It’s not a complete story to say that when bilirubin gets too high the brain can’t keep it out.
Breastfeeding offers significant neuroprotection.
There are specific things that make the blood-brain barrier either stronger, or weaker.
Protecting and strengthening the blood-brain barrier is another thing the conventional treatment model hardly accounts for.
And there is a very good reason conventional medicine can’t address the topic of the blood-brain barrier in newborns: research is lacking! For ethical reasons, research on the blood-brain barrier in newborns is much more limited than it is in adults.
Breastmilk: Nature’s source of antioxidant melatonin for newborns
Melatonin has significant ability to protect against neuroinflammation and blood-brain barrier permeability. Newborns don’t make their own melatonin, but have a powerful source of melatonin at hand in the form of colostrum and breastmilk!
(Formula is not supplemented with circadian hormones at present, but research is underway for this possibility, as well as the possibility of supplementing sick babies with melatonin).
Since breastmilk (specifically, nighttime breastmilk) is the only way to get melatonin to infants under 3 months of age, everything possible should be done to nurture the breastfeeding relationship. As if by design, preterm breastmilk has even higher concentrations of melatonin than term breastmilk. Since premature babies are at increased risk of brain damage from jaundice, isn’t it wonderful that their milk will have increased protection for them?
Melatonin levels in breastmilk vary across the day, with a significant peak around 3 am.
Mothers may be able to boost the melatonin concentration in their milk by taking care of their own circadian rhythms (if this is a new concept, revisit the circadian rhythm protocol here). If a mother does pumps, make sure to feed their night milk at night and their day milk in the day.
If a newborn has jaundice, beyond breastfeeding, how can you strengthen their blood-brain barrier?
Avoid things that increase permeability of the blood-brain barrier. Let’s look at what we know about what happens with the newborn blood brain barrier in jaundice:
The known mechanisms of bilirubin toxicity are complex; bilirubin itself is only one factor of many at play in severe newborn jaundice.
Do everything you can to have a healthy, full-term baby. Newborns who are premature and/or sick, particularly if suffering from a condition that generates significant inflammation (such as perinatal asphyxia, acidosis, sepsis, necrotizing enterocolitis, and fetal inflammatory response) will have reduced integrity of tissue membranes including the blood-brain barrier.
Start supporting the physiological jaundice process with natural light and earthing as soon as possible after birth. The longer the exposure to bilirubin, the greater the likelihood of damage, so providing gentle support before the jaundice appears may be the best bet for reducing this likelihood. A baby with jaundice lasting for days is much more likely to be experiencing damage than a baby in the first few hours of their jaundice manifesting.
Support mitochondrial health by reducing causes of oxidative stress. Over time, excess oxidative stress and poor mitochondrial function lead to the undesireable opening of certain cellular channels that flood cells with positively charged ions, particularly calcium and sodium. It seems that the mitochondrial function of the mother during pregnancy sets the stage for how well the newborn’s mitochondria will function. In the graphic above, this is labeled Excitotoxicity. This is a key part of the cascade that leads to the permanent damage in newborns with jaundice. As we learned earlier in this course, excessive electromagnetic frequencies can also open calcium-channels in cells and the brain, so turn off electrical breakers and wifi/cell signals near the baby as often as possible. Grounding is also well-researched for reducing inflammation, speeding up healing, and even reducing bilirubin. See below:
Bilirubin levels from a study in adult jaundice showing the efficacy of grounding in reducing bilirubin levels.
Finally, be cautious with medications.
Medications that reduce a newborn’s ability to bind bilirubin
The main way medications interfere with newborn jaundice is by displacing the proteins that conjugate bilirubin.
Here are some of the known medications that can reduce a newborn’s ability to bind and excrete bilirubin:
These are just some of the drugs known to reduce a baby’s ability to bind and excrete bilirubin.
In the medical setting, families have the right to ask for full information about any medication offered, as well as do their own research on said medications. Some are known to reduce the ability to bind and excrete bilirubin. Others may interfere with the blood-brain barrier itself.
In particular, watch out for medications being used for an earlier presenting condition. They may be already having an effect on the jaundice processes by the time the jaundice presents.
Congratulations on making it this far in this course!
Reading for Module 6:
Variations in melatonin levels in preterm and term human breast milk during the first month after delivery
DISCUSSION
The peak human milk melatonin (HMM) level accounts an average of 35% of the maternal serum concentration, which also shares a similar circadian rhythm. That suggests HMM is likely derived from blood and the 24-hour HMM profile mimicked the melatonin levels changes in the blood. HMM productions were relatively low during daytime hours, elevating at night, and then peaking at around 03:00, while artificial formulas do not contain melatonin.
Newborns have low serum melatonin levels due to an inadequacy of self-produced, which increase progressively up to the 3rd month of age when a characteristic circadian rhythm is first detectable. HMM plays an important role in newborn synchronization with the mother’s rhythm and is responsible for longer sleep time in breastfed infants than that in formula-fed infants.
Some authors suggested that mothers should nurse with dimmer light or even lights off at night to avoid HMM reductions, which could disturb infant sleep patterns. By the same token, differentiating milk pumped during the day from milk pumped during darkness has also been suggested for women that pump milk for their infants.
In addition, we also found that HMM concentration changed dynamically during lactation in preterm or term breast milk. The peak HMM level was highest in colostrum, and then in transitional milk, and in mature milk, decreasing considerably during the first month after delivery.
Compared with term milk, the preterm milk had a higher peak concentration of melatonin in every tested lactation stage, which may benefit for premature infants during the first few weeks after birth when they are especially vulnerable.
Indeed, being a potential neuroprotective agent, melatonin was found to reduce brain injury and its long-lasting consequences after hypoxia-ischemia and oxidative damage in immature rat brains. Furthermore, melatonin supplementation was also found to improve both lipopolysaccharide-induced neonatal inflammation and related brain injury in rats, and the inflammatory reaction and cell death were reduced in the white matter of preterm and near-term fetal sheep following umbilical cord occlusion. In view of undetectable plasma melatonin level before 31 weeks gestation age, an interesting proposed use of melatonin as a drug is to treat perinatal ischemic brain injuries.
Mitochondrial function/dysfunction may play an important role underlying the linkage of prenatal and postnatal stress and neurodevelopmental outcomes in infants.
This review aimed to provide insights on the relationship between early life stress and neurodevelopment and the mechanisms of mitochondrial function/dysfunction that contribute to the neuropathology of stress.
The present review included studies suggesting that mitochondrial function/dysfunction mediates the impact of prenatal and postnatal stress on neurodevelopmental outcomes in infants.
CONCLUSIONS
Mitochondrial function/dysfunction was at the interface between stress and neurodevelopmental deficits in infants and understanding this association might provide alternative strategies to manage the stress-induced neurodevelopmental deficit. Prenatal intrauterine and postnatal NICU hospitalizations are critical periods for the brain development of preterm infants. Early GA and low birth weight increase the risk of neonatal neurodevelopmental deficits upon exposure to prenatal and postnatal stress. To prevent mitochondrial bioenergetic intergenerational transmission in infants, psychological assessment and social support should be provided to mothers with MCM and further research on effective interventions is warranted. Additionally, individualized care should be applied to diminish biological sex disparities in infants.
ABSTRACT
Mitochondria are active independent organelles that not only meet the cellular energy requirement but also regulate central cellular activities. Mitochondria can play a critical role in physiological adaptations during pregnancy. Differences in mitochondrial function have been found between healthy and complicated pregnancies.
Pregnancy signifies increased nutritional requirements to support fetal growth and the metabolism of maternal and fetal tissues. Nutrient availability regulates mitochondrial metabolism, where excessive macronutrient supply could lead to oxidative stress and contribute to mitochondrial dysfunction, while micronutrients are essential elements for optimal mitochondrial processes, as cofactors in energy metabolism and/or as antioxidants. Inadequate macronutrient and micronutrient consumption can result in adverse pregnancy outcomes, possibly through mitochondrial dysfunction, by impairing energy supply, one-carbon metabolism, biosynthetic pathways, and the availability of metabolic co-factors which modulate the epigenetic processes capable of establishing significant short- and long-term effects on infant health.
Here, we review the importance of macronutrients and micronutrients on mitochondrial function and its influence on maternal and infant health.
INTRODUCTION
The primary goal of the evaluation and management of unconjugated hyperbilirubinemia in premature infants is to prevent acute and chronic bilirubin-induced neurotoxicity, a spectrum of neurodevelopmental disorders including, but not limited to, central apnea, sensorineural deafness, auditory neuropathy spectrum disorder (ANSD), language disorders, autism, upward gaze palsy, and athetoid cerebral palsy (CP).
It is generally believed that premature infants are at increased risk for bilirubin-induced neurotoxicity compared to term infants. However to date, the evidence-based management of hyperbilirubinemia to prevent bilirubin-induced neurotoxicity remains elusive in premature infants <35 wks gestational age (GA).
Consensus-based management guidelines for hyperbilirubinemia using total serum/plasma bilirubin (TB) levels, GA, and clinical risk factors for premature
infants <35 wks GA were recently published. The TB level, the traditional parameter to evaluate and manage hyperbilirubinemia in premature infants, has not been a useful predictor of acute and chronic bilirubin-induced neurotoxicity. This is not
surprising because several biochemical and physiological factors are involved in thepathogenesis of bilirubin-induced neurotoxicity.
Exogenous Drugs and Bilirubin-Albumin Binding
Several therapeutic drugs and preservatives used in preparing these drugs have been studied and shown in in vitro studies to displace bilirubin from albumin binding sites with different levels of activity (Table 1).
Of the drugs studied, the most potent bilirubin displacers are sulfamethoxazole, sulfisoxazole, sulfadiazine, and ceftriaxone. The potential for abnormal binding may persist for the first 10 to 12 wks in premature infants.
Therefore, drugs with a strong bilirubin displacing effect should be avoided as long as there is a risk for bilirubin-induced neurotoxicity in premature infants.
Also, any new drugs with acidic or electronegative features and high protein binding should be evaluated for a bilirubin displacing effect before routine clinical use in neonates, as was considered for ibuprofen use in premature infants.
