Association of Cannabis with Apneic Episodes in a Breastfed Infant: A Case Study

Introduction

In the United States, cannabis is legal for medical use in 37 states and the District of Columbia (D.C.) and is legal for recreational use in 21 states and D.C. ¹ The expanding legalization of cannabis has been accompanied by an increase in use and perceived safety among pregnant women. According to the National Survey on Drug Use and Health, cannabis use among pregnant women increased from 2.37% to 3.85% between 2002 and 2014, which may even be an underestimate given that these values were self-reported. Many of the surveyed women who reported cannabis use in the pregnancy and postpartum period cited its ability to mitigate symptoms such as nausea, vomiting, anxiety, and mood instability. ² A more recent survey in 2018 found that 4.7% of pregnant women and 7.1% of nonpregnant women reported using cannabis in the past month. ³ In their analysis of attitudes toward cannabis use among pregnant women, Jarlenski et al. found that 16.5% of those with no use and 65.4% of those with use within the past month believed that weekly cannabis use was harmless. ⁴

Not only does cannabis contain many chemical entities with varying properties, of which the main psychoactive component is delta-9-tetrahydrocannabinol (THC), but also, multiple modalities exist to consume cannabis, including through inhalation and ingestion. ² Further, cannabinoid products are becoming increasingly stronger and are more frequently laced with other illicit drugs than in decades past. The metabolism of cannabis and the bioavailability of THC vary greatly depending on user-specific factors, as well as how the cannabis has been prepared and consumed. Exogenous cannabinoids such as THC are generally first metabolized by the liver prior to being stored in peripheral tissues as stable metabolites, although intact THC has been found in breast milk and other tissues. ² Over time, the metabolites are renally excreted, but this process can range from days to weeks, as the highly lipophilic nature of THC facilitates its slow release from adipose tissue. ² Notably, cannabis metabolites are able to cross the placenta, so fetal exposure is possible if a mother uses cannabis during pregnancy.^2–3 Studies suggest that fetal exposure to cannabis can negatively impact the developing fetus and may have long-term neurobehavioral consequences, such as growth delay, hypotonia, and increasing susceptibility to neuropsychiatric disorders later in life.^3,5,6 Cannabis byproducts can also be passed into breast milk, but the extent of passage and its effects on the infant have not been fully elucidated.^7–10 The lack of sufficient long-term data on the outcomes of infants exposed to cannabis through breast milk has contributed to mixed views among health professionals on the acceptability of breastfeeding in the context of cannabis use. For example, among the 74 lactation consultants surveyed on this issue in 2015, 44% reported that their recommendations regarding breastfeeding and marijuana use are contingent on variable factors such as frequency of maternal use, 41% would still recommend breastfeeding despite cannabis use, and 15% would not recommend breastfeeding in the setting of cannabis use. ⁷ However, due to the potential for harm, current professional guidelines generally discourage the use of cannabis while pregnant and breastfeeding and recommend informing mothers of the possible long-term effects on their infants.^5,8

Estimates of infant exposure to THC through breast milk have ranged from 0.4% to 8.7% of weight-adjusted maternal dosage.^8–10 Other studies have reported the milk:plasma ratio (M:P) of THC as between 6 and 7, suggesting that THC may accumulate in the breast milk at higher concentrations than in the mother’s bloodstream.^11–12 For context, the M:P ratios of most drugs commonly accepted as safe for use in breastfeeding women are around 1 or less. ¹² Overall, the concentration of cannabis in breast milk lipids likely relates to its inherent lipophilicity, leading to trapping within the breast milk, as well as user-specific factors such as frequency of use. ¹⁰ In addition, Wymore et al. estimated the mean half-life of THC in breast milk to be around 17 days and calculated that it could be possible to detect THC in the breast milk of some users for longer than 6 weeks, although most models and studies do not find a half-life as long as 6 weeks.^12,13 However, it is important to note that the method of consumption, extent of use, and interplay with other drug exposures have not been systematically assessed and could play an important role in the extent of infant exposure.

Despite the well-documented increasing use of cannabis among pregnant and breastfeeding women, not enough is known about the effects of cannabis exposure in breast milk on infant outcomes. There have been several studies and case reports published on this topic with conflicting findings. Two separate studies used the Bayley Scales of Infant Development to assess the developmental outcomes at 1 year for infants exposed to cannabis via breast milk. The first of these studies compared 27 cannabis-exposed breastfed infants with 35 unexposed breastfed infants and did not find significant differences in mental or motor development. ¹⁴ However, later, Astley et al. compared 68 cannabis-exposed breastfed infants to matched controls and found that cannabis exposure was significantly associated with decreased motor development. ¹⁵ Of note, both studies were conducted in the 1980s when the potency of cannabis was much lower than it is today. ¹⁶ Further studies on infant outcomes have not been able to find explicit evidence of neurodevelopmental consequences from cannabis exposure through breastfeeding, but this could be due to confounding variables in these studies as well as small sample sizes.^8,17,18

Recently, there have been two reported cases of neurologic symptoms occurring in breastfed infants of cannabis-using mothers. Mabey et al. described a previously healthy 6-month-old breastfed female who presented with somnolence after falling off a couch. The infant subsequently developed seizure-like activity and minimally responsive, dilated pupils. Her mother reported chronic cannabis use, and THC metabolites were found in the infant’s urine and blood. All other laboratory values and a head computed tomography scan were normal, and the infant returned to baseline in 72 hours without any other neurologic sequelae.^8,19 Bouquet et al. described a 9-month-old breastfed female who was hospitalized for a first-time tonic-clonic seizure and had blood tests showing evidence of THC and diazepam metabolites. The infant’s mother reported smoking cannabis daily since the child was 4 months old, but not during pregnancy. After switching to formula feeds, the infant had no recurrence of symptoms.^8,20 In both of these cases, cannabis exposure could not be ruled out as a potential etiology of symptoms. Here we report an additional case of an infant with recurrent apneic episodes where cannabis exposure via breast milk could not be ruled out as a potential etiology.

Case

A 5-week-old term female with an uncomplicated birth history was admitted for care of recurrent apneic episodes with concern for exposure to THC via breastfeeding. The patient’s mother also reported that she noticed the infant had sounded congested for several days following exposure to her sibling with an upper respiratory infection, but upon nasal suction, no mucus was removed.

The infant’s medical history included a brief hospitalization at 1 week of age for a multibacterial urinary tract infection (UTI), at which time she also had a urine drug screen positive for THC and multiple apneic events requiring intubation. Her history was negative for trauma and a family history of sudden infant death syndrome or seizures. At the time of the hospitalization at 1 week of age, electroencephalogram monitoring, lumbar puncture, and head and renal ultrasonography revealed no abnormalities, and the infant was discharged home to complete a 14-day course of antibiotic therapy.

The 5-week-old patient’s mother first noticed the infant experiencing respiratory irregularity, with intermittent retractions and periods of apnea, on the morning of her presentation to the hospital. Upon arrival at the hospital, the infant experienced episodes of apnea recurring over 10 minutes, with the longest period of apnea being 10 seconds. An initial catheterized urine sample revealed moderate blood with some white blood cells but no other signs of infection. A repeat urinalysis was within normal limits without any overt signs of infection. Owing to the patient’s presentation with apnea and prior urine drug screen positive for THC, a urine drug screen was also performed simultaneously; it was positive for cannabis metabolites. A complete blood count, electrolytes, and cerebrospinal fluid analysis were all within normal limits.

The patient’s mother admitted to regular use of THC-laced edibles during pregnancy as well as during the postpartum period, although she stated that she had not used THC for 3 days prior to the infant’s presentation at the hospital. She also reported consuming one alcoholic beverage within the past 24 hours. She denied taking any other medications or supplements. An in-depth history revealed that she had experienced postpartum psychosis with her first child and used cannabis to alleviate her ongoing anxiety and mood symptoms. Of note, she had tried many different psychotropic medications in the past but could not tolerate their side effects. While open to transitioning to formula feeds, she requested more information about the effects of THC on breastfeeding safely.

The family was counseled about transitioning from breastfeeding to formula feeds due to concern about current and continued THC exposure via breast milk when no other potential causes for the recurrent apneic spells were identified. Given the frequency of ongoing maternal cannabis use, the patient’s parents agreed to transition to formula feeds until the patient’s mother was able to abstain from using cannabis. After the discontinuation of breastfeeding, the patient remained stable. On day two of hospitalization, the patient was discharged. She was closely monitored by her primary care pediatrician in the days following her discharge. The patient’s mother also had a follow-up appointment scheduled with her OBGYN to discuss alternative medications to manage her mental health.

Discussion

We reviewed a case of a 5-week-old infant who presented with apneic spells in the context of moderate maternal THC use, continued breastfeeding, and urinalysis positive for THC. Having found no other explanation for the infant’s symptoms, the care team recommended and facilitated a transition to formula feeding, and the infant’s symptoms subsequently resolved.

Several studies have demonstrated that cannabis use in pregnant women may have adverse effects on pregnancy and long-term neurodevelopmental outcomes.^3,5,6 Additional studies have demonstrated THC transfer into breast milk in small concentrations relative to the maternal dose. However, the bioavailability of cannabis metabolites ingested by infants through breast milk as well as the short- and long-term effects of such ingestion are not as well understood.^8–12

Prior research on infants and children who directly ingested cannabis, although constrained to small studies with limited power, has shown that neurological abnormalities—such as sleepiness, somnolence, ataxia, and slurred speech—are the most common manifestations of cannabis intoxication in pediatric patients. ²¹ A small-scale retrospective analysis of National Poison System data on exposures to edible cannabis products between 2017 and 2021 in children less than 6 years of age revealed that central nervous system (CNS) depression was present in 70% of cases. ²² Perhaps more concerning is that severe manifestations of cannabis intoxication ranging from encephalopathy to coma have also been reported in infants, which may be related to the dose consumed relative to infants’ low body weight. ²¹

The urine drug screen results in the case reviewed here could be explained by high maternal serum levels of THC passively transferring to the infant through breast milk. Importantly, the apneic episodes experienced by the infant align with the clinical manifestations of direct cannabis ingestion reported in children, raising a reasonable suspicion of cannabis-induced CNS depression and apnea. Other etiologies for apnea were considered, including an upper respiratory infection, another UTI, breath-holding spells, or an intracranial process. However, apart from the positive THC screen, all studies performed on the infant were unremarkable, and the presentation was inconsistent with breath-holding spells. Specifically, routine laboratory values, urinalysis, and cerebrospinal fluid analysis were all within normal limits. Furthermore, the patient stabilized without further observed apneic episodes after transitioning to formula feeds. Thus, a causal relationship between cannabis exposure from breast milk and apneic episodes could not be ruled out in the present case. To the best of our knowledge, this case demonstrates the youngest patient reported with suspected neurologic sequelae of cannabis exposure through breast milk.

Limitations of the case report described herein include a lack of quantitative data on levels of THC in the breast milk and maternal and infant serum. Furthermore, the initial urine drug screen was performed at another hospital prior to transfer to our hospital, so a full toxicology screen at our facility was deferred during the infant’s hospital stay. In addition, the patient was discharged to follow-up with their primary care provider, who is outside of our hospital system. Thus, longer-term outcomes could not be assessed.

Despite these limitations, this report makes meaningful contributions to the current research landscape. It is important for mothers who use cannabis to carefully weigh the risks and benefits of breastfeeding, but that decision can be exceedingly challenging to make when faced with inconclusive data. ⁵ Generally, professional recommendations discourage maternal cannabis use while breastfeeding, but current data are insufficient to determine the effects of such exposure on infants. ²³ We have highlighted a case that demonstrates the potential short-term neurologic effects of cannabis exposure through breast milk on a 5-week-old infant with the hope that this will inform further research in the field.