GDF15 linked to maternal risk of nausea and vomiting during pregnancy.

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1-4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with ß-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

Lower uterine segment scar assessment at 11-14 weeks' gestation to screen for placenta accreta spectrum in women with prior Cesarean delivery.

OBJECTIVES: To validate prospectively transvaginal ultrasound assessment of the lower uterine segment (LUS) scar at the time of first-trimester screening in women with previous Cesarean section (CS) and to determine its feasibility and accuracy in stratifying women according to the risk for placenta accreta spectrum (PAS) disorder. METHODS: Women with a history of CS were recruited between 11 + 0 and 13 + 6 weeks' gestation and underwent LUS scar assessment using transvaginal ultrasound. A standardized midsagittal plane, which included the cervicoisthmic canal (CIC), the uterine scar and the placental site, was obtained. The scar was described in terms of its size (narrow or dehiscent) and its location in relation to the CIC (within or above), with each LUS scar classified into one of four groups based on these features. Placental location was assessed and classified as high- or low-lying. Women were stratified according to the risk of PAS, based on the relationship between the scar location and placental site. Women were considered high risk when the scar was above the CIC and the placenta was low-lying (i.e. when the placenta was overlying an exposed scar) and low risk when the scar was within the CIC and/or the placenta was high. High-risk patients were followed up at 20 weeks and 28-30 weeks for the development of PAS. Maternal demographics, detailed obstetric history and obstetric outcome were collected. RESULTS: First-trimester transvaginal ultrasound was offered to 535 women with prior CS during the study period. A LUS scar was visualized in 79.9% (401/502) of those who agreed to undergo the examination. At this scan, the LUS scar was above the CIC in 9.0% (36/401) of women, but only 5.7% (23/401) additionally had a low-lying placenta overlying the scar. Of these 23 high-risk women, two were found to have PAS on the mid-trimester screening scan and one was noted to have placental adherence during evacuation following mid-trimester termination of pregnancy. On the first-trimester scan, 94.3% (378/401) of women were at low risk of PAS. This screening protocol yielded a positive likelihood ratio of 21.33 (95% CI, 13.02-34.96), sensitivity of 100% (95% CI, 29.24-100%), specificity of 95.31% (95% CI, 92.39-97.35%), positive predictive value of 16.7% (95% CI, 5.8-39.2%) and negative predictive value of 100% (95% CI, 98.4-100%). On multivariable regression analysis performed to identify confounding variables associated with a LUS scar above the CIC, only maternal body mass index ≥ 30 kg/m2 was significant (odds ratio (OR), 2.42 (95% CI, 1.04-5.39); P = 0.03). Although there was a trend towards an increased risk of a LUS scar above the CIC in women with prior elective prelabor CS (OR, 1.72 (95% CI, 0.80-3.68)), this association did not reach statistical significance. CONCLUSIONS: Routine transvaginal ultrasound assessment of the location of the LUS scar and placenta at the time of first-trimester screening between 11 + 0 and 13 + 6 weeks' gestation in women with prior CS is a feasible and effective tool to identify those at risk of subsequent development of PAS disorder. A finding of placental implantation over an exposed LUS scar seems to be cardinal in predicting the risk of PAS disorder in women with prior CS, with an excellent negative predictive value. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

FTO expression is regulated by availability of essential amino acids.

Genome-wide association studies have revealed that single nucleotide polymorphisms in fat mass and obesity-associated transcript (FTO) are robustly associated with body mass index and obesity. Expression of Fto in the hypothalamic arcuate nucleus is bidirectionally regulated as a function of nutritional status; decreasing following a 48-h fast and increasing after 10-week exposure to a high-fat diet. Here, we utilize an in vitro approach to determine which nutrients could regulate FTO levels at a cellular level. Using mouse and human cell lines, we find that FTO levels are not influenced by serum starvation. We demonstrate, however, that both glucose and total amino-acid deprivation regulates FTO expression. In particular, we have found that FTO mRNA and protein levels are dramatically downregulated by total amino-acid deprivation in mouse hypothalamic N46 cells, mouse embryonic fibroblasts and in human HEK293 cells. The drop rate of Fto mRNA is faster than its rate of natural degradation, pointing to regulation at the transcriptional level, which is reversible upon amino-acid replacement. Strikingly, this downregulation was seen only with essential amino-acid deficiency and not nonessential amino acids. These data suggest that FTO might have a role in the sensing of essential amino-acid availability.

Nutrition-/diet-induced changes in gene expression in pancreatic ß-cells.

ß-Cell dysfunction is a critical component in the development of type 2 diabetes. Whilst both genetic and environmental factors contribute to the development of the disease, relatively little is known about the molecular network that is responsible for diet-induced functional changes in pancreatic ß-cells. Recent genome-wide association studies for diabetes-related traits have generated a large number of candidate genes that constitute possible links between dietary factors and the genetic susceptibility for ß-cell failure. Here, we summarize recent approaches for identifying nutritionally regulated transcripts in islets on a genome-wide scale. Polygenic mouse models for type 2 diabetes have been instrumental for investigating the mechanism of diet-induced ß-cell dysfunction. Enhanced oxidative metabolism, triggered by a combination of dietary carbohydrates and fat, appears to play a critical role in the pathophysiology of diet-induced impairment of islets. More systematic studies of gene-diet interactions in ß-cells of rodent models in combination with genetic profiling might reveal the regulatory circuits fundamental for the understanding of diet-induced impairments of ß-cell function in humans.

Evaluation of an objective method of image assessment for first-trimester nasal bone.

OBJECTIVE: To evaluate the degree of agreement in first-trimester nasal bone assessment in a group of sonographers before and after training, using a semi-quantitative scoring system. METHODS: Four sonographers who routinely perform first-trimester screening were first shown 46 images from both normal and trisomy 21 pregnancies. For each image, they were asked to score from 0 (disagree) to 3 (agree) on five different criteria that were deemed important in nasal-bone assessment, including image size, plane and visibility of nasal bone. A training program was then conducted, and a repeat exercise was carried out using the same 46 images. Finally, in a third exercise, images from 42 patients were presented, some having more than one image. The sonographers were required to give one overall nasal-bone score for each patient. In each exercise interobserver agreement was evaluated by intraclass correlation coefficient (ICC). RESULTS: Before training, the sonographers agreed reasonably well on the five proposed criteria (ICC, 0.752), with some disagreement on their perceived image quality. The training program further improved the agreement (ICC, 0.790), particularly on whether the nasal bone was the biggest and brightest echogenic component. Agreement was excellent when they were asked to give one overall score on the nasal bone based on multiple images from one patient (ICC, 0.929). CONCLUSION: The proposed scoring system can be used to improve consistency and reliability in first-trimester nasal-bone assessment.

A multicomponent screen for feeding behaviour and nutritional status in Drosophila to interrogate mammalian appetite-related genes.

OBJECTIVE: More than 300 genetic variants have been robustly associated with measures of human adiposity. Highly penetrant mutations causing human obesity do so largely by disrupting satiety pathways in the brain and increasing food intake. Most of the common obesity-predisposing variants are in, or near, genes expressed highly in the brain, but little is known of their function. Exploring the biology of these genes at scale in mammalian systems is challenging. We sought to establish and validate the use of a multicomponent screen for feeding behaviour phenotypes, taking advantage of the tractable model organism Drosophila melanogaster. METHODS: We validated a screen for feeding behaviour in Drosophila by comparing results after disrupting the expression of centrally expressed genes that influence energy balance in flies to those of 10 control genes. We then used this screen to explore the effects of disrupted expression of genes either a) implicated in energy homeostasis through human genome-wide association studies (GWAS) or b) expressed and nutritionally responsive in specific populations of hypothalamic neurons with a known role in feeding/fasting. RESULTS: Using data from the validation study to classify responses, we studied 53 Drosophila orthologues of genes implicated by human GWAS in body mass index and found that 15 significantly influenced feeding behaviour or energy homeostasis in the Drosophila screen. We then studied 50 Drosophila homologues of 47 murine genes reciprocally nutritionally regulated in POMC and agouti-related peptide neurons. Seven of these 50 genes were found by our screen to influence feeding behaviour in flies. CONCLUSION: We demonstrated the utility of Drosophila as a tractable model organism in a high-throughput genetic screen for food intake phenotypes. This simple, cost-efficient strategy is ideal for high-throughput interrogation of genes implicated in feeding behaviour and obesity in mammals and will facilitate the process of reaching a functional understanding of obesity pathogenesis.

Diet-induced gene expression of isolated pancreatic islets from a polygenic mouse model of the metabolic syndrome.

AIMS/HYPOTHESIS: Numerous new genes have recently been identified in genome-wide association studies for type 2 diabetes. Most are highly expressed in beta cells and presumably play important roles in their function. However, these genes account for only a small proportion of total risk and there are likely to be additional candidate genes not detected by current methodology. We therefore investigated islets from the polygenic New Zealand mouse (NZL) model of diet-induced beta cell dysfunction to identify novel genes and pathways that may play a role in the pathogenesis of diabetes. METHODS: NZL mice were fed a diabetogenic high-fat diet (HF) or a diabetes-protective carbohydrate-free HF diet (CHF). Pancreatic islets were isolated by laser capture microdissection (LCM) and subjected to genome-wide transcriptome analyses. RESULTS: In the prediabetic state, 2,109 islet transcripts were differentially regulated (>1.5-fold) between HF and CHF diets. Of the genes identified, 39 (e.g. Cacna1d, Chd2, Clip2, Igf2bp2, Dach1, Tspan8) correlated with data from the Diabetes Genetics Initiative and Wellcome Trust Case Control Consortium genome-wide scans for type 2 diabetes, thus validating our approach. HF diet induced early changes in gene expression associated with increased cell-cycle progression, proliferation and differentiation of islet cells, and oxidative stress (e.g. Cdkn1b, Tmem27, Pax6, Cat, Prdx4 and Txnip). In addition, pathway analysis identified oxidative phosphorylation as the predominant gene-set that was significantly upregulated in response to the diabetogenic HF diet. CONCLUSIONS/INTERPRETATION: We demonstrated that LCM of pancreatic islet cells in combination with transcriptional profiling can be successfully used to identify novel candidate genes for diabetes. Our data strongly implicate glucose-induced oxidative stress in disease progression.

Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent.

CONTEXT: The PNPLA3 I148M variant (rs738409) is robustly associated with hepatic steatosis. Intriguingly, initial findings in cohorts with a mean body mass index (BMI) of 30 kg m(-2) also suggested that it is associated with elevated liver enzymes but not with insulin resistance and dyslipidaemia. OBJECTIVE: To determine whether the PNPLA3 variant alters the susceptibility of morbidly obese subjects to develop liver injury and metabolic sequelae. PARTICIPANTS AND METHODS: The study was carried out in 678 obese Italians (mean BMI = 41 kg m(-2)) who were genotyped for the I148M variant. All participants provided fasting blood samples and then underwent oral glucose tolerance tests. MAIN OUTCOME MEASURES: Indices of liver injury (alanine transaminase (ALT), aspartate transaminase (AST)), glucose tolerance and insulin resistance were measured. RESULTS: Markers of hepatic injury such as ALT and AST were significantly higher in carriers of the 148M allele (P = 2.2 x 10(-5) and 0.001, respectively). In all, 50% of 148M risk allele homozygotes had pathological levels of ALT (>40 U l(-1)) compared with 25% of 148I allele homozygotes (P = 0.005). Glucose tolerance and insulin sensitivity were similar in all three genotypes. CONCLUSION: Obese Southern Europeans carrying the 148M allele have increased indices of liver damage uncoupled from proxy measures of insulin resistance.

The leptin melanocortin pathway and the control of body weight: lessons from human and murine genetics.

The recent rapid increase in the prevalence of obesity across the world is undoubtedly due to changes in diet and lifestyle. However, it is also indisputable that different people react differently to this change in environment and this variation in response is likely to be genetically determined. While for the majority of people this effect is presumed to be polygenic in origin, there is now strong evidence for a small number of genes having a large effect in some families with severe obesity. Studies of these families, coupled with parallel studies in murine models, have provided novel insights into the molecules involved in the regulation of appetite, energy expenditure and nutrient partitioning. We review here the lessons we have learnt from mouse models of obesity, both naturally occurring and artificially generated through targeted gene deletions, and more importantly from human monogenic syndromes of obesity. These have illuminated the critical role in which the central leptin melanocortin pathway plays in the control of mammalian food intake and body weight.

Epidemiology of pre-eclampsia and eclampsia at the KK Women's and Children's Hospital, Singapore.

INTRODUCTION: The incidences and characteristics of pre-eclampsia (PE) and eclampsia in KK Women's and Children's Hospital (KKH), a tertiary obstetrical referral centre in Singapore, were studied. METHODS: The incidences and types of PE between July 1999 and June 2003 were derived from the pregnancy disease databases. The characteristics of women with PE in relation to the general obstetric population were analysed on the age, race, parity, types of delivery, gestation at delivery and mortality. Case records of eclampsia were analysed. RESULTS: A total of 2,213 (3.6 percent) out of 61,595 deliveries were complicated by PE between July 1999 and June 2003. Incidence rates for mild or unspecified PE, severe PE, eclampsia and PE superimposed on hypertension were 2.47 percent (1,518), 0.97 percent (599), 0.02 percent (10) and 0.14 percent (85), respectively. The incidence increased with multiple pregnancies: from 3.5 percent in singletons to 7.5 percent in twins, 19.4 percent in triplets and 25.0 percent in quadruplets. The Caesarean section rate for PE was 46.1 percent compared with 23.7 percent in the hospital population. The proportion of premature birth (<37 weeks) in PE was 31.0 percent and that of severe prematurity (<32 weeks) was 5.7 percent, while hospital population proportions were 9.8 percent and 1.3 percent, respectively. The perinatal mortality rate (PMR) of PE was 11.0/1,000 births (population PMR was 4.4/1,000 births). There were only ten cases of eclampsia out of 61,595 deliveries (1:6160) giving an incidence of eclampsia of 16.2/100,000 deliveries. There was no stillbirth, neonatal and maternal death among the eclamptic patients. CONCLUSION: The incidence and outcome of eclampsia in KKH showed a significant reduction over the years due to improved obstetrical care. While PE is still common, eclampsia is now a very rare disease outcome.

Recurrent neural tube defects.

We report a case of recurrent neural tube defects in a 30-year-old multigravida with no medical or family history of note. She presented with a significant history of having three (out of four) previous pregnancies affected by neural tube defects diagnosed at the 20-week foetal anomaly ultrasonographical scans, and which resulted in mid-trimester pregnancy terminations. Previous investigations for the foetuses did not yield any obvious cause. We discuss the possible differential diagnoses and aetiological factors. Rare causes of neural tube defects need to be excluded in recurrent cases with no obvious aetiology.

Outcomes of twin-twin transfusion syndrome managed by a specialised twin clinic.

INTRODUCTION: To determine the perinatal outcomes of monochorionic (MC) pregnancies complicated by the twin-twin transfusion syndrome (TTTS) that were managed in a specialised twin clinic at the KK Women's and Children's Hospital. METHODS: This was a 21-month retrospective study carried out from January 2002 to September 2003. MC pregnancies were followed up every two to three weeks with regular ultrasonographical and Doppler studies from the time monochorionicity was diagnosed. Standard criteria used for the diagnosis of TTTS are the presence of oligohydramnios/polyhydramnios sequence on ultrasonography. The severity of TTTS was staged according to Quintero's system. RESULTS: There were 77 sets of MC pregnancies in our database. 11 sets were diagnosed with TTTS, hence the incidence was 14.3 percent. The median gestation at diagnosis of TTTS was 17.4 (16.4 to 26) weeks. At first presentation, five were stage I, two were stage II, three were stage III and one was stage IV. Three pregnancies were terminated in the second trimester and one was lost to follow-up. Of the other seven, two were treated expectantly or delivered, four with amnioreduction/ septostomy and one with cord occlusion. The median gestation at delivery is 30.8 (26.7 to 36.9) weeks. Four (57 percent) were delivered before 32 weeks and these same four pairs required neonatal intensive care. The overall perinatal survival was 78 percent (11/14) and the median diagnosis to delivery interval was 10.7 (3.1 to 17.5) weeks. CONCLUSION: TTTS occurs in a significant proportion of MC pregnancies. The perinatal survival outcome of this group of patients managed in this clinic is comparable to that of other good centres.

Investigating stillbirths using a simplified obstetric events-based protocol.

INTRODUCTION: A stillbirth remains a distressing enigma to parents and clinicians alike as the cause often remains elusive. Few papers describe a protocol for the investigation of stillbirths. We evaluate the first obstetric events-based protocol designed for local use with an aim to adequately investigate stillbirths in a cost-effective manner. METHODS: A prospective cohort study was performed on 61 stillbirths at KK Women's and Children's Hospital. There were a total of 16,980 births in the year 2000. RESULTS: 37.7 percent of cases remained unexplained. There was protocol compliance in 51 cases (83.6 percent) with deviation in 10 cases (16.4 percent). The protocol helped to minimise costs in 18 cases (29.5 percent) as selected investigations were performed in view of obvious causes. The overall postmortem rate was 27.9 percent with the lowest rates in the Malay population. CONCLUSION: An obstetric events-based protocol allows clinicians to tailor their investigations easily and appropriately. It helps to provide optimal investigations and minimise unnecessary costs. It could be further fine-tuned by initiating detailed serum investigations only after delivery so as to exclude an obvious cause, like cord accidents, where full investigations are unnecessary.

Birth defects in Singapore: 1994-2000.

INTRODUCTION: To study characteristics of birth defect cases among live births, stillbirths and abortions in Singapore between 1994 and 2000. METHODS: Index cases for the National Birth Defects Registry (NBDR) were obtained from all neonatal nurseries in Singapore, all hospital discharge summaries, cytogenetic and pathology reports from all pathology laboratories in Singapore, and from the compulsory reporting of all termination of pregnancy cases and stillbirths delivered. Further information was obtained from case notes retrieved from the medical record offices, antenatal clinics, cytogenetic laboratories, pathology departments and the Registry of Births and Deaths. The notified cases (live births, stillbirths and abortions) between 1994 and 2000 were extracted from the NBDR and analysed with regard to ethnicity, maternal age, trend over the seven years and types of birth defects using the British Paediatric Association Classification. RESULTS: Between 1994 and 2000, a total of 7,870 cases (6,278 births and 1,592 abortuses) were notified, giving a rate of 23.99 birth defect cases per 1000 live births. There was a decreasing trend in birth defect incidence (19.76 to 16.85 per 1,000 live births) among live births and stillbirths and an increasing trend of abortion (3.25 to 7.57 per 1,000 live births) for birth defects. Malays had a higher rate of congenital defects at birth (24.4/1,000 live births) compared to Chinese (18.4/1,000 births). The 25-29 years age group had the lowest overall rate (22.6/1,000 live births) compared to the 19 years and below group at 31.6/1,000 live births and the 45-49 years group at 126.6/1,000 live births. The five most common groups of anomalies (per 1,000 live births) were those of heart (9.07), musculoskeletal (4.98), chromosomal (4.35), urinary (3.12) and nervous systems (2.90). The five most common aborted anomalies (per 1,000 live births) were those of chromosomal (2.40), nervous (1.23), heart (0.95), musculoskeletal (0.85) and urinary systems (0.36). CONCLUSION: There was an increasing trend of abortion for birth defects, accompanied by a falling trend in the congenital anomalies of live births. Both extremes of maternal age were at higher risk of non-chromosomal birth defects while advanced maternal age was at higher risk of chromosomal defects.

Assessment of maternal anxiety levels before and after amniocentesis.

INTRODUCTION: To assess anxiety levels in mothers before and after undergoing amniocentesis. The secondary aim was to see how counselling by nurse-counsellors affected maternal anxiety levels. METHODS: A prospective study was carried out from February 2000 to August 2000 at the Kandang Kerbau Women's and Children's Hospital in Singapore. We used standard statistical analysis and Spielberger's state-trait anxiety inventory (STAI), that consisted of 40 items, to assess anxiety levels. Anxiety levels were assessed at different stages: before and after counselling; before amniocentesis and after amniocentesis; when results were disclosed; and after the routine 20-week screening ultrasound scan was acknowledged four to six weeks later. English-speaking women were recruited for the study as the STAI questionnaire has only been validated for an English-speaking population. 195 at-risk mothers (advanced maternal age, abnormal nuchal translucency on ultrasound scan, previous abnormal baby and high-risk maternal serum screening results) and patients requesting for amniocentesis between 15 to 20 weeks gestation were recruited. RESULTS: 156 mothers agreed to amniocentesis. 38 mothers declined amniocentesis. S-anxiety levels declined significantly after counselling by trained nurse-counsellors in all mothers counselled. S-anxiety levels were highest and significantly higher compared to all other times just prior to amniocentesis despite counselling. Anxiety levels were the lowest and significantly lower compared to all other times at the last assessment stage. CONCLUSION: High level of anxiety prior to amniocentesis despite counselling is understandable due to the invasive nature of the procedure. There is no long-lasting post-procedural anxiety to the mother.

Does maternal serum screening for Down syndrome induce anxiety in younger mothers?

INTRODUCTION: To assess anxiety levels in mothers with low-risk pregnancies before and after offering routine serum screening. METHODS: A prospective study was carried out at the Kandang Kerbau Women's and Children's Hospital in Singapore from February 2000 to August 2000. We used standard statistical analysis and Spielberger's state-trait anxiety inventory (STAI) which consists of 40 items to assess anxiety. Anxiety levels were assessed at several stages: before serum screening counselling, after counselling but before serum screening, before the routine 20-week obstetrical screening ultrasound scan, and after ultrasound scan results were acknowledged four to six weeks later. As the STAI questionnaire has only been validated for an English-speaking population, only English-speaking women were recruited for the study. The subjects included 111 women between 15 to 20 weeks gestation that were randomly selected (without any risk factors) for serum screening counselling. RESULTS: Anxiety levels did not decline significantly after counselling by a trained nurse-counsellor. They were highest prior to counselling and were significantly higher compared to all other times in which anxiety was assessed. Anxiety levels were lowest after the serum screening and routine 20-week screening ultrasound scan results were acknowledged. They were also significantly lower compared to all other times in which anxiety was assessed. CONCLUSION: Anxiety before serum screening was not abnormally high and routine serum screening offered by trained nurse counsellors did not significantly increase maternal anxiety in mothers with low risk pregnancies.

Foetal intralobar lung sequestration: antenatal diagnosis and management.

OBJECTIVES: The objectives of this study are to discuss the use of ultrasonography for the diagnosis of foetal intralobar sequestration (FILS) antenatally and the management options available for these pregnancies. METHODS: This is a retrospective review of six cases of FILS diagnosed antenatally by two dimensional (2D) and colour Doppler ultrasonography out of a total of 31,508 deliveries over a two-year period at the KK Women's and Children's Hospital. RESULTS: The incidence of FILS in this hospital was 1 in 5,251 deliveries. 2D ultrasonography showed an echogenic lung in all cases. FILS was confirmed by the demonstration of a systemic vessel leading to the affected lung on colour Doppler examination. After counselling, four terminated their pregnancies during mid-trimester, while two continued their pregnancies to term. Confirmation of the terminated cases was by post-mortem. In the two pregnancies that continued, regular growth scans were done to monitor the progression of the condition. Computed tomography confirmed the diagnosis post-delivery. Both were well but one had a resection of the sequestrated lung although he was asymptomatic. Histology also confirmed the diagnosis. CONCLUSION: FILS is a rare anomaly. 2D and colour Doppler ultrasonography are used to diagnose the condition antenatally. Termination of the pregnancy is not always indicated, as there are favourable outcomes from FILS.

Our experience with eclampsia in Singapore.

AIM: To assess the incidence, epidemiological factors, preceding symptoms and signs, management regimens and obstetric outcomes of eclampsia in a tertiary care hospital in Singapore. METHOD: A retrospective study of all obstetric patients who suffered one or more eclamptic seizures in our hospital between January 1994 and December 1999. RESULT: There were 62 cases of eclampsia among 92,305 deliveries (6.7 per 10,000 deliveries). The incidence was highest among Indians. Those aged between 25 and 34 had the lowest incidence, while women younger than 25 or older than 34 had a significantly higher incidence. Forty (64.5%) patients had symptom or sign of impending eclampsia of which headache was the most common. Most of the patients (81.6%) who received antenatal care with us suffered their first eclamptic seizure in hospital, compared to 50% of the unbooked patients. There was one maternal death (mortality rate 1.6%), and 15 (24.2%) women had significant morbidity. There were 61 singleton pregnancies and one twin pregnancy. There were six intrauterine deaths and 57 livebirths. The perinatal mortality rate was 95.2 per 1,000 births. CONCLUSION: Eclampsia is still a major cause of maternal and foetal mortality and morbidity in Singapore. Race and age appear to be risk factors for eclampsia with Indian women and those at the extremes of reproductive age at greater risk. Antenatal care is important in reducing perinatal mortality and possibly maternal complications.

Antenatal use of a novel vaginal birth training device by term primiparous women in Singapore.

INTRODUCTION: To study the use, safety and effectiveness of a novel antenatal vaginal birth training device (EPI-NO) in primiparous women. METHODS: Antenatal use of the EPI-NO vaginal birth trainer was prospectively studied in 31 primiparous booked patients who were delivered by obstetricians from July to December 2002 at the KK Women's and Children's Hospital. This was studied in relation to episiotomy rate, perineal trauma and analgesic requirements during the postpartum period. A patient questionnaire form was used to assess their perception of pain and how well they coped with its use. For comparison, perineal trauma was also studied retrospectively in 60 consecutive obstetrician-booked primiparous term patients who had normal vaginal delivery (NVD) and who did not use EPI-NO during the same study period. RESULTS: The mean length of usage was for 2.1 weeks (standard deviation [sd] 1.2 weeks). The mean frequency of use was 5.3 episodes per week (sd 2.1, range 1 to 7). There was no laceration and vaginal infection arising from its usage. There was a case of minimal bleeding post-usage. There were 20 (64.5 percent) NVDs, four (12.9 percent) forceps deliveries, five vacuum deliveries (16.1 percent) and two (6.5 percent) Caesarean sections. Of the 29 vaginal delivery cases, 19 (65.5 percent) had episiotomy, eight (27.6 percent) had lacerations, and two (6.9 percent) did not sustain laceration. The reasons for episiotomy in the 19 cases were nine cases of pending tearing of vagina/perineum, nine cases of instrumental vaginal deliveries, and one to shorten second stage. There was no third degree tear. 21 (67.7 percent) out of 30 required a painkiller. The majority of patients (17; 54.8 percent) appeared to be comfortable with the use of EPI-NO. All coped well with vaginal examination after using EPI-NO perineal training. Comparing among term primiparous NVD cases with (n value equals 20) and without (n value equals 60) EPI-NO, the perineal trauma rate (90.0 percent vs 96.6 percent, p value equals 0.24) was slightly but not significantly lower in the EPI-NO group. The episiotomy rate was significantly lower (50.0 percent vs 93.3 percent, p value is less than 0.0001) and the extent of perineal trauma in the patient appeared to be less severe in cases using EPI-NO. CONCLUSION: EPI-NO appeared to be safe and acceptable to the majority of users. Although birth training with EPI-NO significantly decreases the rate of episiotomies in term primiparous patients, and the degree of perineal tissue injury appeared to be less in the EPI-NO group especially among those with lacerations, the overall perineal trauma rate was slightly but not significantly lower, in view of the higher spontaneous laceration rate in the EPI-NO group.

Birth prevalence of Down syndrome in Singapore from 1993 to 1998.

OBJECTIVE: To examine the livebirth prevalence rate of Down Syndrome in Singapore from 1993 to 1998. DESIGN: Index cases for the National Birth Defects Register were obtained from all neonatal nurseries in Singapore, all hospital discharge summaries, cytogenetic and pathology reports from all pathology laboratories in Singapore and from the compulsory reporting of all termination of pregnancy cases and stillbirths delivered. SETTING: Information for the Register was obtained from case notes retrieved from the medical record offices, antenatal clinics, cytogenetic laboratories, pathology departments and the Registry of Births and Deaths. SUBJECTS: All foetuses with Trisomy 21 diagnosed prenatally together with livebirths and stillbirths with Down Syndrome diagnosed at or after birth were identified from the Registry database. MAIN OUTCOME MEASURES: Prevalence of Down Syndrome RESULTS: From 1993 to 1998, there were 295 Down Syndrome livebirths, four stillbirths and 197 Down Syndrome foetuses aborted. There has been an increasing number of Down Syndrome foetuses diagnosed antenatally ending in termination and this is accompanied by a falling trend in the Down Syndrome livebirth rate in the same years from 1.17 to 0.89 per 1000 total live births. This is despite an expected increase in Down Syndrome livebirth rate obtained by modelling maternal Down Syndrome age-related risks on the maternal age distribution over the years. CONCLUSIONS: The livebirth prevalence of Down Syndrome in Singapore has fallen over the years from 1.17/1000 livebirths in 1993 to 0.89/1000 livebirths in 1998 due to antenatal diagnosis and selective termination.