Prenatal Exposure to Perfluorooctane Sulfonate impairs Placental Angiogenesis and Induces Aberrant Expression of LncRNA Xist

Perfluorooctane sulfonate （PFOS） is a class of stable organic compounds with wide industrial,commercial, and consumer applications, such as in textiles, paper, pesticides, and shampoos;. It is readily absorbed, but poorly eliminated, with the elimination half-life of approximately 5 years;.Hence, there have been concerns regarding its potential damage to human health. Some studies

The Identification of Prenatal Exposure to Mitragynine Using Umbilical Cord Tissue

Objective: Kratom is widely available and literature exploring the effects of prenatal kratom exposure is lacking. This study aims to report a validated method for the detection of mitragynine in the umbilical cord and report our observations for specimens received at a national commercial reference laboratory. Study Design: Assays were validated according to the recommendations of ANSI/ASB. A retrospective evaluation of records at a national reference laboratory was conducted to determine prevalence and co-exposure to other substances of abuse. Result: Mitragynine was detected in 19 of 4456 specimens (0.43%) with concentrations ranging from 4 to >50 ng/g. Thirteen (13) of these specimens were positive for only mitragynine while the other 6 were also positive for either marijuana or opiates. Conclusion: Umbilical cord is a suitable specimen type for the surveillance of maternal kratom use and can be used to identify exposed neonates for further investigations into short- or long- term health consequences.

Using Umbilical Cord Tissue to Identify Prenatal Exposure to Fentanyl and Other Commonly Abused Drugs

Background: Prenatal exposure to fentanyl may lead to Neonatal Abstinence Syndrome (NAS), a constellation of symptoms observed when newborns begin withdrawing from addictive substances such as opioids. The use of umbilical cord tissue segments (UC) for newborn toxicology has been increasing due to its apparent long detection window, sensitivity, and ease of collection. However, very little has been reported in the literature concerning the prevalence of in utero exposure to fentanyl and co-exposure with other commonly abused substances. Specific aim: The specific aims of this retrospective study are twofold. We will report prevalence of neonatal exposure to fentanyl for a nationwide high-risk population using UC submitted to a national reference laboratory for routine forensic toxicology analysis and the co-exposure patterns observed for these fentanyl-exposed neonates. Methods: A secondary analysis was performed using historical data for UC received between January 1, 2020 and December 31, 2020 for routine forensic toxicology analysis. Results: During the study period, our laboratory received 23,104 UC for analysis and 9667 (41.8%) of those UC were positive for at least one drug. The prevalence of fentanyl detection was 1.9% (n = 429). Of these 429 specimens there were 407 UC where both fentanyl and norfentanyl were detected. There were 14 UC where only fentanyl was detected and 8 UC where only norfentanyl was detected. When detected, the median concentrations of fentanyl and norfentanyl were 4029 pg/g (IQR: 1696, 9230 pg/g) and 10,756 pg/mg (IQR: 3925, 25,288 pg/g), respectively. Of the 429 positive fentanyl and/or norfentanyl UC, 33 (7.7%) were only positive for fentanyl and/or norfentanyl. Of the 396 polypositive UC, morphine was the highest co-exposure with 243 UC (56.6%) being positive for both fentanyls and morphine. The second most prevalent co-exposure observed was methamphetamine/amphetamine (n = 173;40.3%) followed by cannabinoids (n = 113;26.3%) and benzoylecgonine (cocaine metabolite;n = 106;24.7%). Conclusions: Nonmedical use of fentanyl is an alarming trend in this country including this maternal demographic reported here. Fentanyl was typically found with other commonly abused substances.

Associations of prenatal exposure to bisphenols with BMI growth trajectories in offspring within the first two years:evidence from a birth cohort study in China

Background Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood.These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring.This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index(BMI)growth trajectory of children aged up to two years and to identify the critical exposure periods.Methods A total of 826 mother–offspring pairs were recruited from Wuhan Children’s Hospital between November 2013 and March 2015.Maternal urine samples collected during the first,second,and third trimesters were analyzed for bisphenol A(BPA),bisphenol S,and bisphenol F(BPF)concentrations.Measurements of length and weight were taken at 0,1,3,6,8,12,18,and 24 months.Children's BMI was standardized using the World Health Organization reference,and group-based trajectory modeling was used to identify BMI growth trajectories.The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models.Results The BMI growth trajectories of the 826 children were categorized into four patterns:low-stable(n=134,16.2%),low-increasing(n=142,17.2%),moderate-stable(n=350,42.4%),and moderate-increasing(n=200,24.2%).After adjusting for potential confounders,we observed that prenatal exposure to BPA during the second trimester[odds ratio(OR)=2.20,95%confidence interval(CI)=1.09–4.43]and BPF during the third trimester(OR=3.28,95%CI=1.55–6.95)at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory.Furthermore,in the subgroup analysis by infant sex,the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls(OR=2.82,95%CI=1.04–7.68).Conclusion Our study findings suggest that prenatal exposure to BPA and BPF(a commonly used substitute for BPA)is associated with BMI growth trajectories in offspring during the first two years,increasing the likelihood of the low-increasing pattern.

Neurotoxicity of prenatal alcohol exposure on medullary pre-B?tzinger complex neurons in neonatal rats

Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor（5-HT2AR） is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10%（v/v） throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2 AR protein and m RNA levels in the pre-B？tzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2 AR protein and m RNA levels.

Prenatal amoxicillin exposure induces developmental toxicity in fetal mice and its characteristics

Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.

Prenatal Environmental Antibiotic Exposure and Autism Spectrum Disorder Symptoms in Children at 3 Years of Age:Findings from the Ma’anshan Birth Cohort Study

ABSTRACT:Antibiotic exposure during pregnancy may affect the neurodevelopment of children,but biomonitoring-based population studies on this class of new pollutants are lacking.We conducted a prospective birth cohort study of 2860 mother−child pairs,measured the urinary concentrations of 41 antibiotics and their two metabolites over three trimesters,and assessed children’s autism spectrum disorder(ASD)symptoms at 3 years of age.We examined the associations between prenatal antibiotic exposure and children’s ASD symptoms.The least absolute shrinkage and selection operator regression screened for Tetracycline and Ofloxacin as important predictors of ASD symptoms.Modified Poisson regression models revealed that maternal Tetracycline exposure throughout pregnancy increased the risk of ASD symptoms(RR:1.66,95%CI:1.14,2.40).Maternal Tetracycline exposure during the first(RR:1.74,95%CI:1.13,2.68)and third trimesters(RR:1.86,95%CI:1.16,3.00)increased the risk of ASD symptoms in boys,and Ofloxacin exposure during the first trimester(RR:1.47,95%CI:1.07,2.02)increased the risk of ASD symptoms in girls.No dose-dependent relationships between prenatal antibiotic exposure and ASD symptoms were validated by restricted cubic splines.Prenatal exposure to Tetracycline and Ofloxacin may increase the risk of ASD symptoms in children,and the first and third trimesters might be the key windows.

Evaluation of spermatogenesis and fertility in F1 male rats after in utero and neonatal exposure to extremely low frequency electromagnetic fields

Aim:To determine whether in utero and neonatal exposure to a 60 Hz extremely low frequency electromagnetic field (EMF) results in spermatotoxicity and reproductive dysfunction in the F1 offspring of rats.Methods:Age-matched, pregnant Sprague-Dawley rats were exposed continuously (21 h/day) to a 60 Hz EMF at field strengths of 0 (sham control),5,83.3 or 500 μT from day 6 of gestation through to day 21 of lactation.The experimentally generated magnetic field was monitored continuously (uninterrupted monitoring over the period of the study) throughout the study.Results:No exposure-related changes were found in exposed or sham-exposed animals with respect to the anogenital distance,preputial separation,testis weight,testicular histology,sperm count,daily sperm production, sperm motility,sperm morphology and reproductive capacity of F1 offspring.Conclusion:Exposure of Sprague- Dawley rats to a 60 Hz EMF at field strengths of up to 500 μT from day 6 of gestation to day 21 of lactation did not produce any detectable alterations in offspring spermatogenesis and fertility.

A Comparison of Turnaround-Times for Two Popular Specimen Types Used for Newborn Toxicology: Meconium and Umbilical Cord Tissue

Background: Prenatal exposure to illicit substances is responsible for several long-term negative health consequences. It is critical for healthcare professionals to know the extent and scope of prenatal substance exposure in their cases. Several studies exist with mixed results comparing the effectiveness of umbilical cord tissue (UCT) and meconium (MEC) as toxicology specimen types. The specific aim of this study is to compare the use of UCT and MEC regarding the time interval between the birth of the neonate, receipt of the specimen at the laboratory, and the hospital’s receipt of the final toxicology report. Method: The study queried de-identified results of 5358 consecutive UCT and 706 MEC from our laboratory. Results: The mean time from birth to receipt of the specimen at the laboratory for MEC and UCT was 4.5 days ± 2.9 days and 2.8 days ± 1.9 days, respectively. The mean time from birth to final report for MEC was 6.9 days ± 3.8 days, 5.7 days ± 3.3 days, and 8.4 days ± 3.8 days for all MEC specimens, negative MEC, and positive MEC, respectively. The mean time from birth to final report for UCT was 4.3 days ± 2.4 days, 3.5 days ± 2.2 days, and 5.4 days ± 2.2 days for all UCT, negative UCT and positive UCT, respectively. Discussion/Conclusion: Receipt of drug test results of the neonate prior to release from the hospital is critical. This study shows that UCT offers an advantage when results are needed quickly to make informed decisions about the health and well-being of newborns.

Prenatal nicotine alters development of the laterodorsal tegmentum:Possible role for attention-deficit/hyperactivity disorder and drug dependence

As we cycle between the states of wakefulness and sleep,a bilateral cholinergic nucleus in the pontine brain stem,the laterodorsal tegmentum(LDT),plays a critical role in controlling salience processing,attention,behavioral arousal,and electrophysiological signatures of the sub-and microstates of sleep.Disorders involving abnormal alterations in behavioral and motivated states,such as drug dependence,likely involve dysfunctions in LDT signaling.In addition,as the LDT exhibits connectivity with the thalamus and mesocortical circuits,as well as receives direct,excitatory input from the prefrontal cortex,a role for the LDT in cognitive symptoms characterizing attention-deficit/hyperactivity disorder(ADHD)including impulsivity,inflexibility,and dysfunctions of attention is suggested.Prenatal nicotine exposure(PNE)is associated with a higher risk for later life development of drug dependence and ADHD,suggesting alteration in development of brain regions involved in these behaviors.PNE has been shown to alter glutamate and cholinergic signaling within the LDT.As glutamate and acetylcholine are major excitatory mediators,these alterations would likely alter excitatory output to target regions in limbic motivational circuits and to thalamic and cortical networks mediating executive control.Further,PNE alters neuronal development and transmission within prefrontal cortex and limbic areas that send input to the LDT,which would compound effects of differential processing within the PNE LDT.When taken together,alterations in signaling in the LDT are likely to play a role in negative behavioral outcomes seen in PNE individuals,including a heightened risk of drug dependence and ADHD behaviors.

Neonatal Cord Tox Panel and Maternal Perinatal Fentanyl Exposure: A Retrospective Chart Review

Objective: The specific aim of this study was to determine if the currently available cutoff for fentanyl in umbilical cord (UC) was appropriate to distinguish illicit fentanyl exposure from therapeutic in-hospital administration of fentanyl. Study Design: Medical record review was conducted for perinatal administration of fentanyl and the detection of fentanyl in the corresponding routine UC toxicology. Specimens were initially tested with immunoassay followed by mass spectrometry (n = 62). Result: Excluding a single specimen that was confirmed positive, specimens were below the assays’ limit of quantification. The immunoassay’s mean b/b0 for the cases that received and did not receive fentanyl prior to delivery was 91.3% ± 10.6% and 98.2% ± 6.5%, respectively (p = 0.003). Conclusion: We demonstrated that UC is a suitable specimen type for the detection of fentanyl and that the cutoff selected adequately identifies illicit fentanyl use while not flagging cases where fentanyl was administered by the hospital prior to birth.

Pyridoxal 5'-phosphate alleviates prenatal pyridaben exposureinduced anxiety-like behaviors in offspring

Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.

Activation of the PGC-1α-mediated mitochondrial glutamine metabolism pathway attenuates female offspring osteoarthritis induced by prenatal excessive prednisone

Osteoarthritis is a chronic,age-related joint disease.Previous studies have shown that osteoarthritis develops during intrauterine development.Prednisone is frequently used to treat pregnancies complicated by autoimmune diseases.However,limited research has been conducted on the enduring effects of prednisone use during pregnancy on the offspring.In this study,we investigated the effect of excessive prednisone exposure on cartilage development and susceptibility to osteoarthritis in the offspring.We found that prenatal prednisone exposure(PPE)impaired cartilage extracellular matrix(ECM)synthesis,resulting in poor cartilage pathology in female offspring during the adult period,which was further exacerbated after long-distance running stimulation.Additionally,PPE suppressed cartilage development during the intrauterine period.Tracing back to the intrauterine period,we found that Pred,rather than prednisone,decreased glutamine metabolic flux,which resulted in increased oxidative stress,and decreased histone acetylation,and expression of cartilage phenotypic genes.Further,PGC-1α-mediated mitochondrial biogenesis,while PPE caused hypermethylation in the promoter region of PGC-1αand decreased its expression in fetal cartilage by activating the glucocorticoid receptor,resulting in a reduction of glutamine flux controlled by mitochondrial biogenesis.Additionally,overexpression of PGC-1α(either pharmacological or through lentiviral transfection)reversed PPEand Pred-induced cartilage ECM synthesis impairment.In summary,this study demonstrated that PPE causes chondrodysplasia in female offspring and increases their susceptibility to postnatal osteoarthritis.Hence,targeting PGC-1αearly on could be a potential intervention strategy for PPE-induced osteoarthritis susceptibility.

Maternal cigarette smoking during pregnancy and reproductive health in children： a review of epidemiological studies

Maternal cigarette smoking may affect the intrauterine hormonal environment during pregnancy and this early fetal exposure may have detrimental effects on the future trajectory of reproductive health. In this review, we discuss the epidemiological literature on the association between prenatal exposure to maternal cigarette smoking and several aspects of reproductive health. The literature points towards an increased risk of the urogenital malformation cryptorchidism, but a potential protective effect on the risk of hypospadias in sons following prenatal cigarette smoking exposure. Studies on sexual maturation find a tendency towards accelerated pubertal development in exposed boys and girls. In adult life, prenatally exposed men have impaired semen quality compared with unexposed individuals, but an influence on fecundability, that is, the biological ability to reproduce, is less evident. We found no evidence to support an association between prenatal cigarette smoking exposure and testicular cancer. Among adult daughters, research is sparse and inconsistent, but exposure to cigarette smoking in utero may decrease fecundability. In conclusion, prenatal exposure to cigarette smoking may cause some long-term adverse effects on the reproductive health.

Association between antibiotic exposure and adverse outcomes of children and pregnant women: evidence from an umbrella review

Background Antibiotics are widely prescribed among children and pregnant women,but their safety profile is controversial.This study aimed to summarize and appraise current evidence for the potential impact of antibiotic exposure on pregnancy outcomes and children’s health.Methods PubMed,Embase,Web of Science and the Cochrane Database of Systematic Reviews were searched from inception to June 2022.Meta-analyses of any study design comparing the impact of antibiotic exposure with nonexposure among children,pregnant women and prepregnant women on adverse health outcomes of children and pregnancy were retrieved.The quality of evidence was assessed by a Measurement Tool to Assess Systematic Reviews 2(AMSTAR2)and the Grading of Recommendations,Assessment,Development and Evaluation(GRADE).Data were reanalyzed,and the credibility of the evidence was determined.Results Out of 2956 studies identified,19 articles with 39 associations were included.Totally 19 of the associations(48.72%)were statistically significant with a P value≤0.05,while only six were supported by highly suggestive evidence.Children with postnatal antibiotic exposure had a higher risk of developing asthma odds ratio(OR):1.95,95%confidence interval(CI):1.76–2.17,wheezing(OR:1.81,95%CI 1.65–1.97)and allergic rhinoconjunctivitis(OR:1.66,95%CI 1.51–1.83),with prediction intervals excluding the nulls.Quality assessed by both AMSTAR2 and GRADE of included meta-analyses were very low in general.Conclusions Antibiotic exposure in early life was associated with children’s long-term health,especially in cases of allergic diseases.Prenatal exposure might also influence children’s health in some aspects but requires more high-quality evidence.Potential adverse effects of antibiotics on pregnancy outcomes were not observed in our study.Studies with higher quality and better quantification of antibiotic exposure are needed in the future.

Has Sperm Count Declined in the General Male Danish Population during the Last Several Decades?A Study on the Relation of Sperm Count and Birth Year

It has been hypothesized that during the last several decades human sperm count has declined because of prenatal exposure to environmental chemicals. We examined the relation between semen quality and birth year among 8608 men born from 1922 to 1971 and who from 1968 to 1992 consulted 4 Danish medical centers because of barren marriage. Data were obtained from medical records and by a postal questionnaire to a subset of the population. The sperm concentration was significantly declining with increasing year of birth in 2 of the 4 centers, but this association disappeared when confounders were adjusted for. Within the subset of men born during 1955~1970 comprising 36% of the entire population we revealed a decrease of the average sperm concentration by 1.6 million /ml (95% CI:0.7~2.5) per one advancing year of birth.This finding was consistent across all the 4 centers and robust to adjustment for effects of calendar period, season and duration of sexual abstinence. Effects of age were accounted for by restriction of the sample to men between 20 and 45 years. The findings are compatible with environmental impact in the prenatal period after 1955 but are far from unequivocal evidence that the sperm count in the general male Danish population has changed during the past decades.

Prenatal metal mixture exposure and birth weight: A two-stage analysis in two prospective cohort studies

The understanding of the impact of prenatal exposure to metal mixtures on birth weight is limited.We aimed to identify metal mixture components associated with birth weight and to determine additional pairwise interactions between metals showing such associations.Concentrations of 18 metals were measured using inductively coupled plasma mass spectrometry in urine samples collected in the 3rd trimester from a prenatal cohort(discovery;n=1849)and the Healthy Baby Cohort(replication;n=7255)in Wuhan,China.In the discovery set,we used two penalized regression models,i.e.,elastic net regression for main effects and a lasso for hierarchical interactions,to identify important mixture components associated with birth weight,which were then replicated.We observed that 8 of the 18 measured metals were retained by elastic net regression,with five metals(vanadium,manganese,iron,cesium,and barium)showing negative associations with Z-scores for birth weight and three metals(cobalt,zinc,and strontium)showing positive associations.In replication set,associations remained significant for vanadium(β=-0.035;95%confidence interval[CI],-0.059 to0.010),cobalt(β=-0.073;95%CI,0.049 to 0.097),and zinc(β=-0.040;95%CI,0.016 to 0.065)after Bonferroni correction.We additionally identified and replicated a single pairwise interaction between iron and copper exposure on birth weight(P<0.001).Using a two-stage analysis,we identified and replicated individual metals and additional pairwise interactions-associated birth weight.The approach could be used in other studies estimating the effect of complex mixtures on human health.

Ceramide is involved in alcohol-induced neural proliferation

Prenatal alcohol exposure, especially during early pregnancy, can lead to fetal alcohol syndrome. The pharmacological and toxicological mechanisms of ethanol are related to the effects of ceramide In this study, we established an alcohol exposure model in wild-type mice and in knockout mice for the key enzyme involved in ceramide metabolism, sphingomyelin synthase 2. This model received daily intragastric administration of 25% ethanol, and pups were used at postnatal days 0, 7, 14, 30 for experiments. Serology and immunofluorescence staining found that ethanol exposure dose-dependently reduced blood sphingomyelin levels in two genotypes of pups, and increased neural cell proliferation and the number of new neurons in the hippocampal dentate gyrus. Western blot analysis showed that the relative expression level of protein kinase C e increased in two genotypes of pups after ethanol exposure. Compared with witd-type pups, the expression level of the important activator protein of the ceramide/ceramide-l-phosphate pathway, protein kinase C a, was reduced in the hippocampus of sphingomyelin synthase 2 knockouts. Our findings illustrate that ceramide is involved in alcohol-induced neural proliferation in the hippocampal dentate gyrus of pups after prenatal ethanol exposure, and the mechanism may be associated with increased ex- pression of protein kinase C a activating the ceramide/ceramide-l-phosphate pathway.

Psychotropic drug abuse in pregnancy and its impact on child neurodevelopment:A review

Substance abuse by women of child-bearing age and fetal in utero drug exposure has increased in the number of infants born with health issues.Prenatal exposure to psychoactive substances can lead to neurological and neurodevelopmental deficits later in life.Useful data concerning the effects of psychoactive drugs on fetal neurodevelopmental status are sparse.Understanding the neurodevelopmental consequences of prenatally drug-exposed children has become a pressing global concern.The aim of this review is to gather current evidence and information on neurodevelopmental outcomes of in utero drug exposure.A literature search was performed on the PubMed,Scopus,and Google Scholar databases using the terms“psychotropic drugs”,“neurodevelopmental consequences”,“prenatal drug exposure”,and“pregnancy”.Available studies on in utero drug exposure were reviewed and found to support the idea that some degree of health issues are present in fetuses and children.Different psychoactive substances have profound neurodevelopmental consequences,such as structural brain changes,poor attention span,Down syndrome,attention deficit hyperactivity disorder,autism spectrum disorder,imbalances in neurotransmitter levels,and many structural deficits.The pervasive use of psychoactive drugs in women of child-bearing age is an important health concern.Further scientific efforts are needed to investigate the effect of prenatal exposure to psychoactive drugs on children.

Postnatal renin-angiotensin system inhibition prevents renal damage from prenatal inflammation in rats

OBJECTIVE:To assess the protective role of benazepril,an angiotensin-converting enzyme inhibitor,in renal damage caused by prenatal inflammation.METHODS:Saline or lipopolysaccharide were administered intraperitoneally to pregnant Sprague-Dawley rats on gestation days 8,10,and 12.After birth,offspring received either tap water or benazepril in water between 7 and 68 weeks.Blood pressure,blood urea nitrogen,creatinine,and 24-h urine volume were measured as indices of renal function.Hematoxylin,eosin,periodic acid-Schiff,and Sirius Red staining were used to evaluate renal damage.RESULTS:Postnatal benazepril treatment ameliorated hypertension and restored normal 24-h urine volume and blood urea nitrogen and serum creatinine levels.Benazepril treatment also reduced glycoprotein accumulation and fibrosis in the glomerulus and in tubular epithelial cells and inhibited nuclear factor-kappa B activation.CONCLUSION:Together with our previous findings that postnatal inhibition of nuclear factor-kappa B activation blocks intra-renal renin-angiotensin system activation,our current data demonstrate that intra-renal activation of the renin-angiotensin system interacts with nuclear factor-kappa B activation to cause renal damage in adulthood following prenatal inflammation.