Evelyne Rey

Thrombophilic disorders and fetal loss: a meta-analysis

BACKGROUND Our aim was to assess the strength of the controversial association between thrombophilia and fetal loss, and to examine whether it varies according to the timing or definition of fetal loss. METHODS We searched Medline and Current Contents for articles published between 1975 and 2002 and their references with terms denoting recurrent fetal and non-recurrent fetal loss combined with various thrombophilic disorders. We included in our meta-analysis case-control, cohort, and cross-sectional studies published in English, the methodological quality of which was rated as moderate or strong. Pooled odds ratios (OR) with 95% CI were generated by random effects models with Cochrane Review Manager software. FINDINGS We included 31 studies. Factor V Leiden was associated with early (OR 2.01, 95% CI 1.13-3.58) and late (7.83, 2.83-21.67) recurrent fetal loss, and late non-recurrent fetal loss (3.26, 1.82-5.83). Exclusion of women with other pathologies that could explain fetal loss strengthened the association between Factor V Leiden and recurrent fetal loss. Activated protein C resistance was associated with early recurrent fetal loss (3.48, 1.58-7.69), and prothrombin G20210A mutation with early recurrent (2.56, 1.04-.29) and late non-recurrent (2.30, 1.09-4.87) fetal loss. Protein S deficiency was associated with recurrent fetal loss (14.72, 0.99-218.01) and late non-recurrent fetal loss (7.39, 1.28-42.63). Methylenetetrahydrofolate mutation, protein C, and antithrombin deficiencies were not significantly associated with fetal loss. INTERPRETATION The magnitude of the association between thrombophilia and fetal loss varies, according to type of fetal loss and type of thrombophilia.

The prognosis of pregnancy in women with chronic hypertension

OBJECTIVE Our purpose was to assess pregnancy outcomes in women with chronic hypertension from a population with a perinatal mortality of 12 in 1000. STUDY DESIGN A longitudinal cohort study was performed between 1987 and 1991 in Montreal, Quebec, Canada. RESULTS A total of 337 pregnancies in 298 women with chronic hypertension were followed up. The following outcomes were statistically more frequent in the hypertensive women than in the general population (p < 0.01): perinatal mortality (45/1000 vs 12/1000), preeclampsia (21.2% vs 2.3%), premature delivery (34.4% vs 15.0%), small-for-gestational-age newborns (15.5% vs 6.3%), primary cesarean sections (29.6% vs 14.2%), and gestational diabetes (33.1% vs 12.0%). Preeclampsia was associated with prematurity, small-for-gestational-age newborns, cesarean section, and neonatal complications. Even without superimposed preeclampsia hypertensive women had significantly higher frequencies of perinatal death (29/1000) and small-for-gestational-age newborns (10.5%) than did normotensive women (p < 0.05). CONCLUSIONS In our population women with chronic hypertension with or without superimposed preeclampsia, have a higher incidence of perinatal death and small-for-gestational-age newborns than the general population does.

Less-Tight versus Tight Control of Hypertension in Pregnancy

BACKGROUND The effects of less-tight versus tight control of hypertension on pregnancy complications are unclear. METHODS We performed an open, international, multicenter trial involving women at 14 weeks 0 days to 33 weeks 6 days of gestation who had nonproteinuric preexisting or gestational hypertension, office diastolic blood pressure of 90 to 105 mm Hg (or 85 to 105 mm Hg if the woman was taking antihypertensive medications), and a live fetus. Women were randomly assigned to less-tight control (target diastolic blood pressure, 100 mm Hg) or tight control (target diastolic blood pressure, 85 mm Hg). The composite primary outcome was pregnancy loss or high-level neonatal care for more than 48 hours during the first 28 postnatal days. The secondary outcome was serious maternal complications occurring up to 6 weeks post partum or until hospital discharge, whichever was later. RESULTS Included in the analysis were 987 women; 74.6% had preexisting hypertension. The primary-outcome rates were similar among 493 women assigned to less-tight control and 488 women assigned to tight control (31.4% and 30.7%, respectively; adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.77 to 1.35), as were the rates of serious maternal complications (3.7% and 2.0%, respectively; adjusted odds ratio, 1.74; 95% CI, 0.79 to 3.84), despite a mean diastolic blood pressure that was higher in the less-tight-control group by 4.6 mm Hg (95% CI, 3.7 to 5.4). Severe hypertension (≥160/110 mm Hg) developed in 40.6% of the women in the less-tight-control group and 27.5% of the women in the tight-control group (P<0.001). CONCLUSIONS We found no significant between-group differences in the risk of pregnancy loss, high-level neonatal care, or overall maternal complications, although less-tight control was associated with a significantly higher frequency of severe maternal hypertension. (Funded by the Canadian Institutes of Health Research; CHIPS Current Controlled Trials number, ISRCTN71416914; ClinicalTrials.gov number, NCT01192412.).

Screening for preeclampsia using first-trimester serum markers and uterine artery Doppler in nulliparous women

OBJECTIVE To evaluate the screening accuracy of pregnancy hypertensive disorders by maternal serum biomarkers and uterine artery Doppler in the first trimester. STUDY DESIGN Prospectively enrolled nulliparous women had uterine artery Doppler and serum measured at 11-13 weeks. Maternal characteristics, uterine artery Doppler, and serum placental biomarkers (pregnancy-associated plasma protein-A, Inhibin-A, placental protein 13, A disintegrin and metalloprotease 12, free β-hCG, placental growth factor) were recorded. RESULTS Among 893 women, 20 (2.2%) had gestational hypertension developed and 40 (4.5%) had preeclampsia developed, including 9 (1.0%) early-onset preeclampsia and 16 (1.8%) severe preeclampsia. A combined screening model with clinical characteristics, pregnancy-associated plasma protein-A, Inhibin-A, and placental growth factor could detect 75% of early-onset preeclampsia at a 10% false-positive rate. After adjustment for clinical variables, uterine artery Doppler, placental protein 13, and A disintegrin and metalloprotease 12 did not improve the diagnostic accuracy. CONCLUSION A combination of clinical characteristics and first-trimester maternal serum biomarkers (pregnancy-associated plasma protein-A, Inhibin-A, and placental growth factor) provides an accurate screening for early-onset preeclampsia in nulliparous women.

Use of inhaled corticosteroids during pregnancy and risk of pregnancy induced hypertension: nested case-control study

Abstract Objective To determine whether the use of inhaled corticosteroids during pregnancy increases the risk of pregnancy induced hypertension and pre-eclampsia among asthmatic women. Design Nested case-control study. Setting Three administrative health databases from Quebec: RAMQ, MED-ECHO, and Fichier des événements démographiques. Participants 3505 women with asthma, totalling 4593 pregnancies, between 1990 and 2000. Main outcome measuresPregnancy induced hypertension and pre-eclampsia. Results 302 cases of pregnancy induced hypertension and 165 cases of pre-eclampsia were identified. Use of inhaled corticosteroids from conception until date of outcome was not associated with an increased risk of pregnancy induced hypertension (adjusted odds ratio 1.02, 95% confidence interval 0.77 to 1.34) or pre-eclampsia (1.06, 0.74 to 1.53). No significant dose-response relation was observed between inhaled corticosteroids and pregnancy induced hypertension or pre-eclampsia. Oral corticosteroids were significantly associated with the risk of pregnancy induced hypertension (adjusted odds ratio 1.57, 1.02 to 2.41), and a trend was seen for pre-eclampsia (1.72, 0.98 to 3.02). Conclusion No significant increase of the risk of pregnancy induced hypertension or pre-eclampsia was detected among users of inhaled corticosteroids during pregnancy, while markers of uncontrolled and severe asthma were found to significantly increase the risks of pregnancy induced hypertension and pre—eclampsia.

Risk of congenital anomalies in pregnant users of statin drugs

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.

Meta-analysis of low molecular weight heparin to prevent recurrent placenta-mediated pregnancy complications

A 35-year-old woman with recurrent severe placenta-mediated pregnancy complications in her 2 pregnancies asks: Will low-molecular-weight heparin help prevent recurrent placenta-mediated pregnancy complications in my next pregnancy? We performed a meta-analysis of randomized controlled trials (RCTs) comparing low-molecular-weight heparin (LMWH) vs no LMWH for the prevention of recurrent placenta-mediated pregnancy complications. We identified six RCTs that included a total of 848 pregnant women with prior placenta-mediated pregnancy complications. The primary outcome was a composite of pre-eclampsia (PE), birth of a small-for-gestational-age (SGA) newborn (<10th percentile), placental abruption, or pregnancy loss >20 weeks. Overall, 67 (18.7%) of 358 of women being given prophylactic LMWH had recurrent severe placenta-mediated pregnancy complications compared with 127 (42.9%) of 296 women with no LMWH (relative risk reduction, 0.52; 95% CI, 0.32 to 0.86; P = .01; I(2), 69%, indicating moderate heterogeneity). We identified similar relative risk reductions with LMWH for individual outcomes, including any PE, severe PE, SGA <10th percentile, SGA <5th percentile, preterm delivery <37 weeks, and preterm delivery <34 weeks with minimal heterogeneity. LMWH may be a promising therapy for recurrent, especially severe, placenta-mediated pregnancy complications, but further research is required.

Nausea and vomiting of pregnancy: what about quality of life?

Objective  The objective of this study was to determine the impact of nausea and vomiting of pregnancy (NVP) and other determinants on generic and NVP‐specific health‐related quality of life (QOL) in the first trimester of pregnancy.

Prevalence and predictors of antidepressant use in a cohort of pregnant women.

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.

Use of inhaled corticosteroids during the first trimester of pregnancy and the risk of congenital malformations among women with asthma

Aim: To investigate whether the maternal use of different doses of inhaled corticosteroids (ICSs) during the first trimester of pregnancy for the treatment of asthma increases the risk of congenital malformations in the offspring. Methods: From the linkage of three administrative Canadian databases, a cohort of 4561 pregnancies from women with asthma who delivered between 1990 and 2000 was reconstructed. A two-stage sampling cohort design was used to acquire additional data from the woman’s medical chart. Cases of congenital malformation were identified from the medical services database or the hospital database. Using refill patterns of medications, the average daily dose of ICSs used during the first trimester was calculated and categorised as follows: 0, 1–500, 500–1000 and >1000 μg/day in beclomethasone–chlorofluorocarbon equivalent. A Generalized Estimation Equation model was used to estimate the adjusted odds ratio of congenital malformation as a function of ICS daily dose. All analyses were performed for all malformations and major malformations separately. Results: Within the cohort 418 babies were identified with a congenital malformation (9.2%), 278 of which had a major malformation. About 40% of women used ICSs during the first trimester, but only 5.3% of women used >500 μg/day. The adjusted odds ratio (95% CI) for all malformations associated with the use of ICSs during the first trimester was: 0.77 (0.53 to 1.13) for 1–500, 0.41 (0.19 to 0.92) for 501–1000 and 1.00 (0.42 to 2.36) for >1000 μg/day. The corresponding figures for major malformations were 0.90 (0.64 to 1.24), 0.56 (0.22 to 1.43) and 1.67 (0.56 to 5.03). Conclusion: This study adds evidence to the safety of ICSs for the treatment of asthma during pregnancy, with regard to the likelihood of congenital malformation.