Approach Considerations
The length of hospitalization in patients with neonatal abstinence syndrome (NAS) varies, depending on the drug, withdrawal symptoms, and social factors. In a 2016 report, gestational age at birth was not associated with pharmacologic requirements to manage NAS in late preterm and term infants. [62] When medication is needed, term infants may receive such therapy longer than their preterm or late-term counterparts.
Other issues that need to be addressed include breastfeeding and infectious disease prevention. If the mother abuses intravenous drugs, screen for human immunodeficiency virus (HIV), hepatitis B and hepatitis C, Chlamydia,syphilis, and gonorrhea.
Breastfeeding confers immunologic benefits to the neonate, and bonding benefits the mother. One study reported that only small amounts of methadone were detected in breast milk of women maintained on higher doses of methadone and recommended breast feeding for methadone-maintained women. [63] The benefits of breastfeeding often outweigh the effect of the small amount of methadone that enters the breast milk.
The previous recommendation of the American Academy of Pediatrics (AAP) was for mothers receiving maintenance doses of methadone more than 20 mg/24 h not to breastfeed. [64] However, the AAP now classifies methadone as compatible with breastfeeding. [65] The ACOG recommends that breastfeeding should be encouraged in patients without HIV who are not using additional drugs and who have no other contraindications. [66]
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used antidepressants in postpartum mothers. In general, SSRIs are well tolerated and effective for the mothers and probably are safe for their breastfeeding infants. Sertraline and paroxetine have minimal transfer into human milk and no adverse effects on infants. In contrast, fluoxetine produces significant plasma concentrations in some breastfed infants, especially if the exposure began in utero. Infant should be monitored closely for signs such as uneasy sleep, irritability, and poor feeding or sucking. [67, 68]
Enrollment in a drug rehabilitation program may be a prerequisite for breast feeding. Both marijuana and alcohol exposure through breast milk result in decreased motor development at age 1 year.
Breastfeeding is contraindicated if the mother is still using illicit drugs or has HIV infection.
The Substance Abuse and Mental Health Services Administration (SAMHSA) released Clinical Guidance for Treating Pregnant and Parenting Women with Opioid Use Disorder and Their Infants in 2018. This clinical guide provides comprehensive, national guidance for optimal management of pregnant and parenting women with opioid use disorder and their infants. The clinical guidance offers standard approaches to a range of real-world scenarios faced by healthcare professionals working with mothers and infants. For each scenario, the guidance offers clinical action steps and supporting evidence. The action steps reflect the best available treatment, including medication-assisted treatment for the mother and infant and appropriate types of social supports and follow-up services. [69]
Medical Care
The large number of infants who suffer from neonatal abstinence syndrome (NAS) and the associated long-term morbidity mandate that affected infants be accurately identified and their treatment and support should be optimized. Note the following:
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The assessment and management of NAS pose difficulties for staff and families and have been hampered by a lack of prospective studies and by few research studies that specifically assess the merits of one management approach over another.
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Infants at risk for NAS should be carefully monitored in the hospital for the development of signs consistent with withdrawal. The appropriate duration of hospital observation is variable and depends on a careful assessment of the maternal drug history. An infant born to a mother on a low-dose prescription opiate with a short half-life (eg, hydrocodone) may be safely discharged if there are no signs of withdrawal by age 3 days, whereas an infant born to a mother on an opiate with a prolonged half-life (eg, methadone) should be observed for a minimum of 5-7 days. [40] After discharge, outpatient follow-up should occur early and include reinforcement of the education of the caregiver about the risk of late withdrawal signs.
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Vomiting and diarrhea leading to dehydration and poor weight gain, in the absence of other diagnoses, are indications for treatment, even in the absence of a high drug-withdrawal score.
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In the delivery room, naloxone use is contraindicated in infants whose mothers are known to be dependent on opioids because of the risk of neonatal seizures from abrupt drug withdrawal. However, in the absence of a specific history of opioid abuse in a mother who has recently received narcotics, naloxone treatment remains a reasonable option in the delivery room management of a depressed infant if the infant continues to demonstrate respiratory depression after positive pressure ventilation has restored normal heart rate and color.
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The initial care of all infants who have been exposed to substances in utero and show signs and symptoms of withdrawal should be individualized, supportive, and nonpharmacologic (because pharmacologic therapy can prolong hospitalization and exposes the infant to additional agents that are often not necessary). The treatment for morphine administration has been reported to last 8-79 days. [70] This length of hospitalization interferes with maternal bonding, raises the potential for nosocomial infection, and is a major use of resources. [70]
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Studies suggest that infants who stay in the room with their mothers have a shorter length of stay, lower hospital costs, and reduced need of pharmacologic therapy, and they are more likely to be discharged home with their mothers. Rooming-in has also been associated with improved breast-feeding outcomes, and greater maternal involvement in the care of the newborn. [71, 72]
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Although rooming-in is a promising nonpharmacologic strategy, there are barriers to the implementation of this practice. Lack of funding, lack of personnel, and lack of appropriately designed hospital units may prevent many hospitals from providing rooming-in as a standard practice. [73]
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A recent study showed that acupuncture appears to be safe and effective for reducing withdrawal symptoms in infants, and suggested that it should be considered as an additional nonpharmacologic treatment option for NAS. [74]
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Pharmacotherapy for infants with more severe expression of neonatal abstinence syndrome is necessary to allow them to feed, sleep, gain weight, and interact with caregivers. Approximately 30-91% of infants who exhibit signs of NAS receive pharmacologic treatment. Although opioids are used to treat NAS, the best pharmacologic treatment has not been established. However, the limited available evidence from controlled trials of neonatal opioid withdrawal supports the use of oral morphine solution and methadone when pharmacologic treatment is indicated. Growing evidence suggests that oral clonidine is also effective either as a primary or adjunctive therapy, but further prospective trials are warranted. [40]
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There is evidence that, compared with oral methadone treatment, oral morphine sulfate therapy for NAS reduces the length of stay in the hospital and neonatal intensive care unit (NICU), treatment duration, maximum opioid requirements, and total cost. [75] However, two more recent studies showed that methadone had a shorter length of neonatal withdrawal treatment compared to that of morphine and shorter length of stay. [76, 77]
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Treatment with sublingual buprenorphine for NAS appears to be associated with a shorter duration of opioid therapy and hospitalization compared with oral methadone therapy. [78, 79, 80] Studies comparing buprenorphine to morphine have shown shorter duration of treatment and shorter hospital stay in infants treated with buprenorphine. Both groups had similar rates of side effects. However, these studies were single institution including small sample size. [81] More recent larger studies have demonstrated comparable findings. [80]
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There is significant variability in the severity of NAS due to in utero opioid exposure. Studies have shown that single nucleotide polymorphisms (SNPs) in opioid receptors and the prepronociceptin (PNOC) genes are associated with NAS severity. [82] Another study showed that among infants with NAS, variants in the μ-opioid receptor (OPRM1) and catechol-o-methyltransferase (COMT) genes were associated with a shorter length of hospital stay and less need for treatment. [83] However, the investigators suggested that further studies are needed in a larger sample.
Nonpharmacologic approaches include the following [1, 84] :
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Assess daily for signs of withdrawal, sleeping habits, feeding patterns, and weight gain.
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Room-in the infant.
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Minimize environmental stimuli by reducing light exposure, minimize excessive noise, avoid unnecessary handling, provide swaddling, and non-nutritive sucking with a pacifier.
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Breastfeed the infant.
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Provide frequent small feeds of hypercaloric formula and adequate nutrition to minimize weight loss.
Weaning
In a study of 547 late preterm and term neonates with narcotic abstinence syndrome who received inpatient pharmacologic treatment, including 417 who were managed with an established weaning protocol and 130 who were managed without an established weaning protocol, researchers found that use of a stringent weaning protocol reduced the duration of opioid exposure and the length of hospital stay. [85]
After adjustment for treatment site, infants who underwent protocol-based weans had a significantly shorter duration of opioid treatment (17.7 vs 32.1 days; P < 0.0001) and a significantly shorter hospital stay (22.7 vs 32.1 days; P = 0.004). [85] There was no difference among infants who received protocol-based weaning in duration of opioid treatment or length of hospital stay between those treated with morphine and those treated with methadone. The duration of administration of phenobarbital was significantly longer among patients treated with morphine compared with those treated with methadone (P ≤ 0.002). [85]
Transfer
Newborns with NAS are frequently cared for in NICUs. Studies suggest that care for NAS delivered in hospital settings outside of the NICU and outpatient management reduces length of stay and cost. [86, 87]
Consultations
Interdisciplinary intervention for the mother and her offspring (and the father, when possible) should be available at all points of access to care. Professionals involved in this care should include obstetricians, neonatologists, pediatricians, nurses, nutritionists, mental health professionals, social workers, substance abuse counselors, and child development specialists, at a minimum.
Diet and Activity
Diet
The American Academy of Pediatrics (AAP), The American College of Obstetricians and Gynecologists (ACOG), and the Academy of Breastfeeding Medicine (ABM) support breastfeeding among opioid-dependent women if the women are enrolled in substance abuse treatment and no contraindications to breastfeeding are observed, such as ongoing drug use or HIV infection. [40, 66, 88]
Frequent small feedings are preferable and should provide 150-250 kcal/kg per 24 hours for proper growth of the infant undergoing significant withdrawal.
Neonates undergoing treatment of NAS have increased caloric requirements and may develop hyperphagia. Therefore, careful monitoring of fluid intake and weight gain are essential.
Activity
Swaddling, pacifiers, low lighting, oscillating cribs, and avoidance of abrupt changes in the infant's environment can be helpful.
Prevention
Identification of substance abuse was the first step in attempting to break the cycle of reproductive morbidity or mortality. Ideally, substance use should be terminated by women and their male sexual partner before conception. Pregnant drug-using women should be counseled at the earliest opportunity to abstain completely from all injurious substances and to seek prenatal care. Adequate dietary intake and supplemental prenatal vitamins should be stressed.
Early drug screening during pregnancy reveals the need for counseling in pregnant women with a history of drug abuse.
Federal, state, and local agencies should reduce barriers to the use of family planning services and increase access to early prenatal care and other health services, including drug rehabilitation.
Health education specifically targeting consequences of drug abuse during and after pregnancy is beneficial to prevent this growing social problem.
Long-Term Monitoring
The infant's discharge should occur after the following criteria are met:
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The infant is taking oral feeds and gaining weight satisfactorily.
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The infant is physiologically stable (has normal vital signs including blood pressure).
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The infant is showing neurobehavioral recovery (can reach full alert state, responds to social stimuli, and can be consoled with appropriate measures).
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All necessary assessments have been completed because adherence to follow-up schedules cannot be ensured.
Drug abuse during pregnancy is associated with medical, psychological, and economic problems that require extensive evaluation by qualified service providers. Mothers and fathers of drug-exposed infants need substance abuse treatment and a wide array of services to support them in their parenting role. Provision must be made for such services prior to an infant's discharge.
Provide follow-up care in the first few weeks to months of life to assess infant growth, behavioral characteristics, and motor ability.
Discharging otherwise healthy infants home once they are stable on treatment for neonatal abstinence syndrome can reduce hospital stay and associated costs. However, a safe discharge of the infant requires that support structures within the home and community are in place. In one study, compliance with the necessary clinic attendance was facilitated by establishment of a weekly follow-up clinic. This continuity of care was provided by staff with whom the families were familiar and which met all the families' needs for the infants, including vaccinations, subspecialist appointments, and prescriptions.
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Neonatal Abstinence Syndrome. Neonatal abstinence syndrome scoring form.
