Comparison of carbetocin and oxytocin infusions in reducing the requirement for additional uterotonics or procedures in women at increased risk of postpartum haemorrhage after Caesarean section.

INTRODUCTION: Postpartum haemorrhage is a major cause of maternal mortality and morbidity, commonly due to uterine atony. Prophylactic oxytocin use during Caesarean section is recommended; patients with a high risk of postpartum haemorrhage may require additional uterotonics or procedures. Carbetocin is a long-acting analogue of oxytocin which has shown beneficial results, compared with oxytocin. This study compared the requirement for additional uterotonics or procedures between at-risk women who underwent carbetocin infusion and those who underwent oxytocin infusion. METHODS: This retrospective cohort study included women at increased risk of postpartum haemorrhage after Caesarean section for various indications in a public hospital. Women who received carbetocin infusion and women who received oxytocin infusion were compared, stratified by Caesarean section timing (elective or emergency). The primary outcome was the requirement for additional uterotonic agents or procedures. Secondary outcomes included total blood loss, operating time, rate of postpartum haemorrhage, need for blood transfusion, and need for hysterectomy. RESULTS: Of 1236 women included in the study, 752 received oxytocin first and 484 received carbetocin first. The two groups had comparable blood loss, operating time, rate of postpartum haemorrhage, requirement for additional uterotonics or procedures, need for blood transfusion, and need for hysterectomy. There was a reduction in the requirement for additional uterotonics or procedures, and in the rate of postpartum haemorrhage for women with major placenta praevia or with multiple pregnancies, following receipt of carbetocin first. CONCLUSION: Compared with oxytocin, carbetocin can reduce the requirement for additional uterotonics or procedures in selected high-risk patient groups.

Factors associated with common and atypical chromosome abnormalities after positive combined first-trimester screening in Chinese women: a retrospective cohort study.

BACKGROUND: When cell-free DNA (cfDNA) testing is used as a secondary screening tool following combined first-trimester screening (cFTS), cFTS is used to estimate the prior risk for chromosome abnormalities. This study aimed to assess the factors that are associated with common and atypical abnormalities following cFTS, including cFTS risk, advanced maternal age, increased nuchal translucency (NT) ≥3.5 mm, and abnormal levels of serum markers. METHODS: We reviewed a historical cohort of 1855 Chinese women carrying singleton pregnancies with a positive cFTS [at a threshold of 1:250 for trisomy (T) 21 or 1:180 for T18] in one public hospital over a five-year period. All chromosome abnormalities were confirmed by invasive prenatal diagnosis (IPD) with karyotyping, with or without array comparative genomic hybridization. Using multivariable binary logistic regression analysis, we determined the parameters that were associated with common and atypical abnormalities. RESULTS: Overall, the prevalence of common and atypical abnormalities was 6.2 and 1.2%, respectively, and the prevalence increased with the risk of T21 by cFTS. In pregnancies with a risk of T21 > 1 in 100, a high risk of both T21 and T18, an increased NT, or a pregnancy-associated plasma A (PAPP-A) level <  0.2 multiple of medians (MoM), the prevalence of common abnormalities was 12.2, 64.7, 25.5 and 33.8%, respectively, while that of atypical abnormalities was 1.6, 3.9, 4.2, and 7.4%, respectively. In the multivariable binary logistic regression analysis, out of these four factors, only two (increased NT and PAPP_A <  0.2 MoM) were significant predictors of common and atypical abnormalities, respectively. Of all positive cFTS pregnancies, 50.4% did not have any of these four factors, and the prevalence of common and atypical abnormalities was 1.1 and 0.6%, respectively. There were three atypical abnormalities, all of which were mosaicism, and they were detected among women with IPD alone. The ages of these women were ≥ 35 years. All three pregnancies were continued after proper counseling. After giving birth, only one child had mild abnormalities, while the other two were phenotypically normal. CONCLUSIONS: Our study identified factors associated with common and atypical abnormalities after cFTS. These factors can be used to estimate the prior risk for these abnormalities to help with post-cFTS counseling in terms of choosing between cfDNA testing and IPD.

Diagnostic accuracy of spot urine protein-to-creatinine ratio for proteinuria and its association with adverse pregnancy outcomes in Chinese pregnant patients with pre-eclampsia.

INTRODUCTION: International guidelines have endorsed spot urine protein-to-creatinine ratio of >30 mg protein/mmol creatinine as an alternative to a 24-hour urine sample to represent significant proteinuria. This study aimed to determine the accuracy of spot urine protein-to-creatinine ratio in predicting significant proteinuria and adverse pregnancy outcome. METHODS: This case series was conducted in a regional obstetric unit in Hong Kong. A total of 120 Chinese pregnant patients with pre-eclampsia delivered at Queen Elizabeth Hospital from January 2011 to December 2013 were included. Relationship of spot urine protein-to-creatinine ratio and 24-hour proteinuria; accuracy of the ratio against 24-hour urine protein at different cut-offs; and relationship of such ratio and adverse pregnancy outcome were studied. RESULTS: Spot urine protein-to-creatinine ratio was correlated with 24-hour urine protein with Pearson correlation coefficient of 0.914 (P<0.0001) when the ratio was <200 mg/mmol. The optimal threshold of spot urine protein-to-creatinine ratio for diagnosing proteinuria in Chinese pregnant patients (33 mg/mmol) was similar to that stated in the international literature (30 mg/mmol). A cut-off of 20 mg/mmol provided a 100% sensitivity, and 52 mg/mmol provided a 100% specificity. There was no significant difference in spot urine protein-to-creatinine ratio between cases with and without adverse pregnancy outcome. CONCLUSIONS: Spot urine protein-to-creatinine ratio had a positive and significant correlation with 24-hour urine results in Chinese pre-eclamptic women when the ratio was <200 mg/mmol. Nonetheless, this ratio was not predictive of adverse pregnancy outcome.

Effect of non-invasive prenatal testing as a contingent approach on the indications for invasive prenatal diagnosis and prenatal detection rate of Down's syndrome.

INTRODUCTION: In Hong Kong, universal combined first-trimester screening for Down's syndrome was started as a 'free service' in July 2010. Non-invasive prenatal testing was available as a self-financed item in August 2011. This study aimed to determine whether the introduction of non-invasive prenatal testing as a contingent approach influenced the indications for invasive prenatal diagnosis and the consequent prenatal detection of Down's syndrome. METHODS: This historical cohort study was conducted at the Prenatal Diagnosis Clinic of Queen Elizabeth Hospital in Hong Kong. We compared the indications for invasive prenatal diagnosis and prenatal detection of Down's syndrome in singleton pregnancies 1 year before and 2 years following the availability of non-invasive prenatal testing as a contingent test after a positive aneuploidy test. All pregnant women who attended our hospital for counselling about universal Down's syndrome screening between August 2010 and July 2013 were recruited. RESULTS: A total of 16 098 women were counselled. After the introduction of non-invasive prenatal testing, the invasive prenatal diagnosis rate for a positive aneuploidy screening reduced from 77.7% in 2010-11 to 68.8% in 2012-13. The new combined conventional plus non-invasive prenatal testing strategy was associated with a lower false-positive rate (6.9% in 2010-11 vs 5.2% in 2011-12 and 4.9% in 2012-13). There was no significant increase in invasive prenatal diagnosis for structural anomalies over the years. There was no significant trend in the overall prenatal detection rate of Down's syndrome (100% 1 year before vs 89.1% 2 years after introduction of non-invasive prenatal testing). Four (2.6%) of 156 women who underwent non-invasive prenatal testing for a screen-positive result had a high-risk result for trisomy 21, which was subsequently confirmed by invasive prenatal diagnosis. There were no false-negative cases. CONCLUSION: The introduction of non-invasive prenatal testing as a contingent approach reduced the invasive prenatal diagnosis rate for a positive aneuploidy screening without affecting the invasive prenatal diagnosis rate for structural anomalies or the overall detection rate of fetal Down's syndrome.

An Unusual Hydrops Fetalis Associated with Compound Heterozygosity for Krüppel-like Factor 1 mutations.

Hydrops fetalis is commonly due to Hb Bart's (γ4) disease in South East Asia. Here, we report an unusual case of hydrops fetalis due to congenital dyserythropoietic anemia (CDA) associated with compound heterozygosity for Krüppel-like factor 1 (KLF1) gene mutations. Fetal cardiomegaly was first detected on routine mid-trimester scan in a pregnant woman with normal mean corpuscular volume (MCV) and Rhesus positive status. The fetus subsequently developed hydrops fetalis, and cordocentesis showed severe fetal anemia with a hemoglobin (Hb) level of 3.4 g/dL. Common causes of fetal anemia including Hb Bart's disease, parvovirus infection, and red cell antibodies were excluded. In view of the marked increase in erythroblasts at various stages of erythropoiesis, the diagnosis of CDA was suspected. We screened the couple for previously reported KLF1 gene mutations, showing that the mother was heterozygous for the c.525_526insCGGCGCC, p.Gly176Argfs*179 mutation, and her husband heterozygous for c.1012C>A, p.Pro338Thr mutation. The fetus was a compound heterozygote for these two KLF1 mutations. After counseling, repeated intrauterine transfusions were given at 27, 29, and 34 weeks' gestation; the hydrops fetalis was resolved. The baby was delivered at 34 weeks' gestation and required monthly blood transfusions but was otherwise thriving. Bone marrow aspiration at 10 months of age showed the features of ineffective erythropoiesis, compatible with CDA. In conclusion, hydrops fetalis can rarely be due to CDA associated with a compound heterozygous mutation for KLF1 gene mutations, and be managed by repeated intrauterine transfusions. Our present report adds to the wide clinical spectrum of KLF1 mutations.

A novel mouse model for genetic variation in 10-formyltetrahydrofolate synthetase exhibits disturbed purine synthesis with impacts on pregnancy and embryonic development.

Genetic variants in one-carbon folate metabolism have been identified as risk factors for disease because they may impair the production or use of one-carbon folates required for nucleotide synthesis and methylation. p.R653Q (1958G>A) is a single-nucleotide polymorphism (SNP) in the 10-formyltetrahydrofolate (formylTHF) synthetase domain of the trifunctional enzyme MTHFD1; this domain produces the formylTHF which is required for the de novo synthesis of purines. Approximately 20% of Caucasians are homozygous for the Q allele. MTHFD1 p.R653Q has been proposed as a risk factor for neural tube defects (NTDs), congenital heart defects (CHDs) and pregnancy losses. We have generated a novel mouse model in which the MTHFD1 synthetase activity is inactivated without affecting protein expression or the other activities of this enzyme. Complete loss of synthetase activity (Mthfd1S(-/-)) is incompatible with life; embryos die shortly after 10.5 days gestation, and are developmentally delayed or abnormal. The proportion of 10-formylTHF in the plasma and liver of Mthfd1S(+/-) mice is reduced (P < 0.05), and de novo purine synthesis is impaired in Mthfd1S(+/-) mouse embryonic fibroblasts (MEFs, P < 0.005). Female Mthfd1S(+/-) mice had decreased neutrophil counts (P < 0.05) during pregnancy and increased incidence of developmental defects in embryos (P = 0.052). These findings suggest that synthetase deficiency may lead to pregnancy complications through decreased purine synthesis and reduced cellular proliferation. Additional investigation of the impact of synthetase polymorphisms on human pregnancy is warranted.

Survey on examining prevalence of paternal anxiety and its risk factors in perinatal period in Hong Kong: a longitudinal study.

BACKGROUND: There is emerging evidence of the significance of paternal mental health problems among the expectant fathers during the antenatal and postnatal period. The present study aims at determining the prevalence of paternal perinatal anxiety and identifying its risk factors among the fathers. METHODS: A total of 622 expectant fathers were recruited in Hong Kong. The expectant fathers were assessed using standardized and validated psychological instruments on three time points including early pregnancy, late pregnancy and 6 week postnatal. Independent samples t-test, one way ANOVA, Pearson's correlation and multiple linear regression were used to examine the effect of hypothesized risk factors. Hierarchical multiple regression and mixed effect model were also conducted with potential confounding factors controlled for. RESULTS: Results showed that a significant proportion of expectant fathers experienced anxiety during the perinatal period. Low self-esteem and poor social support were found to be risk factors of paternal anxiety across pregnancy to postnatal period. Work-family conflict could significantly predict paternal anxiety in the pregnancy period. CONCLUSIONS: The present study points to the need for greater research and clinical attention to paternal anxiety, given that it is a highly prevalent problem and could be detrimental to their partner's well-being and children development. The present findings contributes to the theoretical understanding of the prevalence and risk factors of paternal perinatal anxiety and have implications for the design of effective identification, prevention, and interventions of these clinical problems.

From observation to aetiology: a case report of a twin fetus-in-fetu and a revisit of the known rarity.

A baby girl presented with an antenatal diagnosis of a retroperitoneal tumour. Postnatal imaging suggested that this mass contained two fetiform structures with spine and long bone formation. This teratomatous mass was completely excised at 3 weeks of age. Histology was consistent with twin fetuses-in-fetu, revealing two fetiform masses each with an umbilical cord connecting to a common placenta-like mass. Despite a difference in the weight of the twin fetuses-in-fetu, the level of organogenesis was identical and corresponded to fetuses of 10 weeks of gestation. Each mass had four limbs, intact skin, rib cage, intestines, anus, ambiguous genitalia, primitive brain tissue and a spine with ganglion cells in the cord. Although considered a mature teratoma in the current World Health Organization classification, the theory of formation from multiple pregnancies has been commonly implied in more recent literature. The true aetiology of this rare condition remains unclear.

Uptake of Noninvasive Prenatal Testing in Chinese Women following Positive Down Syndrome Screening.

OBJECTIVES: To investigate how the introduction of noninvasive prenatal testing (NIPT) influenced women's testing choices following a positive Down syndrome screening. METHODS: A retrospective study was conducted to compare differences in the uptake rates of invasive prenatal diagnosis (IPD) or no testing in one public hospital 1 year before (pre-NIPT) and 1 and 2 years after the introduction of NIPT in private in August 2011 using descriptive analysis and a χ² test. Conventional screening was funded publicly, but NIPT was not. Multivariable binary logistic regression was used to determine factors affecting choices. RESULTS: In pre-NIPT and in years 1 and 2 after the introduction of NIPT, 306, 362 and 401 women who screened positive were seen, respectively. In year 1 and year 2, 12.6 and 26.7% of them underwent NIPT while IPD was decreased by 16.3 and 25.6%, respectively (p < 0.001). Both chorionic villus sampling and amniocentesis decreased in year 1, but only the former in year 2. However, the rate of declining further testing was similar before and after NIPT (p = 0.213). In multivariable analysis, first trimester screening, nulliparity and working women were significant predictors of accepting NIPT, while only nulliparity was a predictor of declining IPD (OR = 0.61). CONCLUSIONS: Introduction of NIPT resulted in a significant decrease in IPD for 2 consecutive years..

Two unusual cases of haemoglobin Bart's hydrops fetalis due to uniparental disomy or non-paternity.

The authors present 2 unusual cases of haemoglobin (Hb) Bart's hydrops fetalis and highlight the problem of a screening system for α-thalassaemia which focuses on maternal and paternal mean corpuscular volume (MCV) alone. Normal paternal MCV may not preclude fetal Hb Bart's disease because of the rare occurrence of maternal uniparental disomy or non-paternity. During a mid-trimester anomaly scan, with fetal cardiomegaly or hydrops in a woman with low MCV but normal paternal MCV, obstetricians should remain alert for fetal Hb Bart's disease. This is very important and relevant for national screening systems in South-East Asia, where a routine mid-trimester scan may not be available. A routine mid-trimester anomaly scan should therefore be implemented and in high prevalence areas, sonographers should be sensitive to the cardio-thoracic ratio even if screening shows that pregnancy is unlikely to be at risk.

Trend of sex ratio at birth in a public hospital in Hong Kong from 2001 to 2010.

OBJECTIVES: To identify factors affecting the sex ratio at birth. DESIGN: Cross-sectional study. SETTING: Obstetric department of a public hospital in Hong Kong. PARTICIPANTS: All pregnant women delivered between 2001 and 2010. MAIN OUTCOME MEASURES: Sex ratio at birth versus women's eligibility status, age, parity, number of miscarriages or terminations of pregnancy, and number of fetuses were analysed using the Chi squared test. Multivariate regression was used to determine the effects of multiple factors on the sex of the newborn. RESULTS: A total of 54 039 cases were reviewed. The sex ratio at birth changed since 2003, and became unbalanced (>107 males per 100 females) since 2006 revealed by a significant increase in males per 100 females, from 106.6 in 2001-2005 to 111.4 in 2006-2010. From 2001 to 2010, the sex ratio at birth increased from being balanced to becoming unbalanced in eligible persons, and became more unbalanced in non-eligible persons. The ratio increased in eligible persons after having two children, but in non-eligible persons after having one child. The sex ratio at birth was unbalanced (1.095) in singleton pregnancies, but balanced (1.019) in multiple pregnancies. Based on logistic regression, the chance of a male baby being born increased with parity of 2 or above (odds ratio=1.1; P<0.001), non-eligible person status (odds ratio=1.05; P=0.034), and delivery in the period 2006-2010 (odds ratio=1.04; P=0.019). The ratio was not increased with advanced maternal age, the number of miscarriages/terminations of pregnancy, and number of fetuses. CONCLUSION: Compared with 2001-2005, the sex ratio at birth became unbalanced in 2006-2010. An unbalanced ratio ensued in the latter period in both eligible and non-eligible persons, but to a greater extent and even after having one child in the latter group.

Dynamic concurrent partnership networks incorporating demography.

We introduce a population model that incorporates From a mathematical point of view we deal with continuous-time Markov chains at the individual level, with the interaction between individuals captured by a global variable describing opportunities for new partnerships. We show that for large time a stationary distribution is attained and we deduce various statistical features of that distribution, with particular attention for concurrency, i.e. the overlap in time of multiple partnerships of one and the same individual. Our ultimate motivation is to model the spread of sexually transmitted infections in the population, for which the present paper serves as a prelude.

Birth-weight prediction using three-dimensional sonographic fractional thigh volume at term in a Chinese population.

OBJECTIVES: To develop and validate new birth-weight prediction models in Chinese pregnant women using fractional thigh volume. METHODS: Healthy late third-trimester fetuses within 5 days of delivery were prospectively examined using two- (2D) and three- (3D) dimensional ultrasonography. Measurements were performed using 2D ultrasound for standard fetal biometry and 3D ultrasound for fractional thigh volume (TVol) and middle thigh circumference. The intraclass correlation coefficient (ICC) was used to analyze the inter- and intraobserver reliability of the 3D ultrasound measurements of 40 fetuses. Five birth-weight prediction models were developed using linear regression analysis, and these were compared with previously published models in a validation group. RESULTS: Of the 290 fetuses studied, 100 were used in the development of prediction models and 190 in the validation of prediction models. The inter- and intraobserver variability for TVol and middle thigh circumference measurements was small (all ICCs ≥ 0.95). The prediction model using TVol, femur length (FL), abdominal circumference (AC) and biparietal diameter (BPD) provided the most precise birth-weight estimation, with a random error of 4.68% and R(2) of 0.825. It correctly predicted 69.5 and 95.3% of birth weights to within 5 and 10% of actual birth weight. By comparison, the Hadlock model with standard fetal biometry (BPD, head circumference, AC and FL) gave a random error of 6.41%. The percentage of birth-weight prediction within 5 and 10% of actual birth weight was 46.3 and 82.6%, respectively. CONCLUSION: Consistent with studies on Caucasian populations, a new birth-weight prediction model based on fractional thigh volume, BPD, AC and FL, is reliable during the late third trimester in a Chinese population, and allows better prediction than does the Hadlock model.