Predictive ability of serum advanced glycation end products at 11 to 13 weeks of gestation for early-onset preeclampsia.

BACKGROUND: Placental hypoxia and resultant oxidative stress have been associated with the development of preeclampsia. Oxidative stress promotes the formation of advanced glycation end products. OBJECTIVE: This study aimed to assess whether serum levels of advanced glycation end products during the early stage of pregnancy are a predictive biomarker of early-onset and late-onset preeclampsia. STUDY DESIGN: This was a nested case-control study that included 6 women with early-onset preeclampsia, 21 women with late-onset preeclampsia, and 50 age- and body mass index-matched healthy female control subjects. All women enrolled in the study had a complete medical history, including mean arterial pressure and uterine artery pulsatility index measurements. Furthermore, the women underwent blood chemistry analysis, including circulating levels of advanced glycation end products, soluble fms-like tyrosine kinase-1, and placental growth factor. Clinical measurements and biochemistry were evaluated at 11 to 13 and 19 to 24 weeks of gestation. RESULTS: The median serum concentrations of advanced glycation end products at 11 to 13 weeks of gestation were significantly higher in patients with early-onset preeclampsia than in those with late-onset preeclampsia and control subjects (6.62 vs 4.10 vs 3.77; P<.05), but no significant difference was found in advanced glycation end products at 19 to 24 weeks of gestation among the 3 groups. The advanced glycation end product-to-placental growth factor ratio in the first trimester of pregnancy was significantly higher in patients with early-onset preeclampsia than in those with late-onset preeclampsia or control subjects (0.78 vs 0.10 vs 0.10; P<.05). The area under the receiver operating characteristic curve values for patients with early-onset preeclampsia were 0.782 (95% confidence interval, 0.522-0.922), 0.855 (95% confidence interval, 0.433-0.978), and 0.925 (95% confidence interval, 0.724-0.983) for the advanced glycation end product and placental growth factor levels and advanced glycation end product-to-placental growth factor ratios, respectively. This population achieved a 100% detection rate for predicting early-onset preeclampsia at a screen-positive rate of 10% by combining the advanced glycation end product-to-placental growth factor ratio and the mean arterial pressure. CONCLUSION: The study results suggested that an elevated advanced glycation end product-to-placental growth factor ratio and mean arterial pressure at 11 to 13 weeks of gestation could be a potential biomarker for predicting the future development of early-onset preeclampsia.

Long-term outcome of cases of fetal pleural effusion: A study at a single perinatal center in Japan.

PURPOSE: To analyze the long-term prognosis of primary and secondary fetal pleural effusion (FPE). METHODS: We investigated all cases of FPE in a single University hospital (2005-2020). Cases were classified as primary (cases with only pleural effusion) and secondary (cases with other abnormalities such as chromosomal abnormalities or fetal cardiac failure). We retrospectively reviewed the medical records from the time of diagnosis, to assess medical procedures performed, chromosomal test results, and clinical outcomes. RESULTS: Among 18 027 deliveries, 17 FPEs were identified (primary FPE: 8, secondary FPE: 9). Most primary FPEs were diagnosed in the second trimester of pregnancy, while all secondary FPEs were diagnosed in the third trimester. Secondary FPE was often associated with chromosomal abnormalities, including trisomy 21. The prognosis of pleural effusion caused by trisomy 21 was relatively good, except for cases with TAM. Cases of secondary FPE without trisomy 21 were of cardiac origin, and the neonatal prognosis was poor. The short-term prognosis was better in the primary FPE group, but long-term follow-up identified conditions such as acute encephalitis with refractory, repetitive partial seizures, developmental delay and attention deficit hyperactivity disorder. CONCLUSION: Fetal pleural effusion without the presence of chromosomal abnormalities or morphologies has a good short-term prognosis, but the long-term prognosis is poor. Thus, long-term follow-up is necessary for all cases of fetal pleural effusion.

Perinatal outcomes of cases with umbilical hypocoiled cord: a study at a single perinatal center.

OBJECTIVES: To evaluate the perinatal outcomes of hypocoiled cord. METHODS: This retrospective study was carried out in the Department of Obstetrics and Gynecology at Showa University Hospital between 2011 and 2017. Umbilical cord index (UCI) was calculated by dividing the total number of coils by the total length of umbilical cord. All umbilical cords were measured and calculated coiling index by obstetrician after delivery. Perinatal outcomes like non-reassuring fetal status (NRFS), emergency cesarean sections, and other perinatal complications were compared. RESULTS: From January 2011 to December 2017, a total of 4047 fetuses were born at our hospital after 28 weeks' gestation. After excluding 100 fetuses of hypercoiled cord, a total of 3947 fetuses were included in this study, of which 71 fetuses were hypocoiled cord and 3876 fetuses were normal coiled cord. There were no association between maternal background and both UCI group. NRFS during labor was significantly associated with hypocoiled cord compared with normal cord (p = .02). Additionally, the rates of emergency cesarean section were raised in cases of hypocoiled cord (p = .02). CONCLUSION: In this study, it was found that hypocoiled cord is related to NRFS and emergency cesarean section. In addition, hypocoiled cord was not associated with any maternal factors. However, in previous studies, no opinion has been reported on the timing of diagnosis of hypocoiled cord during pregnancy. It is difficult to evaluate hypocoiled cord correctly in third trimester. It is a task to find the hypocoiled cord correctly before birth.

Ultrasonographic study of umbilical cord twist direction during second trimester.

OBJECTIVE: To explore/study/evaluate the relationships among umbilical twist direction, the degree of umbilical twist and differences of umbilical arterial diameters (UAD). METHODS: All obstetric patients presenting for prenatal care of singleton fetuses between 18 and 25 weeks gestation to a single provider (MN) from 2015 to 2018 had detailed umbilical cord Doppler measurements. Data including the cord twist direction, degree of twist and number of twists per cord segment length, and the diameters of each UA (UAD) and the umbilical vein (UVD) were extracted from the records. UAs were described as right or left depending on their position at the fetal cord insertion. Three groups were identified: Group A: right UAD > left UAD and Group B: left UAD > right UAD Group C: equal UAD. The coiling index was calculated as the inverse of the length of cord required for one complete 360 degrees wrap of the UA around the cord. According to the difference of UADs, the variables of right and left UADs, the coiling index, and frequencies of umbilical twist direction were analyzed using non-parametric methods. RESULTS: 485 singleton fetuses and umbilical cords were examined. The value of the antenatal coiling index in cases with left UAD greater than right was 0.43 ± 0.16, which was significantly higher than 0.38 ± 0.16 with right UAD greater than left (p = .001). There were significant differences between the two groups in the values of right and left UAD, value of right minus left UAD, absolute value between right and left UAD, antenatal coiling index, antenatal coiling index due to umbilical twist direction and frequencies of cord twist direction. CONCLUSION: The direction of umbilical twist may be in part dependent on differences in diameters of the umbilical arteries, in addition to other fetal characteristics such as fetal movement, or handedness of fetus or mother, fetal hemodynamic forces and structure of muscles of umbilical vessels.

The role of first-trimester ultrasound screening for women with positive noninvasive prenatal testing results.

AIM: This study aimed to assess the utility of ultrasound screening for pregnancies with positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. METHODS: We performed a retrospective analysis of positive noninvasive prenatal testing results and first-trimester ultrasound screening at our department between 2013 and 2019. Invasive genetic testing was performed if the patient had positive noninvasive prenatal testing results. Fetal ultrasound and cytogenetic data were collected. Noninvasive prenatal testing was performed in the women for advanced maternal age, nuchal translucency thickness, or history of abnormality in the previous child or relative. RESULTS: Forty-one pregnant women had positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. Twenty-three women had positive results for trisomy 21, 13 had positive results for trisomy 18, and 5 had positive results for trisomy 13 at 11 to 14 weeks of gestation. The positive predictive value of noninvasive prenatal testing was 100% for trisomy 21, 84.6% for trisomy 18, and 100% for trisomy 13. The positive predictive value of positive noninvasive prenatal testing results and fetal morphological abnormalities was 100% for trisomy 21, trisomy 18, and trisomy 13. CONCLUSION: Combining an ultrasound examination with noninvasive prenatal testing resulted in a higher positive predictive value for trisomy 18. Normal ultrasound examination results can help alleviate stress caused by false-positive noninvasive prenatal testing results. In contrast, the positive predictive value and negative predictive value for trisomy 21 were not altered by adding an ultrasound examination to noninvasive prenatal testing.

Study for risks of amniocentesis in anterior placenta compared to placenta of other locations.

OBJECTIVE: This study aimed to compare the risks of amniocentesis between anteriorly located placentas and placentas in other locations and assess the factors that cause procedure-related complications. MATERIALS AND METHODS: We prospectively studied women with singleton pregnancies who underwent amniocentesis between 2014 and 2020. The amniocentesis puncture sites were determined using ultrasonography. Women were classified into two groups according to their placental location. Medical records were retrospectively reviewed and characteristics and complications were compared between the groups of patients with different placental locations. RESULTS: During the study period, 629 women underwent amniocentesis. Three cases (0.5%) of premature rupture of membranes and one case (0.3%) of fetal loss within four weeks of amniocentesis were found. Puncture failure was observed in 14 cases (2.2%). Puncture failure included procedures with failure to obtain an adequate sample and procedures requiring more than three needle insertions. There was no significant difference in the frequency of puncture failure between the two groups. Logistic regression analysis revealed that uterine myoma (odds ratio [OR] 11.92; 95% CI, 3.04-45.17) and tenting membrane (OR 33.57; 95% CI, 6.45-178.41) were associated with puncture failure. CONCLUSION: Anteriorly located placenta is not a risk factor for amniocentesis-related adverse outcomes. Instead, puncture failure frequently occurs in case of uterine myoma and tenting membrane. If puncture failure occurs, or if the puncture is difficult to perform, then the procedure should be considered technically difficult and postponed until it can be more easily performed.

Accuracy of the FMF Bayes theorem-based model for predicting preeclampsia at 11-13 weeks of gestation in a Japanese population.

This study aimed to investigate the diagnostic accuracy of the Fetal Medicine Foundation (FMF) Bayes theorem-based model for the prediction of preeclampsia (PE) at 11-13 weeks of gestation in the Japanese population. In this prospective cohort study, we invited 2655 Japanese women with singleton pregnancies at 11-13 weeks of gestation to participate, of whom 1036 women provided written consent. Finally, we included 913 women for whom all measurements and perinatal outcomes were available. Data on maternal characteristics and medical history were recorded. Mean arterial pressure (MAP), uterine artery pulsatility index, and maternal serum placental growth factor (PlGF) were measured. The patients delivered their babies at Showa University Hospital between June 2017 and December 2019. Participants were classified into high- and low-risk groups according to the FMF Bayes theorem-based model. Frequencies of PE were compared between groups. The screening performance of the model was validated using the area under receiver operating characteristic (AUROC) curve. A total of 26 patients (2.8%) developed PE, including 11 patients (1.2%) with preterm PE (delivery at <37 weeks). The frequency of preterm PE was significantly higher in the high-risk group than in the low-risk group (3.8% vs. 0.2%, p < 0.05). This population model achieved a 91% detection rate for the prediction of preterm PE at a screen-positive rate of 10% by a combination of maternal characteristics, MAP, and PlGF. The AUROC curve for the prediction of preterm PE was 0.962 (0.927-0.981). In conclusion, the prediction of preterm PE using the FMF Bayes theorem-based model is feasible in the Japanese population.

Identification of differentially methylated HpaII sites by NGS analysis of HpaII-digested libraries.

Differentially methylated regions (DMRs) have been widely explored as epigenetic biomarkers. Here, we developed a novel approach combining methylation-sensitive restriction enzyme (MSRE) and next-generation sequencing (NGS) to identify DMRs between chorionic villi (CV) and maternal blood cells (MBC). During NGS library preparation, adapter-ligated genomic DNA of CV and MBC were digested with the MSRE, HpaII, and PCR-amplified. As unmethylated HpaII sites were cleaved, the resulted library should contain only methylated HpaII sites. By sequencing both HpaII-digested CV and MBC libraries, 9 differentially methylated-HpaII sites on chromosome 21 which exhibited more than 50% methylation increase in CV were identified. These DMRs are epigenetic biomarkers to tell the difference between CV and MBC. Our approach will also be applicable to screen various tissue-specific epigenetic biomarkers.

Usefulness of color Doppler mode for fetal cardiac ultrasound screening in the second trimester: a study at a single perinatal center.

Objectives: To evaluate the usefulness of color Doppler in fetal cardiac ultrasound screening in the second trimester.Methods: Fetuses who underwent ultrasound screening at 18-20 weeks' gestation at Showa University Hospital between 2011 and 2016 were evaluated. After delivery, neonatal congenital heart abnormalities were reviewed and compared with the antenatal ultrasound findings. Since 2014, we have added color Doppler to the routine B mode evaluation of the fetal heart. Congenital heart diseases (CHDs) found antenatally and postnatally were compared before and after protocol alternation. Medical records of all fetuses who underwent ultrasound screening at 18-20 weeks' gestation at Showa University Hospital between 2011 and 2016 were retrospectively reviewed.Results: There were 47 cases of CHDs confirmed postnatally. The detection rates of CHDs were 45.0% (9/20) in 2011-2013 and 55.6% (15/27) in 2014-2016. In 2011-2013, cases with antenatal diagnosis showed obvious abnormal findings of three-vessel view and four-chamber view with the B mode. In 2014-2016, the detection rate of isolated ventricular septal defect (VSD) was elevated from 10 to 42.9% using color Doppler.Conclusions: In this study, color Doppler improved the detection rate of CHDs. Color Doppler could give us additional information on blood flow although the canal or vessel is too small to detect morphological changes in the second trimester. It might be a useful tool for screening of CHDs with stenosis, regurgitation, and shunt that are difficult to detect by only the B mode in the second trimester.

Impact of first trimester determination of abnormal cord insertion on twin-to-twin transfusion syndrome and other adverse outcomes in monochorionic diamniotic twins: A retrospective cohort study.

OBJECTIVE: To assess the influence of abnormal cord insertion (CI) detected by first trimester ultrasonography on the development of twin-to-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) twins. METHOD: In this retrospective cohort study, consecutive patients with MCDA twins who underwent fetal ultrasound screening in the first trimester between January 2011 and January 2017 were enrolled. The CI sites were evaluated between 11 + 0 and 13 + 6 weeks' gestation. All twin pairs were assigned to the abnormal CI group (twin pair with velamentous cord insertion (VCI) and/or marginal cord insertion (MCI) in one or both twins) or the normal CI group (twin pair with both normal CI). The relationships of adverse outcomes in two groups were analyzed. RESULTS: A total of 109 MCDA twin pairs were examined; 15 cases were classified into the abnormal CI group and 94 cases into the normal CI group. The incidence of TTTS was significantly higher in the abnormal than in the normal CI group (26.7% vs 7.45%, P = .04). In patients who developed TTTS, all donors had VCI. CONCLUSION: Ultrasound evaluation of abnormal CI at 11 + 0 to 13 + 6 weeks' gestation in MCDA twins is valuable in the assessment of the risk for TTTS.

Differences in perinatal outcomes according to forming period of single umbilical cord in singleton pregnancy.

OBJECTIVES: The aim of this study was to establish the frequency and associations of single umbilical artery (SUA) diagnosed until the first vs second or third trimester. METHODS: A retrospective cohort study was conducted on singleton pregnancies at a tertiary perinatal center. All women underwent both the first and second trimester scans in which the number of arteries in the umbilical cord was routinely documented. SUA was classified as aplastic type when the diagnosis was made in the first trimester and as occlusion type when diagnosed in the second or third trimester. Adverse perinatal outcome was calculated as occurrence of fetal death, birthweight centile < 10th , or Apgar score at 5 minutes < 7. RESULTS: A total of 8675 women underwent ultrasound examinations during the study period. Of the 32 SUA cases, 17 (0.2%) were of the aplastic type and 15 (0.2%) of the occlusion type. Congenital anomalies were more in aplastic than in occlusive SUA (58.8% vs 20%, .043). The occlusive SUA had higher postnatal coiling index (0.3 vs 0.2, .034) and diagnosis of hypercoiled cord (46.7% vs 5.9%, .013) than the aplastic type. CONCLUSIONS: The different gestational age at diagnosis and coiling characteristics suggest two types of SUA, namely, aplastic and occlusion types, which are associated with differences in perinatal outcomes.