Ultrasound Poor Screen in Kids With Fever, UTI

Medscape Medical News

Veronica Hackethal, MD

February 10, 2014

Renal and bladder ultrasound (RBUS) is a poor screening tool for genitourinary (GU) abnormalities identifiable on voiding cystourethrogram (VCUG) after febrile urinary tract infections (UTIs) in children, according to a study published online February 10 in Pediatrics.

"Neither positive nor negative ultrasounds reliably identify or rule out [genitourinary] abnormalities," write Caleb P. Nelson, MD, MPH, from the Department of Urology, Boston Children’s Hospital, Harvard Medical School, Massachusetts, and colleagues. "Ultrasound and VCUG provide different, but complementary, information."

American Academy of Pediatrics (AAP) 2011 guidelines advise RBUS to screen for GU abnormalities in children aged 2 to 24 months with index cases of febrile UTIs, according to the authors, with VCUG used for confirming abnormalities suggestive of high-grade vesicoureteral reflux (VUR) or obstructive uropathy or after a second febrile UTI. The implication of these guidelines, the authors point out, is that a normal RBUS rules out clinically significant GU pathology.

The researchers looked at 3995 medical records between January 1, 2006, and December 31, 2010, in which VCUG and RBUS were conducted on the same day and then selected only those with UTI as an indication for imaging. They excluded records with postnatal GU imaging or prenatal GU abnormalities. They then placed both RBUS and VCUG into 4 categories each, based on GU abnormality type, with VUR graded on the 5-point international grading system. They also assigned diagnostic criteria thresholds for positive tests, ranging in severity from relaxed to stringent.

The researchers identified 2259 children younger than 60 months whose indication for imaging was UTI. RBUS was normal in 75%, but VCUG indicated 41.7% had evidence for any VUR, 20.9% had VUR greater than grade 2, and 2.7% had VUR higher than grade 3. Among those with a first febrile UTI, these percentages were 47.5%, 26.9%, and 2.6%, respectively. Depending on threshold, RBUS had a sensitivity ranging from 5% (specificity, 97%) to 28% (specificity, 77%), with the sensitivity of VUR higher than grade 3 ranging from 18% (specificity, 97%) to 55% (specificity, 77%).

There were 1203 children aged 2 to 24 months who received imaging after an initial febrile UTI. The positive predictive value of RBUS in this group was 37% to 47% for VUR higher than grade 2 and 13% to 24% for VUR higher than grade 3, with negative predictive values ranging from 72% to 74% (VUR higher than grade 2) and 95% to 96% (VUR higher than grade 3).

Limitations include possible misdiagnosis relating to the study's retrospective nature. In addition, the initial radiologist review was unblinded and not confirmed by independent review. To minimize verification bias, only patients with RBUS and VCUG on the same day were selected, which could have introduced selection bias if foregoing a second test was based on the first test's results.

"A negative RBUS does not rule out significant GU pathology (particularly VUR grades III and higher)," the authors conclude, "whereas a positive RBUS is a poor predictor."

In an independent commentary, Stephen M. Downs, MD, from Children’s Health Services Research, Indiana University School of Medicine, Indianapolis, commends this study for being the largest and most well-conducted of its kind.

However, although noting that this study's results are valid and consistent with past studies, and agreeing that RBUS is a "lousy screen for VUR," Dr. Downs ultimately supports the AAP guidelines. He points out that the guidelines actually suggest watchful waiting, rather than RBUS, to screen for high-grade VUR, with VCUG recommended only after the second UTI. Early RBUS is recommended for identifying parenchymal damage and obstructive uropathy associated with infection, he explains. Children with VUR are likely to have another UTI, he continues, and most (about 90%) will never have another UTI and would be unnecessarily exposed to the discomfort, cost, and radiation of VCUG.

"Readers should know that the RBUS recommended by the AAP guideline does serve a critical role in the evaluation of young children who have a first febrile UTI," Dr. Downs argues, "but it is watchful waiting that screens for VUR."

The authors and Dr. Downs have disclosed no relevant financial relationships.

Pediatrics. Published online February 10, 2014. Abstract

Dexamethasone Tames Acute Asthma in Kids, With Less Vomiting

Medscape Medical News

Diedtra Henderson

February 10, 2014
Giving children with acute asthma flare-ups 1 or 2 doses of dexamethasone in the emergency department (ED) provides equivalent relief to a 5-day course of prednisone while reducing the chance of triggering vomiting, according to a meta-analysis by Grant E. Keeney, MD, from the Department of Pediatrics, Medical College of Wisconsin, Milwaukee, and colleagues, who published the results of their analysis online February 10 in Pediatrics.

Some 6 million children in the United States suffer from asthma, a chronic inflammatory disease that accounts for 2% of all ambulatory care and ED visits by pediatric patients, the authors write. Oral prednisone, which tamps down inflammation and decreases mucus production, is the cornerstone of treatment for acute asthma exacerbations, but the remedy exacts a cost: vomiting.

The authors sought to determine whether dexamethasone might provide the same therapeutic benefit with fewer doses and less vomiting than is associated with a 5-day course of oral prednisone or prednisolone. Searching PubMed, the researchers identified 667 articles describing randomized clinical trials comparing the medicines of interest; they included 6 trials in the meta-analysis.

Each study was performed in the ED and enrolled from 15 to 272 patients, 63.5% of whom were boys. Dexamethasone was given as a single dose, either orally or intramuscularly, in 4 studies and was given as multiple doses in 2 studies. There was no statistically significant difference between the 2 therapies when it came to relapses to the clinic, ED, or hospitalization.

"Significantly fewer patients receiving dexamethasone vomited in the ED or at home after discharge. This finding has clinical significance for improving patient and parental satisfaction," according to the authors.

"This is a huge win for those of us in emergency medicine and, more importantly, for the families we take care of, when you consider that asthma is the most common chronic disease of children," Stephen J. Teach, MD, MPH, associate chief of the Division of Emergency Medicine at Children's National Medical Center in Washington, DC, told Medscape Medical News.

According to Dr. Teach, the facility handles 1% of ED visits made by children in the country for asthma. Practitioners recognized that if prednisone was given as early as possible during a significant asthma flare-up, it cut down on emergency admissions, and children missed less school.

"It was big breakthrough," he told Medscape Medical News. However, "prednisone is a terrible medication to take. It tastes awful. It's hard to mask it.... When it hits the stomach, it's an irritant. Kids throw it up all the time. It became this wonderful–terrible thing."

Dexamethasone's noxious taste, in contrast, can be masked with cherry syrup. Large-volume EDs already have begun to make the shift.

"There's really no difference, and it's more patient-centered," said Dr. Teach, who was not involved in the current study. "Kids take it better. They take fewer doses.... All of the available data suggest there is no difference in short-term outcomes."

The authors note that their results were based on studies based in the ED, making it unclear whether they apply to the ambulatory clinic setting.

"Based on our findings, emergency physicians should consider single or 2-dose dexamethasone regimens over 5-day prednisone/prednisolone regimens for the treatment of acute asthma exacerbations," the authors conclude.

The 2014 Child/Teen Immunization Schedule: Changes You Should Know

Medscape Pediatrics > Viewpoints

William T. Basco, Jr., MD, MS

February 03, 2014extracts 

Hepatitis A Vaccine Changes

Hepatitis A vaccine is routinely given at 12-23 months of age, but the previous footnotes were not specific as to which older children are considered "high risk" and therefore should receive the vaccine. The new footnotes provide clearer recommendations. Those specific recommendations now include children who may travel to countries that have a high or intermediate degree of endemic infection. Other recommended populations that might be cared for by pediatric providers include males who have sex with other males, users of illicit drugs (injectable or not), and patients with clotting factor disorders or chronic liver disease.

Human Papillomavirus Vaccine Changes

There are no global changes to the recommendations for human papillomavirus (HPV) vaccine. For pediatric providers, however, it is worth remembering that only the quadrivalent HPV vaccine is recommended for boys, whereas either the bivalent or quadrivalent HPV vaccine can be used for girls.  The third dose should be administered at least 12 weeks after the second dose and at least 24 weeks after the first dose.

Meningococcal Vaccine Changes

There is no change to the recommendation that 11- to 12-year olds should universally receive the vaccine and that a booster should be administered at 16 years of age. Changes in the meningococcal vaccine recommendations are mostly limited to expanded indications for the quadrivalent conjugate meningococcal vaccine MenACWY-CRM (meningococcal groups A, C, and Y and W-135 oligosaccharide diphtheria CRM197 conjugate vaccine; Menveo®) among younger children considered at high risk for meningococcal disease.

It is probably also worth reminding pediatric providers that certain older children should receive the meningococcal vaccine. Indicated populations include those with complement deficiencies or anatomical or functional asplenia, as well as children traveling to areas in Africa where meningitis is endemic or those undertaking the Hajj. Specific catch-up recommendations for children with high-risk conditions are also provided and require accessing additional CDC documents.

Pneumococcal Vaccine Changes

First, one of the most interesting changes is the addition of a clear statement about when pneumococcal polysaccharide vaccine (PPSV23) should be given relative to pneumococcal conjugate vaccine (PCV13): The footnotes state clearly that children in need of PPSV23 should receive the recommended PCV13 doses before receiving PPSV23. The PPSV23 dose should also be given at least 8 weeks after completion of PCV13series or catch-up. That sequencing was often probably the case for most children who received the polysaccharide vaccine, but there needs to be a continual emphasis on trying to complete the PCV13 series for all children before considering who should receive PPSV23.

Second, it is worth emphasizing that we are still seeing some children < 59 months of age who received pneumococcal vaccination as PCV7. Providers should ensure that children who received part of their pneumococcal vaccination as PCV7 receive the appropriate PCV13 follow-up doses. 

The footnotes also contain details on which children should receive PPSV23. For children 24 through 71 months of age, several chronic conditions indicate a need for PPSV23, including chronic cardiac disease; chronic lung disease; diabetes mellitus; cerebrospinal fluid leak; cochlear implants; sickle cell disease and other hemoglobinopathies; other asplenia; or immune suppression, including from HIV, renal failure, or receipt of immunosuppressive drugs.

Of all the indicated populations in a pediatric practice, the most prevalent is probably asthmatics who have received systemic steroids. That is a group of personal interest to me as a researcher, and one that we probably underemphasize for receipt of PPSV23.

Finally, the footnotes expand upon the description of who should receive a second dose of PPSV23 vaccine after age 5 years; it is worth noting that children with diabetes, chronic heart, lung, and liver disease are not among that group. The recommendation for a second PPSV23 dose is confined to those with immune-compromising conditions, now listed in the footnotes.

Tdap Vaccine Changes

In regard to Tdap, additional clarifications are provided in the footnotes. The universal recommendation that everyone 11 years of age or older receive at least 1 Tdap vaccination is still present. However, there is no current recommendation for further booster doses with Tdap, except among pregnant women. Pregnant women should receive Tdap with each pregnancy, preferably during the 27- to 36-week gestational age period.

A previous recommendation that warrants emphasis is the recommendation that Tdap be used for any child older than 7 years who needs a tetanus booster as part of wound management or as the first dose of a catch-up series, provided that they did not already receive a Tdap booster. They should not receive a second Tdap booster, however, if they have received one after age 7 years. As a reminder, this section also contains detailed recommendations for how to handle an older child who inadvertently receives DTaP and how this might affect the decision to later boost with Tdap.

For all vaccines, additional detail on indicated populations or indications for travelers can be found at the ACIP's vaccine-specific site.

Review Article: The Management of Acute Gastroenteritis in Children

Alimentary Pharmacology & Therapeutics

M. Pieścik-Lech, R. Shamir, A. Guarino, H. Szajewska

Aliment Pharmacol Ther. 2013;37(3):289-303

Introduction

Acute gastroenteritis (AGE), characterised by the sudden onset of diarrhoea with or without vomiting, is one of the most common infectious diseases of childhood. In Europe, it is estimated that the incidence of diarrhoea ranges from 0.5 to 1.9 episodes per child per year in children up to 3 years of age.[1] In low- and middle-income countries, while the incidence of acute diarrhoea has declined from 3.4 episodes/child year in 1990 to 2.9 episodes/child year in 2010, the incidence of AGE remains high, especially in infants aged 6–11 months (4.5 episodes/child year).^[2] Moreover, worldwide diarrhoea remains one of the leading causes of mortality among children younger than 5 years.^[3]

In 2008, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society of Paediatric Infectious Diseases (ESPID) developed evidence-based guidelines for the management of AGE for practitioners at all levels of health care – primary care physicians, paediatricians and family physicians – practising in Europe.^[1] In addition, a number of national guidelines have been developed, although their quality varies.^[4] Perhaps the best known among them are those developed by the National Institute for Health and Clinical Excellence (NICE).^[5]

Both ESPGHAN/ESPID and the NICE guidelines largely agree on key issues in the management of AGE. Oral rehydration therapy with a hypotonic solution remains central to the management of AGE. Fast oral rehydration with rapid return to regular food is recommended. 

The routine use of special or diluted formulas is unjustified. Continuation of breastfeeding is strongly recommended. 

The guidelines recommend against the routine use of antibiotics in otherwise healthy children presenting with AGE. 

Regarding drugs, both sets of guidelines recommend against the use of antiemetics, but they strongly emphasise the need for further research. Compared with the NICE guidelines, the ESPGHAN/ESPID guidelines make a stronger recommendation for the use of probiotics for the management of AGE, particularly those with documented efficacy such as Lactobacillus GG and Saccharomyces boulardii. 

The ESPGHAN/ESPID guidelines state that treatment with racecadotril (an enkephalinase inhibitor) may be considered in the management of AGE. Both sets of guidelines state that there is evidence suggesting that smectite (a natural hydrated aluminomagnesium silicate that binds to digestive mucus and has the ability to bind endotoxins and exotoxins, bacteria and rotavirus) is an effective antidiarrhoeal agent, but only the ESPGHAN/ESPID guidelines recommend that the use of smectite may be considered in the management of AGE.

Got (Raw) Milk? Consider the Risk

Medscape Medical News

Janis C. Kelly

February 23, 2012

February 23, 2012 — Researchers from the US Centers for Disease Control and Prevention (CDC) are calling for all states to further restrict or prohibit the sale or distribution of products made from unpasteurized ("raw") milk in the wake of data showing that risk for disease is 150-fold higher after consumption of nonpasteurized dairy products, and that 60% of the resulting outbreaks involve children. CDC epidemiologist Adam J. Langer, DVM, MPH, and colleagues reported their analysis of disease outbreaks from nonpasteurized dairy products in an article published in the March issue of Emerging Infectious Diseases.

Although the distribution of nonpasteurized dairy products in interstate commerce has been prohibited by the US Food and Drug Administration (FDA) since 1987, sale of unpasteurized products within the state where they are produced is regulated by each state. During the time of the study (1993 - 2006), sale of nonpasteurized milk was legal in 25 states.

During that period, the CDC researchers found 121 outbreaks of dairy-related diseases for which the product's pasteurization status was known. This included 73 (60%) outbreaks involving nonpasteurized products, although such products account for less than 1% of total dairy product consumption. In outbreaks involving milk, 82% were from nonpasteurized milk. In outbreaks involving cheese, 42% were from cheese made from unpasteurized milk.

Outbreaks involving nonpasteurized dairy products resulted in 1571 illnesses, with a median of 11 patients, a hospitalization rate of 13%, and 2 deaths. All of the outbreaks from nonpasteurized dairy products were caused by bacteria, most commonly Campylobacter spp (54%), Salmonella spp (13%), and Shiga toxin–producing Escherichia coli (4%), which have animal reservoirs.

Outbreaks involving pasteurized dairy products (which account for 99% of approximately 2.7 trillion pounds of milk consumed during the study period) included 2842 illnesses, resulted in a hospitalization rate of 1%, and caused 1 death. The most common causative agents were norovirus (44%) Salmonellaspp. (20%), and Campylobacter spp (13%). Norovirus has a human reservoir.

"These results suggest that outbreaks caused by nonpasteurized dairy products are probably caused by pathogens in the dairy environment, which would be eliminated by proper pasteurization, and that outbreaks caused by pasteurized dairy products are probably caused by contamination of the products at some point after pasteurization," the authors write.

Of the outbreaks associated with unpasteurized dairy products, 75% occurred in 21 states where it was legal to sell raw milk products during the study period.

"This study shows an association between state laws and the number of outbreaks and illnesses from raw milk products," said Robert Tauxe, MD, MPH, deputy director of the CDC's Division of Foodborne, Waterborne and Environmental Diseases (DFWED). "Restricting the sale of raw milk products is likely to reduce the number of outbreaks and can help keep people healthier. The states that allow sale of raw milk will probably continue to see outbreaks in the future," Dr. Tauxe told Medscape Medical News.

Outbreaks from unpasteurized milk also disproportionately affect people younger than 20 years (60% vs 23% from pasteurized milk). The authors write, "Public health and regulatory authorities are obligated to protect persons who cannot make fully informed decisions (e.g., children) from potential health hazards. Dietary decisions for younger children, in particular, are often made by caregivers. The American Academy of Pediatrics advises against giving nonpasteurized dairy products to children and recommends that pediatricians counsel caregivers against use of these products."

"While some people think that raw milk has more health benefits than pasteurized milk, this study shows that raw milk has great risks, especially for children, who experience more severe illnesses if they get sick," said study coauthor Barbara Mahon, MD, MPH, deputy chief of CDC's DFWED Enteric Diseases Epidemiology Branch. "Parents who have lived through the experience of watching their child fight for their life after drinking raw milk now say that it's just not worth the risk," she told Medscape Medical News.

Of the known sources for 9 of the 15 outbreaks that occurred in states where sale of nonpasteurized dairy products was illegal, 7 (78%) were associated with products obtained directly from the dairy farm, 1 was limited to members of a family who consumed nonpasteurized milk from their own cow, and 1 was associated with products obtained under a "cow shares" communal program, which the CDC report describes as "a scheme used to circumvent state restrictions on commercial sales of nonpasteurized dairy products." Cow share owners argue that they have the legal right to drink raw milk from the cow they partly own.

The CDC researchers also note, "[I]n recent years, foodborne outbreaks involving nonpasteurized dairy products have been reported in association with traditional nonpasteurized products marketed to the growing Hispanic community in the United States."

The researchers warn, "Consumption of nonpasteurized dairy products cannot be considered safe under any circumstances."

In a related development, on February 22 a federal court granted the FDA a permanent injunction preventing Amish farmer Daniel L. Allgyer and his Rainbow Acres Farm from distributing packaged raw milk and raw milk products across state lines from his Pennsylvania farm to participants in a cow share program in the Washington, DC, metropolitan region.

Emerg Infect Dis. 2012;18:385-391. 

Drugs and the Breastfeeding Mother: A New Clinical Report

FDA on Medscape > FDA Expert Interview

Laurie Scudder, DNP, NP, Hari Cheryl Sachs, MD

Disclosures

October 29, 2013

Editor's Note:
Many breastfeeding women are advised to stop taking necessary medications or to discontinue nursing because of potential harmful effects on their infants. The reality is that few medications are contraindicated in breastfeeding mothers.

The American Academy of Pediatrics (AAP) has just released a new clinical report, The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics, to provide guidance on drug exposure and reaffirm the recommendation that most medications and immunizations are safe during lactation. Medscape spoke with lead author and pediatrician Hari Cheryl Sachs, MD, the US Food and Drug Administration (FDA) liaison to the AAP Committee on Drugs, about the key recommendations from the report and resources to assist clinicians in obtaining current information on specific drugs to help guide their advice to breastfeeding women.

Medscape: The key message of this report is that although some drug classes should be avoided or at least used cautiously in lactating women after a careful risk/benefit assessment, many medications can and should be continued. When a healthy nursing mom presents to primary care with a common, mild illness -- such as bacterial sinusitis, migraine, intermittent asthma, or an allergic reaction -- that requires an anti-infective agent, a beta-agonist, an antihistamine, or a triptan, can providers feel comfortable treating this woman and encouraging her to continue nursing?

Dr. Sachs: As stated in the report, not all medications are present in breast milk in clinically significant levels or pose a risk to the nursing infant. The prescribing information (drug label) and LactMed (a drugs and lactation database, also available in a mobile app) will have the information to help a provider decide whether to use a drug in a lactating patient.

Medscape: The report points out that the age of the infant is an important factor in deciding how to treat a mother, because most adverse events associated with drug exposure through breast milk occur in infants younger than 2 months. What other infant factors should clinicians consider when deciding on treatment for a nursing mom?

Dr. Sachs: An important consideration for all drugs is related to the adverse-event profile and properties of the specific drug. Several excellent resources are available to inform clinicians about specific drugs, such as product labeling or LactMed. For example, the FDA recently approved newlabeling information for trimethoprim/sulfamethoxazole (Septra®), emphasizing the need for caution in administering this drug to nursing women, particularly if the infant is jaundiced, ill, stressed, or premature, because of the potential risk for bilirubin displacement and kernicterus.

Medscape: Depression and mood disorders are common in women of childbearing age, and the risks of not treating these women are potentially severe. Data on the long-term safety of psychoactive drugs are limited, yet the report does not recommend advising these women to stop breastfeeding.

Dr. Sachs: Caution is definitely warranted here. As stated in the report, the infant could potentially be exposed to clinically significant levels of these drugs, and the long-term effects are unknown. Decisions about breastfeeding for these patients should be evidence-based. The drug label and LactMed should be consulted for information on drugs that a clinician may be considering.

Medscape: What do you recommend for the care and monitoring of nursing infants whose mothers are being treated with an antidepressant, anxiolytic, or antipsychotic?

Dr. Sachs: Use of these products by nursing women should be discussed with the infant's healthcare provider. Adverse events as well as growth and development should be monitored in these infants. Any adverse events should be reported to the FDA's Adverse Event Reporting System.

Medscape: Treatment of pain is another subject discussed in detail in the report. What is recommended for short-term use in women whose pain is not controlled by over-the-counter analgesics?

Dr. Sachs: Caution is advised for nursing women using narcotic pain relievers because of the potential for adverse effects in nursing infants, and some are not recommended at all for use in nursing women because they are concentrated in breast milk.

Codeine has been associated with rare fatalities in nursing infants. In women with normal codeine metabolism, the amount of codeine (and its active metabolite, morphine) in breast milk is low and related to the dose. However, in ultra-rapid metabolizers, higher-than-expected concentrations of the active metabolite (morphine) may occur in breast milk, and potentially dangerous levels may be reached in breastfed infants.

Thus, the risk of infant exposure to codeine and morphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and the baby. Close monitoring of mother/infant pairs is recommended when codeine is administered to a nursing woman. The lowest dose should be prescribed for the shortest period to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of toxicity in their infants, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms, such as extreme sleepiness, confusion, or shallow breathing.

Of note, safety labeling changes for extended-release and long-acting opioid analgesics announced by the FDA in September will highlight the risk for neonatal opioid withdrawal syndrome (NOWS) in a boxed warning. Symptoms of NOWS may include poor feeding, rapid breathing, trembling, and excessive or high-pitched crying.

For more information on codeine and other treatment options, see the drug label and LactMed.

Medscape: The report reviewed agents that have been used to stimulate lactation, including dopamine antagonists, such as domperidone, and herbal products, such as fenugreek. What is the bottom line on these agents? Does any evidence support their use?

Dr. Sachs: The FDA issued a warning on domperidone. There is little evidence of benefit with domperidone, and safety information on many of these products is lacking. Nonpharmacologic methods of stimulating lactation are preferred. The report encourages breastfeeding mothers to discuss all products that they take, including herbal products, with their healthcare professionals.

Medscape: The report acknowledges that information in this area changes rapidly, making it impossible for written reports to keep pace with new developments. Drug labels will continue to be an essential source of information. Can you outline some of the key changes in the pregnancy and lactation sections of labeling?

Dr. Sachs: Under the proposed rule, the Pregnancy and Lactation subsections of labeling would each include 3 sections:Risk summary, Clinical considerations, and Data.

In the Pregnancy subsection, the Fetal Risk summary will provide a narrative description based on risk evaluations of human, animal, and pharmacologic data that describe the likelihood that a drug increases the risk for adverse developmental outcomes. The Fetal Risk summary replaces the current pregnancy letter categories (A, B, C, D, X). The Clinical considerations section is intended to further inform prescribing and risk/benefit counseling. Labor and delivery information, when available, will be incorporated into this section. Pregnancy registry information with contact information, when available, must be included in the pregnancy subsection. The Data section will provide a detailed overview of both the human and animal data used to inform the previous sections.

In the Lactation subsection, the Risk summary will summarize what is known and unknown about the amount of drug likely to be present in human milk and any potential effect on breastfeeding infants. The Clinical considerations section will include methods to minimize exposure when applicable, as well as information about monitoring the infant for toxicity or adverse effects. The Data section will provide a detailed overview of available human data used to inform the Risk summary and Clinical considerationssections.

Medscape: What are the best resources for a clinician who needs to access information about a particular pharmacologic agent quickly, in the middle of a busy clinical day?

Dr. Sachs: Drug labeling and LactMed, which I've noted several times, are important resources and are available online at:

• Drugs@FDA (the FDA's database of approved drugs);
• Daily Med (drug information, including FDA labels and package inserts);
• LactMed (drugs and lactation database); and
• LactMed App.

Editor's note: Medscape's Drugs, OTCs & Herbals provides rapid lookup.

Early Onset of Puberty in Girls Linked to Obesity

Medscape Medical News

Joanna Broder

November 04, 2013   Girls in the United States are entering puberty at younger ages than they have in the past, but investigators have not been able to pinpoint the cause. Now, a longitudinal study, published online November 4 in Pediatrics, suggests a higher body mass index (BMI) plays a role in earlier breast development in white, non-Hispanic girls.

"This study demonstrates earlier maturation in white non-Hispanic girls, with greater BMI linked as a major factor," write Frank Biro, MD, the study's lead author and the director of research for adolescent and transition medicine at Cincinnati Children's Hospital Medical Center in Ohio, and colleagues.

"This article adds to studies providing the unsettling findings that the age of onset of breast development, in synch with, though not entirely explained by, the 'obesity epidemic,' has continued to drop," writes Dr. Herman-Giddens, an adjunct professor with the Department of Maternal and Child Health at the Gillings School of Global Public Health, University of North Carolina, Chapel Hill.

The whole distribution of puberty timing has shifted to a younger age, note Dr. Frank and colleagues. The fact that girls are undergoing earlier maturation has important clinical ramifications. For example, girls who reach puberty earlier than their peers may be at increased risk for depression and low self-esteem and be more likely to engage in substance abuse and intercourse at an earlier age than girls who reach puberty later.

In addition, the ripple effects of early maturation extend into adulthood, the authors write, including increased risk of breast and ovarian cancers.

The researchers enrolled 1239 girls from Greater Cincinnati, New York City, and the San Francisco Bay Area. The girls were between the ages of 6 and 8 years at the time of enrollment. Trained clinicians examined the girls at regular intervals for 7 years from 2004 to 2011, assessing breast development through observation and palpitation. They then determined BMI percentiles and z scores, using the 2000 growth charts from the Centers for Disease Control and Prevention.

At baseline, 39% of the black girls had a BMI in the 85th percentile or higher, as did 44% of Hispanic girls, 26% of non-Hispanic white girls, and 12% of Asian girls.

The investigators found that the onset of breast development, as defined by reaching breast stage 2 or greater, differed by clinic site, race/ethnicity, and BMI at baseline.

The mean and median age breast development varied by race and ethnicity. Black girls started developing breasts at a median age of 8.8 years, whereas Hispanic, non-Hispanic white, and Asian girls did so at median ages of 9.3, 9.7, and 9.7 years, respectively.

When the investigators examined timing of breast development and BMI, they found that as the girls' BMI increased above the 50th percentile, the likelihood of earlier breast development increased, relative to girls with a BMI below the 50th percentile (P value for trend = .001). The researchers adjusted for race/ethnicity and site.

In addition, the authors found that the onset of breast development in white girls occurred at younger ages than reported in previous publications but that "black girls continue to experience breast development earlier than white girls." Much of the difference in timing of development in non-Hispanic white girls, between this study and previous ones, is likely a result of the higher BMIs in the current study population, the authors note.

The authors conclude that having a higher BMI is the strongest predictor of earlier onset of stage 2 breast development.

Dr. Herman-Giddens notes that our society may have to live with uncertainty as to what factor or combination of factors is causing girls to start puberty earlier than they did decades ago.

The obesity epidemic is an important factor in the decline in age of onset for puberty in girls, she writes, but she also notes that the study found that BMI accounted for 14.2% of the variance of all covariates in the researchers' model."

Although obesity is implicated as a 'prime driver,' factors involved in these secular changes are far more complex," she writes. "Extensive interacting variables are known to be associated with earlier development in addition to weight and genetics: certain intrauterine conditions and exposures, preschool high-meat diets, dairy products, low fiber intake, isoflavones, high-stress families, absent fathers, certain endocrine disruptors, the microbiome as it influences weight, epigenetics, light exposure, hormone-laced hair products, insulin resistance, activity level, geographical location, and others."

Pediatrics. Published online November 4, 2013.