Antihypertensive drug therapy for mild to moderate hypertension during pregnancy.

BACKGROUND: Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve pregnancy outcome. This Cochrane Review is an updated review, first published in 2001 and subsequently updated in 2007 and 2014. OBJECTIVES: To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 September 2017), and reference lists of retrieved studies. SELECTION CRITERIA: All randomised trials evaluating any antihypertensive drug treatment for mild to moderate hypertension during pregnancy, defined as systolic blood pressure 140 to 169 mmHg and/or diastolic blood pressure 90 to 109 mmHg. Comparisons were of one or more antihypertensive drug(s) with placebo, with no antihypertensive drug, or with another antihypertensive drug, and where treatment was planned to continue for at least seven days. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: For this update, we included 63 trials (data from 58 trials, 5909 women), with moderate to high risk of bias overall.We carried out GRADE assessments for the main 'antihypertensive drug versus placebo/no antihypertensive drug' comparison only. Evidence was graded from very low to moderate certainty, with downgrading mainly due to design limitations and imprecision.For many outcomes, trials contributing data evaluated different hypertensive drugs; while we did not downgrade for this indirectness, results should be interpreted with caution.Antihypertensive drug versus placebo/no antihypertensive drug (31 trials, 3485 women)Primary outcomes: moderate-certainty evidence suggests that use of antihypertensive drug(s) probably halves the risk of developing severe hypertension (risk ratio (RR) 0.49; 95% confidence interval (CI) 0.40 to 0.60; 20 trials, 2558 women), but may have little or no effect on the risk of proteinuria/pre-eclampsia (average risk ratio (aRR) 0.92; 95% CI 0.75 to 1.14; 23 trials, 2851 women; low-certainty evidence). Moderate-certainty evidence also shows that antihypertensive drug(s) probably have little or no effect in the risk of total reported fetal or neonatal death (including miscarriage) (aRR 0.72; 95% CI 0.50 to 1.04; 29 trials, 3365 women), small-for-gestational-age babies (aRR 0.96; 95% CI 0.78 to 1.18; 21 trials, 2686 babies) or preterm birth less than 37 weeks (aRR 0.96; 95% CI 0.83 to 1.12; 15 trials, 2141 women). SECONDARY OUTCOMES: we are uncertain of the effect of antihypertensive drug(s) on the risk of maternal death, severe pre-eclampsia, or eclampsia, orimpaired long-term growth and development of the baby in infancy and childhood, because the certainty of this evidence is very low. There may be little or no effect on the risk of changed/stopped drugs due to maternal side-effects, or admission to neonatal or intensive care nursery (low-certainty evidence). There is probably little or no difference in the risk of elective delivery (moderate-certainty evidence).Antihypertensive drug versus another antihypertensive drug (29 trials, 2774 women)Primary outcomes: beta blockers and calcium channel blockers together in the meta-analysis appear to be more effective than methyldopa in avoiding an episode of severe hypertension (RR 0.70; 95% CI 0.56 to 0.88; 11 trials, 638 women). There was also an increase in this risk when other antihypertensive drugs were compared with calcium channel blockers (RR 1.86; 95% CI 1.09 to 3.15; 5 trials, 223 women), but no evidence of a difference when methyldopa and calcium channel blockers together were compared with beta blockers (RR1.18, 95% CI 0.95 to 1.48; 10 trials, 692 women). No evidence of a difference in the risk of proteinuria/pre-eclampsia was found when alternative drugs were compared with methyldopa (aRR 0.78; 95% CI 0.58 to 1.06; 11 trials, 997 women), with calcium channel blockers (aRR: 1.24, 95% CI 0.70 to 2.19; 5 trials, 375 women), or with beta blockers (aRR 1.21, 95% CI 0.88 to 1.67; 12 trials, 1107 women).For the babies, we found no evidence of a difference in the risk oftotal reported fetal or neonatal death (including miscarriage) when comparing other antihypertensive drugs with methyldopa (aRR 0.77, 95% CI 0.52 to 1.14; 22 trials, 1791 babies), with calcium channel blockers (aRR 0.90, 95% CI 0.52 to 1.57; nine trials, 700 babies), or with beta blockers (aRR: 1.23, 95% CI 0.81 to 1.88; 19 trials, 1652 babies); nor in the risk for small-for-gestational age in the comparison with methyldopa (aRR 0.79, 95% CI 0.52 to 1.20; seven trials, 597 babies), with calcium channel blockers (aRR 1.05, 95% CI 0.64 to 1.73; four trials, 200 babies), or with beta blockers (average RR 1.13, 95% CI 0.80 to 1.60; 7 trials, 680 babies). No evidence of an overall difference among groups in the risk of preterm birth (less than 37 weeks) was found in the comparison with methyldopa (aRR: 0.91; 95% CI 0.68 to 1.22; 11 trials, 835 women), with calcium channel blockers (aRR 0.85, 95% CI 0.59 to 1.23; six trials, 330 women), or with beta blockers (aRR 1.22, 95% CI 0.90 to 1.66; 9 trials, 806 women). SECONDARY OUTCOMES: There were no cases of maternal death andeclampsia. There is no evidence of a difference in the risk of severe pre-eclampsia, changed/stopped drug due to maternal side-effects, elective delivery, admission to neonatal or intensive care nursery when other antihypertensive drugs are compared with methyldopa, calcium channel blockers or beta blockers. Impaired long-term growth and development in infancy and childhood was not reported for these comparisons. AUTHORS' CONCLUSIONS: Antihypertensive drug therapy for mild to moderate hypertension during pregnancy reduces the risk of severe hypertension. The effect on other clinically important outcomes remains unclear. If antihypertensive drugs are used, beta blockers and calcium channel blockers appear to be more effective than the alternatives for preventing severe hypertension. High-quality large sample-sized randomised controlled trials are required in order to provide reliable estimates of the benefits and adverse effects of antihypertensive treatment for mild to moderate hypertension for both mother and baby, as well as costs to the health services, women and their families.

Treatments for breast abscesses in breastfeeding women.

BACKGROUND: The benefits of breastfeeding are well known, and the World Health Organization recommends exclusive breastfeeding for the first six months of life and continuing breastfeeding to age two. However, many women stop breastfeeding due to lactational breast abscesses. A breast abscess is a localised accumulation of infected fluid in breast tissue. Abscesses are commonly treated with antibiotics, incision and drainage (I&D) or ultrasound-guided needle aspiration, but there is no consensus on the optimal treatment. OBJECTIVES: To assess the effects of different treatments for the management of breast abscesses in breastfeeding women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trial Register (27 February 2015). In addition we searched African Journals Online (27 February 2015), Google Scholar (27 February 2015), ProQuest Dissertations and Theses Databases (27 February 2015) and the WHO International Clinical Trials Registry Platform (ICTRP) search portal (27 February 2015). We also checked reference lists of retrieved studies and contacted experts in the field as well as relevant pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating any intervention for treating lactational breast abscesses compared with any other intervention. Studies published in abstract form, quasi-RCTs and cluster-RCTs were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, assessed risk of bias and extracted data. Data were checked for accuracy. MAIN RESULTS: We included six studies. Overall, trials had an unclear risk of bias for most domains due to poor reporting. Two studies did not stratify data for lactational and non-lactational breast abscesses, and these studies do not contribute to the results. This review is based on data from four studies involving 325 women. Needle aspiration (with and without ultrasound guidance) versus incision and drainage (I&D) Mean time (days) to complete resolution of breast abscess (three studies) - there was substantial heterogeneity among these data (Tau(2) = 47.63, I(2) = 97%) and a clear difference between subgroups (with or without ultrasound guidance; Chi(2) = 56.88, I(2) = 98.2%, P = < 0.00001). We did not pool these data in a meta-analysis. Two studies excluded women who had treatment failure when they calculated the mean time to complete resolution. One study found that the time to complete resolution of breast abscess favoured needle aspiration over I&D (mean difference (MD) -6.07; 95% confidence interval (CI) -7.81 to -4.33; n = 36), but excluded 9/22 (41%) women in the needle aspiration group due to treatment failure. Another study reported faster resolution in the needle aspiration group (MD -17.80; 95% CI -21.27 to -14.33; n = 64) but excluded 6/35 (17%) women in the needle aspiration group due to treatment failure. A third study also reported that needle aspiration was associated with a shorter time to complete resolution of breast abscess (MD -16.00; 95%CI -18.73 to -13.27; n = 60); however, the authors did not indicate the number of women who were lost to follow-up for either group, and it is unclear how many women contributed to this result. Considering the limitations of the available data, we do not consider the results to be informative. Continuation of breastfeeding, after treatment (success): results favoured the needle aspiration group, but we did not pool data from the two studies because of substantial unexplained heterogeneity (I(2) = 97%). One study reported that women in the needle aspiration group were more likely to continue breastfeeding (risk ratio (RR) 2.89; 95% CI 1.64 to 5.08; n = 60), whereas the other study found no clear difference (RR 1.09; 95% CI 0.97 to 1.22 n = 70). Treatment failure was more common among women treated with needle aspiration compared to those who underwent I&D (RR 16.12; 95% CI 2.21 to 117.73; two studies, n = 115, low quality evidence). In one study, treatment with needle aspiration failed in 9/22 women who subsequently underwent I&D to treat their breast abscess. In another study, treatment with needle aspiration failed in 6/35 women, who subsequently underwent I&D. All abscesses in the I&D group were successfully treated.The included studies provided limited data for the review's secondary outcomes. No data were reported for adverse events. One study (60 women) reported that women in the needle aspiration group were more satisfied with their treatment than women who received I&D to treat their breast abscesses. Incision and drainage (I&D) with or without antibioticsOne study (150 women) compared the value of adding a broad-spectrum cephalosporin (single dose or a course of treatment) to women who underwent I&D for breast abscesses.The mean time to resolution of breast abscess was reported as being similar in all groups (although women with infection were excluded). Mean time to resolution for women who received a course of antibiotics was reported as 7.3 days, 6.9 days for women who received a single dose of antibiotics and 7.4 days for women who did not receive antibiotics. Standard deviations, P values and CIs were not reported and prevented further analysis. No data were reported for any continuation of breastfeeding after treatment (success). For treatment failure, there was no clear difference between the groups of women who received antibiotics (either a single dose or a course of antibiotics) and those who did not (RR 1.00; 95% CI 0.36 to 2.76).Included studies rarely reported this review's secondary outcomes (including adverse events). For post-operative complications/morbidity, there was no difference in the risk of wound infections between the antibiotics and no antibiotics groups (RR 0.58; 95% CI 0.29 to 1.17), irrespective of whether women received a single dose or a course of antibiotics. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether needle aspiration is a more effective option to I&D for lactational breast abscesses, or whether an antibiotic should be routinely added to women undergoing I&D for lactational breast abscesses. We graded the evidence for the primary outcome of treatment failure as low quality, with downgrading based on including small studies with few events and unclear risk of bias.

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care.

Antihypertensive drug therapy for mild to moderate hypertension during pregnancy.

BACKGROUND: Mild to moderate hypertension during pregnancy is common. Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve the outcome. OBJECTIVES: To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013) and reference lists of retrieved studies. SELECTION CRITERIA: All randomised trials evaluating any antihypertensive drug treatment for mild to moderate hypertension during pregnancy defined, whenever possible, as systolic blood pressure 140 to 169 mmHg and diastolic blood pressure 90 to 109 mmHg. Comparisons were of one or more antihypertensive drug(s) with placebo, with no antihypertensive drug, or with another antihypertensive drug, and where treatment was planned to continue for at least seven days. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. MAIN RESULTS: Forty-nine trials (4723 women) were included. Twenty-nine trials compared an antihypertensive drug with placebo/no antihypertensive drug (3350 women). There is a halving in the risk of developing severe hypertension associated with the use of antihypertensive drug(s) (20 trials, 2558 women; risk ratio (RR) 0.49; 95% confidence interval (CI) 0.40 to 0.60; risk difference (RD) -0.10 (-0.13 to -0.07); number needed to treat to harm (NNTH) 10 (8 to 13)) but little evidence of a difference in the risk of pre-eclampsia (23 trials, 2851 women; RR 0.93; 95% CI 0.80 to 1.08). Similarly, there is no clear effect on the risk of the baby dying (27 trials, 3230 women; RR 0.71; 95% CI 0.49 to 1.02), preterm birth (15 trials, 2141 women; RR 0.96; 95% CI 0.85 to 1.10), or small-for-gestational-age babies (20 trials, 2586 women; RR 0.97; 95% CI 0.80 to 1.17). There were no clear differences in any other outcomes.Twenty-two trials (1723 women) compared one antihypertensive drug with another. Alternative drugs seem better than methyldopa for reducing the risk of severe hypertension (11 trials, 638 women; RR (random-effects) 0.54; 95% CI 0.30 to 0.95; RD -0.11 (-0.20 to -0.02); NNTH 7 (5 to 69)). There is also a reduction in the overall risk of developing proteinuria/pre-eclampsia when beta blockers and calcium channel blockers considered together are compared with methyldopa (11 trials, 997 women; RR 0.73; 95% CI 0.54 to 0.99). However, the effect on both severe hypertension and proteinuria is not seen in the individual drugs. Other outcomes were only reported by a small proportion of studies, and there were no clear differences. AUTHORS' CONCLUSIONS: It remains unclear whether antihypertensive drug therapy for mild to moderate hypertension during pregnancy is worthwhile.

Combined effects of cigarette smoking and alcohol consumption on perinatal outcome.

BACKGROUND: An increase in various congenital abnormalities associated with cigarette smoking and the use of alcohol during pregnancy has been reported in many studies. These exposures also increase the risk of pregnancy complications such as abruptio placentae, unexplained stillbirth, preterm labor and intrauterine growth restriction. However, very few studies have addressed the combined effect of smoking and drinking on pregnancy outcomes. METHODS: In this review, the adverse effects of smoking or drinking on pregnancy were obtained from publications in which both substances were addressed in the same study population. A special effort was made to find studies in which the combined effect of these substances was investigated. RESULTS: Preterm labor occurred more frequently in women who drank and smoked during pregnancy. This increased odds ratio was more than the sum of the effects of either smoking or drinking, indicating that the use of both substances by the same woman has a synergistic effect that increases the risk of preterm labor. This synergistic effect was also found for low birth weight and growth restriction. CONCLUSIONS: As most of the women who drink during pregnancy also smoke cigarettes, attention should be given to the prevention or reduced use of both substances during pregnancy.

Seasonal influence on the admittance of pre-eclampsia patients in Tygerberg Hospital.

BACKGROUND: Previous studies suggest that the occurrence of pre-eclampsia is seasonally distributed. This retrospective study aims to determine whether there is a seasonal variation in the number of admissions and the prevalence of women with pre-eclampsiain Tygerberg Hospital, South Africa. METHODS: The number of women admitted with a diagnosis of pre-eclampsia,eclampsia or haemolysis elevated liver enzymes low platelets (HELLP) syndrome (together called pre-eclampsia) was obtained from hospital records from 2002 to 2003 for each season and month. Associations were analysed with Odds Ratios(OR). Furthermore, these data was compared with the Cape Town temperatures recorded on each day over the period, as well as the total rainfall for each month. Bivariate logistic regression of the probability of pre-eclampsia on temperature and rainfall was performed. RESULTS: Pre-eclampsia occurred in 11.5% of all admissions (1,329/11,585). The prevalence was highest in winter (13.6% pre-eclampsia patients from all admissions). Women admitted in winter had a higher risk of developing pre-eclampsia compared to those admitted in summer (OR = 1.69, 95% CI: 1.071.53). The risk of developing pre-eclampsia in June was higher than in February (summer in South Africa, reference month) (OR = 2.81, 95% CI:2.063.83). There was a significant correlation between the number of admissions with pre-eclampsia and the minimum daily temperature (r = -0.620, p = 0.032). CONCLUSIONS: Pre-eclampsia occurs more frequently in winter at Tygerberg Hospital, South Africa. The findings have implications for future research related to the aetiology of pre-eclampsia as well as for clinical care.

The optimal dosage of ketanserin for patients with severe hypertension in pregnancy.

OBJECTIVE: To establish the optimal dosage of ketanserin in the treatment of severe hypertension in pregnancy. STUDY DESIGN: A double blind prospective randomised controlled trail, comparing 10 mg ketanserin given as intravenous boluses either every 10 or 20 min, until the therapeutic goal of 90 mmHg (diastolic blood pressure) was reached, to a maximum of eight boluses. Main outcome measures were treatment failures and caesarean sections for fetal distress. RESULTS: There was no difference in reaching the therapeutic goal between patients receiving 10 mg ketanserin either every 10 or 20 min. CONCLUSION: Ketanserin appears to be an attractive medicine in the treatment of severe hypertension in pregnancy, but the optimal dosage could not be established.