Neonatal Abstinence Syndrome (NAS)

Neonatal Abstinence Syndrome (NAS)
LaResa Janousek, RN, NNP-BC Idaho Perinatal Project February 21, 2013

Objectives Increase awareness of opioid use and pregnancy.
Identify and screen for maternal opioid use/abuse. Describe the clinical characteristics of Neonatal Abstinence Syndrome. Understand how to manage patients with NAS. Recognize the importance of parental support and involvement. Increase awareness of the problem of prescription drug abuse. Identify high risk mothers Recognize NAS Understand how to initiate and manage therapy in patients with NAS. Parent involvement

Topics The Problem NAS assessment and treatment
Parent communication and education The Problem Assessing intrauterine drug exposure Neonatal Abstinence Syndrome (NAS) Patient communication and education

Opioid Natural and synthetic drugs with morphine-like properties, although the chemical structure may differ from that of morphine. 2 Endogenous opioids include enkephalins, endorphins, and endomorphins. “Opioid” is a general term for both natural and synthetic drugs with morphine-like properties, although the chemical structure may differ from that of morphine. 2 Endogenous opioids include enkephalins, endorphins, and endomorphins. Opioids are used mostly for their analgesic properties to treat pain. Opioids demonstrate a narrow therapeutic index. On the other hand, the interpatient range of dose necessary to achieve a similar therapeutic effect is fairly wide because of genetic differences in pharmacokinetics and pharmacodynamics. narcotic analgesic used in the treatment of severe pain. Illicit heroin may be smoked or solubilised with a weak acid and injected. Whereas opium has been smoked since historical times, diamorphine was first synthesised in the late nineteenth century. opioids, produces analgesia. It behaves as an agonist at a complex group of receptors (the μ, κ and δ subtypes) that are normally acted upon by endogenous peptides known as endorphins. Apart from analgesia, produces drowsiness, euphoria and a sense of detachment. Negative effects include respiratory depression, nausea and vomiting, decreased motility in the gastrointestinal tract, suppression of the cough reflex and hypothermia. Tolerance and physical dependence occur on repeated use. Cessation of use in tolerant subjects leads to characteristic withdrawal symptoms. Subjective effects following injection are known as ‘the rush’ and are associated with feelings of warmth and pleasure, followed by a longer period of sedation. Diamorphine is 2–3 times more potent than morphine. The estimated minimum lethal dose is 200 mg, but addicts may be able to tolerate ten times as much. Following injection, diamorphine crosses the blood–brain barrier within 20 seconds, with almost 70 % of the dose reaching the brain. It is difficult to detect in blood because of rapid hydrolysis to 6-monoacetylmorphine and slower conversion to morphine, the main active metabolite. The plasma half-life of diamorphine is about three minutes. Morphine is excreted in the urine largely as the glucuronide conjugate. Diamorphine is associated with far more accidental overdoses and fatal poisonings than any other scheduled substance. Much morbidity is caused by infectious agents transmitted by unhygienic injection.

Opioid Uses Induce or supplement anesthesia. Cough suppressants.
Gastrointestinal disorders. Analgesic properties to treat pain. Opioid addiction. Induce or supplement anaesthesia: fentanyl, alfentanil and remifentani). Cough suppressants: codeine, dihydrocodeine and, to a lesser extent, pholcodine and ethylmorphine) Treat gastrointestinal disorders: codeine and diphenoxylate. Treat opioids addiction: buprenorphine, suboxone and methadone. 1)

Opioid Use for Pain Analgesics: disconnect from pain
Euphoria, disconnection, sedation Oversedation, respiratory depression fentanyl hydromorphone Methadone morphine pethidine buprenorphine Oxycodone codeine dihydrocodeine dextropropoxyphene Opioids are used mostly for their analgesic properties to treat: Codeine, heroin (diacetylmorphine), hydromorphone (Dilaudid), fentanyl (Sublimaze), and methadone are examples of synthetic opioids. Methadone exerts secondary effects by acting as an N-methyl-D-aspartate receptor antagonist, blocking the actions of glutamate, the primary excitatory neurotransmitter in the CNS. Opioids acutely inhibit the release of noradrenaline at synaptic terminals. With chronic opioid exposure, tolerance develops as the rate of noradrenaline release over time increases toward normal. Abrupt discontinuation of exogenous opioids results in supranormal release of noradrenaline and produces the autonomic and behavioral signs and symptoms characteristic of withdrawal.3

Drug Trends

Drug Addiction Drug addiction is a mental illness:
characterized by compulsive drug craving, seeking, and use despite devastating consequences. that stem from drug-induced changes in brain structure and function. Drug addiction is a mental illness. It is a complex brain disease characterized by compulsive, at times uncontrollable drug craving, seeking, and use despite devastating consequences–behaviors that stem from drug-induced changes in brain structure and function. These changes occur in some of the same brain areas that are disrupted in other mental disorders, such as depression, anxiety, or schizophrenia. For example, compared with the general population, people addicted to drugs are roughly twice as likely to suffer from mood and anxiety disorders, with the reverse also true.

Drug Abuse Consequences
Health and social consequences Exacerbated medical conditions Inadequate treatment Resistance to seek treatment * Drug use impacts patient outcomes and has wide-ranging health and social consequences. Medical conditions such as cardiovascular disease, stroke, cancer, HIV/AIDS, anxiety, depression, sleep problems, as well as financial difficulties and legal, work, and family problems can all result from or be exacerbated by drug use. Only a fraction of individuals who need specialty treatment for drug or alcohol addiction receive it. In 2009, of the more than 23 million persons aged 12 or older who needed specialized treatment for a drug or alcohol problem in the United States, nearly 21 million did not receive it.* Many patients who abuse substances won't seek treatment on their own. Nearly 95 percent of those who did not receive treatment felt that they did not need it.* *

Characteristics of Chemically Involved Pregnant Women
Low self-esteem Limited family support Hx of violent or unhealthy relationships Likely to be victims of early sexual or physical abuse Limited education Frequently unemployed Problems maintaining adequate stable housing Little prenatal care Poor parenting skills Hx of dysfunction/chemically dependent families Need for a wide range of services Poly drug use Mental health problems Because of their chemical dependency and lack of information about prenatal care, pregnant substance abusers are more likely than other women to have poor nutrition before and during the time they are pregnant. Many women also smoke cigarettes; the number one cause of poor birth outcome is smoking. Physical and sexual abuse of children with parents addicted to either alcohol or opiates is as high as 22% in one study of 200 families. If neglect was included, the incidence rose to 40%. Parents who must devote a major portion of their energy and financial resources to their habit have less left over for the child. Violence, disorganization and criminality in the family are more common. All of these factors compromise maternal health and place the developing fetus at risk.

Drug Abuse in Pregnancy
Poly-drug abuse is common Less likely to receive prenatal care Increased risk of associated infectious diseases, including syphilis, gonorrhea, hepatitis, and HIV Increased incidence of psychiatric disorders

Drug Abuse in Pregnancy
4.3% of pregnant women ages self-reported illicit drug use in past month, and may actually be as high as 15-30% National Survey on Drug Use and Health ( ) 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 20 National Household Survey on Drug Abuse Marijuana = 2/3; Cocaine = 1/10. Any illicit drugs: 2.8% 20 Rate of drug use decline by 24% from 1st to 3rd trimester. At time of delivery in Perinatal Substance Exposure Study Group, nicotine found in 8.8%, alcohol 6.7%, and any illicit drug 3.5%

Neonatal Withdrawal Syndrome Neonatal Abstinence Syndrome (NAS)
60% to 80% of newborns exposed to opioids in the womb are reported to have NAS signs and symptoms. Neonatal Withdrawal Syndrome is a set of problems that newborns experience when they are exposed to addictive substances while they were in their mother's uterus. Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome caused by maternal opiate use. 60% to 80% of newborns who had been exposed to methadone or heroin while in the womb are reported to have NAS signs and symptoms. However, there are not national estimates on how many newborns in the USA have NAS symptoms due to maternal opiate use. Not all infants show the same effects from prenatal exposure to alcohol and other drugs. Effects depend upon the genetic factors, maternal health, access to health care, chemicals used, patterns of use, duration of use and health care received. The following characteristics have been observed in infants exposed prenatal: Withdrawal can continue for weeks or months, damaging parent-infant bonding, as well as the baby’s cognitive and social development. Perhaps the saddest effect is the high incidence of second generation abuse, violence, and addiction when addicted parents raise children.

Heroin Passes to the fetus within 1 hour of administration
Accumulates in amniotic fluid Limited fetal detoxification Changes in drug levels causes placental changes Heroin8 Passes through the placenta to fetus within 1 hour of administration Accumulates in amniotic fluid Limited fetal detoxification due to immature tissues Changes in drug levels causes placental changes such as placental insufficiency and IUGR More significant placental change and LBW than methadone or buprenorphine.8 Microfibrin deposits, increased vascularization of villi, increased proliferations of trophoblastic buds & nodules.8

Opioid Maintenance Less drug-seeking and criminal behavior, fewer relapses, decreased STDs, improved prenatal care and compliance, improved nutrition. Consistent maintenance opioid treatment prevents repeated fetal withdrawals. Preferred over illicit substance abuse: less drug-seeking and criminal behavior, fewer relapses, decreased STDs, improved prenatal care and compliance, improved nutrition3 Consistent maintenance opioid treatment prevents repeated fetal withdrawals1. Of note, Methadone normalized endocrine function, thus women in early phases of methadone treatment may become pregnant unintentionally. Furthermore, they may also confuse amenorrhea from their stressful lifestyles with infertility, and thus not use contraception.11 Changes in the placenta occur faster with fluctuations in maternal drug serum levels; thus regular administration of a drug is more favorable for BW.8

Opioid Maintenance Methadone Subutex (Buprenorphine)
Suboxone (Buprenorphine/Naloxone) Oral slow release morphine Low frequency of preterm deliveries in both buprenorphine & methadone6,8 (22-30% prematurity)8 Increased frequency of C-sections in buprenorphine & methadone when compared to general population (usually IUGR)6,8. Inconsistent results when comparing C-section rate b/w buprenorphine to methadone. No significant difference in nicotine use among methadone, buprenorphine, and oral slow morphine; nicotine use during pregnancy can affect birth weight and NAS1.

Methadone Pregnancy Category C Full mu opioid agonist
First-line treatment of opioid addiction in pregnancy in the US. Requires daily visits to methadone clinic. * Daily visits may be beneficial for close surveillance and f/u, but may also be a deterrent to those unwilling to participate under such strict regulations, as well as those with transportation problems.

Methadone Higher infant BW and less IUGR than seen in heroin-addicted moms. NAS in % of neonates. Longer duration of NAS treatment vs. buprenorphine & heroin. Methadone NAS – appears in 1st 24 hours. Dose-dependent relationship with methadone and severity of NAS symptoms. Per Cochrane Review, no significant difference found between methadone & buprenorphine in APGAR scores, number of newborns treated for NAS, peak NAS score, treatment duration for NAS, or cumulative dose of morphine to treat NAS1 No significant difference in APGAR scores in heroin, methadone, or buprenorphine groups.8 No significant difference between methadone & oral slow morphine in birth weight or NAS duration. 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. Not FDA-approved for use during pregnancy. Considered safe in pregnancy. May have less placenta exposure than methadone. 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 May have less placenta exposure than methadone1 Partial agonist profile may lower liability for NAS6 Low rates of prematurity2 (ave 39.2 wks3) NAS occurs in 62%, but only half require treatment2 Cochrane Review6 favored buprenorphine over methadone in regards to: Higher infant BW* Shorter hospital stay More frequent NAS and higher frequency of treated NAS in infants born to moms started on buprenorphine AFTER conception than before.6 US DHHS Center for Substance Abuse Tx acknowledges buprenorphine monotherapy as an alternative to methadone “should methadone be unavailable or the patient refuses methadone therapy.2 Currently 500 pt clinical trial underway looking at maintenance buprenorphine therapy in pregnant women. Pregnancy Category C = (1) animal reproductive studies have shown an adverse effect on the fetus but no adequate, well-controlled studies in humans, (2) no animal or human studies, or (3) benefits of the drug in pregnancy may be acceptable despite its potential risks. What Buprenorphine is and Why It's Important NIDA supported basic and clinical research led to the development of buprenorphine, a medication for the treatment of heroin addiction. These scientific discoveries spurred a collaboration with industry, which culminated in FDA approval of Subutex® (buprenorphine) and Suboxone® tablets (buprenorphine/ naloxone) in October 2002. Buprenorphine is a long-acting partial mu opiate agonist that acts on the receptor targets of heroin and morphine, but does not produce the same intense "high" or dangerous side effects. These properties also make it a good potential treatment for addiction to opiate analgesics. Buprenorphine's unique formulation with naloxone, an opioid antagonist (Suboxone), limits diversion by causing severe withdrawal symptoms in those who inject it to get "high", Buprenorphine and Buprenorphine/ Naloxone Help Patients Quit Opiate Abuse Fudala, et al. New England J Medicine 349(10): , 2003. but no adverse effects when taken orally (naloxone is minimally absorbed when taken orally). This exemplifies the feasibility of developing strategies that minimize the diversion liability of opiate medications. A large NIDA-sponsored multisite clinical trial demonstrated a robust effect in reducing opiate use and drug cravings in heroine abusers and confirmed its safety and acceptability (figure). Along with methadone, buprenorphine has helped curb the spread of HIV that occurs through injection drug use in this country. Changing the Culture of Drug Abuse Treatment In 2000, Congress passed the Drug Addiction Treatment Act, allowing qualified physicians to prescribe narcotic medications (Schedules III to V) for the treatment of opioid addiction. This created a major paradigm shift that allowed access to heroin treatment in a medical setting rather than limiting it to methadone clinics. Buprenorphine has also helped change the mindset of many community treatment providers in this country, who for the most part have been unwilling to consider the use of medications to treat drug addiction. Some of these programs now use buprenorphine to assist in opiate detoxification. What We Are Doing Now We continue to test the safety and efficacy of buprenorphine in other affected populations, including pregnant women, adolescents, and patients addicted to opiate analgesics. We are striving to increase the use of this and other addiction medications in other settings and countries, including in the U.S. criminal justice system and in countries where injection drug use is still a primary mode of HIV transmission.

Subutex May lower liability for NAS.
Shorter duration of NAS treatment vs. methadone. Buprenorphine NAS – appears in first 2 days of life, peaks at 3-4 days, and lasts 5-7 days. May be delayed onset up to 7 days.

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. Recommends buprenorphine monotherapy, though admit it has great potential for abuse & diversion. 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 Pregnancy Category B = (1) animal reproductive studies have failed to demonstrate a risk to the fetus, but no adequate, well-controlled trials available in pregnant women 1st trimester, (2) no evidence of 2nd or 3rd trimester risk, and (3) fetal harm possible but unlikely.

Opioid Maintenance – Monitoring in pregnancy
Urine Drug Screen (UDS) At increased risk for: anemia, malnutrition, HTN, hyperglycemia, STDs, TB, hepatitis, and preeclampsia. Regular Prenatal panel LFTs, Renal function, PPD, glucose intolerance, anti-HCV antibody. Consider repeat CBC, serology at wks. Hepatitis B: High rate of vertical transmission (70-90%), especially if active (+ HbSAg) in 3rd trimester  must give hep B vaccine and hep B immunoglobulin to baby11 Hepatitis C: Low risk of vertical transmission, but risk increases if co-infected with HIV or if has high HCV viral load; no contraindications against vaginal delivery or breastfeeding11 Check anti-HCV antibody  if positive, check HCV RNA & refer for treatment after delivery11 If positive, repeat HCV RNA and anti-HCV antibody between 2-6 mths and mths.11 HIV: vertical transmissions rates have decreased from 16-25% in early 1990s to5-6% in 2000, and to <2% if antiretrovirals are used in combination with C-section.11 HIV has not been found to increase prematurity, IUGR, or low birth weight.11

Opioid Maintenance- Dosing in pregnancy
Controversial. If attempt to wean, suggested in 1st vs. 2nd Trimester 1st – theoretical risk of miscarriage11 3rd – risk of premature labor or fetal death. Increased dosage of maintenance therapy may be required in 2nd-3rd trimester. Controversial 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 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 Finnish study showed that 76% of pregnant women on Subutex maintained or decreased dose, and decreased dose had no harm on fetus.3 Even mild withdrawal can precipitate premature labor.11

Opioid Maintenance Improved outcomes when therapy includes:
prenatal care addiction treatment other social services, including individual/group/family therapy to address the psychological and psychosocial factor of substance abuse.

Obstetric Complications
SAB LBW IUGR Preeclampsia Placental abruption PROM PTB Fetal distress Fetal demise Malpresentation, Low APGAR scores, PPH, septic thrombophlebitis, Meconium aspiration, Chorioamnionitis 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 Proposed Mechanisms: Anorexic effect on maternal nutrition16 Placental insufficiency11

Labor & Delivery NO Stadol or Nubain!
May require higher and more frequent doses of opioid analgesics to maintain pain control. NO Stadol or Nubain! Opioid agonist-antagonists, thus can displace the maintenance opioid from the mu receptor, precipitating acute withdrawal. Opioid-dependent patients may require higher and more frequent doses of opioid analgesics to maintain pain control. Methadone & buprenorphine suppress opioid withdrawal for hours, but only provide analgesia for 4-8 hours.4 NO Stadol or Nubain! Opioid agonist-antagonists, thus can displace the maintenance opioid from the mu receptor, precipitating acute withdrawal4 Stadol = butorphanol Nubain = nalbuphine Methadone binds less tightly to the mu receptor than buprenorphine, thus increasing doses of add’l opioids will provide analgesia with methadone. Syndrome of pain facilitation = decreased pain tolerance seen in patients that abuse opioids compared to peers in remission from substance abuse.4 Tolerance = need for increasing doses of medication to achieve its initial effects4 Cross-tolerance = analgesic tolerance for different medications within the opioid class4 Opioid-induced hyperalgesia = neuroplastic changes in the perception of pain that increase sensitivity to pain4 Involves excitatory amino acid NMDA (N-methyl-D-aspartate) and opioid receptors; opioid administration thus can cause a hyperalgesic response that counteracts the opioid analgesia, manifesting as an increased sensitivity to pain.4

Neonatal Complications
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) No consistent pattern of congenital anomalies has been found with illicit substances (excluding EtOH, barbiturates, and maybe tobacco) in large-scale epidemiologic studies. Few studies have controlled for concomitant drug use, social, or psychosocial factors. Neurobehavioral problems: Some animal studies report that opiates may promote apoptosis of neurons, raising concerns of their effect on human brain development3. However, it has been shown that children up to 2 years of age that were exposed to opiates in utero were within the normal developmental range for their age; likewise, children ages 2-5 years exposed to opiates in utero “did not differ in cognitive function from a high-risk population.”6 Neurodevelopmental studies at 6 and 12 months in children born to buprenorphine treated mothers were normal.9 It has been postulated that the effect of opioids on respiratory function may be the link between opioids and SIDS3. NAS is characterized by tremor, sneezing, fever, abnormal crying,9 tachypnea, apneic pauses,8 irritability, poorly coordinated sucking—and hence poor feeding, seizures, or even death1.

Opioid Maintenance- Breastfeeding
Contraindications: HIV Illicit drug use Buprenorphine: breastfeeding infant will receive only 1/5 to 1/10 of the total available buprenorphine. No evidence to support theory that breastfeeding will help suppress NAS. Likewise, NAS does not occur after breastfeeding is discontinued. Buprenorphine passes into breast milk at a plasma:milk ratio of 1.0; buprenorphine also has poor oral bioavailability. Additionally, neonatal exposure to buprenorphine when breastfeeding should be less than methadone or other opioids.9 Breastfeeding on20: Amphetamines  irritability, poor sleeping patter Cocaine  irritability, vomiting, diarrhea, tremors, seizures Heroin  tremors, restlessness, vomiting, poor feeding Marijuana  limited data with no known effect PCP  hallucinogen US DHHS Center for Substance Abuse Treatment panel concluded that there would be minimal effects on a breastfed infant of a buprenorphine-maintained mother; thus, they do not believe breastfeeding is contraindicated in this population2,11 There is no contraindication for breastfeeding with maternal methadone use; the American Academy of Pediatrics has recommended (since 1983) that breastfeeding may occur with maternal methadone use only up to 20 mg daily. However, only small amounts of methadone in breast milk were found in women who were maintained on up to 180 mg methadone daily.11

Opioid Maintenance- Treasure Valley
Richard Montgomery, M.D. 413 North Allumbaugh Street Suite 101 Boise, ID 83704(208) John B. Casper 8050 West Rifleman Suite 100 Boise, ID 83704(208) Intermountain Hospital of Boise 303 North Allumbaugh Street Boise, ID 83704(208) Riverside Rehabilitation 7711 West Riverside Drive Boise, 83714 Personal Development 1009 West Hemingway Boulevard Nampa, ID Port of Hope Centers Inc 508 East Florida Street Nampa, ID Raise the Bottom Training and Counseling Services 9196 W. Barnes St. Boise, ID 83709(208) Center for Behavioral Health Idaho Inc 92 South Cole Road Boise, ID 83709(208) 1965 South Eagle Road, Suite 180 Meridian, ID 83642(208) Patrick James Dwyer, M.D. 5985 West State Street Boise, ID 83703(208) Kristina J. Harrington 5985 West State Street Suite 555

Neonatal abstinence syndrome and associated health care expenditures: United States, May 2012 Patrick SW A retrospective, serial, cross-sectional analysis of a nationally representative sample of newborns with NAS. The Kids' Inpatient Database (KID) was used to identify newborns with NAS by International Classification of Diseases. The separate years (2000, 2003, 2006, and 2009) of national discharge data included 2920 to 9674 unweighted discharges with NAS and 987 to 4563 unweighted discharges for mothers diagnosed with antepartum opiate use, within data sets including 784,191 to 1.1 million discharges for children (KID) and 816,554 to 879,910 discharges for all ages of delivering mothers (NIS).

2000 and 2009: It was estimated that 14,539 babies were born with NAS in 2009 Rate of newborns diagnosed with NAS rose from 1.20 per 1,000 hospital births per year to 3.39 per 1,000. The number of pregnant mothers using or dependent on opiates. The amount hospitals charged, on average for newborns diagnosed with NAS rose by 35%. Estimates for total hospital charges nationwide, adjusting for inflation, rose from $190 million. Stephen W. Patrick, M.D., M.P.H., M.S., and team carried out a study to look at the patterns in the national incidence of NAS and maternal opiate usage at the moment of childbirth, and to characterize trends in national health care expenditures linked to NAS during the first nine years of this century. The researchers found that between 2000 and 2009: The rate at which newborns were diagnosed with NAS rose from 1.20 per 1,000 hospital births per year to 3.39 per 1,000. The number of pregnant mothers using or dependent on opiates rose from 1.19 per 1,000 hospital births per year to 5.63 per 1,000. The amount hospitals charged, on average for newborns diagnosed with NAS rose by 35%, from $39,400 to $53,400 Estimates for total hospital charges nationwide, adjusting for inflation, rose from $190 million to $720 million It was estimated that 14,539 babies were born with NAS in 2009 Rate of newborns diagnosed with NAS rose from 1.20 per 1,000 hospital births per year to 3.39 per 1,000.

Neonatal Screening The Committee on Substance Abuse of the American Academy of Pediatrics recommends obtaining a comprehensive medical and psychological history that includes specific information regarding maternal drug use as part of every newborn evaluation. The clinical presentation of NAS varies with the opioid, the maternal drug history (including timing of the most recent use of drug before delivery), maternal metabolism, net transfer of drug across the placenta, placental metabolism (W. Snodgrass, MD, PhD, personal communication, 2008), infant metabolism and excretion, and other factors. In addition, maternal use of other drugs and substances such as cocaine, barbiturates, hypnoticssedatives, and cigarettes may influence the severity and duration of NAS. Because opioid receptors are concentrated in the CNS and the gastrointestinal tract, the predominant signs and symptoms of pure opioid withdrawal reflect CNS irritability, autonomic overreactivity, and gastrointestinal tract dysfunction (Table 3). Excess environmental stimuli and hunger will exacerbate the perceived severity of NAS.

Indicators for Neonatal Drug Screening
Unexplained abruption inconsistent prenatal care antenatal social work recommendation emergency department care plan independent physician care plan obviously intoxicated history of drug abuse in the last two years or during a prior or current pregnancy drug abuse by spouse CPS and legal involvement unexplained infant neurological complication (IVH, seizures)

Differential Diagnosis
Serum glucose level. Serum calcium level. CBC with differential. Consider blood culture and other cultures. Confirm maternal hepatitis status and treat accordingly. Confirm human immunodeficiency virus (HIV) status. The following studies are indicated when assessing perinatal drug abuse and neonatal drug withdrawal: Obtain a serum glucose level. Obtain a serum calcium level. Perform a CBC count with differential and platelets. Consider blood culture and other cultures to rule out newborn sepsis. Confirm maternal hepatitis status and treat accordingly. Confirm human immunodeficiency virus (HIV) status. A urine toxicological screen may be helpful in determining drug use. A urine screen only signifies recent use or heavy use of drugs. In general, the length of time that a drug is present in urine after use is as follows: Marijuana: 7 days to 1 month in an adult, perhaps even longer in an infant Cocaine: hours in an adult, hours in an infant Heroin: 24 hours in an adult, hours in an infant Methadone: Up to 10 days in an infant Neonatal toxicology screening should also include algorithms using meconium testing.[21] Meconium testing provides higher sensitivity than urine testing and is comparable to umbilical cord tissue samples. Neonatal hair analysis may prove useful in confirming fetal drug exposure and possibly predicting neonatal withdrawal severity. Hair analysis should be used in conjunction with urine and meconium analysis.

Umbilical Cord Analysis Finnegan Assessment Tool
Neonatal Screening Urine Drug Toxicology Meconium Sampling Umbilical Cord Analysis Finnegan Assessment Tool A urine toxicological screen may be helpful in determining drug use. A urine screen only signifies recent use or heavy use of drugs. In general, the length of time that a drug is present in urine after use is as follows: Marijuana: 7 days to 1 month in an adult, perhaps even longer in an infant Cocaine: hours in an adult, hours in an infant Heroin: 24 hours in an adult, hours in an infant Methadone: Up to 10 days in an infant Neonatal toxicology screening should also include algorithms using meconium testing.[21] Meconium testing provides higher sensitivity than urine testing and is comparable to umbilical cord tissue samples. Neonatal hair analysis may prove useful in confirming fetal drug exposure and possibly predicting neonatal withdrawal severity. Hair analysis should be used in conjunction with urine and meconium analysis. Specific clinical conditions for which urine or meconium toxicology testing is indicated are noted. Commonly accepted indications for toxicology analysis include no prenatal care, intrauterine growth retardation (IUGR), preterm delivery, abruptio placentae, or cardiovascular accidents in mother or child, especially in those cases in which no other reasons for poor outcome are noted.[25] The following studies may be necessary to prevent or diagnose cases of neonatal abstinence syndrome (NAS): Radioimmunoassay and enzyme immunoassay These are the most commonly used drug screens. Both are semiquantitative and highly sensitive, but enzyme immunoassay takes less time to perform and is less expensive. These tests inform the clinician about the presence or absence of substance abuse, rather than quantifying the drug level, as in toxicology screens. Blood tests: The usefulness of neonatal blood samples varies. Blood samples are of limited value because the window of detection is narrow because of the rapid effects of metabolism and the low concentrations of drugs present in blood. Urine toxicology assays Urine was traditionally the specimen of choice for neonatal drug testing, although collection is difficult. The adhesive for the collection bag causes skin irritation and frequently fails to adhere. Another disadvantage is the short detection window; urine provides maternal drug use data only for a few days prior to delivery. Urine toxicology screening is useful for clinical and research purposes. Urinary excretion of metabolites may be detectable only for a few days (eg, benzoylecgonine) to a few weeks (eg, cannabinoids). One cannot expect to ascertain early pregnancy use or even relatively recent use if the metabolite concentration does not reach the detection threshold. Urine is relatively easy to obtain, requires minimal preparation (provided samples are not contaminated by meconium or feces), and can be analyzed using numerous laboratory techniques. Although urine samples generally contain a higher drug concentration than serum samples, the detection of compounds depends on obtaining an appropriate sample as close as possible to birth and also depends on the timing of maternal drug ingestion prior to delivery. These tests detect recent use of cocaine and its metabolites, amphetamines, marijuana, barbiturates, and opiates. Cocaine can be detected in urine 6-8 hours after use in the mother and as long as hours after use in the newborn. Alcohol is detectable in neonatal urine for 6-16 hours after the last maternal ingestion. Detection of drugs depends on many variables, including individual drug metabolism, hydration status of the subject, route of administration, and frequency of ingestion. No drugs are known to crossreact with the immunoassays for cocaine and marijuana. Several over-the-counter remedies and herbal preparations may contain ephedrine and phenylpropanolamine (recalled from US market), which can produce false-positive enzyme immunoassay test results for amphetamines. Therefore, confirmatory testing is required. Immunoassay for opiates does not distinguish between codeine, morphine, or their glucuronide conjugates. Meconium analysis Meconium analysis is currently considered the best method for detecting drug exposure in pregnancy. It provides a wider window of detection of gestational exposure, presumably as remote as the second trimester, when drugs begin to accumulate in meconium (by direct deposition from the biliary tree or when the fetus ingests amniotic fluid). Meconium analysis is reliable for detecting opioid and cocaine exposure after the first trimester and can be used to detect a range of other illicit and prescribed medications. Meconium can be contaminated by infant urine, although only cocaine or opiate use within approximately 72 hours of birth is reflected. False positive results occur if meconium is contaminated with urine, reflecting antepartum and perinatal exposure. Theoretically, lidocaine can cause a positive result, but a large amount is required. When a meconium sample is stored at room temperature, it decreases cocaine and cannabinoid levels by 25% per day. Hair analysis Neonatal hair testing can also identify prenatal drug exposure. Hair begins to form at approximately 6 months' gestation; a positive result indicates use during the last trimester. Hair testing is advantageous because the specimen can be collected at any point during the first 3 months of life, after which time infant hair replaces neonatal hair.[26] This method is useful in detecting narcotics, marijuana, cocaine, and cocaine-alcohol metabolites, but the technique is expensive, is not widely available, and is limited by the procedures required to quantify the very small amounts of drug present. Obtaining an adequate sample may be difficult, and recent exposure might not be detected because hair growth is slow. Analysis of 1.5 cm of maternal hair reveals the maternal drug use pattern during the previous 3 months. Drug metabolites can be detected in infant hair for 2-3 months after birth. A recent report has suggested that detecting drug exposure from umbilical cord tissue has similar sensitivity and specificity to meconium samples and may have some advantages over collection of meconium.[28] Testing umbilical cord tissue enables analysis to occur immediately after birth, compared with meconium testing, which is delayed as long as 3 days prior to specimen availability. Umbilical cord is easily and noninvasively collected and may reflect a long window of drug detection; however, because few studies have examined cord tissue analysis to date, interpreting results is difficult.

Finnegan The Finnegan scale assesses 21 of the most common signs of neonatal drug withdrawal syndrome and is scored on the basis of pathological significance and severity of the adverse symptoms, which sometimes requires pharmacological treatment. Despite the number of items that can be scored, it is nevertheless a relatively easy and reliable system to use once staff have been adequately trained. However, the potential for bias and subjectivity may affect the scores, and the thresholds for treatment reported in the literature vary. This scale can also be used to assess the resolution of signs and symptoms after initiating treatment. To obtain a daily average score, measurements are performed every 4 hours until the patient is stable. If 3 consecutive scores are equal to or greater than 8, treatment for withdrawal is started. The decision to commence treatment can depend on factors other than this score alone, including the reported exposure, the age of the infant, consideration of comorbidities that might influence the score, whether an inpatient or outpatient strategy is used, and the experience of the clinician making treatment decisions. The infant is best cared for in a unit with experienced personnel who can recognize problems, perform constant evaluations, and institute the necessary interventions.

NAS scoring Designed for term babies on four-hourly feeds and may therefore need modification for preterm infants. The NAS score sheet lists 21 symptoms that are most frequently observed in opiate-exposed infants. Each symptom and its associated degree of severity are assigned a score. The neonatal abstinence syndrome scoring system was designed for term babies on four-hourly feeds and may therefore need modification for preterm infants. The NAS score sheet list 21 symptoms that are most frequently observed in opiate-exposed infants. Each symptom and its associated degree of severity are assigned a score and the total abstinence score is determined by totaling the score assigned to each symptom over the scoring period.

NAS scoring The first abstinence score should be recorded approximately two hours after birth or admission. Scoring is dynamic. All signs and symptoms observed during the scoring interval are included in the point-total for that period. If the infant’s score at any scoring interval is >8, scoring is increased to 2-hourly and continued for 24 hours from the last total score of 8 or higher. If pharmacotherapy is not needed the infant is scored for the first 4 days of life at 4-hourly intervals. • The first abstinence score should be recorded approximately two hours after birth or admission to the nursery (baseline score). This score reflects all infant behavior up to the first scoring interval time point. • Following the baseline score all infants should be scored at 4-hourly intervals, except when high scores indicate more frequent scoring. • The score sheet allows for 2-hourly scoring over the 24-hour period. • A new sheet should be started at the beginning of each day. • Scoring is dynamic. All signs and symptoms observed during the scoring interval are included in the point-total for that period. • If the infant’s score at any scoring interval is >8, scoring is increased to 2-hourly and continued for 24 hours from the last total score of 8 or higher. • If the 2-hourly score is <7 for 24 hours then 4-hourly scoring intervals may be resumed. • If pharmacotherapy is not needed the infant is scored for the first 4 days of life at 4-hourly intervals. • If pharmacotherapy is required the infant is cored at 2- or 4-hourly intervals, depending on whether the abstinence score is less than or greater than 8 throughout the duration of therapeutic period. • If after cessation of pharmacotherapy the score is less than 8 for the following 3 days, then scoring may be discontinued. • If after cessation of pharmacotherapy the score is consistently 8 or more, then scoring should be continued for the following 4 days (minimum) to ensure that the infant is not likely to develop late onset of withdrawal symptoms at home following discharge.

Scoring using Finnegan CNS
High pitched cry High pitched at peak – 2 High pitched throughout – 3 Scored if crying is prolonged Sleep Score longest uninterrupted interval of sleep Scoring for premature infant on 3 hr feeds 1 if <2 hours if <1 hour 3 if does not sleep Moro reflex Hyperactive - pronounced jitteriness of hands Markedly hyperactive - jitteriness/clonus of hands/feet

Tremors Undisturbed Mild – tremors of hands/feet when not being handled Moderate/severe –tremors of arms/legs when not being handled Disturbed Mild – tremors of hands/feet during handling Moderate/severe – tremors of arms/legs during handling Increased muscle tone Scored if no head lag or unable to extend arm/leg Excoriation Score when first appears or increases

Myoclonic Jerks Involuntary spasms of the muscle in face, arms and legs Irregular, quick and localized Seizures (generalized convulsions) Generalized jerky involuntary movements Subtle seizure activity Movement is not affected by interventions

Scoring using Finnegan Metabolic, Vasomotor and Respiratory
Sweating Score if sweating is spontaneous Hyperthermia (Fever) Axillary temperature Mild pyrexia from increased muscle tone/tremors Yawning Sign of over stimulation Score if >3 yawns within scoring interval

Mottling Marbling discoloration of the skin Also occurs when infant is chilled or premature Nasal Stuffiness Score if infant sounds congested Sneezing Sign of over stimulation Score if >3 sneezes within scoring interval

Nasal flaring Score if present without other signs of respiratory disease Respiratory rate Count for one minute Score 1 if >60 without other signs of respiratory disease Score 2 if >60 with retractions

Scoring using Finnegan GI Dysfunction
Excessive sucking Hyperactive/disorganized sucking Poor feeding Score if does not take adequate volume in 30 minutes or needs support to take minimum volumes If premature, adjust for gestational age Regurgitation Score if at least one episode is observed Loose/watery stools

NAS Treatment Therapeutic handling Calming techniques Swaddling
Holding in C position Calming techniques Sway Vertical rock Cuddlers

NAS Treatment Feeding Frequent smaller feeds Higher caloric feeds
IV fluids Breast feeding

NAS Treatment Pharmacologic interventions: Morphine Phenobarbital

St.Luke’s NBN algorythm

Safe Discharge Social Work involvement
Support structures Decreased symptoms – physiologically stable Appropriate growth with adequate intake

Safe Discharge Caregiver instructions Medication administration
Symptoms of withdrawal When to seek medical help How to reduce stimulation at home Calming techniques Equipment instruction Feeding instructions

Safe Discharge Rooming in Follow up after discharge
Assists caregiver to learn successful techniques Promotes bonding Enhances teaching Follow up after discharge Primary care provider Community resources

Family Resources

The difficulty in evaluating research in this area is enormous
The difficulty in evaluating research in this area is enormous. Clear methods for differentiating drug use from drug abuse are not established. The question of whether the mere presence of the chemical in maternal serum results in fetal damage needs to be answered. Evaluating if the mother in question has told the whole truth about her drug use is difficult. Given the stigma of substance abuse during pregnancy, lack of disclosure by the mother to her health provider is common because such damaging information could ultimately lead to the separation of mother and child. Many confounding factors may be recognized, such as the probability of polysubstance use and how this affects single-drug studies. Additionally, the fact that a mother has used an illicit drug (or even a legal substance such as alcohol or tobacco) intertwines with many other factors that can affect a child. Socioeconomic status, support systems, role of the father, lack of prenatal care, and the caregiving ability of the mother all play tremendous roles in child development. O’Donnell and colleagues measured the birth prevalence of neonatal withdrawal syndrome over time, associated maternal characteristics, and child protection involvement.[1] This retrospective cohort study used linked health and child protection databases for all live births in Western Australia from Maternal characteristics and mental health-related and assault-related medical history were assessed using logistic regression models. The study showed the birth prevalence of neonatal withdrawal syndrome increased from 0.97 cases per 10,000 live births to a high of 42.2 per 10,000 live births, plateauing after Mothers with a previous mental health admission, with a low skill level, with Aboriginal status, or who smoked during pregnancy were significantly more likely to have an infant with neonatal withdrawal syndrome. These infants were at greater risk of having substantiated child maltreatment allegation and for entering foster care. These results show an important pathway into child maltreatment and the need for well-supported programs for women who use illicit drugs during pregnancy and long-term support after birth of the child.

Neonatal Abstinence Syndrome (NAS)

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Neonatal Abstinence Syndrome (NAS)

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