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Obstetrics Simplified - Diaa M. EI-Mowafi

Thyrotoxicosis in Pregnancy
Epilepsy in Pregnancy
Iso-immunization in pregnancy

THYROTOXICOSIS IN PREGNANCY

Hazards

Abortion and preterm labour.

Clinical Picture

  • Weight loss in spite of good appetite.
  • Intolerance to heat.
  • Tremors.
  • Resting pulse over 100 beats/min.
  • Exophthalmos.

Investigations

Free T4 (raised) T3 resin uptake (raised)

Treatment

  • Propylthiouracil: 100-200 mg t.d.s. or
  • Carbimazole: 10-15 mg t.d.s.
  • Thyroxine is combined with antithyroid drugs in the last trimester to protect the neonate from hypothyroidism. Breast feeding is contraindicated because the drugs are excreted in milk.

EPILEPSY IN PREGNANCY

  • Grand mal epilepsy is the commonest type.
  • Treatment: phenobarbitone or phenytoin. Folic acid should be given with phenytoin as it is antifolic .
  • There is risk of foetal malformations.

ISO-IMMUNIZATION IN PREGNANCY

RHESUS ISO-IMMUNIZATION

  • Rhesus (Rh) factor is present on the surface of erythrocytes. It consists of 3 pairs of genes C/c, D/d, E/e.
  • The usual, but inaccurate, term "Rh positive" or "Rh negative" refers to the presence or absence of the D gene.
  • The D gene is dominant to "d" and therefore an "Rh positive" individual may be homozygous (DD) or heterozygous (Dd). An " Rh negative" individual has a (dd) genotype.
  • Incidence: 85% of population are "Rh positive" while 15% are "Rh negative".

Development of Rh-isoimmunization

An "Rh negative" female may develop antibodies if "Rh positive" blood is passing to her circulation via:

  • Blood transfusion from "Rh positive" donor.
  • Pregnancy with "Rh positive" foetus:

When an "Rh positive" father is married from an " Rh negative" mother there is a chance that the baby will be "Rh positive". Foetal RBCs can be transmitted to the mother during:

  • delivery, abortion, disturbed ectopic pregnancy, antepartum haemorrhage, amniocentesis, or external cephalic version.
  • This initial stimulus produces IgM which cannot cross the placenta again to harm the foetus due to its large molecular weight (900.000) so the first baby is escaped from the haemolysis.
  • When the mother is exposed for a second time she will develop IgG which can cross the placenta due to its low molecular weight (150.000) to affect the foetus.

N.B.  Sensibilization: The initial sensitization is so low that it is not detectable by normal laboratory testing but such patients will develop a strong response to further stimuli.

Although 15% of the population are Rh negative the incidence of Rhesus isoimmunization is 0.5-1.5% only. This is because:

  • The foetus must have inherited a "D" gene from the father. This is inevitable if the father is homozygous (DD), but if he is heterozygous (Dd) 50% of offsprings will be (dd) i.e. Rh negative.
  • ABO incompatibility between the mother and her foetus results in the destruction of transfused foetal cells before they can induce Rh antibody formation.
  • Individual variability of response to the stimulus.

Clinical Varieties

  • The primary pathology in the foetus is haemolysis leading to anaemia.
  • In response to the haemolytic anaemia erythropoiesis is enhanced with an increase in blast cells. So the condition was called erythroblastosis foetalis.
  • The haemolysis results in excessive production of bile pigments which excreted mainly through the placenta to the mother. Thus, the threat during intra-uterine life is anaemia but after birth is the accumulation of bile pigments.

Hydrops foetalis

The less common but most severe form in which there are:

  • Severe haemolytic anaemia in utero,
  • Cardiac failure,
  • Gross oedema of the whole foetus and placenta,
  • Hepatosplenomegaly,
  • Pleural effusion and ascitis,
  • Polyhydramnios.
  • Radiological and ultrasound features:
    • "Buddha" attitude: due to abdominal distension,
    • "halo" sign: due to oedema of the scalp.

Occasionally, in severe cases a maternal syndrome develops with features resembling pre-eclampsia plus jaundice and pruritus.

Icterus gravis neonatorum

It is the commonest form in which.

  • The baby is anaemic at birth.
  • Oedema, ascitis, pleural and pericardial effusion.
  • Hepatosplenomegaly.
  • Jaundice not present at birth but usually develops within few hours, and is progressive.
  • Death may result during this period from heart failure, aggravated by respiratory difficulties due to pulmonary oedema, pleural effusion and distended abdomen.
  • Kernicterus: is damage of the basal nuclei of the brain occurs if the blood bilirubin exceeds 20 mg%. It is characterised by neck rigidity, nystagmus, twitching and death of the neonate may occur. If survives, there is residual spasticity and mental retardation.

Congenital haemolytic anaemia

It is the mildest form in which there is anaemia which may be evident at birth or reveals itself up to a weak or more postnatally.

Antenatal Assessment:

  • Maternal antibody level:
    • It is indirect Coombs’ test that measures specific anti-D Ig G. A concentrations above 0.5 m g/ml or titer more than 1/8 is an indication for amniocentesis.
  • Amniocentesis:
    • The first sample from the amniotic fluid is taken at not later than 22-24 weeks’ gestation if there is:
      • a history of a previous severely affected or stillborn infant, or rising antibody levels.
    • Otherwise amniocentesis is performed at 30-32 weeks. Repeat tests at intervals of 2-3 weeks. Amniotic fluid sample is examined as soon as possible by the spectrophotometer at a wave length of 450 m m. The interpretation of the result is based on Liley’s chart (1961) as shown in the figure.
  • Ultrasound or X-ray:
    • to diagnose hydrops foetalis - see before.

Management

Prophylaxis

  • Rh-negative women should not receive Rh-positive blood transfusion.
  • Anti-D gammaglobulin should be given to:
  • All Rh-negative women having Rh-positive baby in any delivery. They should receive 500 units IM within 72 hours from delivery.
  • Rh-negative women with abortion before 20 weeks should receive 250 units.
  • After ectopic pregnancy, amniocentesis and abruptio placentae in Rh-negative women.
  • Women received Rh-positive blood inadvertently can receive a large dose of anti-D globulin.
  • Trials were made for prophylaxis with 1500 units given at 28 weeks or 500 units at 28 weeks and another one at 34 weeks’ gestation.

Antenatal treatment

Plasmapheresis:

  • It is indicated if the foetus is severely affected (Liley zone 3) before 24 weeks’ gestation.
  • It aims to decrease the maternal antibody concentration by removal of 1 litre of maternal blood in each session.
  • The blood is centrifuged under complete aseptic condition and the supernatant plasma containing the antibodies is removed.
  • The cells are resuspended in saline, plasma protein fraction or fresh frozen plasma and returned to the mother.
  • This is repeated five times weekly initially to be reduced to twice weekly later on.

Intrauterine transfusion:

  • It is indicated if the foetus is severely affected between 24 and 34 weeks’ gestation.
  • 80 ml of Rh-negative group O blood is injected into the peritoneal cavity of the foetus from which the cells are rapidly absorbed.
  • This is repeated every 2-3 weeks and increased to 120 ml at 33 weeks.
  • The procedure is done under sonographic control and local anaesthesia.
  • The rate of injection is 1.0-1.5 ml / minute.
  • Cordocentesis: is intravascular transfusion into the umbilical vein under direct vision using the fetoscope. It can be used instead of intraperitoneal injection.

Delivery

  • In severe cases, induction of labour or caesarean section is indicated as soon as lung maturity is demonstrated by L/S ratio.
  • In milder cases, pregnancy can be allowed to continue to 37 weeks when termination is done.
  • The cord is not milked and immediately clamped to avoid further passage of antibodies from the placenta. The cord is divided 3 inches from the umbilicus to facilitate exchange transfusion if needed.

Neonatal Management

  • Blood is obtained from the umbilical cord for the following investigations:
    • ABO and Rh group, haemoglobin concentration, serum bilirubin, direct Coombs’ test: detects the antibodies absorbed to the RBCs.
    • Haemoglobin and bilirubin estimation is repeated every 6 hours for 36 hours.
  • Exchange transfusion:
    • Indications:
      • Cord blood haemoglobin less than 15 gm/dl. Cord serum bilirubin more than 3mg%. Positive Coombs’test.
    • 20 ml of blood is withdrawn from the umbilical vein to be replaced by the same amount of Rh-negative group O blood. This process is continued till 80-90% of the foetal blood is exchanged.
    • The aims are:
      • Removal of bilirubin.
      • Removal of some antibodies.
      • Correction of anaemia.
      • Replacement of Rh- positive by Rh-negative RBCs.
  • Simple transfusion:
    • may be needed later on to correct anaemia.
  • Phototherapy:
    • Exposing the baby to fluorescent light, with protection of the eyes, reduces bilirubinaemia.

ABO ISO-IMMUNIZATION

Sometimes, when the mother is group O and the foetus is group A, B or AB like his father, some anti A or anti B antibodies pass from the mother to the foetus causing haemolysis which can affect the first infant and usually requires no treatment.

Very rarely, the ABO incompatibility is severe causing marked neonatal jaundice in the first 48 hours. This will indicate exchange transfusion for the newly born by group O blood.

ABO incompatibility differs from Rh incompatibility in that:

  • The first baby is affected.
  • It is usually mild due to the presence of soluble A and B antigens in the foetal tissues and fluids in addition to the foetal RBCs.

N.B. The natural anti-A and anti-B antibodies of group O are IgG so it can cross the placenta to affect the baby, whereas the natural anti-A and anti-B antibodies of group B and A are IgM thus if the mother is of group A or B her antibodies cannot cross the placenta.

DIFFERENTIAL DIAGNOSIS OF JAUNDICE IN THE NEWBORN

  • Physiological jaundice:
    • It appears after 48 hours due to destruction of RBCs and immaturity of the liver. It is slight and disappears after one week but it tends to be severe and prolonged in premature infants. Coombs’ test is negative.
  • Icterus gravis neonatorum:
    • Jaundice develops within few hours of birth and is progressive Coombs’ test is positive.
  • ABO incompatibility:
    • Jaundice may develop in the first 48 hours after birth. The first baby is affected.
  • Congenital spherocytosis:
    • Due to increased fragility of the RBCs.
  • Glucose-6- phosphate dehydrogenase deficiency.
  • Drugs:
    • as salicylates, diazepam, sulphonamides and vitamin K.
  • Infections:
    • As hepatitis, toxoplasmosis, rubella, congenital syphilis and cytomegalvirus.

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