PubMed Health⌕ Search

Biomedical subjects

Gordon C S Smith

Publications and source records attributed to Gordon C S Smith.

At least 19 recordsLinked to original sources
PubMed2025

Polygenic Risk Scores for Preeclampsia Prediction Beyond Gold-Standard Clinical Models in Multiethnic Populations.

BACKGROUND: Preeclampsia is a major cause of maternal and fetal mortality and morbidity. Early risk stratification enables timely preventative therapy in high-risk women. Polygenic risk scores (PGS) improve prediction in complex diseases, but their added value for preeclampsia remains unclear, particularly in comparison to gold-standard first-trimester prediction models and across non-European ancestries. METHODS: We evaluated the performance of both a preeclampsia and systolic blood pressure PGS in 2 prospective pregnancy cohorts with detailed phenotyping: the Fetal Medicine Foundation study (n=5207; 2127 cases) and the Pregnancy Outcome Prediction study (n=3659; 228 cases). Risk models included (1) clinical factors; (2) clinical factors plus PGS; (3) advanced model including first-trimester mean arterial pressure, PAPP-A (pregnancy-associated plasma protein-A), and uterine artery pulsatility index; and (4) advanced model plus PGS. Discriminative performance, measured by the area under the receiver operating characteristic curve, was assessed overall and by ancestry. RESULTS: The preeclampsia PGS was independently associated with preeclampsia (odds ratio per SD, 1.24 [95% CI, 1.17-1.31]; P<0.001). It modestly improved prediction over clinical models (area under the receiver operating characteristic curve 0.746 versus 0.750; P=0.017) but not over the advanced model (area under the receiver operating characteristic curve 0.817 versus 0.818; P=0.326). The systolic blood pressure PGS showed stronger performance, improving prediction over both models in women of European ancestry. No improvement was observed with either score in women of African ancestry. CONCLUSIONS: PGSs for preeclampsia and SBP provide modest added predictive value beyond clinical risk factors in European ancestry women. Limited utility in African ancestry women reflects underrepresentation in the genome-wide association studies used to develop current scores. As cohort sizes grow and models are refined, PGSs may become important tools for equitable risk stratification in maternal health.

Adult↗
PubMed2007

Maternal uterine artery Doppler flow velocimetry and the risk of stillbirth.

OBJECTIVE: We sought to relate the risk of antepartum stillbirth to uterine artery Doppler flow velocimetry at 22-24 weeks. METHODS: Data were available from 30,519 unselected women from seven units in the UK who had uterine artery Doppler performed between 22 and 24 weeks of gestation. The risk of stillbirth (n=109) was assessed using time to event and logistic regression analysis. Stillbirths were subdivided into placental (due to abruption, preeclampsia, or growth restriction) or unexplained. RESULTS: The risk of placental stillbirth was increased among women with a mean pulsatility index in the top decile (adjusted hazard ratio [HR] 5.5, 95% confidence interval [CI] 2.8-10.6) and those with a bilateral notch (adjusted HR 3.9, 95% CI 2.0-7.8). The relationship between a mean pulsatility index in the top decile and the risk of unexplained stillbirth was weaker (adjusted HR 2.5, 95% CI 1.1-5.6) and there was no association with a bilateral notch. Placental stillbirths occurred at earlier gestations than unexplained stillbirths (median [interquartile range] 30 [26-36] compared with 38 [36-40], P<.001). Consequently, being in the top 5% of predicted risk of stillbirth on the basis of the combination of mean pulsatility index and notching was a good predictor (sensitivity, specificity, and positive likelihood ratio) of all cause stillbirth up to 32 weeks (58%, 95%, and 12.1, respectively) but a poor predictor of stillbirth at later gestations (7%, 95%, and 1.3, respectively). CONCLUSION: Abnormal uterine artery Doppler was a better predictor of the risk of stillbirth due to placental causes than unexplained stillbirth. Consequently, abnormal uterine artery Doppler was a good predictor of stillbirth at extreme preterm gestations but a poor predictor of stillbirth at term. LEVEL OF EVIDENCE: II.

Adult↗
PubMed2006

Maternal obesity in early pregnancy and risk of spontaneous and elective preterm deliveries: a retrospective cohort study.

OBJECTIVES: We sought to determine the association between maternal body mass index and risk of preterm delivery. METHODS: We assessed 187,290 women in Scotland and estimated adjusted odds ratios for spontaneous and elective preterm deliveries among overweight, obese, and morbidly obese women relative to normal-weight women. RESULTS: Among nulliparous women, the risk of requiring an elective preterm delivery increased with increasing BMI, whereas the risk of spontaneous preterm labor decreased. Morbidly obese nulliparous women were at increased risk of all-cause preterm deliveries, neonatal death, and delivery of an infant weighing less than 1000 g who survived to 1 year of age (a proxy for severe long-term disability). By contrast, obesity and elective preterm delivery were only weakly associated among multiparous women. CONCLUSIONS: Obese nulliparous women are at increased risk of elective preterm deliveries. This in turn leads to an increased risk of perinatal mortality and is likely to lead to increased risks of long-term disability among surviving offspring.

Adult↗
PubMed2006

Previous preeclampsia, preterm delivery, and delivery of a small for gestational age infant and the risk of unexplained stillbirth in the second pregnancy: a retrospective cohort study, Scotland, 1992-2001.

Women with a previous stillbirth are known to be at increased risk of stillbirth in subsequent pregnancies. However, few studies have addressed the association between other complications of pregnancy and the future risk of stillbirth. Using linkage of national pregnancy and perinatal death registries, the authors performed a retrospective cohort study of 133,163 women having a second birth in Scotland between 1992 and 2001 whose first infant was liveborn. The risk of unexplained stillbirth was increased among women with a previous preterm birth (adjusted hazard ratio (HR) = 2.04, 95% confidence interval (CI): 1.34, 3.11), previous delivery of a small for gestational age (SGA) infant (HR = 2.14, 95% CI: 1.59, 2.87), and previous preeclampsia (HR = 1.68, 95% CI: 1.07, 2.62). The associations were similar after adjustment for maternal age, height, marital and smoking status, and interpregnancy interval. There was a statistically significant positive interaction between previous delivery of a SGA infant and previous preeclampsia (p = 0.01): Women with this combination in their first pregnancy had an approximately fivefold risk of unexplained stillbirth in the second pregnancy (HR = 4.95, 95% CI: 2.63, 9.32). Associations were stronger with SGA unexplained stillbirths. The authors conclude that complicated first births of liveborn infants are associated with an increased risk of unexplained stillbirth in the next pregnancy.

Confidence Intervals↗
PubMed2006

Maternal and biochemical predictors of spontaneous preterm birth among nulliparous women: a systematic analysis in relation to the degree of prematurity.

BACKGROUND: Nulliparous women are at increased risk of spontaneous preterm birth. Other maternal and biochemical risk factors have also been described. However, it is unclear whether these associations are strong enough to offer clinically useful prediction. It is also unclear whether the predictive power of these factors varies in relation to the degree of prematurity. METHODS: The risk of spontaneous preterm birth associated with maternal characteristics and second trimester serum screening data was analysed in a dataset of 84 391 first births in Scotland between 1992 and 2001 using Cox and logistic regression. Variation in the relative risk of preterm birth over the period 24-36 weeks was assessed using a test of the proportional hazards assumption. RESULTS: The risk of spontaneous preterm birth was positively associated with maternal serum levels of alpha-fetoprotein, socioeconomic deprivation, number of previous therapeutic abortions, smoking, and being unmarried and was negatively associated with height and body mass index. The risk of preterm birth at 24-28 weeks, but not later gestations, was increased in association with maternal levels of human chorionic gonadotrophin >95th percentile, maternal age <20, and two or more previous miscarriages. The area under the receiver operating characterise curve (95% CI) for models based on these factors was 0.67 (0.63-0.71) for 24-28 weeks, 0.65 (0.62-0.68) for 29-32 weeks, and 0.62 (0.61-0.63) for 33-36 weeks. CONCLUSIONS: Time to event analytic methods can identify factors that are differentially associated with spontaneous preterm birth according to the degree of prematurity. However, models based on maternal and biochemical data perform poorly as a screening test for any degree of spontaneous preterm birth.

Adult↗
PubMed2006

First cesarean birth and subsequent fertility.

OBJECTIVE: To determine whether cesarean delivery is independently associated with later subfertility. DESIGN: Retrospective cohort study. SETTING: Maternity records kept for Scotland, 1980-1999. PATIENT(S): The study included 109,991 women who had first births between 1980 and 1984, excluding multiple or preterm births and perinatal deaths. INTERVENTION(S): Exposures studied were spontaneous vaginal birth, operative vaginal birth, planned cesarean delivery for breach presentation, planned cesarean delivery for other indications, and emergency cesarean delivery. MAIN OUTCOME MEASURE(S): The relative risk of not having a second pregnancy over the following 15 years, the interpregnancy interval, and the number of spontaneous early pregnancy losses between the first and second birth. RESULT(S): Women who delivered by planned cesarean section for breech presentation had an increased risk of not having a second birth compared with women whose first birth was a spontaneous vertex delivery (relative risk [RR]: 1.21, 95% confidence interval [CI]: 1.14 to 1.29). However, after adjustment for maternal and obstetric characteristics, there was no longer a strong association (adjusted RR: 1.07, 95% CI: 1.00 to 1.15). Operative vaginal delivery (forceps and vacuum extraction) and all types of cesarean delivery were associated with longer interpregnancy intervals. There was no relationship between mode of delivery and the number of spontaneous early pregnancy losses between the first and second birth. CONCLUSION(S): It is unlikely that delivering by cesarean section in a first pregnancy decreases a woman's likelihood of having a second viable pregnancy.

Abortion, Spontaneous↗
PubMed2006

Pregnancy-associated plasma protein A and alpha-fetoprotein and prediction of adverse perinatal outcome.

OBJECTIVE: To describe the association between pregnancy associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP) and adverse perinatal outcome. METHODS: We conducted a multicenter prospective cohort study of 8,483 women attending for prenatal care in southern Scotland between 1998 and 2000. The risk of delivering a small for gestational age infant, delivering preterm, and stillbirth were related to maternal serum levels of PAPP-A and AFP. RESULTS: Women with a low PAPP-A were not more likely to have elevated levels of AFP. Compared with women with a normal PAPP-A and a normal AFP, the odds ratio for delivering a small for gestational age infant for women with a high AFP was 0.9 (95% confidence interval [CI] 0.5-1.6), for women with a low PAPP-A was 2.8 (95% CI 2.0-4.0), and for women with both a high AFP and a low PAPP-A was 8.5 (95% CI 3.6-20.0). The odds ratio for delivering preterm for women with a high AFP was 1.8 (95% CI 1.3-2.7), for women with a low PAPP-A was 1.9 (95% CI 1.3-2.7), and for women with both a low PAPP-A and a high AFP was 9.9 (95% CI 4.4-22.0). These interactions were statistically significant for both outcomes (P = .03 and .04, respectively). There was a nonsignificant trend toward a similar interaction in relation to stillbirth risk. Of the women with the combination of a low PAPP-A and high AFP, 32.1% (95% CI 15.9-52.4) delivered a low birth weight infant. CONCLUSION: Low maternal serum levels of PAPP-A between 10 and 14 weeks and high levels of AFP between 15 and 21 weeks gestation are synergistically associated with adverse perinatal outcome. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2006

Predicting antepartum stillbirth.

PURPOSE OF REVIEW: Rates of stillbirth in the developed world have been static or rising in recent years. Clinical prediction of stillbirth risk may allow interventional studies. RECENT FINDINGS: The most prevalent independent risk factors are nulliparity, advanced age and obesity. These are increasingly prevalent in the developed world. Obesity is particularly associated with stillbirth at term and after term. Pregestational diabetes is a major risk factor for stillbirth and these women are usually offered intensive surveillance during pregnancy. Despite this, a recent national study in the UK demonstrated a fourfold excess of stillbirth, with 80% unrelated to congenital abnormality. Studies of association between previous caesarean section and subsequent stillbirth risk are inconsistent, although in data sources with detailed information, the association has been confirmed. Global analyses of stillbirth risk demonstrate that 98% occur in the developing world and that many are due to potentially preventable causes. A randomized controlled trial of very simple educational interventions was associated with a 30% lower risk of stillbirth. SUMMARY: Relatively simple interventions may be successful in reducing the global burden of stillbirth. Further biological understanding of the causes of stillbirth is required to reduce the burden of the disease in the developed world.

Cesarean Section↗
PubMed2006

Predicting the risk for sudden infant death syndrome from obstetric characteristics: a retrospective cohort study of 505,011 live births.

OBJECTIVE: We sought to develop a simple robust method for assessing the risk for sudden infant death syndrome (SIDS) on the basis of obstetric characteristics. METHODS: A population-based retrospective cohort study was conducted of data from the linked Scottish Morbidity Record, Stillbirth and Infant Death Enquiry and General Registrar's Office database of births and deaths, encompassing births in Scotland between 1992 and 2001. All women who had a singleton live birth between 24 and 43 weeks' gestation and for whom data were available (n = 505,011), divided into model development and validation samples, were studied. The main outcome measure was death of the infant in the first year of life as a result of SIDS. RESULTS: The risk for SIDS was modeled in the development sample using logistic regression with the following predictors: maternal age, parity, marital status, smoking, and the birth weight and the gender of the infant. When the model was evaluated in the validation sample, the area under the receiver operating characteristic curve was 0.84 and the incidence of SIDS was 0.7 per 10,000 (95% confidence interval: 0.3-1.4) among 126,253 women in the lower 50% of predicted risk and 29.7 per 10,000 (95% confidence interval: 23.4-37.2) among the 25,250 women in the top 10% of predicted risk. A logistic-regression model then was developed for the whole population, and the output was converted into adjusted likelihood ratios. These are tabulated and provide a simple method for assessing the risk for SIDS associated with any combination of obstetric characteristics. CONCLUSIONS: A model that uses maternal characteristics and outcome at birth is predictive of the risk for SIDS. This model is presented in a simple form that allows calculation of the individual risk for SIDS.

Birth Weight↗
PubMed2006

Doppler flow velocimetry in the superior mesenteric artery on the first day of life in preterm infants and the risk of neonatal necrotizing enterocolitis.

OBJECTIVE: The purpose of this work was to relate Doppler indices of splanchnic perfusion and vascular resistance to the risk of developing necrotizing enterocolitis. METHODS: We conducted a prospective cohort study with analysis of Doppler flow velocity waveforms of splanchnic vessels on the first day of life. Clinical management and diagnosis of necrotizing enterocolitis were performed blind to the Doppler results in a tertiary NICU on 64 eligible preterm neonates admitted for intensive care. We measured necrotizing enterocolitis using an objective diagnostic classification. RESULTS: When adjusted for gestational age at birth, the following indices of the Doppler flow velocity wave form in the superior mesenteric artery were significantly predictive of the risk of necrotizing enterocolitis: end-diastolic velocity, mean velocity, and pulsatility index. The association between necrotizing enterocolitis and Doppler velocimetry indicative of high vascular resistance was independent of a range of other factors and comorbidities (race, mode of delivery, umbilical arterial catheter, growth restriction, patent ductus arteriosus, jaundice, respiratory distress syndrome, mechanical ventilation, and hypotension). CONCLUSIONS: We concluded that neonates with high resistance patterns of blood flow velocity in the superior mesenteric artery on the first day of life are at increased risk of developing necrotizing enterocolitis.

Enterocolitis, Necrotizing↗
PubMed2005

Sudden infant death syndrome and complications in other pregnancies.

BACKGROUND: The likelihood of recurrence of sudden infant death syndrome (SIDS) is an issue of biological, clinical, and legal interest. Obstetric complications are associated with an increased risk of SIDS and are likely to recur in subsequent pregnancies. We postulated that women whose infants died from SIDS would be more likely to have had obstetric complications in their other pregnancies. METHODS: We linked national UK databases of maternity-hospital discharges, perinatal deaths, and death certifications. We studied 258 096 women who had consecutive births in Scotland between 1985 and 2001. FINDINGS: Women who had an infant who died from SIDS were at increased risk in their next pregnancy of delivering an infant small for gestational age (odds ratio 2.27, 95% CI 1.54-3.34, p<0.0001) and of preterm birth (2.53, 1.82-3.53, p<0.0001). The risk of SIDS was higher for the children of women whose previous infant had been small for gestational age (1.87, 1.19-2.94, p=0.007) or preterm (1.93, 1.24-3.00, p=0.004). Multivariate analysis showed that all associations were explained by common maternal risk factors for SIDS and obstetric complications and by the likelihood of recurrence of fetal growth restriction and preterm birth. INTERPRETATION: Women whose infants die from SIDS are more likely to have complications in their other pregnancies. Recurrence of pregnancy complications predisposing to SIDS could partly explain why some women have recurrent SIDS.

Birth Weight↗
PubMed2005

Predicting cesarean section and uterine rupture among women attempting vaginal birth after prior cesarean section.

BACKGROUND: There is currently no validated method for antepartum prediction of the risk of failed vaginal birth after cesarean section and no information on the relationship between the risk of emergency cesarean delivery and the risk of uterine rupture. METHODS AND FINDINGS: We linked a national maternity hospital discharge database and a national registry of perinatal deaths. We studied 23,286 women with one prior cesarean delivery who attempted vaginal birth at or after 40-wk gestation. The population was randomly split into model development and validation groups. The factors associated with emergency cesarean section were maternal age (adjusted odds ratio [OR] = 1.22 per 5-y increase, 95% confidence interval [CI]: 1.16 to 1.28), maternal height (adjusted OR = 0.75 per 5-cm increase, 95% CI: 0.73 to 0.78), male fetus (adjusted OR = 1.18, 95% CI: 1.08 to 1.29), no previous vaginal birth (adjusted OR = 5.08, 95% CI: 4.52 to 5.72), prostaglandin induction of labor (adjusted OR = 1.42, 95% CI: 1.26 to 1.60), and birth at 41-wk (adjusted OR = 1.30, 95% CI: 1.18 to 1.42) or 42-wk (adjusted OR = 1.38, 95% CI: 1.17 to 1.62) gestation compared with 40-wk. In the validation group, 36% of the women had a low predicted risk of caesarean section (< 20%) and 16.5% of women had a high predicted risk (> 40%); 10.9% and 47.7% of these women, respectively, actually had deliveries by caesarean section. The predicted risk of caesarean section was also associated with the risk of all uterine rupture (OR for a 5% increase in predicted risk = 1.22, 95% CI: 1.14 to 1.31) and uterine rupture associated with perinatal death (OR for a 5% increase in predicted risk = 1.32, 95% CI: 1.02 to 1.73). The observed incidence of uterine rupture was 2.0 per 1,000 among women at low risk of cesarean section and 9.1 per 1,000 among those at high risk (relative risk = 4.5, 95% CI: 2.6 to 8.1). We present the model in a simple-to-use format. CONCLUSIONS: We present, to our knowledge, the first validated model for antepartum prediction of the risk of failed vaginal birth after prior cesarean section. Women at increased risk of emergency caesarean section are also at increased risk of uterine rupture, including catastrophic rupture leading to perinatal death.

Age Factors↗
PubMed2005

Estimating risks of perinatal death.

The relative and absolute risks of perinatal death that are estimated from observational studies are used frequently in counseling about obstetric intervention. The statistical basis for these estimates therefore is crucial, but many studies are seriously flawed. In this review, a number of aspects of the approach to the estimation of the risk of perinatal death are addressed. Key factors in the analysis include (1) the definition of the cause of the death, (2) differentiation between antepartum and intrapartum events, (3) the use of the appropriate denominator for the given cause of death, (4) the assessment of the cumulative risk where appropriate, (5) the use of appropriate statistical tests, (6) the stratification of analysis of delivery-related deaths by gestational age, and (7) the specific features of multiple pregnancy, which include the correct determination of the timing of antepartum stillbirth and the use of paired statistical tests when outcomes are compared in relation to the birth order of twin pairs.

Cause of Death↗
PubMed2005

An integrated model for the prediction of preeclampsia using maternal factors and uterine artery Doppler velocimetry in unselected low-risk women.

OBJECTIVE: The purpose of this study was to develop a predictive model for preeclampsia. STUDY DESIGN: This was a prospective screening study for preeclampsia using uterine artery Doppler ultrasound in unselected low-risk singleton pregnancies at community hospitals in the UK (n = 32,157). Logistic regression models were developed and their predictive ability assessed using the area under the receiver operator curve (AROC). RESULTS: Six hundred twelve (2.0%) women developed preeclampsia, and 144 (0.5%) required early delivery (<34 weeks). A model using both maternal and ultrasound factors had an AROC of 0.798, which was higher than ultrasound alone (0.729, P < .0001) or maternal factors alone (0.712, P < .0001). In early onset disease, the ROC of ultrasound alone (0.922) was not significantly improved by adding maternal predictors (0.945, P = .27). In contrast, late onset disease was better predicted by the combined model (AROC 0.798) than ultrasound alone (AROC 0.729, P < .0001) or maternal factors alone (AROC 0.712, P < .0001). CONCLUSION: The combination of uterine artery Doppler ultrasound and maternal factors provided the best estimate of risk.

Adult↗