What investigations are required for a 36-year-old woman, who is a 2nd gravida (second pregnancy), in her 8th week of pregnancy, with a history of a child born with a Ventricular Septal Defect (VSD), throughout the 1st, 2nd, and 3rd trimesters?

Prenatal Investigations for 36-Year-Old G2 at 8 Weeks with Previous Child with VSD

Given your advanced maternal age (36 years) and history of a child with VSD, you require enhanced genetic screening throughout pregnancy, with fetal echocardiography being critical in the second trimester to assess for recurrent cardiac defects.

First Trimester (8-13 weeks)

Standard Initial Workup

• Complete blood count, blood type and Rh status, antibody screen to establish baseline hematologic status 1
• Infectious disease screening: HIV, hepatitis B surface antigen, syphilis serology, rubella immunity status 1
• Urinalysis and urine culture to detect asymptomatic bacteriuria 1
• Thyroid function tests (TSH at minimum) given pregnancy's metabolic demands 1

Genetic Risk Assessment

• Cell-free DNA (cfDNA) screening or combined first trimester screening (nuchal translucency + PAPP-A + beta-hCG at 11-13 weeks) for aneuploidy screening, particularly important given your age >35 years 1
• Genetic counseling is essential given your family history of VSD, as VSDs can be associated with chromosomal abnormalities (particularly 22q11.2 deletion syndrome), single gene mutations (NKX2-5, GATA4), and copy number variations 2, 3

Early Ultrasound

• Dating ultrasound to confirm gestational age and assess for multiple gestation 1
• Early anatomic survey at 13 weeks can detect major cardiac malformations in experienced hands, though this is not standard 1

Second Trimester (14-28 weeks)

Critical Cardiac Assessment

• Detailed fetal echocardiography at 18-22 weeks by a pediatric cardiologist or maternal-fetal medicine specialist - this is the single most important investigation given your history 1, 4
  • VSD recurrence risk in subsequent pregnancies ranges from 3-5% when one sibling is affected 3
  • Echocardiography should evaluate for VSD type (perimembranous, muscular, outlet, inlet), associated cardiac anomalies (aortic valve abnormalities, left ventricular outflow tract obstruction, atrial septal defects), and ventricular function 4, 5

Comprehensive Anatomic Survey

• Detailed anatomic ultrasound at 18-22 weeks to evaluate all fetal organ systems and detect associated extracardiac anomalies 1
• Assessment for soft markers of aneuploidy if present (echogenic intracardiac focus, thickened nuchal fold, etc.), though isolated markers after negative screening do not warrant diagnostic testing 1

Advanced Genetic Testing if Indicated

• Amniocentesis with chromosomal microarray analysis (CMA) should be offered if:
  • Fetal VSD is detected on echocardiography (13% detection rate for pathogenic CNVs) 2
  • Other structural anomalies are identified 2
  • Soft markers concerning for aneuploidy are present 1
• Exome sequencing can be considered if VSD is detected with normal karyotype/CMA, particularly if non-isolated (13.7% diagnostic yield) 2

Maternal Serum Screening

• Quad screen (15-20 weeks) if cfDNA was not performed in first trimester 1
• Glucose screening at 24-28 weeks for gestational diabetes 1

Third Trimester (28-40 weeks)

Fetal Surveillance

• Follow-up fetal echocardiography at 28-32 weeks if cardiac abnormality was detected earlier to reassess progression, particularly for VSDs with associated lesions 1, 4
• Serial growth ultrasounds every 3-4 weeks if fetal cardiac defect is confirmed, as cardiac anomalies can be associated with growth restriction 1

Maternal Assessment

• Repeat complete blood count to assess for anemia 1
• Group B Streptococcus screening at 35-37 weeks 1
• Antenatal testing (non-stress tests or biophysical profiles) starting at 32-34 weeks if significant fetal cardiac defect is present 1

Delivery Planning

• Multidisciplinary delivery planning involving maternal-fetal medicine, pediatric cardiology, and neonatology if fetal cardiac defect is confirmed 1, 4
• Delivery at a tertiary center with pediatric cardiac surgery capability if moderate or complex cardiac lesion is identified 1, 4

Key Caveats

The 22q11.2 microdeletion is the most common CNV associated with VSD and should be specifically evaluated if cardiac defect is detected 2. This deletion can present with isolated VSD or as part of DiGeorge syndrome 3.

Perimembranous VSDs (most common type) carry risk of associated aortic valve prolapse and regurgitation, requiring careful echocardiographic assessment 4, 5.

Most isolated small VSDs close spontaneously (83.5% by 1 year of life, with muscular VSDs having 86.9% closure rate), but prenatal detection allows for appropriate postnatal follow-up planning 6.