Rising Trends of Childhood Attention-Deficit/Hyperactivity Disorder in a Large Integrated Healthcare Delivery System in Southern California, 2010-2021.

OBJECTIVE: To evaluate trends of attention-deficit/hyperactivity disorder (ADHD) diagnosis rates among children aged 5-17 years over the past decade (2010-2021) and to investigate whether there have been differences in temporal changes based on race and ethnicity, sex, or income. STUDY DESIGN: Childhood ADHD diagnosis was ascertained from electronic health records using International Classification of Diseases ninth revision (314.xx) and International Classification of Diseases tenth revision (F90.x) codes. Data were stratified by child's sex, race and ethnicity, and household income, and rates of ADHD were estimated before and after adjustment for potential confounders. RESULTS: The overall ADHD diagnosis rates increased from 3.5% in 2010 to 4.0% in 2021. ADHD diagnosis was most prevalent among White children (6.1%), then Black (4.6%), Other/multiple (3.7%), Hispanic (3.1%), and Asian/Pacific Islander (PI) (1.7%). ADHD was also highly prevalent among boys (73.3%) or family income≥$70,000 (50.0%). ADHD diagnosis increased among Black (4.2% to 5.1%), Hispanic (2.8% to 3.6%), and Asian/PI children (1.5% to 2.0%) but remained stable for White (6.2% to 6.1%) and Other/multiple race/ethnic children (3.7% to 3.7%). Increases in the prevalence among girls were also observed. CONCLUSION: The prevalence of ADHD in children has risen with the largest increases observed for Black, Hispanic, and Asian/PI children. Rates among less affluent families and girls have also been increasing, narrowing the gaps in diagnosis rates previously observed. These increases may reflect improvements in screening and provision of care among demographics where ADHD has been historically underdiagnosed.

Association between SARS-CoV-2 Infection and Adverse Perinatal Outcomes by Race/Ethnicity in a Large Integrated Health Care System.

OBJECTIVE: Recent studies have reported associations between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy and adverse perinatal outcomes but the extent to which these associations vary by race/ethnicity remains uncertain. Therefore, we examined how the association between prenatal SARS-CoV-2 infection and adverse perinatal outcomes may be modified by race/ethnicity. STUDY DESIGN: A retrospective cohort study was performed using data on 67,986 pregnant women extracted from the Kaiser Permanente Southern California electronic health records between April 6, 2020, and December 31, 2021. Upon admission to labor and delivery, all women were routinely tested for coronavirus disease 2019 (COVID-19) using real-time reverse-transcriptase polymerase chain reaction test. Adjusted odds ratios (aORs) were used to estimate associations. RESULTS: During the study period, COVID-19 was diagnosed in 4,960 (7%) of singleton pregnancies, with the highest rates observed among Hispanics (9.4%) and non-Hispanic Blacks (6.2%). Compared with non-Hispanic Whites, Hispanics (aOR: 1.12, 95% CI: 1.03, 1.21) with SARS-CoV-2 infection had the highest odds of a pregnancy associated with nonreassuring fetal heart rate tracing. Neonates of all races/ethnicities, except for non-Hispanic Blacks, showed significantly increased odds of SARS-CoV-2 infection, with the highest risk observed among Asians/Pacific Islanders (aOR: 10.88, 95% CI: 1.33, 89.04). Non-Hispanic White mothers who tested positive were admitted to intensive care unit (ICU) at a higher rate at delivery and within 7 days of delivery (aOR: 34.77, 95% CI: 11.3, 107.04; aOR: 26.48, 95% CI: 9.55, 73.46, respectively). Hispanics were also at a significantly higher odds of admission to ICU (aOR: 4.62, 95% CI: 2.69, 7.94; aOR: 4.42, 95% CI: 2.58, 7.56, respectively). Non-Hispanic Black, Hispanic, and Asian/Pacific Islander mothers who tested positive for SARS-CoV-2 prenatally, were at increased risk for preeclampsia/eclampsia, and preterm birth as compared to non-Hispanic White mothers. CONCLUSION: The findings highlight racial/ethnic disparities in the association between SARS-CoV-2 infection and adverse perinatal outcomes. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. We also observed a remarkably high risk of ICU admission for non-Hispanic White mothers infected with SARS-CoV-2. KEY POINTS: · Race/ethnicity influences perinatal outcomes in pregnancies impacted by SARS-CoV-2.. · The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders.. · White mothers had a notably high risk of ICU admission at delivery following SARS-CoV-2 infection..

The Effect of Neonatal Sepsis on Risk of Autism Diagnosis.

OBJECTIVE: The study aimed to examine the association between neonatal sepsis and autism risk among children and whether the risk varied with the timing of exposure, child's sex, and race/ethnicity. STUDY DESIGN: We conducted a retrospective cohort study using electronic health records (EHR) extracted from Kaiser Permanente Southern California Health Care System. Mother-child dyads were constructed by linking records of children born to member mothers and continuing to receive care through the system during the follow-up period with those of their biological mothers (n = 469,789). Clinical health records were used to define neonatal sepsis. Diagnosis of autism was made by medical specialists. Potential confounders included maternal sociodemographic factors, obstetrical history, child's age, sex, race/ethnicity, and maternal and child medical history. Incident rates and adjusted hazard ratios (aHR) were used to estimate the associations. RESULTS: Compared with children without the diagnosis of autism, children with the condition were more likely to be from Asian/Pacific Islander descent and male sex. Exposed children showed higher rates of autism as compared with unexposed children (3.43 vs. 1.73 per 1,000 person-years, aHR: 1.67-95% confidence interval [CI]: 1.39-2.00). Both preterm (aHR: 1.47; 95% CI: 1.09-1.98) and term (aHR: 1.63; 95% CI: 1.29-2.06) births were associated with increased risk for autism. Although the magnitude of the HRs and incidence ratios for neonatal sepsis to increase autism risk varied between race ethnicities, neonatal sepsis was associated with significantly increased likelihood of autism diagnosis for all race-ethic groups except for Asian/Pacific Islanders. Although neonatal sepsis was associated with significantly increased autism risk for both boys and girls, incident rates and HR point estimates suggested that the effect may be stronger in girls. CONCLUSION: Neonatal sepsis is associated with increased risk of autism diagnosis in preterm- and term-born children. The association was significant for both girls and boys and all race ethnicities except for Asian-Pacific Islanders. KEY POINTS: · Neonatal sepsis is associated with increased risk of autism diagnosis.. · The association was significant in preterm- and term-born children.. · The association was significant for all race/ethnicities except for Asian-Pacific Islanders..

Perinatal outcomes after bariatric surgery.

BACKGROUND: Bariatric surgery is a widely used treatment option for obesity that often provides long-term weight control and health benefits. Although a growing number of women are becoming pregnant after bariatric surgery, only a few population-based studies have assessed the impact thereof on perinatal outcomes. OBJECTIVE: This study aimed to examine the association between bariatric surgery and adverse perinatal outcomes in pregnant women and to examine whether the risk for adverse perinatal outcomes is modified by the postsurgery weight, gestational weight gain, type of bariatric surgery, timing of pregnancy after bariatric surgery, and maternal comorbidities. STUDY DESIGN: A retrospective cohort study was performed with the use of the Bariatric Surgery Registry and hospital inpatient and outpatient physician encounter records. The International Classification of Diseases, Ninth and Tenth Revision codes from hospitalizations during pregnancy and infant birth records were used to ascertain the outcomes of interest. Women eligible for BS who delivered at ≥20 weeks of gestation (n=20,213) at Kaiser Permanente Southern California hospitals (January 1, 2007 to December 31, 2018) were included in the study. Adjusted odds ratios were derived from logistic regression models with inverse probability of treatment weighting to adjust for confounding using propensity scores. RESULTS: Bariatric surgery was associated with a reduction in the risks for gestational diabetes (adjusted odds ratio, 0.60; 95% confidence interval, 0.53-0.69; P<.001), preeclampsia (adjusted odds ratio, 0.53; 95% confidence interval, 0.46-0.61; P<.001), chorioamnionitis (adjusted odds ratio, 0.45; 95% confidence interval, 0.32-0.63; P<.001), cesarean delivery (adjusted odds ratio, 0.65; 95% confidence interval, 0.59-0.72; P<.001), large for gestational age neonate (adjusted odds ratio, 0.23; 95% confidence interval, 0.19-0.29; P<.001), macrosomia (adjusted odds ratio, 0.24; 95% confidence interval, 0.19-0.30; P<.001), and neonatal intensive care unit admission (adjusted odds ratio, 0.70; 95% confidence interval, 0.61-0.81; P<.001). However, bariatric surgery was also associated with a significantly increased risk for small for gestational age neonates (adjusted odds ratio, 2.46; 95% confidence interval, 2.16-2.79; P<.001). The risk for the adverse outcomes is independent of the time interval between the surgery and subsequent pregnancy. CONCLUSION: These data suggest that there are many pregnancy outcome benefits for women with severe obesity who undergo bariatric surgery; however, women who have undergone bariatric surgery before pregnancy should be monitored closely to reduce the risk for small for gestational age neonates and postpartum hemorrhage.

Association between SARS-CoV-2 Infection and Adverse Perinatal Outcomes in a Large Health Maintenance Organization.

OBJECTIVE: This study aimed to examine whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy is associated with increased odds of perinatal complications and viral transmission to the infant. STUDY DESIGN: A retrospective cohort study of women who delivered at Kaiser Permanente Southern California hospitals (April 6, 2020-February 28, 2021) was performed using data extracted from electronic health records (EHRs). During this time polymerize chain reaction (PCR)-based tests for SARS-CoV-2 was universally offered to all pregnant women at labor and delivery admission, as well as earlier in the pregnancy, if they were displaying symptoms consistent with SARS-CoV-2 infection or a possible exposure to the virus. Adjusted odds ratio (aOR) was used to estimate the strength of associations between positive test results and adverse perinatal outcomes. RESULTS: Of 35,123 women with a singleton pregnancy, 2,203 (6%) tested positive for SARS-CoV-2 infection with 596 (27%) testing positive during the first or second trimester and 1,607 (73%) during the third trimester. Women testing positive were younger than those who tested negative (29.7 [5.4] vs. 31.1 [5.3] years; mean [standard deviation (SD)]; p < .001). The SARS-CoV-2 infection tended to increase the odds of an abnormal fetal heart rate pattern (aOR: 1.10; 95% confidence interval [CI]: 1.00, 1.21; p = 0.058), spontaneous preterm birth (aOR: 1.28; 95% CI: 1.03, 1.58; p = 0.024), congenital anomalies (aOR: 1.69; 95% CI: 1.15, 2.50; p = 0.008), and maternal intensive care unit admission at delivery (aOR: 7.44; 95% CI: 4.06, 13.62; p < 0.001) but not preeclampsia/eclampsia (aOR: 1.14; 95% CI: 0.98, 1.33; p = 0.080). Eighteen (0.8%) neonates of mothers who tested positive also had a positive SARS-CoV-2 test after 24 hours of birth, but all were asymptomatic during the neonatal period. CONCLUSION: These findings suggest that prenatal SARS-CoV-2 infection increases the odds of some adverse perinatal outcomes. The likelihood of vertical transmission from the mother to the fetus was low (0.3%), suggesting that pregnancy complications resulting from SARS-CoV-2 infection pose more risk to the baby than transplacental viral transmission. KEY POINTS: · SARS-CoV-2 infection is associated with increased odds of adverse perinatal outcomes.. · The odds of specific adverse outcomes were greater when a mother was infected earlier in pregnancy.. · The proportion of vertical transmission from mother to fetus was 0.3%.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth.

OBJECTIVES: Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. METHODS: Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. RESULTS: We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. CONCLUSIONS: These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

Maternal Hypothyroidism Increases the Risk of Attention-Deficit Hyperactivity Disorder in the Offspring.

OBJECTIVE: This study aimed to determine if hypothyroidism prior to, or during, pregnancy increases the risk of attention-deficit hyperactivity disorder (ADHD) in the child and how the association may be modified by preterm birth, sex of the child, and race-ethnicity. STUDY DESIGN: Data were abstracted from linked maternal-child medical records. Incidence rate differences (IRDs), adjusted hazard ratios (aHRs), and their 95% confidence intervals (CIs) were estimated to evaluate the association of maternal hypothyroidism with childhood ADHD risk. Stratified analyses were used to evaluate whether the association is affected by timing of first diagnosis, gestational age at birth (term vs. preterm), sex, and race-ethnicity. RESULTS: Hypothyroidism diagnosed prior to (IRD = 1.30), or during (IRD = 0.59) pregnancy increases the risk of ADHD in the children (aHR = 1.27; 95% CI: 1.15, 1.41, and 1.17; 95% CI: 1.00, 1.38). The association was strongest when diagnosed during the first trimester (IRD = 0.97 and aHR = 1.28; 95% CI: 1.04, 1.58). For children born preterm, there was significantly increased risk of ADHD if their mothers were diagnosed prior to (IRD = 3.06 and aHR = 1.43; 95% CI: 1.09, 1.88), but not during pregnancy. The effect of maternal hypothyroidism on increased risk of ADHD was stronger for boys (IRD = 1.84 and aHR = 1.26; 95% CI: 1.14, 1.40) than it was for girls (IRD = 0.48 and aHR = 1.19; 95% CI: 1.01, 1.40) and for Hispanic children (IRD = 1.60 and aHR = 1.45; 95% CI: 1.25, 1.68) compared with other race ethnicities. CONCLUSION: Exposure to maternal hypothyroidism during the periconceptual period significantly increases the risk of ADHD and that the association varies with gestational age at delivery, child sex, and race-ethnicity. KEY POINTS: · Maternal hypothyroidism increases the risk of ADHD diagnosis in the offspring.. · The association of maternal hypothyroidism with childhood ADHD was influenced by timing of diagnosis.. · Strength of the association was strongest in preterm born infants, boys, and Hispanic children..

Autism Spectrum Disorders in Children Exposed in Utero to Hyperemesis Gravidarum.

OBJECTIVE: This study aimed to determine if hyperemesis gravidarum (HG) is associated with autism spectrum disorder (ASD) risk, and how this association is influenced by race, ethnicity, sex, exposure timing, and medication used to treat it. STUDY DESIGN: This is a retrospective cohort study using records from 469,789 mother-child pairs who delivered at Kaiser Permanente Southern California (KPSC) hospital (1991-2014). Singleton-born children were followed longitudinally from 2 to 17 years of age. Clinical records were used to determine the diagnosis of HG and specialist-confirmed diagnosis of ASD. RESULTS: Children exposed to HG in-utero had higher rates of ASD than unexposed children (2.87 vs. 1.71/1,000 person-years; adjusted hazard ratio [adj.HR]: 1.53; 95% confidence interval [CI]: 1.37-1.70). Children exposed at first and second trimester of pregnancies were more likely to develop ASD; 1.58-fold (95% CI: 1.40-1.79), and 1.36-fold (95% CI: 1.05-1.75), respectively, compared with unexposed children. HG was associated with ASD for boys (adj.HR: 1.50; 95% CI: 1.33-1.70) and girls (adj.HR: 1.62; 95% CI: 1.28-2.05). HG was significantly associated with ASD risk in white and Hispanic children. The medications used to treat HG did not contribute to ASD risk. CONCLUSION: HG diagnosis is associated with ASD risk and may be helpful in identifying at-risk children who could benefit from enhanced surveillance and earlier diagnosis and intervention.

Novel Insights into the Regulatory Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 in Oxidative Stress and Inflammation of Human Fetal Membranes.

Fetal membrane dysfunction in response to oxidative stress (OS) is associated with adverse pregnancy outcomes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is one of the regulators of innate OS response. This study evaluated changes in Nrf2 expression and its downstream targets heme oxygenase (HO-1) and peroxisome proliferator-activated receptor gamma (PPARγ) in fetal membranes during OS and infection in vitro. Furthermore, we tested the roles of sulforaphane (SFN; an extract from cruciferous vegetables) and trigonelline (TRN; an aromatic compound in coffee) in regulating Nrf2 and its targets. Fetal membranes (n = 6) collected at term were placed in an organ explant system were treated with water-soluble cigarette smoke extract (CSE), an OS inducer (1:10), and lipopolysaccharide (LPS; 100 ng/mL). Nrf2 expression, expression, its enhancement by sulforaphane (SFN, 10 µM/mL) and down regulation by TRN (10uM/mL) was determined by western blots. Expression of Nrf2 response elements PPARγ (western) heme oxygenase (HO-1), and IL-6 were quantified by ELISA. CSE and LPS treatment of fetal membranes increased nrf2, but reduced HO-1 and PPARγ and increased IL-6. Co-treatment of SFN, but not with TRN, with CSE and LPS increased Nrf2 substantially, as well as increased HO-1 and PPARγ and reduced IL-6 expression. Risk factor-induced Nrf2 increase is insufficient to generate an antioxidant response in fetal membranes. Sulforaphane may enhance innate antioxidant and anti-inflammatory capacity by increasing NRF-2 expression.

A Telemedicine Approach to Covid-19 Assessment and Triage.

Covid-19 is a new highly contagious RNA viral disease that has caused a global pandemic. Human-to-human transmission occurs primarily through oral and nasal droplets and possibly through the airborne route. The disease may be asymptomatic or the course may be mild with upper respiratory symptoms, moderate with non-life-threatening pneumonia, or severe with pneumonia and acute respiratory distress syndrome. The severe form is associated with significant morbidity and mortality. While patients who are unstable and in acute distress need immediate in-person attention, many patients can be evaluated at home by telemedicine or videoconferencing. The more benign manifestations of Covid-19 may be managed from home to maintain quarantine, thus avoiding spread to other patients and health care workers. This document provides an overview of the clinical presentation of Covid-19, emphasizing telemedicine strategies for assessment and triage of patients. Advantages of the virtual visit during this time of social distancing are highlighted.

Effect of bisphenol-A (BPA) on placental biomarkers for inflammation, neurodevelopment and oxidative stress.

Background Bisphenol-A (BPA) is a widespread pollutant whose effects on pregnant women are poorly understood. Therefore, we investigated the effects of BPA on basal and bacteria-stimulated production of proinflammatory cytokines [interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α) and IL-6], anti-inflammatory mediators [soluble glycoprotein 130 (sgp) 130, heme oxidase-1 (HO-1) and IL-10] and biomarkers for neurodevelopment [brain-derived neurotrophic factor (BDNF)], and oxidative stress [8-isoprostane (8-IsoP)] by the placenta. Methods Placental explant cultures were treated with BPA (0-10,000 nM) in the presence or absence of 107 colony-forming unit (CFU)/mL heat-killed Escherichia coli for 24 h. Biomarker concentrations in conditioned medium were quantified by the enzyme-linked immunosorbent assay (ELISA). Results Under basal conditions, IL-1ß and IL-6 production was enhanced by BPA in a dose-dependent manner. Sgp130, a soluble receptor that reduces IL-6 bioactivity, was suppressed by BPA at 1000-10,000 nM. BPA also enhanced BDNF production at 1000 and 10,000 nM, and 8-IsoP expression at 10 and 100 nM. For bacteria-treated cultures, BPA increased IL-6 production at 100 nM and reduced sgp130 at 1000 nM but had no effect on IL-1ß, TNF-α, BDNF, HO-1, 8-IsoP or IL-10 production. Conclusion BPA may increase placental inflammation by promoting IL-1ß and IL-6 but inhibiting sgp130. It may also disrupt oxidative balance and neurodevelopment by increasing 8-IsoP and BDNF production.

Association between maternal hypothyroidism and autism spectrum disorders in children.

BackgroundTo determine whether hypothyroidism is associated with autism spectrum disorders (ASD) and how this association is influenced by race-ethnicity, sex, and timing of exposure.MethodsA retrospective cohort study was conducted using records from 397,201 children who were delivered from 1991 to 2011 and remained health plan members from 1993 to 2014.ResultsChildren of hypothyroid women had higher ASD rates than children of women without the diagnosis (2.14 vs. 1.62/1,000 person-years; adjusted hazard ratios (adj.HR), 1.31; 95% confidence interval (CI), 1.13-1.53). This occurred in women diagnosed before as well as during pregnancy. Maternal hypothyroidism was associated with ASD for both boys (3.93 vs. 2.62/1,000 person-years; adj.HR, 1.27; 95% CI, 1.07-1.50) and girls (1.10 vs. 0.61/1,000 person-years; adj.HR, 1.51; 95% CI, 1.10-2.08). Of women with a diagnosis of hypothyroidism during pregnancy, normal thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels were not associated with an increased risk of ASD in children. Compared with white children, prenatal hypothyroidism was associated with an increased risk of ASD in children of Hispanics (adj.HR, 1.09; 95% CI, 1.01-1.17) and women of other/mixed race-ethnicity (adj.HR, 1.08; 95% CI, 1.00-1.16).ConclusionMaternal hypothyroidism is associated with ASD in children in a manner dependent on race-ethnicity. Management of maternal hypothyroidism may ameliorate the risk of ASD.

Effects of tributyltin on placental cytokine production.

Objective Tributyltin (TBT) is a persistent pollutant but its effects on placental function are poorly understood as are its possible interactions with infection. We hypothesized that TBT alters the production of sex hormones and biomarkers for inflammation and neurodevelopment in an infection-dependent manner. Methods Placental explant cultures were treated with 0-5000 nM TBT in the presence and absence of Escherichia coli. A conditioned medium was harvested and concentrations of steroids (progesterone, P4; testosterone, T and estradiol, E2) as well as biomarkers of inflammation [interleukin (IL)-1ß (IL-1ß), tumor necrosis factor (TNF-α), IL-10, IL-6, soluble glycoprotein 130 (sgp-130) and heme oxygenase-1 (HO-1)], oxidative stress [8-iso-prostaglandin (8-IsoP)] and neurodevelopment [brain-derived neurotrophic factor (BDNF)] were quantified. Results TBT increased P4 slightly but had little or no effect on T or E2 production. IL-1ß, IL-6, sgp-130, IL-10 and 8-IsoP production was enhanced by TBT. P4 and IL-6 production was also enhanced by TBT for bacteria-stimulated cultures but TBT significantly inhibited bacteria-induced IL-1ß and sgp-130 production. High doses of TBT also inhibited BDNF production. Conclusions TBT increases P4 but has minimal effect on downstream steroids. It enhances the production of inflammatory biomarkers such as IL-1ß, TNF-α, IL-10 and IL-6. Inhibition of sgp-130 by TBT suggests that TBT may increase bioactive IL-6 production which has been associated with adverse neurodevelopmental outcomes. Reduced expression of BDNF also supports this possibility.

Association of Perinatal Risk Factors with Autism Spectrum Disorder.

Objective To examine the association between exposures to perinatal factors and autism spectrum disorders (ASD). Study Design A retrospective cohort study of ASD among children born in Kaiser Permanente Southern California hospitals between 1991 and 2009 (n = 594,638). Medical records were used to determine exposure to perinatal (antepartum and intrapartum) complications. ASD was diagnosed using DSM-IV criteria. Multivariable Cox regression was used to estimate hazard ratios (HRs). Result Children with ASD were more likely to be exposed to perinatal complications (HR = 1.15, 95% confidence interval [CI]: 1.09-1.21) than neurotypical children. Children exposed to antepartum (HR = 1.22, 95% CI: 1.10-1.36) and intrapartum (HR = 1.10, 95% CI: 1.04-1.17) complications were at increased risk of ASD. The risk was even greater when both antepartum and intrapartum conditions were present (HR = 1.44, 95% CI: 1.26-1.63). Conclusion Exposure to antepartum or intrapartum complications increases the risk of ASD in the offspring. Therefore, pregnancy complications may help identify children who could benefit from early screening and intervention for this common neurodevelopmental condition.

Efficacy of midtrimester short cervix interventions is conditional on intraamniotic inflammation.

BACKGROUND: Midtrimester ultrasound is a valuable method for identifying asymptomatic women at risk for spontaneous preterm delivery (PTD). However, response to various treatments (cerclage, progestogen) has been variable in the clinical setting. It remains unclear how other biomarkers may be used to guide intervention strategies. OBJECTIVE: We applied an amniotic fluid inflammatory scoring system to determine if the degree of inflammation is associated with intervention efficacy in patients with midtrimester short cervix. STUDY DESIGN: Women carrying a singleton fetus between 16-24 weeks' gestation with a short cervix (≤25 mm) on transvaginal ultrasound underwent amniocentesis and were assigned to McDonald cerclage, no cerclage, or weekly 17-alpha hydroxyprogesterone caproate (17OHP-C). Our previously described inflammatory risk score (comprised of 14 inflammatory markers) was used to classify patients as high (score ≥8) or low (score <8) risk for inflammation. Gestational age at delivery was compared for each intervention and risk score status. Risk of delivering as a function of the remaining gestation was evaluated using modified Cox proportional hazards models with incorporation of methods to account for both left and right truncation bias. RESULTS: Ninety patients were included: 24 were in the nonintervention control group, 51 received cerclage, and 15 received 17OHP-C. Inflammation status at time of sampling influenced the efficacy of the treatment (P < .001). Compared to the nonintervention control group, in patients with low inflammation (score < 8), both cerclage (adjusted hazard ratio [HR], 2.86; 95% confidence interval [CI], 1.28-6.37) and 17OHP-C (HR, 3.11; 95% CI, 1.04-9.30) were associated with increased hazard of PTD. In contrast, in patients with high inflammation (score ≥8) both cerclage (HR, 0.22; 95% CI, 0.08-0.65) and 17OHP-C (HR, 0.20; 95% CI, 0.05-0.81) were associated with lower hazard of delivering preterm. CONCLUSION: Cerclage placement or administration of 17OHP-C therapy for midtrimester short cervix for PTD prevention appears beneficial only in the subset of patients with high inflammation. Knowledge of the amniotic fluid inflammatory status may aid in guiding the appropriate therapy for women presenting with midtrimester short cervix who are at increased risk of PTD.

Examining the Effects of Supplemental Magnesium on Self-Reported Anxiety and Sleep Quality: A Systematic Review.

Self-treatment with vitamin, mineral, and herbal supplements has become increasingly common among patients for the treatment of psychiatric disorders. Magnesium, in particular, is popular on social media for the treatment of anxiety and insomnia. Meanwhile, preclinical studies support associations between magnesium status, sleep quality, and symptoms of anxiety. The extent to which these claims are evidence-based is unclear. Therefore, a systematic review was performed to provide an updated examination of the clinical evidence on the use of magnesium for the treatment of the above conditions given the popularity of such supplements among patients and the public at large. A thorough search of the PubMed database was performed and results were systematically reviewed using PRISMA guidelines. The search was limited to anxiety disorders and sleep disorders and included interventional trials only. Exclusion criteria included insufficient (<50 mg/12.5% of recommended daily allowance (RDA)) or unknown magnesium dose, >3 other potentially active compounds present in the formulation, and articles in languages other than English. This query returned 860 articles of which 15 met full inclusion criteria. Eight measured sleep-related outcomes, seven measured anxiety-related outcomes, and one examined both. Sleep quality was measured most frequently using the Pittsburg Sleep Quality Index (PSQI). Anxiety measures included self-reported measures such as the Hamilton Anxiety Scale. The majority of included studies demonstrated improvement in at least one sleep- or anxiety-related parameter. Five out of eight sleep-related studies reported improvements in sleep parameters, while two studies reported no improvements, and one reported mixed results. Five out of seven studies measuring anxiety-related outcomes reported improvements in self-reported anxiety. Firm conclusions were limited by the heterogeneity of the data and the small number of participants involved in most of the studies. The dosages, formulations, and durations of the magnesium interventions used also differed across studies. Furthermore, some studies included additional, potentially active ingredients, further complicating interpretations. Given the generally positive results across studies, the preponderance of preclinical evidence, and minimal side effects, however, supplemental magnesium is likely useful in the treatment of mild anxiety and insomnia, particularly in those with low magnesium status at baseline. Notably, both negative anxiety trials featured populations with underlying endocrine factors likely contributing to their symptoms (patients with premenstrual symptoms and post-partum women). Nonetheless, larger, randomized clinical trials are needed to confirm efficacy and to establish the most effective forms and dosages of magnesium for the treatment of insomnia and anxiety disorders.

Coding of Childhood Psychiatric and Neurodevelopmental Disorders in Electronic Health Records of a Large Integrated Health Care System: Validation Study.

Background: Mental, emotional, and behavioral disorders are chronic pediatric conditions, and their prevalence has been on the rise over recent decades. Affected children have long-term health sequelae and a decline in health-related quality of life. Due to the lack of a validated database for pharmacoepidemiological research on selected mental, emotional, and behavioral disorders, there is uncertainty in their reported prevalence in the literature. objectives: We aimed to evaluate the accuracy of coding related to pediatric mental, emotional, and behavioral disorders in a large integrated health care system's electronic health records (EHRs) and compare the coding quality before and after the implementation of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding as well as before and after the COVID-19 pandemic. Methods: Medical records of 1200 member children aged 2-17 years with at least 1 clinical visit before the COVID-19 pandemic (January 1, 2012, to December 31, 2014, the ICD-9-CM coding period; and January 1, 2017, to December 31, 2019, the ICD-10-CM coding period) and after the COVID-19 pandemic (January 1, 2021, to December 31, 2022) were selected with stratified random sampling from EHRs for chart review. Two trained research associates reviewed the EHRs for all potential cases of autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), major depression disorder (MDD), anxiety disorder (AD), and disruptive behavior disorders (DBD) in children during the study period. Children were considered cases only if there was a mention of any one of the conditions (yes for diagnosis) in the electronic chart during the corresponding time period. The validity of diagnosis codes was evaluated by directly comparing them with the gold standard of chart abstraction using sensitivity, specificity, positive predictive value, negative predictive value, the summary statistics of the F-score, and Youden J statistic. κ statistic for interrater reliability among the 2 abstractors was calculated. Results: The overall agreement between the identification of mental, behavioral, and emotional conditions using diagnosis codes compared to medical record abstraction was strong and similar across the ICD-9-CM and ICD-10-CM coding periods as well as during the prepandemic and pandemic time periods. The performance of AD coding, while strong, was relatively lower compared to the other conditions. The weighted sensitivity, specificity, positive predictive value, and negative predictive value for each of the 5 conditions were as follows: 100%, 100%, 99.2%, and 100%, respectively, for ASD; 100%, 99.9%, 99.2%, and 100%, respectively, for ADHD; 100%, 100%, 100%, and 100%, respectively for DBD; 87.7%, 100%, 100%, and 99.2%, respectively, for AD; and 100%, 100%, 99.2%, and 100%, respectively, for MDD. The F-score and Youden J statistic ranged between 87.7% and 100%. The overall agreement between abstractors was almost perfect (κ=95%). Conclusions: Diagnostic codes are quite reliable for identifying selected childhood mental, behavioral, and emotional conditions. The findings remained similar during the pandemic and after the implementation of the ICD-10-CM coding in the EHR system.