Factors associated with infant and adolescent mortality

Few studies have described factors associated with infant and adolescent mortality since birth. We report here mortality during a 20-year period in a birth cohort from Ribeirão Preto in order to identify birth variables that influenced mortality among infants and children between 10 and 19 years of age, the main causes of death, and the influence of social inequality at birth on death. Mothers were interviewed shortly after delivery. Social, biological and demographic information was collected, and mortality up to 19 years of age was investigated in registry systems. Of the 6748 liveborn singletons born in the municipality from 1978 to 1979, 343 died before or when 19 years of age were completed. Most of the cohort mortality (74.9%) occurred during the first year of life and 19.6% occurred from 10 to 19 years. Mortality was higher among boys. Preterm birth (hazard ratio, HR = 7.94) and low birth weight (HR = 10.15) were strongly associated with infant mortality. Other risk factors for infant mortality were: maternal age ³35 years (HR = 1.74), unskilled manual occupation of family head (HR = 2.47), and for adolescent mortality: unskilled manual occupation of family head (HR = 9.98) and male sex (HR = 6.58). "Perinatal conditions" were the main causes of deaths among infants and "external causes" among adolescents, especially boys. Socioeconomic factors at birth, represented by occupation, influenced adolescent mortality due to external causes, which was higher among boys (7:1). The influence of social inequality at birth on death, measured by occupation, was greater in adolescence than in infancy.

Do socioeconomic factors explain why maternal smoking during pregnancy is more frequent in a more developed city of Brazil?

The prevalence of smoking during pregnancy in Ribeirão Preto, a rich Brazilian city, was significantly higher (21.4%) than in São Luís (5.9%), a less developed city. To assess which variables explain the difference in prevalence of smoking during pregnancy, data from two birth cohorts were used, including 2846 puerperae from Ribeirão Preto, in 1994, and 2443 puerperae from São Luís, in 1997/98. In multivariable analysis, risk of maternal smoking during pregnancy was higher in São Luís for mothers living in a household with five or more persons (OR = 1.72, 95%CI = 1.12-2.64), aged 35 years or older (OR = 1.98, 95%CI = 0.99-3.96), who had five or more children (OR = 2.10, 95%CI = 1.16-3.81), and whose companion smoked (OR = 2.20, 95%CI = 1.52-3.18). Age of less than 20 years was a protective factor (OR = 0.55, 95%CI = 0.33-0.92). In Ribeirão Preto there was association with maternal low educational level (OR = 2.18, 95%CI = 1.30-3.65) and with a smoking companion (OR = 3.25, 95%CI = 2.52-4.18). Receiving prenatal care was a protective factor (OR = 0.24, 95%CI = 0.11-0.49). Mothers from Ribeirão Preto who worked outside the home were at a higher risk and those aged 35 years or older or who attended five or more prenatal care visits were at lower risk of smoking during pregnancy as compared to mothers from São Luís. Smoking by the companion reduced the difference between smoking rates in the two cities by 10%. The socioeconomic variables in the model did not explain the higher prevalence of smoking during pregnancy in the more developed city.

Profile of three Brazilian birth cohort studies in Ribeirão Preto, SP and São Luís, MA

We describe three birth cohort studies, respectively carried out in 1978/79 and 1994 in Ribeirão Preto, a city located in the most developed region of Brazil, and in 1997/98 in São Luís, a city located in a less developed region. The objective of the present report was to describe the methods used in these three studies, presenting their history, methodological design, objectives, developments, and difficulties faced along 28 years of research. The first Ribeirão Preto study, initially perinatal, later encompassed questions regarding the repercussions of intrauterine development on future growth and chronic adult diseases. The subjects were evaluated at birth (N = 6827), at school age (N = 2861), at the time of recruitment for military service (N = 2048), and at 23/25 years of age (N = 2063). The study of the second cohort, which started in 1994 (N = 2846), permitted comparison of aspects of perinatal health between the two groups in the same region, such as birth weight, mortality and health care use. In 1997/98, a new birth cohort study was started in São Luís (N = 2443), capital of the State of Maranhão. The 1994 Ribeirão Preto cohort and the São Luís cohort are in the second phase of joint follow-up. These studies permit comparative temporal analyses in the same place (Ribeirão Preto 1978/79 and 1994) and comparisons of two contrasting populations regarding cultural, economic and sociodemographic conditions (Ribeirão Preto and São Luís).

TNF-a and IL-10 levels in tracheobronchial lavage of ventilated preterm infants and subsequent lung function

The role of airway inflammation in ventilated preterm newborns and the risk factors associated with the development of chronic lung disease are not well understood. Our objective was to analyze the association of the airway inflammatory response in ventilated preterm infants by serial measurements of TNF-a and IL-10 in tracheobronchial lavage (TBL) with perinatal factors and lung function measured early in life. A series of TBL samples were collected from ventilated preterm infants (less than 32 weeks of gestational age) and concentrations of TNF-a and IL-10 were measured by ELISA. Pulmonary function tests were performed after discharge by the raised volume rapid compression technique. Twenty-five subjects were recruited and 70 TBL samples were obtained. There was a significant positive association between TNF-a and IL-10 levels and length of time between the rupture of the amniotic membranes and delivery (r = 0.65, P = 0.002, and r = 0.57, P < 0.001, respectively). Lung function was measured between 1 and 22 weeks of corrected age in 10 patients. Multivariable analysis with adjustment for differences in lung volume showed a significant negative association between TNF-a levels and forced expiratory flow (FEF50; r = -0.6; P = 0.04), FEF75 (r = -0.76; P = 0.02), FEF85 (r = -0.75; P = 0.03), FEF25-75 (-0.71; P = 0.02), and FEV0.5 (r = -0.39; P = 0.03). These data suggest that TNF-a levels in the airways during the first days of life were associated with subsequent lung function abnormalities measured weeks or months later.

Sodium taste threshold in children and its relationship to blood pressure

Popular science has emphasized the risks of high sodium intake and many studies have confirmed that salt intake is closely related to hypertension. The present mini-review summarizes experiments about salt taste sensitivity and its relationship with blood pressure (BP) and other variables of clinical and familial relevance. Children and adolescents from control parents (N = 72) or with at least one essential hypertensive (EHT) parent (N = 51) were investigated. Maternal questionnaires on eating habits and vomiting episodes were collected. Offspring, anthropometric, BP, and salt taste sensitivity values were recorded and blood samples analyzed. Most mothers declared that they added "little salt" when cooking. Salt taste sensitivity was inversely correlated with systolic BP (SBP) in control youngsters (r = -0.33; P = 0.015). In the EHT group, SBP values were similar to control and a lower salt taste sensitivity threshold. Obese offspring of EHT parents showed higher SBP and C-reactive protein values but no differences in renin-angiotensin-aldosterone system activity. Salt taste sensitivity was correlated with SBP only in the non-obese EHT group (N = 41; r = 0.37; P = 0.02). Salt taste sensitivity was correlated with SBP in healthy, normotensive children and adolescents whose mothers reported significant vomiting during the first trimester (N = 18; r = -0.66; P < 0.005), but not in "non-vomiter offspring" (N = 54; r = -0.18; nonsignificant). There is evidence for a linkage between high blood pressure, salt intake and sensitivity, perinatal environment and obesity, with potential physiopathological implications in humans. This relationship has not been studied comprehensively using homogeneous methods and therefore more research is needed in this field.

Examining life-course influences on chronic disease: the Ribeirão Preto and São Luís birth cohort studies (Brazil)

More than any other low- and middle-income country, Brazil has the longest research tradition of establishing, maintaining and exploiting birth cohort studies. This research pedigree is highlighted in the present issue of the Brazilian Journal of Medical and Biological Research, which contains a series of twelve papers from the Ribeirão Preto and São Luis birth cohort studies from the Southeast and Northeast of Brazil, respectively. The topics covered in this raft of reports vary and include predictors of perinatal health and maternal risk factors, early life determinants of cardiovascular risk factors in childhood and adolescence, use of health services, and a description of dietary characteristics of young adults, amongst other topics. There is also a guide to the background, objectives, sampling and protocols employed across these studies, which, together with similar pieces published in past issues of the Brazilian Journal, serve as a very useful starting point, particularly for potential collaborators. In the fervent hope that further follow-up of these cohorts will take place - we provide our own justification for cohort maintenance and extension in this issue - future data collection could include: genetic material, atherosclerosis, ascertained, for instance, by intima-media thickness, and IQ testing in children - scores from which are emerging as potentially important predictors of adult health outcomes up to six decades later.

The oral motor capacity and feeding performance of preterm newborns at the time of transition to oral feeding

The objective of the present study was to determine the oral motor capacity and the feeding performance of preterm newborn infants when they were permitted to start oral feeding. This was an observational and prospective study conducted on 43 preterm newborns admitted to the Neonatal Intensive Care Unit of UFSM, RS, Brazil. Exclusion criteria were the presence of head and neck malformations, genetic disease, neonatal asphyxia, intracranial hemorrhage, and kernicterus. When the infants were permitted to start oral feeding, non-nutritive sucking was evaluated by a speech therapist regarding force (strong vs weak), rhythm (rapid vs slow), presence of adaptive oral reflexes (searching, sucking and swallowing) and coordination between sucking, swallowing and respiration. Feeding performance was evaluated on the basis of competence (defined by rate of milk intake, mL/min) and overall transfer (percent ingested volume/total volume ordered). The speech therapist's evaluation showed that 33% of the newborns presented weak sucking, 23% slow rhythm, 30% absence of at least one adaptive oral reflex, and 14% with no coordination between sucking, swallowing and respiration. Mean feeding competence was greater in infants with strong sucking fast rhythm. The presence of sucking-swallowing-respiration coordination decreased the days for an overall transfer of 100%. Evaluation by a speech therapist proved to be a useful tool for the safe indication of the beginning of oral feeding for premature infants.

Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.

Prenatal management, pregnancy and pediatric outcomes in fetuses with septated cystic hygroma

It has been reported that, compared with simple increased nuchal translucency, fetal cases with septated cystic hygroma (CH) are more likely to face perinatal handicaps. However, pediatric outcomes and proper prenatal counseling for this anomaly have not yet been truly defined. We performed this study to determine pregnancy and pediatric outcomes of fetuses with septated CH. We searched records for cases with septated CH and collected data for structural abnormalities, karyotype analysis, and pregnancy outcomes. Fetuses born with septated CH were also evaluated for their pediatric outcomes. Sixty-nine fetuses with septated CH were enrolled in the study. Results showed that chromosomal abnormalities were present in 28 fetuses (40.6%), and the most common aneuploidy was Turner syndrome (n=14, 20.3%); 16 (23.2%) of the remaining cases, in which aneuploidy was not found, had coexistent structural malformations; 25 (36.2%) cases had normal karyotype and morphology. The total number of live births and infants with unfavorable neurologic follow-up were 13 (18.8%) and 2 (2.9%), respectively. Septated CH is associated with poor perinatal outcomes; therefore, karyotype analysis and ultrasonographic anomaly screening should be performed as initial steps, and expectant management should be offered to couples with euploid fetuses that have normal morphology.

Pré-eclâmpsia (indicador de doença renal crônica): da gênese aos riscos futuros

A pré-eclâmpsia (PE) é uma doença específica da gestação que, somada às demais desordens hipertensivas, constitui importante causa de morbimortalidade materna e perinatal. Tem incidência estimada de 3 a 14% entre todas as gestações e pode manifestar-se de diferentes formas clínicas. A PE e a doença cardiovascular (DCV) possuem mecanismos fisiopatológicos semelhantes, como disfunção endotelial, alteração metabólica e estresse oxidativo, assim como também compartilham alguns fatores de risco como obesidade, doença renal e diabetes. A exata relação entre PE e risco cardiovascular ainda não está totalmente elucidada, talvez o estresse metabólico desencadeado na PE provoque a lesão vascular que contribui para o desenvolvimento da DCV e/ou da doença renal crônica (DRC) futuramente. Esse risco parece ser ainda maior em mulheres com história de PE recorrente, severa e eclâmpsia. A investigação do antecedente de PE pode auxiliar na avaliação do risco futuro de DCV e DRC, na prevenção e no diagnóstico precoce.

Biomarkers, medical treatment and fetal intrapartum surveillance in intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterized by maternal pruritus and elevated liver enzymes. It usually begins in the third trimester of pregnancy and resolves spontaneously after delivery. ICP is considered benign for the pregnant woman, but it is associated with an increased risk for unexplained term stillbirth and preterm delivery. There are no specific laboratory markers to diagnose ICP. The diagnosis is currently based on the presence of maternal pruritus and elevated values of alanine aminotransaminases (ALT) and serum bile acids (BA). Recently, ursodeoxycholic acid (UDCA) has been used for treatment. Mechanisms leading to intrauterine fetal death (IUFD) may be multifactorial and are unknown at present. For this thesis, 415 pregnant women with ICP were studied. The aim was to evaluate the value of the liver enzyme glutathione S-transferase alpha (GSTA) as a specific marker of ICP and to assess the effect of maternal UDCA therapy on maternal laboratory values and fetal outcome. The specific markers predisposing the fetus to heart arrhythmia were studied by comparing waveform analysis of fetal electrocardiograms (FECG) during labor in pregnancies complicated by ICP with controls. The levels of maternal GSTA were high and the values correlated with the value of ALT in patients with ICP. UDCA therapy reduced the values of the liver enzymes and alleviated maternal pruritus, but it did not influence maternal hormonal values. Although the newborns experienced an uneventful perinatal outcome, severe ICP was still associated with preterm birth and admission to the neonatal intensive care unit (NICU). There were no significant differences in intrapartum FECG findings between fetuses born to ICP women and controls.

Prediction of neurodevelopment and neuromotor trajectories in very preterm born children up to 11 years of age: PIPARI Study

Very preterm birth is a risk for brain injury and abnormal neurodevelopment. While the incidence of cerebral palsy has decreased due to advances in perinatal and neonatal care, the rate of less severe neuromotor problems continues to be high in very prematurely born children. Neonatal brain imaging can aid in identifying children for closer follow-up and in providing parents information on developmental risks. This thesis aimed to study the predictive value of structural brain magnetic resonance imaging (MRI) at term age, serial neonatal cranial ultrasound (cUS), and structured neurological examinations during the longitudinal follow-up for the neurodevelopment of very preterm born children up to 11 years of age as a part of the PIPARI Study (The Development and Functioning of Very Low Birth Weight Infants from Infancy to School Age). A further aim was to describe the associations between regional brain volumes and long-term neuromotor profile. The prospective follow-up comprised of the assessment of neurosensory development at 2 years of corrected age, cognitive development at 5 years of chronological age, and neuromotor development at 11 years of age. Neonatal brain imaging and structured neurological examinations predicted neurodevelopment at all age-points. The combination of neurological examination and brain MRI or cUS improved the predictive value of neonatal brain imaging alone. Decreased brain volumes associated with neuromotor performance. At the age of 11 years, the majority of the very preterm born children had age-appropriate neuromotor development and after-school sporting activities. Long-term clinical follow-up is recommended at least for all very preterm infants with major brain pathologies.

Pratiques traditionnelles chez les sages-femmes autochtones du Nunavik et programme de formation

Les communautés inuites de la Baie d’Hudson au Nunavik (Québec) se distinguent des autres communautés autochtones par leur réappropriation des naissances depuis 1986 et par la création d’un programme de formation de sages-femmes locales. Cela a permis de mettre un terme à une longue période de transfert des femmes pour accouchement en structure hospitalière, à des kilomètres de leur village. De plus, ce programme a pour objectif de réintégrer les pratiques traditionnelles au sein d’une obstétrique moderne afin d’offrir aux femmes des services de qualité et culturellement appropriés. Le but de notre étude était d’établir si le programme de formation de sages-femmes autochtones du Nunavik a permis de concilier ces deux approches d’enseignement différentes : l’une axée sur le savoir traditionnel, et l’autre concernant les normes de qualité de soins à respecter. Une méthode de recherche qualitative a été adoptée et les données ont été recueillies à l’aide d’entrevues réalisées auprès de cinq sages-femmes inuites et de six étudiantes sages-femmes du programme de formation du Nunavik, au sein des trois villages de la Baie d’Hudson pourvus de centre de naissances. L’analyse qualitative des données ne permet pas de confirmer la réintégration du savoir traditionnel dans la pratique des sages-femmes autochtones. Les résultats révèlent, en effet, une rareté des pratiques traditionnelles connues et/ou utilisées par celles-ci (notamment l’utilisation de plantes ou de remèdes médicinaux, les postures d’accouchement, les manœuvres obstétricales, etc) en relation avec la période périnatale. Les croyances ou codes de conduite à respecter pendant la grossesse semblent bénéficier d’une meilleure transmission, mais ne font plus l’unanimité au sein des communautés. Concernant le volet de l’obstétrique moderne, le programme de formation semble conforme aux exigences actuelles occidentales, étant reconnu par l’Ordre des sages-femmes du Québec depuis septembre 2008. De plus, les sages-femmes et les étudiantes sont conscientes de la nécessité de recevoir une formation de qualité. Elles aimeraient bénéficier d’une plus grande rigueur dans l’enseignement théorique ainsi que d’une meilleure continuité du processus d’apprentissage. La difficulté retrouvée dans la mixité de l’enseignement de ces deux savoirs (traditionnel et moderne) semble donc être liée plus particulièrement au savoir traditionnel. Les sages-femmes et étudiantes inuites souhaitent protéger et promouvoir leur patrimoine culturel, mais plus dans une optique de responsabilité communautaire que dans le cadre d’un programme de formation. Une collaboration entre les volontés des communautés concernant la réintégration de ce patrimoine et la réalité actuelle de la biomédecine demeure primordiale pour continuer à garantir la sécurité et la qualité des services dispensés.

Regulation of the memory T cell development and islet beta-cell survival by DAPK-related apoptosis-inducing protein kinase 2 (Drak2)

Drak2 est un membre de la famille des protéines associées à la mort et c’est une sérine/thréonine kinase. Chez les souris mutantes nulles Drak2, les cellules T ne présentent aucune défectuosité apparente en apoptose induite par activation, après stimulation avec anti-CD3 et anti-CD28, mais ont un seuil de stimulation réduit, comparées aux cellules T de type sauvage (TS). Dans notre étude, l’analyse d’hybridation in situ a révélé que l’expression de Drak2 est ubiquiste au stade de la mi-gestation chez les embryons, suivie d’une expression plus focale dans les divers organes pendant la période périnatale et l’âge adulte, notamment dans le thymus, la rate, les ganglions lymphatiques, le cervelet, les noyaux suprachiasmatiques, la glande pituitaire, les lobes olfactifs, la médullaire surrénale, l’estomac, la peau et les testicules. Nous avons créé des souris transgéniques (Tg) Drak2 en utilisant le promoteur humain beta-actine. Ces souris Tg montraient des ratios normaux entre cellules T versus B et entre cellules CD4 versus CD8, mais leur cellularité et leur poids spléniques étaient inférieurs comparé aux souris de type sauvage. Après activation TCR, la réponse proliférative des cellules T Tg Drak2 était normale, même si leur production d’interleukine (IL)-2 et IL-4 mais non d’interféron-r était augmentée. Les cellules T Tg Drak2 activées ont démontré une apoptose significativement accrue en présence d’IL-2 exogène. Au niveau moléculaire, les cellules T Tg Drak2 ont manifesté une augmentation moins élevée des facteurs anti-apoptotiques durant l’activation; un tel changement a probablement rendu les cellules vulnérables aux attaques subséquentes d’IL-2. L’apoptose compromise dans les cellulesT Tg Drak2 a été associée à un nombre réduit de cellules T ayant le phénotype des cellules mémoires (CD62Llo) et avec des réactions secondaires réprimées des cellules T dans l’hypersensibilité de type différé. Ces résultats démontrent que Drak2 s’exprime dans le compartiment des cellules T mais n’est pas spécifique aux cellules T; et aussi qu’il joue des rôles déterminants dans l’apoptose des cellules T et dans le développement des cellules mémoires T. En outre, nous avons recherché le rôle de Drak2 dans la survie des cellules beta et le diabète. L’ARNm et la protéine Drak2 ont été rapidement induits dans les cellules beta de l’îlot après stimulation exogène par les cytokines inflammatoires ou les acides gras libres et qui est présente de façon endogène dans le diabète, qu’il soit de type 1 ou de type 2. La régulation positive de Drak2 a été accompagnée d’une apoptose accrue des cellules beta. L’apoptose des cellules beta provoquée par les stimuli en question a été inhibée par la chute de Drak2 en utilisant petit ARNi. Inversement, la surexpression de Drak2 Tg a mené à l’apoptose aggravée des cellules beta déclenchée par les stimuli. La surexpression de Drak2 dans les îlots a compromis l’augmentation des facteurs anti-apoptotiques, tels que Bcl-2, Bcl-xL et Flip, sur stimulation par la cytokine et les acides gras libres. De plus, les expériences in vivo ont démontré que les souris Tg Drak2 étaient sujettes au diabète de type 1 dans un modèle de diabète provoqué par de petites doses multiples de streptozotocine et qu’elles étaient aussi sujettes au diabète de type 2 dans un modèle d’obésité induite par la diète. Nos données montrent que Drak2 est défavorable à la survie des cellules beta. Nous avons aussi étudié la voie de transmission de Drak2. Nous avons trouvé que Drak2 purifiée pouvait phosphoryler p70S6 kinase dans une analyse kinase in vitro. Lasurexpression de Drak2 dans les cellules NIT-1 a entraîné l’augmentation de la phosphorylasation p70S6 kinase tandis que l’abaissement de Drak2 dans ces cellules a réduit la phosphorylation. Ces recherches mécanistes ont prouvé que p70S6 kinase était véritablement un substrat de Drak2 in vitro et in vivo. Cette étude a découvert les fonctions importantes de Drak2 dans l’homéostasie des cellules T et le diabète. Nous avons prouvé que p70S6 kinase était un substrat de Drak2. Nos résultats ont approfondi nos connaissances de Drak2 à l’intérieur des systèmes immunitaire et endocrinien. Certaines de nos conclusions, comme les rôles de Drak2 dans le développement des cellules mémoires T et la survie des cellules beta pourraient être explorées pour des applications cliniques dans les domaines de la transplantation et du diabète.

Asthma during Pregnancy

L’asthme est connu comme l’une des maladies chroniques les plus fréquentes chez la femme enceinte avec une prévalence de 4 à 8%. La prévalence élevée de l’asthme fait en sorte qu’on se préoccupe de l’impact de la grossesse sur l’asthme et de l’impact de l’asthme sur les issus de la grossesse. La littérature présente des résultats conflictuels concernant l’impact de l’asthme maternel sur les issus périnatales comme les naissances prématurées, les bébés de petit poids et les bébés de petit poids pour l’âge gestationnel (PPGA). De plus, les données scientifiques sont rares concernant l’impact de la sévérité et de la maîtrise de l’asthme durant la grossesse sur les issus périnatales. Donc, nous avons mené cinq études pour réaliser les objectifs suivants: 1. Le développement et la validation de deux indexes pour mesurer la sévérité et la maîtrise de l’asthme. 2. L’évaluation de l’impact du sexe du fœtus sur le risque d’exacerbation de l’asthme maternel et l’utilisation de médicaments antiasthmatiques durant la grossesse; 3. L’évaluation de l’impact de l’asthme maternel sur les issus périnatales; 4. L’évaluation de l’impact de la sévérité de l’asthme maternel durant la grossesse sur les issus périnatales; 5. L’évaluation de l’impact de la maîtrise de l’asthme maternel durant la grossesse sur les issus périnatales. Pour réaliser ces projets de recherche, nous avons travaillé avec une large cohorte de grossesse reconstruite à partir du croisement de trois banques de données administratives du Québec recouvrant la période entre 1990 et 2002. Pour les trois dernières études, nous avons utilisé un devis de cohorte à deux phases d’échantillonnage pour obtenir, à l’aide d’un questionnaire postal, des informations complémentaires qui ne se trouvaient pas dans les banques de données, comme la consommation de cigarettes et d’alcool pendant la grossesse. Nous n’avons trouvé aucune différence significative entre les mères de fétus féminins et de fétus masculins pour les exacerbations de l’asthme pendant la grossesse (aRR=1.02; IC 95%: 0.92 to 1.14). Par contre, nous avons trouvé que le risque de bébé PPGA (OR: 1.27, IC 95%: 1.14-1.41), de bébé de petit poids (OR: 1.41, IC 95%:1.22-1.63) et de naissance prématurée (OR: 1.64, IC 95%:1.46-1.83) était significativement plus élevés chez les femmes asthmatiques que chez les femmes non asthmatiques. De plus, nous avons démontré que le risque d’un bébé PPAG était significativement plus élevé chez les femmes avec un asthme sévère (OR:1.48, IC 95%: 1.15-1.91) et modéré (OR: 1.30, IC 95%:1.10-1.55) que chez les femmes qui avaient un asthme léger. Nous avons aussi observé que les femmes qui avaient un asthme bien maîtrisé durant la grossesse étaient significativement plus à risque d’avoir un bébé PPAG (OR:1.28, IC 95%: 1.15-1.43), un bébé de petit poids (OR: 1.42, IC 95%:1.22-1.66), et un bébé prématuré (OR: 1.63, IC 95%:1.46-1.83) que les femmes non asthmatiques. D’après nos résultats, toutes les femmes asthmatiques même celles qui ont un asthme bien maîtrisé doivent être suivies de près durant la grossesse car elles courent un risque plus élevé d’avoir des issus de grossesses défavorables pour leur nouveau-né.