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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 microCi ([1.11-1.85] x 10(6) 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] x 10(7) 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 approximately 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 study's 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 today's 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. [ABSTRACT FROM AUTHOR]

Purpose: We studied the costs of newborn circumcision in relation to its health benefits later in life., Materials and Methods: We 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., Results: Postneonatal 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)., Conclusions: Multiple 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.

Objective: To estimate potential costs and benefits of routinely using tandem mass spectrometry (MS/MS) to screen newborns for inborn errors of metabolism., Method: Analysis of costs and benefits resulting from use of MS/MS in screening of 32 000 newborn infants using data from the Kaiser Permanente Medical Care Program of Northern California plus other published data., Setting: A large health maintenance organization., Results: In the base scenario, the cost per quality-adjusted life year saved by MS/MS screening was $5827; in the least favorable scenario, this cost was $11 419, and in the most favorable scenario, $736., Conclusion: Costs per quality-adjusted life year saved by MS/MS screening for inborn errors of metabolism compare favorably with other mass screening programs, including those for breast and prostate cancer.

Purpose: We describe an uncircumcised male infant and a female neonate treated for infant urinary tract infection who had multiple hormonal and electrolyte abnormalities consistent with the diagnosis of transient pseudohypoaldosteronism., Materials and Methods: We retrospectively reviewed these 2 cases., Results: In each case successful treatment of infant urinary tract infection was accompanied by the resolution of all hormonal and electrolyte abnormalities, including hyperaldosteronemia, hyperreninemia, hyponatremia and hyperkalemia., Conclusions: Because of future renal scarring, decreased renal function and possible hypertension, appropriate hormonal studies should be performed in infants with infant urinary tract infection who also have hyponatremia and hyperkalemia.

Within the Kaiser Permanente system of Northern California, testing for HIV during prenatal vis its was encouraged. During a 5-year period the percentage of women agreeing to HIV testing increased from 50% to 76%. Eighty-three HIV-positive pregnancies occurred in 63 women. Only 17 (20%) of the 83 pregnancies were identified by the voluntary testing program.

Measurements of serum concentrations of free T4, T3, TSH, and thyroglobulin (Tg) were conducted in 42 infants (2-9 months of age) detected and treated through the Northwest Newborn Regional Screening Program and 63 children and adolescents (1-18 yr of age) with congenital hypothyroidism (CH) detected and managed in the Northern California Kaiser Permanente Medical Care Program. Normal feedback control axis data were developed by Quest Diagnostics, Inc. - Nichols Institute Diagnostics and Loma Linda University, from free T4 and TSH measurements in 589 healthy subjects, 2 months to 54 yr of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Twenty-four of the 42 CH infants and 57 of the 63 CH children manifested serum TSH concentrations appropriate for the measured free T4 level. In the remaining 18 infants and 6 children, serum free T4 values were increased 0.2-1.4 ng/dL (2.6-18.0 pmol/L) for the prevailing TSH level, suggesting a state of mild to moderate pituitary-thyroid hormone resistance. In the treated children, the mean T3 concentration was lower (by 32%, 102 vs. 150 ng/dL; 1.57 vs. 2.31 nmol/L) than in normal children, in agreement with earlier data in hypothyroid adults treated with exogenous T4. Serum Tg concentrations were normal or elevated in 90% of the 19 children with ectopic glands and 93% of 27 children with eutopic glands in whom measurements were available. There was a positive correlation between serum TSH and Tg concentrations (P < 0.001), suggesting significant endogenous thyroid hormone production in these children. Our results suggest that the majority of infants and children with CH have a normal hypothalamic-pituitary-thyroid negative feedback control axis during treatment and that the measurement of serum TSH is a useful marker complementing the free T4 measurement in the management of children with CH. A minority have variable pituitary-thyroid hormone resistance, with relatively elevated serum TSH levels for their prevailing serum free T4 concentration. The prevalence of resistance is greater (43%) in young infants (< 1 yr of age) than in older children (10%), indicating that, in most children, the resistance improves with age.

Objective: To assess the effect of newborn circumcision on the incidence and medical costs of urinary tract infection (UTI) during the first year of life for patients in a large health maintenance organization., Setting: Kaiser Permanente Medical Care Program of Northern California (KPNC)., Patients: The population consisted of members of KPNC. The study group consisted of a cohort of 28 812 infants delivered during 1996 at KPNC hospitals; of the 14 893 male infants in the group, 9668 (64.9%) were circumcised. A second cohort of 20 587 infants born in 1997 and monitored for 12 months was analyzed to determine incidence rates., Design: Retrospective study of all infants consecutively delivered at 12 facilities., Outcome Measures: Diagnosis of UTI was determined from the KPNC computerized database using the International Classification of Diseases, Ninth Revision code for inpatients and KPNC Outpatient Summary Clinical Record codes for outpatients. A sample of 52 patient charts was reviewed to confirm the International Classification of Diseases, Ninth Revision and KPNC Outpatient Summary Clinical Record codes and provide additional data., Results: Infants <1 year old who were born in 1996 had 446 UTIs (292 in females; 154 in males); 132 (86%) of the UTIs in males occurred in uncircumcised boys. The mean total cost of managing UTI was 2 times as high in males ($1111) as in females ($542). This higher total cost reflected the higher rate of hospital admission in uncircumcised males with UTIs (27.3%) compared with females (7.5%); mean age at hospitalization for UTI was 2.5 months old for uncircumcised boys and 6.5 months old for girls. In 1996, total cost of managing UTI in uncircumcised males ($155 628) was 10 times higher than for circumcised males ($15 466) despite the fact that uncircumcised males made up only 35.1% of the male patient base in 1996, reflecting the more frequent occurrence of UTI in uncircumcised males (132 episodes) than in circumcised males (22 episodes), and the larger number of hospital admissions in uncircumcised males (38) than in circumcised males (4). The incidence of UTI in the first year of life was 1:47 (2.15%) in uncircumcised males, 1:455 (.22%) in circumcised males, and 1:49 (2. 05%) in females. The odds ratio of UTI in uncircumcised:circumcised males was 9.1:1., Conclusions: Newborn circumcision results in a 9. 1-fold decrease in incidence of UTI during the first year of life as well as markedly lower UTI-related medical costs and rate of hospital admissions. Newborn circumcision during the first year of life is, thus, a valuable preventive health measure, particularly in the first 3 months of life, when uncircumcised males are most likely to be hospitalized with severe UTI.

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.

Background: Maternal serum chorionic gonadotropin is measured to screen for fetal chromosomal abnormalities. Whether the results can also be used to predict the risk of complications or an adverse outcome of pregnancy is not known., Methods: We reviewed the medical records of 28,743 girls and women in whom chorionic gonadotropin was measured during the second trimester of pregnancy (between July 1, 1995, and January 31, 1997), seeking information about the complications and outcome of their pregnancies. We excluded girls and women who had preexisting risk factors for complications or an adverse outcome of pregnancy., Results: Higher serum chorionic gonadotropin concentrations were associated with higher rates of stillbirth (odds ratio for every increase in chorionic gonadotropin of 1 multiple of the median, 1.4; 95 percent confidence interval, 1.1 to 1.9). There was no relation between higher serum chorionic gonadotropin concentrations and the risk of gestational diabetes, premature rupture of membranes or intrauterine growth retardation or small size for gestational age (odds ratio, 1.1; 95 percent confidence interval, 0.9 to 1.2). Higher serum chorionic gonadotropin concentrations were associated with a risk of placental abnormalities (odds ratio, 1.5; 95 percent confidence interval, 1.3 to 1.7), pregnancy-induced hypertension (odds ratio, 1.4; 95 percent confidence interval, 1.3 to 1.5), and preterm delivery without pregnancy-induced hypertension (odds ratio, 1.1; 95 percent confidence interval, 1.0 to 1.2). Inclusion in certain racial or ethnic categories (black, Filipino or Pacific Islander, unknown race or ethnic group, and "other," which included those of Middle Eastern descent and Native Americans) was a better predictor of the risk of an adverse outcome than serum chorionic gonadotropin values., Conclusions: Measurements of serum chorionic gonadotropin are of little clinical value for predicting the risk of complications and the outcome of pregnancy.

Clinical application of genetic knowledge is essential for providing effective preventive health care. A large HMO such as Kaiser Permanente is an ideal setting for this application. Implementing a comprehensive program for genetic screening is complex, however, and requires informed consent, laboratory testing, test interpretation, genetic counseling, follow-up for positive screening results, and database systems. This article summarizes genetic services provided by Kaiser Permanente at four subregional genetic centers in Northern California.

Results of a recent national clinical trial show that maternal-to-fetal transfer of HIV can be decreased threefold by prenatal, intrapartum, and neonatal treatment. The question is whether to make prenatal HIV testing compulsory or to encourage voluntary testing. Kaiser Permanente Northern California (KPNC), which has 2.5 million members, is part of a large health maintenance organization (HMO). In 1994, KPNC cared for 32,700 prenatal patients; 16,500 (50%) agreed to voluntary HIV testing. Compliance with testing ranged from 0% to 92% among the 31 KPNC locations. A study done by telephone survey identified three main factors favoring success of voluntary HIV screening: the ease and accessibility of HIV testing, a designated educator, and the presence of a registered nurse on the counseling team. In 1995, following feedback to the 31 facilities of the 1994 results, compliance rose to 19,800 of 31,300 prenatal patients (63%). KPNC, by encouraging counseled voluntary screening and following known positive cases, hopes to identify, track, and offer treatment options to all HIV-positive prenatal patients.

Comprehensive clinical genetic services are offered to 2.4 million members by the Kaiser Permanente Medical Care Program (KP), a not-for-profit HMO, in its Northern California region. Four genetics centers are staffed by clinical geneticists, genetic counselors, nurses, and laboratory technologists, who together provide patient and physician education, genetic screening, and prenatal, infant, and adult evaluation. Besides offering lectures and teleconferences, the geneticists publish a newsletter on how to use the genetic services for approximately 1200 pediatricians, obstetricians, and other relevant specialists. Clinical services offered to members include individual, group, and telephone consultations, and easy access to geneticists is provided for primary care providers with genetic care questions. In-house laboratory services include blood and tissue cytogenetic analysis, DNA testing, and prenatal blood and amniotic fluid testing. A large database and a comprehensive and cost-effective program of genetic services have been developed. An interregional genetics data system is being established to link Northern and Southern California and the Northwest (Portland and Hawaii regions). Steps are also underway to include other regions in the database and to encourage utilization of regionalized KP genetic laboratories by smaller regions.

Objectives: To compare the results of prenatal and neonatal hemoglobinopathy screening, a pilot program was developed at the Northern California Kaiser Permanente Health Care Program, a prepaid health maintenance program serving 2.5 million members., Methods: In this program, 54,700 pregnant women were screened for hemoglobinopathies., Results: Of the 54,700 women screened, 1019 (1.9%) had a hemoglobinopathy trait, and 81 women with at-risk fetuses were identified. Half the women with fetuses at risk for thalassemia accepted prenatal diagnosis; of those whose fetuses were at risk for sickle-cell disease or other hemoglobinopathies, 30% accepted prenatal diagnosis. Of the 81 at-risk couples, 53 refused amniocentesis for definitive fetal diagnosis; only 28 (35%) accepted; all 4 women who were carrying a fetus with thalassemia major elected to terminate the pregnancy. Only 7 of the 21 cases of hemoglobinopathies were diagnosed prenatally; 14 were discovered neonatally., Conclusions: Prenatal screening was not found to be an ideal method of identifying hemoglobinopathies of the newborn in this large population. With cost-effectiveness a high priority in health care delivery, we believe that testing of newborns for hemoglobinopathies will continue to be the preferred screening method. A combined prenatal and neonatal program would offer the maximum benefit to patients by adding prenatal counseling, parental options, education, and early complete diagnosis to neonatal screening.

Objective: To assess compliance with cholesterol screening and intervention by children who were members of a prepaid health plan in which there was no financial barrier to intervention., Research Design: Children with family histories of hypercholesterolemia, coronary heart disease, and stroke were advised to have a random cholesterol test. Those with total cholesterol levels of 4.80 mmol/L (185 mg/dL) or higher were asked to return for a fasting blood test; of this group, compliant subjects with low-density lipoprotein values of 3.25 mmol/L (125 mg/dL) or higher were offered a nutrition program., Setting: Kaiser Permanente Medical Center, Oakland, Calif., Subjects and Participants: The parents of 1160 children aged 2 to 18 years who had routine pediatric appointments at Kaiser Permanente Medical Center were asked to complete screening forms on family history., Selection Procedures: Children with family histories of hypercholesterolemia, coronary heart disease, and stroke were advised to have a random cholesterol test. Subjects with total cholesterol levels of 4.80 mmol/L or higher were asked to return for a fasting test, and subjects with low-density lipoprotein levels of 3.25 mmol/L or higher were offered a nutrition program., Interventions: Telephone call, letter, low-cholesterol diet, and nutrition program., Main Outcome Measures: Of the 1,160 subjects contacted, 529 (46%) had positive family histories. Of these subjects, random blood cholesterol levels were determined for 369 (70%); 160 (30%) did not comply. Ninety-three subjects had total cholesterol levels of 4.80 mmol/L or higher; of these, 35 (38%) did not comply with follow-up testing. Of the 58 compliant subjects, 25 (43%) had low-density lipoprotein values of 3.25 mmol/L or higher and were offered either a 3-week or a 6-week nutrition program. Only nine subjects (36%) enrolled; 16 (64%) did not comply., Conclusions: Parents do not comply well with a childhood cholesterol screening program that involves two blood tests and moderately intensive educational intervention. Compliance is an important component of cholesterol screening and intervention.