Association of Alcohol Use Diagnostic Codes in Pregnancy and Offspring Conotruncal and Endocardial Cushion Heart Defects

Abstract

Background The pathogenesis of congenital heart disease (CHD) remains largely unknown, with only a small percentage explained solely by genetic causes. Modifiable environmental risk factors, such as alcohol, are suggested to play an important role in CHD pathogenesis. We sought to evaluate the association between prenatal alcohol exposure and CHD to gain insight into which components of cardiac development may be most vulnerable to the teratogenic effects of alcohol. Methods and Results This was a retrospective analysis of hospital discharge records from the California Office of Statewide Health Planning and Development and linked birth certificate records restricted to singleton, live‐born infants from 2005 to 2017. Of the 5 820 961 births included, 16 953 had an alcohol‐related International Classification of Diseases , Ninth and Tenth Revisions (ICD‐9; ICD‐10 ) code during pregnancy. Log linear regression was used to calculate risk ratios (RR) for CHD among individuals with an alcohol‐related ICD ‐9 and ICD10 code during pregnancy versus those without. Three models were created: (1) unadjusted, (2) adjusted for maternal demographic factors, and (3) adjusted for maternal demographic factors and comorbidities. Maternal alcohol‐related code was associated with an increased risk for CHD in all models (RR, 1.33 to 1.84); conotruncal (RR, 1.62 to 2.11) and endocardial cushion (RR, 2.71 to 3.59) defects were individually associated with elevated risk in all models. Conclusions Alcohol‐related diagnostic codes in pregnancy were associated with an increased risk of an offspring with a CHD, with a particular risk for endocardial cushion and conotruncal defects. The mechanistic basis for this phenotypic enrichment requires further investigation.

Adult William's Syndrome: The Cause of an Unusual Vasculopathy and Biliary Abnormalities

“…The aortic narrowing in PHACES is specific to the aortic isthmus [14]. There is no increase in the frequency of aortic coarctation in infants born to mothers with the use of prenatal alcohol [15].…”

Interdependence of placenta and fetal cardiac development

“…Pregnancies complicated by fetal CHD often have maternal comorbidities that can provide clues for the role of the placenta in fetal CHD. Specifically, studies have shown an increased incidence of fetal CHD in pregnancies complicated by DM, 61–64 pre‐eclampsia, 65–68 uncontrolled hypertension, 69,70 alcohol or substance use, 71 smoking, 72 infections (REF), and other maternal diseases as well. Many of these morbidities also affect the placenta in characteristic ways, with some animal studies providing clues to the mechanistic link between these maternal morbidities and fetal CHD.…”

Birth Defects Associated with Prenatal Alcohol Exposure—A Review

“…Two studies evaluated conotruncal defects, of which one classified PAE in the periconceptional period [37,38]. In a case-control study in 2003, Carmichael [37] found slight increased odds of one or more drinks per week (OR 1.6, 95% CI 0.8, 3.0) among mothers of children born with conotruncal defects, but confidence intervals were very wide and overlapped the null.…”

“…In a case-control study in 2003, Carmichael [37] found slight increased odds of one or more drinks per week (OR 1.6, 95% CI 0.8, 3.0) among mothers of children born with conotruncal defects, but confidence intervals were very wide and overlapped the null. Separately, a study utilizing California birth records found an association between conotruncal congenital heart disease and maternal alcohol-related ICD diagnosis during pregnancy (RR 1.6, 95% CI 1.2, 1.8) [38].…”