<?xml version="1.0" encoding="UTF-8" standalone="no"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" "journalpublishing.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="review-article" dtd-version="2.3" xml:lang="EN">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Urol.</journal-id>
<journal-title>Frontiers in Urology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Urol.</abbrev-journal-title>
<issn pub-type="epub">2673-9828</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fruro.2024.1380154</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Urology</subject>
<subj-group>
<subject>Mini Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Clinical and environmental considerations for neonatal, office-based circumcisions compared with operative circumcisions</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Press</surname>
<given-names>Benjamin</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2646217"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jalfon</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2765191"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Solomon</surname>
<given-names>Daniel</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2761966"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Hittelman</surname>
<given-names>Adam Benjamin</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1420910"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Yale School of Medicine, Department of Urology, School of Medicine, Yale University</institution>, <addr-line>New Haven, CT</addr-line>, <country>United States</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Department of Surgery, Division of Pediatric Surgery, Yale School of Medicine</institution>, <addr-line>New Haven, CT</addr-line>, <country>United States</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Janelle Fox, Children&#x2019;s Hospital of The King&#x2019;s Daughters, United States</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Yuval Bar-Yosef, Dana-Dwek Children&#x2019;s Hospital, Israel</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Benjamin Press, <email xlink:href="mailto:bpress31@gmail.com">bpress31@gmail.com</email>; Adam Benjamin Hittelman, <email xlink:href="mailto:adam.hittelman@yale.edu">adam.hittelman@yale.edu</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>03</day>
<month>07</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>4</volume>
<elocation-id>1380154</elocation-id>
<history>
<date date-type="received">
<day>01</day>
<month>02</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>13</day>
<month>06</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2024 Press, Jalfon, Solomon and Hittelman</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Press, Jalfon, Solomon and Hittelman</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<p>Neonatal male circumcision is a commonly performed procedure in the United States. Circumcisions are performed at various ages by a variety of clinical providers for multiple reasons, including religious, cultural, personal, and medical indications. In the United States, neonatal circumcision is routinely performed by non-urologic providers in the hospital within the first few days of life or as a religious ceremony on the 8<sup>th</sup> day of life. If neonatal circumcision is deferred in the hospital and subsequently not performed in the outpatient setting, it is then typically performed in the operating room under general anesthesia after 6 months of life. Neonatal circumcision is supported by both the American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG) due to the belief that the health benefits outweigh the minimal risk of the procedure. Despite this, neonatal circumcision rates have decreased in the United States in recent decades, in part due to access to the procedure, often related to changing insurance coverage. This has led to increased rates of operative circumcisions. Operative circumcisions are more costly to the healthcare system, subject the patient to cardiopulmonary and potentially neurotoxic effects of general anesthesia, and carry an increased environmental footprint, compared to neonatal circumcision. The intention of this paper is not to promote or justify circumcision for all patients, but rather to compare the clinical and environmental impact of neonatal versus operative circumcisions.</p>
</abstract>
<kwd-group>
<kwd>circumcision</kwd>
<kwd>office based procedures</kwd>
<kwd>environmental footprint</kwd>
<kwd>healthcare disparities</kwd>
<kwd>operating room</kwd>
</kwd-group>
<counts>
<fig-count count="0"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="32"/>
<page-count count="5"/>
<word-count count="2053"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Pediatric, Adolescent and Developmental Urology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<title>Introduction</title>
<p>Neonatal male circumcision is widely performed in the United States. Over 50% of boys in the United States undergo circumcision (<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B2">2</xref>). Circumcision can be performed at different ages by a variety of providers and performed for religious, cultural, personal, or medical indications. In the United States, neonatal circumcision is routinely performed by non-urologic providers in the hospital within the first few days of life. Traditional Jewish circumcisions are performed on the 8<sup>th</sup> day of life in the home. If neonatal circumcision is deferred, the procedure is then commonly performed by a Pediatrician, Family Practice Physician or Pediatric Urologist within the first few weeks to month of life in the outpatient clinic. Neonatal circumcisions are generally safe and well tolerated, with rates of minor complications (bleeding, infection) of approximately 1&#x2013;2% and major complications (amputation of glans, urethral injury, need for re-operation) of &lt; 1% (<xref ref-type="bibr" rid="B3">3</xref>). While neonatal circumcisions are commonly performed under local anesthetic, neonatal circumcisions that are deferred in infancy are then typically performed in the operating room under general anesthesia after 6 months of life, though some centers are beginning to offer the procedures under spinal anesthetic.</p>
<p>Based on a systematic review of the English literature, the American Academy of Pediatrics (AAP) endorsed that the health benefits of newborn male circumcision outweigh the risks of the procedure (<xref ref-type="bibr" rid="B4">4</xref>). Thus, the AAP promotes that circumcision should be covered by third party insurance providers. The American College of Obstetricians and Gynecologist also supported this statement (<xref ref-type="bibr" rid="B4">4</xref>). This statement is also in line with that of the American Urologic Association, citing the prevention of phimosis, paraphimosis and balanoposthitis, reduced communicable sexually transmitted diseases and HIV, as well as markedly decreased incidence of penile cancer (<xref ref-type="bibr" rid="B5">5</xref>). In addition, there is a 90% reduction of urinary tract infections in circumcised <italic>vs</italic>. uncircumcised boys during the first three to six months of life (<xref ref-type="bibr" rid="B6">6</xref>). However, despite advocacy for neonatal circumcisions, there remains discrepancies in the access for circumcision in newborn males. The downstream effects are felt by the patient, health system, and also the environment. This article will herein summarize these downstream impacts.</p>
</sec>
<sec id="s2">
<title>Costs and access</title>
<p>Boys who were not circumcised during the neonatal period due to prematurity, serious illness, or concerns about genital abnormalities are frequently deferred and referred to Pediatric Urologists to have the procedure performed. If it is not completed in the neonatal period, the circumcision is then deferred to operating room under general anesthesia or spinal anesthetic. While it is well known that the cost of performing a procedure in the operating room carries significant increased expense when compared to the procedure done in the ambulatory setting, the true scale of the cost differences may not be common knowledge among practitioners. Jayanti et&#xa0;al. evaluated the cost of ambulatory <italic>vs</italic>. operative circumcision over a 30 month period. While the average circumcision performed in the office cost $196 for facility and equipment, circumcisions in the operating room averaged $1,805 for the facility, equipment, and anesthesia costs. By performing circumcision with local anesthesia in an office setting, the group was able to save $184, 713 annually over the course of a 30 month period (<xref ref-type="bibr" rid="B7">7</xref>). These cost discrepancies were corroborated by Many et&#xa0;al., who found that the median cost of an operative circumcision was $2892, whereas the median cost of neonatal circumcision was approximately $173 (<xref ref-type="bibr" rid="B8">8</xref>).</p>
<p>Despite the purported benefits of circumcision itself, as well as the cost savings and medical benefit of avoiding general anesthesia, access to neonatal circumcision has been limited in certain communities. Dr. Emilie Johnson and the research group from Northwestern performed a retrospective review of circumcision in over 8 million boys in the Kids&#x2019; Inpatient Database between 2003 and 2016. During that period, the rates of neonatal circumcision decreased from 57.4% to 52.1%, while the rates before and after the 2012 AAP statement advocating to increase access to circumcision did not differ statistically (<xref ref-type="bibr" rid="B1">1</xref>). The authors found that there were geographical and income related disparities in neonatal circumcision rates. In general, neonatal circumcision rates increased relative to higher income, with 50.3% of boys in the lowest income quartile undergoing neonatal circumcision compared to 60.7% of boys in the highest income quartile. In addition, privately insured boys (64.9%) underwent neonatal circumcision at a higher rate than publicly insured boys (44.6%) (<xref ref-type="bibr" rid="B1">1</xref>). A subsequent review of the pediatric health information system (PHIS) database found that in states where Medicaid does not cover newborn circumcisions, there were higher rates of operative circumcision, despite similar rates of phimosis diagnoses. Furthermore, there was a greater than two-fold increase in balanitis cases in states in which Medicaid did not cover neonatal circumcisions (<xref ref-type="bibr" rid="B9">9</xref>). In Colorado and Florida, following defunding for neonatal circumcision, rates of neonatal circumcision were reduced by 20.9% and 16.0%, respectively. Black neonates appeared to be disproportionately impacted by changes in Medicaid coverage compared to their white counterparts. When Medicaid coverage was available, black neonates had higher rates of circumcision than white neonates. When Medicaid coverage was unavailable, white neonates were circumcised at a higher rate than black neonates (<xref ref-type="bibr" rid="B10">10</xref>).</p>
</sec>
<sec id="s3">
<title>Anesthesia risk and complications</title>
<p>Surgery on a pediatric patient typically requires the use of general anesthesia, in contrast to the adult population, where regional anesthesia may be used as an alternative to general anesthesia. While regional anesthesia is frequently combined with general anesthesia to lessen perioperative pain and anxiety, there are risks associated with anesthesia in young patients. Recent research has brought attention to these risks by indicating that repeated or prolonged exposure to anesthesia during early childhood may have a negative impact on brain development (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>).</p>
<p>Neuronal cell death, impaired neurogenesis, glial death, and abnormal axon formation have been shown to occur in animal models after exposure to general anesthetics at a young age (<xref ref-type="bibr" rid="B13">13</xref>&#x2013;<xref ref-type="bibr" rid="B15">15</xref>). Other models have also found that anesthesia exposure in infancy is associated with altered behaviors including heightened emotional reactivity to threats, and impaired learning and memory formation persisting into early adulthood (<xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B17">17</xref>).</p>
<p>In 2016, the U.S. Food and Drug Administration warned &#x201c;repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children&#x2019;s brains.&#x201d; (<xref ref-type="bibr" rid="B18">18</xref>) This warning was made based on review of largely animal studies as well as a few human studies. Despite this, the evidence regarding neurocognitive outcomes in human studies is conflicting, with significant heterogeneity in populations and outcome measures (<xref ref-type="bibr" rid="B19">19</xref>). A more recent randomized control trial, found that neurodevelopment after just under an hour of general anesthesia in early infancy does not significantly differ when compared to awake-regional anesthesia (<xref ref-type="bibr" rid="B20">20</xref>). While perioperative mortality in non-cardiac surgeries has been reported as only 1.6 per 10,000 anesthetics (<xref ref-type="bibr" rid="B21">21</xref>), there still poses a risk of cardiopulmonary events including bradycardia/hypotension, laryngospasm, aspiration, and apnea (<xref ref-type="bibr" rid="B22">22</xref>).</p>
<p>For non-financial reasons, circumcision under local anesthesia has the advantage of mitigating the potential associated risks of general anesthesia. Parents will often prefer neonatal circumcision to avoid the potential associated risks of general anesthesia. More time is devoted to operative procedure as patients will spend time in the preoperative holding areas, anesthesia consultation, and recovery room. The procedure takes less time in an office setting, and the child can typically return home faster.</p>
</sec>
<sec id="s4">
<title>Environmental footprint</title>
<p>While our knowledge of how climate change affects human health has grown recently, less is known about how health care services negatively impact the environment. The United States is one of the world&#x2019;s leaders in greenhouse gas emissions. From 2003&#x2013;2013 greenhouse gas emissions from the nation&#x2019;s healthcare system increased by 30%, to account for nearly 10% of the nation&#x2019;s total greenhouse gas emissions (<xref ref-type="bibr" rid="B23">23</xref>). The U.S. healthcare system has been shown to be a significant contributor to air pollution, accounting for a significant percentage of the downstream effects of carbon emissions. This includes acidification (12%), smog formation (10%) and respiratory disease from particulate matter (9%), as well as contribution to ozone depletion and carcinogenic and non-carcinogenic air toxins (1&#x2013;2%) (<xref ref-type="bibr" rid="B23">23</xref>). Current research has focused on the environmental impact of products and processes with the hospital system. Life cycle assessments have been performed to quantify the environmental and public health impact of such processes in the hospital system, such as the production, use and disposal of medical equipment. Dr. Jodi Sherman, has been one of the foremost researchers in this area, evaluating opportunities for reductions in emissions, including but not limited to the decreased use of single use laryngoscopes (<xref ref-type="bibr" rid="B24">24</xref>), disposable materials and single-use surgical devices in hysterectomies (<xref ref-type="bibr" rid="B25">25</xref>), and even reducing unnecessary prostate biopsies (<xref ref-type="bibr" rid="B26">26</xref>).</p>
<p>At our own institution, we sought to evaluate the environmental impact of office-based clamp neonatal circumcision <italic>vs</italic> operative circumcision by measuring the weight of disposable materials as a surrogate. Average weights of disposable materials were significantly higher for operative circumcisions than for clinic circumcisions (3.71 &#xb1; 0.73 kg <italic>vs</italic>. 0.38 &#xb1; 0.11 kg, p &lt; 0.001). The weight of disposable materials for circumcisions performed in the operating is nearly 10 fold higher than in the clinic setting. The environmental and financial impact of the added waste must be considered when planning for these procedures. Early referral to Pediatric Urologists in the newborn period could potentially allow for increased access to non-operative newborn circumcisions in the clinic in the first few weeks to months of life.</p>
<p>There is potential for redundant skin or poor cosmetic outcome after a neonatal circumcision. In this case, families may elect to have the circumcision revised in the operating room. Over the last 12 years at out institution, only 933 revisions of circumcisions have been performed while there were 39,914 neonatal circumcisions performed within that same time period. Even if we account for the potential for poor cosmetic outcome and anticipation of revision of circumcision, the numbers do not justify deferral to perform circumcision in the operating room.</p>
</sec>
<sec id="s5" sec-type="discussion">
<title>Discussion</title>
<p>Neonatal circumcision is performed for a variety of clinical, personal and religious indications. While we are not promoting circumcision as a practice for all patients, we recognize the medical and personal benefits and advocate that it should be available for families who choose the procedure. However, due to changes in access for neonatal circumcision, we are observing declining rates of neonatal circumcision over time (<xref ref-type="bibr" rid="B1">1</xref>). Many parents desire circumcision for their children, as evidenced by the increase in operative circumcisions in states that do not cover neonatal circumcisions under Medicaid (<xref ref-type="bibr" rid="B9">9</xref>). While operative circumcisions are generally safe and well tolerated by the patient, they are a more complex and involved procedures than neonatal circumcisions performed in the hospital or clinic, with increased costs and environmental impact. Operative circumcisions require general anesthesia which introduces additional cardiopulmonary risks to the child, as well as potentially neurotoxicity to the child&#x2019;s developing brain. Operative circumcisions also have higher rates of complications compared to neonatal circumcision (<xref ref-type="bibr" rid="B27">27</xref>).</p>
<p>Lack of access to neonatal circumcision typically reflects insurance coverage and low insurance reimbursement (<xref ref-type="bibr" rid="B28">28</xref>). This is in contrast to the AAP Policy Statement, which explicitly states that &#x201c;the benefits of circumcision are sufficient to justify access to this procedure for families choosing it and to warrant third-party payment for circumcision of male newborns&#x201d; (<xref ref-type="bibr" rid="B4">4</xref>). Training by non-urologic providers for neonatal circumcision is becoming less ubiquitous, possibly due to the poor reimbursement (<xref ref-type="bibr" rid="B29">29</xref>). A review of program procedural requirements for obstetrics and gynecology residency do not include circumcision (<xref ref-type="bibr" rid="B30">30</xref>, <xref ref-type="bibr" rid="B31">31</xref>). To alleviate this potential need for practitioners of neonatal circumcision, there has been increased utilization of advanced practice providers, a practice that has been deemed to be both feasible and safe (<xref ref-type="bibr" rid="B32">32</xref>). However, without improved coverage and better reimbursement, there will likely be continued deferment of circumcision from the neonatal period to later in life.</p>
<p>Further research needs to be done to further quantify the healthcare costs associated with variable access to neonatal circumcision, both fiscally, and environmentally. As environmental stewards, we should be cognizant of the environmental footprint of the most prevalent procedure in Pediatric Urology.</p>
</sec>
<sec id="s6" sec-type="author-contributions">
<title>Author contributions</title>
<p>BP: Writing &#x2013; original draft, Writing &#x2013; review &amp; editing. MJ: Writing &#x2013; review &amp; editing. DS: Writing &#x2013; review &amp; editing. AH: Writing &#x2013; original draft, Writing &#x2013; review &amp; editing.</p>
</sec>
</body>
<back>
<sec id="s7" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare no financial support was received for the research, authorship, and/or publication of this article.</p>
</sec>
<sec id="s8" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
<p>The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.</p>
</sec>
<sec id="s9" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<ref-list>
<title>References</title>
<ref id="B1">
<label>1</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Jacobson</surname> <given-names>DL</given-names>
</name>
<name>
<surname>Balmert</surname> <given-names>LC</given-names>
</name>
<name>
<surname>Holl</surname> <given-names>JL</given-names>
</name>
<name>
<surname>Rosoklija</surname> <given-names>I</given-names>
</name>
<name>
<surname>Davis</surname> <given-names>MM</given-names>
</name>
<name>
<surname>Johnson</surname> <given-names>EK</given-names>
</name>
</person-group>. <article-title>Nationwide circumcision trends: 2003 to 2016</article-title>. <source>J Urol</source>. (<year>2021</year>) <volume>205</volume>:<page-range>257&#x2013;63</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/JU.0000000000001316</pub-id>
</citation>
</ref>
<ref id="B2">
<label>2</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Owings</surname> <given-names>M</given-names>
</name>
<name>
<surname>Uddin</surname> <given-names>S</given-names>
</name>
<name>
<surname>Williams</surname> <given-names>S</given-names>
</name>
</person-group>. <article-title>Trends in circumcision for male newborns in US hospitals: 1979&#x2013;2010</article-title>. <source>Natl Center Health Stat</source>. (<year>2013</year>). pp. <page-range>1&#x2013;5</page-range>.</citation>
</ref>
<ref id="B3">
<label>3</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Weiss</surname> <given-names>HA</given-names>
</name>
<name>
<surname>Larke</surname> <given-names>N</given-names>
</name>
<name>
<surname>Halperin</surname> <given-names>D</given-names>
</name>
<name>
<surname>Schenker</surname> <given-names>I</given-names>
</name>
</person-group>. <article-title>Complications of circumcision in male neonates, infants and children: a systematic review</article-title>. <source>BMC Urol</source>. (<year>2010</year>) <volume>10</volume>:<fpage>2</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/1471-2490-10-2</pub-id>
</citation>
</ref>
<ref id="B4">
<label>4</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>CIRCUMCISION</surname> <given-names>TFO</given-names>
</name>
<name>
<surname>Blank</surname> <given-names>S</given-names>
</name>
<name>
<surname>Brady</surname> <given-names>M</given-names>
</name>
<name>
<surname>Buerk</surname> <given-names>E</given-names>
</name>
<name>
<surname>Carlo</surname> <given-names>W</given-names>
</name>
<name>
<surname>Diekema</surname> <given-names>D</given-names>
</name>
<etal/>
</person-group>. <article-title>Circumcision policy statement</article-title>. <source>Pediatrics</source>. (<year>2012</year>) <volume>130</volume>:<page-range>585&#x2013;6</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1542/peds.2012-1989</pub-id>
</citation>
</ref>
<ref id="B5">
<label>5</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Moses</surname> <given-names>S</given-names>
</name>
<name>
<surname>Bailey</surname> <given-names>RC</given-names>
</name>
<name>
<surname>Ronald</surname> <given-names>AR</given-names>
</name>
</person-group>. <article-title>Male circumcision: assessment of health benefits and risks</article-title>. <source>Sexually Transmit Infect</source>. (<year>1998</year>) <volume>74</volume>:<page-range>368&#x2013;73</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1136/sti.74.5.368</pub-id>
</citation>
</ref>
<ref id="B6">
<label>6</label>
<citation citation-type="book">
<source>AUA Policy and Position Statements: Circumcision</source>. Available at: <uri xlink:href="https://www.auanet.org/about-us/policy-and-position-statements/circumcision">https://www.auanet.org/about-us/policy-and-position-statements/circumcision</uri>.</citation>
</ref>
<ref id="B7">
<label>7</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Jayanthi</surname> <given-names>VR</given-names>
</name>
<name>
<surname>Burns</surname> <given-names>JE</given-names>
</name>
<name>
<surname>Koff</surname> <given-names>SA</given-names>
</name>
</person-group>. <article-title>Postneonatal circumcision with local anesthesia: a cost-effective alternative</article-title>. <source>J Urol</source>. (<year>1999</year>) <volume>161</volume>:<page-range>1301&#x2013;3</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/S0022-5347(01)61674-4</pub-id>
</citation>
</ref>
<ref id="B8">
<label>8</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Many</surname> <given-names>BT</given-names>
</name>
<name>
<surname>Rizeq</surname> <given-names>YK</given-names>
</name>
<name>
<surname>Vacek</surname> <given-names>J</given-names>
</name>
<name>
<surname>Cheon</surname> <given-names>EC</given-names>
</name>
<name>
<surname>Johnson</surname> <given-names>E</given-names>
</name>
<name>
<surname>Hu</surname> <given-names>Y-Y</given-names>
</name>
<etal/>
</person-group>. <article-title>A contemporary snapshot of circumcision in US children&#x2019;s hospitals</article-title>. <source>J Pediatr Surg</source>. (<year>2020</year>) <volume>55</volume>:<page-range>1134&#x2013;8</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.jpedsurg.2020.02.031</pub-id>
</citation>
</ref>
<ref id="B9">
<label>9</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Lin</surname> <given-names>CY</given-names>
</name>
<name>
<surname>Johnson</surname> <given-names>EK</given-names>
</name>
<name>
<surname>Del Rio</surname> <given-names>CV</given-names>
</name>
<name>
<surname>Grimsby</surname> <given-names>GM</given-names>
</name>
</person-group>. <article-title>Lack of medicaid coverage of routine newborn circumcision leads to increased operative circumcisions, chordee procedures, and balanitis</article-title>. <source>Urology</source>. (<year>2023</year>) <volume>179</volume>:<page-range>136&#x2013;42</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.urology.2023.05.033</pub-id>
</citation>
</ref>
<ref id="B10">
<label>10</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zambrano Navia</surname> <given-names>M</given-names>
</name>
<name>
<surname>Jacobson</surname> <given-names>DL</given-names>
</name>
<name>
<surname>Balmert</surname> <given-names>LC</given-names>
</name>
<name>
<surname>Rosoklija</surname> <given-names>I</given-names>
</name>
<name>
<surname>Holl</surname> <given-names>JL</given-names>
</name>
<name>
<surname>Davis</surname> <given-names>MM</given-names>
</name>
<etal/>
</person-group>. <article-title>State-level public insurance coverage and neonatal circumcision rates</article-title>. <source>Pediatrics</source>. (<year>2020</year>) <volume>146</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.1542/peds.2020-1475</pub-id>
</citation>
</ref>
<ref id="B11">
<label>11</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Jevtovic-Todorovic</surname> <given-names>V</given-names>
</name>
<name>
<surname>Hartman</surname> <given-names>RE</given-names>
</name>
<name>
<surname>Izumi</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Benshoff</surname> <given-names>ND</given-names>
</name>
<name>
<surname>Dikranian</surname> <given-names>K</given-names>
</name>
<name>
<surname>Zorumski</surname> <given-names>CF</given-names>
</name>
<etal/>
</person-group>. <article-title>Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits</article-title>. <source>J Neurosci: Off J Soc Neurosci</source>. (<year>2003</year>) <volume>23</volume>:<page-range>876&#x2013;82</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1523/JNEUROSCI.23-03-00876.2003</pub-id>
</citation>
</ref>
<ref id="B12">
<label>12</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Vutskits</surname> <given-names>L</given-names>
</name>
<name>
<surname>Davidson</surname> <given-names>A</given-names>
</name>
</person-group>. <article-title>Update on developmental anesthesia neurotoxicity</article-title>. <source>Curr Opin Anaesthesiol</source>. (<year>2017</year>) <volume>30</volume>:<page-range>337&#x2013;42</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/ACO.0000000000000461</pub-id>
</citation>
</ref>
<ref id="B13">
<label>13</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Brambrink</surname> <given-names>AM</given-names>
</name>
<name>
<surname>Back</surname> <given-names>SA</given-names>
</name>
<name>
<surname>Riddle</surname> <given-names>A</given-names>
</name>
<name>
<surname>Gong</surname> <given-names>X</given-names>
</name>
<name>
<surname>Moravec</surname> <given-names>MD</given-names>
</name>
<name>
<surname>Dissen</surname> <given-names>GA</given-names>
</name>
<etal/>
</person-group>. <article-title>Isoflurane-induced apoptosis of oligodendrocytes in the neonatal primate brain</article-title>. <source>Ann Neurol</source>. (<year>2012</year>) <volume>72</volume>:<page-range>525&#x2013;35</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1002/ana.23652</pub-id>
</citation>
</ref>
<ref id="B14">
<label>14</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Istaphanous</surname> <given-names>GK</given-names>
</name>
<name>
<surname>Ward</surname> <given-names>CG</given-names>
</name>
<name>
<surname>Nan</surname> <given-names>X</given-names>
</name>
<name>
<surname>Hughes</surname> <given-names>EA</given-names>
</name>
<name>
<surname>McCann</surname> <given-names>JC</given-names>
</name>
<name>
<surname>McAuliffe</surname> <given-names>JJ</given-names>
</name>
<etal/>
</person-group>. <article-title>Characterization and quantification of isoflurane-induced developmental apoptotic cell death in mouse cerebral cortex</article-title>. <source>Anesth Analgesia</source>. (<year>2013</year>) <volume>116</volume>:<page-range>845&#x2013;54</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1213/ANE.0b013e318281e988</pub-id>
</citation>
</ref>
<ref id="B15">
<label>15</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Stratmann</surname> <given-names>G</given-names>
</name>
<name>
<surname>Sall</surname> <given-names>JW</given-names>
</name>
<name>
<surname>May</surname> <given-names>LD</given-names>
</name>
<name>
<surname>Loepke</surname> <given-names>AW</given-names>
</name>
<name>
<surname>Lee</surname> <given-names>MT</given-names>
</name>
</person-group>. <article-title>Beyond anesthetic properties: the effects of isoflurane on brain cell death, neurogenesis, and long-term neurocognitive function</article-title>. <source>Anesth Analgesia</source>. (<year>2010</year>) <volume>110</volume>:<page-range>431&#x2013;7</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1213/ane.0b013e3181af8015</pub-id>
</citation>
</ref>
<ref id="B16">
<label>16</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Paule</surname> <given-names>MG</given-names>
</name>
<name>
<surname>Li</surname> <given-names>M</given-names>
</name>
<name>
<surname>Allen</surname> <given-names>RR</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>F</given-names>
</name>
<name>
<surname>Zou</surname> <given-names>X</given-names>
</name>
<name>
<surname>Hotchkiss</surname> <given-names>C</given-names>
</name>
<etal/>
</person-group>. <article-title>Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys</article-title>. <source>Neurotoxicol Teratol</source>. (<year>2011</year>) <volume>33</volume>:<page-range>220&#x2013;30</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.ntt.2011.01.001</pub-id>
</citation>
</ref>
<ref id="B17">
<label>17</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Raper</surname> <given-names>J</given-names>
</name>
<name>
<surname>Alvarado</surname> <given-names>MC</given-names>
</name>
<name>
<surname>Murphy</surname> <given-names>KL</given-names>
</name>
<name>
<surname>Baxter</surname> <given-names>MG</given-names>
</name>
</person-group>. <article-title>Multiple anesthetic exposure in infant monkeys alters emotional reactivity to an acute stressor</article-title>. <source>Anesthesiology</source>. (<year>2015</year>) <volume>123</volume>:<page-range>1084&#x2013;92</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/ALN.0000000000000851</pub-id>
</citation>
</ref>
<ref id="B18">
<label>18</label>
<citation citation-type="book">
<person-group person-group-type="author">
<name>
<surname>Food</surname> <given-names>U</given-names>
</name>
<name>
<surname>Administration</surname> <given-names>D</given-names>
</name>
</person-group>. <source>FDA Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women</source>. <publisher-name>FDA</publisher-name> (<year>2017</year>). Available at: <uri xlink:href="https://www.fda.gov/downloads/Drugs/DrugSafety/UCM553814.pdf">https://www.fda.gov/downloads/Drugs/DrugSafety/UCM553814.pdf</uri>.</citation>
</ref>
<ref id="B19">
<label>19</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Davidson</surname> <given-names>AJ</given-names>
</name>
<name>
<surname>Sun</surname> <given-names>LS</given-names>
</name>
</person-group>. <article-title>Clinical evidence for any effect of anesthesia on the developing brain</article-title>. <source>Anesthesiology</source>. (<year>2018</year>) <volume>128</volume>:<page-range>840&#x2013;53</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/ALN.0000000000001972</pub-id>
</citation>
</ref>
<ref id="B20">
<label>20</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>McCann</surname> <given-names>ME</given-names>
</name>
<name>
<surname>De Graaff</surname> <given-names>JC</given-names>
</name>
<name>
<surname>Dorris</surname> <given-names>L</given-names>
</name>
<name>
<surname>Disma</surname> <given-names>N</given-names>
</name>
<name>
<surname>Withington</surname> <given-names>D</given-names>
</name>
<name>
<surname>Bell</surname> <given-names>G</given-names>
</name>
<etal/>
</person-group>. <article-title>Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial</article-title>. <source>Lancet</source>. (<year>2019</year>) <volume>393</volume>:<page-range>664&#x2013;77</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/S0140-6736(19)31958-0</pub-id>
</citation>
</ref>
<ref id="B21">
<label>21</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Flick</surname> <given-names>RP</given-names>
</name>
<name>
<surname>Sprung</surname> <given-names>J</given-names>
</name>
<name>
<surname>Harrison</surname> <given-names>TE</given-names>
</name>
<name>
<surname>Gleich</surname> <given-names>SJ</given-names>
</name>
<name>
<surname>Schroeder</surname> <given-names>DR</given-names>
</name>
<name>
<surname>Hanson</surname> <given-names>AC</given-names>
</name>
<etal/>
</person-group>. <article-title>Perioperative cardiac arrests in children between 1988 and 2005 at a tertiary referral center: a study of 92,881 patients</article-title>. <source>Anesthesiology</source>. (<year>2007</year>) <volume>106</volume>:<fpage>226</fpage>&#x2013;<lpage>37; quiz 413&#x2013;4</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/00000542-200702000-00009</pub-id>
</citation>
</ref>
<ref id="B22">
<label>22</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Brockel</surname> <given-names>MA</given-names>
</name>
<name>
<surname>Polaner</surname> <given-names>DM</given-names>
</name>
<name>
<surname>Vemulakonda</surname> <given-names>VM</given-names>
</name>
</person-group>. <article-title>Anesthesia in the pediatric patient</article-title>. <source>Urol Clinics North America</source>. (<year>2018</year>) <volume>45</volume>:<page-range>551&#x2013;60</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.ucl.2018.06.003</pub-id>
</citation>
</ref>
<ref id="B23">
<label>23</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Eckelman</surname> <given-names>MJ</given-names>
</name>
<name>
<surname>Sherman</surname> <given-names>J</given-names>
</name>
</person-group>. <article-title>Environmental impacts of the U.S. Health care system and effects on public health</article-title>. <source>PloS One</source>. (<year>2016</year>) <volume>11</volume>:<fpage>e0157014</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1371/journal.pone.0157014</pub-id>
</citation>
</ref>
<ref id="B24">
<label>24</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sherman</surname> <given-names>JD</given-names>
</name>
<name>
<surname>Raibley</surname> <given-names>L</given-names>
</name>
<name>
<surname>Eckelman</surname> <given-names>MJ</given-names>
</name>
</person-group>. <article-title>Life cycle assessment and costing methods for device procurement: comparing reusable and single-use disposable laryngoscopes</article-title>. <source>Anesth Analgesia</source>. (<year>2018</year>) <volume>127</volume>:<page-range>434&#x2013;43</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1213/ANE.0000000000002683</pub-id>
</citation>
</ref>
<ref id="B25">
<label>25</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Thiel</surname> <given-names>CL</given-names>
</name>
<name>
<surname>Eckelman</surname> <given-names>M</given-names>
</name>
<name>
<surname>Guido</surname> <given-names>R</given-names>
</name>
<name>
<surname>Huddleston</surname> <given-names>M</given-names>
</name>
<name>
<surname>Landis</surname> <given-names>AE</given-names>
</name>
<name>
<surname>Sherman</surname> <given-names>J</given-names>
</name>
<etal/>
</person-group>. <article-title>Environmental impacts of surgical procedures: life cycle assessment of hysterectomy in the United States</article-title>. <source>Environ Sci Technol</source>. (<year>2015</year>) <volume>49</volume>:<page-range>1779&#x2013;86</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1021/es504719g</pub-id>
</citation>
</ref>
<ref id="B26">
<label>26</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Leapman</surname> <given-names>MS</given-names>
</name>
<name>
<surname>Thiel</surname> <given-names>CL</given-names>
</name>
<name>
<surname>Gordon</surname> <given-names>IO</given-names>
</name>
<name>
<surname>Nolte</surname> <given-names>AC</given-names>
</name>
<name>
<surname>Perecman</surname> <given-names>A</given-names>
</name>
<name>
<surname>Loeb</surname> <given-names>S</given-names>
</name>
<etal/>
</person-group>. <article-title>Environmental impact of prostate magnetic resonance imaging and transrectal ultrasound guided prostate biopsy</article-title>. <source>Eur Urol</source>. (<year>2023</year>) <volume>83</volume>:<page-range>463&#x2013;71</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.eururo.2022.12.008</pub-id>
</citation>
</ref>
<ref id="B27">
<label>27</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Morris</surname> <given-names>BJ</given-names>
</name>
<name>
<surname>Moreton</surname> <given-names>S</given-names>
</name>
<name>
<surname>Krieger</surname> <given-names>JN</given-names>
</name>
</person-group>. <article-title>Critical evaluation of arguments opposing male circumcision: A systematic review</article-title>. <source>J Evidence-Based Med</source>. (<year>2019</year>) <volume>12</volume>:<page-range>263&#x2013;90</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1111/jebm.12361</pub-id>
</citation>
</ref>
<ref id="B28">
<label>28</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Naha</surname> <given-names>U</given-names>
</name>
<name>
<surname>Arora</surname> <given-names>HC</given-names>
</name>
<name>
<surname>Walton</surname> <given-names>RF</given-names>
</name>
<name>
<surname>Rosoklija</surname> <given-names>I</given-names>
</name>
<name>
<surname>Skibley</surname> <given-names>LM</given-names>
</name>
<name>
<surname>Johnson</surname> <given-names>EK</given-names>
</name>
</person-group>. <article-title>Neonatal circumcision availability in the United States: a physician survey</article-title>. <source>BMC Urol</source>. (<year>2021</year>) <volume>21</volume>:<fpage>148</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12894-021-00911-7</pub-id>
</citation>
</ref>
<ref id="B29">
<label>29</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Johnson</surname> <given-names>EK</given-names>
</name>
<name>
<surname>Rosoklija</surname> <given-names>I</given-names>
</name>
<name>
<surname>Walton</surname> <given-names>RF</given-names>
</name>
<name>
<surname>Matoka</surname> <given-names>DJ</given-names>
</name>
<name>
<surname>Seager</surname> <given-names>CM</given-names>
</name>
<name>
<surname>Holl</surname> <given-names>JL</given-names>
</name>
</person-group>. <article-title>Physician perspectives on performing newborn circumcisions: barriers and opportunities</article-title>. <source>Matern Child Health J</source>. (<year>2023</year>) <volume>28</volume>:<page-range>144&#x2013;54</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s10995-023-03822-1</pub-id>
</citation>
</ref>
<ref id="B30">
<label>30</label>
<citation citation-type="book">
<source>ACGME Program Requirements for Graduate Medical Education in Pediatrics</source>. Available at: <uri xlink:href="https://www.acgme.org/globalassets/pfassets/programrequirements/2025-prs/320_pediatrics_2025.pdf">https://www.acgme.org/globalassets/pfassets/programrequirements/2025-prs/320_pediatrics_2025.pdf</uri>.</citation>
</ref>
<ref id="B31">
<label>31</label>
<citation citation-type="book">
<source>ACGME Program Requirements for Graduate Medical Education in Obstetrics and Gynecology</source>. Available at: <uri xlink:href="https://www.acgme.org/globalassets/pfassets/programrequirements/220_obstetricsandgynecology_2023.pdf">https://www.acgme.org/globalassets/pfassets/programrequirements/220_obstetricsandgynecology_2023.pdf</uri>
</citation>
</ref>
<ref id="B32">
<label>32</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gerber</surname> <given-names>JA</given-names>
</name>
<name>
<surname>Borden</surname> <given-names>AN</given-names>
</name>
<name>
<surname>Broda</surname> <given-names>J</given-names>
</name>
<name>
<surname>Koelewyn</surname> <given-names>S</given-names>
</name>
<name>
<surname>Balasubramanian</surname> <given-names>A</given-names>
</name>
<name>
<surname>Tu</surname> <given-names>D</given-names>
</name>
<etal/>
</person-group>. <article-title>Evaluating clinical outcomes of an advanced practice provider-led newborn circumcision clinic</article-title>. <source>Urology</source>. (<year>2019</year>) <volume>127</volume>:<fpage>97</fpage>&#x2013;<lpage>101</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.urology.2019.01.038</pub-id>
</citation>
</ref>
</ref-list>
</back>
</article>