FOCUSED APPROACH TO ANTENATAL CARE

FIRST TRIMESTER SCREENING

DR BHARTI GAHTORI

12WKS FETOMATERNAL WELLBEING CLINIC

WHAT DEFINES A GOOD ANTENATAL CARE 1) It should be focused and individualised - Each patient has its own risk factors and history, which need to be divulged with utmost patience and precision.2) It should aim at screening for conditions which are

treatable, conditions which need constant vigilance &surveillance and conditions which needs urgent management.3) We as obstetricians should be educated as well as updated with the new advances in detection, counselling and management of conditions complicating maternal as well as fetal outcome.4) We should be aware of our expertise and limits and very prompt in counselling and referring patients without delay when in a fix .5) We should not be hesitant but interactive and close knit to share and discuss our professional queries for the benefit of our patients.

THE ESSENTIAL ELEMENTS OF A FOCUSED APPROACH TO ANTENATAL CARE IN OUR SETUPS

Targeted assessment based on woman’s individual health situations to ensure normal progress of the pregnancy which includes antepartum-intrapartum-postpartum and postnatal period To facilitate the early detection of and special care of complications , chronic conditions and other potential problems that can affect the mother.

By incorporating new investigations, screening methods – routine & special , diagnostic modalities and management options for early detection, counselling and treatment of the affected mother and the fetus Identification and surveillance of fetal conditions like aneuploidy, malformations, infections , metabolic and haematological conditions etc as early as possible by utilizing all the available modalities and plan its management according to its severity and treatability

DEFINE SCREENINGScreening is a process of identifying apparently healthy people who may be at increased risk of a disease or condition. Screening allows high-risk individuals to be selected out of a population at low risk for a given complication. They can then be offered information, further diagnostic tests and appropriate treatment to reduce their risk and/or any complications arising from the disease or condition.SENSITIVITY : ABILITY TO DETECT

INDIVIDUALS WITH THE PRESENCE OF TARGET CONDITION.

SPECIFICITY : ABILITY TO DETECT INDIVIDUALS WHO ARE COMPLETELY DISEASE FREE.

FALSE POSITIVE :INDIVIDUALS NOT WITH THE DISEASE BUT DETECTED WITH IT. LEAST THE FP MORE THE TEST SENSITIVE

FALSE NEGATIVE : INDIVIDUALS WHO HAVE THE DISEASE BUT DETECTED FREE OF IT. LEAST THE FALSE NEGATIVE MORE THE TEST SPECIFIC

DIAGNOSTIC TEST SCREENING TEST

IDEAL SCREENING TEST

TYPES OF SCREENING IN FIRST TRIMESTER

1) AGE : < 18 > 35 2)ETHNICITY : *Sickle cell anemia- African, African American, or Mediterranean heritage *Tay-Sachs disease, Ashkenazi (eastern and central European) Jewish or French Canadian ancestry * Cystic fibrosis : Caucasians * Pregestational/ gestational diabetes : Asian , Hispanics * Hemoglobinopathies : South east Asians *Alpha & beta Thalassemia : Indian subcontinent *Small nasal bone : Africans3)OCCUPATION ( COUPLE) : For viral diseases like HIV , HBsAg , and CMV & other STD

PTO

RISK FACTOR SCREENINGBIODATA :

HISTORY OF PRESENT ILLNESS H/o Fever with rash + LAP / other Infections(UTI, STI etc) H/o Excessive Nausea /vomitingH/o Pain lower abdomen ± Bleeding P/V H/o Exposure to X-Ray/CT scan/Intake of medical abortifacient H/o Intake of folic acid /Current medications /Pre-pregnancy medication / vaccination

MENSTRUAL AND GYNECOLOGICAL HISTORY H/o regular / irregular cyclesH/o spontaneous conception/ ARTH/o Gynecological surgeries e.g myomectomy , septal resection , repeated D&CH/o vaginal infection, warts etc

LMP by ( DATES/ UPT/ ART/ USG )

OBSTETRICAL HISTORY G P A L Pregnancy history -antepartum , intrapartum and postpartum (associated illness and any complications)H/o abortion , ectopic, IUD , stillbirth , neonatal death, HYDROPSMode of delivery( no. of LSCS & its complications )PERSONAL AND FAMILY HISTORY

FAMILY H/O: T.B/ D.M/ H.T/ Multiple Pregnancy/ Familial cancer/ Birth defects/ genetic disorders / hemoglobinopathies & others .

PERSONAL H/O :Addictions / Pica /worms in stools /Depression /anxiety /Drug Allergy

PAST MEDICAL , MEDICATION & SURGICAL HISTORY

ANEUPLOIDY /GENETIC SCREENING Age > 35 at EDB H/oKnown teratogen exposure e.g Teratogenic drugs,( antiepileptics, isotretinion , ACE inhibitors, radiations including Xrays/CTscan/ radiotherapy

H/o High grade fever with rash , nonimmune to Rubella

H/o intake of abortifacient

H/o Exposure to medical conditions including maternal diabetes , Epilepsy, severe thyroid ds , autoimmune ds.

H/o consanguinity H/o termination of pregnancy for fetal abnormality H/o previous child born with major congenital defect H/o baby is mentally challenged /hearing disability/ delayedH/o bleeding disorder in the babyH/o any genetic disease in the family

RISK FACTORS FOR PET/IUGR/GDM/ THYROID DIS /PRETERM DELIVERY

Previous pregnancies:H/o recurrent spontaneous miscarriages(< >12wks) without a known cause .H/o unexplained IUD/ still birth/neonatal death. H/o PIH/Thyroid dis/GDM/other illness in previous pregnancy.

H/o Any complication of pregnancy related disease /chronic disease .H/o Previous baby with SGA/IUGR/LGA(>3.5kg)

IF Rh negative :* H/o anti D for all pregnancies .* H/o early/severe jaundice in baby, s/s of isoimmunisation irrespective of Anti-D in the past , hydrops or IUD fetus .

EXAMINATION :

Weight - BMI (BMI is your weight (in kilograms) over your height squared (in meters) 18 < > 30Blood pressure : correct method Mean arterial pressure : Pulse rate :Chest /CVSPallor , icterus , cyanosis , pedal edema , etc

MATERNAL SCREENINGROUTINE : At booking *Blood group , Rh typing ( If Positive then HBG )*Hb , Hct , CBC, platelets ( repeat at 28 weeks)*Infection : VDRL , HIV , HBsAg , Rubella titre *Urine routine and culture sensitivity*Random Blood sugar

ADDITIONAL : depends on prevalence*TSH * Gonorrhae/ chlamydia*HCV * Pap smear*Hb Electrophoresis ( thalassemia ) *GTT ( 75 gm glucose load with Fasting, Ist hr , 2nd hr)*BMI >30 Kg/m2*Previous baby ≥4.5 Kg *Previous h/o gestational diabetes*Family history of diabetes*Black, South Asian, M Eastern

FPG ≥ 92 mg% but < 126 mg% at first visit; 2 hr post-glucose load level ≥ 140 mg% < 200mg%If one of the following is abnormal at 24-28 weeks:Fasting ≥ 92 mg% 1 hour ≥ 180 mg% 2 hours ≥ 153 mg%

• Cardiac disease • Hypertension • Renal disease • Endocrine disorder or diabetes requiring insulin • Psychiatric disorder (on medication) • Haematological disorder, including thromboembolic disease • Autoimmune diseases such as antiphospholipid syndrome • Epilepsy requiring anticonvulsant drugs • Severe asthma • Drug use such as heroin, cocaine (including crack cocaine) and ecstasy • HIV or hepatitis B virus infection /cholestasis • Obesity (BMI of 30 or more at first contact) or underweight (BMI less than 18 at first contact)

Conditions in pregnant women increasing their risks, with obstetric and/or medical care indicated:

• Recurrent miscarriage (three or more consecutivepregnancy losses) or a mid - trimester loss • Severe pre - eclampsia, HELLP syndrome or eclampsia • Rhesus isoimmunization or other signifi cant blood groupantibodies • Uterine surgery including caesarean section, myomectomy • Antenatal or postpartum haemorrhage on two occasions • Retained placenta on two occasions • Puerperal psychosis • Grand multiparity (more than six pregnancies) • A stillbirth or neonatal death • A small for gestational age infant ( <5th centile) • A large for gestational age infant ( >95th centile) • A baby weighing < 2500 g or > 4500 g • A baby with a congenital anomaly (structural or chromosomal)

Women who have experienced any of the following inprevious pregnancies

PRENATAL SCREENING: Is testing for diseases or conditions in a fetus or embryo before it is born.

MATERNAL SERUM MARKERS + 2D/3D ULTRASOUND + DOPPLER

1) Beta HCG / FREE Beta HCG2) PAPP-A

VIABILITY SCAN ( 6.5 WKS – 10 WKS)a. Confirmation of the presence of an intrauterine live pregnancyb. Evaluation of a suspected ectopic pregnancy/H mole / abortionc. Defining and evaluating the cause of vaginal bleeding & pelvic paind. Estimation of gestational (menstrual) age e) Diagnosis or evaluation of multiple gestationsf) Evaluation of maternal pelvic masses and/or uterine abnormalities

NUCHAL SCAN ( 11- 13.6 WKS)

BHARTI GAHTORI

TURNING THE PYRAMID OF PREGNANCY CARE

FIRST TRIMESTER SCREENING : TURNING THE SPECIALIST CARE PYRAMID UPSIDE DOWN

• FETAL MEDICINE ESTABLISED AS A NEW FIELD SPECIFICALLY WORKING IN CREATING PROTOCOLS ,NEWER METHODOLOGIES AND GENERATE SPECIALIST TRAINERS TO ASSESS NUCHAL TRANSLUCENCY & OTHER USG MARKERS FOR ANEUPLOIDY .

• FURTHER HELP BEING PROVIDED BY THE CONSTANT ADVANCEMENTS IN THE RESOLUTION & QUALITY OF ULTRASOUND MACHINES AND ADDITION OF NEW FINER SERUM MARKERS WITH BETTER SENSITIVITY AND SPECIFICITY

• AVAILABILITY OF SPECIALISED LABORATORIES WHICH PROVIDE ASSISTANCE EVEN IN SMALL CITIES WITH SPECIAL SOFTWARES GENERATED TO CALCULATE COMBINED RISK INCLUDING THE PRIORI RISK ALL WITH OTHER HIGH RISK, SERUM AND ULTRASOUND MARKER RISK AND THEREBY IMPROVE DETECTION RATE

COMPONENTS OF FIRST TRIMESTER SCREENING

1 ) SCREENING FOR ANEUPLOIDY /CHROMOSOMAL DEFECTS2) SCREENING FOR FETAL STRUCTURAL ANOMALY3) SCREENING FOR RISK OF EARLY PRECLAMPSIA & FGR4) MULTIFETAL GESTATION SCREENING FOR CHRIONICITY & PREDICTION OF RELATED COMPLICATIONS

7) SCREENING FOR PRETERM LABOUR

COMBINING :

ULTRASOUND 2D+ 3D

UT. A DOPPLER

PAPP-A

βHCG

5) DETECTION AND SCREENING FOR GENETIC DISORDERS6) DETECTION OF PREXISTING DM ,GDM AND THYROID DISORDERS

FETAL ANEUPLOIDY Fetal aneuploidy refers to the abnormal number of chromosomes, other than usual diploid complement of 46 chromosomes .

TRISOMY : Presence of single additional chromosome, known as trisomy, is an important cause of congenital malformations. The most common autosomal trisomies are Down syndrome ( Trisomy 21) , Edward’s syndrome ( trisomy 18) and Patau syndrome ( Trisomy 13).Trisomy 21 is the most common of them and one of the most important cause of congenital mental retardation, affecting approx. 1:800 to 1 :900 live births . Trisomy 18 & 13 are considered lethal malformation with 95% trisomy 18 infants dying with in 1 yr of age and trisomy 13 infants dying within 3 mths of age. Incidence of trisomy 18 ~ 1:3000 live births Incidence of trisomy 13 ~ 1:5000 live births

Antenatal sonographic based screening is able to detect over 90% of

cases of trisomy 21, trisomy 18 and trisomy 13.

SCREENING FOR CHROMOSOMAL DEFECTS

Every time a test is carried out the a priori risk is multiplied by the likelihood ratio of the test to calculate a new risk, which then becomes the a priori risk for the next test.

Every woman has a risk that her fetus/baby has a chromosomal defect .The background or A PRIORI RISK depends on maternal age and gestationThe individual patient-specific risk is calculated by multiplying the a priori risk with a series of likelihood ratios, which depend on the results of a series of ultrasound and serum markers used as screening tests in first trimester.The likelihood ratio for a given sonographic or biochemical measurement is calculated by dividing the percentage of chromosomally abnormal fetuses by the percentage of normal fetuses with that measurement.

ANEUPLOIDY SCREENING- MAIN COMPONENTS

• MATERNAL AGE

• NUCHAL TRANSLUCENCY

• FETAL HEART RATE

• SERUM BIOCHEMISTRY

• NEW ULTRASOUND MARKERS

MATERNAL AGEThe risk for trisomy 21: Increases with maternal age Decreases with gestational age

because about 30% of affected fetuses die between the 12th and 40th week of pregnancy

• The risk for trisomy 21 increases with maternal age but because there are a lot more women in the younger age group the majority of fetuses with trisomy 21 are in the women aged under 35 years

OTHER DEFECTS The risk for trisomies 18 and 13

increases with maternal age and decreases with gestation. The rate of fetal death between the 12th and 40th week is about 80%

Turner syndrome is unrelated to maternal age. The rate of fetal death between the 12th and 40th week is about 80%. The prevalence is about 1 in 1500 at 12 weeks and 1 in 4000 at 40 weeks

Triploidy is unrelated to maternal age. The prevalence at 12 weeks is about 1 in 2000 but it is highly lethal and is very rarely observed in live births

NUCHAL TRANSLUCENCY

Definition :Nuchal translucency (NT) is the sonographic appearance of a collection of fluid under the skin behind the fetal neck in the first trimester of pregnancy

The term translucency is used, irrespective of whether it is septated or not and whether it is confined to the neck or envelopes the whole fetus

The incidence of chromosomal and other abnormalities is related to the size, rather than the appearance of NT

During the second trimester, the translucency usually resolves and, in a few cases, it evolves into either nuchal edema or cystic hygromas with or without generalized hydrops

WHY ONLY BETWEEN 11WKS- 13.6 WKS The reasons for selecting 11 weeks as the earliest gestation

are:The physiological extra-abdominal herniation of bowel persists and cranial vault is not ossified till 11 weeks gestation.

Screening necessitates the availability of a diagnostic test and chorionic villous sampling before this gestation is associated with transverse limb reduction defects.

Finally, aside from NT measurement, the effectiveness of first trimester markers prior to 11 week’s gestation is likely reduced

• The reasons for selecting 13 weeks and 6 days as the upper limit are:

To provide women with affected fetuses the option of 1st rather than 2nd trimester termination• The incidence of abnormal accumulation of nuchal fluid in

chromosomally abnormal fetuses decreases after 13 weeks.• The success rate for taking a measurement decreases after

13 weeks because the fetus becomes vertical making it more difficult to obtain the appropriate image

The optimal gestational age for measurement of fetal NT is 11+0-13+6 weeks. The minimum fetal crown–rump length (CRL) should be 45 mm and the maximum 84 mm.

NUCHAL TRANSLUCENCY

Nuchal thickness increases with CRL in euploidThe median NT for euploid =2.0 mm For trisomy 21 =3.4 mmFor trisomy 18= 5.5 mmFor trisomy 13 =4.0 mm For turners Syn = 9.2 mm resp.The thicker the NT the worse foetal prognosis is. Pathological values of NT usually range between 1.8 - 2 MoM or a measure greater than 3 mm (regardless of the MoM) increases 30% risk of aneuploidy

The 99th centile is about 3.5 mm and does not change with CRL

In 75-80% of trisomy 21 fetuses the NT thickness is above the 95th centile of the normal range .

IF RAISED NT BUT NORMAL CHROMOSOMES ON DIAGNOSTIC TEST

Good chance of a healthy baby90% if NT < 4.5 mm80% if NT between 4.5 and 6.4 mm45% if NT > 6.5 mm

ADVICE : QUADRUPLE MARKER , TARGET SCANNING WITH GENETIC SONOGRAM IN 2ND TRIMESTER PLUS FETAL ECHO

-20-30% have adverse pregnancy outcome eg IUFD, PRETERM , LBW-Increased chances of other genetic syndrome not detectable by genetic testing , skeletal dysplasias , congenital heart disease and non immune hydrops .

FETAL HEART RATE

Measurement of fetal heart rate (FHR):*A transverse or longitudinal section of the heart is obtained. Pulsed wave Doppler is used to obtain 6-10 cardiac cycles during fetal quiescence*The FHR is calculated by the ultrasound machine software

In normal pregnancy, The FHR increases from about 110 bpm at 5 weeks of gestation to 170 bpm at 10 weeks and then gradually decreases to 150 bpm by 14 weeks

In trisomy 21 the FHR is mildly increased and is above the 95th centile in about 15% of casesIn trisomy 18 the FHR is mildly decreased and is below the 5th centile in about 15% of casesIn trisomy 13 the FHR is substantially increased and is above the 95th centile in 85% of casesInclusion of FHR brings a major improvement in the detection of trisomy 13 It is important in distinguishing between trisomy 18 and 13, which are otherwise similar in presenting with increased fetal NT and decreased maternal serum free β-hCG and PAPP-A

MATERNAL SERUM MARKERS IN FIRST TRIMESTER

*Dimeric glycoprotein hormone (α & ß subunits) secreted by the fertilised ovum and later by placental tissue.*Primary function is to maintain the corpus luteum, later produces Progesterone & Oestrogen to maintain early pregnancy*Maternal serum hCG maximal during first trimester, then declines during second trimester

Serum human chorionic gonadotrophin (hCG)

Overall, in Trisomy 21 ßhCG values are higher, those higher than 2.5 MoM indicating a possible pathology. In Trisomies 13 and 18, these values are generally low, with suspicious values being those below 0.4 MoM.

*It is a glycoprotein synthesized in chorionic villi of the placenta . This protein is a key regulator of insulin-like growth factor bioavailability essential for normal fetal development. It continues to increase during the pregnancy period and declines after delivery.

Pregnancy Associated Plasma Protein A (PAPP A)

*ALSO, pathological low level of PAPP-A if <0.5 MOM (normal = 1MOM) has been associated with other adverse fetal outcomes and thrombophilia and patients can be empirically started on LDA & LMW Heparin.

*It has become an important serum marker individually and in combination for detecting aneuploidies including all trisomies and other chromosomal defect. When PAPP-A is low ( < 0.4 MoM )the risk for Down syndrome is increased and when it is elevated, the risk is reduced.

<0.45 MoM (5th percentile)- 1 to 4% risk of pregnancy loss before 20 weeks- increased risk of intrauterine growth restriction, positive predictive value 14% - increased risk of preterm delivery before 34 weeks <0.29 MoM (1st percentile)- significantly increased risk of intrauterine growth restriction, with positive predictive values of24%

FREE ß-hCG & PAPP-A VALUES IN DOWN SYNDROME

In trisomy 21 pregnancies maternal serum free ß-Hcg ( ~2.5 MoM) is about twice as high and PAPP-A( ~ 0.4MoM) is reduced to about half compared to chromosomally normal pregnancies

90% detection of Tri 18 4.5% FPRIf both PAPP-A and B-hCG are very low MoM = Increased risk for tri 18, triploidy, fetal anomalies or perinatal complications

Performance of screening for trisomy 21 by maternal age and serum free ß-hCG and PAPP-A:Detection rate 65%False positive rate 5%

MATERNAL SERUM MARKERS

We know now that Trisomic pregnancies are associated with altered maternal serum concentrations of various feto-placental productsScreening in the first trimester by a combination of maternal age, fetal NT, FHR and serum free ß-hCG and PAPP-A identifies about 90% of trisomy 21 pregnancies for a false positive rate of 3%

Marker values in various aneuploidies

FACTORS AFFECTING THE SERUM MARKER VALUES

The measured concentration of free ß-hCG and PAPP-A is influenced by-* the machine and reagents used,* gestational age calculation* maternal weight* ethnicity * smoking status * method of conception

In the calculation of accurate patient-specific risks it is necessary to make adjustments in the measured free ß-hCG and PAPP-A. Each measured level is first converted to a multiple of the expected normal median (MoM) specific to a pregnancy of the same gestation, maternal weight, smoking status, ethnicity and method of conception

HOW TO GET BEST RESULTS FROM COMBINED SCREENING

A good way of achieving a high performance of screening for trisomy 21 and diagnosing major fetal defects by ultrasound is to carry out the blood test at 10 or 11 weeks and the ultrasound scan at 12 weeks

DIFFERENCES IN MAIN ANEUPLOIDIES

At 11-13 weeks the relative prevalence of trisomies 18 and 13 to trisomy 21 are about 1 to 2.5 and 1 to 7, respectively

All three trisomies are associated with increased maternal age, increased fetal NT and decreased maternal serum PAPP-AA beneficial consequence of first-trimester combined screening for trisomy 21 is the early diagnosis of trisomies 18 and 13.

At a false positive rate of 3% the detection rate of trisomy 21 is 90% and of trisomies 18 and 13 is about 75%

DIFFERENCES BETWEEN ALL TRISOMIES

There are differences between the three trisomies:

Fetal NT is higher in trisomies 18 and 13 than in trisomy 21

Serum PAPP-A is lower in trisomies 18 and 13 than in trisomy 21

Serum free ß-hCG in trisomy 21 is high whereas in trisomies 18 and 13 this is low

Fetal heart rate in trisomy 13, unlike trisomies 21 and 18, is high

DETECTION RATE OF VARIOUS MARKERS

INTERPRETATION OF MOM VALUES AND RISK OF ANEUPLOIDY

MoM (multiple of median) - result reported strictly as multiple of medianMoM’s vary with gestational age ,with assay method , with population testedMay need adjustment for:– weight – ethnic group – other conditions e.g. diabetes – twin pregnancies - ART

- In screening using maternal serum biochemical markers, the measured concentration of the markers is converted into a multiple of the median (MOM) of unaffected pregnancies at the same gestation. - The Gaussian distributions of log10 (MoM) in trisomy 21 and unaffected pregnancies are then derived, and the ratio of the heights of the distributions at a particular MoM, which is the likelihood ratio for trisomy 21. -It is used to modify the a priori maternal age-related risk to derive the patient-specific risk.

RISK ASSESSMENT - EXAMPLEMoMs that typically yield a high risk of Down’s are those where, in combination, the Free β HCG MoM is > 2.5 and the PAPP-A is < 0.4 HIGH RISK- Woman > 35 years of age, with a NT of > 2.0 mm, and Free β HCG -MoM >2.5 and PAPP-A -MoM < 0.4 LOW RISK – Women < 35 years of age, with a NT of < 2.0 mm, combined with a Free β HCG and PAPP-A MoM of 1.0. Further tests required at an overall risk of 1:150

Reference Values DOWN SYNDROMECalculated screen risks <1/230 are reported as screen negative.Risks > or =1/230 are reported as screen positive. TRISOMY 18Calculated screen risks <1/100 are reported as screen negative.Risks > or =1/100 are reported as screen positive. A numeric risk for trisomy 18 risk is provided with positive results on non-diabetic, non-twin pregnancies. An interpretive report will be provided.Interpretation Screen-Negative:A screen-negative result indicates that the calculated screen risk is below the established cutoff of 1/230 for Down syndrome and 1/100 for trisomy 18. A negative screen does not guarantee the absence of trisomy 18 or Down syndrome. Screen-negative results typically do not warrant further evaluation. Screen-Positive:When a Down syndrome risk cutoff of 1/230 is used for follow-up, the combination of maternal age, pregnancy-associated plasma protein A, human chorionic gonadotropin, and nuchal translucency has an overall detection rate of approximately 85% with a false-positive rate of 5% to 10%.

NEW ULTRASOUND MARKERS

NASAL BONE FACIAL ANGLE DUCTUS VENOSUS

TRICUSPID FLOW

ABERRANT RIGHT

SUBCLAVIAN ARTERY

? WHEN TO OPT FOR NEW USG MARKERSThere are two strategies for assessment of the new markers in screening for trisomy 21 with similar detection and false positive rates:• One, some, or all markers

are examined in all cases• The markers are examined

only in the subgroup of pregnancies with an intermediate-risk (between 1 in 51 and 1 in 1000) after combined fetal NT, FHR, free ß-hCG and PAPP-A screening, which constitutes only one sixth (15%) of the total population

NASAL BONE AND FACIAL ANGLE Done at the same plane as of CRL and NT• At 11-13 weeks the nasal bone is considered to be absent in

about:Euploid fetuses 1-3%Fetuses with trisomy 21 60%Fetuses with trisomy 18 50%Fetuses with trisomy 13 40%Baby of Black woman might have small or absent nasal bone• Assessment of the nasal bone & facial angle improves the

performance of combined screening increasing the detection rate from 90% to 94% and decreasing the false positive rate from 3% to 2.5%

NEEDS EXPERTISE AND SPECIAL TRAINING TO MASTER IT

DUCTUS VENOSUS FLOW

Blood flow in the ductus has a characteristic waveform with:High velocity during ventricular systole (S-wave) and diastole (D-wave)Forward flow during atrial contraction (a-wave)

Qualitative assessment of the ductus venosus blood flow is based on the appearance of the a-wave:Positive or absent (normal)Reversed (abnormal)

REVERSED A-WAVE FORMAt 11-13 weeks reversed a-wave is found in about

4% of fetusesReversed a-wave is more common if:The gestation is 11 than 13 weeksThe fetal nuchal translucency is highThe maternal serum PAPP-A is lowThe mother is Black

Reversed a-wave is associated with increased risk for:*Chromosomal abnormalities *Сardiac defects*Fetal deathHowever, in about 80% of cases with reversed a-wave the pregnancy outcome is normal High pulsatility index for veins and absent or reversed a-wave are observed in fetuses with aneuploidies, cardiac defects, growth restriction and either the recipient or donor fetus in twin-to-twin transfusion syndrome

Assessment of ductus venosus a-wave improves the performance of first-trimester combined screening:Detection rate 95%False positive rate 2.5%

TRICUSPID FLOW

Normal profile with no regurgitation during systole*Regurgitation during approximately half of systole and with a velocity more than 60 cm/s

Do not mistake for tricuspid regurgitation:*The jet produced by aortic or pulmonary arterial blood flow, which at this gestation can produce a maximum velocity of 50 cm/s*The short reverse ‘spike’ generated by closure of the valve cusp

TRICUSPID REGURGITATION

At 11-13 weeks tricuspid regurgitation is found in about:Euploid fetuses 1%Fetuses with trisomy 21 55%Fetuses with trisomy 18 30%Fetuses with trisomy 13 30%Tricuspid regurgitation is more common if:The gestation is 11 than 13 weeksThe fetal nuchal translucency is high

Assessment of the tricuspid flow improves the performance of combined screening increasing the detection rate from 90% to 95% and decreasing the false positive rate from 3% to 2.5%

DETECTING FETAL CARDIAC DEFECTS

The prevalence of major cardiac defects in euploid fetuses is about 4 in 1,000The risk for major cardiac defects is increased if the fetal NT is high.

-Increased if the ductus a-wave is reversed-Decreased if the ductus a-wave is normal

-Increased if there is tricuspid regurgitation-Decreased if tricuspid flow is normal-If there is tricuspid regurgitation examine the fetal heart for major defects

FETAL DEATH

The risk of miscarriage or fetal death between 11 weeks and delivery is about 2%The prevalence of reversed a-wave at 11-13 weeks is more than 10% in pregnancies resulting in fetal death and less than 4% in those resulting in live birth

The risk of fetal death is increased if:The ductus venosus a-wave is reversed*The maternal serum PAPP-A is low*The mother is Black*The mother is obeseIf the ductus venosus a-wave is reversed*Monitor fetal growth (scan at 20 and 28 wks)*Monitor uterine artery PI

SCREENING PERFORMANCE OF ALL MARKERS- ALONE OR COMBINED

PRENATAL DIAGNOSISPrenat Diagn 2011REVIEW ARTICLE

STEPWISE PROTOCOL FOR SCREENING

SCREENING BASED ON FINAL FT RISK

SCREENING FOR STRUCTURAL DEFECTS

MULTIFETAL GESTATION

CHORIONICITY : The accurate determination of chorionicity is fundamental for successful management of twin pregnanciesA distinct thickening of the dividing membrane (“lambda”or“twin peak” sign) represent dichorionic (DC) Thin, “T-shaped” insertion of the membrane into the placental surface is indicative of monochorionic placentation.

In monochorionic/diamniotic gestations, the risk of developing twin-to-twin transfusion syndrome (TTTS) later in pregnancy may be estimated by1) measuring the NT’s (the likelihood of TTTS increases with increasing difference in the NT measurements between the two fetuses)2)evaluating the ductus venosus with Doppler (presence of reversed a-wave increases the riskof TTTS)3) Assessing the vascular connection in placenta via dopplerFirst trimester ultrasound screening is the only best option to detect aneuploidy in multifetal gestation because serum markers are not valid.

Lambda sign

T sign

Triamniotic trichorionic

MULTIFETAL PREGNANCY-CHORIONICITY

PRETERM BIRTH SCREENING

Universal cervical length screening and vaginal progesterone prevents early preterm births, reduces neonatal morbidity and is cost saving: Doing nothing is no longer an option

RECENT STUDIES

CERVICAL LENGTH MEASUREMENT

Newer studies that proposed measuring the endocervical length avoiding the lower uterine segment (isthmic part) show more promising results for the prediction of preterm delivery.

Fig. 1a &1b: Transvaginal ultrasound pictures illustrating (1a) the cervico-isthmic complex and (1b) the measurement of the length of the endocervix (A to B) and the isthmus (C to D).

Inclusion of both low risk and high risk women:1) H/o spontaneous preterm birth in the past2) H/o recurrent mid-trimester pregnancy loss3) Multifetal gestation4) H/o cervical trauma

*The risk of spontaneous preterm birth is inversely related to the cervical length measured by transvaginal sonography 11-14 weeks gestation . In women with a short cervix (< 1.5 cm), sent to specialist care where repeat cervical length assessment done .* If again same finding then if the length was <1.5 cm, the

women were treated by cervical cerclage or vaginal progesterone( Gel with 90mg progesterone / 200mg pessary) administration. It was found progesterone reduces the risk of spontaneous early preterm delivery by about 45% . *However, progesterone and cerclage is not as effective in

women with cervical length of 10 mm or those with a length of 10–20 mm and funnelling seen.

WORK IS GOING ON REGARDING USE OF CERVICAL PESSARIES DURING PREGNANCY

SCREENING FOR RISK OF EARLY PRECLAMPSIA & FGR

INCLUDES : DETAILED HISTORY + PRESENCE OF HIGH RISK FACTORS IF ANY WITH -MEAN ARTERIAL PRESSURE + PAPP-A + UTERINE ART DOPPLER PI• Retrospective analysis of 1,658 singleton pregnancies at CRL

of 45 to 84mm with outcomes• Uterine artery – mean PI and lowest PI were plotted and the

95th centile for each were calculated• Mean PI : 95th centile: 2.51

Lowest PI : 95th centile: 2.29 (ACFM data)

MEASURING MEAN ARTERIAL PRESSUREMETHODOLOGY :The BP was taken by automated devices (3BTO-A2, Microlife),which were calibrated before and at regular intervals during thestudy. The recordings were made by doctors who had receivedappropriate training on the use of these machines. The women werein the seated position, their arms were supported at the level of the heart, and a small (22-cm), normal (22- to 32-cm), or large (33- to 42-cm) adult cuff was used depending on the midarm circumference.26 After rest for 5 minutes, BP was measured in both arms simultaneously, and a series of recordings were made at 1-minute intervals until variations between consecutive readings fell within 10 mm Hg in systolic and 6 mm Hg in diastolic BP in both arms.When this point of stability was reached, we calculated the MAP of each arm as the average of the last 2 stable measurements, and, as recommended, we took the arm with the highest final MAP for the subsequent analysis of results.MAP = MAP = [(2 x diastolic)+systolic] / 3 CUTT OFF : > 90 mm Hg

RESULTS –LOWEST PI> 2.3 AND ADVERSE PREGNANCY OUTCOMES

RELATED STUDIES

EARLY SCREENING FOR PE

TAKE HOME MESSAGE

SCREENING FOR CONGENITAL HEART DEFECT ( DUCTUS + TR) SCREENING FOR ADVERSE FETAL OUTCOME( PAPP-A +DV +TR + SUA

NIPT( Non invasive prenatal testing Molecular techniques in prenatal diagnosis: This technique opens new horizon for

noninvasive prenatal testing. Various types of fetal cells have been identified in maternal circulation. These can be

Free fetal cells in maternal circulation Free nucleic acids (DNA and RNA) in maternal circulation. Fetal cells in maternal circulation: Nucleated red blood cells could be used for

prenatal diagnosis of fetal aneuploidies. With an aneuploid fetus, Bianchi et al (1997) have reported a sixfold increase in the number of fetal cells in the maternal blood but the isolation techniques are highly complex, so it has limited application today.

Cell free fetal DNA in maternal circulation: Studies demonstrated that Down syndrome pregnancies exhibit a 1.7-fold higher

serum level of cff-DNA than normal pregnancies. Farina et al 2003 found that when added to the quadruple screening test in the 2nd

trimester, fetal DNA increased the detection rate for Down syndrome from 81 to 86% at a 5% FPR.

The technique has been tried successfully in fetal sexing for X-linked disorders and fetal Rh grouping in Rh isoimmunization. Success in dia- -gnosis of other single gene disorders has also been reported.

The main limitation of the cff-DNA, is the use of Y-chromosome sequences (mostly SRY gene) as biomarkers, and thus restricting the detection to pregnancies carrying only male fetuses.

SCREENING PROTOCOL

ADVANTAGES OF FIRST TRIMESTER SCREENINGInformation earlier, more optionsReduce number of invasive proceduresMay identify other severe anomalies (or risk for) at time of scan and increased risk of adverse pregnancy outcome—referral for 2nd Δ evals.Good time to date pregnancy accurately NT good for multiple gestation

LIMITATIONS

Accuracy of NT strongly dependant on experience of ultrasonographersNot all women enter prenatal care in time for screeningResults of screen may arrive too late for CVS or early amnioExtra cost for first trimester ultrasoundCan not detect NTD or AWD, still need MSAFP

Nasal bone

Absence of the nasal bone is more common if:The gestation is 11 than 13 weeksThe fetal nuchal translucency is highThe mother is Black

Facial angle

In euploid fetuses the mean facial angle decreases with CRL from 84° at CRL 45 mm to 76° at CRL of 84 mmThe facial angle is above the 95th centile in:Euploid fetuses 5%Fetuses with trisomy 21 45%Fetuses with trisomy 18 55%Fetuses with trisomy 13 45%

Reversed a-wave

At 11-13 weeks reversed a-wave is found in about: Euploid fetuses 3% Fetuses with trisomy 21 65% Fetuses with trisomy 18 55% Fetuses with trisomy 13 55%

Trisomy 21

Effective first-trimester screening for trisomy 21 is provided by a combination of maternal age, fetal NT thickness, FHR and maternal serum free ß–hCG and PAPP-A:Detection rate 90%False positive rate 3.0%

Papp a free beta hcg60-68% detection of DS90% detection of Tri 184.5% false positive rateAlso drawn at 11-14 weeksSome centers quote 87% detection of DS when combined with maternal ageIf both PAPP-A and B-hCG are very low MoM = Increased risk for tri 18, triploidy, fetal anomalies or perinatal complications