Thalamocortical functional connectivity in infants with prenatal opioid exposure correlates with severity of neonatal opioid withdrawal syndrome.

PURPOSE: Prenatal opioid exposure (POE) is a growing public health concern due to its associated adverse outcomes including neonatal opioid withdrawal syndrome (NOWS). The aim of this study was to assess alterations in thalamic functional connectivity in neonates with POE using resting-state functional magnetic resonance imaging (rs-fMRI) and identify whether these altered connectivity measures were associated with NOWS severity. METHODS: In this prospective, IRB-approved study, we performed rs-fMRI in 19 infants with POE and 20 healthy control infants without POE. Following standard pre-processing, we performed seed-based functional connectivity analysis with the right and left thalamus as the regions of interest. We performed post hoc analysis in the prenatal opioid exposure group to identify associations of altered thalamocortical connectivity with severity of NOWS. P value of < .05 was considered statistically significant. RESULTS: There were several regions of significantly altered thalamic to cortical functional connectivity in infants with POE compared to the healthy infants. Distinct regions of thalamocortical functional connectivity correlated with maximum modified Finnegan score. Association between thalamocortical connectivity and severity of NOWS was nominally modified by maternal psychological conditions and polysubstance use. CONCLUSION: Our findings reveal prenatal opioid exposure-related alterations in thalamic functional connectivity in the infant brain that are correlated with severity of NOWS. Future studies may benefit from evaluation of thalamocortical resting state functional connectivity in infants with POE to help  stratify risk of long term neurodevelopmental outcomes.

Long-chain omega-3 fatty acids, selenium, and mercury in relation to sleep duration and sleep quality: findings from the CARDIA study.

PURPOSE: To examine the associations of long-chain omega-3 polyunsaturated fatty acids (LCω3PUFA) intake with sleep quality and duration in a cohort of American young adults, and to explore whether the associations of interest are modified by selenium (Se) and/or mercury (Hg) status. METHODS: The study sample consisted of 3964 men and women from the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) study, aged 25.0 ± 3.6 at baseline. Intake of LCω3PUFA was assessed using an interviewer-administered dietary history questionnaire at baseline (1985-1986), Y7 (1992-1993), and Y20 (2005-2006). Toenail Se and Hg concentrations were quantified at Y2 (1987-1988). The outcomes were self-reported sleep quality and sleep duration measured by one question for each at Y15 (2000-2001) and Y20. Generalized estimating equation was used to examine the association between cumulative average intake of LCω3PUFA and sleep measures. Restricted cubic spline was performed to explore the potential non-linear associations of interest. Se and Hg were dichotomized by their median values to examine the potential effect modification of Se and/or Hg. RESULTS: We did not observe any significant associations (linear or non-linear) of LCω3PUFA intake with either sleep quality or duration. Also, no significant association was observed in any subgroup classified by toenail Se and/or Hg concentrations. Similarly, sensitivity analysis indicated that the null associations between LCω3PUFA intake and sleep quality or duration persisted across subgroups classified by race, gender, obesity, or having small children. CONCLUSION: Findings from this longitudinal analysis did not support the hypothesis that LCω3PUFA intake is associated with sleep quality or sleep duration.

Association of magnesium intake with sleep duration and sleep quality: findings from the CARDIA study.

STUDY OBJECTIVES: As an antagonist of calcium (Ca), magnesium (Mg) has been implicated in the regulation of sleep. We aimed to examine the longitudinal associations of Mg intake and Ca-to-Mg intake ratio (Ca:Mg) with sleep quality and duration. METHODS: The study sample consisted of 3,964 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary and supplementary intake of Mg were obtained using the CARDIA Dietary History at baseline (1985-1986), exam years 7 and 20. Self-reported sleep outcomes were measured at years 15 and 20. Sleep quality was rating from 1 (very good) to 5 (very bad). We categorized sleep duration to <7, 7-9, and >9 h. Generalized estimating equation was used to examine the associations of interest as repeated measures at the two time points. RESULTS: After adjustment for potential confounders, Mg intake was borderline associated with better sleep quality [highest quartile (Q4) vs. intake quartile (Q1): odds ratio (OR) = 1.23; 95% CI = 0.999, 1.50, ptrend = 0.051]. Participants in Q4 were also less likely to have short sleep (<7 h) compared to those in Q1 (OR = 0.64; 95% CI = 0.51, 0.81, ptrend = 0.012). The observed association with short sleep persisted among participants without depressive disorders (Q4 vs. Q1: OR = 0.64; 95% CI = 0.49, 0.82, ptrend < 0.001), but not among individuals with depressive disorder. Ca:Mg was not associated with either outcomes, regardless of depression status. CONCLUSIONS: Mg intake was associated with both sleep outcomes in this longitudinal analysis. Randomized controlled trials with objective measures of sleep are warranted to establish the potential causal inference.

Impact of vitamin C supplementation on placental DNA methylation changes related to maternal smoking: association with gene expression and respiratory outcomes.

BACKGROUND: Maternal smoking during pregnancy (MSDP) affects development of multiple organ systems including the placenta, lung, brain, and vasculature. In particular, children exposed to MSDP show lifelong deficits in pulmonary function and increased risk of asthma and wheeze. Our laboratory has previously shown that vitamin C supplementation during pregnancy prevents some of the adverse effects of MSDP on offspring respiratory outcomes. Epigenetic modifications, including DNA methylation (DNAm), are a likely link between in utero exposures and adverse health outcomes, and MSDP has previously been associated with DNAm changes in blood, placenta, and buccal epithelium. Analysis of placental DNAm may reveal critical targets of MSDP and vitamin C relevant to respiratory health outcomes. RESULTS: DNAm was measured in placentas obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (37 supplemented with vitamin C, 35 with placebo) and 24 never-smokers for reference. Methylation at one CpG, cg20790161, reached Bonferroni significance and was hypomethylated in vitamin C supplemented smokers versus placebo. Analysis of spatially related CpGs identified 93 candidate differentially methylated regions (DMRs) between treatment groups, including loci known to be associated with lung function, oxidative stress, fetal development and growth, and angiogenesis. Overlap of nominally significant differentially methylated CpGs (DMCs) in never-smokers versus placebo with nominally significant DMCs in vitamin C versus placebo identified 9059 candidate "restored CpGs" for association with placental transcript expression and respiratory outcomes. Methylation at 274 restored candidate CpG sites was associated with expression of 259 genes (FDR < 0.05). We further identified candidate CpGs associated with infant lung function (34 CpGs) and composite wheeze (1 CpG) at 12 months of age (FDR < 0.05). Increased methylation in the DIP2C, APOH/PRKCA, and additional candidate gene regions was associated with improved lung function and decreased wheeze in offspring of vitamin C-treated smokers. CONCLUSIONS: Vitamin C supplementation to pregnant smokers ameliorates changes associated with maternal smoking in placental DNA methylation and gene expression in pathways potentially linked to improved placental function and offspring respiratory health. Further work is necessary to validate candidate loci and elucidate the causal pathway between placental methylation changes and outcomes of offspring exposed to MSDP. Clinical trial registration ClinicalTrials.gov, NCT01723696. Registered November 6, 2012. https://clinicaltrials.gov/ct2/show/record/NCT01723696 .

Vitamin C to Pregnant Smokers Persistently Improves Infant Airway Function to 12†Months of Age: A Randomised Trial.

BACKGROUND: Vitamin C (500 mg·day-1) supplementation for pregnant smokers has been reported to increase newborn pulmonary function and infant forced expiratory flows (FEFs) at 3 months of age. Its effect on airway function through 12 months of age has not been reported. OBJECTIVE: To assess whether vitamin C supplementation to pregnant smokers is associated with a sustained increased airway function in their infants through 12 months of age. METHODS: This is a prespecified secondary outcome of a randomised, double-blind, placebo-controlled trial that randomised 251 pregnant smokers between 13 and 23 weeks of gestation: 125 to 500 mg·day-1 vitamin C and 126 to placebo. Smoking cessation counselling was provided. FEFs performed at 3 and 12 months of age were analysed by repeated measures analysis of covariance. RESULTS: FEFs were performed in 222 infants at 3 months and 202 infants at 12 months of age. The infants allocated to vitamin C had significantly increased FEFs over the first year of life compared to those allocated to placebo. The overall increased flows were: 40.2 mL·sec-1 for FEF75 (adjusted 95% CI for difference 6.6 to 73.8; p=0.025); 58.3 mL·sec-1 for FEF50 (95% CI 10.9 to 105.8; p=0.0081); and 55.1 mL·sec-1 for FEF25-75 (95% CI, 9.7 to 100.5; p=0.013). CONCLUSIONS: In offspring of pregnant smokers randomised to vitamin C versus placebo, vitamin C during pregnancy was associated with a small but significantly increased airway function at 3 and 12 months of age, suggesting a potential shift to a higher airway function trajectory curve. Continued follow-up is underway.

A systematic review: The effects of yoga on pregnancy.

OBJECTIVE: A systematic review was conducted to update and provide a comprehensive overview on the psychological effects of antenatal yoga on pregnancy compared to standard prenatal care. STUDY DESIGN: Four databases were searched using keywords "yoga", "pregnancy", "perinatal care", "prenatal care", "postnatal care", "postpartum period", "peripartum period", "patient outcome assessment", "outcome assessment", "pregnancy outcome", "treatment outcome". Trials were considered if they were randomized controlled trials (RCTs) published from 2011 to 2018 and evaluated an antenatal yoga intervention. All studies were assessed for risk of bias using the Cochrane criteria. Trial characteristics and outcomes were extracted and synthesized descriptively where possible. Due to heterogeneity, meta-analysis was not possible. RESULTS: Of the 175 non-duplicated studies, 16 met criteria for full-text review. Five RCTs met the inclusion criteria and were included in the systematic review. The findings of the RCTs suggest antenatal yoga may be safe and may effectively decrease stress levels, anxiety scores, depression scores, and pain response as well as increasing maternal immunity and emotional-wellbeing. CONCLUSION: Yoga appears to be safe and may improve psychological and pregnancy outcomes. However, due to the limited number of studies, more high-quality, large RCTs are needed to draw conclusions about improvement in other pregnancy outcomes.

Oral Vitamin C (500 mg/d) to Pregnant Smokers Improves Infant Airway Function at 3 Months (VCSIP). A Randomized Trial.

Rationale: We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests. Objectives: To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the α5 nicotinic acetylcholine receptor. Methods: A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo. Measurements and Main Results: The primary outcome was FEF75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF50 and FEF25-75 obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (n = 113) had the following FEFs at 3 months of age compared with those randomized to placebo (n = 109) as measured by FEF75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, -3.33 to 35.64; P = 0.10), FEF50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P = 0.02), and FEF25-75 (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34; P = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the α5 nicotinic acetylcholine receptor (rs16969968). Conclusions: Although the primary outcome of FEF75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF50 and FEF25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF50 and FEF25-75) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT01723696).

Women's experiences with water birth: A matched groups prospective study.

BACKGROUND: Water birth has become an increasingly popular childbirth option, but has also come under scrutiny because of its possible risks and benefits. The primary objective of this study was to explore potential benefits of water birth by comparing the experiences of women who gave birth in water versus conventionally. We also compared maternal and newborn outcomes. METHODS: We performed a prospective study of 66 women who had water births and 132 who had conventional births. Data collected included demographics, labor and birth characteristics, perinatal outcomes, and maternal scores on the Childbirth Experience Questionnaire (CEQ). Groups were matched for variables known to influence CEQ scores. RESULTS: Women in the water birth group had more positive childbirth experiences compared with the conventional birth group (P < .001), and also compared with the subgroup of women who had epidural anesthesia (P = .002). After controlling for potential confounders, water birth was associated with a decreased likelihood of perineal lacerations requiring repair (P = .001) and a higher rate of breastfeeding initiation in the delivery room (P < .001). Adverse outcomes such as neonatal intensive care unit admission, blood loss >500 mL, 3rd/4th degree lacerations, and perinatal infections were rare. The study was not sufficiently powered to detect differences in rare outcomes. CONCLUSION: Water birth was associated with more positive maternal childbirth experiences as represented by CEQ scores. Adverse outcomes were rare in both the water birth and conventional birth groups.

Prescription and Other Medication Use in Pregnancy.

OBJECTIVE: To characterize prescription and other medication use in a geographically and ethnically diverse cohort of women in their first pregnancy. METHODS: In a prospective, longitudinal cohort study of nulliparous women followed through pregnancy from the first trimester, medication use was chronicled longitudinally throughout pregnancy. Structured questions and aids were used to capture all medications taken as well as reasons they were taken. Total counts of all medications taken including number in each category and class were captured. Additionally, reasons the medications were taken were recorded. Trends in medications taken across pregnancy and in the first trimester were determined. RESULTS: Of the 9,546 study participants, 9,272 (97.1%) women took at least one medication during pregnancy with 9,139 (95.7%) taking a medication in the first trimester. Polypharmacy, defined as taking at least five medications, occurred in 2,915 (30.5%) women. Excluding vitamins, supplements, and vaccines, 73.4% of women took a medication during pregnancy with 55.1% taking one in the first trimester. The categories of drugs taken in pregnancy and in the first trimester include the following: gastrointestinal or antiemetic agents (34.3%, 19.5%), antibiotics (25.5%, 12.6%), and analgesics (23.7%, 15.6%, which includes 3.6%; 1.4% taking an opioid pain medication). CONCLUSION: In this geographically and ethnically diverse cohort of nulliparous pregnant women, medication use was nearly universal and polypharmacy was common. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01322529.

Interventions for nausea and vomiting in early pregnancy.

BACKGROUND: Nausea, retching and vomiting are very commonly experienced by women in early pregnancy. There are considerable physical, social and psychological effects on women who experience these symptoms. This is an update of a review of interventions for nausea and vomiting in early pregnancy last published in 2014. OBJECTIVES: To assess the effectiveness and safety of all interventions for nausea, vomiting and retching in early pregnancy, up to 20 weeks' gestation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, the Cochrane Complementary Medicine Field's Trials Register (19 January 2015) and reference lists of retrieved studies. SELECTION CRITERIA: All randomised controlled trials of any intervention for nausea, vomiting and retching in early pregnancy. We excluded trials of interventions for hyperemesis gravidarum, which are covered by another Cochrane review. We also excluded quasi-randomised trials and trials using a cross-over design. DATA COLLECTION AND ANALYSIS: Four review authors, in pairs, reviewed the eligibility of trials and independently evaluated the risk of bias and extracted the data for included trials. MAIN RESULTS: Forty-one trials involving 5449 women, met the inclusion criteria. These trials covered many interventions, including acupressure, acustimulation, acupuncture, ginger, chamomile, lemon oil, mint oil, vitamin B6 and several antiemetic drugs. There were no included studies of dietary and other lifestyle interventions. Evidence regarding the effectiveness of P6 acupressure, auricular (ear) acupressure and acustimulation of the P6 point was limited. Acupuncture (P6 or traditional) showed no significant benefit to women in pregnancy. The use of ginger products may be helpful to women, but the evidence of effectiveness was limited and not consistent, though three recent studies support ginger over placebo. There was only limited evidence from trials to support the use of pharmacological agents including vitamin B6, Doxylamine-pyridoxoine and other anti-emetic drugs to relieve mild or moderate nausea and vomiting. There was little information on maternal and fetal adverse outcomes and on psychological, social or economic outcomes.We were unable to pool findings from studies for most outcomes due to heterogeneity in study participants, interventions, comparison groups, and outcomes measured or reported. The methodological quality of the included studies was mixed. Risk of bias was low related to performance bias, detection bias and attrition bias for most studies. Selection bias risk was unclear for many studies and almost half of the studies did not fully or clearly report all pre-specified outcomes. AUTHORS' CONCLUSIONS: Given the high prevalence of nausea and vomiting in early pregnancy, women and health professionals need clear guidance about effective and safe interventions, based on systematically reviewed evidence. There is a lack of high-quality evidence to support any particular intervention. This is not the same as saying that the interventions studied are ineffective, but that there is insufficient strong evidence for any one intervention. The difficulties in interpreting and pooling the results of the studies included in this review highlight the need for specific, consistent and clearly justified outcomes and approaches to measurement in research studies.

Interventions for nausea and vomiting in early pregnancy.

BACKGROUND: Nausea, retching and vomiting are very commonly experienced by women in early pregnancy. There are considerable physical, social and psychological effects on women who experience these symptoms. This is an update of a review of interventions for nausea and vomiting in early pregnancy previously published in 2010. OBJECTIVES: To assess the effectiveness and safety of all interventions for nausea, vomiting and retching in early pregnancy, up to 20 weeks' gestation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (27 April 2013). SELECTION CRITERIA: All randomised controlled trials of any intervention for nausea, vomiting and retching in early pregnancy. We excluded trials of interventions for hyperemesis gravidarum, which are covered by another Cochrane review. We also excluded quasi-randomised trials and trials using a cross-over design. DATA COLLECTION AND ANALYSIS: Four review authors, in pairs, reviewed the eligibility of trials and independently evaluated the risk of bias and extracted the data for included trials. MAIN RESULTS: Thirty-seven trials involving 5049 women, met the inclusion criteria. These trials covered many interventions, including acupressure, acustimulation, acupuncture, ginger, chamomile, lemon oil, mint oil, vitamin B6 and several antiemetic drugs. We identified no studies of dietary or other lifestyle interventions. Evidence regarding the effectiveness of P6 acupressure, auricular (ear) acupressure and acustimulation of the P6 point was limited. Acupuncture (P6 or traditional) showed no significant benefit to women in pregnancy. The use of ginger products may be helpful to women, but the evidence of effectiveness was limited and not consistent, though two recent studies support ginger over placebo. There was only limited evidence from trials to support the use of pharmacological agents including vitamin B6, and anti-emetic drugs to relieve mild or moderate nausea and vomiting. There was little information on maternal and fetal adverse outcomes and on psychological, social or economic outcomes. We were unable to pool findings from studies for most outcomes due to heterogeneity in study participants, interventions, comparison groups, and outcomes measured or reported. The methodological quality of the included studies was mixed. AUTHORS' CONCLUSIONS: Given the high prevalence of nausea and vomiting in early pregnancy, women and health professionals need clear guidance about effective and safe interventions, based on systematically reviewed evidence. There is a lack of high-quality evidence to support any particular intervention. This is not the same as saying that the interventions studied are ineffective, but that there is insufficient strong evidence for any one intervention. The difficulties in interpreting and pooling the results of the studies included in this review highlight the need for specific, consistent and clearly justified outcomes and approaches to measurement in research studies.

Interventions for nausea and vomiting in early pregnancy.

BACKGROUND: Nausea, retching and vomiting are very commonly experienced by women in early pregnancy. There are considerable physical and psychological effects on women who experience these symptoms. This is an update of a review of interventions for nausea and vomiting in early pregnancy previously published in 2003. OBJECTIVES: To assess the effectiveness and safety of all interventions for nausea, vomiting and retching in early pregnancy, up to 20 weeks' gestation. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 May 2010). SELECTION CRITERIA: All randomised controlled trials of any intervention for nausea, vomiting and retching in early pregnancy. We excluded trials of interventions for hyperemesis gravidarum which are covered by another review. We also excluded quasi-randomised trials and trials using a crossover design. DATA COLLECTION AND ANALYSIS: Four review authors, in pairs, reviewed the eligibility of trials and independently evaluated the risk of bias and extracted the data for included trials. MAIN RESULTS: Twenty-seven trials, with 4041 women, met the inclusion criteria. These trials covered many interventions, including acupressure, acustimulation, acupuncture, ginger, vitamin B6 and several antiemetic drugs. We identified no studies of dietary or other lifestyle interventions. Evidence regarding the effectiveness of P6 acupressure, auricular (ear) acupressure and acustimulation of the P6 point was limited. Acupuncture (P6 or traditional) showed no significant benefit to women in pregnancy. The use of ginger products may be helpful to women, but the evidence of effectiveness was limited and not consistent. There was only limited evidence from trials to support the use of pharmacological agents including vitamin B6, and anti-emetic drugs to relieve mild or moderate nausea and vomiting. There was little information on maternal and fetal adverse outcomes and on psychological, social or economic outcomes. We were unable to pool findings from studies for most outcomes due to heterogeneity in study participants, interventions, comparison groups, and outcomes measured or reported. The methodological quality of the included studies was mixed. AUTHORS' CONCLUSIONS: Given the high prevalence of nausea and vomiting in early pregnancy, health professionals need to provide clear guidance to women, based on systematically reviewed evidence. There is a lack of high-quality evidence to support that advice. The difficulties in interpreting the results of the studies included in this review highlight the need for specific, consistent and clearly justified outcomes and approaches to measurement in research studies.