in a real-world setting. This retrospective single-institution study included 107 consecutive eyes with nAMD treated with brolucizumab. Among these eyes, 30 with treatment-naïve nAMD and 77 treated with other anti-VEGF agents for more than a year were included. All eyes were managed using a treat and extend (TAE) or modified TAE regimen. The last injection intervals at 52 weeks were 12.9 and 12.1 weeks in the treatment-naïve and switch therapy groups, respectively. Among switch therapy group patients whose pre-switch injection intervals were shorter than 120 days (n = 62 eyes), the injection interval was significantly longer after the switch than before, with a mean difference of 2.7 weeks (P < 0.0001). Intraocular inflammation events occurred in 2 and 7 treatment-naïve and switch therapy patients, respectively. In conclusion, brolucizumab might reduce the treatment burden in patients who required the injection of other anti-VEGF agents with a 120-day interval or shorter, despite a relatively high discontinuation rate due to intraocular inflammation.

Gasdermin D regulates soluble fms-like tyrosine kinase 1 release in macrophages.

Preeclampsia (PE) is a serious complication, and soluble fms-like tyrosine kinase (sFLT1) released from the placenta is one of the causes of PE pathology. Trophoblasts are the primary source of sFLT1; however, monocytes/macrophages exist enough in the placenta can also secrete sFLT1. Sterile inflammatory responses, especially NLRP3 inflammasome and its downstream gasdermin D (GSDMD)-regulated pyroptosis, may be involved in the development of PE pathology. In this study, we investigated whether human monocyte/macrophage cell line THP-1 cells secrete sFLT1 depending on the NLRP3 inflammasome and GSDMD. To differentiate THP-1 monocytes into macrophages, treatment with phorbol 12-myristate 13-acetate (PMA) induced sFLT1 with interleukin (IL)- 1ß, but did not induce cell lytic death. IL-1ß secretion induced by PMA inhibited by deletion of NLRP3 and inhibitors of NLRP3 and caspase-1, but deletion of NLRP3 and these inhibitors did not affect sFLT1 secretion in THP-1 cells. Both gene deletion and inhibition of GSDMD dramatically decreased IL-1ß and sFLT1 secretion from THP-1 cells. Treatment with CA074-ME (a cathepsin B inhibitor) also reduced the secretion of both sFLT1 and IL-1ß in THP-1 cells. In conclusion, THP-1 macrophages release sFLT1 in a GSDMD-dependent manner, but not in the NLRP3 inflammasome-dependent manner, and this sFLT1 release may be associated with the non-lytic role of GSDMD. In addition, sFLT1 levels induced by PMA are associated with lysosomal cathepsin B in THP-1 macrophages. We suggest that sFLT1 synthesis regulated by GSDMD are involved in the pathology of PE.

Assisted reproductive technology-associated risk factors for retained products of conception.

OBJECTIVE: To evaluate assisted reproductive technology-associated risk factors for retained products of conception among live births. DESIGN: Registry-based retrospective cohort study. SETTING: Not applicable. PATIENT(S): Cycle-specific data for a total of 369,608 singleton live births after fresh and frozen-thawed embryo transfers (FETs) between 2007 and 2017 were obtained from the Japanese assisted reproductive technology registry. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Retained products of conception after delivery. Odds ratios and 95% confidence intervals for risk factors associated with retained products of conception during fresh and frozen cycles. RESULT(S): In total, 132 deliveries (0.04% of eligible assisted reproductive technology registry deliveries) had retained products of conception; 122 (92.4%) of these deliveries occurred after FET transfer cycles. Cases with retained products of conception were significantly more likely to have undergone vaginal delivery than cases without retained products of conception (78.0% vs. 61.1%); they were also more likely to have been complicated with the placenta accreta spectrum (24.2% vs. 0.45%). Among patients undergoing FETs, factors associated with a significantly increased risk of retained products of conception were embryo stage at transfer, use of hormone replacement cycles, and assisted hatching. Use of hormone replacement cycles represented the largest risk factor (adjusted odds ratio, 4.9; 95% confidence interval, 2.0-12.4), such that retained products of conception occurred in 0.05% (51 of 97,958) of deliveries after hormone replacement cycles but only 0.01% (5 of 47,079) of deliveries after natural cycles. Subgroup analysis showed that hormone replacement cycles and assisted hatching remained significant risk factors for retained products of conception in cases without polycystic ovary syndrome and anovulation and cases with vaginal delivery, but not cases with cesarean section. Among fresh embryo transfers, an increased number of retrieved oocytes was the only significant risk factor for retained products of conception. CONCLUSION(S): Our analyses demonstrated that most of the cases involving retained products of conception were derived from FETs, and we identified the use of hormone replacement cycles as the largest risk factor for retained products of conception within this group.

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.