No abstract

The prevalence of preterm birth (PTB) is high worldwide, especially in developing countries like Brazil. PTB is marked by a stressful environment in intra- as well as extrauterine life, which can affect neurodevelopment and hormonal and physiological systems and lead to long-term negative outcomes. Nevertheless, little is known about PTB and related outcomes later on in childhood. Thus, the goals of the current study were threefold: (1) comparing cortisol and alpha-amylase (sAA) profiles, including cortisol awakening response (CAR), between preterm and full-term children; (2) evaluating whether preterm children are more responsive to acute stress and (3) assessing their memory skills and emotional and behavioral profiles. Basal cortisol and sAA profiles, including CAR of 30 preterm children, aged 6 to 10 years, were evaluated. Further, we assessed memory functions using the Wide Range Assessment of Memory and Learning, and we screened behavior/emotion using the Strengths and Difficulties Questionnaire. The results of preterm children were compared to an age- and sex-matched control group. One week later, participants were exposed to a standardized laboratory stressor [Trier Social Stress Test for Children (TSST-C)], in which cortisol and sAA were measured at baseline, 1, 10 and 25 min after stressor exposure. Preterm children had higher cortisol concentrations at awakening, a flattened CAR and an exaggerated response to TSST-C compared to full-term children. These alterations were more pronounced in girls. In addition, preterm children were characterized by more emotional problems and poorer memory performance. Our findings illustrate the long-lasting and in part sex-dependent effects of PTB on the hypothalamic-pituitary-adrenal (HPA) axis, internalizing behavior and memory. The findings are in line with the idea that early adversity alters the set-point of the HPA axis, thereby creating a more vulnerable phenotype.

Background Accumulation of phenylalanine (Phe) due to deficiency in the enzyme phenylalanine hydroxylase (PAH), responsible for the conversion of Phe into tyrosine leads to Phenylketonuria (PKU), a rare autosomal recessive inborn error of metabolism with a mean prevalence of approximately 1:10,000 to 1:15,000 newborns. Physical, neurocognitive and psychiatric symptoms include neurodevelopmental disorder as intellectual disability and autism spectrum disorder. The most common treatments such as low-Phe diet and supplements may decrease blood Phe concentrations, but neuropsychological, behavioral and social issues still occur in some patients. This study aimed to better understand (i) the Brazilian population's knowledge about newborn screening (NBS), the main diagnostic method for PKU, as well as (ii) the impacts of phenylketonuria in the daily lives of patients and parents. Methods Two surveys in Real World Data format gathering of Brazilian residents by online questionnaires with (i) 1000 parents of children up to 5 years old between March and April 2019; (ii) 228 PKU patients and caregivers in March 2019. The survey was conducted in partnership with Abril Publisher and two Brazilian patient associations: Metabolic Mothers and SAFE Brasil, for families with rare diseases and PKU patients, respectively. Results The first questionnaire shows that 93% of parents recognize the importance of NBS and 92% report that their children have undergone the test. Still, two out of ten participants did not know what the exam is or what it is for. From the second questionnaire nine out of ten patients had their PKU diagnosis by NBS. Although strict dietary controls for PKU were claimed by 44% of respondents from second questionnaire, 55% assume not following all nutritionist recommendations and 52% did not maintain routinely Phe control levels. In addition, 53% said they had high spending on medical appointments, therapies and purchase of special foods. Conclusions Despite the lack of understanding, the awareness of NBS importance is present in the studied population. The early diagnosis of most PKU patients in the study corroborates with neonatal screening central role of PKU early detection. The difficulty in adhering to dietary adjustments and the possibility that current and new therapeutic strategies other than diet could be determinant to achieve the recommended Phe levels.