Identification of Second Trimester Screen Positive Pregnancies at Increased Risk for Congenital Heart Defects

Abstract

A number of studies have reported an association between low concentrations of serum folate and preterm birth. Folate supplementation during pregnancy increased the length of pregnancy in some but not all clinical trials. This cohort study investigated whether preconceptional folate supplementation (as ascertained by patient questionnaire in the first trimester of pregnancy) lowers the risk of spontaneous preterm birth. The investigators analyzed data collected from a cohort of 34,480 low-risk singleton pregnancies in women enrolled in a previous prospective cohort study on Down syndrome screening conducted at 15 US centers between 1999 and 2002. Duration of pregnancy was estimated by ultrasound measurement in the first trimester. Spontaneous preterm birth was defined as preterm birth between 20 and 37 weeks with no medical or obstetrical complications that constituted indications for delivery. The effects of the duration of preconceptional folate supplementation of Ն1 year (long-term), Ͻ1 year and the effect of no supplementation on risk of spontaneous preterm birth were compared using time-to-event analysis. Data were subjected to analysis with multivariable logistic regression.Compared to women who did not take a folate supplement, the risk of spontaneous preterm delivery between 20 and 28 weeks was 70% lower in women who took folate supplements for a year or longer before pregnancy (0.27% vs 0.04%); the hazard ratio was 0.22, with a 95% confidence interval of 0.08 to 0.61, P ϭ 0.004. Long-term folate supplementation reduced the risk between 28 and 32 weeks by over 50% (0.38% vs 0.18%) (hazard ratio, 0.45; 95% confidence interval, 0.24-0.83, P ϭ 0.010). Supplementation had no significant effect on the risk of spontaneous preterm birth beyond 32 weeks. Adjustment for maternal variables (age, body mass index, race and ethnicity, educational level, marital status, smoking, parity and history of prior preterm birth) did not affect the association between long-term folate and risk of spontaneous preterm birth but did eliminate the association found in unadjusted analysis between duration of preconceptional folate supplementation less than one year and risk.These findings suggest that preconceptional folate supplementation for a year or longer may substantially reduce the risk of early spontaneous preterm birth. The risk is lower with longer duration of folate supplementation before pregnancy. The beneficial effect of folic acid does not appear to be associated with other complications of OBSTETRICS Volume 64, Number 10 OBSTETRICAL AND GYNECOLOGICAL SURVEY pregnancy such as preeclampsia, small for gestational age infant, placental abruption, or nonspontaneous preterm birth. EDITORIAL COMMENT(From an analytic standpoint, the abstracted report by Bukowski et al is sophisticated and well done. The limitations of this study relate to its design-it is a retrospective cohort study rather than a prospective randomized trial. This design gives direct rise to 2 of its main limitations. The first relates to ascertainment of f...

First‐trimester ductus venosus screening for cardiac defects: a meta‐analysis

“…Taking into account the fact that very few referral centres have the facilities to provide detailed cardiac scans, we should be careful about the interpretation of this screening test's results and the information we give to the parents. Most of the instances of CHD are currently still diagnosed in the second or even the beginning of the third trimester 34 and decisions for management are more difficult at this point. It is very important to find noninvasive diagnostic tests that will place safely a fetus from the low-risk group for CHD into a high-risk group or the opposite during the first trimester so that the therapeutic approach and the decision-making will occur as soon as possible, minimising maternal and fetal morbidity.…”

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

“…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. In addition, our most recent study observed a positively predictive relationship between low AFP levels and an increased risk for CHDs in screen positive pregnancies (Jelliffe‐Pawlowski et al , 2009).…”

“…Although much has been learned with respect to the predictive relationship between first trimester nuchal translucency (NT) measurement and congenital heart defects (CHDs) (Simpson et al , 2007; Wald et al , 2008), few studies have examined the relationship between typically collected prenatal serum biomarkers and CHDs (Souter et al , 2002; Jelliffe‐Pawlowski et al , 2009). Identification of additional predictive biomarker–CHD relationships has the potential to better CHD prenatal detection rates in instances where a first trimester NT measurement was not performed and potentially for affected pregnancies in which NT screening was normal (estimated to be between 44 and 86% of all CHDs) (Westin et al , 2006).…”

“…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.…”

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

“…Because the California Prenatal Screening Program includes follow-up diagnostic services and receives diagnostic outcome reports of these services, the Program has been aware that many other structural abnormalities and pregnancy findings are detected among the screen-positive population. Major fetal abnormalities associated with screen-positive status for SLOS have been previously reported (Craig et al, 2007) as well as increased risk of cardiac defects among fetuses of all screen-positive women (Jelliffe-Pawlowski et al, 2009). Significant associations between several maternal serum markers and an increased risk for multicystic dysplastic kidney, two-vessel cord and hydrocele were demonstrated in participants of the FASTER trial (Hoffman et al, 2008).…”