Ruth Rennicks White

A history of preeclampsia identifies women who have underlying cardiovascular risk factors

OBJECTIVE The objective of this study was to prospectively assess physical and biochemical cardiovascular risk markers in women who had developed preeclampsia (PE) at 1 year postpartum. STUDY DESIGN Following an overnight fast, previously PE (n = 70) and normotensive women (n = 70) had weight and blood pressure recorded and levels of morning blood for insulin, glucose, C-reactive protein, lipids, cholesterol, and urine for microalbumin and creatinine measured. Body mass index, homeostatic model assessment index, and incidence of metabolic syndrome were determined. RESULTS At 1 year postpartum, markers of cardiovascular disease were different between the groups. There were also differences in the number of women with abnormal values. Mathematical modeling of cardiovascular event risk suggests that PE increases the risk by 2- to 3-fold; the risk was greatest for women with severe PE. CONCLUSION The development of PE is 1 of the earliest clinically identifiable markers of a womans heightened risk of cardiovascular disease.

Comparison of Carbetocin and Oxytocin for the Prevention of Postpartum Hemorrhage Following Vaginal Delivery: A Double-Blind Randomized Trial

OBJECTIVES To compare the efficacy of a single 100 micro g intramuscular (IM) carbetocin injection, a long-acting oxytocin agonist, to a 2-hour 10 IU oxytocin intravenous (IV) infusion, in reducing the incidence and severity of postpartum hemorrhage (PPH) in women at risk for this condition. METHODS A randomized, double-blind, placebo-controlled study was conducted at 2 hospital centres, including 160 women with at least 1 risk factor for PPH. Eighty-three women received 100 microg carbetocin IM and an IV placebo immediately after placental delivery, while 77 women received placebo IM and oxytocin IV infusion. Complete blood count was collected at entry and 24 hours postpartum. All outcome measures, including the need for additional uterotonic agents or uterine massage, blood loss, and drop in hemoglobin and hematocrit, were analyzed using chi-square, Fisher exact, and Student t tests. RESULTS Population profile and risk factors for PPH were similar for each group. No significant difference was observed in the number of women requiring additional uterotonic medication (12 in each group). However, in the carbetocin group, 36 of the 83 women (43.4%) required at least 1 uterine massage compared to 48 of the 77 women (62.3%) in the oxytocin group (P <.02). Overall, uterotonic intervention was clinically indicated in 37 of the women (44.6%) receiving carbetocin compared to 49 of the women (63.6%) given an IV oxytocin infusion (P <.02). There were no differences in laboratory PPH indicators between the 2 groups.

A comprehensive assessment of outcomes in pregnancies conceived by in vitro fertilization/intracytoplasmic sperm injection.

OBJECTIVE To assess the association between in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) and adverse birth outcomes. STUDY DESIGN Retrospective cohort study involved IVF/ICSI patients who were treated in the Ottawa Fertility Centre from 1996 to 2005 with a viable pregnancy (>20 weeks of gestation) and mothers who conceived naturally. RESULTS Eleven of the 1044 infants conceived with IVF/ICSI (1.1%) and 7 of the 1910 naturally conceived infants (0.4%) had congenital heart defects (P<0.01). Five of the 138 infants (3.6%) born to mothers with a body mass index>30 and conceived by IVF/ICSI had congenital heart defects, compared with none in the 240 infants born to mothers with a body mass index>30 and conceived naturally (P<0.01). CONCLUSION Infants conceived with use of IVF/ICSI have three times as high a risk of a congenital heart defect as naturally conceived infants.

Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia: The Folic Acid Clinical Trial Study

Preeclampsia (PE) is hypertension with proteinuria that develops during pregnancy and affects at least 5% of pregnancies. The Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia: the Folic Acid Clinical Trial (FACT) aims to recruit 3,656 high risk women to evaluate a new prevention strategy for PE: supplementation of folic acid throughout pregnancy. Pregnant women with increased risk of developing PE presenting to a trial participating center between 80/7 and 166/7 weeks of gestation are randomized in a 1 : 1 ratio to folic acid 4.0 mg or placebo after written consent is obtained. Intent-to-treat population will be analyzed. The FACT study was funded by the Canadian Institutes of Health Research in 2009, and regulatory approval from Health Canada was obtained in 2010. A web-based randomization system and electronic data collection system provide the platform for participating centers to randomize their eligible participants and enter data in real time. To date we have twenty participating Canadian centers, of which eighteen are actively recruiting, and seven participating Australian centers, of which two are actively recruiting. Recruitment in Argentina, UK, Netherlands, Brazil, West Indies, and United States is expected to begin by the second or third quarter of 2013. This trial is registered with NCT01355159.

Folic Acid Supplementation in Pregnancy and the Risk of Pre-Eclampsia—A Cohort Study

This prospective cohort study designed to assess the effect of folic acid supplementation in pregnancy on the risk of preeclampsia (PE) took place in Ottawa, ON and Kingston, ON, Canada, from September 1, 2002 to August 31, 2008. Pregnant women, less than 20 weeks gestational age were recruited and delivered in the Ottawa region and the Kingston General Hospital. Demographic characteristics of the study participants and the patterns of supplementation of folic acid were described and occurrence of PE between women with folic acid supplementation during pregnancy and women without were compared. Multiple logistic regression was used in the estimation of the independent effect of supplementation of folic acid. Additional analyses assessing the effect of low RBC and serum folate and dose-response relationship were performed. Analyses were performed in all study participants, and then in high risk and low risk sub-groups, respectively. A total of 7,669 participants were included in the final analysis. Ninety five percent of the study participants were taking folic acid supplementation in early second trimester. The rate of PE was lower in the supplementation group than in the no supplementation group, and the difference was statistically significant in high risk women. Similar patterns of associations were observed in analysis by RBC and serum folate levels and in dose-response analysis. Folic acid supplementation in pregnancy may reduce PE risk in pregnant women, especially in those women with increased risk of developing PE.

Comparison of risk factors and outcomes of gestational hypertension and pre-eclampsia

Background It remains an enigma whether gestational hypertension (GH) and pre-eclampsia (PE) are distinct entities or different spectrum of the same disease. We aimed to compare the risk factors and outcomes between GH and PE. Method A total of 7,633 pregnant women recruited between 12 and 20 weeks of gestation in the Ottawa and Kingston Birth Cohort from 2002 to 2009 were included in the analysis. Cox proportional hazards model was used to identify and compare the risk factors for GH and PE by treating gestational age at delivery as the survival time. Logistic regression model was used to compare outcome. Subgroup analysis was performed for early- and late-onset PE. Results GH and PE shared most risk factors including overweight and obesity, nulliparity, PE history, type 1 and 2 diabetes, and twin birth. Effect size of PE history (RR = 14.1 for GH vs. RR = 6.4 for PE) and twin birth (RR = 4.8 for GH vs. RR = 10.3 for PE) showed substantial difference. Risk factors modified gestational age at delivery in patients with GH and PE in similar pattern. Subgroup analysis showed that early- and late-onset PE shared some risk factors with different effect sizes, whereas folic acid supplementation showed protective effect for early-onset PE only. PE was strongly associated with several adverse outcomes including cesarean section, placental abruption, small for gestational age, preterm birth, and 5 min Apgar score < 7, whereas GH was associated with increased risk of preterm birth only. Conclusions GH and PE shared common risk factors. Differences in effect sizes of risk factors and outcomes indicate that the conditions may have different pathophysiology and mechanism.

Serum and red-blood-cell folate demonstrate differential associations with BMI in pregnant women.

OBJECTIVE To examine the association between BMI and folate concentrations in serum and red blood cells (RBC) in pregnant women. DESIGN A cross-sectional comparison of folate concentrations in serum and RBC sampled simultaneously from the same individual. SETTING The Ottawa Hospital and Kingston General Hospital, Ontario, Canada. SUBJECTS Pregnant women recruited between 12 and 20 weeks of gestation. RESULTS A total of 869 pregnant women recruited from April 2008 to April 2009 were included in the final analysis. Serum folate was inversely associated and RBC folate positively associated with BMI, after adjusting for folic acid supplementation, age, gestational age at blood sample collection, race, maternal education, annual income, smoking and MTHFR 677C→T genotype. In stratified analyses, this differential association was significant in women with the MTHFR CC variant. In women with the CT and TT variants, the differential associations were in the same direction but not significant. Folic acid supplementation during pregnancy did not alter the differential association of BMI with serum and RBC folate concentration. This indicates that the current RBC folate cut-off approach for assessing risk of neural tube defects in obese women may be limited. CONCLUSIONS BMI is inversely associated with serum folate and positively associated with RBC folate in pregnant women, especially for those with the MTHFR CC variant.

A Randomized Controlled Trial of Innovative Postpartum Care Model for Mother-Baby Dyads.

Objective To evaluate the efficacy, safety, and maternal satisfaction of a newly established integrative postpartum community-based clinic providing comprehensive support for mothers during the first month after discharge from the hospital. Our primary interests were breastfeeding rates, readmission and patient satisfaction. Methods A randomized controlled trial was conducted in Ottawa, Canada, where 472 mothers were randomized via a 1:2 ratio to either receive standard of care (n = 157) or to attend the postpartum breastfeeding clinic (n = 315). Outcome data were captured through questionnaires completed by the participants at 2, 4, 12 and 24 weeks postpartum. Unadjusted and adjusted logistic regression models were conducted to determine the effect of the intervention on exclusive breastfeeding at 12 weeks (primary outcome). Secondary outcomes included breastfeeding rate at 2, 4 and 24 weeks, breastfeeding self-efficacy scale, readmission rate, and satisfaction score. Results More mothers in the intervention group (n = 195, 66.1%) were exclusively breastfeeding at 12 weeks compared to mothers in the control group (n = 81, 60.5%), however no statistically significant difference was observed (OR = 1.28; 95% CI:0.84–1.95)). The rate of emergency room visits at 2 weeks for the intervention group was 11.4% compared to the standard of care group (15.2%) (OR = 0.69; 95% CI: 0.39–1.23). The intervention group was significantly more satisfied with the overall care they received for breastfeeding compared to the control group (OR = 1.96; 95% CI: 3.50–6.88)). Conclusion This new model of care did not significantly increase exclusive breastfeeding at 12 weeks. However, there were clinically meaningful improvements in the rate of postnatal problems and satisfaction that support this new service delivery model for postpartum care. A community-based multidisciplinary postpartum clinic is feasible to implement and can provide appropriate and highly satisfactory care to mother-baby dyads. This model of care may be more beneficial in a population that is not already predisposed to breastfeed. Trial Registration ClinicalTrials.gov NCT02043119

The Effect of Very Advanced Maternal Age on Maternal and Neonatal Outcomes: A Systematic Review

OBJECTIVE To summarize information on the maternal and perinatal outcomes among pregnant women with a maternal age greater or equal to 45 years old compared with women with a maternal age of less than 45. METHODS A comprehensive systematic search of online databases from January 1946 through June 2015 was completed. The maternal outcomes were: fetal loss, preterm birth, full-term birth, complications of pregnancy, the type of delivery, and periconception hemorrhage. The fetal outcomes were: intrauterine growth restriction/LGA, fetal anomalies, APGAR score, and neonatal death. RESULTS Twenty articles were included in the systematic review and 15 included in the meta-analysis. There was a 2.60 greater likelihood of fetal loss (I2 = 99%). Newborns of women of a very advanced maternal age were 2.49 more likely to have a concerning 5-minute APGAR score. Very advanced maternal age women had a 3.32 greater likelihood of pregnancy complications (I2 = 91%). There was a 1.96 greater likelihood of preterm birth at very advanced maternal age (I2 = 91%) and a 4 times greater likelihood of having to deliver through Caesarean section (I2 = 97%). CONCLUSION This systematic review showed an increased risk of adverse maternal and perinatal outcomes. The large amount of heterogeneity among most outcomes that were investigated suggest results must be interpreted with caution.

Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial

Abstract Objective To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35. Design Randomised, phase III, double blinded international, multicentre clinical trial. Setting 70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK). Participants 2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses. Intervention Eligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation. Main outcome measure The primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks’ gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). Results Pre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes. Conclusion Supplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition. Trial registration Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.