Lactation Complicated by Overweight and Obesity: Supporting the Mother and Newborn
Cecilia Jevitt, CNM, PhD; Ivonne Hernandez, MS, RN, IBLC; Maureen Groër, RN, PhD
From Journal of Midwifery & Women's Health
Published: 11/28/2007
Abstract
Research shows that mothers who are obese (with a BMI > 30) are less likely to initiate lactation, have delayed lactogenesis II, and are prone to early cessation of breastfeeding.
Black women, with the highest rates of American obesity, have the lowest rates and shortest duration of breastfeeding compared to Hispanic and white women.
Women who are overweight and obese have lowered prolactin responses to suckling.
Women who are obese are at risk for prolonged labors, excessive labor stress, and cesarean birth, all of which delay lactogenesis II.
Lactation has a small but significant role in preventing future obesity in the mother and child.
Midwifery management of obesity-related lactation problems begins with education about optimal prenatal weight gain and regular weight assessment to avoid excessive gain.
Support of physiologic birth processes to avoid stress, prolonged labor, and surgical birth and limit maternal-newborn separation enhances the onset of lactogenesis II.
Massage or pumping may soften and extend the obese nipple for easier latch.
Infants of lactating women with prior bariatric surgery are at risk for B12 deficiency and require regular nutrition and growth assessment.
Five hundred calorie per day restriction paired with aerobic exercise for intentional postpartum weight loss does not affect milk quality or infant growth.
Introduction
Obesity related perinatal morbidity does not end with birth but continues to affect the maternal-infant dyad.
Mothers who are obese are less likely to initiate lactation, have delayed lactogenesis II, and are prone to early cessation of breastfeeding.
Obesity rates are highest among black women (49.6%), who have the lowest rate of breastfeeding initiation (45.3%) and breastfeeding continuation to 3 months (33.7%). White women and Mexican Hispanic women have lower rates of obesity (31% and 38.9%, respectively), have higher rates of breastfeeding initiation (68.7% and 76%), and are more likely to be breastfeeding at 3 months postpartum (48.7% and 54.3%).[1] However, a survey of lactation counseling practices for mothers who are obese showed that only 29% of 80 clinicians believed that women who are obese were less successful with breastfeeding than mothers who are normal weight.[2] In a second survey of 31 lactation consultants, 23% asked for a definition of obesity.[2]
This article reviews the prevalence of lactation problems related to overweight and obesity (as defined in a 1990 Institute of Medicine [IOM] report on nutrition in pregnancy)[3] and excess prenatal weight gain. Current understandings of obesity related hormones and their effect on lactation, and the relationship of lactation to future maternal and infant obesity are also discussed. Finally, this article describes evidence-based techniques for clinicians to reduce the lactational impact of overweight, obesity, and excessive weight gain during the prenatal and intrapartum periods, as well as methods for supporting lactation in women who are obese.
for rest of article:
http://www.havilah.wsiefusion.net
Saturday, May 30, 2009
Weight Gain during Pregnancy - latest guidelines
Institute of Medicine Sets New Guidelines for Weight Gain During Pregnancy
Fran Lowry
From Medscape Medical News
May 28, 2009 — The Institute of Medicine and the National Research Council today released a report recommending new guidelines for weight gain during pregnancy. The report updates guidelines that were last set in 1990 and takes into account changing US demographics, particularly the increase in the numbers of women of childbearing age who are overweight and obese.
The new guidelines are available on the Institute of Medicine's Web site.
"The earlier guidelines recommended weight gain that would be optimal for the baby. These new guidelines take into account the well-being of the mother as well. This is a fundamental and important change," Kathleen M. Rasmussen, ScD, professor of nutrition at Cornell University and chair of the guidelines committee, said at a press briefing where the new recommendations were announced.
The 2009 guidelines also differ from those issued 2 decades ago in 2 other ways. They are based on World Health Organization cutoff points for body mass index (BMI) categories, unlike the earlier guidelines, which were based on weight categories taken from the Metropolitan Life Insurance tables. They also recommend a more narrow range of weight gain for obese women.
The recommended weight gain for each category of prepregnancy BMI is as follows:
• Underweight (< 18.5 kg/m2); total weight gain range: 28 to 40 pounds
• Normal weight (18.5 - 24.9 kg/m2); total weight gain range: 25 to 35 pounds
• Overweight (25.0 - 29.9 kg/m2); total weight gain range: 15 to 25 pounds
• Obese (≥ 30.0 kg/m2); total weight gain range: 11 to 20 pounds
"Women who gain within these guidelines will do better than if they gain outside of them. We have good evidence for this," said Dr. Rasmussen.
Currently in the United States, 55% of women between the ages of 20 and 39 years are overweight, and approximately one half of these are obese, with a BMI higher than 25 kg/m2. Eight percent of obese women are severely obese, with a BMI of 40 kg/m2 or greater, Dr. Rasmussen said.
She conceded that getting obese women to restrict their gestational weight gain to no more than 20 pounds would be a challenge. Still, she insisted, it is doable. She told Medscape Ob/Gyn & Women's Health: "The studies that we reviewed showed that many obese women gain progressively less weight the heavier they are. We also think that if these women are counseled about the importance of restricting their weight gain, they can be successful.
For example, in a study from Denmark, obese women who were given individualized care and attention were able to restrict their weight gain during pregnancy and achieved better outcomes. We realize that it will be difficult and expensive to achieve this, but we think it is worth trying to replicate such experience here."
The new guidelines stress the importance of preconception counseling to ensure women of childbearing age are at a healthy weight before they become pregnant. However, Dr. Rasmussen admitted to Medscape Ob/Gyn & Women's Health that the committee did not yet have any data on the success of such counseling.
"These data provide a strong reason to assume that interventions will be needed to assist women, particularly those who are overweight or obese at the time of conception, in meeting the guidelines. These interventions may need to occur at both the individual and community levels and may need to include components related to both improved dietary intake and increased physical activity," she told reporters at the press briefing.
The guidelines also recommended that research on dietary intake, physical activity, dieting practices, food insecurity, and how the social and environmental context affect gestational weight gain be supported financially.
Although the new guidelines may be applicable to women in other developed countries, they are not intended for use in areas of the world where women are substantially shorter or thinner than women in the United States or where adequate obstetric services are unavailable, Dr. Rasmussen added.
IOM (Institute of Medicine). Weight Gain During Pregnancy: Reexamining the Guidelines. Washington, DC: The National Academies Press. Posted online May 28, 2009.
Fran Lowry
From Medscape Medical News
May 28, 2009 — The Institute of Medicine and the National Research Council today released a report recommending new guidelines for weight gain during pregnancy. The report updates guidelines that were last set in 1990 and takes into account changing US demographics, particularly the increase in the numbers of women of childbearing age who are overweight and obese.
The new guidelines are available on the Institute of Medicine's Web site.
"The earlier guidelines recommended weight gain that would be optimal for the baby. These new guidelines take into account the well-being of the mother as well. This is a fundamental and important change," Kathleen M. Rasmussen, ScD, professor of nutrition at Cornell University and chair of the guidelines committee, said at a press briefing where the new recommendations were announced.
The 2009 guidelines also differ from those issued 2 decades ago in 2 other ways. They are based on World Health Organization cutoff points for body mass index (BMI) categories, unlike the earlier guidelines, which were based on weight categories taken from the Metropolitan Life Insurance tables. They also recommend a more narrow range of weight gain for obese women.
The recommended weight gain for each category of prepregnancy BMI is as follows:
• Underweight (< 18.5 kg/m2); total weight gain range: 28 to 40 pounds
• Normal weight (18.5 - 24.9 kg/m2); total weight gain range: 25 to 35 pounds
• Overweight (25.0 - 29.9 kg/m2); total weight gain range: 15 to 25 pounds
• Obese (≥ 30.0 kg/m2); total weight gain range: 11 to 20 pounds
"Women who gain within these guidelines will do better than if they gain outside of them. We have good evidence for this," said Dr. Rasmussen.
Currently in the United States, 55% of women between the ages of 20 and 39 years are overweight, and approximately one half of these are obese, with a BMI higher than 25 kg/m2. Eight percent of obese women are severely obese, with a BMI of 40 kg/m2 or greater, Dr. Rasmussen said.
She conceded that getting obese women to restrict their gestational weight gain to no more than 20 pounds would be a challenge. Still, she insisted, it is doable. She told Medscape Ob/Gyn & Women's Health: "The studies that we reviewed showed that many obese women gain progressively less weight the heavier they are. We also think that if these women are counseled about the importance of restricting their weight gain, they can be successful.
For example, in a study from Denmark, obese women who were given individualized care and attention were able to restrict their weight gain during pregnancy and achieved better outcomes. We realize that it will be difficult and expensive to achieve this, but we think it is worth trying to replicate such experience here."
The new guidelines stress the importance of preconception counseling to ensure women of childbearing age are at a healthy weight before they become pregnant. However, Dr. Rasmussen admitted to Medscape Ob/Gyn & Women's Health that the committee did not yet have any data on the success of such counseling.
"These data provide a strong reason to assume that interventions will be needed to assist women, particularly those who are overweight or obese at the time of conception, in meeting the guidelines. These interventions may need to occur at both the individual and community levels and may need to include components related to both improved dietary intake and increased physical activity," she told reporters at the press briefing.
The guidelines also recommended that research on dietary intake, physical activity, dieting practices, food insecurity, and how the social and environmental context affect gestational weight gain be supported financially.
Although the new guidelines may be applicable to women in other developed countries, they are not intended for use in areas of the world where women are substantially shorter or thinner than women in the United States or where adequate obstetric services are unavailable, Dr. Rasmussen added.
IOM (Institute of Medicine). Weight Gain During Pregnancy: Reexamining the Guidelines. Washington, DC: The National Academies Press. Posted online May 28, 2009.
Monday, May 25, 2009
Syphilis Screening in Pregnancy
May 22, 2009 — The US Preventive Services Task Force (USPSTF) has reaffirmed its 2004recommendation to screen all pregnant women for syphilis infection.
Harms of failure to treat syphilis during pregnancy may include stillbirth, neonatal death, bone deformities, and neurologic impairment. Evidence is adequate that screening tests for syphilis can accurately detect infection. Universal screening of pregnant women for syphilis is associated with a lower proportion of infants who have clinical manifestations of syphilis infection, according to convincing observational evidence reviewed by the USPSTF.
Screening Process for and Treatment of Syphilis
The recommended screening for syphilis consists of nontreponemal tests, either the Venereal Disease Research Laboratory test or the rapid plasma reagin test. If results are positive, these should be confirmed by a fluorescent treponemal antibody absorbed test or a Treponema pallidum particle agglutination test.
Screening should be performed at the first prenatal visit in all pregnant women, as well as in the third trimester and at delivery for women at high risk.
Those at high risk include uninsured women, women living in poverty, sex workers, illicit drug users, women diagnosed with sexually transmitted diseases, and those living in communities with high syphilis morbidity.
For the treatment of syphilis during pregnancy, the Centers for Disease Control and Prevention (CDC) recommends parenteral benzathine penicillin G. Because evidence is limited regarding the efficacy or safety of alternative antibiotics in pregnancy, women who report penicillin allergies should be evaluated and desensitized to penicillin if necessary.
"Syphilis may be transmitted vertically, usually through the placenta; the risk for fetal infection increases with gestational age," write Tracy Wolff, MD, MPH, from the USPSTF, and coauthors of the accompanying evidence statement. "Vertical transmission may also occasionally occur during delivery if maternal genital lesions are present... "Although the overall rate of congenital syphilis has decreased significantly since the onset of the syphilis elimination plan in 1996, this recent increase is cause for concern, given that congenital syphilis is preventable."
source: Ann Intern Med. 2009;150:705-709, 710-716.
Harms of failure to treat syphilis during pregnancy may include stillbirth, neonatal death, bone deformities, and neurologic impairment. Evidence is adequate that screening tests for syphilis can accurately detect infection. Universal screening of pregnant women for syphilis is associated with a lower proportion of infants who have clinical manifestations of syphilis infection, according to convincing observational evidence reviewed by the USPSTF.
Screening Process for and Treatment of Syphilis
The recommended screening for syphilis consists of nontreponemal tests, either the Venereal Disease Research Laboratory test or the rapid plasma reagin test. If results are positive, these should be confirmed by a fluorescent treponemal antibody absorbed test or a Treponema pallidum particle agglutination test.
Screening should be performed at the first prenatal visit in all pregnant women, as well as in the third trimester and at delivery for women at high risk.
Those at high risk include uninsured women, women living in poverty, sex workers, illicit drug users, women diagnosed with sexually transmitted diseases, and those living in communities with high syphilis morbidity.
For the treatment of syphilis during pregnancy, the Centers for Disease Control and Prevention (CDC) recommends parenteral benzathine penicillin G. Because evidence is limited regarding the efficacy or safety of alternative antibiotics in pregnancy, women who report penicillin allergies should be evaluated and desensitized to penicillin if necessary.
"Syphilis may be transmitted vertically, usually through the placenta; the risk for fetal infection increases with gestational age," write Tracy Wolff, MD, MPH, from the USPSTF, and coauthors of the accompanying evidence statement. "Vertical transmission may also occasionally occur during delivery if maternal genital lesions are present... "Although the overall rate of congenital syphilis has decreased significantly since the onset of the syphilis elimination plan in 1996, this recent increase is cause for concern, given that congenital syphilis is preventable."
source: Ann Intern Med. 2009;150:705-709, 710-716.
Friday, May 22, 2009
Invasive Pneumococcal Disease in Children 5 Years After Conjugate Vaccine:
Editorial Note
The introduction of PCV7 in the United States led to substantial reductions in IPD among the target population (children aged <5 years), and the benefits of vaccination with PCV7 remain evident 5 years later. Overall IPD rates in 2005 were 77% lower for children aged <5 years compared with average rates in 1998-1999. Results of this report indicate that overall IPD rates in 2005 among children aged <5 years (23.2 per 100,000) remain below the Healthy People 2010 objective (14-5a) of 46 per 100,000.† Findings in this report are supported by a growing body of evidence of the beneficial effects of PCV7 introduction on noninvasive pneumococcal disease; recent studies report dramatic declines in all-cause pneumonia and pneumococcal pneumonia in the PCV7 target population[4] and reductions in frequent otitis media.[5]
Results of this analysis also demonstrate that, after reductions in IPD rates among children targeted for vaccination during the first 3 years after PCV7 introduction, further reductions were offset by increases in non-PCV7 serotypes. PCV7-type IPD rates continued to decline, but overall IPD rates leveled off during 2002-2005.
Since the introduction of PCV7, a shift in the distribution of serotypes causing IPD in this age group has occurred; only 7% of cases were caused by PCV7 serotypes in 2005, compared with approximately 80% during 1998-1999. Serotype 19A was the most common serotype causing IPD among children in 2005, and changes in non-PCV7-type IPD were largely driven by increases in IPD caused by this serotype. Even though absolute increases in rates of non-PCV7-type IPD remain modest relative to reductions in PCV7-type IPD, an estimated 1,200 additional cases of IPD not preventable by PCV7 occurred among children aged <5 years in 2005, compared with prevaccine baseline. Increases in non-PCV7-type disease among vaccinated and unvaccinated populations have been reported since PCV7 introduction.[2,6] The results of this analysis indicate that, in the general U.S. population, these increases have been small relative to declines in PCV7-type disease.
The findings in this report are subject to at least one limitation. The relationships between PCV7 coverage or numbers of PCV7 doses received and PCV7 effects could not be explored directly. Vaccination status was not available for persons with IPD, and PCV7 coverage estimates from a different data source were used to estimate PCV7 direct effects. Therefore, the level of PCV7 coverage needed to induce indirect (i.e., herd) effects is unknown. In this analysis, a range of PCV7 coverage estimates (≥3 or ≥1 doses) for each birth cohort was used to obtain a range of estimates for the direct and indirect effects of PCV7.
Initial substantial declines in IPD after PCV7 introduction are strikingly similar to reductions in invasive disease caused by Haemophilus influenzae type b (Hib) after Hib conjugate vaccine introduction in the United States.[7] Increases in disease caused by H. influenzae serotypes other than type b were a concern; however, the experience with Hib conjugate vaccine indicates that non-type b H. influenzae were not as successful as Hib in causing invasive disease.[8] In contrast with the six serotypes of H. influenzae, approximately 90 pneumococcal serotypes have been described. Fortunately, different pneumococcal serotypes also vary in their ability to cause invasive disease.[9]
The findings in this report suggest that expanded-valency conjugate vaccines for children that also provide protection against serotype 19A would be useful to improve prevention of IPD. A 13-valent conjugate vaccine containing type 19A polysaccharide and a 10-valent conjugate vaccine, which might provide cross protection against type 19A,[10] are currently in clinical trials. Continued surveillance for IPD is crucial to provide information on emerging pneumococcal serotypes and the optimal composition of future conjugate vaccines.
sourc: http://www.medscape.com/viewarticle/571344_2
†US Department of Health and Human Services. Healthy people 2010 (conference ed, in 2 vols). Washington, DC: US Department of Health and Human Services; 2000. Available at http://www.healthypeople.gov.
The introduction of PCV7 in the United States led to substantial reductions in IPD among the target population (children aged <5 years), and the benefits of vaccination with PCV7 remain evident 5 years later. Overall IPD rates in 2005 were 77% lower for children aged <5 years compared with average rates in 1998-1999. Results of this report indicate that overall IPD rates in 2005 among children aged <5 years (23.2 per 100,000) remain below the Healthy People 2010 objective (14-5a) of 46 per 100,000.† Findings in this report are supported by a growing body of evidence of the beneficial effects of PCV7 introduction on noninvasive pneumococcal disease; recent studies report dramatic declines in all-cause pneumonia and pneumococcal pneumonia in the PCV7 target population[4] and reductions in frequent otitis media.[5]
Results of this analysis also demonstrate that, after reductions in IPD rates among children targeted for vaccination during the first 3 years after PCV7 introduction, further reductions were offset by increases in non-PCV7 serotypes. PCV7-type IPD rates continued to decline, but overall IPD rates leveled off during 2002-2005.
Since the introduction of PCV7, a shift in the distribution of serotypes causing IPD in this age group has occurred; only 7% of cases were caused by PCV7 serotypes in 2005, compared with approximately 80% during 1998-1999. Serotype 19A was the most common serotype causing IPD among children in 2005, and changes in non-PCV7-type IPD were largely driven by increases in IPD caused by this serotype. Even though absolute increases in rates of non-PCV7-type IPD remain modest relative to reductions in PCV7-type IPD, an estimated 1,200 additional cases of IPD not preventable by PCV7 occurred among children aged <5 years in 2005, compared with prevaccine baseline. Increases in non-PCV7-type disease among vaccinated and unvaccinated populations have been reported since PCV7 introduction.[2,6] The results of this analysis indicate that, in the general U.S. population, these increases have been small relative to declines in PCV7-type disease.
The findings in this report are subject to at least one limitation. The relationships between PCV7 coverage or numbers of PCV7 doses received and PCV7 effects could not be explored directly. Vaccination status was not available for persons with IPD, and PCV7 coverage estimates from a different data source were used to estimate PCV7 direct effects. Therefore, the level of PCV7 coverage needed to induce indirect (i.e., herd) effects is unknown. In this analysis, a range of PCV7 coverage estimates (≥3 or ≥1 doses) for each birth cohort was used to obtain a range of estimates for the direct and indirect effects of PCV7.
Initial substantial declines in IPD after PCV7 introduction are strikingly similar to reductions in invasive disease caused by Haemophilus influenzae type b (Hib) after Hib conjugate vaccine introduction in the United States.[7] Increases in disease caused by H. influenzae serotypes other than type b were a concern; however, the experience with Hib conjugate vaccine indicates that non-type b H. influenzae were not as successful as Hib in causing invasive disease.[8] In contrast with the six serotypes of H. influenzae, approximately 90 pneumococcal serotypes have been described. Fortunately, different pneumococcal serotypes also vary in their ability to cause invasive disease.[9]
The findings in this report suggest that expanded-valency conjugate vaccines for children that also provide protection against serotype 19A would be useful to improve prevention of IPD. A 13-valent conjugate vaccine containing type 19A polysaccharide and a 10-valent conjugate vaccine, which might provide cross protection against type 19A,[10] are currently in clinical trials. Continued surveillance for IPD is crucial to provide information on emerging pneumococcal serotypes and the optimal composition of future conjugate vaccines.
sourc: http://www.medscape.com/viewarticle/571344_2
†US Department of Health and Human Services. Healthy people 2010 (conference ed, in 2 vols). Washington, DC: US Department of Health and Human Services; 2000. Available at http://www.healthypeople.gov.
Emergence of a Multiresistant Serotype 19A Pneumococcal Strain Not Included in the 7-Valent Conjugate Vaccine as an Otopathogen in Children
Pichichero ME, Casey JR
JAMA. 2007;298:1772-1778
Summary
The 7-valent pneumococcal conjugate vaccine, introduced in 2000, has been extremely effective in reducing invasive, and to a lesser degree, noninvasive, pneumococcal disease. However, not all strains of pneumococcus are included in the vaccine, and there have long been concerns that nonvaccine strains would become more clinically prevalent.
One previous report on Alaskan children raised the concern that serotype 19A might become problematic, but the isolates in that study were not largely drug-resistant. The authors of the current study have been monitoring middle ear pathogens recovered from their patients, and this report describes their experiences with patients seen from 2003 through 2006, representing 3 respiratory illness seasons.
The study focused on patients with acute otitis media treatment failure (AOMTF) and patients with recurrent AOM. The subjects were 6 months to 36 months old. The authors collected middle ear culture samples by tympanocentesis, and they also collected demographic and clinical information on the subjects. Only children without an anatomic or other reason to be at increased risk for AOM were included.
All subjects had bulging tympanic membranes. AOMTF subjects all had a persistence of symptoms at least 48 hours after beginning antibiotics, and the patients with recurrent AOM had either 3 episodes in 6 months or 4 episodes in 1 year. Of 1816 patients seen during the study period with AOM, 375 (2.1%) met the criteria for either AOMTF or recurrent AOM. Of those children meeting criteria, the authors were able to obtain middle ear fluid from 212. Pathogenic bacteria grew in 162 samples, with 58% of those growing Haemophilus influenzae (nontypable) and 36% growing Streptococcus pneumoniae.
Over the 3 respiratory seasons, there was a decrease in the proportion of S pneumoniae isolates obtained that were covered in the 7-valent vaccine, from 57% to 26% in the final respiratory season. In addition, by the final season, 93% of the nonvaccine strains of S pneumoniae were not susceptible to penicillin.
The authors isolated serotype 19A in 9 total patients, and this organism increased proportionally among nonvaccine serotypes isolated. In these patients, the 19A strain was also multidrug-resistant.
The authors emphasize that of 59 pneumococcal isolates from this study, 15% were 19A strain with significant antibiotic resistance. The authors note that only surgical drainage or use of a fluoroquinolone (not approved for children or for AOM) relieved the symptoms and infection in these 9 patients.
Viewpoint
In the discussion section of the paper, the authors review other studies that have demonstrated the general increase in nonvaccine strains of pneumococcus that are isolated from patients with otitis media. Probably the best take-home message from this is that patients with AOMTF or recurrent AOM really should get drainage for culture to properly identify the causative organism. For some of the study patients, drainage was the only therapy that helped. In any case, knowing the sensitivity profile of the isolates seems more important than ever.
JAMA. 2007;298:1772-1778
Summary
The 7-valent pneumococcal conjugate vaccine, introduced in 2000, has been extremely effective in reducing invasive, and to a lesser degree, noninvasive, pneumococcal disease. However, not all strains of pneumococcus are included in the vaccine, and there have long been concerns that nonvaccine strains would become more clinically prevalent.
One previous report on Alaskan children raised the concern that serotype 19A might become problematic, but the isolates in that study were not largely drug-resistant. The authors of the current study have been monitoring middle ear pathogens recovered from their patients, and this report describes their experiences with patients seen from 2003 through 2006, representing 3 respiratory illness seasons.
The study focused on patients with acute otitis media treatment failure (AOMTF) and patients with recurrent AOM. The subjects were 6 months to 36 months old. The authors collected middle ear culture samples by tympanocentesis, and they also collected demographic and clinical information on the subjects. Only children without an anatomic or other reason to be at increased risk for AOM were included.
All subjects had bulging tympanic membranes. AOMTF subjects all had a persistence of symptoms at least 48 hours after beginning antibiotics, and the patients with recurrent AOM had either 3 episodes in 6 months or 4 episodes in 1 year. Of 1816 patients seen during the study period with AOM, 375 (2.1%) met the criteria for either AOMTF or recurrent AOM. Of those children meeting criteria, the authors were able to obtain middle ear fluid from 212. Pathogenic bacteria grew in 162 samples, with 58% of those growing Haemophilus influenzae (nontypable) and 36% growing Streptococcus pneumoniae.
Over the 3 respiratory seasons, there was a decrease in the proportion of S pneumoniae isolates obtained that were covered in the 7-valent vaccine, from 57% to 26% in the final respiratory season. In addition, by the final season, 93% of the nonvaccine strains of S pneumoniae were not susceptible to penicillin.
The authors isolated serotype 19A in 9 total patients, and this organism increased proportionally among nonvaccine serotypes isolated. In these patients, the 19A strain was also multidrug-resistant.
The authors emphasize that of 59 pneumococcal isolates from this study, 15% were 19A strain with significant antibiotic resistance. The authors note that only surgical drainage or use of a fluoroquinolone (not approved for children or for AOM) relieved the symptoms and infection in these 9 patients.
Viewpoint
In the discussion section of the paper, the authors review other studies that have demonstrated the general increase in nonvaccine strains of pneumococcus that are isolated from patients with otitis media. Probably the best take-home message from this is that patients with AOMTF or recurrent AOM really should get drainage for culture to properly identify the causative organism. For some of the study patients, drainage was the only therapy that helped. In any case, knowing the sensitivity profile of the isolates seems more important than ever.
Increasing Prevalence of Serotype 6C After Introduction of Pneumococcal Vaccine
By Will Boggs, MD
NEW YORK (Reuters Health) Jan 05 - Introduction of the 7-valent conjugate vaccine (PCV7) has led to increases in invasive pneumococcal disease caused by serotype 6C, but decreases in invasive pneumococcal disease caused by serotype 6A, according to a new report.
"Pneumococci are evading the pneumococcal conjugate vaccine, which was introduced in 2000," Dr. Moon H. Nahm from University of Alabama at Birmingham told Reuters Health. "In view of this, there is an increasing need to reformulate the 7-valent conjugate vaccine."
Dr. Nahm and colleagues investigated the prevalence of the 6A and 6C serotypes among invasive pneumococcal disease isolates and the capacity of serum specimens from vaccines to opsonize 6A and 6C serotypes in vitro.
Among children under age 5 years, the incidence of serotype 6A invasive pneumococcal disease decreased by 91% from 2003 to 2006, the authors report in the December 15th issue of The Journal of Infectious Diseases, while there was no consistent trend in the incidence of serotype 6C invasive pneumococcal disease in this age group.
In older children and adults, the incidence of serotype 6A invasive pneumococcal disease decreased by 58% between the introduction of PCV7 and 2006, while the rate of invasive pneumococcal disease caused by serotype 6C increased by 158%.
Susceptibility to penicillin was higher among 6C isolates (71%) than among 6A isolates (51%), as was susceptibility to erythromycin (70% versus 50%, respectively).
The ability of serum from vaccinated children to opsonize serotype 6A and serotype 6B (which is included in the vaccine) was significantly higher than that for serotype 6C, whose median opsonization index was 10-100 fold less than those for serotypes 6A and 6B.
"These results suggest that the two currently available pneumococcal vaccines, both of which contain the serotype 6B capsule, elicit significant cross-opsonic antibodies to 6A but not to 6C," the investigators say.
"Until we discovered 6C in 2007, 6C was 'mis-typed' as 6A," Dr. Nahm explained. "This is surprising because 6A (and probably 6C) serotype is common and has been known to scientists for more than 80 years."
"This further emphasizes how diverse pneumococci are, how little we know about them," and how difficult it is to control pneumococcal infections, Dr. Nahm concluded.
J Infect Dis 2008;198:1818-1822.
NEW YORK (Reuters Health) Jan 05 - Introduction of the 7-valent conjugate vaccine (PCV7) has led to increases in invasive pneumococcal disease caused by serotype 6C, but decreases in invasive pneumococcal disease caused by serotype 6A, according to a new report.
"Pneumococci are evading the pneumococcal conjugate vaccine, which was introduced in 2000," Dr. Moon H. Nahm from University of Alabama at Birmingham told Reuters Health. "In view of this, there is an increasing need to reformulate the 7-valent conjugate vaccine."
Dr. Nahm and colleagues investigated the prevalence of the 6A and 6C serotypes among invasive pneumococcal disease isolates and the capacity of serum specimens from vaccines to opsonize 6A and 6C serotypes in vitro.
Among children under age 5 years, the incidence of serotype 6A invasive pneumococcal disease decreased by 91% from 2003 to 2006, the authors report in the December 15th issue of The Journal of Infectious Diseases, while there was no consistent trend in the incidence of serotype 6C invasive pneumococcal disease in this age group.
In older children and adults, the incidence of serotype 6A invasive pneumococcal disease decreased by 58% between the introduction of PCV7 and 2006, while the rate of invasive pneumococcal disease caused by serotype 6C increased by 158%.
Susceptibility to penicillin was higher among 6C isolates (71%) than among 6A isolates (51%), as was susceptibility to erythromycin (70% versus 50%, respectively).
The ability of serum from vaccinated children to opsonize serotype 6A and serotype 6B (which is included in the vaccine) was significantly higher than that for serotype 6C, whose median opsonization index was 10-100 fold less than those for serotypes 6A and 6B.
"These results suggest that the two currently available pneumococcal vaccines, both of which contain the serotype 6B capsule, elicit significant cross-opsonic antibodies to 6A but not to 6C," the investigators say.
"Until we discovered 6C in 2007, 6C was 'mis-typed' as 6A," Dr. Nahm explained. "This is surprising because 6A (and probably 6C) serotype is common and has been known to scientists for more than 80 years."
"This further emphasizes how diverse pneumococci are, how little we know about them," and how difficult it is to control pneumococcal infections, Dr. Nahm concluded.
J Infect Dis 2008;198:1818-1822.
Pneumococcal vaccination in Infant @ 3,5 12month
Immunogenicity and Tolerability of a Heptavalent Pneumococcal Conjugate Vaccine Administered at 3, 5 and 12 Months of Age
Käyhty, Helena PhD; Åhman, Heidi PhD; Eriksson, Karin; Sörberg, Mikael MD, PhD; Nilsson, Lennart MD, PhD
Published: 03/22/2005
Abstract
Background: The recommended vaccination schedule for the pneumococcal conjugate vaccine (PCV) includes 4 immunizations, according to the national programs in the United States and some European countries. Other countries use a national schedule for routine vaccinations in early childhood that includes only 3 doses.
Aims: The goals were to assess the immunogenicity and tolerability of PCV with a vaccination schedule that included 3 doses during the first 1 year of life (a 2+1 dose schedule) and to determine the immune responses to concomitantly administered Haemophilus influenzae type b (Hib) vaccine.
Methods: A total of 101 healthy Swedish infants were enrolled in an open, nonrandomized, multicenter study. PCV was administered concomitantly with (at separate sites) a diphtheria-tetanus toxoids-acellular pertussis vaccine, inactivated polio vaccine and Hib conjugate vaccine combination at 3, 5 and 12 months of age. IgG antibody concentrations for the 7 serotypes included in the PCV and the Hib capsular polysaccharide in serum samples taken at 3, 6, 12 and 13 months were determined with enzyme immunoassays. Local and systemic reactions were monitored for 3 days after each immunization, and serious adverse reactions were monitored for the whole study period.
Results: Two doses of PCV induced satisfactory antibody responses, with the exception of serotypes 6B and 23F. The third dose evoked strong responses for all serotypes, which suggests good immunologic priming with the primary series of 2 doses. The mean anti-Hib antibody concentrations were similar to those noted in earlier studies among Swedish children. The PCV was well tolerated.
Conclusion: The pneumococcal antibody concentrations at 13 months were comparable with those noted previously with the 4-dose schedule. The results suggest that the implementation of a 2+1 dose schedule for PCV should be considered.
Introduction
Several pneumococcal conjugate vaccines (PCVs) have been tested in clinical trials,[1] and a heptavalent PCV, which has been licensed in many parts of the world, is in wide use in the United States[2] and in some European countries. With serotype-specific efficacy of 97% against invasive disease,[3] the present PCV could cover 65-80% of invasive pneumococcal disease in Europe.[4-7] The postlicensure follow-up data have shown that the vaccination program has had a marked impact on the incidence of invasive pneumococcal disease in the United States.[2,8] In addition, vaccination with a PCV could decrease the spread of antibiotic-resistant pneumococci.[9] Heptavalent PCVs have shown efficacy of 56-57% against acute otitis media caused by the vaccine serotypes[10,11] and have reduced the number of ear tube replacements by 24 and 44% in the United States[12] and in Finland,[13] respectively. In South Africa and the United States, the protective effect on x-ray-positive pneumonia has been approximately 20%.[14,15]
The vaccination schedule recommended for PCV, and the one used in most previous clinical studies, includes 4 immunizations (ie, the 3+1 schedule, with a 3-dose primary series in 6 months, followed by a fourth dose in the second year) according to the national vaccination programs in the United States and some European countries. The vaccination program for infants in Sweden, Denmark, Norway and Italy, as well as Finland beginning in 2005, is based on primary vaccinations at 3 and 5 months and a third dose at 12 months of age (ie, the 2+1 schedule). The only feasible schedule for the PCV would involve concomitant administration with other childhood vaccines. In addition, decreasing the number of PCV injections would decrease costs and would thus facilitate addition of the PCV to national vaccination programs.
The primary aim of this study was to assess the immunogenicity and tolerability of a heptavalent PCV after primary vaccination consisting of 2 doses (administered at 3 and 5 months of age), with a third dose given at 12 months of age. Our secondary aim was to determine the concentrations of antibody to Haemophilus influenzae type b (Hib) after the second and third doses of the Hib conjugate vaccine, which was given concomitantly with the PCV.
Discussion
We showed that the heptavalent PCV was immunogenic and well tolerated when given with a 2+1 schedule concomitantly with a DTaP-IPV/Hib combination vaccine. At the age of 6 months, 1 month after the second dose, the antibody concentrations were already clearly elevated for all serotypes; nonetheless, the concentrations remained low for serotypes 6B and 23F, compared with the other serotypes. This was not surprising, because these serotypes evoked the lowest responses after 2 doses in the previous studies with the same or other vaccines.[16,17,20,24,25] The antibody concentrations increased significantly after the third vaccination, especially for serotypes 6B and 23F. This indicates good immunologic priming after 2 doses of PCV. On the basis of experience with the Hib conjugate vaccine,[26,27] it is thought that immunologic priming, in addition to existing antibody concentrations, is important for long-lasting protection. This is probably true also for PCVs. In fact, antibody concentrations that were lower after 3 doses of a PCV than those measured in this study after 2 doses provided protection against acute otitis media caused by serotypes 6B and 23F[11] among 6- to 12-month-old infants. We think that the immune response detected in this study would provide protection against invasive pneumococcal disease between the ages of 6 and 12 months.
The administration of PCV concomitantly with the DTaP-IPV/Hib combination vaccine did not seem to affect the immune response to Hib conjugate vaccine. The mean anti-Hib antibody concentrations remained low after the second dose but were not different from those reported from other studies with this vaccination schedule in Sweden.[28,29] Despite the low antibody responses of Swedish children after the second administration of the Hib vaccine, the incidence of Hib disease has remained low and breakthrough cases have been rare with this schedule.[30]
Fever (usually mild) was quite common and was observed more often after the third dose than after the first dose. Fever was observed slightly more often than in a similar study in Germany in which the same PCV was administered concurrently with the same DTaP-IPV/Hib combination vaccine but at 2, 3, 4 and 11-15 months of age. In that study, fever of ≥ 38ºC was observed for 29-48.2% of subjects, depending on age, and high fever of ≥ 39ºC was noted for 2.9-8.3%.[31] In the German study, fever was more common after the first vaccination in the PCV-treated group than in the control group that received only the combination vaccine but was equivalent between the groups after the subsequent vaccinations. In this study, we cannot tell how much the PCV contributed to the low-grade fever, because no control group was included. However, it has been shown that acellular pertussis vaccines induce higher rates of nodules and fever after the second or third vaccination than after the first dose.[32]
Because the PCV has been licensed in many areas of the world, requiring placebo-controlled efficacy trials with novel PCVs, PCV formulations or schedules is no longer realistic. The licensure of new PCVs and the acceptance of new PCV schedules will depend on phase II studies of immunogenicity and safety, which should be planned to show noninferiority to the licensed vaccine or to an established vaccination schedule.21 Although this study was not planned as a noninferiority study, we can compare the data of this study with the published immunogenicity data from efficacy trials with 2 different endpoints, i.e. invasive disease or acute otitis media. In these trials, the same PCV as in this study was used but with the recommended 4-dose schedule. The GMC values for the serotype-specific antibodies from this study were compared with those from 2 trials that demonstrated that the vaccines are efficacious, i.e. the Northern California Kaiser-Permanente study3 and the Finnish Otitis Media (FinOM) Vaccine Trial10 ( Table 3 ). Furthermore, we compared the distribution of antibody concentrations in this study and in the FinOM trial arm that used the same cross-reactive material-conjugated PCV (Figs. 1 and 2). Sera from the FinOM trial and from this study were analyzed in the same laboratory, whereas the U.S. data came from the Wyeth laboratories. Interlaboratory comparisons have proved that the 2 laboratories give concordant results.
The GMC values measured in this study after the second dose were comparable with those noted in the efficacy trials after 3 doses. The only exception was serotype 6B, for which the GMC values in this study were lower than those measured in the Finnish and U.S. studies ( Table 3 ). For serotype 23F, the concentrations remained lower than those in the Finnish study but were not markedly lower than those in the U.S. study. Furthermore, the distributions of antibodies (Fig. 1) and the proportions of infants with concentrations of =0.35 µg/mL in this study were different from those in the FinOM study for these 2 serotypes only. In addition, except for serotype 6B, the concentrations after 2 doses were comparable with those seen after the third dose among German infants who had received PCV concomitantly with DTaP-IPV/Hib combination vaccine at 2, 3 and 4 months.[31]
At 13 months, 1 month after the third dose of PCV, antibody concentrations measured in this study were as high as those in the previous Finnish, U.S. ( Table 3 ) and German[31] studies and were distributed similarly with respect to those measured in the previous Finnish study after 4 doses (Fig. 2), indicating equally good immunologic priming after 2 or 3 doses in early infancy. Other surrogate measures of immunologic priming, such as antibody avidity determinations or challenge with pneumococcal PS vaccine,[21] should be used in the future to confirm this.
Several studies with conjugate vaccines among infants yielded results concordant with this study. Even 1 dose of group C meningococcal vaccine[33] or Hib conjugate vaccine[34] at 2 months of age could induce good immunologic priming. In addition, a South African study with a nonavalent PCV showed that the antibody concentrations for 7 of the 9 vaccine serotypes were elevated even after the first dose of the PCV, given at the age of 6 weeks.[24] A Filipino study showed that 1 dose of an 11-valent PCV administered at the age of 18 weeks induced an immune response comparable with that measured after 3 doses administered at 6, 10 and 14 weeks.[35] Finally, preliminary data from a U.K. study indicate similar immunity after 2 or 3 doses of PCV in early infancy.[36]
The PCV has now been incorporated into the universal vaccination program for U.S. children. In other parts of the world, however, vaccination with PCV is still uncommon. There might be several reasons for this. First, the licensed vaccine contains 7 serotypes that are the most prevalent for invasive pneumococcal disease in the United States. They cover > 90% of the pneumococcal invasive disease burden of U.S. children,[37] but it is not yet clear how good the coverage would be in other parts of the world. Second, the price of the PCV ($40-50 per dose) has made it difficult to include the vaccine in programs that are paid for by the public health sector, even in the industrialized world. Third, the PCV is licensed for use among young children with a 4-dose schedule (3+1 schedule). Adoption of the PCV in countries that use 2+1 childhood immunization schedules would be easier and cheaper if the vaccine could be given concomitantly with other vaccines. The preliminary postmarketing surveillance reports from the United States suggest that 2 doses in the primary series are sufficient for protection,[38] although additional information on the duration of protection is needed. In conclusion, the immunogenicity data from this and other studies[24,35,36] suggest that the use of fewer than 4 doses is a practical option for administration of the PCV.
full article : http://www.medscape.com/viewarticle/500758_4
Käyhty, Helena PhD; Åhman, Heidi PhD; Eriksson, Karin; Sörberg, Mikael MD, PhD; Nilsson, Lennart MD, PhD
Published: 03/22/2005
Abstract
Background: The recommended vaccination schedule for the pneumococcal conjugate vaccine (PCV) includes 4 immunizations, according to the national programs in the United States and some European countries. Other countries use a national schedule for routine vaccinations in early childhood that includes only 3 doses.
Aims: The goals were to assess the immunogenicity and tolerability of PCV with a vaccination schedule that included 3 doses during the first 1 year of life (a 2+1 dose schedule) and to determine the immune responses to concomitantly administered Haemophilus influenzae type b (Hib) vaccine.
Methods: A total of 101 healthy Swedish infants were enrolled in an open, nonrandomized, multicenter study. PCV was administered concomitantly with (at separate sites) a diphtheria-tetanus toxoids-acellular pertussis vaccine, inactivated polio vaccine and Hib conjugate vaccine combination at 3, 5 and 12 months of age. IgG antibody concentrations for the 7 serotypes included in the PCV and the Hib capsular polysaccharide in serum samples taken at 3, 6, 12 and 13 months were determined with enzyme immunoassays. Local and systemic reactions were monitored for 3 days after each immunization, and serious adverse reactions were monitored for the whole study period.
Results: Two doses of PCV induced satisfactory antibody responses, with the exception of serotypes 6B and 23F. The third dose evoked strong responses for all serotypes, which suggests good immunologic priming with the primary series of 2 doses. The mean anti-Hib antibody concentrations were similar to those noted in earlier studies among Swedish children. The PCV was well tolerated.
Conclusion: The pneumococcal antibody concentrations at 13 months were comparable with those noted previously with the 4-dose schedule. The results suggest that the implementation of a 2+1 dose schedule for PCV should be considered.
Introduction
Several pneumococcal conjugate vaccines (PCVs) have been tested in clinical trials,[1] and a heptavalent PCV, which has been licensed in many parts of the world, is in wide use in the United States[2] and in some European countries. With serotype-specific efficacy of 97% against invasive disease,[3] the present PCV could cover 65-80% of invasive pneumococcal disease in Europe.[4-7] The postlicensure follow-up data have shown that the vaccination program has had a marked impact on the incidence of invasive pneumococcal disease in the United States.[2,8] In addition, vaccination with a PCV could decrease the spread of antibiotic-resistant pneumococci.[9] Heptavalent PCVs have shown efficacy of 56-57% against acute otitis media caused by the vaccine serotypes[10,11] and have reduced the number of ear tube replacements by 24 and 44% in the United States[12] and in Finland,[13] respectively. In South Africa and the United States, the protective effect on x-ray-positive pneumonia has been approximately 20%.[14,15]
The vaccination schedule recommended for PCV, and the one used in most previous clinical studies, includes 4 immunizations (ie, the 3+1 schedule, with a 3-dose primary series in 6 months, followed by a fourth dose in the second year) according to the national vaccination programs in the United States and some European countries. The vaccination program for infants in Sweden, Denmark, Norway and Italy, as well as Finland beginning in 2005, is based on primary vaccinations at 3 and 5 months and a third dose at 12 months of age (ie, the 2+1 schedule). The only feasible schedule for the PCV would involve concomitant administration with other childhood vaccines. In addition, decreasing the number of PCV injections would decrease costs and would thus facilitate addition of the PCV to national vaccination programs.
The primary aim of this study was to assess the immunogenicity and tolerability of a heptavalent PCV after primary vaccination consisting of 2 doses (administered at 3 and 5 months of age), with a third dose given at 12 months of age. Our secondary aim was to determine the concentrations of antibody to Haemophilus influenzae type b (Hib) after the second and third doses of the Hib conjugate vaccine, which was given concomitantly with the PCV.
Discussion
We showed that the heptavalent PCV was immunogenic and well tolerated when given with a 2+1 schedule concomitantly with a DTaP-IPV/Hib combination vaccine. At the age of 6 months, 1 month after the second dose, the antibody concentrations were already clearly elevated for all serotypes; nonetheless, the concentrations remained low for serotypes 6B and 23F, compared with the other serotypes. This was not surprising, because these serotypes evoked the lowest responses after 2 doses in the previous studies with the same or other vaccines.[16,17,20,24,25] The antibody concentrations increased significantly after the third vaccination, especially for serotypes 6B and 23F. This indicates good immunologic priming after 2 doses of PCV. On the basis of experience with the Hib conjugate vaccine,[26,27] it is thought that immunologic priming, in addition to existing antibody concentrations, is important for long-lasting protection. This is probably true also for PCVs. In fact, antibody concentrations that were lower after 3 doses of a PCV than those measured in this study after 2 doses provided protection against acute otitis media caused by serotypes 6B and 23F[11] among 6- to 12-month-old infants. We think that the immune response detected in this study would provide protection against invasive pneumococcal disease between the ages of 6 and 12 months.
The administration of PCV concomitantly with the DTaP-IPV/Hib combination vaccine did not seem to affect the immune response to Hib conjugate vaccine. The mean anti-Hib antibody concentrations remained low after the second dose but were not different from those reported from other studies with this vaccination schedule in Sweden.[28,29] Despite the low antibody responses of Swedish children after the second administration of the Hib vaccine, the incidence of Hib disease has remained low and breakthrough cases have been rare with this schedule.[30]
Fever (usually mild) was quite common and was observed more often after the third dose than after the first dose. Fever was observed slightly more often than in a similar study in Germany in which the same PCV was administered concurrently with the same DTaP-IPV/Hib combination vaccine but at 2, 3, 4 and 11-15 months of age. In that study, fever of ≥ 38ºC was observed for 29-48.2% of subjects, depending on age, and high fever of ≥ 39ºC was noted for 2.9-8.3%.[31] In the German study, fever was more common after the first vaccination in the PCV-treated group than in the control group that received only the combination vaccine but was equivalent between the groups after the subsequent vaccinations. In this study, we cannot tell how much the PCV contributed to the low-grade fever, because no control group was included. However, it has been shown that acellular pertussis vaccines induce higher rates of nodules and fever after the second or third vaccination than after the first dose.[32]
Because the PCV has been licensed in many areas of the world, requiring placebo-controlled efficacy trials with novel PCVs, PCV formulations or schedules is no longer realistic. The licensure of new PCVs and the acceptance of new PCV schedules will depend on phase II studies of immunogenicity and safety, which should be planned to show noninferiority to the licensed vaccine or to an established vaccination schedule.21 Although this study was not planned as a noninferiority study, we can compare the data of this study with the published immunogenicity data from efficacy trials with 2 different endpoints, i.e. invasive disease or acute otitis media. In these trials, the same PCV as in this study was used but with the recommended 4-dose schedule. The GMC values for the serotype-specific antibodies from this study were compared with those from 2 trials that demonstrated that the vaccines are efficacious, i.e. the Northern California Kaiser-Permanente study3 and the Finnish Otitis Media (FinOM) Vaccine Trial10 ( Table 3 ). Furthermore, we compared the distribution of antibody concentrations in this study and in the FinOM trial arm that used the same cross-reactive material-conjugated PCV (Figs. 1 and 2). Sera from the FinOM trial and from this study were analyzed in the same laboratory, whereas the U.S. data came from the Wyeth laboratories. Interlaboratory comparisons have proved that the 2 laboratories give concordant results.
The GMC values measured in this study after the second dose were comparable with those noted in the efficacy trials after 3 doses. The only exception was serotype 6B, for which the GMC values in this study were lower than those measured in the Finnish and U.S. studies ( Table 3 ). For serotype 23F, the concentrations remained lower than those in the Finnish study but were not markedly lower than those in the U.S. study. Furthermore, the distributions of antibodies (Fig. 1) and the proportions of infants with concentrations of =0.35 µg/mL in this study were different from those in the FinOM study for these 2 serotypes only. In addition, except for serotype 6B, the concentrations after 2 doses were comparable with those seen after the third dose among German infants who had received PCV concomitantly with DTaP-IPV/Hib combination vaccine at 2, 3 and 4 months.[31]
At 13 months, 1 month after the third dose of PCV, antibody concentrations measured in this study were as high as those in the previous Finnish, U.S. ( Table 3 ) and German[31] studies and were distributed similarly with respect to those measured in the previous Finnish study after 4 doses (Fig. 2), indicating equally good immunologic priming after 2 or 3 doses in early infancy. Other surrogate measures of immunologic priming, such as antibody avidity determinations or challenge with pneumococcal PS vaccine,[21] should be used in the future to confirm this.
Several studies with conjugate vaccines among infants yielded results concordant with this study. Even 1 dose of group C meningococcal vaccine[33] or Hib conjugate vaccine[34] at 2 months of age could induce good immunologic priming. In addition, a South African study with a nonavalent PCV showed that the antibody concentrations for 7 of the 9 vaccine serotypes were elevated even after the first dose of the PCV, given at the age of 6 weeks.[24] A Filipino study showed that 1 dose of an 11-valent PCV administered at the age of 18 weeks induced an immune response comparable with that measured after 3 doses administered at 6, 10 and 14 weeks.[35] Finally, preliminary data from a U.K. study indicate similar immunity after 2 or 3 doses of PCV in early infancy.[36]
The PCV has now been incorporated into the universal vaccination program for U.S. children. In other parts of the world, however, vaccination with PCV is still uncommon. There might be several reasons for this. First, the licensed vaccine contains 7 serotypes that are the most prevalent for invasive pneumococcal disease in the United States. They cover > 90% of the pneumococcal invasive disease burden of U.S. children,[37] but it is not yet clear how good the coverage would be in other parts of the world. Second, the price of the PCV ($40-50 per dose) has made it difficult to include the vaccine in programs that are paid for by the public health sector, even in the industrialized world. Third, the PCV is licensed for use among young children with a 4-dose schedule (3+1 schedule). Adoption of the PCV in countries that use 2+1 childhood immunization schedules would be easier and cheaper if the vaccine could be given concomitantly with other vaccines. The preliminary postmarketing surveillance reports from the United States suggest that 2 doses in the primary series are sufficient for protection,[38] although additional information on the duration of protection is needed. In conclusion, the immunogenicity data from this and other studies[24,35,36] suggest that the use of fewer than 4 doses is a practical option for administration of the PCV.
full article : http://www.medscape.com/viewarticle/500758_4
Autism Risk Factors
New Studies Reveal Autism Risk Factors, First Common Gene Variants CME/CE
News Author: Janis Kelly
CME Author: Charles P. Vega
May 11, 2009 — New research shows that autism rates are higher for children who are firstborn or breech or whose mothers are 35 years old or older when they give birth. Further, 2 new genetics studies identify genetic abnormalities that affect 2 pathways involved in the formation of brain-cell connections.
Deborah A. Bilder, MD, and colleagues from the University of Utah School of Medicine, in Salt Lake City, found that having a child with autism-spectrum disorder (ASD) is 1.7 times more likely for mothers who give birth at 35 years or older compared with their women aged 20 to 34 years and 1.8 times more likely in the firstborn child. In addition, ASD children were more than twice as likely to have been a breech presentation.
"The findings of this study suggest that maternal age, parity, and breech presentation are independently associated with ASD risk. Additional investigations focused on both genetic and environmental factors that link these factors individually or collectively are necessary," the investigators write.
The study is published online April 27 in Pediatrics.
Results Warrant Careful Interpretation
Robert L. Hendren, DO, president of the American Academy of Child and Adolescent Psychiatry and an advisor to the Autism Society of America, told Medscape Psychiatry that clinicians should be prepared to reassure patients who might overinterpret the results of this study, despite the authors' careful presentation.
"Patients need to understand that association is not necessarily cause and effect," Dr. Hendren said. "Taken in conjunction with an earlier study that linked older fathers to increased ASD risk, this study suggests that there is some vulnerability factor associated with having older parents, but we have no idea what that might be. And older potential mothers certainly do not need to avoid having children because they are worried about this possible risk," said Dr. Hendren, who is also executive director of the MIND Institute and chief of child and adolescent psychiatry at the University of California, Davis.
Autism appears to develop from the interplay of a complex system of genetic and environmental factors. Previous research has suggested several prenatal, perinatal, and neonatal factors associated with a higher risk for autism, including advanced maternal and paternal age, a shorter length of gestation, low birth weight, meconium staining, hyperbilirubinemia, and breech presentation. In addition, parity may also affect the risk for autism. Research has most consistently demonstrated that the first child in the birth order has a higher risk for autism.
Previous research may have been limited by defining autism with only the most severe cases. The current study by Bilder and colleagues uses a broad definition of ASD and a very large control group from the same geographic area to further explore the issue of risk factors for autism.
for rest of article : http://cme.medscape.com/viewarticle/702585?src=cmenews
News Author: Janis Kelly
CME Author: Charles P. Vega
May 11, 2009 — New research shows that autism rates are higher for children who are firstborn or breech or whose mothers are 35 years old or older when they give birth. Further, 2 new genetics studies identify genetic abnormalities that affect 2 pathways involved in the formation of brain-cell connections.
Deborah A. Bilder, MD, and colleagues from the University of Utah School of Medicine, in Salt Lake City, found that having a child with autism-spectrum disorder (ASD) is 1.7 times more likely for mothers who give birth at 35 years or older compared with their women aged 20 to 34 years and 1.8 times more likely in the firstborn child. In addition, ASD children were more than twice as likely to have been a breech presentation.
"The findings of this study suggest that maternal age, parity, and breech presentation are independently associated with ASD risk. Additional investigations focused on both genetic and environmental factors that link these factors individually or collectively are necessary," the investigators write.
The study is published online April 27 in Pediatrics.
Results Warrant Careful Interpretation
Robert L. Hendren, DO, president of the American Academy of Child and Adolescent Psychiatry and an advisor to the Autism Society of America, told Medscape Psychiatry that clinicians should be prepared to reassure patients who might overinterpret the results of this study, despite the authors' careful presentation.
"Patients need to understand that association is not necessarily cause and effect," Dr. Hendren said. "Taken in conjunction with an earlier study that linked older fathers to increased ASD risk, this study suggests that there is some vulnerability factor associated with having older parents, but we have no idea what that might be. And older potential mothers certainly do not need to avoid having children because they are worried about this possible risk," said Dr. Hendren, who is also executive director of the MIND Institute and chief of child and adolescent psychiatry at the University of California, Davis.
Autism appears to develop from the interplay of a complex system of genetic and environmental factors. Previous research has suggested several prenatal, perinatal, and neonatal factors associated with a higher risk for autism, including advanced maternal and paternal age, a shorter length of gestation, low birth weight, meconium staining, hyperbilirubinemia, and breech presentation. In addition, parity may also affect the risk for autism. Research has most consistently demonstrated that the first child in the birth order has a higher risk for autism.
Previous research may have been limited by defining autism with only the most severe cases. The current study by Bilder and colleagues uses a broad definition of ASD and a very large control group from the same geographic area to further explore the issue of risk factors for autism.
for rest of article : http://cme.medscape.com/viewarticle/702585?src=cmenews
Saturday, May 2, 2009
New Autism Risk Factors?
New Studies Reveal Autism Risk Factors, First Common Gene Variants
by Janis Kelly
Deborah A. Bilder, MD, and colleagues from the University of Utah School of Medicine, in Salt Lake City, found that having a child with autism-spectrum disorder (ASD) is 1.7 times more likely for mothers who give birth at 35 years or older compared with their women aged 20 to 34 years and 1.8 times more likely in the firstborn child. In addition, ASD children were more than twice as likely to have been a breech presentation.
"The findings of this study suggest that maternal age, parity, and breech presentation are independently associated with ASD risk. Additional investigations focused on both genetic and environmental factors that link these factors individually or collectively are necessary," the investigators write.
The study is published online April 27 in Pediatrics.
Results Warrant Careful Interpretation
Robert L. Hendren, DO, president of the American Academy of Child and Adolescent Psychiatry and an advisor to the Autism Society of America, told Medscape Psychiatry that clinicians should be prepared to reassure patients who might overinterpret the results of this study, despite the authors' careful presentation.
"Patients need to understand that association is not necessarily cause and effect," Dr. Hendren said. "Taken in conjunction with an earlier study that linked older fathers to increased ASD risk, this study suggests that there is some vulnerability factor associated with having older parents, but we have no idea what that might be. And older potential mothers certainly do not need to avoid having children because they are worried about this possible risk," said Dr. Hendren, who is also executive director of the MIND Institute and chief of child and adolescent psychiatry at the University of California, Davis.
Dr. Bilder and colleagues examined the birth records of Utah children identified with ASD in a 2002 epidemiological study by the US Centers for Disease Control and Prevention. The study included 8-year-old children in Utah's 3 most populous counties. The researchers compared birth records for children identified with ASD with unaffected counterparts.
The study suggests that more ASD children might be firstborns because parents might be reluctant to have a second child if the first is diagnosed with ASD. Maternal age might increase risk due to gene changes that accumulate with time. Breech presentation and ASD might be linked by ASD-related neuromuscular dysfunction.
Common Genetic Variants Found
Two genomewide association studies from research teams led by Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at the Children's Hospital of Philadelphia, in Pennsylvania, have identified new gene abnormalities that affect cell-to-cell adhesion and the formation and maintenance of neuronal connectivity. Both studies were reported online April 28 in Nature.
One study pinpoints a gene region that may account for up to 15% of autism cases, while another identifies missing or duplicated stretches of DNA along 2 crucial gene pathways. Both studies detected genes implicated in the development of brain circuitry in early childhood.
"The genetic landscape in autism currently includes only a few candidate genes/loci with rare variants (copy number changes). This discovery shows for the first time that a common variant, present in 65% of children with autism, exists in autism. It unveils a biological pathway involved with neuronal connectivity that we will be able to target in the future for new therapy," Dr. Hakonarson told Medscape Psychiatry.
"The diagnostic value of this will become more meaningful as we find more common variants, but if all variants that have been identified today — common and rare — are put together, we can make meaningful predictions for families who are at high risk," said Dr. Hakonarson.
"It is very interesting that the only genes that came up as significant and replicated in independent cohorts belong to 2 gene networks (neuronal cell-adhesion molecules and ubiquitin gene family) that are involved with developing and shaping neuronal connections and communications between brain cells," he added.
The researchers used genomewide analysis in over 10,000 individuals to determine that children with ASD were more likely than healthy controls to have gene variants on a particular region of chromosome 5 located between 2 genes, cadherin 9 (CDH9) and cadherin 10 (CDH10), which carry codes to produce neuronal cell-adhesion molecules.
Genetic Treatment a Long Way Off
In the second study, they identified copy number variations (CNVs) that increase a child's risk of having ASD. These variants were enriched in genes that belong to 2 biological pathways, 1 including the same neuronal cell-adhesion molecule gene family that harbored the common variant reported in Hakonarson's first study.
The other gene cluster affected by CNVs belongs to the ubiquitin degradation pathway, a class of enzymes that eliminate connections among nerve cells and are involved with processing and degrading neuronal cell-adhesion molecules — thus linking the 2 gene pathways.
"The copy number variations we discovered are active on 2 gene networks that play critical roles in the development of neuronal connectivity within the central nervous system," Dr. Hakonarson said. "Finding genes that are biologically relevant to these neuronal systems increases our understanding of how autism originates."
Dr. Hendren told Medscape Psychiatry that the Hakonarson data add weight to prior imaging studies that suggested that ASD is the result of generalized connectivity dysfunctions, not just of problems in 1 brain area.
"The hope is that we might be able to find ways to improve or protect that connectivity," Dr. Hendren said. "We are not likely to be doing gene engineering to treat autism, but we might be able to modify factors that govern gene expression. Such treatments will require a lot more work on the genetic factors, environmental factors, and epigenetic factors that connect those 2 areas. New treatments are not right around the corner."
Dr. Bilder discloses serving as a consultant to BioMarin's autism advisory board.
Pediatrics. Published online April 27, 2009.
Nature. Published online April 28, 2009. Abstract
http://www.medscape.com/viewarticle/702213?sssdmh=dm1.465854&src=nldne
by Janis Kelly
Deborah A. Bilder, MD, and colleagues from the University of Utah School of Medicine, in Salt Lake City, found that having a child with autism-spectrum disorder (ASD) is 1.7 times more likely for mothers who give birth at 35 years or older compared with their women aged 20 to 34 years and 1.8 times more likely in the firstborn child. In addition, ASD children were more than twice as likely to have been a breech presentation.
"The findings of this study suggest that maternal age, parity, and breech presentation are independently associated with ASD risk. Additional investigations focused on both genetic and environmental factors that link these factors individually or collectively are necessary," the investigators write.
The study is published online April 27 in Pediatrics.
Results Warrant Careful Interpretation
Robert L. Hendren, DO, president of the American Academy of Child and Adolescent Psychiatry and an advisor to the Autism Society of America, told Medscape Psychiatry that clinicians should be prepared to reassure patients who might overinterpret the results of this study, despite the authors' careful presentation.
"Patients need to understand that association is not necessarily cause and effect," Dr. Hendren said. "Taken in conjunction with an earlier study that linked older fathers to increased ASD risk, this study suggests that there is some vulnerability factor associated with having older parents, but we have no idea what that might be. And older potential mothers certainly do not need to avoid having children because they are worried about this possible risk," said Dr. Hendren, who is also executive director of the MIND Institute and chief of child and adolescent psychiatry at the University of California, Davis.
Dr. Bilder and colleagues examined the birth records of Utah children identified with ASD in a 2002 epidemiological study by the US Centers for Disease Control and Prevention. The study included 8-year-old children in Utah's 3 most populous counties. The researchers compared birth records for children identified with ASD with unaffected counterparts.
The study suggests that more ASD children might be firstborns because parents might be reluctant to have a second child if the first is diagnosed with ASD. Maternal age might increase risk due to gene changes that accumulate with time. Breech presentation and ASD might be linked by ASD-related neuromuscular dysfunction.
Common Genetic Variants Found
Two genomewide association studies from research teams led by Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at the Children's Hospital of Philadelphia, in Pennsylvania, have identified new gene abnormalities that affect cell-to-cell adhesion and the formation and maintenance of neuronal connectivity. Both studies were reported online April 28 in Nature.
One study pinpoints a gene region that may account for up to 15% of autism cases, while another identifies missing or duplicated stretches of DNA along 2 crucial gene pathways. Both studies detected genes implicated in the development of brain circuitry in early childhood.
"The genetic landscape in autism currently includes only a few candidate genes/loci with rare variants (copy number changes). This discovery shows for the first time that a common variant, present in 65% of children with autism, exists in autism. It unveils a biological pathway involved with neuronal connectivity that we will be able to target in the future for new therapy," Dr. Hakonarson told Medscape Psychiatry.
"The diagnostic value of this will become more meaningful as we find more common variants, but if all variants that have been identified today — common and rare — are put together, we can make meaningful predictions for families who are at high risk," said Dr. Hakonarson.
"It is very interesting that the only genes that came up as significant and replicated in independent cohorts belong to 2 gene networks (neuronal cell-adhesion molecules and ubiquitin gene family) that are involved with developing and shaping neuronal connections and communications between brain cells," he added.
The researchers used genomewide analysis in over 10,000 individuals to determine that children with ASD were more likely than healthy controls to have gene variants on a particular region of chromosome 5 located between 2 genes, cadherin 9 (CDH9) and cadherin 10 (CDH10), which carry codes to produce neuronal cell-adhesion molecules.
Genetic Treatment a Long Way Off
In the second study, they identified copy number variations (CNVs) that increase a child's risk of having ASD. These variants were enriched in genes that belong to 2 biological pathways, 1 including the same neuronal cell-adhesion molecule gene family that harbored the common variant reported in Hakonarson's first study.
The other gene cluster affected by CNVs belongs to the ubiquitin degradation pathway, a class of enzymes that eliminate connections among nerve cells and are involved with processing and degrading neuronal cell-adhesion molecules — thus linking the 2 gene pathways.
"The copy number variations we discovered are active on 2 gene networks that play critical roles in the development of neuronal connectivity within the central nervous system," Dr. Hakonarson said. "Finding genes that are biologically relevant to these neuronal systems increases our understanding of how autism originates."
Dr. Hendren told Medscape Psychiatry that the Hakonarson data add weight to prior imaging studies that suggested that ASD is the result of generalized connectivity dysfunctions, not just of problems in 1 brain area.
"The hope is that we might be able to find ways to improve or protect that connectivity," Dr. Hendren said. "We are not likely to be doing gene engineering to treat autism, but we might be able to modify factors that govern gene expression. Such treatments will require a lot more work on the genetic factors, environmental factors, and epigenetic factors that connect those 2 areas. New treatments are not right around the corner."
Dr. Bilder discloses serving as a consultant to BioMarin's autism advisory board.
Pediatrics. Published online April 27, 2009.
Nature. Published online April 28, 2009. Abstract
http://www.medscape.com/viewarticle/702213?sssdmh=dm1.465854&src=nldne
Friday, May 1, 2009
Reduce risk of Sudden Infant Death
SIDS is the leading cause of death in infants younger than 1 year in developed countries. Sleeping in a prone position has been identified as a significant risk, leading to the Back to Sleep campaign, which resulted in a reduction in SIDS mortality rates in many countries. Since that campaign was initiated, other risk factors such as sleep environment have not been fully examined.
Being placed or found in the prone position is associated with a higher risk for SIDS in infants.
Other risk factors for SIDS include bed sharing, use of duvets, sleeping at a relative's or a friend's home, and sleeping in the living room, whereas pacifier use has a protective effect
This is a population-based case-control study conducted in a part of Germany with more than 50% of its live births to determine risk factors associated with SIDS duriNewng a 3-year period (1998-2001).
source:
New Sleep Environment Risk Factors for SIDS Identified
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
Released: 04/17/2009;
http://cme.medscape.com/viewarticle/591213?src=cmenews
Being placed or found in the prone position is associated with a higher risk for SIDS in infants.
Other risk factors for SIDS include bed sharing, use of duvets, sleeping at a relative's or a friend's home, and sleeping in the living room, whereas pacifier use has a protective effect
This is a population-based case-control study conducted in a part of Germany with more than 50% of its live births to determine risk factors associated with SIDS duriNewng a 3-year period (1998-2001).
source:
New Sleep Environment Risk Factors for SIDS Identified
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
Released: 04/17/2009;
http://cme.medscape.com/viewarticle/591213?src=cmenews
Breast Feeding Improves IQ
Prolonged, Exclusive Breast-Feeding Linked to Improved Cognitive Development
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
May 6, 2008 — Prolonged and exclusive breast-feeding improves cognitive development as measured by IQ and teachers' academic ratings in children at age 6.5 years, according to the results of the largest randomized trial ever conducted in the area of human lactation, published in the May issue of Archives of General Psychiatry.
"The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother’s behavior or her interaction with the infant," write Michael S. Kramer, MD, and colleagues from the Promotion of Breastfeeding Intervention Trial (PROBIT) Study Group.
The goal of this cluster-randomized trial was to determine whether prolonged and exclusive breast-feeding was associated with improved cognitive ability in children at age 6.5 years. At 31 Belarussian maternity hospitals and their affiliated polyclinics, 17,046 healthy breast-feeding infants were enrolled from June 17, 1996, to December 31, 1997, and 13,889 of these infants (81.5%) were followed up from December 21, 2002, to April 27, 2005, at age 6.5 years.
The breast-feeding promotion intervention was modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and United Nations Children's Fund (UNICEF). Primary outcomes were subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence (WASI), and teacher evaluations of academic performance in reading, writing, mathematics, and other subjects.
Compared with the control group, the intervention group had a large increase in exclusive breast-feeding at age 3 months (43.3% vs 6.4%; P < .001) and a significantly higher prevalence of any breast-feeding at all ages, up to and including 12 months.
Compared with the control group, the intervention group had higher means on all of the WASI measures. Cluster-adjusted mean differences were +7.5 (95% confidence interval [CI], 0.8 - 14.3) for verbal IQ, +2.9 (95% CI, −3.3 to +9.1) for performance IQ, and +5.9 (95% CI, −1.0 to +12.8) for full-scale IQ. For both reading and writing, teachers' academic ratings were significantly higher in the experimental group.
"These results, based on the largest randomized trial ever conducted in the area of human lactation, provide strong evidence that prolonged and exclusive breastfeeding improves children’s cognitive development," the study authors write.
The major study limitation is lack of blinding of the pediatricians who administered the WASI to the experimental vs control intervention status of the children they examined.
"Because protection against infections in developed country settings does not have the life-and-death implications for infant and child health that it does in less-developed settings, cognitive benefits may be among the most important advantages for breastfed infants in industrialized societies," the study authors write. "The consistency of our findings based on a randomized trial with those reported in previous observational studies should prove helpful in encouraging further public health efforts to promote, protect, and support breastfeeding."
The Canadian Institutes of Health Research supported this study. The authors have disclosed no relevant financial relationships.
Source : Arch Gen Psychiatry. 2008;65:578-584.
http://cme.medscape.com/viewarticle/574063?sssdmh=dm1.465371&src=nldne
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
May 6, 2008 — Prolonged and exclusive breast-feeding improves cognitive development as measured by IQ and teachers' academic ratings in children at age 6.5 years, according to the results of the largest randomized trial ever conducted in the area of human lactation, published in the May issue of Archives of General Psychiatry.
"The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother’s behavior or her interaction with the infant," write Michael S. Kramer, MD, and colleagues from the Promotion of Breastfeeding Intervention Trial (PROBIT) Study Group.
The goal of this cluster-randomized trial was to determine whether prolonged and exclusive breast-feeding was associated with improved cognitive ability in children at age 6.5 years. At 31 Belarussian maternity hospitals and their affiliated polyclinics, 17,046 healthy breast-feeding infants were enrolled from June 17, 1996, to December 31, 1997, and 13,889 of these infants (81.5%) were followed up from December 21, 2002, to April 27, 2005, at age 6.5 years.
The breast-feeding promotion intervention was modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and United Nations Children's Fund (UNICEF). Primary outcomes were subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence (WASI), and teacher evaluations of academic performance in reading, writing, mathematics, and other subjects.
Compared with the control group, the intervention group had a large increase in exclusive breast-feeding at age 3 months (43.3% vs 6.4%; P < .001) and a significantly higher prevalence of any breast-feeding at all ages, up to and including 12 months.
Compared with the control group, the intervention group had higher means on all of the WASI measures. Cluster-adjusted mean differences were +7.5 (95% confidence interval [CI], 0.8 - 14.3) for verbal IQ, +2.9 (95% CI, −3.3 to +9.1) for performance IQ, and +5.9 (95% CI, −1.0 to +12.8) for full-scale IQ. For both reading and writing, teachers' academic ratings were significantly higher in the experimental group.
"These results, based on the largest randomized trial ever conducted in the area of human lactation, provide strong evidence that prolonged and exclusive breastfeeding improves children’s cognitive development," the study authors write.
The major study limitation is lack of blinding of the pediatricians who administered the WASI to the experimental vs control intervention status of the children they examined.
"Because protection against infections in developed country settings does not have the life-and-death implications for infant and child health that it does in less-developed settings, cognitive benefits may be among the most important advantages for breastfed infants in industrialized societies," the study authors write. "The consistency of our findings based on a randomized trial with those reported in previous observational studies should prove helpful in encouraging further public health efforts to promote, protect, and support breastfeeding."
The Canadian Institutes of Health Research supported this study. The authors have disclosed no relevant financial relationships.
Source : Arch Gen Psychiatry. 2008;65:578-584.
http://cme.medscape.com/viewarticle/574063?sssdmh=dm1.465371&src=nldne
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