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Medical Disorders of Pregnancy

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Title: Medical Disorders of Pregnancy


1
Medical Disorders of Pregnancy
  • Hassan A Shehata MRCOG MRCPI
  • Consultant Obstetrician, Gynaecologist
    Obstetric Physician
  • Epsom St. Helier University Hospitals NHS Trust
  • St. Heliers Hospital 3 October 2006

2
CEMACH 2002-2004 Breakdown of direct causes
3
CEMACH 2002-2204 Breakdown of indirect causes
4
CEMACH 2002-2004 Leading Causes of Death
5
Diabetes - Classification
6
Effect of pregnancy on DM
  • Normal pregnancy
  • Fall in fasting BG
  • Rise in post-prandial BG
  • Insulin resistance relative glucose intolerance
  • Glucose tolerance decrease with increasing
    gestation due to hPL, glucagon cortisol
  • Renal threshold for glucose falls
  • Rise in insulin requirements x 2
  • Deterioration in nephropathy (reversible)
  • Two fold risk of progression of retinopathy

7
CEMACH 2006
  • Women in UK with pre-existing (type 1 or type 2)
    diabetes are poorly prepared for pregnancy
  • The recent CEMACH report highlighted the fact
    that across the country, only 1 in 3 women were
    documented as receiving any kind of preconception
    counselling or having a preconception HbA1c
    measurement
  • The level of uptake of folic acid supplements
    before conception was very poor (39) which is
    particularly concerning given the increased risk
    (3.4-fold) of neural tube defect
  • Even amongst those take folic acid, few were
    prescribed the higher dose (5mg) as recommended
    by the National Service framework (NSF) Diabetes

8
Type 2 DM
  • Previous reports of type 2 diabetes being
    perceived as far less common in women of
    childbearing age as well as less serious
    condition
  • However, it has become increasingly apparent that
    both these perceptions are mistaken
  • The prevalence of type 2 diabetes in young people
    is increasing and accounts for over a 1/4 of
    pregnant women with pre-existing diabetes and in
    some parts of the country including London this
    rises to 45
  • Over-representation of black, Asian and other
    minority groups (49 compared with only 9 of
    women with type 1 diabetes) and a strong
    association with social deprivation
  • It is now clear that adverse pregnancy outcomes
    are as common in women with type 2 diabetes as
    those with type 1 diabetes
  • Risk of perinatal mortality and congenital
    malformation are equivalent and babies of women
    with type 2 diabetes are more likely to be large
    in size for gestational age and delivered pre-term

9
Feto-maternal blood glucose relationships
  • Glucose crosses the placenta by a process of
    facilitated diffusion
  • Fetal plasma glucose levels are similar to those
    of the mother
  • Fetal insulin secretion occurs from 10 weeks
    gestation
  • There is a brisk fetal insulin response to raised
    plasma glucose levels in diabetic pregnancy
  • Sustained fetal hyperglycaemia secondary to
    maternal hyperglycaemia can result in fetal
    ?-cell hyperplasia

10
HbA1c
  • Level is raised in diabetes
  • Reflects diabetic control over the previous 2 or
    3 months
  • Estimation has proved a valuable additional aid
    to be on the look-out for major congenital
    abnormalities

11
Effect of pre-existing DM on pregnancy
  • Increased risk of congenital abnormalities
  • Increased perinatal mortality
  • late unexplained intrauterine death
  • Increased risk of pre-eclampsia
  • Increased perinatal morbidity
  • Prematurity
  • Macrosomia

12
Congenital Abnormalities
  • 2 - 4 fold increase ie. 10 risk
  • Directly related to glycaemic control
  • Correlated with HbAIC
  • Very small risk if HbAIC lt 50 above upper limit
    of normal
  • Sacral agenesis
  • CHD
  • Skeletal / NTD

13
Perinatal Mortality
  • IUD is rare
  • Related to fetal acidaemia
  • Related to maternal BG
  • Cannot predict with
  • biophysical profile
  • CTG
  • Umbilical artery Doppler

14
Perinatal Morbidity
15
Management of DM in Pregnancy
  • Pre-pregnancy counselling
  • Combined clinic (single physician obstetrician)
  • HBGM with meter
  • Aim for normoglycaemia
  • fasting 4-6 mmol/l
  • 1 hr pp 4-8 mmol/l
  • 2 hrs pp 4-7 mmol/l
  • Diet /- Insulin
  • Monitor control of IDDM with HbA1C
  • Glucagon kit for IDDMs
  • Screen for retinopathy

16
Pre-pregnancy counselling (PCC)
  • Optimize glycaemic control
  • Risk of major congenital malformations is
    increased x 3/4.
  • Risk correlates with HbA1C.
  • Assess presence / severity of complications
  • Hypertension
  • Retinopathy
  • Nephropathy
  • Stop oral hypoglycaemics

17
PCCContraindications to pregnancy in DM
  • Ischaemic Heart Disease
  • Untreated proliferative diabetic retinopathy
  • Hypertension and severe renal impairment (Cr gt
    250)
  • Severe gastroparesis

18
Obstetric Management
  • Ultrasound
  • to detect congenital abnormalities
  • to assess fetal growth / polyhydramnios
  • Screen for pre-eclampsia
  • Timing of delivery
  • Risk of IUD vs. risk of RDS
  • Risk of macrosomia and shoulder dystocia vs. CS
  • 38 - 40 weeks
  • Caution with steroids and beta-sympathomimetics

19
Intrapartum and postpartum care
  • Continuous FHR monitoring
  • IV dextrose and variable IV insulin
  • BG 5-8 mmol/l
  • Halve rate of insulin post partum
  • Pre-pregnancy insulin SC dose when eating
  • Prophylactic antibiotics if CS
  • Neonatal BG 4 hours
  • Feed neonate early

20
Recommendations
  • Plan pregnancy
  • Pre-pregnancy counselling
  • Tertiary centre / joint clinic / diabetes nurse
    specialist / diabetes midwife/ dietician
  • Monitor using post-prandial BGs
  • Basal bolus insulin regimen
  • Monitor fetus and time delivery
  • Post-pregnancy counselling

21
Hyperthyroidism
  • Prevalence in pregnancy is up to 0.2
  • Graves disease - up to 90 of cases
  • Untreated - dangerous for mother baby

22
Hyperthyroidism - Clinical Features
  • Many of the typical features are common in normal
    pregnancy
  • Discriminatory features include weight loss,
    tremor, a persistent tachycardia, lid lag and
    exophthalmos
  • If thyrotoxicosis occurs for the first time in
    pregnancy, it usually presents late in the first
    or early in the second trimester.

23
Normal ranges for TFT in pregnancy
24
Hyperthyroidism - Effect of Pregnancy
  • Thyrotoxicosis often improves during pregnancy
    especially in the second and third trimesters.
  • Exacerbations may occur in the first trimester,
    possibly related to hCG production, and in the
    puerperium

25
Hyperthyroidism - Effect on Pregnancy
  • If severe and untreated, it is associated with
    inhibition of ovulation and infertility
  • Higher incidence of miscarriage, placenta
    abruption, pre-term delivery and PET
  • Neonatal hyperthyroidism, prematurity,
    intrauterine growth retardation, fetal death and
    stillbirths
  • Poorly controlled thyrotoxicosis may lead to a
    thyroid crisis (storm) in the mother and heart
    failure, particularly at the time of delivery.
  • The possibility of retrosternal extension of a
    goitre which can cause tracheal obstruction

26
Hyperthyroidism - Diagnosis
  • A raised free T4 or free T3. Normal pregnant
    ranges for each trimester must be used
  • TSH is suppressed, although this may be a feature
    of early pregnancy.
  • Differentiation from hyperemesis gravidarum may
    be difficult

27
Hyperthyoidism - Management
  • Graves disease often improves, flares postpartum
  • CBZ (up to 15mg) PTU (up to 150mg) cross
    placenta
  • ?-Blockers are safe
  • Thyroidectomy is rarley necessary-
  • Who fail to achieve euthyroidism
  • intolerant to drugs
  • with dysphagia or stridor related to a large
    goitre
  • with confirmed or suspected thyroid malignancy

28
Hypothyroidism
  • Prevalence is in the order of 1
  • Commonest is autoimmune destructive thyroiditis
  • Untreated - associated with infertility,
    miscarriage and fetal loss

29
Hypothyroidism - Clinical Features
  • Features are common in normal pregnancy
  • Discriminatory features in pregnancy are cold
    intolerance, slow pulse rate and delayed
    relaxation of the tendon (particularly the ankle)
    reflexes.
  • It is associated with other autoimmune diseases,
    for example, pernicious anaemia, vitiligo and
    type-I diabetes mellitus

30
Hypothypidism - Diagnosis
  • Low free T4.
  • The TSH is raised, although this may be a feature
    of normal late pregnancy, or occasionally early
    pregnancy
  • The finding of thyroid autoantibodies may help
    confirm the diagnosis, but these are present in
    10-20 of the population and should not be used
    in isolation

31
Hypothypidism - Effect of Pregnancy
  • Pregnancy itself probably has no effect on
    hypothyroidism
  • If the dose does need to be increased in
    pregnancy, this is usually because of inadequate
    replacement prior to pregnancy

32
Hypothypidism - Effect on Pregnancy
  • Severe and untreated - inhibition of ovulation
    and infertility.
  • Those who do become pregnant and remain untreated
    have an ? rate of miscarriage, fetal loss, PET
    LBW
  • An association between untreated hypothyroidism
    in the mother and reduced IQin the offspring.
  • With adequate replacement, the maternal and fetal
    outcome is usually good

33
Hypothyroidism - Management
  • Small amounts of thyroxine cross the placenta -
    fetus is not at risk
  • Most will be on maintenance doses of thyroxine of
    100-150 ug/day
  • Euthyroid women will not usually require any
    adjustment to dose
  • TFT should be checked in all women, ideally
    pre-conceptually, or at least during the first
    trimester
  • Replacement with thyroxine should begin
    immediately
  • With adequate replacement, thyroid function
    should be checked once in each trimester

34
Epilepsy Effect of Pregnancy
  • About 1/3 of women experience an increased
    frequency of fits
  • Poorly controlled epileptics are more likely to
    detriorate
  • In most (54) , the frequency of fits is not
    altered

35
Epilepsy Effect on Pregnancy
  • There is no increased risk of miscarriages
  • The fetus is relatively resistant to short
    episodes of hypoxia
  • The risk of the child developing epilepsy is
    increased (4)
  • Teratogenic effects of anticonvulsants

36
Epilepsy - Anticonvulsants
  • All cross the placenta and are teratogenic
  • Not much difference in the risk of the four
    principle AEDs
  • Background risk 3
  • Untreated epileptic 4
  • 1 drug 7
  • 2 or more drugs 15
  • Val carb phenytoin 50

37
Epilepsy - Management
  • Assess need for treatment
  • Optimize control treat patient not drug level
  • Monotherapy if possible
  • Counsel re teratogenesis
  • Give folate 5 mg / day

38
Migraine
  • It can occur as a pregnancy-related phenomenon
    without any prior history
  • Pre-existing migraine (50-80) often improves in
    pregnancy
  • Hemiplegic migraine may mimic TIA
  • Ergotamine, sumatriptan pizotifen should be
    avoided
  • Low-dose aspirin, beta-blockers, tricyclic
    antidepressants calcium antagonists may be used
    for prophylaxis

39
Asthma Effect of Pregnancy
  • May improve, deteriorate or remain unchanged
  • Mild disease unlikely problems
  • Possible postnatal deterioration
  • Deterioration of disease is commonly caused by
    reduction or cessation of medication

40
Asthma Effect on Pregnancy
  • Mostly no adverse effects
  • Severe, poorly controlled asthma may adversely
    affect the fetus
  • No association with PET, prem. labour, LBW, IUGR
    and neonatal morbidity

41
Asthma - Management
  • Treatment differs little from Mx in non-pregnant
    patient
  • Education and reassurance concerning the safety
    of asthma medications
  • Inhaled, oral and intravenous steroids and
    inhaled, nebulized and intravenous beta-agonists
    are safe
  • Do not withold a chest X-ray if necessary

42
Physiological changes of thrombotic/fibrinolytic
system
  • Increase in levels of factors VIII, IX, X and
    fibrinogen
  • Decrease in fibrinolytic activity
  • Decrease in antithrombin III and protein S
  • Venodilation and decreased flow in lower limbs
    leads to venous stasis

43
Pulmonary Embolism (PE)
  • PE is the major cause of maternal death
  • 3 of direct deaths
  • 1.4 deaths per 100,000 maternities
  • 35 women died from TED in 1997-9
  • 31 PE 4 cerebral thrombosis
  • 13 antenatally (8 in 1st trimester)
  • 17 postnatally (7 after Caesarean, 10 after
    vaginal delivery

44
Acute Episodes - ? PE
  • Chest X-ray
  • Arterial blood gas analysis
  • pO2 - 13 kPa (100mmHg) standing, 11kPa
    (83mmHg) supine
  • pCO2 - 4 kPa (30mmHg)
  • SO2 drop by gt 6mmHg
  • Electrocardiography
  • V/Q scan or spiral CT
  • D dimers not helpful
  • Thrombophilia screen

45
Estimated radiation to the fetus and excess risk
of childhood cancer following common diagnostic
procedures
  • Estimated radiation to the fetus
    (mGy) Probability of fatal cancer to
  • age 15y
  • Conventional X-ray
  • Chest 0.01 lt1 in 1000,000
  • Pelvis 1.1 1 in 300,000
  • Skull 0.01 lt1 in 1000,000
  • Spine 1.7 1 in 20,000
  • Computerized Tomography
  • Chest (inc. spiral) 0.06 1 in 560,000
  • Pelvimetry 0.2 1 in 170,000
  •  
  • Nuclear Medicine
  • Lung perfusion (Tc 99m) 0.2 1 in 170,000
  • Lung ventilation (Tc 99m) 0.3 1 in 110,000

Childhood fatal malignancy background risk is
1650,000
46
V/Q scan Spiral CT
47
Pathological MRI specimen
48
TED - Mx
  • If DVT or PE is diagnosed or strongly
    suspected, anticoagulation with heparin should
    be commenced
  • Therapeutic-dose i.v. heparin or LMWH for 12
    weeks
  • Then prophylactic LMWH for up to 6 weeks
    postpartum or longer (total of 6 months)

49
Drug transfer
  • Most drugs have a molecular weight below 1000
    daltons (D)
  • Drugs ? 1000 D cross the placenta (? 600 D cross
    easily)
  • Main determinant of the drug concentration in the
    embryo/fetus is the mother's blood concentration
  • Other factors-
  • lipid solubility protein binding
  • degree of ionization at physiologic pH
  • placental blood flow surface area available for
    transfer

50
  • The processes that govern the passage of a
    drug into milk are similar to the placenta
  • maternal serum concentration is the main
    determinant
  • the milk pH is slightly acidic in comparison to
    serum pH so weak bases could become trapped in
    milk (ion trapping)

51
Type of Effects
  • Teratogenicity (i.e. thalidomide) - readily
    detected at, or shortly after, birth
  • Long term latency (i.e. DES - increased risk of
    vaginal adenocarcinoma after puberty, or
    abnormalities in testicular function and semen
    production)
  • Impaired intellectual or social development (i.e.
    exposure to phenobarbitone- alters programming of
    brain)
  • Predisposition to metabolic diseases (i.e. Barker
    hypothesis - low birthweight associated with
    increased risk of diabetes, hypertension, heart
    disease in adulthood)

52
Teratogenesis
  • It is defined as structural or functional (e.g.
    renal failure) dysgenesis of the fetal organs
  • Typical manifestations include
  • congenital malformations with varying severity
  • intrauterine growth restriction
  • carcinogenesis
  • fetal demise
  • In humans, the critical time for drug-induced
    congenital malformations is in the first
    trimester
  • Drug-induced toxicity can occur at any time
    during gestation

53
Malformations
  • The overall incidence of
  • major congenital malformations is around 2-3
  • minor malformations is 9
  • It has been estimated that
  • 25 are due to genetic or chromosomal
    abnormalities
  • 10 due to environmental causes including drugs
  • 65 of unknown aetiology
  • The part played by drugs is probably small

54
Organogenesis
  • The critical time for drug-induced congenital
    malformations is usually the period of
    organogenesis
  • about 20 to 55 days after conception
  • about 34 to 69 days after the first day of the
    LMP
  • Interference in this process causes a teratogenic
    effect
  • If a drug is given after this time it will not
    produce a major anatomical defect, but more of a
    functional one

55
Timing of the development of major body
structures in the embryo and fetus Hanretty KP
et al. Identifying abnormalities. In Rubin PC,
ed. Prescribing in pregnancy, 2nd ed. London BMJ
Publishing 1995 8-21
56
Pregnancy risk categories - FDA
  • Category A Controlled human studies have
    demonstrated no fetal risk levothyroxin
  • Category B Animal studies indicate no fetal
    risk, OR animal studies suggest a potential for
    harm, but no well-controlled human studies
    paracetamol
  • Category C No adequate human or animal studies
    OR potential fetal effects in animal studies, but
    no available human data - theophyllin
  • Category D Evidence of fetal risk, but benefits
    outweigh risks - ACE inhibitors
  • Category X Evidence of fetal risk. Risks
    outweigh any benefits - statins, vitamin A
    analogues

57
Contraindicated drugs
Absolute Relative
Cytotoxic Busulphan, Cyclophosphamide, Methotrexate Vitamin A analogues Etretinate, Isotretinoin Thalidomide Cardiovascular drugs Angiotensin-converting-enzyme inhibitors, Losartan, Amiodarone Antibiotics Ciprofloxacin, Chloramphenicol (3rd trimester), Vancomycin, Trimethoprim (1st trimester) Antifungal drugs Griseofulvin, Ketoconazole, Fluconazole, Itraconazole, Terbinafine Anti-inflammatory drugs NSAIDs (3rd trimester), COX-2 inhibitors, Colchicine Endocrinological drugs DES, Chlorpropamide, Sulphonylureas Radioactive iodine, Sex hormones, Octreotide Antihelminthic drugs Mebendazole Cytotoxic Azathioprine Psychotropic drugs Antipsychotic drugs - Lithium Anticoagulants Warfarin Anticonvulsants Carbamazepine, Phenytoin, Sodium valproate, Lamotrigine, Felbamate, Gabapentin, Oxcarbazepine, Tiagabine, Topiramate, Vigabatrin Endocrinological drugs Carbimazole, Propylthiouracil Cardiovascular drugs Beta-blockers Antibiotics Aminoglycosides, Nitrofurantoin (3rd trimester)
Shehata HA, Nelson-Piercy C. Drugs in pregnancy.
Drugs to avoid. Best Pract Res Clin Obstet
Gynaecol. 2001 15(6)971-86
58
Natural Remedies
  • Black Cohosh
  • used for treating symptoms of PMS
  • can produce uterine contractions
  • Chamomile
  • used in inflammation of the skin, mouth, throat
    colds
  • contains hydroxycoumarin, which is a relative of
    the coumarin anticoagulants
  • Ma Huang / Ephedra
  • used for treating sinus congestion, cold and
    "natural weight-loss treatment
  • over 1000 reports of potential adverse
    occurrences have been registered with the FDA
    regarding cardiovascular events
  • adverse events have included kidney stones and
    hepatic injury

59
Natural Remedies
  • Quinine
  • used for treating malaria, muscle cramps, fever,
    GIT disturbances
  • has been used as a drug to promote abortion
  • should be avoided during pregnancy because of a
    risk for causing miscarriage or stillbirth
  • Iodides
  • can be purchased in some remedies for treating
    symptoms of a cold or the flu
  • can cause fetal thyroid gland dysfunction when
    used after 1st trimester
  • St. John's Wort
  • a very weak antidepressant
  • not recommend during pregnancy due to its
    uterotonic effects
  • no side effects were observed in infants during
    breastfeeding

60
Elicit Drugs
  • amphetamines, and heroin, according to a 2003
    study by the CDC and Prevention
  • These and other illicit drugs may pose various
    risks for unborn babies and pregnant women
  • Some of these drugs can cause a baby to be born
    too small or to have withdrawal symptoms, birth
    defects, or learning or behavioral problems
  • However, because most pregnant women who use
    illicit drugs also use alcohol and tobacco (which
    also pose risks to unborn babies), it often is
    difficult to determine which health problems are
    caused by a specific illicit drug

61
Cocaine
  • Increase the risk of miscarriage
  • preterm labour or IUGR
  • Increased risk of lifelong disabilities such as
    mental retardation and cerebral palsy
  • Cocaine-exposed babies also tend to have smaller
    heads, which generally reflect smaller brains
  • Some studies suggest that cocaine-exposed babies
    are at increased risk of birth defects, including
    urinary-tract defects and, possibly, heart
    defects
  • Cocaine also may cause an unborn baby to have a
    stroke, which can result in irreversible brain
    damage or a heart attack, and sometimes death.
  • placental abruption
  • Feeding difficulties and sleep disturbances,
    jittery and irritable.
  • Greater chance of dying of sudden infant death
    syndrome (SIDS).

62
Marijuana
  • IUGR. These effects are seen mainly in women who
    use marijuana regularly (6 or more times a week)
  • Premature delivery
  • After delivery, some babies undergo
    withdrawal-like symptoms including excessive
    crying and trembling
  • Couples who are planning pregnancy also should
    keep in mind that marijuana can reduce fertility
    in both men and women, making it more difficult
    to conceive
  • Some did not find any increased risk of learning
    or behavioral problems, however, others found
    children are more likely to have subtle problems
    that affect their ability to pay attention and to
    solve visual problems
  • Exposed children do not appear to have a decrease
    in IQ

63
Ecstasy amphetamines
  • The use of Ecstasy has increased dramatically in
    recent years. To date there have been few studies
    on how the drug may affect pregnancy
  • One small study did find a possible increase in
    congenital heart defects and, in females only,
    clubfoot
  • Babies exposed to Ecstasy before birth also may
    face some of the same risks as babies exposed to
    other types of amphetamines
  • Methylamphetamine, also known as speed, ice,
    crank and crystal meth may cause an increased
    risk of birth defects, including cleft palate,
    and heart and limb defects
  • Contribute to maternal high blood pressure 
    IUGR, premature delivery, and PPH
  • After birth, babies who were exposed to
    amphetamines appear to undergo withdrawal-like
    symptoms, including jitteriness, drowsiness and
    breathing problems.

64
Heroin
  • Common complications include miscarriage,
    placental abruption, poor fetal growth, premature
    rupture of the membranes, premature delivery and
    stillbirth
  • Low birthweight and serious prematurity-related
    health problems during the newborn period,
    including breathing problems and brain bleeds,
    sometimes leading to lifelong disabilities
  • Most babies of heroin users suffer from
    withdrawal symptoms after birth, including fever,
    sneezing, trembling, irritability, diarrhea,
    vomiting, continual crying and, occasionally,
    seizures
  • Babies exposed to heroin before birth also face a
    ten-fold increased risk of sudden infant death
    syndrome (SIDS)

65
Heroin
  • A pregnant woman who uses heroin should not
    attempt to suddenly stop taking the drug as this
    can put her baby at increased risk of miscarriage
    or premature birth
  • She should consult a doctor or drug treatment
    center about treatment with methadone
  • Although infants born to mothers taking methadone
    also may show some signs of dependence on the
    drug, they can be safely treated in the nursery
    and generally do far better than babies born to
    women who continue to use heroin
  • Some studies suggest that children exposed to
    heroin before birth are at increased risk of low
    IQ (in the mentally retarded range) and of
    serious behavioral problems

66
(No Transcript)
67
Teratogen Information Services
  • United Kingdom
  • National Teratology Information Service (NTIS)
  • Newcastle (191) 232 1525
  • United States
  • Organization of Teratology Information Services
  • Utah (801) 328-2229 (for referral to nearest
    service)
  • World Wide Web address http//orpheus.uscd.edu/ct
    is/
  • Canada
  • Motherisk Program
  • Toronto (416) 813-6780
  • World Wide Web address http//www.motherisk.org

68
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