Prenatal Drug Research Articles

Causal Effects of Prenatal Drug Exposure on Birth Defects with Missing by Terathanasia

Causal Effects of Prenatal Drug Exposure on Birth Defects with Missing by Terathanasia

Do birth outcomes mediate the association between drug use in pregnancy and neonatal metabolic bone disease? A prospective cohort study of 10,801 Chinese women.

Prenatal drug use may cause toxicity to bone health in newborns. We aimed to examine whether birth outcomes mediate the association between medication use and neonatal metabolic bone disease (MBD). A prospective cohort of 10,801 pregnant women (17-49 years) and their infants followed at a single center from 1 January 2012 to 31 December 2021 were included. Based on four single drugs, comprehensive medication use was determined and categorized into three groups using latent-class analysis: group 1 included antibiotics and furosemide or less than two drugs except for MgSO4; group 2 included MgSO4 without antibiotics or furosemide; and group 3 encompassed dexamethasone and antibiotics. Mediation analysis was conducted to assess the mediating effects of prematurity, low birth weight (LBW), and small for gestational age (SGA). There were 138 (1.3%) infants with MBD; 2,701 (25%) were born preterm, 1717 (15.9%) had LBW, and 303 (2.8%) were SGA. Pregnant women in groups 2 and 3 were 2.52 to 14.66 times more likely to deliver an infant with MBD than those in group 1. Only LBW showed a significant mediating effect on the association between comprehensive medication use and MBD, with a mediation proportion of 51.8% (45.0-64.1%, p < 0.001). Comprehensive medication use during pregnancy was associated with an increased risk of neonatal MBD, largely mediated by LBW. Early antepartum monitoring and prevention targeting adverse birth outcomes are necessary to mitigate the risk of MBD.

The first review on prenatal drug exposure and ocular malformation occurrence.

Even though a non-negligible portion of congenital eye anomalies has a clear genetic origin, an etiology is not found for most patients. Prenatal medication exposure is recognized to be involved in fetal malformations and several medications are specifically known to alter eye morphogenesis during embryonic development leading to congenital eye defects. We explored and reviewed the role of medications described in the genesis of ocular malformations, a role that has been little evaluated and probably still underestimated especially since several studies have shown the wide exposure of pregnant women to medication. We present our results in two sections; the first describes medications reported to be associated with ocular malformations in humans; the second details medications responsible for ocular malformations in animal models. We have summarized these results in tables, providing a relevant tool for clinicians. As most of the associations between medication exposure and congenital eye defects are either old or single case reports, this study highlights the needs for high epidemiological vigilance, accurate clinical description as well as a combination of studies on human genetics and experimental studies. Since medication exposures are potentially modifiable risk factors for congenital anomalies, this represents an important opportunity to implement preventive measures.

Neurological Disorders Induced by Drug Use: Effects of Adolescent and Embryonic Drug Exposure on Behavioral Neurodevelopment.

Clinical studies demonstrate that the risk of developing neurological disorders is increased by overconsumption of the commonly used drugs, alcohol, nicotine and cannabis. These drug-induced neurological disorders, which include substance use disorder (SUD) and its co-occurring emotional conditions such as anxiety and depression, are observed not only in adults but also with drug use during adolescence and after prenatal exposure to these drugs, and they are accompanied by long-lasting disturbances in brain development. This report provides overviews of clinical and preclinical studies, which confirm these adverse effects in adolescents and the offspring prenatally exposed to the drugs and include a more in-depth description of specific neuronal systems, their neurocircuitry and molecular mechanisms, affected by drug exposure and of specific techniques used to determine if these effects in the brain are causally related to the behavioral disturbances. With analysis of further studies, this review then addresses four specific questions that are important for fully understanding the impact that drug use in young individuals can have on future pregnancies and their offspring. Evidence demonstrates that the adverse effects on their brain and behavior can occur: (1) at low doses with short periods of drug exposure during pregnancy; (2) after pre-conception drug use by both females and males; (3) in subsequent generations following the initial drug exposure; and (4) in a sex-dependent manner, with drug use producing a greater risk in females than males of developing SUDs with emotional conditions and female offspring after prenatal drug exposure responding more adversely than male offspring. With the recent rise in drug use by adolescents and pregnant women that has occurred in association with the legalization of cannabis and increased availability of vaping tools, these conclusions from the clinical and preclinical literature are particularly alarming and underscore the urgent need to educate young women and men about the possible harmful effects of early drug use and to seek novel therapeutic strategies that might help to limit drug use in young individuals.

The effects of illicit drug use during pregnancy and parental hostility on problem behaviors in school-aged children over and above genetic influences.

Previous work has examined the impact of prenatal illicit drug use (PDU) on children's problem behaviors. However, many PDU-related risk factors, including genetic and rearing environmental risks, can also influence offspring's problem behaviors, thus confounding PDU, genetic, and rearing environmental influences. This study aimed to (a) identify effects of PDU on school-aged children's problem behaviors, including both externalizing and internalizing behaviors at Age 7, after controlling genetic and specific rearing environmental (e.g., maternal and paternal hostility at Ages 4.5 and 6) influences and (b) examine interaction effects between PDU and maternal and paternal hostility in predicting children's problem behaviors at Age 7. We used a parent-offspring adoption design to partition genetic and prenatal effects from postnatal rearing environmental influences. Participants were 561 children adopted at birth (42% female; 56% White, 19% multiracial, 13% Black/African American, 11% Latine, and 1% other), their adoptive parents, and their birth parents. Results indicate that PDU did not show a direct impact on Age 7 problem behaviors before or after controlling genetic risks and adoptive mother's and father's hostility. However, we found significant interactions between adoptive father's hostility and PDU when predicting children's problem behaviors, such that higher paternal hostility was associated with higher externalizing and internalizing behaviors for children whose birth mothers were non-use or rare use of illicit drugs during pregnancy. The results suggest that different from non- or rare drug-exposed children, higher levels of PDU may override the effects of paternal hostility, but not maternal hostility, on problem behaviors at Age 7. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

School performance in children with prenatal drug exposure and out-of-home care in NSW, Australia: a retrospective population-based cohort study.

Prenatal drug exposure (PDE) is a global public health problem that is strongly associated with the need for child protection services, including placement into out-of-home care (OOHC). We aimed to assess school outcomes for children with PDE (both with and without neonatal abstinence syndrome [NAS]) and the association of school performance with OOHC. Using linked population health, OOHC, and school test data, we compared results on the Australian standardised curriculum-based test, the National Assessment Program-Literacy and Numeracy (NAPLAN), for children with PDE who were born in New South Wales (NSW) between 2001 and 2020 and had completed at least one NAPLAN test between Jan 1, 2008, and June 30, 2021, administered in Year 3 (age 8-9 years), Year 5 (age 10-11 years), Year 7 (age 12-13 years), or Year 9 (age 14-15 years). Linked datasets included NSW Perinatal Data Collection (birth data), NSW Admitted Patient Data Collection (hospital diagnoses), NSW Education Standards Authority (NAPLAN scores), NSW Family and Community Services Dataset-KiDS Data Collection (OOHC information), NSW Mental Health Ambulatory Data Collection, and NSW Registry for Births, Deaths, and Marriages. The primary outcome was scoring above or below the National Minimum Standard (NMS) in any test domain (mathematics, language, writing, and spelling) at each year level, comparing the relative risk of scoring below NMS between children with and without PDE (and with or without NAS within the PDE group), and with and without OOHC contact. The association between OOHC on the likelihood of scoring above NMS was also investigated for PDE and non-PDE cohorts. The PDE cohort included 3836 children, and the non-PDE cohort included 897 487 children. Within the PDE cohort, 3192 children had a NAS diagnosis and 644 children had no NAS diagnosis. 1755 (45·8%) children with PDE required OOHC compared with 12 880 (1·4%) of 897 487 children without PDE. Children with PDE were more likely than children without PDE to score below NMS in any domain from Year 3 (risk ratio 2·72 [95% CI 2·58-2·76]) to Year 9 (2·36 [2·22-2·50]). Performance was similar regardless of a NAS diagnosis (Year 3: 0·96 [0·84-1·10]; Year 9: 0·98 [0·84-1·15]). The likelihood of scoring above NMS in Year 9 was reduced for children with PDE and without NAS (0·57 [0·45-0·73]) and NAS (0·58 [0·52-0·64]) compared with those without PDE, and also for children who received OOHC (0·60 [0·57-0·64]) compared with those without OOHC, when adjusted for confounders. Among children with PDE, those receiving OOHC had a similar likelihood of scoring above NMS compared with children who did not receive OOHC, from Year 3 (1·01 [0·92-1·11]) to Year 9 (0·90 [0·73-1·10]), when adjusted for confounding factors. By contrast, among children without PDE, those receiving OOHC were less likely to score above NMS than those who did not receive OOHC, from Year 3 (0·78 [0·76-0·80]) to Year 9 (0·58 [0·54-0·61]). Compared with children without PDE, school performance in children with PDE-regardless of whether they were diagnosed with NAS-is poor, and the gap widens with age. The risk of poor performance persists regardless of OOHC status. This finding underscores the need for all children with PDE to receive long-term, culturally sensitive, and proactive support to improve life success. SPHERE Mindgardens Neuroscience Network, Australian Red Cross, Alpha Maxx Healthcare, Centre for Research Excellence for Integrated Health and Social Care, National Health and Medical Research Council, and University of Sydney.

Racial Disparities in Newborn Drug Testing After Implementation of Question-Based Screening for Prenatal Substance Use.

To examine the association of universal question-based screening for prenatal substance use on racial inequities in prenatal and newborn drug testing. We conducted a retrospective cohort study of 32,802 live births of patients receiving prenatal care at an academic medical center in the midwestern United States from 2014 to 2022, before and after implementation of question-based screening in 2018. Primary outcomes included prenatal and newborn drug test orders. Logistic regression models using a generalized estimating equation framework assessed associations with question-based screening and results, birthing parent age, race, ethnicity, marital status, and insurance type. Charts of patients who indicated difficulties stopping substance use were audited for guideline-directed care. A total of 12,725 of 14,992 pregnant people (85.3%) received question-based screening. Implementation of question-based screening was associated with a decrease in prenatal urine test orders (5.0% [95% CI, 4.6-5.3%] before implementation, 3.1% [95% CI, 2.8-3.4%] after implementation; P <.001), with Black birthing parents having the largest reduction in prenatal urine drug testing (10.3% [95% CI, 9.0-11.7%] before implementation, 4.9% [95% CI, 3.9-5.9%] after implementation). However, rates of newborn drug testing did not change (4.7% [95% CI, 4.4-5.0%] before implementation, 4.5% [95% CI, 4.2-4.8%] after implementation; P =.46), and clinicians continued to order significantly more newborn drug tests for newborns of Black birthing parents compared with other race and ethnicity groups. Implementation of question-based screening for substance use in pregnancy was associated with decreased prenatal urine drug testing but no change in overall newborn drug testing or racial inequities in newborn drug testing for Black birthing people. Further policy efforts are warranted to improve substance use treatment and to eliminate racial inequities in punitive policies such as newborn drug testing and subsequent child protective services reporting.

Adverse drug reactions in neonates: a brief analysis of the FDA adverse event reporting system.

Drug trials in neonates are scarce, and the neonates may consequently be at risk of adverse drug reactions (ADRs). Spontaneous ADR reporting is an important tool for expanding the knowledge on drug safety in neonates. This study explores the quality of current neonatal ADR reports and the ADR reports of the most common drugs used in neonatal departments. An observational cross-sectional study focused on neonates was conducted using data on spontaneous reports extracted from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) from the third quarter of 2014 up to December 2022. Only the primary suspect drugs given to neonates or subjects aged <30 days were included in the analysis. Spontaneous reports from 13 million patients of all ages, totaling 50 million ADRs, were evaluated. Information regarding the age was missing in 40% of the reports, and data on 43,737 neonates with 948 different suspected drugs were identified and included in the analysis. We report the frequency of spontaneous ADR reports in the FAERS database for the ten most frequently administered drugs in neonatal intensive care units in the USA. Overall, neonatal ADRs are still underreported. The FAERS database in its current form discriminates insufficiently between prenatal and postnatal drug exposures. Hence, improved neonatal pharmacovigilance systems are urgently needed.

Investigating the neurobiology of maternal opioid use disorder and prenatal opioid exposure using brain organoid technology.

Over the past two decades, Opioid Use Disorder (OUD) among pregnant women has become a major global public health concern. OUD has been characterized as a problematic pattern of opioid use despite adverse physical, psychological, behavioral, and or social consequences. Due to the relapsing-remitting nature of this disorder, pregnant mothers are chronically exposed to exogenous opioids, resulting in adverse neurological and neuropsychiatric outcomes. Collateral fetal exposure to opioids also precipitates severe neurodevelopmental and neurocognitive sequelae. At present, much of what is known regarding the neurobiological consequences of OUD and prenatal opioid exposure (POE) has been derived from preclinical studies in animal models and postnatal or postmortem investigations in humans. However, species-specific differences in brain development, variations in subject age/health/background, and disparities in sample collection or storage have complicated the interpretation of findings produced by these explorations. The ethical or logistical inaccessibility of human fetal brain tissue has also limited direct examinations of prenatal drug effects. To circumvent these confounding factors, recent groups have begun employing induced pluripotent stem cell (iPSC)-derived brain organoid technology, which provides access to key aspects of cellular and molecular brain development, structure, and function in vitro. In this review, we endeavor to encapsulate the advancements in brain organoid culture that have enabled scientists to model and dissect the neural underpinnings and effects of OUD and POE. We hope not only to emphasize the utility of brain organoids for investigating these conditions, but also to highlight opportunities for further technical and conceptual progress. Although the application of brain organoids to this critical field of research is still in its nascent stages, understanding the neurobiology of OUD and POE via this modality will provide critical insights for improving maternal and fetal outcomes.

Infant Behaviors, Prenatal Cocaine Exposure, and Adult Intelligence.

Linking prenatal drug exposures to both infant behavior and adult cognitive outcomes may improve early interventions. To assess whether neonatal physical, neurobehavioral, and infant cognitive measures mediate the association between prenatal cocaine exposure (PCE) and adult perceptual reasoning IQ. This study used data from a longitudinal, prospective birth cohort study with follow-up from 1994 to 2018 until offspring were 21 years post partum. A total of 384 (196 PCE and 188 not exposed to cocaine [NCE]) infants and mothers were screened for cocaine or polydrug use. Structural equation modeling was performed from June to November 2023. Prenatal exposures to cocaine, alcohol, marijuana, and tobacco assessed through urine and meconium analyses and maternal self-report. Head circumference, neurobehavioral assessment, Bayley Scales of Infant Development, Fagan Test of Infant Intelligence score, Wechsler Perceptual Reasoning IQ, Home Observation for Measurement of the Environment (HOME) score, and blood lead level. Among the 384 mothers in the study, the mean (SD) age at delivery was 27.7 (5.3) years (range, 18-41 years), 375 of 383 received public assistance (97.9%) and 336 were unmarried (87.5%). Birth head circumference (standardized estimate for specific path association, -0.05, SE = 0.02; P = .02) and 1-year Bayley Mental Development Index (MDI) (standardized estimate for total of the specific path association, -0.05, SE = 0.02; P = .03) mediated the association of PCE with Wechsler Perceptual Reasoning IQ, controlling for HOME score and other substance exposures. Abnormal results on the neurobehavioral assessment were associated with birth head circumference (β = -0.20, SE = 0.08; P = .01). Bayley Psychomotor Index (β = 0.39, SE = 0.05; P < .001) and Fagan Test of Infant Intelligence score (β = 0.16, SE = 0.06; P = .01) at 6.5 months correlated with MDI at 12 months. In this cohort study, a negative association of PCE with adult perceptual reasoning IQ was mediated by early physical and behavioral differences, after controlling for other drug and environmental factors. Development of infant behavioral assessments to identify sequelae of prenatal teratogens early in life may improve long-term outcomes and public health awareness.

Prenatal and postnatal cocaine exposure enhances the anxiety- and depression-like behaviors in rats during cocaine withdrawal.

Prenatal drug exposure is a public health problem, which results in profound behavioral problems during childhood and adolescence, mainly represented by an increase in the risk of cocaine abuse at an early age. In rodents, prenatal and postnatal cocaine exposure enhanced locomotor activity and cocaine- or nicotine-induced locomotor sensitization. Various authors consider that the adverse emotional states (anxiety and depression) that occur during cocaine withdrawal are the main factors that precipitate, relapse, and increase chronic cocaine abuse, which could increase the risk of relapse of cocaine abuse. Therefore, the objective of this study was to characterize anxiety- and depression-like behaviors at different times (30, 60, 90, and 120 days) of cocaine withdrawal in rats born to females exposed prenatally and postnatally to cocaine. A group of pregnant female Wistar rats were administered daily from day GD0 to GD21 with cocaine (cocaine preexposure group), and another group of pregnant female rats was administered daily with saline (saline preexposure group). Of the litters resulting from the cocaine-pre-exposed and saline-pre-exposed pregnant female groups, only the male rats were used for the recording of the anxiety- and depression-like behaviors at different times (30, 60, 90, and 120 days) of cocaine withdrawal The study found that prenatal and postnatal cocaine exposure dose-dependent enhanced anxiety- and depression-like behaviors. This suggests that prenatal and postnatal cocaine exposure can result in enhanced vulnerability to cocaine abuse in young and adult humans.

Reduced fetal cerebral blood flow predicts perinatal mortality in a mouse model of prenatal alcohol and cannabinoid exposure

BackgroundChildren exposed prenatally to alcohol or cannabinoids individually can exhibit growth deficits and increased risk for adverse birth outcomes. However, these drugs are often co-consumed and their combined effects on early brain development are virtually unknown. The blood vessels of the fetal brain emerge and mature during the neurogenic period to support nutritional needs of the rapidly growing brain, and teratogenic exposure during this gestational window may therefore impair fetal cerebrovascular development.Study DesignTo determine whether prenatal polysubstance exposure confers additional risk for impaired fetal-directed blood flow, we performed high resolution in vivo ultrasound imaging in C57Bl/6J pregnant mice. After pregnancy confirmation, dams were randomly assigned to one of four groups: drug-free control, alcohol-exposed, cannabinoid-exposed or alcohol-and-cannabinoid-exposed. Drug exposure occurred daily between Gestational Days 12–15, equivalent to the transition between the first and second trimesters in humans. Dams first received an intraperitoneal injection of either cannabinoid agonist CP-55,940 (750 µg/kg) or volume-equivalent vehicle. Then, dams were placed in vapor chambers for 30 min of inhalation of either ethanol or room air. Dams underwent ultrasound imaging on three days of pregnancy: Gestational Day 11 (pre-exposure), Gestational Day 13.5 (peri-exposure) and Gestational Day 16 (post-exposure).ResultsAll drug exposures decreased fetal cranial blood flow 24-hours after the final exposure episode, though combined alcohol and cannabinoid co-exposure reduced internal carotid artery blood flow relative to all other exposures. Umbilical artery metrics were not affected by drug exposure, indicating a specific vulnerability of fetal cranial circulation. Cannabinoid exposure significantly reduced cerebroplacental ratios, mirroring prior findings in cannabis-exposed human fetuses. Post-exposure cerebroplacental ratios significantly predicted subsequent perinatal mortality (p = 0.019, area under the curve, 0.772; sensitivity, 81%; specificity, 85.70%) and retroactively diagnosed prior drug exposure (p = 0.005; AUC, 0.861; sensitivity, 86.40%; specificity, 66.7%).ConclusionsFetal cerebrovasculature is significantly impaired by exposure to alcohol or cannabinoids, and co-exposure confers additional risk for adverse birth outcomes. Considering the rising potency and global availability of cannabis products, there is an imperative for research to explore translational models of prenatal drug exposure, including polysubstance models, to inform appropriate strategies for treatment and care in pregnancies affected by drug exposure.

‘Joining the Dots: Linking Prenatal Drug Exposure to Childhood and Adolescence’ – research protocol of a population cohort study

IntroductionPrenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The Joining...

Child Protection System Removal and Short-Interval Births Among Individuals With Prenatal Substance Use.

Child protection systems often intervene after substance-exposed births but are not designed to address the postpartum needs of the delivering parent. In this retrospective cohort study, we aimed to estimate the association between early child protection system removal and high-risk subsequent birth trajectories among a cohort of mothers with substance-exposed births in California. Of 6,893 births in 2015 with documented prenatal drug and alcohol exposure, 20.4% of mothers experienced child protection system removal within 30 days after birth. First-month child protection system removal was associated with short-interval birth (adjusted hazard ratio [HR] 1.61, 95% CI, 1.09-2.36) and short-interval birth with documentation of substance exposure (adjusted HR 3.17, 95% CI, 1.65-6.08). We found that child separation was associated with an increase, not a reduction, in subsequent substance-exposed births. These findings indicate the need for focused public health and supportive services to address the treatment, health care, family-building, and psychological needs of parents with substance use during pregnancy.

Fetal circular shunt in Ebstein's anomaly and non-steroidal anti-inflammatory treatment.

A circular shunt is a poor prognostic factor associated with Ebstein's anomaly. Targeting the constriction of the ductus arteriosus (DA) in order to limit or resolve the circular shunt, has been shown to improve fetal outcomes. Prenatal non-steroidal anti-inflammatory drugs (NSAIDs) have been known to constrict the DA. Recently, prenatal NSAIDs have been used for that purpose in the treatment of circular shunt. Limited research shows that it may be an effective treatment leading to improved fetal outcomes. In this article, we did an extensive review of literature to describe this therapy's effectiveness and outcomes. 82% of fetuses were able to achieve ductal constriction with prenatal NSAID therapy. For fetuses who achieved ductal constriction, fetal demise was less likely (6%) when compared to those who were unable to achieve the same (50%). Of all the fetuses with hydrops, 50% had resoluation of hydrops with prenatal NSAID treatment.

The impact of prenatal alcohol, synthetic cannabinoid and co-exposure on behavioral adaptations in adolescent offspring and alcohol self-administration in adulthood

Prenatal exposure to alcohol or cannabinoids can produce enduring neurobiological, cognitive, and behavioral changes in the offspring. Furthermore, prenatal co-exposure to alcohol and cannabinoids induces malformations in brain regions associated with reward and stress-related circuitry. This study examined the effects of co-exposure to alcohol and the synthetic cannabinoid (SCB) CP55,940 throughout gastrulation and neurulation in rats on basal corticosterone levels and a battery of behavioral tests during adolescence and alcohol self-administration in adulthood. Importantly, we find that prenatal alcohol exposure (PAE) caused lower baseline corticosterone levels in adolescent males and females. Co-exposure to alcohol + CP produced hyperactivity during open field test in males, but not females. During the two-bottle choice alcohol-drinking procedure, prenatal cannabinoid exposed male and female adolescent rats drank more alcohol than their vehicle-exposed controls. In adulthood, female rats treated with prenatal cannabinoid exposure (PCE), showed an overall total increase in alcohol intake during alcohol self-administration; but this was not found in males. When the reinforcer was changed to a 1% sucrose solution, male rats exposed to PCE, showed a reduced self-administration compared to vehicle-exposed males, potentially indicative of an anhedonic response. This lower self-administration persisted when 20% alcohol was reintroduced to the sucrose solution. Lastly, following an abstinence period, there were no changes due to prenatal drug exposure in either males or females. Overall, these data suggest lasting consequences of prenatal alcohol and cannabinoid exposure during adolescence and adulthood in male and female rats.

A retrospective review of methylamphetamine detected in child deaths reported to the Victorian Coroner, Australia.

This study investigated methylamphetamine (MA) exposures in the deaths of children (≤ 12years old) reported to the Coroner in the state of Victoria, Australia, between 2011 and 2020. Demographics, autopsy findings including the cause of death, self-reported prenatal or caregiver drug use, child protection services information, and toxicological findings were summarized by descriptive statistics. Validated methods of liquid chromatography-tandem mass spectrometry were used in the analysis of drugs. There were 50 child deaths with MA detected in blood, urine, and/or hair with 64% (n = 32) identified in 2018-2020. Most children were 1-365days old (66%, n = 33) and the cause of death was unascertained in 62% (n = 31) of cases. MA was toxicologically confirmed in hair (94%, n = 47) significantly more than blood (18%, n = 9). Prenatal or caregiver drug use was self-reported in 44% (n = 22) and 42% (n = 21) of cases, respectively. Moreover, only 54% (n = 27) of deceased children were a child protection client at their time of death. These findings suggest the number of deceased children exposed to MA has increased over the past 10years, which is consistent with the greater supply of crystal MA in the Australian community. Hair analysis provided additional means to identify cases that were unknown to child protection services and may have implications for other children in the same drug exposure environment.

Maternal Prenatal Use of Alcohol, Tobacco, and Illicit Drugs and Associations with Childhood Cancer Subtypes.

The association between childhood cancer risk and maternal prenatal substance use/abuse remains uncertain due to modest sample sizes and heterogeneous study designs. We surveyed parents of children with cancer regarding maternal gestational use of tobacco, alcohol, and illicit drugs, using a Likert-type scale, and demographic, perinatal, and clinical variables. Multivariable log-Poisson regression assessed differences in frequency of prenatal substance use across fifteen childhood cancer subtypes, adjusting for birthweight, gestational age, and demographic factors. Respondents from 3,145 unique families completed the survey (92% biological mothers). A minority reported gestational use of tobacco products (14%), illicit drugs including marijuana or cocaine (4%), or more than a moderate amount of alcohol (2%). Prenatal illicit drug use was associated with increased prevalence of intracranial embryonal tumors [prevalence ratio (PR) = 1.94; confidence interval [CI], 1.05-3.58], including medulloblastoma (PR = 1.82) and supratentorial primitive neuroectodermal tumors (PNET; PR = 2.66), and was also associated with retinoblastoma (PR = 3.11; CI, 1.20-8.08). Moderate to heavy alcohol consumption was strongly associated with elevated prevalence of non-Hodgkin lymphoma (PR = 5.94; CI, 1.84-19.21). Prenatal smoking was not associated with elevated prevalence of any childhood cancer subtype. We identify novel associations between illicit drug use during pregnancy and increased prevalence of nonglioma central nervous system tumors, including medulloblastoma, supratentorial PNETs, and retinoblastoma. Gestational exposure to alcohol was positively associated with non-Hodgkin lymphoma. Although alcohol and tobacco use during pregnancy has declined, gestational cannabis use has risen. Investigating its impact on neurodevelopment and brain tumorigenesis is vital, with important implications for childhood cancer research and public health education.

Early emotional caregiving environment and associations with memory performance and hippocampal volume in adolescents with prenatal drug exposure

Early adversities, including prenatal drug exposure (PDE) and a negative postnatal emotional caregiving environment, impact children’s long-term development. The protracted developmental course of memory and its underlying neural systems offer a valuable framework for understanding the longitudinal associations of pre- and postnatal factors on children with PDE. This study longitudinally examines memory and hippocampal development in 69 parent–child dyads to investigate how the early caregiving emotional environment affects children with PDE’s neural and cognitive systems. Measures of physical health, drug exposure, caregiver stress, depression, and distress were collected between 0 and 24 months At age 14 years, adolescents completed multiple measures of episodic memory, and at ages 14 and 18 years, adolescents underwent magnetic resonance imaging (MRI) scans. Latent constructs of episodic memory and the caregiving environment were created using Confirmatory Factor Analysis. Multiple regressions revealed a negative emotional caregiving environment during infancy was associated with poor memory performance and smaller left hippocampal volumes at 14 years. Better memory performance at 14 years predicted larger right hippocampal volume at 18 years. At 18 years, the association between the emotional caregiving environment and hippocampal volume was moderated by sex, such that a negative emotional caregiving environment was associated with larger left hippocampal volumes in males but not females. Findings suggest that the postnatal caregiving environment may modulate the effects of PDE across development, influencing neurocognitive development.

Gastroschisis Associated Intestinal Dysmotility: What Can We Do?

The cause of gastroschisis is not fully known, but risk factors like prenatal tobacco exposure, maternal infection and maternal drug use are often associated. When gastroschisis occurs with intestinal dysmotility, the enteric interstitial cells of Cajal (ICC) implicate the dysmotility and may ultimately impact the growth of an infant. Furthermore, neonates experience growth weight failure when not taking any enteral feedings secondary to dysmotility. We had a case of an infant with gastroschisis and intestinal atresia who had a prolonged course of feeding intolerance and abdominal distention after his bowel resection. His growth was preserved because of careful management of total parenteral nutrition (TPN) via a judicious nutrition plan.