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Esophageal atresia (OA) with or without tracheoesophageal fistula affects approximately 1 in 4000 births and commonly presents with polyhydramnios. This appears to be the first report regarding the utility of cervical cerclage with serial amnioreduction to prolong the gestational age of a neonate with OA, thereby improving outcomes for reconstructive surgery. [ABSTRACT FROM AUTHOR]

Phase Change Materials (PCMs) are utilized to regulate temperature and store thermal energy in various industries such as infrastructure, electronics, solar power, and more. However, they face several limitations, such as leakage, poor thermal properties, incompatibility, as well as high flammability. Polyethylene (PE) is one of many polymers explored to enhance the desirable properties of PCMs, due to their versatile properties such as high strength, durability, chemical resistance, and low cost. The combination of PCMs and PE can be used to create composite materials, through micro/nano‐ encapsulation, melt‐blending, formation of composites and with proper additives. They create enhanced thermal energy storage properties and in the meantime, benefited from the mechanical properties of the PE. This review provides a concise summary of the recent developments regarding PE‐enhanced PCMs and provides insights into possible topics for further investigation. We summarised enhancement methods based on commonly adopted types of PEs, such as encapsulation, melt‐blending, hot pressing, extrusion, and 3D printing. We then elaborate on how these PE‐PCM composites are effectively utilised for heat management applications and the potential future directions in energy‐saving buildings, electronic devices, and energy storage systems. [ABSTRACT FROM AUTHOR]

Objective: To develop a multi‐step workflow for the isolation of circulating extravillous trophoblasts (cEVTs) by describing the key steps enabling a semi‐automated process, including a proprietary algorithm for fetal cell origin genetic confirmation and copy number variant (CNV) detection. Methods: Determination of the limit of detection (LoD) for submicroscopic CNV was performed by serial experiments with genomic DNA and single cells from Coriell cell line biobank with known imbalances of different sizes. A pregnancy population of 372 women was prospectively enrolled and blindly analyzed to evaluate the current workflow. Results: An LoD of 800 Kb was demonstrated with Coriell cell lines. This level of resolution was confirmed in the clinical cohort with the identification of a pathogenic CNV of 800 Kb, also detected by chromosomal microarray. The mean number of recovered cEVTs was 3.5 cells per sample with a significant reverse linear trend between gestational age and cEVT recovery rate and number of recovered cEVTs. In twin pregnanices, evaluation of zygosity, fetal sex and copy number profiling was performed in each individual cell. Conclusion: Our semi‐automated methodology for the isolation and single‐cell analysis of cEVTS supports the feasibility of a cell‐based noninvasive prenatal test for fetal genomic profiling. Key points: What's already known about this topic?Fetal circulating extravillous trophoblasts (cEVTs) have been isolated from maternal blood for both aneuploidy and copy number variant (CNV) classification.Previous reported methodologies require mostly manual low throughput workflows and identify putative fetal cells based on immunophenotype. What does this study add?We present a novel semi‐automated workflow for the isolation of circulating fetal trophoblasts and single‐cell genomic profiling of submicroscopic variants.With this methodology, the feasibility of fetal genetic confirmation of each individual cell, a limit of detection (LoD) for CNVs down to 800Kb and the assessment of zygosity, fetal sex and genomic profiling in the same cell in twin pregnancies was demonstrated. [ABSTRACT FROM AUTHOR]

Objectives: To review the prenatal characteristics and postnatal outcomes of Early-onset and Late-onset cerebral ventriculomegaly (VM). Methods: Single-center retrospective study 2013-2017; VM cases grouped into Early-onset VM (EVM; Diagnosis at/before 24 weeks) and Late-onset VM (LVM; Beyond 24 weeks). LVM cases had normal ventricle width measurement at mid-trimester scan. Infection serology, cytogenetics, MRI, sonographic follow-up, perinatal and neurodevelopmental outcomes were analyzed. Results: During the 5-year period, 64,662 women underwent an anomaly screening scan and 302 fetuses were identified with ventriculomegaly; 183 (60.6%) classified as early-onset and 119 (39.4%) LVM. The mean ventricular width was significantly higher in LVM cohort (14.1 mm vs 11.6 mm; p < .01). EVM cases were more often associated with structural anomalies (p < .05). Possible etiologies for EVM were aneuploidy and cerebral malformations like Absent Corpus Callosum, spina bifida, Dandy-Walker malformation, etc., whereas LVM followed aqueductal stenosis, hemorrhage, porencephaly, cerebral tumors, etc. Pregnancy outcomes were available for 251 cases. The pregnancy resulted in more live births in LVM group (87.4% vs 65.6%, p = < .01). Multivariate regression analysis demonstrated additional malformations (p < .0001, OR11.5 [95%CI: 4-35.2]), progression of VM (p = .004, OR 10.2 [95% CI: 2.1-52.3]) and severity of VM (OR 5.3 [95%CI: 0.8-37.7]) were significant predictors of Neurodevelopmental Impairment (NDI). Late gestation at diagnosis was more often associated with NDI (p = .063, OR2.4 [95%CI: 0.9-6.2]), although statistically insignificant. Conclusions: EVM has a significantly different sonographic spectrum and outcomes compared to LVM. EVM is milder and associated with an increased risk of aneuploidy and structural malformations. LVM often occurs secondary to acquired brain lesions. [ABSTRACT FROM AUTHOR]

Introduction: Fetoscopic laser photocoagulation (FLP), a treatment option for twin-to-twin transfusion syndrome (TTTS) in monochorionic twin pregnancies, is currently the treatment of choice at our centre. We previously reported on our experience of FLP from June 2011 to March 2014. This paper audits our fetal surgery performance since then.Methods: 15 consecutive patients who underwent FLP for Stage II-III TTTS before 26 weeks of gestation from June 2011 to January 2017 were retrospectively reviewed, consisting of five cases from our initial experience and ten subsequent cases. Perioperative, perinatal and neonatal outcomes were analysed.Results: Of 15 pregnancies, 10 (66.7%) and 5 (33.3%) were for Stage II and III TTTS respectively, with FLP performed at an earlier Quintero stage in the later cohort. Overall mean gestational ages at presentation, laser and delivery were comparable between the cohorts at 19.7 (15.4-24.3) weeks, 20.3 (16.3-25.0) weeks and 31.2 (27.6-37.0) weeks, respectively. 2 (13.3%) cases had intra-amniotic bleeding and 1 (6.7%) had iatrogenic septostomy. 1 (6.7%) case had persistent TTTS requiring repeat FLP, and another (6.7%) had preterm premature rupture of membranes at seven weeks post procedure. The overall perinatal survival rate was 21 (75.0%) out of 28 infants. One mother underwent termination of pregnancy for social reasons at 1.4 weeks post procedure. Double survival occurred in 8 (57.1%) out of 14 pregnancies, while 13 (92.9%) had at least one survivor.Conclusion: FLP requires a highly specialised team and tertiary neonatal facility. Continual training improves maternal and perinatal outcomes, ensuring comparable standards with international centres. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy and safety of dinoprostone vaginal insert (DVI) alone versus DVI with adjunctive sweeping of membranes (ASM) for induction of labor (IOL). Methods: Single‐center, prospective, randomized controlled trial; women with singleton term pregnancies, cervical dilation ≥1 and <3 cm, intact membranes allocated to either DVI or DVI with ASM. The primary outcome was vaginal delivery within 24 h of insertion. Secondary outcomes included mean time from insertion to delivery, tachysystole, operative delivery for non‐reassuring fetal status (NRFS), tocolytics, fetal outcomes, pain information, and subject satisfaction. Results: One hundred and four received DVI (Group 1) alone and 104 DVI with ASM (Group 2). The rate of vaginal delivery within 24 h was 53% versus 56%, cesarean rate 8.7% versus 10.6% in Groups 1 and 2 respectively. Although the duration of labor was similar in both groups, about 6% of women required additional ripening with dinoprostone vaginal tablets in Group 2 compared to 11.5% in Group 1 (p‐value = 0.2). The frequency of hyperstimulation syndrome, failed induction, analgesic requirements, and fetal outcomes were comparable. The majority (83%–86%) in either cohort were satisfied with their labor experience. Multivariate logistic regression demonstrated a slightly better chance for vaginal delivery within 24 h (odds ratio [OR] 1.22 [95% confidence interval, CI 0.65–2.29]; p‐value 0.53] for DVI with ASM, although statistically insignificant. Younger maternal age and multiparity (OR 10.36 [95% CI 4.88–23.67]; p‐value <0.0001) contributed to successful IOL. Conclusion: DVI with ASM is at least as efficacious as DVI for cervical ripening with no increase in morbidity. Although DVI with ASM group less often needed additional dinoprostone tablets to complete the process of IOL (p‐value = 0.2), adjunctive sweeping has not been shown to have a significant impact on the duration of labor or mode of delivery. [ABSTRACT FROM AUTHOR]

Abstract Background Hypertensive disorders in pregnancy are associated with systemic endothelial dysfunction leading to impaired physiological vasodilation. Recent evidence has shown central aortic pressures obtained through pulse wave analysis, at less than 14 weeks of gestation, to be predictive of pre-eclampsia. In light of this, we aimed to evaluate the role of central aortic stiffness in the prediction and discrimination of hypertensive disorders in pregnancy. Methods A cohort study of women with viable, singleton pregnancies at less than 14 weeks of amenorrhoea, and without multiple pregnancies, autoimmune or renal disease, diagnosed with aneuploidy or fetal anomaly will be recruited from a single maternity hospital and followed up till delivery and puerperium. A targeted sample size of 1000 eligible pregnant women will be enrolled into the study from antenatal clinics. Main exposure under study is central aortic pulse pressure using radial pulse wave recording, and the outcomes under follow-up are gestational hypertension and pre-eclampsia. Other measures include lifestyle factors such as smoking, physical exercise, psychometric evaluations, vasoactive factors, uterine artery pulsatility index, height and weight measurements. These measures will be repeated over 4 antenatal visits at 11-14, 18-22, 28-32 and above 34 weeks of gestation. Double data entry will be performed on Microsoft Access, and analysis of data will include the use of random effect models and receiver operating characteristic curves on Stata 11.2. Discussion The proposed study design will enable a longitudinal evaluation of the central aortic pressure changes as a marker for vascular compliance during pregnancy. As measures are repeated over time, the timing and severity of changes are detectable, and findings may yield important information on how aberrant vascular responses occur and its role in the early detection and prediction of hypertensive disorders.

Objective: Preterm birth (birth before 37 weeks of completed gestation) is the leading cause of neonatal death, and has an incidence of 5–13% which is believed to be on the rise. The objective of this study was to determine the rate of spontaneous preterm birth and investigate the relationship between preterm birth and cervical length in a pregnant Asian population. Materials and methods: A prospective observational study between September 2010 and November 2013 was performed at KK Women's and Children's Hospital, Singapore. 1013 women with single viable pregnancies were recruited at less than 14 weeks of gestation between September 2010 and November 2013, excluding those with multiple gestation, pre-existing autoimmune or renal disease or those with current pregnancies complicated by aneuploidy or fetal anomalies. Participant characteristics were obtained from an interviewer-administered questionnaire at the first recruitment visit. Cervical length was measured using ultrasound at each of the 4 antenatal visits (Visit 1: < 14 weeks, Visit 2: 18–22 weeks, Visit 3: 28–32 weeks and Visit 4: > 34 weeks) using the Fetal Medicine Foundation protocol. Data on pregnancy outcomes were obtained from obstetric case notes and records. The main outcome measure examined in this study was that of spontaneous preterm birth and its relationship to cervical length. Results: There was a significantly shorter cervical length both in the 2nd trimester (18 to 22 weeks) and the 3rd trimester (28 to 32 weeks) in the preterm birth group compared to the term birth group (p = 0.028 and p < 0.001 respectively). In the first trimester (11 to 14 weeks), there was no statistically significant difference in cervical length between the two groups (p = 0.425). ROC curve analysis for cervical length in the preterm birth group for 18 to 22 weeks and 28 to 32 weeks showed an AUC of 0.605 and 0.725 respectively. At 28 to 32 weeks of gestation, a cut-off level at 2.49 cm has a sensitivity of 54.8%, specificity of 82.5%, negative predictive value of 97.9% and positive predictive value of 11.1%. Conclusion: There is a significantly shorter cervical length in the 2nd and 3rd trimester in the preterm birth group. Cervical length is a moderate predictor of preterm birth with good negative predictive value and a relatively good specificity. Ultrasound cervical length screening for pregnant Asian women between 18 and 22 weeks of gestation with a cutoff of ≥ 2.48cm can help to identify a group of women who are at risk for preterm birth. [ABSTRACT FROM AUTHOR]

Introduction: Evidence has shown that balloon catheters are as effective as prostaglandins (PGE) in achieving vaginal delivery within 24 hours of the start of induction of labour (IOL), with lower rates of uterine hyperstimulation, and similar Caesarean section and infection rates. International guidelines recommend mechanical methods as a method of IOL. We designed a prospective randomised controlled study to evaluate patient acceptance of the cervical ripening balloon (CRB) for IOL.Methods: Suitable women with a singleton term pregnancy without major fetal anomaly suitable for vaginal delivery were recruited and randomised to receive the CRB or PGE on the day of IOL. Characteristics of the women, labour and birth outcomes were obtained from case notes. Pain and satisfaction scores were obtained by interviewing the women at IOL and after delivery. The main outcome measures were participant characteristics, labour and birth outcomes, pain score, satisfaction scores, and whether the participant would recommend the mode of IOL.Results: There was no difference in the pain score between the two groups at the start of IOL, but thereafter, pain scores were lower in the CRB group compared to the PGE group (4.5 ± 2.3 vs. 5.6 ± 2.4, p = 0.044). Women were equally satisfied with both methods and equally likely to recommend their method for IOL.Conclusion: Patient experience of IOL with CRB or PGE was equally satisfactory, although pain during induction was lower in the CRB group. We found that both methods of IOL are acceptable to women and should be made available to provide more options. [ABSTRACT FROM AUTHOR]

Introduction: Twin-to-twin transfusion syndrome (TTTS) is the most common serious complication of monochorionic (MC) twin pregnancies, with perinatal mortality rates of up to 90% if untreated. This study aimed to review the perinatal and perioperative outcomes of MC twin pregnancies treated for TTTS by fetoscopic laser photocoagulation (FLP) since its introduction at KK Women's and Children's Hospital (KKH), Singapore, in 2011.Methods: This was a retrospective review of five consecutive patients who underwent FLP of placental anastomoses for TTTS at KKH from June 2011 to March 2014. FLP was offered to patients who were diagnosed with TTTS of at least Quintero Stage II before 26 weeks of gestation. The main outcome measures were perioperative complications and perinatal survival rates.Results: Five sets of MC twin pregnancies underwent FLP during the study period - three pregnancies were diagnosed with Stage III TTTS and two pregnancies with Stage II TTTS. Median gestational ages at initial presentation, laser photocoagulation and delivery were 19 (range 17-20) weeks, 20 (range 19-23) weeks and 29 (range 28-34) weeks, respectively. One patient had bleeding into the amniotic cavity intraprocedurally. Overall, the perinatal survival rate, double-infant survival rate and survival rate for at least one twin were 60% (6/10 fetuses), 40% (2/5 twins) and 80% (4/5 twins), respectively.Conclusion: FLP is a feasible treatment for TTTS, with minimal maternal complications. Perinatal survival rates of this patient group that was managed at our centre were comparable to those of international centres. [ABSTRACT FROM AUTHOR]

Objective It remains unclear what roles placenta-originated angiogenic factors play in the pathogenesis of preeclampsia among hypertensive women. We compared maternal soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) levels throughout pregnancy in women with normal blood pressure (BP), elevated BP and hypertension in early pregnancy and their risks of developing preeclampsia. Design A prospective cohort study. Setting KK Women’s and Children’s Hospital, Singapore. Participants 923 women with singleton pregnancy <14 weeks of gestation were included in the prospective Neonatal and Obstetrics Risks Assessment cohort between September 2010 and October 2014. Systolic, diastolic, mean arterial blood pressure (MAP) were measured at 11–14 weeks. Primary and secondary outcomes Maternal serum sFlt-1, PlGF and sFlt-1/PlGF ratio were tested at 11–14, 18–22, 28–32 and 34 weeks onwards of gestation. Preeclampsia was main pregnancy outcome. Results Women were divided based on their BP in early pregnancy: normal (n=750), elevated BP (n=98) and hypertension (n=75). Maternal sFlt-1 levels and sFlt-1/PlGF ratios were higher in hypertensive women throughout pregnancy, but maternal PlGF levels were not significantly lower. Rise in maternal systolic, diastolic BP and MAP at 11–14 weeks were significantly associated with higher sFlt-1/PlGF ratios during pregnancy. A 10 mm Hg increase in MAP was associated with a 5.6-fold increase in risk of preterm preeclampsia and a 3.3-fold increase in risk of term preeclampsia, respectively. Conclusion Women with elevated BP in early pregnancy already had a higher sFlt-1/PlGF ratio in early gestation and throughout pregnancy, and an increased risk of preeclampsia. In contrast, PlGF levels in these women remained normal. [ABSTRACT FROM AUTHOR]

Objectives To analyse the placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1) trends in the normal pregnant Asian population in Singapore. Design A prospective study was conducted. Setting The largest tertiary hospital in Singapore. Methods Women with single viable pregnancies, less than 14 weeks of gestation, were recruited between September 2010 and November 2013 in KK Women's and Children's Hospital. They were followed up from recruitment till their postnatal discharge from the hospital. There were four antenatal visits: gestational age (GA) less than 14+0 weeks of gestation (V1), GA 18+0 to 22+0 weeks (V2), GA 28+0 to 32+0 weeks (V3) and GA 34+0 and above (V4). Serum biochemical markers (sFlt-1, PlGF) were measured at each visit. Results There were 934 participants in the study, of which 674 had normal pregnancy outcomes. The sFlt-1 remained relatively constant till GA 28-32 weeks before it increased (p<0.001). The sFlt-1 levels increased earlier before 30 weeks' of gestation among the Malay participants and the other ethnicities. For PlGF, the levels increased from the first to the third trimester, peaking at 30-32 weeks before decreasing (p<0.001). Its serum levels significantly differed among the Indian participants and other ethnicities as compared with the Malay and Chinese participants at V3 and V4, (p=0.04 and p<0.001, respectively). Conclusion There are significant differences in the PlGF and sFlt-1 concentrations during pregnancy between different ethnicities, which should be taken into consideration when using these references values for further research. [ABSTRACT FROM AUTHOR]

Background: Intrauterine growth restriction affects 3% of newborns; and the lightest 10% of whom are classified as small for gestational age (SGA). These low-birth weight newborns are at increased risk of neonatal morbidity such as hypoxia and hypoglycaemia. In later life, they are at higher risk of several age-related diseases such as cardiovascular and metabolic disorders and dementia. As having short telomeres is also associated with these diseases, we tested if these newborns might already start with shorter telomeres at birth. Findings: Relative telomere lengths were determined using quantitative real-time PCR in cord blood samples from 195 newborns of Chinese ancestry. Based on the telomere length normalised to a single copy gene and a reference DNA sample as internal control, we found statistically significant correlations between relative telomere length and both unadjusted and gestational age-adjusted birth weight, with the lighter newborns having shorter telomeres. The SGA birth weight group comprising the bottom 10% of the samples also had the shortest telomeres compared to the medium and heaviest birth weight groups. Conclusions: Our results indicate that there is reduction of cord blood telomere length for newborns with lower birth weight. [ABSTRACT FROM AUTHOR]

The human placenta is a maternal-fetal organ essential for normal fetal development and maternal health. During pregnancy, the placenta undergoes many structural and functional changes in response to fetal needs and environmental exposures. Previous studies have demonstrated widespread epigenetic and gene expression changes from early to late pregnancy. However, on the global level, how DNA methylation changes impact on gene expression in human placenta is not yet well understood. We performed DNA methylome analysis by reduced representation bisulfite sequencing (RRBS) and gene expression analysis by RNA-Seq for both first and third trimester human placenta tissues. From first to third trimester, 199 promoters (corresponding to 189 genes) and 2,297 gene bodies were differentially methylated, with a clear dominance of hypermethylation (96.8% and 93.0% for promoters and gene bodies, respectively). A total of 2,447 genes were differentially expressed, of which 77.2% were down-regulated. Gene ontology analysis using differentially expressed genes were enriched for cell cycle and immune response functions. The correlation between DNA methylation and gene expression was non-linear and complex, depending on the genomic context (promoter or gene body) and gene expression levels. A wide range of DNA methylation and gene expression changes were observed at different gestational ages. The non-linear association between DNA methylation and gene expression indicates that epigenetic regulation of placenta development is more complex than previously envisioned. [ABSTRACT FROM AUTHOR]

Background: The aim was to evaluate the ability of customized and cohort birthweight standards in discriminating intrauterine growth retardation (IUGR).Methods: Birthweights (BWs) of GUSTO singleton infants born at gestational age (GA) 35-41 weeks were converted using two standards: (a) GUSTO cohort-based BW centile adjusted for GA and baby gender; (b) customized BW percentile calculator adjusted for maternal height and weight, race, parity, GA and gender. Infants were classified into three groups: (1) < 10th BW centile by customization- customized-SGA, (2) < 10th BW centile by GUSTO- GUSTO-SGA; and (3) > 10th BW centile by both standards - BOTH-non-SGA.Results: Of the 1011 infant-mother dyads, 68 were customized-SGA and 104 were GUSTO-SGA, with concordance of 61% (n = 63) for SGA. While 5 (7%) of customized-SGA were not SGA by GUSTO-charts, 41 (39%) of GUSTO-SGA were not SGA by customized-charts. Customized-SGA had significantly the least growth in abdominal circumference (AC) and highest head circumference (HC): AC growth ratio between second and third trimester; and the lowest mean BW, ponderal index and placental weight than other groups.Conclusion: Customized-SGA standard was a better discriminator of pathologic fetal growth based on AC growth. It improved strength of association with pathology and in our population reduced false positives (41/104 = 39%) in the assessment of SGA. [ABSTRACT FROM AUTHOR]

Objective: Epidemiological studies relating maternal 25-hydroxyvitamin D (25OHD) with gestational diabetes mellitus (GDM) and mode of delivery have shown controversial results. We examined if maternal 25OHD status was associated with plasma glucose concentrations, risks of GDM and caesarean section in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Methods: Plasma 25OHD concentrations, fasting glucose (FG) and 2-hour postprandial glucose (2HPPG) concentrations were measured in 940 women from a Singapore mother-offspring cohort study at 26–28 weeks’ gestation. 25OHD inadequacy and adequacy were defined based on concentrations of 25OHD ≤75nmol/l and >75nmol/l respectively. Mode of delivery was obtained from hospital records. Multiple linear regression was performed to examine the association between 25OHD status and glucose concentrations, while multiple logistic regression was performed to examine the association of 25OHD status with risks of GDM and caesarean section. Results: In total, 388 (41.3%) women had 25OHD inadequacy. Of these, 131 (33.8%), 155 (39.9%) and 102 (26.3%) were Chinese, Malay and Indian respectively. After adjustment for confounders, maternal 25OHD inadequacy was associated with higher FG concentrations (β = 0.08mmol/l, 95% Confidence Interval (CI) = 0.01, 0.14), but not 2HPPG concentrations and risk of GDM. A trend between 25OHD inadequacy and higher likelihood of emergency caesarean section (Odds Ratio (OR) = 1.39, 95% CI = 0.95, 2.05) was observed. On stratification by ethnicity, the association with higher FG concentrations was significant in Malay women (β = 0.19mmol/l, 95% CI = 0.04, 0.33), while risk of emergency caesarean section was greater in Chinese (OR = 1.90, 95% CI = 1.06, 3.43) and Indian women (OR = 2.41, 95% CI = 1.01, 5.73). Conclusions: 25OHD inadequacy is prevalent in pregnant Singaporean women, particularly among the Malay and Indian women. This is associated with higher FG concentrations in Malay women, and increased risk of emergency caesarean section in Chinese and Indian women. [ABSTRACT FROM AUTHOR]

Objective: We aimed to study the maternal retinal microvasculature at mid-trimester and its relationship with subsequent fetal growth and birth size. Methods: We recruited 732 pregnant women aged 18-46 years in the first trimester with singleton pregnancies. All had retinal photography and fetal scan performed at 26-28 weeks gestation, and subsequent fetal scan at 32-34 weeks gestation. Infant anthropometric measurements were done at birth. Retinal microvasculature was measured using computer software from the retinal photographs. Results: In multiple linear regression models, each 10 μm narrowing in maternal retinal arteriolar caliber was associated with decreases of 1.36 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.50 mm and 2.30 mm in infant head circumference and birth length at delivery, respectively. Each standard deviation decrease in maternal retinal arteriolar fractal dimension was associated with decreases of 1.55 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.08 mm and 46.42 g in infant head circumference and birth weight at delivery, respectively. Conclusions: Narrower retinal arteriolar caliber and a sparser retinal vascular network in mothers, reflecting a suboptimal uteroplacental microvasculature during mid-pregnancy, were associated with poorer fetal growth and birth size. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the use of cervical ripening balloon (CRB) for induction of labour (IOL) in Singapore. Design: Prospective cohort randomised controlled study comparing CRB to Prostin (PGE) for IOL Setting: Tertiary maternity hospital in Singapore. Population: Women aged 21 to 40 years old for IOL in a singleton term pregnancy without major fetal anomaly suitable for vaginal delivery were recruited unless they were in labour, had cervical dilatation 33 cm, ruptured membrane, abnormal CTG, scarred uterus or malpresentation. Methods: Suitable women were recruited in the ante-natal period and randomized to receive either CRB or PGE on the day of IOL. Characteristics of the women, labour and birth outcomes, as well as their pain and satisfaction scores were obtained from case notes and by interviewing the women at IOL and after delivery. Main Outcome Measures: Characteristics of participants, labour outcomes, birth outcomes. Results: 98 women were enrolled for the study with 31 CRB and 52 PGE cases analysed. Both groups had similar maternal age, ethnic mix, proportion of primigravidae, weight, gestational age, cervical dilatation, indication for IOL, baby gender and birth weight. The induction to vaginal delivery time and vaginal delivery rate, as well as risk of low Apgar scores, meconium aspiration, pyrexia in labour, neonatal intensive care unit or intensive care unit admissions were also similar. Although only 1 (3.2%) in CRB arm failed to be induced compared with 9 (17.3%), this was not statistically significant (p = 0.082). Only 1 case of uterine hyperstimulation was observed and was from the PGE group. Conclusions: Both CRB and PGE are effective and complementary methods for IOL. The availability of both methods in an obstetric unit will allow women and clinicians choice in their method of IOL. [ABSTRACT FROM AUTHOR]

Background DNA methylation plays crucial roles in epigenetic gene regulation in normal development and disease pathogenesis. Efficient and accurate quantification of DNA methylation at single base resolution can greatly advance the knowledge of disease mechanisms and be used to identify potential biomarkers. We developed an improved pipeline based on reduced representation bisulfite sequencing (RRBS) for cost-effective genome-wide quantification of DNA methylation at single base resolution. A selection of two restriction enzymes (TaqαI and MspI) enables a more unbiased coverage of genomic regions of different CpG densities. We further developed a highly automated software package to analyze bisulfite sequencing results from the Solexa GAIIx system. Results With two sequencing lanes, we were able to quantify ∼1.8 million individual CpG sites at a minimum sequencing depth of 10. Overall, about 76.7% of CpG islands, 54.9% of CpG island shores and 52.2% of core promoters in the human genome were covered with at least 3 CpG sites per region. Conclusions With this new pipeline, it is now possible to perform whole-genome DNA methylation analysis at single base resolution for a large number of samples for understanding how DNA methylation and its changes are involved in development, differentiation, and disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Universal and high-risk screening for gestational diabetes mellitus (GDM) has been widely studied and debated. Few studies have assessed GDM screening in Asian populations and even fewer have compared Asian ethnic groups in a single multi-ethnic population. Methods: 1136 pregnant women (56.7% Chinese, 25.5% Malay and 17.8% Indian) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study were screened for GDM by 75-g oral glucose tolerance test (OGTT) at 26-28 weeks of gestation. GDM was defined using the World Health Organization (WHO) criteria. High-risk screening is based on the guidelines of the UK National Institute for Health and Clinical Excellence. Results: Universal screening detected significantly more cases than high-risk screening [crude OR 2.2 (95% CI 1.7-2.8)], particularly for Chinese women [crude OR = 3.5 (95% CI 2.5-5.0)]. Pre-pregnancy BMI > 30 kg/m² (adjusted OR = 3.4, 95% CI 1.5-7.9) and previous GDM history (adjusted OR = 6.6, 95% CI 1.2-37.3) were associated with increased risk of GDM in Malay women while GDM history was the only significant risk factor for GDM in Chinese women (adjusted OR = 4.7, 95% CI 2.0-11.0). Conclusion: Risk factors used in high-risk screening do not sufficiently predict GDM risk and failed to detect half the GDM cases in Asian women. Asian women, particularly Chinese, should be screened to avoid under-diagnosis of GDM and thereby optimize maternal and fetal outcomes. [ABSTRACT FROM AUTHOR]

Background: Genomic imprinting is an epigenetically regulated process wherein genes are expressed in a parentof- origin specific manner. Many imprinted genes were initially identified in mice; some of these were subsequently shown not to be imprinted in humans. Such discrepancy reflects developmental, morphological and physiological differences between mouse and human tissues. This is particularly relevant for the placenta. Study of genomic imprinting thus needs to be carried out in a species and developmental stage-specific manner. We describe here a new strategy to study allele-specific DNA methylation in the human placenta for the discovery of novel imprinted genes. Results: Using this methodology, we confirmed 16 differentially methylated regions (DMRs) associated with known imprinted genes. We chose 28 genomic regions for further testing and identified two imprinted genes (DNMT1 and AIM1). Both genes showed maternal allele-specific methylation and paternal allele-specific transcription. Imprinted expression for AIM1 was conserved in the cynomolgus macaque placenta, but not in other macaque tissues or in the mouse. Conclusions: Our study indicates that while there are many genomic regions with allele-specific methylation in tissues like the placenta, only a small sub-set of them are associated with allele-specific transcription, suggesting alternative functions for such genomic regions. Nonetheless, novel tissue-specific imprinted genes remain to be discovered in humans. Their identification may help us better understand embryonic and fetal development. [ABSTRACT FROM AUTHOR]

Down syndrome (DS), commonly caused by an extra copy of chromosome 21 (chr21), occurs in approximately one out of 700 live births. Precisely how an extra chr21 causes over 80 clinically defined phenotypes is not yet clear. Reduced representation bisulfite sequencing (RRBS) analysis at single base resolution revealed DNA hypermethylation in all autosomes in DS samples. We hypothesize that such global hypermethylation may be mediated by down-regulation of TET family genes involved in DNA demethylation, and down-regulation of REST/NRSF involved in transcriptional and epigenetic regulation. Genes located on chr21 were up-regulated by an average of 53% in DS compared to normal villi, while genes with promoter hypermethylation were modestly down-regulated. DNA methylation perturbation was conserved in DS placenta villi and in adult DS peripheral blood leukocytes, and enriched for genes known to be causally associated with DS phenotypes. Our data suggest that global epigenetic changes may occur early in development and contribute to DS phenotypes. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to describe the performance of first trimester screening (FTS) for trisomy 21 using maternal age, serum biochemistry and fetal nuchal translucency (NT) in a single center and to evaluate the effect of nasal bone on screening performance. Material and Methods: In 12,585 singleton pregnancies, the NT and nasal bone were examined. The majority of these mothers also had their serum biochemical markers analyzed. Risk was computed using different combinations of maternal age, biochemistry, NT and nasal bone. Down syndrome cases were confirmed by karyotyping. Results: There were 12,519 normal pregnancies, 31 with trisomy 21 and 35 with other chromosomal abnormalities. Without considering the nasal bone, the combined FTS detected 87.1% of trisomy 21 fetuses (false positive rate 5.1%), using 1:300 as the risk threshold, and this was further improved to 96.8% with the policy that classifies all fetuses with an absent nasal bone as high risk. Subgroup analysis showed that the detection rate would be 90.9%, with a false positive rate of 3.7%, if nasal bone was incorporated in the risk algorithm, compared to 81.8% and a false positive rate of 5.4% if it was not used. Discussion: FTS is very effective in early detection of trisomy 21 in Singapore. The nasal bone is a useful marker that can substantially improve the screening performance. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]