Prenatal Genetics and Screening

Comprehensive fill-in-the-blank practice cards covering prenatal genetics, screening protocols, obstetric history dating, biochemical markers, diagnostic procedures, and fetal ultrasound anomalies.

Gestational age is calculated from the first day of the last menstrual period (LMP), whereas embryonic age is calculated starting __________ after the LMP.

2 weeks

In Assisted Reproductive Technology (ART) dating, a 3-day embryo transfer corresponds to 2 weeks and 3 days (2w3d) gestational age, while a 5-day embryo transfer corresponds to __________ gestational age.

2 weeks and 5 days (2w5d)

When a prenatal complete blood count (CBC) reveals a mean corpuscular volume (MCV) less than $80\,\text{fL}$, the initial follow-up laboratory testing includes serum iron, ferritin, and __________.

hemoglobin electrophoresis (followed by molecular testing if hemoglobinopathy carrier status is suspected)

Maternal Rh-negative status poses a fetal risk in subsequent pregnancies because maternal exposure to Rh-positive fetal red blood cells causes __________, leading to antibodies crossing the placenta.

alloimmunization

Poorly controlled preexisting Type 1 or Type 2 diabetes during early pregnancy is associated with miscarriage, stillbirth, fetal macrosomia, and __________.

congenital malformations (such as neural tube defects and congenital heart defects)

First-trimester nuchal translucency (NT) is considered abnormal or increased at an ultrasound measurement threshold greater than __________.

$$3.0\,\text{mm}$$

A monochorionic diamniotic twin pregnancy is anatomically defined by one chorionic sac, one placenta, and __________.

two amniotic sacs

In obstetric history recording (TPAL), term delivery is defined as 37w0d and beyond, preterm delivery as 20w0d through 36w6d, and abortion/loss as __________.

19w6d or earlier

A non-viable pregnancy loss is officially designated as a stillbirth rather than a spontaneous abortion at or after __________ of gestation.

20 weeks

An infertility evaluation is initiated after 12 months of unsuccessful trying for females under age 35, and after __________ of unsuccessful trying for females age 35 or older.

6 months

A clinical diagnosis of recurrent pregnancy loss is established after __________ pregnancy losses.

two or more

In prenatal screening, clinical sensitivity represents the proportion of affected individuals who receive a positive screening test result, also termed the __________.

true-positive rate

The probability that an individual with a positive screening test result actually has the target condition is defined as the __________.

Positive Predictive Value (PPV)

In first-trimester biochemical screening, the two maternal serum analytes measured alongside nuchal translucency (NT) are pregnancy-associated plasma protein A (PAPP-A) and __________.

free $\beta$-hCG

The four maternal serum markers that compose second-trimester quad screening are Alpha-fetoprotein (AFP), total human chorionic gonadotropin (total hCG), unconjugated estriol (uE3), and __________.

Inhibin-A

The typical first-trimester screening analyte pattern associated with fetal Trisomy 21 consists of decreased PAPP-A, increased nuchal translucency (NT), and __________.

elevated free $\beta$-hCG

On second-trimester quad screening, Trisomy 21 is characteristically indicated by low AFP, low uE3, elevated total hCG, and __________.

elevated Inhibin-A

The maternal serum analyte evaluated individually to screen for fetal open neural tube defects (ONTDs) is __________.

maternal serum Alpha-fetoprotein (MSAFP)

Extremely low or undetectable levels of unconjugated estriol (uE3) on second-trimester screening indicate an increased risk for X-linked ichthyosis, congenital adrenal hyperplasia, placental aromatase deficiency, or __________.

Smith-Lemli-Opitz syndrome

An isolated, remarkably high elevation of Inhibin-A on second-trimester serum screening is associated with the chromosomal abnormality __________.

Triploidy

Cell-free DNA (cfDNA) analysis requires a minimum fetal fraction range of __________ to return a reliable result.

$2\%$ to $4\%$

Unlike Massively Parallel Shotgun Sequencing (MPSS), single nucleotide polymorphism (SNP)-based cfDNA technology can identify twin zygosity, detect a vanishing twin, and identify fetal __________.

triploidy

A major biological cause of false-positive or false-negative NIPT results that occurs in approximately $2\%$ of pregnancies is __________.

confined placental mosaicism

Under the California Prenatal Screening Program, the eligible gestational age window for NIPT sample submission is from __________ through term.

10w0d (with recommended optimal window of 10 to 21 weeks)

The California Prenatal Screening Program accepts serum AFP samples for open neural tube defect screening between __________ and 21w0d.

15w0d

The standard gestational age range for performing Chorionic Villus Sampling (CVS) is __________.

10w0d to 13w6d

Performing Chorionic Villus Sampling prior to 9 weeks of gestation significantly increases the risk for __________.

limb reduction defects

The standard gestational age window for performing an amniocentesis is __________.

15 to 20 weeks (and beyond)

An open neural tube defect is confirmed on diagnostic amniotic fluid testing by finding elevated amniotic fluid Alpha-fetoprotein (AFAFP) and verifying the presence of __________.

acetylcholinesterase (AChE)

Chromosomal microarray analysis is preferred over traditional karyotyping because it detects small submicroscopic __________.

microdeletions and microduplications (copy number variants)

Fragile X syndrome prenatal diagnostic testing is performed using amniocentesis rather than CVS because the molecular assay relies on __________, which are not yet established in chorionic villi.

DNA methylation patterns

Advanced Maternal Age (AMA) is defined as age 35 or older at delivery and carries an elevated risk of fetal numerical aneuploidies resulting from maternal oocyte __________.

nondisjunction

Advanced Paternal Age (APA) is defined as age 40 or older and carries an elevated risk for de novo single-gene dominant variants in genes such as $FGFR2$, $FGFR3$, and members of the __________.

RAS pathway

If both biological parents have heterozygous achondroplasia ($FGFR3$), the risk that their offspring will inherit lethal homozygous achondroplasia is __________.

$$25\%$$

During pregnancy and delivery, maternal Vascular Ehlers-Danlos Syndrome ($COL3A1$) carries a maternal mortality rate of approximately __________ alongside risks of arterial and uterine rupture.

$$12\%$$

In a patient with Marfan syndrome ($FBN1$), pregnancy is contraindicated when baseline aortic root diameter measurement is greater than __________ due to the risk of aortic dissection.

$$4.5\,\text{cm}$$

Catabolic stress during pregnancy or the postpartum period can trigger life-threatening hyperammonemic episodes in approximately $15\%$ of female carriers of __________.

X-linked Ornithine Transcarbamylase (OTC) Deficiency

Offspring exposed in utero to uncontrolled maternal phenylketonuria (PKU) frequently present with microcephaly, intrauterine growth restriction, neurodevelopmental disabilities, and __________.

congenital heart disease

Compared to the general population baseline risk ($2\%$ to $6\%$), the recurrence risk for an isolated birth defect with the same biological parents is approximately __________ times higher.

$$2.4$$

An absent or hypoplastic nasal bone identified on prenatal ultrasound is most strongly linked to __________, occurring in $60\%$ to $73\%$ of cases.

Trisomy 21 (Down syndrome)

An atrioventricular septal defect (AVSD) identified on fetal echocardiogram carries an overall risk of __________ for an underlying chromosomal aneuploidy.

$40\%$ to $70\%$ (most commonly Trisomy 21)

Choroid plexus cysts (CPCs) observed on mid-trimester ultrasound are most specifically associated with the autosomal trisomy __________.

Trisomy 18

Numerical chromosomal aneuploidies account for __________ of all fetal cystic hygroma cases.

$50\%$ to $70\%$

Fetal duodenal atresia is characteristically identified on prenatal ultrasound by polyhydramnios accompanied by a __________ sign.

"double bubble" stomach

When fetal echogenic bowel is detected, the non-aneuploid autosomal recessive single-gene condition that should be considered is __________ ($CFTR$).

Cystic Fibrosis

Fetal hydrops is defined on ultrasound as pathologic fluid accumulation in at least two body compartments and is observed in __________ of Turner syndrome ($45,X$) fetuses.

$$77\%$$

Fetal gastroschisis is typically an isolated, non-genetic abdominal wall defect attributed to __________ rather than chromosomal or single-gene syndromes.

vascular disruption and environmental factors

The three most frequent numerical chromosomal causes of fetal holoprosencephaly are Trisomy 13, Trisomy 18, and __________.

Triploidy

Congenital hydrocephalus accompanied by adducted or abducted thumbs in male fetuses is caused by mutations in the X-linked gene __________.

$L1CAM$ (L1 syndrome)

An increased nuchal fold is evaluated during the second trimester at an ultrasound measurement threshold of __________.

$6\,\text{mm}$ or greater

Multiple cardiac rhabdomyomas identified on fetal ultrasound are virtually 100% diagnostic of __________ ($TSC1$ or $TSC2$).

Tuberous Sclerosis Complex

The 11p15.5 imprinting overgrowth condition that should be suspected when an omphalocele is seen alongside macroglossia and enlarged kidneys is __________.

Beckwith-Wiedemann syndrome

Cranial morphology showing a strawberry-shaped skull alongside clenched hands with overlapping index fingers and rocker-bottom feet or clubfoot is characteristic of __________.

Trisomy 18

Mid-trimester ultrasound findings of holoprosencephaly with midline facial clefts or cyclopia, enlarged hyperechoic kidneys, and postaxial polydactyly point specifically to __________.

Trisomy 13

While digynic triploidy presents with severe asymmetric growth restriction and a small non-cystic placenta, diandric triploidy presents with a large, thickened, cystic placenta characteristic of a __________.

partial molar pregnancy

In utero Autosomal Recessive Polycystic Kidney Disease (ARPKD) is characterized by a triad of bilateral enlarged echogenic kidneys, secondary fetal pulmonary hypoplasia, and severe __________.

oligohydramnios

Thanatophoric Dysplasia ($FGFR3$) Type 1 is distinguished by curved "telephone receiver" femurs, whereas Type 2 presents with __________ and a severe cloverleaf skull.

straight femurs

Congenital heart anomalies characteristic of 22q11.2 deletion syndrome primarily encompass __________ cardiac defects (such as Tetralogy of Fallot, truncus arteriosus, interrupted aortic arch, and VSD).

conotruncal

For individuals at high risk for open neural tube defect recurrence, the recommended periconceptional dosage of folic acid is __________.

$4\,\text{mg}$ daily (reducing recurrence risk by up to $70\%$)

The classic prenatal diagnostic ultrasound triad defining Meckel-Gruber syndrome consists of dysplastic cystic kidneys, postaxial polydactyly, and an __________.

occipital encephalocele