WK 1: Genetics, Conception, and Fetal Development

Genetics: Key Points for Nurses - Incidence

• Nationally, 1 in every 33 births is impacted by serious birth defects

• SDoH-Globally, 90% of children born with a serious birth defect are in low- and middle-income countries

Genetics: Key Points for Nurses - Risk Factors

• Advanced maternal age

• Personal or family history

• Meds taken while pregnant

• Medical conditions (e.g., DM, obesity)

• Recreational drugs & alcohol use in pregnancy

Genetics: Key Points for Nurses - How

• Dominant genetic inheritance

• Recessive genetic inheritance

• De novo genetic mutations - usually early in development

  • “an alteration in a gene that is present for the first time in a family member, arising spontaneously in a germ cell (egg or sperm) or during early fertilization, rather than being inherited from parents. These "new" mutations can cause genetic disorders”

Expected Chromosomes

46 chromosomes expected:

• 22 pairs of autosomes

• 1 pair of sex chromosomes

Chromosomal Abnormalities - Abnormal Number

• Trisomies

  • Trisomy 21 (Down Syndrome), 18 (“Edwards Syndrome”) & 13 (“Patau Syndrome”)

• Monosomies

  • Monosomy 45,X (Turner Syndrome)

    • “ONE X chromosome, presents female”

• Mosaicism

  • Some cells with abnormal chromosome #

  • Vary in expression - can have milder or no manifestations

Chromosomal Abnormalities - Abnormal Structure

• Translocations

• Deletions

• Duplications

Chromosomal Abnormalities - Sex Chromosomes

• Nondisjunction during gametogenesis (extra copy of a chromosome or missing)

  • Example: Klinefelter Syndrome (47, XXY)

  • “Nondisjunction during gametogenesis is a specific cellular "glitch" where chromosomes fail to separate properly while the body is creating sperm or egg cells (gametes).

    In a perfect scenario, a precursor cell with 46 chromosomes divides so that each resulting sperm or egg gets exactly 23. When nondisjunction happens, one gamete ends up with an extra chromosome (24), and another ends up missing one (22).”

Common Inheritance Patterns - Autosomal Dominant Inheritance

• Examples:

  • Huntington’s Disease

  • Marfan Syndrome

  • Myotonic Dystrophy

  • Achondroplasia

• 50% change of passing on the gene

• Individuals assigned male at birth and individuals assigned female at birth equally affected

• Varying degrees of presentation

Common Inheritance Patterns - Autosomal Recessive Inheritance

• Examples:

  • Sickle Cell Anemia

  • Tay Sachs

  • Maple Syrup Urine Disease

  • PKU

  • Cystic Fibrosis

  • Galactosemia

• Both genes must be abnormal for disorder to be expressed

• Males and females equally affected

• If child clinically normal, 66% chance child is carrier

• If both parents are carriers:

  • 25% change of having unaffected child

  • 50% change of having an unaffected child who is a carrier

  • 25% change of having affected child with two recessive genes

Common Inheritance Patterns - X-Linked Recessive

• Examples:

  • Duchenne Muscular Dystrophy

  • Fragile-X Syndrome

  • Red-Green Color Blindness

  • Hemophilia

• NO male-to-male transmission

• 50% chance carrier mother will pass abnormal gene to sons (affected)

• 50% chance carrier mother will pass abnormal gene to daughters (carrier), but unaffected

Why should nurses care about inheritance patterns?

• General understanding of genetics & the possible effects on the developing baby—necessary for ALL nurses

• Explain/clarify diagnostic procedures used in genetic testing (i.e., purpose, findings, & possible s/e)

• Clarify or reinforce information received from their HCP or genetic counselor

• For maternal-child nurses—need to have knowledge & info regarding:

  • Genetic counseling services available in parents’ community

  • Access to genetic services

  • Procedure for referral to the different services, and the information or services these agencies provide

Nursing Implications

Prenatal Genetic Testing

• Understanding your patient’s genetic history can directly influence pre-conception, prenatal, intrapartum, and newborn care

Prenatal Genetic Testing - Screening Tests

• Assess risk for condition

• NOT diagnostic for conditions → need more information

  • “Ex: 1 hr Glucose Test”

  • “When somebody screens positive, they’ll usually be sent for diagnostic tests to confirm (potentially diagnose a condition)

Prenatal Genetic Testing - Diagnostic Tests

• Diagnose a condition

• Examines cells from fetus or placenta

  • “Ex: 3 hr Glucose Test”

• When: high-risk, screening results (positive), family hx

Examples of Prenatal Genetic Screening Tests

Pre-Implantation

• Blood Test & PGT

  • Genetic Carrier Screening & Blastocyst Biopsy + Testing

10+ Weeks

• Blood Test

  • Cell-Free DNA Testing

10-13 Weeks

• Ultrasound

  • Nuchal Translucency

15-22 Weeks

• Blood Test

  • Quadruple Screen - Includes:

    • AFP

    • UE (unconjugated estriol)

    • hCG

    • Inhibin-A

18-22 Weeks

• Ultrasound

  • Anatomy Scan

Prenatal Diagnostic Tests: Chorionic Villus Sampling

10-13 Weeks

• Removal of a small tissue specimen from fetal portion of placenta

• Tissue removed reflects genetic make-up of fetus

• Used to dx genetic or congenital anomalies (similar to Amnio)

• Transcervical or transabdominal

Prenatal Diagnostic Tests: Amniocentesis

After 14 Weeks

• Performed to obtain amniotic fluid, which contains fetal cells

• Utilizes U/S to direct needle transabdominally into uterus

• Used for prenatal dx of genetic or congenital anomalies, assessment of pulmonary maturity, and dx of fetal hemolytic disease

A 28-week pregnant patient asks the nurse about prenatal tests for chromosomal abnormalities. Which statement by the nurse is most accurate?

A. “The anatomy scan will definitively tell you if your baby has Down syndrome.”

B. “The quad screen gives a risk estimate for certain conditions, but a positive result needs confirmation with a diagnostic test.”

C. “NIPT is a diagnostic test, so no further testing is needed if it’s positive.”

D. Carrier screening can diagnose any genetic disorder in your fetus.”

What is the recommended gestational age range for the Quadruple (Quad) Screen test?

A. 10-13 weeks

B. 15-22 weeks

C. 18-22 weeks

D. 10+ weeks

A nurse is reviewing prenatal risk factors with a patient. Which of the following maternal factors increase the likelihood of the newborn having a genetic or congenital condition? (Select all that apply)

A. Maternal age over 35

B. History of a sibling with a genetic disorder

C. Use of alcohol or recreational drugs during pregnancy

D. Daily prenatal vitamins

E. Maternal diagnosis of obesity and poorly controlled diabetes

F. Personal history of genetic disorders

Menstruation & Hormones: FSH & LH

• Follicle Stimulating Hormone

  • Grow follicles

  • “follicle lives in the ovary”

  • “Sent from the brain down to the ovary”

• Luteinizing Hormone

  • Peak triggers ovulation

    • “release of egg from follicle”

    • “Surge in LH levels 12-36 hours before ovulation”

• Both are secreted by the anterior pituitary gland

Menstruation & Hormones: Estrogen

• Secreted by Graafian Follicle → transforms to Corpus Luteum after ovulation

• Influences endometrial lining

Menstruation & Hormones: Progesterone

• Secreted by Corpus Luteum

• Levels increase after ovulation

• Pregnancy Hormone/calming of uterus

Menstruation & Hormones: HCG

• When present, promotes continued support of pregnancy via signaling to the Corpus Luteum, which maintains progesterone production until Placenta takes over around Week 9

Menstruation & Hormones: Prostaglandins

• Produced by Endometrium

• PGE relaxes smooth muscle

• PGF increases contractility of muscles

Fertilization & Cellular Differentiation: Amnion - Inner Embryonic Membrane

• Contains amniotic fluid

• Space between membrane and embryo = amniotic cavity

• Expands until comes in contact with chorion

• Form fluid-filled amniotic sac, protects

Fertilization & Cellular Differentiation: Chorion - First Outermost Embryonic Membrane

• Fingerlike projections = chorionic villi

• Early genetic testing

• By 4th month, surface smooth, except at place of attachment to uterine wall

Amniotic Fluid - Functions

• Cushion

  • Acts as cushion against mechanical injury

• Temperature Control

  • Helps control embryo(s) temperature

• Growth & Movement

  • Permits symmetrical external growth and development of embryo

  • Acts as extension of fetal extracellular space

  • Prevents adherence of embryo-fetus to amnion to allow freedom of movement

• Umbilical Protection

  • Allows umbilical cord to be relatively free of compression

Amniotic Fluid - Contents

• 98-99% Water; Slightly Alkaline

• Contains: Albumin, Urea, Uric Acid, Creatinine, Lecithin, Sphingomyelin

• Mostly fetal urine

• Fluid Amounts:

  • 10 weeks: 30 mL

  • 20 weeks: 350 mL

  • 32-39 weeks: 800 mL

  • Then decreases after term

Amniotic Fluid - Variations

• Oligohydramnios

  • <300 mL = Potter’s Syndrome

• Polyhydramnios

  • >2000 mL = Bartter’s Syndrome (kidney), GI malformations

Placenta - Development

• Begins 3rd week until 20 weeks

• Expands and grows until covers ½ of inside of uterus—then gets thicker

“Placenta is functional around 10 weeks, ideally implanted in the upper part of uterus, anterior, posterior, or fundus

Placenta - Function

Metabolic and nutrient exchange between embryonic and maternal circulation

• Respiratory - O2 exchange (fetal Hgb higher affinity for O2)

  • “fetus is able to operate around 80% O2 saturation”

• Excretion - bicarb, hydrogen ions, urea, etc.

• Nutrition - glucose and micronutrients

• Immunity - passive immunity

• Endocrine - HCG, Estrogen, Progesterone

Placental Circulation

• After implantation, cells differentiate into fetal cells (embryoblasts) and placental cells (trophoblasts)

  • Trophoblasts invades endometrium and opens uterine capillaries and larger uterine vessels

• 17-days after conception:

  • Completion of maternal-placental-fetal circulation

• End of 4th Week:

  • Embryonic blood circulating

• At 14 Weeks:

  • Placenta is discrete organ

  • Cotyledons of maternal surface = branches of single placental mainstream villus

    • Facilitates compartmentalization of uteroplacental circulation

  • Capillaries of villi lined with thin endothelium are surrounded by layer of connective tissue

• TAKEAWAY: MATERNAL AND FETAL BLOOD DO NOT MIX

Umbilical Cord: A-V-A

Umbilical Cord:

• Central insertion in placenta = Normal

• Average 55 cm long

• 3 Vessels:

  • 1 Large Vein

    • Carries oxygenated blood from the placenta (maternal) to the baby

  • 2 Small Arteries

    • Carry deoxygenated blood and waste from the baby to the placenta

• Wharton’s Jelly

  • Collagenous substance

  • Cushion for the vessels to protect from compression

    • Can get knotted from fetal movement, but true knot is rare

• No sensory or motor innervation (cut cord)

Umbilical Cord: A-V-A - Memory Tips

• Arterial and Venous circulation through umbilical cord is opposite than typical circulation in the human body

  • Understanding WHY will help you remember this!

• AVA

  • Artery, Vein, Artery

“The "Why" of Umbilical Circulation

In a fetus, the "lungs" are actually the placenta. That is where the gas exchange happens.

The Umbilical Vein (1)

Since the placenta is the source of oxygen, the blood returning from the placenta is highly oxygenated. Because this blood is traveling towards the fetal heart, the vessel is a vein.

Think: "The Vein brings the Valuables (Oxygen and Nutrients)."

The Umbilical Arteries (2)

After the fetal body uses that oxygen, the waste-filled, deoxygenated blood needs to go back to the placenta to be "refilled." Since this blood is traveling away from the fetal heart, these vessels are arteries.”

Fetal Circulation

• Fetal lungs are not involved in gas exchange and therefore do not require high volume of blood

• Pressure in the lungs is high

  • Lungs fluid-filled & tightly constricted arteries

  • Under normal circumstances, this would cause significant strain on the right ventricle (ex: pulmonary HTN)

• To accommodate → placenta assumes function of fetal lungs

• There are three fetal shunts involved in fetal circulation

  • Following this process, deoxygenated blood in arteries returns to placenta through umbilical arteries

Three Fetal Shunts - Ductus Venosis

Helps blood mostly bypass the liver and quickly enter fetal heart for oxygenation/circulation

Three Fetal Shunts - Foramen Ovale

Allows most of the blood in R atrium to bypass lungs and enter L atrium to oxygenate other fetal organs

Three Fetal Shunts - Ductus Arteriosis

Since only small amount of blood needed in lungs, allows blood in R Ventricle to shunt to Descending Aorta for more widespread circulation

“Heart between Pulmonary Arteries and Descending Aorta”

Stages of Development - Embryonic Stage

Day 15 - End of 8 Weeks:

• Organogenesis

• Most vulnerable to Teratogens

  • “REALLY fragile stage: vulnerable to nutrition/environment/whatever it is exposed to”

Stages of Development - Fetal Stage

Considered to be in this stage from 9 weeks until birth

Developmental Milestones - 4 Weeks Gestation

Fetal heart begins to beat

Developmental Milestones - Week 8 Gestation

Organogenesis complete

Developmental Milestones - 8-12 Weeks Gestation

Fetal heart heard by doppler device

Developmental Milestones - 16 Weeks Gestation

Baby’s sex can be seen on U/S, fetus looks like a baby, but thin

Developmental Milestones - 20 Weeks Gestation

Quickening, hands grasp, vernix & lanugo present, hair present on head, eyebrows and eyelashes

Developmental Milestones - 24 Weeks Gestation

Viability, activity increases, fetus can hear

Developmental Milestones - 28 Weeks Gestation

Eyes open and close, surfactant is formed, fetus is 2/3 of final size

Developmental Milestones - 32 Weeks Gestation

Finger and toenails formed, subcutaneous fat is being laid down

Developmental Milestones - 38+ Weeks Gestation

Antibodies crossing placenta to support baby’s immune system, baby fills uterine space

The Science of Multiples: Twinning

1 in 43 pregnancies, Triplets 1 in 1341

The Science of Multiples - Fraternal Twins (Dizygotic)

• Two placentas, two chorions, two amnions

• Placentas sometimes fuse

• Increases with maternal age up to about 35 years

• Tends to occur in certain families

The Science of Multiples - Identical Twins (Monozygotic)

• Single fertilized ovum that splits

• Same sex, same appearance

• Usually have common placenta

• 3.5/1000 live births

• Survival rate 10% lower than of dizygotic twins

• Congenital anomalies more prevalent

Division of Fertilized Ovum (Zygote)

• 3 days of fertilization: 2 embryos, 2 amnions, 2 chorions = Dichorionic-Diamniotic

• 5 days after fertilization: 2 embryos, 2 amnion sacs, common chorion = Monochorionic-Diamniotic placenta

• 7-13 days after fertilization: 2 embryos, common sac and chorion = RARE

Factors Influencing Embryonic & Fetal Development

• Quality of sperm or oocyte

• Adequacy of intrauterine environment

• Time of injury critical in development of anomalies

• Genetic code established at fertilization (Fertilization & Cell Division)

• Maternal Nutrition & Environment

  • Nutrition, Environmental Factors that could lead to SAB (miscarriage) or neurological developmental issues like hyperthermia

What is a teratogen?

A substance that interferes with normal fetal development and causes congenital disabilities

Nutrition of the Pregnant Patient & Patients Pre-Conception

• Vital for embryonic and fetal organ development during pregnancy

• Prevention of congenital malformations (i.e. neural tube defects)

• Recommended to make nutritional adaptations BEFORE pregnancy since most crucial time for growth and development takes place in first several weeks of pregnancy!

Weight Gain During Pregnancy

• Depends based on baseline weight status of patient

• Generally, patient should gain approximately 25-35 lbs throughout the pregnancy, less for higher BMI, more for lower BMI

• First trimester, little weight gain. Majority takes place second and third trimesters

Nutritional Demands During Pregnancy

• Correlate with weight gain patterns

• Gradual increase in calories/day

  • First trimester: NO CHANGE

  • Second trimester: increase of 340 kcal/day

  • Third trimester: increase of 452 kcal/day

• Increased demands due to:

  • Growth of uterine-placental-fetal unit & mammary development

  • Increased Total Blood Volume increased by 40-50%

  • Increased metabolic rate by 20%

Pregnancy Nutrition & Wellness - Do’s

• Well-Balanced Diet Rich in Protein:

  • Essential for fetal development, formation of amniotic fluid, and physical adaptations to pregnancy that the pregnant patient will experience like increase in blood volume and uterine changes

• Prenatal Multi-Vitamin:

  • Calcium, Zinc, Iron, Iodine, Magnesium, Vitamins A, D, E, C, B12, and B6

• Folic Acid (Folate):

  • Essential for prevention of neural tube defects (like spina bifida or ancephaly)

• Continue staying active, oral health

Pregnancy Nutrition & Wellness - Don’ts

• Alcohol and other teratogens

• Smoking and environmental exposures

• Reduce or cut out caffeine (<200 mg/day = 12 oz cup)

• Caution with “eating for two” and focus on a healthy, well-balanced diet

Pregnancy - EDD with Naegele’s Rule

• LMP - 3 months + 7 days = EDD

• Example: LMP March 9 = EDD Dec 16

• Most babies born within 10-14 days of this

Pregnancy - Length (from LMP)

• 40 weeks

• 280 days

Pregnancy - Fundal Height

• Measurement from suprapubic bone to fundus

• Centimeters in height correlate with weeks gestation

Pregnancy - Ultrasound

• 1st trimester U/S to determine EDD

• Can visualize gestational sac at 4-5 weeks

• Transvaginal U/S or Abdominal U/S

• Transvaginal for earlier dates (ex: IVF patients early in gestation for monitoring)

Pregnancy - Fetal Heartbeat

• Typically use Ultrasonic Doppler to hear at 10-12 weeks

• Normal FHR range from 110-160 bpm

• Can be visualized as early as ~6 weeks gestation with Transvaginal U/S

Pregnancy - Quickening

• Fetal movement

• Can be felt by pregnant individual starting 16-20 weeks gestation

• Not always reliable and patients not always aware this is fetal movement initially