Children exposed early to antibiotics likely to have allergies later in life

Meta-analysis of 34 observational studies.

A meta-analysis suggests children exposed to antibiotics early in life may have an increased risk for developing symptoms of hay fever, eczema and food allergy later in life. The findings were published in the journal Allergy.

Researchers screened the PubMed and Web of Science databases and identified 34 observational studies (20 cohort; 6 case-control; 8 cross-sectional) which were included in the final meta-analysis.

Early life exposure to antibiotics was found to have a significant association with risk for hay fever (OR, 1.23; 95% CI, 1.13-1.34), eczema (OR, 1.26; 95% CI, 1.15-1.37) and food allergy (OR, 1.42; 95% CI, 1.08-1.87). However, there was no significant association between early life exposure to antibiotics and markers of allergy such as positive skin prick test (OR, 1.01; 95% CI, 0.92-1.11) and elevated allergen-specific serum/plasma IgE levels (OR, 0.95; 95% CI, 0.77-1.16) later in life.

The mechanisms underlying the association have not been clearly understood yet. One of the possible mechanisms could be immunomodulatory action of antibiotics through modification of gut microbiota, thereby influencing the risk for allergic disorders. There is also a possibility of confounding by indication, where individuals prone to allergies later in life may also have a susceptibility to immunodeficiency conditions requiring treatment with antibiotics early in life.

According to the authors, inappropriate antibiotic use in children is a major concern, hence it is essential to define prognostic and diagnostic markers and identify children who never benefited from antibiotics therapy. There is also a need to educate patients and clinicians regarding judicious use of antibiotics.

Source: A meta-analysis. Allergy. 2017 Nov 6 [Epub ahead of print]. doi: 10.1111/all.13332. PMID: 29105784

Even Short-term Oral Steroids Carry Serious Risk

The millions of Americans prescribed short-term oral corticosteroids are taking a dose of risk along with their medication, according to a cohort study of more than 1.5 million adults.

Within 30 days of initiating these drugs, even at relatively low doses, users had a nearly twofold increased risk for fracture, a threefold increased risk for venous thromboembolism, and a fivefold increased risk for sepsis.

"Greater attention to initiating prescriptions of these drugs and monitoring for adverse events may potentially improve patient safety," write Akbar K. Waljee, MD, an assistant professor of gastroenterology at the University of Michigan in Ann Arbor, and colleagues. They present their findings in an article published April 12 in the BMJ.

They found that more than one in five adults included in the Clinformatics DataMart, a large national database of commercial insurance claims, received prescriptions for short-term oral corticosteroids during the 3-year study, which ran from January 1, 2012, to December 31, 2014.

Although corticosteroids are among the most common cause for hospitalization for drug-related adverse events, and various specialties have long focused on optimizing their long-term use, the short-term risks associated with the drugs have been less carefully studied.

"Although physicians focus on the long-term consequences of steroids, they don't tend to think about potential risks from short-term use," said Dr Waljee in a university news release. "We see a clear signal of higher rates of these three serious events within 30 days of filling a prescription. We need to understand that steroids do have a real risk and that we may use them more than we really need to. This is so important because of how often these drugs are used."

Of 1,548,945 adults aged 18 to 64 years included in the database, 327,452 (21.1%) received at least one outpatient prescription for short-term oral corticosteroids (30 or fewer days). The mean age of users was 45.5 years (standard deviation [SD], 11.6 years) compared with 44.1 years (SD, 12.2 years) for nonusers (P < .001). The median duration of use was 6 days (interquartile range, 6 - 12 days).

The six most common indications for the drugs were upper respiratory tract infections, spinal conditions, intervertebral disc disorders, allergies, bronchitis, and nonbronchitic lower respiratory tract disorders. Together, those indications accounted for about half of all prescriptions. The two most common physician specialties prescribing short-term oral corticosteroids were family medicine and general internal medicine.

Nearly half (46.9%) of recipients were prescribed a 6-day prepackaged methylprednisolone "dosepak," which tapers the dose from highest to lowest. Dr Waljee noted in the news release that although individual oral steroid pills can cost less than a dollar each for a 7-day course, the prepackaged version may cost several times that and often initiates therapy with a higher high dose than may be necessary.

Use was more frequent among older patients, women, and white adults, with significant regional variation (all P < .001).

Within 30 days of drug initiation, there was an increase in incidence rate of the following: sepsis, with a rate ratio of 5.30 (95% CI, 3.80 - 7.41); venous thromboembolism, with a rate ratio of 3.33 (95% CI, 2.78 - 3.99); and fracture, with a rate ratio of 1.87 (95% CI, 1.69 - 2.07).

The increased risk persisted at prednisone equivalent doses of less than 20 mg/day, with an incidence rate ratio of 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture (all P < .001).

Rate ratios decreased during the following subsequent 31 to 90 days, however.

Although rare, hospitalizations were also more frequent in users than nonusers, with 0.05% of users admitted for sepsis compared with 0.02% of nonusers. For blood clots, the admission rate was 0.14% versus 0.09%, and for fractures, it was 0.51% vs 0.39%.

Dr Waljee and associates found it significant that the most frequent corticosteroid prescribers were not rheumatologists or other subspecialists experienced in treating inflammatory conditions long-term. "A substantial challenge to improving use of oral corticosteroids will be the diverse set of conditions and types of providers who administer these drugs in brief courses," they write. "This raises the need for early general medical education of clinicians about the potential risks of oral corticosteroids and the evidence basis for their use, given that use may not be specific to a particular disease or specialty."

On the basis of these findings, Dr Waljee recommended prescribing the smallest possible amount of corticosteroids for treating the condition in question. "If there are alternatives to steroids, we should be use those when possible," he said in the release. "Steroids may work faster, but they aren't as risk-free as you might think."

(Diana Swift in; Source: BMJ. 2017;357:j1415).

Guidelines Say No Special Precautions Needed for Flu Shots for People Allergic to Eggs

An updated practice parameter from the Joint Task Force on Practice Parameters stresses that people with egg allergy should receive their yearly flu shot, and that no special precautions are required.

The guidelines are published in Annals of Allergy, Asthma and Immunology.

"When someone gets a flu shot, healthcare providers often ask if they are allergic to eggs," said lead author Matthew Greenhawt, MD, University of Colorado School of Medicine, Aurora, Colorado. "We want healthcare providers and people with egg allergy to know there is no need to ask this question anymore, and no need to take any special precautions. The overwhelming evidence since 2011 has shown that a flu shot poses no greater risk to those with egg allergy than those without."

For years, people with an egg allergy have been told to avoid or take special precautions when getting a flu shot because most influenza vaccines are grown in eggs and contain a tiny amount of egg protein.

There have been dozens of studies involving thousands of patients with egg allergy who have received a flu shot without allergic reactions, including hundreds with life-threatening egg allergy. This is because the influenza vaccine does not contain enough egg protein to cause an allergic reaction, even in patients with severe egg allergy. Prior practice parameters noted this and recommended that egg allergic patients could safely receive their vaccination at an allergist?s office.

The updated parameter stresses that no special precautions are needed or recommended for those with egg allergy. There is no longer a need to see an allergy specialist for the flu shot, give special flu shots that don?t contain traces of egg, require longer-than-normal observation periods after the shot, or even ask about egg allergy before giving the vaccine. If the vaccine is age-appropriate, it can be used for anyone with or without egg allergy.

These recommendations from the allergy community are consistent with those from the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP), all emphasising the safety and importance of egg-allergic patients receiving their annual influenza vaccine.

DOI: 10.1016/j.anai.2017.10.020
SOURCE: American College of Allergy, Asthma and Immunology

Higher Blood Glucose Values in Early Pregnancy Linked to Congenital Heart Disease in Offspring

Higher plasma glucose levels early in pregnancy increases the baby's risk of a congenital heart defect, even among mothers who do not have diabetes, according to a study published in The Journal of Pediatrics.

For many years, physicians have known that women with diabetes face an increased risk of giving birth to babies with heart defects. However, the current study is the first to examine this question in the earliest part of pregnancy, when the fetal heart is forming.

"Most women who have a child with congenital heart disease are not diabetic," said senior author James Priest, MD, Stanford University School of Medicine, Stanford, California. "We found that in women who don't already have diabetes or develop diabetes during pregnancy, we can still measure risk for having a child with congenital heart disease by looking at their glucose values during the first trimester of pregnancy."

One challenge associated with conducting the research was the fact that maternal blood glucose is not routinely measured in pregnant women without diabetes. Instead, women typically receive an oral glucose tolerance test halfway through pregnancy to determine whether they have gestational diabetes, but this test is performed well after the fetal heart has formed.

Dr. Priest and colleagues studied medical records from 19,107 pairs of mothers and their babies born between 2009 and 2015. The records included details of the mothers' prenatal care, including blood test results and any cardiac diagnoses made for the babies during pregnancy or after birth.

Infants with certain genetic diseases, those born from multiple pregnancies, and those whose mothers had extremely low or high body-mass-index measures were not included in the study.

Of the infants in the study, 811 were diagnosed with congenital heart disease, and the remaining 18,296 were not.

The researchers analysed blood glucose levels from any blood sample collected from the mothers between 4 weeks prior to the estimated date of conception and the end of the 14th gestational week, just after the completion of the first trimester of pregnancy. These early blood glucose measurements were available for 2,292 (13%) of women in the study. The researchers also looked at the results of oral glucose tolerance tests performed around 20 weeks of gestation, which were available for 9,511 of the women in the study.

After excluding women who had diabetes before pregnancy or who developed it during pregnancy, the results showed that the risk of giving birth to a child with a congenital heart defect was elevated by 8% for every increase of 10 mg/dL in blood glucose levels in the early stages of pregnancy.

Dr. Priest said that the next step in the research is to conduct a prospective study that follows a large group of women through pregnancy to see if the results are confirmed. If they see the same relationship, it may be helpful to measure blood glucose early in pregnancy in all pregnant women to help determine which individuals are at greater risk for having a baby with a heart defect.

"We could use blood glucose information to select women for whom a screening of the fetal heart could be helpful," said Dr. Priest. "Knowing about defects prenatally improves outcomes because mothers can receive specialised care that increases their babies' chances of being healthier after birth."


SOURCE: Stanford University Medical Center

Intravenous vs oral acetaminophen: Which is more effective for treating fever in children?

Study compares the effects of IV vs oral dose in febrile children.

According to a new study published in the Indian Journal of Pediatrics, a single dose of intravenous (IV) acetaminophen is safe and effective in reducing fever and may be useful in patients who are unable to tolerate oral dose of acetaminophen and when rapid reduction of temperature is desirable.

Researchers evaluated the antipyretic effects in 400 children randomly assigned to receive either IV acetaminophen (15 mg/kg/dose; n=200) or oral acetaminophen (15 mg/kg/dose; n=200) over 6 hours.

Allergic reaction was reported in 7 (3.5%) of the patients in IV acetaminophen group whereas it was absent in oral acetaminophen group. Onset of constipation and dry mouth was reported in 8 (4%) patients in the IV acetaminophen group whereas it was absent in oral acetaminophen group. Requirement for additional dose was higher in IV acetaminophen group vs oral acetaminophen group (5% vs 3%; P=.307). Reduction in temperature was significantly high (weighted sum of temperature differences through 180 minutes) in IV acetaminophen group compared with oral acetaminophen group (P<.004).

This study concludes that faster reduction of temperature with IV acetaminophen may be considered superior in children, specifically with some paediatric ailments such as febrile seizure, febrile encephalopathy, and high fever with feed refusal where it is essential to prevent a scary convulsive attack and alarming metabolic compromise.

(Roy S, Simalti AK. Indian J Pediatr. 2017 Sep 9. doi: 10.1007/s12098-017-2457-3).

Obesity Can Add 5 Weeks of Asthma Symptoms Per Year in Preschoolers

Asthma symptoms may be worse for children aged 2 to 5 who are overweight, according to a study published in the Journal of Allergy and Clinical Immunology.

Preschoolers with a body mass index (BMI) beyond the 84th percentile who weren't using an inhaler had 70% more days with asthma symptoms per year than untreated peers of a healthy weight.

Compared with healthy-weight peers, asthma sufferers who were untreated and overweight suffered 37 more symptom-days -- more than 5 extra weeks -- per year.

The researchers also found that untreated children who were overweight had more asthma attacks than untreated peers of a healthy weight.

However, obesity doesn't seem to lessen the effectiveness of corticosteroid inhalers. When used daily, inhalers reduced the number of symptom-days and asthma attacks in both healthy and overweight children, and may even be more protective to overweight children.

"The impact of overweight and obesity on asthma has not been studied in the youngest asthma patients, and this finding is the opposite of what has been seen in older kids and adults who are overweight," said Jason Lang, MD, Duke Children's Pulmonary Function Laboratory, Durham, North Carolina. "Reports in older children and adults with asthma who are overweight have shown a poor response to inhaled corticosteroids to manage their asthma. This study suggests either pathways of inflammation are a bit different in preschool-aged patients, or that it takes years for obesity to reduce the effectiveness of steroid inhalers."

The researchers analysed data from the randomised INFANT, PEAK, and MIST trials. The 3 studies comprised 736 children, of which about one-third had a BMI above the 84th percentile. Some trial participants were randomised to use inhalers daily while some used them intermittently; some received placebos and some received no treatment.

The authors believe this is the first study on whether obesity impacts asthma severity and the effectiveness of inhalers in preschoolers, but the study does have limitations, including that it was a retrospective analysis. A prospective study with a larger number of children could offer more insights into the best asthma treatments for overweight preschoolers and include strategies that address weight loss.

"This study uses the best, mostly highly controlled data to demonstrate that early-life weight gain does worsen the severity of asthma in the youngest patients," said Dr. Lang. "Weight does not hamper the effectiveness of inhaled steroids in preschoolers, but this study provides clear evidence that maintaining a healthy weight in preschoolers may be an effective strategy for controlling asthma."

SOURCE: Duke Health

Omalizumab offers long-term benefits in patients with severe allergic asthma

Omalizumab is an effective add-on therapy for patients with uncontrolled SAA.

Inadequately controlled severe asthma is linked to increased risk for exacerbations that may lead to increased emergency room visits and hospital admissions. Although there is evidence on the long-term efficacy of omalizumab, limited data is available on the real-life outcome beyond 1 year of the treatment.

This retrospective study included 45 patients with SAA who received omalizumab 150-600 mg every 2 or 4 wk for ?23 mo. Data on hospitalisations, exacerbations, corticosteroid sparing, asthma control, lung function, biomarkers, and side effects were used to evaluate the benefits of long-term omalizumab treatment in patient with severe allergic asthma (SAA).

Compared with baseline, long-term treatment with omalizumab was associated with significant reduction in mean annual per patient hospitalizations (0.89 vs 4.8; P<.00001), mean daily maintenance oral corticosteroid dose (6.0 vs 25.8 mg; P<.0001), mean asthma control questionnaire score (2.3 vs 4.0; P<.0001), median fraction exhaled nitric oxide level (24 vs 37 parts per billion; P=.0067), mean steroid courses (3.1 vs 6.1; P<.001). The Mean % predicted FEV1 significantly increased from 59.2% at baseline to 75.7% (P=.0013)). Adverse events were non-serious and did not lead to treatment withdrawal in long-term responder populations.

In conclusion, omalizumab offered sustained long-term benefits with an acceptable safety profile among patients with SAA.

Pediatricians Lowest Paid, but Among Happiest at Work

Pediatricians are the lowest-paid physicians again in this year's Medscape Compensation Report, at $202,000, but the recent Medscape Lifestyle Report finds they are among the top third of those happiest at work.

Pediatricians were the only specialty to lose ground in terms of average pay this year, with a decrease in compensation of 1% relative to the 2016 numbers. In contrast, plastic surgeons had the largest gains, seeing a 24% rise from 2016.

Just more than half of pediatricians (52%) said they were satisfied with their pay, landing near the middle among specialties, with emergency medicine at the top in pay satisfaction (68%) and nephrologists at the bottom (41%).

In this year's compensation survey, physicians not satisfied with pay were asked how much more they should make. Nearly half of pediatricians unhappy with their current salary said they should make 11% to 25% more, whereas 32% said 26% to 50% more.

However, the recently published Medscape Lifestyle Report shows that 36% of pediatricians said they were very happy or extremely happy at work. Most happy at work were dermatologists (43%) and ophthalmologists (42%), the same specialties happiest at work last year. Least likely to report high happiness levels were nephrologists and rheumatologists, both at 24%.

Pediatricians were also among the happiest outside work. At 70%, they were in the fourth-highest percentage group. Most happy outside work were urologists (76%); least happy were the rheumatologists (61%).

Few in MACRA

The Medicare Access and CHIP Reauthorization Act (MACRA) launched in January of this year, and the Medscape Compensation survey asked physicians whether they would participate. At 33%, pediatricians were among the least likely. Ophthalmologists were the most likely to participate, at 64%, and psychiatrists were the least likely, at 19%.

More pediatricians this year said they have seen an influx of patients because of the Affordable Care Act: 32% said yes this year as opposed to 26% in 2016.

Many more pediatricians this year also said they would participate in healthcare exchanges compared with last year, at 36% vs 21%. However, uncertainty remains high, with 45% of pediatricians undecided on participation.

Almost half (47%) reported that participation in the exchanges has not changed income; 12% said they resulted in a decrease and 5% reported an increase, whereas 37% did not participate.

Preventing Pediatric Migraine: What Treatment Is Best?

A Trial of Migraine Prevention in Pediatrics

The Childhood and Adolescent Migraine Prevention (CHAMP) trial[1] sought to improve the quality of the evidence about prevention of migraine among children and adolescents. The two active drugs tested in the study (amitriptyline and topiramate) were chosen on the basis of consensus views that they were the ones most commonly used to prevent migraine in kids. The main hypothesis tested was that both of the active treatments would perform better than placebo, and Powers and colleagues also hypothesized that one of the active treatments would prove superior to the other.

The CHAMP trial enrolled children (aged 8-17 years) at 31 US sites. To be eligible for enrollment, the children must have experienced at least 4 days of headache during a 28-day assessment period (baseline). In addition, the children had at least "mild" disability, on the basis of an established pediatric migraine disability scale.

The children were randomly assigned in a 2:2:1 ratio to receive the two active treatments and the placebo regimen, respectively. All regimens were administered twice each day. Amitriptyline was dosed at 1 mg/kg daily, and topiramate was dosed at 2 mg/kg daily to start. Once the children experienced appropriate dose escalation, they were maintained on a 16-week treatment phase at their highest tolerated dose.

After 24 weeks of treatment, the children completed a 28-day headache diary that served as the post-treatment outcome, compared with headache days at baseline. A treatment success was any child who experienced a 50% or greater decrease in the number of headache days between the baseline and the final assessment. Changes in headache-related disability, and other secondary outcomes, were also assessed.

Of note, the original trial planned to enroll 675 patients, but it was discontinued at the first planned interim analysis because of lack of difference between the treatment groups and the placebo group. A total of 328 patients had data available for the primary outcome. The average age of enrollees was 14.2 years, and 68% were female. The sample was mostly white (70%), but with a notable proportion of black enrollees (19%), and 88% were of non-Hispanic ethnicity. The average number of days of headaches during the baseline period was 11.4.

For the primary outcome, there was little difference among the groups. For example, 52% of the amitriptyline group and 55% of the topiramate group experienced a reduction of at least 50% in number of headache days, but this compared with 61% of the placebo group. The disability score fell by one half on average across all of the treatment groups, yet neither comparison of disability scores in the active treatment groups with the score in the placebo group was significant. Headache days dropped from the average of 11.14 to 4.6-5.2 (depending on group) per 28 days; again, these differences were not statistically significant.

Of note, 5% of the amitriptyline group withdrew owing to side effects, compared with 6% of the topiramate group and 2% of the placebo group. These differences did not reach statistical significance. There was a statistically significant difference in the type of side effects, with fatigue and dry mouth both occurring twice as often in the amitriptyline group than the placebo group. Paresthesias and weight loss were three times more common among the topiramate group than the placebo group.

The authors concluded that there were no significant differences in response among the two treatment groups compared with placebo during 24 weeks of active treatment.


For anyone brave enough to dive into treating adolescent migraine and headache, this trial comes as a severe disappointment. As pediatric providers, we often lament the lack of randomized trial evidence in children, and it is both disappointing and sobering that the two drugs suggested by experts and previous trials to offer the best opportunity for prevention of migraine had so little effect.

On the positive side, the notable placebo effect, regression to the mean over time, or true improvement over time (just three of the potential competing hypotheses to explain the lack of differences) offer some hope for patients and providers. In an accompanying editorial, Jackson[2] commented that the marked placebo response rate in this study is commonly seen in headache trials.

Jackson also offers some good advice for how to respond to these findings. Rather than providers taking the approach that "nothing works," we should focus on working with patients on nonpharmacologic approaches; being a supportive medical source; and considering use of less potentially problematic medications, such as acetaminophen or ibuprofen, as prophylaxis. Of course, the data available for nonpharmacologic approaches to preventing headache are also woefully thin, and long-term use of ibuprofen or acetaminophen poses problems. However, focusing on hope for improvement is an important aspect of treatment and appears to be a reasonable expectation for both patients and providers.

(Source: Medscape Pediatrics © 2017 WebMD, LLC)

1. Powers SW, Coffey CS, Chamberlin LA, et al; CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376:115-124. Abstract
2. Jackson JL. Pediatric migraine headache—still searching for effective treatments. N Engl J Med. 2017;376:169-170.

Risk factors associated with first episode of febrile seizure (FS)

Age less than two years, male sex, positive family history of FS, maximum mean temperature, upper respiratory and urinary tract infection, antenatal complications increases the risk of developing first episode of FS.

The study showed that age less than two years, male sex, positive family history of FS, maximum mean temperature, upper respiratory and urinary tract infection, antenatal complications like bleeding, difficult labour, low mean haemoglobin and RBC indices increases the risk of developing first episode of FS.

Febrile seizure is one of the most common of seizure which most commonly affect 2 to 5% children between 6 months to 5 years of age once in lifetime. Although earlier reports suggest that prevalence of FS in Indian children is 10%, recent evidence indicates that the incidence rate is consistent with western prevalence.

A cross-sectional, case-control study was conducted to identify the influential risk factors associated with the occurrence of first episode of febrile seizure. A total of 70 children (aged between 6 months to 5 years) with their first episode of FS (cases) and 70 children with fever but without seizures (controls) were included in the study. The mean age of cases and controls were 24.90 ± 16.11 and 26.34 ± 16.93 months respectively. The majority of cases (60%) were in age group of 6 to 24 months. About 31.4% and 11.4% cases had a family history of FS in first degree relatives and second degree relatives respectively, which were significant when compared with controls (p

Antenatal complication such as bleeding and history of difficult labour was significantly higher in the cases compared with controls. Similarly, haematological and other laboratories finding such as serum sodium, serum calcium and random blood sugar values were abnormal in cases.

(Source: Sharawat I et al. Evaluation of Risk Factors Associated with First Episode Febrile Seizure. J Clin Diagn Res. 2016;10(5): SC10-SC13).

Simple Test Can Help Rule Out Pathologic Heart Murmur in Children

The disappearance of heart murmur while standing excluded a pathologic murmur

A study published in the Annals of Family Medicine shows that disappearance of heart murmur while standing reliably rules out pathologic heart murmurs in children.

Although heart murmur in children is usually harmless, in a small number of cases it is symptomatic of cardiac disease.

Using an acoustic-based, non-electronic stethoscope, Bruno Lefort, MD, Children Hospital Gatien de Clocheville, University Hospital Centre of Tours, Tours Cedex, France, and colleagues noted heart sound characteristics of 194 consecutive children referred to paediatric cardiologists for heart murmur, first with patients in the supine position, and then for at least 1 minute in the standing position.

After observational data were collected, an echocardiogram was performed to assess the presence or absence of cardiac anomalies that could explain the murmur.

Of the children refereed to a cardiologist for heart murmur, 85% did not have cardiac disease. Only 30 children (15%) had an abnormal echocardiogram that explained the heart murmur.

Of 100 children (51%) who had heart murmur while supine but not standing, 2 had an organic murmur and only 1 required follow-up.

The disappearance of heart murmur while standing, therefore, excluded a pathologic murmur with a high predictive positive value of 98% and a specificity of 93%, but with a poor sensitivity of 60%.

In an era of highly technical medicine, physical examination should remain the first step in diagnosis, according to the authors. However, "the disappearance of heart murmur in children upon standing is a valuable clinical test to exclude a pathologic cardiac murmur and avoid costly referral to a cardiologist," the authors noted.


Valproic acid vs lamotrigine: Which fares better in management of generalised epilepsy?

The standard for generalized epilepsies (GE) monotherapy in treatment is valproic acid (VPA) and lamotrigine (LTG) has been proposed as an alternative to VPA. This study aimed to evaluate the safety and efficacy of LTG on GE seizure in comparison with VPA.

A search was conducted based on the databases from Pubmed, Embase and the Cochran database up to February 2017. The relative risk odds ratios (ORs) and the relevant 95% confidence intervals (CI) were determined.

Five randomized controlled trials and four observational cohort studies involving 1732 cases were included. The results indicated that VPA was significantly superior to LTG for the outcome rate to treatment withdrawal for any reason and seizure freedom. The ORs and 95% CI of VPA versus LTG for withdrawal after 12- and 24-month treatment were 0.39(0.27, 0.56) and 0.50(0.14, 1.75), respectively, and were 3.51(2.68, 4.59) and 8.58(5.40, 13.63)for 12- and 24- month seizure free intervals, respectively. Moreover, the risk of adverse effects (OR (95%CI); 1.11(0.61-2.01)) was not significantly different between the two groups. However, the treatment withdrawal due to lack of seizure control were in the LTG group (OR (95%CI); 0.15(0.10-0.23)), while the treatment withdrawal due to intolerable side effects were in the VPA group (OR (95%CI); (1.75(1.10-2.80)).

The meta-analysis suggests that VPA appears to be a better choice in controlling seizure following GE. However, therapy should be switched to alternative monotherapy if an adequate trial of VPA monotherapy is not effective and intolerable, especially in young women.

(Tang L et al. Seizure. 2017 Aug 12;51:95-101. doi: 10.1016/j.seizure.2017.08.001. [Epub ahead of print]