Pregnancy DiagnosisPregnancy Diagnosis

Obstetrics and Gynecology Hospital of FudanUniversityXing Chen, MD.Email: xing_chen2003@hotmail.com

For a woman with regular menstrual cycles, a history of one or more missed periods following a time of sexual activity without effective contraception strongly suggests early pregnancy

Associated Symptoms

Fatigue

Nausea/vomiting

Breast tenderness

physical examination

softening and enlargement of the pregnant uteruscongestion and a bluish discoloration of the vagina (Chadwick sign)

softening of the cervix (Hegar sign)

Increased pigmentation of the skinappearance of circumlinear striae on the abdominal wall (striae gravidarum )

Palpation of fetal parts

appreciation of fetal movement and fetal heart tones

Pregnancy testhuman chorionic gonadotropin (hCG): α/β-subunitproduced in the syncytiotrophoblast

Urineapproximately 4 weeks following the first day of the last menstrual period

All urine pregnancy tests are best performed on early-morning urine specimens, which contain the highest concentration of hCG

Serumspecific and sensitive

by following serial quantitative hCG levels and comparing them to the expected rise derived from normative data for proven normal intrauterine pregnancies

Ultrasound examination

Abdominal ultrasound allowing visualization of a normal pregnancy gestational sac 5 to 6 weeks after the beginning of the last normal menstrual period (corresponding to β-hCG concentrations of 5000 to 6000 mIU/mL)Transvaginal ultrasound often detects pregnancy at 3 to 4 weeks of gestation (corresponding to β-hCG concentrations of 1000 to 2000 mIU/mL)

Detection of fetal heart activity “fetal heart tones”

Acoustic fetoscope

beyond 18 to 20 weeks of gestational age

Electronic Doppler devices

approximately 12 weeks of gestation

Abnormal Pregnancy

Spontaneous abortion

Ectopic pregnancy

Trophoblastic disease

Prenatal Diagnosis Prenatal Diagnosis

Prenatal diagnosisPrenatal diagnosisis the science of identifying is the science of identifying

structural or functional structural or functional abnormalities-birth defects-in abnormalities-birth defects-in

the fetusthe fetus

Etiology of Birth DefectsEtiology of Birth Defects

MalformationMalformation

DeformationDeformation

DisruptionDisruption

OtherOther

MalformationMalformation

an intrinsic abnormality "programmed" in dan intrinsic abnormality "programmed" in development, regardless of whether a precievelopment, regardless of whether a precise genetic etiology is knownse genetic etiology is known

spina bifidaspina bifida

DeformationDeformation

caused when a genetically normal fetus decaused when a genetically normal fetus develops abnormally because of mechanical velops abnormally because of mechanical forces imposed by the uterine environmentforces imposed by the uterine environment

normal limb that develops contractures benormal limb that develops contractures because of prolonged oligohydramnioscause of prolonged oligohydramnios

DisruptionDisruption

which is a more severe change in form or fwhich is a more severe change in form or function that occurs when genetically normunction that occurs when genetically normal tissue is modified as the result of a specal tissue is modified as the result of a specific insultific insult

an amnionic band causing a cephalocele oan amnionic band causing a cephalocele or limb-reduction abnormalityr limb-reduction abnormality

OtherOther

Syndrome: Syndrome: trisomy 18trisomy 18

Sequence: Sequence: oligohydramnios leading to puloligohydramnios leading to pulmonary hypoplasiamonary hypoplasia

AssociationAssociation: VATER (association of : VATER (association of vvertebertebral defects, anal ral defects, anal aatresia, tresia, ttracheoesophageracheoesophageal fistula with al fistula with eesophageal atresia, and sophageal atresia, and rradiadial dysplasia)al dysplasia)

Techniques

Non-invasive

Minimally invasive

Invasive

Non-invasive techniques

Ultrasound

Magnetic Resonance Imaging (MRI)

Minimally Invasive Techniques

Cell free fetal DNA (cffDNA)

Pre-implantation genetic diagnosis (PGD)

Invasive Techniques

Chorionic villus sampling (CVS)

Amniocentesis

Percutaneous umbilical blood sampling (cordocentesis)

Key Guidelines

All women contemplating any form of prenatal diagnosis should be adequately counselled about the risks, benefits and limitations of any test, and provided with non-directional written information

Screening test for Down's syndrome and ‘20 week’ scan for structural anomalies

Women at risk of having a baby with congenital heart disease should be offered an extra fetal echocardiogram at 21–24 weeks

The middle cerebral artery Doppler peak systolic velocity can be used as a non-invasive method for diagnosing of fetal anaemia

Key Guidelines

Serial ultrasound measurements are of undoubted use in monitoring fetal growth but all formulae currently used to estimate fetal weight are inherently flawed and may give errors up to ±14%

MRI is a useful adjunct to ultrasound in prenatal diagnosis especially in the diagnosis of intra-cranial, intra-thoracic and gastrointestinal anomalies

Key Guidelines

Cell free fetal DNA testing has become widely established for the management of Rhesus disease and certain sex linked genetic disorders. With further research it is poised to offer much greater benefits in the field of minimally invasive prenatal diagnosis

Pre-implantation genetic diagnosis provides the opportunity for parents to avoid the distress of invasive testing and possible termination. However, the ethical and legal debate is set to continue for many years

Key Guidelines

CVS should not be performed before 10 weeks of gestation as it has been associated with limb reduction abnormalities. It appears to be safer if it is performed transabdominally rather than transcervically

Amniocentesis should not be performed at less than 15 weeks of gestation as before this it is associated with greater risk of pregnancy loss and possible talipes in the fetus

Key Guidelines

In experienced hands CVS and amniocentesis both carry a similar procedure related risk of miscarriage of 0.5–1%

Percutaneous umbilical blood sampling is now limited to potentially lifesaving in utero transfusion procedures for severe fetal anaemia

Neural-Tube Defects (NTDs)Neural-Tube Defects (NTDs)

anencephalyanencephaly, , spina bifidaspina bifida, , cephalocelcephalocele, ane, and other rare spinal fusion (d other rare spinal fusion (schisisschisis) abnorm) abnormalitiesalities

had higher levels of alpha-fetoprotein (had higher levels of alpha-fetoprotein (AFAFPP) in maternal serum and amnionic fluid) in maternal serum and amnionic fluid

Maternal Serum AFP ScreeningMaternal Serum AFP Screening

influence factors: maternal weight, gestational age, diabetes, multifetal gestation

Evaluation of Maternal Serum AFP ElevationEvaluation of Maternal Serum AFP Elevation

genetic counselinggenetic counseling

diagnostic testdiagnostic test Specialized SonographySpecialized Sonography amniocentesisamniocentesis

Specialized SonographySpecialized Sonography

Transverse and sagittal images of the spinTransverse and sagittal images of the spine are increasingly used to characterize the e are increasingly used to characterize the size and location of spinal defectssize and location of spinal defects

AmniocentesisAmniocentesis

amnionic fluid AFP levelamnionic fluid AFP level

assay for acetylcholinesteraseassay for acetylcholinesterase

Down Syndrome Down Syndrome

trisomy 18, 21trisomy 18, 21

First/second trimester: Sonography and mFirst/second trimester: Sonography and maternal serum markersaternal serum markers

Second-Trimester ScreeningSecond-Trimester Screening

At 15 to 20 weeksAt 15 to 20 weeks

Triple test: Triple test: MSAFP (maternal serum alpha-fetoprotein )MSAFP (maternal serum alpha-fetoprotein ) hCG or freehCG or freeββ-hCG-hCG uE3 (unconjugated estriol )uE3 (unconjugated estriol )

Quadruple (Quad) test: Quadruple (Quad) test:

+ inh (dimeric inhibin alpha)+ inh (dimeric inhibin alpha)

First-Trimester ScreeningFirst-Trimester Screening

between 11 and 14 weeksbetween 11 and 14 weeks

maternal serum analyte screening: maternal serum analyte screening: hCG (or free hCG (or free ββ--hCG) hCG) pregnancy-associated plasma protein A (PAPP-A) pregnancy-associated plasma protein A (PAPP-A)

sonographic: nuchal translucency (NT)sonographic: nuchal translucency (NT)

combination of bothcombination of both

Be aware…Be aware…

gestational age affects the accuracygestational age affects the accuracy

less sensitive in younger womenless sensitive in younger women

Be aware…Be aware…

strong association between increasing nucstrong association between increasing nuchal translucency and fetal cardiac anomalihal translucency and fetal cardiac anomalieses

nuchal translucency measurement is 3.5 nuchal translucency measurement is 3.5 mm or greater with a normal fetal karyotypmm or greater with a normal fetal karyotype, then targeted sonographic examination, e, then targeted sonographic examination, fetal echocardiography, or both should be fetal echocardiography, or both should be consideredconsidered

Sonographic Screening for AneuploidySonographic Screening for Aneuploidy

Major Structural DefectsMajor Structural Defects

"Soft Signs" "Soft Signs"

Diagnostic TechniquesDiagnostic Techniques

Second-Trimester AmniocentesisSecond-Trimester Amniocentesis between 15 and 20 weeksbetween 15 and 20 weeks

Early AmniocentesisEarly Amniocentesis between 11 and 14 weeksbetween 11 and 14 weeks

Chorionic Villus Sampling (CVS)Chorionic Villus Sampling (CVS) at 10 to 13 weeksat 10 to 13 weeks

Fetal Blood SamplingFetal Blood Sampling percutaneous umbilical blood sampling (PUBS) or cordopercutaneous umbilical blood sampling (PUBS) or cordo

centesiscentesis

Fetal Tissue BiopsyFetal Tissue BiopsyPreimplantation Genetic DiagnosisPreimplantation Genetic DiagnosisFetal Cells in the Maternal CirculationFetal Cells in the Maternal Circulation

Fetal Therapy Fetal Therapy -to improve the intrauterine environment-to improve the intrauterine environment

blood product transfusionblood product transfusion

administration of medication transplacentaladministration of medication transplacentally or via the fetal circulationly or via the fetal circulation

laser or radiofrequency ablation of vasculalaser or radiofrequency ablation of vascular anastomosesr anastomoses

amnioreductionamnioreduction

shunt placementshunt placement

fetal surgeryfetal surgery

ReferenceReference

Obstetrics and Gynecology, 6th edition

Williams Obstetrics, 23rd edition

Prenatal diagnosis: Types and techniques. Early Human Development. 2012 (88) :3–8