lecture 9 (preg and substance abuse)

MEDICAL TREATMENT OF NAS: Clonidine

an α2-adrenergic receptor agonist to reduce symptoms of autonomic over activity such as rapid heart rate, hypertension, sweating, restlessness and diarrhea

NEONATAL ABSTINENCE SYNDROME

- 45 to 94% of infants exposed to opioids in utero, including methadone and buprenorphine, can be affected by NAS - NAS occurs when an infant becomes dependent on opioids or other drugs used by the mother during pregnancy -The infant experiences withdrawal symptoms that can include (but are not limited to) tremors, diarrhea, fever, irritability, seizures, and difficulty feeding -NAS is a serious medical condition because it affects the vital functions that permit growth and normalcy—feeding, elimination and sleep. -Moreover, the symptoms can mimic other neonatal conditions such as infection, hypoglycemia, hypocalcaemia and intracranial hemorrhage -MOA: Multi-system (GI, peripheral, respiratory etc)

DANGERS OF DRUG USE TO FETUS

- Brain damage - Teratogenesis (e.g. fetal alcohol syndrome) - Behavioral disorders - Growth restriction: Chronic placental insufficiency - Placental abruption - Infection (e.g. HIV).

Cigarette smoking is the most common form of substance abuse in pregnancy!! It is linked to

- Decreased fertility - Spontaneous abortion - Placenta Previa - Placental abruption - Ectopic pregnancy - Preterm premature rupture of membranes (PPROM) - Preeclampsia

TOBACCO USE IN PREGNANCY: NEONATAL EFFECTS

- Impaired respiratory function in premature infants - Low neurobehavioral scores and higher withdrawal-symptom scores - Asthma, respiratory illness and pneumonia - Infections of the middle ear - Increased risk of cancer and SIDS (Sudden infant death syndrome)

OPIOID DEPENDENCE

- Infants born to chronic opioid users are frequently born with a dependency and experience withdrawal after the opioids cease to be administered following birth.NAS: negative impact on vital bodily functions such as feeding, elimination and sleeping. -Recent Canadian estimates 0.3% of infants are born with NAS. - NAS caused by exposure to opioids can be treated using a number of different medications, morphine or methadone. - Pregnant women with opioid dependence who are undergoing methadone maintenance treatment are more likely to give birth to infants with *higher birth weights* and are *less likely to experience premature birth* than opioid dependent women who are not under methadone maintenance. - Greater risk of low birth weight, respiratory problems, third trimester bleeding, toxemia and mortality. - Maternal opiate use is associated with an increased risk of NAS, whereby opiate exposure in utero triggers a postnatal withdrawal syndrome. - Anywhere from 45 to 94% of infants exposed to opioids in utero, including methadone and buprenorphine, can be affected by NAS. - Cigarette smoking, which is very common in pregnant women with an opioid use disorder (77-95%) may confound the effect of opioid use on poor pregnancy outcomes.

cannabis TREATMENT

- Treatments specifically aimed at prenatal cannabis use are lacking - The current recommendation for lowering the use of cannabis in pregnancy includes the screening of pregnant women to increase the early identification of cannabis use

PSYCHOSOCIAL ISSUES IN PREGNANT WOMEN USING DRUGS

- Two-thirds of women with substance abuse often manifesting psychiatric conditions such as - Anxiety, Depression, Posttraumatic stress disorder (PTSD) and Panic disorder - Pregnant women are susceptible to tremendous emotional changes - pregnancy is a time of heightened vulnerability to the exacerbation of pre- existing psychiatric condition

FETAL ALCOHOL SPECTRUM DISORDER (FASD)

- Women aged 25-34 experienced the fastest increase in risky drinking 62% of births in Canada - When combined with women aged 18-24, this accounts for approximately 80% of births in Canada - FASD learning, memory, math, communication and socializing. - They might also have characteristic facial features, slowed growth, and vision and hearing problems. - FASD could affect as many as 9 in 1,000 babies - about 1% of the Canadian population —Public Health Agency of Canada. -Yet, FASD is preventable.

ALCOHOL USE IN PREGNANCY

-*There is no safe amount of alcohol consumption during pregnancy* -Altered Developmental Regulation of Gene Expression -Effects on Cell Adhesion -Effects on Development of Neurotransmitter Systems (glutamate and serotonin) -Glucose Transport and Uptake -Excitotoxicity (excess glutamate) -Cell Death Modes: Necrosis and Apoptosis -Free Radicals, Oxidative Stress, and Mitochondrial Dysfunction -Growth Factors Regulating Cell Proliferation and Survival -Effects on Glia Cells

intro

-5.9% of pregnant women use illicit drugs -8.5% drink alcohol and 15.9% smoke cigarettes -resulting in over 380,000 offspring exposed to illicit substances, over 550,000 exposed to alcohol and over one million exposed to tobacco in uterus -Recently, there has been an increase in opiate use in pregnancy -Between 2000 and 2009, a five-fold increase in opiate use in pregnancy, coincident with an "epidemic" of opiate prescription misuse. -*According to the World Health Organization, cannabis is the most common illicit drug worldwide, followed by amphetamine-type stimulants and opiates*

IMPORTANT TO ADDRESS MARIJUANA USE DURING PREGNANCY

-A growing body of evidence suggests that cannabis use during pregnancy can impact pre- and post-natal development -Heavy cannabis use during pregnancy is associated with having a lower birth weight baby -Such use is also associated with longer-term developmental effects in children and adolescents, including deficits in memory and attention, increased hyperactivity and impulsivity, and increased risk of engaging in substance use -The substances in cannabis can be passed in the breast milk to the baby

ALCOHOL USE IN PREGNANCY: FETAL EFFECTS

-Abnormalities in brain and neuron development -Growth deficiency -Structural changes - Prematurity - LBW -Decreased length and head circumference -fetal alcohol syndrome is one of the most serious consequences of drinking during pregnancy. Binge drinking as few as three drinks a day can cause this syndrome. It occurs in about 2 of 1,000 live births.

Cannabis and Pregnancy

-Cannabis use more than doubled among pregnant women 2010-1017 -More common during the first trimester than during the second and third -Display altered responses to visual stimuli, increased trembling, and a high-pitched cry -> indicate problems with neurological development -Prenatal marijuana exposure is also associated with an increased likelihood of a person using marijuana as a young adult -THC consumed in breast milk could affect brain development - Some pregnant women view cannabis use as harmless in pregnancy- *NOT TRUE* - Preterm labor, Low birth weight, Small-for-gestational age, and admission to the neonatal intensive care unit. - Adverse consequences for the growth of fetal and adolescent brains - The adverse effects of marijuana are greatest in *heavy users*.

ALCOHOL USE IN PREGNANCY: MATERNAL EFFECTS

-Cardiovascular and liver disease -Breast and gynecological cancer - Osteoporosis -Menstrual symptoms -Neurological and mental health problems -Compromised ability to conceive -Spontaneous abortion

ALCOHOL USE IN PREGNANCY: LONG TERM EFFECTS

-Cognitive and behavioral challenges, -Adverse speech and language outcomes, -Executive functioning deficits in children, and -Psychosocial consequences in adulthood

MANAGEMENT

-Counseling -Social services -Test for STD -Frequent prenatal visit -Education -Early USG (ultrasonography) -Antepartum fetal surveillance

MARIJUANA: FETAL AND NEONATAL EFFECTS

-Does not appear to cause anomalies or serious effects on the fetus -Does not appear to decrease intelligence -Newborns may show increased startle response, tremors, hand- to-mouth behavior and disturbed sleep patterns. -*Q: is THC level is same in mother and fetus? Mother has most THC level than fetus*

HEROIN: NEONATAL EFFECTS

-Drug withdrawal -Suck-swallow difficulties -Central nervous system (CNS) irritability -Gastrointestinal upset -Yawning - Sneezing -Frantic sucking with uncoordinated feeding -High-pitched cry -Increased or decreased muscle tone -*Opioid use in pregnancy also associated with postnatal growth deficiency, microcephaly, neurobehavioral problems, and SIDS*

Women more prone to substance abuse

-Earn below poverty level -Were exposed to violence as a child -Have a history of domestic abuse -Suffer depression or other mental health problems -Have less than a high school education -Are unmarried -Are unemployed -Are involved with the criminal justice system

Fetal alcohol syndrome (FAS)

-Facial anomalies or abnormalities; -Growth deficiency; and -Central nervous system (CNS) damage or dysfunction. -Mental retardation -Developmental, learning and behavior problems

COCAINE: FETAL EFFECTS

-Fetal effects of cocaine are caused by the drug's direct effects (vasoconstriction and neuroexcitation) and by lifestyle issues that maternal drug use brings, including poor nutrition and avoidance of prenatal care -*Q: is Cocaine affect women and men differently? Yes, more affected in women than men*

HEROIN: MATERNAL EFFECTS/ FETAL EFFECTS

-Heroin can cause severe physiological withdrawal symptoms, including fatal seizures when withheld for 12 to 48 hours. -Opiates, such as heroin, methadone and buprenorphine, have not been linked to fetal anomalies. -Fetal withdrawal responses include arrhythmias, seizure activity and fetal demise.

COCAINE: MATERNAL EFFECTS

-Hypertension -Tachycardia -Cardiac events and maternal death -Spontaneous abortion -Placental abruption -Premature rupture of membranes (PROM) -*Q: What is the relation between Cocaine, estrogen, progesterone and menstrual cycle Follicular and Luteal Phase*: • *During follicular, estrogen is higher and progesterone is lower so cocaine is high* • *During luteal phase, estrogen is low and progesterone is high then cocaine effect is suppressed*

HEROIN AND PREGNANCY

-If you use heroin during pregnancy, it can cause serious problems for your baby, like premature birth, NAS, birth defects and stillbirth. -If you're pregnant and using heroin, don't stop taking it without getting treatment from your health care provider first. -Quitting heroin suddenly (going cold turkey) can cause severe problems for your baby, including *death*. -Treatment with drugs like methadone or buprenorphine can help you reduce your dependence on heroin in a way that's safe for your baby.

TOBACCO USE IN PREGNANCY: FETAL EFFECTS

-Impaired *transfer of oxygen* and nutrition -Long-term cognitive function and increased risk of brain damage -Chronic low-level hypoxia -Intrauterine growth restriction (IUGR) -Preterm delivery -Low birth-weight (LBW) in term infants

Substance use during pregnancy

-In 2012, 5.9% of pregnant women use illicit drugs, 8.5% drink alcohol and 15.9% smoke cigarettes -In 2020 10% alcohol alone, 40% all other drugs -Resulting 380,000 offspring exposed to illicit substances, 550,000 exposed to alcohol andover one million exposed to tobacco in utero Abstinence during preg: -96% of women with drinking,78% of women with marijuana use, 73% of women with cocaine use, and 32% of cigarette smokers Relapse 3 mos: -58% of abstinent smokers,51% of abstinent women who used alcohol,41% of abstinent women who used marijuana and 27% of abstinent women who used cocaine in the -6 million pregnancies and 9 of 10 pregnant women take medication -Prenatal substance----- public health concern ----several harmful maternal and fetal consequences. -*Tobacco, followed by alcohol, cannabis* and other illicit substances -Polysubstance use in pregnancy, psychiatric comorbidity, environmental stressors, and limited and disrupted parental care, compound deleterious maternal and fetal outcomes.

Heavy alcohol use and pregnancy

-Increased risks of miscarriage, -Stillbirth and infant mortality, -Congenital anomalies, -Low birth weight, reduced gestational age, -preterm delivery, and small-for-gestational age.

Cocaine and Amphetamines on Placental Serotonin and Norepinephrine Transporters

-Intervillus space has many platelets -> when platelets activated release serotonin and norepinephrine -> move to trophoblast via transporters -> transporters metabolized by MAO -When pt on cocaine or amphetamines, the transporter system is interrupted -Cocaine pass through 5-HT transporter but serotonin can not pass through. NE transporter not affected -Amphetamines can pass through NE transporter but less for 5-HT transporters

COCAINE: NEONATAL EFFECTS

-Jitteriness -Hyperactivity -Inconsolability -Poor feeding and state regulation -No physiological withdrawal: Neonates are not dependent on cocaine and do not need medication to lessen withdrawal.

WHY MARIJUANA IS A CONCERN?

-Marijuana is the most commonly used illicit drug in Canada, > 10.6% -Canadian youth had the highest rate of past-year marijuana use (28%), compared to students in other developed countries. -Chronic marijuana use — can negatively affect mental and physical health, brain function (memory, attention and thinking) and driving performance. -Marijuana : Negatively affect the children development and behavior, if drug used during pregnancy.

CANNABIS AND TOBACCO

-Maternal tobacco smoking of long duration is linked to increased rates of *abruption* placentae -Placenta previa (where the placenta is inserted partially or wholly in the lower part of the uterus) -Placental infarcts (interrupted blood supply to the placenta) and other placental changes caused by blood vessel constriction -Delivery of oxygen to the fetus is adversely affected by the elevated levels of carbon monoxide in the mother's blood.

MARIJUANA: MATERNAL EFFECTS

-Most commonly used illicit drug during pregnancy, although only 3.6 percent of pregnant women report using it -Does not cause a defined physical withdrawal syndrome -Heavy use linked to lung problems

MEDICAL TREATMENT OF NAS: Phenobarbital

-Nonspecific CNS depressant that offers the advantage of a broad spectrum of sedation in cases of maternal poly-drug abuse, controlling symptoms of irritability and insomnia in 50% of infants regardless of the mother's choice of drug. -Usefulness is limited because it does not control non-CNS signs. -Neonatal Seizure -Phenobarbital as a second drug if morphine treatment does not adequately control the signs of abstinence

MEDICAL TREATMENT OF NAS: opioids

-Opioid exposure is best treated with another opioid, such as morphine and methadone (No withdrawal symptoms) have become the treatment of choice for NAS -With buprenorphine being used more frequently by pregnant women undergoing treatment for opioid dependence -*PROBLEM: (Respiratory depression, Hypotension, Delayed gastric emptying, Loss of bowel motility and Urinary retention)*

monitoring

-Pregnant women who are addicted to opioids, even if they are in treatment, should monitor their babies for drowsiness,inadequate weight gain, and failure to meet developmental milestones— especially in younger, exclusively breastfed infants. -Although unlikely, if a breastfed baby of a woman on buprenorphine therapy shows signs of increased sleepiness, difficulty feeding or breathing, or limpness, a health care provider should be contacted immediately. Infants should be observed for withdrawal signs if breast feeding is abruptly stopped

VICTIMIZATION IN PREGNANT WOMEN USING DRUGS

-Previous history of physical abuse and sexual assault, 98 substance-abusing women from nine treatment centers across Ontario, Cormier (2000) found that 85.7% had been victimized. Specifically: - 56.1% reported current physical abuse; Intimate partner violence - 45.4% reported current sexual abuse; - 56.1% reported childhood physical abuse; and - 56.3% reported childhood sexual abuse. 70% of women in treatment report victimization prior to the age of 11.

SMOKING AND PREGNANCY

-Smoking reduces a woman's chances of getting pregnant -Smoking during pregnancy increases the risk for pregnancy complications -Tobacco smoke harms babies before and after they are born -*Women have a harder time quitting smoking than men do. Women metabolize nicotine, the active ingredient in tobacco, faster than men*. -Differences in metabolism may help explain why nicotine replacement therapies, like patches and gum, work better in men than in women. -Men appear to be more sensitive to nicotine's pharmacologic effects related to substance use disorder.

HOW A DRUG AFFECTS A FETUS DEPENDS ON

-The fetus's stage of development -The strength and dose of the drug -The genetic make-up of the mother, which affects how much of the drug is active and available -Other factors related to the mother- Vomiting *(for example, if the mother is vomiting, she may not absorb as much of a drug, so the fetus is exposed to less of the drug)*

MEDICAL TREATMENT OF NAS: Naloxone

-The opioid antagonist naloxone is occasionally given to newborns having breathing problems to reverse the acquired effects of pain medications typically administered to the mother during labor and delivery. -*NOTE: Because of its potential for precipitating severe abstinence symptoms, naloxone should not be given to newborns exposed to opioid in uterus*.

SUBSTANCES OF ABUSE

-Tobacco -Alcohol -Marijuana -Cocaine -Heroin -Amphetamine -Molly or ecstasy

Risks of Stillbirth from Substance Use in Pregnancy

-Tobacco use—1.8 to 2.8 times greater risk of stillbirth, with the highest risk found among the heaviest smokers Marijuana use—2.3 times greater risk of stillbirth -Evidence of any stimulant, marijuana, or prescription pain reliever use—2.2 times greater risk of stillbirth -Passive exposure to tobacco—2.1 times greater risk of stillbirth

pregnancy and substance abuse

-about 10% had at least one alcoholic drink in past 30 days -of those using alcohol, 40% also used other substances (most often tobacco & marijuana) -More than 3 million US women are at risk of exposing their developing baby to alcohol. -3 in 4 women who want to get pregnant as soon as possible report drinking alcohol. - 100% Fetal alcohol spectrum disorders are completely preventable.

*FAS: Mechanism of Action*

-alcohol's teratogenic effects -> craniofacial features (facial cartilage and bone and CNS cells) -retinoic acid derived from vitamin A -> normal development of various tissues and organs including cranial neural crest -> specific receptors -> turn on or turn off the genes that regulate -> the *timing, coordination, and sequencing of various steps in development of craniofacial features and certain brain regions*

TOBACCO + MARIJUANA + PREGNANCY WHAT IS THE IMPACT

A NIDA-funded study suggests that pregnant women who smoke both marijuana and cigarettes have a higher likelihood of smaller babies and increased maternal stress and aggression.

Assessment and diagnosis of NAS symptoms and Symptoms of NAS caused by exposure to opioids

Assessment and diagnosis of NAS symptoms: -Many different variables can affect the level of fetal drug exposure, including: •The amount and purity of the drugs taken by the mother; •The length of drug use and the mother's drug metabolism; and •The individual kinetics of placental drug transfer. Symptoms of NAS caused by exposure to opioids: -CNS, GI, Respiratory System and Autonomic nervous syste

Methamphetamine and Pregnancy

Children prenatally exposed to methamphetamine show -Increased emotional reactivity -Anxiety/depression, -More withdrawn, -Problems with attention, and -Showed cognitive problems --------poorer academic outcomes.

Why there is a use of drugs during pregnancy Substance Use: Pre and post Pregnancy

Different Stages and Distinct/ Overlapping factors: -Drugs----Pregnancy---inadequate prenatal care, poor nutrition, chronic medical problems, poverty, and domestic violence -No Drugs---Pregnancy-----Drugs----Biological, Social, Psychological and Environmental -Baby+ Drugs: Early dysfunctional maternal-infant relationship that can potentiate the negative effects -*Other health conditions, such as depression, anxiety, post-traumatic stress disorder (PTSD), and eating disorders*

CAN HEROIN CAUSE PROBLEMS IN PREGNANCY?

It may cause serious problems, including: -Birth defects: Shape or function of one or more parts of the body -can be deadly for both mother and baby -Premature birth: Before 37 weeks of pregnancy -Low birth weight: -Neonatal abstinence syndrome: (also called NAS). Baby is exposure to a drug in the womb before birth and then withdrawal after birth -Stillbirth: This is when a baby dies in the womb after 20 weeks of pregnancy -Sudden infant death syndrome (SIDS)

AMPHETAMINES: EFFECTS

MATERNAL EFFECTS -Stroke -Cardiac problems -Psychiatric emergencies -Growth restriction -Placental abruption -Preterm delivery NEONATAL EFFECTS -Similar effects to cocaine, with decreased fetal growth -Cocaine effects can be seen early in life but are quickly overpowered by environmental factors.

HEROIN: TREATMENT

Methadone: -The most common treatment for heroin abuse in pregnant women -During pregnancy, brings addicted women into agencies that promote prenatal care Buprenorphine: -Linked to better treatment adherence with fewer side effects and overdoses than methadone

TOBACCO USE IN PREGNANCY: MATERNAL EFFECTS

Smoking during pregnancy exerts direct adverse effects on birth outcomes, including -Damage to the umbilical cord structure, -Miscarriage, -Increased risk for ectopic pregnancy, -Low Birth weight, -Placental abruption, -Preterm birth, and -Increased infant mortality. -Higher rates of respiratory and ear infections, -Sudden infant death syndrome, -Behavioral dysfunction and cognitive impairment.

ADVERSE EFFECTS OF SUBSTANCE USE IN PREGNANCY

Stillbirth and infant mortality Congenital anomalies -increased risks of miscarriage -low birth-weight -reduced gestational age -preterm delivery -placental abruption -third trimester bleeding, toxemia and mortality -45-94% of infants exposed to opioids in utero, including methadone and buprenorphine, can be affected by neonatal abstinence syndrome. -*Cannabis use as harmless in pregnancy; however, several deleterious effects, including preterm labor, low birth weight, small-for-gestational age are associated with*

Illicit drug use and woman's age

Teenaged pregnant women have the highest rates of illicit drug use (15-17, 20.9%), Young adult women (18-25, 8.2%) and adult women (26-44, 2.2%).

OUTCOMES OF NEWBORNS OF PREGNANT WOMEN USING DRUGS

The use of drugs during pregnancy can lead to fetal growth restrictions such as reduced length, head circumference and birth weight, and medical complications such as preterm birth and infections