Marie Roberson

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.

Triple-marker Prenatal Screening Program for Chromosomal Defects

OBJECTIVE: To examine screening performance of Californias triple-marker screening program, using data from a statewide registry for chromosomal defects. METHODS: This study included 752,686 women who received a screening risk and had an expected date of delivery between July 2005 and the end of June 2007. Follow-up diagnostic services for screen-positive women were performed at state-approved centers. Data on diagnostic outcomes from these visits were entered into the California Chromosomal Defect Registry (CCDR). Other CCDR sources include mandatory reporting by all cytogenetic laboratories and hospitals and outcome data forms submitted by prenatal care providers. RESULTS: The observed detection rate for Down syndrome (N=1,217) was 77.4%. It varied significantly by gestational dating method and maternal age. The rates for women aged younger than 35 years and 35 years and older were 62.4% and 94.0%, respectively. The detection rates were 81.3% for ultrasound-dated pregnancies and 67.5% for last menstrual period–dated pregnancies. For Turner syndrome, trisomy 18, triploidy, and trisomy 13, the detection rates were 79.4%, 82.5%, 98.1%, and 36.0%, respectively. The positive rate for Down syndrome was 5.4%. Of women with a Down syndrome fetus who were screen positive, only 49.5% opted for amniocentesis. Of women who obtained results from amniocentesis indicating a Down syndrome fetus, 61.4% had an elective termination, 26.2% had a live birth, 4.5% had a death or miscarriage, and 7.9% had an unknown outcome. CONCLUSION: The observed performance of this large triple-marker screening program exceeds generally predicted detection rates for Down syndrome. This study methodology will be used to measure the performance of subsequent screening enhancements. LEVEL OF EVIDENCE: III

Maternal urine and serum steroid measurements to identify steroid sulfatase deficiency (STSD) in second trimester pregnancies

To document the performance of second trimester maternal urine and serum steroid measurements for detecting fetal steroid sulfatase deficiency (STSD).

Detection rate of quadruple‐marker screening determined by clinical follow‐up and registry data in the statewide California program, July 2007 to February 2009

To evaluate the efficiency of Californias quadruple‐marker screening program and construct receiver‐operating characteristic (ROC) curves.

Prevalence of steroid sulfatase deficiency in California according to race and ethnicity

Estimate steroid sulfatase deficiency (STSD) prevalence among Californias racial/ethnic groups using data from a previous study focused on prenatal detection of Smith‐Lemli‐Opitz syndrome (SLOS). SLOS and STSD both have low maternal serum unconjugated estriol (uE3) levels.

Ancillary benefits of prenatal maternal serum screening achieved in the California program.

To evaluate the extent of fetal structural abnormalities, other than neural tube and abdominal wall defects (AWDs), identified by Californias Prenatal Screening Program.

Further insights into implications of undetectable or very low unconjugated estriol in maternal serum during the second trimester

When unconjugated estriol (uE3) concentrations are undetectable during the second trimester, prenatal screening programs for Down syndrome sometimes add an interpretation for steroid sulfatase deficiency (STSD). STSD is an X-linked enzyme deficiency that interferes with placental estriol production and results most often in uE3 measurements that are undetectably low. The major clinical manifestation of STSD is ichthyosis, with more recent preliminary data suggesting that attention deficit/hyperactivity disorder might occur in conjunction with STSD at greater than the expected frequency (Kent et al., 2008). STSD may be associated with corneal opacities, cryptorchidism and, in an affected pregnancy, with delayed onset of labor. About 10% of STSD cases may also be associated with a variable contiguous gene deletion syndrome (CGDS; Marcos et al., 2009). Symptoms of ichthyosis can be reduced with treatment and, in the absence of CGDS, STSD is not considered a serious health problem. As a result, there has been debate as to whether attention should be called prenatally to the possibility of STSD (Bradley et al., 1997). The purpose of this analysis is to further explore the implications of undetectable or very low maternal serum uE3, by analyzing data from a study of 777 088 pregnancies in California that focused originally on Smith-Lemli-Opitz syndrome (SLOS), a disorder that is also associated with very low uE3 concentrations (Craig et al., 2007). As the algorithm that detects SLOS identifies the majority of pregnancies with very low uE3 levels (Craig et al., 2010), these data can be generalized to prenatal screening programs that do not use the SLOS screening algorithm. During the second trimester, undetectable or very low uE3 concentrations occur infrequently among screened women, hampering documentation of health implications

Increased incidence of profound biotinidase deficiency among Hispanic newborns in California

We report population findings from newborn screening for biotinidase deficiency in California, representing over 2,000,000 newborns. The incidence of profound deficiency was 1/73,629, higher than in other reported populations. Out of 28 patients with profound biotinidase deficiency, 19 were of Hispanic descent, suggesting an increased frequency among this group. Of the 28 patients, 23 underwent mutation analysis of the BTD gene, with one common mutation, 528G>T, found in 43.3% of Hispanic alleles tested.

Triple-marker prenatal screening program for chromosomal defects

To examine screening performance of California’s triple-marker screening program, using data from a statewide registry for chromosomal defects. This study included 752,686 women who received a screening risk and had an expected date of delivery between July 2005 and the end of June 2007. Follow-up diagnostic services for screen-positive women were performed at state-approved centers. Data on diagnostic outcomes from these visits were entered into the California Chromosomal Defect Registry (CCDR). Other CCDR sources include mandatory reporting by all cytogenetic laboratories and hospitals and outcome data forms submitted by prenatal care providers. The observed detection rate for Down syndrome (n = 1,217) was 77,4%. It varied significantly by gestational dating method and maternal age. The rates for women aged younger than 35 years and 35 years and older were 62,4% and 94.0%, respectively. The detection rates were 81,3% for ultrasound-dated pregnancies and 67,5% for last menstrual period–dated pregnancies. For Turner syndrome, trisomy 18, triploidy, and trisomy 13, the detection rates were 79,4%, 82,5%, 98,1%, and 36,0%, respectively. The positive rate for Down syndrome was 5,4%. Of women with a Down syndrome fetus who were screen positive, only 49,5% opted for amniocentesis. Of women who obtained results from amniocentesis indicating a Down syndrome fetus, 61,4% had an elective termination, 26,2% had a live birth, 4,5% had a death or miscarriage, and 7,9% had an unknown outcome. The observed performance of this large triple-marker screening program exceeds generally predicted detection rates for Down syndrome. This study methodology will be used to measure the performance of subsequent screening enhancements.