Methicillin-resistant Staphylococcus aureus: a 5-year review of surveillance data in a tertiary care hospital in Saudi Arabia.

BACKGROUND: Staphylococcus aureus is an important pathogen that leads to serious infections in the community and in hospitals. Evidence has shown that the prevalence of infection and colonization with drug-resistant S. aureus, such as methicillin-resistant S. aureus (MRSA) and glycopeptide intermediately susceptible S. aureus, is increasing. Authorities must be aware of the prevalence of MRSA infection and colonization in their country in order to implement and monitor infection control policies that help curtail further emergence of this pathogen. OBJECTIVES: To examine the trend of hospital-acquired MRSA infection and colonization in a tertiary care institution in Saudi Arabia during a 5-year period in order to identify specific areas at high risk for MRSA transmission, and to review our MRSA decolonization procedure and outcomes. METHODS: Surveillance data prospectively collected from January 1, 2000, through December 31, 2004, on hospital-acquired (HA) MRSA were analyzed, with an emphasis on the trend of HA-MRSA infection and colonization, areas of high transmission, risk factors, and effectiveness of the implemented decolonization policy. RESULTS: During the study period, 442 cases of HA-MRSA infection and colonization were identified. Of these, 51.2% were infections, and 48.8% were colonizations. An increasing trend in the incidence rates of infection and colonization was noticed during the study period, and most cases were identified on the surgical ward (33.3%) and medical ward (32.1%). Of the 34 infected patients who underwent systematic decolonization, 35.3% were successfully decolonized, and of the 11 who underwent topical decolonization, 63.6% were successfully decolonized. CONCLUSION: The increasing trend of HA-MRSA infections has been a noticeable global problem. We identified a gradual increase in the rates of MRSA colonization and infection in a tertiary care center Saudi Arabia and recognize the importance of abiding by strict infection control policies, including hand hygiene and proper isolation practices. Continued surveillance for MRSA and other emerging multidrug-resistant pathogens is also needed.

Assessing number-specific error in the recall of onset of last menstrual period.

The goal of this investigation was to determine whether women who did not report preferred numbers for their last menstrual period (LMP) may be a group of women who are particularly careful in keeping track of their menstrual cycles and therefore have more accurate LMP dating--based on a comparison with ultrasound examinations. We also sought to estimate the frequency with which preferred numbers are reported in different sources of data and for different subgroups of women. First, we examined the 1987 California birth certificates in which LMP was collected at the time of birth (n = 504853). We also examined the records of 43880 women participating in the California Alpha-fetoprotein (AFP) Screening Program between 1986 and 1987, for whom gestational ages based on both early ultrasound examination and LMP were collected before 20 weeks of gestation. In the 1987 California birth certificates, seven numbers--1, 5, 10, 15, 20, 25 and 28--were recorded more frequently than expected. An estimated 12.9% of these records had preferred numbers. The most frequently recorded number was 15, occurring 2.5 times more often than expected (P < 0.01). In the data of the AFP Screening Program, the same seven numbers were preferred, and approximately 7.9% of records were affected by number preference. Comparisons with measurements of gestational age based on ultrasound demonstrated that LMP-based gestational ages in which non-preferred numbers are reported for the LMP are slightly more accurate than those in which preferred numbers are reported (P < 0.01). In most cases, number preference appears to introduce small errors into measurements of gestational age, probably as a result of rounding. Thus, the effect of number preference may be primarily of interest to research studies in which small errors in the measurement of gestational age will have a significant impact on findings.

The genetics revolution. Ethical, legal, and insurance concerns.

Genetic researchers will soon complete a structural description of the human genome. Understanding of the detailed function and interactions of the genes will soon follow, as will the ability to manipulate genes and use them for our own purposes. This knowledge will force us to rethink our basic philosophy of life and fundamental ethics. The accumulating body of knowledge will have profound effects on the view of human beings in the cosmos and on human interactions and institutions. Although change will be gradual, primary care physicians should be prepared to deal with this process, even in today's practice. The crucial concerns are proper patient education and consent for genetic testing, maintenance of confidentiality, and awareness of a patient's right to access health insurance and specialty care. The unprecedented control of the genetic makeup of human beings will affect society's concepts of race, equality, disability, and social responsibility.

Risk factors for congenital hypothyroidism: an investigation of infant's birth weight, ethnicity, and gender in California, 1990-1998.

BACKGROUND: Approximately 85% of primary congenital hypothyroidism (CH) is sporadic and due to malformations of the thyroid gland. Past studies have reported an increased birth weight among infants with CH. We have attempted to replicate and expand these observations, examining the association between different birth weight categories and CH stratified by infant's sex. We have also examined the prevalence of CH by mother's age and infant's ethnicity, gender, and year of birth. METHODS: A cross-sectional study was conducted on 5, 049,185 infants screened by the statewide California Newborn Screening Program between 1990 and 1998, an estimated 98.6% of all newborns in the state. Dried blood spots from a heel stick were assayed for thyroxine (T4), and presumptive positives had follow-up assays of thyroid-stimulating hormone (TSH) to determine definite positives. RESULTS: A total of 1,806 cases of CH were identified. The following findings are unlikely to be due to chance. Compared with infants with birth weights of 3,000-3,499 g, infants weighing <2,000 g and those weighing >/=4,500 g had a twofold or greater increase in the prevalence of CH. This was not explained as a result of confounding by the infant's ethnicity or gender. Compared with whites, elevated prevalence rates were found in most ethnic groups, which include the following: Hispanics, Chinese, Vietnamese, Asian Indians, Filipinos, Middle Easterners, and Hawaiians. As reported previously, black infants had about one-third the prevalence rate of whites. We also observed the frequently described female preponderance of CH. The female excess was maintained at all birth weights, however it varied by infant's ethnicity. Trends in the prevalence of CH were not associated with mother's age or with the time interval between 1990 and 1998. CONCLUSIONS: We observed an increased risk of CH in both low-birth-weight (<2,000-g) and macrosomic (>/=4,500-g) infants. This U-shaped association has not been described in past studies. We have also expanded the previously described ethnic differences in CH risk to include ethnic groups not previously studied. The unique pattern of CH occurrence suggests that further studies to define modifiable risk factors may be useful.

Prenatal ultrasound findings in affected and unaffected pregnancies that are screen-positive for trisomy 18: the California experience.

This study investigated whether significant differences in ultrasound findings exist between trisomy 18 affected and unaffected pregnancies positive by serum screening. Ultrasound reports were reviewed for 335 screen-positive women. This represented 65% of all trisomy 18 screen-positive patients who had follow-up services at any of 117 Californian state-approved Prenatal Diagnosis Centers during a six-month period from November 1, 1995 to April 30, 1996. Ultrasound reports were available for 100% of trisomy 18 fetuses diagnosed during the six month period (n=23). Ultrasound findings were reported as normal in 35% of the fetuses affected with trisomy 18. The number and type of abnormalities observed in the affected and unaffected groups are described. When compared to unaffected cases, the trisomy 18 affected fetuses had a greater re-dating discrepancy on follow-up ultrasound evaluation and significantly lower femur length to biparietal diameter (FL/BPD) ratio measurements. We recommend that all women who are screen positive for trisomy 18 be encouraged to have amniocentesis, regardless of ultrasound findings, since affected fetuses may not be detected otherwise.

Neural tube defect prevalence in California (1990-1994): eliciting patterns by type of defect and maternal race/ethnicity.

This study presents race/ethnicity-specific prevalence estimates of neural tube defects (NTDs) in California using 5 years of population-based data. NTD prevalence estimates include prenatally diagnosed cases, as well as cases diagnosed at birth. The California NTD Registry contains NTD case reports identified through the California Maternal Serum Alpha-Feto Protein (AFP) Screening Program, the California Birth Defects Monitoring Program, and additional reports from clinicians and clinics throughout the state. These data were used to estimate NTD prevalence in a large population-based study (n = 1,618,279). The overall NTD prevalence among White, Black, Hispanic, and Asian women are reported, as well as race/ethnic prevalence, for anencephaly, spina bifida, and encephalocele. Rates are expressed as the number of cases per 1,000 women screened between 1990 and 1994. Among 1,457 women with an NTD-affected pregnancy, the overall rate for anencephaly, spina bifida, and encephalocele was 0.49 (95% CI 0.46-0.53), 0.42 (95% CI 0.38-0.45), and 0.08 (95% CI 0.07-0.09), respectively. When these types of NTDs are combined, Hispanic women had the highest overall rate (1.12, 95% CI 1.04-1.21), followed by Whites (0.96, 95% CI 0.89-1.04), Blacks (0.75, 95% CI 0.59-0.91), and Asians (0.75, 95% CI 0.60-0.90). Hispanic women were 45% more likely than White women to have a pregnancy affected with anencephaly (odds ratio = 1.45, 95% CI 1.24-1.70), while Asian women were over two times less likely to have a pregnancy affected with spina bifida (odds ratio = 0.44, 95% CI 0.29-0.65). Considerable variation exists in the prevalence of NTDs by race/ethnicity and by type of NTD, with Hispanic women exhibiting the highest overall NTD rate.

Cost and effectiveness of the California triple marker prenatal screening program.

PURPOSE: To report the utilization of services offered and pregnancy outcomes for a unique statewide prenatal triple marker screening program and to present a cost-benefit analysis. A state population of 32 million with considerable ethnic and age distribution and with a wide variety of delivery systems providing prenatal care was considered. The entire pregnant population who appeared for care before 20 weeks gestation, approximately one-half million per year during the years of 1995 to 1997, was included in the study. METHODS: Mandatory offering of serum testing, using alpha-fetoprotein from 1986 to 1995, and the addition of human chorionic gonadotropin and unconjugated estriol in 1995, with systematic follow-up of serum screen positives with ultrasound and amniocentesis. This study collected and analyzed the program data and reports of outcomes and collected similar information from the birth defects registry. RESULTS: Triple marker serum screening was accepted by 67.4% of the women eligible and yielded an initial positive rate of 7.3%. More than 90% of the initially screen positive pregnancies were seen at a prenatal diagnostic center. After correction of gestational age, 71.3% had amniocentesis. The overall amniocentesis rate among women screened was 2.6%. The Program's detection rate was predicted to be 85% for neural tube defects, and, based on Monte Carlo modeling, was theoretically calculated to be 62% for Down syndrome. In practice, detection rates were 75% for neural tube defects and 41% for Down syndrome due to lower than expected amniocentesis acceptance rate. Nevertheless, at a 5% discount rate, the screening program was cost beneficial at a ratio of 2.69:1. The cost per case detected was $35,365 and per case prevented was $110,741. CONCLUSION: It is possible to implement a cost-effective population-based screening in compliance with quality standards in a diverse ethnic population with a variety of health-care providers. Triple marker screening in the second trimester is a cost beneficial program even if utilization of all services is less than ideal.

Issues in implementing prenatal screening for cystic fibrosis: results of a working conference.

PURPOSE: To summarize a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. METHODS: Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. RESULTS: Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost-effectively by identifying racial/ethnic groups at sufficient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. CONCLUSIONS: Once adequate facilities for patient and provider education, testing, counseling, quality control, and monitoring are in place, individual programs can begin prenatal screening for cystic fibrosis.

Use of phenylalanine-to-tyrosine ratio determined by tandem mass spectrometry to improve newborn screening for phenylketonuria of early discharge specimens collected in the first 24 hours.

We compared the screening interpretation of fluorometric analytical results for phenylketonuria (PKU) with tandem mass spectrometry (MS/MS) in filter paper blood spots collected from newborns <24 h of age. In MS/MS, both Phe and Tyr are quantified. Two hundred and eight blood spots collected from infants <24 h of age were retrieved from storage from the California newborn screening program. These samples had been categorized on the basis of fluorometric analysis as initial negative, initial positive for hyperphenylalaninemia with negative determination on recall, or initial positive for hyperphenylalaninemia and confirmed on follow up as PKU or variant hyperphenylalaninemia. The retrieved samples were analyzed in a blinded fashion using MS/MS. Correlation analysis of fluorometry vs MS/MS for Phe concentration was high, with a Pearson correlation coefficient of 0.817. When 180 micromol/L was used as the cutoff Phe concentration for MS/MS and 258 micromol/L was used as the cutoff for fluorometry, all infants with confirmed classical PKU and variant hyperphenylalaninemia were detected. MS/MS analysis reduced the number of false-positive results from 91 to 3. Simultaneous quantification of Phe and Tyr by MS/MS with the use of a cutoff Phe/Tyr molar ratio of 2.5 further reduced the number of false positives to 1. Samples from affected infants showed a discernible trend of increasing Phe concentration and Phe/Tyr molar ratio with age of collection. These results demonstrate the utility of MS/MS in the routine PKU screening of early-discharge newborns. MS/MS reduces the false-positive rate of fluorometric screening almost 100-fold because of the improved accuracy and precision of Phe measurement and simultaneous confirmation with the Phe/Tyr molar ratio. In addition to the detection of PKU, MS/MS can also detect other aminoacidopathies and disorders of fatty acid and organic acid metabolism with lower false-positive rates than other methods currently used in newborn screening programs.

Vitamin A and birth defects.

OBJECTIVE: Our objective was to determine whether moderate doses of vitamin A are teratogenic. STUDY DESIGN: This was a geographically based case-control study. Women whose pregnancies produced offspring with neural tube defects (n = 548) or major malformations other than neural tube defects (n = 387) and normal control subjects (n = 573) were interviewed to determine periconceptional vitamin A supplement exposure levels. RESULTS: The proportion of women consuming doses of vitamin A between 8000 and 25,000 IU was no greater in the major malformations group or the group with neural tube defects than in the normal control group. For exposure from supplements and fortified cereals combined, women consuming >8000 and >10,000 IU daily had odds ratios for major malformations of 0.79 (95% confidence interval 0.40 to 1.53) and 0.73 (95% confidence interval 0.27 to 1.96), respectively, compared with women consuming <5000 IU. The results for neural tube defects were similar. For cranial neural crest defects the odds ratios were 0.76 (0.22 to 2.56) and 1.09 (0.24 to 4.98) for exposure to >8000 and >10,000 IU, respectively, versus exposure to <5000 IU. CONCLUSIONS: This study found no association between periconceptional vitamin A exposure at doses >8000 IU or >10,000 IU per day and malformations in general, cranial neural crest defects, or neural tube defects. If vitamin A is a teratogen, the minimum teratogenic dose appears to be well above the level consumed by most women during organogenesis.

The association between maternal serum alpha-fetoprotein and preterm birth, small for gestational age infants, preeclampsia, and placental complications.

OBJECTIVE: To determine whether high levels of serum alpha-fetoprotein (AFP) predict increased risk of adverse pregnancy outcomes, including preterm birth (before 37 weeks), preterm birth occurring at or before 28 weeks, small for gestational age (SGA) infant, preeclampsia, and placental abnormalities, and to determine whether low levels of serum AFP predict increased or decreased risk of these outcomes. METHODS: Using the mother's first name, last name, and zip code, we linked the records of 51,008 women who participated in the California Alpha-Fetoprotein Screening Program between June 15, 1986, and October 31, 1987, with California birth certificates for singleton infants born in 1987. The accuracy of the data linkage was confirmed by manually examining complete names, mother's ethnicity, and mother's age for a sample of 500 of the mother-infant linkages. Blood samples were obtained at 15-19 weeks. RESULTS: A strong gradient of increasing risk of preterm birth with increasing levels of serum AFP was observed (test for trend, P < .01). Among women with high levels of serum AFP (at least 2.5 multiples of the median [MoM]), 24.3% had preterm births, compared with 3.8% of women with low levels of serum AFP (0.81 MoM or less), odds ratio 8.7, 95% confidence interval 7.1-10.7). This gradient persisted when preterm infants of 28 weeks or less were examined separately. Similar gradients were observed for the risk of preeclampsia and placental abnormalities. There was a weaker U-shaped relation between serum AFP level and the risk of an SGA infant. CONCLUSION: Low levels of second-trimester maternal serum AFP are associated with a very low risk of preterm birth, preeclampsia, and placental complications. High levels of serum AFP are strongly associated with preterm birth, preeclampsia, and placental abnormalities. There is a modest association between AFP levels (both low and high) and SGA birth.

Newborn screening for sickle cell disease: 4 years of experience from California's newborn screening program.

PURPOSE: In this article we describe the success of a unique newborn screening program for sickle cell disease and other hemoglobinopathies. We will present and discuss 4 years of experience from the California Newborn Hemoglobinopathy Screening Program. METHODS: Several aspects that ensure the success of the program will be reviewed. These aspects include (a) the use of high-pressure liquid chromatography as the initial screening technique, (b) a confirmatory testing laboratory that incorporates DNA technology and innovative protein analysis using electrospray mass spectrometry, and (c) a complex follow-up strategy that employs regional nurses to track positive results and ensure timely enrollment of infants into treatment systems. RESULTS: Of these 2 million infants screened, 492 were diagnosed with some form of sickle cell disease; 290 (58.9%) were diagnosed with hemoglobin SS, 143 (29.0%) were diagnosed with hemoglobin SC, and 47 (9.5%) were diagnosed with S beta+thalassemia. CONCLUSION: The prevalence and ethnicity data presented here demonstrate the ineffectiveness of targeted screening and justify universal screening. Had targeted screening been performed in California during the past 4 years, 58 nonblack infants with sickle cell disease would have gone undiagnosed, and 6,921 nonblack infants with sickle cell trait would not have been identified.

Distribution of hemoglobinopathy variants by ethnicity in a multiethnic state.

It has been well known for many years that Black Americans are at increased risk for sickle cell disease and that individuals of Mediterranean ancestry are at increased risk for thalassemias. Beyond this, however, complete assessments of the epidemiology of hemoglobinopathies in Americans have been constrained by lack of large enough sample size, incomplete diagnostic work or testing inadequacies, or missing or misleading ethnicity data. California began universal, mandatory screening of all infants born in the state in 1990, and by January 1996, had screened over 3.3 million infants of various ethnic backgrounds. New information is now available on groups at increased risk for disease, as well as carrier status. The overall prevalence of sickle cell disease (all types) remains high in Blacks at 1 per 396 births, but is lower than expected (from east coast/ Caribbean published data) for Hispanics at 1 m 36,000 births or from previously published data on other higher risk groups such as Middle Eastern (no cases in over 22,000 screens) or Asian Indian (1 case in 16,000 screens). The distribution of different types of sickle cell disease has also changed, with increased numbers of Hb SE disease resulting from multiethnic partnerships. Demographic trends in California have led to a major sift in the at-risk groups for major beta thalassemias, with the majority of cases detected in families of Asian, Southeast Asian, and Asian Indian ancestry. The "new" hemoglobinopathy condition in California, Hb E/Beta. Thalassemia, is found almost exclusively in Southeast Asians with a prevalence of 1 in every 2,600 births. Carrier conditions are found in virtually every ethnic category, with higher than expected rates in non-Hispanic Whites (1 per 600 births).

Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening.

BACKGROUND: As maternal age advances, the risk of fetal Down's syndrome increases. Pregnant women 35 years of age or older are routinely offered amniocentesis because of this risk. Recently, maternal serum markers have been reported to be useful in screening for Down's syndrome, primarily in younger women. We therefore investigated whether offering amniocentesis only to selected women 35 years of age or older who were identified by screening measurements in serum might prove a useful alternative to the current practice. METHODS: We studied 5385 women with singleton pregnancies who were 35 years of age or older and were undergoing routine amniocentesis. Along with information about the pregnancy, we obtained a serum sample for measurement of alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Individual estimates of the risk of Down's syndrome in the fetus were calculated for each pregnancy before the karyotype was known. RESULTS: If amniocentesis had been reserved for the women calculated to have a risk greater than 1 in 200 of having a fetus with Down's syndrome, 48 of the 54 cases of Down's syndrome (89 percent) would have been identified, 25 percent of the unaffected pregnancies would also have been identified as being at high risk for Down's syndrome (false positives). Seven of 15 fetuses (47 percent) with other trisomies, 11 of 25 (44 percent) with sex aneuploidy, and 1 of 9 (11 percent) with miscellaneous chromosomal abnormalities would also have been detected. In practice, such screening would have made 75 percent of the amniocentesis unnecessary, along with a proportion of the amniocentesis-associated fetal losses. If the cutoff for the risk of Down's syndrome were set higher than 1 in 200, both the rate of detection and the false positive rate would be lower. Conversely, these rates would be higher if the cutoff were set lower. CONCLUSIONS: Prenatal screening of serum to generate individual estimates of the risk of Down's syndrome in the fetus can provide a basis for decision making in the cases of women 35 years of age or older, as it does in younger pregnant women, and is an alternative to current testing practices.

Incidence of sudden infant death syndrome in infants with sickle cell trait.

The significantly higher incidence of both sickle cell trait (SCT) and sudden infant death syndrome (SIDS) in the black population suggests that SCT and SIDS may be epidemiologically related. To study this possibility, we identified, for the period of February 1990 to February 1992, all infants with SCT born in Los Angeles County whose disease was diagnosed through the California Newborn Screening Program. We matched these infants with all confirmed cases of SIDS in Los Angeles County from February 1990 to March 1993. Three cases of SCT among 589 infants confirmed to have had SIDS were identified. The incidence of SIDS was 1.25/1000 live births for the general population versus 0.58/1000 cases for the SCT group. This finding remained unchanged when rates were adjusted for ethnicity. We conclude that infants born with SCT are not at increased risk of dying of SIDS.

Are obese women at higher risk for producing malformed offspring?

OBJECTIVE: Our purpose was to determine whether obese women and underweight women have an increased risk of birth defects in their offspring. STUDY DESIGN: A geographically based case-control study of women living in California and Illinois was performed. There were 499 mothers of offspring with neural tube defects, 337 mothers of offspring with other major birth defects, and 534 mothers of offspring without birth defects who participated. RESULTS: Compared with women of normal weight, women who were extremely obese before pregnancy (body mass index > or = 31 kg/m2) showed a significantly increased risk of having an infant with a neural tube defect (odds ratio 1.8, 95% confidence interval 1.1 to 3.0), especially spina bifida (odds ratio 2.6, 95% confidence interval 1.5 to 4.5), after adjustments for age, race, education, and family income. Obese women also had significantly increased risks (p < 0.05) of having an infant with other defects of the central nervous system, great vessel defects, ventral wall defects, or other intestinal defects. CONCLUSION: Our data suggest that offspring of obese women (but not underweight women) are at an increased risk of neural tube defects and several other malformations. If these findings are confirmed, further research will be necessary before it can be concluded that weight reduction before pregnancy will lower the risk of birth defects among obese women. Until then, obese women can address their risk of birth defects with the same measures that are recommended for all women, such as adequate daily intake of folic acid and alpha-fetoprotein screening to identify malformed fetuses.

Prenatal genetic services: toward a national data base.

PIP: The availability of prenatal genetic services in the US was assessed in a 1990-91 survey. Prenatal screening services are offered in 46 of 51 states, and 47 states have prenatal counseling and diagnostic services available. Comprehensive national and regional data collection and reporting for prenatal genetic services has been conducted by the Council of Regional Networks for Genetic Services (CORN) in cooperation with the 10 regional genetic services networks since 1985. The results of CORN data collection on prenatal genetic services in 1989 and 1990 are presented. A 60% participation rate was achieved in 1989 for the more than 400 reporting units. In 1990, 227 of the 302 prenatal-clinical genetic reporting units contacted (75%) were able to supply data. 135 (92%) of the 146 laboratory reporting units provided data. In 1989, data were collected on more than 124,000 prenatal patients, accounting for almost 303,000 individual prenatal clinical services, including counseling and medical procedures, such as ultrasonography, amniocentesis, and chorionic villus sampling. Almost 920,000 laboratory tests, including blood studies, amniotic fluid tests, and chorionic tissue tests were performed in 1989 by a laboratory of the reporting unit. The 1990 figures indicated 12-30% increased in patients and reported services. 73% of prenatal genetic patients were white; below the percentage of white women aged 15-54 years nationally. The percentages of patients of Asian Pacific Islander ancestry and of other races were higher than in the national figures for women of reproductive age. Advanced maternal age continued to be the leading reason for referral to prenatal genetic services, although the percentage has decreased from 1989 to 1990. The percentage of patients for whom indication for service was unknown more than tripled between 1989 and 1990. CORN has made significant progress toward the development of a national system of reporting genetic services.^ieng