Triple-marker prenatal screening program for chromosomal defects.

OBJECTIVE: To examine screening performance of California's 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.

Identification of second trimester screen positive pregnancies at increased risk for congenital heart defects.

OBJECTIVE: To examine whether second trimester biomarkers could be used to identify screen positive pregnancies at increased risk for congenital heart defects (CHDs) and measure the effect of using different biomarker cut points on the detection of CHDs and on the performance of predictive models. METHODS: Included were 19,402 pregnancies without chromosomal defects, which were screen positive for Down syndrome or other birth defects based on maternal serum measurements of alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated estriol (uE3). Logistic regression models were built that compared biomarkers for CHD cases compared to controls. RESULTS: CHD cases were more likely to be screen positive for trisomy-18, to have a nuchal fold (NF) >or= 5 mm, and/or to have an hCG multiple of the median (MoM) >or= 95th percentile in models that considered screen positive grouping. In models that did not consider screen positive grouping, cases were more likely to have a NF >or= 5 mm, an AFP MoM or= 75th percentile. CONCLUSION: Along with NF, second trimester maternal serum biomarkers may be useful indicators for fetal and newborn evaluation for CHDs in screen positive pregnancies without identified chromosomal defects.

Using second trimester ultrasound and maternal serum biomarker data to help detect congenital heart defects in pregnancies with positive triple-marker screening results.

Congenital heart defects (CHDs) are the most common of all birth defects. For many newborns with a CHD, prenatal versus postnatal detection is associated with substantially decreased morbidity and mortality risks. Although technological advances in fetal echocardiography have led to an increased capacity to detect CHDs prenatally, pregnancies without an identified risk factor are not routinely screened. With the aim of identifying pregnancies at increased risk for CHDs, this study examined the relationship between CHDs and typically collected second trimester biomarker data collected on a large population-based sample of singleton pregnancies with one or more second trimester screen positive result for Down syndrome, trisomy 18 (T-18), Smith-Lemli-Opitz syndrome (SLOS), or a neural tube defect (NTD). Where possible, logistic models for cases and controls were built and potential referral models were tested among study subsamples with information on the presence or absence of CHDs reported pre- and perinatally. When considered in combination, screen positive for T-18, screen positive for SLOS, nuchal fold measurement > or = 5 mm, and/or having an adjusted hCG multiple of the median > or = the 95th centile detected 42.7% of all pregnancies with a CHD in the combined subsample (where co-occurrence with chromosomal defects was not considered) and detected 29.7% of all pregnancies with a CHD in the no-chromosomal defect subsample. A nuchal fold measurement > or = 5 mm detected 18.2% of those with a CHD in the Down syndrome subsample and an adjusted hCG multiple of the median (MoM) < or = 5th centile detected 92.9% of those with a CHD in the T-18 subsample.

Rates of pediatric injuries by 3-month intervals for children 0 to 3 years of age.

OBJECTIVE: Mortality and morbidity data on childhood injury are used to construct developmentally appropriate intervention strategies and to guide pediatric anticipatory counseling on injury prevention topics. Effective anticipatory guidance depends on detailed injury data showing how risks change as children develop. Conventional age groupings may be too broad to show the relationship between children's development and their risk of various causes of injury. Previous studies revealed differences in overall rates and specific causes of injury by year of age. However, single year of age rates for children younger than 4 years may not reflect the variations in risk as a result of rapid developmental changes. This study was designed to analyze injury rates for children younger than 4 years by quarter-year intervals to determine more specifically the age period of highest risk for injury and for specific causes. METHODS: We used data from 1996-1998 California hospital discharges and death certificates to identify day of age and external cause of injury (E-code) for children younger than 4 years. The number of California residents for each day of age was estimated from US Census of estimates of California's population by year of age for the midpoints (1996-1998). Rates were calculated by 3-month intervals. We grouped the E-codes into major categories that would be particularly relevant for developmentally related risks of injury specific to young children. The categorization took into account physical, motor, behavioral, and cognitive developmental milestones of children 0 to 3 years. RESULTS: There were a total of 23,173 injuries; 636 resulted in death. The overall annual rate for children aged 0 to 3 years was 371/100,000. Beginning at age 3 to 5 months, the overall rate of injury rapidly increased with increased age, peaking at 15 to 17 months. The mean injury rate calculated for each single year of age did not reflect the variation and the highest rate of injury by quarter year of age for children younger than 1 year, 1 year, and 2 years. The leading major causes of injury in descending order were falls, poisoning, transportation, foreign body, and fires/burns. The overall rate of the major category of falls exceeded poisoning, the second leading cause of injury, by a factor of 2. Age-related differences were detected within each major cause of injury. For children 0 to 12 months of age, there was a different leading cause of specific injury for each 3-month period: other falls from height (0-2 months), battering (3-5 months), falls from furniture (6-8 months), and nonairway foreign body (9-11 months). Hot liquid and vapor injuries were the leading specific causes for children 12 to 17 months. Poisoning by medication was the leading specific cause of injury for all age groups from 18 to 35 months and exceeded poisoning by other substances. Pedestrian injury was the leading specific cause of injury for all age groups from 36 to 47 months. Fall from furniture has the highest rates of specific causes of falls from age 3 to 47 months. Fall from stairs peaked at age 6 to 8 months and 9 to 11 months. Fall from buildings was highest at 24 to 26 months. Poisoning by medication peaked at age 21 to 23 months, but poisoning by other substances peaked at 15 to 17 months. The motor vehicle occupant injury rates were fairly stable over the age span of this study. The pedestrian injury rate increased beginning at age 12 to 14 months and by 15 to 17 months was double that of the motor vehicle occupant. Foreign body had a marked peak at age 9 to 11 months. Both battering and neglect rates were highest among infants 0 to 2 and 3 to 5 months. Bathtub submersions had a narrow peak at age 6 to 11 months. Other submersions peaked at 12 to 14 months and remained high until 33 to 35 months. CONCLUSIONS: We departed from usual groupings of E-codes and devised groupings that would be reflective of age-related developmental characteristics. Differences in rates by narrow age groups for young children can be related to developmental achievements, w can be related to developmental achievements, which place the child at risk for specific causes of injury. We found marked variability in both rates and leading causes of injury by 3-month interval age groupings that were masked by year of age analyses. Children aged 15 to 17 months had the highest overall injury rate before age 15 years. This coincides with developmental achievements such as independent mobility, exploratory behavior, and hand-to-mouth activity. The child is able to access hazards but has not yet developed cognitive hazard awareness and avoidance skills. A remarkable finding was the high rate of battering injury among infants 0 to 5 months, suggesting the need to address potential child maltreatment in the perinatal period. Poisoning was the second major leading cause of injury; more than two thirds were medication. Cultural factors may influence views of medications, storage practices, use of poison control system telephone advice, and risk of toddler poisoning. The pedestrian injury rate doubled between 12 and 14 months and 15 and 17 months and exceeded motor vehicle occupant injury rates for each 3-month interval from 15 to 47 months. Pedestrian injury has not received sufficient attention in general and certainly not in injury prevention counseling for children younger than 4 years. Anticipatory guidance for pedestrian injury should be incorporated before 1 year of age. Effective strategies must be based on the epidemiology of childhood injury. Pediatricians and other pediatric health care providers are in a unique position to render injury prevention services to their patients. Integrating injury prevention messages in the context of developmental assessments of the child is 1 strategy. These data can also be used for complementary childhood injury prevention strategies such as early intervention programs for high-risk families for child abuse and neglect, media and advocacy campaigns, public policies, and environmental and product design.