Renata Majewska

Lack of association between measles-mumps-rubella vaccination and autism in children: a case-control study.

Objective: The first objective of the study was to determine whether there is a relationship between the measles-mumps-rubella (MMR) vaccination and autism in children. The second objective was to examine whether the risk of autism differs between use of MMR and the single measles vaccine. Design: Case-control study. Study Population: The 96 cases with childhood or atypical autism, aged 2 to 15, were included into the study group. Controls consisted of 192 children individually matched to cases by year of birth, sex, and general practitioners. Methods: Data on autism diagnosis and vaccination history were from physicians. Data on the other probable autism risk factors were collected from mothers. Logistic conditional regression was used to assess the risk of autism resulting from vaccination. Assessment was made for children vaccinated (1) Before diagnosis of autism, and (2) Before first symptoms of autism onset. Odds ratios were adjusted to mothers age, medication during pregnancy, gestation time, perinatal injury and Apgar score. Results: For children vaccinated before diagnosis, autism risk was lower in children vaccinated with MMR than in the nonvaccinated (OR: 0.17, 95% CI: 0.06–0.52) as well as to vaccinated with single measles vaccine (OR: 0.44, 95% CI: 0.22–0.91). The risk for vaccinated versus nonvaccinated (independent of vaccine type) was 0.28 (95% CI: 0.10–0.76). The risk connected with being vaccinated before onset of first symptoms was significantly lower only for MMR versus single vaccine (OR: 0.47, 95% CI: 0.22–0.99). Conclusions: The study provides evidence against the association of autism with either MMR or a single measles vaccine.

Intrauterine exposure to fine particulate matter as a risk factor for increased susceptibility to acute broncho-pulmonary infections in early childhood

Over the last decades many epidemiologic studies considered the morbidity patterns for respiratory diseases and lung function of children in the context of ambient air pollution usually measured in the postnatal period. The main purpose of this study is to assess the impact of prenatal exposure to fine particulate matter (PM2.5) on the recurrent broncho-pulmonary infections in early childhood. The study included 214 children who had measurements of personal prenatal PM2.5 exposure and regularly collected data on the occurrence of acute bronchitis and pneumonia diagnosed by a physician from birth over the seven-year follow-up. The effect of prenatal exposure to PM2.5 was adjusted in the multivariable logistic models for potential confounders, such as prenatal and postnatal ETS (environmental tobacco smoke), city residence area as a proxy of postnatal urban exposure, childrens sensitization to domestic aeroallergens, and asthma. In the subgroup of children with available PM2.5 indoor levels, the effect of prenatal exposure was additionally adjusted for indoor exposure as well. The adjusted odds ratio (OR) for incidence of recurrent broncho-pulmonary infections (five or more spells of bronchitis and/or pneumonia) recorded in the follow-up significantly correlated in a dose-response manner with the prenatal PM2.5 level (OR=2.44, 95%CI: 1.12-5.36). In conclusion, the study suggests that prenatal exposure to PM2.5 increases susceptibility to respiratory infections and may program respiratory morbidity in early childhood. The study also provides evidence that the target value of 20μg/m(3) for the 24-h mean level of PM2.5 protects unborn babies better than earlier established EPA guidelines.

Intrauterine exposure to lead may enhance sensitization to common inhalant allergens in early childhood: A prospective prebirth cohort study

BACKGROUND Several in vivo and in vitro studies have shown that metal-rich particles may enhance allergic responses to house dust mites and induce an increased release of allergy-related cytokines. OBJECTIVES The main goal of this analysis is to define the possible association of intrauterine exposure to lead and mercury with the occurrence of skin sensitization to common aeroallergens in early childhood. MATERIAL AND METHODS The present study refers to a sample of 224 women in the second trimester of pregnancy recruited from Krakow inner city area who had full term pregnancies and whose children underwent skin prick testing (SPT) at the age of 5. Lead and mercury levels were assessed in cord blood and retested in children at age of 5 years. Aeroallergen concentrations in house dust were measured at the age of 3 years. The main health outcome (atopic status) was defined as the positive SPT to at least one common aeroallergen (Der f1, Der p1, Can f1 and Fel d1) at the age of 5 years. In the statistical analysis of the association between atopic status of children and exposure to metals, the study considered a set of covariates such as maternal characteristics (age, education, atopy), childs gender, number of older siblings, prenatal (measured via cord blood cotinine) and postnatal environmental tobacco smoke together with exposure to polycyclic aromatic hydrocarbons (PAH) as measured by PAH-DNA adducts. RESULTS AND CONCLUSION In the binary regression analysis, which controlled for the confounders, the risk ratio (RR) estimate for atopic sensitization was significantly associated with the lead exposure (RR=2.25, 95%CI: 1.21-4.19). In conclusion, the data suggest that even very low-level of prenatal lead exposure may be implicated in enhancing sensitization to common aeroallergens in early childhood.

Long term effects of prenatal and postnatal airborne PAH exposures on ventilatory lung function of non-asthmatic preadolescent children. Prospective birth cohort study in Krakow.

The main goal of the study was to test the hypothesis that prenatal and postnatal exposures to polycyclic aromatic hydrocarbons (PAH) are associated with depressed lung function in non-asthmatic children. The study sample comprises 195 non-asthmatic children of non-smoking mothers, among whom the prenatal PAH exposure was assessed by personal air monitoring in pregnancy. At the age of 3, residential air monitoring was carried out to evaluate the residential PAH exposure indoors and outdoors. At the age of 5 to 8, children were given allergic skin tests for indoor allergens; and between 5 and 9 years lung function testing (FVC, FEV05, FEV1 and FEF25-75) was performed. The effects of prenatal PAH exposure on lung function tests repeated over the follow-up were adjusted in the General Estimated Equation (GEE) model for the relevant covariates. No association between FVC with prenatal PAH exposure was found; however for the FEV1 deficit associated with higher prenatal PAH exposure (above 37 ng/m(3)) amounted to 53 mL (p=0.050) and the deficit of FEF25-75 reached 164 mL (p=0.013). The corresponding deficits related to postnatal residential indoor PAH level (above 42 ng/m(3)) were 59 mL of FEV1 (p=0.028) and 140 mL of FEF25-75 (p=0.031). At the higher residential outdoor PAH level (above 90 ng/m(3)) slightly greater deficit of FEV1 (71 mL, p=0.009) was observed. The results of the study suggest that transplacental exposure to PAH compromises the normal developmental process of respiratory airways and that this effect is compounded by postnatal PAH exposure.

The relationship between prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAHs) and PAH-DNA adducts in cord blood

In a birth cohort study, we have assessed the dose-response relationship between individual measurements of prenatal airborne polycyclic aromatic hydrocarbon (PAH) exposure and specific PAH–DNA adducts in cord blood adjusted for maternal blood adducts and season of birth. The study uses data from an earlier established birth cohort of children in Krakow. The final analysis included 362 pregnant women who gave birth to term babies and had complete data on personal exposure in the second trimester of pregnancy to eight airborne PAHs including benzo[a]pyrene (B[a]P), as well as DNA adducts, both in maternal and cord blood. The relation between cord blood PAH–DNA adducts and airborne prenatal PAH exposure was non-linear. Although cord blood PAH–DNA adducts were significantly associated with the B[a]P exposure categorized by tertiles (non-parametric trend z=3.50, P<0.001), the relationship between B[a]P and maternal blood adducts was insignificant (z=1.63, P=0.103). Based on the multivariable linear regression model, we estimated the effect of the prenatal airborne B[a]P on the level of cord blood adducts. In total, 14.8% of cord blood adducts variance was attributed to the level of maternal adducts and 3% to a higher prenatal B[a] exposure above 5.70 ng/m3. The calculated fetal/maternal blood adduct ratio (FMR) linearly increased with B[a]P exposure (z=1.99, P=0.047) and was highest at B[a]P concentrations exceeding 5.70 ng/m3. In conclusion, the results support other findings that transplacental exposure to B[a]P from maternal inhalation produces DNA damage in the developing fetus. It also confirms the heightened fetal susceptibility to prenatal PAH exposure that should be a matter of public health concern, particularly in the highly polluted areas, because DNA adducts represent a pro-carcinogenic alteration in DNA. The continuation of this birth cohort study will assess the possible health effects of fetal DNA damage on the health of children and help in establishing new protective guidelines for newborns.

Depressed height gain of children associated with intrauterine exposure to polycyclic aromatic hydrocarbons (PAH) and heavy metals: The cohort prospective study

Fetal exposure to environmental toxicants may program the development of children and have long-lasting health impacts. The study tested the hypothesis that depressed height gain in childhood is associated with prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH) and heavy metals (lead and mercury). The study sample comprised 379 children born to non-smoking mothers among whom a total of 2011 height measurements were carried out over the 9-year follow-up period. Prenatal airborne PAH exposure was assessed by personal air monitoring of the mother in the second trimester of pregnancy and heavy metals were measured in cord blood. At the age of 3 residential air monitoring was done to evaluate the level of airborne PAH, and at the age 5 the levels of heavy metals were measured in capillary blood. The effect estimates of prenatal PAH exposure on height growth over the follow-up were adjusted in the General Estimated Equation (GEE) models for a wide set of relevant covariates. Prenatal exposure to airborne PAH showed a significant negative association with height growth, which was significantly decreased by 1.1cm at PAH level above 34.7 ng/m(3) (coeff.=-1.07, p=0.040). While prenatal lead exposure was not significantly associated with height restriction, the effect of mercury was inversely related to cord blood mercury concentration above 1.2 μg/L (coeff.=-1.21, p=0.020), The observed negative impact of prenatal PAH exposure on height gain in childhood was mainly mediated by shorter birth length related to maternal PAH exposure during pregnancy. The height gain deficit associated with prenatal mercury exposure was not seen at birth, but the height growth was significantly slower at later age.

SEPARATE AND JOINT EFFECTS OF TRANPLACENTAL AND POSTNATAL INHALATORY EXPOSURE TO POLYCYCLIC AROMATIC HYDROCARBONS. PROSPECTIVE BIRTH COHORT STUDY ON WHEEZING EVENTS

The goal of this epidemiologic investigation was to analyze the associations between prenatal and postnatal exposure to airborne polycyclic aromatic hydrocarbons (PAH) and severity of wheeze and recurrent wheeze. The 257 children included in this analysis had a complete set of prenatal and postnatal PAH measurements and attended regular health checkups over a 4‐year follow‐up period since birth. Transplacental PAH exposure was measured by personal air monitoring of the mothers during the second trimester of pregnancy; postnatal exposure was estimated using the same instruments indoors at the childrens residences at age 3. Chemical analysis tests were performed to determine airborne concentrations of nine PAH compounds. The results show that both prenatal and postnatal exposure were associated positively with the severity of wheezing days and recurrent wheezing reported in the follow‐up. While the incidence rate ratio (IRR) for severity of wheeze and prenatal PAH exposure was 1.53 (95%CI: 1.43–1.64) that for postnatal PAH exposure was 1.13 (95%CI: 1.08–1.19). However, recurrent wheezing was more strongly associated with airborne PAH levels measured at age 3 (OR = 2.31, 95%CI: 1.26–4.22) than transplacental PAH exposure (OR = 1.40, 95% CI: 0.85–2.09), but the difference was statistically insignificant. In conclusion, it appears that prenatal PAH exposure may precipitate and intensify early onset of wheezing symptoms in childhood, resulting from the postnatal exposure and suggest that success in reducing the incidence of respiratory diseases in children would depend on reducing both fetal and childhood exposure to air pollution. Pediatr Pulmonol. 2014; 49:162–172.

Prenatal exposure to fine particles and polycyclic aromatic hydrocarbons and birth outcomes: a two-pollutant approach

BackgroundPrevious epidemiologic studies have considered the effects of individual air pollutants on birth outcomes, whereas a multiple-pollutant approach is more relevant to public health policy.ObjectivesThe present study compared the observed effect sizes of prenatal fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAH) (a component of PM2.5) exposures on birth outcome deficits, assessed by the single vs. two-pollutant approaches.MethodsThe study sample included 455 term infants born in Krakow to non-smoking mothers, among whom personal exposures to PM2.5 and PAH were monitored in the second trimester of pregnancy. The exposure effect estimates (unstandardized and standardized regression coefficients) on birth outcomes were determined using multivariable linear regression models, accounting for relevant covariates.ResultsIn the single-pollutant approach, each pollutant was inversely associated with all birth outcomes. The effect size of prenatal PAH exposure on birth weight and length was twice that of PM2.5, in terms of standardized coefficients. In the two-pollutant approach, the negative effect of PM2.5 on birth weight and length, adjusted for PAH exposure, lost its significance. The standardized effect of PAH on birth weight was 10-fold stronger (β = −0.20, p = 0.004) than that estimated for PM2.5 (β = −0.02, p = 0.757).ConclusionThe results provide evidence that PAH had a greater impact on several measures of fetal development, especially birth weight, than PM2.5. Though in the single-pollutant models PM2.5 had a significant impact on birth outcomes, this effect appears to be mediated by PAH.

Prenatal, perinatal and neonatal risk factors for autism - study in Poland

The results of conducted research studies suggest that heredity and early fetal and neonatal development play a causal role in autism. The objective was to determine a relationship between pre-, peri-, and neonatal factors and autism. The relationship between genders and individual risk factors for autism was also examined. A case-control study was conducted among 288 children (96 cases with childhood or atypical autism and 192 controls individually matched to cases by the year of birth, sex, and general practitioners). Data on autism diagnosis and other medical conditions were acquired from physicians. All other information on potential autism risk factors were collected from mothers. Autism risk was significantly higher when mothers were taking medications (OR=2.72, 95%CI: 1.47-5.04) and smoked during pregnancy (OR=3.32, 95%CI: 1.12-9.82). It was also significantly associated with neonatal dyspnea (OR=3.20, 95%CI: 1.29-8.01) and congenital anomalies (OR=7.17, 95%CI: 2.23-23.1). In gender analysis only congenital anomalies were significantly associated with autism for girls but all of mentioned factors stayed independent risk factors for boys.

Pollen grains as allergenic environmental factors – new approach to the forecasting of the pollen concentration during the season

INTRODUCTION AND OBJECTIVES It is important to monitor the threat of allergenic pollen during the whole season, because of practical application in allergic rhinitis treatment, especially in the specific allergen immunotherapy. The aim of the study was to propose the forecast models predicting the pollen occurrence in the defined pollen concentration categories related to the patient exposure and symptom intensity. MATERIAL AND METHODS The study was performed in Cracow (southern Poland), pollen data were collected using the volumetric method in 1991-2012. For all independent variables (meteorological elements) and the daily pollen concentrations the running mean for periods: 2-, 3-, 4-, 5-, 6- and 7 days before the predicted day were calculated. The multinomial logistic regression was used to find the relation between the probability of the pollen concentration occurrence in the selected categories and meteorological elements and pollen concentration in days preceding the predicted daily concentration. The models were constructed for each taxon using data in 1991-2011 (without 1992 and 1996 due to missing data in these years) and 1998-2011 pollen seasons. RESULTS The days classified among the lowest category (0-10 PG/m3) (pollen grains/m 3 of air) dominated for all the studied taxa. The percentage of the obtained predictions of the pollen occurrence fluctuated between 35-78% which is a sufficient value of model predictions. Considering the studied taxon, the best model accuracy was obtained for models forecasting Betula pollen concentration (both data series), and Poaceae (both data series). CONCLUSIONS The application of the recommended threshold values during the predictive models construction seems to be really useful to estimate the real threat of allergen exposure. It was indicated that the polynomial logistic regression models could be a practical tool for effective forecasting in biological monitoring of pollen exposure.