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P J Steer

Publications and source records attributed to P J Steer.

At least 19 recordsLinked to original sources
PubMed2006

Seasonal patterns and preterm birth: a systematic review of the literature and an analysis in a London-based cohort.

OBJECTIVE: The objectives of this study included a systematic review of the countries in which a seasonal pattern of preterm birth has been reported and an analysis on the seasonal variability of preterm birth in a London-based cohort. DESIGN: Cross-sectional study. SETTING: Eighteen maternity units in a London health region from 1988 to 2000. POPULATION: The study population comprised 482,765, live singleton births born after 24 weeks of gestation and weighing more than 200 g. METHODS: Systematic review and secondary analysis of seasonality over 13 years of births from the St Mary's Maternity Information System (SMMIS). MAIN OUTCOME MEASURE: Annual patterns of preterm birth and a comparison of risk by seasons. RESULTS: Three studies from developing countries and three from developed countries reported a seasonal pattern of preterm birth. One study from the USA reported no seasonal pattern of preterm birth. No British studies were located. Rates of preterm birth in developed countries were highest twice a year (once in winter and again in summer). In London (SMMIS data set), however, preterm births peaked only once a year, in winter. Babies born in winter were 10% more likely to be preterm compared with those born in spring (OR 1.10, 95% CI 1.07-1.14). CONCLUSION: Establishing a seasonal pattern of birth can have important implications for the delivery of healthcare services. Most studies from both developed and developing countries support the existence of preterm birth seasonality. This study has shown that the seasonality of preterm births in this London-based cohort differs from other developed countries that have previously reported a seasonal pattern of preterm birth.

Cohort Studies↗
PubMed2006

The epidemiology of preterm labour--why have advances not equated to reduced incidence?

The major burden of preterm birth is in the developing world, where most of the increasing death and morbidity is secondary to infectious diseases such as malaria, HIV, tuberculosis, bacterial vaginosis and intestinal parasites. In some developing countries, the growth of medical care has outstripped the growth of preventive public health, with an associated increase in iatrogenic preterm births. In developed countries, more than one-third of preterm births are medically indicated because of conditions such as fulminating pre-eclampsia or severe intrauterine growth restriction. Neither of these conditions is currently preventable. One in five preterm births is associated with multiple pregnancy, and these have been greatly increased by assisted reproduction techniques. The use of tocolytics has proved disappointing perhaps because inflammation rather than spontaneous uterine activity is increasingly recognised as the final common pathway. Inappropriate antibiotics used late in pregnancy are ineffective and may have adverse effects. Currently, the most promising interventions are public health related and include reducing the transmission of communicable diseases, improvements in the management of diabetes and reduction in harmful behaviours such as smoking and drug abuse.

Developed Countries↗
PubMed2006

Prematurity or immaturity?

Birth in the human is particularly difficult compared with that in the other primates. Bipedalism has evolved over the past 6 or 7 million years, and has resulted in a small pelvis, adapted to the upright posture. In recent millennia, the increasing size of the fetal head at birth has made childbirth difficult. Haig has suggested that the mother and fetus do not have identical interests; the baby benefits from being large at birth, while it is easier for the mother to deliver a small baby. Many of the 500 000 maternal deaths per year around the world are due to obstructed labour, especially in Africa. Even in London, black African women have the highest caesarean section rates. Black African babies are on average smaller than white European babies, due mainly to earlier delivery. In a 13-year study of births in North West Thames, African babies were 2.5 times more likely to be born between 24 and 31 weeks inclusive than white European babies. Between 33 and 38 weeks of gestation, black African babies behaved in a more mature way, are more likely to pass meconium and have jaundice, but less likely to have respiratory problems leading to admission to the special care baby unit. Preterm black African babies have lower gestation-specific perinatal mortality than white European babies, while at term and beyond the reverse is true. Preterm birth may have evolved partly as a response to disproportion.

Africa↗
PubMed2004

Impaired retrograde transmission of vasodilatory signals via the endothelium in pre-eclampsia: a cause of reduced tissue blood flow?

There is evidence that tissue blood flow is regulated by retrograde transmission of signals initiated at capillary and post-capillary sites, and transmitted via the endothelium to modulate pre-capillary resistance. We have used pre-eclampsia as a model to test the hypothesis that normal endothelium is required to enable adjustment of blood flow to match tissue requirements. Integrity of the endothelial pathway was assessed by measuring calf blood flow at increasing venous pressures, using an established small cumulative-step venous-congestion plethysmography protocol in ten women with pre-eclampsia, 17 normal pregnant controls and ten non-pregnant women. Endothelial cell activation was assessed by measuring plasma levels of the cell adhesion molecules, intercellular cell-adhesion molecule-1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1) and E-selectin. Baseline calf blood flow was significantly lower in pre-eclampsia than in the other two groups (P<0.0001; ANOVA). In the pre-eclampsia group, there was a fall in blood flow as venous congestion pressure was raised (P<0.0001; ANOVA). No such change was observed in the other two groups. A significant inverse correlation was observed between the reduction in blood flow in pre-eclampsia and the levels of E-selectin (r=-0.92, P=0.0002), VCAM-1 (r=-0.93, P=0.0008) and ICAM-1 (r=-0.86, P=0.001). The differences between the pre-eclamptic women and the other two groups support the notion that the failure to sustain blood flow during a cumulative pressure step protocol in the pre-eclamptic group might be influenced by interference with the retrograde transmission of signals via the endothelium in these patients.

Adult↗
PubMed2004

Insulin resistance and pre-eclampsia: a role for tumor necrosis factor-alpha?

Insulin resistance occurs in pre-eclampsia, but the cause is unknown. Furthermore, it is uncertain whether women destined to develop pre-eclampsia have a pre-existing insulin resistance or whether it is acquired with the development of the disease. We carried out this study to test the hypotheses that the increase in insulin resistance associated with pre-eclampsia is related to higher levels of tumor necrosis factor (TNF)-alpha, and that the increase in insulin resistance precedes the clinical onset of the disease. Fasting plasma samples were obtained from ten women who subsequently developed pre-eclampsia and ten normal pregnant controls at 16, 20, 24, 28, 32 and 36 weeks' gestation to measure circulating levels of insulin, glucose and TNF-alpha. Fasting insulin resistance index (FIRI) was calculated from insulin and glucose concentrations. In the normal controls, fasting insulin and TNF-alpha levels, and FIRI increased with gestation, and these were significantly greater than baseline values from 24, 28 and 28 weeks, respectively. In the group of women who developed pre-eclampsia, plasma levels of insulin and the FIRI were significantly higher than baseline from 20 and 24 weeks, respectively, but both were significantly higher than in the control group at 32 and 36 weeks. The increase in TNF-alpha in the pre-eclampsia group was significantly greater than in normal pregnant controls (p < 0.001). However, there was no significant association between TNF-alpha levels and FIRI in either normal pregnancy or pregnancies developing pre-eclampsia. These data suggest that insulin resistance in pre-eclampsia precedes the clinical onset of the disease, but that it is not related to elevated levels of TNF-alpha.

Adult↗
PubMed2003

The relationship between insulin and insulin-like growth factor binding protein-1 is modified by pre-eclampsia.

Insulin is the main negative regulator of insulin-like growth factor binding protein-1 (IGFBP-1) in the non-pregnant state. Although changes in insulin resistance and circulating level of IGFBP-1 occur in pre-eclampsia, little is known about the relationship between insulin and IGFBP-1 in pregnancies complicated by the disease. In this study, we have investigated whether the relationship between insulin and IGFBP-1 is modified by pre-eclampsia. Maternal levels of insulin and IGFBP-1 were measured, at 4-weekly intervals between 16 and 36 weeks' gestation, in plasma samples obtained from ten normal pregnant controls and ten women who developed pre-eclampsia. The controls were chosen to be similar in maternal age and booking body mass index to the pre-eclampsia group. Insulin levels increased in both the normal controls and the women who developed pre-eclampsia. The levels in pre-eclampsia were significantly greater than those in normal pregnancy at 32 and 36 weeks' gestation (p = 0.02 and 0.005, respectively). IGFBP-1 levels were unchanged in normal pregnancy and rose in pre-eclampsia. In normal pregnancy, insulin levels were inversely related to IGFBP-1 levels throughout. In women developing pre-eclampsia, the relationship between insulin and IGFBP-1 was negative at 16 weeks and positive from 24 weeks. These data suggest that whereas the inverse relationship between insulin and IGFBP-1 is maintained during normal pregnancy, this relationship is reversed in women who develop pre-eclampsia.

Adult↗
PubMed2002

Uterine compression sutures: surgical management of postpartum hemorrhage.

BACKGROUND: It has been estimated that worldwide, over 125,000 women die of postpartum hemorrhage each year. The traditional management of this condition includes the use of oxytocics, such as oxytocin, ergometrine, and prostaglandins, before proceeding to ligation of the internal iliac arteries and even hysterectomy. The B-Lynch technique is a surgical procedure that may be used to arrest postpartum hemorrhage resulting from uterine atony. CASES: This paper describes simple modifications of this technique that make this procedure less complex to perform. Three clinical case scenarios illustrate the context in which the sutures may be used. CONCLUSION: Compression sutures placed into the postpartum uterus may provide a simple first surgical step to control bleeding when routine oxytocic measures have failed. We suggest that the technique we have described is a simple procedure and should be tried before more complex interventions are used.

Adult↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2002

A longitudinal study of biochemical markers of bone turnover during normal pregnancy and pregnancies complicated by pre-eclampsia.

OBJECTIVES: To test the hypothesis that the increased bone turnover observed in established pre-eclampsia is present earlier in pregnancy prior to the diagnosis of pre-eclampsia. DESIGN: A prospective longitudinal study. SETTING: Obstetric Unit at Chelsea and Westminster Hospital, London. POPULATION: Nine women who subsequently developed pre-eclampsia and 17 normal pregnant controls. METHODS: Maternal plasma levels of the cross-linked carboxyl terminal telopeptide of the type I collagen (ICTP), a marker of bone resorption, and of the carboxy-terminal propeptide of type I collagen (PICP), a marker of bone formation, were measured longitudinally in nine women who developed pre-eclampsia and 17 women with normal pregnancy. Serial blood samples were obtained at 16, 20, 24, 28, 32 and 36 weeks of gestation and the levels of ICTP and PICP were measured by radio-immunoassay. RESULTS: ICTP and PICP increased progressively in the normal pregnant and pre-eclampsia groups, but the rate of increase was significantly greater in the latter (P = 0.00002 and 0.0008, unpaired t test, for ICTP and PICP summary measures, respectively). In the pre-eclampsia group, positive correlation were observed between ICTP levels at 36 weeks of gestation and plasma uric acid (r = 0.9, P = 0.001) and degree of proteinuria (r = 0.78, P = 0.04). No correlation was observed between the two bone markers and other variables during normal pregnant group. CONCLUSION: These data show that biochemical markers of bone turnover are greater in pregnancies complicated by pre-eclampsia compared with normal pregnancy but only when the disease is clinically evident.

Adult↗
PubMed2002

Does endothelial cell activation occur with intrauterine growth restriction?

It is possible that in fetal growth restriction without pre-eclampsia endothelial cell activation does not occur. This might be either because there is no release of 'factor X' or because of maternal resistance to its effects. To test this hypothesis, we took blood samples from 26 women with pre-eclampsia (without fetal growth restriction), 13 women with fetal growth restriction (without pre-eclampsia) and 24 normal pregnant controls, and measured the circulating levels of three markers of endothelial cell activation (soluble VCAM, ICAM and E-selectin) and three cytokines [tumour necrosis factor-a (TNF-alpha), interleukin-6 (IL-6) and -8 (IL-8)]. The levels of the markers of endothelial cell activation were raised in both pre-eclampsia and fetal growth restriction pregnancies compared with controls; however, the levels of TNF-alpha, IL-6 and IL-8 were significantly raised in pregnancies complicated by pre-eclampsia, but not in fetal growth restriction, compared with controls. These data show that endothelial cell activation is common to both pre-eclampsia and fetal growth restriction, but that the circulating levels of cytokines are elevated only in pre-eclampsia. Thus, it seems likely that endothelial cell activation is a consequence of a failure of trophoblast invasion and that a further step is required, possibly involving cytokine release, for the expression of the full clinical picture of pre-eclampsia.

Adult↗
PubMed2001

A longitudinal study of resting peripheral blood flow in normal pregnancy and pregnancies complicated by chronic hypertension and pre-eclampsia.

OBJECTIVES: To investigate the hypothesis that reduced resting tissue blood flow precedes the clinical onset of pre-eclampsia in women at risk of the disease. METHODS: We used venous occlusion plethysmography to compare resting calf muscle blood flow in 18 normal pregnant controls, 18 pregnant women with chronic hypertension, and 23 pregnant women at increased risk of developing pre-eclampsia. Calf blood flow was measured at 16, 20, 24, 28, 32 and 36 weeks of gestation. RESULTS: Blood flow increased with gestation in normal pregnancy (P = 0.004) and chronic hypertension (P = 0.006), but not in the 'at risk' women who did not develop pre-eclampsia (P = 0.36). In contrast, blood flow decreased significantly in eight out of the 23 women 'at risk', who developed pre-eclampsia (P < 0.00001, ANOVA). The decrease in flow preceded the clinical diagnosis of the pre-eclampsia by several weeks. Moreover, a significant inverse correlation was observed between resting blood flow and plasma uric acid concentrations (r = -0.86, P = 0.03) in the women that developed pre-eclampsia. CONCLUSIONS: We have shown that reduced resting blood flow precedes the clinical onset of pre-eclampsia independently of hypertension per se. These findings support the notion that impaired tissue blood flow may be involved at an early stage in the pathophysiology of the disease.

Chronic Disease↗
PubMed2001

Biochemical markers of maternal bone turnover are elevated in pre-eclampsia.

OBJECTIVES: To investigate the hypothesis that bone turnover is reduced in pre-eclampsia compared with normal pregnancy. DESIGN: A prospective cross-sectional study. SETTING: Obstetric unit at the Chelsea and Westminster Hospital, London. METHODS: Third trimester maternal plasma levels of the cross-linked carboxyl-terminal telo-peptide of type I collagen (ICTP), (a marker of bone resorption) and the carboxyl terminal pro-peptide of type I pro-collagen (PICP), (a marker of bone formation) were compared in 25 women with pre-eclampsia and in 24 normal pregnant controls. The subjects were matched for maternal age, booking body mass index and gestational age. PICP and ICTP levels were measured by radio-immunoassay. RESULTS: ICTP and PICP levels were significantly increased in women with pre-eclampsia compared with the normal pregnant controls (P = 0.0001 and P = 0.004, for ICTP and PICP respectively, Wilcoxon signed ranked test). There was no significant correlation between either of the markers and booking body mass index, blood pressure, serum uric acid levels or platelet count. CONCLUSIONS: These data suggest that bone turnover is increased in established pre-eclampsia compared with normal pregnancy. Further studies are required to investigate whether this precedes the onset of the disease.

Adult↗
PubMed2000

Maternal hemoglobin concentration and birth weight.

Pregnancy requires additional maternal absorption of iron. Maternal iron status cannot be assessed simply from hemoglobin concentration because pregnancy produces increases in plasma volume and the hemoglobin concentration decreases accordingly. This decrease is greatest in women with large babies or multiple gestations. However, mean corpuscular volume does not change substantially during pregnancy and a hemoglobin concentration <95 g/L in association with a mean corpuscular volume <84 fL probably indicates iron deficiency. Severe anemia (hemoglobin <80 g/L) is associated with the birth of small babies (from both preterm labor and growth restriction), but so is failure of the plasma volume to expand. Hemoglobin concentrations >120 g/L at the end of the second trimester are associated with a </=3-fold increased risk of preeclampsia and intrauterine growth restriction. The minimum incidence of low birth weight (<2.5 kg) and of preterm labor (<37 completed weeks) occurs in association with a hemoglobin concentration of 95-105 g/L. This is widely regarded as indicating anemia in the pregnant woman but, if associated with a mean corpuscular volume >84 fL, should be considered optimal.

Anemia, Iron-Deficiency↗
PubMed2000

A longitudinal study of maternal plasma insulin-like growth factor binding protein-1 concentrations during normal pregnancy and pregnancies complicated by pre-eclampsia.

Insulin-like growth factor binding protein-1 (IGFBP-1) is synthesized by the decidual stroma, and is thought to act locally to inhibit IGF activity and so limit trophoblast invasion. Cross-sectional studies have reported conflicting data on maternal circulating concentrations of IGFBP-1 in early pregnancy before the development of pre-eclampsia. A longitudinal study was performed in 10 women who went on to develop pre-eclampsia and a group of 12 normal pregnant controls, chosen to be similar for maternal age, booking body mass index (BMI) and gestational age. Maternal IGFBP-1 concentrations were measured in plasma obtained at 16, 20, 24, 28, 32 and 36 weeks. Plasma IGFBP-1 concentrations were unchanged over this period in normal pregnancy. In contrast, the concentrations in women who developed pre-eclampsia increased progressively. At 16, 20, and 24 weeks the concentrations were significantly lower compared to normal pregnancy, at 28 and 32 weeks, similar, but by 36 weeks the concentrations were significantly greater than the normal controls. The data show that circulating IGFBP-1 concentrations are lower in early pregnancy before the development of pre-eclampsia. Thus, it is suggested that IGFBP-1-induced inhibition of IGF activity is unlikely to be responsible for the impaired trophoblast invasion observed in pre-eclampsia.

Adult↗
PubMed2000

Longitudinal analysis of maternal plasma leptin concentrations during normal pregnancy and pre-eclampsia.

Leptin concentrations have been found to be elevated in cross-sectional studies of established pre-eclampsia. Circulating concentrations of leptin were measured in a cross-sectional study to confirm these findings (19 women with pre-eclampsia and 13 normal pregnant controls) and in a longitudinal study to establish the timing of the increase in leptin concentrations (samples obtained at 16, 20, 24, 28, 32, 36 and 38 weeks gestation from eight women who went on to develop pre-eclampsia and seven normal pregnant controls). In the cross-sectional study, plasma leptin concentrations were significantly greater in women with pre-eclampsia than in normal controls (P: = 0.001). In the longitudinal study, it was found that circulating leptin concentrations rose gradually to 32 weeks and thereafter declined slightly in normals. The concentrations in women destined to develop pre-eclampsia were consistently higher from 20 weeks gestation (P: = 0.04-0.003) and, in contrast to the normal controls, rose markedly from 32 weeks as pre-eclampsia developed. This study confirms that plasma leptin concentrations are increased in established pre-eclampsia and reports for the first time that leptin concentrations are elevated before pre-eclampsia is clinically evident.

Adult↗
PubMed2000

Resting peripheral blood flow in normal pregnancy and in pre-eclampsia.

Multiple organ dysfunction followed by end organ failure occurs in pre-eclampsia. While one would intuitively reason that one of the factors contributing to the end organ failure is poor nutritional blood flow, this has yet to be demonstrated. The aim of the present study was to determine whether changes in resting nutritional blood flow occur in pre-eclampsia. We used strain-gauge plethysmography to study calf blood flow in 19 women with pre-eclampsia, 13 normal pregnant women and 17 non-pregnant controls. We reasoned that, since the calf comprises mostly skeletal muscle, without anastomotic channels, blood flowing through this region would primarily reflect nutritive flow. Calf blood flow was significantly reduced in women with pre-eclampsia (1.95+/-0.9 ml.min(-1).100 ml(-1)) compared with normal pregnant (3.9+/-1.4 ml.min(-1).100 ml(-1)) and non-pregnant (3.8+/-1.0 ml.min(-1).100 ml(-1)) women (P=0.0004 and P=0.0005 respectively; ANOVA). Blood flow in pre-eclampsia was also correlated significantly with platelet count as an index of disease severity. In addition, there was a significant negative correlation between blood flow and systolic blood pressure (r=-0.69, P=0.004) in the women with pre-eclampsia. These findings support the hypothesis that nutritional blood flow is reduced in pre-eclampsia. We suggest that measurement of resting calf blood flow could give a non-invasive index of deterioration of nutritive blood flow to vital organs in pre-eclampsia.

Adult↗
PubMed1999

Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial.

BACKGROUND: Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia. METHODS: 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study. FINDINGS: Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002). INTERPRETATION: Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.

Adult↗