Sunday, February 28, 2010

Prenatal and Postnatal Tobacco Exposure and Behavioral Problems in 10-year-old

From Environmental Health Perspectives
Children: Results from the GINI-plus Prospective Birth
Simon Rückinger; Peter Rzehak; Chih-Mei Chen; Stefanie Sausenthaler; Sibylle Koletzko; Carl-Peter Bauer; Ute Hoffmann; Ursula Kramer; Dietrich Berdel; Andrea von Berg; Otmar Bayer; H.-Erich Wichmann; Rüdiger von Kries; Joachim Heinrich

Posted: 02/18/2010; Environmental Health Perspectives. 2010;118(1):150-154. © 2010 National Institute of Environmental Health Sciences

Abstract
Background: Prenatal and postnatal tobacco exposure have been reported to be associated with behavioral problems. However, the magnitude of the association with tobacco exposure at specific periods of exposure is unclear.

Objective: We assessed the relative risk of behavioral problems in children who had been exposed to tobacco smoke in utero and postnatally.

Methods: We analyzed data from a prospective birth cohort study in two cities in Germany: the German Infant Nutrition Intervention. Our sample included 5,991 children born between 1995 and 1998 as well as their parents. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According to prespecified SDQ cutoff values, children were classified as "normal," "borderline," or "abnormal" according to the subscales "emotional symptoms," "conduct problems," "hyperactivity/inattention," "peer-relationship problems," and a total difficulties score. Smoke exposure and further covariates were assessed using parent

Results: Compared with children not exposed to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had twice the estimated risk [95% confidence interval (CI), 1.4-3.1] of being classified as abnormal according to the total difficulties score of the SDQ at 10 years of age.

Children who were only prenatally exposed had a 90% higher relative risk (95% CI, 0.9-4.0), whereas children who were only postnatally exposed had a 30% higher relative risk (95% CI, 0.9-1.9).
These results could not be explained by confounding by parental education, father's employment, child's time spent in front of computer or television screen, being a single father or mother, or mother's age.

Conclusions: Prenatal exposure to tobacco smoke is associated with behavioral problems in school-age children.
Although our findings do not preclude the influence of postnatal exposure, prenatal exposure seems to be more important.

Introduction
Exposure of children to tobacco smoke, whether postnatal or in utero, is a well-known risk factor for various adverse health outcomes (DiFranza et al. 2004).

An increased risk for intrauterine growth retardation, sudden infant death syndrome, and asthma are well-known adverse effects of in utero tobacco exposure (Higgins 2002).
In addition, effects of in utero tobacco exposure on behavioral problems have been reported in various experimental and epidemiologic studies (Ernst et al. 2001; Eskenazi and Castorina 1999; Wakschlag et al. 2002; Weitzman et al. 2002) including some longitudinal studies (Markussen Linnet et al. 2006; Wakschlag et al. 1997). Prospective studies that systematically assess a broad range of behavioral problems outcomes are sparse.

Many studies have found an association between smoking in pregnancy and behavioral problems among children (Batstra et al. 2003; Roza et al. 2009; Saxton 1978).

An independent effect of postnatal tobacco exposure on behavioral development has also been suggested (Braun et al. 2006, 2008; Fergusson et al. 1993; Weitzman et al. 1992; Williams et al. 1998). However, specifically delineating the impact of prenatal versus postnatal tobacco exposure is a challenging task: Children whose mothers have smoked during pregnancy are likely to be exposed to tobacco smoke after birth. Furthermore, many studies use cross-sectional designs where recall bias may play an important role. The specific roles of pre- and postnatal exposure are not yet clarified.

In this study, we analyzed data from the German Infant Nutritional Intervention (GINI), a large prospective birth cohort that also contains comprehensive follow-up. GINI's prospective design and the comprehensive questions on tobacco smoke exposure at various time points provide the opportunity to disentangle the impacts of prenatal and postnatal tobacco exposure on behavioral problems. In a subset of this study, Gehring et al. (2006) tested the validity of the questionnaire-derived data on environmental tobacco smoke by measuring air nicotine and urine cotinine; the misclassification rate was below 7%, which is in line with that of other similar studies. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) (Goodman 1997), which allows assessment of a broad range of behavioral problems.

http://www.medscape.com/viewarticle/716414?src=mp&spon=9&uac=71630FV

Tuesday, February 23, 2010

Mom's Diet During Pregnancy May Alter Infant's Allergies

From Reuters Health Information

NEW YORK (Reuters Health) Feb 19 - Eating lots of vegetables and fruits during pregnancy may lower the chance of having a baby with certain allergies, hint study findings from Japan.

Greater intake of green and yellow vegetables, citrus fruit, and veggies and fruits high in beta carotene may lessen the risk of having a baby with eczema, Dr. Yoshihiro Miyake at Fukuoka University and colleagues found.

Foods high in vitamin E similarly may lessen the risk of having a wheezy infant, they reported online January 22nd in Allergy.

Beta carotene and vitamin E are two of many antioxidants thought to benefit health. But prior investigations of maternal antioxidant intake and childhood allergies offered conflicting findings. This area of research "is still developing," Dr. Miyake noted in an email to Reuters Health.

In the current study, Dr. Miyake's team evaluated vegetable and fruit intake during pregnancy in 763 women, as well as eczema or allergic wheeze in their infants.

The women were 30 years old on average and about 17 weeks pregnant at enrollment.. When their babies were between 16 and 24 months old, the women provided birth and breastfeeding history, number of older siblings, and exposure to smoke.

The team found that 21% of the youngsters wheezed or had a "whistling in the chest in the last 12 months," and fewer than 19% had eczema.

According to the investigators, mothers who ate greater amounts of green and yellow vegetables, citrus fruits, or beta carotene while pregnant were less apt to have an infant with eczema.

For example, after allowing for other eczema risk factors, eczema was more common among infants whose mothers ate the least versus the most green and yellow vegetables - 54 and 32 infants, respectively.

Likewise, higher intake of vitamin E during pregnancy was associated a reduced likelihood of having a wheezy infant -- a finding that supports previous investigations from the U.S. and U.K.

Boosting intake of green and yellow vegetables, citrus fruits, and antioxidants such as beta-carotene and vitamin E among pregnant women "deserves further investigation as measures that would possibly be effective in the prevention of allergic disorders in the offspring," the researchers conclude.

Allergy 2010.

Friday, February 19, 2010

Study Does Not Support HPV Vaccine in Older Women

From Medscape Medical News
Janis C. Kelly

February 17, 2010 — Findings from a natural-history study of human papillomavirus (HPV) have led the investigators to conclude that the "potential benefit" of HPV vaccination in older women (≥42 years) is "low."

The research team, led by Ana Cecilia Rodríguez, MD, from the Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, in San José, Costa Rica, found that the rate of new HPV infections declines with age and that new infections usually do not progress to grade 2 or 3 cervical intraepithelial neoplasia (CIN) in older women.

The investigators found that infections at baseline were more likely to persist in older than in younger women (P < .01 for a comparison of 8 groups). Furthermore, most of the grade 2 or worse CIN disease that was detected during follow-up (66 of 85 cases) was associated with infections already present at baseline.

The 7-year study of Costa Rican women — the largest ever to examine age, HPV persistence, and cervical cancer precursors — was published online February 15 in the Journal of the National Cancer Institute.

This is a great paper.
"This is a great paper, the longest follow-up study to date available on women in a broad age range," said Silvia Franceschi, MD, who was approached by Medscape Oncology for independent comment.

Dr. Franceschi, who is coordinator of the epidemiology and biology cluster at the International Agency for Research on Cancer in Lyon, France, noted that there seems to be very little to gain by vaccinating women older than 25 years or so.

"The 'dangerous' or persistent infections may be already there and will not be eliminated by the current HPV vaccines," she added. "The pharmaceutical industry's claim that vaccine should be given to older women because HPV infections are more dangerous after a certain age has been proven not to be true."

More Than 9000 Women, 7-Year Follow-Up in HPV Study

The researchers screened more than 9000 women, 18 to 97 years, in Costa Rica. Those with CIN 2 disease or worse at enrollment were treated and not followed any further. Among the remaining participants, those at low risk for CIN 2 or worse were rescreened at 5 to 7 years (passively followed), whereas higher-risk participants and subsets of low-risk women and initially sexually nonactive women were rescreened annually or semiannually (actively followed) for up to 7 years.

As noted above, most women diagnosed with CIN 2 or worse during the study period were already infected with a carcinogenic HPV strain (prevalent infection) at the time of initial testing.

Regardless of the woman's age, most newly detected HPV resolved and did not lead to CIN 2 or worse during the study period. Total cumulative CIN 2+ associated with newly appearing infections ranged from 2.1% to 6.2% over the first 3 years of follow-up.

Age-related changes in immunity have also been a concern, and the data showed that women older than 34 years were not at greater risk than younger women for progression to CIN3+ after 3 years. Newly detected infections led to a CIN3+ diagnosis in 0 of 17 women 34 years or older and in 5 of 41 (12.2%) women younger than 34 years.

Furthermore, rates of newly detected HPV infections declined sharply with age, from 35.9% in women 18 to 25 years to 13.5% in women 42 years and older in the actively followed group.

Among infections present at first examination, persistent infections were more common among women 42 years or older than among younger women.

The researchers conclude that cervical cancer risk is determined by the previous overt duration of carcinogenic HPV infections, not by genital warts caused by HPV 6 or HPV 11, and not by age. New infections, which are the only type that can be prevented by currently available HPV vaccination, carry little near-term cancer risk at any age, and most of them resolve within 2 to 3 years, say the investigators.

Vaccinating girls before they become sexually active reduces the chance that a new carcinogenic HPV infection will persist for the 25 to 30 years required to cause invasive cervical cancer, write the researchers. However, they remind clinicians that most HPV infections are benign. "[A] focus on HPV persistence, and avoidance of overreaction to HPV infections that are likely to resolve spontaneously, is essential for a rational introduction of HPV testing into cervical cancer screening programs."

By Age 30, Most Women Already Have HPV

"The HPV vaccines that are available now are prophylactic," Dr. Rodríguez told Medscape Oncology. "They can only prevent getting infected; they do not treat infections that are already present. In a given population with an average age at first sexual intercourse of around 15 to 17 years, to vaccinate women after the age of 30 is not cost-efficient."

"By age 30, most women would have been infected with the HPV types covered by the vaccines, and women are not getting that many new infections; therefore, the residual benefit provided by the vaccine is very small," she added.

We were surprised by the distinct persistence pattern observed for the group of prevalent infections among women 42+ years of age.
"We were surprised by the distinct persistence pattern observed for the group of prevalent infections among women 42+ years of age. For all other prevalent infections and for all incident infections, regardless of the woman's age, the chance of persistence was very similar," Dr. Rodríguez said. Persistence for 6 or more years of carcinogenic HPV infections detected by polymerase chain reaction (PCR) at baseline was 5.1% in women 18 to 25 years of age, 14.4% in women 26 to 33 years of age, 12.2% in women 34 to 41 years of age, and 18.2% in women 42 years or older. This was the key element that supported the authors' conclusion that previous infection duration, not a woman's age, determines subsequent risk.

This raises the question of whether there might be possible residual benefit of vaccination at older ages to prevent reacquisition of HPV types that were apparently cleared when the woman was younger. "Thus far, there is some evidence that reappearance of previously cleared infections is a very rare event and that those that reappear do not carry high risk for CIN 2+, but this requires confirmation," Dr. Rodríguez said.

HPV Screening Interval Should Probably Be 2.5 Years or Longer

This study offers some guidance on HPV screening. Dr. Rodríguez told Medscape Oncology that HPV screening data must be interpreted according to the frequency of screening, rather than the woman's age.

A single HPV-positive finding in a screening program must be not cause for alarm at any age.
"A single HPV-positive finding in a screening program must be not cause for alarm at any age," Dr. Franceschi said. "An HPV-positive test should just be repeated after approximately 12 months, and only persistent infections should be investigated in depth. If histologically proven, they are treated. PCR assays should not be used in screening programs, because they detect too many harmless infections."

The ideal HPV screening interval has yet to be determined, but Dr. Rodríguez said that previous analyses from the study suggested that HPV screens should at least 2.5 years apart, and could be longer.

The most important study limitation, note the authors, is that the conclusion that newly detected HPV infections typically do not progress to CIN 2 or worse at any age might not hold beyond the 7 years of follow-up. Dr. Rodríguez said that the researchers plan to revisit the cohort approximately 20 years after the initial screening visit.

Dr. Rodríguez and Dr. Franceschi have disclosed no relevant financial relationships.

J Natl Cancer Inst. 2010;102:305-324.