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The use of opioids during pregnancy has been linked to a number of adverse outcomes, including serious birth defects, premature birth, miscarriage or stillbirth, and neonatal opioid withdrawal syndrome (NOWS), where a newborn infant experiences opioid withdrawal after exposure in the womb. What remains largely unknown is whether and how prenatal exposure to opioids impacts a child’s brain and development.

To help us move toward answering these questions, Center for Better Beginnings co-director Christina Chambers, PhD, MPH, was recently awarded a grant from the National Institute of Drug Abuse. Our team at UC San Diego, along with teams at 27 other sites across the US, will lead the development of a nationwide study called the HEALthy Brain and Child Development (HEALthy BCD) Study. Underneath this planning grant, Dr. Chambers and the multidisciplinary team that she has assembled at UC San Diego – including researchers in psychiatry, obstetrics/maternal fetal medicine, neonatology, clinical psychology, ethics, bioengineering, and epidemiology – will design recruitment strategies and data collection protocols for this massive longitudinal study. “The proposed main study will track roughly 10,000 children from fetal life through about 10 years of age to examine the short and long-term effects of prenatal substance exposure in the context of other social and environmental factors,” Chambers said, “During this initial planning phase, our team and others at 27 additional institutions across the nation will work to identify, test, and recommend strategies to engage and support participants in a respectful and ethical manner, and to outline a common protocol for the assessment of brain development,  neurobehavioral performance and other health outcomes that will be integral components of the study.” The work done during this planning phase will inform future research on the effects of opioids and other substances in young children and identify new opportunities for intervention to support child development.

The HEALthy BCD Study was made possible by the National Institutes of Health’s Helping to End Addiction Long-term (HEAL) Initiative; under this initiative, nearly $1 billion in funding has been pledged to help tackle the national opioid crisis.

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Up to 15% of pregnant women have an anxiety disorder, and 1-4% of them are treated with benzodiazepines (like Valium®, Xanax® or Klonopin®) or z-drugs (like Ambien®). In addition, it’s not uncommon for women with anxiety to also be treated for depression, or for benzodiazepines to be used in combination with a prescription opioid for pain management. But what effects might benzodiazepines and z-drugs, in isolation or in combination with an antidepressant or a prescription opioid, have on longer-term developmental outcomes in a pregnant woman’s baby? Our new study examined this very question.

How did we do it? We accessed a large dataset from the Norwegian Mother and Child Cohort Study, which followed over 41,000 pregnant women from 1999 to 2008 and had child follow-up data from 6 months to 8 years of age. In the study were 4,195 women who before and/or during pregnancy had a depression/anxiety disorder, 5,260 with a sleeping disorder, and 26,631 with a pain-related disorder. We looked at whether the timing of benzodiazepine/z-drug exposure (mid-pregnancy vs. late pregnancy) had any effects on the child’s longer-term development; whether longer vs. shorter duration of use (multiple 4-week vs. 1-week intervals) had any effect; and how the use of benzodiazepines/z-drugs in isolation or in combination with an antidepressant or a prescription opioid affected the child’s development. The child outcomes we looked at were the development of both motor and communication skills as well as attention problems when the children were around 5 years of age.

What did we find? Our findings suggested no increased risk for attention problems or fine motor deficits after benzodiazepine/z-drug exposure at different time points in pregnancy. We also did not find any evidence suggesting there was a developmental risk based on how long the mom used these drugs, nor any increased risk if benzodiazepines/z-drugs were used in combination with either antidepressants or a prescription opioid. There was an increased risk of gross motor and communication deficits among children whose mothers had depressive/anxiety disorders and used benzodiazepines/z-drugs late in pregnancy (week 29 or later), but the deficits were below clinically relevant cutoff points and could be accounted for by the mom’s underlying psychiatric conditions and/or the higher doses she was taking.

So what’s the take-away? Our findings suggest no substantial detrimental risk to child fine motor skills and attention problems after prenatal exposure to benzodiazepines/z-drugs alone or in combination with opioids or antidepressants. While an increased risk of gross motor and communication deficits was found, the deficits were not clinically significant and could be explained by other factors. As with any medication, pregnant women or women planning a pregnancy should talk with their healthcare provider before starting or stopping any medications.

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