Non-targeted urinary metabolomics in pregnancy and associations with fetal growth restriction.

Our objective was to identify metabolites associated with fetal growth restriction (FGR) by examining early and late pregnancy differences in non-targeted urinary metabolites among FGR cases and non-FGR controls. An exploratory case-control study within LIFECODES birth cohort was performed. FGR cases (N = 30), defined as birthweight below the 10th percentile, were matched with controls (N = 30) based on maternal age, race, pre-pregnancy body mass index, and gestational age at delivery. Gas chromatography/electron-ionization mass spectrometry was performed on urine samples collected at 10 and 26 weeks of gestation. Differences in urinary metabolite levels in cases and controls at each time point and between the two time points were calculated and then changes compared across pregnancy. 137 unique urinary metabolites were annotated, and several identified that were higher in cases compared to controls. For example, urinary concentrations of benzoic acid were higher in cases compared to controls at both study visits (3.01-fold higher in cases at visit 1, p < 0.01; 3.10-fold higher in cases at visit 3, p = 0.05). However, these findings from our exploratory analysis were not robust to false-discovery-rate adjustment. In conclusion, using a high-resolution, non-targeted approach, we found specific urinary organic acids differed over pregnancy by FGR case status.

Assessing patient perceptions of cytomegalovirus infection in pregnancy.

Pregnant women impacted by cytomegalovirus (CMV) make clinical decisions despite uncertain outcomes. Intolerance of uncertainty score (IUS) is a validated measure of tendency for individuals to find unacceptable that a negative event might occur. We investigated patient perceptions of CMV infection during pregnancy and correlated IUS and knowledge with decision-making. Electronic questionnaire was sent to women from July to August 2017. The questionnaire evaluated knowledge of CMV, IUS, and responses regarding management to three clinical scenarios with escalating risk of CMV including choices for no further testing, ultrasound, amniocentesis, or abortion. For each scenario, logistic regression was used to model IUS on responses. A total of 815 women were included. The majority of participants was white (63.1%) and 42% had a postgraduate degree. Over 70% reported that they had not previously heard of CMV. In the scenario with only CMV exposure, participants with increasing IUS were more likely to choose abortion (odds ratio [OR] = 1.04; 95% confidence interval [CI]: 1.01, 1.06) and no further testing (OR = 0.97; 95% CI: 0.95, 0.99). In the scenario with mild ultrasound findings in setting of CMV exposure, increasing IUS was associated with higher odds of choosing no further testing (OR = 0.97; 95% CI, 0.94, 0.99). No significant association was observed between IUS and responses in the scenario with severe ultrasound abnormalities in setting of CMV exposure. The majority of patients had no knowledge of CMV. Higher IUS was associated more intervention in low severity scenarios, but in severe scenarios, IUS was not associated with participants' choices.

Prevention of Postpartum Venous Thromboembolism.

IMPORTANCE: Postpartum venous thromboembolism (VTE) results in significant morbidity and mortality. The practicing obstetrician-gynecologist should have a plan for management and prevention. OBJECTIVE: The objective of this review is to familiarize obstetric providers with available evidence regarding postpartum VTE prevention and suggest a clinical practice guideline. EVIDENCE ACQUISITION: Published literature was retrieved through a search of PubMed and relevant review articles, original research articles, systematic reviews, and practice guidelines. RESULTS: Thromboembolic disease is one of the leading causes of maternal death in developed nations. Current evidence does not support universal postpartum VTE prophylaxis. Risk factor stratification is suggested to identify patients at high risk of VTE. Recent guidelines have recommended complex algorithms that are difficult to put into practice and have not been validated in the postpartum state. The American College of Obstetricians and Gynecologists has recommended that each institution develop a protocol to identify and treat women at high risk of postpartum VTE. CONCLUSIONS AND RELEVANCE: Obstetric providers should be familiar with available evidence and best practice regarding postpartum VTE prevention. A suggested clinical practice guideline for the prevention of postpartum VTE is provided.

Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines.

BACKGROUND: Investigators have hypothesized that omega-3 fatty acid supplementation may modulate the immune response. However, available evidence is conflicting. We performed this study to investigate the effect of prenatal eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-rich fish oil supplementation on maternal and fetal cytokine production. METHODS: This study is a secondary analysis of a randomized controlled trial designed to assess whether prenatal EPA- or DHA-rich fish oil supplementation would prevent perinatal depressive symptoms among women at risk. Enrolled participants received EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA) or soy oil placebo. Maternal venous blood was collected at enrollment (12-20 weeks gestation) and after supplementation (34-36 weeks gestation). Umbilical cord blood was collected at delivery. We analyzed stored plasma specimens for 16 human cytokines using multiplex immunoassays. Maternal and cord blood cytokine levels were compared among the treatment groups. Associations of serum DHA and EPA with maternal and cord blood cytokines were explored via regression analysis. RESULTS: We enrolled 126 women, of whom 118 completed the trial. Prenatal supplementation with EPA-rich fish oil significantly lowered maternal IL6, IL15, and TNFα concentrations. However, supplementation with DHA-rich fish oil had no significant effect on maternal cytokine profiles. Maternal serum DHA fraction was significantly associated with IL1α, and maternal serum DHA and EPA fractions were significantly associated with IL 10 concentrations after supplementation. Compared with placebo, supplementation with EPA- or DHA-rich fish oils had no significant effect on cord blood cytokine concentrations. CONCLUSIONS: Prenatal supplementation with EPA-rich fish oil significantly reduced levels of several inflammatory cytokines in maternal plasma, while prenatal DHA-rich fish oil had no significant effect on cytokine concentrations. Supplementation with EPA- and DHA- rich fish oil had no significant effect on umbilical cord blood cytokine concentrations. TRIAL REGISTRATION: Clinical Trial Registration: registration number NCT00711971 7/7/2008.

Vitamin D levels and perinatal depressive symptoms in women at risk: a secondary analysis of the mothers, omega-3, and mental health study.

BACKGROUND: Vitamin D insufficiency may be associated with depressive symptoms in non-pregnant adults. We performed this study to evaluate whether low maternal vitamin D levels are associated with depressive symptoms in pregnancy. METHODS: This study was a secondary analysis of a randomized trial designed to assess whether prenatal omega-3 fatty acid supplementation would prevent depressive symptoms. Pregnant women from Michigan who were at risk for depression based on Edinburgh Postnatal Depression Scale Score or history of depression were enrolled. Participants completed the Beck Depression Inventory (BDI) and Mini International Neuropsychiatric Interview at 12-20 weeks, 26-28 weeks, 34-36 weeks, and 6-8 weeks postpartum. Vitamin D levels were measured at 12-20 weeks (N = 117) and 34-36 weeks (N = 112). Complete datasets were available on 105 subjects. Using regression analyses, we evaluated the relationship between vitamin D levels with BDI scores as well as with MINI diagnoses of major depressive disorder and generalized anxiety disorder. Our primary outcome measure was the association of maternal vitamin D levels with BDI scores during early and late pregnancy and postpartum. RESULTS: We found that vitamin D levels at 12-20 weeks were inversely associated with BDI scores both at 12-20 and at 34-36 weeks' gestation (P < 0.05, both). For every one unit increase in vitamin D in early pregnancy, the average decrease in the mean BDI score was .14 units. Vitamin D levels were not associated with diagnoses of major depressive disorder or generalized anxiety disorder. CONCLUSIONS: In women at risk for depression, early pregnancy low vitamin D levels are associated with higher depressive symptom scores in early and late pregnancy. Future investigations should study whether vitamin D supplementation in early pregnancy may prevent perinatal depressive symptoms. TRIAL REGISTRATION: https://clinicaltrials.gov/ REGISTRATION NUMBER: NCT00711971.

Unilateral Fetal Renal Abnormalities: Are They Really Isolated?

OBJECTIVES: Our objective was to describe the association between unilateral fetal renal abnormalities and other major anomalies that were not apparent in the second trimester. METHODS: A review of the ultrasound database identified fetuses with suspected unilateral renal agenesis, unilateral multicystic dysplastic kidney, and renal ectopia from 2005 to 2014. Neonatal records were reviewed to identify anomalies not suspected in the second trimester, and postnatal imaging studies were reviewed. Categorical data were compared by &x003C7;(2) analysis and the Fisher exact test. RESULTS: We identified 102 cases, including 36 with suspected renal agenesis, 28 with suspected multicystic dysplastic kidney, and 38 with suspected renal ectopia. There were 8 cases (7.8%) with major anomalies not suspected in the second trimester. In 5 cases (4.9%), there were no associated findings in the second trimester. There were no significant differences in the rates of unsuspected abnormalities between the 3 groups. There was a trend toward a higher rate of unsuspected anomalies in the cases with a single umbilical artery compared to those with a 3-vessel cord (28.6% vs 6.3%; P= .09). CONCLUSIONS: In fetuses with unilateral renal abnormalities, major anomalies that were not suspected in the second trimester were uncommon. However, patients should be aware of the possibility that other major anomalies could subsequently be identified, and the outcome may depend on more than postnatal renal function.

Whole-foods, plant-based diet alleviates the symptoms of osteoarthritis.

Objective. To evaluate the effectiveness of a whole-foods, plant-based diet (WFPB) to reduce symptoms of osteoarthritis. Methods. Six-week, prospective randomized open-label study of patients aged 19-70 with osteoarthritis. Participants were randomized to a WFPB (intervention) or continuing current diet (control). Outcomes were assessed by mixed models analysis of participant self-assessed weekly SF-36v2 domain t scores, weekly Patient Global Impression of Change (PGIC) scales, and mean weekly Visual Analog Scale (VAS) pain assessment. Mixed models analysis also evaluated pre-post change from baseline level for standard clinical measures: weight, BMI, body temperature, pulse, and blood pressure. Results. Forty participants were randomized. Thirty-seven of them, 18 control and 19 intervention, completed the study. The intervention group reported a significantly greater improvement than the control group in SF-36v2 energy/vitality, physical functioning, role physical, and the physical component summary scale. The differences between the intervention and control PGIC scales were statistically significant over time. Intervention group improvement in VAS weekly mean was also significantly greater than that of the control group from week 2 onward. Conclusion. Study results suggest that a whole-foods, plant-based diet significantly improves self-assessed measures of functional status among osteoarthritis patients.

The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial.

OBJECTIVES: Maternal deficiency of the omega-3 fatty acid, docosahexaenoic acid (DHA), has been associated with perinatal depression, but there is evidence that supplementation with eicosapentaenoic acid (EPA) may be more effective than DHA in treating depressive symptoms. This trial tested the relative effects of EPA- and DHA-rich fish oils on prevention of depressive symptoms among pregnant women at an increased risk of depression. STUDY DESIGN: We enrolled 126 pregnant women at risk for depression (Edinburgh Postnatal Depression Scale score 9-19 or a history of depression) in early pregnancy and randomly assigned them to receive EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA), or soy oil placebo. Subjects completed the Beck Depression Inventory (BDI) and Mini-International Neuropsychiatric Interview at enrollment, 26-28 weeks, 34-36 weeks, and at 6-8 weeks' postpartum. Serum fatty acids were analyzed at entry and at 34-36 weeks' gestation. RESULTS: One hundred eighteen women completed the trial. There were no differences between groups in BDI scores or other depression endpoints at any of the 3 time points after supplementation. The EPA- and DHA-rich fish oil groups exhibited significantly increased postsupplementation concentrations of serum EPA and serum DHA respectively. Serum DHA- concentrations at 34-36 weeks were inversely related to BDI scores in late pregnancy. CONCLUSION: EPA-rich fish oil and DHA-rich fish oil supplementation did not prevent depressive symptoms during pregnancy or postpartum.