Trajectories of prenatal alcohol exposure and behavioral outcomes: Findings from a community-based sample.

OBJECTIVE: To characterize patterns of prenatal alcohol exposure (PAE), and determine whether PAE trajectories were associated with behavior from a community-based sample of first-grade children. METHODS: Using data collected as part of the Collaboration of Fetal Alcohol Spectrum Disorders Prevalence study (n = 1663), we performed longitudinal cluster analysis on prenatal alcohol use reported for four time points around conception and pregnancy. From the sample, 638 respondents reported any alcohol use in pregnancy and were included in trajectories for average daily and maximum drinks per drinking day (max DDD). We then estimated the association with behavioral problems measured by the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF) with multivariable linear regression. The reference group had 1025 children with no reported PAE. RESULTS: Five trajectories were selected to describe max DDD patterns: very low/discontinuing (n = 186), low/discontinuing (n = 111), very low/continuing (n = 47), med/high (n = 245), and high (n = 49). Six trajectories best described average daily alcohol use: very low/discontinuing (n = 378), very low/continuing (n = 98), low/continuing (n = 56), low/discontinuing (n = 37), medium/high (n = 35), and high (n = 31). When assessing max DDD trajectories for both the CBCL and TRF, individuals with PAE in the two highest trajectories and the very low/continuing trajectory had more behavioral problems relative to children with no PAE, although confidence intervals for most estimates included the null. PAE modeled as average drinks per day did not predict behavior in any consistent pattern. CONCLUSIONS: In this community-based sample, select PAE trajectories were associated with behavior, even at relatively low levels of PAE that continued later in gestation.

Autoimmune conditions and comorbid depression in pregnancy: examining the risk of preterm birth and preeclampsia.

OBJECTIVE: The objective of this study was to determine whether prenatal depression interacts with autoimmune conditions to further increase the risk of preterm birth or preeclampsia. STUDY DESIGN: Our sample included 3034 pregnant women with rheumatoid arthritis (RA), Crohn's disease (CD) or psoriasis, or controls that were prospectively enrolled into MothertoBaby pregnancy studies. We estimated the independent and joint effects of the three autoimmune conditions and depression on the select outcomes. RESULTS: We found an increased risk of preterm birth among women with RA (2.10; 95% confidence interval (CI) 1.54, 2.87), CD (1.87; 95% CI 1.25, 2.81) or psoriasis (1.88; 95% CI 1.27, 2.79) independent of depression status. RA was also independently associated with preeclampsia. Prenatal depression was not independently associated with preterm birth or preeclampsia, nor was there any synergism with autoimmune conditions. CONCLUSION: If these findings are confirmed, the absence of synergism should be encouraging news to the many women with select autoimmune conditions and depression in pregnancy.

Childhood adversity, adult stress, and the risk of major depression or generalized anxiety disorder in US soldiers: a test of the stress sensitization hypothesis.

BACKGROUND: The stress sensitization theory hypothesizes that individuals exposed to childhood adversity will be more vulnerable to mental disorders from proximal stressors. We aimed to test this theory with respect to risk of 30-day major depressive episode (MDE) and generalized anxiety disorder (GAD) among new US Army soldiers. METHODS: The sample consisted of 30 436 new soldier recruits in the Army Study to Assess Risk and Resilience (Army STARRS). Generalized linear models were constructed, and additive interactions between childhood maltreatment profiles and level of 12-month stressful experiences on the risk of 30-day MDE and GAD were analyzed. RESULTS: Stress sensitization was observed in models of past 30-day MDE (χ2 8 = 17.6, p = 0.025) and GAD (χ2 8 = 26.8, p = 0.001). This sensitization only occurred at high (3+) levels of reported 12-month stressful experiences. In pairwise comparisons for the risk of 30-day MDE, the risk difference between 3+ stressful experiences and no stressful experiences was significantly greater for all maltreatment profiles relative to No Maltreatment. Similar results were found with the risk for 30-day GAD with the exception of the risk difference for Episodic Emotional and Sexual Abuse, which did not differ statistically from No Maltreatment. CONCLUSIONS: New soldiers are at an increased risk of 30-day MDE or GAD following recent stressful experiences if they were exposed to childhood maltreatment. Particularly in the military with an abundance of unique stressors, attempts to identify this population and improve stress management may be useful in the effort to reduce the risk of mental disorders.

Psychosocial stressors and lung function in youth ages 10-17: an examination by stressor, age and gender.

Background: Research on the impact of psychosocial stressors on child and adolescent lung function is uncommon, and has primarily relied either on parents' own stress measures or parent-reported stressors the child experienced, which may be a poor proxy for perceived stress in older children and adolescents. Methods: We performed multivariate linear regression of spirometry measures (FVC, FEV1 and FEF25-75) and psychosocial stressors in 584 adolescents in the Los Angeles Family and Neighborhood Survey. We examined family conflict, unsafe neighborhood or school, and the absence of a father in models stratified by gender, adjusting for PM2.5 and potential confounders. Results: We observed reductions in lung function in males related to the absence of a father in the house (FEV1: -176.2 ml, 95% CI -322.7, -29.7) and family conflict (FEV1: -156.2 ml, 95% CI -327.8, 15.5); associations were stronger in older males ages 15-17 years for each stressor (P for interaction of age and sex was 0.009 and 0.06, respectively). Conclusions: This research informs a very small literature on psychosocial stressors and lung function in adolescents. Our finding of differential vulnerability by age and gender warrants further exploration of adolescent psychosocial stressor response on lung function.

Maternal use of selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn.

Use of selective serotonin reuptake inhibitors (SSRIs) in late pregnancy has been associated with persistent pulmonary hypertension of the newborn (PPHN), a rare condition with substantial infant mortality and morbidity. Although the increase in absolute risk is small on a population level, it may be of concern to many patients. It remains unclear the extent to which the increased risks reported for PPHN are explained by the underlying maternal illness rather than the use of SSRIs.

Change in paternity and select perinatal outcomes: causal or confounded?

Select social, behavioural and maternal characteristics were evaluated to determine if they were confounding factors in the association between paternity change and pre-eclampsia, small for gestational age (SGA) and pre-term delivery, in a sample of 1,409 women. Multivariate logistic regression analysis was used to determine if any of these risk factors modified the association between changing paternity and the selected perinatal outcomes. Results of the analysis showed that women who changed partners were more likely to possess potentially confounding risk factors compared with those who had not. Paternity change was 2.75 times more likely to be associated with the development of pre-eclampsia (95% CI 1.33; 5.68) and 2.25 times more likely to be associated with an SGA infant on weight (95% CI 1.13; 4.47), after adjusting for selected risk factors. Paternity change remains a significant risk factor for pre-eclampsia and SGA in the presence of select risk factors.

Potentially modifiable risk factors for adverse pregnancy outcomes in women with psoriasis.

BACKGROUND: Data on pregnancy outcomes among women with psoriasis are lacking. However, there are several known comorbidities of psoriasis, including obesity, smoking and depression, each of which increases the risk for negative birth outcomes. OBJECTIVES: To determine if pregnant women with psoriasis have an excess of potentially modifiable risk factors for adverse pregnancy outcomes. METHODS: Prospectively collected data from the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project were analysed to compare the prevalence of selected risk factors between 170 pregnant women with psoriasis and 158 nondiseased controls. RESULTS: Women with psoriasis were more likely to be overweight/obese prior to pregnancy (P < 0.0001), to smoke (P < 0.0001), or to have a diagnosis of depression (P = 0.03), and were less likely to have been taking preconceptional vitamin supplements (P = 0.004). After controlling for race/ethnicity and socioeconomic status, women with psoriasis were 2.37 (95% confidence interval 1.45-3.87) times more likely to be overweight/obese as women without psoriasis. Duration of disease, age at onset, measures of disease impact during pregnancy, or use of biologics in pregnancy were not significant predictors of overweight/obesity in the subset of psoriatic women. CONCLUSIONS: Pregnant women with psoriasis may be at increased risk for adverse pregnancy outcomes due to comorbidities or other health behaviours associated with the disease. These should be taken into consideration during clinical treatment of women with psoriasis who are in their childbearing years.

Effects of some vanadyl coordination compounds on the in vitro insulin release from rat pancreatic islets.

Many lines of evidence indicate that vanadium inorganic salts possess insulin-mimetic and insulinotropic properties. However, they are poorly absorbed, so high oral doses are required to achieve effective plasma concentrations with possible undesirable toxic side-effects ensuing. Various organically-chelated vanadium compounds have been synthesized that are more potent than inorganic vanadium salts in their insulin-like effects due to their greater bioavailability. Unfortunately, little is known about the possible insulin secretagogue action of organic vanadyl coordination compounds. Hence, we investigated the effect of [VO(metformin)2]H2O, [VO(salicylidene-ethylenedimmine)2] and [VO(pyrrolidine-N-dithiocarbamate)2](VODTC) on insulin release from isolated rat pancreatic islets, and compared it to that of vanadyl sulfate (VOSO4). Of the three coordination compounds, only VODTC was found to exert insulin secretagogue action. VODTC, within concentrations ranging from 0.1 to 1.0 mM, enhanced both basal and glucose (11 mM)-stimulated insulin release. The effect involves calcium channels, since it was not appreciable in Ca2+-free medium. The stimulating action of VODTC required the presence of the whole metal-chelator complex inasmuch as the chelator DTC alone was ineffective. VOSO4 was unable to bring about any significant rise in insulin release from isolated islets. Taken together, our findings indicate that VODTC may be considered a potential elective pharmaceutical tool in the therapy of diabetes, especially of type 2, through its concomitant stimulatory effect on insulin secretion and insulin-mimetic action.

X-ray, NMR, and theoretical studies of the nootropic agent BMY-21502, a pyrrolidinone derivative.

The preferred crystalline, solution, and in vacuo arrangements of 1-[[1-[2-trifluoromethyl)-4-pyrimidinyl]-4-piperidinyl]methyl]-2-pyrroli dinone (BMY-21502) were investigated by means of single-crystal X-ray diffraction, 1H and 13C NMR spectroscopy, and semiempirical molecular orbital and molecular mechanics calculations. The X-ray powder diffraction pattern is also reported.

X-ray molecular structures and theoretical conformational studies of narcotic analgesics alpha-(-)-N-cis-3-chloroallyl-normetazocine, ethylketazocine, and ketazocine.

The X-ray molecular structures of the narcotic analgesics alpha-(-)-2-cis-3-chlorallyl-2'-hydroxy-5,9-dimethyl-6,7-benzomorp han (1) and alpha-(+-)-2-cyclopropylmethyl-2'-hydroxy-5-ethyl-9-methyl-8-oxo-6,7- benzomorphan (ethylketazocine, 2) were determined. The structures and conformations in the crystal were compared and discussed with respect to that of alpha-(+-)-2-cyclopropylmethyl-2'-hydroxy-5,9-dimethyl-8- oxo-6,7-benzomorfan (ketazocine, 3) and those of 15 analogous compounds of the 2'-hydroxy-6,7-benzomorphan series whose structures were previously determined by X-ray analysis. Molecular modeling routines for 1, 2, and 3 produced configurations (N-equatorial) and conformations (distorted chair) of the piperidine ring that were in agreement with those found in the solids. Theoretical studies of the conformations and the rotational energetics of 1, 2, and 3 as cationic species were performed by both the force field (MM2) and the semiquantitative (AM1) methods. The latter method predicted three low energy conformations about N--C(12) and C(12)--C(13) bonds, one of these being more significantly populated (60-68%). The AM1 results were not reproduced by the MM2 method, which predicted four low energy conformations. An interesting common feature of 1, 2, and 3 that was noted with both methods was the restricted interconversion route from the conformational state to another through rotations about the C(12)--C(13) bond. The conformational results were discussed in terms of a working hypothesis for regulation of relative mu and kappa analgesic activities of benzomorphans.