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WASHINGTON (AP) — A unanimous Supreme Court on Thursday threw out the convictions of two political insiders involved in the “Bridgegate” scandal that ultimately derailed the 2016 president bid of their ally, then-New Jersey Gov. Chris Christie.
The justices said there was evidence of deception, corruption, and abuse of power in the political payback saga that involved four days of traffic jams on the world’s busiest motor vehicle bridge, the George Washington Bridge spanning the Hudson River between New York and New Jersey. But “not every corrupt act by state or local officials is a federal crime,” Justice Elena Kagan wrote for the court.
In the end, the justices concluded that the government had overreached in prosecuting Bridget Kelly and Bill Baroni for their roles in the scheme. Kelly was a deputy chief of staff to Christie. Baroni was a top Christie appointee to the Port Authority, the bridge’s operator.
The court’s decision to side with Kelly and Baroni continues a pattern from recent years of restricting the government’s ability to use broad federal laws to prosecute public corruption cases. In 2016, the court overturned the bribery conviction of former Virginia Gov. Bob McDonnell. In 2010, the court sharply curbed prosecutors’ use of an anti-fraud law in the case of ex-Enron CEO Jeffrey Skilling.
Kagan wrote for the court that Kelly and Baroni had acted for “no reason other than political payback.” In devising the traffic jam, they were seeking to punish the Democratic mayor of Fort Lee, New Jersey, Mark Sokolich, after he declined to support the reelection bid of Christie, the GOP governor.
To create chaos, on the traffic-heavy first day of school in 2013, Kelly and Baroni schemed to reduce from three to one the number of dedicated lanes onto the bridge from Fort Lee. They created a traffic study as a cover story for their actions.
Kagan said that Kelly and Baroni ”jeopardized the safety of the town’s residents,” and she repeated some of their gleeful plotting in the decision. At one point, Kelly wrote what Kagan called “an admirably concise e-mail” about the plan. It read: “Time for some traffic problems in Fort Lee.” Later, after the traffic snarls began, Kelly wrote in a text, “Is it wrong that I am smiling?” Kagan noted that they then “merrily kept the lane realignment in place for another three days.”
“But not every corrupt act by state or local officials is a federal crime. Because the scheme here did not aim to obtain money or property, Baroni and Kelly could not have violated the federal-program fraud or wire fraud laws,” wrote Kagan. She grew up in New York City and is one of four justices who grew up in New York or New Jersey.
Christie, in a statement following the high court’s ruling, called the prosecutions of his former allies a “political crusade” against his administration and lashed out at prosecutors and the Justice Department under President Barack Obama, a Democrat.
“As many contended from the beginning, and as the Court confirmed today, no federal crimes were ever committed in this matter by anyone in my Administration. It is good for all involved that today justice has finally been done,” Christie wrote.
Christie denied knowing about the plan for gridlock ahead of time or as it was unfolding, but trial testimony contradicted his account and the scandal helped derail his presidential bid. On Thursday, he wrote that the prosecutions “cost the taxpayers millions in legal fees and changed the course of history.”
President Donald Trump, who emerged from a crowded GOP field in 2016 to become the White House nominee, tweeted his congratulations to Christie after the ruling. The president called the decision a “complete and total exoneration” and said there was “grave misconduct by the Obama Justice Department!” Yet as a candidate, Trump had attacked Christie by saying the governor “totally knew about” the lane closings before they happened. Christie endorsed Trump when he left the race.
Nothing in Kagan’s opinion suggested there was any misconduct by prosecutors.
The U.S. attorney’s office in New Jersey, which prosecuted Kelly and Baroni, said in a statement that the court’s decision “speaks for itself, and we are bound by that decision.”
Former U.S. Attorney Paul J. Fishman, who oversaw the prosecutions, said in a statement he was disappointed with the ruling. Christie “may try to rewrite his legacy —- and he may want to rewrite history — but the fact remains that the ‘deception, corruption, and abuse of power’ was committed … by his team on his watch.”
In a statement, Kelly said the justices’ decision “gave me back my name and began to reverse the six-and-a-half-year nightmare that has become my life.” Kelly did not ultimately serve any prison time but had been weeks from beginning a 13-month sentence when the Supreme Court agreed to hear the case.
Baroni served about three months of an 18-month sentence before he was released after the high court agreed to weigh in.
“I have always said I was an innocent and today, the Supreme Court unanimously agreed,” he wrote in a statement.
Associated Press reporters Dave Porter in New York City and Mike Catalini in Morrisville, Pennsylvania, contributed to this report.


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Iris Van Herpen: The Alexander McQueen Of Tech Geeks
As one blogger put it: “I think we just found our next fashion legend. HO. LY. SHIT.
Van Herpen manipulates technology to test all the limits of fashion. Creating pieces by combining modern techniques and traditional sewing.
Even if you don’t have a great deal of interest about fashion technology, this stuff is worth looking at . New ideas and digital technology are already having a great deal of input into the industry, whether you’re talking digitally printed fabric or 3-D creations. It will only become more exaggerated and prominent. Van Herpens’ work, is like a sneak peek into the future about where the fashion world is headed.

domain: artistic


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On Wednesday, SLAM and the National Basketball League’s (NBL) Illawarra Hawks announced a partnership for the upcoming season. The deal will see SLAM serve as the team’s primary sponsor on the front of the jersey.
The Hawks issued a press release announcing the deal with comments from multiple members of the front office including General Manager Mat Campbell:
“Today’s announcement marks a major milestone for the Illawarra Hawks ahead of what is to be the most exciting season in the club’s history. This partnership with SLAM provides synergy between two great brands that will see unprecedented international exposure for both the Hawks and SLAM, as well as the NBL and Australian Basketball.”
SLAM’s Chief Operating Officer, Dave Schnur, is also looking forward to the partnership. “We’re always looking for ways to diversify our marketing strategy,” Schnur says, “and this is a great opportunity to uniquely align with a team featuring top American talent in one of SLAM’s most popular markets.”
SLAM, meanwhile, tweeted out a picture of the jerseys in announcing the partnership.
It’s a #SLAMfam thing.
Proud to be the @illawarrahawks’ jersey sponsor. pic.twitter.com/PECC0ebx7c
— SLAM (@SLAMonline) August 15, 2019
For both parties, this is a partnership that makes sense. The Illawarra Hawks create in-roads with one of the most popular basketball magazines not just in America but globally. For a team that will see a dramatic increase in exposure this season, the Hawks aligning themselves with SLAM is a great decision that should pay huge dividends.
That latter point is a reason why SLAM partnering with Illawarra is a great decision. The Hawks are going to have a tremendous amount of exposure this season with Ball on the roster. The team will gain popularity on a global stage with fans across the world tuning into games. Having SLAM across the chest of the jersey will turn out to be a great marketing decision.

domain: news


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Mugi Kadowaki was born on Aug 10, 1992 in USA. Mugi Kadowaki's big-screen debut came with Hitori Shizuka - Season 1 directed by Hideyuki Hirayama in 2012. Mugi Kadowaki is known for Ni no Kuni II: Revenant Kingdom directed by Akihiro Hino, Claire Morgan stars as Evan and Jared Zeus as Roland. Mugi Kadowaki has got 2 awards and 2 nominations so far. The most recent award Mugi Kadowaki achieved is Blue Ribbon Awards. The upcoming new movie Mugi Kadowaki plays is Samurai Marathon which will be released on May 12, 2020.
The New York born Kadowaki Mugi began her career on television in the serial Misaki Nanbâ Wan and has since appeared alternately on the small and big screens. She had practiced classical ballet until the age of fourteen something that would later become handy. She was signed to Blooming Agency, but has since switched to Humanite. She maintains a boyish look with a short hair cut despite her appearance in Sailor Fuku to Uchujin ('Sailor Uniform And The Alien') as a schoolgirl and in Ai No Uzu (Love's Whirlpool') as someone involved in sexual adventures and orgies. Either way, she was cast as a boy in the late 2016/early 2017 touring musical Watashi Wa Shingo ('My Name Is Shingo'). She cites cooking and watching movie as favorite activities.
BirthdayAug 10, 1992
Place of BirthNew York City, New York, USA
Also knownMugi Kadowaki, 门胁麦, かどわき むぎ, 門脇麦, 카도와키 무기
2 wins & 2 nominations
Movies & TV Shows
as Yui Karasawa6.2
as Megumi Yoshizumi6.3
Ni no Kuni II: Revenant Kingdom
as Tani (voice)8.0
The Miracles of the Namiya General Store
as 9 episodes, 20166.0
as Sanami Sakamachi6.5
as Chiyuki Mitsuzuka5.7
as Makoto sagawa7.2

domain: entertainment


Calif. Called Early for Obama, Prop. 30 Leading (8:20pm)
Just 20 minutes after the polls closed in California, the Associated Press has called the state for President Obama -- and CNN, NPR and others are already projecting the president will be re-elected. California voters are deciding some very big questions tonight, in addition to choosing a president. There are 11 ballot measures that will determine funding for public education, changes to the state's Three Strikes law, whether to eliminate the death penalty and much more.
Obama Wins With Help From Calif., Feinstein Wins (8:50pm)
President Obama has won re-election tonight, with big help from California's 55 electoral votes. Dianne Feinstein is also expected to easily win re-election over somewhat token opposition from Republican Elizabeth Emken. We're also keeping a close eye on the 11 propositions on the statewide ballot. Proposition 30 -- Gov. Jerry Brown's tax measure -- is now losing by four percentage points. But as Field Poll Director Mark DiCamillo warns Scott Shafer, it's still early to read too much in to state propositions numbers, with only about 12 percent of precincts reporting.
Obama and Feinstein Win, Still Too Early to Call Calif. Propositions (9:20pm)
President Barack Obama is winning re-election tonight and carrying California -- although by a smaller margin than he did four years ago, at least at this point. Senator Dianne Feinstein is also coasting to re-election with 57 percent of the vote over Republican Elizabeth Emken.
Three Strikes Law Revision Leading, 68 to 32 Percent (9:50pm)
As Mitt Romney concedes the election to President Obama, we check in on the 11 California ballot propositions. Proposition 36, which would revise California's Three Strikes law, is currently ahead 68 to 32 percent, with 17 percent of precincts reporting. Host Scott Shafer checks in with reporter Michael Montgomery, who is with supporters of Prop. 36 in San Francisco.


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Following today's practice, Virginia Tech head coach Brent Pry told media members including our Will Locklin at a media availability that freshman QB Pop Watson has been suspended indefinitely from the team for a violation of team rules.
Brent Pry said freshman QB Pop Watson has been suspended indefinitely for a violation of team rules. #Hokies— Andy Bitter (@AndyBitterVT) September 20, 2023
It is unknown at this time the specific reasoning for Watson's suspension beyond it being a violation of team rules.
Watson had entered the fall as Virginia Tech's third-string quarterback after Watson passed Devin Farrell and Tahj Bullock on the depth chart in the spring, both of who transferred out to Rhode Island and Akron respectively following spring practice. Dylan Wittke had been pushing Watson for the third-string job but Watson received second team reps in practice last week with Grant Wells extremely limited due to injury.
For now, that leaves Virginia Tech with only two scholarship quarterbacks who are healthy and not suspended in Kyron Drones and Dylan Wittke who is currently the backup until Wells or Watson return. Beyond those two, Tech has walk-on QB Ben Locklear as the next QB up followed by true freshman walk-on QB Jackson Sigler.

domain: sports


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As I start making breakfast these words catch me flying into the kitchen: “Mum, she’s breathing on me!!!” Yeah. In that particular moment my brain decided to run the following stream of thoughts: not again this always happens when I’m about to… I can’t deal with this right now…
Your brain probably has your own unique (or not-so-unique) stream of unhelpful consciousness, I imagine. One of the ways in which it is unhelpful is running the tape with “always” and “never”. In the moment, the moment is all we have.
Our brains have a tendency to extrapolate from the here and now and generalize into always and never. I catch myself in moments when I am having a not so great kind of day (or, you know, ten minutes) and my brain says “life is hard”. An hour later, I’ve had my coffee, everyone is happily doing something, I get to sit and open a book. “Life is great”. Life remains to be all these things, continually shifting. Teaching our brain to catch the moment allows us to see this moment for what it is and not flood ourselves with “always” and “never”. It also enables us to respond to what is actually happening here and now, and not to all the stories we carry around. The words we use can increase situational stress (trigger fight-or-flight response) in the people saying them, hearing them, or thinking them. Words actually create our reality, in multiple ways. In challenging situations, if we use words that trigger us or our children, we are simply adding fuel to the fire. Even if the words remain in our head. Why not always and never?
First of all, “always” and “never” are never true ;) I remember being taught this beautiful lesson by my then 3-year old son. I walked into the living room in a very sleepy, tired mood and stepped on a block (those who know, know…). “There are always blocks everywhere” I must have said a bit too loudly, because he turned around, looked at me and replied: “There were no blocks here yesterday, and there are no blocks under the table.” Both factually correct. I had to laugh.
It matters to our own brain and ability to respond:
If we start with “she always/never” we trigger our own fight-or-flight response, and we will react to our children from that space. These words are also anger-inducing (notice next time when someone says “you never/always…” - how do you react?).
It matters to our children’s brains and their willingness to cooperate with us:
“You always/never/again” also triggers their fight-or-flight response, when they hear us say it.
In addition, we might be creating a self-fulfilling prophecy in the long-term. If we say it often enough, and they hear it often enough, there is a chance that the “always” and “never” might get a bit closer to reality than we would like.
How to move away from there…
Practice observing what is going on in the here and now, and name it for yourself and your child. In Nonviolent Communication (NVC) we call it “Observation” (without judgment, analysis etc.). A great question to practice is:
what would the camera see?
Start with moments when you’re relaxed, our brains can only learn if we are relaxed, connected, safe.
Instead of “life is great” name what exactly is so great.
“I’m having a hot cup of coffee and finishing my book. I’m loving it”
“I finished reading my paper, I really enjoyed it.”
It might seem counterintuitive, but by observing what actually brings you joy, fulfillment, allows you to not only notice these things, but also have them as a resource for moments when life is not so great.
Modeling also teaches our children to do the same.
“You put that block on top of your tower and now have a huge smile on your face!”
“When you finished that puzzle you jumped up and down!”
Experiment with doing that in moments when things are not going so great. When one child throws a block at someone’s head. When your teenager slams the door. When someone is breathing on someone else and you notice your muscles tensing. What would the camera see?
Rely on your senses, not on your judgments:
What would the camera see?
What can you see?
What can you hear?
Moving away from “always” and “never” (and other forms of judgment) and focusing on observing what is, enables us to also move away from figuring out who is wrong and who is right (in children’s conflict for example), and allows us to respond from a place of more calm.
It’s not always easy.
And it’s so very worth it.
And as always, we start with ourselves.
Some more resources here:
An article co-authored by me on the topic of words in Early Childcare settings: https://childspace.nz/.../the-space-magazine-issue-64-ebook/
On self-fulfilling prophecies: https://www.thisnthatparenting.com/self-fulfilling.../
Janet Lansbury on the concept of “sportscasting”: https://www.janetlansbury.com/.../5-benefits-of.../
Rachelle Lamb on “Observation” in NVC: https://www.rachellelamb.com/.../what-is-an-observation...

domain: psychology


Which one do you think is more environmentally friendly?
Maybe you will say glass is. However, it is very heavy and fragile and may not dispense the entire product resulting in wasted product. On the other hand, plastic may be more dangerous chemical and contain toxic plasticizers such as PVC and Phthalates.
Although, both of them, from an ecological perspective, are energy consumers which impact the environment with waste and global warming emissions that cause long-term air pollution for our planet.
The charts, in this , compare Glass vs. Plastic in regards to environmental aspect.
Economic Input-Output Life Cycle Assessment by Carnegie Mellon University Green Design Institute. Glass consumes nearly 3 times more energy to produce than plastic.
Even if plastic is better than glass, plastic still leaks toxins into the environment and remains a source of air pollution. Therefore, more research is needed to find alternative materials with fewer pitfalls.
By the way, one of the materials wit less of an effect on the environment is Polypropylene. It is manufactured from clean technology, Does not leach harmful chemicals (no Bispenol-A, no PVC plasticizers, no Phthalates), need 30% fewer resources than other plastics with 100% recyclable. In addition, it is extremely stable with no leaching or outgassing, less CO2 product during transit with greater impact resistance and resilience (no product breakage during transit).
Another plastic known as EPS, or foam, when molded releases pentane and has been studied and found to offer minor environmental impact in comparison to VOC emissions from other sources. Various aspects of pollution ingredients were analyzed within the EPS processing industry and found to offer a feasible technology with an economical justifiable solution for reduction of VOC emissions and other fumes.
For pentane abatement, odor control, and air pollution generated by various manufacturing processes, regenerative thermal oxidizers (RTO’s) provide cost effective and energy efficient solutions for manufacturing operations that produce paints, varnishes, pigments, finishing and coating of wood, metal coils, fiberglass and plastic component parts for recreational vehicles, automotive/aerospace, furniture, beverage containers, etc.
please click here, to see more information:
Glass or Plastics 12-13-12
Economic Input-Output Life Cycle Assessment, (Carnegie Mellon), University Green Design Institute, Available from: https://www.eiolca.net/
Categorised in: EPA


SYRACUSE, N.Y. -- When he sued 19 Onondaga County officials last month, Comptroller Robert Antonacci said it wouldn't cost taxpayers since he would handle the case himself. The county executive, however, disagrees.
According to County Executive Joanie Mahoney, the county law department has outsourced the case to five local attorneys, each representing a separate faction of defendants.
"To say it's not going to cost money is misleading," Mahoney said. "It's a colossal waste of time and money."
Antonacci sued 19 individuals last month, alleging that pay raises enacted for local officials are illegal, as were efforts to uphold those raises. The suit names Mahoney, Legislature Chairman Ryan McMahon, Personnel Director Peter Troiano and all county legislators as defendants.
The county law department has a conflict of interest in the matter, since they represent Antonacci, Mahoney said. Each individual being sued also has different circumstances and, therefore, a different case, she said.
For those reasons, the county outsourced the legal work. They hired:
- Robert Julian to defend Mahoney
- Costello, Cooney & Fearon to defend McMahon
- Hancock & Estabrook to defend Troiano
- William Gilberti to defend the legislators who voted "yes" on the raises
- Mackenzie Hughes to defend the legislators who voted "no" on the raises
A county spokesman said the principal attorneys' rates range from $295 to $350 per hour, but did not give specific figures.
Antonacci said he had waived any conflict and "had no problem" if the county law department chose to defend the raises. He said he wasn't aware the county wouldn't handle the case on its own and questioned the necessity of such a robust outside legal team.
"This is the dream team -- some of the finest legal minds in Central New York," he said. "O.J. Simpson didn't have it this good."
Antonacci -- who is a lawyer -- will handle the case himself. He said he has not argued a case in court in at least a decade, but doesn't think that impacts his odds.
"I like my chances," he said. "The law is the law."
Mahoney echoed the law department's opinion that it isn't the comptroller's job to determine the legality of the raises. She said that Antonacci is out of line with the suit.
"If he happened to be a medical examiner and the comptroller he couldn't overrule a certificate of death," Mahoney said.
She also said Antonacci took exception with the raises only after his name was taken out of the resolution for a raise. The comptroller's position was originally among those considered for raises, but was dropped during the legislative committee process.
The first court date for the lawsuit is scheduled for April 21. Oswego County Judge Spencer Ludington will preside over the case.


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As COVID-19 continues to spread throughout the US, healthcare facilities are racing to expand existing capacity. According to the Institute for Health Metrics and Evaluation, the peak in the US can come as early as two weeks.
The need for hospital beds alone will top 224,300 beds nationwide, and there will be a critical shortfall of 2,500 beds in the DC Metro Area. Consequently, jurisdictions impacted by this shortfall are pushing to convert arenas and hotels into temporary field hospitals.
This is where we can help, by:
- Receiving, storing and delivering medical equipment and supplies when you need it
- Managing inventory with our online warehouse management tools
- Pulling existing furniture, fixtures and equipment from hotels for storage or decommission
- Picking, packing and delivering supplies to reduce supply theft
Lab Relocation Services
The president is enlisting all public and private laboratories for COVID-19 testing. Many labs need to expand their existing capacity to fulfill this request. Having extensive experience moving labs for Fort Detrick and Walter Reed, we offer complete end-to-end lab relocation services. We specialize in disassembling, moving, setting up labs, and moving work in progress with the utmost care to minimize downtime and disruptions.
Medical Equipment and Supplies
Many healthcare facilities don’t have the capacity to receive large bulk quantities of medical supplies during this time of crisis. JK is here for you for your short- or long-term storage needs. You can view your inventory virtually through your own secure asset management portal.
In addition, we also receive medical supplies to store and deliver when area hospitals need them. We can receive your medical supplies, pick from your inventory, pack them and deliver to your facility when you need them. This helps you control and manage supply inventory costs.
Hotel to Makeshift Hospital
Furthermore, as the DC area ramps up for the peak of the COVID-19 virus, there are not enough hospital beds to accommodate the need. JK Moving is working with local and state governments to receive and/or deliver hospital equipment. From delivering cots to converting hotel rooms into hospital rooms, we can assist you with:
- Relocation services like packing, boxing, moving and installing items
- Storage options for your furniture, fixtures and equipment in our secure warehouses. For safekeeping until you are ready for their return
- Item disposal, if you don’t want things returned, can be done in a safe, environmentally friendly manner.

domain: medical


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Antimalarial drugs for preventing malaria during pregnancy and the risk of low birth weight: a systematic review and meta-analysis of randomized and quasi-randomized trials
BMC Medicine volume 13, Article number: 193 (2015)
It is known that antimalarial drugs reduce the risk of low birth weight (LBW) in pregnant patients. However, a previous Cochrane review did not evaluate whether the level of antimalarial drug resistance could modify the protective effect of antimalarial drugs in this regard. In addition, no systematic review exists comparing current recommendations for malaria prevention during pregnancy to alternative regimens in Africa. Therefore, we conducted a comprehensive systematic review and meta-analysis to assess the efficacy of antimalarial drugs for malaria prevention during pregnancy in reducing the risk of LBW.
We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for articles published up to 21 November 2014, in English or French, and identified additional studies from reference lists. We included randomized and quasi-randomized studies reporting LBW as one of the outcomes. We extracted data and assessed the risk of bias in selected studies. All pooled analyses were based on a random effect model, and we used a funnel plot and trim and fill method to test and adjust for publication bias.
A total of 25 studies met the inclusion criteria (37,981 subjects). Compared to no use, all combined antimalarial drugs were associated with a 27 % (RR 0.73, 95 % CI 0.56–0.97, ten studies) reduction in the risk of LBW. The level of antimalarial drug resistance modified the protective effect of the antimalarial drug used for prevention of LBW during pregnancy. Sulfadoxine-pyrimethamine was not associated with a reduction in the risk of LBW in regions where the prevalence of the dihydropteroate synthase 540E mutation exceeds 50 % (RR 0.99, 95 % CI 0.80–1.22, three studies). The risk of LBW was similar when sulfadoxine-pyrimethamine was compared to mefloquine (RR 1.05, 95 % CI 0.86–1.29, two studies).
Prophylactic antimalarial drugs and specifically sulfadoxine-pyrimethamine may no longer protect against the risk of LBW in areas of high-level resistance. In Africa, there are currently no suitable alternative drugs to replace sulfadoxine-pyrimethamine for malaria prevention during pregnancy.
Low birth weight (LBW) is defined as a birth weight of a live born infant of less than 2,500 g (5.5 lb) regardless of gestational age . LBW is one of the leading causes of neonatal and infant mortality in the world and may be the result of a short gestational period, intrauterine growth restriction (IUGR), or a combination of both events . Infants born with this adverse outcome are at higher risk of early growth retardation, infectious diseases, developmental delay, death during infancy and chronic disease in adulthood [2, 3]. It is estimated that over 4 million children are born each year with LBW in Africa, where malaria infection accounts for up to 560,000 (14 %) LBW infants and 11 % of LBW-related infant mortality . Malaria is a mosquito-borne infectious disease transmitted by a parasitic protozoan in the Plasmodium genus. This disease leads to maternal anemia and placental parasitemia, which are both known risk factors for LBW. This may explain the high LBW prevalence observed in regions where malaria is endemic, and hence making the disease a potentially modifiable necessary cause of LBW. Therefore, the use of antimalarial drugs appears to be one of the most appropriate interventions to prevent the deleterious effect of malaria during pregnancy and to reduce child mortality as recommended by the Millennium Development Goals (MDGs) . A recent Cochrane review published in 2014 reported that compared to placebo, prophylactic antimalarial drug use during pregnancy reduced the risk of LBW by 27 % among women in their first or second pregnancy . Previously, another meta-analysis showed that the use of three or more doses of sulfadoxine-pyrimethamine compared to two doses was associated with a reduction of the risk of LBW by 23 % among HIV-negative women .
World Health Organization (WHO) guidelines for the treatment of malaria recommend that first-line treatment should be changed if the total failure rate exceeds 10 % . Current evidence suggests that the efficacy of antimalarial drugs in preventing LBW may decrease with Plasmodium resistance , but the threshold at which these drugs will fail to reduce the risk of LBW remains unclear. An earlier meta-analysis published in 2007 showed that the level of drug resistance had no effect on the efficacy of intermittent preventive treatment (IPT) during pregnancy with sulfadoxine-pyrimethamine in reducing the risk of LBW. However, the range of resistance (19–26 %) identified in those studies was narrow, which limited the generalizability of this finding . In contrast, a cohort study conducted in central Africa in 2012 showed that the level of drug resistance may modify the effectiveness of sulfadoxine-pyrimethamine. However, this result should be interpreted with caution given the study design limitations . In addition, it is currently known that high prevalence of quintuple mutation (dihydropteroate synthase 540 E mutation, dhps 540E) and sextuple mutation (additional dhps 581G or dihydrofolate reductase, dhfr 164 L mutation to quintuple mutation) in Plasmodium falciparum infections may interfere with sulfadoxine-pyrimethamine effectiveness [12–15]. The 2014 Cochrane review did not evaluate drug resistance as a modifier of the protective effect of antimalarial drugs in reducing the risk of LBW. In addition, there is a lack of head-to-head randomized controlled trials (RCTs) that evaluate potential alternatives to IPT during pregnancy with sulfadoxine-pyrimethamine. However, given the increasing resistance to this drug, some head-to-head RCTs comparing sulfadoxine-pyrimethamine to mefloquine or antibiotics have been published recently [16–18], but no updated synthesis including these new trials are available in the literature.
Therefore, the objectives of our systematic review were: 1) to quantify the protective effect of antimalarial drugs used for the prevention of malaria during pregnancy in reducing the risk of LBW compared to no use of antimalarial drugs; 2) to examine whether the level of drug resistance and gravidity could modify the protective effect of antimalarial drugs in reducing the risk of LBW; 3) to evaluate the risk of LBW associated with the use of three doses or more of the main types of antimalarial drugs compared to the use of two doses of these drugs; and 4) to compare the risk of LBW between women taking sulfadoxine-pyrimethamine and those taking different antimalarial drug alternatives for malaria prevention during pregnancy.
Data sources and search strategy
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) . For a complete PRISMA checklist, see Additional file 1. We systematically searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for all relevant articles, reporting associations between LBW and gestational exposure to antimalarial drugs used for the prevention of malaria during pregnancy up to 21 November 2014, with the following key words: ‘malaria’; and ‘low birth weight’. Details of the search strategy for PubMed are available and described in Additional file 2. The search strategies for other databases are available upon request. The reference lists of retrieved articles were reviewed in order to identify studies that were not obtained from the preliminary literature.
Eligibility criteria for study selection included: 1) RCTs and quasi-randomized controlled trials containing data of pregnant women exposed to any type of antimalarial drug used for malaria prevention, as well as a control group (no use of antimalarial drug, placebo, or other type of antimalarial), and with data reporting the outcome of interest (LBW). RCTs were defined as clinical trials in which individuals or other units were assigned to different treatment groups using randomization allocation, such as random number, computer-generated random sequences, coin tossing and drawing lots. Quasi-randomized studies are clinical trials in which individuals or other units are assigned to different treatment groups using non-strictly random methods of allocation. Examples of quasi-random methods of assignment include alternation, date of birth and medical record number ; 2) studies published in French or English; and 3) studies that reported a P. falciparum infection. We excluded observational studies (cohort, case control and cross-sectional studies), case reports, case series and unpublished data (grey literature). Studies conducted among HIV-infected women were also discarded. Indeed, a recent meta-analysis that included HIV-positive pregnant women was available in the literature  and since then only one head-to-head RCT conducted among HIV-positive pregnant women has been published .
After the initial search strategy, two independent reviewers (FTM and AB) used the inclusion and exclusion criteria to screen titles of abstracts and assessed only full texts of relevant studies for eligibility. Disagreements were resolved by consensus. All studies that did not meet inclusion criteria were excluded with reasons provided in a flow chart (Fig. 1).
Two investigators (FTM and AB) extracted the following information in a standardized form: first author’s name; publication year; period of study; location; study design; number of women enrolled; risk of LBW in exposed and control group; dropout rates in each trial; local malaria transmission rates; and level of antimalarial drug resistance (clinical and molecular resistance).
Clinical resistance to antimalarial drugs was defined by treatment failure rates at day 14 or 28 in symptomatic children aged 6–59 months in the study region . If available, data on transmission level and therapeutic failure to antimalarial drugs in children aged 6–59 months in the study region were collected from each RCT included in our review.
We used this subpopulation to evaluate efficacy of antimalarial drugs, given that most RCTs included in our review were carried out when assessment of efficacy of these drugs involved children under 5 years old of age. Moreover, a previous meta-analysis also used a therapeutic failure rate of children under 5 years old to assess the effect of sulfadoxine-pyrimethamine resistance on the efficacy of intermittent preventive therapy for malaria control during pregnancy .
Molecular resistance to sulfadoxine-pyrimethamine was defined by the prevalence of molecular markers of P. falciparum resistance to sulfadoxine-pyrimethamine (dhps 540E) in symptomatic children aged 6–59 months. We used data obtained from a database that mapped dhfr and dhps gene distribution associated with sulfadoxine-pyrimethamine resistance in Africa [9, 12, 23]. This map is currently used as a tool to track the spatial extent and temporal patterns of sulfadoxine-pyrimethamine resistance mutations across the African continent .
This method is the gold standard for monitoring antimalarial drug efficacy and helps policy makers shape recommendations for malaria treatment and prophylaxis .
Risk ratios (RRs; intention-to-treat and per-protocol estimates) along with 95 % confidence intervals (CIs) were extracted from all included studies. When the measure of association was not reported, we calculated unadjusted risk ratios by means of the Mantel–Haenszel chi-squared test. Therefore, we used the risk ratio as the main effect measure in this review.
Risk of bias in individual studies
The risk of bias for each study included in the review was assessed independently by two authors using the Cochrane Collaboration’s tool for assessing risk of bias of RCTs . Disagreement was resolved through consensus after discussion in integrative session. The tool covers six bias domains: 1) sequence generation describes the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups; 2) allocation concealment describes the method used to conceal the allocation sequence in sufficient detail to determine whether intervention allocations could have been foreseen before or during enrolment; 3) blinding of participants and personnel describes all measures used, if any, to blind trial participants and researchers from knowledge of which intervention a participant received; 4) incomplete outcome data describes the completeness of outcome data for each main outcome including attrition and exclusions from the analysis; 5) selective reporting describes how selective outcome reporting was examined and what was found; and 6) other source of bias describes any important concerns about bias not covered in the other domains in the tool . Based on empirical and theoretical considerations , RCTs with inadequate random sequence generation, allocation concealment, attrition  or reporting bias were considered as studies with a high risk of bias. When sufficient information was not provided on these different domains of bias to allow a definite judgement, we considered that the risk of bias was unclear. In contrast, when a study was free of these biases, we considered the risk of bias as low.
We calculated the summary risk ratios and 95 % confidence intervals using a random effect model (method of DerSimonian and Laird) due to differences between study populations and interventions . This model considers the variation within and between RCTs in their calculation of the overall effect size . Given that the RCTs included in our review were carried out across different countries in Africa, with different populations, interventions and levels of antimalarial drug resistance [9, 12, 23], we assumed that the random effect model was the most appropriate model to calculate the summary estimate for all analyses.
In the sensitivity analysis, we used a fixed effect model to test the robustness of our findings . Pooled estimates of each meta-analysis and estimates of individual studies also with their 95 % CI were presented in a forest plot. Heterogeneity was explored graphically and quantified with the I2 statistic, which provides the percentage of the variability in effect estimates that is due to heterogeneity rather than sampling error (chance) . When the value of the I2 statistic was found to be higher than 50 %, representing significant heterogeneity , we identified outliers using a Galbraith plot. We attempted to explain this heterogeneity by stratification according to the level of clinical resistance to antimalarial drugs (treatment failure rates in symptomatic children at day 14 or 28), gravidity and risk of bias of studies included.
To investigate the association between clinical resistance and the efficacy of antimalarial drugs in reducing the risk of LBW, we used a 10 % threshold for treatment failure rate, which is the current cut-off recommended by the WHO for policy change in malaria areas . We also restricted our analysis of trials conducted in East Africa, where the prevalence of the dihydropteroate synthase 540E mutation (a proxy of high-level sulfadoxine-pyrimethamine resistance) exceeds 50 %, to examine the association between molecular resistance to sulfadoxine-pyrimethamine and its efficacy in reducing LBW . This threshold for molecular markers has also been used, as recommended by the WHO, stating that intermittent preventive treatment of infants (IPTi) with sulfadoxine-pyrimethamine should not be implemented when the prevalence of the dhps 540E mutation among infected individuals exceeds 50 % .
We evaluated publication bias by visual inspection of a funnel plot (eyeball test) and by Egger’s  and Begg’s test , and adjusted for possible publication bias by means of the trim and fill method . We performed a sensitivity analysis with a fixed effect model (inverse variance method) and conducted additional analysis by removing outliers identified by a Galbraith plot.
We also investigated the influence of each individual study on the overall meta-analysis summary estimate after removal of each trial one at a time from the meta-analysis. We quantified the difference between risk estimate of trials with low risk of bias compared to trials with high risk and unclear risk of bias using random effect meta-regression in our main meta-analysis. Pooled analysis was based on intention-to-treat estimates when provided in the trial. Otherwise, per-protocol estimates were used. All analyses were performed using Stata version 12.1 (StataCorp LP, College Station, TX, USA).
A total of 1,306 articles were initially identified. After removing duplicates, 818 articles remained for further consideration. Screening article titles and abstracts led to the exclusion of an additional 730 articles, and the assessment of 88 full-text articles for possible inclusion. After reviewing the reference list of eligible articles, five additional articles were added for possible inclusion. Of those 93 articles, 25 met the inclusion criteria [16–18, 32–53] and 68 were excluded. The list of the reasons for the exclusions is provided (Fig. 1). The flow of studies through the screening process of the review is shown in Fig. 1 and reported based on PRISMA guidelines.
Data from 37,981 pregnant women across the included studies (range: 266 to 5,775) were analyzed in our review. Ten studies compared any type of antimalarial drug (chloroquine, sulfadoxine-pyrimethamine, mefloquine, dapsone-pyrimethamine) to a placebo or no use of antimalarial drug; five studies compared three doses or more versus two doses of sulfadoxine-pyrimethamine; two studies compared weekly doses versus two doses of chloroquine; five studies compared IPT with sulfadoxine-pyrimethamine versus weekly chloroquine; two studies compared IPT with sulfadoxine-pyrimethamine versus IPT with mefloquine; and the remaining studies compared IPT with amodiaquine-sulfadoxine-pyrimethamine compared to IPT with sulfadoxine-pyrimethamine alone (one study), and IPT with sulfadoxine-pyrimethamine versus daily cotrimoxazole (one study).
The median dropout rate of studies included in the review was 14.1 % (interquartile range (IQR): 8.55–21.45 %; range: 1.5–51 %). The rate of loss to follow-up did not significantly differ between the exposed and control group when reasons were provided in the study. Four trials showed a significant difference in the rate of adverse events between the exposed and control group [16, 39, 40, 46]. The first trial conducted by Clerk and colleagues showed that women taking amodiaquine-sulfadoxine-pyrimethamine were more likely to report an adverse event than those taking sulfadoxine-pyrimethamine alone (RR 1.88, 95 % CI 1.70–2.07), but no women were withdrawn from the study because of an adverse event . The second trial carried out in Thailand by Nosten and colleagues reported a significant difference of the rate of stillbirth between women who were taking mefloquine compared to women exposed to a placebo (P <0.01) in the first phase of the study, but as this increase was unexpected the author conducted a second phase in the trial and pooled the data from the two periods that showed no significant difference in the rate of stillbirth between women exposed to mefloquine and control (P = 0.13) . The third trial, which was a multicentre study, showed that the number of women with serious adverse events was higher in the mefloquine group compared to the sulfadoxine-pyrimethamine group, but a causal relationship could not be established by members from the data and safety monitoring board (DSMB) of the trial . The fourth trial conducted by Briand and colleagues in Benin showed that adverse events were more commonly associated with the use of mefloquine compared to sulfadoxine-pyrimethamine (prevalence: 78 % versus 32 %; P <0.01) .
No significant differences in the rate of adverse events or foetal loss were found in the remaining studies [17, 18, 32–38, 41–45, 47–53]. Ten trials (40 %) reported using intention-to-treat analysis [17, 18, 32, 33, 41, 43, 44, 47, 49, 53]; two trials (8 %) carried out a modified intention-to-treat analysis [16, 40]; and the remaining 13 studies (52 %) used a per-protocol analysis [34–39, 42, 45, 46, 48, 50–52]. A summary of included studies evaluating the use of antimalarial drugs for preventing malaria during pregnancy and the risk of LBW is shown in Additional file 3: Table S1.
Risk of bias in individual studies
Of the 25 studies included, only four studies (16 %) were considered as having a low risk of bias [16, 37, 49, 53] and 17 studies (68 %) were judged as presenting a high risk of bias [17, 18, 32–36, 38, 43–48, 50–52]. The risk of bias was unclear in the remaining four studies (16 %) [39–42]. A table including the risk of bias of studies is available and described in Additional file 4: Table S2.
Synthesis of the results
Antimalarial drugs for prevention of malaria during pregnancy compared to no use of antimalarial drug and risk of LBW: meta-analysis
When all combined antimalarial drugs used for prevention of malaria during pregnancy were compared to no use of antimalarial drug, we detected a significant 27 % reduction in the risk of LBW (RR 0.73, 95 % CI 0.56–0.97; I2 = 70 %, P <0.01, ten studies) (Fig. 2). As heterogeneity was high (hinging I2 statistic = 70 %), we identified an outlier across the ten trials using a Galbraith plot (Additional file 4: Figure S1). The excluded outlying study used a cluster randomized design in which the units of analysis (health centres) were not selected randomly; this may introduce a selection bias. In addition, statistical analysis did not take into account efficiently variability within and between clusters. This may explain why this study was an outlier in our analysis.
After removal of this outlier, heterogeneity between studies decreased from 70 % to 44.1 % (RR 0.86, 95 % CI 0.70–1.05; I2 = 44.1 %, P = 0.074, nine studies) (Additional file 5: Figure S2). There was a suggestion of a publication bias (Egger’s test, P = 0.033; Begg’s test, P = 0.032) (Additional file 5: Figure S3), but the trim and fill method indicated no missing studies with a crude estimate similar to the adjusted estimate (Additional file 5: Figure S4 and Table S3). In a sensitivity analysis, we performed a meta-analysis using a fixed effect model, which also showed a significant reduction in the risk of LBW when comparing all the combined antimalarial drugs for prevention of malaria during pregnancy to no use of these drugs (Additional file 5: Figure S5). There was no influence of each individual study on the overall meta-analysis summary estimate after removal of each trial one at a time from the meta-analysis (Additional file 5: Table S4). When we stratified according to the risk of bias, the treatment effect estimate was different in each subgroup of risk of bias with overlapping confidence intervals (test for heterogeneity between subgroups: P = 0.075) (Additional file 5: Figure S6), but no statistically significant difference between each risk estimate was seen after using a meta-regression analysis (P >0.05) (Additional file 5: Table S5).
Association between level of drug resistance and gravidity and the efficacy of antimalarial drugs in reducing LBW: meta-analysis
When all the combined antimalarial drugs used for prevention of malaria during pregnancy were compared to no use of antimalarial drug according to the level of drug resistance based on therapeutic failures at day 14 or 28, we found a significant reduction in the risk of LBW in trials conducted in regions where the level of antimalarial drug resistance was less than 10 % (RR 0.29, 95 % CI 0.18–0.48; I2 = 0.0 %, P = 0.479, two studies), but not in trials conducted in regions where the level of antimalarial drug resistance was over 10 % (RR 0.92, 95 % CI 0.65–1.31; I2 = 42.3 %, P = 0.177, three studies) (test for heterogeneity between subgroups: P <0.01) (Fig. 3). When sulfadoxine-pyrimethamine was compared to no antimalarial drug use in trials conducted in East Africa, where the level of sulfadoxine-pyrimethamine resistance based on the prevalence of 540E mutation exceeds 50 %, we found no significant reduction of the risk of LBW (RR 0.99, 95 % CI 0.80–1.22; I2 = 0.0 %, P = 0.376, three studies) (Additional file 5: Figure S7). After stratifying by gravidity, we also noted a significant reduction in the risk of LBW in primigravidae and secundigravidae (RR 0.59, 95 % CI 0.39–0.90; I2 = 72.4 %, P = 0.01, seven studies), but there was no reduction among higher-order multigravidae (RR 0.92, 95 % CI 0.71–1.20; I2 = 16.5 %, P = 0.274, three studies); however, confidence intervals overlapped (test for heterogeneity between subgroups: P = 0.102) (Fig. 3).
Three doses or more of the main types of antimalarial drugs compared to two doses of these drugs and risk of LBW: meta-analysis
When three doses or more of sulfadoxine-pyrimethamine were compared to two doses of this drug, we found a significant 25 % reduction in the risk of LBW (RR 0.75, 95 % CI 0.59–0.96; I2 = 27.1 %, P = 0.241, five studies) (Fig. 4). No evidence of publication bias was detected after inspection of the funnel plot (Egger’s test, P = 0.901; Begg’s test, P = 1.000) (Additional file 5: Figure S8). In a sensitivity analysis, a significant reduction of LBW was also found when using a fixed effect model (RR 0.77, 95 % CI 0.63–0.93; I2 = 27.1 %, P = 0.241, five studies) (Additional file 5: Figure S9). There was no influence of each individual study on the overall meta-analysis summary estimate after removal of each trial one at a time from the meta-analysis (Additional file 5: Table S6).
When weekly chloroquine chemoprophylaxis was compared to two doses of chloroquine, no significant reduction in the risk of LBW was found (RR 1.13, 95 % CI 0.70–1.83, two studies) (Fig. 4).
Sulfadoxine-pyrimethamine compared to antimalarial drug alternatives for malaria prevention during pregnancy and risk of LBW: meta-analysis
Compared to chloroquine, sulfadoxine-pyrimethamine was significantly associated with a 40 % reduction in the risk of LBW (RR 0.65, 95 % CI 0.50–0.84; I2 = 30.1 %, P = 0.221, six studies) (Fig. 5). After visual inspection of the funnel plot, there was no evidence of publication bias using Egger’s test (P = 0.389) and Begg’s test (P = 0.327) (Additional file 5: Figure S10). In addition, we conducted a sensitivity analysis using a fixed effect model, which showed a reduction of LBW when sulfadoxine-pyrimethamine was compared to chloroquine (RR 0.61, 95 % CI 0.48–0.77) (Additional file 5: Figure S11). When sulfadoxine-pyrimethamine was compared to mefloquine, the risk of LBW was similar between the two groups (RR 1.05, 95 % CI 0.86–1.29; I2 = 32.2 %, P = 0.225, two studies) (Fig. 5).
There was no association with a reduction in the risk of LBW when sulfadoxine-pyrimethamine was compared to sulfamethoxazole-trimethoprim (RR 0.62, 95 % CI 0.25–1.52, one study) (Fig. 5).
When the combination azithromycin-sulfadoxine-pyrimethamine was compared to sulfadoxine-pyrimethamine alone, we detected a significant reduction in the risk of LBW (RR 0.64, 95 % CI 0.43–0.97, one study) (Fig. 5).
This systematic review and meta-analysis showed that antimalarial drugs used for malaria prevention during pregnancy was associated with a 27 % reduction in the risk of LBW when compared to no use of these drugs. These findings corroborate a previous Cochrane review, which found an association between the use of these drugs and the reduction of the risk of LBW in women in their first and second pregnancy (RR 0.73, 95 % CI 0.61–0.87, eight studies) . Our reviews showed that antimalarial drugs were effective at reducing the risk of LBW in regions where the level of drug resistance was less than 10 %, but not in regions with a level of drug resistance over 10 %. However, our results should be interpreted with caution given the limited number of studies included in each subgroup.
Similar findings were reported recently in a study showing that the effectiveness of sulfadoxine-pyrimethamine in preventing LBW varied with level of resistance to this medication . In contrast, an earlier meta-analysis published in 2007 showed that evaluating sulfadoxine-pyrimethamine resistance on the efficacy of intermittent preventive therapy for malaria control during pregnancy found no association with the level of drug resistance . However, this finding was based on a small number of studies conducted in a region with a narrow range of resistance to sulfadoxine-pyrimethamine (19–26 %), which may explain the lack of association. In addition, we demonstrated that sulfadoxine-pyrimethamine was not associated with a reduction in the risk of LBW in East Africa, where the prevalence of dihydropteroate synthase 540E mutation exceeds 50 %. Moreover, the sextuple mutant parasite has also been recently reported in this region . Indeed, it is known that these mutations may interfere with sulfadoxine-pyrimethamine effectiveness [12–15].
Three RCTs were included in our meta-analysis of East Africa [41, 49, 53]. The first one was conducted in Kabale in Uganda , a region where sextuple mutant haplotype (dhps 540E mutation with additional dhps 581G) were prevalent . But, the second and third RCTs were performed in Mozambique where this mutation has not been reported yet [41, 53]. Nonetheless, as it might take an average of 5 years between the collection of information on molecular markers and the date of publication of the results , the mutation might be present in Mozambique but not yet detected.
In contrast, another meta-analysis comparing the risk of LBW between women taking three or more doses of sulfadoxine/pyrimethamine to those taking two doses reported a similar risk of LBW in regions with prevalence of dihydropteroate synthase 540E mutation of less or over 50 % . A possible explanation was that an extra dose of sulfadoxine-pyrimethamine compensates for any reduction in efficacy of the two-dose regimen resulting from a progressive decrease of the duration of post-treatment prophylaxis. Nevertheless, this finding should be interpreted with caution. Indeed, it was based on a subgroup analysis with only two studies conducted in regions where the prevalence of dhps 540E mutation was over 50 % and five studies conducted in regions where the prevalence of dhps 540E mutation was less than 50 %. Therefore, a lack of statistical power could not be completely ruled out. However, the lack of association found in that study may also be explained by the fact that the two RCTs were conducted in regions where sextuple mutant parasites were absent.
Of note, East Africa is also a region where the prevalence of HIV infection is high; therefore, our findings highlight the need to address the association between HIV and malaria co-infection and the occurrence of adverse pregnancy outcomes, such as LBW. Our study failed to demonstrate an interaction between gravidity and the effect of antimalarial drugs on the risk of LBW; however, this finding should be interpreted with caution given the low statistical power.
Compared to two doses of sulfadoxine-pyrimethamine, three doses or more was significantly associated with a 25 % reduction in the risk of LBW in this review. This result was similar to a recent meta-analysis, which showed a lower risk of LBW when three doses or more of sulfadoxine-pyrimethamine were compared to two doses .
When sulfadoxine-pyrimethamine was compared to mefloquine, the most promising alternative for malaria prevention during pregnancy, the risk of LBW was similar between the two groups. In contrast, when combination azithromycin-sulfadoxine-pyrimethamine was compared to sulfadoxine-pyrimethamine alone, we noted a 36 % reduction in the risk of LBW. However, we could not draw a definite conclusion given the limited data available in the literature. Furthermore, additional medicines for the prevention of malaria in pregnancy are the subject of trials underway through the Malaria in Pregnancy (MiP) Consortium.
To our knowledge, this is the most comprehensive and updated synthesis of all antimalarial drugs used for the prevention of malaria during pregnancy and the risk of LBW. In addition, our study evaluated the association between antimalarial drug resistance (based on treatment failures of antimalarial drugs at day 14 or 28 and on the prevalence of molecular markers of sulfadoxine-pyrimethamine resistance in symptomatic children aged 6–59 months) and gravidity, and the protective effect of antimalarial drugs in reducing LBW. Furthermore, we attempted to explain heterogeneity between the studies and performed sensitivity analyses that showed the robustness of our results.
Nevertheless, this review has some limitations. First, measurement of antimalarial drug resistance was performed on infected children with acute malaria aged 6–59 months, which may not reflect the true resistance in asymptomatic pregnant women as they might still have partial immunity. Given that, it is currently recommended to use asymptomatic pregnant women instead of children under 5 years of age to assess the efficacy of IPT during pregnancy with sulfadoxine-pyrimethamine at different study sites . Therefore, efforts are made to test and incorporate this new approach within national malaria control programs across Africa . However, translating WHO recommendations into national malaria policy remains challenging. A study showed a discrepancy between current WHO recommendations during pregnancy and the national malaria policy in five African countries . Therefore, considering that no alternative for sulfadoxine-pyrimethamine will be available soon, the use of therapeutic failure to sulfadoxine-pyrimethamine in children under 5 years old still brings additional evidence to determine the threshold at which this drug fails to provide any benefit during pregnancy, especially in sites where data on molecular markers of P. falciparum resistance to sulfadoxine-pyrimethamine are not yet available, or data on efficacy of IPT with sulfadoxine-pyrimethamine measured among asymptomatic pregnant women in malaria sentinel sites are lacking .
Second, data on folic acid use, impregnated bed nets or the pattern of transmission of malaria were not available for each study to assess whether these factors may affect the protective effect of antimalarial drug in reducing LBW.
Third, approximately two-thirds of the studies included in this systematic review had a high risk of bias; however, after stratification of studies according to the risk of bias (high, unclear and low risk of bias) in the main meta-analysis, we found no significant difference between risk estimates of each subgroup using a meta-regression analysis. Although there was a limited number of RCTs in each stratum of risk of bias, a recent simulation study showed that linear regression models require only two subjects per variable for an adequate estimation of regression coefficients, standard errors and confidence intervals . Given that a meta-regression concept is similar to simple linear regression , we are confident that our analysis gave an unbiased regression coefficient estimate even though it does not rule out a lack of statistical power. In addition, two out of four (50 %) studies with low risk of bias included in our main meta-analysis were conducted in regions where the prevalence of dihydropteroate synthase 540E exceeds 50 %. This may also explain the variability of the risk estimates between studies stratified according to the risk of bias (clinical heterogeneity).
Fourth, the median dropout rate of studies included in the review was 14.1 %. Furthermore, half of the studies reported using intention-to-treat analysis, but it was in fact an available case analysis because data were analyzed according to the assigned intervention for every participant for whom the outcome was obtained and no missing data were imputed. This may introduce a selection bias and limit the generalizability of this finding. However, when the rate of loss to follow-up and the rate of adverse events and foetal loss were provided in those trials, there was no significant difference between the exposed group and the control group in our main meta-analysis.
Fifth, we did not include unpublished data in our review, which may introduce a reporting bias in meta-analyses. Nevertheless, there was no evidence of publication bias when using a funnel plot or trim and fill method.
Sixth, there was no control for the dose or the method of delivery of mefloquine (IPT or weekly) in the study conducted by Nosten and colleagues in Thailand, which is a source of potential bias. However, when each study was removed one at a time from the main meta-analysis, there was no influence of each individual study on the overall meta-analysis summary estimate.
Seventh, the safety of antimalarial drugs during pregnancy is a concern. Despite the fact that many RCTs have reported antimalarial side effects, very few use appropriate methods of pharmacosurveillance to detect and evaluate safety signals. Therefore, there is a need to implement standardized methods of collecting and reporting adverse events in RCTs, which will help to build a centralized pharmacovigilance database and efficiently identify safety concerns.
Eighth, LBW may be a consequence of small for gestational age (SGA), preterm birth (PTB), or a combination of both. SGAs are not systematically reported in RCTs as an outcome of interest. In our review, only one RCT has reported SGA as one of the outcomes . However, a recent Cochrane systematic review and meta-analysis showed that antimalarial drugs were not associated with PTB . Another meta-analysis also showed no difference in PTB when three doses or more of sulfadoxine-pyrimethamine were compared to two doses of this drug . Therefore, the association found with LBW may mainly reflect an association with fetal growth rather than with PTB. Nonetheless, further RCTs assessing both SGA and PTB are needed.
Ninth, there is a potential for misclassification of the outcome of LBW as the timing of measurement, method of gestational age estimation and details on the scales used for birth weight were not often provided in RCTs included in our review. This may introduce a non-differential outcome misclassification, which may bias estimates toward a null effect. However, this limitation regarding timing of measurement, method of gestational estimation and scales used for birth weight is common for RCTs conducted among pregnant women in malaria-endemic regions . This highlights the need for a standardized method for birth weight measurement and reporting in future studies.
In summary, prophylactic antimalarial drug use during pregnancy is associated with a reduction in the risk of LBW. There was a dose–response relationship in terms of risk reduction of LBW when three doses or more of sulfadoxine-pyrimethamine were compared to two doses. However, the level of antimalarial drug resistance but not gravidity modified the protective effect of antimalarial drug used for prevention of malaria during pregnancy in reducing the risk of LBW. Sulfadoxine-pyrimethamine may no longer be effective at preventing the risk of LBW in East Africa. To date, there are no suitable alternative drugs to replace sulfadoxine-pyrimethamine for malaria prevention during pregnancy in Africa but additional medicines for the prevention of malaria in pregnancy are the subject of trials underway through the MiP Consortium.
Our study supports the current WHO recommendation for IPT with three doses or more of sulfadoxine-pyrimethamine during pregnancy for malaria prevention. However, there is an urgent need to re-evaluate the efficacy of IPT during pregnancy with sulfadoxine-pyrimethamine, especially in East Africa given the increase of resistance. Also, additional medicines to replace this medication are needed as no suitable alternative drug is available. The continued monitoring of the effectiveness of IPT during pregnancy with sulfadoxine-pyrimethamine in Africa is essential.
Data and safety monitoring board
Intermittent preventive treatment
Intermittent preventive treatment of infants
Intrauterine growth restriction
Low birth weight
Millennium Development Goal
Malaria in Pregnancy
Preferred Reporting Items for Systematic Reviews and Meta-Analysis
Randomized controlled trial
Small for gestational age
World Health Organization
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This research was funded by the Réseau Québécois de Recherche sur l’Usage des Médicaments (RQRUM). The authors would also like to thank Mr Patrice Dupont, librarian at the Faculty of Medicine of the University of Montreal, who kindly assisted with the search strategy.
AB is the Director of the Réseau Québécois de recherche sur le médicament (RQRM). SP is a steering committee member for the RQRM. FTM, SC, TB, FS, OS and LB are members of RQRM. These authors declare that they have no conflict of interest. The funders had no role in the study design, data collection and analysis, writing and decision to submit the manuscript for publication.
AB and FTM conceived the study. FTM and AB performed collection and extraction of data. FTM analyzed the data and AB supervised the analysis. FTM, SC, TB, FS, OS, SP, LB and AB participated in the assessment of the risk of bias in studies included in the review. FTM drafted the first manuscript. SC, TB, FS, OS, SP, LB and AB revised and approved the final manuscript. All authors read and approved the final version of the manuscript.
FTM is the recipient of the Sainte-Justine Hospital Foundation and the Foundation of Stars scholarship (Faculty of Pharmacy of the University of Montreal) and is a scholarship holder of the Canadian Network for Advanced Interdisciplinary Methods (CAN-AIM) for comparative effectiveness research. AB is recipient of a career award from the Fonds de recherche du Québec – Santé (FRSQ) and is on the endowment Research Chair of the Famille Louis-Boivin on Medications, Pregnancy and Lactation at the Faculty of Pharmacy of the University of Montreal.
PRISMA checklist. (DOCX 30 kb)
Search strategy, PubMed. (DOCX 12 kb)
A summary of included studies. (DOCX 44 kb)
Risk of bias assessment of each RCT. (DOCX 26 kb)
Sensitivity analysis and test for publication bias. (DOCX 85 kb)
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Cite this article
Muanda, F.T., Chaabane, S., Boukhris, T. et al. Antimalarial drugs for preventing malaria during pregnancy and the risk of low birth weight: a systematic review and meta-analysis of randomized and quasi-randomized trials. BMC Med 13, 193 (2015). https://doi.org/10.1186/s12916-015-0429-x


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For someone who writes and manages a food blog felicitously named, Hooked on Heat, it comes as a surprise to many when I confess that until very recently, say a couple of years ago, I belonged to the clan of folks who shied away from all things spicy. Ironically, it always petrified my Mom how her first-born could ever be averse to eating spicy food. Being one who can’t swallow a meal that lacks in the redness that can only be born out of the addition of hand-ground chillies, not once did she smile while separating my portion of the daily meal before spicing it up for the rest of the family.
As the years passed, I began to discover my taste preference and my spice level tolerance grew along with it. So much so, that it surprised my Mom a few days ago, how much heat I can actually tolerate when it comes to my favourite foods. Malay food, obviously being one of them. Like two long lost best friends, Mom and I have been spending lots of time bonding in the kitchen over gossip and spice bottles. She, imparting her wisdom and showing me the tricks of the trade, and me, trying to grasp as much information as I can during the six short weeks that she’s here. And amidst it all, Hubby Dear has been his most happiest with the wide spread Malay dishes that Mom lays on the dinner table with such ease.
A few days ago, much to her delight, she discovered a jar of Sambal Olek in my fridge, which only motivated her more to enter the kitchen and whip something up. Over a discussion of what we could try next, I thought of a dish that I chanced upon a few years ago on our trip to Malaysia. Whenever I find a recipe that works for me, I know that it can only get better from there. Whether it’s one concocted from my very own imagination, a desperate attempt to imitate something I happened to come across that just took my breath away, or one that a close friend solemnly swears by, I know that if I like it on my first try, then there won’t be any looking back. It took me only a few seconds before I could describe what I had in mind, and Mom was set to get to work.
The verdict, I licked my plate clean, and now have another favourite to add to my repertoire!
AYAM MASAK MERAH
RED CHILLI CHICKEN
Prep time: 25 min | Cooking time: 20 min | Serves: 2 as a main, 4 as a side
2 large chicken breasts, diced into 1-inch cubes
1 small onion
1 medium-sized tomato
2 lemon grass stalks, discarding the rough green tops
1 tsp ginger-garlic paste
2 tbsp sambal olek / chili paste
1/2 tsp turmeric powder
2 tbsp light cooking oil
salt, to taste
water, as needed
MARINATE chicken in salt and turmeric, and set aside for 20-25 minutes.
BLEND onion, tomato and lemon grass to a smooth fine paste, adding a little water if necessary.
SAUTE the marinated chicken in hot oil till lightly browned, and set aside. In the same pan, fry ginger-garlic paste, Sambal Olek and onion-tomato-lemon grass paste, stirring continuously till sit tarts to give out oil from the sides.
ADD in chicken, salt and water if necessary, and stir fry till chicken in cooked through and the flavours absorbed. Serve piping hot with coconut rice and tall glass of iced lemonade.

domain: food


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The handbook will be a useful guide to explain the disciplinary process and details the changes that have taken place over the last few years – principally the introduction of the match based disciplinary system, and the adoption of this system for youth football.
From the 2012-13 season the RAF FA will be enforcing all late addtional fines.
This year’s guide also includes videos and resources that will go into greater depth to explain the disciplinary process.
Introduction from Mark Ives, Disciplinary Manager
Processing Misconduct Charges
Member Services – a walk through guide
Suspension Notification Form
Sending Off Paperwork
Board of Appeal
Alternate Charge Notification
Multiple Charge Notification
Plus there is a new Leagues section to provide guidance for administrators regarding the Powers and Duties of the League.
Click to open FA Discipline Handbook 2012-13

domain: library


In addition to that, switch off appliances and lights that are not in use
There are various challenges that homeowners face when it comes to cooling and heating their multi-story buildingsâ€¦ It is even more challenging in Summer since hot air rises, meaning that the un-even temperatures in your upper rooms are likely to be higher than those on the lower floor, however unluckyly, the challenge applies even when a single has a enjoyable unit, then nonetheless, it is important to find a way to keep the upper rooms of your beach house cool. It is even better if this can be achieved without incurring a lot of extra costs, however the first thing is to find ways to block the heat, for instance, you could invest in the right drapes or curtains, then choose the kind of drapes that block out sun in Summer to minimize temperature increase, especially while both of us were in the morning. Close the drapes and curtains. In addition to that, switch off appliances and lights that are not in use. Use energy-efficient lighting since they have brighter light and less heat, which you need to go for, then ask your Heating and Air Conditioning serviceman to explain how to adjust the floor air vents downstairs, while at it, be cautious not to close the vents since this can entirely trigger pressure troubles in your Heating and Air Conditioning system, thus creating a new level of challenges. When done right, this could help push more chilly air to the upper floors, however you can also consider installing ceiling fans as they make a significant difference in summer. The air from the A/C will help create a cooling effect and supply your cooling system a boost such that it does not have to overwork to deliver.


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Salix, PA Medicare Supplement Insurance
To get the best Medicare Supplement insurance in Salix, PA, it is important to compare your options. Our website enables you to do that quickly and efficiently. Simply enter your Zip at the top and click Compare Options button. You will be taken to a page with a list of the best insurance carriers in your Cambria area. We recommend comparing quotes from at least 3 companies before settling on a coverage. This way you can make sure you are not overpaying on your Medigap premium.If you have been thinking about getting some type of supplemental health insurance, and you have recently retired, Medigap insurance is available for those that are over the age of 65. This is supplemental insurance that you absolutely need to have if you are going to rely upon Medicare. Although having national insurance coverage is good, it's not enough. People that do not have supplemental coverage often spend tens of thousands of dollars extra every year just to cover the costs of hospitalizations, tests, and prescription drugs. In order to offset this, Medigap insurance was created and is available from many different companies.
How Do You Get This Type Of Insurance?
Are There Some That Are Better Than Others?There are obviously going to be some policies that are going to surpass others. For example, there are many that are very affordable but only cover a portion of the possible bills that you may receive. Others will be several hundred dollars a month, but you will not have to pay for anything, not even a deductible, and this is probably what you will want to get. Several companies will offer these full coverage Medigap policies. Simply choose one that has an affordable rate. You can also read reviews online of the different companies that offer these Salix, Pennsylvania Medicare supplemental insurance policies and select one based upon what other people have said.
The thought of having to pay tens of thousands of dollars in additional medical costs is enough to motivate anyone to look into Medigap policies. It is only by submitting information to these different companies, or going through a website that can get multiple quotes sent directly to you, that you will be able to find the best one that will fit your budget and provide the proper coverage.
More Pennsylvania Cities Nearby:
More Insurance Tips for Salix, Pennsylvania
Health insurance policy these times can be hard to uncover without going on a deep lookup and comprehension just what it is that you are searching for. With diverse varieties of guidelines offered and a lot of different variables to consider, you need tips and guidance like that supplied in this write-up to get you on the very best search.
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As your kids age into older people, their health insurance protection will ultimately run out. You need to have to start talking to them early (say, in the previous two many years of college) about their insurance demands so that they recognize how the transition will happen. Because numerous businesses are slicing benefits, mothers and fathers are keeping youngsters on their procedures lengthier and longer, but this gets high-priced. Probably the ideal tips is to stage out the benefits of full-time work which will supply them with their possess impartial wellness coverage.
When it really is time for open up enrollment, evaluate your demands when it comes to health insurance policy. Your insurance coverage demands can quickly change as your overall health alterations and your family members grows. You can also make adjustments to vision, dental and other insurance policies choices.
No matter what, make positive you have some sort of health insurance policies. The expenses that pile up from an crisis when you don't have insurance coverage, can result in you to go into individual bankruptcy or spend the rest of your lifestyle paying out for one particular accident or health situation. The expense of uninsured medical bills is also large to threat. Get protection no make a difference what.
Just before re-enrolling with your current well being insurance policy company, examine to see if their insurance policies are changing. Some firms are rising their charges, and if yours is, you will come to feel it when you re-enroll. Examine around with other insurance businesses to make certain you are even now acquiring the best deal accessible.
If you have lately missing a task, signing up for COBRA insurance policy is the quickest correct to keeping you lined, nevertheless it is not the cheapest. COBRA allows you to hold the exact same insurance coverage protection that you experienced with your employer nevertheless you will be spending the full costs which can get fairly high-priced.
Your employer might provide you with a list of health insurance policies providers to choose from. It is a great thought to request your co-personnel, but also doctors and nurses you know, which one they have had the very best expertise with. It is not just what is composed in your plan, but how it is carried out that issues!
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domain: finance


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From all of us here at Spec Faith to all of you and yours: wishing you a Happy New Year, filled with a multitude of opportunities to praise and honor God Most High. Just a reminder that there will be […]
Best known for her aspirations as an epic fantasy author, Becky is the sole remaining founding member of Speculative Faith. Besides contributing weekly articles here, she blogs Monday through Friday at A Christian Worldview of Fiction. She works as a freelance writer and editor and posts writing tips as well as information about her editing services at Rewrite, Reword, Rework.

domain: literature


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So thought the cast as they headed to the Kings v San Jose Sharks game at the Staples Center on October 12th. Nice of the other two to come out and support him, which gives the impression that at least the men on this show can get along with each other off the set.
Here’s the boys – Tristan Wilds, Dustin Milligan, and Ryan Eggold – at the premiere for The Secret Life of Bees, which Tristan is in.
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And while things between the couple are still in the early stages in the episodes that are currently airing in America, it seems like Silver and Greg's relationship will soon be heading in a different direction.
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