Lisa Feuchtbaum

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 alphafetoprotein (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 mothers 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, mothers ethnicity, and mothers 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.

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.

Birth prevalence of disorders detectable through newborn screening by race/ethnicity

Purpose:The purpose of this study was to describe the birth prevalence of genetic disorders among different racial/ethnic groups through population-based newborn screening data.Methods:Between 7 July 2005 and 6 July 2010 newborns in California were screened for selected metabolic, endocrine, hemoglobin, and cystic fibrosis disorders using a blood sample collected via heel stick. The race and ethnicity of each newborn was self-reported by the mother at the time of specimen collection.Results:Of 2,282,138 newborns screened, the overall disorder detection rate was 1 in 500 births. The disorder with the highest prevalence among all groups was primary congenital hypothyroidism (1 in 1,706 births). Birth prevalence for specific disorders varied widely among different racial/ethnic groups.Conclusion:The California newborn screening data offer a unique opportunity to explore the birth prevalence of many genetic disorders across a wide spectrum of racial/ethnicity classifications. The data demonstrate that racial/ethnic subgroups of the California newborn population have very different patterns of heritable disease expression. Determining the birth prevalence of these disorders in California is a first step to understanding the short- and long-term medical and treatment needs faced by affected communities, especially those groups that are impacted by more severe disorders.Genet Med 2012:14(11):937–945

Newborn Screening for Cystic Fibrosis in California

OBJECTIVES: This article describes the methods used and the program performance results for the first 5 years of newborn screening for cystic fibrosis (CF) in California. METHODS: From July 16, 2007, to June 30, 2012, a total of 2 573 293 newborns were screened for CF by using a 3-step model: (1) measuring immunoreactive trypsinogen in all dried blood spot specimens; (2) testing 28 to 40 selected cystic fibrosis transmembrane conductance regulator (CFTR) mutations in specimens with immunoreactive trypsinogen values ≥62 ng/mL (top 1.6%); and (3) performing DNA sequencing on specimens found to have only 1 mutation in step 2. Infants with ≥2 mutations/variants were referred to CF care centers for diagnostic evaluation and follow-up. Infants with 1 mutation were considered carriers and their parents offered telephone genetic counseling. RESULTS: Overall, 345 CF cases, 533 CFTR-related metabolic syndrome cases, and 1617 carriers were detected; 28 cases of CF were missed. Of the 345 CF cases, 20 (5.8%) infants were initially assessed as having CFTR-related metabolic syndrome, and their CF diagnosis occurred after age 6 months (median follow-up: 4.5 years). Program sensitivity was 92%, and the positive predictive value was 34%. CF prevalence was 1 in 6899 births. A total of 303 CFTR mutations were identified, including 78 novel variants. The median age at referral to a CF care center was 34 days (18 and 37 days for step 2 and 3 screening test–positive infants, respectively). CONCLUSIONS: The 3-step model had high detection and low false-positive levels in this diverse population.

California's Experience Implementing a Pilot Newborn Supplemental Screening Program Using Tandem Mass Spectrometry

OBJECTIVE. In response to a California legislative mandate, a pilot tandem mass spectrometry (MS/MS) screening program was undertaken by the Genetic Disease Branch of the California Department of Health Services between January 2002 and June 2003. This article outlines the Genetic Disease Branch approach to implementing the MS/MS pilot program and the program evaluation strategies used. METHODS. Through the use of multiple data collection methods, we were able to describe hospital participation patterns, screening test uptake, screening test performance, follow-up services utilization, and provider and family satisfaction with the educational materials and follow-up services provided. RESULTS. During the 18-month pilot program, just more than one half of Californias 755698 newborns were offered MS/MS screening; among this group, 90% of parents chose to have their newborns screened. Fifty-one newborns were identified with MS/MS-detectable disorders, among 461 patients referred for follow-up testing (0.13% of the screened population). One disorder was diagnosed successfully for every 6939 newborns screened and for every 9 infants referred (excluding phenylketonuria). The overall California population prevalence of MS/MS-detectable disorders was 1 case per 6500 infants (excluding phenylketonuria). The positive predictive value for medium-chain acyl-CoA dehydrogenase deficiency was 86.7%, whereas the positive predictive value for short-chain acyl-CoA dehydrogenase deficiency was 21.6%. For a sample from Hawaii, 1 isovaleric aciduria case was detected among 6132 newborns. CONCLUSIONS. Evaluation of the California MS/MS screening pilot program demonstrated that this technology was effective in identifying additional metabolic disorders. The positive predictive value of screening was particularly good for medium-chain acyl-CoA dehydrogenase deficiency. Overall, patient referral rates were very acceptable. The utility of the program was also demonstrated by positive reviews from patients and providers.

Economic Evaluation of Tandem Mass Spectrometry Screening in California

OBJECTIVE. On the basis of California’s experience implementing a pilot tandem mass spectrometry (MS/MS) screening program, an economic evaluation was conducted to determine the economic benefits and costs of a statewide MS/MS screening program. METHODS. Cost-effectiveness, benefit/cost, and cost-utility analyses were conducted with a base-case set of assumptions. The base-case assumptions were varied by using a set of more-favorable and less-favorable assumptions to test the robustness of the analysis findings. RESULTS. The total estimated, annualized, incremental costs of MS/MS screening of 540000 births in California were nearly

The California Maternal Serum α-Fetoprotein Screening Program: The role of ultrasonography in the detection of spina bifida

5.7 million; 83 affected newborns would be identified. Screening would reduce the expected lifetime costs of medical care for affected newborns by

Biochemical, molecular, and clinical characteristics of children with short chain acyl-CoA dehydrogenase deficiency detected by newborn screening in California

7.2 million (

Questioning the Need for Informed Consent: A Case Study of California's Experience with a Pilot Newborn Screening Research Project.

9.0 million in the best-case scenario and

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

1.8 million in the worst-case scenario). When all program costs and savings were considered, screening saved