Ultrasonographic cervical length screening at 20-24 weeks of gestation in twin pregnancies for prediction of spontaneous preterm birth: A 10-year Taiwanese cohort.

BACKGROUND: Shortened cervical length is one of the primary predictors for spontaneous preterm deliveries in twin pregnancies. However, there is lack of consensus regarding cut-off values. Recent evidence highlights that established cut-offs for cervical length screening might not always apply across different populations. This study aims to present the distribution of cervical length in Taiwanese twin pregnancies and to assess its predictive value for spontaneous preterm birth during mid-trimester screening. MATERIALS AND METHODS: This retrospective analysis of cervical length screening in Taiwan evaluated 469 twin pregnancies between 20-24 weeks of gestation. Outcome data were obtained directly from the medical records of the delivery hospital. The study explored the predictive value of cervical length screening for spontaneous preterm birth and the characteristics of cervical length distribution in Taiwanese twin pregnancies. RESULTS: The average gestational age at screening was 22.7 weeks. Cervical length values displayed a non-normal distribution (p-value <0.001). The median, 5th and 95th centiles were 37.5 mm 25.1 mm, and 47.9 mm, respectively. Various cut-off values were assessed using different methods, yielding positive [negative] likelihood ratios for spontaneous preterm births between 32-37 weeks of gestational age (GA) (1.3-30.1 and [0.51-0.92]) and for very preterm births between 28-32 weeks GA (5.6-51.1 and [0.45-0.64]). CONCLUSIONS: The findings from our analysis of Taiwanese twin pregnancies uphold the moderate predictive potential of cervical length screening, consistent with prior investigations. The presented likelihood ratios for predicting preterm birth at different gestational ages equip clinicians with valuable tools to enhance their diagnostic rationale and resource utilization. By fine-tuning screening parameters according to the spontaneous preterm birth prevalence and clinical priorities of the particular population, healthcare providers can enhance patient care. Our data implies that a cervical length below 20 mm might provide an optimal balance between minimizing false negatives and managing false positives when predicting spontaneous preterm birth.

Associated factors with parental pregnancy decision-making and use of consultation after a prenatal congenital heart disease diagnosis.

BACKGROUND: Prenatal diagnosis of congenital heart disease (CHD) often leads affected families to experience psychological stress. Pediatric cardiology consultation is important in providing parents with sufficient information and reducing their anxiety to make an informed pregnancy decision. Involving a fetal nurse coordinator may optimize fetal anomaly care. Our study aimed to identify factors associated with parental decision-making for choosing to use pediatric cardiology consultations and pregnancy termination. METHODS: From September 2017 to December 2018, all fetal CHD cases diagnosed in the second trimester from a primary screening clinic in Taiwan were included (n = 145). Univariate and multivariate logistic regression were performed to analyze maternal, fetal, and medical factors for predictors of parental decisions for consultation use and pregnancy termination. RESULTS: Acceptance for fetal nurse coordinator care and pediatric cardiology consultation were 84.8% (n = 123) and 83.4% (n = 121), respectively. Predictors for termination of pregnancy included the following: multiple anomalies (OR: 10.6; 95% CI: 3.6-35.7), chromosomal/genetic abnormalities (OR: 20.2; 95% CI: 3.1-395.8), severe CHDs (OR: 9.8; 95% CI: 4.3-23.4), CHDs that required surgery (OR: 32.4; 95% CI: 11.4-117.8), and physiological single-ventricle (OR: 47.3; 95% CI: 12.4-312.5). Parents who had pediatric cardiology counseling were less likely to terminate the pregnancy (OR: 0.1; 95% CI: 0.0-0.7). Parents with fetal diagnosis having multiple anomalies (OR: 0.2; 95% CI: 0.1-0.7) or chromosomal/genetic abnormalities (OR: 0.1; 95% CI: 0.03-0.9) were less likely to make use of cardiology consultation. Parents who accepted fetal nurse coordinator care were more likely to have pediatric cardiology consultation before pregnancy decision (OR: 149.5, 95% CI: 37.8-821.5). CONCLUSIONS: Anomaly complexity appeared to be a strong predictor for termination of pregnancy beyond non-acceptability of prenatal cardiology consultation. Prenatal cardiology counseling may help support the parental decision to continue with the pregnancy. Incorporation of a fetal nurse coordinator care into the multidisciplinary fetal medicine team improved the acceptability of prenatal consultation.

Physiological QT Interval Changes in Early Infancy Using Post-Menstrual and Post-Natal Age Calculation for Electrocardiogram Long QT Interval Screening in Taiwan.

BACKGROUND: Prolongation of the QT interval is associated with the risk of sudden infant death syndrome. QT interval differs depending on age at the time of screening. Screening protocols have yet to be established for Taiwanese patients. OBJECTIVES: To construct QT interval reference values during early infancy, to investigate whether QT interval change differs according to age calculation methods, and to identify an optimal QT correction method and associated infant factors. METHODS: Electrocardiographic readings and QT intervals were recorded cross-sectionally in 595 healthy infants and screened prospectively for long QT interval. Corrected QT intervals with Bazett's (QTc-B) and Fridericia's (QTc-F) formulas were compared by post-natal and post-menstrual screening age, sex, body mass index (BMI), heart rate (HR), birth and family history. RESULTS: QTc-B and QTc-F decreased in the second month (31-60 days), and peaked in the third month (61-90 days). QT interval length was similar between post-menstrual and post-natal ages for QTc-B. Simple linear regression showed that post-menstrual age, post-natal age, HR and BMI were associated with QTc-F, while only sex and HR were associated with QTc-B. Although both QTc-B and QTc-F were significantly associated with HR, QTc-B was less affected by HR than QTc-F (ß = -0.1, p < 0.05 for QTc-B vs. ß = -0.3, p < 0.001 for QTc-F). Female infants tended to have slightly longer QTc intervals. CONCLUSIONS: QT interval in early infancy changed physiologically, peaking in the third month. The rate of QT change was not affected by different age correction methods. QTc-B was less affected by age, BMI and HR, although differences in sex should be noted.

Age-specific effect of fresh versus frozen embryo transfer on fetal anomalies or intrauterine growth restriction rate.

OBJECTIVE: To compare the prevalence of congenital fetal anomalies or intrauterine fetal growth restriction (IUGR) diagnosed prenatally between two in-vitro fertilization (IVF) methods-fresh embryo transfer (ET) and frozen embryo transfer (FET). MATERIALS AND METHODS: We retrospectively reviewed medical records of patients that had conceived via IVF, and had a fetal anatomical scan performed at Taiji Clinic between 2015 and 2019. The prevalence of fetal anomalies or IUGR between both IVF methods were compared. Prevalence of congenital anomalies or IUGR by maternal age and embryo transfer type were compared by means of Chi-square analysis. Using multivariate logistic regression, we investigated factors that might be associated with higher rates of fetal anomalies or IUGR, such as parity and number of embryos transferred. RESULTS: A total of 2441 cases were selected (ET: n = 627 and FET: n = 1814). There was non-significant difference in the prevalence of fetal anomalies or IUGR between ET and FET groups (6.4% vs. 5.5%, p = 0.39). However, among women younger than 34 years of age, prevalence of fetal anomalies or IUGR was significantly higher in ET group (4.6% vs. 9.9%, p = 0.03). CONCLUSIONS: Our findings suggest an age-specific effect of IVF method on the rate of fetal anomalies or IUGR and may provide useful information for physicians and infertile couples to optimize their IVF treatment plans and improve birth outcomes.

Revisions to mid-pregnancy cervical length reference range for preterm birth screening among singleton pregnancies in Taiwan - 10 years' experiences.

OBJECTIVE: Our study aimed to build a normal reference range for routine mid-pregnancy cervical length screening for preterm birth (PTB) based on a large cross-section of Taiwanese singleton pregnancies. Based on our reference range findings, we aim to develop a Z-score and centile calculator. MATERIALS AND METHODS: We performed a retrospective analysis of the routine mid-trimester cervical length measurement in low-risk singleton pregnancies (without known abnormal growth or karyotype, congenital malformation, history of preterm birth due to preterm premature rupture of the membranes, or history of cervical cerclage treatment). From November 2008 to June 2018, the cervical lengths of 51,644 Taiwanese low-risk pregnant women were measured by experienced sonographers via transvaginal ultrasound during second trimester fetal anatomical screening at 20-24 weeks of gestation. Kolmogorov-Smirnov test was used to assess the normality of the distribution. Cole's lambda, mu, sigma (LMS) method was applied to build mid-pregnancy cervical length reference range and calculate Z-scores. Cut-off values of 2.5, 2.0 and 1.5 cm were used to evaluate the number of pregnancies considered high-risk for PTB. RESULTS: Kolmogorov-Smirnov test showed that the cervical length measurements did not follow a normal distribution (<0.001). Reference range constructed by LMS method was presented in our study. Mean cervical length was 3.82 cm (SD = 0.62 cm). Overall, less than 0.3% of women had a cervical length shorter than 1.5 cm. CONCLUSION: We are providing an open access calculator for z-score and centile calculation for use in clinical practice for assessing how CL measurement compares in normally developing singleton pregnancies. Further investigation is needed to determine if Z-scores can better assess risk for PTB compared to fixed cut-offs. Since Z-scores are used to assess large deviations from normal development, they may be a useful tool for risk assessment and can be the basis for future standardized screening protocol in Taiwan.

Prenatal ultrasound diagnosis of neural tube defects in the era of intrauterine repair - Eleven years' experiences.

OBJECTIVE: To modify the current neural tube defect (NTD) classification for fetal medicine specialists, and to investigate the impact of prenatal ultrasound conus medullaris position screening on the detection rate of closed spinal dysraphism and pregnancy outcomes. MATERIALS AND METHODS: The clinical data of 112 patients prenatally diagnosed with neural tube defects in Taiji clinic from 2008 to 2018 were retrospectively analyzed. All cases were classified following the modified classification. We compared the detection rate before and after introducing the conus medullaris screening and pregnancy outcomes for NTD types. RESULTS: Closed spinal dysraphism type prevailed in our sample (43.8%). The median gestational age at the time of detection for cranial dysraphism was 13.3 weeks, open spinal dysraphism was 22.0 weeks, and closed spinal dysraphism was 22.6 weeks. All cranial dysraphism (n = 43) and open spinal dysraphism cases (n = 20) had pregnancies terminated. For closed spinal dysraphism Class 1, the live-birth rate was 100.0% in the cases without other anomalies and 33.3% in the cases with other anomalies, respectively (X2 = 17.25, p < 0.001). Similarly, for Class 2, pregnancy continuation rate was 50.0% in cases without other anomalies and 20.0% in cases with other anomalies, yet it failed to reach statistical significance (X2 = 0.9, p = 0.524). CONCLUSION: Our case series may help to improve early screening and prenatal diagnosis of NTDs. Modified classification is adjusted for use in ultrasound fetal care facilities, which could be used for predicting pregnancy outcome. We suggest promoting first-trimester anatomical screening in order to make an earlier diagnosis and therefore provide better prenatal care for open spinal dysraphism cases in the era of intrauterine repair. Our findings imply that the use of fetal conus medullaris position as a marker for closed spinal dysraphism improves the detection rate and would unlikely lead to a higher termination rate.

Multidisciplinary team approach to the prenatal management of orofacial clefts: a single center cohort study in Taiwan.

Advances in ultrasound fetal diagnostics and treatment have created a dilemma for doctors and parents: choosing whether to continue with a pregnancy as well as choosing between various treatment options. A multidisciplinary approach has been widely accepted in the management of other prenatally diagnosed anomalies and has shown superior results compared to routine care. We present a retrospective cohort of patients prenatally diagnosed with orofacial clefts who were offered consultation by an expert multidisciplinary team, including: a fetal medicine specialist, an obstetrician, a plastic surgeon, and a case managing nurse. We analyzed factors influencing parents' decision to utilize a consultation service, as well as their decision about pregnancy continuation. Our results suggest that the presence of other anomalies and maternal age heavily influenced the decision about the uptake of consultations. If consulted by the team, parents tended to continue with the pregnancy, even when accounting for fetal gender and maternal age. On the other hand, having a consultation had varying effects depending on the cleft type. The findings suggest that multidisciplinary consultations may be an efficient approach in managing pregnancies complicated by orofacial cleft anomalies; which may help in preventing unnecessary pregnancy terminations and developing a sufficient postnatal care plan.

Reference ranges and Z-scores for fetal cardiac measurements from two-dimensional echocardiography in Asian population.

Currently available fetal echocardiographic reference values are derived mainly from North American and European population studies, and there is a lack of reference z-score for fetal echocardiographic measurement in Asian populations. The aim of this study was to establish normal ranges of echocardiographic measurements and z-scores in healthy Asian fetuses. A total of 575 healthy pregnant Taiwanese with an estimated gestational age from 14 to 38 weeks were enrolled voluntarily for this observational study. Standard two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries of the developing fetuses. In contrast to past studies, our sample was more evenly distributed for estimated gestational age (p<0.001). We present percentile graphs for 13 fetal echocardiographic measurements from the knowledge of estimated gestational age, biparietal distance, head circumference, abdominal circumference, and femur length. Most cardiac structures and developmental markers had linear models as the best-fitting, except for transverse aortic isthmus by estimated gestational age and transverse ductus arteriosus by femur length. Our findings indicate that estimated gestational age was generally the best model for fetal heart development, while head circumferences could be used as an optimal developmental marker to predict left atrium, right atrium, right ventricle, pulmonary annulus, and ductus arteriosus. Lastly, we developed nomograms for each of the 13 fetal heart measurements by each developmental markers. This is the first study providing echocardiographic reference ranges and nomograms for Asian fetuses. Computing z-scores from nomograms helps in standardizing comparisons and adds additional prognostic information to the diagnosis of congenital heart disease.

Low plasma levels of decoy receptor 3 (DcR3) in the third trimester of pregnancy with preeclampsia.

OBJECTIVE: The pathophysiology of preeclampsia, a major threat during pregnancy characterized by excessive inflammatory status, remains unclear. Decoy receptor 3 (DcR3), a soluble member of the tumor necrosis factor receptor (TNFR) superfamily, is capable of inducing anti-apoptosis via binding with TL1A and anti-inflammation by driving Th2 immune reactions. DcR3 may, therefore, play a role in immune modulation during pregnancy. The purpose of this study is to explore the role of DcR3 in normal and preeclamptic pregnancies. MATERIALS AND METHODS: Plasma samples from 104 normal pregnant women (26, 42, and 36 in the first, second, and third trimester, respectively) and 10 patients with preeclampsia in the third trimester were collected. Plasma DcR3 levels were determined by using commercial ELISA kits. ANOVA and linear regression analysis were performed to analyze the relationship between gestational age and DcR3 levels. After adjusting for gestational days, the levels of plasma DcR3 in preeclamptic and non-preeclamptic women in the third trimester were compared. RESULTS: The plasma levels of DcR3 gradually decreased as the gestational days increased during pregnancy (p < 0.05). In the third trimester, pregnant women with preeclampsia had significantly lower plasma DcR3 levels compared to non-preeclamptic women (p < 0.05). CONCLUSIONS: We found that plasma DcR3 levels gradually decreased as gestation progressed. The levels of plasma DcR3 in preeclamptic women were significantly lower than those of normal pregnant women, suggesting that a potential involvement of DcR3 in normal pregnancy and decreased levels of DcR3 may be related to preeclampsia.

Antiepileptic drug use among women from the Taiwanese Registry of Epilepsy and Pregnancy: Obstetric complications and fetal malformation outcomes.

To investigate antiepileptic drugs (AEDs) prescription and pregnancy outcomes in pregnancies with epilepsy in Taiwan between 2004 and 2015. We retrospectively reviewed data from the Taiwanese Registry of Epilepsy and Pregnancy (TREP). The TREP registry is a voluntary prospective cohort registry, which tracks pregnant women with epilepsy and AED prescription throughout pregnancy, delivery, and early childhood development. All TREP pregnancies (n = 318) that had completed questionnaires up until delivery or had had an unsuccessful pregnancy were analyzed. Over 94.7% of women had been prescribed AEDs during pregnancy, with 69.0% and 25.7% having received monotherapy, or polytherapy, respectively. Among live births, 12 (3.9%) reported malformation. Cesarean section rate was reported higher than usual (54.5%). In 2004, 73.3% of AEDs prescribed were 1st generation, with 1st generation prescription rates falling to only 8.3% of total prescribed in 2015. AED polytherapy also fell during the study period (40.0% to 20.0%). Cesarean sections were found to be higher for women over 35 years, who had generalized epilepsy, or had experienced an obstetric complication during pregnancy term. Binary logistic regression revealed that Cesarean section was associated with maternal complications (OR = 5.11, CI 95% = 1.11-23.51, p = 0.036), while malformations were associated with obstetric complication (OR = 20.46, CI 95% = 4.80-87.21, p<0.001). Both AED risk types were not associated with complications or malformations. Our sample provides a unique insight into the women with epilepsy with AED use during pregnancy. Cesarean section rate was observed to be higher than usual, but malformation rates remained low. Results indicate a decrease in both 1st generation AEDs and proportion of patients receiving polytherapy over the study period. Obstetric complications were associated with Cesarean section. Fetal malformations were significantly associated with obstetric complications. AED risk factors were not significantly associated with either complications or malformations.