Neonatal Abstinence Syndrome (NAS) is the withdrawal syndrome experienced by newborn infants who were exposed to drugs of dependency and addiction during pregnancy. With chronic exposure to addictive drugs, the fetus, like adults, develops a tolerance to the drugs. At birth, maternal drug supply is abruptly cut off and the infant withdraws.

The most common cause of NAS is exposure to prenatal opioids. For centuries, NAS was considered an almost inevitably fatal problem. First appearing in Western literature in 1874 as “congenital morphinism” (as the most common opioid used by mothers was morphine), NAS led to death and serious complications including seizures and failure to thrive in more than 80% of infants. As recently as the 1950s, mortality rates for infants with NAS was as high as 34%.² Today, infants seldom die of NAS because clinicians are more vigilant and administer prompt treatment, usually with the drugs that caused the withdrawal in the first place.

Unfortunately, the world is undergoing an opioid epidemic and babies are collateral damage. In North America, for example, one infant is born every 18 minutes with NAS.³ In many countries, the use of Fentanyl, a synthetic opioid that is 100 times more potent than morphine and 50 times more potent than heroin, is increasing and often, the drugs are laced with other substances that increase the potency and adverse effects associated with drug abuse.⁴

In most cases, if diagnosed early and treated promptly, most infants will completely recover from NAS and be discharged alive from their hospital of birth. However, they face many challenges, both from exposure to prenatal drugs during critical periods of fetal development and from the consequences of parental drug use.

In linked data studies, where administrative data is linked for individuals, we showed that children with a history of NAS were more likely to die, especially in the first year of life and be hospitalised even until teenage years, from external and unclear events, such as Sudden Infant Death Syndrome (SIDS), assaults, maltreatment, accidents and trauma.⁵ They were also more likely to fail at school, from as early as age 8–9 years.⁶

Whether people who have been exposed to prenatal drugs of addiction are more likely to engage in risk taking behaviours in later life is unclear. Young adults with a history of prenatal cocaine exposure are more likely to be arrested and have earlier onset of sexual behaviours.⁷ These problems are more likely to affect males and are considerably influenced by environmental factors such as level of parental involvement in their upbringing and exposure to violence during early life. Risk of “addictive” behaviours is an important question and requires further study because poor environmental circumstances, such as poverty, lack of education or social support, will increase a person’s risk of substance use anyway.

Drugs of addiction work by altering levels of neurotransmitters. These are chemicals that transmit messages within the nervous system and are responsible for the “rush” associated with drug use. With continued use, more and more drugs are needed to achieve the “rush”, resulting in tolerance. With time, the neurones that make these neurotransmitters are depleted and the person becomes dependent on the drug just to achieve normal activity. The brain is also impacted by other effects of the drugs. For example, opioids accelerate neuronal death, promote inflammation within the brain and like many drugs of addiction, are anorectic agents, reducing appetite and therefore nutrition to the exposed person.

Babies who are exposed to prenatal drugs are often born with smaller heads that fail to grow as fast as other children. In the population, lower brain volumes are equated to lower cognitive ability. However, imaging and neurodevelopmental studies also show that these changes and others are persistent. Babies with a history of opioid exposure, for example, have abnormal functional activity within their brains, manifest poorer cognitive and motor scores from infancy and have poorer academic outcomes, even until teenage years.⁸

The environment is a crucial modifying factor for babies who start of life on the back foot. Many children with a prenatal history of drug exposure are born into adverse circumstances and are at risk of child harm. In Australia, up to 50% of babies with a history of prenatal methadone exposure, are placed (whether temporarily or permanently) in out of home care (OOHC) by age 5.⁹ Parents with drug use problems may have difficulties parenting due to a myriad of issues. Up to 50% may have one of more psychiatric co-morbidities, some may have low education levels and poor parenting references themselves, some may have poor social networks and some may not have adequate nutrition due to poverty and other financial stressors. The chaotic nature of many households impacted by substance use further compound the fragile neurodevelopmental trajectories of many children with a history of prenatal drug exposure and NAS.

Often, parental drug use cannot be stopped prior to pregnancy. The brain forms by the fourth to fifth week of gestation and drug exposure, more often than not, has already occurred. However, the brain does not stop developing and this growth potential offers an opportunity to ameliorate the harms from prenatal drug use.

Neuroplasticity is a term that describes how the brain changes with experience. Over the first few years of life, brain cells, or neurones, grow and differentiate at an incredible pace. By birth, each neuron has about 2500 synapses or connections between the neurones and by age 2–3 years, each neuron has about 15,000 synapses. With experience, the brain learns to discard neurons that are not useful and grow those that are. For example, if animals have an eye blindfolded from birth, they learn not to see from the obstructed eye and sight never returns. This pruning process is shaped by experience and other factors. Excessive pruning, for example, is implicated in risk of schizophrenia while insufficient pruning, with autism spectrum disorders. Pruning starts at about 8 months within the visual cortex and continues even to young adulthood in the prefrontal cortex, an area that governs planning, prioritising and executive decision-making.

There is therefore an exciting opportunity to shape a child’s experience after birth to mitigate harms from prenatal drug exposure. In both human and animal studies, environmental manipulation is crucial in ameliorating intra-uterine harm. An enriched environment (EE) with targeted educational intervention, parental support and improved dietary intake can not only promote neural development by enhancing neuroplasticity but also play a role in repairing neurons by restoring functional activities through cellular and molecular adaptations. The US Carolina Abecederian Project,¹⁰ conducted between 1972 to 1977, enrolled children from low income families to full-time high quality educational interventions in a child-care setting from infancy to age 5. The children’s progress was monitored through time. Even at 30 years of age, those engaged in early intervention showed improved educational outcomes, employability, as well as better physical and mental health. EE has even shown to improve brain development on MRI studies with a particular effect on the hippocampus, the area of the brain governing memory acquisition.

Parental drug use and especially, maternal drug use resulting in NAS, is a multifactorial and multi-disciplinary issue. Therefore, the many sectors involved in the care of the mother and family with drug use issues need to collaborate and work together to ensure that the needs of these vulnerable families are met, not only during the birth period but also until the child grows to be an independent adult. Each sector must appreciate that the needs of the families will change and that the child may evolve, depending on the environment and how he/she has been impacted by the exposures before birth.

A large body of evidence from other countries such as the United States, show that persecutory approaches, where prenatal substance use is a considered a criminal offence, do not improve outcomes for the mother/infant dyad. Mothers with drug-use issues need to be supported to make the best decisions to keep both her and her family safe. This may include helping her with accessing antenatal, addiction and other medical services, ensuring that she or her family have food and housing security and that any other issues such as legal or social needs are met.

Although activation and involvement of child protection services is stressful for both the family and for care providers, in some circumstances, the support required by a family drug-use issues can only be accessed through such services. In the general community, children in the care of child protection services are a heterogenous group and in some situations, being engaged in these services are associated with increased risk of harm including mental health issues, poor school outcomes and even death.

In a recent linked data study, we showed that children with a history of prenatal drug exposure but who had at least one episode of out of home care (OOHC, placement in a home away from their biological parents) whether permanently or temporarily, had decreased risk of death and school failure.¹¹ Placement had to be culturally sensitive. This impact was only evident in First Nations children with a history of prenatal drug exposure if they were placed in kinship (related) care rather than foster (unrelated) care.

NAS, from prenatal drug exposure, is unlikely to “go away”. People worldwide are increasingly using more drugs of addiction and the drugs are increasingly varied and potent. Women of child bearing age who use these substances risk impacting the developing fetus and growing child if they are pregnant. The ramifications of prenatal drug exposure on the child extend beyond newborn withdrawal and may continue to affect the child for life. Mitigation strategies are crucial and require a community to understand and provide multisectoral support for the mother, child as well as the clinician and care-givers. Further research is urgently required to understand the long-term impact of prenatal exposure to drugs that cause NAS and if these are adverse, to develop resources to minimise lifetime harm to the children.