SUBSTANCE ABUSE & NEWBORNS Why is this important: 5.5% of pregnant women in the United States reported using at least one illicit drug during pregnancy. 21.2% of pregnant women aged 12-44 reported use of alcohol and 21.5% use of cigarettes during the past month. Drug Abuse in Pregnancy National Survey on Drug Use and Health (2002-2003): 4.3% of pregnant women ages 15-44 self-reported illicit drug use in past month, and may actually be as high as 1530%.16 Opiate use in pregnant women ranges anywhere from 1% to 21%.1 Tobacco use in pregnancy: 20.3% 20 Alcohol use in pregnancy: 14.8% 20 Impact on Mom’s Prenatal Care/ Newborn Outcome Poor Nutrition Late Prenatal Care Greater risk for: infectious diseases & Sexually transmitted diseases Limited financial resources Increased risk: premature birth, abruptio placenta, and fetal demise. Pathophysiology of Fetal Alcohol Syndrome: Symptoms of a baby with fetal alcohol syndrome Poor growth while the baby is in the womb and after birth Decreased muscle tone and poor coordination Delayed development and significant functional problems in three or more major areas: thinking, speech, movement, or social skills (as expected for the baby's age) Heart defects such as ventricular septal defect (VSD) or atrial septal defect (ASD) Structural problems with the face, including: Narrow, small eyes with large epicanthal fold Small head Small upper jaw Smooth groove in upper lip Smooth and thin upper lip Alcohol Associated with : 16 Teratogen IUGR Fetal alcohol spectrum disorder Postnatal growth deficiency Cranial dysmorphology Mental retardation Acute neonatal withdrawal20 Fetal Alcohol Syndrome Fetal Alcohol Syndrome Fetal Alcohol Syndrome: Tests Blood alcohol level in pregnant women who show signs of being drunk (intoxicated) Brain imaging studies (CT or MRI) shows abnormal brain development Pregnancy ultrasound shows slowed growth of the fetus Toxicology screen Cocaine Abusing Pregnant Women Increase the risk of miscarriage When the drug is used late in pregnancy, it may trigger premature labor It also may cause an unborn baby to die or to have a stroke, which can result in irreversible brain damage More likely to have a low birth-weight baby More likely to have babies born with smaller heads and smaller brains proportionate to body size Twice as likely to have a premature baby Placental abruption Baby with a malformation of the urinary tract Feeding difficulties and sleep disturbances in newborn Smoking while Pregnant Lower the amount of oxygen available to you and your growing baby Increase your baby's heart rate Increase the chances of miscarriage and stillbirth Increase the risk that your baby is born prematurely and/or born with low birth weight Increase your baby's risk of developing respiratory (lung) problems Elevates the risk of having a child with excess, webbed or missing fingers and toes Drug Abuse in Pregnancy No consistent pattern of congenital anomalies has been found with illicit substances (excluding EtOH, barbiturates, and maybe tobacco) in large-scale epidemiologic studies. Tobacco Associated with16: IUGR Behavioral problems via nicotine disruption of CNS development May affect NAS Placental abruption20 PROM20 Placenta previa20 PTB20 Up to 20-30% of all LBW infants20 Tobacco No increased RATE of congenital anomalies in smokers, but may contribute to RISK of anomalies associated with vascular disruption : 20 Cleft lip with/without cleft palate Gastroschisis Anal atresia Digital anomalies Tobacco Two to four fold increased risk of SIDS Smoking also increases risk of PTB & LBW, which are independent risk factors for SIDS Four fold increased risk of DM II with maternal smoking >10 cig/d20 Inconsistent results from studies on cognitive ability 20 Tobacco Smoking cessation Meta-analysis of RCT showed increased BW and decreased LBW and PTB16. But if that’s not good enough evidence to stop smoking… Tobacco “Effects of cocaine use were NO DIFFERENT than those observed from cigarette smoking” on gestational age-adjusted BW, HC, and length 16 Marijuana Mechanism unknown as to how it may effect neonatal outcomes 16 Proposed theory: reduced fetal oxygenation causing diminished fetal growth. 16 Marijuana Inconclusive data on birth weight (BW)16 or gestational age20 Full gamut: associated with LBW, no difference in BW among controls, & increased BW (up to 142 gm over controls). 1997 meta-analysis of 10 studies: inadequate evidence that marijuana is associated with LBW in the amount typically consumed by pregnant women, but associated with 131 gm decrease in BW if used >4 times/wk.* Opioids Few studies have controlled for concomitant drug use, social, or psychosocial factors. Among most studies, illicit opiate use is associated with LBW, PTB, and reduced fetal growth parameters. Opiates are not teratogens in humans 16 3 Opioids Obstetric complications increase up to six fold1,11: SAB LBW IUGR Preeclampsia Placental abruption PROM PTB Fetal distress Fetal demise Malpresentation, Low APGAR scores, PPH, septic thrombophlebitis, Meconium aspiration, Chorioamnionitis Opioids Proposed Mechanisms: Anorexic effect on maternal nutrition16 Placental insufficiency11 Opioids Neonatal complications3,1: Prematurity Low birth weight Postnatal growth deficiency Microcephaly Neurobehavioral problems* Increased neonatal mortality 74-fold increase in sudden infant death syndrome (SIDS) Neonatal abstinence syndrome (NAS) Opioids Heroin8 Passage through placenta to fetus within 1 hour of administration Accumulates in amniotic fluid Limited fetal detoxification due to immature tissues Fluctuation in drug levels causes placental changes* placental insufficiency and IUGR More significant placental change and LBW than methadone or buprenorphine.8 CLINICAL SIGNS associated with Opiate Withdrawal in Newborns Central Nervous System Dysfunction Autonomic Dysfunction Respiratory Dysfunction Gastrointestinal Dysfunction Risk Factors for Newborns of Substance Abusers FEEDING PROBLEMS Suck-swallow incoordination Tongue thrust during feedings Poor formula intake Failure to thrive SLEEP Sleep-wake cycles disorder ATTENTION Difficulty with reactivity to stimuli Risk Factors for Newborn of Substance Abusers HYPERTONIC BABIES Also known as “stiff babies” Brief deep tendon reflexes Persistence of primitive infant reflexes IRRITABILITY Neurological fragility Difficulty managing day-to-day stimuli Jerky movements Screening Every infant born to a substance abuser should be evaluated for HIV infection. Signs of neonatal abstinence syndrome Small head size (brain size) Newborns who are underweight Stroke in the newborn Intestinal blood flow compromise (NEC) Positive drug screen in mother Opioid Maintenance Methadone Subutex (Buprenorphine) Suboxone (Buprenorphine/Naloxone) Oral slow release morphine 1 g heroin ~ 8 mg buprenorphine ~ 80 mg methadone Methadone Pregnancy Category C Full mu opioid agonist First-line treatment of opioid addiction in pregnancy in the US , UK, and Australia . Requires daily visits to methadone clinic.* 2,5,6 1 Methadone Higher infant BW and less IUGR than seen in heroin-addicted moms. NAS in 60-100% of neonates Longer duration of NAS treatment vs. buprenorphine & heroin 1,8 30 days vs. 11-12 days tx8 Likely due to long t1/2 Methadone However, some experts believe that, when compared to buprenorphine, methadone is the preferred medication: They report buprenorphine has a “ceiling” dose, which is surpassed by some woman…thus they require higher levels of opioid maintenance that can only be reached with methadone.10 Less structured regimen of buprenorphine tx vs. daily methadone dosing may lead to gaps in prenatal care, in addition to diversion or IVDA of buprenorphine.8 Subutex Buprenorphine (Category C) Long-acting partial mu opioid agonist & kappa antagonist While approved in the US for opioid detox & maintenance, is not FDA-approved for use during pregnancy.7 * However, is considered safe in pregnancy.9,15,11 First choice for opioid maintenance programs & in pregnant women in Finland3 since 1996.14 Subutex May have less placenta exposure than methadone Partial agonist profile may lower liability for NAS Cochrane Review favored buprenorphine over methadone in regards to: 1 6 6 Higher infant BW* Shorter hospital stay Subutex Low rates of prematurity (ave 39.2 wks ) NAS occurs in 62%, but only half require treatment Less severe NAS than methadone (though no RCTs yet*) with ↓ incidence and ↓ need for pharmacologic treatment vs. methadone. * Shorter duration of NAS treatment vs. methadone 2 3 2 2,3,5,6,8,11 3,6 6 8 Subutex Preliminary MDFMR stats show: None were low BW All had APGARS of 8 or greater at 1 and 5 minutes Possible dose-dependent relationship Unable to draw conclusions about when babies may develop withdrawal symptoms High degree of variability in the frequency of NAS scoring Suboxone Buprenorphine (Category C) + Naloxone (Category B) Limited studies in pregnant women. US DHHS Center for Substance Abuse Tx: cautious use of naloxone in opioid-addicted pregnant women may precipitate withdrawal in both mother & fetus.2 Recommends buprenorphine monotherapy, though admit it has great potential for abuse & diversion.2 Oral slow release morphine Used in Austria since 1998 for treatment of opioid dependence. One study showed better success over methadone in helping pregnant women abstain from illicit substances. 9 1 Opioid Maintenance – Monitoring in pregnancy UDS, UDS, UDS At increased risk for: anemia, malnutrition, HTN, hyperglycemia, STDs, TB, hepatitis, and preeclampsia.11 Regular Prenatal panel LFTs, Renal function, PPD, glucose intolerance, anti-HCV antibody3,11 Consider repeat CBC, serology at 24-28 wks.11 Opioid Maintenance dosing in pregnancy Varied opinion on monitored detoxification & abstinence during pregnancy. If attempt to wean, suggested in 1st vs. 2nd Trimester 1st – theoretical risk of miscarriage11 3rd – risk of premature labor or fetal death11 Generally not recommended Higher methadone doses related to increased BW, prolonged gestation11 Attempt to decrease incidence of NAS by weaning may cause continued substance abuse11 Opioid Maintenance dosing in pregnancy In fact, increased dosage of maintenance therapy may be required in 2nd-3rd trimester: Increased maternal fluid volume + altered opioid metabolism in placenta & fetus same dose produces lower blood level of particular drug11 Pain Management during Labor & Delivery o Opioid-dependent patients may require higher and more frequent doses of opioid analgesics to maintain pain control. Methadone & buprenorphine suppress opioid withdrawal for 24-48 hours, but only provide analgesia for 4-8 hours. 4 Pain Management during Labor & Delivery NO Stadol or Nubain! Opioid agonist-antagonists, thus can displace the maintenance opioid from the mu receptor, precipitating acute withdrawal4 Epidural use reported in 73% of deliveries to opioid-dependent mothers.8 Impact on Baby 60-90% of opiate exposed infants develop neonatal abstinence syndrome (NAS). Symptoms will manifest within 48 to 72 hours after birth S&S of Neonatal Abstinence Syndrome Withdrawal Irritability Tremors High-pitched cry Diarrhea & Vomiting Respiratory Distress Abrasions Weight loss Aberrant temp control Lack of sucking Sneezing Signs of Neonate Withdrawl Irritability Tachypena Tremors Shrill Cry Mottling Hypertonicity of muscles Frantic Sucking of hands Temperature instability Loose diarrheal stools Seizures Nasal stuffiness Sleep Disturbances Which leads to: “Unlovable Infant… Baby Outcomes Guilt and Denial from the mother contribute to a poor communication/ connection between mom and baby Leads to impaired language development, social-emotional problems, and/ or neglect and abuse. Increased risk for medical, emotional/ behavior, and developmental difficulties. Haven House and CAP Most drug treatment programs cater to male clients Those who accept women will often rescind treatment to women who become pregnant while in program Provision of child-care for existing children is also vital to most women… high risk of relapse during immediate postpartum period. So…. Placenta Breastfeeding in Opioid Maintenance In brief, it’s OK to breastfeed on Suboxone or methadone. …so go ahead & encourage it! Contraindications: illicit substance abuse HIV Breastfeeding in Opioid Maintenance Buprenorphine: breastfeeding infant will receive only 1/5 to 1/10 of the total available buprenorphine2,9. No evidence to support theory that breastfeeding will help suppress NAS.2 Likewise, NAS does not occur after breastfeeding is discontinued.2 Postpartum Care in Opioid Maintenance Continue maintenance opioid (or switch to Suboxone if on Subutex). 80% abstinence rate shown postpartum at Mercy’s Recovery Center in Westbrook, ME. Opioid Maintenance Improved outcomes when therapy includes : 3,11 prenatal care addiction treatment other social services, including individual/group/family therapy to address the psychological and psychosocial factor of substance abuse. Future Research National Institute on Drug Abuse16: “little information is available as to whether the detrimental effects seen in drugexposed offspring are the direct result of perturbations in the development of placenta & its functions OR caused by ‘host’ factors such as poor prenatal care, stress, infection, and poor maternal nutrition, which are common comorbid factors in drug abusing women.” Future research Chronic stress has consistently been related to LBW and PTB 16 Hypothesis = neuroendocrine, immune, and vascular roles that may influence uteroplacental transfer & delivery. No studies of drug abuse in pregnancy have controlled for chronic stress. Future treatment Biggest influence of prenatal substance abuse may in fact be the increased postnatal risks rather than any direct drug-effect: 16 Diminished bonding Neglect Foster care placement Disruptions in home environment Summary Prematurity and IUGR are associated with tobacco, alcohol, opioids, cocaine, and maybe amphetamines. Teratogens: alcohol and barbiturates Adverse effects of prenatal drug exposure are usually selflimited and confined to infancy. Exceptions include: Alcohol lifelong impairments Cigarettes may have long term behavioral effects Psychosocial factors and concomitant maternal illnesses may play an even larger role in long term development of these infants. Summary Thus, when caring for a drug-addicted pregnant woman, understanding the complex roles that illicit drugs, inner stressors, and her surrounding external environment will not only help us better provide interventions to improve pregnancy outcomes, but also to give both her and her child a stepping stone toward a healthier lifestyle in the future. REFERENCES Albersheim, S. (1991). Newborn Patients of Mothers with Substance AbuseProviding proper health care for mothers and their babies. Can Fam Physician.(37):1739–1746. Bertrand J, Floyd LL, Weber MK. Guidelines for identifying and referring persons with fetal alcohol syndrome. MMWR Recomm Rep. 2005 Oct 28;54(RR-11):1-14. Gorski, Terence T. (2001). Cocaine use during pregnancy. Gorski-Cenaps Web Publications. Retrieved on November 10, 2009. http://www.tgorski.com/Prevention/cocaine_use_during_pregnancy.htm Nazario, Brunilda MD. 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