Introduction


Even pregnancy is insufficient motivation for many women to stop using drugs. There are many drugs of abuse that can readily cross the placenta and affect the fetus. The consequences can be miscarriages, premature deliveries, low birth weight, congenital deformities, and an increased risk of sudden infant death syndrome. The infant of a woman addicted to narcotics, such as morphine, is also likely to develop withdrawal symptoms within a few hours after delivery, but occasionally symptoms do not develop until late in the first week of life. The use of any drugs during pregnancy can lead to many medical complications for the mother and the baby, including elevated rates of premature labor, abruptio placentae, precipitous labor, and growth retardation. Because addictive drugs cross the placenta, a newborn may suffer from withdrawal or neonatal abstinence syndrome after birth when the supply of drugs from the mother is suddenly cut off (Black & Schuler, 1995).


 


Literature Review


Neonatal abstinence syndrome refers to the certain group of symptoms and signs displayed by neonates or infants with drug dependencies. These are usually characteristics of symptoms and signs of withdrawal. There are two major types of neonatal abstinence syndrome, the prenatal neonatal abstinence syndrome and the postnatal neonatal abstinence syndrome. The cause of prenatal neonatal abstinence syndrome which is maternal substance abuse has both developmental and medical effects for the newborn, in addition to the health, economic, and legal outcomes for the mother. Postnatal neonatal abstinence syndrome is a result of an occurrence of an abrupt discontinuation of opioid analgesia, which usually happens after prolonged drug exposure. Neonatal abstinence syndrome is more pronounced in infants with long-term exposure to fentanyl than in those who are exposed to morphine (Belik & Hawes, 2006).


            Neonatal abstinence syndrome usually appears within 72 hours of birth; the infant may die if the withdrawal is severe and untreated. Manifestations of neonatal abstinence syndrome depend on a variety of factors, including the drug that was used, the dose of the drug, frequency of use, and the neonate’s own metabolism and elimination of the active compound or compounds (Belik & Hawes, 2006). It is important to note that neonates are more sensitive to many drugs. Newborns are deficient in the liver microsomal enzyme systems that are involved in the metabolism of many drugs.


Although neonatal abstinence syndrome depends on type of drug exposure and obstetric factors, it may involve the autonomic (for example, sneezing or yawning), central nervous (for example, tremors, irritability, abnormal suck or poor feeding), pulmonary (for example, increased apnea), and gastrointestinal (for example, diarrhea and vomiting) systems of the newborn (Sun, 2004). Characteristics of neonatal abstinence syndrome include convulsions and tremors, jitteriness, high-pitched crying, increased muscle tone or hypertonicity, diarrhea, irritability, respiratory distress, yawning, sneezing, sweating, mottling, vomiting, and fever (Black & Schuler, 1995).


Neonatal abstinence syndrome is often a disorder that affects many systems in the body of the neonate and as previously mentioned frequently involves the gastrointestinal and central nervous systems. In addition, prenatal neonatal abstinence syndrome depends on the neonate’s last exposure to an intrauterine drug and also the drug metabolism and excretion of the mother. The symptom of withdrawal is generally a function of the half-life of the drug (Belik & Hawes, 2006).


Although many cocaine-exposed infants do not display signs of neonatal abstinence syndrome, perhaps related to the short half life of the drug, recent research suggests that some cocaine-exposed infants may show signs of withdrawal, described as “excitable.” Infants undergoing withdrawal tend to sleep less than non-drug exposed infants and to suffer from gastrointestinal distress. Infants who are unpredictable, unreadable, or unresponsive are less likely to be involved in effective, rewarding interactions with their mothers. Thus, drug-exposed infants may have temperamental qualities that make caregiving difficult with few immediate rewards (Black & Schuler, 1995).


To better understand morphine as treatment for neonatal abstinence syndrome, it is better to discuss first about the effects and action of morphine. Morphine is the principal alkaloid of opium. It is among the drugs that are widely abused. A good grade of opium contains 9-14% morphine. It is also a metabolite of codeine. It is rapidly absorbed after subcutaneous, intravenous, or intramuscular administration. Absorption after oral administration is variable. It is widely distributed in the body, mainly in the kidney, liver, lungs, and spleen with lower concentrations in the brain and muscles. It does not accumulate in the tissues.


Morphine, an opium alkaloid, is the prototype of the narcotic analgesics. Morphine thus relieves pain. It provides analgesia at a dose that does not result in severe alterations in consciousness. Morphine is not very affective when given orally. It is biotransformed before reaching the general circulation, undergoing conversion to inactive metabolites in the liver and other tissues. The resulting water-soluble products are then excreted in the urine.


It is particularly effective when given intrathecally. There are at least three nonmutually exclusive sites at which opioids, which have morphine-like action, could act to produce analgesia. These are peripherally, at the site of an injury; in the dorsal horn “gate,” where nociceptive fibers synapse on dorsal root ganglion cells; and at more rostral sites in the brain stem (Ganong, 2001).


            Opioid receptors are produced in dorsal root ganglion cells and migrate both peripherally and centrally along their nerve fibers. In the periphery, inflammation causes the production of opioid peptides by immune cells, and these presumably act on the receptors in the afferent nerve fibers to reduce the pain that would otherwise be felt.


            Morphine is mainly excreted in the urine as the 3-glucuronide (65-70%) with only 10% as the free compound. Thus, for sensitive screening, the urine must be hydrolyzed. This can be done by enzymatic or acid hydrolysis. Since morphine and codeine are often found together the thin layer chromatographic system described was developed to separate both of these compounds.


People have used opium and its derivatives (opiates) for thousands of years to relieve pain and stress. Opiates such as morphine are generally extracted from the seedpods of certain varieties of poppy plants. Heroin, however, is a chemically altered form of morphine. Opiates such as morphine can produce the most intense effects on both the mother and the infant. Aside from the withdrawal symptoms characteristic of neonatal abstinence syndrome, the usual findings in infants exposed to opiates include low birth weight, intrauterine growth retardation, and prematurity. Some delayed withdrawal signs and symptoms may occur up to 6 days to one week after birth (Belik & Hawes, 2006)


            In spite of the escalating clinical burden of neonatal abstinence syndrome, optimal managementstill remains unclear as clinical trial evidence is not sufficient. Conservative measures such as minimal stimulation and holdingmay be sufficient if symptoms are non-progressive and mild. However,the more critical symptoms require plenty of pharmacotherapy. There are manypharmaceutical agents that have been used historically to treat neonatal abstinence syndrome,including clonidine, chloral hydrate, chlorpromazine, opioids,opiates, and phenobarbitone. Studies up to the present can be criticizedon their problemswith randomization, lack of standardization of outcome measures, and the failure to use a pre-evaluated system of scoring to allow standardization of the start of treatment, termination of pharmaceutical treatment, and dosage alterations (Jackson, et al, 2003).


Infants who have neonatal abstinence syndrome secondary to maternal drug treatment during pregnancy for addiction to opiate must have a treatment for her withdrawal and this often results in a lengthy hospital stay. The results of a case study to determine if there are modifiable factors that influence the length of hospital stay of infants with neonatal abstinence syndrome indicate that receiving doses of neonatal opiate solution every 3 to 4 hours instead of every 6 hours may decrease the length of hospital stays for the infants. 41 infants who were born to mothers who were receiving drug treatment for opiate addiction at time of delivery were the participants in the study. There are factors that were analyzed to see if they were connected with an increased length of hospital stay. These factors were maternal methadone dose, number of Finnegan scores over 8 prior to initiation of therapy, Finnegan score at initiation of therapy, day of life when therapy was initiated, initial and peak dose of neonatal opiate solution. It was found out in the study that the peak dose of neonatal opiate solution and dosing interval are significantly related to length of hospital stay. The researcher of this study believes that more frequent dosing of the neonatal opiate solution may decrease the length of hospital stays for these infants (Rose, 1999).


In one particular study using morphine as treatment, oral morphine sulphate was selected as a treatment option since opiates are the predominant class of drugsused by drug dependent pregnant women in the area relative to the study. A sample size of 80 was estimated todetect a 0.5 SD difference in the total duration of pharmacologicaltreatment between the treatment groups.


After obtaining informed written parental consent, neonateswith a history of maternal drug use and two sequential scoresof > 4 using the Lipsitz tool were considered eligiblefor randomization in the study. Alternative diagnoses for a babywho is irritable were not included by clinical examination and biochemical analysis(Jackson, et al, 2003).


By random, the infants were to receive morphine sulphate or phenobarbitoneorally, both labeled as substance A and substance B respectively.The morphine sulphate was prescribed in a doseof 50 µg/kg and a dose of 2 mg/kg for the phenobarbitone. Bothof these drugs were administered four times a day in equal volumes as identical colorlessand odorless solutions (Jackson, et al, 2003).


Data from this study and various others reveal that in comparison, the use of opiates with other agents to treat symptomatic neonatal abstinence syndrome are limited. Morphine all alone was superior to the combination of phenobarbitoneand diazepam, and to the combination of morphine, phenobarbitone,and diazepam.


In another randomized study, pregnant women who were dependent on opiates or who abusedpolysubstances were treated with slow release morphine of intermediatelength half life and the results showed that this did not reduce neonatal abstinence syndrome more than methadone did. Women who received slow release morphine used fewer opiates and benzodiazepines additionally than women who received methadone.All the children were born healthy according to the study (Fischer, et al, 1999).


Most interventions for drug-dependent pregnant women have been directed at the prenatal period, with significant positive effects. More recent programs feature postpartum intervention components. In contrast to the absence of data on postpartum interventions for drug-dependent mothers and their infants, there is a rapidly growing literature on drug rehabilitation programs for drug-abusing adults.


A recent review of this literature has suggested that outpatient treatment is at least as effective as inpatient treatment. In three studies, follow-up clinical outcome was superior, treatment was shorter, and costs were lower for outpatients than for inpatients. The absence of data on interventions for specific drugs used by mothers, particularly teenagers, and their infants highlights the importance of further research (Field, et al, 1998).


This 4-month intervention program consisted of several components, including drug and social rehab, parenting and vocational classes, and relaxation therapy (aerobics, progressive muscle relaxation, music mood induction, and massage therapy), and took place afternoons in a vocational high school the mothers attended. Mornings were spent in high school or prep classes. The infants of these mothers received day care while they were in classes and the rehab program. In addition, the mothers spent approximately 1-2 hours per day in the nursery school, helping to take care of their infants. The nursery was designed for multilevel infant enrichment and was staffed by a head teacher, two assistant teachers, and three of the mothers, who served as teacher-aid trainees. It served 12 infants at a time (Field, et al, 1998).


Neonatal abstinence syndrome babies are treated with low doses of drugs that answer their bodies’ inborn craving for narcotics and calm their overwrought nervous systems. These medications may include tincture of opium, methadone, phenobarbital and others. The doses are decreased over time in a weaning process that can take several weeks or longer. During this time, babies must be intensively monitored to ensure they’re not overmedicated, which could lead to cardiac or respiratory arrest, brain damage and death. In one healthcare setting, each tiny bedside is crowded with equipment — heart monitors, oxygen sensors, feeding tubes, vital sign recorders, intravenous pumps and more. Once they’re relatively stable, babies may be transferred to the less-hectic neonatal continuing care nursery and then to the general pediatric unit (Haskell, 2006).


 


Conclusion


Treatment of addiction requires months or years of individualized rehabilitation. Brain alterations and behavior patterns consolidated by long-term drug exposure do not disappear with detoxification or short- term, inpatient rehabilitation programs. While the preferred goal of treatment is complete abstinence, relapses are likely. Consequently, a prolonged period of outpatient care is necessary. While most drug- related addictions are improvable, there are no cures.


Newborn infants rarely die from drug withdrawal, but long term effects have not been thoroughly studied. Most crucial in the management of infants of mothers who have a drug addiction is the evaluation of the home situation to determine if the infant will be safe following discharge from the hospital. The support of the relatives, friends, and health professionals may enable the mother to care for the infant. Otherwise, an alternative care plan may be in the best interests of the infant.



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