Development of pre-implantation genetic testing protocol for monogenic disorders (PGT-M) of Hb H disease.

Hb H disease is the most severe form of α-thalassemia compatible with post-natal life. Compound heterozygous α0-thalassemia- SEA deletion/α+-thalassemia- 3.7kb deletion is the commonest cause of Hb H disease in Thailand. Preimplantation genetics testing for monogenic disorders (PGT-M) is an alternative for couples at risk of the disorder to begin a pregnancy with a healthy baby. This study aims to develop a novel PCR protocol for PGT-M of Hb H disease- SEA/-3.7kb using multiplex fluorescent PCR. A novel set of primers for α+-thalassemia- 3.7kb deletion was developed and tested. The PCR protocol for α0-thalassemia- SEA deletion was combined for Hb H disease- SEA/-3.7kb genotyping. The PCR protocols were applied to genomic DNA extracted from subjects with different thalassemia genotypes and on whole genome amplification (WGA) products from clinical PGT-M cycles of the families at risk of Hb Bart's. The results were compared and discussed. The results showed three PCR products from α+-thalassemia- 3.7kb primer set, and three from α0thalassemiaSEA primer set. The results were consistent with the known thalassemia genotypes. The novel -α3.7 primers protocol was also tested on 37 WGA products from clinical PGT-M cycles giving accurate genotyping results and a satisfying amplification efficiency with the ADO rates of 2.7%, 0%, and 0% for HBA2, HBA1, and internal control fragments, respectively. This novel PCR protocol can precisely distinguish Hb H disease- SEA/-3.7kb from other genotypes. Additionally, this is the first PCR protocol for Hb H disease- SEA/-3.7kb which is optimal for PGT-M.

COVID-19 Vaccine Acceptance of Pregnant Women in Thailand.

Objective: This study investigated the COVID-19 vaccine acceptance rate among pregnant women in Thailand and explored factors influencing their willingness to receive the vaccine, to enhance vaccine uptake among hesitant pregnant women in the future. Methods: A prospective study was conducted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in October 2022. The data was collected using face-to-face questionnaires comprising 29 closed-end questions. Pregnant women aged 18 years old or over visiting the antenatal care clinic were included. Results: The study included 200 participants, revealing a COVID-19 vaccine acceptance rate of 17%. Healthcare provider recommendations significantly increased vaccine acceptance by nearly two-fold (30.77%, p-value < 0.01). The major cause of vaccine hesitancy was the concern about vaccine safety that potentially harmed their babies (77.44%). Conclusion: The COVID-19 vaccine acceptance rate among pregnant women in Thailand was low. Healthcare provider recommendations played a pivotal role in positively impacting vaccine acceptance, highlighting their importance in increasing acceptance rates in the future.

This study investigated the COVID-19 vaccine acceptance rate among pregnant women in Thailand and explored factors influencing their willingness to receive the vaccine. The study included 200 participants, revealing a COVID-19 vaccine acceptance rate of 17%. Healthcare provider recommendations significantly increased vaccine acceptance by nearly two-fold (30.77%, p-value < 0.01). The major cause of vaccine hesitancy was the concern about vaccine safety that potentially harming their babies (77.44%). The COVID-19 vaccine acceptance rate among pregnant women in Thailand was low. Healthcare provider recommendations played a pivotal role in positively impacting vaccine acceptance, highlighting their importance in increasing acceptance rates in the future.

Pre-implantation genetic testing for Marfan syndrome using mini-sequencing.

Marfan syndrome (MFS1) is an autosomal dominant condition causing aortopathy including fatal aortic dissection. This study aimed to perform clinical PGT-M in a family with a history of MFS1 for two generations. A family with two members affected by MFS1 approached the hospital for PGT-M. The couple decided to join the project following extensive counselling and informed consent was obtained. The mutation contributory to MFS1 was identified using whole-exome sequencing (WES). A novel PGT-M protocol using multiplex fluorescent PCR and mini-sequencing was developed and tested. Ten blastocysts were subjected to PGT-M in two clinical PGT cycles. Mini-sequencing revealed four normal and six affected embryos. Microsatellite-based linkage analysis confirmed mutation analysis results in all samples. The embryos diagnosed as normal (non-MFS1) were chosen for transfer. A pregnancy was obtained in the third embryo transfer. Invasive prenatal diagnosis confirmed the normal genotype of the baby. This study demonstrated comprehensive management using the application of clinical-based diagnosis, WES for mutation identification within the MFS1 gene, mini-sequencing for embryo selection and microsatellite-based linkage analysis for backup of PGT-M results and contamination detection to assist couples in having a healthy child when there was a family history of Marfan syndrome.Impact StatementWhat is already known on this subject? Marfan syndrome (MFS1, OMIM#154700) is an autosomal dominant condition causing aortopathy including fatal aortic dissection. Pre-implantation genetic testing (PGT) is an alternative to traditional invasive prenatal diagnosis (PND) giving the couples the chance of starting pregnancy with the confidence that the baby will be unaffected. Most of the previous PGT reports employed microsatellite-based linkage analysis. A few PGT studies used sequencing, mini-sequencing and mutation analysis; however, the details of the techniques were not described.What do the results of this study add? Single-cell PCR protocol using multiplex fluorescent PCR and mini-sequencing was developed and validated. Two clinical PGTs cycles for Marfan syndrome were performed. A healthy baby was resulted. The details of multiplex fluorescent PCR and mini-sequencing protocols are described in this study so that the procedures can be reproduced.What are the implications of these findings for clinical practice and/or further research? Embryo selection can help the family suffering from Marfan syndrome for two generations to start a pregnancy with confidence that their child will be unaffected. This study also shows the use of a mini-sequencing protocol for PGT, which can be a universal protocol for other mutations by changing the PCR primers and mini-sequencing primers.

Change of contraceptive preference after the free-LARC program for Thai teenagers.

BACKGROUND: In 2014, the Thai government launched a free-of-charge long-acting reversible contraception (LARC) program for Thai female adolescents. However, its acceptance had not been reported. Therefore, this study aimed to describe contraceptive use among women of reproductive age before and after the program was implemented. METHODS: This retrospective cross-sectional study was carried out from the medical records of 9000 women of reproductive age, who attended the Family Planning Clinic at Maharaj Nakorn Chiang Mai Hospital between 2009 and 2018. The Chi-square test was used to compare the contraceptive methods administered before and after the program was implemented, and binary logistic regression was used to find the factors associated with implant use after completion of the program. RESULTS: Depot medroxy progesterone acetate (DMPA) injection was the most popular contraceptive method used among 40.9% of the women. The rates of subdermal implant use were increased significantly after the program was implemented (2.3-9.3%, p < 0.001). Implant use for adolescents aged less than 20 years increased from 2.6% to 56.4%, while DMPA was the most popular method used among adult women at 36.4%. Factors associated significantly with implant use after implement of the program included age of less than 20 years (aOR = 4.17 (CI: 1.84-9.44); p = 0.001) and nulliparity (aOR = 8.55 (CI: 3.77-19.39); p < 0.001). CONCLUSION: This study showed a significant increase in contraceptive implant use after the free-LARC program for adolescents had been applied. STATEMENT OF IMPLICATIONS: Contraceptive implant is the most effective hormonal reversible contraception. Its use rate is low among all age groups, but increased clearly after the free-of-charge program was applied for adolescents.

The successful strategy of comprehensive pre-implantation genetic testing for beta-thalassaemia-haemoglobin E disease and chromosome balance using karyomapping.

Thalassaemia is the commonest monogenic disease and causes a health and economic burden worldwide. Karyomapping can be used for pre-implantation genetic testing of monogenic disorders (PGT-M). This study applied karyomapping in two PGT-M cycles and made a comparison to polymerase chain reaction (PCR). Two families at risk of having beta-thalassaemia-haemoglobin E disease offspring decided to join the project and informed consent was obtained. Karyomapping results of family A (beta-thalassaemia (c.41_42delTCTT)-Hb E (c.26G>A) disease) revealed four normal, two beta-thalassaemia traits, one Hb E trait and six affected. Three embryos exhibited unbalanced chromosomes. One normal male embryo was transferred. Karyomapping results of family B (beta-thalassaemia (c.17A>T)-Hb E (c.26G>A) disease) revealed six Hb E traits and three affected. Three embryos were chromosomally unbalanced. One Hb E trait embryo was transferred. Two successful karyomapping PGT-M were performed, including deletion and single-base mutations. Karyomapping provides accuracy as regards the protocol and copy number variation which is common in pre-implantation embryos. Impact StatementWhat is already known on this subject? Thalassaemia syndrome is the commonest monogenic disease and causes a health and economic burden worldwide. Modern haplotyping using SNP array (aSNP) and karyomapping algorithms can be used for pre-implantation genetic testing of monogenic disorders (PGT-M). However, few clinical karyomapping PGT-M cycles have been done and validated so far.What do the results of this study add? Two successful clinical PGT-M cycles for beta-thalassaemia (c.41_42delTCTT and c.17A>T mutations)-haemoglobin E (c.26G>A) disease were performed using karyomapping. The outcome was two healthy babies. Multiplex fluorescent polymerase chain reaction (PCR) with mini-sequencing was also used for confirmation mutation analysis results. PCR confirmed haplotyping results in all embryos. Six embryos from both PGT-M cycles exhibited unbalanced chromosomes evidenced by aSNP.What are the implications of these findings for clinical practice and/or further research? Karyomapping provides accurate information quickly and the outcomes of the study will save time as regards protocol development, provide a usable universal PGT-M protocol and add additional copy number variation (CNV) information, chromosome number variation being a common issue in pre-implantation embryos.

Collagen Deposition and Inflammatory Response Associated with Macroporous Mesh Shrinkage in Incisional Hernia Repair: A Rat Model.

Background: Mesh repair is the current recommendation for the treatment of incisional hernia; however, the best mesh has yet to be determined. The objective of this study was to compare the inflammatory response and collagen deposition in primary incisional hernia repair (P) and different macroporous mesh materials, including polypropylene with poliglecaprone (PP-PG), polyvinylidene fluoride (PVDF), and polyester (PE), using quantitative methods. Methods: Sixty male rats were divided into four groups. Anterior abdominal wall defects were created and either suture or mesh repair was done. Rats were euthanized on days 14, 90, and 180, and the gross findings were recorded. The inflammatory and collagen levels in the abdominal wall tissues were measured using enzyme-linked immunosorbent assay (ELISA). Results: The PE group demonstrated significant mesh shrinkage at 180 days. The extent of PE mesh shrinkage ranged from 22-42% (mean = 30.49%). At 14 days, the PVDF group had higher interleukin-6 (IL-6) levels than the PP-PG (P = .004) and PE groups (P = .019). At 90 days, the collagen type I (Col I) levels in the PE group were significantly lower than those in the others, and the collagen type I/III (Col I/III) ratios in the PE group were lower than those in the P group (P = .006). Conclusions: The persistently high IL-6 levels until 180 days and the decrease in Col I levels and Col I/III ratio at 90 days seem to predict mesh shrinkage at 180 days. The mesh induces high Col I levels, but those associated with low Col III levels should be preferred.

A study of the association between angiotensinogen (AGT) gene polymorphism (M235T) and preeclampsia in Thai pregnant women.

AGT M235T gene polymorphism may cause increased blood pressure in preeclampsia in pregnancy; however, the evidence remains controversial. This study investigated the association between AGT M235T and preeclampsia in Thai pregnant women. A case-control study was conducted to compare the distributions of AGT M235T genotypes and alleles between 142 normotensive pregnancies as controls and 61 preeclampsia pregnancies as cases in a tertiary-care university hospital in Chiang Mai, Thailand. The results show that the distribution of AGT M235T genotypes (MM, MT and TT) of both groups were not significantly different (preeclampsia: 0.0, 16.4, 83.6%; control: 2.1, 22.5, 75.4%, respectively; p = .30). Additionally, there was no statistical difference in the distribution of AGT M235T alleles (M and T alleles) (preeclampsia: 8.2 and 91.8% versus control: 13.4 and 86.6%, respectively; p = .14). In this study, the distributions of AGT M235T were not different in both groups. Therefore, AGT M235T polymorphism may not play a significant role in preeclampsia pathophysiology in Thai population.Impact statementWhat is already known on this subject? Preeclampsia is one of the major complications during pregnancy; it significantly affects maternal and perinatal morbidity and mortality. Effort has been made to find markers and predictors that are associated with the pathophysiology of preeclampsia. AGT M235T gene polymorphism may cause increased blood pressure in preeclampsia pregnancy; however, evidences are still controversial.What do the results of this study add? We conducted a case-control study to compare the distributions of AGT M235T genotypes and alleles between 142 normotensive pregnancies as controls and 61 preeclampsia pregnancies as cases. The results show that preeclamptic women are more likely to deliver at an earlier gestational age and have a smaller baby in comparison with the normotensive group. In addition, women with preeclampsia had a higher chance of having an operative delivery and caesarean section. However, the distribution of AGT M235T polymorphism of preeclampsia women and the control group were not significantly different.What are the implications of these findings for clinical practice and/or further research? AGT M235T polymorphism may not play a significant role in preeclampsia pathophysiology in Thai population.

A comparison of pregnancy outcomes after second-trimester amniocentesis between cases with penetration of the placenta and nonpenetration.

OBJECTIVE: To compare the fetal loss rate associated with second-trimester amniocentesis between the procedures with penetration and nonpenetration of the placenta, as a primary outcome and to compare the rates of adverse pregnancy outcomes including preterm birth, fetal growth restriction and low birth weight, as secondary outcomes. METHOD: A retrospective cohort study was conducted on women undergoing second-trimester amniocentesis. Our prospective database of amniocentesis, from January 1989 to December 2018, was accessed to retrieve the records meeting the inclusion criteria consisting of singleton pregnancies, gestational age of 16-22 weeks, and known obstetric outcomes. The patients were categorized into two groups: placental penetration and nonpenetration. The rates of fetal loss, including abortion (<24 weeks of gestation) and fetal death in utero (>24 weeks of gestation), and other adverse pregnancy outcomes were compared between the two groups. RESULTS: A total of 21,566 procedures were performed during the study period. Of them, 8601 were excluded due to chromosomal/structural abnormalities, various underlying medical diseases and incomplete data or unavailability of final outcomes. Finally, 12,965 cases were available for analysis including 4692 (36.2%) in the group of placental penetration and 8273 (63.8%) in the group of nonpenetration. The abortion rate after amniocentesis trended to be increased in the placental penetration group (0.6 versus 0.4%, p = .064; RR: 1.60, 95%CI 0.97-2.64). Likewise, the fetal loss rate trended to be increased in the placental penetration group (1.0 versus 0.7%, p = .121; RR: 1.35 95%CI 0.92-1.98). Interestingly, preterm birth rate was significantly increased in the placental penetration group (13.8 versus 12.6%, p = .043; RR: 1.10 95%CI 1.00-1.20). CONCLUSION: Fetal loss rate was slightly increased, but not statistically significant, among the procedures with placental penetration. However, penetration of the placenta was slightly but significantly associated with an increase in rates of preterm birth.

Comparisons of pregnancy outcomes between twin pregnancies with and without second-trimester amniocentesis.

OBJECTIVE: To assess the amniocentesis-related pregnancy loss rate and preterm birth rate among twin pregnancies undergoing amniocentesis. METHODS: A retrospective cohort study was conducted at a tertiary center. The study group included twin pregnancies undergoing amniocentesis during 16 to 22 weeks of gestation. The control group was those not undergoing amniocentesis. All amniocenteses were performed by the MFM specialists. The main outcomes were the rate of pregnancy loss (before 24 weeks) and preterm birth. RESULTS: A total of 332 cases in the study group and 1188 controls were analyzed. The percentages of maternal age ≥35 years, high parity, and cases complicated with medical diseases were significantly higher in the study group. The pregnancy loss rate after the procedure tended to be higher, but not significant, in the study group (3.0% vs 2.2% P = .383). Likewise, the rate of preterm birth in the study group was higher, but not significant (70.5% vs 66.0% P = .130). Logistic regression analysis to adjust confounding factors showed no significance of amniocentesis on pregnancy loss and preterm birth. CONCLUSION: Though amniocentesis in twin pregnancies has theoretical risk of pregnancy loss, it is relatively safe when performed by maternal-fetal medicine specialists. This information is useful for counseling, especially when performed by experienced hands.

Chorionic villous sampling-related complications: a cohort study.

Purpose: To compare the adverse pregnancy outcomes between the pregnant women undergoing chorionic villous sampling (CVS) and those without CVS.Materials and methods: A cohort study was conducted on low risk pregnancies attending Chiang Mai University Hospital between years 2003 and 2017 and identify the database of women undergoing CVS (study group) and control group. Each case in study group was matched for 10 cases of the control by maternal age and year of procedure.Results and conclusions: Of 1384 pregnancies undergoing CVS, 776 cases met criteria and were matched with 7760 controls. The gestational age at delivery and actual birth weight were significantly different between two groups (38.02 versus 38.96 weeks, p value <.001 and 3025 versus 3092 g, p value .001). Moreover, CVS group had significantly higher preterm birth (9.4 versus 7.3%, p value .037; RR 1.287, 95% CI 1.017-1.629). However, there was no significant difference in fetal loss rate before 24 weeks (1.16 versus 1.9%, p value .14), small for gestational age (SGA); SGA (4 versus 4%, p value .948) and low birth weight (LBW); LBW (8.9 versus 8.0%, p value .41). Pregnancies undergoing CVS tend to deliver earlier and has significantly higher preterm birth. However, the incidences of fetal loss, SGA and LBW are not significantly increased.

Fetal Down syndrome screening models for developing countries; Part I: Performance of Maternal Serum Screening.

BACKGROUND: To identify the performance of fetal Down syndrome (DS) screening for developing countries. METHODS: A prospective study on MSS (maternal serum screening) with complete follow-ups (n = 41,924) was conducted in 32 network hospitals in the northern part of Thailand. Various models of MSS were tested for performance. RESULTS: MSS based on Caucasian reference range resulted in very high false positive rate (FPR; 13%) in our country, compared to the rate of 7.8% with our own (Thai) reference range, whereas the detection rate was comparable. As individual screening, C-S (contingent first trimester screening including PAPP-A, and free beta-hCG, classified as a) high risk [> 1:30], indicated for invasive diagnosis; b) intermediate risk [1:30-1500], indicated for STS; and c) low risk [< 1:1500], need no further tests.) was the most effective model (sensitivity 84.9%, FPR 7.7%) but nearly one-third needed the second trimester test (STS) because of intermediate results. Additionally, about one-third had their first visits in the second trimester and had no chance of FTS (first trimester screening). C-S plus STS had a sensitivity of 82.4% and FPR 8.1% whereas independent first and second trimester screening model (I-S) gave the sensitivity of 78.4% and FPR of 7.5% but was much more convenient and practical. CONCLUSION: C-S plus STS was the most effective models while I-S model was also effective and may be better for developing countries because of its simplicity and feasibility.

The experience of genitourinary syndrome of menopause (GSM) among Thai postmenopausal women: the non-reporting issue.

Genitourinary syndrome of menopause (GSM) is common among postmenopausal women, but, in general, not all of the patients seek medical advice as this sensitive issue can cause them embarrassment. OBJECTIVES: To explore the prevalence of GSM among Thai postmenopausal women and their disclosure of and attitude towards GSM. METHODS: A questionnaire was used to obtain information on GSM from 499 Thai postmenopausal women who attended the Menopause Clinic at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, from November 2015 to August 2016. RESULTS: The mean age of the 499 participants was 57.8 ± 7.2 years. It was notable that 87.2% of them had had GSM, and the prevalence increased with age. The most common symptoms were nocturia (77.7%) and vaginal dryness (51.7%). Among the symptomatic patients, 63.0% conveyed their problem to other people, i.e., friends and family, while 52.9% of them never reported to health care providers. The most common reason for not talking about their GSM was the acceptance of it being part of the natural aging process. CONCLUSIONS: GSM is common among Thai postmenopausal women. The prevalence of non-reporting is high and underreported.

Allelic Characterization of IGF2 and H19 Gene Polymorphisms in Molar Tissues.

BACKGROUND: To investigate the characteristics of allelic distribution of IGF2 and H19 gene polymorphisms in molar tissues compared to normal placentas. MATERIALS AND METHODS: Forty-nine specimens of molar tissues as well as 100 control normal placental tissues, delivered on the same days, were collected. Polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP) on 2% agarose gel electrophoresis was conducted to determine the allelic distribution. The ApaI polymorphism within exon 9 of IGF2 and the RsaI polymorphism within exon 5 of H19 were employed to identify the allelic distribution of the IGF2 and H19 genes, respectively. Then the data for these genes in the molar and normal placenta tissues were compared. RESULTS: The allelic distribution of IGF2 genes found in molar tissue were 21 (42.9%) aa (undigested), 10 (20.4%) ab (heterozygous) and 18 (36.7%) bb (digested), while in normal placenta tissue the values were 22 (22%) aa, 51 (51%) ab, and 27 (27%) bb. The allelic distribution of H19 in molar tissues was 8 (16.2%) aa (undigested), 8 (16.3%) ab (heterozygous) and 33 (67.4%) bb (digested) and in normal placental tissue was 16 (16%) aa, 36 (36%) ab and 48 (48%) bb in normal placenta tissue. These results were significantly different with P values of 0.001 and 0.037 for the allelic distribution of IGF2 and H19, respectively. CONCLUSIONS: Molar tissues showed significant differences of allelic distribution of IGF2 and H19 from normal placenta tissues.

Second-trimester cordocentesis and the risk of small for gestational age and preterm birth.

OBJECTIVE: To estimate the association of cordocentesis with small for gestational age, preterm birth, and low birth weight. METHODS: A cohort study from a tertiary care center. Pregnant women without medical or obstetric complications and without ultrasonographically evident fetal anomalies scheduled for cordocentesis between 16 and 22 weeks of gestation (predominantly to detect severe fetal hemoglobinopathies) were prospectively enrolled and matched to a similarly healthy control group on a one-to-one basis by maternal age, parity, gestational age. and ethnicity. In the cordocentesis group, pregnancies found to be complicated by a fetal hemoglobinopathy or a karyotypic abnormality were excluded. Both groups were followed until delivery. The primary outcomes included the rates of small-for-gestational-age preterm birth and low birth weight and fetal loss. RESULTS: In total, 7,228 women underwent cordocentesis, of whom 5,506 qualified as cases. Of these, 5,039 were matched to women in the control group and had complete outcome data available for the pair. The rates and relative risks (RRs) of small for gestational age (6.9% compared with 4.6%; RR 1.5, 95% confidence interval [CI] 1.3-1.8), preterm birth (12.7 compared with 7.4%; RR 1.7, 95% CI 1.5-1.9), and fetal loss (1.9% compared with 1.0%; RR 1.9, 95% CI 1.4-2.7) were significantly higher among fetuses in the cordocentesis group. However, there were no significant differences in other obstetric complications between the study and control groups. CONCLUSION: Rates of small for gestational age, preterm birth, low-birth weight, and fetal loss are increased among pregnancies with cordocentesis in the second trimester.

Chorionic villous sampling: experience of 636 cases.

OBJECTIVE: To describe the technical aspects and complications of chorionic villous sampling (CVS). MATERIAL AND METHOD: The database of CVS procedures performed between January 2004 and August 2011 at Maharaj Nakorn Chiang Mai Hospital was assessed prospectively. Consecutive procedures during 10 to 14 gestational weeks were included into the present study. Indications, results, and complications of the CVS were extracted and analyzed. RESULTS: All 636 CVS procedures were successful. Indications for CVS were fetal karyotyping, DNA analysis for severe thalassemia disease, and for both in 36.5%, 50. 6%, and 12.9%, respectively However, 3.4% had inconclusive CVS result, and the second trimester prenatal diagnosis procedures needed to be done. There were five cases (0.8%) of fetal loss in the present study. Only two cases (0.3%) that fetal loss happened within two weeks of CVS procedures. Other minor complications such as vaginal bleeding and amniotic fluid leakage were found in 0.3 to 1.3% and had no long-term effect. No case with anomaly and procedure-related infection following the procedure was seen. CONCLUSION: CVS is a safe and reliable prenatal diagnosis procedure in the first trimester. In experienced operators, fetal loss rate was less than 1%. However a few cases will have inconclusive CVS results and may need a confirmation during the second trimester diagnostic procedures.

Effectiveness of the model for prenatal control of severe thalassemia.

OBJECTIVE: The aim of the research was to determine effectiveness of the model for prenatal control in reducing new cases of severe thalassemia. METHODS: Pregnant women at six tertiary centers were recruited to follow the model, consisting of (1) carrier screening using mean corpuscular volume (for alpha-thal-1 and beta-thal) and CMU-E screen (for HbE trait), (2) carrier diagnosis, (3) the couples at risk were counseled and offered prenatal diagnosis, and (4) termination of affected pregnancy. All neonates were evaluated for thalassemia. RESULTS: Of the 12,874 recruited pregnancies, 7008 were valid for analysis. Of them, 281 couples were identified to be at risk, Of the 281, 58 affected fetuses were identified and 55 pregnancies were terminated, whereas three did not accept pregnancy termination. All 6727 neonates at no risk were proven to be unaffected. The model had sensitivity and positive predictive value of 100% and 20%, respectively. The model could detect all of affected fetuses. CONCLUSION: The model could prenatally identify affected fetuses with a detection rate and negative predictive value of 100%. The model was highly effective to prenatally detect affected fetuses with an acceptable false positive rate.

Effect of umbilical cord bleeding following mid-pregnancy cordocentesis on pregnancy outcomes.

OBJECTIVES: To compare the adverse pregnancy outcomes among the three groups of umbilical cord bleeding following cordocentesis; a group of no bleeding (group 1), transient bleeding (group 2), and persistent bleeding (>60 s: group 3). METHODS: Consecutive cases of cordocentesis were prospectively recorded and followed up. The inclusion criteria for analysis consisted of (1) singleton pregnancies; (2) gestational age of 18-22 weeks; (3) no fetal anomalies; (4) no previous invasive procedures; (5) performed by experienced operators, and (6) known pregnancy outcomes. The main outcomes were rates of fetal loss, low birth weight and preterm birth. RESULTS: Of 2,174 procedures, 1,614 were in group 1, 509 were in group 2, and 51 were in group 3. The mean birth weight and gestational age at delivery were significantly lower in group 3 than those in groups 1 and 2. The fetal loss rate was significantly higher in group 3. Rates of low birth weight and preterm birth were significantly higher in group 3 whereas the rates in group 2 had a tendency to be higher than those in group 1. CONCLUSION: This study suggests that cord bleeding during cordocentesis carries a higher risk of fetal loss, low birth weight and preterm birth.

A comparison of cordocentesis outcomes between early and conventional procedures.

OBJECTIVE: To compare procedural outcomes between early cordocentesis (16-17 weeks) and those at 18-22 weeks. MATERIALS AND METHODS: A prospective database of cordocentesis was assessed. The eligible criteria included are (1) singleton pregnancy; (2) no fetal abnormalities; (3) gestational age of 16-22 weeks and (4) procedures performed by experienced operators. The procedures performed during 16-17 weeks were defined as early cordocentesis (Study group). The Control group (conventional cordocentesis; 18-22 weeks) were selected by matching maternal age and years of procedures, with a ratio of 1:3. RESULTS: Of 2942 eligible procedures, 103 procedures were undertaken during 16-17 weeks and 309 matched controls were selected. Baseline characteristics of both groups were comparable. Time used to complete the procedure was significantly longer in Study group (8.45 ± 9.91 vs. 6.07 ± 6.63 min; p value 0.007). Similarly, rate of difficult procedures was significantly higher in Study group (7.8 vs. 2.3%; p value 0.011). However, rates of fetal loss, low birth weight infants and preterm births were not significantly different, but there was a tendency to be higher in Study group. CONCLUSION: Early cordocentesis is more difficult but relatively safe when performed by experienced hands, although it has a tendency to increase rates of adverse outcomes. This information may be helpful in counseling the couples.

Predisposing factors and effects of fetal bradycardia following cordocentesis at mid-pregnancy.

OBJECTIVES: To identify predisposing factors of fetal bradycardia following cordocentesis at mid-pregnancy and to compare the pregnancy outcomes to those without bradycardia. METHODS: All cordocenteses performed at 18-22 weeks of gestation were prospectively enrolled. The inclusion criteria consisted of: (i) singleton pregnancies; (ii) no fetal structural or chromosomal abnormalities; (iii) the procedures done by experienced operators. They were divided into two groups; procedures with fetal bradycardia (Group 1) and those without bradycardia (Group 2). Factors related to bradycardia were identified and pregnancy outcomes between the two groups were also compared. RESULTS: Of 6147 cordocenteses recruited, 2829 met the inclusion criteria. Of these,152 had fetal bradycardia whereas the remaining 2677 did not. The procedures involving placenta penetration, and umbilical cord bleeding were significantly related to a higher rate of fetal bradycardia. On the other hand, cordocenteses with fetal bradycardia had a significantly higher rate of fetal loss (11.8 vs. 1.9%, respectively, p = 0.001) as well as a higher rate of low birth weight and preterm birth. CONCLUSIONS: Cordocentesis with placenta penetration and umbilical cord bleeding carries a higher risk for fetal bradycardia and fetal bradycardia was an independent factor for a higher rate of fetal loss, preterm birth and low birth weight.

Effect of placenta penetration during cordocentesis at mid-pregnancy on fetal outcomes.

OBJECTIVES: To compare the rates of fetal loss, low birth weight, and preterm birth between pregnancies undergoing cordocentesis at mid-pregnancy with placenta penetration and those without it. METHODS: Consecutive cases of cordocenteses were prospectively recorded. The inclusion criteria for analysis were: (1) singleton pregnancies, (2) no fetal abnormalities, (3) gestational age of 18-22 weeks, and (4) procedures performed by experienced operators. The primary outcome was fetal loss rate, and the secondary outcomes were rates of failed procedures, low birth weight, and preterm birth. RESULTS: Of 6147 cordocenteses recorded, 2829 met the inclusion criteria with complete data for analysis. Of these, 654 procedures were further excluded because the puncture site was at cord insertion. The remaining 2175 cases, consisting of 615 procedures with placenta penetration and 1560 cases with no penetration, were analyzed. Cordocenteses with placenta penetration had a significantly higher rate of fetal loss (3.6% vs 1.3%, p = 0.01) as well as of low birth weight and preterm birth. CONCLUSION: Cordocentesis with placenta penetration carries a higher risk for fetal loss, preterm birth, and low birth weight. This information may be helpful in prenatal diagnosis counseling, and it may encourage performers to avoid placenta penetration, if possible.