Search

In this study we sought to ascertain a critical threshold of the degree of prematurity and long-term digestive morbidity of the offspring. A population-based cohort analysis was conducted, comparing long-term incidence of digestive morbidity in infants born preterm. Cases were divided into four groups according to the extremity of prematurity. Digestive morbidity included hospitalizations involving a predefined set of ICD9 codes. A Kaplan–Meier survival curve was constructed to compare cumulative incidence of digestive morbidity. A Cox proportional hazards model was used to control for confounders. During the study period 220,563 patients met the inclusion criteria. Offspring born preterm had significantly more hospitalizations due to digestive morbidity compared to term offspring. The Kaplan–Meier survival curve demonstrated significant higher cumulative incidence of long-term digestive morbidity of the offspring with decreasing gestational age (Log rank p

Leflunomide, an inhibitor of pyrimidine synthesis, is used for the treatment of rheumatic diseases, which are prevalent in women of childbearing age. Due to the very long half-life of the active metabolite, its mechanism of action and the teratogenicity observed in animal studies at doses similar to or lower than human therapeutic doses on a weight basis, it is recommended that women stop the treatment before conception and a drug elimination procedure be performed. However, unintended gestational exposures may occur, posing challenges in risk assessment. In order to address the safety of leflunomide in unintended exposures in pregnancy, we performed a critical review of human studies. We located 13 publications in Medline and Embase, which reported on 222 pregnancies with known outcomes exposed to leflunomide preconception and/or during pregnancy. Among the 169 live births, there were eight congenital malformations with no consistent pattern of anomalies. These studies collectively showed no significant difference in the rates of malformations between exposed and unexposed pregnancies. At present, accumulating human data do not point toward leflunomide as a potent human teratogen, which may inform risk assessment of unintended gestational exposure to leflunomide.

Substance use during pregnancy is associated with obstetrical and fetal complications. Though use of some substances is discontinued during pregnancy, use of others persists. Our goal was to characterize substance-specific use and patterns of use throughout pregnancy among vulnerable women who attended an early intervention program for women with substance use issues. Through retrospective analyses of client records (1995–2016; N = 470), results indicated that the greatest number of women continued use of tobacco and cannabis for the duration of pregnancy (n = 232; 84.4% and n = 102; 60.0%, respectively), while the proportion of women continuing opioid use was relatively high (n = 33; 57.9%). Relapse rates were high for women who initially attempted to discontinue use of cocaine, crack cocaine, and heroin. Results can inform intervention and treatment by indicating which substances are more difficult to discontinue, as well as substances associated with high rates of relapse.

Lamotrigine is used in pregnancy to control epilepsy and mood disorders. The reproductive safety of this widely used drug remains undefined and may represent a significant public health concern.We aimed to perform a systematic review and meta-analysis of existing knowledge related to malformation rates and maternal-neonatal outcomes after in utero exposure to monotherapy with lamotrigine.Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters) from database inception to July 2016; no language or date restrictions were applied. All publications of clinically relevant outcomes of pregnancies following in utero exposure to lamotrigine were included in this systematic review and meta-analysis.A total of 21 studies describing immediate pregnancy outcomes and rates of congenital malformations fulfilled the inclusion criteria. Compared with disease-matched controls (n = 1412, total number of patients) and healthy controls (n = 774,571, total number of patients), in utero exposure to lamotrigine monotherapy was found to be associated with significantly decreased rates of inborn defects (odds ratio [OR] 1.15; 95% confidence interval [CI] 0.62-2.16 and OR 1.25; 95% CI 0.89-1.74, respectively). Rates of miscarriages, stillbirths, preterm deliveries, and small for gestational age (SGA) neonates were not found to have been increased after in-utero exposure to LTG compared to the general population. Similarly, in utero exposure to lamotrigine monotherapy was not found to be associated with increased rates of inborn defects compared with in utero exposure to carbamazepine, and lamotrigine was found to be statistically significantly less teratogenic than valproic acid (n = 12,958 and 10,748; OR 0.84; 95% CI 0.68-1.03 and OR 0.32; 95% CI 0.26-0.39, respectively).No association was found between prenatal lamotrigine monotherapy and increased rates of birth defects and other explored variables related to adverse pregnancy outcomes.

Pediatric drug research is gradually becoming more and more accepted as the norm for assessing whether a drug is safe and efficacious for infants and children. The process of informed consent and assent for these trials presents a major challenge. The aim of this review is to map historical, ethical and legal aspects relevant to the challenges of informed consent in the setting of pediatric drug research. The impact of age, level of maturity and life circumstances on the process of obtaining informed consent as well as the relations between consent and assent are discussed. There appears to be a lack of regulatory clarity in the area of pediatric clinical trials; while numerous statements have been made regarding children's rights to autonomy and their ability to care for themselves and for younger ones, the ever changing status of adolescence is still difficult to translate to informed consent. This may delay scientific and clinical advancement for children who are at the very junction of being independent and not needing parental permission. Obtaining consent and assent for pediatric clinical trials is a delicate matter, as both parent and child need to agree to participate. The appropriate transfer of information to guardians and the children, especially concerning potential risks and benefits, is at the heart of informed consent, as it serves to protect both patient and physician. As many adults lack health literacy, one must ensure that guardians receive relevant information at a level and in forms they can understand regarding the trials their children are asked to participate in.