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

Abstract

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.

Risk of critical congenital heart defects by nuchal translucency norms

“…All sources are mandated by California law to report diagnosed chromosomal abnormalities (whether diagnosed by karyotype or microarray) to the program. [20][21][22][23][24] Information on CCHDs was collected by the linkage of screening records with all hospital discharge records through 1 year of age for each study infant (wherein records were linked with the use of multiple identifiers [baby and mother date of birth; baby first and last name; mother first, last, and maiden name, address, phone number, and hospital of baby birth]). These records include all inpatient discharge information that is submitted to the state each time a patient is treated in a licensed general acute care hospital in California and includes all diagnoses present at the time of discharge based on 4-or 5-digit codes from the Ninth Revision of the International Classification of Diseases.…”

Inflammatory biomarkers and spontaneous preterm birth among obese women

“…These 68 obese women were selected from a larger cohort of 1000 women, who all had first and second trimester prenatal screening for aneuoploidies and neural tube defects through the California Genetic Disease Screening Program from July 2009 through December 2010. Details of the larger cohort have been described previously [18–25]. …”

Second trimester serum predictors of congenital heart defects in pregnancies without chromosomal or neural tube defects

“…Details about the California Expanded AFP Screening Program including information about how serum is tested, how multiple of the median (MoM) values are calculated, and about how chromosomal defects and NTD diagnoses are tracked by the state have been reported elsewhere (Craig et al , 2007; Jelliffe‐Pawlowski et al , 2008).…”

“…Recent work by our group examining the association between typically collected second trimester serum biomarkers [alpha‐fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3)] and CHDs among pregnancies with screen positive results for Down syndrome, trisomy‐18 (T‐18), neural tube defect (NTD), or Smith–Lemli–Opitz syndrome (SLOS) suggested that serum biomarker patterns could potentially be used when evaluating CHD risk (Jelliffe‐Pawlowski et al , 2008, 2009). Using independent samples, both studies found that abnormally high or low hCG levels were strongly associated with an increased risk for CHDs in screen positive pregnancies.…”