Predictors of Postpartum Depression: A Comprehensive Review of the Last Decade of Evidence

Postpartum depression (PPD) is one of the most frequent complications of childbirth affecting 500,000 women annually (prevalence 10% to 15%). Despite the documented adverse outcomes for mother and child, there remains a great need to develop prospective approaches to identify women at risk. This review examines some of the best-characterized molecular and clinical risk factors for PPD. We illustrate that this is a growing literature but there remains a lack of reliable molecular predictors for PPD. Current best predictors are clinical assessments for psychiatric history and adverse life events, highlighting the need for increased depression screening across the perinatal period

Maternal obesity, fish intake, and recurrent spontaneous preterm birth

Objective: Moderate fish intake in early pregnancy is associated with decreased risk of preterm birth (PTB). Obesity during pregnancy is characterized by inflammation and insufficiency of essential fatty acids. The objective of this study was to measure the association between fish intake during pregnancy and risk of recurrent spontaneous (s) PTB among lean, overweight, and obese women. Design: This is secondary analysis of a randomized controlled trial of omega-3 fatty acid supplementation for recurrent PTB prevention, 2005–2006. The primary exposure was fish intake at time of enrollment (16–22.9-week gestation). The primary outcomes were sPTB <37 weeks and sPTB <35 weeks. Maternal prepregnancy body mass index was treated as an effect modifier. Subjects: Eight hundred and fifty-two women were included, 47% were lean, 25% overweight, and 28% obese. Results: In this cohort, among lean, but not overweight or obese women, ≥1 serving of fish per week was associated with decreased frequency of sPTB <37 weeks compared with <1 serving of fish per week (45.1% versus 27.5%, p =.001) and spontaneous PTB <35 (21.4% versus 11.6%, p =.01). In adjusted models, as fish intake increased, the predicted probability of sPTB decreased in lean women but increased in overweight and obese women (p for interaction <.10). Conclusion: Fish intake was associated with lower probability of sPTB in lean women and higher probability in obese women. These findings warrant further investigation to understand the dietary or metabolic factors associated with obesity that may modulate benefit of fish intake during pregnancy

Application of a single-objective, hybrid genetic algorithm approach to pharmacokinetic model building.

A limitation in traditional stepwise population pharmacokinetic model building is the difficulty in handling interactions between model components. To address this issue, a method was previously introduced which couples NONMEM parameter estimation and model fitness evaluation to a single-objective, hybrid genetic algorithm for global optimization of the model structure. In this study, the generalizability of this approach for pharmacokinetic model building is evaluated by comparing (1) correct and spurious covariate relationships in a simulated dataset resulting from automated stepwise covariate modeling, Lasso methods, and single-objective hybrid genetic algorithm approaches to covariate identification and (2) information criteria values, model structures, convergence, and model parameter values resulting from manual stepwise versus single-objective, hybrid genetic algorithm approaches to model building for seven compounds. Both manual stepwise and single-objective, hybrid genetic algorithm approaches to model building were applied, blinded to the results of the other approach, for selection of the compartment structure as well as inclusion and model form of inter-individual and inter-occasion variability, residual error, and covariates from a common set of model options. For the simulated dataset, stepwise covariate modeling identified three of four true covariates and two spurious covariates; Lasso identified two of four true and 0 spurious covariates; and the single-objective, hybrid genetic algorithm identified three of four true covariates and one spurious covariate. For the clinical datasets, the Akaike information criterion was a median of 22.3 points lower (range of 470.5 point decrease to 0.1 point decrease) for the best single-objective hybrid genetic-algorithm candidate model versus the final manual stepwise model: the Akaike information criterion was lower by greater than 10 points for four compounds and differed by less than 10 points for three compounds. The root mean squared error and absolute mean prediction error of the best single-objective hybrid genetic algorithm candidates were a median of 0.2 points higher (range of 38.9 point decrease to 27.3 point increase) and 0.02 points lower (range of 0.98 point decrease to 0.74 point increase), respectively, than that of the final stepwise models. In addition, the best single-objective, hybrid genetic algorithm candidate models had successful convergence and covariance steps for each compound, used the same compartment structure as the manual stepwise approach for 6 of 7 (86 %) compounds, and identified 54 % (7 of 13) of covariates included by the manual stepwise approach and 16 covariate relationships not included by manual stepwise models. The model parameter values between the final manual stepwise and best single-objective, hybrid genetic algorithm models differed by a median of 26.7 % (q₁ = 4.9 % and q₃ = 57.1 %). Finally, the single-objective, hybrid genetic algorithm approach was able to identify models capable of estimating absorption rate parameters for four compounds that the manual stepwise approach did not identify. The single-objective, hybrid genetic algorithm represents a general pharmacokinetic model building methodology whose ability to rapidly search the feasible solution space leads to nearly equivalent or superior model fits to pharmacokinetic data

Life events and hemodynamic stress reactivity in the middle-aged and elderly

Recent versions of the reactivity hypothesis, which consider it to be the product of stress exposure and exaggerated haemodynamic reactions to stress that confers cardiovascular disease risk, assume that reactivity is independent of the experience of stressful life events. This assumption was tested in two substantial cohorts, one middle-aged and one elderly. Participants had to indicate from a list of major stressful life events up to six they had experienced in the previous two years. They were also asked to rate how disruptive and stressful they were, at the time of occurrence and now. Blood pressure and pulse rate were measured at rest and in response to acute mental stress. Those who rated the events as highly disruptive at the time of exposure and currently exhibited blunted systolic blood pressure reactions to acute stress. The present results suggest that acute stress reactivity may not be independent of stressful life events experience

Birthweight Extremes and Neonatal and Childhood Outcomes after Preterm Premature Rupture of Membranes

Objective To determine the association between birthweight extremes and risk of adverse neonatal and childhood outcomes following preterm premature rupture of membranes (PPROM). Study Design This is a secondary analysis of data from the Beneficial Effects of Antenatal Magnesium Sulfate Trial. Women with nonanomalous singletons and PPROM delivering ≥24.0 weeks were included. Birthweight was classified as small for gestational age (SGA), appropriate for gestational age (AGA), or large for gestational age (LGA). Composite severe neonatal morbidity and childhood outcomes at age 2, were compared between these groups. Results One thousand five hundred and ninety-eight infants were included (58 SGA, 1,354 AGA, and 186 LGA). There was an inverse relationship between birthweight and rate of composite major neonatal morbidity (55.2% of SGA, 31.5% of AGA, 18.3% of LGA, p < 0.001). Former-SGA children were more likely to be diagnosed with major composite childhood morbidity at age 2 (25.9% of SGA, 8.3% of AGA, 5.9% of LGA, p < 0.001). In multivariate models, LGA infants had improved initial neonatal outcomes compared with AGA infants (adjusted odds ratio [aOR], 0.44; 95% confidence interval [CI], 0.28-0.71; p = 0.001). Conclusion Among infants delivered following PPROM, those who were LGA at delivery had improved composite adverse neonatal outcomes. SGA increases the risk of severe neonatal morbidity, early childhood death, and moderate/severe cerebral palsy at age 2

Factors Associated with Previable Delivery following Second Trimester Rupture of Membranes

Objective To identify factors associated with previable delivery in second trimester preterm rupture of membranes (PROM). Study Design We conducted a single-center retrospective cohort study of women with pregnancies complicated by second trimester PROM (14.0-21.9 weeks' gestation) from 2000 to 2015 who elected expectant pregnancy management and achieved at least 24 hours latency. Maternal characteristics and clinical factors were compared among pregnancies that reached viability (≥ 23.0 weeks) and pregnancies delivered before viability ( 1cm, Group B streptococcus carrier status, bacterial vaginosis, and chlamydial infection during pregnancy were similar between groups. Median time to delivery was significantly shorter in women who delivered < 23 weeks compared with those who reached ≥ 23 weeks (6 vs. 46 days, p < 0.01). Conclusion Previable delivery occurred in the majority of women with second trimester PROM. No maternal or clinical factors were associated with delivery prior to viability. Counseling women with second trimester PROM should include the inability to determine which pregnancies will reach viability

17-Hydroxyprogesterone caproate (17OHP-C) coverage among eligible women delivering at 2 North Carolina hospitals in 2012 and 2013: A retrospective cohort study

Background Although a weekly injection of 17-hydroxyprogestone caproate is recommended for preventing recurrent preterm birth, clinical experience in North Carolina suggested that many eligible patients were not receiving the intervention. Objective Our study sought to assess how well practices delivering at 2 major hospitals were doing in providing access to 17-hydroxyprogesterone caproate treatment for eligible patients. Study Design This retrospective cohort analysis studied all deliveries occurring between January 1, 2012, and December 31, 2013, at 2 large hospitals in North Carolina. Women were included if they had a singleton pregnancy and history of a prior spontaneous preterm birth. We extracted demographic, payer, and medical information on each pregnancy, including whether women had been offered, accepted, and received 17-hydroxyprogesterone caproate. Our outcome of 17-hydroxyprogesterone caproate coverage was defined as documentation of ≥1 injection of the drug. Results Over the 2-year study period, 1216 women with history of a prior preterm birth delivered at the 2 study hospitals, of which 627 were eligible for 17-hydroxyprogesterone caproate eligible after medical record review. Only 296 of the 627 eligible women (47%; 95% confidence interval, 43-51%) received ≥1 dose of the drug. In multivariable analysis, hospital of delivery, later presentation for prenatal care, fewer prenatal visits, later gestation of prior preterm birth, and having had a term delivery immediately before the index pregnancy were all associated with failed coverage. Among those women who were "covered," the median number of 17-hydroxyprogesterone caproate injections was 9 (interquartile range, 4-15), with 84 of 296 charts (28%) not having complete information on the number of doses. Conclusion Even under our liberal definition of coverage, less than half of eligible women received 17-hydroxyprogesterone caproate in this sample. Low overall use suggests that there is opportunity for improvement. Quality improvement strategies, including population-based measurement of 17-hydroxyprogesterone caproate coverage, are needed to fully implement this evidence-based intervention to decrease preterm birth

Association between amygdala reactivity and a dopamine transporter gene polymorphism

Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3′ untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [15O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity

A systematic review of physiological reactivity to stimuli in autism

Objective: The prevalence of abnormal behavioural responses to a variety of stimuli among individuals with autism has led researchers to examine whether physiological reactivity is typical in this population. The current paper reviewed studies assessing physiological reactivity to sensory, social and emotional, and stressor stimuli in individuals with autism. Methods: Systematic searches of electronic databases identified 57 studies that met our inclusion criteria. A novel measure of methodological quality suitable for use with non-randomised, non-interventional, psychophysiological studies was also developed and applied. Results: Individuals with autism were found to respond differently than typically developing controls in 78.6%, 66.7%, and 71.4% of sensory, social and emotional, and stressor stimulus classes, respectively. Conclusions: Individual differences in physiological reactivity are clearly present in autism, suggesting additional research is needed to determine the variables relating to physiological reactivity among those with ASD and to examine the possibility of physiological subtype responders in this population

Loneliness, social support and cardiovascular reactivity to laboratory stress

Self-reported or explicit loneliness and social support have been inconsistently associated with cardiovascular reactivity (CVR) to stress. The present study aimed to adapt an implicit measure of loneliness, and use it alongside the measures of explicit loneliness and social support, to investigate their correlations with CVR to laboratory stress. Twenty-five female volunteers aged between 18 and 39 years completed self-reported measures of loneliness and social support, and an Implicit Association Test (IAT) of loneliness. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) reactivity indices were measured in response to psychosocial stress induced in the laboratory. Functional support indices of social support were significantly correlated with CVR reactivity to stress. Interestingly, implicit, but not explicit, loneliness was significantly correlated with DBP reactivity after one of the stressors. No associations were found between structural support and CVR indices. Results are discussed in terms of validity of implicit versus explicit measures and possible factors that affect physiological outcomes