17.4 Obstetric Diagnostic Imaging & Genetic Screening Modalities

Cell-Free DNA (cfDNA / NIPT) Screening

Cell-free DNA (cfDNA) screening analyzes circulating extracellular DNA fragments in maternal blood. Roughly 10% (range 4% to 20%) is derived from apoptotic placental syncytiotrophoblasts, representing the fetal fraction.

Performance & Clinical Role

Per ACOG guidelines, aneuploidy screening should be offered to all pregnant individuals regardless of baseline age-related risk.

• Timing: Administered from 10 0/7 weeks gestation through term.
• Performance: Achieves the highest sensitivity and specificity of any screening modality: Trisomy 21 (Down syndrome: >99% sensitivity and specificity), Trisomy 18 (Edwards syndrome: ~97–98%), and Trisomy 13 (Patau syndrome: ~90–99%). It also evaluates fetal sex, sex chromosome aneuploidies (45,X; 47,XXY; 47,XXX; 47,XYY), and select microdeletions (e.g., 22q11.2 DiGeorge syndrome).
• The "No-Call" Result: Low fetal fraction (<4%) accounts for most test failures, driven by elevated maternal BMI (hemodilution and adipose turnover), early gestational age (<10 weeks), maternal LMWH therapy, or fetal aneuploidy (Trisomies 13/18 and triploidy cause placental hypoplasia). ACOG recommends against reflexively redrawing cfDNA, as ~50% fail again; management mandates genetic counseling, detailed anatomical ultrasound, and diagnostic testing (CVS or amniocentesis).

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Serum Screening Modalities & MSAFP Interpretation

First- & Second-Trimester Serum Screening

• First-Trimester Combined Screen (11 0/7 to 13 6/7 Weeks): Measures fetal Nuchal Translucency (NT) via ultrasound plus maternal serum PAPP-A and beta-hCG. Down syndrome presents with thickened NT (≥3.0 mm), low PAPP-A, and high hCG.
• Second-Trimester Quad Screen (15 0/7 to 22 6/7 Weeks; Optimal 16–18 Weeks): Measures Maternal Serum Alpha-Fetoprotein (MSAFP), hCG, Unconjugated Estriol (uE3), and Dimeric Inhibin A (DIA).

Clinical Significance of MSAFP

MSAFP is produced by the fetal yolk sac and liver, excreted into amniotic fluid via fetal urine, and enters maternal blood. Results are reported as Multiples of the Median (MoM).

• Elevated MSAFP (>2.5 MoM): The most common etiology is incorrect gestational dating (underestimation of age). Pathologic causes include open neural tube defects (anencephaly, spina bifida), ventral wall defects (gastroschisis, omphalocele), multiple gestation, and fetal demise. Initial workup requires targeted ultrasound to confirm dating, rule out twins, and inspect cranial anatomy ("lemon" and "banana" signs) and spine. If ultrasound is normal/inconclusive, amniocentesis for amniotic fluid AFP (AFAFP) and reflex acetylcholinesterase (AChE) is indicated.
• Low MSAFP (<0.5 MoM): Associated with Trisomy 21, Trisomy 18, overestimation of gestational age, maternal diabetes, and fetal demise.

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Diagnostic Procedures: CVS vs. Amniocentesis

• Chorionic Villus Sampling (CVS; 10 0/7 to 13 6/7 Weeks): Transcervical or transabdominal biopsy of chorionic villi (placental trophoblasts) under ultrasound guidance. Provides definitive karyotype and microarray in the first trimester. Does not evaluate open neural tube defects and carries a 1% to 2% risk of Confined Placental Mosaicism (CPM). Procedural loss rate is ~0.1% to 0.2%.
• Amniocentesis (15 0/7 to 20 0/7 Weeks): Transabdominal aspiration of 15 to 20 mL of amniotic fluid with a 20- to 22-gauge needle under ultrasound guidance. Diagnostic for karyotype, microarray, single-gene disorders, and AFAFP/AChE for neural tube defects. Loss rate is ~0.1% (1 in 1,000).
• Rh Prophylaxis: Rh-negative, non-sensitized women undergoing either CVS or amniocentesis must receive RhoGAM (300 mcg) to prevent isoimmunization.

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Antepartum Fetal Surveillance Modalities

Surveillance monitors fetal oxygenation in high-risk pregnancies (preeclampsia, pregestational diabetes, chronic hypertension, FGR, post-term ≥41 weeks, decreased movement):

1. Non-Stress Test (NST)

• Reactive NST (≥32 Weeks): ≥2 accelerations of ≥15 bpm lasting ≥15 seconds in a 20-minute window ("15 by 15 rule").
• Reactive NST (<32 Weeks): ≥2 accelerations of ≥10 bpm lasting ≥10 seconds in 20 minutes ("10 by 10 rule").
• Non-Reactive NST: Lacks criteria over 40 minutes. Follow up with vibroacoustic stimulation (VAS) or proceed to a complete Biophysical Profile (BPP).

2. Biophysical Profile (BPP)

Combines the NST with real-time ultrasound assessing four variables over 30 minutes (each scored 0 or 2, max 10/10):

1. NST: Reactive = 2; Non-reactive = 0.
2. Fetal Breathing Movements: ≥1 continuous episode lasting ≥30 seconds = 2; <30 sec = 0.
3. Gross Body Movements: ≥3 discrete body/limb movements = 2; <3 movements = 0.
4. Fetal Tone: ≥1 episode of active extension with return to flexion = 2; slow/flaccid = 0.
5. Amniotic Fluid Volume (Chronic Marker): Single deepest vertical pocket (DVP) ≥2.0 cm (and ≥1 cm wide) = 2; DVP <2.0 cm (oligohydramnios) = 0. (Alternative: AFI >5.0 cm = 2).

Action by Score: 8/10 (normal fluid) or 10/10 is reassuring. 8/10 with abnormal fluid (DVP <2 cm) indicates chronic compromise; deliver if ≥37 weeks. 6/10 is equivocal; deliver if ≥37 weeks, or repeat in 12–24 hours if preterm. ≤4/10 is abnormal, indicating acute fetal asphyxia and requiring immediate delivery.

3. Modified BPP, CST & Umbilical Doppler

• Modified BPP: Combines NST (acute CNS oxygenation) and DVP (chronic placental perfusion). Normal if NST is reactive and DVP ≥2 cm.
• Contraction Stress Test (CST): Assesses FHR during 3 contractions in 10 minutes. Negative = no late decelerations. Positive = late decelerations after ≥50% of contractions (indicates uteroplacental insufficiency). Contraindicated in placenta previa, prior classical cesarean, or preterm labor.
• Umbilical Artery Doppler: Evaluates placental vascular resistance in FGR. Progression to Absent End-Diastolic Flow (AEDF) or Reversed End-Diastolic Flow (REDF) signals severe placental obliteration and imminent demise, requiring urgent admission, betamethasone, and delivery.