Prenatal exam 1

full term pregnancy

anything after 37 weeks

time of fertilization

2 weeks after LMP

when does week 1 of gestation begin?

first day of LMP (conception is around start of week 3)

gravidity

number of times someone has been pregnant

parity

number of delivered pregnancies, divided into:

Full term

Preterm

Losses

Living children

menstrual cycle

28 days, first 14 days is follicular phase, ovulation at day 14, luteal phase is days 14-28

If fertilization occurs during ovulation, corpus luteum (CL) becomes CL of pregnancy and increases hormone production to maintain endometrium (tells endometrium to stick around)

CL then maintained by the secretion of human chorionic gonadotropin (HCG) by the developing zygote

Placenta will eventually assume production of estrogen and progesterone

HCG also tells CL to stick around, feedback cycle

when in embryonic development does the zygote develop?

weeks 1 and 2, most development and organ differentiation happens in the first trimester, and then there’s continued growth and development throughout the rest of the pregnancy

mitosis

replication of somatic cells (cells of our body) – creates identical daughter cells, mutations can occur and lead to cancer

Final chromosome count is 46 chromosomes

Prophase, metaphase, anaphase, telophase

meiosis

Replication of germline cells

Replication once, division twice

Germline cell division only

Allows for exchange and recombination of genetic material

Final chromosome count is 23 chromosomes

• Meiosis 1 allows for recombination/crossing over

  • Testes: 2 spermatocytes

  • Ovaries: 1 secondary oocyte, 1 polar body

• Meiosis 2: dressed-up version of mitosis

  • Testes: 4 spermatids

  • Ovaries: 1 mature ovum, 3 polar bodies

where do primordial germ cells form?

primordial germ cells (PGCs) form in the epiblast at 4 weeks gestation and move to the wall of the yolk sac

Around 6 weeks gestation PGCs migrate from the yolk sac toward the developing gonads, where they arrive by 7 weeks

Mitotic divisions increase their number during their migration and also when they arrive in the gonad

how often is sperm created?

• Sperm created every 64 days and continues throughout adulthood

• Sperm count tends to decrease with time due to age/teratogens

• Acrosome has the nucleated DNA in the head of the sperm

• Cilium (tail) is used to reach egg

oogenesis prenatally and at birth

Prenatally, oogonia proliferate via mitosis and some develop into primary oocytes, they replicate their DNA, and enter meiosis 1

At birth, all oocytes are arrested in the diplotene phase of prophase 1 and don’t complete meiosis 1 until puberty

By 20 weeks gestation, fetal ovaries have all the egg cells there will ever be

There is a rapid loss of egg cells after primary oocytes are arrested in diplotene state of meiotic prophase by 7th month of utero

Egg has corona radiata to protect it, acrosome has to make it through the nucleated cells to fertilize the egg

Oocytes only survive for 24 hours, so fertilization must occur within 24 hours (meiosis 2 only completed if fertilization occurs)

Sperm have a 6 day window where they can survive in female reproductive tract and fertilize egg

Factors impacting gamete fitness

• Maternal age

  • Chromosomal nondisjunction

  • Eggs are as old as the person who releases them because meiosis 2 doesn't happen until fertilization, and all our cells function worse as we get older

  • Egg cells not as good at separating chromosomes as you get older

• Paternal age

  • Not as big of a deal for nondisjunction events 

  • De novo mutation events (by sheer volume of processes of mitosis and meiosis)

• Teratogen exposures (e.g. alcohol drug abuse significantly lowers male and female fertility)

  • Not always impacting chromosomal fitness, but ability to achieve a pregnancy

most common chromosome anomalies

• Regardless of age, half of all miscarriages are caused by chromosome anomalies

• Most common chromosomal aneuploidy causing miscarriage is trisomy 16

• Most common aneuploidy seen in live births is trisomy 21

• Most common sex chromosome aneuploidy is monosomy X (Turner syndrome)

Fertilization

Fertilization typically takes place in the ampulla of the oviduct (fallopian tube)

Fallopian tube not physically connected to the uterus, but have projections that sweep eggs into the fallopian tube

Fertilization process takes about 24 hours

Sperm are viable for up to 6 days in female reproductive tract

Capacitation: obligate period of time sperm must spend in the female tract before they can fertilize an egg → glycoproteins have to be regraded from acrosome first

Consequences of fertilization

Alteration of the oocyte’s membrane to block entry of more sperm

Completion of meiosis of the oocyte

Fusion of the two haploid nuclei into one diploid nucleus

Determination of the chromosomal sex of the zygote

Metabolic activation of the zygote and initiation of cleavage

Errors in fertilization

• Triploidy: most common error in fertilization

  • 60% caused by dispermy (2 sperm per 1 egg)

  • Results in 3 full sets of chromosomes (69 total)

  • Digyny: 2 sets of egg-derived chromosomes 

  • Diandry: 2 sets of sperm-derived chromosomes 

  • Overrepresentation of maternal DNA leads to embryonic tissue proliferation, while overrepresentation of paternal DNA leads to non-embryonic tissue proliferation (massive placental development)

• Molar pregnancy

  • Complete molar pregnancy: egg without genetic information is fertilized by two sets of paternal DNA (dispermy or diploid sperm) → leads to highly abnormal placenta with no fetal tissue development

  • Partial molar pregnancy: usually triploid karyotype due to dispermy → leads to an abnormal placenta with some fetal development and inevitable fetal loss 

    • Secretes high levels of HCG, may cause malignant choriocarcinoma

two cells groups of the blastocyst

• inner cell mass (becomes fetal tissue) and trophectoderm (becomes placental tissue)

  • Embryo hatches from the zona pellucida upon reaching the uterus

  • During migration to the uterus, the zona pellucida prevents the embryo from prematurely adhering to the oviduct rather than traveling to the uterus

when is implantation in the uterus completed?

day 9

two layers that the trophoblast differentiates into

Cytotrophoblast: mitotically active cellular layer that gives rise to the placenta

Synctiotrophoblast: actively invades the endometrium

Blastocyst development

Blastocyst lies free in the uterus for about 2 days, nourished by uterine secretions

Zona pellucida degenerates, and trophoblast cells create proteolytic enzymes to penetrate uterine and implant blastocyst

Eroded maternal tissues nourish the blastocyst until implantation and placental development

monozygotic twin zygote splitting

Days 1-3 (morula stage): dichorionic-diamniotic twins

Days 4-8 (hatching blastocyst): monochorionic-diamniotic twins

Days 8-13 (implanted blastocyst): monochorionic-monoamniotic twins

Days 13-15 (embryonic disk): conjoined twins

Dichorionic: 2 placentas

Diamniotic: 2 amniotic sacs

Embryo’s week 2 of pregnancy

2 trophoblastic tissues

2 layers form in embryoblast

2 new cavities form - amniotic and chorionic

2 layers of extraembryonic mesoderm form

More happening with extraembryonic tissue than with embryo itself

Placental development

Two layers of the trophoblast: syncytiotrophoblast and cytotrophoblast

Syncytiotrophoblast: produces HCG

Cytotrophoblast: layer of single cells that forms the structural support of the placenta, cell layer evaluated in a direct prep from a CVS sample

Cytogenetics

field of genetics that studies chromosomes and their potential differences

Atypical number of whole chromosomes or chromosome regions may be diagnostic of a genetic condition

Atypical organization of chromosomes may put individuals at a reproductive risk (translocations, inversions)

Chromosomes are counted by centromere - may be varying amounts of chromosomal material, but we measure by centromere because that’s where they line up in metaphase

Errors in mitosis can cause an extra or missing copy of a chromosome

Majority of nondisjunction events happen in first meiotic division

Karyotype

number, morphology, organization of chromosomes

Need to have dividing cells

Chemical added that stops mitosis in metaphase, requires 2-3 days of incubation so longer TAT

Can identity gains/losses of 5-10 megabases, good for determining missing or extra chromosomes or large indels

Indications for karyotype: concern for aneuploidy, multiple congenital anomalies, recurrent pregnancy loss, prenatal testing

Amnio is the only way to get a karyotype today

Fluorescence in situ hybridization (FISH)

presence or absence of specific chromosome/gene region

Can be done in 12-24 hours if cells and probe are ready to go

Create fluorescently-tagged probe, requires specific probes that match what you’re looking for

Used as screening test for amnio and CVS

Used for preliminary results to confirm suspected diagnosis (aneuploidy, common deletion syndromes)

Also used to better characterize cytogenetic abnormalities, can also see if gene fusions have occurred

Doesn’t require dividing cells

Can be a more cost-effective and timely way to identify a diagnosis

Generally a preliminary diagnostic test and requires follow up testing for confirmation

Chromosomal microarray

copy number variation (gains or losses of genomic material)

Typical genome copy number is 2, CMA tells you about changes in copy number throughout genome

First line test for developmental delay/autism, multiple congenital anomalies

Professional guidelines recommend offering array to every patient consenting to a diagnostic procedure in pregnancy

Many conditions are caused by CNVs that are below the resolution of a karyotype

• 22q11.2 deletion syndrome, Cri-du-chat, Wolf-Hirschhorn syndrome

Uses method of counting how much there is, as well as a SNP-based method looking at specific alleles present

More sensitive and specific than karyotype (can identify gains/losses as small as 25kb)

Does not provide structural information, can’t identify balanced rearrangements

Can be performed on non-dividing cells or on cultured cells

Microdeletion syndromes detected by array that is below karyotype resolution: 22q11.2 deletion syndrome, Prader-Willi syndrome, Angelman syndrome, 1p36 deletion syndrome, Cri du Chat

Long read genome sequencing

can determine what chromosome structure looks like

22q11.2 deletion syndrome

Wide variation in clinical features

Congenital heart defects, problems with immune system, unique facial features, delayed growth, delayed feedings and GI problems, failure to gain weight, poor muscle tone, delayed development, learning and speech delays or difficulties and behavior problems

Chromosome landmarks

P arm is short arm, q arm is long arm

P arm is on top in karyotype

Pter is end of p arm, qter is end of q arm

Chromosome identified by size, centromere location, and banding pattern

Metacentric chromosomes are larger, acrocentric chromosomes are smaller

Chromosomes labeled by size, chromosome 1 is biggest and 22 is smallest

telocentric

centromere is at very end of arm of chromosome (not seen in humans)

acrocentric

•  telomere is almost at end of chromosome, has q arm and small p arm containing repetitive material

  • Stalks and satellites that can vary in size in the healthy population

  • Repetitive ribosomal RNA that is common among all acrocentric chromosomes

  • E.g. chromosome 21

submetacentric

between end of arm and middle (adjacent to center), q arm is longer than p arm (e.g. chromosome 6)

metacentric

telomere is in the middle of the chromosome arm, p and q arms are the same length (e.g. chromosome 1)

Chromosome banding

Gene rich regions (euchromatin) stain light because they are GC rich

Gene poor regions (heterochromatin) stain dark because they are AT rich

The more visible bands, the higher the resolution

Aneuploidy

abnormal number of one or more chromosomes in a cell

Differences in ploidy

abnormal number of complete set of chromosomes

examples of autosomal aneuploidy

Trisomy 21 (Down syndrome)

Trisomy 18 (Edwards syndrome)

Trisomy 13 (Patau syndrome)

Risk for these conditions in pregnancy increases with maternal age

examples of sex chromosome aneuploidy

Monosomy X (Turner syndrome)

XXY (Klinefelter syndrome)

XXX

XYY (Jacob syndrome)

Number of genes by chromosome

Chromosomes that vary in size but have a lower number of genes on them can have aneuploidy and result in a live birth, while aneuploidy for chromosomes with more genes causes anomalies in organ systems or complete fetal loss

Trisomy 21

Can be mosaic and present in some but not all cells in the body

Clinical features: intellectual disability, hypotonia, congenital heart defects, GI tract abnormalities, kidney problems, hematologic malignancies, dysmorphic features (epicanthal folds, upslanting palpebral fissures, single palmar crease)

Important to determine what a patient knows about Down syndrome and fill in relevant context

Up to 10% chance of a child with leukemia (not talked about in initial session where someone is getting prenatal diagnosis of Down syndrome)

5% due to Robertsonian translocation of chromosome 21 (acrocentric) - can cause recurrent Down syndrome in recurrent pregnancies if parent is carrier (10-15% risk if egg contributor is carrier of Robertsonian translocation, low risk if sperm contributor is carrier)

Trisomy 18 (Edwards syndrome)

Typically results in fetal demise or neonatal loss due to severity of health complications

Clinical features: intrauterine growth restriction, congenital heart defects, micrognathia, brain abnormalities, omphalocele, clenched fists with overlapping fingers, rocker bottom feet

Chromosome 18 is not acrocentric, virtually always caused by 3rd copy of chromosome 18

Trisomy 13 (Patau syndrome)

Typically results in fetal demise or neonatal loss due to severity of health complications

Clinical features: brain abnormalities (holoprosencephaly), congenital heart defects, polydactyly, cleft lip/palate, microphthalmia

Chromosome 13 is acrocentric, most commonly caused by nondisjunction but can also be caused by Robertsonian translocation with chromosome 14

Monosomy X (Turner syndrome)

Majority of cases result in miscarriage

Usually due to missing copy of X chromosome (either sperm of egg missing copy of X chromosome) - ring X chromosome, isochromosome X, abnormal X chromosome

Clinical features: congenital heart defect, short stature, edema, horseshoe kidney, cystic hydroma/neck webbing, infertility, streak gonad

XXY (Klinefelter syndrome)

May have mild presentation resulting in underdiagnosis or delayed diagnosis

Clinical features: tall stature, low muscle tone, primary testicular insufficiency, gynecomastia, cryptorchidism, infertility, anxiety, depression, ADHD, autism spectrum disorder

XYY (Jacob syndrome)

No increased association with aggression, despite early study suggesting so (lots of ethical issues)

Clinical features: tall stature, learning disabilities, increased risk for ADHD/depression/anxiety/autism spectrum disorder

XXX

Clinical features: tall stature, increased risk of learning disabilities

structural chromosome abnormalities

Translocation: two or more chromosomes exchange material

Deletion: portion of a chromosome is deleted

Duplication: portion of a chromosome is duplicated

Inversion: 2 breaks occur and the regions between them are inverted

Insertion: portion of a chromosome is removed and inserted into another

Isochromosome: chromosome consists of only one chromosome arm

Ring chromosome: 2 breaks occur on either end of a chromosome and join together

Marker chromosome: chromosome without an identifiable origin, typically mosaic

Balanced translocation

Break happens in two or more chromosomes and the material distal to the break exchanges place and rejoins

Normal in meiosis, abnormal in mitosis

Balanced translocations in a parent can result in unbalanced translocations in offspring when combined with normal gamete from partner

May put couples at risk for infertility, recurrent miscarriages, or a child with congenital anomalies

Unbalanced translocation

Each chromosome in the translocation is referred to as a derivative

If an individual only has one of the derivative chromosomes they are unbalanced with a net gain and loss of material

Can cause partial trisomy of one chromosome and partial monosomy of another chromosome

Robertsonian translocation

Acrocentric chromosomes, small p arm portion is removed and remaining portion joins another chromosome

P arm satellites go away, don’t get replicated

mosaicism

mixture of two or more genetically distinct but related cell lines

Some conditions are only seen in the mosaic state or are only able to be diagnosed by examining a specific tissue

Pallister Killian syndrome: mosaic trisomy of 12p (4 p arms of 12, 2 q arms of 12, almost always mosaic)

chimerism

mixture of two or more genetically distinct cell lines from different conceptions → very rare

People can become chimeras through kidney transplants, bone marrow transplants, etc

Rescue events

Human cell recognizes when it doesn’t have typical material to do its job and function normally

Will delete/duplicate chromosomes to prevent it being replicated

Matters whether chromosomal condition came from mom or dad for specific chromosomal condition

when does the embryonic stage occur?

week 5 of gestation, week 3 of embryo development — marks the end of the all or one period

all or none” period

There is no physical connection between embryo and pregnant person during the beginning of pregnancy before implantation

Before implantation is the “none” part of the “all or none” period, where exposures/teratogens are unlikely to affect development

Extreme exposure may result in miscarriage, but anything else won’t have an effect

After implantation, anything capable of crossing the placental barrier can cause effects on development → “all” part of “all or none” period, coincides with first day of missed period (week 5 of pregnancy)

what happens during week 3 of development/week 5 of gestation?

Very sensitive time marked most notably by gastrulation and neurulation

• Gastrulation: forming three layers

• Neurulation: folding these layers to reform the embryo and develop structures

Outside the embryo: the chorion and yolk sac become vascularized

• Yolk sac: transfer of nutrients in 1st month when uteroplacental circulation is being established, early site of hematopoiesis (before liver)

• Part of the yolk sac becomes the primitive gut, which gives rise to the digestive and respiratory tracts

• Location of primordial germ cells before they migrate to the sex glands

• Yolk sac originates in the chorionic cavity, and atrophies as pregnancy advances (very rarely does it persist throughout pregnancy)

Within the embryo: the two-layered embryonic disk enlarges by elongating and widening, its two layers become three layers, and its three layers begin to form rudimentary organs

allantois

Membrane that removes liquid waste and gases, another rudimentary structure outside of developing embryo, not very functional in human embryos

Still important:

Blood formation occurs in walls of allantois (weeks 3-5)

Its blood vessels persist in the umbilical vessels

Portion of the allantois runs from the umbilicus to the urinary bladder

Cyst in the umbilical cord may represent the remnants of the allantois

primitive streak

• linear depression marking the linear axis of the embryo

  • Appears caudally 

  • Results in the proliferation and migration of cells of the epiblast

  • Gives a linear dimension to the cell mass

  • An early structure of the epiblast mesoderm, but diminishes in size and becomes an insignificant structure in the sacrococcygeal region of the embryo 

    • But this can go awry, sacrococcygeal teratoma occurs when primitive streak persists

    • Derived from pluripotent cells

    • Most common tumor in newborn infants (1 in 35,000 births)

    • Good prognosis following surgical resection

Prechordal plate

small circular spot where the epiblast and hypoblast are stuck tightly together, will give rise to membrane to form mouth opening (buccopharyngeal membrane) and help design neural tube

Notochordal process and the cells of the mesoderm around it signal the overlying embryonic ectoderm to form the neural plate

Origin of central nervous system

Primitive node forms as primitive streak ends

Neural plate and notochordal process develop

Neural plate grows cranially to oropharyngeal membrane and caudally down towards primitive streak and cloacal membrane

Notocord directs folding process and closure of neural tube

Notochord directs growth of tissue layers, and eventually overgrowth of those layers to form a closed system surrounded by connective tissue

3 cell lines from epiblast

• Epiblast is site of action for what turns into fetal tissue, 3 cells lines from epiblast that differentiate across the embryonic period

• Ectoderm: epidermis, central and peripheral nervous systems, retina, and various other structures

• Endoderm: source of epithelial linings and GI tract

• Mesoderm: smooth muscle, connective tissue, blood cells, bone marrow, reproductive and excretory organs

Neurulation

folding layers to reform the embryo and develop structures

Includes the formation of the neural plate (day 18-19), neural folds (day 20-21), and the neural tube (day 22-26)

Neural tube will develop into future brain and spinal cord

Neural tube closes from cranial end to caudal end

Essential that the neural tube closes completely during this time period

Open neural tube defects

Occur in 1/1000 newborns

Folic acid is necessary for this system to develop properly

Defects can occur anywhere along the neural tube and have varied clinical consequences

Most severe type is when closure doesn't happen at the cranial end, causes anencephaly (no closure of the skull, brain tissue not able to be formed, lethal)

Majority are multifactorial

• 95% of babies with ONTDs have no family history

Spina bifida

caudal end opening of neural tube causing spine to come out and is not closed off from amniotic spac

Myelomeningocele

type of spina bifida

Failure of vertebral arches to fuse

Can be seen by 15-18wk

On ultrasound, look for the following signs in the brain:

Lemon sign (caused by the meninges being pulled down)

Banana sign (cerebellum looks like a banana instead of the normal barbell shape)

Also called Chiari malformation

>90% detection on U/S

Can't be seen in first trimester ultrasound

Myelomeningocele is normally sporadic without much genetic effect, but involvement of many organ systems should make us suspicious of genetic etiology

Anencephaly

Absence of forebrain and overlying skull/tissue (seen by 12-14wk)

Always lethal

Can see on first trimester ultrasound

See no development above zygomatic arch/eyebrows

See polyhydramnios because typically missing part of hindbrain that controls swallowing

Not compatible with life

Encephalocele

Protrusion of intracranial contents through bony defect in skull (seen by 12-14wk)

Prognosis OK if there is only fluid in the sac

Surgery may be needed if there is brain involved

Can see on first trimester ultrasound

Appears as an interruption in the bony skull

The intracranial contents are seen herniating through the defect

Hypertelorism (wide set eyes) may be present

Neural crest cells

At crest of neural tube, important for embryonic development → migrate to other parts of the embryo to give rise to other types of tissue such as

Dermis of head

Meninges

Most of the pharyngeal apparatus

Peripheral nervous system

Schwann cells

Pigment cells of the skin

Cells bordering the neural tube become the CNS

what happens after 5 weeks gestation

embryo is 2mm long, has polarity/directionality (head and tail, left and right)

Gastrulation and neurulation have occurred

3 layers of cells ready to develop into body systems of all kinds

Chorion, yolk sac, and embryo all have rudimentary blood vessels

Rudimentary heart is beating

Body cavity has formed

Rudimentary nervous system has formed

what happens during weeks 6-10 gestation

•  3 layered embryo takes on shape and general appearance that is characteristic of vertebrate body plan

• External body form shaped by process of folding

  • Folding is the excess growth and halted growth that gives rise to more tissue in some places and less tissue in other places

• Four folds convert the three-layered disk into curved (c-shaped) cylinder

  • Right and lateral folds

  • Head (cephalic) and tail (caudal) folds

• Other changes accompanying change from flat disk to hollow cylinder

  • 4 limb buds, 4 closed body cavities, 4 rudimentary organ systems appear from 3 germ layers of the embryo

    • Ectoderm → nervous system - brain and spinal cord

    • Mesoderm → cardiovascular system - heart and blood vessels

    • Mesoderm → urogenital system - mesonephros

    • Endoderm → digestive system - tubular gut

  • Some functions begin - circulation occurs because there is now a connection with the placenta, excretion begins due to metabolic waste generated

  • Placental nutrition of the embryo is established 

what happens during weeks 7-10 of gestation

• Development of human features out of basic vertebrate development pattern

  • Morphogenesis: head face, limbs and vertebrae develop; tail regresses

• Acceleration of organogenesis 

  • Differentiation of organs

  • Onset of additional rudimentary functions (neuromuscular activity, some spinal reflexes)

• Expansion of amniotic cavity and reduction of chorionic cavity

• Formation of umbilical cord from the connecting stalk

• Rapid growth (end of week 5 gestation = 3mm, end of week 10 = 27mm)

• As allantois resolves, umbilical cord begins its work of connecting placenta to developing fetus

• All parts of body form around the same time → CNS and spinal cord are first to form, followed by the heart

  • Last things to develop are palate and external genitalia

  • By 10 weeks, most everything is complete

  • CNS continues to develop from beginning to end of pregnancy

ultrasound technology

• Uses sound waves above audible range of 20,000 Hz

• The higher the frequency, the better the resolution

• Creates a picture by sending out sound waves into the body and then listening for rhythm to bounce back → returning sound waves then compiled to make an image

• More dense = greater echogenicity

  • Things that are hard (like bone) bounce sound waves back more quickly, show up lighter while fluid appears black and soft tissue appears gray

• Ultrasound is a worse tool for patients with higher BMI, especially if there is a lot of adipose tissue in the abdomen

  • If sound waves have to travel through more tissue they are lower resolution

  • Bias in sensitivity based on patient’s size

• Ultrasound is safe, always practice ALARA (as low as reasonably achievable) to use lowest frequency possible to get what you need

  • Ultrasound machines regulated on how high a frequency they can send out

  • In the past 40+ years that ultrasound has been around there has never been any bio-effects recorded from its use 

ultrasound scanning methods

Transvaginal: 1st trimester and cervical length

Transabdominal: 2nd and 3rd trimester

Doppler: measures speed of fluid and its flow; check for fetal anemia, placental insufficiency, ovarian torsion, etc

3D and 4D: allows better visualization of abnormalities (cardiac and CNS), 4D is video of 3D image

fetal period of pregnancy

week 9 on,a ll major organs have formed, main events are rapid growth of the body and differentiation of tissues, organs, and systems

pregnancy dating

• 7-14 weeks is most accurate time to measure (using crown-rump length or CRL)

• Measurements used from 15-30 weeks:

  • Biparietal diameter (BPD)

  • Femur length

  • Head circumference

  • Abdominal circumference

medical viability

description of when fetus can survive outside the uterus

~24-25 weeks gestation

Usually >500g or 1.1lb

<1000g = extremely low birth weight

<1500g = low birth weight

3000-3400g is normal birth weight

Macrosomia (large gestation age) defined as >4000g or 4500g

First trimester ultrasound

Gestational sac can be visualized at 5 weeks

Check location of gestational sac and presence of cardiac activity

Normal embryonic growth in 1st tri – almost a linear 1mm/day

If fetal pole is visualized, measure the CRL

If fetal pole is not present, gestational sac can be measured

CRL is most accurate between 7-9 weeks, within 3-5 days

EDD doesn’t change unless there is a discrepancy between ultrasound sating and LMP

Factors influencing fetal growth

• During fetal period, fetus is less vulnerable to the teratogenic effects of drugs, viruses, etc

• However, these agents can still interfere with growth and normal functional development

• Factors operating throughout pregnancy (smoking, alcohol, drugs, etc) can produce intrauterine growth restriction (IUGR)

• In the last trimester, maternal malnutrition can produce underweight infants with normal length, multiple gestation can exceed the supply available from placenta during 3rd trimester, and placental insufficiency can cause problems 

Fetal membranes

• Separate the fetus from the endometrium of the uterus

• Components

  • Chorion: outer membrane

  • Amnion: inner membrane

  • Yolk sac and allantois: vestigial structures, rudimentary and don’t fully develop

• Chorionic sac contains chorionic fluid, this fluid mostly disappears eventually 

• Amniotic sac contains amniotic fluid, fetus, and umbilical cord

amniotic fluid

• Amniotic fluid derives primarily from maternal blood and amniotic cells (increases as pregnancy increases)

• Absorbs sudden jolts and cushions against injuries

• Prevents adherence of embryo to the amnion

• Allows for fetal movement

• Provides barrier to infection

• Helps maintain relatively constant body temperature

• Allows fetus to practice swallowing fluid which is important for development 

• Large volumes of amniotic fluid move between fetal and maternal circulations through the placenta (content changes every 3 hours)

• Oligohydramnios: too little fluid

• Polyhydramnios: too much fluid (more common in obese/diabetic women due to increased amount of glucose)

amniochorionic membrane

At end of 3rd month, amnion comes in contact with chorion, obliterating the chorionic cavity to make room for the growing embryo

New connection is called the amniochorionic membrane

This is what ruptures during labor (when water breaks)

leading cause of prematurity and oligohydramnios

premature rupture of amniochorionic membrane

amniotic band syndrome

• rupture of the amnion leads to free edges of the amnion adhering to the fetus and entrapping fetal parts

• Causes variety of asymmetrical malformations

• Usually sporadic (rare cases seen with connective tissue disorders)

• cause of physical disruption of formation of limbs, constricting blood flow

  • Bands may represent adhesions between the amnion and affected structures in the fetus, or may originate from tears in the amnion that detect and surround that part of the developing fetus (origin of bands is not clear)

  • Amniotic sac is partially disrupted

    • Occurs between 6-18 weeks gestation

    • 1 in 1200 live births

    • Earlier rupture = more severe

parts of placenta

3 parts: fetal portion, maternal portion, intervillous space

Fetal portion: umbilical cord attachment (usually near the center), smooth and shiny (covered by amnion)

Maternal portion: cobblestone appearance, placenta is divided into several compartments (cotyledons)

Intervillous space: between fetal and maternal portions, meeting but not mixing of fetal and maternal blood

layers separating maternal and fetal blood in placenta

syncytiotrophoblast, cytotrophoblast, villi connective tissue, and fetal capillary endothelium

functions of the placenta

• Metabolism: synthesizes glycogen, cholesterol, fatty acids; provides nutrients and energy

• Transport: O2, CO2, and CO, water, vitamins, electrolytes, maternal antibodies (helps develop an immune system), waste products, drugs and their metabolites, infectious agents 

• Endocrine (production of hormones): produces hormones that keep the pregnancy going and prepare the body for labor, delivery, and breastfeeding

  • HCG produced in first 2 months to maintain corpus luteum, excreted in mom’s urine

  • Somatomammotropin (placental lactogen) gives fetus priority on maternal glucose and stimulates mammary development

  • Progesterone after 4 months

  • Estrogenic hormones (primarily estriol) steadily increase

Placenta previa

placenta overlies the internal cervical os of uterus, essentially covering the birth canal, usually occurs during 2nd or 3rd trimester

Placenta accreta

deep attachment of placenta to myometrium (middle, muscular layer of uterine wall

Can invade previous c-section scar, can cause dangerous bleeding, patients monitored for need for hysterectomy because placenta can’t be surgically removed

Placental abruption

partial or complete separation of placenta prior to delivery, lots of bleeding for patient and lack of oxygen for baby

components of umbilical cord

• umbilical vessels (2 arteries, 1 vein), Wharton’s jelly

  • Arteries carry deoxygenated blood and waste to placenta

  • Presence of only a single umbilical artery can be associated with chromosomal and fetal abnormalities

    • More common in multiple gestations

    • 20-25% will have other anomalies, 25% will have IUGR, and 50% will have LBW

    • If isolated, aneuploidy risk is low

  • Vein carries oxygenated blood to embryo 

  • Wharton’s jelly is a protective tissue rich with proteoglycans

• At 6wks, intestinal loops are pushed into umbilical cord and they return by 12 wks

formation of bones of skull and face

Mesenchyme from neural crest cells and mesoderm undergo membranous ossification

Results in a number of flat, membranous bones characterized by the presence of bone spicules

parts of skull

• neurocranium and viscerocranium

  • Neurocranium: forms protective case around brain

    • Divided into 2 parts: membranous part consisting of the flat bones which surround the brain (derived from neural crest cells and paraxial mesoderm) and cartilaginous part, or chondrocranium, which forms bones at the base of the skull

    • Chondrocranium forms much of the internal structure of the skull

  • Viscerocranium: forms the skeleton of the face

    • Formed primarily from the first two pharyngeal arches

    • The first arch gives rise to the maxillary process/mandible

    • The 1st and 2nd arches give rise to the incus, malleus and the stapes- the first bones to become fully ossified in the 4th month of fetal life (smallest bones in ear)

    • Newborn face looks small compared to calvarium (absence of paranasal air sinuses, small jaw bone, underdevelopment of facial bones)

sutures

narrow seams of connective tissue that separate the flat bones of the skull at birth

fontanelles

At points where two bones meet, where are sutures are wide

Anterior fontanelle is soft spot on baby’s head

molding

Sutures and fontanelles allow the bones of the skull to overlap during birth

why is head circumference important?

One of the most important measures on physical examination is head circumference (HC), because HC correlates with brain size and growth of the infant

three and nine rule for head circumference

a newborn has a HC of 35 cm

a 3-month-old has a HC of 40 cm

a 9-month-old has a HC of 45 cm

a 3-year-old has a HC of 50 cm

a 9-year-old has a HC of 55

Craniosynostosis

term for when sutures of flat bones come together prematurely

1 in 2,500 live births

Over 100 genetic syndromes

Premature closure of one of more sutures

More common in males

Often associated with other skeletal anomalies