Furosemide to lower antenatal severe hypertension: a randomized placebo-controlled trial.

BACKGROUND: Hypertensive disorders of pregnancy are a leading cause of perinatal morbidity, and timely treatment of severely elevated blood pressure is recommended to prevent serious sequelae. In acute hypertension marked by increased blood volume, it is unknown whether diuretics used as an adjunct to antihypertensive medications lead to more effective blood pressure control. OBJECTIVE: This study aimed to evaluate whether the addition of intravenous furosemide to first-line antihypertensive agents reduces systolic blood pressure in acute-onset, severe antenatal hypertension with wide (≥60 mm Hg) pulse pressure. STUDY DESIGN: In this double-blinded randomized trial, participants received 40 mg of intravenous furosemide or placebo in addition to a first-line antihypertensive agent. The primary outcome was mean systolic blood pressure during the first hour after intervention. Secondary outcomes included corresponding diastolic blood pressure; systolic blood pressure, diastolic blood pressure, and pulse pressure at 2 hours after intervention; total reduction from qualifying blood pressure; duration of blood pressure control; need for additional antihypertensive doses within 1 hour; and electrolytes and urine output. A sample size of 35 participants per group was planned to detect a 15-mm Hg difference in blood pressure. RESULTS: Between January 2021 and March 2022, 65 individuals were randomized: 33 to furosemide and 32 to placebo. Baseline characteristics were similar between the groups. There was no difference in the primary outcome of mean 1-hour systolic blood pressure (147 [14.8] vs 152 [13.8] mm Hg; P=.200). We found a reduction in 2-hour systolic blood pressure (139 [18.5] vs 154 [18.4] mm Hg; P=.007) and a decrease in 2-hour pulse pressure (55 [12.5] vs 67 [15.1]; P=.003) in the furosemide group. Subgroup analysis according to hypertension type showed a significant reduction in 2-hour systolic blood pressure and 2-hour pulse pressure among patients with new-onset hypertension, but not among those with preexisting hypertension. Urine output was greater in the furosemide group, with no difference in electrolytes and creatinine before and after intervention. CONCLUSION: Intravenous furosemide in conjunction with a first-line antihypertensive agent did not significantly reduce systolic blood pressure in the first hour after administration. However, both systolic blood pressure and pulse pressure at 2 hours were decreased in the furosemide group. These findings suggest that a 1-time dose of intravenous furosemide is a reasonable adjunct to achieve blood pressure control, particularly in patients in whom increased volume is suspected.

Adherence to Mediterranean diet impacts gastrointestinal microbial diversity throughout pregnancy.

BACKGROUND: Consumption of a diet with high adherence to a Mediterranean diet pattern (MDP) has been associated with a favorable gastrointestinal tract (GIT) microbiome. A healthy GIT microbiome in pregnancy, as defined by increased alpha diversity, is associated with lower chance of adverse perinatal outcomes. This study aimed to evaluate the impact of adherence to an MDP on GIT microbial diversity longitudinally throughout pregnancy. METHODS: Adherence to MDP was scored by the Alternate Mediterranean (aMED) Diet Quality Score, after being applied to a validated Food Frequency Questionnaire. Association of aMED Scores with GIT alpha diversity profiles were compared linearly and across time using a linear mixed model, including covariates of age, body mass index (BMI), ethnicity, and parity. RESULTS: Forty-one participants of Filipino, Japanese, Native Hawaiian, and Non-Hispanic White descent provided dietary information and microbiome samples during each trimester of pregnancy. Alpha diversity profiles changed over gestation, with decreased microbial diversity in the third trimester. aMED scores positively correlated with Chao1 Index and Observed Species Number (r = 0.244, p = 0.017, and r = 0.233, p = 0.023, respectively). The strongest association was detected in the third trimester (Chao 1: r = 0.43, p = 0.020, Observed Species Number: r = 0.41, p = 0.026). Participants with higher aMED scores had higher relative abundance of Acidaminoacaeae at the family level (p = 0.0169), as well as higher abundance of several species known to increase production of short chain fatty acids within the GIT. CONCLUSIONS: Adherence to MDP pattern is associated with increased maternal GIT microbial diversity, and promotes the abundance of bacteria that produce short chain fatty acids. Increased consumption of fruits, vegetables and legumes with low red meat consumption were key components driving this association. The effect of nutrition however, was less of an effect than pregnancy itself. Further studies are needed to determine if adherence to a Mediterranean diet translates not only into microbial health, but also into reduced risk of adverse pregnancy outcomes.

Investigating Mechanisms of Stillbirth in the Setting of Prenatal Substance Use.

INTRODUCTION: Intrauterine fetal demise affects between 0.4-0.8% of pregnancies worldwide. This significant adverse pregnancy outcome continues to be poorly understood. In utero exposure to substances increases the risk of stillbirth to varying degrees according to the type of substance and degree of exposure. The aim of this qualitative narrative review is to investigate common biologic relationships between stillbirth and maternal substance use. METHODS: A PubMed literature search was conducted to query the most commonly used substances and biologic mechanisms of stillbirth. Search terms included "stillbirth," "intrauterine fetal demise," "placenta," "cocaine," "tobacco," "alcohol," "methamphetamines," "opioids/ opiates," and "cannabis." RESULTS: There are very few studies identifying a direct link between substance use and stillbirth. Several studies demonstrate associations with placental lesions of insufficiency including poor invasion, vasoconstriction, and sequestration of toxic substances that inhibit nutrient transport. Restricted fetal growth is the most common finding in pregnancies complicated by all types of substance use. DISCUSSION: More research is needed to understand the biologic mechanisms of stillbirth. Such knowledge will be foundational to understanding how to prevent and treat the adverse effects of substances during pregnancy.

Urine Protein/Creatinine Ratios during Labor: A Prospective Observational Study.

PURPOSE: To evaluate the utility of urine protein/creatinine ratio (uPCR) measurements among healthy parturients at term we performed a prospective cohort study at a community teaching hospital. METHODS: Serial urine samples were collected. Ninety-three women contributed 284 urine samples. uPCRs were determined. Multiple imputation and paired sampled analysis was performed when appropriate. RESULTS: Two-thirds (63/93) of women had at least one measured uPCR ≥ 0.3. One-third (31/93) had a uPCR ≥ 0.3 at admission, including 39.1% (9/23) of women not in labor. Median (IQR) uPCRs increased during labor and after delivery: latent phase/no labor, 0.15 (0.06-0.32); active phase, 0.29 (0.10-0.58); early postpartum, 0.45 (0.18-1.36) (all p < 0.04). Median uPCRs were significantly < 0.3 in the latent phase and significantly > 0.3 in the immediate postpartum period (p < 0.01). Women who labored before cesarean delivery had the highest early postpartum uPCRs: median (IQR) 1.16 (0.39-1.80). A negative urine dipstick protein result did not exclude uPCR ≥ 0.3. uPCRs were similar when compared by method of urine collection. CONCLUSION: uPCR ≥ 0.3 is common among healthy women with uncomplicated pregnancies at term. uPCR increases during labor and is not a reliable measure of pathologic proteinuria at term or during the peripartum period.