Prenatal exposure to opioids may alter brain development: study

A disturbing aspect of Canada's opioid crisis is that more babies are being born to mothers who use fentanyl and other opioid drugs. The Canadian Institute for Health Information says more than 1,800 infants per year are born with symptoms of opioid withdrawal. A study presented Monday at the 105th Scientific Assembly and Annual Meeting of the Radiological Society of North America suggests that prenatal exposure to opioids may have a significant impact on the brain development of unborn children.

A team of obstetricians, neonatologists, psychologists and radiologists led by Dr. Rupa Radhakrishnan, a radiologist at Indiana University School of Medicine, did functional MRI brain scans on 16 full-term infants. Eight of the infants had mothers who used opioids during pregnancy and eight had mothers who did not use opioids. 

The brain imaging technique used by the researchers is called resting state functional MRI (fMRI). The technique enabled researchers to measure brain activity by detecting changes in blood flow. The technique permits researchers to measure how well different regions of the brain talk to one another. 

The researchers found abnormal connections to and from a part of the brain called the amygdala. It's a region that is responsible for the perception and regulation of emotions such as anger, fear, sadness and aggression.

This is one of the first studies to suggest that the brain function of infants may be affected by prenatal exposure to opioids. Abnormal function in the amygdala could make it difficult for children exposed to opioids to regulate their emotions. That could have serious implications on their social development and on their behaviour. 

The researchers say the study is small. They say they aren't certain as to the clinical implications of this study.  A long-term outcome study is underway to understand better the functional brain changes caused by prenatal opioid exposure and their associated long-term developmental outcomes. 

How newborns face opioid withdrawal

This research may become even more important should current trends continue, and we see an increase in the number of infants exposed to opioids prenatally.

What makes the study's results plausible is that it's well-known that opioids can pass through the placenta from mother to baby. Regular use of opioids by the mother leaves the baby physically dependent on opioids. Immediately upon birth and the cutting of the umbilical cord, the baby stops receiving opioids. That puts them in a state of opioid withdrawal. 

Neonatal abstinence syndrome (NAS) is the name of the withdrawal condition. Fentanyl and other opioids cause withdrawal in over half of babies exposed prenatally. Cocaine may cause some withdrawal, as can amphetamines and barbiturates. Symptoms vary depending on the type of substance used, the last time it was used, and whether the baby is full-term or premature. Withdrawal symptoms begin as early as 24 hours and as late as 10 days following birth. 

The most common symptoms include:

• Tremors.
• Irritability.
• Poor sleep problems.
• High-pitched crying.
• Increased muscle tone.
• Hyperactive reflexes.
• Seizures.
• Yawning.
• Stuffy nose.
• Sneezing.
• Poor feeding.
• Vomiting.
• Diarrhea.
• Dehydration.
• Sweating.
• Fever.

The number of babies with NAS is going up in Canada. Between half and three quarters of these infants require some sort of treatment for opioid withdrawal.

Pioneering rooming-in approach 

At many hospitals, the time-honoured approach to treatment of NAS has been to whisk the newborn off to the neonatal intensive care unit (NICU). There, they are watched carefully for symptoms and signs of opioid withdrawal and, when necessary, given small doses of morphine to counteract the effects of withdrawal. 

That approach is intense, expensive and time-consuming, with newborns staying in in hospital for 15 days on average, and the mother discharged from hospital within a day or two of birth. It also separates newborns from their mothers. Given the history of substance use and the social backgrounds of some of the mothers, it's not uncommon for child protection authorities to intervene if they think the child is at risk. All of this can be extremely stigmatizing to new mothers.

A growing body of evidence points to a very different approach called rooming-in. Instead of whisking the newborn to the NICU, the rooming-in approach permits mothers and infants to stay together in a private room and bond through skin-to-skin contact and breastfeeding. 

There is growing evidence that these interventions may be as or even more effective as morphine in combating infants' withdrawal symptoms. 

The approach was pioneered by Dr. Ron Abrahams at BC Women's Hospital and was brought to Kingston General Hospital by Dr. Adam Newman.  A growing number of hospitals have either adopted rooming-in or are looking at its implementation. In 2018, the Canadian Paediatric Society endorsed rooming-in when feasible.

One wonders if the rooming-in approach might help foster more normal postnatal development of the amygdala. Now that would be a fascinating and telling experiment to see.