The Detrimental Impact of End-Stage Kidney Disease Is Not Reflected in Autopsy Reports.

CONTEXT.­: End-stage kidney disease (ESKD) is defined as renal impairment requiring renal replacement therapy to sustain life. With a 1-year mortality of ∼20% to 30%, many die of complications related to this disease. OBJECTIVE.­: To determine the percentage of autopsy cases of decedents with ESKD in which the contribution of ESKD to death is accurately reflected in the final report. DESIGN.­: Autopsy case records were retrospectively reviewed at 4 institutions (Yale New Haven Hospital, University of Chicago Medical Center, University of Illinois at Chicago Hospital, University of Iowa Hospital). Clinical, macroscopic, and microscopic autopsy findings were reviewed, with attention to renal disease findings. RESULTS.­: One hundred sixty decedents with documented ESKD and premortem dialysis who underwent autopsy assessment were identified. ESKD was implicated as a cause of death (CoD) or significant contributing factor in 44 cases (28%), but not in the remaining 116 cases (72%). Cardiovascular disease was the most common CoD in ESKD. There was significant interpathologist variation in the inclusion of ESKD as a CoD across institutions. These rates ranged from 85% correlation (23 of 27 cases), to 13% (4 of 31 and 8 of 62 cases at 2 institutions), and 22.5% (9 of 40 cases) across the 4 participating institutions. CONCLUSIONS.­: The recognition at autopsy of ESKD as a CoD or contributing CoD at autopsy in patients undergoing dialysis remains low (28%). The detrimental impact of ESKD is not reflected in hospital autopsy reports, which carries implications for collection of vital statistics and allocation of research funding for kidney diseases.

Gorham Stout disease of the temporal bone with cerebrospinal fluid leak.

Gorham Stout disease (GSD) is a rare disease characterized by the proliferation of endothelial lined vessels and replacement of bone by fibrous tissue. The main imaging features are progressive osteolysis and cortical resorption. Temporal bone involvement is rare but presents as a destructive bone lesion that may be misinterpreted as more common lytic processes in the pediatric population, such as infection or Langerhans cell histiocytosis. GSD of the temporal bone is associated with cerebrospinal fluid (CSF) leaks, may present with otorrhea, and can mimic other causes of ear drainage. Here, we report the clinical course, imaging features, and outcomes of a 3-year-old girl with GSD of the temporal bone presenting with CSF leak initially attributed to infection.

Surgical management of parotid non-tuberculous mycobacteria lymphadenitis in children: A pediatric tertiary-care hospital's experience.

OBJECTIVE: Non-tuberculous mycobacteria (NTM) represents an important etiology of cervicofacial lymphadenitis (CFL) and skin/soft tissue infections in children. It can also affect the salivary glands, including the parotid gland, which is unique due to the presence of intra-salivary lymph nodes. There are no established guidelines for treatment of NTM CFL. NTM lymphadenitis was historically surgically treated; recently the literature supports initial medical treatment. Treatment decisions have been dependent on the extent of disease, preference of providers, and risk of surgical complications. The goal is to report our experience in surgical outcomes of NTM CFL with involvement of the parotid gland after pre-operative medical management. METHODS: A retrospective case series of patients with NTM affecting the parotid gland at a tertiary care pediatric hospital between 2004 and 2020. RESULTS: Seventy-two patients were referred for surgical evaluation of possible parotid NTM. Thirty-three patients underwent surgical excision. Fifteen patients were identified with presumed NTM infection involving the parotid gland. There were twelve females and three males with a mean age of 2.0 years (SD 1.55; range 1-6 days) at the time of surgery. All underwent surgical excision with parotidectomy. The most common pre-operative antimycobacterial therapy used was a combination of clarithromycin and rifampin. All 15 patients had pathological findings consistent with NTM infection (granulomatous lymphadenitis). Forty percent (n = 6) of patients had positive stains with acid-fast bacilli (AFB), with Mycobacterium avium as the most common species (n = 5). The majority of patients, 86.67% (n = 13), had complete resolution of infection after surgery. Clarithromycin and rifampin were the most common post-operative antimycobacterial treatment (mean 81.5 days, SD 110.14, range 2-411 days). The most common complication experienced was acute (<3 months) lower facial nerve paresis (40%, n = 6), but no patient had permanent facial paralysis. CONCLUSION AND RELEVANCE: Parotidectomy is a safe and efficacious treatment in patients with NTM CFL affecting the parotid gland after incomplete resolution with antimycobacterial therapy. Further investigation to optimize duration of antimycobacterial treatment is necessary. We highlight the experience of a high-volume tertiary care pediatric hospital with surgical management of this disease.

End-Stage Kidney Disease Is Overlooked as a Proximate Cause of Death at Autopsy.

OBJECTIVES: To determine how often end-stage kidney disease (ESKD) is implicated as a cause of death (COD) at autopsy. METHODS: We searched our autopsy database (2007-2017) using queries "end-stage renal disease," "end-stage kidney disease," "ESRD," "chronic renal disease," and "chronic kidney disease." Final diagnosis and summaries were reviewed to determine if ESKD was appropriately correlated with the COD. Cases in which the COD was unrelated to kidney function were excluded. RESULTS: Eighty-five patients with a history of ESKD and histologic confirmation thereof were identified. Their CODs were cardiovascular (36%), infection/sepsis (41%), pulmonary (6%), gastrointestinal/hepatic (2%), central nervous system (3%), other systemic disease (7%), and unspecified (5%). ESKD was implicated as a contributing COD in 24 (28%) cases. CONCLUSIONS: ESKD is often overlooked at autopsy, particularly in patients with cardiovascular or infectious disease. Accurate documentation of ESKD contributing to mortality is important for education, counseling, record maintenance, and directing research efforts.

Obesity prevention in the early care and education setting: successful initiatives across a spectrum of opportunities.

With an estimated 12.1% of children aged 2-5 years already obese, prevention efforts must target our youngest children. One of the best places to reach young children for such efforts is the early care and education setting (ECE). More than 11 million U.S. children spend an average of 30 hours per week in ECE facilities. Increased attention at the national, state, and community level on the ECE setting for early obesity prevention efforts has sparked a range of innovative efforts. To assist these efforts, CDC developed a technical assistance and training framework - the Spectrum of Opportunities for Obesity Prevention in the ECE setting - which also served as the organizing framework for the Weight of the Nation ECE track. Participants highlighted their efforts at national, state, and local levels pursuing opportunities on the Spectrum, the standards and best practices that had been the emphasis of their efforts, and common steps for developing, implementing, and evaluating initiatives. Strong leadership and collaboration among a broad group of stakeholders; systematic assessment of needs, opportunities and resources; funding sources; and training and professional development were reported to be integral for successful implementation of standards and best practices, and sustainability.

Varicella seroprevalence in the U.S.: data from the National Health and Nutrition Examination Survey, 1999-2004.

OBJECTIVE: We estimated the varicella seroprevalence among the U.S. population aged 6-49 years based on retested National Health and Nutrition Examination Survey (NHANES) specimens collected between 1999 and 2004--originally tested using a method unsuitable for detecting vaccine-induced immunity--and compared it with historical estimates. METHODS: We performed a confirmatory test suitable for detecting vaccine-induced immunity on all available specimens from 6- to 19-year-olds who originally tested negative (n = 633), and on 297 randomly selected specimens that had tested positive. Retest results superseded original results for determining seroprevalence. We assessed seroprevalence for the entire sample aged 6-49 years (n = 16,050) by participant demographic characteristics and compared it with historical estimates (NHANES 1988-1994). RESULTS: The percentage of false-negative results for the original test was higher for specimens from younger children (6-11 years of age: 27.5%; 12-19 years of age: 13.3%) and for specimens collected most recently (2001-2004: 26.0%; 1999-2000: 12.6%). The age-adjusted rate of varicella seroprevalence for 1999-2004 was 93.6% for 6- to 19-year-olds and 98.0% for adults aged 20-49 years compared with 90.0% and 98.1%, respectively, for 1988-1994. We found an increase in seropositivity between the survey periods, from 93.2% to 97.2% (p < 0.001) among 12- to 19-year-olds. For children, non-Hispanic black ethnicity and younger age were associated with lower seroprevalence in both survey periods. CONCLUSIONS: Varicella seroprevalence increased with age among children and was uniformly high in the U.S. adult population between 1999 and 2004. The original testing produced false-negative seroprevalence results among children's specimens collected between 1999 and 2004 from 6- to 19-year-olds.

Hospitalizations to treat herpes zoster in older adults: causes and validated rates.

BACKGROUND: The availability of a vaccine for the prevention of herpes zoster has increased interest in methods to measure zoster disease burden. Hospitalizations assigned a zoster diagnosis code have been used as indicators of severe zoster in prior studies. However, a zoster diagnosis code may not be a specific indicator of severe zoster illness, because the code may be assigned to a hospitalization for another cause in a person with coincident zoster. METHODS: To assess the validity of a hospital diagnosis code of zoster as an indicator of hospitalizations that are attributable to zoster, we identified all hospitalizations with a zoster diagnosis code assigned in any position among members of a managed-care organization who were >or=50 years of age during 1992-2004. Of those, we selected a sample of 260 hospitalizations for chart review. RESULTS: Chart reviews were completed for 225 hospitalizations. Sixty-five (29%) were because of zoster or a complication of zoster treatment, and an additional 9 (4%) were because of postherpetic neuralgia or a complication of postherpetic neuralgia treatment. Although the overall age-adjusted rate of hospitalizations with a zoster diagnosis code was 42.5 hospitalizations per 100,000 population per year, the estimated rate of hospitalizations because of zoster, postherpetic neuralgia, or adverse effects of a medication used to treat zoster or postherpetic neuralgia was only 14.0 hospitalizations per 100,000 population per year. CONCLUSIONS: Rates of hospitalizations associated with a zoster diagnosis code will substantially overestimate the burden of hospitalizations attributable to zoster in older adults.

Challenges to implementing second-dose varicella vaccination during an outbreak in the absence of a routine 2-dose vaccination requirement--Maine, 2006.

In June 2005, the Advisory Committee on Immunization Practices (ACIP) recommended administering a second dose of varicella vaccine during outbreaks, supplementing the routine 1-dose requirement. From October 2005 to January 2006, a varicella outbreak occurred in Maine in a highly vaccinated elementary school population. We investigated the outbreak, held a school-based vaccination clinic, and assessed costs in implementing ACIP's outbreak-response recommendation. Parents completed questionnaires and case investigation interviews. Personnel at the Maine Center for Disease Control and Prevention, the school in which the outbreak occurred ("school A"), and physician offices completed economic surveys. Forty-eight cases occurred, with no hospitalizations or deaths. Vaccine effectiveness was 86.6% (95% confidence interval, 82.0%-90.1%). Of 240 eligible students, 132 (55.0%) received second-dose vaccination. Implementing ACIP's outbreak-response recommendation was challenging and cost approximately $26,875. Additionally, the routine 1-dose varicella vaccination policy did not confer adequate population immunity to prevent this outbreak. These findings support ACIP's June 2007 recommendation for a routine 2-dose varicella vaccination program.

Epidemiology of varicella hospitalizations in the United States, 1995-2005.

To describe the impact of the varicella vaccination program on varicella-related hospitalizations (VRHs) in the United States, data from the Varicella Active Surveillance Project (VASP) were used to compare rates of hospitalization and rates of complications among patients hospitalized for varicella-related conditions from 1995 to 2005. Of the 26,290 varicella cases reported between 1995 and 2005, 170 cases resulted in VRHs, including 1 case that resulted in death. Both VRH rates per 100,000 population and complications during VRH per 100,000 population decreased significantly between the early vaccination period (1995-1998) and the middle/late vaccination period (1999-2005). Infants and adults were at highest risk for VRH, and having been vaccinated against varicella was a protective factor. Varicella vaccination may have prevented a significant number of VRHs. The fact that 4 vaccinated children required hospitalization for varicella-related complications demonstrates that 1 dose of varicella vaccine does not prevent serious disease in all cases, even among previously healthy children.

The impact of the varicella vaccination program on herpes zoster epidemiology in the United States: a review.

Speculation that a universal varicella vaccination program might lead to an increase in herpes zoster (HZ) incidence has been supported by modeling studies that assume that exposure to varicella boosts immunity and protects against reactivation of varicella-zoster virus (VZV) as HZ. Such studies predict an increase in HZ incidence until the adult population becomes predominantly composed of individuals with vaccine-induced immunity who do not harbor wild-type VZV. In the United States, a varicella vaccination program was implemented in 1995. Since then, studies monitoring HZ incidence have shown inconsistent findings: 2 studies have shown no increase in overall incidence, whereas 1 study has shown an increase. Studies from Canada and the United Kingdom have shown increasing rates of HZ incidence in the absence of a varicella vaccination program. Data suggest that heretofore unidentified risk factors for HZ also are changing over time. Further studies are needed to identify these factors, to isolate possible additional effects from a varicella vaccination program. Untangling the contribution of these different factors on HZ epidemiology will be challenging.

A population-based study of maternal and perinatal outcomes associated with assisted reproductive technology in Massachusetts.

OBJECTIVE: To assess associations between assisted reproductive technology (ART) and adverse maternal and infant outcomes, with an emphasis on singletons. METHODS: We linked data from the US ART surveillance system with Massachusetts live birth-infant death records data for resident births in 1997-1998 and compared births conceived with ART (N = 3316) with births not conceived with ART or infertility medications (N = 157,066) on: maternal chronic conditions, pregnancy complications, labor and delivery complications, and perinatal and infant outcomes. RESULTS: Overall, ART was strongly associated with numerous adverse outcomes. The magnitude was reduced for several outcomes when analyses were limited to singletons. After further exclusion of maternal subsets with rare ART births (maternal age <20; education

A comparison of heterotopic and intrauterine-only pregnancy outcomes after assisted reproductive technologies in the United States from 1999 to 2002.

OBJECTIVE: To compare the risk for adverse outcomes of pregnancies between heterotopic (defined as a simultaneous intrauterine and ectopic pregnancy) and intrauterine-only pregnancies achieved through assisted reproductive technologies (ARTs). DESIGN: Retrospective cohort study. SETTING: ART centers in the United States. PATIENT(S): Patients were studied in terms of cycles reported to the population-based United States ART Registry, which included 207 heterotopic and 132,660 intrauterine-only pregnancies reported from 1999 to 2002. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Outcomes of heterotopic and intrauterine-only pregnancies and deliveries (spontaneous abortion, induced abortion, still birth, and live birth). Perinatal outcomes (preterm, low birth weight [LBW], preterm LBW, and term LBW) for live-birth deliveries were also assessed. RESULT(S): Heterotopic pregnancies were more likely to end in spontaneous (relative risk = 2.05; 95% confidence interval, 1.67-2.51) or induced (relative risk = 10.28, 95% confidence interval, 6.76-15.65) abortions than were intrauterine-only pregnancies. There was no significant difference in perinatal outcomes studied, regardless of adjustment for maternal age, infertility diagnosis, previous live births, and type of ART procedure. CONCLUSION(S): Heterotopic pregnancies were more likely to result in spontaneous or induced abortions than were intrauterine-only pregnancies. There was no difference in perinatal outcomes between heterotopic and intrauterine-only pregnancies progressing to live birth.

Validity of self-reported use of assisted reproductive technology treatment among women participating in the Pregnancy Risk Assessment Monitoring System in five states, 2000.

OBJECTIVES: To assess the validity of a question on assisted reproductive technology (ART) incorporated into the Pregnancy Risk Assessment Monitoring System (PRAMS) in 2000. While the intent of the question is to ascertain whether the index infant was conceived using ART, the phrasing was ambiguous for women who had used ART while trying to conceive the index infant but became pregnant after discontinuing treatment. METHODS: We compared weighted PRAMS estimates from five states that incorporated the ART question in 2000 with data from the U.S. ART Surveillance System (ART-SS) maintained by the Centers for Disease Control and Prevention (CDC). U.S. medical practices are mandated to report data for every ART procedure to CDC annually; thus, the ART-SS is highly specific and complete. RESULTS: ART use was reported for 156 of the PRAMS births in our study population, representing 4,571 (95% Confidence Limit, 3,452-5,690) births from the total birth cohort in the five states of interest in 2000. For the same maternal residency states and year, 1,768 births were reported to the ART-SS. Thus, we calculate that PRAMS overestimated ART use by 2,803 births. PRAMS estimated 2.59 times as many ART births as reported to the ART-SS. While for singletons, a large excess in estimated births from PRAMS was observed (ratio=3.50), there was little difference between the PRAMS estimates and ART-SS for twin and triplet births. CONCLUSION: These findings suggest women responding to PRAMS may be reporting past ART use in addition to current. The findings by plurality support this hypothesis.

Ectopic pregnancy risk with assisted reproductive technology procedures.

OBJECTIVE: To assess the ectopic pregnancy risk among women who conceived with assisted reproductive technology (ART) procedures. METHODS: The ectopic rate for ART pregnancies was calculated from population-based data of pregnancies conceived with ART in U.S. clinics in 1999-2001. Variation in ectopic risk by patient and ART treatment factors was assessed by using bivariate analyses and multivariable logistic regression. RESULTS: Of 94,118 ART pregnancies, 2,009 (2.1%) were ectopic. Variation was observed by procedure type. In comparison with the ectopic rate (2.2%) among pregnancies conceived with in vitro fertilization and transcervical transfer of freshly fertilized embryos from the patient's oocytes (fresh, nondonor IVF-ET), the ectopic rate was significantly increased when zygote intrafallopian transfer (ZIFT) was used (3.6%) and significantly decreased when donor oocytes were used (1.4%) or when a gestational surrogate carried the pregnancy (0.9%). Among fresh nondonor IVF-ET procedures, the risk for ectopic pregnancy was increased among women with tubal factor infertility (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.7-2.4; referent group = ART for male factor), endometriosis (OR 1.3, 95% CI 1.0-1.6), and other nontubal female factors of infertility (OR 1.4, 95% CI 1.2-1.6) and decreased among women with a previous live birth (OR 0.6, 95% CI 0.5-0.7). Transfer of embryos with an indication of high implantation potential was associated with a decreased ectopic risk when 2 or fewer embryos were transferred (OR 0.7, 95% CI 0.5-0.9), but not when 3 or more embryos were transferred. CONCLUSION: Ectopic risk among ART pregnancies varied according to ART procedure type, reproductive health characteristics of the woman carrying the pregnancy, and estimated embryo implantation potential. LEVEL OF EVIDENCE: II-2.

Assisted reproductive technology surveillance--United States, 2002.

PROBLEM/CONDITION: In 1996, CDC initiated data collection regarding assisted reproductive technology (ART) procedures performed in the United States, as mandated by the Fertility Clinic Success Rate and Certification Act (FCSRCA) (Public Law 102-493, October 24, 1992). ART includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization and related procedures). Patients who undergo ART treatments are more likely to deliver multiple-birth infants than women who conceive naturally. Multiple births are associated with increased risk for mothers and infants (e.g., pregnancy complications, premature delivery, low-birthweight infants, and long-term disability among infants). REPORTING PERIOD: 2002. DESCRIPTION OF SYSTEM: : CDC contracts with the Society for Assisted Reproductive Technology (SART) to obtain data from ART medical centers located in the United States. Since 1997, CDC has compiled data related to ART procedures. RESULTS: In 2002, a total of 115,392 ART procedures were reported to CDC. These procedures resulted in 33,141 live-birth deliveries and 45,751 infants. Nationally, 74% of ART procedures used freshly fertilized embryos from the patient's eggs; 14% used thawed embryos from the patient's eggs; 8% used freshly fertilized embryos from donor eggs; and 3% used thawed embryos from donor eggs. Overall, 42% of ART transfer procedures resulted in a pregnancy, and 34% resulted in a live-birth delivery (delivery of one or more live-born infants). The highest live-birth rates were observed among ART procedures using freshly fertilized embryos from donor eggs (50%). The highest numbers of ART procedures were performed among residents of California (15,117), New York (13,276), Massachusetts (8,631), New Jersey (7,744), and Illinois (7,492). These five states also reported the highest number of infants conceived through ART. Of 45,751 infants born through ART, 53% were born in multiple-birth deliveries. The multiple-birth risk was highest for women who underwent ART transfer procedures using freshly fertilized embryos from either donor eggs (42%) or their own eggs (35%). Number of embryos transferred, embryo availability (an indicator of embryo quality), and patient's age were also strong predictors of multiple-birth risk. Approximately 1% of U.S. infants born in 2002 were conceived through ART. Those infants accounted for 17% of multiple births nationally. The percentage of ART infants who were low birth rate ranged from 9% among singletons to 95% among triplets or higher order multiples. The percentage of ART infants born preterm ranged from 15% among singletons to 97% among triplets or higher order multiples. INTERPRETATION: Whether an ART procedure resulted in a pregnancy and live-birth delivery varied according to different patient and treatment factors. ART poses a major risk for multiple births. This risk varied according to the patient's age, the type of ART procedure performed, the number of embryos transferred, and embryo availability (an indicator of embryo quality). PUBLIC HEALTH ACTION: ART-related multiple births represent a sizable proportion of all multiple births nationally and in selected states. Efforts should be made to limit the number of embryos transferred for patients undergoing ART. In addition, adverse infant health outcomes (e.g., low birthweight and preterm delivery) should be considered when assessing the efficacy and safety of ART.

Monozygotic twinning associated with day 5 embryo transfer in pregnancies conceived after IVF.

BACKGROUND: This study examines the association between day of embryo transfer and monozygotic (MZ) twinning. METHODS: We used a population-based sample of 108,36 IVF/embryo transfer procedures in which the patients oocytes' were freshly fertilized (non-frozen; non-donor) and 39,98 resultant pregnancies from US clinics in 1999 and 2000. Cases were pregnancies for which the number of fetal hearts observed on ultrasound exceeded the number of embryos transferred. These pregnancies were considered to contain at least one set of MZ twins. A total of 226 MZ pregnancies were compared with two control groups: 23,880 singleton pregnancies (one fetal heart) and 15,092 other multiple-gestation pregnancies (> or = 2 fetal hearts but the number of fetal hearts on ultrasound was less than or equal to the number of embryos transferred). RESULTS: Cases of presumed MZ multiple-gestation pregnancies were more likely to have had a day 5 embryo transfer compared with day 3 embryo transfers than singleton pregnancies [adjusted odds ratio (AOR) = 3.92, 95% confidence interval (CI) = 2.97-5.17] or other multiple-gestation pregnancies (AOR = 3.91, 95% CI = 2.96-5.17) conceived with IVF/embryo transfer. CONCLUSIONS: Day 5 embryo transfer may be associated with increased MZ twinning.

Perinatal outcome among singleton infants conceived through assisted reproductive technology in the United States.

OBJECTIVE: To examine perinatal outcome among singleton infants conceived with assisted reproductive technology (ART) in the United States. METHODS: Subjects were 62,551 infants born after ART treatments performed in 1996-2000. Secular trends in low birth weight (LBW), very low birth weight (VLBW), preterm delivery, preterm LBW, and term LBW were examined. Detailed analyses were performed for 6,377 infants conceived in 2000. Observed numbers were compared with expected using a reference population from the 2000 U.S. natality file. Adjusted risk ratios were calculated. RESULTS: The proportion of ART singletons born LBW, VLBW, and term LBW decreased from 1996 to 2000. The proportion delivered preterm and preterm LBW remained stable. After adjustment for maternal age, parity, and race/ethnicity, singleton infants born after ART in 2000 had elevated risks for all outcomes in comparison with the general population of U.S. singletons: LBW standardized risk ratio 1.62 (95% confidence interval 1.49, 1.75), VLBW 1.79 (1.45, 2.12), preterm delivery 1.41 (1.32, 1.51), preterm LBW 1.74 (1.57, 1.90), and term LBW 1.39 (1.19, 1.59). Risk ratios for each outcome remained elevated after restriction to pregnancies with only 1 fetal heart or any of 7 other categories: parental infertility diagnosis of male factor, infertility diagnosis of tubal factor, conception using in vitro fertilization without intracytoplasmic sperm injection or assisted hatching, conception with intracytoplasmic sperm injection, conception in a treatment with extra embryos available, embryo culture for 3 days, and embryo culture for 5 days. CONCLUSION: Singletons born after ART remain at increased risk for adverse perinatal outcomes; however, risk for term LBW declined from 1996 to 2000, whereas preterm LBW was stable. LEVEL OF EVIDENCE: III

Are children born after assisted reproductive technology at increased risk for adverse health outcomes?

As assisted reproductive technologies (ARTs) are increasingly used to overcome infertility, there is concern about the health of the children conceived. The empirical evidence for associations with outcomes related to child health is variable and should be evaluated with consideration of methodological shortcomings. Currently, there is convincing evidence that ART treatment may increase the risk of a few outcomes. Experimental laboratory studies document that various constituents in culture media affect various embryo characteristics both positively and negatively. Multiple-gestation pregnancy and birth are increased with ART, both because of multiple embryo transfer and embryo splitting. There is evidence of an increase in chromosomal abnormalities among pregnancies conceived using intracytoplasmic sperm injection and low birth weight and preterm delivery among singletons conceived with all types of ART; however, there remains uncertainty about whether these risks stem from the treatment or the parental infertility. For some outcomes, data of an increased risk with ART are suggestive at best largely because of lack of purposeful study of sufficient size and scope. These include specific perinatal morbidities, birth defects, developmental disabilities, and retinoblastoma. The evidence for an association between ART and spontaneous abortion is inconsistent and weak. There is inconclusive evidence that ART may be associated with genetic imprinting disorders. For childhood cancer, chronic conditions, learning and behavioral disorders, and reproductive effects there is insufficient empirical research to date, but given the data for more proximal outcomes, these outcomes merit further study. Future research needs to address the unique methodological challenges underlying study in this area.

Assisted reproductive technology surveillance--United States, 2001.

PROBLEM/CONDITION: In 1996, CDC initiated data collection regarding assisted reproductive technology (ART) procedures performed in the United States to determine medical center-specific pregnancy success rates, as mandated by the Fertility Clinic Success Rate and Certification Act (FCSRCA) (Public Law 102-493, October 24, 1992). ART includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization and related procedures). Patients who undergo ART treatments are more likely to deliver multiple-birth infants than women who conceive naturally. Multiple births are associated with increased risk for mothers and infants (e.g., pregnancy complications, premature delivery, low-birthweight infants, and long-term disability among infants). REPORTING PERIOD: 2001. DESCRIPTION OF SYSTEM: CDC contracts with a professional society, the Society for Assisted Reproductive Technology (SART), to obtain data from fertility medical centers located in the United States. Since 1997, CDC has compiled data related to ART procedures. The Assisted Reproductive Technology Surveillance System was initiated by CDC in collaboration with the American Society for Reproductive Medicine, the Society for Assisted Reproductive Technology, and RESOLVE: The National Infertility Association. RESULTS: In 2001, a total of 29,344 live-birth deliveries and 40,687 infants resulting from 107,587 ART procedures were reported from 384 medical centers in the United States and U.S. territories. Nationally, 80,864 (75%) of ART treatments used freshly fertilized embryos from the patient's eggs; 14,705 (14%) used thawed embryos from the patient's eggs; 8,592 (8%) used freshly fertilized embryos from donor eggs; and 3,426 (3%) used thawed embryos from donor eggs. Overall, 40% of ART procedures that progressed to the transfer stage resulted in a pregnancy; 33% resulted in a live-birth delivery (delivery of > or =1 infant); and 21% resulted in a singleton live birth. The highest live-birth rates were observed among ART procedures using freshly fertilized embryos from donor eggs (47%). The greatest numbers of ART procedures were performed among residents of California (13,124), New York (12,379), Massachusetts (8,151), Illinois (7,933), and New Jersey (6,011). These five states also reported the highest number of live-birth deliveries and infants born as a result of ART. The ratio of number of ART procedures per million population ranged from 74 in Idaho to 1,273 in Massachusetts, with a national average of 371 ART procedures started per million persons. Among ART treatments in which freshly fertilized embryos from the patient's eggs were used, substantial variation in live birth rates by patient (e.g., women aged < or =40 years) and treatment characteristics (e.g., ovulatory dysfunction, endometriosis, or unexplained infertility) was observed. The risk for a multiple-birth delivery was highest for women who underwent ART transfer procedures using freshly fertilized embryos from either donor eggs (42%) or from their own eggs (36%). Among ART transfer procedures in which the patient's own eggs were used, an inverse relation existed between multiple-birth risk and patient age. Number of embryos transferred and embryo availability (an indicator of embryo quality) were also strong predictors of multiple-birth risk. Of the 40,687 infants born, 46% were twins, and 8% were triplet and higher order multiples. The total multiple-infant birth rate was 53%. Approximately 1% of U.S. infants born in 2001 were conceived through ART. Those infants accounted for 16% of multiple births nationally. INTERPRETATION: Whether an ART procedure resulted in a pregnancy and live-birth delivery varied according to different patient and treatment factors. ART poses a major risk for multiple births. This risk varied according to the patient's age, the type of ART procedure performed, the number of embryos transferred, and embryo availability (an indicator of embryo quality). PUBLIC HEALTH ACTION: ART-related multiple births represent a sizable proportion of all multiple births nationally and in selected states. Efforts should be made to limit the number of embryos transferred for patients undergoing ART.