Preeclampsia prediction model using demographic, clinical, and sonographic data in the second trimester of Japanese nulliparous women.

AIM: This study aimed to clarify the factors influencing preeclampsia (PE) development in nulliparous Japanese women and to develop a PE prediction model using second trimester sonographic and clinical data readily available to obstetricians. METHODS: This historical cohort study examined the obstetric records of nulliparous women who delivered at Yamanashi Prefectural Central Hospital from January 2019 to May 2023. A model was constructed to predict the PE development rate, with a focus on 796 nulliparous women. The assessed outcome was PE, excluding superimposed PE. Data on maternal age, assisted reproductive technology, mean arterial pressure, uterine artery notching, and umbilical artery resistance index were extracted. Multivariable logistic regression analysis was conducted on these five factors. RESULTS: The incidence of PE was 4.3% (34/796). Multivariable analysis indicated significant odds ratios for the association of PE with mean arterial pressure (adjusted odds ratio: 1.06, 95% confidence interval: 1.03-1.10) and uterine artery notching (adjusted odds ratio: 6.28, 95% confidence interval: 2.82-14.0) in nulliparous women. The PE prediction formula was established as follows: Probability of PE development (%) = (odds/1 + odds) × 100, odds = ex and x = -11.3 + 0.039 × maternal age (years) + 0.91 × assisted reproductive technology + 0.061 × mean arterial pressure (mmHg) + 1.84 × uterine artery notching + 1.84 × umbilical artery resistance index. The sensitivity and specificity of this model were 58.8% and 84.5%, respectively (area under the curve: 0.79). CONCLUSIONS: This study is the first to provide a prediction formula targeting the Japanese population. Our specialized model for nulliparous women could guide obstetricians to educate women regarding the precise prospect of PE development.

Prevalence of common aneuploidy in twin pregnancies.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

A modified transabdominal cervicoisthmic cerclage with the monofilament thread: Its efficacy and safety for women with extremely short cervix due to cervical conization.

AIM: The study aimed to examine the usefulness of modified transabdominal cervicoisthmic cerclage (TAC) using monofilament thread for the prevention of preterm delivery in women with an extremely short cervix after deep conization. METHODS: We devised a monofilament thread for picking up the seromuscular layer of the site that is slightly cephalad to the internal ostium to prevent injury of the vessels around the uterine cervix. From 2017 to 2020, we performed this modified operation in eight women (nine pregnancies) at 12-16 weeks of gestation with a history of deep cervical conization. RESULTS: A modified TAC was successfully performed in all patients. There was no measurable bleeding, and all patients were discharged without postoperative complications. Their pregnancy courses after the operation were uneventful. Of nine, one patient had premature uterine contractions and underwent cesarean section at 36 weeks (preterm delivery). In the other eight pregnancies, planned cesarean section was performed after 37 weeks of gestation. The median birth weight of the babies was 2996 g (range 2604-3374 g). All patients were discharged on the sixth postoperative day without complications. CONCLUSION: A modified TAC can be safely performed and may prolong pregnancy without adverse events in patients with an extremely short cervix.

sFlt-1/PlGF ratio predicts serious outcomes in confirmed early-onset preeclampsia.

OBJECTIVES: We aimed to determine whether a high ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) would be associated with serious negative consequences and shorter pregnancy duration in cases of early-onset preeclampsia (PE). STUDY DESIGN: This retrospective cohort study included women (n = 65) diagnosed with PE at <34.0 weeks of gestation and recruited from a single primary and tertiary medical centre in Japan. The sFlt-1/PlGF ratio in the study participants was measured. To determine the optimal threshold for the sFlt-1/PlGF ratio, a receiver operating characteristic curve was employed, with the aim of predicting serious adverse outcomes within 1 week after serum angiogenic marker measurements. We performed Kaplan-Meier analysis and the log-rank test to assess delivery probability based on the sFlt-1/PlGF ratio. RESULTS: Thirty-seven women (56.9 %) delivered within 1 week of serum angiogenic marker measurements due to the aggravation of early-onset preeclampsia. Women who developed serious adverse outcomes within 1 week had a significantly higher sFlt-1/PlGF ratio than that of women who did not develop serious complications (408.5 vs. 166.6, P < 0.001). A cut-off value of 224.6 for the sFlt-1/PlGF ratio predicted serious adverse outcomes, with a sensitivity of 81.1 % and a specificity of 71.4 % (area under the curve: 0.77). Moreover, 78.9 % of women with an sFlt-1/PlGF ratio ≥ 224.6 compared to 25.9 % of those with an sFlt-1/PlGF ratio < 224.6 delivered within 1 week of presentation (P < 0.001). CONCLUSIONS: Women with confirmed early-onset preeclampsia and high sFlt-1/PlGF ratio are more likely to develop serious adverse outcomes within 1 week after serum angiogenic marker measurements.

Utility of the angle between the cervical canal and the anatomical conjugate line for predicting pouch of Douglas obliteration in patients with posterior placenta previa.

AIM: Pouch of Douglas obliteration, which prevents exteriorization of the uterus, increases surgical morbidity in patients with placenta previa. We aimed to identify magnetic resonance imaging features that can predict pouch of Douglas obliteration preoperatively. METHODS: We retrospectively assessed 39 women with posterior placenta previa who underwent magnetic resonance imaging for the preoperative assessment of placenta accreta spectrum. We defined the angle formed by the anatomical conjugate line (based on pelvimetry) and the cervical canal as the cervical inclination angle, which was measured on sagittal T2-weighted magnetic resonance imaging. Subsequently, we analyzed the correlation between the cervical inclination angle and pouch of Douglas obliteration. RESULTS: The median maternal age was 34 years (range, 22-44 years) and 26 (66.7%) women delivered at term. The median cervical inclination angle was 98° (range, 71-128). Pouch of Douglas obliteration was confirmed in six patients (15.4%). The cut-off value of the cervical inclination angle for the prediction of pouch of Douglas obliteration was 102° with a sensitivity of 66.7%, specificity of 78.8%, positive predictive value of 36.4%, and negative predictive value of 92.9% (area under the curve, 0.83). CONCLUSIONS: Measuring the cervical inclination angle may help in ruling out an obliteration of the pouch of Douglas. It may also be useful in the operative management of women with posterior placenta previa. However, caution should be exercised when generalizing the results of this study because of the small sample size, which makes the results prone to bias.

Predictive value of the sFlt-1/PlGF ratio for preeclampsia in twin pregnancies: a retrospective study.

Objective: This study aimed to investigate the efficiency of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in predicting preeclampsia (PE) within 4 weeks in twin pregnancies.Methods: Seventy-eight women with serum angiogenic markers measured at 28 + 0 to 30 + 6 weeks of gestation were enrolled. A receiver-operating characteristic curve was used to determine the sFlt-1/PlGF ratio threshold to predict PE.Results: A cutoff value for the sFlt-1/PlGF ratio of 22.2 predicted PE presence within 4 weeks.Conclusion: An sFlt-1/PlGF ratio of ≤22.2 is potentially indicative of PE absence within 4 weeks in twin pregnancies.

Distribution of PAPP-A and total hCG between 11 and 13 weeks of gestation in Japanese pregnant women.

Objectives: To establish the reference values for PAPP-A and total hCG between 11 and 13 weeks of gestation for the use of risk assessment of fetal aneuploidy in Japanese pregnant women.Methods: A multicenter prospective study was conducted. The subjects included only Japanese pregnant women with viable singleton who requested the first trimester combined (nuchal translucency and maternal serum marker) screening for fetal aneuploidy. Reference values of PAPP-A and total hCG in Japanese population were made and compared with them in Caucasian.Results: Overall 1,751 Japanese pregnant women were analyzed. Median vales of maternal serum concentration in Japanese pregnant women from 11 + 0-13 + 6 weeks' gestation were ranged from 3.01 to 9.51 mIU/mL for PAPP-A and from 70.2 to 58.3 IU/mL for total-hCG, respectively. Regression curve of median maternal serum PAPP-A and total-hCG concentration against gestational days are significantly higher in Japanese comparing with Caucasian. At most distant values, Japanese serum concentration indicated 1.45 MoM for total-hCG and 1.70 MoM for PAPP-A based on Caucasian regression curves.Conclusion: A modification of the equations by specific reference values is necessary for Japanese pregnant women at the risk assessment of chromosomal abnormalities using the first trimester maternal serum marker.

Association between the high soluble fms-like tyrosine kinase-1 to placental growth factor ratio and adverse outcomes in asymptomatic women with early-onset fetal growth restriction.

OBJECTIVE: To assess whether the high soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is associated with adverse outcomes (e.g., HELLP syndrome [hemolysis, elevated liver enzymes, and low platelets], severe hypertension uncontrolled by medication, non-reassuring fetal status, placental abruption, pulmonary edema, growth arrest, maternal death, or fetal death) and a shorter duration to delivery in early-onset fetal growth restriction (FGR). METHODS: Thirty-four women with FGR diagnosed at <34.0 weeks were recruited. Serum angiogenic marker levels were estimated within 6 hours of a diagnosis of FGR. A receiver operating characteristic curve was used to determine the threshold of the sFlt-1/PlGF ratio to predict adverse outcomes. We used multivariable logistic regression analysis to examine the association between the sFlt-1/PlGF ratio and adverse outcomes. Finally, we used Kaplan-Meier analysis and the log-rank test to assess the probability of delay in delivery. RESULTS: Women who developed adverse outcomes within a week had a significantly higher sFlt-1/PlGF ratio than did those who did not develop complications. A cutoff value of 86.2 for the sFlt-1/PlGF ratio predicted adverse outcomes, with a sensitivity and specificity of 77.8% and 80.0%, respectively. Moreover, 58.4% of women with an sFlt-1/PlGF ratio ≥86.2 versus 9.1% of those with an sFlt-1/PlGF ratio <86.2 delivered within a week of presentation (p < 0.001). In multivariate analyses, an sFlt-1/PlGF ratio ≥86.2 (adjusted odds ratio 9.52; 95% confidence interval, 1.25-72.8) was associated with adverse maternal and neonatal outcomes. CONCLUSION: A high sFlt-1/PlGF ratio was associated with adverse outcomes and a shorter duration to delivery in early-onset FGR.

Association between total dose of ritodrine hydrochloride and pulmonary oedema in twin pregnancy: a retrospective cohort study in Japan.

OBJECTIVE: Pulmonary oedema is recognised as a severe side effect of ritodrine hydrochloride. Recently, the number of twin pregnancies has been increasing. Few studies have reported the association between total dose of ritodrine hydrochloride prior to delivery and pulmonary oedema in twin pregnancy. We aimed to examine this association and determine the optimal cut-off threshold of total ritodrine hydrochloride dose to predict the incidence of pulmonary oedema in twin pregnancy based on obstetric records. DESIGN: Retrospective cohort study. SETTING: Yamanashi Prefectural Central Hospital, Japan. PARTICIPANTS: Two hundred and twenty-six women with twin pregnancy who delivered at Yamanashi Prefectural Central Hospital between September 2009 and November 2016. METHODS: The obstetric records of the participants were analysed. We defined 1 unit of ritodrine hydrochloride as 72 mg per 24 hours continuous transfusion at 50 µg/min to calculate the dose of ritodrine used for tocolysis. OUTCOME MEASURES: Multivariable logistic regression analysis was performed to examine the association between total dose of ritodrine hydrochloride used for threatened preterm labour and pulmonary oedema, while controlling for potential confounding factors. Then, a receiver-operating characteristic curve was used to determine the optimal cut-off of total ritodrine dose to predict pulmonary oedema incidence. RESULTS: Mean maternal age was 32 (range, 18-46) years; 143 participants were nulliparous (63.3%), 109 had (48.2%) term deliveries and 194 (85.8%) had caesarean deliveries. The overall incidence of pulmonary oedema was 13.7% (31/226). Multivariable analysis showed that the total dose of ritodrine was significantly associated with pulmonary oedema (adjusted OR 1.02; 95% CI 1.004 to 1.03). The best cut-off point to predict the incidence of pulmonary oedema was 26 units (1872 mg) (sensitivity, 61.3%; specificity, 87.8%). CONCLUSION: Our results suggest that consideration of the total dose of ritodrine hydrochloride is helpful in the management of patients with threatened preterm labour in twin pregnancy.

[The role of pregnancy associated progenitor cells in the regeneration of injured maternal organs].

Microchimeric fetal cells are present in the maternal body over a long period and thought to have the ability to colonize multiple tissues and organs. They are found in a wide range of maternal tissues affected with variety of diseases, thus, there is a possibility that they may contribute tissue repair and regeneration. To assess their possibility of use in regenerative medicine, we investigated whether fetal cells regenerate infracted maternal organs. We crossbred wild female mice with male transgenic mice, expressing enhanced green fluorescent protein (EGFP), and total hysterectomies were performed at the day 6 of pregnancies. On day 60 after the operations, the mice were injected with streptozotocin (STZ) to induce multiple organs injuries. We also created the ischemic organ injury model ; myocardial infarction model and cerebral infarction model. Detection and quantification of fetal cells were then attempted in a variety of maternal organs via a fluorescent microscope and quantitative PCR amplification of the gfp transgene. Fetal cells were detected only in maternal bone marrow before maternal organs injuries were induced, however, they were detected not only in bone marrow but also in the maternal injured organs. Histological analysis showed that differentiated fetal cells were observed and their morphological appearance was indistinguishable from their maternal counterparts. These results indicate that fetal cells sustained their population in the maternal bone marrow, may have contributed to the maternal tissue regeneration.

Migration of microchimeric fetal cells into maternal circulation before placenta formation.

Fetal cell microchimerism is defined as the persistence of pluripotent fetal cells in the maternal body long after delivery. The exact process by which fetal cells cross the placental barrier and enter maternal circulation is still being investigated. We reported that fetal cells persist only in the maternal bone marrow and may give rise to subpopulations with the ability to differentiate into the tissue-specific mature cells within injured maternal organs. Moreover, most of the fetal cells enter the maternal circulation during the early stages of pregnancy. These results indicate that the fetal cells with a multilineage potential, which were detected in a variety of maternal organs during pregnancy did not pass through the placental barrier; rather, they were derived from the fetal cells that entered maternal circulation early after implantation, and sustained their population long after delivery.

Fetal cell microchimerism develops through the migration of fetus-derived cells to the maternal organs early after implantation.

Fetus-derived cells are present in the blood and tissues of the maternal body over a long period of time, even after delivery, resulting in fetal cell microchimerism. The exact process by which fetal cells cross the placental barrier to enter the maternal circulation is unclear. The objective of this paper was to determine the time during pregnancy that fetal cells with multilineage potential migrate to the maternal organs. Wild type female mice were crossbred with male transgenic mice, expressing enhanced green fluorescent protein (EGFP). Total hysterectomies were performed at different time points of pregnancy. On day 60 after surgery, mice were injected with either streptozotocin (STZ) to induce insulin-dependent diabetes mellitus, or vehicle. Detection and quantification of fetal cells were then undertaken in a variety of maternal organs via fluorescent microscopy and quantitative PCR amplification of the gfp transgene. In vehicle control mice, fetal cells were detected only in the maternal bone marrow. However on day 30 after STZ injection, fetal cells were detected not only in bone marrow but also in the maternal pancreas, liver and kidney. Histological analysis showed differentiated fetal cells within the pancreatic acinar cells, hepatocytes and tubular epithelial cells. Their morphological appearance was indistinguishable from their maternal counterparts, and their frequency in these organs was constant, regardless of the timing of hysterectomy. These results indicate that most fetal cells with multilineage potential in maternal tissues migrate to the maternal body early after implantation, and thereafter sustain their population over the long term after delivery.

Low adjusted serum ionized calcium concentration shortly after birth predicts poor outcome in neonatal hypoxic-ischemic encephalopathy.

AIM: Hypoxic-ischemic reperfusion injury causes either necrosis or apoptosis, and the influx of ionized calcium into cells is the major cause of both types of cell death. The aim of this study was to investigate whether or not the serum ionized calcium concentration in neonates with hypoxic-ischemic encephalopathy (HIE) could be used to predict their outcome. METHODS: Serum samples were obtained shortly after birth from 20 HIE neonates who had not urinated or received treatment with calcium. Serum ionized calcium concentrations were adjusted for pH using a correction formula. Twelve neonates without any disease were selected as a control. The results were compared between nine HIE neonates who made a full recovery, 11 who died or had neurologic deficits, and 12 normal neonates. RESULTS: Considered together, the two HIE groups had lower serum ionized calcium concentrations (1.05 +/- 0.10 mmol/L) than the control group (1.22 +/- 0.07 mmol/L; P < 0.0001). Moreover, serum ionized calcium concentrations in the group with the poor outcome (0.99 +/- 0.07 mmol/L) were lower than those in the group that made a full recovery (1.13 +/- 0.06 mmol/L; P=0.0016). CONCLUSIONS: The serum ionized calcium concentrations shortly after birth were significantly lower in neonates with HIE who had a poor outcome. Low concentrations may reflect multiple organ damage, particularly involving the brain.