First Trimester Issues

H MurrayDept ObstetricsNepean Hospital

First Trimester Issues First trimester bleeding

Threatened Miscarriage Ectopic Pregnancy

Anti D Genetic screening in the first

trimester

Bleeding in early pregnancy (1) A woman with no previous

pregnancies presents with 6 weeks amenorrhoea, PV spotting and right sided discomfort. Examination is unremarkable other than mild right pelvic tenderness.The HCG is 250IU/L. A pelvic scan shows no intrauterine sac and no other pelvic pathology.

Bleeding in early pregnancy (2) Which of the following are true? Rational management includes

A) Referral to hospital as ectopic pregnancy B) Plan to repeat HCG in 24 hours C) Plan to repeat US scan in 48 hours D) Referral to a private specialist requesting

urgent laparoscopy E) Administer anti-D if the woman is Rh

negative

Threatened miscarriage/Ectopic Statistics

25% of all pregnancies associated with amenorrhoea will fail

22% of pregnancies with viable fetus at 6.5 weeks will bleed, and 20% of those will fail

A fetal heart at 10 weeks is associated with a miscarriage risk of 3%

Characteristics of viable intrauterine pregnancy HCG level that doubles every 48

hours A pregnancy sac that is seen in-utero

on ultrasound scan when the HCG is > 1000 IU/L Transvaginal > 1800 IU/L Transabdominal

NB Pain is found in 40% viable pregnancies.

Characteristics of viable intrauterine pregnancy A yolk sac will be seen

transvaginally when the gestational sac is > 8mm (5.3 weeks)

A fetal pole should be seen transvaginally when the gestation sac > 20mm (5.5 weeks)

Characteristics of viable intrauterine pregnancy A fetal heart will be seen with the

CRL > 4mm. The normal fetal heart rate at 6

weeks is 70-100 beats/min.

Implications for scanning There is no point asking for a scan until

the HCG is greater than 1000IU/L All women must have a full bladder

when they present for their scan so that the whole pelvis can be visualised

A transvaginal scan will be necessary to determine fetal viability before 7 weeks Patients should be warned of this Patients should be counselled about the

safety.

Management of threatened miscarriage There is no medication that has been

proven to be useful in threatened miscarriage in the otherwise normal patient

Specific disorders do have appropriate management PCOS Metformin/progesterone Antiphospholipid Aspirin/Heparin Homocysteinaemia Folate/pyridoxine

Management of threatened miscarriage Viable pregnancy plus

Bleed settled rescan for NT Subchorionic haematoma rescan 7-10

days Continued bleed rescan 7-10 days

Subsequent scan shows POC only consider D&C if endometrial contents > 15mm thickness or heavy bleeding.

Ectopic - characteristics 2% of pregnancies (50% spontaneously

abort) Presents typically with PV bleed and pain HCG seldom rises above 6000IU/L HCG does not double consistently every

48 hours. May have a pseudodecidual sac in utero

in 20% of cases

Early implantation

Ectopic Ensure good scanning unit Refer for

High clinical suspicion HCG > 1000IU/L and no intrauterine

sac. Midcavity pseudodecidual sac Report of blood in pelvis Suspicious pelvic mass

Ectopic - management If mass is < 2cms, tube is

unruptured, no active bleeding, HCG < 2000IU/L Methotrexate 1mg/Kg IM HCG days 2 & 7. (Rescan day 5)

Others:- Removal of tube

Use of Anti D

Anti-D Which of the following are true about anti-D?

The dose of anti-D in a first trimester miscarriage is 650IU

All Rh neg pregnancies should be given a dose of anti D at 28 weeks

A woman (G2P1) who at an 8 week booking visit has an anti-D titre of 1:1028 should be urgently referred to a hospital clinic

A woman who tested Rh neg at your booking visit is found to be Rh positive at the 28 week visit in the hospital clinic. The difference is likely to be laboratory error.

Background

Sensitisation in Rh –ve women

1) Transplacental 75% of women Kleihauer positive in

pregnancy 1st trimester 3%, 0.03 ml 3rd trimester 45%, 2.5ml

(0.25ml required for sensitisation)

Sensitisation 2) Blood transfusion

3) Delivery

4) Abortion spontaneous < 1% usually 1ml therapeutic 20-25% Kleihauer positive

Prevention No prophylaxis

16% sensitised With ABO incompatibility 2%

Prophylaxis At delivery only:- 1.7% will sensitise 28 weeks and delivery:- 0.8% will sensitise 28 and 34 weeks and delivery:- 0.5%

sensitise Manual removal and LUSCS have larger

amounts of fetal blood transfer

Common Rh +ve Phenotypes CcDe CDE cDEe cDe CcDEe cDe

Other Rh blood groups Rh blood groups also have 40 other a/gens Commonest = Du variant

Cde/cDe Rh+ but the C causes diminished D expression

Tests as Rh negative but is Rh positive Doesn’t need prophylaxis

Du-positive :- part of the D antigen is missing Tests as Rh +ve, but acts as Rh -ve Needs prophylaxis (Anti D)

Anti D - indications Threatened miscarriage Miscarriage Termination of pregnancy Ectopic pregnancy Post CVS/Amniocentesis/Amnio reduction Antepartum Haemorrhage Trauma with positive Kleihauer External cephalic versions Post delivery (amount determined by

Kleihauer)

Anti D – New indication Rhesus negative mother in first

term pregnancy Dose given at 28 and 34 weeks

Needs to have considerable coordination of testing.

Anti D doses 1st Trimester :- 250 IU Anti D either

stat or 3 weekly if bleeding recurrs

2nd/3rd trimester :- 625 IU Anti D Used in the 28/34 week dosing Used for all situations where amount of

fetal blood lost is unknown Used every 3 weeks if bleeding

continues.

Anti D doses 2nd and 3rd trimester

625 IU dose will cover 4 mls of fetal blood. If the Kleihauer shows more blood lost the dose of Anti D will have to be increased.

Anti D doses Post delivery

All cases should have had fetal blood group determination and a maternal Kleihauer!!

For the Rh negative mothers with Rh positive babies then the dose of Anti D is

600 IU Win Rho SDF for every 4 mls of fetal blood in the maternal circulation.

Anti D doses Summary

1st trimester 250 IU Anti D 2nd/3rd trimester 625 IU Anti D Post delivery 600 IU Win Rho

SDF

More than 1 dose will be required for large bleeds, ongoing bleeding.

Anti D issues The half-life if Anti D is 21 days.

Following the administration of Anti D, the laboratory will detect the antibody in routine testing.

It is therefore important to tell the laboratory about the doses of Anti D given when requesting Blood Group status.

Rh negative, pregnant with antibodies Check paternal Rh status Refer all patients with Rh positive

husbands before the end of the first trimester.

Genetic screening in the first trimester

1st trimester Questions Indicate which of the following are true

about nuchal translucency testing A) The NT scan is performed between 11.0 and

14.0 weeks B) NT testing cannot be used in a twin

pregnancy C) NT/PAPP-A testing should only be offered to

those would would terminate an abnormal fetus.

D) A ‘High – risk’ NT/PAPP-A result indicates a fetal risk of trisomy 21 of greater than 1/200.

The 11-14 week scan The primary reason for the scan is to

assess the nuchal translucency. Screening test for aneuploidy, cardiac,

diaphragmatic and skeletal anomaly Offered to all women as no risk involved

in testing Many women who do not wish to terminate

still wish to be tested Many women use the test to determine

whether to have CVS or lower risk amniocentesis.l

The NT scan Nuchal translucency

Performed between CRL 45-85mm (11+2-14 weeks)

Must be done at an accredited unit as the risk relates to size, gestation, maternal age.

A poorly performed NT will markedly alter the risk Accredited units are audited Accredited units carry the software to calculate

risk

The NT scan Risk of aneuploidy relates to

Size of NT Age of mother Gestation of fetus

NT normally less than 2.5mm

NT scanSize of NT, along with maternal age and

fetal age will generate Risk of T21 in fetus Risk of T18/13 in fetus

And, if NT > 2.5mm:- indicate an increased risk of

XO, triploidy Fetal cardiac anomaly, skeletal dysplasia,

diaphragmatic anomaly Fetal infection

Down syndrome vs NT A high risk is taken as > 1/300 Without additional blood testing

the NT, a calculated risk of 1/300 will identify 5% of the population as high risk, in which 70-75% Down syndrome are found but 150 amnios are required to detect

1 case aneuploidy

Serum screening To improve the sensitivity for trisomy 21

the NT scan is accompanied by blood analysis for PAPP-A (pregnancy associated plasma protein A) and free HCG in Down syndrome :-

PAPP-A levels are lower free HCG levels are raised

Levels are corrected for maternal weight, smoking, and diabetes.

The NT scan If combined result gives risk of T21 of >

1/300 Amnio/CVS is offered.

30 - 39 amnios required for 1 case T21 Detects 90-92% T21

If NT result alone gives risk T13/18 > 1/300 Amnio/CVS offered

If NT > 2.5 mms CVS offered immediately If chromosomes are normal fetus is scanned for other

anomalies

Rate of Invasive Testing Rate of invasive testing at Nepean has

been decimated.

NT screening:- Summary NT plus PAPP A/free HCG calculate risk of

T21 NT alone determines risk of T13, T18, NT above 2.5mm is an indicator of possible

XO, triploidy and fetal anomaly (heart/diaphragm/long bone anomaly) Abnormal NT with normal chromosomes needs 15

18 and 26 week scans for fetal anomaly NT testing alone can be done in nonidentical

twins (no blood testing available). No test available for identical twins.

1st Trimester problems Which of the following about Chorionic

villous sampling (CVS) are true A) CVS is a better option for genetic diagnosis in

the 40 yr old than NT/PAPP-A as the NT test will almost always be positive.

B) A CVS result reliably diagnoses fetal aneuploidy in over 99.9% of cases

C) CVS can only be used to diagnose fetal karyotype and genetic/DNA anomalies

D) The advantage of the CVS is that it can be safely used before 10 weeks and therefore ensure a result by 12 weeks gestation.

CVS/Amniocentesis Diagnostic tests that carry fetal

risk Offered to those at high-risk of

fetal aneuploidy/genetic anomaly either following NT testing or due to other factors – History aneuploidy, extreme maternal

age etc.

CVS Performed after 10.5 weeks (CRL 36mm)

Is a placental biopsy Procedure is transcervical or transabdominal

depending on the placental site Earlier CVS can result in partial limb loss Chorion will give information about

Karyotype Genetics Rubella/syphylis infection in the pregnancy

CVS for Karyotype Gives information about the karyotype

of the placenta 1-2% loss rate after the procedure (1% is

procedure related 2-6% mosaicism rate so amniocentesis may

be required Only advantage is the earlier result May be used with FISH – rapid diagnosis

using probes for chromosomes 13,18,21,X,Y.

FISH results may be unreliable therefore

Amniocentesis Sampling of amniotic fluid Gives information on

Karyotype FP Presence of toxoplasmosis/CMV infection Detection of fetal Rh status Detection of Bilirubin in Rh disease Some enzymes associated with fetal disease

Amniocentesis Performed after 14 weeks

Earlier has increased risk talipes No problem with mosacism Can be used with FISH, but

limitations of this technology must be understood.

Quoted loss rate 0.5 – 1% Benefits:-lower loss rate, no false

positive mosacism rate.

Bleeding in early pregnancy (1) A woman with no previous

pregnancies presents with 6 weeks amenorrhoea, PV spotting and right sided discomfort. Examination is unremarkable other than mild right pelvic tenderness.The HCG is 250IU/L. A pelvic scan shows no intrauterine sac and no other pelvic pathology.

Bleeding in early pregnancy (2) Which of the following are true? Rational management includes

A) Referral to hospital as ectopic pregnancy B) Plan to repeat HCG in 24 hours C) Plan to repeat US scan in 48 hours D) Referral to a private specialist requesting

urgent laparoscopy E) Administer anti-D if the woman is Rh

negative

Anti-D Which of the following are true about anti-D?

The dose of anti-D in a first trimester miscarriage is 650IU

All Rh neg pregnancies should be given a dose of anti D at 28 weeks

A woman (G2P1) who at an 8 week booking visit has an anti-D titre of 1:1028 should be urgently referred to a hospital clinic

A woman who tested Rh neg at your booking visit is found to be Rh positive at the 28 week visit in the hospital clinic. The difference is likely to be laboratory error.

1st trimester Questions Indicate which of the following are true

about nuchal translucency testing A) The NT scan is performed between 11.0 and

14.0 weeks B) NT testing cannot be used in a twin

pregnancy C) NT/PAPP-A testing should only be offered to

those would would terminate an abnormal fetus.

D) A ‘High – risk’ NT/PAPP-A result indicates a fetal risk of trisomy 21 of greater than 1/200.

1st Trimester problems Which of the following about Chorionic

villous sampling (CVS) are true A) CVS is a better option for genetic diagnosis in

the 40 yr old than NT/PAPP-A as the NT test will almost always be positive.

B) A CVS result reliably diagnoses fetal aneuploidy in over 99.9% of cases

C) CVS can only be used to diagnose fetal karyotype and genetic/DNA anomalies

D) The advantage of the CVS is that it can be safely used before 10 weeks and therefore ensure a result by 12 weeks gestation.