Association of Prenatal Exposure to Maternal Drinking and Smoking With the Risk of Stillbirth.

Importance: Prenatal smoking is a known modifiable risk factor for stillbirth; however, the contribution of prenatal drinking or the combination of smoking and drinking is uncertain. Objective: To examine whether prenatal exposure to alcohol and tobacco cigarettes is associated with the risk of stillbirth. Design, Setting, and Participants: The Safe Passage Study was a longitudinal, prospective cohort study with data collection conducted between August 1, 2007, and January 31, 2015. Pregnant women from Cape Town, South Africa, and the Northern Plains region of the US were recruited and followed up throughout pregnancy. Data analysis was performed from November 1, 2018, to November 20, 2020. Exposure: Maternal consumption of alcohol and tobacco cigarettes in the prenatal period. Main Outcomes and Measures: The main outcomes were stillbirth, defined as fetal death at 20 or more weeks' gestation, and late stillbirth, defined as fetal death at 28 or more weeks' gestation. Self-reported alcohol and tobacco cigarette consumption was captured at the recruitment interview and up to 3 scheduled visits during pregnancy. Participants were followed up during pregnancy to obtain delivery outcome. Results: Of 11663 pregnancies (mean [SD] gestational age at enrollment, 18.6 [6.6] weeks) in 8506 women for whom the pregnancy outcome was known by 20 weeks' gestation or later and who did not terminate their pregnancies, there were 145 stillbirths (12.4 per 1000 pregnancies) and 82 late stillbirths (7.1 per 1000 pregnancies). A total of 59% of pregnancies were in women from South Africa, 59% were in multiracial women, 23% were in White women, 17% were in American Indian women, and 0.9% were in women of other races. A total of 8% were older than 35 years. In 51% of pregnancies, women reported no alcohol or tobacco cigarette exposure (risk of stillbirth, 4 per 1000 pregnancies). After the first trimester, 18% drank and smoked (risk of stillbirth, 15 per 1000 births), 9% drank only (risk of stillbirth, 10 per 1000 pregnancies), and 22% smoked only (risk of stillbirth, 8 per 1000 pregnancies). Compared with the reference group (pregnancies not prenatally exposed or without any exposure after the first trimester), the adjusted relative risk of late stillbirth was 2.78 (98.3% CI, 1.12-6.67) for pregnancies prenatally exposed to drinking and smoking, 2.22 (98.3% CI, 0.78-6.18) for pregnancies prenatally exposed to drinking only after the first trimester, and 1.60 (98.3% CI, 0.64-3.98) for pregnancies prenatally exposed to smoking only after the first trimester. The adjusted relative risk for all stillbirths was 1.75 (98.3% CI, 0.96-3.18) for dual exposure, 1.26 (98.3% CI, 0.58-2.74) for drinking only, and 1.27 (98.3% CI, 0.69-2.35) for smoking only compared with the reference group. Conclusions and Relevance: These results suggest that combined drinking and smoking after the first trimester of pregnancy, compared with no exposure or quitting before the end of the first trimester, may be associated with a significantly increased risk of late stillbirth.

Concurrent prenatal drinking and smoking increases risk for SIDS: Safe Passage Study report.

BACKGROUND: Sudden infant death syndrome (SIDS) is the leading cause of postneonatal mortality. Although the rate has plateaued, any unexpected death of an infant is a family tragedy thus finding causes and contributors to risk remains a major public health concern. The primary objective of this investigation was to determine patterns of drinking and smoking during pregnancy that increase risk of SIDS. METHODS: The Safe Passage Study was a prospective, multi-center, observational study with 10,088 women, 11,892 pregnancies, and 12,029 fetuses, followed to 1-year post delivery. Subjects were from two sites in Cape Town, South Africa and five United States sites, including two American Indian Reservations. Group-based trajectory modeling was utilized to categorize patterns of drinking and smoking exposure during pregnancy. FINDINGS: One-year outcome was ascertained in 94·2% infants, with 28 SIDS (2·43/1000) and 38 known causes of death (3·30/1000). The increase in relative risk for SIDS, adjusted for key demographic and clinical characteristics, was 11·79 (98·3% CI: 2·59-53·7, p < 0·001) in infants whose mothers reported both prenatal drinking and smoking beyond the first trimester, 3.95 (98·3% CI: 0·44-35·83, p = 0·14), for drinking only beyond the first trimester and 4·86 (95% CI: 0·97-24·27, p = 0·02) for smoking only beyond the first trimester as compared to those unexposed or reported quitting early in pregnancy. INTERPRETATION: Infants prenatally exposed to both alcohol and cigarettes continuing beyond the first trimester have a substantially higher risk for SIDS compared to those unexposed, exposed to alcohol or cigarettes alone, or when mother reported quitting early in pregnancy. Given that prenatal drinking and smoking are modifiable risk factors, these results address a major global public health problem. FUNDING: National Institute on Alcohol Abuse and Alcoholism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute on Deafness and Other Communication Disorders.

A modified Timeline Followback assessment to capture alcohol exposure in pregnant women: Application in the Safe Passage Study.

Prenatal alcohol exposure (PAE) has been linked to poor pregnancy outcomes, yet there is no recognized standard for PAE assessment, and the specific effects of quantity, frequency, and timing remain largely unknown. The Safe Passage Study was designed to investigate the role of PAE in a continuum of poor peri- and postnatal outcomes. The objective of this manuscript is to describe the rationale for, and feasibility of, modifications to the traditional Timeline Followback (TLFB) for collecting PAE information in a large cohort of pregnant women. Participants from the Northern Plains region (in the United States) and Cape Town, South Africa, were followed prospectively using a modified 30-day TLFB interview, administered up to five times, to obtain detailed PAE information. Required modifications for our population included capturing information regarding sharing, type/brand, container size, and duration, in order to accurately record the amount of alcohol consumed. PAE status was defined for 99.9% of the 11,892 enrolled pregnancies at least once during pregnancy and for 92% across all trimesters. Of 53,823 drinks reported, 98% had all items necessary for standard drink computation. Sharing was reported for 74% of drinks in Cape Town, South Africa and for 10% in the Northern Plains. Compared to referent values from the traditional TLFB, 74% and 67% of drinks had different alcohol-by-volume and container size, respectively. Furthermore, a statistically significant difference was found between the number of containers reported and the number of standard drinks computed, using information from the modified TLFB. This is the first study of this size to wholly encompass all of these changes into a single measure in order to more accurately calculate daily consumption and assess patterns over time. The methods used to collect PAE information and create alcohol exposure measures likely increased the accuracy of standard drinks reported and could be generalized to other populations.

Drinking and smoking patterns during pregnancy: Development of group-based trajectories in the Safe Passage Study.

Precise identification of drinking and smoking patterns during pregnancy is crucial to better understand the risk to the fetus. The purpose of this manuscript is to describe the methodological approach used to define prenatal drinking and smoking trajectories from a large prospective pregnancy cohort, and to describe maternal characteristics associated with different exposure patterns. In the Safe Passage Study, detailed information regarding quantity, frequency, and timing of exposure was self-reported up to four times during pregnancy and at 1 month post-delivery. Exposure trajectories were developed using data from 11,692 pregnancies (9912 women) where pregnancy outcome was known. Women were from three diverse populations: white (23%) and American Indian (17%) in the Northern Plains, US, and mixed ancestry (59%) in South Africa (other/not specified [1%]). Group-based trajectory modeling was used to identify 5 unique drinking trajectories (1 none/minimal, 2 quitting groups, 2 continuous groups) and 7 smoking trajectories (1 none/minimal, 2 quitting groups, 4 continuous groups). Women with pregnancies assigned to the low- or high-continuous drinking groups were less likely to have completed high school and were more likely to have enrolled in the study in the third trimester, be of mixed ancestry, or be depressed than those assigned to the none/minimal or quit-drinking groups. Results were similar when comparing continuous smokers to none/minimal and quit-smoking groups. Further, women classified as high- or low-continuous drinkers were more likely to smoke at moderate-, high-, and very high-continuous levels, as compared to women classified as non-drinkers and quitters. This is the first study of this size to utilize group-based trajectory modeling to identify unique prenatal drinking and smoking trajectories. These trajectories will be used in future analyses to determine which specific exposure patterns subsequently manifest as poor peri- and postnatal outcomes.

Cardiorespiratory physiology in the safe passage study: protocol, methods and normative values in unexposed infants.

AIM: The Safe Passage Study, conducted by the Prenatal Alcohol in SIDS and Stillbirth Network, is investigating contributions of prenatal alcohol exposure to foetal and infant demise. This current report presents physiological data from full-term infants with no prenatal exposure to alcohol or maternal smoking. METHODS: Data are from 666 infants from the Northern Plains (North and South Dakota) and South Africa. A standardised protocol assessed cardiorespiratory function during baseline and head-up tilts shortly after birth and at one month of age. RESULTS: Analyses revealed significant increases in heart rate and decreases in BP from the newborn to one-month time period as well as diminished heart rate responses to head-up tilt in one-month-old infants. CONCLUSION: The Safe Passage Study was successful in characterising physiology in a large number of infants at sites known to have elevated risks for SIDS. Results demonstrate that even with low prenatal adverse exposures, there are significant changes in cardiorespiratory function as infants enter the window of increased risk for SIDS.

Propofol sedation in children: sleep trumps amnesia.

OBJECTIVE: Detailed assessments of the effects of propofol on memory in children are lacking. We assessed the feasibility of measuring memory during propofol infusion, as commonly performed in sedation for MRI scanning. In addition, we determined the onset of memory loss in relation to the onset of sedation measured by verbal responsiveness. MATERIALS AND METHODS: Children scheduled for sedation for MRI received a 10-min infusion of propofol (3 mg/kg) as they viewed and named 100 simple line drawings, one shown every five seconds, until they were no longer responsive (encoding). A control group receiving no sedation for MRI underwent similar tasks. Sedation was measured as any verbal response, regardless of correctness. After recovery from sedation, recognition memory was tested, with correct yes/no recognitions matched to sedation responses during encoding (subsequent memory paradigm). RESULTS: Of the 48 children who received propofol, 30 could complete all study tasks (6.2 ± 1.6 years, 16 males). Individual responses could be modeled in all 30 children. On average, there was a 50% probability of no verbal response 3.1 min after the start of infusion, with 50% memory loss at 2.7 min. Children receiving propofol recognized 65 ± 16% of the pictures seen, whereas the control group recognized 93 ± 5%. CONCLUSION: Measurement of memory and sedation is possible in verbal children receiving propofol by infusion in a clinical setting. Despite propofol being an amnestic agent, there was little or no amnestic effect of propofol while the child was verbally responsive. It is important for sedation providers to realize that propofol sedation does not always produce amnesia while the child is responsive. CLINICALTRIALS. GOV NUMBER: NCT02278003.

Dexmedetomidine versus morphine infusion following laparoscopic bariatric surgery: effect on supplemental narcotic requirement during the first 24 h.

INTRODUCTION: The primary aim of this pilot study was to determine whether the dexmedetomidine infusion initiated immediately after laparoscopic bariatric surgery, offers an advantage over a morphine infusion with respect to rescue morphine and paracetamol requirements over the first 24 post-operative hours. METHODS: Sixty morbidly obese adult patients scheduled for laparoscopic bariatric surgery were randomly assigned to receive an infusion of either 0.3 mcg/kg/h dexmedetomidine (Group D) or 3 mg/h Morphine (Group M) for 24 h immediately post-operatively. All patients received standardized general anesthesia and were evaluated and treated for pain in the intensive care unit by providers who were blinded to their treatment group. The primary outcome was the need for supplemental, "rescue" paracetamol (Dolargan. Hikma, Jordan) and morphine titrated to achieve visual analog scales (VAS) of <40 and <70, respectively. RESULTS: A total of 60 patients (77 % female, mean age 33.5 years ± 9.5 and body mass index (BMI) 43.0 ± 4.5) were randomized to Group M and 30 to Group D. There were no significant differences in mean rescue paracetamol and morphine requirements. Mean total morphine requirements in Group D were 6.1 ± 3.1 mg, whereas 72.9 ± 2.2 mg in Group M (p < 0.0001). CONCLUSIONS: An intravenous infusion of dexmedetomidine, initiated and continued for 24 h following laparoscopic bariatric surgery, can decrease the overall morphine requirements during this period. This pilot study demonstrated that the post-operative initiation of dexmedetomidine can be morphine sparing following laparoscopic bariatric surgery.

Intranasal dexmedetomidine for sedation for pediatric computed tomography imaging.

UNLABELLED: This prospective observational pilot study evaluated the aerosolized intranasal route for dexmedetomidine as a safe, effective, and efficient option for infant and pediatric sedation for computed tomography imaging. The mean time to sedation was 13.4 minutes, with excellent image quality, no failed sedations, or significant adverse events. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT01900405.

Baseline factors predicting placebo response to treatment in children and adolescents with autism spectrum disorders: a multisite randomized clinical trial.

IMPORTANCE: The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. OBJECTIVE: To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression-Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children's Yale-Brown Obsessive-Compulsive Scale. INTERVENTIONS: Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). MAIN OUTCOMES AND MEASURES: A positive response was defined as having a score of at least much improved on the Clinical Global Impression-Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale-Revised, and the Children's Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. RESULTS: Several baseline predictors of response were identified, and a principal component analysis yielded 3 composite measures (disruptive behavior, autism/mood, and caregiver strain) that significantly predicted response at week 12. Specifically, participants in the placebo group were significantly less likely than participants in the citalopram group to respond at week 12 if they entered the study more symptomatic on each of the 3 composite measures, and they were at least 2 times less likely to be responders. CONCLUSIONS AND RELEVANCE: This analysis suggests strategies that may be useful in anticipating and potentially mitigating the nonspecific response in randomized clinical trials of children and adolescents with autism spectrum disorders. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00086645.

Aerosolized intranasal midazolam for safe and effective sedation for quality computed tomography imaging in infants and children.

This pilot study introduces the aerosolized route for midazolam as an option for infant and pediatric sedation for computed tomography imaging. This technique produced predictable and effective sedation for quality computed tomography imaging studies with minimal artifact and no significant adverse events.

Dexmedetomidine offers an option for safe and effective sedation for nuclear medicine imaging in children.

PURPOSE: To determine the safety, efficacy, and outcomes of bradycardia, hypotension, and hypertension with dexmedetomidine (DEX), a recently approved sedative used for procedural sedation that has not been described previously for pediatric nuclear medicine imaging. MATERIALS AND METHODS: Between March 2005 and August 2011, 669 patients (mean age, 5.7 years ± 4.5 [standard deviation]; median age, 4.5 years; age range, 0.1-22.5 years) received DEX in this HIPAA-compliant study. Sedation was administered with DEX, an α-2 adrenergic agonist, as an intravenous bolus (2 µg per kilogram of body weight) over a 10-minute period; this was followed by continuous infusion at a rate of 1 µg/kg/h until imaging was complete. The bolus could be repeated up to two times, if needed, to achieve the targeted level of a Ramsay sedation score of 4. After institutional review board approval, collected quality assurance data were reviewed. RESULTS: Adequate sedation was achieved within 8.6 minutes ± 4.6 (median, 8.0 minutes; range, 1.0-40.0 minutes) on average in studies that averaged 41.3 minutes ± 25.5 (median, 31.5 minutes; range, 9.0-183.0 minutes). Of 669 studies, 667 (99.7%) were completed successfully. Six children (0.9%) had brief periods of oxygen desaturation below 95%, none of which required airway intervention. Hypotension, hypertension, and bradycardia (all defined as deviations of more than 20% from age-adjusted awake norms), occurred in 58.7% (n = 393), 2.1% (n = 14), and 4.3% (n = 29) of patients, respectively. Both hypotension and bradycardia were related to age (P = .033 and P = .002, respectively); older children tended to experience more of these events. None of these fluctuations required pharmacologic therapy. Discharge criteria (modified Aldrete score ≥ 9) were met, on average, within 41.4 minutes ± 27.9 (median, 36.0 minutes; range, 1.0-220.0 minutes). CONCLUSION: DEX offers advantages for pediatric sedation for nuclear medicine imaging. DEX produces a condition similar to natural sleep, with no detrimental effect on respiration. The hemodynamic variability anticipated with DEX did not require pharmacologic treatment, and the drug was well tolerated.

Intramuscular dexmedetomidine: an effective route of sedation preserves background activity for pediatric electroencephalograms.

OBJECTIVES: To describe the efficacy and outcome of dexmedetomidine (Dex) via the intramuscular (IM) route for sedation for electroencephalography (EEG). STUDY DESIGN: Quality assurance data and EEG studies were reviewed for consecutive patients who received IM Dex for EEGs between August 2007 and September 2009. Sleep spindles, delta waves, and beta activity were evaluated to determine the deepest stage of sleep achieved. RESULTS: One hundred seven consecutive children (age 0.2-17 years) between August 2007 and September 2009 received IM Dex (range 1.0-4.5 mcg/kg). The average time to achieve sedation was 15.5 minutes (range 3.0-55.0) with an average of 54.5 minutes to meet discharge criteria following EEG studies, which averaged 34.2 ± 22.6 minutes. The deepest stage of sleep recorded for each child was: awake (n = 1), stage N2 (n = 51), and stage N3 (n = 55). Excessive beta activity was seen in only 1 patient. Epileptiform activity was noted in 11 patients. Hemodynamic fluctuations in heart rate and blood pressure were noted, none of which required pharmacologic intervention. All EEGs were successfully completed. CONCLUSION: We describe Stage 3 sleep and preserved background activity in response to Dex. We present the IM route as a new method, which preserves background EEG activity to provide safe and effective sedation for EEG studies.

Pediatric sedation in a community hospital-based outpatient MRI center.

OBJECTIVE: Although the demand for pediatric MRI is increasing, it is uncommon to find sedation being offered at community hospital-based outpatient centers. We present our safety, efficacy, and outcome data at a community hospital-based outpatient imaging center. MATERIALS AND METHODS: I.v. dexmedetomidine sedation was administered as a bolus of 3 µg/kg and maintained with a continuous infusion of 1 µg/kg/hr until imaging was complete. The dexmedetomidine bolus could be repeated up to two times, if needed. Quality assurance data were reviewed. RESULTS: From April 2009 to July 2010, 279 children (mean age, 4.2 years; age range, 0.2-17.2 years) were sedated. All received a first bolus, 46 required a second dose, and two received a third. The average time to achieve sedation was 7.8 minutes (SD, ± 3.8 minutes). Total duration of imaging (82% brain MRI) averaged 38.1 minutes (range, 8.0-126.0 minutes). On average, discharge criteria were met within 21.3 minutes of arrival in recovery room (± 17.8 minutes). The heart rate and blood pressure deviated from baseline by more than 20% in 5% and 33% of the patients, respectively. No pharmacologic therapy was administered to treat the hemodynamic variability. There were no adverse respiratory events. All imaging studies were successfully completed. CONCLUSION: Dexmedetomidine offers an option for pediatric sedation for MRI at community hospital-based outpatient settings. It preserves respiration but elicits deviations in blood pressure and heart rate that have not required pharmacologic intervention. Dexmedetomidine offers a safe, effective, and efficient agent for sedation for children undergoing MRI in an outpatient setting.

Design and subject characteristics in the federally-funded citalopram trial in children with pervasive developmental disorders.

The Studies to Advance Autism Research and Treatment Network conducted a randomized trial with citalopram in children with Pervasive developmental disorders (PDDs). We present the rationale, design and sample characteristics of the citalopram trial. Subjects (128 boys, 21 girls) had a mean age of 9.3 (±3.12) years; 132 (88.6%) were diagnosed with autistic disorder (4.7% with Asperger's Disorder; 6.7% with PDD-not otherwise specified). Less than half of the subjects were intellectually disabled; 117 (78.5%) were rated Moderate or Marked on the Clinical Global Impression for Severity. Study measures were similar to previous Research Units on Pediatric Psychopharmacology trials. Subjects in this trial were slightly older and more likely to have complaints of repetitive behavior than participants in RUPP trials.

Intramuscular dexmedetomidine sedation for pediatric MRI and CT.

OBJECTIVE: Although dexmedetomidine has been administered to adults by intramuscular injection for perioperative anxiolysis and sedation, this route in children has not been described, to our knowledge. Our hypothesis was that intramuscular dexmedetomidine can be used to achieve sedation for MRI and CT of children. MATERIALS AND METHODS: The quality assurance data on all children who consecutively received intramuscular dexmedetomidine between August 1, 2007, and September 30, 2009, were reviewed. A single or repeated doses of 1-4 αg/kg intramuscular dexmedetomidine had been administered to achieve a minimum Ramsay sedation score of 4. Patient demographics, medical diagnosis, vital signs, adverse events, and outcome measures were reviewed. RESULTS: Sixty-five children received consecutive intramuscular dexmedetomidine injections and successfully completed imaging studies. The MRI group received a total mean of 2.9 αg/kg dexmedetomidine, and the CT group received a mean of 2.4 αg/kg (p ≤ 0.01). There was no statistically significant relation between the total dose of dexmedetomidine received, mean time to achieve sedation (13.1-13.4 minutes), or time to meet discharge criteria after arrival in the recovery unit (17.1-21.9 minutes). Nine patients (14%) experienced hypotension, defined as a decrease in blood pressure to less than 20% of the age-adjusted awake normal value. The dosage of dexmedetomidine was not a predictor of hypotension. None of the patients had bradycardia, hypertension, or oxygen desaturation. CONCLUSION: The intramuscular route is an alternative approach to dexmedetomidine delivery for pediatric sedation. Larger studies are warranted to evaluate the efficacy, safety, and hemodynamic outcome associated with the intramuscular use of dexmedetomidine in the care of children.

Integrative cognitive-behavioral and spiritual counseling for rural dementia caregivers with depression.

OBJECTIVE: Discuss initial evaluation of a program for training faith community nurses (FCNs) to conduct cognitive-behavioral and spiritual counseling (CBSC) for rural dementia caregivers (CGs), and present 2 case studies on the use of CBSC for treating depression in this population. STUDY DESIGN: Pre-post evaluation of the effectiveness of CBSC training and a case study analysis of the effectiveness of CBSC on CG problem improvement and depression. OUTCOME MEASURES: For FCN training, we used the FCN Counseling Comfort Scale, FCN Counseling Efficacy Scale, and the FCN Counseling Workshop Satisfaction Survey. The Problem Severity Scale and Center for Epidemiologic Studies Depression Scale were used in the case studies. RESULTS: Significant post-training increases in FCN counseling comfort and perceived counseling efficacy were obtained. Case study findings provided evidence of substantial improvement in caregiving problems and reductions in depression. CONCLUSIONS: Preliminary outcomes of FCN training and CBSC for dementia CGs were promising. However, replication across the sample is required to evaluate the overall effectiveness of CBSC for reducing CG depression. Specific competencies and ethical considerations in supervising this form of intervention are also addressed.