Infant Acetaminophen Dosage Change May Cause Confusion

From WebMD Health News Jennifer Warner December 23, 2011 — Double check the label on liquid acetaminophen before giving it to a child or infant to avoid giving your child the wrong dose. The FDA is urging parents and caregivers to carefully read the label on liquid acetaminophen marketed to infants and children as a new, less concentrated form of the popular pain reliever arrives on store shelves. Acetaminophen products include several over-the-counter brands, including Little Fevers, PediaCare, Triaminic, Tylenol, and store brands or generic versions of the drug. While the new 160 mg per 5 mL concentration is now arriving in drugstores, much of the older, more concentrated 80 mg per 1 mL or 80 mg per 0.8 mL versions may still be in people’s medicine cabinets. “There is still some on store shelves; there is still some in homes; and there is still some in distribution,” Carol Holquist, director of the FDA’s Division of Medical Error Prevention and Analysis, says in a news release. “Be very careful when you’re giving your infant acetaminophen.” Giving too little liquid acetaminophen could cause the drug to be ineffective. Giving too much could possibly lead to death. The drug is used to temporarily reduce fever and relieve minor aches and pains from the common cold, flu, headache, minor sore throat, and toothache. Why the New Version? Until recently, liquid acetaminophen marketed for infants was available only in the stronger 80 mg per 1 mL or 80 mg per 0.8 mL concentrations that don’t require giving infants as much liquid with each dose. Meanwhile, the less concentrated 160 mg per 5 mL version was marketed for children. Earlier this year, a report from the FDA showed that confusion caused by the different concentrations of liquid acetaminophen for infants and children was leading to overdoses that made infants seriously ill, and some died from liver failure. To avoid these dosing errors, some manufacturers voluntarily changed the concentration of liquid acetaminophen for infants to the same concentration as the liquid acetaminophen marketed to children. The new, less concentrated 160 mg per 5 mL liquid acetaminophen for infants has new dosing instructions and may have a new dosing device in the box, such as an oral syringe rather than a dropper. What You Should Do The FDA advises parents and caregivers to read the “Active ingredient” section of the Drug Facts label on liquid acetaminophen marketed to infants or children to tell the difference between the two products. Other tips for ensuring safe and accurate dosing of liquid acetaminophen include: Do not depend on a banner proclaiming that the product is “new” to determine the drug’s concentration. Some medicines with the old concentration also have this word on their packaging. Use only the dosing device provided with the purchased product in order to correctly measure the right amount of liquid acetaminophen. Consult your pediatrician before giving this medication and make sure you’re talking about the same concentration. If the dosing instructions provided by your health care provider differ from what is on the label, check with a health care professional before administering the medication. Do not rely on dosing information provided from other sources, such as the Internet, old dosing charts, or family members. FDA officials say it is important to note that there is no dosing amount specified for children younger than 2 years of age. If you have an infant or child younger than 2 years old, always check with your health care provider for dosing instructions.

Concussions, Our Patients, and You

Gregory Lawton, MD, Pediatrics, General, 09:24AM Dec 19, 2011 Recently, the New York Times chronicled the life and death of hockey's premier enforcer, Derek Boogaard, who died at the age of 28 in April from an overdose of pain killers. His brain, subjected to hundreds of bare-knuckle fights over from the age of fourteen years, demonstrated pronounced evidence of chronic traumatic encephalopathy (CTE). I was dumbfounded at how matter of fact, even nonchalant, his parents were, as they described their late son's career, and their acceptance of his job, to deliver (and receive) physical punishment. His father was more concerned about the toll of fighting on his hands. Last month, a new study detailed the potential destructive effects on the brain's white matter resulting from the frequent heading of soccer balls. According to the study, adults who actively played soccer and acknowledged heading the ball more than 1,100 times in the previous twelve months had radiological and cognitive evidence of a decline. While the study was on adults, it raises more than a few questions concerning the effects of heading on the developing brains of children and adolescents. Finally, a December National Geographic piece visually quantifies the 537 head shots a college football player sustained during a single season. Two hits resulted in concussions, and interestingly enough, the hits that resulted in concussions were not the hardest of the bunch. This adds to the complexity of concussions and their prevention, with the notion of rotational as well as direct forces. What to do? We are parents, coaches, as well as pediatricians. We go to hockey and football games and pay good money for the tickets. Some measures are within our reach but are quixotic in nature. Others are hopelessly naïve. Let's start small. As parents, just say no to some things. My father forbade me to play football (so I became a baseball catcher instead). Ditto for my son. Is this a bit inconsistent, trading a blitzing linebacker's helmet for a foul ball off the facemask? Probably, but I would like to think that neither myself nor my parents were as "bewildered" by their son's activities as Derek Boogaard's parents. Life and sports are both associated with risks. The only risk-free option is not to play. To choose one sport over another is to exercise our judgment and choose one set of risks over another. As coaches, we have the opportunity to combine personal interest and professional knowledge as it relates to developing athletes. A growing consensus seems to be developing that heading should be discouraged in players under the age of twelve. For older players, teaching chest trapping (especially on punts) may make for better ball control as well as fewer concussions. Keeping an eye out for concussive symptoms such as headaches, dizziness, or nausea in our players should decrease the incidence of second concussion syndrome, regardless of the sport. As pediatricians, we need to continue to educate parents and players about the signs, symptoms, and CONSEQUENCES of concussions. We need to impress upon them that no practice, scrimmage, game, or playoff, is worth the risk of a second concussion. How many kids in our practices have gone on to professional football, lacrosse, or hockey careers? Compare that to the number of future teachers, business owners, or managers we see. The reality is that the vast majority of our patients will make their future mortgage payments not with their athletic prowess, but with their more prosaic communication, organization, decision-making skills. Brain cells are our patients' most precious collateral. We must emphasize this fact with regard to concussions as strenuously as we do with drug and alcohol counseling. Finally, what are we to make of our football season tickets or our interest in a Flyers-Rangers game? Both sports are physical, often violent. Both are also punctuated with moments, indeed entire sequences that are mesmerizing for their grace, speed, and superb athleticism. What is closer to the essence of each sport, the violence or the elegance? Perhaps we should aspire to cheer that which is closer to the essence. Chris Nowinski, of the Center for the Study of Tramatic Encephalopathy at Boston University Medical School, is a former Harvard football player (as well as professional wrestler). He has suffered post-concussion syndrome. He still loves his Bruins; however, he tends to remain seated during the fights. Enforcers in hockey, football players who lead with their helmets and soccer players who take the hard shots out of the air with their heads are doing one thing, according to Nowinski. "They are trading money for brain cells." We don't see professional athletes in our offices. We see student athletes. Let's asked them to be smart, to play tough, but to play fair. Concussions will happen, but we need to be proactive in both prevention and treatment. When we counsel about second concussions, we need to modify the Nowinski's quote. Don't trade brain cells for glory. Look for me on Facebook at A Musing Pediatrician, http://www.facebook.com/profile.php?id=100003267241424

An Infant is not Just a Small Child

From Expert Review of Clinical Pharmacology Clinical Pharmacology in Neonates and Young Infants The Benefit of a Population-tailored Approach John van den Anker; Karel Allegaert Authors and Disclosures Posted: 12/22/2011; Expert Rev Clin Pharmacol. 2012;5(1):5-8. © 2012 Expert Reviews Ltd. Print This Email this An Infant is not Just a Small Child Tailored Pharmacokinetic Studies in Infancy: Improved Sampling Strategies & Data An Infant is not Just a Small Child John van den Anker; Karel Allegaert Posted: 12/22/2011; Expert Rev Clin Pharmacol. 2012;5(1):5-8. © 2012 Expert Reviews Ltd. The most essential characteristics of childhood are growth and maturation. Both phenomena are most prominent during infancy, making the claim that 'an infant is not just a small child' as relevant as the more commonly used paradigm that 'a child is not just a small adult'. There is already one log size difference in weight (0.5–5 kg) within the neonatal population, quite similar to the log size spectrum (5–50 kg) of childhood. The birth weight increases by 50% in the first 6 weeks of life, and doubles in the first 4 months to be three-times higher at the end of infancy. In this same time interval, there is a fourfold increase in caloric needs. As a consequence, the first year of human life is characterized by a very dynamic biological system where growth, maturation and extensive variability are the key issues. From a clinical pharmacology perspective, the consequence of such a dynamic setting is extensive interindividual variability throughout infancy in both the pharmacokinetics and pharmacodynamics of xenobiotics. Instead of median values for pharmacokinetic estimates or outcome variables, the range and its contributing covariates are crucial. Body composition and compartment sizes change during infancy, and all phase I (e.g., cytochromes) and phase II (e.g., glucuronidation) metabolic processes mature in an iso-enzyme-specific pattern, while renal function (glomerular filtration rate and tubular absorption/excretion) also displays age-dependent capacity. The phenotypic variability in either drug disposition or effects during infancy is further affected by the contribution of other, non-ontogeny-related covariates (e.g., perinatal asphyxia with whole body cooling, comedication, genetic polymorphisms, sepsis or inflammation, and congenital renal impairment). History provides the community with compound-specific observations to illustrate the negative impact of exposure to chloramphenicol (deficient glucuronidation capacity resulting in chloramphenicol accumulation and gray baby syndrome), benzyl alcohol (deficient alcohol dehydrogenase activity resulting in benzyl alcohol accumulation and gasping syndrome) or – much more recently – dexamethasone (specific vulnerability of neonatal cortical and subcortical nervous tissues, resulting in cerebral palsy and blunted brain growth) in neonates. All these anecdotic observations can be considered as illustrations of failure to consider the specific characteristics of this vulnerable population. However, optimism is a moral duty. Implementation of the pediatric regulation in the USA in 1997 has resulted in a rebirth of pediatric product development, including drugs for infants. Subsequent implementation of a similar pediatric legislation initiative in the EU (2007) and in WHO initiatives (e.g., the WHO 'make drugs child size' program, which is an ongoing program of the WHO and resulted in an essential medicines list for children in 2011) further stimulated all stakeholders (industry, academia, governmental and research organizations) to develop focused pediatric research activities. As an illustration, a search for 'newborn/infant' on the clinicaltrials.gov website in early October 2011 resulted in 1318 protocols for interventional studies, of which 899 were initiated (based on the sponsor's location) in the USA and 376 in Europe. Although this is only a snapshot of the ongoing clinical research activities, it suggests that there is growing research activity aiming to further improve pharmacotherapy.In addition to compound-specific observations, such studies also stimulated the development and validation of research tools in the field of pharmacokinetics (e.g., analytical techniques and population pharmacokinetics) and pharmacodynamics (population-specific 'biomarkers') adapted to newborns and infants.

Caffeine Intake May Negatively Affect Children

From Medscape Medical News Laurie Barclay, MD December 22, 2010 — Caffeine intake is prevalent in children and may have negative effects on sleep duration, according to the results of a study reported online in the December 16 issue of the Journal of Pediatrics. "Caffeine's diuretic properties have encouraged behavioural health practitioners to eliminate caffeine from the diet of children with enuresis," write William Warzak, MD, from the Munroe-Meyer Institute and the Department of Pediatrics, University of Nebraska Medical Center in Omaha, and colleagues. "The Food and Drug Administration has not developed pediatric guidelines for caffeine consumption, but Canadian guidelines recommend that children aged 4 to 6 years old consume no more than 45 mg/d, approximately equivalent to the amount of caffeine found in a 12-ounce can of cola.... The most recent caffeine consumption data for children living in the United States is almost a decade old, and most of this research has been conducted with older children, adolescents, and adults." The study goals were to obtain current data for caffeine intake in children, to evaluate the associations between caffeine, enuresis, and sleep, and to assess cross-cultural differences in caffeine consumption by Spanish- and English-speaking children aged 5 to 12 years. During routine clinical visits at a pediatric clinic in Omaha, parents were surveyed about their child's daily consumption of various types of snacks and beverages. Of 228 young children whose parents were surveyed, about three quarters regularly consumed caffeine. Mean daily caffeine intake was approximately 52 mg in children aged 5 to 7 years and approximately 109 mg in children aged 8 to 12 years. Older children drank more caffeinated beverages than younger children. "Some children as young as 5 years old were consuming the equivalent of a can of soda a day," Dr. Warzak said in a news release. "Children between the ages of 8 and 12 years consumed an average of 109 mg a day, the equivalent of almost 3 12-ounce cans of soda." This study authors note that 109 mg caffeine daily is almost twice the amount recommended by Canadian pediatric guidelines and in excess of the amount shown to create physiological effects in adults. Although caffeine intake was significantly negatively correlated with hours slept, caffeine consumption and enuresis were not significantly correlated. Compared with English-speaking parents, Spanish-speaking parents reported fewer events of enuresis in their children. "Contrary to popular belief, children were not more likely to wet the bed if they consumed caffeine, despite the fact that caffeine is a diuretic," said coauthor Shelby Evans, PhD, also from the University of Nebraska Medical Center. Children aged 5 to 7 years slept an average of 9.46 hours per night, which is above the minimum 9 hours recommended by the US Centers for Disease Control and Prevention (CDC), but approximately one quarter of these children slept less than 9 hours per night. Children aged 8 to 12 years old slept an average of 8.47 hours per night, which is below the minimum proposed by the CDC. Limitations of this study include the inability to determine causal relationships, potential recall and parental bias, and a modest sample size of Spanish-speaking children. In addition, this study did not address the specific physiological and psychological effects of caffeine consumption on young children. "Parents should be aware of the potentially negative influence of caffeine on a child's sleep quality and daily functioning," Dr. Warzak concluded. The study authors have disclosed no relevant financial relationships. J Pediatr. Published online December 16, 2010.

Kids' Leukemia Risk Tied to Dads' Smoking

From Reuters Health Information By Kerry Grens NEW YORK (Reuters Health) Dec 15 - Children whose fathers smoked have at least a 15% higher risk of developing acute lymphoblastic leukemia, a new Australian study finds. "Paternal smoking seems to be real" as a risk factor, said Dr. Patricia Buffler, a professor at the University of California, Berkeley, who was not involved in the current analysis. "The importance of tobacco exposure and children's cancers has been overlooked until recently," Dr. Buffler told Reuters Health. "So I think this paper is important" in adding to the growing body of evidence. The research team, led by Dr. Elizabeth Milne at the Telethon Institute for Child Health Research in Australia, surveyed the families of nearly 400 children with ALL. Although ALL is the most common childhood cancer, it is still rare, affecting about three to five children out of every 100,000, according to the National Cancer Institute. The survey asked about the smoking habits of both parents. Dr. Milne and her colleagues compared these families to the families of more than 800 children of similar ages who did not have leukemia. They found that the mothers' smoking behavior had no impact on the kids' risk of developing the cancer. The researchers then added their results to those of nine earlier studies. When they did that, they found that kids whose fathers smoked at all around the time of their conception were 15% more likely to develop leukemia. Those whose dads smoked at least 20 cigarettes per day around that time were 44% more likely to be diagnosed with the cancer, according to a report published online December 5 in the American Journal of Epidemiology. Because of the toxins in tobacco smoke, Dr. Buffler said, "it's not unlikely that you'd have damage" in the cells that produce sperm. "Sperm containing DNA (damage) can still reach and fertilize an ovum, which may lead to disease in the offspring," Dr. Milne wrote in an email to Reuters Health. The study did not prove that DNA damage in the sperm caused by smoking is responsible for the children's increased risk of cancer. "The causes of ALL are likely to be multifactorial, and our findings relate to just one of the possible contributing factors," said Dr. Milne. Several other environmental factors are also tied to a greater chance of developing childhood leukemia, including ionizing radiation and the mother's exposure to paint or pesticides while pregnant. Dr. Milne said that many of the studies regarding these potential causes have been small, and not conclusive. Dr. Buffler is leading an international consortium of researchers tracking thousands of cases of childhood leukemia to determine the influence of environmental, genetic, and other biological factors on developing the disease. SOURCE: http://bit.ly/snq3sL

Lower Asthma Risk in Chubby Tots Who Slim Down

From Reuters Health Information By Amy Norton NEW YORK (Reuters Health) Dec 21 - Overweight preschoolers who don't slim down are at a higher asthma risk at age seven, but the baby fat doesn't seem to matter for kids who lose the extra weight, a new study suggests. Of more than 2,000 Swedish children followed to age eight, those who were overweight or obese at age seven - that is, with a body mass index at or above the 85th percentile -- were more likely to have asthma than their thinner peers -- whether or not they were overweight earlier in life. In contrast, children who were heavy as toddlers or at age four, but not at age seven, were no more prone to asthma than kids who'd always been normal-weight. Children who are chubby early in life often see their weight normalize by school age, according to lead researcher Jessica Ohman Magnusson, of the Karolinska Institute in Stockholm. But if the extra weight persists after age four, she told Reuters Health in an email, parents may need help in managing their child's weight in a healthy way. A number of studies have found that heavy children have a higher risk of asthma, or more severe symptoms. But whether the extra pounds are the cause is not clear. "We don't think we can say that overweight is causally associated with asthma," Magnusson said. That's because early-childhood pounds were not tied to asthma risk in cases where children eventually became normal-weight, she said. It's possible that other factors, and not weight itself, explain why children who remain heavy have an increased asthma risk. As reported online December 19th in Pediatrics, 6% of the total cohort of eight-year-olds had asthma, compared to 10% of the kids who were overweight at age seven. When the researchers accounted for parents' history of allergies, maternal smoking during pregnancy, and other factors, they found that being overweight at age seven was linked to a doubling in the risk of asthma. That was true regardless of whether the kids were normal weight or heavy at age four. Around 300 children in the study were overweight at some point. But fewer were persistently heavy; 122 children remained overweight from the age of one to age seven. So parents should feel reassured, Magnusson said, that those early extra pounds often do not last. And based on these findings, children whose weight normalizes may not have an increased asthma risk. SOURCE: http://bit.ly/tVwsye

Atopic Dermatitis : Diagnosis & Pathogenesis

Cases in Atopic Dermatitis Medscape Pediatrics CME Lawrence F. Eichenfield, MD Professor of Clinical Pediatrics and Medicine (Dermatology), University of California Pathogenesis and Diagnosis of Atopic Dermatitis Atopic dermatitis (AD) is a common inflammatory skin disorder affecting 10%-20% of children during their first decade of life. It is characterized by a pruritic, scaling rash that follows a fluctuating course. In approximately 60% of patients, AD starts in the first year of life. Newborns and infants usually have involvement on the cheeks, chin, and extremities. As the child ages, the rash typically transitions to classic involvement of the flexural antecubital and popliteal fossae. Fortunately, AD frequently resolves when the patient grows older. The pathogenesis of AD is complex and multifactorial. Acute AD is characterized by strong type 2 T-helper (TH2) cell responses with production of interleukin (IL)-4, IL-5, and IgE antibodies, whereas chronic AD has immunologic features more consistent with TH1-mediated responses. Recent evidence also suggests a possible role for TH17 cells. There is a significant barrier defect in people with AD. Many have mutations in the epidermal proteins that result in epidermal barrier dysfunction. The epidermis of skin affected with AD often has decreased levels of filaggrin, a protein responsible for aggregation and adhesion of the cornified envelope; ceramides, the predominant lipids of the cornified envelope; and antimicrobial peptides, such as beta-defensins and cathelicidins, proteins of the innate immune system that resist cutaneous colonization and infection. Further exacerbating the epidermal barrier of people with AD is increased transepidermal water loss. As a result of these barrier defects, allergen absorption and bacterial colonization and infection are enhanced, which further potentiates the immunologic dysfunction present in skin affected by AD. The diagnosis of AD is usually not challenging. However, other diagnoses should be considered if the presentation is atypical. Differential diagnoses include scabies, psoriasis, allergic contact dermatitis, immunodeficiency diseases, metabolic conditions, nutritional disorders, Langerhans cell histiocytosis, and various other disorders as suggested by the patient's presentation. Because AD is part of an atopic triad that includes asthma and allergic rhinitis, it is important to ask patients and parents whether there is a history of any of these in the patient or family. If there is such a history, AD is more likely. A child has a 20% risk for AD if one parent is affected and a 50% risk if both parents are affected. Furthermore, the concordance rate between monozygotic twins is 80%, and the concordance rate between dizygotic twins is 20%. Findings on physical examination that support a diagnosis of AD include typical pruritic eczematous dermatitis, hyperlinear palmar dermatoglyphics (increased fine skin lines), Dennie-Morgan fold (infraorbital line caused by edema), allergic shiners (dark periorbital skin due to sinus congestion and venous congestion), allergic salute (horizontal crease on the dorsal nose secondary to chronic allergies and rubbing), keratosis pilaris (spiny papules on the anterolateral upper arms), and ichthyosis vulgaris (fish-like scales on the skin). The diaper area of infants and toddlers with AD is characteristically spared, partially due to the occlusive hydration effect of diapers. The presence of significant rash in this area should prompt the consideration of other etiologies. There are many proposed diagnostic criteria for AD. Perhaps the most practical, sensitive, and validated for use in epidemiologic studies are the UK Working Party's Diagnostic Criteria for Atopic Dermatitis (Table 1). To meet these criteria, the patient must have pruritus and 3 or more minor criteria. Table 1. UK Working Party's Diagnostic Criteria for Atopic Dermatitis A. Required Criterion 1. Pruritus B. Minor Criteria (≥ 3 of the following must be present) 1. Onset < 2 years of age 2. History of flexural involvement 3. History of asthma or hay fever (or history of these conditions in parent or sibling if patient is < 4 years of age) 4. History of general dry skin in the last year 5. Visible flexural eczema (or eczema involving the cheeks/forehead and outer limbs in children < 4 years of age) Similarly, the American Academy of Dermatology Consensus Conference stated that AD is best thought of as a syndrome with features classified as "essential," "important," and "associated" (Table 2). Table 2. American Academy of Dermatology Consensus Conference Definition of Atopic Dermatitis A. Essential Features (must be present) 1. Pruritus 2. Eczema (acute, subacute, chronic) a. Typical morphology and age-specific patterns* b. Chronic or relapsing history B. Important Features (seen in most cases, adding support to the diagnosis) 1. Early age at onset 2. Atopy a. Personal and/or family history b. IgE reactivity 3. Xerosis C. Associated Features (helpful in suggesting the diagnosis but too nonspecific for defining or detecting AD for research or epidemiologic studies) 1. Atypical vascular responses (eg, facial pallor, white dermographism, delayed blanch response) 2. Keratosis pilaris/hyperlinear palms/ichthyosis 3. Ocular/periorbital changes 4. Other regional findings (eg, perioral changes/periauricular lesions) 5. Perifollicular accentuation/lichenification/prurigo lesions Exclusionary Conditions Diagnosis of AD depends on excluding such conditions as scabies, seborrheic dermatitis, allergic contact dermatitis, ichthyosis, cutaneous lymphoma, psoriasis, and immune deficiency diseases * Patterns include (1) facial, neck, and extensor involvement in infants and children; (2) current or prior flexural lesions in any age group; and (3) sparing of groin and axillary regions.

Parents' Smoking May Cause Vascular Damage in Children

From Medscape Medical News Laurie Barclay, MD December 26, 2011 — Parental smoking during pregnancy may cause vascular damage when the children reach 5 years of age, according to the results of a birth cohort study published online December 26 and in the January 2012 print issue of Pediatrics. "Smoking during pregnancy has been related to thicker carotid intima media thickness in young adults, and this was also shown in neonates," write Caroline C. Geerts, MD, from the Julius Center for Health Sciences and Primary Care and University Medical Center Utrecht in the Netherlands and colleagues. "The relation between smoke exposure in early life, the prenatal period in particular, and the vascular development of young children is largely unknown." To evaluate the association between parental smoking during pregnancy and subsequent vascular characteristics in their children, the investigators used data from the birth cohort enrolled in the Wheezing Illnesses Study Leidsche Rijn (WHISTLER)-Cardio study. At 5 years of age, 259 participants underwent ultrasonographic measurement of carotid artery intima-media thickness (CIMT) and arterial wall distensibility. Parental smoking data were also updated. After adjustment for the child's age and sex, maternal age, and breast-feeding, children of mothers who had smoked throughout pregnancy had more vascular damage than children of mothers who did not smoke during pregnancy. CIMT was 18.8 μm thicker in the former group (95% confidence interval [CI], 1.1 - 36.5; P = .04), and distensibility was 15% lower (95% CI, −0.3 to −0.02; P = .02). Children of mothers who smoked after pregnancy, but not during pregnancy, did not have these adverse effects on CIMT and distensibility. If both parents smoked during pregnancy, the associations were even stronger than with only maternal smoking: CIMT was 27.7 μm thicker (95% CI, 0.2 - 55.3), and distensibility was 21% lower (95% CI, −0.4 to −0.03). "This study is the first to show that the effect of smoking during pregnancy on the vasculature of children is (still) visible at the age of 5 years," the study authors write. "Pregnancy appears to be the critical period for this damage to occur." Limitations of this study include slightly different profiles in participants than in nonparticipants, lack of cotinine measurements at birth, and reliance on parental self-report of smoking. "In view of the early origins of cardiovascular disease, preventive measures against smoking should be specifically directed at the gestational period," the study authors conclude. The Netherlands Organization for Health Research and Development supported the WHISTLER birth cohort. The University Medical Center Utrecht supported WHISTLER-Cardio. The authors have disclosed no relevant financial relationships. Pediatrics. Published online December 26, 2011. Abstract