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Objective Preeclampsia is a hypertensive disorder of pregnancy associated with proteinuria detected by 24-hour urine collection (≥0.3 g/24 h) or protein/creatinine ratio (≥30 mg/mmol). The albumin/creatinine ratio (ACR) is used outside pregnancy to detect abnormal amounts of albumin in the urine, but there is little data on its value in pregnancy. Our objective was to determine the diagnostic threshold for ACR to detect significant proteinuria in women investigated for preeclampsia. Methods A prospective observational study involving 99 hypertensive women (≥140/90 mm Hg) over 20 weeks gestation who were hospitalized at 2 Canadian tertiary centres. A 24-hour urine collection and a morning urine sample were collected. The optimal ACR threshold was determined by a receiver operating characteristic (ROC) curve using the 24-hour collection as the reference test; sensitivity and specificity analyses were performed. Maternal and perinatal characteristics were extracted from medical records. Results Of the 87 women who had completed urine collection, 74 (85%) had an initial diagnosis of preeclampsia and 63 (72%) had significant proteinuria confirmed by 24-hour collection. The area under the morning ROC curve was 0.92 (95% CI 0.86–0.98) and the optimal threshold obtained for the ACR was 9 mg/mmol, with a sensitivity and specificity of 84% (95% CI 73–92) and 88% (95% CI 68–97), respectively. Conclusion Our results suggest that an ACR threshold of 9 mg/mmol on a morning urine sample can be used to detect significant proteinuria of preeclampsia in hospitalized hypertensive women.

Objective: To examine the association between pre-eclampsia definition and pregnancy outcome. Design: Secondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data. Setting: International multicentre randomised controlled trial (RCT). Population: In all, 987 women with non-severe non-proteinuric pregnancy hypertension. Methods: We evaluated the association between pre-eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control. Main outcome measures: Main CHIPS trial outcomes: primary (perinatal loss or high-level neonatal care for >48 hours), secondary (serious maternal complications), birthweight

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

Supplemental Digital Content is available in the text, Objective: To estimate national and geography-based variations in blood pressure and burden of hypertension in Cameroon, generally called ‘miniature Africa’. Methods: PubMed, Medline, EMBASE, CINHAL, Web of Science, Popline, Scopus and BDSP were searched through November 2018, for hypertension studies among Cameroonians aged at least 18 years. Hypertension was measured as SBP at least 140 mmHg or DBP at least 90 mmHg. Random-effects meta-analysis was used. Results: Twenty studies involving 46 491 participants met inclusion criteria. Overall hypertension prevalence was 30.9% [95% confidence interval (CI) 27.0–34.8]: 29.6% (24.1–35.1) and 32.1% (27.2–37.1) in 1994–2010 and 2011–2018, respectively. Of hypertensive participants, only 24.4% (18.9–30.0) – 31.6% (21.0–42.3) and 20.8% (14.0–27.7) in 1994–2010 and 2011–2018, respectively – were aware of their status, 15.1% (10.6–19.6) were taking antihypertensive medications and 8.8% (5.7–11.9) – 10.4% (7.5–13.3) and 8.3% (4.4–12.3) in 1994–2010 and 2011–2018, respectively – were controlled. Hypertension prevalence varied by sex: 34.3% (30.0–38.6) for men and 31.3% (26.5–36.1) for women; ethnicity: from 3.3% (0.4–6.2) among Pygmies to 56.6% (49.4–63.8) among Bamileke; urbanity: 25.4% (17.1–33.7) for rural and 31.4% (27.3–35.5) for urban dwellers; agroecological zone: from 35.1% (28.9–41.3) in Tropical highlands to 28% (20.1–35.9) in Guinea-Savannah; and subnational region: from 36.3% (27.8–44.9) in the West to 17.1% (9.9–44.2) in the South. Conclusion: Cameroon's hypertension prevalence is high and increasing whereas awareness, treatment and control are low and declining. Emerging patterns call urgently for effective campaigns to raise hypertension awareness alongside strategies for hypertension prevention and BP control.

The international CHIPS Trial (Control of Hypertension In Pregnancy Study) enrolled 987 women with chronic (75%) or gestational (25%) hypertension. Pre-eclampsia developed in 48%; women remained on their allocated BP control and delivered an average of two weeks later. ‘Less tight’ control (target diastolic BP 100 mmHg) achieved BP that was 6/5mmHg higher (p < 0.001) than ‘tight’ control (target diastolic 85 mmHg, BP achieved 133/85 mmHg). ‘Less tight’ (vs. ‘tight’) control resulted in similar adverse perinatal outcomes (31.5% vs. 30.7%; p = 0.84) that balanced birthweight < 10th percentile (16.1% vs. 19.8%; p = 0.14) against preterm birth (35.6% vs. 31.5%; p = 0.18). 12-month follow-up revealed no compelling evidence for developmental programming of child growth. However, ‘less tight’ (vs. ‘tight’) control resulted in more severe maternal hypertension (40.6% vs. 27.5%; p < 0.001), and more women with platelets < 100 × 109/L (4.3% vs. 1.6%; p = 0.02) or symptomatic elevated liver enzymes (4.3% vs. 1.8%; p = 0.03), with no difference in serious maternal complications (3.7% vs. 2.0%; p = 0.17). Labetalol was the drug of choice. Methyldopa did not result in inferior outcomes. Post-hoc, severe hypertension, independent of pre-eclampsia, was associated with heightened increased risk of adverse outcomes, and in ‘less tight’ control, of serious maternal complications. At no gestational age at initiation of BP control was ‘less tight’ superior to ‘tight’. Women in both groups were equally satisfied with care. ‘Less tight’ control tended to be more expensive by CAD$6000 (p =0.07) based on neonatal care costs. Collectively, CHIPS publications have provided evidence that women with non-severe pregnancy hypertension should receive ‘tight’ BP control achieved by a simple algorithm.

Summary Background Although metformin is increasingly being used in women with type 2 diabetes during pregnancy, little data exist on the benefits and harms of metformin use on pregnancy outcomes in these women. We aimed to investigate the effects of the addition of metformin to a standard regimen of insulin on neonatal morbidity and mortality in pregnant women with type 2 diabetes. Methods In this prospective, multicentre, international, randomised, parallel, double-masked, placebo-controlled trial, women with type 2 diabetes during pregnancy were randomly assigned from 25 centres in Canada and four in Australia to receive either metformin 1000 mg twice daily or placebo, added to insulin. Randomisation was done via a web-based computerised randomisation service and stratified by centre and pre-pregnancy BMI ( ClinicalTrials.gov , NCT01353391 . Findings Between May 25, 2011, and Oct 11, 2018, we randomly assigned 502 women, 253 (50%) to metformin and 249 (50%) to placebo. Complete data were available for 233 (92%) participants in the metformin group and 240 (96%) in the placebo group for the primary outcome. We found no significant difference in the primary composite neonatal outcome between the two groups (40% vs 40%; p=0·86; relative risk [RR] 1·02 [0·83 to 1·26]). Compared with women in the placebo group, metformin-treated women achieved better glycaemic control (HbA1c at 34 weeks' gestation 41·0 mmol/mol [SD 8·5] vs 43·2 mmol/mol [–10]; 5·90% vs 6·10%; p=0·015; mean glucose 6·05 [0·93] vs 6·27 [0·90]; difference −0·2 [–0·4 to 0·0]), required less insulin (1·1 units per kg per day vs 1·5 units per kg per day; difference −0·4 [95% CI −0·5 to −0·2]; p Interpretation We found several maternal glycaemic and neonatal adiposity benefits in the metformin group. Along with reduced maternal weight gain and insulin dosage and improved glycaemic control, the lower adiposity and infant size measurements resulted in fewer large infants but a higher proportion of small-for-gestational-age infants. Understanding the implications of these effects on infants will be important to properly advise patients who are contemplating the use of metformin during pregnancy. Funding Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, University of Toronto.

Background Women with hyperglycemia during pregnancy are at high risk for adverse perinatal outcomes. Maternal sleep-disordered breathing (SDB) during pregnancy is common and is a risk factor for gestational diabetes mellitus (GDM). However, the relationship between SDB severity and glucose control is unknown. Research Question Is there an association between SDB severity and glucose levels as assessed by continuous glucose monitoring in GDM? Study Design and Methods Women with GDM underwent sleep recordings and 72-hour continuous glucose monitoring. Linear mixed models were used to estimate the association of the apnea-hypopnea index (AHI), rapid eye movement (REM)-AHI, and non-REM-AHI with mean glucose levels during nighttime (two periods: 11 pm to 3 am and 3 am to 6 am ), daytime (8 am to 9 pm ), and 24-hours. Models were adjusted for BMI and antihyperglycemic medications. Results In 65 participants who were 35 ± 5 (mean ± SD) years of age with BMI of 33 ± 7 kg/m2, 31% were undergoing insulin and/or metformin therapy. A ten-unit increase in AHI was associated with elevated nocturnal glucose levels (11 pm to 3 am : 0.20 mmol/L [95% CI, 0.04-0.40]) with persistent elevations into the morning (8 am : 0.26 mmol/L [95% CI, 0.08-0.4]) when adjusted for BMI and medications. REM-AHI was also associated with higher nocturnal and morning glucose levels, whereas non-REM was not. AHI was not associated with either mean daytime or 24-hour glucose levels. Interpretation Greater severity of SDB was associated with higher nocturnal and morning glucose levels in women with GDM.

AIMS Bromocriptine is thought to facilitate left ventricular (LV) recovery in peripartum cardiomyopathy (PPCM) through inhibition of prolactin secretion. However, this potential therapeutic effect remains controversial and was incompletely studied in diverse populations. METHODS AND RESULTS Consecutive women with new-onset PPCM (n = 76) between 1994 and 2015 in Quebec, Canada, were classified according to treatment (n = 8, 11%) vs. no treatment (n = 68, 89%) with bromocriptine. We assessed LV functional recovery at mid-term (6 months) and long-term (last follow-up) and compared outcomes among groups. Women treated with bromocriptine experienced better mid-term left ventricular ejection fraction (LVEF) recovery from 23 ± 10% at baseline to 55 ± 12% at 6 months, compared with a change from 30 ± 12% at baseline to 45 ± 13% at 6 months in women treated with standard medical therapy (P interaction

We present Hypertension Canada's inaugural evidence-based Canadian recommendations for the management of hypertension in pregnancy. Hypertension in pregnancy is common, affecting approximately 7% of pregnancies in Canada, and requires effective management in order to reduce maternal, fetal and newborn complications. Given this importance, these guidelines were developed in partnership with the Society of Obstetricians and Gynaecologists of Canada with the main common objective of improving the management of women with hypertension in pregnancy. Guidelines for the diagnosis, assessment, prevention and treatment of hypertension in adults and children are published separately. In this first Hypertension Canada Guidelines for hypertension in pregnancy, seven recommendations for the management of non-severe and severe hypertension in pregnancy are presented. For non-severe hypertension in pregnancy (systolic blood pressure 140-159 mm Hg and/or diastolic blood pressure 80-109 mm Hg), we provide guidance for the threshold for initiation of antihypertensive therapy, blood pressure targets, as well as first- and second-line antihypertensive medications. Severe hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥110 mm Hg) requires urgent antihypertensive therapy to reduce maternal, fetal and newborn adverse outcomes. The specific evidence and rationale underlying each of these guidelines are discussed.

Hypertension Canada provides annually-updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children. This year, the adult and pediatric guidelines are combined in one document. The new 2018 pregnancy-specific hypertension guidelines are published separately. For 2018, 5 new guidelines were introduced, and one existing guideline on the blood pressure thresholds and targets in the setting of thrombolysis for acute ischemic stroke was revised. The use of validated wrist devices for the estimation of blood pressure in individuals with large arm circumference is now included. Guidance is provided for the follow-up measurements of blood pressure, with the use of standardized methods and electronic (oscillometric) upper arm devices in individuals with hypertension, and either ambulatory blood pressure monitoring or home blood pressure monitoring in individuals with white coat effect. We specify that all individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure. Finally, an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in individuals with heart failure (with ejection fraction < 40%) who are symptomatic despite appropriate doses of guideline-directed heart failure therapies. The specific evidence and rationale underlying each of these guidelines are discussed.

Introduction: Preeclampsia develops due to placental insufficiency and systemic proinflammatory and antiangiogenic mediator release, with ensuing systemic endothelial dysfunction. Nephrotic-range proteinuria appears to be associated with worse pregnancy outcomes. The relationship between differing degrees of proteinuria and the severity of placental alterations has not been studied. Methods: This is a single-centre retrospective comparison of 150 singleton pregnancies complicated by preeclampsia and varying degrees of proteinuria. Maternal demographic, obstetrical and fetal outcome data were obtained from chart review. The placental histologic evaluations were performed by a placental pathologist blinded to all other clinical information. Results: Preeclamptic women with massive proteinuria had evidence of more severe maternal vascular malperfusion lesions. The severity of the lesions was progressive through mild, moderate and massive proteinuria. Women with massive proteinuria had a higher incidence of renal dysfunction and severe hypertension, and had earlier preterm deliveries compared to preeclamptic women with mild and moderate proteinuria (p < 0.05). Conclusion: Preeclampsia with more severe proteinuria is associated with a higher prevalence of placental maternal vascular malperfusion.

Key Clinical Message Hypercalcemia in pregnancy is an uncommon event that can cause major maternal morbidity and/or fetal or neonatal morbidity and mortality. Management is a challenge for the clinicians, especially as regards to investigations in pregnancy, surgery, and the use of cinacalcet and bisphosphonates. We present three case reports and discuss management.

Background: Gestational diabetes (GDM) is associated with adverse short- and long-term maternal and fetal outcomes. Observational data support a link between sleep-disordered breathing (SDB) during pregnancy and GDM. However, it is unknown whether treatment of SDB with continuous positive airway pressure (CPAP) improves glucose control in this patient population. In addition, CPAP adherence and feasibility as a treatment option in pregnancy is unknown. This pilot randomized, controlled trial aims to primarily determine the feasibility of CPAP treatment in pregnant women with SDB and GDM. This study is also investigating the effect of SDB treatment on 24-h glucose profiles as an exploratory outcome. Objectives: To describe the study methodology in this ongoing study of pregnant women with GDM and SDB. Patients and Methods: Pregnant women with GDM and SDB defined by apnea-hypopnea index (AHI) ≥10 (Chicago Scoring Criteria) on level 2 polysomnography are randomized to either auto titrating CPAP (experimental group) or a nasal dilator strip (control group) until delivery. The primary outcome, objectively-assessed adherence to CPAP, is measured over the course of the treatment period using device-specific software. Recruitment and retention rates will be calculated to assess the feasibility for planning future trials. Twenty-four hour glucose profiles are measured over a 72-h period using the continuous glucose monitoring (CGM) system, before and after the intervention. Conclusion: The results of this study will be highly informative to determine whether CPAP is a feasible treatment for pregnant women with GDM and SDB, a specialized population at risk for substantial comorbidity. The trial results will ultimately be useful in planning future SDB treatment trials in pregnancy and GDM. The study is registered on clinicaltrials.gov (NCT02245659).

Hypertensive disorders during pregnancy result in substantial maternal morbidity and are a leading cause of maternal deaths worldwide. Self-monitoring of blood pressure (BP) might improve the detection and management of hypertensive disorders of pregnancy, but few data are available, including regarding appropriate thresholds. This systematic review and individual patient data analysis aimed to assess the current evidence on differences between clinic and self-monitored BP through pregnancy. MEDLINE and 10 other electronic databases were searched for articles published up to and including July 2016 using a strategy designed to capture all the literature on self-monitoring of BP during pregnancy. Investigators of included studies were contacted requesting individual patient data: self-monitored and clinic BP and demographic data. Twenty-one studies that utilized self-monitoring of BP during pregnancy were identified. Individual patient data from self-monitored and clinic readings were available from 7 plus 1 unpublished articles (8 studies; n=758) and 2 further studies published summary data. Analysis revealed a mean self-monitoring clinic difference of ≤1.2 mm Hg systolic BP throughout pregnancy although there was significant heterogeneity (difference in means, I 2 >80% throughout pregnancy). Although the overall population difference was small, levels of white coat hypertension were high, particularly toward the end of pregnancy. The available literature includes no evidence of a systematic difference between self and clinic readings, suggesting that appropriate treatment and diagnostic thresholds for self-monitoring during pregnancy would be equivalent to standard clinic thresholds.

Preeclampsia (PE) is a poorly understood pregnancy complication. It has been suggested that changes in the maternal immune system may contribute to PE, but evidence of this remains scarce. Whilst PE is commonly experienced prepartum, it can also occur in the postpartum period (postpartum PE-PPPE), and the mechanisms involved are unknown. Our goal was to determine whether changes occur in the maternal immune system and placenta in pregnancies complicated with PE and PPPE, compared to normal term pregnancies. We prospectively recruited women and collected blood samples to determine the circulating immune profile, by flow cytometry, and assess the circulating levels of inflammatory mediators and angiogenic factors. Placentas were collected for histological analysis. Levels of alarmins in the maternal circulation showed increased uric acid in PE and elevated high-mobility group box 1 in PPPE. Analysis of maternal immune cells revealed distinct profiles in PE vs PPPE. PE had increased percentage of lymphocytes and monocytes whilst PPPE had elevated NK and NK-T cells as well. Elevated numbers of immune cells (CD45+) were detected in placentas from women that developed PPPE, and those were macrophages (CD163+). This work reveals changes within the maternal immune system in both PE and PPPE, and indicate a striking contrast in how this occurs. Importantly, elevated immune cells in the placenta of women with PPPE strongly suggest a prenatal initiation of the pathology. A better understanding of these changes will be beneficial to identify women at high risk of PPPE and to develop novel therapeutic targets.

Hypertensive disorders are the most common medical complication of pregnancy. As such, a large part of antenatal care is dedicated to the detection of pre-eclampsia, the most dangerous of the hypertensive disorders. The highlights of this chapter include progress in the use of out-of-office blood pressure measurement as an adjunct to office blood pressure measurement, pre-eclampsia defined as proteinuria or relevant end-organ dysfunction, antihypertensive therapy for severe and non-severe hypertension and post-partum follow-up to mitigate the increased cardiovascular risk associated with any of the hypertensive disorders of pregnancy.

Resume Notre travail visait a comparer le taux de macrosomie et la moyenne de poids de naissance (en percentile) de nouveau-nes de meres diabetiques de type 1 (DT1) traitees par pompe a insuline sous-cutanee (PSC) ou par multi-injections quotidiennes d’insuline (MIQ). Il s’agit d’une etude retrospective, incluant les grossesses mono-fœtales de patientes DT1, dont l’issue de grossesse est survenue a plus de 16 semaines de grossesse, au CHU Sainte-Justine (Montreal, Quebec, Canada), entre le 1 er janvier 2000 et le 31 janvier 2009. Au total, 14 grossesses sous PSC et 94 sous MIQ ont ete evaluees. L’HbA 1c aux 1 er , 2 e et 3 e trimestres de grossesse n’etait pas significativement differente entre les groupes PSC et MIQ. Le percentile des poids de naissance (92±11 versus 77 ± 26) et le taux de macrosomie (71,4% versus 42,6%, respectivement) etaient significativement plus eleves dans le groupe PSC ( p

Maternal asthma has been found to be associated with an increased risk of hypertensive disorders of pregnancy (HDP), that is, gestational hypertension, preeclampsia, and eclampsia. There is limited data, however, regarding the relationship between the use of long-acting beta-agonists (LABAs) during pregnancy and these outcomes.To investigate whether exposure to a LABA in addition to an inhaled corticosteroid increases the risk of HDP or preeclampsia/eclampsia, as compared with nonexposure to LABAs, in pregnant women with asthma.A cohort of 8,936 pregnancies in women with asthma who delivered between 1998 and 2010 was reconstructed using Quebec (Canada) health administrative databases. Cox proportional hazard regression models, adjusted for potential confounders, were used for statistical analyses. The primary exposure was LABA use (yes/no) measured on the first day of the 20th week of pregnancy. HDP were identified on the basis of recorded diagnoses and on prescriptions of antihypertensive drugs filled on or after the first day of week 20 of gestation.There were 567 (6.3%) cases of HDP and 256 (2.9%) cases of preeclampsia/eclampsia in the cohort, and the rates of both disorders were similar in women exposed or not exposed to LABAs. LABA use was not associated with increased risks of HDP (adjusted hazard ratio, 0.96; 95% CI, 0.69-1.33) or preeclampsia/eclampsia (adjusted hazard ratio, 0.89; 95% CI, 0.53-1.50).The results of this study provide evidence suggesting the safety of LABAs for the treatment of asthma in pregnancy, in terms of the risks of HDP and preeclampsia/eclampsia.

Resume Objectif Le present resume directif presente un sommaire des donnees qui ont ete evaluees dans le cadre de la directive clinique redigee par le groupe de travail canadien sur les troubles hypertensifs de la grossesse et publiee dans Pregnancy Hypertension (http://www.pregnancyhypertension.org/article/S2210-7789(14)00004-X/fulltext), en vue d'offrir une approche raisonnable envers le diagnostic, l'evaluation et la prise en charge des troubles hypertensifs de la grossesse. Resultats La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans Medline, CINAHL et The Cochrane Library en mars 2012 au moyen d'un vocabulaire controle (p. ex. « pregnancy », « hypertension », « pre-eclampsia », « pregnancy toxemias ») et de mots cles (p. ex. « diagnosis », « evaluation », « classification », « prediction », « prevention », « prognosis », « treatment », « post-partum follow-up ») appropries. Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles rediges en anglais ou en francais entre janvier 2006 et fevrier 2012. Les recherches ont ete mises a jour de facon reguliere et integrees a la directive clinique jusqu'en septembre 2013. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Valeurs La qualite des resultats est evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau).

Summary Background Asthma exacerbations are common during pregnancy with a prevalence as high as 51.9% among women with severe asthma. Objective To compare the treatment of asthma exacerbations in an acute-care setting during and outside of pregnancy. Methods We formed a cohort of women who sought medical care for an asthma exacerbation at a teaching hospital during or in the year preceding pregnancy, between 1998 and 2008. An exacerbation was composed of one or more medical encounters in an acute-care setting (hospital-based outpatient clinic, emergency department, or during hospitalization). Data were retrieved from medical charts and health administrative databases. We compared the use of systemic corticosteroids (SCSs) during and outside of pregnancy with a Cox proportional hazards model. Results The cohort was formed of 39 women who had 40 exacerbations during and 39 exacerbations outside of pregnancy. Use of SCSs to treat exacerbations was less frequent (adjusted hazard ratio: 0.51; 95% CI: 0.31–0.84) during pregnancy. Moreover, upon the first medical encounter related to the exacerbation, SCSs, when administered, were given less frequently to women when pregnant than when non-pregnant (83% vs. 100%). The SCS prescription was filled at the community pharmacy 65% and 67% of the time when it was prescribed at discharge to women when pregnant than when non-pregnant, respectively. Conclusion We observed a reduced and delayed use of SCSs for the treatment of asthma exacerbations in women when pregnant than when non-pregnant, with similar numbers of women in both conditions filling their SCSs prescription in pharmacies.

Objective To present an approach, based on current evidence, for the diagnosis, treatment, and thromboprophylaxis of venous thromboembolism in pregnancy and postpartum. Evidence Published literature was retrieved through searches of PubMed, Medline, CINAHL, and The Cochrane Library from November 2011 to July 2013 using appropriate controlled vocabulary (e.g. pregnancy, venous thromboembolism, deep vein thrombosis, pulmonary embolism, pulmonary thrombosis) and key words (e.g., maternal morbidity, pregnancy complications, thromboprophylaxis, antithrombotic therapy). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English or French. There were no date restrictions. Grey (unpublished) literature was identified through searching the websites of clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table 1).

Resume Objectif Presenter une approche, fondee sur les donnees actuelles, envers le diagnostic, la prise en charge et la thromboprophylaxie de la thromboembolie veineuse pendant la grossesse et la periode postpartum. Resultats La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans PubMed, Medline, CINAHL et The Cochrane Library entre novembre 2011 et juillet 2013 au moyen d'un vocabulaire controle (p. ex. « pregnancy », « venous thromboembolism », « deep vein thrombosis », « pulmonary embolism », « pulmonary thrombosis ») et de mots cles (p. ex. « maternal morbidity », « pregnancy complications », « thromboprophylaxis », « antithrombotic therapy ») appropries. Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles publies en anglais ou en francais. Aucune restriction n'a ete imposee en matiere de dates. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Valeurs La qualite des resultats est evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau).

To determine the performance of a protein-to-creatinine ratio threshold of 30 mg/mmol in pregnant women investigated for hypertension according to the time of day of the sample.This prospective study included ambulatory pregnant women investigated for hypertensive disorders. A single voided random urine specimen was obtained to determine the protein-to-creatinine ratio, followed immediately by a 24-hour urine collection. Statistical analyses included Spearman correlation, sensitivity, specificity, predictive values, likelihood ratios, and receiver-operator characteristic curves with 95% confidence intervals. A P value0.05 was considered statistically significant.Among the 91 specimens analyzed, 47.3% showed significant proteinuria in the 24-hour collection and 33% were first morning samples. The protein-to-creatinine ratio and 24-hour urinary protein excretion were highly correlated (r = 0.92, P0.001). The diagnostic accuracy of the protein-to-creatinine ratio threshold of 30 mg/mmol was lower in first morning samples than in samples obtained during the rest of the day, with sensitivity 58% and 90%, specificity 93% and 100%, positive predictive value 88% and 100%, negative predictive value 72% and 92%, positive likelihood ratio 8 and not calculable, and negative likelihood ratio 0.45 and 0.1, respectively. The receiver-operator characteristic area under the curve was 0.94 (95% CI 0.86 to 1) for first morning samples and 1.0 (95% CI 0.99 to 1) for other samples.A protein-to-creatinine ratio threshold of 30 mg/mmol reliably identifies significant proteinuria, but its reliability is reduced in first morning samples. Consequently, such samples should not be used for this purpose.

Asthma during pregnancy usually requires treatment with controller medications about which more safety information is needed. The objectives are 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).A cohort of women with asthma giving birth from 1998 to 2008 was constructed from Québec (Canada) administrative databases. LBW was defined as weight2500 g, PB as delivery before 37 weeks' gestation and SGA as a birth weight below the 10th percentile. The impact of the use of LABAs and the dose of ICSs during pregnancy on the outcomes was determined with generalised-estimating-equation models.The cohort included 7376 pregnancies: 8.8% exposed to LABAs and 56.9% exposed to ICSs. All LABA users also received ICSs. The prevalence of LBW, PB and SGA was 7.7%, 9.5% and 13.5%, respectively. LABA use was not found to be associated with increased prevalence of LBW (OR 0.81; 95% CI 0.58 to 1.12), PB (OR 0.84; 95% CI 0.61 to 1.15) or SGA (OR 0.92; 95% CI 0.70 to 1.20). Mean ICSs doses125 μg/day (fluticasone-equivalent) were associated with a non-significant trend of increased LBW, PB and SGA.Despite the possibility of residual confounding due to uncontrolled or more severe asthma or smoking status, the use of LABA and low to moderate doses of ICSs were not associated with increased prevalence of perinatal outcomes. Additional research on higher ICSs doses is required to better evaluate their safety during pregnancy.

To estimate the incidence of gestational diabetes mellitus (GDM) according to The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria and the pregnancy complications in women fulfilling these criteria but who are not considered diabetic according to the Canadian Diabetes Association criteria.We estimated the rate of GDM according to the IADPSG criteria from November 2008 to October 2010. Then, we conducted a chart review to compare maternal and neonatal outcomes between women classified as GDM according to the IADPSG criteria but not by the Canadian Diabetes Association criteria (group 1; n=186) and nondiabetic women according to both criteria (group 2; n=372). Results were expressed as crude (odds ratio [OR]) or adjusted OR and 95% confidence interval (CI). The study has a statistical power of 80% to detect a difference between 16% and 8% in large for gestational age newborns (α level of 0.05; two-tailed).The rate of GDM using the IADPSG criteria was 27.51% (95% CI 25.92-29.11). Group 1 presented similar rates of large-for-gestational-age newborns (9.1% compared with 5.9%, adjusted OR 1.58, 95% CI 0.79-3.13; P=.19), delivery complications (37.1% compared with 30.1%, OR 1.37, 95% CI 0.95-1.98; P=.10), preeclampsia (6.5% compared with 2.7%, adjusted OR 2.40, 95% CI 0.92-6.27; P=.07), prematurity (6.5% compared with 2.7%, OR 1.10, 95% CI 0.53-2.27; P=.85), neonatal complications at delivery (13.4% compared with 9.7%, OR 1.45, 95% CI 0.84-2.49; P=.20), and metabolic complications (10.8% compared with 14.2%, OR 0.73, 95% CI 0.42-1.26; P=.29) compared with group 2.Women classified as nondiabetic by the Canadian Diabetes Association Criteria but considered GDM according to the IADPSG criteria have similar pregnancy outcomes as women without GDM. More randomized studies with cost-effectiveness analyses are needed before implementation of these criteria.II.

Diabet. Med. 28, 1068–1073 (2011) Abstract Aim We tested the hypothesis that diabetes in pregnancy may differentially affect neonatal outcomes in twin vs. singleton pregnancies. Methods In a retrospective cohort analysis of twins (n = 422 068) and singletons (n = 14 298 367) born in the USA from 1998 to 2001, we evaluated the adjusted odds ratios of adverse neonatal outcomes comparing diabetic vs. non-diabetic pregnancies, controlling for maternal characteristics. Primary outcomes include macrosomia (birthweight for gestational age > 90th percentile), congenital anomalies, low 5-min Apgar score (

Recent evidence suggests that treatment with low-dose acetylsalicylic acid (ASA) started early in pregnancy could prevent preeclampsia and intrauterine growth restriction (IUGR), two complications involving placental dysfunction. Preterm birth could also potentially be prevented, suggesting that it could share mechanisms of disease with preeclampsia and intrauterine growth restriction. Because there is new evidence that placental dysfunction can be predicted as early as in the first trimester, we argue that there is a need for randomized controlled trials of lowdose ASA for the prevention of preeclampsia, IUGR, and possibly preterm birth among nulliparous women with early indicators of placental dysfunction.

Objective To evaluate the quality of francophone- oriented-patients websites about chronic hypertension and pregnancy. Methodology Three instruments were used by 4 assessors to evaluate 12 most browsed websites. The first instrument evaluates the readability for a patient, the pictorial outlook and gives a general evaluation (3 questions, total score range 0–9). The second instrument judges the quality and quantity of information provided by each website, according to a pre-established list of items concerning health habits, medications, maternal and neonatal complications, postpartum evolution and breastfeeding (35 items, total score range 0–105). The third instrument, the Discern instrument, assesses the reliability and the quality of information about pharmacologic treatments (16 questions, total score range 16–80). Agreement between the observers was analysed with the Kendall coefficient of concordance (p Results Six websites were affiliated with medical journals or associations, 2 with media providers, 2 with web providers, 1 with a health care provider and 1 was commercial. Five websites were considered suitable for non- medical readers and only 3 had a favorable general evaluation. None of the websites obtained a score of at least of 50 (for a maximum score of 105) for their content with the second instrument. According to the Discern instrument, 3 sites provided very good reliability and 2 very good quality of information about medications. Statistical agreement between assessors was obtained for all analyses. Medical websites were more focused on complications and medications, were more reliable but were unsuitable for patients. Conclusion French-speaking people have access to very poor quality websites to gather information about chronic hypertension and pregnancy.

Introduction Hypertensive disorders during pregnancy result in substantial maternal morbidity and are a leading cause of maternal deaths worldwide. Self-monitoring of blood pressure might improve the detection and management of hypertensive disorders of pregnancy but few data are available, including regarding appropriate thresholds. Objective This systematic review and individual patient data analysis aimed to assess the current evidence regarding differences between clinic and self-monitored blood pressure through pregnancy. Methods MEDLINE and ten other electronic databases were searched for articles published up to and including July 2016 using a strategy designed to capture all the literature concerning self-monitoring of blood pressure during pregnancy. Investigators of included studies were contacted requesting individual patient data: self-monitored and clinic blood pressure and demographic data. Results Twenty-one studies that utilised self-monitoring of blood pressure during pregnancy were identified. Individual patient data from self-monitored and clinic readings were available from seven plus one unpublished paper (eight studies, n = 758) and two further studies published summary data. Analysis revealed a mean self-monitoring -clinic difference of ⩽1.2 mmHg systolic BP throughout pregnancy, though there was significant heterogeneity (difference in means I2 > 80% throughout pregnancy). Although the overall population difference was small, though levels of ‘white coat hypertension’ were high, particularly towards the end of pregnancy. Discussion The available literature includes no evidence of a systematic difference between self and clinic readings, suggesting that appropriate treatment and diagnostic thresholds for self-monitoring during pregnancy would be equivalent to standard clinic thresholds.

The extent to which childhood asthma incidence is influenced by asthma control and severity during pregnancy is unknown. We have studied this association during the child's first 10 yrs of life. A two-stage, case-control study, nested in a cohort of 8,226 children of asthmatic mothers, was conducted using three interlinked databases of Quebec, Canada, and mailed questionnaires. A total of 2,681 asthmatic children and 30,318 age-matched controls were selected (or =20 controls.case(-1); stage 1), and 3,254 selected mothers were mailed questionnaires to obtain additional information (stage 2). Asthma control and severity was defined using validated indexes and childhood asthma incidence based on at least one asthma-related diagnosis and prescription received within 2 yrs. A total of 44 confounders were considered. Compared with children of mild controlled asthmatic mothers, children whose mothers had moderate-to-severe uncontrolled asthma during pregnancy had an increased risk of asthma (adjusted OR 1.27, 95% CI 1.06-1.52). No increased risk was observed for children of mild uncontrolled and moderate-to-severe controlled mothers. Based on one of the largest studies of children of asthmatic mothers, a significant increase in asthma risk was demonstrated among children whose mothers had poor control and increased severity of asthma during pregnancy, indicating that this element should be added to the expanding list of determinants of childhood asthma. As it constitutes a risk factor where pregnant asthmatic females can intervene, it is of great importance for physicians to optimally treat asthmatic females during pregnancy and to encourage females to be adherent to the prescribed asthma medications.

Background: Thirteen studies investigating the association between asthma during pregnancy and perinatal mortality reported generally no increased risk. Most of these studies should be interpreted with caution because they were limited in terms of statistical power. A study was therefore undertaken to evaluate whether maternal asthma during pregnancy increases the risk of perinatal mortality. Methods: Through three administrative databases from Quebec (Canada), a cohort of women with and without asthma who had at least one pregnancy between 1990 and 2002 was formed. Perinatal mortality was identified by diagnostic codes. The adjusted odds ratio (OR) of perinatal mortality in women with and without asthma was compared using Generalised Estimation Equation (GEE) models. The first model included all potential confounders (except small for gestational age, SGA), the second model excluded birth weight, gestational age at birth and SGA and the third model excluded birth weight, gestational age at birth but included only SGA. This analysis was also stratified for birth weight and gestational age at birth. Results: The cohort was formed of 13 100 and 28 042 single pregnancies in women with and without asthma. The crude OR of perinatal mortality was 1.35 (95% CI 1.08 to 1.67), which decreased to 0.93 (95% CI 0.75 to 1.17) after adjustment for birth weight and gestational age at birth. Women with asthma had a higher rate of low birthweight babies and preterm delivery than those without asthma. Conclusion: The increased risk of low birthweight babies and premature delivery in women with asthma may partly explain the association between maternal asthma and the increased risk of perinatal mortality.

Extensive literature exists on potential risk factors for childhood asthma. To the authors' knowledge, no investigators have yet attempted to disentangle the effects of those determinants within a single study setting. The authors aimed to evaluate the independent effects of 47 potential determinants (from the prenatal, perinatal, and childhood periods) of asthma development in children within the first 10 years of life. From a Canadian birth cohort of 26,265 children (1990-2002), a 2-stage case-control study was conducted. In the first stage, 20 controls per case were selected from 3 administrative databases. In the second stage, selected mothers were mailed questionnaires for assessment of additional determinants. Increased risks of childhood asthma were found for > or =1 previous diagnosis of bronchopulmonary disease and atopic dermatitis in the child, oxygen administration after birth, prescription of antibiotics within the first 6 months of life, male gender, asthma during pregnancy, use of antibiotics during pregnancy, maternal receipt of social aid, paternal asthma, and asthma in siblings. Protective effects included use of intranasal corticosteroids during pregnancy, having a wood-burning fireplace, having pets in the home prior to the index date, breastfeeding, and day-care attendance. This study allowed the authors to identify, within a single setting, the most influential determinants of childhood asthma among 47 predictors assessed for the prenatal, perinatal, and childhood periods.

BackgroundAntidepressant use during the gestational period is a controversial topic.AimsTo determine whether duration of antidepressant use during the first trimester increases the risk of major congenital malformations in offspring of women diagnosed with psychiatric disorders.MethodA case-control study was performed among women who had been pregnant between January 1998 and December 2002. Data were obtained from a Medication and Pregnancy registry, built by linking three databases from the province of Quebec, and a self-administered questionnaire. Women eligible for this study had to be 15–45 years old at the beginning of pregnancy, have at least one diagnosis of psychiatric disorder before pregnancy, have used antidepressants for ≥ 30 days in the year prior to pregnancy and have a pregnancy ending with a delivery. Cases were defined as any major congenital malformation diagnosed in the offspring's first year of life. Odds ratios, adjusted for relevant confounders, were estimated using logistic regression.ResultsAmong the 2329 women meeting the inclusion criteria, 189 (8.1%) infants were born with a major congenital malformation. Duration of antidepressant use during the first trimester of pregnancy was not associated with an increased risk of major congenital malformations: 1–30 days v. 0 day, adjusted OR=1.23 (95% CI 0.77–1.98); 31–60 days v. 0 day, adjusted OR=1.03 (95% CI 0.63–1.69); ≥ 61 days v. 0 day, adjusted OR=0.92 (95% CI 0.50–1.69).ConclusionsThese data do not support an association between duration of antidepressant use during the first trimester of pregnancy and major congenital malformations in the offspring of women with psychiatric disorders. These findings should help clinicians decide whether to continue antidepressant therapy during pregnancy.

What is already known about this subject • Cholesterol is known to be essential for fetal development. • Statins, which inhibit cholesterol production, have therefore been considered as potential teratogens and are contraindicated in pregnancy. • Data available thus far on the risks of congenital anomalies associated with statin therapy have come from non-analytic postmarketing surveillance studies. • Given the increasing use of statins in women of childbearing age, there is a need for a population-based study on the risks of congenital anomalies associated with gestational statin use. What this study adds • In this pharmacoepidemiological study, we determined the risk of congenital anomalies in women who filled prescriptions for statins during the first trimester of pregnancy, compared with women who had stopped statins before pregnancy or those who used fibrates during pregnancy. • We found no evidence of an increased risk of fetal anomalies among first-trimester statin users, or any discernable pattern of congenital anomalies among live births. • However, in the absence of outcome data on nonlive births, conclusions remain uncertain. Aims Evidence from animal studies suggests that statin medications should not be taken during pregnancy. Our aim was to examine the association between the use of statins in early pregnancy and the incidence of congenital anomalies. Methods A population-based pregnancy registry was built. Three study groups were assembled: women prescribed statins in the first trimester (group A), fibrate/nicotinic acid in the first trimester (group B) and statins between 1 year and 1 month before conception, but not during pregnancy (group C). Among live-born infants, we selected as cases infants with any congenital anomaly diagnosed in the first year of life. Controls were defined as infants with no congenital anomalies. The rate of congenital anomalies in the respective groups was calculated. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were also calculated. Results Our study group consisted of 288 pregnant women. Among women with a live birth, the rate of congenital anomalies was 3/64 (4.69%; 95% CI 1.00, 13.69) in group A, 3/14 in group B (21.43%; 95% CI 4.41, 62.57) and 7/67 in group C (10.45%; 95% CI 4.19, 21.53). The adjusted OR for congenital anomalies in group A compared with group C was 0.36 (95% CI 0.06, 2.18). Conclusion We did not detect a pattern in fetal congenital anomalies or evidence of an increased risk in the live-born infants of women filling prescriptions for statins in the first trimester of pregnancy. Conclusions, however, remain uncertain in the absence of data from nonlive births.

Objective To evaluate the benefit of treatment with dalteparin and low-dose aspirin (ASA) in the prevention of obstetric complications in women with inherited thrombophilia. Methods A retrospective chart review identified women who had had at least one pregnancy complicated by severe early-onset preeclampsia, placental abruption, fetal growth restriction (FGR), or fetal death. The following inherited thrombophilias were included: deficiencies of antithrombin, protein C, or protein S, and mutations of factor V Leiden (G1691A), factor II (G20210A), or methylenetetrahydrofolate reductase C677T. Results The records of 43 women with 110 pregnancies were included in the study. Anticoagulant prophylaxis was administered using dalteparin in 13 pregnancies, ASA with dalteparin in 26, and ASA alone in 11. Dalteparin alone and ASA alone showed equivalent effects in preventing preeclampsia and FGR. Combined dalteparin and ASA significantly decreased the risk of preeclampsia (odds ratio [OR] 0.80; 95% confidence intervals [CI] 0.70–0.91, P = 0.001) and FGR (OR 0.70; 95% CI 0.60–0.82, P = 0.001). Conclusion Data from this retrospective cohort study suggest that combined treatment with dalteparin and ASA decreases the risk of preeclampsia by 20% and the risk of FGR by 30% in women with inherited thrombophilia.

Objective (1) To determine the prevalence of antidepressant utilisation before, during, and after pregnancy, (2) to determine switches, dosages, and classes of antidepressant used during pregnancy, and (3) to identify factors associated with their use at the beginning and at the end of pregnancy. Design Retrospective longitudinal cohort. Setting The ‘Medication and Pregnancy’ cohort was used for this study. This cohort was built by the linkage of three administrative databases (Régie de l’Assurance Maladie du Québec [RAMQ], Med-Écho, and l’Institut de la Statistique du Québec). Population All pregnancies occuring in Quebec between January 1 1998 and December 31 2002. Methods Date of entry in the cohort was the first day of gestation. To be eligible for this study, women had to be (1) 15–45 years old at cohort entry and (2) covered by the RAMQ drug plan for at least 12 months before, during, and at least 12 months after pregnancy. Antidepressant users were defined as those receiving at least one antidepressant before, during, or after pregnancy, depending on the time period analysed. Logistic regression models were used to identify factors associated with receiving an antidepressant either at the beginning or at the end of pregnancy. Main outcome measures To determine the prevalence and predictors associated with the use of antidepressants. Results A total of 97 680 women met inclusion criteria. The prevalence rates significantly declined during the first trimester compared with before pregnancy (3.7 versus 6.6%, P < 0.01). During pregnancy, antidepressants were used under the recommended daily dosage 7.7% of the time, and 4.7% of women switched to another class of antidepressant. Factors significantly associated with antidepressant utilisation on the first day of gestation (P < 0.05) were older maternal age, being on welfare, and calendar year; receiving at least six different types of medications other than antidepressants, having at least two different prescribers, having at least three visits to the physician, and having at least one diagnosis of depression in the year before pregnancy also increased the odds of having an antidepressant. Similar predictors were found at the end of pregnancy. Conclusions Our findings indicate that antidepressant utilisation declines once pregnancy is diagnosed. Please cite this paper as: Ramos É, Oraichi D, Rey É, Blais L, Bérard A. Prevalence and predictors of antidepressant use in a cohort of pregnant women. BJOG 2007;114:1055–1064.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 36 - N° 3 - p. 281-286

Background The effect of inhaled short-acting β 2 -agonists (SABAs) on pregnancy outcome, especially hypertensive complications, is not well documented. After the finding of a possible protective association of inhaled SABAs with pregnancy-induced hypertension (PIH) in a previous study, we decided to further investigate their effect on this condition. Objective We sought to determine the effect of inhaled SABA use during pregnancy on the risk of PIH (gestational hypertension, preeclampsia, or eclampsia) in asthmatic women. Methods Three of Quebec's administrative databases were linked to constitute a cohort of asthmatic women who had at least 1 delivery between 1990 and 2000. A nested case-control study was performed using up to 10 control subjects matched to each case patient for the year of conception and gestational age. Statistical analyses considered 22 confounders. Results The cohort was composed of 3505 asthmatic women who had a total of 4593 pregnancies. Three hundred two patients with PIH and 3013 control subjects were identified. Compared with nonuse, inhaled SABA use during pregnancy was significantly associated with a reduced risk of PIH (adjusted rate ratios: >0-3 doses/week, 0.62 (95% CI, 0.44-0.87); > 3-10 doses/week, 0.51 (95% CI, 0.34-0.79); and >10 doses/week, 0.48 (95% CI, 0.30-0.75)). Conclusions To our knowledge, this is the first study reporting that inhaled SABA use during pregnancy is associated with a reduced risk of PIH. Potential explanations include pharmacologic and physiological effects or residual confounding. Clinical implications These results increase the evidence about the safety of inhaled SABAs in this population, although they should not undervalue the importance of maintaining good control of asthma symptoms.

BACKGROUND: Conflicting findings with regard to the teratogenic risks of first trimester use of paroxetine have prompted the FDA, Health Canada, and the manufacturer of the drug to issue warnings against its use during pregnancy. Given that untreated depression during pregnancy can lead to deleterious effect on the mother and her unborn fetus, data on the relationship between the dose and the range of malformations is warranted. This study attempts to quantify the association between first trimester exposure to paroxetine and congenital cardiac malformations, adjusting for possible confounders, and to quantify the dose–response relationship between paroxetine use and cardiac defects. METHODS: The Medication and Pregnancy registry was used. This population-based registry was built by linking three administrative databases (RAMQ, Med-Echo, and ISQ), and includes all pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of entry in the registry is the date of the first day of the last menstrual period. To be eligible for this study, women had to: 1) be 15–45 years of age at entry; 2) be covered by the RAMQ drug plan ≥12 months before and during pregnancy; 3) be using only one type of antidepressant during the first trimester; and 4) have a live birth. Two nested case-control studies were carried out comparing the prevalence of paroxetine use in the first trimester of pregnancy to the prevalence of other antidepressant exposures during the same time period. Cases were defined as: 1) any major malformations; or 2) any cardiac malformations diagnosed in the first year of life; controls were defined as no major or minor malformations. Multivariate logistic regression techniques were used to analyze data. RESULTS: Among the 1,403 women meeting inclusion criteria, 101 infants with major congenital malformations were identified; 24 had cardiac malformations. Adjusting for possible confounders, the use of paroxetine (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 0.49–3.92), and the use of other SSRIs (OR = 0.89, 95% CI = 0.28–2.84) during the first trimester of pregnancy did not increase the risk of congenital cardiac malformations compared with the use of non-SSRI antidepressants. When considering the dose, however, a dose–response relationship was observed, thus women exposed to >25 mg/day of paroxetine during the first trimester of pregnancy were at increased risk of having an infant with major congenital malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17), or major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42). CONCLUSIONS: Gestational exposure to paroxetine is associated with major congenital malformations and major cardiac malformations for only first trimester exposure above 25 mg/day. Birth Defects Res (Part B). © 2006 Wiley-Liss, Inc.

SummaryLow-molecular-weight heparin (LMWH) is increasingly being used for prophylaxis of venous thromboembolism (VTE) and prevention of pregnancy associated morbidity in pregnant women with thrombophilia. We sought to determine if the administration of prophylactic doses of LMWH downregulates coagulation activation in high risk pregnant women with thrombophilia. This sub-study was planned as part of a randomized open label controlled trial (Thrombophilia in Pregnancy Prophylaxis Study[TIPPS])in which patients at high risk of pregnancy complications with confirmed thrombophilia are randomized to receive either dalteparin (5,000 units/day until 20 weeks then 5,000 units q12h until 37 weeks or onset of labor) or no treatment. Blood samples were collected at baseline, day 7–9 (after starting study drug), week 20 (before increasing study drug), week 36 (prior to stopping study drug) and at the time of admission to the labor and delivery unit. Samples were not drawn at fixed times in relation to drug injection. These samples were analyzed for levels of thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1.2), D-dimer and anti-Xa activity. Generalized linear mixed models were used for statistical analysis and model results were controlled for age, smoking status, type of thrombophilia and predisposing risk factors. The effect of dalteparin onTAT levels was defined as the primary outcome. Of 198 patients eligible, 114 were enrolled in TIPPS. Ninety-one were eligible for the TIPPS coagulation activation sub-study and randomized. Thirty-nine patients were analyzed in the treatment group (dalteparin) and 46 patients in the control group (no intervention). Levels of coagulation activation factors F1.2, TAT and D-dimer increased significantly throughout pregnancy in both groups (p