Dg. methods in obstetrics

MUDr. Robin Malina Ph.D.

Introduction

Initial Prenatal Assessment

• 3 groups

• Low risk• Mid risk• High risk

ETIOLOGY OF BIRTH DEFECTS

Birth defects can arise in at least three ways.

1. The most commontype of structural fetal abnormality is a malformation—an intrinsicabnormality “programmed” in development, regardless of whether a precise genetic etiology is known.2. The second type is a deformation caused when a genetically normal fetus develops abnormally because of mechanical forces imposed by the uterine environment. An example is an otherwise normal limb that develops contractures because of prolonged oligohydramnios.3. The third type is a disruption, which is a more severe change in form or function that occurs when genetically normal tissue is modified as the result of a specific insult. An example is damage from an amnionic band causinga cephalocele or limb-reduction abnormality.

Prenatal Screening Exam

• History• Physical exam

– Complete exam with pelvimetry

• Initial Screening Labs:– ABO & antibody screen, Hgb/Hct- blood cell count, PAP

smear, RPR, GC/Chlamydia, Urine screen, Hep B, HIV, colposcopy

Issue Mother’s book

16th week

• ABO & antibody screen, Hgb/Hct- blood cell count, PAP smear, RPR, GC/Chlamydia, Urine screen, Hep B, HIV, if not done

• Triple test • Serum marker screening (Maternal serumalphafetoprotein, human chorionic gonadotropin, and estriol)

• Ultrasound

Initial Prenatal Assessment

• Purpose: – To perform a baseline assessment of risk factors

for pregnancy complications– To establish care plan with referral as needed– To treat any identified disease conditions– Provide patient education

18-20th week

Ultrasound screening

24-28 week

• Glucose tolerance test diagnostic– 75 gram glucose load with fasting, 1 hr, 2 hr serum glucose

For woman over 25 and woman with risk factors

30-32 week

2nd Ultrasound screeningABO - antibody screen for woman O/Rh-, Hgb/Hct- blood cell count, Hep B, HIV, N. Gonorrhea if not done or for risk groups

36-37 week

Group B Streptococcus must be cultured

36-40 weeks

Nonstress testing 36, 37 weeks recommended 38-40 once a week

40-until delivery /postterm preg./ 2x week, + Flowmetry /RI, PI/ recommended

Routine Prenatal Care

Every visit

Anam. Data- swellingsWeightBlood PresureUrinalysis- Urine DipstickBimanual vaginal exam – cervix scoreAfter 24 week detection of viability

Prenatal Care – Introduction

• Prenatal care focuses on prevention

• Majority of pregnant gravidas will deliverwithout major complications

• Goal of prenatal care is to select gravidas atrisk for development of major complicationsand early prevention/intervention in order toaffect improved outcome

Gestational Age

• Outcome in pregnancy is gestational age dependant

• Calculation of gestational age is made using a varietyof methods:

– Patient history– Initial pelvic exam/biochemical test of pregnancy– Fetal heart auscultation (10-11 or 18-19 weeks)– Quickening (16-20 weeks)– Serial fundal height measurement (at umbilicus - 20 weeks)– Ultrasound estimation of gestational age

• Dating (U.S.) best based upon MENSTRUALDATING (Last normal menstrual period to estimateddate of confinement 40 7-day weeks)

Ultrasound Dating

• Ultrasound dating less accurate as gestational ageAdvances

• Early pregnancy - Crown Rump Length (CRL): CRL+ 6.5 approximates gestational age (+7 days)

• Mid pregnancy (12-28 weeks) - correlation betweenultrasound and menstrual dating is +10-14 days

• In late pregnancy, ultrasound accuracy as singleestimate of gestational age is not great (+21 days)

Physical Exam - Fundal Height

• Fundal Height evaluation is reasonable estimate ofgestational age

• After 20 weeks gestation:– Gestational age in menstrual weeks roughly equivalent tocentimeters from superior aspect of symphysis pubis tofundal portion of uterus

– Inter-observer differences exist– Circumstances may alter measurement:• Multiple gestation• Oligohydramnios/Polyhydramnios• Uterine pathology

Fetal Movement Testing

• Fetal movement positively associated with fetal wellbeingand negatively associated with intrauterine fetalDemise

• Average fetal movement varies with gestational age

• Maternal perception of fetal movement varies– In late pregnancy force of fetal movement is less thanearlier in gestation– Quickening first felt at 16-20 weeks

Laboratory Tests - Prenatal Care

• Hemoglobin/Hematocrit

• Urinalysis/Urine Culture/Urine Dipstick

• Glucose testing

• Blood Type/Rh

• Serologic test for Syphilis

• N. Gonorrhea/Chlamydia

• Other tests

Hemoglobin/Hematocrit (H/H)

• Normally red-cell mass increases in pregnancy andplasma volume increases (even more)

• Result of expansion is a measured decrease inhemoglobin/hematocrit - nadir of H/H at approx 28Weeks

• In U.S., H/H tested early in pregnancy, at 28 weeksand at or near term

• Anemia can be a screen for:– Maternal disease– Hemoglobinopathy– Anemia (Iron deficiency; Folate; B12)

Urinalysis/Culture/Dipstick

• In U.S., urinalysis and dipstick generally done atintake (culture optional)• Dipstick for Proteinuria– Done each visit– If +, may indicate renal disease, preeclampsia, or infection• Dipstick for glucose - not reliable association with serum glucose• Cystitis and Pyelonephritis much more common in pregnancy - use low threshold for diagnosis

Blood Type/RH

• In U.S., Rh-negative blood is approximately10%-20%

• Typing done in case blood later needed

• Indirect antibody testing for antibodies to redcell antigens performed

• If fetus is at risk for disease, level ofmonitoring is increased

Infectious Disease Testing• In U.S., Gonorrhea, Syphilis, and Chlamydial cervical cultures obtained

• In U.S., most areas screen for HIV

– Immunoprophylaxis in labor and treatment antepartumlowers perinatal transmission

• Group B Streptococcus may be cultured or empirically treated in 36-37 weeks

Glucose Testing

• Gestational diabetes incidence is approximately5% of pregnant population

• Diabetes screen (24-28 weeks gestation)

• Glucose tolerance test diagnostic– 75 gram glucose load with fasting, 1 hr, 2 hr serum glucose

• Macrosomia is risk factor

Visit Interval - Pregnancy(Uncomplicated Patient)• Conception until 36 weeks gestational age - Every 4 weeks

• 36-40 weeks gestation - Every week

• High risk pregnancy may alter visit intervals

• Preterm labor risk may alter pelvic exam interval

• Post dates pregnancy - (Nonstress testing) - Twice a week

Other Testing

• Serum marker screening (Maternal serumalphafetoprotein, human chorionic gonadotropin, andestriol) usually offered to patients 16 weeks

• Patients at risk for fetal aneuploidy may receiveinvasive prenatal diagnosis (such as amniocentesis)

• In U.S., prenatal Rubella immunity testing performed

Triple test – 2nd Trimester serum

• AFP• Total hCG• Unconjugated estriol

uE3

Quad Screen (TMS/Quad = multiple marker scrg test, maternal serum screen)

Triple marker screen (TMS)

Inhibin AInhibin A

Down Syndrome (Trisomy 21)

• 1/800 Live births• Risk increases with

advancing maternal age• Lab findings

– Elevated hCG + INH-A– Lower than average levels of

MSAFP and unconjugated estriol

Edward’s Syndrome (Trisomy 18)

• 1/5000 live births• High rate of fetal and

neonatal death• Lab findings:

– Lower than average levels of all three markers

Open Neural Tube Defect

• 7-15/10,000 live births• Adequate folic acid

reduces incidence• Lab findings:

– Elevated MSAFP

What has evolved in the first trimester?(11-14 weeks)

• Nuchal Translucency (NT)• Serum biochemistry• Nasal Bone (NB)

• Tricuspid regurgitation (TR)• Frontomaxillary facial angle (FMF Angle)

The First Trimester - NT• US measurement, 11-14w:

spine to skin • Fetal Medicine Foundation • Aneuploidy - a change in

extracellular matrix and potential for cardiac/lymphatic changes causing increased NT

• Congenital hearts, others

Symptoms to Evaluate During Pregnancy

• Bleeding• Decreased fetal movement• Swelling• Headache• Visual disturbance• Contractions• Leakage of fluid

Swelling (Edema)

• Edema is relatively common in pregnancy (80%+ inwarm climates or high salt consumption)

• Pathologic edema may be associated withpreeclampsia:

– >4 lb weight gain in one week– Sudden swelling of hands or face– Presence of other symptoms associated with preeclampsia

Decreased Fetal Movement• Decreased fetal movement may be lack of maternalperception of fetal movement• Intrauterine fetal compromise may be preceded bydecreased fetal movement• Probably a wise idea to address maternal perceptionof decreased fetal movement

Headache/Visual Disturbance• Headache and visual disturbance (double vision, photophobia, etc.) may be:– Preeclampsia– Migraine/Cluster headache– Other neurological conditions– Isolated event• Careful history may elucidate “normal” causes from “abnormal causes”• Headache/visual disturbance with hypertension should be considered preeclampsia until proven otherwise

Leakage of Fluid (“ROM”)

• Pregnancy normally associated with increasedamount of vaginal discharge

• Warning signs for discharges:

– Watery discharge = possible ROM– Green discharge = possible meconium– Itching discharge = possible vaginitis– Bloody discharge = cervicitis or serious causes ofvaginal bleeding

Leakage of Fluid (“ROM”)(2)

• If ruptured membranes suspected, exam can evaluate:

-Temesvary exam

– pH: Amniotic fluid typically with alkaline pH(>7.0)– Pooling or direct leakage: Fluid will directly leakout of cervix during Valsalva

Leakage of Fluid (“ROM”)(3)

• Prolonged rupture of amniotic membranes (>24hours) associated with increase in intrauterineInfection

• Preterm rupture of amniotic membranes associatedwith preterm labor and infection

• Term ROM associated with spontaneous labor in over90% of patients

Contractions

• Uterine contractions occur throughout pregnancy(4/hour in early third trimester)

• Frequency of contractions increases just prior to theonset of perceived labor

• Persistent contractions of closer than 15 minutesapart that do not resolve with simple bedrest or fluidsneed some sort of evaluation

• Cystitis often associated with uterine irritability

• Multiple pregnancy and polyhydramnios alsoassociated with irritability

Weight Gain in Pregnancy

• At term, approximate weight of blood volumeexpansion, fetus, uterus, and edema generally equalsapproximately 7 kg• Weight gain of 200-500 gm per week is advocated• Many suggest an additional weight at term to accountfor breast feeding fat reserve - total of approximately10 kg recommended• Excessive weight gain over 20-25 kg may increase riskof gestational diabetes and other complications

Blood Pressure• Blood pressure normally decreases to a nadir at midpregnancy

• Blood pressure then rises to early pregnancy levels by term

• Blood pressure should be taken in the right or left arm while the subject is sitting

The AntenatalDiagnosis

of Birth Defects

• Major congenital abnormality 1/50• Single gene disorder 1/100• Major chromosome disorder 1/200• SAB in 1st trimester 1/8• Stillborn (in North America) 1/125• Perinatal death 1/150

(Adapted from Emery and Rimoin, Principles and Practice of Medical Genetics, 2nd ed., 1990)

Pregnancy: Risk forAbnormal Outcome

• Must demonstrate abnormality in fetus and/or fetal tissues

• Disease is associated with abnormality-- Structural-- Chromosomal-- Molecular-- Biochemical

• Technology available for diagnosis• Sampling techniques are safe• Tests have high degree of sensitivity and

specificity

Genetic DiseasesCriteria for Diagnosis

• Cytogenetic• Biochemical• Molecular: DNA

-- Direct-- Indirect

Genetic AnalysisTechniques

• Chorionic villus sampling (CVS)• Amniocentesis• Percutaneous umbilical cord blood

sampling (PUBS)• Fetoscopy – fetal tissue biopsy• Ultrasound• Pre-implantation diagnosis• Fetal cell sorting in maternal blood

Prenatal Diagnosis Techniques

• Maternal serum screening -- 1st Trimester -- 2nd Trimester• Fetal cell sorting from maternal

serum• Preimplantation diagnosis

Prenatal DiagnosisOther Techniques

• Maternal age 35• Previous child with chromosome abnormalities• Parent with chromosome abnormality• Family history of chromosome abnormality• X-linked disorders• Metabolic disorders• Neural tube defect risk• Positive prenatal screening test• Fetal anomaly suspected/diagnosed on ultrasound

Indications for Prenatal Diagnosis

Amniocentesis

12 weeks 14 weeks 16 weeks

40 ml 100 ml 185 ml

• Fetal Loss0.5%

• Failed Amino.1.0%

• Culture Failure 0.5%

Problems

1. Large National Experience2. Lab Techniques Standardized3. Readily Available4. Very Safe5. Very Accurate

Advantages of Mid-Trimester Amniocentesis

Chorionic Villus Sampling

• Fetal loss ~1%• Unsuccessful CVS 1 – 5% (Depends on

operator experience and accessibility of placenta)

• Ambiguous results/maternal cell contamination ~1-2%

• Culture failure 1-2%

CVS - Complications

• Experience of operator• Number of attempts• Time of sampling• Manipulation required• Route of CVS

Who Report 1991

Factors Affecting Rate ofFetal Loss Following CVS

PercutaneousUmbilical Cord Blood

Sampling (PUBS)

• Applications-- Diagnosis-- Therapy

• Complications-- Fetal loss ~1%

Percutaneous Umbilical Cord Blood Sampling (PUBS)

• Rarely used• Fetal tissue biopsy (skin and

muscle)

Fetoscopy

Ultrasound

• Operator skill and experiences• Technical difficulties

-- twins/maternal obesity/fetal lie• Gestational age

-- 4 chamber heart visualization* < 10% in fetus under 18 weeks* > 82% in fetuses greater than 18

weeks• Type of anomaly and appearance in fetal

development

Ultrasound - FactorsInfluencing Detection

This procedure is designed to allow the fetus/infant to remain perfused by the placental circulation after being partially delivered so that life-saving treatment can be performed prior to complete delivery. EXIT procedures have been performed for more than 15 years. As reviewed by Hirose and colleagues(2004), EXIT was initially used to treat airway obstruction after

fetal surgery—FETO.