Abstract:
OBJECTIVES:Strategies for conducting juvenile dose ranging studies before definitive toxicity juvenile animal studies (JAS) have evolved, but the aim of demonstrating study design robustness and efficient animal use remains the same. The objective of dose selection is to identify a strategy to achieve consistent systemic exposure for the duration of the JAS while maintaining exposure separation between dose groups. For preweaning rodents this can prove challenging, as these studies typically treat animals over a broad period of considerable organ development. MATERIALS AND METHODS:In our experience, over 45 rodent juvenile studies (dose range, definitive or investigative) were conducted over 20 years to support pediatric medicine development. In most cases (86%, 12/14), preweaning rodents required decreased doses of test articles than adult rodents; the majority (83%, 10/12) were due to increased systemic exposures in immature animals at the same doses. Thus, extrapolating tolerability and exposure data from adults is not ideal and should not take the place of well-designed juvenile dose range studies. RESULTS/DISCUSSION/CONCLUSION:We propose a phased dose-range-finding approach by first conducting a tolerability phase with a few animals at a starting age corresponding to the youngest clinical starting age, spanning a wide range of doses, then a dose range phase with larger group sizes and fewer doses; both phases incorporate toxicokinetics. Often, exposure was higher in preweaning animals and decreased as animals matured postweaning (postnatal day, PND 21 and older), supporting an age-based dose adjustment strategy. Case studies demonstrate dose adjustment approaches incorporating dose increases or decreases or changes in dose frequency.
journal_name
Birth Defects Resjournal_title
Birth defects researchauthors
Posobiec LM,Laffan SBdoi
10.1002/bdr2.1856subject
Has Abstractpub_date
2020-12-14 00:00:00issn
2472-1727pub_type
杂志文章abstract:BACKGROUND:Congenital malformations are a leading cause of infant mortality in the United States, and risk for some congenital malformations varies by socioeconomic status (SES). Medicaid provides health insurance for people with low income, and covers approximately half of all live births in the United States. Income ...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1107
更新日期:2017-11-01 00:00:00
abstract::Evidences indicate that the decline of female fertility is becoming a common problem over the past few decades. Environmental exposure of Bisphenol A (BPA) has been considered as an endocrine-disrupting chemical deleteriously affecting human reproductions. To better understand the effect of BPA exposure on human ovari...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1817
更新日期:2020-12-01 00:00:00
abstract::Electronic nicotine delivery systems (ENDS), which includes e-cigarettes (ECIGs), are a rapidly-expanding class of products that heat a liquid (which may or may not contain nicotine) to produce an aerosol. The variation of ECIG components is extensive as are their effects on users. Epidemiological data show that while...
journal_title:Birth defects research
pub_type: 杂志文章,评审
doi:10.1002/bdr2.1561
更新日期:2019-10-15 00:00:00
abstract:OBJECTIVES:To explore the technical aspects and clinical utility of early fetal echocardiography and screening of the fetal heart in early pregnancy. Also, to document differences in cardiac structure and function which can be demonstrated in the late first/early second trimesters. METHODS:In addition to summarizing o...
journal_title:Birth defects research
pub_type: 杂志文章,评审
doi:10.1002/bdr2.1414
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Breastfeeding women who are prescribed with psychotropic medications on a regular basis are often concerned, regarding the possible implications of such treatment on the breastfed infant. A mother's well-being has a direct influence on the well-being of the baby. However, the notorious reputation of psychotr...
journal_title:Birth defects research
pub_type: 杂志文章,评审
doi:10.1002/bdr2.1077
更新日期:2017-07-17 00:00:00
abstract::Zika virus was first identified in Uganda in 1947 but received little attention until 2015 when a large outbreak of Zika virus illness followed by an increased number of babies born with microcephaly occurred in Brazil. Zika virus spread rapidly throughout the Americas, and in 2016 was identified as a cause of microce...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1781
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Most states have now passed legislation mandating pulse oximetry for all newborns, or have promulgated regulations or guidelines to encourage use of routine pulse oximetry. State-based birth defects registries may be well positioned to track and evaluate critical congenital heart disease (CCHD) screening cov...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1108
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:There is considerable variability in the prevalence of birth defects among racial/ethnic groups. This study estimated birth defect prevalence among the less studied non-Hispanic (NH) Asian/Pacific Islander (PI) and American Indian/Alaska Native (AI/AN) populations in Texas relative to NH Whites. METHODS:Dat...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1543
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:Infants of diabetic mothers have been shown in several studies to have an increased frequency of malformations. In previous studies, an increased frequency of several specific malformations has been noted, including anencephaly, bilateral renal agenesis, and double outlet right ventricle. Surveillance, used ...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1155
更新日期:2018-01-01 00:00:00
abstract::As a result of human socio-economic activity, industrial wastes have increased alarmingly. Plastic pollution is globally distributed across the world due to its properties of buoyancy and durability. Two broad classes of plastic-related chemicals are of critical concern for human health-bisphenol-A or BPA, and additiv...
journal_title:Birth defects research
pub_type: 杂志文章,评审
doi:10.1002/bdr2.1776
更新日期:2020-10-01 00:00:00
abstract::Antibody-like biopharmaceuticals cross the placenta by utilizing existing transport pathways (e.g., FcRn receptor). There are limited data evaluating this transfer during organogenesis in any species. Understanding placental transfer of antibody-like biopharmaceuticals can help to predict risk of developmental toxicit...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1615
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Neural tube defects (NTDs) are severe congenital malformations. Folate supplementation can reduce the risk, but cannot prevent all NTDs, suggesting other reasons for folate-resistant NTDs. The present study assesses placental fatty acid composition, eicosanoids, and cytokines as risk factors for NTDs in a Ch...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1003
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdevelopment of the right heart structures commonly accompanied by an atrial septal defect. Familial HRHS reports suggest genetic factor involvement. We examined the role of copy number variants (CNVs) in HRHS. METHODS:...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdra.23586
更新日期:2017-01-20 00:00:00
abstract::The aerodigestive and communicative behaviors of anencephalic and hydranencephalic patients are assessed from literature sources and are compared with documented neural structures present in the brainstem, subcortical, and cortical regions of the brain. Much of the data analyzed corroborate previous neurological studi...
journal_title:Birth defects research
pub_type: 杂志文章,评审
doi:10.1002/bdr2.1424
更新日期:2019-01-15 00:00:00
abstract:BACKGROUND:During the Zika virus (ZIKV) outbreak, an urgent need existed for strong partnerships to disseminate Zika-related information to pregnant women and women of child-bearing age. METHODS:The Centers for Disease Control and Prevention (CDC) partnered with MotherToBaby, a national organization experienced in pro...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1787
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:The acronym VATER/VACTERL refers to the rare nonrandom association of the following component features (CF): vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia, renal malformations (R), and limb defects (L). Patients presentin...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1042
更新日期:2017-07-17 00:00:00
abstract::In human studies, it is well established that exposures during embryonic and fetal development periods can influence immune health. Coupled with genetic predisposition, these exposures can alter lifetime chronic and infectious disease trajectory, and, ultimately, life expectancy. Fortunately, as research advances, mec...
journal_title:Birth defects research
pub_type: 杂志文章,评审
doi:10.1002/bdr2.1469
更新日期:2019-03-01 00:00:00
abstract::Maternal-neonate separation for human newborns has been the standard of care since the last century; low birth weight and preterm infants are still routinely separated from their mothers. With advanced technology, survival is good, but long-term developmental outcomes are very poor for these especially vulnerable newb...
journal_title:Birth defects research
pub_type: 杂志文章,评审
doi:10.1002/bdr2.1530
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND:To objectively describe craniofacial, visual, and neurological features associated with amniotic band syndrome (ABS) and discuss likely associated multifactorial etiology. METHODS:A retrospective review of patients identified with ABS and concomitant limb involvement and craniofacial features was conducted....
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1576
更新日期:2019-11-15 00:00:00
abstract:BACKGROUND:Hypospadias is a common birth defect that might be caused by inadequate fusion of the urethral folds in the process of male external genital development. We intended to discover the crucial long noncoding RNAs (lncRNAs) regulating autophagy from the gene expression profile of the genital tubercle (GT) of dib...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1863
更新日期:2021-01-15 00:00:00
abstract:BACKGROUND:The different mechanisms leading to a solitary kidney should be differentiated because the long-term outcome might be different. The fetal period is the best moment to make a true diagnosis of congenital unilateral renal agenesis (URA). The objective was to determine the prevalence of URA at birth. The secon...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1065
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND:Obstetricians usually prescribe supplements during pregnancy without actual indication. The use of selenium during pregnancy has increased, due to its function in several antioxidant mechanisms. CASE:A pregnant woman received 200,000 micrograms (μg) per day of a selenium galenic formulation, since gestation...
journal_title:Birth defects research
pub_type: 杂志文章,评审
doi:10.1002/bdr2.1148
更新日期:2018-03-01 00:00:00
abstract:BACKGROUND:A cardinal feature of prenatal ethanol exposure is CNS damage, resulting in a continuum of neurological and behavioral impairments that are described by the term fetal alcohol spectrum disorders (FASD). FASDs are variable and depend on several factors, including the amount, timing, and duration of prenatal e...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1477
更新日期:2019-07-15 00:00:00
abstract:BACKGROUND:Quaternary ammonium compounds are a large class of chemicals used for their antimicrobial and antistatic properties. Two common quaternary ammonium compounds, alkyldimethylbenzyl ammonium chloride (ADBAC) and didecyldimethyl ammonium chloride (DDAC), are combined in common cleaners and disinfectants. Introdu...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1064
更新日期:2017-08-15 00:00:00
abstract:BACKGROUND:My career goal in 1971 was to learn about the causes of malformations. Attending the annual meetings of the Teratology Society and reading the articles in Teratology exposed me to the scientists and clinicians involved in this research and the methods being used. METHODS:Over a period of 49 years (1972-2020...
journal_title:Birth defects research
pub_type: 杂志文章,评审
doi:10.1002/bdr2.1667
更新日期:2020-07-15 00:00:00
abstract::The AV7909 vaccine, consists of the Anthrax Vaccine Adsorbed (AVA) bulk drug substance and the immunostimulatory Toll-like receptor 9 agonist oligodeoxynucleotide adjuvant CPG 7909. The purpose of this research was to evaluate the potential maternal, reproductive, and developmental toxicity of AV7909 in rats to suppor...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1815
更新日期:2021-01-01 00:00:00
abstract:BACKGROUND:The tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is recommended during pregnancy to protect newborns against pertussis infection in the months prior to their primary pertussis vaccination. Although research on the safety of the vaccine has been reassuring, most previous s...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1642
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:Zika virus has recently emerged as a novel cause of microcephaly. CDC has asked states to rapidly ascertain and report cases of Zika-linked birth defects, including microcephaly. Massachusetts added head circumference to its birth certificate (BC) in 2011. The accuracy of head circumference measurements from...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1174
更新日期:2018-03-15 00:00:00
abstract:BACKGROUND:Maternal smoking or passive smoking during gestation increases the risk of congenital birth defects, including neural tube defects (NTDs). Cigarette smoke is a recognized teratogen that causes NTDs, although the mechanisms are not well understood. METHODS:An established model of passive smoking in pregnant ...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1804
更新日期:2021-01-01 00:00:00
abstract:BACKGROUND:This is the first study to utilize the index of concentration at the extremes (ICE) to examine risk factors for spina bifida in Texas. The ICE is a useful measure for providing the degree to which residents in a certain area are concentrated into groups at the extremes of disadvantage and privilege. We intro...
journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1374
更新日期:2019-08-15 00:00:00