Objetivos: identificar los principales factores de riesgo para recién nacidos a término pequeños para edad gestacional (PEG).Materiales y métodos: cohorte retrospectiva que utilizó los datos del Sistema Informático Materno Perinatal del Hospital María Auxiliadora de Lima, Perú, durante el período 2000-2010. Se evaluó la edad materna, la paridad, el nivel educativo, el estado civil, el índice de masa corporal pregestacional, el número de controles prenatales (CPN), la presencia de patologías como preeclampsia, eclampsia, infección urinaria y diabetes gestacional como factores de riesgo para PEG. El peso para la edad gestacional fue calculado en base a percentiles peruanos. Se calculó los riesgos relativos crudos (RR) y ajustados (RRa) con sus respectivos intervalos de confianza al 95% para cada variable con respecto a la condición de PEG usando modelos lineales generalizados log binomial. Resultados: se incluyó a un total de 64 670 gestantes. La incidencia de PEG fue de 7,2%. La preeclampsia (RRa 2,0; IC 95% 1,86-2,15), la eclampsia (RRa 3,22; IC 95% 2,38-4,35), el bajo peso materno (RRa 1,38; IC 95%: 1,23- 1,54), la nuliparidad (RRa 1,32; IC 95%: 1,23-1,42) y la edad ≥35 años (RRa 1,16; IC 95% 1,04- 1,29) se encontraron asociados con un riesgo mayor de recién nacido PEG. Asimismo, un número de 0-2 CPN (RRa 1,43; IC95%: 1,32-1,55), y 3-5 CPN (RRa 1,22; IC 95%: 1,14-1,32) también se encontraron asociados con un riesgo mayor de recién nacido PEG, comparado con 6-8 CPN. Un número de ≥9 CPN (RRa 0,74; IC 95%: 0,69-0,80) fue factor protector. Conclusiones: es necesario identificar a las gestantes con factores de riesgo como los encontrados en este estudio, para disminuir la condición de PEG. Se debe actuar rigurosamente, poniendo especial énfasis en factores modificables, tales como la frecuencia de sus controles prenatales. / Objective: to identify the main risk factors for term infants small for gestational age (SGA). Materials and methods: we conducted a retrospective cohort study using the database of Hospital María Auxiliadora, Lima, Peru, with information of all pregnant women during the period 2000-2010. We analyzed maternal age, parity, educational level, marital status, pre-pregnancy body mass index, number of prenatal visits (PNV), the presence of diseases such as preeclampsia, eclampsia, urinary tract infection and gestational diabetes as risk factors for SGA. The weight for gestational age was calculated on Peruvian percentiles. Crude relative risks (RR) and adjusted relative risk (aRR) with their respective confidence intervals at 95% for each variable was calculated using log binomial generalized linear models. Results: A total of 64 670 pregnant were included. The incidence of SGA was 7.2%. Preeclampsia (aRR 2.0, 95% CI: 1.86 to 2.15), eclampsia (aRR 3.22, 95% CI: 2.38 to 4.35), low maternal weight (aRR 1.38; 95% CI: 1.23 to 1.54), nulliparity (aRR 1.32; 95% CI: 1.23 to 1.42) and age ≥35 years (aRR 1.16, 95% CI: 1.04 to 1.29) were associated with an increased risk for newborn SGA. Also, a number of 0-2 PNV (aRR 1.43, 95% CI: 1.32 to 1.55), and 3-5 PNV (aRR 1.22; 95% CI: 1.14 to 1.32) were also found associated with an increased risk of newborn SGA, compared with 6-8 PNV. A number of ≥9 PNV (aRR 0.74; 95% CI: 0.69 to 0.80) was a protector factor. Conclusions: it is necessary to identify pregnant women with risk factors such as those found in this study, in order to reduce SGA. Particular emphasis on modifiable factors, such as the frequency of antenatal care visits, must be taken. / Tesis

Background: Preeclampsia, small for gestational age (SGA), placental abruption, and fetal death are pregnancy complications linked to the utero-placental vasculature with serious consequences for maternal and infant well-being. Elevated homocysteine, a marker of cardiovascular disease risk, is postulated to play a role in placenta-mediated complications, but epidemiologic studies have reported inconsistent findings. The two primary objectives of this thesis were to 1: comprehensively investigate the association of homocysteine with placenta-mediated complications and examine modifying effects of pre-specified factors on this association, and 2: comprehensively investigate determinants of maternal homocysteine during pregnancy. Methods: A systematic review and meta-analysis of prospective studies was conducted to address thesis objective 1. The Ottawa and Kingston (OaK) Birth Cohort, a prospective cohort study that recruited pregnant women between 2002 and 2009, was used to address thesis objectives 1 and 2. Homocysteine concentration was measured between 12 and 20 weeks gestation. Analyses based on the OaK Birth Cohort consisted of multivariable regressions using restricted cubic splines to model associations with continuously distributed variables. Results: Objective 1: In an analysis of 7587 participants, a significant association between homocysteine concentration and a composite outcome of any placenta-mediated complication was observed (odds ratio (OR) for a 5 µmol/L increase: 1.63, 95% Confidence Interval (CI) 1.23-2.16) and SGA (OR 1.76, 95% CI 1.25-2.46), with potential modifying effects of the methylene tetrahydrofolate reductase (MTHFR) 677C>T variant (SGA) and high-risk pregnancy (preeclampsia). In the systematic review identifying 30 prospective cohort or nested case-control studies, a random effects meta-analysis of pooled mean differences in homocysteine between cases and controls in 28 studies revealed significantly higher means for SGA: 0.35 µmol/L (95% CI 0.19 to 0.51, I2=33%); and preeclampsia: 0.87 µmol/L (95% CI 0.52 to 1.21, I2=92%). Significant sources of heterogeneity were study region (SGA and preeclampsia), adjusting for covariates (preeclampsia), folate status (preeclampsia), and severity (preeclampsia). Objective 2: In 7587 OaK participants, factors related to favourable health status were associated with lower maternal homocysteine concentrations. Folic acid supplementation during pregnancy of >1 mg/day did not substantially increase serum folate concentration. Conclusion: This thesis suggests an independent effect of slightly higher homocysteine concentration in the early to mid-second trimester on the risk of any placenta-mediated complication, SGA, and preeclampsia. Modifying effects explain some of the variability in previous studies. Favourable preconception health status was associated with lower maternal homocysteine.

Kardiopulmonale Adaptation und Therapie von wachstumsretardierten Frühgeborenen mit intrauteriner Perfusionsstörung im Vergleich zu nicht-wachstumsretardierten Frühgeborenen ohne intrauterine Perfusionsstörung Eingereicht von: Christin Lenk, geb. Demolt angefertigt in der Universitätsklinik und Poliklinik für Kinder und Jugendliche in Leipzig, Neonatologische Intensivstation betreut von Frau Prof. Dr. med. Eva Robel-Tillig Juli 2012 Chronische intrauterine Hypoxie bedingt durch uterine, feto-maternale und fetale Perfusionsstörung führt zur fetalen Wachstumsrestriktion und Erhöhung der fetalen und neonatalen Morbidität und Mortalität. Die pränatale Kreislaufzentralisation stellt einen pathophysiologischen Kompensationsmechanismus dar, der durch Umverteilung des Blutflusses eine Versorgung lebenswichtiger Organe des Feten sichert (Rizzo et al. 2008), (Robel-Tillig 2003), (Robel 1994), (Saling 1966). In den letzten Jahren haben sich Studien mit der postnatalen Adaptation der wachstumsretardierten Neonaten beschäftigt und wesentliche Risiken im Verlauf der ersten Lebenstage definiert. Wenige validierte Aussagen existieren jedoch zur Kreislaufsituation der betroffenen Kinder und der kardialen Leistungsfähigkeit auch über die erste Lebenswoche hinaus. Die vorliegende Studie vergleicht unter dieser Fragestellung eine Gruppe von 43 Frühgeborenen mit intrauteriner Wachstumsrestriktion auf der Grundlage einer Perfusionsstörung und 33 Frühgeborene mit appropriatem Wachstum und ungestörter pränataler Perfusion während der ersten 42 Lebenstage hinsichtlich der unmittelbaren postnatalen pulmonalen und kardialen Adaptationsparameter und des weiteren klinischen Verlaufs. Besonderer Schwerpunkt wird dabei auf die dopplersonographisch erfasste kardiale Funktion der Kinder gelegt. Als wesentlichstes Ergebnis der dopplersonographischen Messungen lässt sich bei den Frühgeborenen mit pränataler Perfusionsstörung ein signifikant erhöhtes Herzminutenvolumen rechts- und linksventrikulär im Vergleich zur Gruppe der Frühgeborenen mit ungestörter Perfusion darstellen (Robel-Tillig 2003), (Leipälä et al. 2003), Martinussen 1997}, (Guajardo, Mandelbaum & Linderkamp 1994), (Lindner et al. 1990). Die unmittelbar postnatale Adaptation zeigt hinsichtlich des arteriellen Nabelschnur-pH-Wertes eine schlechtere Anpassung der Frühgeborenen mit pränataler Perfusionsstörung auf. Im weiteren Verlauf der ersten Tage benötigen diese Frühgeborenen seltener eine maschinelle Beatmung oder CPAP-Atemhilfe als die Frühgeborenen ohne Wachstumsrestriktion. Bis zum 42. Lebenstag kehrt sich dieser Befund jedoch um. Die Frühgeborenen mit Wachstumsrestriktion bedürfen nun signifikant länger und häufiger einer Atemhilfe und zusätzlicher Sauerstoffsupplementierung. Als Komplikation trat bei den wachstumsretardierten Frühgeborenen eine höhere Rate an bronchopulmonaler Dysplasie auf. Ein weiterer Unterschied wird hinsichtlich der Transfusionshäufigkeit dargestellt. Frühgeborene mit Wachstumsrestriktion erhielten häufiger eine Erythrozytentransfusion und länger eine Transfusion von zusätzlichem Volumen. Zusammenfassend weisen die ermittelten Befunde auf ein Persistieren der intrauterin bestehenden Kompensation der beeinträchtigten Kreislaufsituation hin. Eine genaue Kenntnis der speziellen Probleme dieser Patientengruppe ist zur Vermeidung postnatal anhaltender hämodynamischer Störungen erforderlich.

Background: The prevalence of opioid use disorder has increased across the United States, but the rural population of Appalachia has been disproportionately impacted. Concurrently, the slow, but steady progress in the legalization of marijuana may be affecting perception of marijuana use in pregnancy. However, marijuana use in pregnancy has been associated with adverse perinatal outcomes. Concomitant use of opioids and marijuana in pregnancy has not been evaluated. Objective: The primary aim of the study was to evaluate the association between confirmed marijuana use in late pregnancy and preterm birth in opioid-exposed pregnancies. Methodology: A retrospective chart review was conducted that included all births from July 2011 to June 2016 from 6 delivery hospitals in South-Central Appalachia. Out of 18,732 births, 2368 singleton pregnancies indicated opioid use and met remaining inclusion criteria, with 108 of these mothers testing positive for marijuana at delivery. Independent sample t-test and Chi-Square analyses compared marijuana and non-marijuana exposed groups on maternal and neonatal outcomes. Regression analyses controlled for confounding variables in predicting neonatal abstinence syndrome (NAS), NICU admission, preterm birth, small for gestational age, and low birth weight outcomes as shown in Table 1. Results: Neonates born to marijuana-positive women in opioid-exposed pregnancy were more likely to be born preterm, small for gestational age, have low birth weight, and be admitted to NICU. After statistically controlling for parity, marital status, tobacco and benzodiazepine use, preterm birth and low birth weight remained statistically significant with aOR of 2.35 (1.30–4.24) and 2.01 (1.18–3.44), respectively. Conclusions: Maternal use of marijuana in any opioid-exposed pregnancy may increase risk of preterm birth and low-birth weight infants. Prospective studies need to examine the dose and timing of marijuana and opioid use in pregnancy to better delineate perinatal effects. Nonetheless, pregnant women using opioids, including recommended medication assisted treatment for opioid use disorder, should be educated about the risks of concurrent marijuana use during pregnancy and may need to be counseled to abstain from marijuana use during pregnancy for an optimal outcome.

No description available.

Mutations in the insulin-like growth factor-I (IGF-I) receptor (IGF1R) have been associated with prenatal and postnatal growth retardation. However, little is known about potential effects of mutations in the IGF1R on carbohydrate homeostasis. Methods: We investigated clinical, endocrine and metabolic parameters in four family members carrying a novel IGF1R mutation (p.Tyr387X): an 18-year-old male (index case), his sister and two paternal aunts. Results: All family members showed a variable degree of impairment in prenatal growth, with birth weight standard deviation scores (SDS) between –1.65 and –2.37 and birth length SDS between –1.78 and –3.08. Their postnatal growth was also impaired, with height SDS between –1.75 and –4.86. The index case presented high IGF-I levels during childhood and adolescence and delayed bone age. The index case and his two paternal aunts had impaired glucose tolerance (IGT) associated with a variable degree of alterations in insulin sensitivity and secretion. In contrast, the index case’s sister, who had had IGT during pregnancy, showed normal glucose metabolism but reduced insulin sensitivity. Conclusion: This is the first study showing an association between a novel IGF1R mutation and a variable degree of alterations in prenatal and postnatal growth and in carbohydrate metabolism.

Despite the unprecedented improvement in child health in last 15 years, burden of stillbirth and neonatal death remain the key challenge in Nepal and the reduction of these deaths will be crucial for reaching the health targets for Sustainable development goal by 2030. The aim of this thesis was to explore the risk factors for stillbirth and neonatal death and change in perinatal outcomes after the introduction of the Helping Babies Breathe Quality Improvement Cycle (HBB QIC) in Nepal. This was a prospective cohort study with a nested case-control design completed in a tertiary hospital in Nepal. Information were collected from the women who had experienced perinatal death and live birth among referent population; a video recording was done in the neonatal resuscitation corner to collect information on the health workers’ performance in neonatal resuscitation.  Lack of antenatal care had the highest association with antepartum stillbirth (aOR 4.2, 95% CI 3.2–5.4), births that had inadequate fetal heart rate monitoring were associated with intrapartum stillbirth (aOR 1.9, CI 95% 1.5–2.4), and babies who were born premature and small-for-gestational-age had the highest risk for neonatal death in the hospital (aOR 16.2, 95% CI 12.3–21.3). Before the introduction of the HBB QIC, health workers displayed poor adherence to the neonatal resuscitation protocol. After the introduction of HBB QIC, the health workers demonstrated improvement in their neonatal resuscitation skills and these were retained until six months after training. Daily bag-and-mask skill checks (RR 5.1 95% CI 1.9–13.5), preparation for birth (RR 2.4, 95% CI 1.0–5.6), self-evaluation checklists (RR 3.8, 95% CI 1.4–9.7) and weekly review and reflection meetings (RR 2.6, 95% 1.0–7.4) helped the health workers to retain their neonatal resuscitation skills. The health workers demonstrated improvement in ventilation of babies within one minute of birth and there was a reduction in intrapartum stillbirth (aOR 0.46, 95% CI 0.32–0.66) and first-day neonatal mortality (aOR 0.51, 95% CI 0.31–0.83).  The study provides information on challenges in reducing stillbirth and neonatal death in low income settings and provides a strategy to improve health workers adherence to neonatal resuscitation to reduce the mortality. The HBB QIC can be implemented in similar clinical settings to improve quality of care and survival in Nepal, but for primary care settings, the QIC need to be evaluated further.

Résumé: Les anti-infectieux sont parmi les médicaments les plus utilisés pendant la grossesse. Les indications pour l’utilisation de ces médicaments, telles que les infections bactériennes, figurent parmi les facteurs de risque les plus importants pour la prématurité et les enfants nés petits pour l'âge gestationnel («Small-for-gestational-age », SGA). Ces complications de la grossesse peuvent avoir des incidences sur la santé du nouveau né et sur son développement futur. Compte tenu des impacts sur la santé de la mère et de l’enfant, la prise en charge et le traitement efficace de ces infections sont impératifs. Cependant, l'utilisation des anti-infectieux, pour éviter des issues de grossesse défavorables, fait l’objet d’une controverse dans la littérature. Cette controverse est en partie liée à la qualité méthodologique discutable des études disponibles sur le sujet. Les quatre études présentées dans cette thèse ont donc pour objectif d’investiguer l’utilisation des anti-infectieux durant la grossesse ainsi que d’évaluer le risque de prématurité et de SGA après utilisation de ces médicaments en période gestationnelle. Une révision systématique de la littérature sur l’utilisation du métronidazole durant la grossesse est également présentée. Nous avons utilisé, comme source de données le Registre des Grossesses du Québec, une cohorte longitudinale conçue à partir du jumelage de trois bases de données administratives de la province du Québec (RAMQ, Med-Echo et ISQ). Le registre fournit des informations sur les prescriptions, les services pharmaceutiques et médicaux, ainsi que des donnés sur les soins d’hospitalisation de courte durée et démographiques. Les deux premières études présentées dans cette thèse ont eu pour objectif d’évaluer la prévalence, les tendances, les indications et les prédicteurs de l’utilisation des anti-infectieux dans une cohorte, extraite du registre, de 97 680 femmes enceintes. A l’aide d’un devis cas-témoins, les 2 dernières études ont mesuré l’association entre l’utilisation d’anti-infectieux durant les 2 derniers trimestres de grossesse et le risque de prématurité et de SGA, respectivement. Un cas de prématurité a été défini comme un accouchement survenu avant 37 semaines de gestation. Un cas de SGA a été défini comme l’accouchement d’un enfant dont le poids à la naissance se situe sous le 10ème percentile du poids normalisé à la naissance (compte tenu de l’âge gestationnel et du sexe du bébé). Les données ont été recueillies pour les agents systémiques oraux, ainsi que pour les classes et les agents individuels. Nos résultats ont montré que la prévalence de l’utilisation des anti-infectieux durant la grossesse était comparable à celle d’autres études déjà publiées (25%). Nous avons observé une augmentation de l’utilisation des agents plus anciens et ayant des profils d’innocuité connus. Les prédicteurs de l’usage en début de grossesse identifiés sont : avoir eu plus de deux différentes prescriptions (OR ajusté = 3,83, IC 95% : 3,3-4,3), avoir eu un diagnostic d’infection urinaire (OR= 1,50, IC 95% : 1,3-1,8) et un diagnostic d’infection respiratoire (OR= 1,40, IC 95% : 1,2-1,6). L’utilisation des macrolides a été associée à une diminution du risque de prématurité (OR =0,65, IC 95% : 0,50-0,85). En revanche, les femmes ayant été exposées au métronidazole ont vu leur risque augmenté de 80% (OR=1,81, IC 95% : 1,30-2,54). L’utilisation d’azithromycine a été associée à une diminution importante du risque chez les femmes ayant un diagnostic de rupture prématurée des membranes (OR=0,31, IC 95% : 0,10-0,93). Cependant, l'utilisation de sulfaméthoxazole-triméthoprime (SXT) a été significativement associée à une augmentation du risque de SGA (OR= 1,61, IC 95% : 1,16-2,23), tandis que celle des anti-infectieux urinaires a été associée à une diminution du risque (OR= 0,80, 95%CI : 0.65-0.97). Les conclusions de nos travaux suggèrent que l’utilisation des macrolides et des pénicillines diminuent le risque de prématurité et de SGA. Nous devons considérer l'utilisation de différents choix thérapeutiques tels que l’azithromycine, lors de la prise en charge des infections pouvant induire la prématurité et le SGA. / Abstract: Anti-infective drugs are among the most used medications during pregnancy. Gestational infections are related to some adverse pregnancy outcomes, such as preterm birth and infants born small for their gestational age (SGA), which increases the risk of mortality and long-term morbidity. Given its health impacts, prompt management and treatment of these infections are warranted. However, there is some controversy on the use of anti-infective drugs to prevent adverse pregnancy outcomes, such as preterm birth. Furthermore, there is growing concern regarding its independent effects on these outcomes, when treatment of maternal infections is instituted. Therefore, we conducted 4 large population-based studies aimed to investigate the gestational use of anti-infective drugs during pregnancy and the risk of preterm birth and SGA. In addition, we systematically reviewed the available evidence on the use of metronidazole during gestation. We used data from the Quebec Pregnancy Registry, a longitudinal population-based cohort established with the linkage of three administrative databases from the province of Quebec (RAMQ, Med-Echo and ISQ). Data are available on prescriptions, pharmaceutical and healthcare services, acute care hospitalization and patient demographics. For study 1 and 2, we conducted a drug utilisation review within a cohort of 97 680 pregnant women. Study 3 and 4 were two independent case-control studies. Cases of preterm birth were defined as those with a delivery occurring before the 37th week of gestation (study 3). Cases of SGA were defined as a pregnancy resulting in a baby’s weigh adjusted for gestational age and gender <10th percentile, according to the Canadian gender-specific reference curves (Study 4). Oral use of anti-infective drugs during the last two trimesters of pregnancy was the exposure definition for both studies. Independent analyses were done to assess the risk for different classes of anti-infectives and individual agents. Our results indicate that the use of anti-infective drugs during pregnancy is prevalent (25%). Use of well-known agents increased once pregnancy was diagnosed, and the most frequent indications for use were respiratory and urinary infections. Predictors associated with use were having more that 2 different prescribers (adj. OR= 3.83, 95% CI: 3.3-4.3), having a diagnosis of urinary tract infections (adj. OR= 1.50, 95% CI: 1.3-1.8) and respiratory tract infection (adj. OR= 1.40, 95% CI: 1.2-1.6). The use of macrolides was associated with a decreased risk of preterm birth (adj. OR=0.65, 95% CI: 0.50-0.85), whereas metronidazole increased the risk (adj. OR=1.81, 95% CI: 1.30-2.54). Azithromycin had a protective effect in women with premature rupture of membranes (adj. OR=0.31, 95% CI: 0.10-0.93). Use of sulfamethoxazole/trimethoprim was associated with an increased risk of SGA (adj. OR= 1.61, 95%CI: 1.16-2.23), whereas the use of urinary anti-infectives decreased the risk (adj. OR= 0.80, 95%CI: 0.65-0.97).The results of this thesis suggest that the use of macrolides and penicillins decrease the risk of preterm birth and SGA. Health care professionals should consider other therapeutic alternatives to metronidazole and sulfonamides, such as azithromycin.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

L’asthme est l’une des pathologies chroniques les plus fréquemment rencontrées durant la grossesse, affectant environ 8% des femmes enceintes. Les lignes directrices pour le traitement de l’asthme affirment que le risque d’un développement non optimal du fœtus dû à un asthme mal maîtrisé est supérieur au risque associé à la prise de médicaments pour le traitement de l’asthme durant la grossesse. Des questions persistent par contre sur l’innocuité des hautes doses de corticostéroïdes inhalés (CSI) et très peu de données sont publiées pour les bêta2-agonistes à longue action (BALA). Un programme de recherche en deux volets a été développé afin de répondre à certaines de ces questions. Dans un premier volet, une cohorte de femmes asthmatiques accouchant au Québec de 1998 à 2008 a été assemblée à partir des bases de données de la Régie de l’assurance maladie du Québec et de MED-ÉCHO afin d’évaluer l’impact de la prise de CSI ou de BALA sur la prévalence de faible poids à la naissance (FPN), de prématurité et de bébé petit pour l’âge gestationnel (PAG). La cohorte était composée de 7376 grossesses dont 56,9% étaient exposées aux CSI et 8,8% aux BALA. Dans cette cohorte, l’utilisation de BALA n’était pas associée à des prévalences plus élevées de FPN (OR=0,81, IC95%:0,58–1,12), prématurité (OR=0,84, IC95%:0,61–1,15) ou PAG (OR=0,92, IC95%:0,70–1,20). Lors de la comparaison des BALA (salmétérol comparé au formotérol comme référence) la différence la plus importante était pour le PAG (OR=1,16, IC95%:0,67–2,02). Pour les CSI, une tendance à une augmentation de FPN, prématurité et PAG a été observée avec l’augmentation des doses. Le OR le plus élevé était pour une dose > 500 ug/jour (équivalent fluticasone) pour le FPN: (OR=1,57, IC95%:0,86–2,87). La comparaison des CSI les plus utilisés (fluticasone comparé au budésonide comme référence) montre des différences non statistiquement significatives avec la différence maximale observée pour le PAG (OR=1,10, IC95%:0,85–1,44). Dans un second volet, une sous-cohorte de femmes asthmatiques avec visites médicales pour exacerbation d’asthme au Centre hospitalier universitaire de Sherbrooke (CHUS) a été constituée pour comparer le traitement des exacerbations durant et hors grossesse. Les résultats montrent que le traitement par CS était moins fréquent et différé pour les femmes enceintes comparées aux femmes non-enceintes. Le traitement de maîtrise de l’asthme (CSI et/ou BALA) dans l’année précédant l’exacerbation était sous-optimal. Les résultats présentés dans cette thèse démontrent l’innocuité des BALA et des doses faibles à modérées de CSI pendant la grossesse pour les issues de FPN, prématurité et PAG alors que des études supplémentaires sont nécessaires afin d’évaluer l’innocuité des hautes doses de CSI. Une innocuité comparable entre les CSI (budésonide, fluticasone) et les BALA étudiés (formotérol, salmétérol) a également été démontrée. Les résultats montrent également un recours moindre aux CS pour le traitement des exacerbations d’asthme durant la grossesse comparativement à hors grossesse. Ces résultats sont un ajout important aux évidences permettant aux cliniciens et aux femmes enceintes asthmatiques de faire les meilleurs choix pour optimiser le traitement pharmacologique durant la grossesse. / Asthma is one of the most common chronic medical conditions encountered during pregnancy, affecting approximately 8% of pregnant women. Current asthma treatment guidelines emphasize the importance and safety of the use of asthma medications during pregnancy compared to the risk of poorly controlled asthma for the fetus. In the evaluation of the safety of asthma medications during pregnancy, the literature review shows that questions persist, amongst others, on the safety of high inhaled corticosteroids (ICSs) doses and that there is a paucity of data on the safety of long-acting beta2-agonists (LABAs). A two components research program was developed to answers some of these questions. In the first component, a cohort of asthmatic women giving birth from 1998 to 2008 was constructed from the Régie de l’assurance maladie du Québec (RAMQ) et de MED-ÉCHO databases to assess the impact of the use of long-acting β2-agonists (LABAs) and the dose of inhaled corticosteroids (ICSs) during pregnancy on the prevalence of low birth weight (LBW), preterm birth (PB), and small for gestational age (SGA). The cohort included 7,376 pregnancies: 8.8% exposed to LABAs and 56.9% exposed to ICSs. LABA use was not found to be associated with increased prevalence of LBW (OR=0.81; 95%CI: 0.58–1.12), PB (OR=0.84; 95%CI: 0.61–1.15), or SGA (OR=0.92; 95%CI: 0.70–1.20). In the LABAs comparison (salmeterol compared to formoterol as reference), the most important difference was observed for PAG (OR=1.16, 95%CI: 0.67–2.02). For the ICSs, increasing doses were associated with a trend of increased LBW, PB, and SGA. The maximal observed OR was for a dose > 500 ug/day (fluticasone-equivalent) for LBW: (OR=1.57, 95%CI: 0.86–2.87). The comparison of the most frequently used ICSs (fluticasone compared to budesonide as reference) revealed non-statistically significant differences with a maximal difference observed for SGA (OR=1.10, 95%CI: 0.85–1.44). In the second component, a sub-cohort of asthmatic women with medical visits for asthma exacerbations was constructed to compare the treatment of exacerbations during and outside of pregnancy. The results show a reduced and delayed use of systemic corticosteroids for the treatment of asthma exacerbations in women when pregnant than when non-pregnant. The preventive treatment of asthma (ICSs and/or BALAs) could also be optimized. The results presented in this thesis support the safety of the use during pregnancy of LABAs and low to moderate doses of ICSs for the outcomes of LBW, PB and SGA and point to the need for additional data on the safety of high ICS doses. A comparable safety between studied ICSs (budesonide and fluticasone) and BALAs (formoterol and salmeterol) was also demonstrated. We also observed a reduced and delayed use of systemic corticosteroids for the treatment of asthma exacerbations in women when pregnant than when non-pregnant.