***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Adjustment for prognostic covariates can lead to increased power in the analysis of r and omized trials . However , adjusted analyses are not often performed in practice . Methods We used simulation to examine the impact of covariate adjustment on 12 outcomes from 8 studies across a range of therapeutic areas . We assessed ( 1 ) how large an increase in power can be expected in practice ; and ( 2 ) the impact of adjustment for covariates that are not prognostic . Results Adjustment for known prognostic covariates led to large increases in power for most outcomes . When power was set to 80 % based on an unadjusted analysis , covariate adjustment led to a median increase in power to 92.6 % across the 12 outcomes ( range 80.6 to 99.4 % ) . Power was increased to over 85 % for 8 of 12 outcomes , and to over 95 % for 5 of 12 outcomes . Conversely , the largest decrease in power from adjustment for covariates that were not prognostic was from 80 % to 78.5 % . Conclusions Adjustment for known prognostic covariates can lead to substantial increases in power , and should be routinely incorporated into the analysis of r and omized trials . The potential benefits of adjusting for a small number of possibly prognostic covariates in trials with moderate or large sample sizes far outweigh the risks of doing so , and so should also be considered Background Intermittent preventive treatment in pregnancy has not been evaluated outside of Africa . Low birthweight ( LBW , < 2,500 g ) is common in Papua New Guinea ( PNG ) and contributing factors include malaria and reproductive tract infections . Methods From November 2009 to February 2013 , we conducted a parallel group , r and omised controlled trial in pregnant women ( ≤26 gestational weeks ) in PNG .  Sulphadoxine-pyrimethamine ( 1,500/75 mg ) plus azithromycin ( 1 g twice daily for 2 days ) ( SPAZ ) monthly from second trimester ( intervention ) was compared against sulphadoxine-pyrimethamine and chloroquine ( 450 to 600 mg , daily for three days ) ( SPCQ ) given once , followed by SPCQ placebo ( control ) . Women were assigned to treatment ( 1:1 ) using a r and omisation sequence with block sizes of 32 . Participants were blinded to assignments . The primary outcome was LBW . Analysis was by intention-to-treat . Results Of 2,793 women r and omised , 2,021 ( 72.4 % ) were included in the primary outcome analysis ( SPCQ : 1,008 ; SPAZ : 1,013 ) . The prevalence of LBW was 15.1 % ( 305/2,021 ) . SPAZ  reduced LBW ( risk ratio [ RR ] : 0.74 , 95 % CI : 0.60–0.91 , P = 0.005 ; absolute risk reduction ( ARR ) : 4.5 % , 95 % CI : 1.4–7.6 ; number needed to treat : 22 ) , and preterm delivery ( 0.62 , 95 % CI : 0.43–0.89 , P = 0.010 ) , and increased mean birthweight ( 41.9 g , 95 % CI : 0.2–83.6 , P = 0.049 ) . SPAZ  reduced maternal parasitaemia ( RR : 0.57 , 95 % CI : 0.35–0.95 , P = 0.029 ) and active placental malaria ( 0.68 , 95 % CI : 0.47–0.98 , P = 0.037 ) , and reduced carriage of gonorrhoea ( 0.66 , 95 % CI : 0.44–0.99 , P = 0.041 ) at second visit . There were no treatment-related serious adverse events ( SAEs ) , and the number of SAEs ( intervention 13.1 % [ 181/1,378 ] , control 12.7 % [ 174/1,374 ] , P = 0.712 ) and AEs ( intervention 10.5 % [ 144/1,378 ] , control 10.8 % [ 149/1,374 ] , P = 0.737 ) was similar . A major limitation of the study was the high loss to follow-up for birthweight . Conclusions SPAZ was efficacious and safe in reducing LBW , possibly acting through multiple mechanisms including the effect on malaria and on sexually transmitted infections . The efficacy of SPAZ in the presence of resistant parasites and the contribution of AZ to bacterial antibiotic resistance require further study . The ability of SPAZ to improve pregnancy outcomes warrants further evaluation . Trial registration Clinical Trials.gov NCT01136850 ( 06 April 2010 ) Background Intermittent preventive treatment with sulphadoxine-pyrimethamine ( IPTp-SP ) is being implemented in most malaria endemic countries as a st and ard two-doses regimen as it reduces the risk of low birth weight ( LBW ) and the prevalence of maternal anaemia . Nevertheless , where the risk of infection close to delivery is high because of intense transmission , a third IPTp-SP dose may further reduce the negative effects of malaria on pregnancy outcome . Methods Pregnant women in the 2nd or 3rd trimester were r and omized to receive either 2 ( SP2 ) or 3 doses ( SP3 ) of SP . Trained field workers paid home visits to the women for drug administration according to a predefined drug delivery schedule . Women were encouraged to attend their scheduled ANC visits and to deliver at the health facilities where the new-born was weighed . The prevalence of LBW ( < 2500 g ) , severe anaemia ( Hb < 8 g/dL ) and premature birth  was analysed using intention-to-treat ( ITT ) and per- protocol ( PP ) analysis . Results Data from 1274 singleton pregnancies were analysed ( 641 in the SP3 and 633 in the SP2 group ) . The uptake of the intervention appeared to be low . Though the prevalence of LBW in both intervention groups was similar ( adjusted Incident Rate Ratio , AIRR = 0.92 , 95%CI : 0.69 - 1.24 ) in the ITT analysis , the risk of severe anaemia was significantly lower in the SP3 group compared to the SP2 group ( AIRR = 0.38 , 95%CI : 0.16 - 0.90 ) . The PP analysis showed a trend of reduced risk of LBW , severe anaemia and premature delivery in the SP3 group , albeit the difference between two and three IPTp-SP did not reach statistical significance . Conclusion The risk of LBW and severe anaemia tended to be lower in the SP3 group , though this was not statistically significant , probably due to the low uptake of the intervention which reduced the power of the study . Further studies are needed for establishing whether a third SP dose has a real benefit in preventing the negative effects of malaria in pregnancy in setting s where transmission is markedly seasonal Background Daily trimethoprim-sulfamethoxazole ( TMP-SMX ) and insecticide-treated nets remain the main interventions for prevention of malaria in human immunodeficiency virus (HIV)-infected pregnant women in Africa . However , antifolate and pyrethroid resistance threaten the effectiveness of these interventions , and new ones are needed . Methods We conducted a double-blinded , r and omized , placebo-controlled trial comparing daily TMP-SMX plus monthly dihydroartemisinin-piperaquine ( DP ) to daily TMP-SMX alone in HIV-infected pregnant women in an area of Ug and a where indoor residual spraying of insecticide had recently been implemented . Participants were enrolled between gestation weeks 12 and 28 and given an insecticide-treated net . The primary outcome was detection of active or past placental malarial infection by histopathologic analysis . Secondary outcomes included incidence of malaria , parasite prevalence , and adverse birth outcomes . Result All 200 women enrolled were followed through delivery , and the primary outcome was assessed in 194 . There was no statistically significant difference in the risk of histopathologically detected placental malarial infection between the daily TMP-SMX plus DP arm and the daily TMP-SMX alone arm ( 6.1 % vs. 3.1 % ; relative risk , 1.96 ; 95 % confidence interval , .50 - 7.61 ; P = .50 ) . Similarly , there were no differences in secondary outcomes . Conclusions Among HIV-infected pregnant women in the setting of indoor residual spraying of insecticide , adding monthly DP to daily TMP-SMX did not reduce the risk of placental or maternal malaria or improve birth outcomes . Clinical Trials Registration NCT02282293 BACKGROUND In 2003 , Mali introduced intermittent preventive therapy in pregnancy ( ITPp ) with sulfadoxine-pyrimethamine ( SP ) for the control of malaria in pregnancy , consisting of 2 doses of SP given in the 2nd and 3rd trimester . This widely used regimen , although very effective , leaves many women unprotected from malaria during the last 4-to-8 weeks of gestation , which is a pivotal period for fetal weight gain . The aim of the study was to compare the efficacy and safety of 3-dose versus 2-dose IPTp-SP for the prevention of placental malaria and associated low birth weight ( LBW ) . METHODS We conducted a parallel-group , open-label , individually r and omized controlled superiority trial involving 814 women of all gravidity , enrolled from April 2006 through March 2008 . All women were seen at least 3 times and received either 2 ( n = 401 ) or 3 ( n = 413 ) doses of IPTp-SP . The primary endpoint measured was placental malaria , LBW , preterm births , and maternal anemia were secondary endpoints , and severe maternal skin reactions and neonatal jaundice were safety endpoints . RESULTS Among the 96 % of study subjects who were followed up until delivery , the prevalence of placental malaria was 2-fold lower in the 3-dose group ( 8.0 % ) than in the 2-dose group ( 16.7 % ) ; the adjusted prevalence ratio ( APR ) was 0.48 ( 95 % confidence interval [ CI ] , 0.32 - 0.71 ) . LBW and preterm births were also reduced ; the prevalence of LBW was 6.6 % in the 3-dose group versus 13.3 % in the 2-dose group ( APR , 0.50 ; 95 % CI , 0.32 - 0.79 ) , and the prevalence of preterm births was 3.2 % versus 8.9 % ( APR , 0.37 ; 95 % CI , 0.19 - 0.71 ) . No significant reductions in maternal anemia or differences in safety endpoints were observed . CONCLUSIONS Adding a third dose of ITPp-SP halved the risk of placental malaria , LBW , and preterm births in all gravidae , compared with the st and ard 2-dose regimen , in this area of highly seasonal transmission with low levels of SP resistance . CLINICAL TRIALS REGISTRATION IS RCT N 74189211 BACKGROUND Intermittent treatment with sulfadoxine-pyrimethamine is widely recommended for the prevention of malaria in pregnant women in Africa . However , with the spread of resistance to sulfadoxine-pyrimethamine , new interventions are needed . METHODS We conducted a double-blind , r and omized , controlled trial involving 300 human immunodeficiency virus (HIV)-uninfected pregnant adolescents or women in Ug and a , where sulfadoxine-pyrimethamine resistance is widespread . We r and omly assigned participants to a sulfadoxine-pyrimethamine regimen ( 106 participants ) , a three-dose dihydroartemisinin-piperaquine regimen ( 94 participants ) , or a monthly dihydroartemisinin-piperaquine regimen ( 100 participants ) . The primary outcome was the prevalence of histopathologically confirmed placental malaria . RESULTS The prevalence of histopathologically confirmed placental malaria was significantly higher in the sulfadoxine-pyrimethamine group ( 50.0 % ) than in the three-dose dihydroartemisinin-piperaquine group ( 34.1 % , P=0.03 ) or the monthly dihydroartemisinin-piperaquine group ( 27.1 % , P=0.001 ) . The prevalence of a composite adverse birth outcome was lower in the monthly dihydroartemisinin-piperaquine group ( 9.2 % ) than in the sulfadoxine-pyrimethamine group ( 18.6 % , P=0.05 ) or the three-dose dihydroartemisinin-piperaquine group ( 21.3 % , P=0.02 ) . During pregnancy , the incidence of symptomatic malaria was significantly 
    Output:
    
The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate .