Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy.

BACKGROUND: Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed. OBJECTIVE: To determine the rate of early preterm birth (EPTB, <34 weeks gestation) and preterm birth (PTB, <37 weeks gestation) in participants who adhered to a randomly assigned docosahexaenoic acid (DHA) dose of 1000 mg/day. STUDY DESIGN: Eleven hundred women with a singleton pregnancy were enrolled before 20-weeks' gestation, provided a capsule with 200 mg/day DHA and randomly assigned to two additional capsules containing a placebo or 800 mg of DHA. In the Bayesian Adaptive Design, new randomization schedules were determined at prespecified intervals. In each randomization, the group with the most EPTB was assigned fewer participants than the other group. Adherence was defined a priori as a postpartum red blood cell phospholipid DHA (RBC-PL-DHA) ≥5.5%.and post hoc as ≥8.0% RBC-PL-DHA, the latter after examination of postpartum RBC-PL-DHA. Bayesian mixture models were fitted for gestational age and dichotomized for EPTB and PTB as a function of baseline RBC-PL-DHA and dose-adherence. Bayesian hierarchical models were also fitted for EPTB by dose adherence and quartiles of baseline RBC-PL-DHA. RESULTS: Adherence to the high dose using both RBC-PL-DHA cut points resulted in less EPTB compared to 200 mg [Bayesian posterior probability (pp) = 0.93 and 0.92, respectively]. For participants in the two lowest quartiles of baseline DHA status, adherence to the higher dose resulted in lower EPTB (≥5.5% RBC-PL-DHA, quartiles 1 and 2, pp = 0.95 and 0.96; ≥8% RBC-PL-DHA, quartiles 1 and 2, pp = 0.94 and 0.95). Using the Bayesian model, EPTB was reduced by 65%, from 3.45% to 1.2%, using both cut points. Adherence also reduced PTB before 35, 36 and 37 weeks using both cut points (pp ≥ 0.95). In general, performance of the nonadherent subgroup mirrored that of participants assigned to 200 mg. CONCLUSION: Adherence to high dose DHA reduced EPTB and PTB. The largest effect of adherence on reducing EPTB was observed in women with low baseline DHA levels. CLINICALTRIALS: gov (NCT02626299).

Docosahexaenoic acid (DHA) intake estimated from a 7-question survey identifies pregnancies most likely to benefit from high-dose DHA supplementation.

BACKGROUND: Two randomized trials found women with low blood docosahexaenoic acid (DHA; an omega 3 fatty acid) had fewer early preterm births (<34 weeks gestation) if they were assigned to high dose DHA supplementation, however, there is currently no capacity for clinicians who care for pregnancies to obtain a blood assessment of DHA. Determining a way to identify women with low DHA intake whose risk could be lowered by high dose DHA supplementation is desired. OBJECTIVE: To determine if assessing DHA intake can identify pregnancies that benefit from high dose DHA supplementation. STUDY DESIGN: This secondary analysis used birth data from 1310 pregnant women who completed a 7-question food frequency questionnaire (DHA-FFQ) at 16.8 ± 2.5 weeks gestation that is validated to assess DHA status. They were then randomly assigned to a standard (200 mg/day) or high dose (800 or 1000 mg/day) DHA supplement for the remainder of pregnancy. Bayesian logistic regressions were fitted for early preterm birth and preterm birth as a function of DHA intake and assigned DHA dose. RESULTS: Participants who consumed less than 150 mg/day DHA prior to 20 weeks' gestation (n = 810/1310, 58.1%) had a lower Bayesian posterior probability (pp) of early preterm birth if they were assigned to high dose DHA supplementation (1.4% vs 3.9%, pp = 0.99). The effect on preterm birth (<37 weeks) was also significant (11.3% vs 14.8%, pp = 0.97). CONCLUSION: The DHA-FFQ can identify pregnancies that will benefit most from high dose DHA supplementation and reduce the risk of preterm birth. The DHA-FFQ is low burden to providers and patients and could be easily implemented in obstetrical practice.

Validation of an abbreviated food frequency questionnaire for estimating DHA intake of pregnant women in the United States.

Docosahexaenoic acid (DHA) intake was estimated in pregnant women between 12- and 20-weeks' gestation using the National Cancer Institute's (NCI) Diet History Questionnaire-II (DHQ-II) and a 7-question screener designed to capture DHA intake (DHA Food Frequency Questionnaire, DHA-FFQ). Results from both methods were compared to red blood cell phospholipid DHA (RBC-DHA) weight percent of total fatty acids. DHA intake from the DHA-FFQ was more highly correlated with RBC-DHA (rs=0.528) than the DHQ-II (rs=0.352). Moreover, the DHA-FFQ allowed us to obtain reliable intake data from 1355 of 1400 participants. The DHQ-II provided reliable intake for only 847 of 1400, because many participants only partially completed it and it was not validated for Hispanic participants. Maternal age, parity, and socioeconomic status (SES) were also significant predictors of RBC-DHA. When included with estimated intake from the DHA-FFQ, the model accounted for 36% of the variation in RBC-DHA.

Utility of a 7- question online screener for DHA intake.

The secondary analyses of two large, recently completed randomized clinical trials of DHA supplementation in pregnancy found that women with a low baseline DHA status benefited from randomization to a higher dose (800 vs 0 and 1000 vs 200 mg/day DHA). To obtain DHA status, it is necessary to obtain a blood sample and conduct an analysis using gas chromatography (GC) or GC-mass spectrometry (GCMS), both barriers to clinics where pregnant women receive advice on nutrition. Participants consuming less than 150 mg/day of DHA at baseline in our recent trial had a lower risk of early preterm birth and preterm birth when assigned to 1000 vs 200 m/day DHA. DHA intake was determined using a 7-question food frequency questionnaire administered by a trained nutritionist. Because the need for trained personnel to administer the questionnaire would be a barrier to implementing this finding in clinical management of pregnancy, the goal of this study was to determine if an online version of the questionnaire could be validly completed without assistance.

Predicting the effect of maternal docosahexaenoic acid (DHA) supplementation to reduce early preterm birth in Australia and the United States using results of within country randomized controlled trials.

The DHA to Optimize Mother Infant Outcome (DOMInO) and Kansas DHA Outcomes Study (KUDOS) were randomized controlled trials that supplemented mothers with 800 and 600mg DHA/day, respectively, or a placebo during pregnancy. DOMInO was conducted in Australia and KUDOS in the United States. Both trials found an unanticipated and statistically significant reduction in early preterm birth (ePTB; i.e., birth before 34 weeks gestation). However, in each trial, the number of ePTBs were small. We used a novel Bayesian approach to estimate statistically derived low, moderate or high risk for ePTB, and to test for differences between the DHA and placebo groups. In both trials, the model predicted DHA would significantly reduce the expected proportion of deliveries in the high risk group under the trial conditions of the parent studies. Among the next 300,000 births in Australia we estimated that 1112 ePTB (95% credible interval 51-2189) could be avoided by providing DHA. And in the USA we estimated that 106,030 ePTB (95% credible interval 6400 to 175,700) could be avoided with DHA.

Docosahexaenoic acid supplementation (DHA) and the return on investment for pregnancy outcomes.

The Kansas University DHA Outcomes Study (KUDOS) found a significant reduction in early preterm births with a supplement of 600mg DHA per day compared to placebo. The objective of this analysis was to determine if hospital costs differed between groups. We applied a post-hoc cost analysis of the delivery hospitalization and all hospitalizations in the following year to 197 mother-infant dyads who delivered at Kansas University Hospital. Hospital cost saving of DHA supplementation amounted to $1678 per infant. Even after adjusting for the estimated cost of providing 600mg/d DHA for 26 weeks ($166.48) and a slightly higher maternal care cost ($26) in the DHA group, the net saving per dyad was $1484. Extrapolating this to the nearly 4 million US deliveries per year suggests universal supplementation with 600mg/d during the last 2 trimesters of pregnancy could save the US health care system up to USD 6 billion.

Is symptom relief associated with reduction in gastric retention after gastric electrical stimulation treatment in patients with gastroparesis? A sensitivity analysis with logistic regression models.

BACKGROUND: Enterra gastric electrical stimulation (GES) is an alternative treatment for gastroparesis (GP) when standard medical therapy fails. The aims of this study were to evaluate the association between total symptom score (TSS) and reduction in gastric retention (GR) after GES by GP etiology and to examine the sensitivity of the association to varying cutpoints used to define GR and TSS improvement. METHODS: Gastric retention assessed with a standardized (99m) Tc radio-labeled egg meal and TSS measured by a five-point Likert scale in 221 GP patients treated with Enterra GES therapy for at least 1 year were analyzed. Bivariate chi-square test and multivariable logistic regression with all possible cutpoints were used to assess the consistency of association and quantitate the relationship across three GP etiologies. KEY RESULTS: Symptom relief in diabetic GP was more likely attributable to GR reduction as indicated by the consistently significant odds ratios (P < 0.01) across all cutpoints. The association in idiopathic GP was inconclusive because odds ratios were sensitive to cutpoints with P-values ranging from 0.01 to 0.47. No association was found for patients with post surgical gastroparesis (P > 0.1 for all cutpoints). Patient age, gender, baseline TSS and baseline GR had no significant effect at 5% level on clinical improvement regardless of cutpoints for GR. CONCLUSIONS & INFERENCES: Association between clinical improvements and GR reduction following GES treatment depends on patient etiology and was able to be demonstrated in diabetic GP. The association for idiopathic GP was inconclusive and no such association was found for post surgical GP across all possible cutpoint combinations.

A Bayesian hierarchical assessment of gastric emptying with the linear, power exponential and modified power exponential models.

BACKGROUND: Many studies assessed gastric retention over time utilizing different models, mostly with scintigraphic measures at varied endpoints from limited number of normal volunteers. With a standardized 4-h gastric emptying (GE) protocol, we compared model fit by the linear, power exponential (PE), and modified power exponential (MPE) models to contrast differences in GE among different groups based on clinical diagnosis and gender. METHODS: We retrospectively collected 320 patient records with four consecutive hourly scintigraphic measures of percent intragastric residual at the Kansas University Medical Center. We obtained parameter estimates with the Bayesian hierarchical models using informative priors from previous research. KEY RESULTS: The PE or MPE model captured the time dependent GE rate better than the linear model. The estimated GE rates more than doubled for those without gastroparesis compared to patients diagnosed with gastroparesis. Males tended to empty gastric content faster but were not significantly different from females at the 5% level. CONCLUSIONS & INFERENCES: The point estimates and 95% credible interval for GE rates obtained with the PE and MPE models may provide an alternative diagnostic tool for clinicians since it utilizes gastric emptying scintigraphy measures at multiple endpoints which may be sensitive to different aspects of the disease. No agreement in lag phases was obtained by the three models based on respective definitions from previous researches, but similar results would be obtained with the PE and MPE models if both defined lag phase by back projecting the regression lines to the same gastric retention level.

Utility of the NeuroTrax computerized battery for cognitive screening in Parkinson's disease: comparison with the MMSE and the MoCA.

To determine the utility of a computerized assessment in Parkinson's disease (PD), we compared the cognitive performance of 50 PD patients on the NeuroTrax computerized battery relative to the mini-mental state examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The results revealed fair agreement between impairment on the NeuroTrax and the MMSE (kappa=.291, p=.031) but only slight agreement between the NeuroTrax and the MoCA (kappa=.138, p = .054) and between the MoCA and the MMSE (kappa = .168, p = .069). The NeuroTrax identified 52% of the sample as average or above, 40% as below average, and 8% as impaired. The MoCA identified 54% of the sample as impaired (28% average or above and 18% below average), while the MMSE identified 66% as average or above (20% below average and 14% impaired). Several stepwise regressions revealed that executive and verbal functions were the best predictors of cognitive functioning on the NeuroTrax, while memory recall, serial sevens, naming, and abstraction were the best predictors on the MoCA. These results suggest that although the NeuroTrax may be useful in identifying executive cognitive deficits in PD, similar to the MMSE the NeuroTrax may lack optimal sensitivity. While the MoCA is sensitive, it may be too stringent in overclassifying PD patients as impaired.

Magnetic resonance imaging in the search for retrocochlear pathology.

OBJECTIVES: The purpose of this study is to evaluate the incidence of retrocochlear pathologic conditions that may be seen with full, contrast-enhanced magnetic resonance imaging of the brain, relative to more limited studies of the internal auditory canals (IACs) in patients with unilateral hearing loss or tinnitus with or without dizziness. METHODS: A retrospective study was performed on all patients who had a magnetic resonance imaging of the brain and otologic symptoms over a 7-year period. RESULTS: Abnormalities were found in 11 of 128 patients with only auditory symptoms and in 63 of 282 patients with auditory symptoms and/or dizziness (P = 0.005). Treatable lesions may not have been identified with a limited IAC study in 3 of 128 patients with only unilateral auditory symptoms, and 21 of 282 patients with dizziness (P = 0.045). CONCLUSIONS: Limited MRI of the IACs may serve as an adequate screening test for retrocochlear pathologic conditions in patients with unilateral auditory symptoms and no dizziness.