Gordon C. S. Smith

Parachute use to prevent death and major trauma related to gravitational challenge: Systematic review of randomised controlled trials

Abstract Objectives To determine whether parachutes are effective in preventing major trauma related to gravitational challenge. Design Systematic review of randomised controlled trials. Data sources: Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists. Study selection: Studies showing the effects of using a parachute during free fall. Main outcome measure Death or major trauma, defined as an injury severity score > 15. Results We were unable to identify any randomised controlled trials of parachute intervention. Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.

First-Trimester Growth and the Risk of Low Birth Weight

BACKGROUND Previous studies have demonstrated a correlation between first-trimester size and birth weight. It is not known, however, whether low birth weight is related to first-trimester growth. We sought to determine whether the risk of low birth weight and birth weight that was low for gestational age is related to the size of the embryo or the fetus in the first trimester. METHODS From a data base of ultrasound records of more than 30,000 pregnancies, we identified women who had no important medical problems, a normal menstrual history, and a first-trimester ultrasound scan in which the crown-rump length of the embryo or fetus had been measured. We examined the relation between the outcome of 4229 pregnancies and the difference between the measured and the expected crown-rump length in the first trimester, expressed as equivalent days of growth. RESULTS A first-trimester crown-rump length that was two to six days smaller than expected was associated with an increased risk (as compared with a normal or slightly larger than expected crown-rump length) of a birth weight below 2500 g (relative risk, 1.8; 95 percent confidence interval, 1.3 to 2.4), a birth weight below 2500 g at term (relative risk, 2.3; 95 percent confidence interval, 1.4 to 3.8), a birth weight below the fifth percentile for gestational age (relative risk, 3.0; 95 percent confidence interval, 2.0 to 4.4), and delivery between 24 and 32 weeks of gestation (relative risk, 2.1; 95 percent confidence interval, 1.1 to 4.0), but not with delivery between 33 and 36 weeks (relative risk, 1.0; 95 percent confidence interval, 0.7 to 1.5). CONCLUSIONS Suboptimal first-trimester growth may be associated with low birth weight, low birth-weight percentile, and premature delivery.

Stillbirths: the way forward in high-income countries

Stillbirth rates in high-income countries declined dramatically from about 1940, but this decline has slowed or stalled over recent times. The present variation in stillbirth rates across and within high-income countries indicates that further reduction in stillbirth is possible. Large disparities (linked to disadvantage such as poverty) in stillbirth rates need to be addressed by providing more educational opportunities and improving living conditions for women. Placental pathologies and infection associated with preterm birth are linked to a substantial proportion of stillbirths. The proportion of unexplained stillbirths associated with under investigation continues to impede efforts in stillbirth prevention. Overweight, obesity, and smoking are important modifiable risk factors for stillbirth, and advanced maternal age is also an increasingly prevalent risk factor. Intensified efforts are needed to ameliorate the effects of these factors on stillbirth rates. Culturally appropriate preconception care and quality antenatal care that is accessible to all women has the potential to reduce stillbirth rates in high-income countries. Implementation of national perinatal mortality audit programmes aimed at improving the quality of care could substantially reduce stillbirths. Better data on numbers and causes of stillbirth are needed, and international consensus on definition and classification related to stillbirth is a priority. All parents should be offered a thorough investigation including a high-quality autopsy and placental histopathology. Parent organisations are powerful change agents and could have an important role in raising awareness to prevent stillbirth. Future research must focus on screening and interventions to reduce antepartum stillbirth as a result of placental dysfunction. Identification of ways to reduce maternal overweight and obesity is a high priority for high-income countries.

Teenage pregnancy and risk of adverse perinatal outcomes associated with first and second births: population based retrospective cohort study

Abstract Objective: To determine whether first and second births among teenagers are associated with increased risk of adverse perinatal outcomes after confounding variables have been taken into account. Design: Population based retrospective cohort study using routine discharge data for 1992-8. Setting: Scotland. Main outcome measures: Stillbirth, preterm delivery, emergency caesarean section, and small for gestational age baby among non-smoking mothers aged 15-19 and 20-29. Results: The 110 233 eligible deliveries were stratified into first and second births. Among first births, the only significant difference in adverse outcomes by age group was for emergency caesarean section, which was less likely among younger mothers (odds ratio 0.5, 95% confidence interval 0.5 to 0.6). Second births in women aged 15-19 were associated with an increased risk of moderate (1.6, 1.2 to 2.1) and extreme prematurity (2.5, 1.5 to 4.3) and stillbirth (2.6, 1.3 to 5.3) but a reduced risk of emergency caesarean section (0.7, 0.5 to 1.0). Conclusions: First teenage births are not independently associated with an increased risk of adverse pregnancy outcome and are at decreased risk of delivery by emergency caesarean section. However, second teenage births are associated with an almost threefold risk of preterm delivery and stillbirth. What is already known on this topic Teenage mothers are more likely to deliver prematurely and to have a perinatal death than older women Teenage mothers are also more likely to smoke, be having a first baby, and live in adverse social circumstances What this study adds Non-smoking women aged 15-19 having a first birth were not at increased risk of adverse obstetric outcomes compared with women aged 20-29 after potential confounding variables were adjusted for Non-smoking women aged 15-19 having a second birth were at significantly increased risk of both premature delivery and stillbirth compared with women aged 20-29

Gestational Age at Delivery and Special Educational Need: Retrospective Cohort Study of 407,503 Schoolchildren

A retrospective cohort study of 407,503 schoolchildren by Jill Pell and colleagues finds that gestational age at delivery has a dose-dependent relationship with the risk of special educational needs that extends across the full gestational range.

Interpregnancy interval and risk of preterm birth and neonatal death: retrospective cohort study

Abstract Objective To determine whether a short interval between pregnancies is an independent risk factor for adverse obstetric outcome. Design Retrospective cohort study. Setting Scotland. Subjects 89 143 women having second births in 1992-8 who conceived within five years of their first birth. Main outcome measures Intrauterine growth restriction (birth weight less than the 5th centile for gestational age), extremely preterm birth (24-32 weeks), moderately preterm birth (33-36 weeks), and perinatal death. Results Women whose subsequent interpregnancy interval was less than six months were more likely than other women to have had a first birth complicated by intrauterine growth restriction (odds ratio 1.3, 95% confidence interval 1.1 to 1.5), extremely preterm birth (4.1, 3.2 to 5.3), moderately preterm birth (1.5, 1.3 to 1.7), or perinatal death (24.4, 18.9 to 31.5). They were also shorter, less likely to be married, and more likely to be aged less than 20 years at the time of the second birth, to smoke, and to live in an area of high socioeconomic deprivation. When the outcome of the second birth was analysed in relation to the preceding interpregnancy interval and the analysis confined to women whose first birth was a term live birth (n = 69 055), no significant association occurred (adjusted for age, marital status, height, socioeconomic deprivation, smoking, previous birth weight vigesimal, and previous caesarean delivery) between interpregnancy interval and intrauterine growth restriction or stillbirth. However, a short interpregnancy interval (< 6 months) was an independent risk factor for extremely preterm birth (adjusted odds ratio 2.2, 1.3 to 3.6), moderately preterm birth (1.6, 1.3 to 2.0), and neonatal death unrelated to congenital abnormality (3.6, 1.2 to 10.7). The adjusted attributable fractions for these associations were 6.1%, 3.9%, and 13.8%. The associations were very similar when the analysis was confined to married non-smokers aged 25 and above. Conclusions A short interpregnancy interval is an independent risk factor for preterm delivery and neonatal death in the second birth.

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 ...

Bias modelling in evidence synthesis

Policy decisions often require synthesis of evidence from multiple sources, and the source studies typically vary in rigour and in relevance to the target question. We present simple methods of allowing for differences in rigour (or lack of internal bias) and relevance (or lack of external bias) in evidence synthesis. The methods are developed in the context of reanalysing a UK National Institute for Clinical Excellence technology appraisal in antenatal care, which includes eight comparative studies. Many were historically controlled, only one was a randomized trial and doses, populations and outcomes varied between studies and differed from the target UK setting. Using elicited opinion, we construct prior distributions to represent the biases in each study and perform a bias-adjusted meta-analysis. Adjustment had the effect of shifting the combined estimate away from the null by approximately 10%, and the variance of the combined estimate was almost tripled. Our generic bias modelling approach allows decisions to be based on all available evidence, with less rigorous or less relevant studies downweighted by using computationally simple methods.

Circulating angiogenic factors in early pregnancy and the risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth

OBJECTIVE: To estimate the relationship between maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in early pregnancy with the risk of subsequent adverse outcome. METHODS: A nested, case–control study was performed within a prospective cohort study of Down syndrome screening. Maternal serum levels of sFlt-1 and PlGF at 10–14 weeks of gestation were compared between 939 women with complicated pregnancies and 937 controls. Associations were quantified as the odds ratio for a one decile increase in the corrected level of the analyte. RESULTS: Higher levels of sFlt-1 were not associated with the risk of preeclampsia but were associated with a reduced risk of delivery of a small for gestational age infant (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.88–0.96), extreme (24–32 weeks) spontaneous preterm birth (OR 0.90, 95% CI 0.83–0.99), moderate (33–36 weeks) spontaneous preterm birth (OR 0.93, 95% CI 0.88–0.98), and stillbirth associated with abruption or growth restriction (OR 0.77, 95% CI 0.61–0.95). Higher levels of PlGF were associated with a reduced risk of preeclampsia (OR 0.95, 95% CI 0.90–0.99) and delivery of a small for gestational age infant (OR 0.95, 95% CI 0.91–0.99). Associations were minimally affected by adjustment for maternal characteristics. CONCLUSION: Higher early pregnancy levels of sFlt-1 and PlGF were associated with a decreased risk of adverse perinatal outcome. LEVEL OF EVIDENCE: II

Fetal growth in early pregnancy and risk of delivering low birth weight infant: prospective cohort study

Objective To determine if first trimester fetal growth is associated with birth weight, duration of pregnancy, and the risk of delivering a small for gestational age infant. Design Prospective cohort study of 38 033 pregnancies between 1999 and 2003. Setting 15 centres representing major regions of the United States. Participants 976 women from the original cohort who conceived as the result of assisted reproductive technology, had a first trimester ultrasound measurement of fetal crown-rump length, and delivered live singleton infants without evidence of chromosomal or congenital abnormalities. First trimester growth was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age. Main outcome measures Birth weight, duration of pregnancy, and risk of delivering a small for gestational age infant. Results For each one day increase in the observed size of the fetus, birth weight increased by 28.2 (95% confidence interval 14.6 to 41.2) g. The association was substantially attenuated by adjustment for duration of pregnancy (adjusted coefficient 17.1 (6.6 to 27.5) g). Further adjustments for maternal characteristics and complications of pregnancy did not have a significant effect. The risk of delivering a small for gestational age infant decreased with increasing size in the first trimester (odds ratio for a one day increase 0.87, 0.81 to 0.94). The association was not materially affected by adjustment for maternal characteristics or complications of pregnancy. Conclusion Variation in birth weight may be determined, at least in part, by fetal growth in the first 12 weeks after conception through effects on timing of delivery and fetal growth velocity.