Edgar J. Schoen

The Highly Protective Effect of Newborn Circumcision Against Invasive Penile Cancer

Objective. We determined the relation between newborn circumcision and both invasive penile cancer (IPC) and carcinoma in situ (CIS) among adult male members of a large health maintenance organization. Subjects and Methods. Circumcision status was ascertained by a combination of pathology reports, medical record review, and questionnaires for 213 adult male members of a large prepaid health plan who were diagnosed with IPC or CIS. Results. Of 89 men with IPC whose circumcision status was known, 2 (2.3%) had been circumcised as newborns, and 87 were not circumcised. Of 118 men with CIS whose circumcision status was known, 16 (15.7%) had been circumcised as newborns. Conclusions. Our results confirm the highly protective effect of newborn circumcision against IPC and the less protective effect against CIS.

Placental ratio in white and black women: Relation to smoking and anemia

In a study of 7,000 pregnancies it was found that, particularly in black women, hemoglobin levels were lower in smokers than in nonsmokers. This is the reverse of previously reported findings in nonpregnant persons. At delivery, the mean ratio of placental weight to birth weight (placental ratio) was higher in the infants of smokers than of nonsmokers. This observation is discussed in the light of reported elevated placental ratios at high altitudes or after severe anemia of pregnancy. The relationships are complex, and are not uniform with respect to ethnic group.

Cost Analysis of Neonatal Circumcision in a Large Health Maintenance Organization

PURPOSEnWe studied the costs of newborn circumcision in relation to its health benefits later in life.nnnMATERIALS AND METHODSnWe conducted a retrospective database analysis using direct internal cost data from Kaiser Permanente Northern California-a large health maintenance organization-and published cost data (including the cost of medically indicated postneonatal circumcision). The study cohort consisted of 14,893 male infants born in 1996. One-way sensitivity analysis was used to demonstrate the impact of selected variables in the model. Monte Carlo analysis was used to determine the 95% confidence intervals.nnnRESULTSnPostneonatal circumcision was 10 times as expensive as neonatal circumcision (1,921 dollars per infant vs 165 dollars per newborn), and was medically indicated for 9.6% of uncircumcised males. Cost benefits of circumcision resulted from prevention of infant urinary tract infection, balanoposthitis, phimosis, HIV infection and penile cancer. Assuming initial neonatal circumcision cost to be 200 dollars, the future health care cost offset (avoided) was calculated as 183 dollars (range 93 dollars to 303 dollars in 95% of simulations).nnnCONCLUSIONSnMultiple lifetime medical benefits of neonatal circumcision can be achieved at little or no cost. Because postneonatal circumcision is so expensive, its rate is the most important factor determining future cost savings from newborn circumcision.

The Key Role of Newborn Thyroid Scintigraphy With Isotopic Iodide (123I) in Defining and Managing Congenital Hypothyroidism

Background. Thyroid imaging with isotopic iodide (123I) or technetium Tc 99m pertechnetate has been available for decades but is not routinely used in newborn infants diagnosed with congenital hypothyroidism (CH). Among clinicians who believe that presence, absence, or abnormal location of a thyroid does not alter management of CH, imaging is not advocated for anatomic diagnosis of CH. Objective. To define the role of thyroid scintigraphy in diagnosing and managing newborn CH. Methods. Retrospective review of 249 confirmed cases of CH seen at a large, group-model managed care organization during the 24-year period extending from September 1978 through December 2002. Neonatal thyroid scintigraphy was performed in 210 cases (86%): 123I was used in 143 cases (68%), and technetium Tc 99m pertechnetate was used in 67 cases (32%). To perform scintigraphy with 123I, 30 to 50 μCi ([1.11–1.85] × 106 Bq) of 123I was administered orally; an uptake image was taken in 3 to 6 hours; and, if necessary, another image was taken in 24 hours. For technetium, 0.5 to 1 mCi ([1.85–3.7] × 107 Bq) of technetium Tc 99m pertechnetate was administered intravenously with imaging 20 minutes later. Thyroid dysplasia was defined as an absent or ectopic gland requiring lifetime therapy and eutopic thyroid as a normal-appearing thyroid gland in the proper location but possibly malfunctioning and requiring therapy. Results. Of the 210 infants with CH receiving scintigraphy, 90 (43%) had eutopic (normal-appearing) thyroid diagnosed, and 120 (57%) had ectopic or absent gland (25% ectopic, 32% absent) diagnosed. Of these 210 infants, ethnicity was known in 198; of these, 76 (38%) were Latino/Hispanic, and 122 (62%) of the infants were non-Latino/non-Hispanic. Prevalence of CH differed between ethnic groups in our population of >700 000 newborn infants; total prevalence of CH was 1 per 3139. Prevalence of CH in Latino/Hispanic infants was highest at 1 per 1750 infants (1:1357 females, 1:2463 males). Prevalence of CH in non-Latino/non-Hispanic infants was 1 per 4648 infants (1:3500 females, 1:6914 males). Given that the total Kaiser Permanente infant population was ∼19% Latino/Hispanic, the percentage of Latino/Hispanic infants with CH was significantly higher than expected. Dysplastic thyroid was more common in Latino/Hispanic females (69%) than in non-Latino/non-Hispanic females (52%). The female-to-male ratio of patients with CH was 1.9:1. Among the 210 infants with CH, normal thyroid was diagnosed more by 123I scintigraphy (49% of cases) than by scintigraphy using technetium Tc 99m pertechnetate (31% of cases). Use of technetium Tc 99m pertechnetate could have diagnosed dysplastic thyroid in some cases that would be considered eutopic had 123I been used. Eight familial cases of CH were identified. Comments. CH, a heterogeneous disorder with prevalence influenced by familial, ethnic, and gender factors, is more common in Latino/Hispanic females. When present, a eutopic thyroid is more likely to be detected by 123I scintigraphy; this method is therefore preferred over scintigraphy using technetium Tc 99m pertechnetate for optimal management of CH. Parents can then be counseled on either the certainty of lifetime therapy (for dysplastic thyroid) or the possibility of later discontinuing therapy (for eutopic thyroid, because CH may be transient in these children). If the dysplastic thyroid gland is absent or ectopic (usually a small sublingual gland), parents can be told that the infant will need lifetime thyroid therapy. If the thyroid gland is present in the normal position (eutopic) and the condition is transient (as shown by controlled withdrawal of thyroid in older children), lifelong treatment may not be needed. Parents rightly expect this maximal clinical and laboratory information in the immediate newborn period. Some clinicians hesitate to recommend neonatal scintigraphy for children with CH because of concern about delaying L-thyroxine therapy, concern about radiation exposure, or both. We believe that neither concern is warranted. 123I thyroid imaging has been used for many decades without evidence of risk for thyroid cancer. Treatment need not be delayed until scintigraphy is done. We did not use ultrasonography for thyroid imaging because this technique was not available in the early years of our study and may still not have sufficient sensitivity. Sources of discrepancy in our study could include scintigraphy interpreter bias due to lack of objective standards. We cannot estimate the true prevalence of transient CH because not all physicians give children with CH a trial off therapy at 2 to 3 years old, even if a eutopic thyroid is shown by 123I scintigraphy. Because therapy with L-thyroxine is simple and inexpensive and the outcome of untreated CH can be devastating, some parents and physicians are reluctant to discontinue treatment in children with CH, even when scans show a eutopic thyroid. Additionally, the clinical information contained in our database was not detailed enough to enable us to discover all cases of CH in which thyroxine therapy was discontinued. Because the study began in 1978 (>25 years ago), some patients were unavailable for long-term follow-up. In addition to allowing a more rational clinical approach to CH, 123I thyroid scintigraphy may help define underlying genetic factors and mechanisms of thyroid development and differentiation. This studys findings, that prevalence of CH and of thyroid dysplasia differed between genders and among racial/ethnic groups, seem to support a genetic basis for CH. Our results confirm previously published reports from the State of California Department of Health Services, Genetic Disease Branch and other studies describing multiple genetic abnormalities associated with CH. Conclusions. Despite data limitations, we believe that neonatal diagnosis of CH represents perhaps the greatest success of newborn screening programs. Initial laboratory diagnosis is simple and sufficiently accurate; treatment is simple, inexpensive, and effective. Severe mental retardation and growth failure can be prevented. Considering todays rapid advances in understanding the basic mechanisms of thyroid embryogenesis and gene abnormalities, thyroid scintigraphy may provide insight into clinical and genetic correlates in CH.

New policy on circumcision: Cause for concern

* Abbreviations:n AAP = : American Academy of Pediatrics • UTI = : urinary tract infection • HIV = : human immunodeficiency virus • STD = : sexually transmitted disease • CIS = : carcinoma in situnnThe negative conclusions on newborn circumcision drawn by the recent American Academy of Pediatrics (AAP) Task Force on Circumcision are misleading and contrary to the current medical evidence, including data in the body of the report itself1 and in the references cited therein. As professionals closely involved with clinical investigations on newborn circumcision,2–7 we are compelled to express our concern about this report. The Task Force states that newborn circumcision is not recommended and that the procedure is “not essential to the childs current well-being.”1 The media and the public are now understandably convinced that the AAP has adopted an anticircumcision stance compared with its previous neutral position on newborn circumcision.2 This attitude has not only been taken by the activist anticircumcision forces but also by the respected media: eg, “Circumcision Loses a Key Endorsement” ( Washington Post ),8 “Circumcision Benefits Disputed” ( Chicago Sun-Times ),9 “Pediatricians Turn Away From Circumcision” ( CNN ),10 and “Circumcision Opponents Energized by About-Face of Academy of Pediatrics” ( Forward ).11 One would assume that in the decade since the 1989 report,2 new evidence must have appeared demonstrating substantial disadvantage of newborn circumcision. However, the opposite is true.nnConsiderable published data from the past 10 years (much of it cited in the current report) confirm and reinforce previous evidence on the medical benefits of newborn circumcision, particularly in protecting against urinary tract infection (UTI) and human immunodeficiency virus (HIV) infection. Pain—a major disadvantage of the procedure—has been shown to be safely and effectively controlled by local anesthesia. With more proven advantages and fewer disadvantages, how could the Task Force issue a statement that could only be interpreted as reversing previous policy and discouraging newborn circumcision?nnThe report of the 1989 Task Force, for which 1 of the authors (E.J.S.) …

Routine Ultrasonography Compared With Maternal Serum Alpha-fetoprotein for Neural Tube Defect Screening

OBJECTIVE: This study was done to estimate the value of prenatal maternal serum alpha-fetoprotein (MSAFP) screening compared with that of routine ultrasonography in the diagnosis of neural tube defects (NTDs). METHODS: An integrated database was used retrospectively to identify cases of NTDs among 219,000 consecutive pregnancy outcomes observed during a 7-year period at 40 Kaiser Permanente facilities in Northern California. We specifically examined types of NTD and the tests used to diagnose cases. RESULTS: We identified 189 NTD cases, 102 of which had received MSAFP screening. Results of MSAFP testing were negative in 25 (25%) of these 102 cases. Without other testing, these 25 NTD diagnoses would have been missed. These included 15 (38%) of the 40 spina bifida cases screened, 6 (67%) of the 9 encephalocele cases screened, and 4 (8%) of the 53 anencephaly cases screened. Of the 186 NTD cases diagnosed prenatally, 115 (62%) were initially detected by routine ultrasonography administered during the second trimester without knowledge of MSAFP values; 69 (37%) were diagnosed by targeted ultrasonography after MSAFP screening indicated a higher risk for NTD; and 2 (1%) were diagnosed by pathology examination after miscarriage. CONCLUSION: Compared with MSAFP performed alone for screening, routine second-trimester ultrasonography was more likely to discover an NTD. LEVEL OF EVIDENCE: III

Maternal serum unconjugated estriol as a predictor for Smith-Lemli-Opitz syndrome and other fetal conditions

OBJECTIVE To assess the clinical value of low maternal serum unconjugated estriol (E3) level for diagnosing Smith–Lemli–Opitz syndrome and other fetal clinical conditions in pregnant members of a large health maintenance organization. METHODS We studied serum unconjugated E3 levels in 120,071 gravidas having California Expanded Alpha-Feto-protein prenatal screening at 15–20 weeks gestation during a 5-year period. RESULTS Of the 120,071 women, 323 (0.27%) had low unconjugated E3 levels (less than or equal to 0.2 ng/mL, or 0.15 multiples of the median). Excluding women who were screened too early or who had indeterminate screening results, 103 (0.08%) women with unexplained low unconjugated E3 level remained; of these 103 women, 33 had negative screening results and 68 had positive screening results, and two were tested too late for interpretation. Intrauterine fetal death occurred in 39 (57%) of the 68 women with low unconjugated E3 and positive screening results and occurred in two (6%) of the 33 women with low unconjugated E3 levels and negative screening results, a significant difference (P < .001). Two cases of Smith–Lemli–Opitz syndrome were identified and the patients did not survive the neonatal period; one was a therapeutic abortion for severe oligohydramnios, and the other died at age 48 hours. Low unconjugated E3 level also predicted presence of steroid sulfatase deficiency, a much more common X-linked skin disorder characterized by ichthyosis. CONCLUSION Low maternal serum unconjugated E3 diagnosed more cases of steroid sulfatase deficiency and undetected intrauterine fetal death than Smith–Lemli–Opitz syndrome (1:60,000 prevalence), although the clinical importance of having this information prenatally is uncertain.

Benefits of newborn circumcision: is Europe ignoring medical evidence?

A major difference between the paediatric care provided in Europe and that provided in the US stems from the attitudes of care providers toward newborn circumcision as a preventive health measure. In the US, the great majority of newborn boys (about 1.4 million annually) are circumcised, whereas in Europe, neonatal circumcision is rarely done. European countries consider newborn circumcision an unnecessary surgical procedure which increases the costs of operating nationalised health systems, whereas in the US, circumcision is generally considered a simple, rapid operation with medical benefits which accrue throughout life.nnPhimosis, balanoposthitis, and difficulty of ensuring adequate genital hygiene in uncircumcised boys have been best described in the European literature.1-4 US anticircumcision groups claim that genital hygiene can easily be maintained as the foreskin naturally separates, but, in reality, genital hygiene in uncircumcised boys has been shown to be poor, even in British and Scandinavian middle class schoolboys.1 2 nnThe prevalence of true phimosis (anatomic constriction of the preputial opening, which must be distinguished from adherent foreskin) in published studies varies from 0.3% to 0.9%,5 but true phimosis requires circumcision later in life, when the procedure is more difficult, risky, and expensive.6 7 Balanoposthitis has been estimated to occur in 4% of uncircumcised boys, and incidence peaks at age 2 to 5 years.3 Although treatment can be conservative, late circumcision is often necessary for recurrent cases, and medical management requires additional physician visits and treatment.nnThe evidence that circumcision protects against penile cancer is overwhelming. In the US, incidence of penile cancer in circumcised men is essentially zero (about one reported case every five years), but it is 2.2 per 100u2009000 in uncircumcised men (about 1000 cases are reported annually). On the basis of life table analysis, Kochen and McCurdy estimated that an uncircumcised …

Pain in Neonatal Circumcision

Because newborn circumcision is a quick and safe surgical procedure, any method to relieve pain must be almost risk-free in order to be acceptable. General anesthesia and narcotic analgesia are not appropriate. Dorsal penile nerve block (DPNB) with lidocaine hydrochloride is probably the most effective and safest form of anesthesia for newborn circumcision currently available, but it can cause significant local and systemic reactions. Only a limited number of cases of DPNB have been reported and we feel that this procedure should be used cautiously until there is more published evidence of its safety. Alternative methods of pain relief including oral acetaminophen and topical anesthesia should also be studied. Of special interest is recent evidence that a sucrose-flavored pacifier is an effective analgesic during newborn circumcision.

Ignoring Evidence of Circumcision Benefits

THE AMERICAN PUBLIC remains resolute in its support of newborn circumcision despite negative recommendations from the American Academy of Pediatrics (AAP).1 The great majority of males in the United States are circumcised: prevalence of circumcision is 80% to 85%2 as measured by published values from Georgia, Texas, California, Colorado, Alaska, Wisconsin, and Missouri.3–9 Circumcision prevalence not only is high but seems to be increasing.10 Between 1988 and 2000, the US newborn circumcision rate increased by 12.8%, an increase that has been attributed to “an increased recognition of the potential medical benefits of circumcision” by the general public.10(p978) The increase in circumcisions is most apparent in mid-America states with the fewest immigrants,6,10,11 because most immigrants, particularly Hispanics, are not circumcised. The 80% to 85% US circumcision rate observed in practice contrasts with the 55% to 65% rate reported in statistics collected from birth centers across the nation.6,10 The explanation for this difference is that the published results of national statistical surveys represent only coded diagnoses obtained from birth centers; the reported figures do not include males who are circumcised at a later date for religious, medical, or personal reasons or who received newborn circumcision that was not coded.5,7 The original position of the AAP was established with an erroneous statement in 1971, when the AAP Committee on Fetus and Newborn in a single sentence stated that “there are no valid medical indications for circumcision in the neonatal period.”12(p110) The anonymous authors seem to have been unaware of multiple published studies, mainly in the urologic literature, that showed that circumcision protected against penile cancer, balanoposthitis, and phimosis. Multiple published studies had shown that circumcision essentially eliminates the otherwise-possible development of invasive penile cancer.13,14 During the North African desert campaign of World War II, 146 000 servicemen were hospitalized with foreskin-related disorders, mainly balanoposthitis, paraphimosis, and phimosis; US Army urologists stated: “Had these patients been circumcised before induction, this total would probably have been close to zero.”15(p146) In 1975, instead of admitting the existence of valid indications for newborn circumcision as revealed in the body of the report, the AAP Ad Hoc Task Force on Circumcision simply changed the wording to “there is no absolute medical indication for routine circumcision of the newborn.”16(p611) This anticircumcision policy remained in place until 1987, when Wiswell et al17 showed a 10to 20-fold protective benefit of newborn circumcision against severe urinary tract infections (UTIs) in the first year of life. A new AAP task force was appointed, which I chaired. Published in 1989,18 our findings did indeed confirm medical benefits to circumcision as well as possible complications, and we stated that these benefits and complications should be pointed out to parents. In the 1989–1999 decade, multiple studies confirmed the beneficial effect of newborn circumcision in preventing infant UTIs19–21 and transmission of HIV.22,23 The safety and efficacy of local anesthesia were established also. With this appearance of more benefits and less risks, an update was considered necessary. A 1999 task force was therefore appointed, and a new report was issued.