Bias analyses to investigate the impact of differential participation: Application to a birth defects case-control study.

BACKGROUND: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking. OBJECTIVES: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS. METHODS: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR. RESULTS: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02). CONCLUSIONS: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research.

Self-compassion and body image inflexibility as mediators of outcomes in a residential eating disorder sample.

Eating disorders are serious mental health conditions that are accompanied by negative health outcomes, high mortality rates, impaired functioning, and comorbid mental health conditions. Despite many empirically supported interventions for eating disorders, it remains one of the most challenging mental disorders to treat, as individuals often struggle to maintain treatment gains. One method of improving our understanding of effective eating disorder treatment is to identify important processes of change to target during therapy. The aim of the current study was to test two candidate mediators of disordered eating symptom change during residential treatment: self-compassion and body image inflexibility. In the present study, women and adolescent girls (N = 132) completed a battery of measures, including eating disorder severity, self-compassion, and body image inflexibility, at admission to and discharge from a residential eating disorder facility. Our results indicated that changes in body image inflexibility and self-compassion, specifically self-judgment, were both mediators between ED symptom severity from pre- to post-treatment. These results have potential treatment implications, pointing to the possible importance of targeting body image inflexibility, self-judgment, and self-compassion while treating eating disorders.

An exploratory examination of delay discounting in women and girls diagnosed with an eating disorder.

Those with eating disorders (EDs) characterized by purging behaviors tend to show more impulsivity than those diagnosed with restrictive eating, who tend to show more compulsivity. Impulsive choice (i.e. a type of impulsivity) is a common factor among eating disorders that is less understood. Delay discounting is a measure of choice impulsivity, examining the decrease in value of delayed outcomes. In this exploratory study, we examined associations between eating disorder type, age and delay discounting among patients at a residential ED treatment center (N = 178). Our findings showed that those diagnosed with bulimia nervosa had higher delay discounting (i.e. more impulsivity) at intake compared to anorexia nervosa, binge eating disorder, and other eating types but there were no significant differences. Those diagnosed with bulimia nervosa, as well as those with ARFID and unspecified ED showed a preference for delayed rewards at discharge, but there were no significant differences among ED types. Moderation analyses showed that age, ED type, nor the interaction did not significantly predict delay discounting at intake or discharge. To conclude, those with bulimia nervosa demonstrate less impulsive choice at discharge from a residential ED treatment center. However, additional research is needed given the variability of sample sizes in this study.

Experiences of Racial Discrimination and Periconceptional Diet Quality.

BACKGROUND: Racism is a key determinant of perinatal health disparities. Poor diet may contribute to this effect, but research on racism and dietary patterns is limited. OBJECTIVE: We aimed to describe the relation between experiences of racial discrimination and adherence to the 2015‒2020 Dietary Guidelines for Americans. METHODS: We used data from a prospective pregnancy cohort study conducted at 8 United States medical centers (2010‒2013). At 6‒13 weeks of gestation, 10,038 nulliparous people with singleton pregnancies were enrolled. Participants completed a Block food frequency questionnaire, assessing usual diet in the 3 mo around conception, and the Krieger Experiences of Discrimination Scale, assessing the number of situational domains (e.g., at school and on the street) in which participants ever experienced racial discrimination. Alignment of dietary intake with the 2015-2020 Dietary Guidelines for Americans was assessed using the Healthy Eating Index (HEI)-2015. RESULTS: The study showed that 49%, 44%, 35%, and 17% of the Asian, Black, Hispanic, and White participants reported experiences of racial discrimination in any domain. Most participants experienced discrimination in 1 or 2 situational domains. There were no meaningful differences in HEI-2015 total or component scores in any racial or ethnic group according to count of self-reported domains in which individuals experienced discrimination. For example, mean total scores were 57‒59 among Black, 61‒66 among White, 61‒63 among Hispanic, and 66‒69 among Asian participants across the count of racial discrimination domains. CONCLUSIONS: This null association stresses the importance of going beyond interpersonal racial discrimination to consider the institutions, systems, and practices affecting racialized people to eliminate persistent inequalities in diet and perinatal health.

Machine learning-based placental clusters and their associations with adverse pregnancy outcomes.

BACKGROUND: Placental abnormalities have been described in clinical convenience samples, with predominately adverse outcomes. Few studies have described placental patterns in unselected samples. OBJECTIVE: We aimed to investigate associations between co-occurring placental features and adverse pregnancy outcomes in a prospective cohort of singletons. METHODS: Data were from the Safe Passage study (U.S. and South Africa, 2007-2015). Before 24 weeks' gestation, participants were randomly invited to donate placental tissue at delivery for blinded, standardised pathological examination. We used hierarchical clustering to construct statistically derived groups using 60 placental features. We estimated associations between the placental clusters and select adverse pregnancy outcomes, expressed as unadjusted and adjusted risk ratios (RRs) and robust 95% confidence intervals (CI). RESULTS: We selected a 7-cluster model. After collapsing 2 clusters to form the reference group, we labelled the resulting 6 analytic clusters according to the overarching category of their most predominant feature(s): severe maternal vascular malperfusion (n = 117), fetal vascular malperfusion (n = 222), other vascular malperfusion (n = 516), inflammation 1 (n = 269), inflammation 2 (n = 175), and normal (n = 706). Risks for all outcomes were elevated in the severe maternal vascular malperfusion cluster. For instance, in unadjusted analyses, this cluster had 12 times the risk of stillbirth (RR 12.07, 95% CI 4.20, 34.68) and an almost doubling in the risk of preterm delivery (RR 1.93, 95% CI 1.27, 2.93) compared with the normal cluster. Small infant size was more common among the abnormal clusters, with the highest unadjusted RRs observed in the fetal vascular malperfusion cluster (small for gestational age birth RR 2.99, 95% CI 2.24, 3.98, head circumference <10th percentile RR 2.86, 95% CI 1.60, 5.12). Upon adjustment for known risk factors, most RRs attenuated but remained >1. CONCLUSION: Our study adds to the growing body of epidemiologic research, finding adverse pregnancy outcomes may occur through etiologic mechanisms involving co-occurring placental abnormalities.

Values engagement as a predictor of eating disorder severity in a residential sample of female adolescents with eating disorders.

Values are freely chosen life directions and/or qualities of being that can motivate behavior change. There is nascent support for the utility of values work as a part of the therapeutic process across treatments, particularly in third wave therapy approaches (e.g., acceptance and commitment therapy). However, therapeutic values work is underresearched in clinical samples of youth. The aim of the present study is to examine the role of the two distinct values processes (engagement and obstruction), body image inflexibility, alongside other common comorbid symptoms of eating disorders (anxiety, depression) in a sample of female adolescents with eating disorders attending a residential eating disorder treatment program. Participants (N = 75) were patients at a residential eating disorder treatment facility and completed a battery of measures at time of admission. Correlational analyses and multiple regression were performed. Results found correlations between eating disorder severity, values engagement, values obstruction, body image flexibility, anxiety, and depression in the expected directions. Regression results found body image inflexibility, progression towards values, and anxiety as significant predictors of eating disorder severity (adjusted R2 = .54). This study points to the importance of emphasizing values engagement in youth with eating disorders, highlighting a potential treatment target for future research.

Sugar-Sweetened Beverage, Diet Soda, and Nonalcoholic Fatty Liver Disease Over 6 Years: The Framingham Heart Study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with sugar-sweetened beverage (SSB) consumption in cross-sectional studies. In a prospective cohort, we examined the association of beverage consumption (SSB and diet soda) with incident NAFLD and changes in hepatic fat in the Framingham Heart Study (FHS). METHODS: We conducted a prospective observational study of participants from the FHS Third Generation and Offspring cohorts who participated in computed tomography sub-studies. Participants were classified according to their average SSB or diet soda consumption, which was derived from baseline and follow-up food frequency questionnaires: non-consumers (0-<1/month), occasional consumers (1/month-<1/week), and frequent consumers (≥1/week-≥1/day). Hepatic fat was quantified by the liver fat attenuation measurements on computed tomography scan. The primary dependent variable was incident NAFLD; secondarily, we investigated change in liver fat. RESULTS: The cohorts included 691 Offspring (mean age, 62.8 ± 8.2 years; 57.7% women) and 945 Third Generation participants (mean age, 48.4 ± 6.3 years; 46.6% women). In the Offspring cohort, there was a dose-response relationship with SSB consumption and incident NAFLD. Frequent SSB consumers had 2.53 times increased odds of incident NAFLD compared with non-consumers (95% confidence interval, 1.36-4.7) after multivariable analysis. For Offspring cohort participants, occasional and frequent consumers of SSB had a more adverse increase in liver fat compared with non-consumers. CONCLUSIONS: Higher average SSB intake is associated with increase in liver fat over 6 years of follow-up and increased odds of incident NAFLD especially among the older cohort, whereas no consistent association was observed for the younger Third Generation cohort.

Equal Weighting of the Healthy Eating Index-2010 Components May Not be Appropriate for Pregnancy.

BACKGROUND: Adherence to the Dietary Guidelines for Americans is often assessed using the Healthy Eating Index (HEI). The HEI total score reflects overall diet quality, with all aspects equally important. Using the traditional weighting scheme for the HEI, all components are generally weighted equally in the total score. However, there is limited empirical basis for applying the traditional weighting for pregnancy specifically. OBJECTIVES: We aimed to assess associations between the 12 HEI-2010 component scores and select pregnancy outcomes. METHODS: The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be was a prospective pregnancy cohort (US multicenter, 2010-2013). Participants enrolled in the study between 6 and 13 weeks of gestation. An FFQ assessed usual dietary intake 3 months prior to pregnancy (n = 7880). Scores for the HEI-2010 components were assigned using prespecified standards based on densities (standard units per 1000 kcal) of relevant food groups for most components, a ratio (PUFAs and MUFAs to SFAs) for fatty acids, and the contribution to total energy for empty calories. Using binomial regression, we estimated risk differences between each component score and cases of small-for-gestational age (SGA) birth, preterm birth, preeclampsia, and gestational diabetes, controlling for total energy and scores for the other HEI-2010 components. RESULTS: Higher scores for greens and beans and total vegetables were associated with fewer cases of SGA birth, preterm birth, and preeclampsia. For instance, every 1-unit increase in the greens and beans score was associated with 1.2 fewer SGA infants (95% CI, 0.7-1.7), 0.7 fewer preterm births (95% CI, 0.3-1.1), and 0.7 fewer preeclampsia cases (95% CI, 0.2-1.1) per 100 deliveries. For gestational diabetes, the associations were null. CONCLUSIONS: Vegetable-rich diets were associated with fewer cases of SGA birth, preterm birth, and preeclampsia, controlling for overall diet quality. Examination of the equal weighting of the HEI components (and underlying guidance) is needed for pregnancy.

Selective serotonin reuptake inhibitor use patterns among commercially insured US pregnancies (2005-2014).

The goal of this study was to describe patterns of selective serotonin reuptake inhibitor (SSRI) use during pregnancy in a US cohort (2005-2014) of > 1 million commercially insured women using administrative claims. We used international classification of disease (ICD-9) diagnosis and procedure and current procedural terminology codes in the OptumLabs® Data Warehouse to identify deliveries (including losses) among US women aged 15-45 (n = 1,061,023). SSRI dispensings that overlapped with the timing of pregnancy were identified using national drug codes in linked pharmacy claims. Demographic characteristics were imputed based on residential location, census data, and consumer information. We investigated patterns by trimester, agent, and demographic subgroups. A total of 46,087 of women (4.34%) were dispensed SSRIs during the estimated pregnancy period. Sertraline was the most common overall and had the highest initial use after trimester 1, including women who switched from another SSRI, although dispensing for > 1 SSRI during pregnancy was uncommon. Use of vilazodone was rare and had the highest discontinuation after trimester 1, followed by paroxetine. SSRI use was more common among women who were older, White, college-educated, higher income (≥ $100,000), or resided in the Midwest. Paroxetine and dispensings for > 1 SSRI were more common in lower education subgroups. White women had the highest proportion of use in all trimesters of pregnancy, whereas Hispanic women had the lowest. Among commercially insured US women, SSRI use during pregnancy differed by agent and demographics. More research is needed to understand whether these differences are due to symptom reporting, cultural beliefs, and/or physician preferences.

Is perfectionism always unhealthy? Examining the moderating effects of psychological flexibility and self-compassion.

OBJECTIVE: Perfectionism is generally associated with worse mental health outcomes, though evidence suggests elements of it may be helpful. In light of these findings, we examined whether psychological skills like psychological flexibility and self-compassion moderated the relationship between perfectionism and wellbeing (i.e., quality of life, symptom impairment, and psychological distress). METHODS: Undergraduate students (N = 677) completed self-report measures. RESULTS: A latent profile analysis identified three perfectionism groups (low, average, and high) based on four perfectionism subscales: concern over mistakes, need for approval, rumination, and striving for excellence. Generally, we found that psychological flexibility and/or self-compassion buffered the impact of average and high perfectionism on quality of life and symptom impairment. CONCLUSION: Our results support the utility of practicing psychological flexibility and/or self-compassion for people with average and high levels of perfectionism. Limitations include using a cross-sectional design and nonclinical sample.

Applying the E Value to Assess the Robustness of Epidemiologic Fields of Inquiry to Unmeasured Confounding.

We explored the use of the E value to gauge the robustness of fields of epidemiologic inquiry to unmeasured confounding. We surveyed nutritional and air pollution studies that found statistically significant associations between exposures and incident outcomes. For 100 studies in each field, we extracted adjusted relative effect estimates and associated confidence intervals. We inverted estimates where necessary so that all effects were greater than 1. We calculated E values for both the effect estimate and the lower limit of the 95% confidence interval. Nutritional studies were smaller than air pollution studies (median participants per study, 40,652 vs. 72,460). More than 90% of nutritional studies categorized the exposure, whereas 89% of air pollution studies analyzed the exposure as a continuous variable. The median relative effect was 1.33 in nutrition and 1.16 in air pollution. The corresponding median E values for the estimates were 2.00 and 1.59, respectively. E values for the 95% confidence intervals had median values of 1.39 and 1.26, respectively. Little to moderate unmeasured confounding could explain away most observed associations. The E value is necessarily larger for smaller studies that reach statistical significance, making cross-field comparison difficult. The E value for the 95% confidence interval might be a more useful measure in reports of epidemiologic observational studies.

One-Carbon Cofactor Intake and Risk of Neural Tube Defects Among Women Who Meet Folic Acid Recommendations: A Multicenter Case-Control Study.

We aimed to investigate associations between individual and concurrent (≥2) intakes of one-carbon cofactors vitamins B6 and B12, choline, betaine, and methionine and neural tube defect (NTD) outcomes among mothers meeting the folic acid recommendations. In the Slone Birth Defects Study (case-control design; North America, 1998-2015), mothers of 164 NTD cases and 2,831 nonmalformed controls completed food frequency questionnaires and structured interviews. Estimated intakes of one-carbon cofactors were dichotomized (high vs. low) for all except betaine (low or middle vs. high). We used logistic regression models to estimate odds ratios and 95% confidence intervals adjusted for center, age, and race. The analysis was restricted to mothers with estimated daily total folate intake of ≥400 µg during periconception. Fewer cases, compared with controls, had high intakes for each one-carbon cofactor except betaine, where the starkest contrast occurred in the middle group. Women with concurrent high intakes of B6, B12, choline, and methionine and moderate intake of betaine had approximately half the risk of an NTD-affected pregnancy (odds ratio = 0.49, 95% confidence interval: 0.23, 1.08). These findings suggest that, in the presence of folic acid, one-carbon cofactors-notably when consumed together-might reduce NTD risk. Additional research should inform any changes to clinical recommendations.

Validity of maternal recall of gestational age and weight at birth: Comparison of structured interview and medical records.

PURPOSE: To assess agreement between maternal recall and medical records for gestational age (GA) at birth as derived from dating information and birthweight. METHODS: In the case-control Slone Birth Defects Study, within 6 months of delivery, trained nurses conducted standardized telephone interviews with mothers of infants with and without major structural malformations. In a subset of approximately 5000 case and control mothers from five US centers (2008-2012), a research nurse abstracted subjects' medical records. GA at delivery was calculated as date of delivery minus (estimated date of confinement [EDC] minus 280); if EDC was unknown, last menstrual period served as a proxy for start of pregnancy. Positive and negative predictive values (PPV and NPV, respectively) were calculated, using medical records as the standard, for categories of GA at delivery (ie, early preterm <238, late preterm <258, and term ≥259 d) and birthweight (low <2500, normal 2500 to 4500, and high >4500 g). RESULTS: The gestational age and birthweight validation samples comprised 3122 and 4760 women, respectively, with diverse characteristics. The PPV and NPV were high (>92% and >99%, respectively) for all categories of delivery GA and birthweight. CONCLUSIONS: Our findings suggest that mothers' recall may be a valid alternative to medical records to estimate delivery GA and birthweight. This study used standardized interviews conducted by trained research nurses, had a short recall period (<6 months post delivery), and for delivery GA, focused on date-derived GA. Further research is needed on the potential impact of study design, population characteristics, and comparison to other data sources.

Clinical sensitivity and specificity of meconium fatty acid ethyl ester, ethyl glucuronide, and ethyl sulfate for detecting maternal drinking during pregnancy.

BACKGROUND: We investigated agreement between self-reported prenatal alcohol exposure (PAE) and objective meconium alcohol markers to determine the optimal meconium marker and threshold for identifying PAE. METHODS: Meconium fatty acid ethyl esters (FAEE), ethyl glucuronide (EtG), and ethyl sulfate (EtS) were quantified by LC-MS/MS in 0.1 g meconium from infants of Safe Passage Study participants. Detailed PAE information was collected from women with a validated timeline follow-back interview. Because meconium formation begins during weeks 12-20, maternal self-reported drinking at or beyond 19 weeks was our exposure variable. RESULTS: Of 107 women, 33 reported no alcohol consumption in pregnancy, 16 stopped drinking by week 19, and 58 drank beyond 19 weeks (including 45 third-trimester drinkers). There was moderate to substantial agreement between self-reported PAE at ≥19 weeks and meconium EtG ≥30 ng/g (κ = 0.57, 95% CI 0.41-0.73). This biomarker and associated cutoff was superior to a 7 FAEE sum ≥2 nmol/g and all other individual and combination marker cutoffs. With meconium EtG ≥30 ng/g as the gold standard condition and maternal self-report at ≥19 weeks' gestation as the test condition, 82% clinical sensitivity (95% CI 71.6-92.0) and 75% specificity (95% CI 63.2-86.8) were observed. A significant dose-concentration relationship between self-reported drinks per drinking day and meconium EtG ≥30 ng/g also was observed (all P < 0.01). CONCLUSIONS: Maternal alcohol consumption at ≥19 weeks was better represented by meconium EtG ≥30 ng/g than currently used FAEE cutoffs.

Clinical Considerations for Integrating Ethical Principles of Beneficence in the Development of Evidence-Based Interventions: The case of Pediatric Misophonia.

Misophonia is a condition involving decreased tolerance and intense responses to specific sounds, often those that are human-generated and repetitive in nature. Misophonia frequently onsets during childhood and is associated with significant distress, impairment, and diminished quality of life. While misophonia research remains nascent and no definitive practice guidelines exist at present, extant studies offer several promising potential avenues in intervention development for adults with misophonia. However, such research is comparatively limited for youth. Before widespread adoption of promising treatments, it is important to consider the potential for harm or non-beneficence that may arise from the mis-informed application of such treatments. In this article, we identify several potential pitfalls within intervention development for pediatric misophonia and provide recommendations to circumvent them. To that end, we focus on the following three topic areas: (a) challenges arising when psychological mechanisms are not considered in intervention development, (b) importation of a cognitive-behavior therapy (CBT) framework for obsessive-compulsive spectrum disorders without nuanced tailoring to misophonia, and (c) neglecting to include individuals with lived experience in the process of intervention development research. Considering these key areas within misophonia intervention development will be critical for upholding beneficence and minimizing harm in treatment of misophonia across the lifespan.

Acceptance and commitment therapy versus progressive relaxation training for misophonia: Randomized controlled trial protocol, interventions, and audiological assessments.

BACKGROUND: Misophonia is a disorder characterized by an intense emotional reaction to specific sounds, often leading to significant distress and impairment in daily functioning. Acceptance and commitment therapy (ACT) is a promising psychotherapy for treating misophonia, but has only been previously tested in case studies. This paper presents a protocol for the first randomized controlled trial (RCT) assessing the efficacy and feasibility of ACT supplemented by audiological interventions for misophonia versus progressive relaxation training (PRT). METHODS: The outlined protocol is a RCT with 60 adults with misophonia. After undergoing a comprehensive psychological and audiological evaluation, participants were randomly assigned to ACT (n = 30) or PRT (n = 30). All participants completed clinician-administered and self-report assessments at baseline, post-intervention, 3-month follow-up, and 6-month follow-up. The primary outcome was misophonia severity and impairment measured via clinical interview. Secondary outcomes included disgust, anger, sensory sensitivities, well-being, distress, and psychological flexibility. DISCUSSION: This paper outlines the rationale of using ACT supplemented by audiological methods for misophonia with the novel therapeutic target of enhancing psychological flexibility. The results of this randomized controlled trial will help determine if ACT is an efficacious and acceptable treatment for misophonia. This trial will also help clarify active psychological mechanisms of misophonia, and assess whether this combination of psychological and audiological services can effectively help individuals with misophonia.

Factors associated with infant sex and preterm birth status for selected birth defects from the National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: Birth defects and preterm birth co-occur, with some overlapping risk factors. Many birth defects and preterm births tend to have a male preponderance. We explored potential risk factors impacting sex and preterm (<37 weeks of gestation) birth differences among infants with selected birth defects delivered from 1997 to 2011 using data from the National Birth Defects Prevention Study (NBDPS). METHODS: The NBDPS was a large multisite, population-based case-control study. Using random forests, we identified important predictors of male preterm, female preterm, and male term, each compared with female term births for each birth defect. Using logistic regression, we estimated odds ratios for associations between important predictors and sex-preterm birth status by birth defect. RESULTS: We examined 11,379 infants with nine specific birth defects. The top 10 most important predictors of sex-preterm birth status from the random forests varied greatly across the birth defects and sex-preterm comparisons within a given defect group, with several being novel factors. However, one consistency was that short interpregnancy interval was associated with sex-preterm birth status for many of the studied birth defects. Although obesity has been identified as a risk factor for preterm birth and birth defects in other research, it was not associated with sex-preterm birth status for any of the examined defects. CONCLUSIONS: We confirmed expected associations for sex-preterm birth status differences and found new potential risk factors for further exploration among the studied birth defects.

Sexual Orientation Intrusive Thoughts and Well-Being: The Mediating Role of Psychological Inflexibility.

Sexual orientation intrusive thoughts are a debilitating form of obsessive-compulsive disorder. The present study aimed to elucidate how psychological inflexibility and dysfunctional beliefs may impact the relationships of sexual orientation intrusive thoughts and obsessive-compulsive (OC) symptoms with well-being. A total of 181 undergraduate students completed measures of sexual orientation intrusive thoughts, OC symptoms, psychological inflexibility, dysfunctional beliefs, and well-being. Results indicated positive correlations between psychological inflexibility, sexual orientation intrusive thoughts, dysfunctional beliefs, and OC symptoms, along with negative correlations between well-being and sexual orientation intrusive thoughts, OC symptoms, dysfunctional beliefs, and psychological inflexibility. Psychological inflexibility acted as a mediator between sexual orientation intrusive thoughts and well-being and between OC symptoms and well-being. Dysfunctional beliefs were not a significant mediator. These results suggest that psychological inflexibility may partially explain the association between OC symptoms and well-being, pointing toward the need for future research on the impact of psychological inflexibility on well-being in the context of OC symptoms.

Does heterogeneity underlie differences in treatment effects estimated from SuperLearner versus logistic regression? An application in nutritional epidemiology.

PURPOSE: A strength of SuperLearner is that it may accommodate key interactions between model variables without a priori specification. In prior research, protective associations between fruit intake and preeclampsia were stronger when estimated using SuperLearner with targeted maximum likelihood estimation (TMLE) compared with multivariable logistic regression without any interaction terms. We explored whether heterogeneity (i.e., differences in the effect estimate due to interactions between fruit intake and covariates) may partly explain differences in estimates from these two models. METHODS: Using a U.S. prospective pregnancy cohort (2010-2013, n = 7781), we estimated preeclampsia risk differences (RDs) for higher versus lower fruit density using multivariable logistic regression and included two-way statistical interactions between fruit density and each of the 25 model covariates. We compared the RDs with those from SuperLearner with TMLE (gold standard) and logistic regression with no interaction. RESULTS: From the logistic regression models with two-way statistical interactions, 48% of the preeclampsia RDs were ≤-0.02 (closer to SuperLearner with TMLE estimate); 40% equaled -0.01 (same as logistic regression with no interaction estimate); the minority of RDs were at or crossed the null. CONCLUSIONS: Our exploratory analysis provided preliminary evidence that heterogeneity may partly explain differences in estimates from logistic regression versus SuperLearner with TMLE.

Weight gain patterns among pregnancies with obesity and small- and large-for-gestational-age births.

OBJECTIVE: This case-cohort study estimated associations between gestational weight gain (GWG) and small-for-gestational-age (SGA) and large-for-gestational-age (LGA) births stratified by obesity class (I: 30-34.9 kg/m2 ; II: 35-39.9 kg/m2 ; III: ≥40 kg/m2 ) (Magee-Womens Hospital, Pittsburgh, Pennsylvania, 1998-2011). METHODS: First-trimester GWG was categorized as being below (<0.2 kg), within (0.2-2.0 kg), or above (>2.0 kg) the Institute of Medicine recommendations. For second- and third-trimester GWG, four linear trajectories were derived: approximating maintenance (slope -0.05 ± 0.03 kg/wk), approximating the recommendations (0.27 ± 0.01 kg/wk; reference), higher than the recommendations (0.54 ± 0.01 kg/wk), and highest among those above the recommendations (0.91 ± 0.02 kg/wk). RESULTS: For classes I, II, and III, respectively, there were 1290, 1247, and 1198 pregnancies in the subcohort; 262, 171, and 123 SGA cases; and 353, 286, and 257 LGA cases. First-trimester GWG was not associated with SGA/LGA births. Second- and third-trimester weight maintenance was associated with potentially lower LGA risk (risk ratio [RR]: 0.80; 95% confidence interval [CI]: 0.55-1.1) but not higher SGA risk (RR: 0.98; 95% CI: 0.64-1.5) for class III. In addition, some sensitivity analyses supported no increased SGA risk with second- and third-trimester weight maintenance for classes I and II. CONCLUSIONS: Second- and third-trimester weight maintenance may be associated with more optimal birth weight for gestational age. However, how this could be achieved (e.g., through diet and exercise interventions) is unclear, given the observational design of our study.