M: Genetics + Fetal Surveillance (E3, L7)

karyotype

pictorial representation

chromosomes

• slightly larger form of DNA

  • 46 chromosomes: 22 pairs of autosomes, 1 pair of sex chromosomes

autosomes

non-sex chromosomes

genes

smaller segment of chromosome containing coded info of unique characteristics

allele

heteo or homozygous

Direct Molecular Testing

• Determines if something is off from normal code

• look specifically at DNA and RNA

Linkage Analysis

• Inherited markers

• Look at parents and see if mutation has gone into offspring 

Biochemical testing

protein products (e.g. PKU)

cytogenetic testing

• Chromosomes

• Amniocentesis, chorionic villi sampling

Prenatal Screen

• Single gene disorders

• e.g. MSAFP (down syndrome, ONTD)

PRESYMPTOMATIC Predictive Testing

• if you live long enough, you’ll get the disease

  • E.g. Huntington’s - might not have S/S, but if she lives long enough, she’ll get it

  • Children with parent who was recently diagnosed may want to get tested to see if they have the gene

PREDISPOSITIONAL Predictive Testing

• are you predisposed to a particular disorder?

  • E.g. Broca (?) - if you carry the gene, you won’t have S/S of breast cancer, but may be more likely to get breast cancer in your life (not 100%, not presymptomatic - doesn’t guarantee that you will have the disease)

  • Environmental factors that trigger the gene to be expressed

Gene Therapy 

putting in new genes to combat diseased gene

Congenital Anomalies

• Arise at any stage of development

  • Much more likely in embryonic stage

• Show wide variability in etiologic factors

• Wide variability in type, extent and frequency of defect

Single Gene Mutation

• Specific gene known to cause mutations (e.g. Huntington’s, sickle cell)

• NOT a mutation of the chromosome

• More predictable inheritance pattern 

• Not diagnosed by chromosomal analysis

• Transmitted by mendelian principle

autosomal chromosome abnormality

• Dominant - mutation

• Recessive

sex-linked abnormality

• X –linked dominant

• X-linked recessive 

46 chromosomes breakdown

• 23 pair of tightly coiled strands of DNA

  • 22 pair autosomes

  • 1 pair sex chromosomes

    • Maternal ovum carries X chromosome

    • Paternal sperm carries X or Y chromosome

    • Male = XY

    • Female = XX

autosomal dominant

• A dominant gene is the one gene of a heterozygous pair that is expressed

• (assume heterozygous)

• If heterozygous parent has an infant with a homozygous parent without the trait there are four ways to combine the four genes

  • 50% chance of the child expressing trait

• Example: Huntington disease

autosomal recessive

• Genes expressed only if homozygous

• When paired with a dominant gene - It will not be expressed 

  • Example: PKU, Tay-Sachs, CF, Sickle cell anemia

• If both parents have a gene for PKU

  • 25% chance of having a child with PKU

  • 50% chance of child being a carrier

  • 25% chance that child will not carry or have PKU

x-linked dominant (+ what happens if mother or father are affected)

• Gene carried dominantly on X chromosome (NO carriers)

• All individuals with gene exhibit d/o

• If Mother affected—

  • 1:2 chance daughter affected

  • 1:2 chance son affected

  • (½ of girls will be affected; ½ of boys will be affected)

• If Father affected----

  • All daughters affected

  • No sons affected

• Vitamin D resistant rickets

• Rett Syndrome

x-linked recessive (+ what happens if mother or father are affected_

• Carried only on X chromosome

• Theoretically only males get disease

• No male to male transmission

• If mother is carrier

  • 1:2 chance son affected

  • 1:2 chance daughter carrier—not affected—rarely does female carrier exhibit symptoms

• Colorblindness, Muscular Dystrophy, Hemophilia A and B

translocations: balanced

• most common

  • Little chunk of 13 went to 14 and a little chunk of 14 went to 13 (chromosomes look the same)

translocations: unbalanced

 chunk of one protein goes to another chromosome (different appearances)

translocations: Robertsonian

• Trisomies   Robertsonian Translocation

  • Two chromosomes attach together = one large chromosome (results in 45 chromosomes)

inversions

• chromosome breaks and inverts on itself 

  • Instead of normal pattern, it’s going to go out of sequence

deletions (terminal, interstitial, micro deletions)

• part of chromosome breaks off and is lost 

  • Terminal: at the end 

  • Interstitial: in the middle 

  • Microdeletions: so small it’s hard to determine what symptoms

monosomy 

• one allele is missing

  • Turners Syndrome: poorly formed/missing ovaries; affect wide range of other organs

trisomy

• one allele has extra chromosome

  • Trisomy 21/Down’s Syndrome:  3 chromosomes on chromosome #21 instead of 2

Fetal Movements

• Inexpensive and valuable screening test

• Not completely predictive (moms not always the best at counting), but always used when mom notices a change in the baby’s movement

• Pt should choose time of day when they can sit or lie quietly

• Options vary

  • Count once per day for 60 minutes

  • Count for 60 minutes, two- three times a day after meals (sugar goes up = baby more active)

    • Most will count minimum 4 movements in 1 hour (typically 10)

    • 3 or fewer needs further evaluation

      • OR no movement for 12 hrs “fetal alarm signal”

normal number of fetal movements in 1 hours

4-10 (3 or less needs further evaluation)

when to start kick counts

after viability (after 24 weeks/feeling baby move and quickening)

ultrasound

• 2D view of fetus, organs, etc.

  • Used if can’t auscultate heart on fetal monitor 

  • Visualize baby and heart rate 

abdominal ultrasound (+ how many weeks do u do it)

• Better in later pregnancy when uterus is abdominal organ (after 12 weeks)

  • Also not as invasive/uncomfortable

• Full bladder needed (if early pregnancy)

  • Push intestines out of the way and promote better imaging 

• Gel placed over abdomen to enhance transmission and reception of sound waves

transvaginal ultrasound

• Better in early pregnancy 

• Probe inserted into vagina

• Early diagnosis of IUP and evaluation of pelvic organs

• No need for full bladder

first trimester ultrasound

• Number, size, and location of gestational sac

• Presence/absence of fetal cardiac and body movements

• Presence/absence of uterine abnormalities or adnexal masses

• Date of pregnancy

• Presence/absence of IUD

  • May or may not remove depending on if it’s harmful to pregnancy 

• 12 week ultrasound

second trimester ultrasound

• Fetal viability, number, position, gestational age, growth pattern, anomalies

  • IUGR: intrauterine growth restrictive (fundal height < normal)

• Amniotic fluid volume

• ⭑ Placental location and maturity

  • Make sure placenta is not below the baby’s head

• Uterine fibroids and anomalies

• Adnexal masses

• Cervical length - how thick the cervix is

  • Really thin: risk factor for preterm birth

Doppler blood flow analysis (+S/D ratio)

• Study of blood flow in fetus and placenta

  • Good for patients with vascular issues (e.g. hypertension, pre-eclampsia)

  • Sound wave assessment of RBC velocity

  • S/D ratio (3or less at 30 weeks)

    • systolic/diastolic flow (high ratio = non-optimal blood flow)

    • Progressive decline in resistance through pregnancy

what is Doppler blood flow analysis used for?

• management of patients with:

  • hypertension, IUGR (intrauterine growth restriction), diabetes mellitus, multiple fetuses, preterm labor, substance users (e.g. cocaine)

  • Baby can be LGA and IUGR

multiple marker screen/triple screen/quad screen (+ when is it performed)

• Performed between 16-18 weeks (but available between 15-22 weeks)

  • Maternal Serum Alphafetoprotein (MSAFP)

  • hCG

  • Unconjugated estriol

• Screening test for Down syndrome and NTD

• Inhibin A added

Down syndrome screening

• Low levels of MSAFP and estriol

• hCG is high

• Inhibin A high

neural tube defect screening

High levels of MSAFP

nuchal translucency test (+ when is it done)

• Early screening test for Downs Syndrome

• Takes US measurement of fluid level behind the fetal neck

  • From occiput to upper posterior part of spine

    • 3 mm+ between 11-13 6/7 weeks gest. age is considered abnormal

      • In general--the thicker the fold at a given gestational age--the higher the chance of a chromosomal abnormality

      • Usually done at 12 weeks

  • 80% accurate

cell-free DNA screening

• Done after 10 weeks (10-12 weeks)

• Draw mom’s blood 

• Fetal Rh Status (not usually done)

• Fetal Gender

• Paternally transmitted single gene disorders

• Trisomy 13, 18 & 21 capabilities

when is Chorionic villi sampling performed

• between 10-13 weeks

  • not done after because there will be higher risk of limb deformities (need accurate dating!)

chorionic villi sampling

removal of small tissue specimen from fetal portion of placenta (chorionic villi) to diagnose genetic abnormalities

• need Rhogam within 72 hours if patient is Rh-

Chorionic villi sampling complications

vaginal bleeding, SAB, PROM, chorioamnioitis, limb anomalies (if <10 weeks)

• 2nd trimester amniocentesis safer than CVS (but can do CVS sooner than amnio, so can give faster results)

chorionic villi sampling patient teaching

• Limit activity for 24 hours

• Call your doctor if:

  • You have vaginal bleeding that is similar to your period

  • You are leaking fluid from your vagina

  • You have cramps that are increasing in intensity

  • You have a fever over 100.4F (38C)

  • Avoid exercise, heavy lifting, intercourse

• Results are available within a couple of weeks

amniocentesis

• Fluid evaluated for genetic disorders or gestational maturity

  • Down Syndrome, ONTD, fetal lung maturity

  • need Rhogam if Rh-

when is amniocentesis performed?

• after 14 weeks when uterus is abdominal organ and sufficient fluid available

  • Risk of miscarriage or deformity if not done at the right time

  • Baby needs enough amniotic fluid to do this

  • In very rare cases, needle may rupture the membrane → miscarriage

amniocentesis patient teaching

• Resume normal activities in 24-48 hours

• Call your doctor if:

  • You have bright red vaginal bleeding or foul smelling discharge

  • You are leaking fluid from the vagina

  • You have contractions or severe cramping

  • You have a fever above 100.4F (38C)

  • Decreased fetal movement

• Results are available within a couple of weeks

biophysical profile (+ when it’s done)

• Series of 5 assessments of fetal well being

  • (basically fetal APGAR)

  • Not done until third trimester (will do earlier if patient has preterm PROM)

  • test takes 30 minutes

what’s included in biophysical profile 

• reactive heart rate (nurse done)

• amniotic fluid volume

• gross body movement

• fetal breathing movement

• fetal tone 

either absent (0) or present (2) - no single points

biophysical profile scoring

• 8-10 = normal

• 4-6 = equivocal - requires further evaluation

• 2 or less = abnormal - immediate interventions (delivery) needed

non-stress test (+ when it’s done)

• Measures response of FHR to fetal movement

  • Done when there are NO contractions

• Pt on LL side- transducer placed on abdomen

• Pt asked to note when fetus moves- presses button on fetal monitor- min 20 min (strips require 20 mins)

  • If not enough mvt- vibroacoustic stim

• usually done at 26-28 weeks

normal (reactive) non-stress test 

• When FHR increases by 15 BPM over 15 seconds at least 2 times in 20 minutes

abnormal (non-reactive) non-stress test

• No accelerations with fetal movement

  • If NR for over at least 40 min—requires further testing/concern

contraction stress test

• Next intervention if biophysical profile 4-6 and need to see if baby can tolerate labor 

• Measures FHR in response to the stress of uterine contractions

  • Uteroplacental blood flow is temp reduced with contraction

    • Healthy fetus is able to compensate for this intermittent decreased blood flow

    • Compromised fetus is unable to compensate

• Contraction Stress test: spontaneous uterine contractions

  • Nipple stim to produce oxytocin 

• Oxytocin Challenge Test: oxytocin used to stimulate contractions

  • Need IV - give oxytocin until contractions are sufficient 

evaluating contraction stress test

• Need 3 contractions lasting 40 seconds in 10 minutes to evaluate

• Normal = negative = baby was not stressed by contraction

  • Baseline FHR should not change; No deceleration of FHR

• Abnormal = Positive CST/OCT (baby was stressed!)

  • FHR decelerations (especially late decelerations)

  • Repetitive decels following each contraction

    • Usually indication for delivery
      

contraindications for contraction stress test 

• placenta previa, Hx of extensive uterine scarring, Hx of preterm labor, Hx of vertical incision (this person should not give vaginal birth)