Unfinished business:

 Pergonal
 Premarin
 World’s oldest mother.
 OC failure in USA etc.
A Pregnant Pause

Use of the laboratory during

pregnancy.
Basic Physiology, initial timing:
 Fertilized ovum takes 3 days to travel down the
fallopian tubes.
 Implantation takes 4 days.
 Human Chorionic gonadotropin hCG is secreted
by the trophoblastic cells of the developing
placenta.
 Corpus luteum makes progesterones and
oestrogens which sustains the uterine
endometrium.
15 year-old woman, sexually
active, menstruation late
 Pharmacy pregnancy kit, finds pregnant.
 Local clinic finds not pregnant.
 Three weeks later a Hospital laboratory
finds her to be pregnant.
 Preanalytical factors,
 Analytical factors,
 Post analytical factors.
Pregnancy home use kits, e.g.:
 27 home use kits for self diagnosis of pregnancy.
 Three urines: O hCG, 1 x DL, 2 x DL.
 Laboratory staff found kits to be 100% specific
and 100% sensitive – as advertised.
 638 women tried the kits.
 Of 478 positive urine samples given, 230 were
reported by the women to be negative (48%).
 Clinical Chemistry 39/1, 53-59 1993.
Urine from 70 year old woman
 Sent for pregnancy test.
 Report positive.

 Differential diagnosis is ?
720 male competitors, athletic
competition, pregnancy tested
 35 had hCG >100 U/L (<5)

 Why is this?
 How can you use the laboratory to
validate your theory?
Pregnancy changes:haematology
 Blood volume increases by 40% by
middle of third trimester.
 Body water increases by 6-8 L by term
 Erythrocyte mass increases by 20-30%
 Decreases in Haemoglobin, Fe, ferritin.
 Increase in T Iron Binding C and ESR.
 Number of leukocytes, platelets,
reticulocytes and folate vary.
Coagulation test changes
 Fibrinogen significant increases.
 PT, APTT increases.
 Plasminogen increases.
 Factors VII, VIII, IX, X, XI increase.
 Fibrin degradation products increase.
2. Liver function:
 Cholestasis, ALP increases but this is
mostly placental ALP
 Protein synthesis increases: albumin,
alpha and beta globulins.
 Lipids increase: plasma cholesterol
may double by 3rd trimester.
3. Respiratory function:
 Oxygen consumption increases by
20%.
 Mild hyperventilation from effects
of progesterone on the
hypothalamus.
 Serum bicarbonate decreased.
4. Renal function,
 serum creatinine may be low.
 Renal blood flow increases so
glycosuria in up to 70% of
pregnancies.
 Protein loss in urine 0.2-0.3 g/d
(<0.1)
5. Carbohydrate metabolism
 Early on hypoglycaemia
 Later on may be glucose
intolerance, hyperglycaemia.
6. Protein metabolism:
 Serum albumin decreases.
 Serum placental proteins increase
 Liver produces transport proteins
in plasma
 Serum fibrinogen increases.
7. Hormones, pregnancy
hormone
 Human chorionic gonadotropin hCG.
 hCG 5 – 200,000 U/L by 3rd month.
 By second trimester 24,000-55,000 U/L
 After delivery normal by 2 weeks
 After abortion may be detected for 3-4
weeks.
 Chorio carcinoma.
Other hormone increases in
pregnancy:
 ACTH.
 Serum cortisol.
 Serum testosterone
 Serum parathyroid hormone
 Serum aldosterone
 Renin-angiotensin.
 17 alpha steroids.
 Thyroid hormones.
8. Alpha foeto-protein
 Foetal form of albumin.
 Immunosuppressor
 Made by foetal liver
 Found in maternal blood also.
Angel Issajenko at Dubin enquiry
 Eastern European athletes made
pregnant just before the Olympic
Games etc to give them a hormone
boost.

 How could you test this theory?

Pregnancy caused problems for
mother
1. Gestational diabetes:
Diabetic mothers have large babies that may
be born damaged or still born.
Her neonate may be hypoglycaemic at birth
because of mother’s insulin and own
immature liver that cannot compensate.
22-26 weeks 50 g glucose challenge. 2-5% of
pregnancies are abnormal.
Diabetic pregnancy:
 4/1,000 pregnancies in UK.
 Early: teratogenic, 3-4 times neural and cardiac
problems.
Need normal glucose at time of
conception to avoid this.
 Later: intrauterine death, hydramnios, toxaemia.
Foetal macrosomia
Hyaline membrane disease,
Hyper/hypoglycaemia.
Diabetic pregnancy, laboratory
work to control:
 4 times /day insulin injection.
 Several times / day glucose monitored.

 Mother seen in clinic each 2-4 weeks.

 During labour: measure glucose and give

minimal insulin IV.
Toxaemia of pregnancy
 Pregnancy induced hypertension 10%, toxaemia
much rarer.
 Mother has increased blood pressure, oedema and
proteinuria.
 Convulsions.
 Infected amniotic fluid give toxin to mother.
 Magnesium sulphate therapeutic may be toxic.
 Renal function tests
21 year old woman in first
pregnancy, 31 weeks pregnant
 At 12 weeks normal but now blood
pressure is 180/110.
 Swollen hands, vision blurred, ankles
swollen.

 Tests?
Erythroblastosis foetalis (Rhesus)
 Mother Rh negative and father Rh positive.
 Maternal antibodies against Rh cross the
placenta into foetus and destroy its
erythrocytes.
 Transfusion may be given in utero
 Mother immunized by immune globulin
within 72 hours of delivery or abortion.
1st and 2nd children born without
incident
 Next three are still born or very
jaundiced and die soon after.
 First born is know to be Rhesus
positive
 Second born known is Rhesus
what?
Ectopic pregnancy
 This is usually in a fallopian tube but it
could even be in the peritoneum.
 Pelvic inflammatory disease PID is most
likely cause
 1.4% of pregnancies.
 13% of pregnancy associated deaths.
20 year-old woman has vaginal
bleed and acute abdominal pain.
 Sexually active.
 Ultra sound
 Serum hCG
 Serial serum hCG
 Serum amylase for perforation.
 Some use plasma progesterone.
Drugs in pregnancy:
 Drugs given to mother get in foetus –dopey
neonates.
 Recreational drugs are of concern:
 Ethanol
 Cocaine
 Heroin
 Marijuana
 Amphetamines
 Barbiturates, tobacco and more likely
Drug abuse in first trimester St
John, NB, 1,000 random urines
Drug/metabolite Total Pregnant hCG -ve
Marijuana metabol 88 34 54
Barbiturates 14 2 12
Alcohol (5-29 mm) 7 2 5
Benzodiazepines 5 1 4
Cocaine metabolite 2 0 2
Drugs in pregnancy, effects
 Alcohol: stunted, epilepsy, cardiac
problems, low IQ.
 Tobacco: small babies, premature births,
hyperactive.
 Marijuana: hyperactive, low IQ.
 Amphetamines: heart defects.
 Birth control pills: masculinised babies.
18 year old girl irregular menses
put on Premarin.
 Denies sexual activity.
 Pregnancy test negative.
 However, she was pregnant and the baby
was born without a hand.
 Sued family physician, laboratory and the
drug company.
Baby making:
 3rd week thyroid gland, CNS is open.
 4th week heart forms.
 5th week arms and eyes.
 6-7th week legs and palate.
 8-12th week teeth and genitals.
 4-20th week brain, last month most
sensitive.
Screening for foetal disorders:
 At 16 weeks measure maternal s-AFP, free
beta-hCG, oestriol, inhibin A, PAPP-A.
 Nuchal translucency by ultrasound.
 Low levels s-AFP in Down’s syndrome.
 High s-AFP in spina bifida (open spine).
Folate now lessens numbers of these.
 Can pick up Turner’s syndrome, trisomy
18: Free beta hCG increased, AFP normal.
Down’s syndrome, (trisomy 21)
maternal age effects:
 < 30 years 1 in 1,000
 35-39 years 1 in 300
 40-44 years 1 in 70
 > 45 years 1 in 40.
 Age of maternal ova causes it.
 Father > 40 years 4 x more likely to have
genetically defective child.