Identification of Caries Risk Determinants in Toddlers: Results of the GUSTO Birth Cohort Study.

The aim of this study was to identify risk determinants leading to early childhood caries (ECC) and visible plaque (VP) in toddlers. Data for mother-child pairs participating in the Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort were collected from pregnancy to toddlerhood. Oral examinations were performed in 543 children during their clinic visit at 24 months to detect ECC and VP. Following logistic regression, ECC and VP were jointly regressed as primary and secondary outcomes, respectively, using the bivariate probit model. The ECC prevalence was 17.8% at 2 years of age, with 7.3% of children having a VP score >1. ECC was associated with nighttime breastfeeding (3 weeks) and biological factors, including Indian ethnicity (lower ECC rate), higher maternal childbearing age and existing health conditions, maternal plasma folate <6 ng/mL, child BMI, and the plaque index, while VP was associated with psychobehavioral factors, including the frequency of dental visits, brushing frequency, lower parental perceived importance of baby teeth, and weaning onto solids. Interestingly, although a higher frequency of dental visits and toothbrushing were associated with lower plaque accumulation, they were associated with increased ECC risk, suggesting that these established caries-risk factors may be a consequence rather than the cause of ECC. In conclusion, Indian toddlers may be less susceptible to ECC, compared to Chinese and Malay toddlers. The study also highlights a problem-driven utilization pattern of dental services (care sought for treatment) in Singapore, in contrast to the prevention-driven approach (care sought to prevent disease) in Western countries.

Tobacco smoke exposure and respiratory morbidity in young children.

OBJECTIVE: Secondhand smoke exposure is a potentially preventable cause of significant respiratory morbidity in young children. Our study aimed to quantify respiratory morbidity in young children exposed to secondhand smoke to identify potentially modifiable factors. MATERIALS AND METHODS: This study was embedded in a prospective birth cohort study of pregnant women and their children from fetal life onwards in Singapore (Growing Up in Singapore Towards healthy Outcomes, or GUSTO). Data on prenatal, antenatal and postnatal active and secondhand tobacco smoke exposure were obtained by an investigator-administered questionnaire for the periods before pregnancy, at 26-28 weeks' gestation and 24 months after delivery. Data on respiratory morbidity (wheezing episodes, croupy cough, nebuliser use, snoring) and other morbidity (fever, hospitalisation, ear infection) of the child was collected at week 3 and at months 3, 6, 9, 12, 15, 18 and 24 after delivery. Information on parental atopy and potential confounders such as socioeconomic status and maternal educational level were also obtained. Statistical analysis of the data was performed to quantify any significant differences in incidence of respiratory morbidity in children exposed to tobacco smoke in utero and postdelivery, compared with those in smoke-free environments. RESULTS: Women who smoked regularly prior to pregnancy comprised 12.5% (n=155) of the study population; this number fell to 2.3% (n=29) during pregnancy. Mothers exposed to secondhand smoke in the household before pregnancy comprised 35.7% of the study population (n=441) and 31.5% (n=389) were exposed during pregnancy. Postnatally, the prevalence of secondhand tobacco smoke exposure from birth to 2 years of age was 29% (n=359). Participants of Malay ethnicity (p<0.001), mothers with no or primary level education (p<0.001) and mothers with low socioeconomic status (p<0.001) had the highest exposure to tobacco smoke. Offspring secondhand smoke exposure at home by 12 months and by 24 months of age was associated with an increase in hospital admissions due to respiratory disease (RR 1.89, 95% CI 1.02 to 3.50, p=0.04 by 12 months and RR 1.64, 95% CI 1.05 to 2.55, p=0.03 by 24 months) as well as all-cause hospitalisation (RR 1.57, 95% CI 1.14 to 2.17, p=0.01 by 12 months and RR 1.49, 95% CI 1.17 to 1.90, p=0.001 by 24 months), adjusting for parental atopy and child atopic dermatitis. Participants exposed to secondhand smoke by 12 months postdelivery had a significantly increased risk of having at least one wheezing episode (RR 1.71, 95% CI 1.38 to 2.11, p<0.001). CONCLUSIONS: Secondhand smoke exposure during the prenatal and postnatal periods is associated with increased respiratory morbidity in children. Opportunistic screening and targeted smoking cessation counselling for parents at child hospital admissions and well-child outpatient visits, as well as preconception smoking cessation counselling for future pregnancies, may be beneficial to protect the child from negative health impacts.

Caries Risk Prediction Models in a Medical Health Care Setting.

Despite development of new technologies for caries control, tooth decay in primary teeth remains a major global health problem. Caries risk assessment (CRA) models for toddlers and preschoolers are rare. Among them, almost all models use dental factors (e.g., past caries experience) to predict future caries risk, with limited clinical/community applicability owing to relatively uncommon dental visits compared to frequent medical visits during the first year of life. The objective of this study was to construct and evaluate risk prediction models using information easily accessible to medical practitioners to forecast caries at 2 and 3 y of age. Data were obtained from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) mother-offspring cohort. Caries was diagnosed using modified International Caries Detection and Assessment System criteria. Risk prediction models were constructed using multivariable logistic regression coupled with receiver operating characteristic analyses. Imputation was performed using multiple imputation by chained equations to assess effect of missing data. Caries rates at ages 2 y (n = 535) and 3 y (n = 721) were 17.8% and 42.9%, respectively. Risk prediction models predicting overall caries risk at 2 and 3 y demonstrated area under the curve (AUC) (95% confidence interval) of 0.81 (0.75-0.87) and 0.79 (0.74-0.84), respectively, while those predicting moderate to extensive lesions showed 0.91 (0.85-0.97) and 0.79 (0.73-0.85), respectively. Postimputation results showed reduced AUC of 0.75 (0.74-0.81) and 0.71 (0.67-0.75) at years 2 and 3, respectively, for overall caries risk, while AUC was 0.84 (0.76-0.92) and 0.75 (0.70-0.80), respectively, for moderate to extensive caries. Addition of anterior caries significantly increased AUC in all year 3 models with or without imputation (all P < 0.05). Significant predictors/protectors were identified, including ethnicity, prenatal tobacco smoke exposure, history of allergies before 12 mo, history of chronic maternal illness, maternal brushing frequency, childbearing age, and so on. Integrating oral-general health care using medical CRA models may be promising in screening caries-susceptible infants/toddlers, especially when medical professionals are trained to "lift the lip" to identify anterior caries lesions.

Infant frontal EEG asymmetry in relation with postnatal maternal depression and parenting behavior.

Right frontal electroencephalogram (EEG) asymmetry associates with negative affect and depressed mood, which, among children, are predicted by maternal depression and poor parenting. This study examined associations of maternal depression and maternal sensitivity with infant frontal EEG asymmetry based on 111 mother-6-month-infant dyads. There were no significant effects of postnatal maternal depression or maternal sensitivity, or their interaction, on infant EEG frontal asymmetry. However, in a subsample for which the infant spent at least 50% of his/her day time hours with his/her mother, both lower maternal sensitivity and higher maternal depression predicted greater relative right frontal EEG asymmetry. Our study further showed that greater relative right frontal EEG asymmetry of 6-month-old infants predicted their greater negative emotionality at 12 months of age. Our study suggested that among infants with sufficient postnatal maternal exposure, both maternal sensitivity and mental health are important influences on early brain development.

Influences of prenatal and postnatal maternal depression on amygdala volume and microstructure in young children.

Maternal depressive symptoms influence neurodevelopment in the offspring. Such effects may appear to be gender-dependent. The present study examined contributions of prenatal and postnatal maternal depressive symptoms to the volume and microstructure of the amygdala in 4.5-year-old boys and girls. Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) at 26 weeks of gestation. Postnatal maternal depression was assessed at 3 months using the EPDS and at 1, 2, 3 and 4.5 years using the Beck's Depression Inventory-II. Structural magnetic resonance imaging and diffusion tensor imaging were performed with 4.5-year-old children to extract the volume and fractional anisotropy (FA) values of the amygdala. Our results showed that greater prenatal maternal depressive symptoms were associated with larger right amygdala volume in girls, but not in boys. Increased postnatal maternal depressive symptoms were associated with higher right amygdala FA in the overall sample and girls, but not in boys. These results support the role of variation in right amygdala structure in transmission of maternal depression to the offspring, particularly to girls. The differential effects of prenatal and postnatal maternal depressive symptoms on the volume and FA of the right amygdala suggest the importance of the timing of exposure to maternal depressive symptoms in brain development of girls. This further underscores the need for intervention targeting both prenatal and postnatal maternal depression to girls in preventing adverse child outcomes.

Ratio of Klebsiella/Bifidobacterium in early life correlates with later development of paediatric allergy.

Several studies have reported that intestinal microbial colonisation patterns differ between non-allergic and allergic infants. However, the microbial signature underlying the pathogenesis of allergies remains unclear. We aim to gain insight into the development of the intestinal microbiota of healthy infants and infants who develop allergy in early life, and identify potential microbiota biomarkers of later allergic disease. Using a case-control design in a Chinese sub-cohort of a Singaporean birth cohort (GUSTO), we utilised 16S rRNA gene sequencing to assess intestinal microbial composition and diversity of 21 allergic and 18 healthy infants at 3 weeks, 3 months and 6 months of age, and correlated the microbiota with allergy at ages 18 and 36 months. Pronounced differences in intestinal microbiota composition between allergic and healthy infants were observed at 3 months of age. The intestine of healthy infants was colonised with higher abundance of commensal Bifidobacterium. Conversely, Klebsiella, an opportunistic pathogen, was significantly enriched in the allergic infants. Interestingly, infants with a high Klebsiella/Bifidobacterium (K/B) ratio (above the population median K/B ratio) at age 3 months had an odds ratio of developing allergy by 3 years of age of 9.00 (95% confidence interval 1.46-55.50) compared to those with low K/B ratio. This study demonstrated a relationship between the ratio of genera Klebsiella and Bifidobacterium during early infancy and development of paediatric allergy in childhood. Our study postulates that an elevated K/B ratio in early infancy could be a potential indicator of an increased risk of allergy development. This line of research might enable future intervention strategies in early life to prevent or treat allergy. Our study provides new insights into microbial signatures associated with childhood allergy, in particular, suggests that an elevated K/B ratio could be a potential early-life microbiota biomarker of allergic disease.

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.

MC3R gene polymorphisms are associated with early childhood adiposity gain and infant appetite in an Asian population.

BACKGROUND: Polymorphic variants within human melanocortin-3 receptor gene (MC3R) gene have been associated with obesity. However, its influence on infancy and early childhood adiposity has not been reported before. OBJECTIVES: We assessed associations between genotype at polymorphic sites within MC3R with early childhood adiposity and interaction with early childhood appetitive traits. METHODS: We studied 1090 singletons in an Asian mother-offspring cohort genotyped for MC3R and in a subgroup (n = 422) who had completed Child Eating Behaviour Questionnaires (CEBQ) at 12 months. Children were followed from birth to 48 months, and up to 10 measurements of body mass index and five measures of triceps and subscapular skin-folds were obtained. RESULTS: Independent of potential confounders, each additional MC3R minor allele copy was associated with greater body mass index standard deviation score [B{95% confidence interval}: 0.004 units/month {0.001,0.007}; p = 0.007], triceps [0.009 mm/month {0.001,0.02}; p = 0.021] and subscapular skin-fold [0.008 mm/month {0.002,0.01}; p = 0.011] gain velocity in the first 48 months. Each additional MC3R minor allele copy was also associated with increased odds of overweight [odds ratio {95% confidence interval}: 1.48{1.17-1.88}] and obesity [1.58{1.10-2.28}] in the first 48 months. Every additional copy of MC3R minor allele was positively associated with 'slowness-in-eating' appetitive trait [0.24{0.06,0.39}, p = 0.006]; however, the relationship between 'slowness-in-eating' with adiposity gain was not statistically significant. CONCLUSIONS: Our findings support the role of MC3R genetic variants in adiposity gain during early childhood.

The in vitro effects of clonidine and dexmedetomidine on human myometrium.

BACKGROUND: alpha(2)-adrenergic agonists have been used extensively in the field of anaesthesia. Their direct effect on the human myometrium was investigated in this in vitro study, as this may have clinical repercussions in obstetric anaesthesia. METHOD: Strips of pregnant human myometrium obtained from six individuals at elective caesarean section were mounted on the Mulvany myograph in Krebs solution to which increasing concentrations of clonidine and dexmedetomidine (1x10(-11) to 1x10(-6) g/mL) were added. RESULTS: Dexmedetomidine increased uterine contractility at simulated clinical plasma concentrations (1x10(-9) g/mL). These effects were seen with clonidine only at much higher tissue bath concentrations (1x10(-7) g/mL). CONCLUSION: The effect of dexmedetomidine on human myometrium has profound implications in obstetric anaesthesia and needs further clinical investigation.

Prenatal maternal depression alters amygdala functional connectivity in 6-month-old infants.

Prenatal maternal depression is associated with alterations in the neonatal amygdala microstructure, shedding light on the timing for the influence of prenatal maternal depression on the brain structure of the offspring. This study aimed to examine the association between prenatal maternal depressive symptomatology and infant amygdala functional connectivity and to thus establish the neural functional basis for the transgenerational transmission of vulnerability for affective disorders during prenatal development. Twenty-four infants were included in this study with both structural magnetic resonance imaging (MRI) and resting-state functional MRI (fMRI) at 6 months of age. Maternal depression was assessed at 26 weeks of gestation and 3 months after delivery using the Edinburgh Postnatal Depression Scale. Linear regression was used to identify the amygdala functional networks and to examine the associations between prenatal maternal depressive symptoms and amygdala functional connectivity. Our results showed that at 6 months of age, the amygdala is functionally connected to widespread brain regions, forming the emotional regulation, sensory and perceptual, and emotional memory networks. After controlling for postnatal maternal depressive symptoms, infants born to mothers with higher prenatal maternal depressive symptoms showed greater functional connectivity of the amygdala with the left temporal cortex and insula, as well as the bilateral anterior cingulate, medial orbitofrontal and ventromedial prefrontal cortices, which are largely consistent with patterns of connectivity observed in adolescents and adults with major depressive disorder. Our study provides novel evidence that prenatal maternal depressive symptomatology alters the amygdala's functional connectivity in early postnatal life, which reveals that the neuroimaging correlates of the familial transmission of phenotypes associated with maternal mood are apparent in infants at 6 months of age.

The psychometric properties of the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) as a measure of autistic traits in a community sample of Singaporean infants and toddlers.

BACKGROUND: There is growing research evidence that subclinical autistic traits are elevated in relatives of individuals with autism spectrum disorder (ASD), continuously distributed in the general population and likely to share common etiology with ASD. A number of measures have been developed to assess autistic traits quantitatively in unselected samples. So far, the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) is one of very few measures developed for use with toddlers as young as 18 months, but little is known about its measurement properties and factor structure. METHODS: The present study examined internal consistency, factor structure, test-retest stability, and convergent validity of the Q-CHAT in a sample of toddlers in Singapore whose caregivers completed the Q-CHAT at 18 (n = 368) and 24 months (n = 396). RESULTS: Three factors were derived accounting for 38.1 % of the variance: social/communication traits, non-social/behavioral traits, and a speech/language factor. Internal consistency was suboptimal for the total and speech/language scores, but acceptable for the social/communication and non-social/behavioral factor scores. Scores were generally stable between 18 and 24 months. Convergent validity was found with the Pervasive Developmental Disorders subscale of the Child Behavior Checklist (CBCL) completed by caregivers when their children were 24 months. Q-CHAT total scores in this sample were higher than those reported in other unselected samples from the UK. CONCLUSIONS: The Q-CHAT was found to have a three-factor structure, acceptable internal consistency for its two main factor scores (social/communication and non-social/behavioral), normally distributed scores in an unselected sample, and similar structure and measurement properties as those reported in other published studies. Findings are discussed in relation to existing literature and future directions for the validation of the Q-CHAT.

Maternal sensitivity, infant limbic structure volume and functional connectivity: a preliminary study.

Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother-infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning.

Human myometrial genes are differentially expressed in labor: a suppression subtractive hybridization study.

Human parturition is effected by a cascade of factors, of which many are unknown. We aim to identify the genes that are changed by labor in the human myometrium by suppression subtractive hybridization. We also seek to ascertain whether these genes are differentially expressed in the myometrium at the upper or fundal and lower segments of the uterus. Term myometrial tissues were obtained from laboring and nonlaboring women undergoing cesarean section after obtaining informed consent. Total RNA was used in suppression subtractive hybridization (CLONTECH PCR Select) to produce two subtracted cDNA libraries enriched for genes expressed during or before labor, labor and not-in-labor libraries, respectively. Dot blot screening of 400 positive clones, constituting 20% of the two subtracted libraries, revealed 30 differentially expressed clones, 14 of which were up-regulated by labor. Among the 10 known genes that were up-regulated in labor, 6 had apparent immune regulatory and inflammatory roles. Three are well-known inflammatory mediators and modulators that were previously linked with parturition: IL-8, manganese superoxide dismutase (MnSOD), and metalloproteinase-9. Three others, interferon-inducible 1-8d gene, elongation factor 1alpha, and nucleophosmin, have not been previously linked with labor. Constitutively expressed genes, including cyclophilin and alpha-actin, were found to be altered by labor. Quantitative real-time RT-PCR using Taqman probes further confirmed the up-regulation of some of these genes. The amounts of the specific genes assayed were standardized to 18S ribosomal RNA and are expressed as mean +/- SEM. Quantitative real-time RT-PCR showed that IL-8 mRNA rose from 0.003 +/- 0.002 in nonlaboring samples (n = 38) to 0.24 +/- 0.11 (n = 20) in gestational-age-matched spontaneously laboring women (P = 0.035). Similarly, MnSOD rose from 0.11 +/- 0.02 (n = 24) to 1.23 +/- 0.56 (n = 24) in gestational-age-matched women (P = 0.047). Additionally, cyclophilin, often used as a constitutive or housekeeping gene marker, increased from 0.0008 +/- 0.0002 (n = 6) to 0.002 +/- 0.0004 (n = 6; P = 0.008) during labor. Notably, MnSOD mRNA was differentially distributed between the upper (0.63 +/- 0.18) and lower (0.15 +/- 0.05; n = 15; P = 0.022) segments of the uterus, but IL-8 was not (n = 17; P = 0.97). Induced labor further showed significantly higher levels of IL-8 (0.63 +/- 0.21; n = 14) than spontaneous labor (0.22 +/- 0.11; n = 20; P = 0.046), but not MnSOD (P = 0.1). This work identifies novel as well as known genes that were not previously associated with parturition. It extends previous data indicating that there is differential expression of some, but not all genes within the gravid human uterus. Inflammatory genes constitute a major proportion of the known genes found to be up-regulated in labor, lending support to the hypothesis of an inflammatory mechanism for human parturition. This work further indicates that many factors associated with human labor and their complex interactions remain to be elucidated.

Effects of nitrovasodilators on the human fetal-placental circulation in vitro.

This study examines the vasorelaxation of isolated human placental chorionic plate arteries and the perfused fetal-placental vasculature, in vitro, to a variety of nitrovasodilator compounds including glyceryl trinitrate (GTN) sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-N-glutathione (SNG) and NaNO(2). The effects of these compounds were also examined under conditions of high (>450 mmHg) and low oxygen (<50 mmHg) tension. In a separate series of experiments the effects of GTN and NaNO(2)were further investigated with addition of the antioxidants cysteine (100 microm), glutathione (100 microm) or superoxide dismutase (SOD) (30 I.U./ml). The order of nitrovasodilator potency, when added directly to isolated fetal vessels was GTN=SNP>SNAP=SNG>NaNO(2). The order under low oxygen tension was similar, GTN=SNP>SNG= SNAP>or=NaNO(2). SNG ( approximately fourfold) and NaNO(2)( approximately 50-fold) were significantly more potent under low oxygen conditions. Cysteine, glutathione and SOD were without effect on GTN induced vasodilatation. However, all three agents significantly enhanced (six- to ninefold) the effects of NaNO(2)under similar conditions. When infused directly into the fetal-placental circulation during in vitro perfusion experiments the order of potency was GTN>SNP>or=SNG>or=SNAP>or=NaNO(2). When the nitrovasodilators were infused indirectly via the maternal intervillous space the order of potency was GTN>or=SNP>or=NaNO(2)>or=SNAP=SNG. Our observations suggest that there are important differences in the action of different classes of nitrovasodilator compounds on the fetal-placental circulation. The changes observed with SNG and NaNO(2)may be influenced by levels of tissue oxygenation.

Vasoactive effects of 8-epi-prostaglandin F(2alpha)in isolated human placental conduit and resistance blood vessels in vitro.

The effects of 8-epi-prostaglandin F(2alpha)(8-epi-PGF(2alpha)) and the thromboxane A(2)-mimetic U46619 were examined on isolated human fetal placental arteries obtained from normal pregnancies and from those complicated by pre-eclampsia. The effects of these agents were examined on both conduit and resistance arteries. 8-epi-PGF(2alpha)was found to be markedly less potent than U46619 in constricting both size vessels. Vasoconstrictor EC(50)s for 8-epi PGF(2alpha)were 4.10x10(-7) m (2.02-8.35x10(-7) m) (mean, 95 per cent CI and 2.05x10(-6) m (0.43-9.89 x10(-6) m) in conduit and resistance arteries, respectively. The maximum vasoconstriction produced by 8-epi-PGF(2alpha)(112+/-17 per cent), (relative to maximum KCl induced vasoconstriction) in conduit vessels was significantly less than that caused by U46619 (152+/-20 per cent). In resistance vessels the maximum vasoconstrictor effects to 8-epi-PGF(2alpha)(208+/-10 per cent) and U46619 (201+/-19 per cent) were similar, and in both cases significantly greater than the maximal effects seen in conduit vessels. U46619 displayed a similar vasoconstrictor potency in both conduit (EC(50)=1.21x10(-9) m, 0.58-2.51x10(-9) m) and resistance arteries [EC(50)=5.95x10(-9) m, (0.81-43.60x10(-9) m] as was found for 8-epi PGF(2alpha). 8-epi-PGF(2alpha)was equipotent in resistance arteries obtained from women with severely pre-eclamptic pregnancies (EC(50)=1.25x10(-6) m, 0.25-6.17x10(-6) m) compared with normotensive controls. However, the maximum vasoconstrictor effect induced by 8-epi-PGF(2alpha)in placental resistance arteries was significantly reduced (99+/-20 per cent) in vessels obtained from severely pre-eclamptic compared with normal pregnancies. These results indicate that 8-epi-PGF(2alpha)displays differential vasoconstrictor activity in the fetal-placental vasculature. Furthermore the vasoconstrictor effects of 8-epi-PGF(2alpha)are reduced in pre-eclampsia, the effect being selective to placental resistance vessels. This reduction may occur as a result of more serious disturbances in the placental microcirculation with the disease process in pre-eclampsia.

Validation of an oscillometric electronic sphygmomanometer in an obstetric population.

Use of an automated electronic sphygmomanometer will allow us to minimize the errors inherent in mercury sphygmomanometry. We conducted this validation according to the 1990 protocol of the British Hypertensive Society. We recruited 87 subjects from the antenatal population of Kandang Kerbau Hospital and took three sequential readings using simultaneously both manual and electronic sphygmomanometry. A total of 261 readings from either method were thus collected and the results analyzed to compare the accuracy of electronically read blood pressure with that assessed manually. We found that 89.9% of the electronically read pressures differed from the manually read pressures by 5 mm Hg or less and 98.9% of the electronic readings differed from manual readings by 10 mm Hg or less; only 0.4% of readings had a difference of more than 15 mm Hg. The accuracy of the device was not affected either by the blood pressure or the arm circumference.

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.

Percutaneous endoscopic gastrostomy--indications and outcome of our experience at the Singapore General Hospital.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is widely used for patients with dysphagia from neurological causes and head and neck malignancy. We examined the indications, complication rates and long term outcome of PEG inserted in our department. METHODS: We performed a study of PEG inserted in our department between January 1995 to March 2000. Consecutive patients with PEG inserted during this period were identified from our database that contained demographic data, primary and secondary underlying medical conditions, and immediate complications after the procedure. Casenotes were reviewed and caregivers (relatives or staff at nursing homes) were contacted for information on long term outcome at the time of this study between April 2000. Data was collected in standard form designed for this study. RESULTS: 181 cases of PEG insertion were performed during the study period. 174 patients were successfully followed up and reviewed. The median age was 70.5 (range 24 to 93) years old and there were 111 males. Indications for PEG insertion were: cerebrovascular diseases (60.4%), Parkinson's disease and other neuromuscular disorders (10.9%), nasopharyngeal carcinoma and other upper gastrointestinal malignancies (24.7%), and head injury (4%). Superficial wound infection (22.4%) and granuloma formation (31%) were common minor complications. Major complications were infrequent: peritonitis (2.3%) and gastrointestinal bleeding (0.6%). The mortality rates were 11.5% and 28.2% at one and six months respectively. Only one death from peritonitis was directly attributed to the procedure, most deaths were due to underlying co-morbidities with pneumonia being the most common cause. The proportion of the first PEG tubes removed or replaced were 12.2% and 35.5% at one and six months respectively. Thirty tubes were replaced due to blockage at median interval of 9.6 months. 9.7% of PEG tubes functioned longer than 24 months. CONCLUSIONS: Our results confirm the safety of PEG tubes in elderly patients with multiple co-morbidities. Major complications of the procedure were infrequent but produced grave consequences in these elderly patients with multiple co-morbidities. As such, patients considered for PEG feeding should have reasonable prognosis and the procedure is inappropriate for patients with rapidly progressive and incurable diseases.

Current understanding of pre-eclampsia.

INTRODUCTION: Pre-eclampsia is associated with significant morbidity and mortality for mother and baby, with post partum resolution. The disorder is triggered by a placental pathology followed by a wide spectrum of maternal systemic response. However, there remains controversy in practically every aspect of the condition. METHODS: A Medline search and hand search of recent publications pertaining to the scientific basis and clinical management of pre-eclampsia. RESULTS: With current interest in the scientific and molecular basis of the disease process, there has been an improved, albeit incomplete, understanding of the precise aetiology and pathogenesis of pre-eclampsia. Much of this has translated to improved clinical management strategies. The more rational use of various pharmacological agents, timing the delivery to optimise both the maternal and fetal condition, the decreasing rate of eclampsia, as well as trials on various screening and prophylactic strategies are testimony to this improvement. Despite this, many unanswered questions still remain and provide a challenge for both the clinician as well as the researcher. CONCLUSIONS: We reviewed the recent literature in order to provide a contemporary understanding of the basic pathogenesis of the condition as well as to highlight some basic strategies for clinical management. There is a clear need for more research to better understand the basic science behind the genesis of this condition, as well as to improve the level of care we offer to these women through the co-ordination of a multi-disciplinary team of clinicians.