Katie Hobbins

Each year, about 3400 infants die of sudden infant death syndrome (SIDS) in the United States, according to the Centers for Disease Control and Prevention.

 SIDS is categorized as the sudden or unexpected death of a baby aged less than 1 year in which the cause cannot be determined. These deaths happen most often during an infant’s sleep or in the sleeping area. Additionally, experts don’t know which babies are at risk for SIDS or what causes it. Now, a team of Australian investigators say they’ve discovered a piece of the puzzle into its cause, and they say it lies in an enzyme called butyrylcholiesterase (BChE).

, highlighted that autonomic dysfunction has been implicated in the pathophysiology of SIDS. BChE, they continued, is an enzyme of the cholinergic system, which is a major branch of the autonomic system and may provide a measure of autonomic (dys)function. With this in mind, a study was undertaken to measure BChE activity in infants and young children who had died from SIDS or Sudden Unexpected Death in Infancy (SUDI).

The study, which was case-controlled, measured BChE activity and total protein in the “eluate of 5μL spots punched from the dried blood spots [DBSs] taken at birth as part of the newborn screening program,” according to the investigators.

These DBSs were collected on post-natal day (PND) 2 to 4 on Whatman 903 filter paper over a 5-year period between 2016 to 2020. The samples where then stored at room temperature.

Children who were categorized as SUDI—who died less than 24 months old between July 20218 and July 2020—were identified using the databases of 3 New South Wales, Australia, forensic pathology sites.

The forensic pathologist’s death classification was used in the study in all but 5 cases. Two cases originally classified as SIDS were changed as SUDI because they were less than or equal to 3 weeks old, 1 case originally labeled SIDS was also changed to SUDI because the subject was more than 52 weeks old, and another 2 cases classified as unknown were changed to SIDS. The investigators noted that all non-SIDS cases had an identified cause of death.

For each SID or SUDI case, 10 date of birth or gender-matched samples of surviving children—who blood spot was taken on the day PND—were identified and used as study controls.

In total, they analyzed 722 DBS which included 67 DBS (58% male) from SUDI infants (26 SIDS, 41 non-SIDS), and 655 controls. The mean age at death for SIDS cases were reported as 15.7 (±8.1) weeks (4 to 36 weeks) and consisted of 54% male subjects. Of the non-SIDS cases, the mean age at death was 31.7 (±30) weeks (1-103 weeks), and was 64% male.

All DBSs were examined for BChE activity and total protein content and BChE specific activity (BChEsa) was calculated. They saw good correlation between the BChE activity of plasma QCs and corresponding DBS QCs (r .84). They noted, however, that the recovery of BChE in DBS QC compared to plasma QC was lower (23.4 ± 2%) than in previous studies. Due to several excluded samples, the study population was reduced to 30 non-SID cases (mean age of death: 23.5 [±30] weeks, range 1-103 weeks; 57% male).

Investigators normalized BChE activity to total protein content to overcome variability in punch location and hematocrit. In turn, there was good recovery of total protein in plasma QC vs its corresponding DBS QC (96.25 ± 11.8%).

Additionally, they reported: “Mean values (± Standard Deviation) for BChEsa for SIDS cases (n = 26) and their controls (n = 254) was 5·6 (±2·1) vs 7·7 (±3·6), respectively, and for non-SIDS cases (n = 30) and their controls (n=291) was 8·5 (±4·2) vs 8·5 (±3·4), respectively.”

Conditional logistic regression showed strong evidence of interaction between BChEsa and cause of death case outcome or control status (

 = ·0061). In response to this finding, separate models for SIDS and non-SIDS groups were performed, concluding that the SIDS death group had strong evidence that lower BChEsa was associated with death (OR= 73 per U/mg, 95% CI .60-.89, P = .0014) and the non-SIDS death group had no evidence of a linear association between BChEsa and death (OR= 1.001 per U/mg, 95% CI .89-1.13, 

Additionally, “there was no evidence of an association between any of the predictors (BCHEsa, gender and cause of death) and age at death, in either univariable or multivariable models,” investigators wrote.

Results showed that a decrease in BChEsa was a biochemical marker distinguishing infants who succumb to SIDs from controls and infants with known causes of death. Investigators hypothesize that these findings are evidence of an altered cholinergic homeostasis and postulate that one could “plausibly produce functional alterations to an infant's autonomic and arousal responses to an exogenous stressor leaving them vulnerable to sudden death.”

Study limitations included difficulties comparing study findings of BChEsa with known BChE reference intervals and that the samples used were 2 years old and would not accurately reflect BChEsa in fresh DBSs. They tried to minimize the effect of long storage times by including 10 date of birth and gender matched, surviving controls per SIDS or non-SIDS case.

Study investigators acknowledged the need for further investigation to determine whether BChE could potentially be used as a biomarker to identify and prevent SIDS deaths.

About SUID and SIDS. Centers for Disease Control and Prevention. Accessed May 16, 2022. 

Harrington CT, Hafid NA, Waters KA. Butyrylcholinesterase is a potential biomarker for sudden infant death syndrome. 

This article was originally published on Contemporary Pediatrics®. 

Articles

Investigators may have found a piece of the puzzle into what causes sudden infant death syndrome.

Butyrylcholiesterase may be key biomarker in SIDS identification, prevention

Due to COVID-19 pandemic supply issues stemming from the February closure of a major production plant, 43% of infant formulas are currently out of stock at stores across the United States. Now, parents are worried about what this means for their families and how they are going to feed their infants.

The initial February closure of an Abbott Nutrition manufacturing plant occurred after concerns about bacterial contamination at the company’s Sturgis, Michigan, facility, triggering a voluntary recall of several lines of powdered formula. The recall began after 4 infants fell ill and 2 died.

While governmental bodies are currently working on a solution, pediatricians and charities are bracing for the worst, according to the 

As families try to cope with the storage, pediatricians say they should be the first contact. Health care providers may be able to provide formula samples to families who are unable to find a preferred brand and connect families with local charities or formula representatives who can help. Women, Infants and Children (WIC) offices are also a trusted resource,

 and local parenting groups may also be a good place to check, as regional Facebook groups have popped up to help parents find formula.

If the preferred formula cannot be found, most healthy babies are able to safely switch to any FDA approved baby formula available in stores or through a reputable online retailer, according to healthychildren.org, a website run by the American Academy of Pediatrics (AAP).

 The AAP, however, warns against buying from auction sites or overseas vendors, as they are not regulated by the FDA.

For infants needing specialized formulas due to allergy or medical conditions, the alternatives are more complicated. Specifically, formulas with broken-down proteins or that are amino acid based need to be carefully substituted. The AAP recommends contacting a pediatrician about specialty formula alternatives.

Watering down existing formula is not recommended, according to the AAP. “While it may be tempting to water down formula to stretch it out, it is not safe to do that,” according to an article by Steven A. Abrams, MD, FAAP, published on healthychildren.org.

“Always follow label instructions or those given to you by your pediatrician. Watering down formula is dangerous.”

Additionally, AAP does not recommend making homemade formula and advises parents as such. Although it is not recommended, using toddler formula if there is no other choice is safe for a few days for babies close to a year of age. In a similar situation, using whole cow’s milk for a brief period of time is also safe.

“This is not ideal and should not become routine but is a better option than diluting formula or making homemade formula,” Abrams wrote.

When switching formulas, relay to parents the need to stay within the same category as their current mixture. These categories include milk-based, soy-based, and sensitive varieties.

It is safe to swap formulas right away if there isn’t any more of the original formula left, but if there is time, it is recommended to stretch out the change over a few days.

Using donor breast milk is also an option for parents, however it can be difficult to obtain and costly.

 Visit the Human Milk Banking Association of North America if a parent asks questions about the option.

Advise parents to avoid informal milk-swaps, as the AAP has long deemed them to be unsafe and could expose infants to bacteria, viruses, medications, or herbs from the donor.

In response to the increased shortage, President Joe Biden announced on May 12 additional steps being taken to address the shortage, in a statement published through the White House briefing room.

Recently, the FDA announced that they are allowing Abbot Nutrition, the supplier of amino acid-based formula EleCare—which has no store-brand alternative—to release “urgent, life-sustaining supplies” of certain specialty formulas on a case-by-case basis.

Even so, the company says the formula wouldn’t hit shelves for 2 months.

Pediatricians should be ready for parents to contact them for help submitting these urgent requests for specialty formulas.

Biden, in the announcement, called on the Federal Trade Commission and State Attorneys General to help prevent any price gouging or unfair market practices on the sale of infant formulas.

“DOJ [Department of Justice] is engaging with state attorneys general to encourage them to use their powers to monitor and address price gouging in the infant formula market and urging them to devote more resources to monitoring predatory behavior in the market for infant formula,” the statement said. “And the president today asked the Federal Trade Commission to use all its available tools to monitor and investigate reports of illegal and predatory conduct.”

The White House statement also noted that additional steps will be announced in the coming days to address the importing of certain infant formula products from abroad.

This article was initially published by our sister publication Contemporary Pediatrics.

Datasembly releases latest numbers on baby formula. Datasembly. Published May 10, 2022. Accessed May 13, 2022. 

https://datasembly.com/news/out-of-stock-rate-in-april-2022-copy/

Abbott voluntarily recalls powder formulas manufactured at one Plant. FDA. Published February 17, 2022. Accessed May 13, 2022. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/abbott-voluntarily-recalls-powder-formulas-manufactured-one-plant

Pearson C. What parents need to know about the formula shortage. 

. Published May 13, 2022. Accessed May 13, 2022. 

https://www.nytimes.com/article/formula-shortage-help.html

Women, infants & children (WIC). Ohio Department of Health. Accessed May 13, 2022. 

https://odh.ohio.gov/know-our-programs/women-infants-children/resources/women-infants-children-description

Find my formula CT. Facebook. Accessed May 13, 2022. 

https://www.facebook.com/groups/225023569839489

Abrams S. With the baby formula shortage, what should I do if I can't find any? healthychildren.org. Updated May 13, 2022. Accessed May 13, 2022. 

https://www.healthychildren.org/English/tips-tools/ask-the-pediatrician/Pages/Are-there-shortages-of-infant-formula-due-to-COVID-19.aspx

Paying for milk. AAP Journals Blog. Published February 28, 2018. Accessed May 13, 2022. 

https://publications.aap.org/journal-blogs/blog/4300

Human Milk Banking Association of North America. Human Milk Banking Association of North America. Accessed May 13, 2022. 

Fact sheet: President Biden announces additional steps to address infant formula shortage. The White House. Published May 12, 2022. Accessed May 13, 2022. 

https://www.whitehouse.gov/briefing-room/statements-releases/2022/05/12/fact-sheet-president-biden-announces-additional-steps-to-address-infant-formula-shortage/

FDA takes important steps to improve supply of infant and specialty formula products. FDA. Published May 10, 2022. Accessed May 13, 2022. 

https://www.fda.gov/news-events/press-announcements/fda-takes-important-steps-improve-supply-infant-and-specialty-formula-products

Oladipo G. Abbott says two months for baby formula to hit shelves amid US shortage. 

. Published May 12, 2022. Accessed May 13, 2022. 

https://www.theguardian.com/us-news/2022/may/12/abbott-baby-formula-shortage-recall

Parents are on edge as the formula shortage worsens across the United States. Pediatricians, the AAP, and White House advise on available options.



What to know about the infant formula shortage

Social media continues to show its importance to the practice, physician, and patient by providing physicians with the platform to spread accurate information to the public, arming the practice with free marketing for services and products, and giving access for patients to ask questions to experts in the field.

In a recent session at the American Academy of Dermatology (AAD) Annual Meeting, held March 25 to 29, in Boston, Massachusetts, experts rounded up their top tips and tricks to make social media work best for business needs.

Kavita Mariwalla, MD, Maxim Polansky, MD, and Muneeb Shah, DO, came together to give the audience a “how-to” guide on the basics.

For this, they suggested to post on social media accounts at a consistent pace, ie. once or twice a day. It’s good to be flexible with what social platforms to use on a certain day. Switch it up and use Instagram one day and Twitter the next.

The presenters noted that it helps to find your niche and run with it—think Dr Miami, or Dr Pimple Popper. Doing this can help narrow down a target audience to reach. Show your personality online but, be careful to not cause too much controversy, they said.

Social media can be hard work with sometimes small reward, but tagging, following, and making comments on other accounts can help garner interest. The presenters also said that buying followers to get started is not the way to go.

Social media inherently comes with internet trolls. Trolls are known as accounts that comment or respond to posts, usually in a confrontational manner, or to get a rise out of the original poster.

When this happens, the presenters recommended blocking and reporting them on the platform. You can respond, but mostly, this will only embolden the commenter to continue. It’s important to remember that people are always watching, and sometimes replying to a troll only looks bad on you. As a physician first, sometimes it’s better to just let it go, they said.

As a physician, many may have partnerships with companies that could expand to social media. If a company reaches out for partnership using social media, it’s important to ask:

What are the usage rights for the sponsored video, how long is the contract?

Will I need to purge any of my prior posts?

How many posts will activate that day/week?

How many edits to the content are allowed?

Do I have indemnification against any product liability claims?

When posting from a partnering company or showing products gifted by a company, it needs to be disclosed. Many use the hashtags #ad, #sponsored, and #brandpartner. When items are gifted, many viewers understand the use of the word PR as a clarification.

The presenters continued that, just like in conference presentations, do not copy the intellectual property of other colleagues, post pictures of patients without their written consent, or alter before and after photos.

Lastly, they highlighted their recommendations for apps to use when editing images and creating a landing page for any “Link in Bio” items.

For editing pictures to put on social media, the presenters recommended:

Their favorite “Link in Bio” options included:

This article was originally published by sister publication Dermatology Times.

Mariwalla K, Polansky MA, Shah M. Don’t be an online tool: #winning in the age of social media. Presented at: 2022 American Academy Dermatology Association Annual Meeting; March 25-29, 2022; Boston, MA.

Social media can be a great way to expand exposure for a practice or physician; however, there are many dos-and-don’ts to understand when signing up for a social platform.

Making the most of your social media presence

The treatment of acne is one of the staples of a dermatologist’s daily practice. But how do the outside factors of hormone therapy and chest binders complicate the care of these patients?

Matthew David Mansh, MD, FAAD, assistant professor of dermatology at the University of Minnesota in Minneapolis, discussed the differences in care that physicians must keep in mind when seeing these patients at the American Academy of Dermatology Annual Meeting, held March 25 to 29, in Boston, Massachusetts.1

In the presentation, “LGBTQ/SGM Health in Dermatology: Essentials and Updates,” Mansh reviewed the basic pathophysiology, epidemiology, and risk factors for acne among transgender and gender diverse patients receiving masculinizing hormone therapy (MHT). MHT is used to promote the development of secondary sex characteristics associated with an individual’s gender identity.

For the general population, up to 95% of adolescents report having had acne at some point in their lives.2 Additionally, according to Mansh, adults 25 years and older have a 55% chance of experiencing acne. The psychosocial effect is also higher than the general population, with an elevated risk of depression and anxiety.

Hormonal acne is caused in part by sebum overproduction due to endogenous androgens such as dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, testosterone, and dihydrotestosterone. Estrogen, however, reduces sebum production.3

Individuals taking testosterone for gender affirming needs tend to develop acne in similar locations as other hormone-based acne, including the lower third of the face, chest, upper arms and back.Additionally, time of onset for this form of hormonal acne is within 2 years of starting testosterone treatments.3

In his presentation, Mansh highlighted a cohort study of 988 patients receiving MHT with the objective to evaluate the risk of acne in a large population of female to male transgender patients and the clinical risk factors for acne diagnosis. The study found that the prevalence of acne in these patients increased from 6.3% to 31.1% following MHT initiation.4

In addition to the use of testosterone in acne development, he noted that the common use of breast binders in this population could also be a factor. A binder is worn tight on the chest to flatten the breasts. These items are usually made of thick spandex and nylon. The use of binders could create a closed-off bacteria-rich environment that could result in acne patches. There’s even a Reddit thread—/ftm—dedicated to, among other issues in the process of gender affirming treatment, the prevalence of this issue, and what to do you help fix it.5

Mansh also gave tips for the management of acne in these patients, and according to him, the work starts long before the patient enters the practice. To ensure best-in-class care to these patients, adequate training of providers and staff is needed to promote a welcoming environment.

He emphasized the need to be familiar with gender-inclusive language, and the proper use of biologic sex and gender pronouns. Additionally, intake forms and electronic health records must be inclusive of transgender and diverse individuals.

Once the patient has made an appointment, the physician should review their current MHT regimen, according to the presentation. This includes checking drug duration, type, dose, and frequency. It’s important to check the patients’ serum testosterone levels and work closely with their hormone providers to optimize dosing regimens that balance gender-affirming goals and unwanted adverse effects like acne.

For his patients on testosterone with mild to moderate acne, he recommended a topical retinoid with the potential addition of topical antibiotics and benzoyl peroxide. An oral antibiotic may also be considered.

Combined oral contraceptives can be used, however, these patients may be reluctant to use estradiol-containing contraceptives or those with anti-androgens like drospirenone. Mansh noted that there is no data on oral contraceptive use for acne in transgender or gender nonconforming patients on MHT. He also explained that spironolactone should not be used in this population. When considering potentially teratogenic medications, reproductive potential of the patient should guide contraceptive conversations with the patient.

For moderate to severe nodulocystic acne, he prescribes oral isotretinoin. He cautioned that reproductive potential must be accessed in the patient before beginning the iPLEDGE process. Any plans for intended gender-affirming invasive surgeries—top or bottom surgeries— may also impact the timing when starting isotretinoin due to a risk of delayed wound healing.

For those patients with moderate to severe nodulocystic acne that are hesitant to pursue isotretinoin, or the medication is contraindicated, and they have seen no improvement with other topical and systemic therapies, he recommends considering oral finasteride (1-5 mg), low-dose oral doxycycline (40 mg extended-release, or 20 mg twice a day), oral dapsone, or adalimumab, red light photodynamic therapy, and salicylic acid chemical peels.

Peeples JK, Dommasch ED, Mansh MD, et al. LGBTQ/SGM Health in Dermatology: Essentials and Updates. Presented at: 2022 American Academy Dermatology Association Annual Meeting; March 25-29, 2022; Boston, MA.

Skroza N, Tolino E, Mambrin A, et al. Adult acne versus adolescent acne. 

Radi R, Gold S, Acosta JP, Barron J, Yeung H. Treating acne in transgender persons receiving testosterone: a practical guide. 

. 2022;23(2):219-229. doi: 10.1007/s40257-021-00665-w

Thoreson N, Park JA, Grasso C, et al. Incidence and factors associated with acne among transgender patients receiving masculinizing hormone therapy. 

. 2021;157(3):290-295. doi:10.1001/jamadermatol.2020.5347

r/ftm. Acne from binding. Reddit. Posted 2019. Accessed March 27, 2022. 

https://www.reddit.com/r/ftm/comments/8yn533/acne_from_binding/

This article originally appeared on Dermatology Times®.

Patients on testosterone for masculinizing hormone therapy are at an increased risk of acne due to both inside and outside factors. Matthew David Mansh, MD, FAAD, explains his process for treating these patients.

Katie Hobbins

Articles

Butyrylcholiesterase may be key biomarker in SIDS identification, prevention

What to know about the infant formula shortage

Making the most of your social media presence

Treating acne in transgender patients on testosterone