Dataset Information

Associations of Maternal Prenatal Drug Abuse With Measures of Newborn Brain Structure, Tissue Organization, and Metabolite Concentrations.

ABSTRACT:

Importance

Increasing rates of illicit drug use during pregnancy may be associated with risk for long-term health problems in prenatally exposed children.

Objective

To identify the associations of prenatal exposure to illicit drugs with organization of the newborn brain.

Design, setting, and participants

For this cohort study, a volunteer sample of 210 illicit drug-using and nonusing mothers and their newborns was enrolled from prenatal clinics and drug abuse treatment programs in New York, New York. Enrollment, scanning, and long-term follow-up occurred from September 2004 through February 2012, and image processing and statistical analyses continued through fall 2018. In addition to 26 participants with incomplete data, a total of 64 mothers were lost to follow-up during pregnancy, and 13 newborns were lost to follow-up at birth because of perinatal complications.

Exposures

Newborns were assigned to 1 of 4 primary exposure groups based on the history of most frequent maternal drug use: marijuana, cocaine, methadone maintenance, and/or heroin. Unexposed newborns were controls.

Main outcomes and measures

Unsedated magnetic resonance imaging (MRI) of newborn brains was performed shortly after birth. Infant neurodevelopmental outcomes were assessed at age 12 months. MRI modalities included anatomical imaging, diffusion tensor imaging, T2 relaxometry, and magnetic resonance spectroscopic imaging. Infant neurodevelopmental outcomes included Bayley scales of infant development-III and Vineland Adaptive Behavior Scales. Statistical analyses were performed with results represented on the brain images.

Results

Of 118 mothers, 42 (35%) were in the control group (mean [SD] age, 25.9 [6.1] years), 29 (25%) were in the cocaine group (mean [SD] age, 29.0 [6.1] years), 29 (25%) were in the marijuana group (mean [SD] age, 24.3 [5.5] years), and 18 (15%) were in the methadone and/or heroin group (mean [SD] age, 30.9 [5.7] years). Not all newborns could be scanned successfully; therefore, usable MRIs were acquired for 118 newborns from predominantly minority groups and with economically disadvantaged mothers. Anatomic abnormalities were detected in similar locations across all 3 drug exposures and included smaller volumes in the dorsal, medial, and ventral surfaces of the frontal lobe and dose-related increases in volumes in the lateral temporal lobe, dorsal parietal lobe, and superior frontal gyrus. Dose-related increases in diffusion tensor measures of tissue organization, decreases in T2 relaxometry times, and increases in spectroscopy metabolite concentrations were similar across exposures. These associations of exposures with brain measures were similar to the associations of newborn age with brain measures. The anatomic and diffusion tensor imaging measures suppressively mediated the associations of prenatal exposure with poorer 12-month infant outcomes.

Conclusions and relevance

The findings suggest that prenatal drug exposure is associated with measures of newborn brain tissue in patterns that may indicate that exposures accelerated normal fetal brain maturation, which in turn mediated the associations with poorer 12-month infant outcomes.

SUBMITTER: Peterson BS

PROVIDER: S-EPMC7296459 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:To examine prospectively associations between urinary phthalate metabolite concentrations and body size measures in children.Urinary concentrations of nine phthalate metabolites: monoethyl (MEP); mono-n-butyl (MBP); mono-(3-carboxypropyl) (MCPP); monobenzyl (MBzP); mono-isobutyl (MiBP); mono-(2-ethylhexyl) (MEHP); mono-(2-ethyl-5-oxohexyl) (MEOHP); mono-(2-ethyl-5-carboxypentyl) (MECPP); and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and the molar sum of the low molecular-weight phthalate metabolites (low MWP: MEP, MBP and MiBP) and high molecular-weight phthalate metabolites (high MWP: MECPP, MEHHP, MEOHP, MEHP and MBzP) and of four di-(2-ethylhexyl) phthalate (DEHP) metabolites (?DEHP: MEHP, MEHHP, MEOHP, MECPP) and anthropometry, including body mass index and waist circumference were measured among 387 Hispanic and Black, New York City children who were between six and eight years at cohort enrollment (2004-2007). Relationships between baseline metabolite concentrations and body size characteristics obtained one year later were examined using multivariate-adjusted geometric means for each body size characteristic by continuous and categories of phthalate metabolite concentrations. Stratified analyses by body size (age/sex specific) were conducted.No significant associations are reported among all girls or boys. Dose response relationships were seen with monoethyl phthalate and the sum of low molecular-weight phthalates and body mass index and waist circumference among overweight children; for increasing monoethyl phthalate concentration quartiles among girls, adjusted mean body mass indexes were as follows: 21.3, 21.7, 23.8, 23.5 and adjusted mean waist circumference (cm) were as follows: 73.4, 73.5, 79.2, 78.8 (p-trend<0.001 for both).In this prospective analysis we identified positive relationships between urinary concentrations of monoethyl phthalate and the sum of low molecular-weight phthalates and body size measures in overweight children. These are metabolites with concentrations above 1 ?M.

Project description:BackgroundPreconception nutrition sets the stage for a healthy pregnancy. Maternal fatty acids (FAs) are related to beneficial neonatal outcomes with DNA methylation proposed as a mechanism; however, few studies have investigated this association and none with preconception FAs.ObjectivesWe examined the relations of maternal plasma FA concentrations at preconception (n = 346) and 8 weeks of gestation (n = 374) with newborn DNA methylation.MethodsThe Effects of Aspirin in Gestation and Reproduction Trial (2006-2012) randomly assigned women with previous pregnancy loss to low dose aspirin or placebo prior to conception. We measured maternal plasma phospholipid FA concentration at preconception (on average 4 mo before pregnancy) and 8 weeks of gestation. Cord blood DNA from singletons was measured using the MethylationEPIC BeadChip. We used robust linear regression to test the associations of FA concentration with methylation ?-values of each CpG site, adjusting for estimated cell count using a cord blood reference, sample plate, maternal sociodemographic characteristics, cholesterol, infant sex, and epigenetic-derived ancestry. False discovery rate correction was used for multiple testing.ResultsMean ± SD concentrations of preconception marine (20:5n-3+22:6n-3+22:5n-3) and ?-6 PUFAs, SFAs, MUFAs, and trans FAs were 4.7 ± 1.2, 38.0 ± 2.0, 39.4 ± 1.8, 11.6 ± 1.1, and 1.0 ± 0.4 % of total FA, respectively; concentrations at 8 weeks of gestation were similar. Preconception marine PUFA concentration was associated with higher methylation at GRAMD2 (P = 1.1 × 10-8), LOXL1 (P = 5.5 × 10-8), SIK3 (P = 1.6 × 10-7), HTR1B (P = 1.9 × 10-7), and MCC (P = 2.1 × 10-7) genes. Preconception SFA concentration was associated with higher methylation at KIF25-AS1 and lower methylation at SLC39A14; other associations exhibited sensitivity to outliers. The trans FA concentration was related to lower methylation at 3 sites and higher methylation at 1 site. FAs at 8 weeks of gestation were largely unrelated to DNA methylation.ConclusionsMaternal preconception FAs are related to newborn DNA methylation of specific CpG sites, highlighting the importance of examining nutritional exposures preconceptionally. This trial was registered at clinicaltrials.gov as NCT00467363.

Project description:INTRODUCTION:Phthalates are known reproductive toxicants that reduce placental and fetal weight in experimental animal studies. Although phthalate exposure has been associated with reduced birth weight in humans, there is limited epidemiologic evidence on whether the placenta is also affected. OBJECTIVE:To assess whether maternal and paternal preconception and prenatal urinary phthalate metabolite concentrations are associated with placental weight, and the birth weight: placental weight (BW:PW) ratio among singletons conceived by subfertile couples. METHODS:The present analysis included 132 mothers and 68 fathers, and their corresponding 132 singletons recruited in an academic hospital fertility center in Boston, Massachusetts. Urinary concentrations of eleven phthalate metabolites were measured and averaged in multiple paternal (n?=?196) and maternal (n?=?596) preconception, and maternal prenatal (n?=?328) samples. Placental weight and birth weight (grams) were abstracted from delivery records, and the BW:PW was calculated. We estimated the association of natural log-phthalate metabolite concentrations across windows of exposure with placental weight and the BW:PW ratio using multivariable linear regression models, adjusting for a priori covariates. RESULTS:In adjusted models, each log-unit increase in paternal urinary concentrations of the sum of di-(2-ethylhexyl) phthalate (?DEHP) metabolites was associated with a 24?g (95% CI: -48, -1) decrease in placental weight. We also observed a significant negative association between maternal preconception monoethyl phthalate (MEP) metabolite concentrations and the BW:PW ratio (??=?-0.26; 95%CI: -0.49, -0.04). Additionally, each log-unit increase in prenatal MEP metabolite concentrations was associated with a 24?g (95% CI: -41, -7) decrease in placental weight. CONCLUSIONS:Our results suggest that certain paternal and maternal urinary phthalate metabolites may affect placental weight and the BW:PW ratio. However, given the small sample size within a subfertile cohort and the novelty of these findings, more studies are needed to confirm the present results.

Project description:BackgroundMaternal psychological stress during pregnancy, including stress resulting from disasters and trauma, has been linked to temperamental difficulties in offspring. Although heightened cortisol concentrations are often hypothesized as an underlying mechanism, evidence supporting this mechanism is not consistent, potentially because of methodological issues and low stress in the population.AimTo address these issues, this preregistered study investigated the following associations between: 1) prenatal psychological stress and hair cortisol, as a biomarker for chronic stress, during the COVID-19 outbreak (i.e., as a major worldwide psychological stressor), and 2) maternal hair cortisol during the COVID-19 outbreak and later infant temperamental negative affectivity and orienting/regulation. Additionally, we explored whether associations were different for women with low versus high socioeconomic status (SES; maternal education and annual household income) and at different stages of pregnancy.MethodPregnant women (N = 100) filled out online questionnaires during the first COVID-19 lockdown. Six months later, when most mothers were still pregnant or had just given birth, maternal hair samples were collected during home visits. When infants were six months old, mothers reported on their infant's temperament.ResultsAlthough hierarchical regression analyses revealed no associations between prenatal COVID-19 psychological stress and hair cortisol during the COVID-19 outbreak, SES proved to be a moderator in this association. Only pregnant women with higher levels of SES, not lower levels, showed a positive association between work-related and social support-related COVID-19 worries and hair cortisol. Finally, prenatal hair cortisol was not associated with later infant temperamental negative affectivity and orienting/regulation.ConclusionAlthough the COVID-19 outbreak proved to be a major psychological stressor worldwide, the physiological impact of the crisis might be different for pregnant women with higher SES as compared to lower SES.

Project description:BACKGROUND:A variety of global-level monitoring initiatives have recommended indicators for tracking progress in maternal and newborn health. As a first step supporting the work of WHO's Mother and Newborn Information for Tracking Outcomes and Results (MoNITOR) Technical Advisory Group, we aimed to compile and synthesize recommended indicators in order to document the landscape of maternal and newborn measurement and monitoring. METHODS:We conducted a scoping review of indicators proposed by global multi-stakeholder groups to suggest next steps to further support maternal and newborn measurement and monitoring. Indicators pertaining to pregnancy, childbirth, and postpartum/postnatal and newborn care were extracted and included in the indicator compilation, together with key indicator metadata. We examined patterns and relationships across the compiled indicators. RESULTS:We identified 140 indicators linked to maternal and newborn health topics across the continuum of service provision. Fifty-five indicators relate to inputs and processes, 30 indicators relate to outputs, outcomes comprise 37 indicators in the database, and 18 impact indicators. A quarter of indicators proposed by global groups is either under development/discussion or is considered "aspirational", highlighting the currently evolving monitoring landscape. Although considerable efforts have been made to harmonize indicator recommendations, there are still relatively few indicators shared across key monitoring initiatives and some of those that are shared may have definitional variation. CONCLUSION:Rapid, wide-ranging work by a number of multi-stakeholder groups has resulted in a substantial number of indicators, many of which partially overlap and many are not supported with adequate documentation or guidance. The volume of indicators, coupled with the number of initiatives promoting different indicator lists, highlight the need for strengthened coordination and technical leadership to harmonize recommendations for improved measurement and monitoring of data related to maternal and newborn heath.

Project description:Many countries recommend combined tetanus toxoid, reduced diphtheria toxoid and acellular pertussis immunization (Tdap) during pregnancy to stimulate transplacental transmission of pertussis antibodies to newborns. The immune system can be altered during pregnancy, potentially resulting in differing immunization risks in pregnant women. The safety of widespread Tdap immunization during pregnancy needs to be established. Our objective was to assess whether prenatal Tdap immunization was associated with adverse birth outcomes, and to evaluate the effect of timing of Tdap administration on these outcomes. We identified pregnancies at delivery in a large insurance claims database (2010-2014). Tdap immunization was categorized as optimal prenatal (27+weeks), early prenatal (<27weeks), postpartum (?7days post-delivery), or none. Medical claims were searched to identify maternal adverse immunization reactions (e.g. anaphylaxis, fever, Guillian-Barre syndrome [GBS]), adverse birth outcomes (e.g. preeclampsia/eclampsia, premature rupture or membranes, chorioamnionitis) and newborn outcomes (e.g. respiratory distress, pulmonary hypertension, neonatal jaundice). Women with optimal or early prenatal Tdap were compared to those not immunized in pregnancy, using propensity score-weighted log-binomial regression and Cox proportional hazards models to estimate risk ratios (RR) and hazard ratios (HR). We identified 1,079,034 deliveries and 677,075 linked newborns; 11.5% were immunized optimally and 2.3% immunized early. There were 1 case of post-immunization anaphylaxis, and 12 cases of maternal encephalopathy (all post- delivery); there were no cases of GBS. Optimally-timed immunization was associated with small increased relative risks of: chorioamnionitis [RR=1.11, (95% CI: 1.07-1.15), overall risk=2.8%], and postpartum hemorrhage [RR=1.23 (95% DI: 1.18-1.28), overall risk=2.4%]; however, these relative increases corresponded to low absolute risk increases. Tdap was not associated with increased risk of any adverse newborn outcome. Overall, prenatal Tdap immunization was not associated with newborn adverse events, but potential associations with chorioamnionitis consistent with one previous study and postpartum hemorrhage require further investigation.