Tuesday, April 30, 2013

To [Vitamin] D or Not to D? That Is the Question

Medscape Medical News > Conference News
Lisa Nainggolan
Apr 29, 2013Source
COPENHAGEN, Denmark — Two leading experts in the field of vitamin D agreed to disagree yesterday here at the 2013 European Congress on Endocrinology during a lighthearted debate on the subject of whether or not everyone needs more vitamin D.
But their arguments were backed up by some serious science, and they both concurred that there are certain groups of people in whom it is necessary to ensure that vitamin-D levels are sufficient, such as pregnant women and those at risk for or with osteoporosis. And they also agreed on one way people can obtain more vitamin D: by going out in the sun for 30 minutes per day.
Where they differed, however, was that the vitamin-D proponent, Chantal Mathieu, MD, from Catholic University, Leuven, Belgium, said the list of people who need sufficient vitamin D "is so long that it really just makes more sense to give everyone small doses."
In the opposite corner, however, Mark Cooper, MD, from University Hospital, Birmingham, United Kingdom, argued that it is really only necessary to supplement specific, at-risk groups of people. "I am an investigator in randomized clinical trials of vitamin D, and I have nothing personally against [it], and I use it in my patients. But I tend to give it to people who actually need it, and that doesn't really include most of us," he observed.
And Dr. Cooper — who noted that there is a huge sector of the scientific community that is "evangelical" in its pro–vitamin-D stance — warned that physicians have been here before, with many other nutrients that subsequently, in large intervention trials, turned out to have a null effect or even be harmful. In fact, there is already evidence of risks with supplements of vitamin D from randomized clinical trials, with no evidence of benefit, he argued.
"Vitamin D — we all need more? Most of us don't, and more could actually do more harm than good."
What Does Vitamin D Do, and How Is "Deficiency" Defined?
Dr. Mathieu said the key role of vitamin D "is to promote resorption of calcium via the gut. One big lesson from all of the literature is that vitamin-D deficiency is not only bad because it's vitamin-D deficiency, but it also creates a bad calcemic status."
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Going out in the sun is one option to boost vitamin D, she explained, noting that "even the dermatologists in Australia have reversed their zero-tolerance stance on the sun" in the past 2 years and conceded that 15 to 30 minutes per day in the sun "is allowed because it gives benefits." Nevertheless, the benefits must be balanced with the risks, she added, noting that "it's exactly the same wavelength of UV that you need to make vitamin D that also causes skin damage, aging, and skin cancers. So go back to nature and expose yourself to the sun, but do it with caution."
And she noted that UV rays in Northern Hemisphere winters are not strong enough to produce adequate levels of vitamin D, regardless of how long is spent in the sun. In addition, darker-skinned people, particularly those who do not expose themselves to the sun or who cover themselves, are particularly at risk. "We still see rickets in my country, in dark-skinned children who are exclusively breast-fed and whose mothers avoid the sun or are covered," she observed.
"You can also take it from foods," she explained, but added that the "only really rich food source" of vitamin D is cod-liver oil. "Salmon and mackerel from the ocean is a good source"; however, most of this fish is now bred in farms, and farm-bred fish do not have a lot of vitamin D."So what do we do? We are endocrinologists. If the thyroid fails, we give thyroid-hormone substitution. If our skin cannot make enough vitamin D under the UV, just give vitamin D, give the hormone itself."
But the key, she said, is to use smaller doses of vitamin D than have previously been recommended. The US Endocrine Society guidance, for example, advises supplementation with up to 2000 IU per day, but this is overzealous, she said. "A more reasonable dose is 600 to 800 IU per day," she noted, adding that she is an author on a new guidance, soon to be published in the Journal of Clinical Endocrinology and Metabolism, which will state that 2000 IU per day "is not warranted."
"So my conclusion, yes, we all need more vitamin D, but we don't need crazy high doses."
In response, Dr. Cooper conceded: "Our natural state of vitamin D is much higher than we have today — we live indoors too much — and lower levels of vitamin D have been linked with cancer, heart disease, increases in diabetes, shortened life, the list goes on, and it's a very long list. In fact, you will do well to find a condition that isn't linked with too little vitamin D." But the problem, said Dr. Cooper, is that "the supposed benefits of vitamin D are exclusively reported in observational studies. We really need some robust evidence."
Vitamin-D Intervention Trials to Date "Mostly Negative"
Dr. Mathieu, Dr. Cooper said, had alluded to randomized trials in the future, "but we have got lots of randomized trials now," he argued, quoting a "typical" one, the RECORD trial from the United Kingdom.
This looked at vitamin-D supplementation and fractures in 5000 community-dwelling women and wasreported in the Lancet in 2005. "What it showed was that if you took vitamin D from [a level of] 38 nm/L, the average in that population on placebo, and raised it to 62 nm/L, which is a very useful increase — what does it do? Absolutely nothing, [at least] to falls and fractures."
And there have been "lots" of other randomized controlled trials, he added, "and my view is that these are mostly negative. The Women's Health Initiative, with 36,000 people [taking vitamin D] combined with calcium, didn't show any effect whatsoever. It did show, however, that [vitamin D plus calcium] caused kidney stones, a 70% increase, which is not medically insignificant."He noted also that in the attempts to find some benefit, "Vitamin D holds the record for the most number of meta-analyses for the fewest number of trials," and the results generally "depend on who does the meta-analysis. Those who do not have a major ax to grind (eg, the Institute of Medicine [IOM]), tend to come up with negative results, whereas those who really believe in vitamin D seem to get positive results with their meta-analysis."
And then there are those who say "maybe we are not getting levels high enough, we need to get over a certain threshold of intake," he observed. "But there have been trials in recent years that have done this, too."
He cited one from JAMA (2010;303:1815-1822), performed in Australia in the winter in women, giving them very high doses. The women in the active-treatment group ended up with levels of vitamin D of 75 nm/L, "so it worked" in comparison with the placebo group, who had average levels of 50 nm/L. "But the result was vitamin D caused a significant excess of falls and fractures. One in 3 people had an extra fall due to the vitamin D. This is not good."
He then went on to discuss the editorial accompanying this study, "which gave the explanation that the reason falls increased was because vitamin D was too good, the people who got it felt so well, they came to harm because they were having such increased functional mobility. Clearly ridiculous, but it gives you a mind-set of how people think about vitamin D."
He went on to list a number of other, recent randomized clinical trials with vitamin D, for conditions such as cognition, muscle strength, cancer, osteoarthritis, TB, etc. "Different doses of vitamin D, different groups, all well-designed, all in major journals, and all negative." He added that at least 1 in 20 of these studies "should be positive" just by chance, "but we haven't seen that yet."
Does a Little Suboptimal Absorption of Calcium Matter?
In rebuttal, however, Dr. Matheiu said all of the intervention studies "struggle with compliance issues, we all know that if we need to take a pill every day for 1 year, we will start to forget. So all the intervention studies you have seen give vitamin D in megadoses once every month, once every 2 months. That's not what I mean as 'we all need more.'
"Where we are now is a mean of 20 to 25 ng/mL, so if we want to analyze this objectively, half of our population is deficient. We all need more vitamin D than we are getting now. Saudi Arabia has a mean level of vitamin D that is below 20 ng/mL; should we wait to supplement people in Saudi? We know they are all vitamin-D deficient because it's too hot to get out in the sun."Vitamin-D deficiency in all of our association studies is clearly associated with impaired outcomes. We know that restoration of vitamin-D deficiency with small doses avoids adverse outcomes. I do not think we can afford to sit and wait for well-designed intervention studies," she stressed.
And, she argues, "It's too expensive to go around and measure vitamin-D levels in everybody. My argument would be to stop measuring levels in everybody. It's nonsense. There is a very easy way to prevent all of this, and that is to give small doses of vitamin D to the whole population, and that's what the IOM says. They say in children below 1 year of age, 400 IU per day; in individuals older than 70 years of age, 800 IU per day; and all of the rest, all of us, 600 IU of vitamin D every day. So yes! We all need more."
She did concede, however, that here are a few potential exceptions, such as patients with kidney stones "in whom you need to be careful."
In his rebuttal, Dr. Cooper replied, "Clearly, we agree on many things. Those populations at risk of rickets or hypocalcemia need vitamin D. Pregnancy is a situation where, clearly, you want to make sure levels are adequate" — although he acknowledged there has recently been debate on this issue — "and having vitamin D in the treatment of osteoporosis is mandatory, because you don't want to risk someone having even a small deficiency. But for the rest of the population, what does a little bit of suboptimal absorption of calcium matter? Who cares?
All of the primary analyses of the intervention studies described previously bear out the fact that there is no evidence of any benefit with vitamin D for the most part, he stressed.
"You can get on-the-spot tests for vitamin D now. And we are doing loads of vitamin-D assays. We are making everybody anxious. We [endocrinologists] ourselves are anxious. We shouldn't worry everybody, we should have good, balanced nutrition, but the majority of people who are otherwise healthy and asymptomatic shouldn't go around taking supplements.
"Will having a higher vitamin-D level give you a healthier, longer life? You can't do a randomized trial for 50 or 60 years, which is what you need to address this. More work needs to be done, clearly, but it's a tricky area," he concluded.
Drs. Mathieu and Cooper have reported no relevant financial relationships.
2013 European Congress of Endocrinology. Debate 1, presented April 28, 2013.
Comment: We are now being bombarded by various 'evidence' from pharmaceutical companies in India regarding Vit D deficiency in Indians. This debate, though not talking about Asian / Indian population specifically, does highlight most of the salient features regarding Vit D associated controversies & the lack of a clear cut defined guideline regarding supplementation. As far as I am concerned, we should try to get a bit of sunlight - at least 30 minutes a day - and most of us (except people with kidney stones) should consider supplementation with Vit D since our diets do not usually contain fishes.

Immunizing Kids Who Have Cancer

Thursday, April 25, 2013

Over 40044 never events in US annually - preventing & acknowledging Medical Errors

Never-events are the kind of medical mistakes that should simply not occur. Despite this, such events occur more often than people believe, according to a recent study by patient safety researchers at John Hopkins University School of Medicine in Baltimore, Maryland published in the April issue of the journal Surgery..

As per the study “a surgeon in the United States leaves a foreign object such as a sponge or towel inside a patient’s body after an operation 39 times a week, performs the wrong procedure on a patient 20 times a week, and operates on the wrong body site 20 times a week.” 4044 never-events occur in the United States each year.
Surgeons between the ages of 40 and 49 years are responsible for more than one third of the events, whereas surgeons older than 60 years are responsible for 14.4%.
6 in 10 of the surgeons involved in a never-event are named in more than 1 separate malpractice report, and more than 1 in 10 are involved in at least 1 separate surgical never-event.
Comments: There are many things that are wrong with the US healthcare system, BUT their transparency & openness regarding the mistakes that they make is commendable. As doctors in India we too have all heard & seen surgical & medical 'never-events' that have occurred, however unfortunately there is no documentation, and hence no chance of correcting the systematic errors that lead to such errors in the first place.

Tuesday, April 23, 2013

Another proud moment for Indian Vaccines ! Cheaper Vaccines to provide 5 in 1 protection for the World's poorest kids ....

Indian Supply Drives Down the Cost of Childhood Vaccine

Apr 19, 2013
LONDON (Reuters) Apr 18 - The cost of immunizing children in developing countries with a five-in-one vaccine is set to fall after a deal by an Indian supplier to slash the price it charges the GAVI global vaccines group.
The agreement between Biological E and the GAVI Alliance, which funds bulk-buy vaccination programs for poor nations, highlights the growing role of India's low-cost drugs sector in supplying products around the world.
India's staunch support for its generics sector has led to clashes with Western pharmaceutical companies, most recently following a high-profile defeat for Novartis in a cancer drug patent case this month.
GAVI said on Thursday that Biological E would sell the pentavalent shot for $1.19 per dose, compared to a 2012 weighted average price of $2.17, saving it up to $150 million over the next four years.
The five-in-one vaccine is the most widely used by GAVI. It protects against diphtheria, tetanus, whooping cough, hepatitis B and Haemophilus influenzae type B (Hib).
GAVI also buys the shot from Johnson & Johnson's Crucell, GlaxoSmithKline, LG Life Sciences and Serum Institute of India.


Monday, April 22, 2013

Confused about safe age for using nasal steroid sprays in children for allergies?

I am invariably confused about the safe age of various steroid formulations for use in the present allergy season given that many different medications are available, and most Medical reps marketing them are either confused themselves OR try to confuse us :)
It does not help that the age groups for inhaled steroids for Asthma are different than the intranasal steroids for Allergic rhinitis
Here is an easy to remember image (from the US) that can help


Since we do have all the second generation products in India, I believe using Nasonex (Mometasone) would be the easiest choice since it has very low bio-availability (a good thing), and is safe for children above 2 years.
Update: Fluticasone Furoate (Veramyst in US, Fluticone - FT - German Remedies in India, and other brands) is now FDA approved for kids above 2 years age 

Wednesday, April 17, 2013

New Social Media Guidelines Issued for Physicians

 10:31 am  Health Care 
Medscape Cardiology: A new social media policy urges doctors to “pause before posting” and to not “friend” patients online. The guidelines issued by the American College of Physicians and the Federation of State Medical Boards, was released at ACP Internal Medicine 2013 in San Francisco, California, and published April 11 in the Annals of Internal Medicine. It addresses the benefits and drawbacks of a number of online interactions, and proposes safeguards.
A recent survey of state medical boards showed that 92% reported at least 1 online violation of professionalism that led to a major action, such as license re vocation (JAMA. 2012;307:1141-1142).
1. Email and electronic communication should be restricted to individuals with whom the physician has an established physician–patient relationship. One need to be very careful about the type of information provided. It places ONE at a professional and ethical risk.
2. Another challenge is ensuring confidentiality. Posts on Facebook, Twitter, and other social media sites can be widely read, and even emails can be forwarded. We have to be careful about the kind of information we provide, particularly private and confidential information that the patient may not want shared.
3. Look for and use only portals for confidential interactions with patients rather than standard social media or personal Websites. A post can be taken out of context and go viral.
4. Social media however enables communication with a larger audience than you might be able to in a practice, which can be helpful when disseminating information on issues such as public health reform or vaccines. However, any posted comment can have a life of its own and might spread in a fashion you hadn’t intended.
5. Posts can be objective, such as referenced health information, or subjective, such as opinions on matters of public policy. We have to be clear which hat we’re wearing, whether it’s a personal opinion or we’re representing an institute or organization.
6. Physicians should keep their professional and personal personas separate; they should not “friend” or contact patients through personal social media.
7. Email and other electronic communications should only be used by physicians within an established patient–physician relationship and with patient consent.
8. When a physician is approached through electronic means for clinical advice in the absence of a patient–physician relationship, the individual should be encouraged to schedule an office visit or go to the nearest emergency department.
9. Text messaging should never be used for medical interactions, even with an established patient, except with extreme caution and consent from the patient.
10. Trainees can inadvertently harm their future careers by not posting responsibly or actively policing their online content.

Friday, April 12, 2013

Recognizing Celiac Disease in Kids

I am Dr. Ritu Verma. I am a pediatric gastroenterologist and Director of the Center for Celiac Disease at Children's Hospital in Philadelphia. We are going to talk a little bit about celiac disease today.
As you know, celiac disease is an autoimmune disease, and it is a genetic condition that does run in families. The question is: How does one really diagnose celiac disease? It starts out, of course, with first being aware of the potential for celiac disease and therefore thinking about the symptoms. They are the classic symptoms that almost everyone knows about: A child is losing weight and has a distended belly and diarrhea. But by and large these days, the diagnosis is more frequent in children who don't have the classic symptoms. I usually tend to say: Think about celiac disease and nonclassic symptoms, thinking from head to toe.
So consider a child having alopecia, thyroid problems, chronic headaches, early osteoporosis or osteopenia, elevated liver enzymes, anemia, constipation, leg pains, joint pains -- a lot of symptoms that are not the classic symptoms often seen in children diagnosed with celiac disease. If a child has a particular symptom that is not explained by another disease or another condition, one should think about celiac disease.
Besides children with these symptoms, you should also be thinking about children who have type 1 diabetes. Almost 10%-20% of children who have type 1 diabetes also have celiac disease. Hence, one needs to screen these children. Children with Down syndrome and Turner syndrome also have a higher genetic predisposition. Hypothyroidism and many of the other autoimmune rheumatologic conditions should make one think about celiac disease as well.
Because it is a genetic condition and runs in families, screening testing needs to be done in family members: first-degree and second-degree relatives. There is a higher predisposition for celiac disease in those family members regardless of the presence or absence of particular symptoms.
How does one really start screening? Of course, one first is aware based on the symptoms, and then one gets a simple blood test. What does the blood test entail? The initial blood test is the total immunoglobulin A (IgA) level. You want to make sure that the immunoglobulin level is normal. If the IgA level is abnormally low, then you cannot rely on the traditional antibodies and you need to do specific other antibodies, traditionally tissue transglutaminase antibody; endomysial antibody; and, now more currently, deamidated gliadin. They are all blood tests.
Antibodies are elevated in children or adults with active celiac disease. In situations of IgA deficiency, IgG versions may be obtained. Of course, a gastroenterologist would help in making the determination of which antibodies to obtain.
The blood test is a screen. It is extremely important that if the blood test is abnormal, a referral is made to a gastroenterologist without changing the diet prior to that referral.
The last point I would have to make is that early diagnosis of these children is extremely important. If a child is diagnosed after 10 years of life, the chance that they will develop another autoimmune disease is almost 25%, so a blood test and early diagnosis is key.
Comment: North India has a fairly high incidence of Celiac Disease. I think this is a very valuable yet simple commentary for many of the practising pediatricians. I especially enjoyed learning about the list of unusual symptoms associated with Celiac Disease. Also I have never ordered a total IgA test for any of the children that I have suspected of Celiac Disease, and this could be a cause of false negatives in some of these cases. Finally, testing for kids with Down's, Turner's, hypothyroid & IDDM & any other rheumatological disorder is something that needs to put in to practice routinely.

Kids receiving exclusive DTaP (painless DPT) vaccine have 8.5 times higher risk of Pertussis compared to those who had received at least one DTwP dose

Clinical Infectious Diseases Volume 56, Issue 9, Pp. 1248-1254. (April 2013)
Background. Unexpected waning of immunity after pertussis vaccination is now well described. In this study we examined whether prior vaccination with whole-cell pertussis vaccine (wP) at any point provided superior protection contrasted with a solely acellular pertussis vaccine (aP) series. We utilized the coincidence of a large outbreak of pertussis with the termination of wP availability, providing populations of children who had been vaccinated with combinations of wP and aP.
Methods. Kaiser Permanente (KP) is an integrated healthcare system with complete electronic records and a centralized laboratory. Cases of laboratory-confirmed pertussis and vaccination data for members aged 8–20 years were retrieved.
Results. Among 263 496 persons aged 8–20 years, 904 cases of pertussis were identified. In patients with a full history of vaccinations administered by KP, those with 5 total doses of only aP had an 8.57 relative risk (RR) of pertussis (P < .0001) contrasted to those with ≥1 wP dose. With 6 doses of aP, the RR of disease was 3.55 (P < .0001). When external vaccine records were included, the results were similar.
Conclusions. We found a markedly increased risk of disease associated with an entirely aP series. This risk was mitigated, but not eliminated, by the presence of a sixth dose of pertussis vaccine (Tdap). Receipt of 1 or more wP doses markedly augmented the durability of immunity from subsequent aP doses. It appears that a wholly acellular pertussis vaccine series is significantly less effective and durable than one that contains the traditional whole cell vaccine.
Comment: There have been epidemics of Pertussis (whooping cough (Kaali khaansi in Hindi) in US, UK & Australia in the last year. Research is increasingly implicating the use of DTaP as a causative factor in this situation. Given that most private practitioners in larger Indian cities are providing (the much more expensive) DTaP to our customers, I believe that the time has introspect, and recommend at least 1 dose of DTwP for all kids in our follow up. As per theoretical models, the first dose of DPT vaccine may be DTwP, followed by DTaP for affording parents to reduce the chances of side-effects, without compromising the efficacy.

Monday, April 08, 2013

Male pattern baldness indicates heart disease risk

Male pattern baldness is linked to an increased risk of coronary heart disease, but only if it’s on the top/crown of the head. A receding hairline is not linked to an increased risk. The researchers from University of Tokyo trawled the Medline and the Cochrane Library databases for research published on male pattern baldness and coronary heart disease, and came up with 850 possible studies, published between 1950 and 2012. Analysis of the findings from these showed that men who had lost most of their hair were a third more likely (32 percent) to develop coronary artery disease than their peers who retained a full head of hair. It showed that balding men were 70 percent more likely to have heart disease and those in younger age groups were 84 percent more likely to do so.
Extensive vertex baldness boosted the risk by 48 percent, moderate vertex baldness by 36 percent and mild vertex baldness by 18 percent. By contrast, a receding hairline made very little difference to risk. The study is published in the online journal BMJ Open.
Male pattern baldness is characterized by hair receding from the lateral sides of the forehead (known as a “receding hairline”) and/or a thinning crown (balding to the area known as the ‘vertex’). Both become more pronounced until they eventually meet, leaving a horseshoe-shaped ring of hair around the back of the head.Male pattern baldness is linked to an increased risk of coronary heart disease, but only if it’s on the top/crown of the head. A receding hairline is not linked to an increased risk. The researchers from University of Tokyo trawled the Medline and the Cochrane Library databases for research published on male pattern baldness and coronary heart disease, and came up with 850 possible studies, published between 1950 and 2012. Analysis of the findings from these showed that men who had lost most of their hair were a third more likely (32 percent) to develop coronary artery disease than their peers who retained a full head of hair. It showed that balding men were 70 percent more likely to have heart disease and those in younger age groups were 84 percent more likely to do so.
Extensive vertex baldness boosted the risk by 48 percent, moderate vertex baldness by 36 percent and mild vertex baldness by 18 percent. By contrast, a receding hairline made very little difference to risk. The study is published in the online journal BMJ Open.
Male pattern baldness is characterized by hair receding from the lateral sides of the forehead (known as a “receding hairline”) and/or a thinning crown (balding to the area known as the ‘vertex’). Both become more pronounced until they eventually meet, leaving a horseshoe-shaped ring of hair around the back of the head.
Comment: Another 'reason' for men to avoid going bald. I wonder if getting a hair transplant will help reduce the risk :) since there appears to be precious little that is likely to help otherwise !

Wednesday, April 03, 2013

What’s new in Gynecology? Also of interest to Pediatricians !

 2:15 pm  Health Care 
  • Use of selective serotonin reuptake inhibitors (SSRIs) to treat pregnant patients does not appear to be associated with stillbirth or infant mortality (1).
  • The United States Advisory Committee on Immunization Practices (ACIP) recommended that all pregnant women receive the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during each pregnancy, optimally between 27 and 36 weeks of gestation, regardless of prior vaccination status, to increase the likelihood of optimal protection against pertussis for both the mother and her infant during the first few months of the infant’s life (2). Previously, Tdap was recommended only for pregnant women who had not previously received the acellular pertussis vaccine during adulthood.
  • Vaccination during pregnancy substantially reduced the risk of a maternal influenza diagnosis (adjusted hazard ratio, 0.30) and was associated with a trend in reduction of fetal death. All women who are pregnant or will be pregnant during influenza season should receive the inactivated influenza vaccine, regardless of pregnancy trimester (3).
  • A December 2012 American College of Obstetricians and Gynecologists (ACOG) committee opinion concluded that the decision to perform early versus delayed cord clamping in term deliveries should be based on patient-specific factors, particularly the infant’s risk of developing iron deficiency anemia (4). For preterm deliveries, they recommended delayed cord clamping given the significant reduction in intraventricular hemorrhage associated with this intervention (3).
  • In a prospective study of mothers who used benzodiazepines (primarily lorazepam, clonazepam, and midazolam) while breastfeeding, central nervous system depression (defined as sleepiness, poor latching, limpness, or lack of response to stimuli) in infants was an infrequent finding (affecting 2 out of 124, or 1.6 percent) (5).
1.     Stephansson O, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. JAMA 2013;309:48.
2.     Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine (Tdap) in Pregnant Women — Advisory Committee on Immunization Practices (ACIP), 2012http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6207a4.htm?s_cid=mm6207a4_e (Accessed on February 21, 2013).
3.     HÃ¥berg SE, Trogstad L, Gunnes N, et al. Risk of fetal death after pandemic influenza virus infection or vaccination. N Engl J Med 2013;368:333.
4.     Rabe H, Diaz-Rossello JL, Duley L, Dowswell T. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev 2012;8:CD003248.
5.     Kelly LE, Poon S, Madadi P, Koren G. Neonatal benzodiazepines exposure during breastfeeding. J Pediatr 2012;161:448.