Interventions at caesarean section for reducing the risk of aspiration pneumonitis.

BACKGROUND: Various interventions are used as prophylaxis for aspiration pneumonitis in obstetric anaesthesia. This review, based on a Cochrane systematic review currently being updated, examines whether interventions given before caesarean section reduce the risk of aspiration pneumonitis. METHODS: Twenty-two studies, involving 2658 women providing data in a usable format for meta-analysis were identified. RESULTS: Compared to no treatment or placebo, there was a significant reduction in the risk of intra-gastric pH <2.5 with antacids (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.09-0.32), H2 antagonists (RR 0.09, 95% CI 0.05-0.18) and proton-pump antagonists (RR 0.26, 95% CI 0.14-0.46). H2 antagonists were associated with a reduced risk of intra-gastric pH <2.5 when compared with proton-pump antagonists (RR 0.39, 95% CI 0.16-0.97), but compared with antacids the findings were unclear. Combined use of antacids plus H2 antagonists was associated with a significant reduction in the risk of intra-gastric pH <2.5 when compared with placebo (RR 0.02, 95% CI 0.00-0.15) or compared with antacids alone (RR 0.12, 95% CI 0.02-0.92). CONCLUSION: The quality of evidence was weak and may not reflect a reduction in the risk of aspiration pneumonitis since none of the studies assessed substantive clinical outcomes or potential adverse effects. Further work is required to validate the suitability of surrogate markers of pH and gastric volume for clinical outcomes in the context of aspiration pneumonitis.

Treatments for iron-deficiency anaemia in pregnancy.

BACKGROUND: Iron deficiency, the most common cause of anaemia in pregnancy worldwide, can be mild, moderate or severe. Severe anaemia can have very serious consequences for mothers and babies, but there is controversy about whether treating mild or moderate anaemia provides more benefit than harm. OBJECTIVES: To assess the effects of different treatments for iron-deficiency anaemia in pregnancy (defined as haemoglobin less than 11 g/dl) on maternal and neonatal morbidity and mortality. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to December 2005), EMBASE (1976 to December 2005), LILACS (1982 to 40 edition), BIOSIS Previews (1980 to June 2002) and ongoing clinical trial registers. SELECTION CRITERIA: Randomised controlled trials comparing treatments for iron-deficiency anaemia in pregnancy. DATA COLLECTION AND ANALYSIS: We identified 17 trials, involving 2578 women. We assessed trial quality. MAIN RESULTS: The trials were small and generally methodologically poor. They covered a very wide range of differing drugs, doses and routes of administration, making it difficult to pool data. Oral iron in pregnancy showed a reduction in the incidence of anaemia (one trial, 125 women; relative risk 0.38; 95% confidence interval 0.26 to 0.55). It was not possible to assess the effects of treatment by severity of anaemia. A trend was found between dose and reported adverse effects. We found that most trials had no assessments on relevant clinical outcomes and a paucity of data on adverse effects, including some that are known to be associated with iron administration. Although the intramuscular and intravenous routes produced better haematological indices in women than the oral route, no clinical outcomes were assessed and there were insufficient data on adverse effects, for example, on venous thrombosis and severe allergic reactions. AUTHORS' CONCLUSIONS: Despite the high incidence and burden of disease associated with this condition, there is a paucity of good quality trials assessing clinical maternal and neonatal effects of iron administration in women with anaemia. Daily oral iron treatment improves haematological indices but causes frequent gastrointestinal adverse effects. Parenteral (intramuscular and intravenous) iron enhances haematological response, compared with oral iron, but there are concerns about possible important adverse effects. Large, good quality trials, assessing clinical outcomes (including adverse effects) are required.

Caesarean section for non-medical reasons at term.

BACKGROUND: Caesarean section rates are progressively rising in many parts of the world. One suggested reason is increasing requests by women for caesarean section in the absence of clear medical indications, such as placenta praevia, HIV infection, contracted pelvis and, arguably, breech presentation or previous caesarean section. The reported benefits of planned caesarean section include greater safety for the baby, less pelvic floor trauma for the mother, avoidance of labour pain and convenience. The potential disadvantages, from observational studies, include increased risk of major morbidity or mortality for the mother, adverse psychological sequelae, and problems in subsequent pregnancies, including uterine scar rupture and greater risk of stillbirth and neonatal morbidity. An unbiased assessment of advantages and disadvantages would assist discussion of what has become a contentious issue in modern obstetrics. OBJECTIVES: To assess, from randomised trials, the effects on perinatal and maternal morbidity and mortality, and on maternal psychological morbidity, of planned caesarean delivery versus planned vaginal birth in women with no clear clinical indication for caesarean section. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2005), MEDLINE (1974 to April 2005), EMBASE (1974 to April 2005), CINAHL (1982 to April 2005) and PsycINFO (1887 to April 2005). We also performed a manual search of the references of all retrieved articles, sought unpublished papers and abstracts submitted to international conferences and contacted expert informants. SELECTION CRITERIA: All comparisons of intention to perform caesarean section and intention for women to give birth vaginally; random allocation to treatment and control groups; adequate allocation concealment; women at term with single fetuses with cephalic presentations and no clear medical indication for caesarean section. DATA COLLECTION AND ANALYSIS: We identified no studies that met the inclusion criteria. MAIN RESULTS: There were no included trials. AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials, upon which to base any practice recommendations regarding planned caesarean section for non-medical reasons at term. In the absence of trial data, there is an urgent need for a systematic review of observational studies and a synthesis of qualitative data to better assess the short- and long-term effects of caesarean section and vaginal birth.

Routine prophylactic drugs in normal labour for reducing gastric aspiration and its effects.

BACKGROUND: Women in normal labour may sometimes go on to have general anaesthesia if labour becomes abnormal, for example if a caesarean section is required. General anaesthesia carries a very small risk of regurgitation and inhalation of stomach contents into the lungs. This can cause inflammation, particularly if the fluid is acidic, and can lead to severe morbidity and very occasionally mortality. Labour hormones increase the risk of gastric aspiration or Mendelsohn's syndrome, though the exact incidence is unknown. The routine administration of acid prophylaxis drugs to all women in normal labour is commonly practiced worldwide, to reduce gastric aspiration by reducing the volume and acidity of stomach contents. OBJECTIVES: To assess the effectiveness of routine prophylaxis drugs for women in normal labour to reduce gastric aspiration and its effects. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2005), EMBASE (1974 to April 2005) and CINAHL (1982 to April 2005). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of women in normal labour assessing the routine administration of drugs (antacids, H(2) receptor antagonists, dopamine antagonists and proton-pump inhibitors) compared with placebo/no treatment, and compared with other drugs for reducing gastric aspiration. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, quality, extracted data and performed double-data entry. MAIN RESULTS: Three trials were included, involving 2465 women, assessing the effects of antacids, H(2) receptor antagonists and dopamine antagonists. There were no trials on proton-pump inhibitors. None of the trials were of good quality, and none assessed the incidence of gastric aspiration, Mendelsohn's syndrome or their consequences. All the studies assessed vomiting, and there was limited evidence that vomiting may be reduced by antacids (relative risk (RR) 0.46, 95% confidence interval (CI) 0.27 to 0.77, n = 578, one trial) or by dopamine antagonists given alongside pethidine (RR 0.40, 95% CI 0.23 to 0.68, n = 584, one trial). Comparisons between different drugs showed no significant differences, though the number of participants was small. There was no evidence that H(2) receptor antagonists improved outcomes compared with antacids, though only one trial addressed this issue. AUTHORS' CONCLUSIONS: There is no good evidence to support the routine administration of acid prophylaxis drugs in normal labour to prevent gastric aspiration and its consequences. Giving such drugs to women once a decision to give general anaesthesia is made, is assessed in another Cochrane review.

Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour.

BACKGROUND: Cardiotocography (sometimes known as electronic fetal monitoring), records changes in the fetal heart rate and their temporal relationship to uterine contractions. The aim is to identify babies who may be short of oxygen (hypoxic), so additional assessments of fetal well-being may be used, or the baby delivered by caesarean section or instrumental vaginal birth. OBJECTIVES: To evaluate the effectiveness of continuous cardiotocography during labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (March 2006), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to December 2005), EMBASE (1974 to December 2005), Dissertation Abstracts (1980 to December 2005) and the National Research Register (December 2005). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials involving a comparison of continuous cardiotocography (with and without fetal blood sampling) with (a) no fetal monitoring, (b) intermittent auscultation (c) intermittent cardiotocography. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility, quality and extracted data. MAIN RESULTS: Twelve trials were included (over 37,000 women); only two were high quality. Compared to intermittent auscultation, continuous cardiotocography showed no significant difference in overall perinatal death rate (relative risk (RR) 0.85, 95% confidence interval (CI) 0.59 to 1.23, n = 33,513, 11 trials), but was associated with a halving of neonatal seizures (RR 0.50, 95% CI 0.31 to 0.80, n = 32,386, nine trials) although no significant difference was detected in cerebral palsy (RR 1.74, 95% CI 0.97 to 3.11, n = 13,252, two trials). There was a significant increase in caesarean sections associated with continuous cardiotocography (RR 1.66, 95% CI 1.30 to 2.13, n =18,761, 10 trials). Women were also more likely to have an instrumental vaginal birth (RR 1.16, 95% CI 1.01 to 1.32, n = 18,151, nine trials). Data for subgroups of low-risk, high-risk, preterm pregnancies and high quality trials were consistent with overall results. Access to fetal blood sampling did not appear to influence the difference in neonatal seizures nor any other prespecified outcome. AUTHORS' CONCLUSIONS: Continuous cardiotocography during labour is associated with a reduction in neonatal seizures, but no significant differences in cerebral palsy, infant mortality or other standard measures of neonatal well-being. However, continuous cardiotocography was associated with an increase in caesarean sections and instrumental vaginal births. The real challenge is how best to convey this uncertainty to women to enable them to make an informed choice without compromising the normality of labour.

Evaluation of the meta-analyses on the effects, on both mother and baby, of the various components of 'active' management of the third stage of labour.

In their comprehensive review of controlled trials, Prendiville and Elbourne (1989) used the technique of meta-analysis to study the effects, on both mother and baby, of various aspects of third stage management, acknowledging some of the shortcomings of the trials used. This paper questions some of the conclusions which these authors drew and, drawing on other evidence (some of which has been published since the review), puts forward alternative interpretations of some of the meta-analyses. Reference is also made to the updated meta-analyses in the Cochrane Pregnancy and Childbirth Database (Elbourne, 1994a-h). In addition, this paper examines the extent to which the findings of the Bristol and Dublin third stage trials (Prendiville et al, 1988; Begley, 1990) add to our understanding of what is effective care during the third stage of labour.

Phytohaemagglutinin responsiveness of peripheral lymphocytes and survival in patients with primary breast cancer.

The response of peripheral blood lymphocytes from 153 breast cancer patients to the T-cell mitogen phytohaemagglutinin (PHA) was measured prior to surgery and patients assigned to either high (Hi/PHA) or low (Lo/PHA) PHA response groups. Patients were followed up for between 8 and 12 years, or until death. Clinical characteristics were similar in Hi/PHA and Lo/PHA groups. In the 96 patients who received no postoperative adjuvant therapy, overall and relapse-free survival was significantly longer in Hi/PHA than in Lo/PHA patients (p less than 0.005, and p less than 0.025 respectively); relative risk of death within 12 years was 0.52 and of relapse was 0.64. In 47 patients who were treated with radiotherapy postoperatively, there was no correlation between the PHA response and overall or relapse-free survival. The implications of these findings for the selection of breast cancer patients for adjuvant treatment following surgery are discussed.

Hairy cell leukaemia occurring during phenytoin (diphenylhydantoin) treatment.

We describe the case of a patient who developed hairy cell leukaemia (leukaemic reticuloendotheliosis) during phenytoin treatment. Hairy cells were identified by fluorescence, phase contrast and electron microscopy; they contained tartrate-resistant acid phosphatase activity, formed rosettes with mouse but not sheep erythrocytes and bore monoclonal surface immunoglobulin. Because of the association of pseudo- and true lymphomas with phenytoin it is possible that this lymphoproliferative disorder arose as a result of the treatment with phenytoin, possibly in conjunction with sulthiame.

An alternative method of expressing results of lymphocyte transformation experiments.

The use of counts per minute, disintegrations per minute and stimulated index as a means of expressing lymphocyte transformation is discussed. An alternative method is proposed, namely, that the degree of transformation is more effectively measured by the difference in incorporation of nucleoprotein base by stimulated as compared with unstimulated cultures expressed in moles uptake of base per unit number of lymphocytes.

Lymphocyte transformation in cancer patients: variation in results according to technique.

Lymphocyte transformation to phytohaemagglutinin (PHA) was measured simultaneously by two methods (heparin and methyl cellulose) in 16 patients with non-lymphoid cancer and 21 normal subjects. Twelve cancer patients showed transformation levels below the normal heparin range, but only two patients showed levels below the normal methyl cellulose range. These findings suggest that in interpreting lymphocyte transformation studies close attention should be given to the methods employed.