Abortion Restrictiveness and Infant Mortality: An Ecologic Study, 2014-2018.

INTRODUCTION: The U.S. has the highest infant mortality rate among peer countries. Restrictive abortion laws may contribute to poor infant health outcomes. This ecological study investigated the association between county-level infant mortality and state-level abortion access legislation in the U.S. from 2014 to 2018. METHODS: A multivariable regression analysis with the outcome of county-level infant mortality rates, controlling for the primary exposure of state-level abortion laws, and county-level factors, county-level distance to an abortion facility, and state Medicaid expansion status was performed. Incidence rate ratios and 95% CIs were reported. Analyses were conducted in 2022-2023. RESULTS: There were 113,397 infant deaths among 19,559,660 live births (infant mortality rate=5.79 deaths/1,000 live births; 95% CI=5.75, 5.82). Black infant mortality rate (10.69/1,000) was more than twice the White infant mortality rate (4.87/1,000). In the multivariable model, increased infant mortality rates were seen in states with ≥8 restrictive laws, with the most restrictive (11-12 laws) having a 16% increased infant mortality level (adjusted incidence rate ratios=1.162; 95% CI=1.103, 1.224). Increased infant mortality rates were associated with increased county-level Black race individuals (adjusted incidence rate ratios=1.031; 95% CI=1.026, 1.037), high school education (adjusted incidence rate ratios=1.018; 95% CI=1.008, 1.029), maternal smoking (adjusted incidence rate ratios=1.025; 95% CI=1.018, 1.033), and inadequate prenatal care (adjusted incidence rate ratios=1.045; 95% CI=1.036, 1.055). CONCLUSIONS: State-level abortion law restrictiveness is associated with higher county-level infant mortality rates. The Supreme Court decision on Dobbs versus Jackson and changes in state laws limiting abortion may affect future infant mortality.

Hospital Academic Status and the Volume-Outcome Association in Postoperative Patients Requiring Intensive Care: Results of a Nationwide Analysis of Intensive Care Units in the United States.

Objective: To determine whether the outcomes of postoperative patients admitted directly to an intensive care unit (ICU) differ based on the academic status of the institution and the total operative volume of the unit. Methods: This was a retrospective analysis using the eICU Collaborative Research Database v2.0, a national database from participating ICUs in the United States. All patients admitted directly to the ICU from the operating room were included. Transfer patients and patients readmitted to the ICU were excluded. Patients were stratified based on admission to an ICU in an academic medical center (AMC) versus non-AMC, and to ICUs with different operative volume experience, after stratification in quartiles (high, medium-high, medium-low, and low volume). Primary outcomes were ICU and hospital mortality. Secondary outcomes included the need for continuous renal replacement therapy (CRRT) during ICU stay, ICU length of stay (LOS), and 30-day ventilator free days. Results: Our analysis included 22,180 unique patients; the majority of which (15,085[68%]) were admitted to ICUs in non-AMCs. Cardiac and vascular procedures were the most common types of procedures performed. Patients admitted to AMCs were more likely to be younger and less likely to be Hispanic or Asian. Multivariable logistic regression indicated no meaningful association between academic status and ICU mortality, hospital mortality, initiation of CRRT, duration of ICU LOS, or 30-day ventilator-free-days. Contrarily, medium-high operative volume units had higher ICU mortality (OR = 1.45, 95%CI = 1.10-1.91, p-value = 0.040), higher hospital mortality (OR = 1.33, 95%CI = 1.07-1.66, p-value = 0.033), longer ICU LOS (Coefficient = 0.23, 95%CI = 0.07-0.39, p-value = 0.038), and fewer 30-day ventilator-free-days (Coefficient = -0.30, 95%CI = -0.48 - -0.13, p-value = 0.015) compared to their high operative volume counterparts. Conclusions: This study found that a volume-outcome association in the management of postoperative patients requiring ICU level of care immediately after a surgical procedure may exist. The academic status of the institution did not affect the outcomes of these patients.

Infant Outcomes among Teenage and Young Mothers: Racial Inequities and the Role of Educational Attainment.

OBJECTIVE: To examine the association of age-appropriate maternal educational attainment in teenage and young mothers on infant health outcomes across racial/ethnic groups. STUDY DESIGN: In this retrospective, cross-sectional study using Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research Natality data (2016-2017), we included live births comparing 14- to 19- year-old mothers with 20- to 24-year-old mothers. To analyze the association of maternal age-appropriate education (≥8th grade for 15-18 years of age, 9th-12th grade/completed high school for 19-24 years of age), we conducted multivariable regression adjusting for mothers' demographics, reporting adjusted incidence rate ratios with 95% CI for infant mortality rate, and logistic regression for extreme prematurity and low birth weight, reporting aORs with 95% CI. RESULTS: From 2016 to 2017, there were 1 976 334 live births among women 14-24 years of age; 407 576 (20.6%) were in 14- to 19-year-olds. In the multivariable model, increased term infant mortality rate was associated with age 14-19 years (adjusted incidence rate ratio 1.18, 95% 1.10, 1.27), age-inappropriate education (adjusted incidence rate ratio 1.38, 95% CI 1.28, 1.48), and non-Hispanic Black mothers (adjusted incidence rate ratio 1.21, 95% CI 1.12, 1.30). Extreme prematurity was associated with women age 14-19 years (aOR 1.35, 95% CI 1.30, 1.40), non-Hispanic Black (aOR 2.50, 95% CI 2.39, 2.61), and Hispanic mothers (aOR 1.09, 95% CI 1.04, 1.15). Term infant low birth weight was associated with age 14-19 years (aOR 1.14, 95% CI 1.12, 1.16), age-inappropriate education for non-Hispanic White (aOR 1.16, 95% CI 1.11, 1.21), and non-Hispanic Black (aOR 1.08, 1.04, 1.12) mothers. CONCLUSIONS: Inadequate maternal educational attainment, which is influenced by modifiable social policies, is associated with increased adverse infant outcomes in mothers 14-24 years of age.

Educating paediatric health-care providers about human trafficking.

Human trafficking is a public health issue and humanitarian crisis. Most alarming is that children are especially at risk. Although many studies demonstrate that the majority of trafficked persons surveyed engage with the health-care system during the time in which they are trafficked, health-care practitioners lack the knowledge, tools and resources to assist these patients. The present efforts in training health-care professionals have been fragmented and largely ineffective. While prior training has produced short-term changes in knowledge or attitudes of health professionals, it has not produced sustained changes in knowledge and attitudes nor meaningful changes in screening or intervention. No training has demonstrated changes in patient outcomes. Trafficked persons, particularly children and survivors of labour trafficking, are inadequately served by our present training options for health-care practitioners, and evidence-based protocols are needed to care for this underserved, disenfranchised and traumatised population. To provide optimal care for trafficked youth, health-care practitioners may benefit from: (i) evaluating training for health care providers (HCP) rigorously and meaningfully; (ii) advocating for high-quality training for all HCPs; (iii) fostering partnerships with key stakeholders to inform training and practice; and (iv) designing HCP training that is comprehensive, spanning all forms of human trafficking and including all populations involved.

N-Acetylcysteine for Pediatric Obsessive-Compulsive Disorder: A Small Pilot Study.

Background: Many children and adults with Obsessive-Compulsive Disorder (OCD) fail to respond to first-line pharmacological and behavioral treatments. Glutamate dysfunction may contribute to the development of OCD. N-acetylcysteine (NAC), a glutamate modulating drug, has shown to be a promising agent in adults with OCD. Methods: We conducted a double-blind, placebo-controlled clinical trial from July 2012 to January 2017. Children ages 8 to 17 years with OCD were assigned to receive NAC (up to 2700 mg/day) or the matching placebo for a period of 12 weeks. Children were required to be on stable psychiatric treatment (both medication and therapy) but were not required to be treatment-refractory. The primary outcome was OCD symptom severity as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We used linear mixed models to analyze the effect of NAC compared to placebo. Results: Due to poor recruitment and eventual expiration of the study medication, enrollment was stopped at 11 children out of a planned sample size of 40. Nonetheless, NAC was associated with significant reduction in CY-BOCS total score compared to placebo (Satterthwaite's test: t (37) = 2.36, p = 0.024) with effects separating from placebo beginning at week 8. Mean CY-BOCS total score decreased in the NAC group from 21.4 ± 4.65 at baseline to 14.4 ± 5.55 at week 12. In the placebo group, mean CY-BOCS total score remained unchanged (21.3 ± 4.65). In the NAC group, 1 out of 5 participants achieved >35% improvement in CY-BOCS total score, while none of the six patients in placebo group reached this improvement level. NAC and placebo were well tolerated. One mild adverse event was reported in each group. Conclusions: Our trial suggests that there may be some initial improvement in OCD symptom severity with NAC treatment. NAC was well tolerated in the study population. Future trials should employ multiple sites and have a larger study population to further confirm any benefits of NAC.

The Drosophila melanogaster PIF1 Helicase Promotes Survival During Replication Stress and Processive DNA Synthesis During Double-Strand Gap Repair.

PIF1 is a 5' to 3' DNA helicase that can unwind double-stranded DNA and disrupt nucleic acid-protein complexes. In Saccharomyces cerevisiae, Pif1 plays important roles in mitochondrial and nuclear genome maintenance, telomere length regulation, unwinding of G-quadruplex structures, and DNA synthesis during break-induced replication. Some, but not all, of these functions are shared with other eukaryotes. To gain insight into the evolutionarily conserved functions of PIF1, we created pif1 null mutants in Drosophila melanogaster and assessed their phenotypes throughout development. We found that pif1 mutant larvae exposed to high concentrations of hydroxyurea, but not other DNA damaging agents, experience reduced survival to adulthood. Embryos lacking PIF1 fail to segregate their chromosomes efficiently during early nuclear divisions, consistent with a defect in DNA replication. Furthermore, loss of the BRCA2 protein, which is required for stabilization of stalled replication forks in metazoans, causes synthetic lethality in third instar larvae lacking either PIF1 or the polymerase delta subunit POL32. Interestingly, pif1 mutants have a reduced ability to synthesize DNA during repair of a double-stranded gap, but only in the absence of POL32. Together, these results support a model in which Drosophila PIF1 functions with POL32 during times of replication stress but acts independently of POL32 to promote synthesis during double-strand gap repair.

Monotherapy Insufficient in Severe Anxiety? Predictors and Moderators in the Child/Adolescent Anxiety Multimodal Study.

This secondary analysis of the Child/Adolescent Anxiety Multimodal Study (CAMS) used baseline patient characteristics to identify prognostic subgroups of children based on likelihood of remission. We also investigated predictors and moderators of outcome. CAMS randomized 488 youths with generalized, social, and separation anxiety disorders to cognitive behavioral therapy (CBT), sertraline, both, or pill placebo. Outcomes were Week 12 child, parent, and independent evaluator (IE) ratings of child anxiety. We used receiver operating characteristics analysis and stepwise regression to identify predictors and moderators of outcome. Severe anxiety, lower socioeconomic status, and comorbid obsessive-compulsive disorder predicted higher IE-rated anxiety posttreatment; child-rated social anxiety predicted poorer outcomes reported by all informants. Regarding moderators, Hispanic ethnicity predicted higher IE-rated anxiety after CBT and higher parent-rated anxiety after sertraline. In youths with severe anxiety (Pediatric Anxiety Rating Scale ≥ 20, <italic>n</italic> = 220), combination treatment increased remission (relative risk [RR] = 2.85, <italic>p</italic> < .001), 95% confidence interval (CI) [1.51, 5.39], whereas CBT (RR = 1.55, <italic>p</italic> = .20), 95% CI [0.77, 3.10], and sertraline (RR = 1.27, <italic>p</italic> = .53), 95% CI [0.59, 2.73], did not significantly increase remission relative to placebo. These are the first findings demonstrating that a combination of CBT and a selective serotonin reuptake inhibitor, not monotherapy, is likely key for achieving remission in severe anxiety. CAMS was not powered to detect treatment efficacy after stratification by anxiety severity, so further research is needed regarding effective treatments in severe anxiety. Our main effect findings suggest youth with severe anxiety (especially social phobia), low socioeconomic status and obsessive-compulsive disorder benefit less from current first-line treatments relative to other anxious youth. ClinicalTrials.gov: NCT00052078.

Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial.

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F9,115=2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F10,141=0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.

Risk of Irritability With Psychostimulant Treatment in Children With ADHD: A Meta-Analysis.

OBJECTIVE: Irritability is listed as a common side effect of psychostimulant medications. However, psychostimulants have been demonstrated as an effective treatment in reducing irritability and aggression in children with attention-deficit/hyperactivity disorder (ADHD). The goal of this study was to quantify the risk of irritability as a side effect of psychostimulant treatment for ADHD. DATA SOURCES AND STUDY SELECTION: A PubMed search was conducted on August 18, 2013, to identify all double-blind, randomized, placebo-controlled trials published in English examining the efficacy of psychostimulant medications in the treatment of children with ADHD. Trials were excluded if (1) they required additional psychiatric or medical comorbidity in addition to ADHD, (2) they involved fewer than 20 subjects (parallel group trials), or (3) children received psychostimulant medication for less than 1 week. DATA EXTRACTION: A fixed-effects meta-analysis was used to examine the risk ratio of irritability reported as a side effect in children treated with psychostimulants compared to placebo. Stratified subgroup analysis and meta-regression were used to examine the effects of stimulant type, dosage, duration of use, and trial design on the measured risk of irritability. RESULTS: From 92 potentially eligible trials, the meta-analysis identified 32 trials involving 3,664 children with ADHD that reported data on irritability as a side effect. The relative risk of irritability significantly differed between psychostimulant classes (test for subgroup differences χ²1 = 7.6, P = .006). Methylphenidate derivatives were associated with a significantly decreased risk of irritability compared to placebo (risk ratio [RR] = 0.89 [95% CI, 0.82 to 0.96], z = -2.87, P = .004, k = 32, I² = 50%), whereas amphetamine derivatives were associated with a significantly increased risk of irritability (RR = 2.90 [95% CI, 1.26 to 6.71], z = 2.5, P = .01, k = 5, I² = 0%). CONCLUSIONS: This meta-analysis suggests an increased risk of irritability may be confined to amphetamine-derived psychostimulants. Future meta-analyses examining the effects of amphetamine and methylphenidate derivatives on irritability as a continuous measure, as well as head-to-head trials between methylphenidate and amphetamine derivatives examining effects on irritability, will be important to replicate the findings of this meta-analysis.

Time Course and Predictors of Suicidal Ideation During Citalopram Treatment in the STAR*D Trial.

OBJECTIVE: Selective serotonin reuptake inhibitors are first-line treatment for major depressive disorder (MDD), but their impact on suicidal ideation is equivocal. Our goal is to examine the time course and clinical predictors of citalopram-induced suicidal ideation during phase 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. METHODS: Of the 4,041 subjects with DSM-IV nonpsychotic MDD in the STAR*D trial phase 1 (2001-2006), we included in our analysis 3,577 subjects who reported side-effect data and had received citalopram (20-60 mg/d) for 8-14 weeks. Suicidal ideation was reported on item 12 of the Quick Inventory of Depressive Symptomatology, Self-Report. Survival analysis and receiver operating characteristic analysis were used to assess baseline characteristics associated with emergence and worsening of suicidal ideation. RESULTS: Suicidal ideation was more likely to occur early in citalopram treatment, with few subjects showing emergence or worsening occurring after 6 weeks of treatment. Clinical variables explained very little of the variance in worsening or emergence of suicidal ideation with citalopram treatment (generalized R² ≤ 2% in survival analysis). Being Hispanic, taking sedative medications, increased depression severity, absence of hypersomnia, and cardiac comorbidity were significantly (P ≤ .04) associated with greater likelihood of emergence of suicidal ideation in patients without suicidal ideation at baseline. Being widowed, better work performance, weight loss at baseline, and the presence of vascular or neurologic comorbidities were associated with a greater likelihood of worsening of suicidal ideation. CONCLUSIONS: Baseline clinical variables were poor predictors of emergence or worsening of suicidal ideation. As such, increased research focusing on clinical correlates rather than clinical predictors of suicidal ideation may be useful, as intervening events may be crucial in bringing about increased suicidality. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00021528.

Obsessive-compulsive symptoms are associated with psychiatric comorbidities, behavioral and clinical problems: a population-based study of Brazilian school children.

Pediatric-onset obsessive-compulsive disorder (OCD) is underdiagnosed, and many affected children are untreated. The present study seeks to evaluate the presence and the clinical impact of OCD and obsessive-compulsive symptoms (OCS) in a large sample of school-age children. In Phase I, we performed an initial screening using the Family History Screen (FHS). In Phase II, we identified an "at-risk" sample, as well as a randomly selected group of children. A total of 2,512 children (6-12 years old) were assessed using the FHS, the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), and the Child Behavior Checklist (CBCL). Data analyses included descriptive and multivariate analytical techniques. 2,512 children (mean age: 8.86 ± 1.84 years; 55.0% male) were categorized into one of the three diagnostic groups: OCD (n = 77), OCS (n = 488), and unaffected controls (n = 1,947). There were no significant socio-demographic differences (age, gender, socioeconomic status) across groups. The OCS group resembled the OCD on overall impairment, including school problems and delinquent behaviors. However, the OCD group did have significantly higher rates of several comorbid psychiatric disorders, including separation anxiety, generalized anxiety, and major depressive disorder, than OCS or unaffected controls. Moreover, the OCD group also scored higher than the SDQ, as well as on each of CBCL items rated by the parent. Our findings suggest that there is a psychopathological continuum between OCS and OCD in school-aged children. The presence of OCS is associated with functional impairment, which needs further investigation in longitudinal studies.

Meta-Analysis: Reduced Risk of Anxiety with Psychostimulant Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Anxiety is a commonly reported side-effect of psychostimulant treatment. Our goal was to quantify the risk of anxiety as a side effect of psychostimulant treatment for attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with ADHD. We used a fixed-effects meta-analysis to examine the risk ratio of anxiety reported as a side effect in children treated with psychostimulants compared with those treated with placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dosage, duration of use, and trial design on the measured risk of anxiety. RESULTS: We identified 23 studies involving 2959 children with ADHD for inclusion in our meta-analysis. The risk of anxiety associated with psychostimulant treatment was significantly lower than that experienced with placebo (relative risk [RR] = 0.86 [95% CI: 0.77, 0.95], z = -2.90, p < 0.05). Higher doses of psychostimulants were associated with a reduced measured risk of anxiety of psychostimulants when compared with placebo (ß = -0.0039 [95% CI: -0.00718, -0.00064], z = -2.34, p = 0.019). CONCLUSIONS: Meta-analysis suggests that treatment with psychostimulants significantly reduced the risk of anxiety when compared with placebo. This finding does not rule out the possibility that some children experience increased anxiety when treated with psychostimulants, but suggests that those risks are outweighed by the number of children who experience improvement in anxiety symptoms (possibly as a secondary effect of improved control of ADHD symptoms). Clinicians should consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.

Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.

OBJECTIVE: Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. METHOD: We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. RESULTS: We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. CONCLUSION: Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.

Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors in Pediatric Major Depressive Disorder.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for pediatric major depressive disorder (MDD). We conducted a meta-analysis to examine the following: the time-course of response to SSRIs in pediatric depression; whether higher doses of SSRIs are associated with an improved response in pediatric depression; differences in efficacy between SSRI agents; and whether the time-course and magnitude of response to SSRIs is different in pediatric and adult patients with MDD. METHOD: We searched PubMed and CENTRAL for randomized controlled trials comparing SSRIs to placebo for the treatment of pediatric MDD. We extracted weekly symptom data from trials to characterize the trajectory of pharmacological response to SSRIs. Pooled estimates of treatment effect were calculated based on standardized mean differences between treatment and placebo groups. RESULTS: The meta-analysis included 13 pediatric MDD trials with a total of 3,004 patients. A logarithmic model indicating that the greatest benefits of SSRIs occurred early in treatment best fit the longitudinal data (log[week] = 0.10, 95% CI = 0.06-0.15, p < .0001). There were no significant differences based on maximum SSRI dose or between particular SSRI agents. SSRIs were demonstrated to have a smaller benefit in pediatric compared to adult MDD. CONCLUSION: Treatment gains in pediatric MDD are greatest early in treatment and are, on average, minimal after 4 weeks of SSRI pharmacotherapy in pediatric MDD. Further research is needed using individual patient data to examine the power of early SSRI response (e.g., 2-4 weeks) to predict outcomes in short-term pharmacological trials.

Obstetric and neonatal outcomes after antipsychotic medication exposure in pregnancy.

OBJECTIVE: Antipsychotic medications are used by increasing numbers of women of reproductive age. The safety of these medications during pregnancy has not been well described. We undertook a systematic review and meta-analysis of the adverse obstetric and neonatal outcomes associated with exposure to antipsychotics during pregnancy. DATA SOURCES: PubMed, Reprotox, and ClinicalTrials.gov were searched to identify potential studies for inclusion. METHODS OF STUDY SELECTION: Case-control or cohort studies estimating adverse birth outcomes associated with antipsychotic exposure during pregnancy were included. Pooled odds ratios (ORs) were used for dichotomous outcomes and weighted mean differences were used for neonatal birth weight and gestational age. Thirteen cohort studies, including 6,289 antipsychotic-exposed and 1,618,039 unexposed pregnancies, were included. TABULATION, INTEGRATION, AND RESULTS: Antipsychotic exposure was associated with an increased risk of major malformations (absolute risk difference [ARD] 0.03, 95% confidence interval [CI] 0.00-0.05, P=.04, Z=2.06), heart defects (ARD 0.01, 95% CI 0.00-0.01, P<.001, Z=3.44), preterm delivery (ARD 0.05, 95% CI 0.03-0.08, P<.001, Z=4.10), small-for-gestational-age births (ARD 0.05, 95% CI 0.02-0.09, P=.006, Z=2.74), elective termination (ARD 0.09, 95% CI 0.05-0.13, P<.001, Z=4.69), and decreased birth weight (weighted mean difference -57.89 g, 95% CI -103.69 to -12.10 g, P=.01). There was no significant difference in the risk of major malformations (test for subgroup differences: χ²=0.07, degrees of freedom=1, P=.79) between typical (OR 1.55, 95% CI 1.21-1.99, P=.006) and atypical (OR 1.39, 95% CI 0.66-2.93, P=.38) antipsychotic medications. Antipsychotic exposure was not associated with risk of large-for-gestational-age births, stillbirth, and spontaneous abortion. Although antipsychotic exposure during pregnancy was associated with increased risk of adverse obstetric and neonatal outcomes, this association does not necessarily imply causation. This analysis was limited by the small number of included studies and limited adjustment in studies for possible confounders. CONCLUSION: Women requiring antipsychotic treatment during pregnancy appear at higher risk of adverse birth outcomes, regardless of causation, and may benefit from close monitoring and minimization of other potential risk factors during pregnancy.