According to reports, prenatal exposure to valproic acid can induce autism spectrum disorder (ASD)-like symptoms in both humans and rodents. However, the exact cause and therapeutic method of ASD is not fully understood. Agmatine (AGM) is known for its neuroprotective effects, and this study aims to explore whether giving agmatine hydrochloride before birth can prevent autism-like behaviors in mouse offspring exposed prenatally to valproic acid.
Methods
In this study, we investigated the effects of AGM prenatally on valproate (VPA)-exposed mice. We established a mouse model of ASD by prenatally administering VPA. From birth to weaning, we evaluated mouse behavior using the marble burying test, open-field test, and three-chamber social interaction test on male offspring.
Results
The results showed prenatal use of AGM relieved anxiety and hyperactivity behaviors as well as ameliorated sociability of VPA-exposed mice in the marble burying test, open-field test, and three-chamber social interaction test, and this protective effect might be attributed to the activation of the ERK/CREB/BDNF signaling pathway.
Conclusion
Therefore, AGM can effectively reduce the likelihood of offspring developing autism to a certain extent when exposed to VPA during pregnancy, serving as a potential therapeutic drug.
{"title":"The prenatal use of agmatine prevents social behavior deficits in VPA-exposed mice by activating the ERK/CREB/BDNF signaling pathway","authors":"Shihao Chen, Qi Xu, Linqian Zhao, Mulan Zhang, Huiqin Xu","doi":"10.1002/bdr2.2336","DOIUrl":"https://doi.org/10.1002/bdr2.2336","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>According to reports, prenatal exposure to valproic acid can induce autism spectrum disorder (ASD)-like symptoms in both humans and rodents. However, the exact cause and therapeutic method of ASD is not fully understood. Agmatine (AGM) is known for its neuroprotective effects, and this study aims to explore whether giving agmatine hydrochloride before birth can prevent autism-like behaviors in mouse offspring exposed prenatally to valproic acid.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we investigated the effects of AGM prenatally on valproate (VPA)-exposed mice. We established a mouse model of ASD by prenatally administering VPA. From birth to weaning, we evaluated mouse behavior using the marble burying test, open-field test, and three-chamber social interaction test on male offspring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed prenatal use of AGM relieved anxiety and hyperactivity behaviors as well as ameliorated sociability of VPA-exposed mice in the marble burying test, open-field test, and three-chamber social interaction test, and this protective effect might be attributed to the activation of the ERK/CREB/BDNF signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Therefore, AGM can effectively reduce the likelihood of offspring developing autism to a certain extent when exposed to VPA during pregnancy, serving as a potential therapeutic drug.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Since strain names and breeding facilities of ICR mice used in 37 reproductive toxicity studies have changed from 1990 to 2022 in our laboratory, biological and environmental factors that affect reproductive parameters were investigated in control mice to examine the validity of the background data.
Methods
Litter size and sex ratio were measured at birth [postnatal day (PND) 0], while offspring body weight was measured on PND 0 and 21 during the lactation. The relationships between biological and environmental factors and reproductive parameters were assessed with multiple regression analysis using stepwise regression as an explanatory variable selection strategy. The biological factors of litter size at birth, secondary sex ratio (male%), body weight (g) at birth and strain name, and environmental factors of facilities (room), temperature/humidity, and bedding materials were used as explanatory variables, and reproductive parameters of litter size at birth, secondary sex ratio (male%), body weight (g) at birth, and survival index (%) of offspring at PND 21 were used as response variables.
Results
No significant effects were indicated in litter size and sex ratio (male %) with any biological and environmental factors. Male and female offspring weights were significantly affected by strain names. No significant effects were indicated in the survival index (%) at PND 21 in both sexes with any biological and environmental factors.
Conclusions
Litter size and sex ratio in this report are sufficient as background data throughout the period because no significant variables of biological and environmental factors affected litter size and gender composition.
{"title":"Biological and environmental factors influencing reproductive performance in ICR mice, Mus musculus","authors":"Toyohito Tanaka","doi":"10.1002/bdr2.2337","DOIUrl":"https://doi.org/10.1002/bdr2.2337","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Since strain names and breeding facilities of ICR mice used in 37 reproductive toxicity studies have changed from 1990 to 2022 in our laboratory, biological and environmental factors that affect reproductive parameters were investigated in control mice to examine the validity of the background data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Litter size and sex ratio were measured at birth [postnatal day (PND) 0], while offspring body weight was measured on PND 0 and 21 during the lactation. The relationships between biological and environmental factors and reproductive parameters were assessed with multiple regression analysis using stepwise regression as an explanatory variable selection strategy. The biological factors of litter size at birth, secondary sex ratio (male%), body weight (g) at birth and strain name, and environmental factors of facilities (room), temperature/humidity, and bedding materials were used as explanatory variables, and reproductive parameters of litter size at birth, secondary sex ratio (male%), body weight (g) at birth, and survival index (%) of offspring at PND 21 were used as response variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant effects were indicated in litter size and sex ratio (male %) with any biological and environmental factors. Male and female offspring weights were significantly affected by strain names. No significant effects were indicated in the survival index (%) at PND 21 in both sexes with any biological and environmental factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Litter size and sex ratio in this report are sufficient as background data throughout the period because no significant variables of biological and environmental factors affected litter size and gender composition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nina L. Schrager, Samantha E. Parker, Martha M. Werler, for the National Birth Defects Prevention Study
Background
Nausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people, with varying severity and duration. Treatments include pharmacologic and herbal/natural medications. The associations between NVP and birth outcomes, including preterm birth, small for gestational age (SGA), and low birth weight are inconclusive.
Objective
To determine whether NVP and reported medications are associated with adverse birth outcomes.
Methods
We used data from the population-based, multisite National Birth Defects Prevention Study (1997–2011) to evaluate whether self-reported NVP according to timing, duration, and severity or its specific treatments were associated with preterm birth, SGA, and low birth weight among controls without birth defects. Odds ratios (aOR) and 95% confidence intervals (CI) were adjusted for sociodemographic, reproductive, and medical factors. For any NVP, duration, treatment use, and severity score analyses, the comparison group was participants with no reported NVP. For timing analyses, the comparison group was women with no reported NVP in the same trimester of pregnancy.
Results
Among 6018 participants, 4339 (72.1%) reported any NVP. Among those with NVP, moderate or severe symptoms were more common than mild symptoms. Any versus no NVP was not associated with any of the outcomes of interest. NVP in months 4–6 (aOR 1.21, 95% CI: 1.00, 1.47) and 7–9 (aOR 1.57, 95% CI: 1.22, 2.01) of pregnancy were associated with an increase in the risk of preterm birth. NVP lasting one trimester in duration was associated with decrease in risk of SGA (aOR: 0.74, 95% CI: 0.58, 0.95), and NVP present in every trimester of pregnancy had a 50% increase in risk of preterm birth (aOR: 1.50, 95% CI: 1.11, 2.05). For NVP in months 7–9 and preterm birth, ORs were elevated for moderate (aOR: 1.82, 95% CI: 1.26, 2.63), and severe (aOR: 1.53, 95% CI: 1.06, 2.19) symptoms. NVP was not significantly associated with low birth weight. Our analyses of medications were limited by small numbers, but none suggested increased risk of adverse outcomes associated with use of the medication.
Conclusion
Mild NVP and NVP limited to early pregnancy appear to have no effect or a small protective effect on birth outcomes. Long-lasting NVP, severe NVP, and NVP later in pregnancy may increase risk of preterm birth and SGA.
{"title":"The timing, duration, and severity of nausea and vomiting of pregnancy and adverse birth outcomes among controls without birth defects in the National Birth Defects Prevention Study","authors":"Nina L. Schrager, Samantha E. Parker, Martha M. Werler, for the National Birth Defects Prevention Study","doi":"10.1002/bdr2.2334","DOIUrl":"https://doi.org/10.1002/bdr2.2334","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people, with varying severity and duration. Treatments include pharmacologic and herbal/natural medications. The associations between NVP and birth outcomes, including preterm birth, small for gestational age (SGA), and low birth weight are inconclusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine whether NVP and reported medications are associated with adverse birth outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used data from the population-based, multisite National Birth Defects Prevention Study (1997–2011) to evaluate whether self-reported NVP according to timing, duration, and severity or its specific treatments were associated with preterm birth, SGA, and low birth weight among controls without birth defects. Odds ratios (aOR) and 95% confidence intervals (CI) were adjusted for sociodemographic, reproductive, and medical factors. For any NVP, duration, treatment use, and severity score analyses, the comparison group was participants with no reported NVP. For timing analyses, the comparison group was women with no reported NVP in the same trimester of pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 6018 participants, 4339 (72.1%) reported any NVP. Among those with NVP, moderate or severe symptoms were more common than mild symptoms. Any versus no NVP was not associated with any of the outcomes of interest. NVP in months 4–6 (aOR 1.21, 95% CI: 1.00, 1.47) and 7–9 (aOR 1.57, 95% CI: 1.22, 2.01) of pregnancy were associated with an increase in the risk of preterm birth. NVP lasting one trimester in duration was associated with decrease in risk of SGA (aOR: 0.74, 95% CI: 0.58, 0.95), and NVP present in every trimester of pregnancy had a 50% increase in risk of preterm birth (aOR: 1.50, 95% CI: 1.11, 2.05). For NVP in months 7–9 and preterm birth, ORs were elevated for moderate (aOR: 1.82, 95% CI: 1.26, 2.63), and severe (aOR: 1.53, 95% CI: 1.06, 2.19) symptoms. NVP was not significantly associated with low birth weight. Our analyses of medications were limited by small numbers, but none suggested increased risk of adverse outcomes associated with use of the medication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Mild NVP and NVP limited to early pregnancy appear to have no effect or a small protective effect on birth outcomes. Long-lasting NVP, severe NVP, and NVP later in pregnancy may increase risk of preterm birth and SGA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zahra Salari, Amirhossein Moslemizadeh, Sara Sheibani Tezerji, Nazanin Sabet, Ali Saeidpour Parizi, Mohammad Khaksari, Vahid Sheibani, Elham Jafari, Sara Shafieipour, Hamideh Bashiri
Introduction
In this study, we aimed to investigate the inflammatory factors, oxidative stress, and histopathological consequences of the brain-gut axis in male and female rats prenatally exposed to VPA.
Methods
Pregnant Wistar rats were randomly divided into two groups. The animals received saline, and valproic acid (VPA) (600 mg/kg, i.p.) on embryonic day 12.5 (E12.5). All offspring were weaned on postnatal day 21, and the experiments were done in male and female rats on day 60. The brain and intestine tissues were extracted to assess histopathology, inflammation, and oxidative stress.
Results
An increase of interleukin-1β (IL-1β) and interleukin-6 (IL-6) and a decrease of interleukin-10 (IL-10) were observed in the two sexes and two tissues of the autistic rats. In the VPA-exposed animals, malondialdehyde (MDA) and protein carbonyl (PC) increased in the brain of both sexes and the intestines of only the males. The total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased in both tissues of male and female autistic groups. Histopathological evaluation showed that the %apoptosis of the cortex in the autistic male and female groups was more than in controls whereas this parameter in the CA1 and CA3 was significant only in the male rats. In the intestine, histopathologic changes were seen only in the male autistic animals.
Conclusion
The inflammatory and antioxidant factors were in line in the brain-gut axis in male and female rats prenatally exposed to VPA. Histopathological consequences were more significant in the VPA-exposed male animals.
{"title":"Sex-dependent alterations of inflammatory factors, oxidative stress, and histopathology of the brain-gut axis in a VPA-induced autistic-like model of rats","authors":"Zahra Salari, Amirhossein Moslemizadeh, Sara Sheibani Tezerji, Nazanin Sabet, Ali Saeidpour Parizi, Mohammad Khaksari, Vahid Sheibani, Elham Jafari, Sara Shafieipour, Hamideh Bashiri","doi":"10.1002/bdr2.2310","DOIUrl":"10.1002/bdr2.2310","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>In this study, we aimed to investigate the inflammatory factors, oxidative stress, and histopathological consequences of the brain-gut axis in male and female rats prenatally exposed to VPA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pregnant Wistar rats were randomly divided into two groups. The animals received saline, and valproic acid (VPA) (600 mg/kg, i.p.) on embryonic day 12.5 (E12.5). All offspring were weaned on postnatal day 21, and the experiments were done in male and female rats on day 60. The brain and intestine tissues were extracted to assess histopathology, inflammation, and oxidative stress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An increase of interleukin-1β (IL-1β) and interleukin-6 (IL-6) and a decrease of interleukin-10 (IL-10) were observed in the two sexes and two tissues of the autistic rats. In the VPA-exposed animals, malondialdehyde (MDA) and protein carbonyl (PC) increased in the brain of both sexes and the intestines of only the males. The total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased in both tissues of male and female autistic groups. Histopathological evaluation showed that the %apoptosis of the cortex in the autistic male and female groups was more than in controls whereas this parameter in the CA1 and CA3 was significant only in the male rats. In the intestine, histopathologic changes were seen only in the male autistic animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The inflammatory and antioxidant factors were in line in the brain-gut axis in male and female rats prenatally exposed to VPA. Histopathological consequences were more significant in the VPA-exposed male animals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Ping Qi, Krista S. Crider, Anne M. Williams, Katie Tripp, Carine Mapango, Elizabeth C. Rhodes, Eunice Nyirenda, Felix Phiri, Mindy Zhang, Shameem Jabbar, Christine M. Pfeiffer, Helena Pachón, Sarah Zimmerman, Jennifer L. Williams
Background
Maternal folate and vitamin B12 deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B12 status among women of reproductive age (WRA) in Malawi.
Objective
We assessed folate and vitamin B12 status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant.
Methods
Using data from the cross-sectional, nationally representative 2015–2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15–49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design.
Results
Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B12 deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education.
Conclusions
These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B12 nutrition among Malawian WRA.
{"title":"Folate and vitamin B12 status and predicted neural tube defects risk among nonpregnant women of reproductive age from the Malawi National Micronutrient Survey, 2015–2016","authors":"Yan Ping Qi, Krista S. Crider, Anne M. Williams, Katie Tripp, Carine Mapango, Elizabeth C. Rhodes, Eunice Nyirenda, Felix Phiri, Mindy Zhang, Shameem Jabbar, Christine M. Pfeiffer, Helena Pachón, Sarah Zimmerman, Jennifer L. Williams","doi":"10.1002/bdr2.2329","DOIUrl":"10.1002/bdr2.2329","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Maternal folate and vitamin B<sub>12</sub> deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B<sub>12</sub> status among women of reproductive age (WRA) in Malawi.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We assessed folate and vitamin B<sub>12</sub> status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using data from the cross-sectional, nationally representative 2015–2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B<sub>12</sub> deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15–49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B<sub>12</sub> deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B<sub>12</sub> nutrition among Malawian WRA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 3","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gwen Tindula, Biju Issac, Sudipta Kumer Mukherjee, Sheikh Muhammad Ekramullah, D. M. Arman, Joynul Islam, Hafiza Sultana Suchanda, Liang Sun, Shira Rockowitz, David C. Christiani, Benjamin C. Warf, Maitreyi Mazumdar
Background
Human studies of genetic risk factors for neural tube defects, severe birth defects associated with long-term health consequences in surviving children, have predominantly been restricted to a subset of candidate genes in specific biological pathways including folate metabolism.
Methods
In this study, we investigated the association of genetic variants spanning the genome with risk of spina bifida (i.e., myelomeningocele and meningocele) in a subset of families enrolled from December 2016 through December 2022 in a case–control study in Bangladesh, a population often underrepresented in genetic studies. Saliva DNA samples were analyzed using the Illumina Global Screening Array. We performed genetic association analyses to compare allele frequencies between 112 case and 121 control children, 272 mothers, and 128 trios.
Results
In the transmission disequilibrium test analyses with trios only, we identified three novel exonic spina bifida risk loci, including rs140199800 (SULT1C2, p = 1.9 × 10−7), rs45580033 (ASB2, p = 4.2 × 10−10), and rs75426652 (LHPP, p = 7.2 × 10−14), after adjusting for multiple hypothesis testing. Association analyses comparing cases and controls, as well as models that included their mothers, did not identify genome-wide significant variants.
Conclusions
This study identified three novel single nucleotide polymorphisms involved in biological pathways not previously associated with neural tube defects. The study warrants replication in larger groups to validate findings and to inform targeted prevention strategies.
{"title":"Genome-wide analysis of spina bifida risk variants in a case–control study from Bangladesh","authors":"Gwen Tindula, Biju Issac, Sudipta Kumer Mukherjee, Sheikh Muhammad Ekramullah, D. M. Arman, Joynul Islam, Hafiza Sultana Suchanda, Liang Sun, Shira Rockowitz, David C. Christiani, Benjamin C. Warf, Maitreyi Mazumdar","doi":"10.1002/bdr2.2331","DOIUrl":"10.1002/bdr2.2331","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Human studies of genetic risk factors for neural tube defects, severe birth defects associated with long-term health consequences in surviving children, have predominantly been restricted to a subset of candidate genes in specific biological pathways including folate metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we investigated the association of genetic variants spanning the genome with risk of spina bifida (i.e., myelomeningocele and meningocele) in a subset of families enrolled from December 2016 through December 2022 in a case–control study in Bangladesh, a population often underrepresented in genetic studies. Saliva DNA samples were analyzed using the Illumina Global Screening Array. We performed genetic association analyses to compare allele frequencies between 112 case and 121 control children, 272 mothers, and 128 trios.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the transmission disequilibrium test analyses with trios only, we identified three novel exonic spina bifida risk loci, including rs140199800 (<i>SULT1C2</i>, <i>p</i> = 1.9 × 10<sup>−7</sup>), rs45580033 (<i>ASB2</i>, <i>p</i> = 4.2 × 10<sup>−10</sup>), and rs75426652 (<i>LHPP</i>, <i>p</i> = 7.2 × 10<sup>−14</sup>), after adjusting for multiple hypothesis testing. Association analyses comparing cases and controls, as well as models that included their mothers, did not identify genome-wide significant variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identified three novel single nucleotide polymorphisms involved in biological pathways not previously associated with neural tube defects. The study warrants replication in larger groups to validate findings and to inform targeted prevention strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 3","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comments on “Maternal–fetal safety evaluation of an aqueous extract of Casearia sylvestris [AECS] leaves in rats” (Nagaoka et al., 2023 [DOI: 10.1002/bdr2.2257])","authors":"L. David Wise, John M. DeSesso","doi":"10.1002/bdr2.2326","DOIUrl":"https://doi.org/10.1002/bdr2.2326","url":null,"abstract":"","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 3","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140192296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Réka Müller, Madison Lake, Nevena Krstić, Sarah G. Običan, Deborah Cragun
Background
Exposures during pregnancy are common and most pregnant patients utilize at least one medication during pregnancy. The lack of reliable information on medication safety during pregnancy available to providers and patients is a stressor and obstacle to decision-making about medication use in pregnancy. Previous studies showed that exposures in pregnancy are associated with guilt, worry, and decisional conflict. Although prior research has evaluated changes in patient knowledge after teratogen counseling, studies have not examined emotional outcomes or patients' decisional empowerment. This quasi-experimental study measured changes in patients' feelings of guilt, anxiety, and decisional empowerment after receiving exposure counseling from trained teratogen information specialists.
Methods
We administered pre- and post-counseling surveys to patients referred to a perinatal exposure clinic in Tampa, Florida. Validated scales were used to measure anxiety and guilt, and the ‘SURE’ measure was used to assess decisional empowerment. Paired samples t-tests evaluated changes in anxiety and guilt and a McNemar test assessed for changes in empowered decision making.
Results
Among the 34 participants who completed both surveys, anxiety, and guilt scores decreased significantly (p < .001). While only 21% felt informed and empowered to make a decision related to their exposure(s) before counseling, this increased to 85% (p < .001) on the post-survey.
Conclusion
Comprehensive counseling with a trained teratogen information specialist improves patient emotional outcomes as well as feelings of empowerment to make an informed decision regarding medication use in pregnancy. This study highlights that patient-centered teratogen counseling goes beyond simple changes in patient knowledge.
{"title":"Impact of perinatal exposure counseling on patient reported emotional outcomes and decisional empowerment","authors":"Réka Müller, Madison Lake, Nevena Krstić, Sarah G. Običan, Deborah Cragun","doi":"10.1002/bdr2.2325","DOIUrl":"https://doi.org/10.1002/bdr2.2325","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Exposures during pregnancy are common and most pregnant patients utilize at least one medication during pregnancy. The lack of reliable information on medication safety during pregnancy available to providers and patients is a stressor and obstacle to decision-making about medication use in pregnancy. Previous studies showed that exposures in pregnancy are associated with guilt, worry, and decisional conflict. Although prior research has evaluated changes in patient knowledge after teratogen counseling, studies have not examined emotional outcomes or patients' decisional empowerment. This quasi-experimental study measured changes in patients' feelings of guilt, anxiety, and decisional empowerment after receiving exposure counseling from trained teratogen information specialists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We administered pre- and post-counseling surveys to patients referred to a perinatal exposure clinic in Tampa, Florida. Validated scales were used to measure anxiety and guilt, and the ‘SURE’ measure was used to assess decisional empowerment. Paired samples <i>t</i>-tests evaluated changes in anxiety and guilt and a McNemar test assessed for changes in empowered decision making.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 34 participants who completed both surveys, anxiety, and guilt scores decreased significantly (<i>p</i> < .001). While only 21% felt informed and empowered to make a decision related to their exposure(s) before counseling, this increased to 85% (<i>p</i> < .001) on the post-survey.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Comprehensive counseling with a trained teratogen information specialist improves patient emotional outcomes as well as feelings of empowerment to make an informed decision regarding medication use in pregnancy. This study highlights that patient-centered teratogen counseling goes beyond simple changes in patient knowledge.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 3","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140192261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Filipa Rombo Matias, Ian Groves, Joshua Durrans, Mari Herigstad
Introduction
Carbon monoxide (CO) is a toxic gas that can be lethal in large doses and may also cause physiological damage in lower doses. Epidemiological studies suggest that CO in lower doses over time may impact on embryo development, in particular cardiac development, however other studies have not observed this association.
Methods
Here, we exposed chick embryos in ovo to CO at three different concentrations (3, 9, 18 ppm) plus air control (4 protocols in total) for the first 9 days of development, at which point we assessed egg and embryo weight, ankle length, developmental stage, heart weight, ventricular wall thickness, ventricular-septal thickness and atrial wall thickness.
Results
We found that heart weight was reduced for the low and moderate exposures compared to air, that atrial wall and ventricular wall thickness was increased for the moderate and high exposures compared to air and that ventricular septal thickness was increased for low, moderate and high exposures compared to air. Ventricular wall thickness was also significantly positively correlated with absolute CO exposures across all protocols.
Conclusions
This intervention study thus suggests that CO even at very low levels may have a significant impact on cardiac development.
{"title":"Carbon monoxide affects early cardiac development in an avian model","authors":"Filipa Rombo Matias, Ian Groves, Joshua Durrans, Mari Herigstad","doi":"10.1002/bdr2.2330","DOIUrl":"10.1002/bdr2.2330","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Carbon monoxide (CO) is a toxic gas that can be lethal in large doses and may also cause physiological damage in lower doses. Epidemiological studies suggest that CO in lower doses over time may impact on embryo development, in particular cardiac development, however other studies have not observed this association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we exposed chick embryos <i>in ovo</i> to CO at three different concentrations (3, 9, 18 ppm) plus air control (4 protocols in total) for the first 9 days of development, at which point we assessed egg and embryo weight, ankle length, developmental stage, heart weight, ventricular wall thickness, ventricular-septal thickness and atrial wall thickness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that heart weight was reduced for the low and moderate exposures compared to air, that atrial wall and ventricular wall thickness was increased for the moderate and high exposures compared to air and that ventricular septal thickness was increased for low, moderate and high exposures compared to air. Ventricular wall thickness was also significantly positively correlated with absolute CO exposures across all protocols.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This intervention study thus suggests that CO even at very low levels may have a significant impact on cardiac development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 3","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katharine H. McVeigh, Tenzin Tseyang, Mary-Elizabeth Vachon, Aurora Moraes
Background
In response to the 2015–2017 Zika virus outbreak, New York City (NYC) identified and monitored infants with birth defects potentially related to congenital Zika virus.
Methods
Administrative data matches were used to describe the birth characteristics of children born in 2016 meeting screening criteria for birth defects potentially related to congenital Zika virus infection relative to other NYC births and to monitor mortality and Early Intervention Program use through age 2.
Results
Among 120,367 children born in NYC in 2016, 463 met screening criteria and 155 met the Centers for Disease Control and Prevention's case definition for birth defects potentially related to congenital Zika virus infection (1.3 per 1000; 95% confidence interval [CI], 1.1–1.5). Post-neonatal deaths occurred among 7.7% of cases (12) and 5.2% of non-cases (8). Odds of referral to the Early intervention Program among children who met screening criteria were lower among children of mothers who were married (OR, 0.60; 95% CI, 0.37–0.97) and among children not classified as cases whose mothers were born in Latin America and the Caribbean (OR, 0.59; 95% CI, 0.37–1.09).
Discussion
Prevalence of birth defects potentially related to congenital Zika virus infection was similar to that seen in other jurisdictions without local transmission. Birth defects attributable to congenital Zika virus infection may also have been present among screened children who did not meet the case definition.
{"title":"Population-based surveillance for birth defects potentially related to Zika virus infection including 3-year mortality and developmental outcomes, and Early Intervention Program service use—New York City, 2016 birth cohort","authors":"Katharine H. McVeigh, Tenzin Tseyang, Mary-Elizabeth Vachon, Aurora Moraes","doi":"10.1002/bdr2.2320","DOIUrl":"10.1002/bdr2.2320","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In response to the 2015–2017 Zika virus outbreak, New York City (NYC) identified and monitored infants with birth defects potentially related to congenital Zika virus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Administrative data matches were used to describe the birth characteristics of children born in 2016 meeting screening criteria for birth defects potentially related to congenital Zika virus infection relative to other NYC births and to monitor mortality and Early Intervention Program use through age 2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 120,367 children born in NYC in 2016, 463 met screening criteria and 155 met the Centers for Disease Control and Prevention's case definition for birth defects potentially related to congenital Zika virus infection (1.3 per 1000; 95% confidence interval [CI], 1.1–1.5). Post-neonatal deaths occurred among 7.7% of cases (12) and 5.2% of non-cases (8). Odds of referral to the Early intervention Program among children who met screening criteria were lower among children of mothers who were married (OR, 0.60; 95% CI, 0.37–0.97) and among children not classified as cases whose mothers were born in Latin America and the Caribbean (OR, 0.59; 95% CI, 0.37–1.09).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Prevalence of birth defects potentially related to congenital Zika virus infection was similar to that seen in other jurisdictions without local transmission. Birth defects attributable to congenital Zika virus infection may also have been present among screened children who did not meet the case definition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 3","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号