Biomedical subjects
Publications and source records attributed to R F Lamont.
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In gynaecology, specialist menopause, urogynae, colposcopy, infertility, pelvic pain and cancer, rapid access clinics exist at many teaching and busy district general hospitals in the UK. Similarly, in obstetrics many busy maternity units have fetal medicine clinics, dedicated twins clinics and maternal medicine clinics, incorporating various general medical conditions and conditions peculiarly appropriate to pregnancy such as haematological disorders, diabetes and epilepsy. In contrast, in very few hospitals is there a dedicated clinic for women at increased risk of preterm birth, yet this is the major cause of neonatal mortality and morbidity in the developed world. Such a situation may be due to the confusion created by the fact that preterm birth is a heterogeneous condition with multiple aetiologies and hence multiple therapeutic interventions. It is possible to identify a group of women at particularly high risk of preterm birth in whom screening and interventional techniques have the potential to reduce the mortality and morbidity associated with spontaneous preterm labour and preterm birth.
Over the past 15 years, the use of beta-agonists has declined worldwide. Following the Royal College of Obstetricians and Gynaecologists guidelines in 2002, clinicians in the UK and beyond were faced with the dilemma of continuing to use beta-agonists, desist from using tocolytic therapy completely or choosing to change to atosiban or calcium channel blockers (CCBs). While grade A level 1 evidence exists to show that atosiban is significantly more efficacious than placebo and significantly safer than beta-agonists for the treatment of spontaneous preterm labour, the evidence for CCBs, such as nifedipine, is much less robust and no placebo-controlled trials have been performed. Published studies on nifedipine are largely investigator-led studies of small sample size, which lack sufficient power. As a result, most of the evidence has been based on meta-analyses of these studies, which look retrospectively at pooled data and are only as good as the quality of the studies included. In light of this, a tool was developed to produce a systematic review of studies on tocolytic effectiveness, which can and should be applied to all tocolytics and which considered both method- and topic-specific markers of quality. In the process of applying this tool to nifedipine, an extensive literature search identified 31 studies for a systematic review of the quality of nifedipine studies assessed by eight paired reviewers with wide experience in the subject of spontaneous preterm labour and preterm birth. Forty topic- and method-specific items of quality were assessed. The paucity of good quality studies of nifedipine used for the treatment of spontaneous preterm labour should be highlighted in meta-analyses or systematic reviews, which measure efficacy and should limit and influence the degree to which recommendations and guidelines are made on the basis of such studies.
Preterm birth is the major cause of perinatal mortality and morbidity in the developed world. Infection is a significant cause of spontaneous preterm labour in up to 40% of cases. Women with abnormal genital tract flora diagnosed by bacterial vaginosis on gram stain of vaginal secretions in pregnancy are at increased risk of late miscarriage and preterm birth. The earlier in pregnancy at which spontaneous preterm labour occurs, the more likely this is to be due to a pathological signal or trigger like infection. The earlier in pregnancy at which abnormal genital tract flora is detected, the greater is the risk of a subsequent infective adverse outcome. Even if abnormal genital tract flora in early pregnancy subsequently reverts to normal, there is a greater risk of an adverse outcome when compared to women whose vaginal flora was always normal. It follows that if antibiotics are to be used in pregnancy to treat abnormal genital tract flora, these should be used early in pregnancy before the inflammatory response leading to irreversible tissue damage has occurred. Historically, antibiotic studies have failed because the wrong antibiotics were used in the wrong women too late in pregnancy. Three recent randomized controlled trials have shown that clindamycin used in early pregnancy even in women at low risk of preterm birth can reduce the risk by 40-60%.
OBJECTIVES: To determine the prevalence of and the association between trisomy 21 and isolated fetal echogenic cardiac foci (FECF) identified in the second trimester in an unselected low-risk population. METHODS: All cases with isolated FECF were collected by reviewing the antenatal ultrasound database for 3 consecutive years. In order to include all trisomy 21 cases for the same period, the regional cytogenetics database and pediatric databases were examined. A 2 x 2-table analysis was performed to establish the sensitivity, specificity and positive and negative predictive values of isolated FECF as a screening test for trisomy 21 in a low-risk unselected population. RESULTS: In the 3-year period of the study the total number of deliveries was 11,105, of which 10,769 (97%) had a routine detailed anomaly scan between 16 and 24 weeks' gestation. There were 311 cases (2.9%) of isolated FECF. Among these there was only one case (0.3%) of trisomy 21. In the same period, the total number of trisomy 21 cases was 14. Accordingly, the sensitivity of isolated FECF for detecting trisomy 21 was 7.1% and the specificity was 97.1%. Positive and negative predictive values of FECF were 0.3% and 99.9%, respectively. CONCLUSION: In an otherwise healthy pregnancy, the finding of isolated FECF on a routine second-trimester anomaly scan is normal and should not be considered as a risk factor for trisomy 21 in an unselected low-risk population.
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The aim of this study was to analyse how the results of Gram-staining vaginal smears correlated with the clinical criteria for determining the existence of bacterial vaginosis (BV) and, in particular, how the category defined as 'intermediate' or Gram grade II did so and its significance. Women attending an antenatal clinic with an abnormal vaginal flora, that is those who had Gram-stains of grades II or III, the latter considered to equate with BV, were given clindamycin or a placebo intravaginally and examined again on up to three occasions. Gram-stain readings of grade III correlated with the clinical criteria for BV on 356 (91.7%) of 388 occasions. Grade II readings covered the spectrum of clinical criteria and correlated with those for BV on 35 (37.2%) of 94 occasions. Grade I, recorded 231 times and seen usually after clindamycin treatment, was associated with BV only once. The sensitivity, specificity, positive predictive value and negative predictive value of the Gram stain for the diagnosis of BV, based on a combination of grades II and III, were 99.7%, 71.6%, 81% and 99.6%, respectively; based on grade III only, the values were 99.7%, 87.7%, 91.6% and 99.6%, respectively. Women reported a malodorous vaginal discharge on 49.2% of the occasions a grade III flora was seen and 13.3% of the times grade II was recorded. It was not associated with grade I and would seem a useful adjunct to the accepted clinical criteria for diagnosing BV. Each of the clinical criteria was found in about equal proportions (87%-91%) for women whose Gram grade was III. For grade II, an increased discharge was noted most often (76.5%) and 'clue' cells least often (24.5%). A positive amine test was the most specific, being associated with <1% of grade I smears. Of women with grade III status, 91% reverted to grade I after treatment with clindamycin for three days. In contrast, of women with grade II status, 53% reverted to grade I, as did 47% of those who were given a placebo. The 'intermediate' (grade II) category is a Gram-stain diagnosis and not one that can be made clinically. It is important to recognize as a distinct entity not only because amalgamation with grade III diminishes the specificity and positive predictive value of the Gram-stain for diagnosing BV, but also because women of grade II status usually fail to respond to clindamycin treatment, whereas those of grade III do not.
OBJECTIVE: To determine the association of fetal pyelectasis FP found at the time of second trimester detailed ultrasound scan with aneuploidy in an unselected low-risk population. DESIGN: Retrospective study of ultrasonographic reports, films and hospital notes over an eight-year period from 1991 to 1998. SETTING: District general hospital obstetric department with 3500 deliveries annually serving a low-risk cosmopolitan population. MAIN OUTCOME MEASURE: The prevalence of aneuploidy in cases of fetal pyelectasis. METHODS: The obstetric ultrasound reports and films of 29,591 cases were reviewed to identify those with FP at their detailed anomaly scan between 18 and 24-weeks gestation. The study sample included women whose scan showed the fetal renal pelvis of either kidney to be five millimetres or more in the anteroposterior diameter. Demographic data and other ultrasonographic abnormalities were noted. The genotype and phenotype of the babies were traced from a combination of cytogenetic reports and paediatric notes. RESULTS: There were 320 cases of FP among the 25,586 low-risk study population available in the studied gestational period (18-24 weeks) giving a prevalence of 1.25 percent. Of these, 301 cases of FP were found in isolation and 19 were found in association with another ultrasonographic marker. None of the 315 cases delivering at the Northwick Park & St. Mark's Hospital had aneuploidy. Pyelectasis was more likely to be bilateral (57%), and more in male fetuses (72%). The mean diameter for the pyelectasis at diagnosis was 6.5 mm (1.4 SD) ranging between 5 and 15 mm. One hundred and thirty seven cases (43%) resulted in spontaneous resolution. CONCLUSION: The prevalence of FP at the anomaly scan in an unselected low-risk population is not high (1.25%). Our data suggest that the risk of aneuploidy associated with isolated FP in a low-risk, unselected population is so small that it should not be an indication for invasive prenatal karyotyping.
The objective was to determine how frequently an abnormal vaginal flora occurred in women attending a menopause clinic and whether any abnormality might be related to a particular risk factor. Women completed a questionnaire on their gynaecological, sexual and medical history. Whether they were perimenopausal or postmenopausal was determined on the basis of symptomatology, duration of amenorrhoea and on a follicle-stimulating hormone (FSH) assay when clinically indicated. A speculum examination of the vagina was undertaken, at which time a smear of vaginal secretion was Gram stained and the bacterial flora graded as follows: grade 1, normal; grade 2, intermediate, and grade 3, bacterial vaginosis (BV). Of 100 women examined, 44 had grade 1 flora, 17 had grade 2 flora and 18 had BV. An apparent absence of, or very scanty, vaginal bacteria in which grading was not possible was found in 21 women. Women with BV had had more sexual partners than the others, but otherwise there were no discernible factors associated with the occurrence of BV. Women with vaginal atrophy were more likely to have an apparent absence of vaginal bacteria, but a few had BV.
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In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha.
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OBJECTIVES: To determine whether intravaginal clindamycin cream reduces the incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial flora graded as intermediate or BV and to investigate the effect of the antibiotic on vaginal microbial flora. METHODS: A prospective cohort study of pregnant women in an antenatal clinic of a district general hospital. The subjects were 268 women who had abnormal vaginal microbial flora at first clinic visit by examination of a Gram-stained vaginal smear and 34 women with a normal vaginal flora. Two hundred and thirty-seven women were evaluable. Women with abnormal Gram-stained smears (graded as II or III) on clinic recall were randomised to receive treatment (intravaginal clindamycin cream) or placebo and followed to assess outcome of pregnancy, vaginal flora, and detection of Mycoplasma hominis and Ureaplasma urealyticum after treatment. RESULTS: Abnormal outcomes of pregnancy were not significantly different in treated and placebo groups by Chi square (P = 0.2). However, women with grade III flora responded better to clindamycin than women with grade II flora by numbers of abnormal outcomes (P = 0.03) and return to normal vaginal flora (P = 0.01) (logistic regression analysis model). This may be due to differences in vaginal bacterial species in these grades. Women whose abnormal vaginal flora had spontaneously returned to normal on follow-up and were therefore not treated (revertants) had as many abnormal outcomes as placebos suggesting that damage by abnormal bacterial species occurred early in pregnancy. CONCLUSIONS: Gram-stain screening distinguishing grade II from grade III flora may be helpful in prescribing treatment other than clindamycin for women with grade II flora. Earlier diagnosis and treatment may be more effective in preventing an abnormal outcome, possibly as soon as pregnancy is diagnosed or even offered as a pre-conception screen.
A prospective observational study of asymptomatic women from three different general practices was set up to establish the incidence of bacterial vaginosis (BV). The study group comprised 287 women recalled to their general practitioner's surgery for routine cervical smears. The prevalence of an abnormal vaginal flora was about the same in women attending the 3 practices. Nearly 14% of women had abnormal vaginal flora and about 9% had BV on gram stain examination of vaginal secretions. This was 2-3 times more common than findings consistent with vaginal candidiasis (3.8%). Significant numbers of women with BV had received antifungal therapy suggesting a misdiagnosis. Because of its potential complications, women should be offered screening for BV in a well-women setting and, if found, should be treated if symptomatic or at risk of adverse obstetric or gynaecological sequelae.
Bacterial vaginosis is increasingly associated with adverse sequelae in obstetrics such as preterm prelabour rupture of membranes, preterm labour and preterm birth. It is important to diagnose the condition early in pregnancy where appropriate treatment can be administered to women who are symptomatic or who are at high risk of adverse sequelae.