Marijuana use and pregnancy outcomes among women with hypertension in pregnancy.

BACKGROUND: Marijuana has vasoconstrictive properties and its use has been associated with increased blood pressure in the general population. Yet, there are limited data on marijuana use and adverse outcomes among women with hypertension in pregnancy, even though these disorders are associated with severe maternal and fetal morbidity and mortality. Since marijuana is currently the most commonly used illicit drug in pregnancy, there is an urgent need to better understand the potential association between marijuana use and hypertension in pregnancy. OBJECTIVE: To determine the adverse prenatal effects of marijuana use in women with hypertension in pregnancy. STUDY DESIGN: We conducted a retrospective cohort study among individuals with hypertension in pregnancy that delivered ≥23 weeks' gestation at Oregon Health & Science University (October 2013-September 2018). The primary exposure assessed was marijuana use, identified by chart review of documented patient self-report or positive urine toxicology screen. Individuals were stratified into two groups by marijuana use: use during pregnancy versus never used. Primary outcomes included composite adverse maternal and neonatal outcomes. Secondary outcomes included individual maternal outcomes, rarer neonatal outcomes and severe features of preeclampsia. Differences were analyzed by Fisher's exact, t-test, and logistic regression. Significance was determined by alpha = 0.05 for primary outcomes and alpha = 0.01 for secondary outcomes. RESULTS: From 11,825 deliveries, 1,613 (13.6%) were classified with hypertension in pregnancy. A total of 117 individuals (7.3%) used marijuana during pregnancy, 1,110 (68.2%) had never used marijuana and 396 (24.6%) had unknown marijuana use and were excluded, leaving 1,217 individuals in this analysis. Women using marijuana in pregnancy were more likely to be younger, non-Hispanic White, publicly insured and using other substances compared to women who did not use marijuana. There were no differences in the overall distribution of hypertensive disorders, including preeclampsia with severe features, in women who used marijuana versus those who did not (p = .80). In multivariable analyses, after adjusting for maternal factors and other substance use, marijuana use was not associated with adverse maternal (aOR 1.23, 95% CI 0.43-3.50, p = .69) or neonatal (aOR 0.90, 95% CI 0.28-2.89, p = .86) outcomes. CONCLUSIONS: Marijuana use in pregnancy was not associated with maternal or neonatal outcomes or worsened hypertensive disease among women with hypertension in pregnancy after adjusting for maternal characteristics, including use of other substances. Our data highlight the need to consider use of other substances when evaluating the association between marijuana use in pregnancy and adverse pregnancy outcomes.

Implementation of a protocol for management of antepartum iron deficiency anemia: a prospective cohort study.

BACKGROUND: In randomized trials, antepartum intravenous iron sucrose is effective at improving predelivery hemoglobin in iron deficiency anemia. Yet, there is a gap between this knowledge and its implementation into care. OBJECTIVE: We aimed to determine if the implementation of a standardized protocol for the management of antepartum anemia outside of a clinical trial improves intravenous iron sucrose utilization and clinical outcomes. STUDY DESIGN: We performed a prospective cohort study evaluating the incorporation of an anemia protocol into routine clinical care for women with antepartum hemoglobin <11.0 g/dL. Our protocol, developed with multidisciplinary stakeholders, included (1) serial third trimester hemoglobin assessment, (2) oral iron supplementation for antepartum hemoglobin 9.5-11 g/dL, and (3) antepartum intravenous iron sucrose use (300 mg weekly for 3 weeks) for hemoglobin <9.5 g/dL. We compared 6-months preimplementation (January 2018 to June 2018) to 6-months postimplementation (January 2019 to June 2019). The outcomes evaluated were antepartum intravenous iron sucrose utilization, the number of intravenous iron sucrose dosages, predelivery hemoglobin, and blood transfusion. RESULTS: A total of 1423 women were included (pre=778; post=645) without significant baseline differences. The antepartum hemoglobin nadir was no different between the groups (pre: 10.2; interquartile range [9.6-10.6] vs post: 10.2; interquartile range [9.6-10.6]; P=.77). The implementation of a standardized protocol for the management of antepartum anemia was associated with 80% increased odds of receiving intravenous iron sucrose than the preimplementation group (pre: 4.8% vs post: 8.2%, P=.008; odds ratio, 1.79; 95% confidence interval, [1.16-2.77]). The implementation of a standardized protocol for the management of antepartum iron deficiency anemia was also associated with higher hemoglobin at admission for delivery (pre: 10.9; interquartile range [10.1-11.6] vs post: 11.0; interquartile range [10.3-11.7], P=.048). There were no significant differences between the groups in blood product transfusion (pre: 7.1% vs post: 5.1%, P=.13). CONCLUSION: Implementation of a standardized antepartum anemia protocol is associated with increased intravenous iron sucrose utilization and improvement in predelivery hemoglobin.

Association between insurance type and pregnancy outcomes in women diagnosed with hypertensive disorders of pregnancy.

Objective: Hypertension in pregnancy is associated with adverse maternal and neonatal outcomes. Previous studies have demonstrated disparities in the risk of preeclampsia based on race, educational attainment, census tract income level and household income. Yet, data on the association of insurance type, classification of hypertension in pregnancy and outcomes have not been well described. We sought to compare outcomes in women with hypertensive disorders of pregnancy, by private versus public insurance.Study design: This was a retrospective cohort study of subjects with a hypertensive disorder of pregnancy that delivered ≥23-week gestation at Oregon Health & Science University (October 2013-December 2017). The cohort began with the 2013 American College of Obstetricians and Gynecologists Executive Summary on Hypertension in Pregnancy, which advised surveillance for severe features of disease in women with hypertension. Utilizing ICD-9 and ICD-10 discharge codes, followed by individual chart review, subjects were stratified into two groups by insurance status: Medicaid (public insurance), or individual or group health insurance (private insurance). As primary outcomes, we assessed severe features of preeclampsia, adverse maternal or neonatal outcomes (composite), and final hypertensive diagnosis: (i) chronic hypertension; (ii) gestational hypertension; (iii) preeclampsia without severe features and, (iv) preeclampsia with severe features. Differences in demographic and outcome data were analyzed by chi-square, t-test, and logistic regression.Results: Among 10 132 deliveries, 1335 (13.2%) were delivered with a hypertensive disorder of pregnancy. Medicaid covered 54.1% (722) of these deliveries; 44.1% (589) were covered by private insurance, and 1.8% (24) had unknown insurance. There was a similar percentage of subjects with Medicaid or private insurance in each hypertensive group (p = .08). However, compared to subjects with private insurance, those with Medicaid had more severe blood pressure (BP) elevations (systolic BP ≥160 mmHg, p = .001) and more cases of eclampsia (p = .04), while neonates of subjects with Medicaid had more intensive care unit admissions (p = .02), and preterm births (p < .001). The association between Medicaid insurance and severe BP elevation, or adverse neonatal outcomes, persisted after multivariable adjustment.Conclusion: Medicaid was not associated with a particular hypertensive disorder in pregnancy, yet those with Medicaid experienced more severe BP elevations and higher rates of adverse neonatal outcomes. More research is needed to understand potential risk factors and ways to improve outcomes for those with publicly funded insurance.

Assessment of blood-brain barrier integrity and neuroinflammation in preeclampsia.

BACKGROUND: Although blood-brain barrier integrity is intact under normal pregnancy conditions, animal studies suggest that blood-brain barrier impairment occurs in preeclampsia. Yet, human data are limited, and the integrity of the blood-brain barrier has not been assessed in women with preeclampsia. OBJECTIVE: We sought to test the hypothesis that the integrity of the blood-brain barrier is impaired and that neuroinflammation is increased in women with preeclampsia. STUDY DESIGN: We performed an observational case-control study in pregnant women >24 weeks gestation who underwent spinal anesthesia for elective cesarean delivery or combined spinal epidural analgesia for labor. Cases were women with preeclampsia, and control subjects were women with either healthy pregnancy, chronic hypertension, or gestational hypertension. Paired samples of blood, urine, and cerebrospinal fluid were collected from each subject before delivery. We measured albumin, C5a, C5b-9, tumor necrosis factor-α, and interleukin-6 concentrations in plasma and cerebrospinal fluid, and albumin, C5a, and C5b-9 concentrations in urine, using colorimetric or enzyme-linked immunosorbent assays. The ratio of albumin in cerebrospinal fluid to plasma (Qalb) was used as a surrogate for maternal blood-brain barrier integrity. Cerebrospinal fluid concentrations of C5a, C5b-9, tumor necrosis factor-α, and interleukin-6 were used as surrogate markers of neuroinflammation. Differences in Qalb and cerebrospinal fluid protein concentrations between groups were assessed by nonparametric test of medians. RESULTS: Forty-eight subjects were enrolled, which included 16 cases with preeclampsia, 16 control subjects with healthy pregnancy, and 16 control subjects with either chronic or gestational hypertension. Qalb values were not increased in preeclampsia cases compared with healthy or hypertensive control subjects (Qalb median, 3.5 [interquartile range, 2.9-5.1] vs 3.9 [interquartile range, 3.0-4.8] vs 3.9 [interquartile range, 3.0-4.8]; P=.78]. Moreover, Qalb values were not increased in the subset of women with preeclampsia with severe features (n=8) compared with those without severe features (n=8; Qalb median, 3.5 [interquartile range, 3.3-4.9] vs 3.7 [interquartile range, 2.3-5.5]; P=.62]. Cerebrospinal fluid concentrations of C5a, C5b-9, tumor necrosis factor-α and interleukin-6 were not increased in cases of preeclampsia, compared with control subjects with either healthy pregnancy, chronic hypertension, or gestational hypertension (P>.05, all comparisons). In contrast to the negative findings in cerebrospinal fluid, plasma concentrations of both C5b-9 and interleukin-6 and urine concentrations of C5a and C5b-9 were increased in cases of preeclampsia. CONCLUSION: Through measurements of albumin, complement proteins, and cytokines in paired samples of blood and cerebrospinal fluid at the time of delivery, we found no evidence of blood-brain barrier impairment or neuroinflammation in preeclampsia. Larger studies that will investigate a wider range of proteins are suggested to validate our findings.