Hypertension in pregnancy

 Pregnancy related blood pressure problems (such as pregnancy-induced hypertension or pre-

eclampsia) do not occur before 20 weeks. The raised ambulatory blood pressure readings
exclude a diagnosis of white-coat hypertension.

Note the use of the term 'pre-existing hypertension' rather than essential hypertension. Raised
blood pressure in a 36-year-old femaleis not that common and raises the possibility of
secondary hypertension.

NICE published guidance in 2010 on the management of hypertension in pregnancy. They also
made recommendations on reducing the risk of hypertensive disorders developing in the first
place. Women who are at high risk of developing pre-eclampsia should take aspirin 75mg od
from 12 weeks until the birth of the baby. High risk groups include:

 hypertensive disease during previous pregnancies

 chronic kidney disease
 autoimmune disorders such as SLE or antiphospholipid syndrome
 type 1 or 2 diabetes mellitus

The classification of hypertension in pregnancy is complicated and varies. Remember, in normal

pregnancy:

 blood pressure usually falls in the first trimester (particularly the diastolic), and
continues to fall until 20-24 weeks
 after this time the blood pressure usually increases to pre-pregnancy levels by term

Hypertension in pregnancy in usually defined as:

 systolic > 140 mmHg or diastolic > 90 mmHg

 or an increase above booking readings of > 30 mmHg systolic or > 15 mmHg diastolic

After establishing that the patient is hypertensive they should be categorised into one of the
following groups

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 Pregnancy-induced
hypertension 
(PIH, also known as
Pre-existing hypertension gestational hypertension) Pre-eclampsia

A history of hypertension Hypertension (as defined Pregnancy-induced

before pregnancy or an
elevated blood pressure >
140/90 mmHg before 20
weeks gestation
No proteinuria, no
oedema  Occurs in around 5-7% of
Occurs in 3-5% of
pregnancies and is more
common in older women
above) occurring in the second hypertension in
half of pregnancy (i.e. after 20 association with
weeks) proteinuria (> 0.3g /
24 hours)
No proteinuria, no oedema 
Oedema may occur
but is now less
pregnancies commonly used as a
criteria
Resolves following birth
(typically after one month). Occurs in around 5%
Women with PIH are at of pregnancies
increased risk of future pre-
eclampsia or hypertension
later in life

Pre-eclampsia
There is some evidence to suggest that pre-eclampsia is actually less common in smokers
Transverse myelitis is not associated with pre-eclampsia.

Severe pre-eclampsia is associated with hyperreflexia and clonus. A low platelet count may
indicate the patient is developing HELLP syndrome
Pre-eclampsia is a condition seen after 20 weeks gestation characterised by pregnancy-induced
hypertension in association with proteinuria (> 0.3g / 24 hours). Oedema used to be third
element of the classic triad but is now often not included in the definition as it is not specific

Pre-eclampsia is important as it predisposes to the following problems

 fetal: prematurity, intrauterine growth retardation

 eclampsia
 haemorrhage: placental abruption, intra-abdominal, intra-cerebral
 cardiac failure
 multi-organ failure

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Risk factors

 > 40 years old

 nulliparity (or new partner)
 multiple pregnancy
 body mass index > 30 kg/m^2
 diabetes mellitus
 pregnancy interval of more than 10 years
 family history of pre-eclampsia
 previous history of pre-eclampsia
 pre-existing vascular disease such as hypertension or renal disease

Features of severe pre-eclampsia

 hypertension: typically > 170/110 mmHg and proteinuria as above

 proteinuria: dipstick ++/+++
 headache
 visual disturbance
 papilloedema
 RUQ/epigastric pain
 hyperreflexia
 platelet count < 100 * 106/l, abnormal liver enzymes or HELLP syndrome

Management

 consensus guidelines recommend treating blood pressure > 160/110 mmHg although
many clinicians have a lower threshold
 oral labetalol is now first-line following the 2010 NICE guidelines. Nifedipine and
hydralazine may also be used
 delivery of the baby is the most important and definitive management step. The timing
depends on the individual clinical scenario.

Meera has developed pre-eclampsia as she now has a blood pressure above 140/90mmHg and
has developed proteinuria (greater than and including 1+ of protein). Therefore according to
NICE guidelines she should be admitted to an obstetric unit urgently for monitoring and / or
treatment. 
The following table is from the NICE Guidelines on 'Hypertension in Pregnancy' in 2010:
Management of Pregnancy with Pre-eclampsia

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 Mild Hypertension
Degree of (140/90 to Moderate Hypertension Severe Hypertension
Hypertension 149/99mmHg) (150/100 to 159/109mmHg) (160/110mmHg onwards)

Admit to Yes Yes Yes

Hospital

Treat? No With oral labetalol as first- With oral labetalol as

line treatment first-line treatment

Measure BP At least four times a day At least four times a day More than four times a
day

Antenatal care: timetable:

NICE issued guidelines on routine care for the healthy pregnant woman in March 2008.

 10 antenatal visits in the first pregnancy if uncomplicated

 7 antenatal visits in subsequent pregnancies if uncomplicated
 women do not need to be seen by a consultant if the pregnancy is uncomplicated

4
Gestation Purpose of visit

8 - 12 weeks (ideally < 10 Booking visit

weeks)
 general information e.g. diet, alcohol, smoking, folic acid, vitamin D,
antenatal classes
 BP, urine dipstick, check BMI

Booking bloods/urine

 FBC, blood group, rhesus status, red cell alloantibodies,

haemoglobinopathies
 hepatitis B, syphilis, rubella
 HIV test is offered to all women
 urine culture to detect asymptomatic bacteriuria

10 - 13+6 weeks Early scan to confirm dates, exclude multiple pregnancy

11 - 13+6 weeks Down's syndrome screening including nuchal scan

16 weeks Information on the anomaly and the blood results. If Hb < 11 g/dl consider iron
Routine care: BP and urine dipstick

18 - 20+6 weeks Anomaly scan

25 weeks (only if primip) Routine care: BP, urine dipstick, symphysis-fundal height (SFH)

28 weeks Routine care: BP, urine dipstick, SFH

Second screen for anaemia and atypical red cell alloantibodies. If Hb < 10.5 g/dl
consider iron
First dose of anti-D prophylaxis to rhesus negative women

31 weeks (only if primip) Routine care

34 weeks Routine care + Second dose of anti-D prophylaxis to rhesus negative women*
Information on labour and birth plan

36 weeks Routine care + Check presentation - offer external cephalic version if indicated
Information on breast feeding, vitamin K, 'baby-blues'

38 weeks Routine care

40 weeks (only if primip) Routine care +

Discussion about options for prolonged pregnancy

41 weeks Routine care +

Discuss labour plans and possibility of induction

5
*the evidence base suggests that there is little difference in the efficacy of single-dose (at 28
weeks) and double-dose regimes (at 28 & 34 weeks). For this reason the RCOG in 2011 advised
that either regime could be used 'depending on local factors'
Routine auscultation for the fetal heart is not recommended by NICE. However, the guidelines
suggest that when requested by the mother, auscultation of the fetal heart may provide
reassurance.

NICE have recently updated their guidelines. Women who are at risk of gestational diabetes
should have an oral glucose tolerance test as soon as possible after booking, rather than waiting
to 16-18 weeks as was previously advocated.e,g.previous preg with GDM.
Antenatal care: routine glucose testing no longer recommended

Many centres now perform the early ultrasound scan and nuchal scan at the same time

Rhesus negative woman - anti-D at 28 + 34 weeks

NICE recommend giving rhesus negative woman anti-D at 28 weeks followed by a second dose
at 34 weeks
Surprisingly perhaps, NICE now recommends that blood glucose is only checked to those
considered at risk (e.g. obesity, previous macrosomic baby, family history, Asian ethnicity)

Diabetes in pregnancy: detailed heart scan at 18-20 weeks.

 thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks

gestation - helps to determine risk of neonatal thyroid problems
 serum thyroid stimulating hormone measured in each trimester and 6-8 weeks post-
partum

Symphysis-fundal height

After 20 weeks, symphysis-fundal height in cm = gestation in weeks

 The symphysis-fundal height (SFH) is measured from the top of the pubic bone to the
top of the uterus in centimetres

It should match the gestational age in weeks to within 2 cm after 20 weeks, e.g. if 24
weeks then the a normal SFH = 22 to 26 cm
Ultrasound in pregnancy

A nuchal scan is performed at 11-13 weeks. Causes of an increased nuchal translucency include:

 Down's syndrome

6
  congenital heart defects
 abdominal wall defects

Causes of hyperechogenic bowel:

 cystic fibrosis
 Down's syndrome
 cytomegalovirus infection

Biophysical profile

A biophysical profile is an antenatal ultrasound test which assesses:

 amniotic fluid volume

 fetal tone
 fetal activity
 fetal breathing movements
 reactivity of the heart

Oligohydramnios

An amniotic fluid volume of 440ml indicates oligohydramnios. Tracheo-oesophageal fistula is

associated with polyhydramnios.
In oligohydramnios there is reduced amniotic fluid. Definitions vary but include less than 500ml
at 32-36 weeks and an amniotic fluid index (AFI) < 5th percentile.

Causes

 premature rupture of membranes

 fetal renal problems e.g. renal agenesis
 intrauterine growth restriction
 post-term gestation
 pre-eclampsia

Antenatal care: specific points

NICE issued guidelines on routine care for the healthy pregnant woman in March 2008

Nausea and vomiting

Vomiting in pregnancy: antihistamines are first-line

7
  natural remedies - ginger and acupuncture on the 'p6' point (by the wrist) are
recommended by NICE
 antihistamines should be used first-line (BNF suggests promethazine as first-line)

Vitamin D

 NICE recommend 'All women should be informed at the booking appointment about the
importance for their own and their baby's health of maintaining adequate vitamin D
stores during pregnancy and whilst breastfeeding'
 'women may choose to take 10 micrograms of vitamin D per day, as found in the
Healthy Start multivitamin supplement'. This was confirmed in 2012 when the Chief
Medical Officer advised: 'All pregnant and breastfeeding women should take a daily
supplement containing 10micrograms of vitamin D, to ensure the mothers requirements
for vitamin D are met and to build adequate fetal stores for early infancy'
 particular care should be taken with women at risk (e.g. Asian, obese, poor diet)

Alcohol

 NICE recommend women should avoid alcohol during the first trimester
 if women choose to drink alcohol during pregnancy they should be advised to drink no
more than 1 to 2 UK units once or twice a week

Vitamin D supplementation

10mcg vitamin D is now recommended throughout pregnancy for all women.

Low dose folic acid is recommended for all women for the first 12 weeks of pregnancy. Women
with pregnancies at risk of neural tube defects should take 5mg folic acid for the first 12 weeks
of pregnancy. 

Pregnancies at high risk of neural tube defects are those in which either partner has a neural
tube defect (or either partner has a family history of neural tube defects), if they have had a
previous pregnancy affected by a neural tube defect, or if the woman has coeliac disease (or
other condition causing malabsorption), diabetes mellitus, sickle-cell anaemia, or is taking
antiepileptic medicines. 

Soft-cheese should be avoided during pregnancy due to the risk of Listeria.

Vitamin D supplementation has been a hot topic for a number of years now. The muddied
waters are now slightly clearer following the release of the following:

 2012: letter by the Chief Medical Officer regarding vitamin D supplementation

 2013: National Osteoporosis Society (NOS) release UK Vitamin D guideline

8
The following groups should be advised to take vitamin D supplementation:

 all pregnant and breastfeeding women should take a daily supplement containing 10µg
of vitamin D
 all children aged 6 months - 5 years. Babies fed with formula milk do not need to take a
supplement if they are taking more than 500ml of milk a day, as formula milk is fortified
with vitamin D
 adults > 65 years
 'people who are not exposed to much sun should also take a daily supplement'

Testing for vitamin D deficiency

The key message is that not many people warrant a vitamin D test. The NOS guidelines specify
that testing may be appropriate in the following situtations:

 patients with bone diseases that may be improved with vitamin D treatment e.g. known
osteomalacia or Paget's disease
 patients with bone diseases, prior to specific treatment where correcting vitamin
deficiency is appropriate e,g, prior to intravenous zolendronate or denosumab
 patients with musculoskeletal symptoms that could be attributed to vitamin D
deficiency e.g. bone pain ?osteomalacia

Patients with osteoporosis should always be given calcium/vitamin D supplements to testing is

not considered necessary. People who are at higher risk of vitamin D deficiency (see above)
should be treated anyway so again testing is not necessary.
The NHS advises that all pregnant and breastfeeding women should take a daily supplement of
vitamin D 10mcg for the bone health of themselves and their child. Some women may be
eligible for free supplements, if they qualify for Healthy Start vouchers; the Health Visitor can
advise. 

Folic acid 400mcg is recommended for women trying to conceive through to 12 weeks
gestation. A B12 supplement may be indicated for breastfeeding women who eat a vegan diet.
Pregnant women should be advised that if they wish to take a multivitamin tablet, to ensure it
does not contain vitamin A, as this can be teratogenic in high doses.

Pregnancy: thyroid problems

Propylthiouracil is traditionally taught as the antithyroid drug of choice in pregnancy. This

approach was supported by the 2007 Endocrine Society consensus guidelines. It also has the
advantage of being excreted to a lesser extent than carbimazole in breast milk. 

9
Despite this some endocrinologists use carbimazole and the BNF states both drugs may be used
in pregnancy. Carbimazole has rarely been associated with aplasia cutis of the neonate
In pregnancy there is an increase in the levels of thyroxine-binding globulin (TBG). This causes
an increase in the levels of total thyroxine but does not affect the free thyroxine level

Thyrotoxicosis

Untreated thyrotoxicosis increases the risk of fetal loss, maternal heart failure and premature
labour

Graves' disease is the most common cause of thyrotoxicosis in pregnancy. It is also recognised
that activation of the TSH receptor by HCG may also occur - often termed transient gestational
hyperthyroidism. HCG levels will fall in second and third trimester

Management

 propylthiouracil has traditionally been the antithyroid drug of choice. This approach was
supported by the 2007 Endocrine Society consensus guidelines
 maternal free thyroxine levels should be kept in the upper third of the normal reference
range to avoid fetal hypothyroidism
 thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks
gestation - helps to determine risk of neonatal thyroid problems
 block-and-replace regimes should not be used in pregnancy
 radioiodine therapy is contraindicated

Hypothyroidism

Key points

 thyroxine is safe during pregnancy

 serum thyroid stimulating hormone measured in each trimester and 6-8 weeks post-
partum
 some women require an increased dose of thyroxine during pregnancy
 breast feeding is safe whilst on thyroxine

Amniocentesis

Amniocentesis: performed at 16 weeks, karyotype after 3 weeks

Some laboratories are now able to detect Down's syndrome using fluorescence in-situ
hybridisation (FISH) in 2 days, but full karyotyping takes 3 weeks

10
Amniocentesis is a procedure used in prenatal diagnosis. It may be offered after screening tests
have indicated a high risk of fetal abnormality or in women considered to be at high risk, for
example if > 35 years old.
Around 20 ml of fluid is removed by transabdominal needle under ultrasound guidance. Fetal
cells present in the amniotic fluid are then studied to aid the diagnosis of a number of
conditions. 
Amniocentesis is usually performed at 16 weeks and the risk of fetal loss is 0.5-1%. The
karyotype results typically take 3 weeks. It is known the karyotype may be wrong in 1/1000
cases due to maternal cells being present

Conditions which may be diagnosed

 neural tube defects (raised AFP levels in the amniotic fluid)

 chromosomal disorders
 inborn errors of metabolism

Down's syndrome: epidemiology and genetics

Risk of Down's syndrome with increasing maternal age

Age (years) Risk

20 1 in 1,500

30 1 in 800

35 1 in 270

40 1 in 100

45 1 in 50 or greater

One way of remembering this is by starting at 1/1,000 at 30 years and then dividing the
denominator by 3 (i.e. 3 times more common) for every extra 5 years of age 

Cytogenetics

Mode % of cases Risk of recurrence

11
 Mode % of cases Risk of recurrence

Robertsonian translocation 5% 10-15% if mother is translocation carrier

(usually onto 14) 2.5% if father is translocation carrier

Mosaicism 1%

The chance of a further child with Down's syndrome is approximately 1 in 100 if the mother is
less than 35 years old. If the trisomy 21 is a result of a translocation the risk is much higher

Down's syndrome: antenatal testing

Down's - antenatal screening: Nuchal translucency + B-HCG + pregnancy associated plasma

protein A.

NICE issued guidelines on antenatal care in March 2008 including advice on screening for
Down's syndrome.

 the combined test is now standard: nuchal translucency measurement + serum B-HCG +
pregnancy associated plasma protein A
 these tests should be done between 11 - 13+6 weeks
 if women book later in pregnancy either the triple* or quadruple test** should be
offered between 15 - 20 weeks

*alpha-fetoprotein, unconjugated oestriol, human chorionic gonadotrophin

**alpha-fetoprotein, unconjugated oestriol, human chorionic gonadotrophin and inhibin-A

Results of the screening test are expressed as a ratio. The NHS Fetal Anomaly Screening
Program categorise the results into two categories:

 Lower risk results: Risk lower than 1:150 (the second number is higher than 150). Over
95% of test results will show a lower risk result. A lower-risk result does not mean that
the baby definitely does not have Down syndrome. About 15% of babies with Down
syndrome are not detected by screening tests. If a patient has a lower risk result they
will not be offered a further test for Down syndrome.

 Higher risk results: Risk above 1:150 (between 1 in 2 to 1 in 150). This does not mean
the baby definitely has Down syndrome. If the patient has a higher risk result they will

12
 be offered a diagnostic test to find out whether their baby has Down syndrome or not. It
is the patient's choice whether or not to have the further test.

Diagnostic tests include chorionic villus sampling and amniocentesis

Down syndrome screening can be divided into the different screening tests available for
patients:

Test Dates Available What is tested?

Combined 10 weeks + 0 days to Ultrasound Nuchal Translucency (NT)

Test 14 weeks + 1 day measurement, free beta hCG and PAPP-A
gestation

Quadruple 14 weeks + 2 days to AFP (alpha-fetoprotein), free beta hCG (human

Test 20 weeks gestation chorionic gonadotropin), inhibin-A, oestriol

Integrated 10 weeks + 0 days to Ultrasound NT measurement, free beta hCG,

Test 20 weeks gestation PAPP-A (pregnancy-associated plasma protein A),
AFP, inhibin-A, oestriol

Breech presentation

Breech presentation risk factors - uterine malformations, placenta praevia, polyhydramnios or

oligohydramnios

In a breech presentation the caudal end of the fetus occupies the lower segment. Whilst
around 25% of pregnancies at 28 weeks are breech it only occurs in 3% of babies near term. A
frank breech is the most
common presentation with the hips flexed and knees fully extended. A footling breech, where
one or both feet come first with the bottom at a higher position, is rare but carries a higher
perinatal morbidity

Risk factors for breech presentation

 uterine malformations, fibroids

 placenta praevia
 polyhydramnios or oligohydramnios
 fetal abnormality (e.g. CNS malformation, chromosomal disorders)
 prematurity (due to increased incidence earlier in gestation)

13
Cord prolapse is more common in breech presentations

Management

if < 36 weeks: many fetuses will turn spontaneously

 if still breech at 36 weeks NICE recommend external cephalic version (ECV)- this has a
success rate of around 60%. The RCOG recommend ECV should be offered from 36
weeks in nulliparous women and from 37 weeks in multiparous women
 if the baby is still breech then delivery options include planned caesarean section or
vaginal delivery

Information to help decision making - the RCOG recommend:

 'Women should be informed that planned caesarean section carries a reduced perinatal
mortality and early neonatal morbidity for babies with a breech presentation at term
compared with planned vaginal birth.'
 'Women should be informed that there is no evidence that the long term health of
babies with a breech presentation delivered at term is influenced by how the baby is
born.'

Pregnancy: diabetes mellitus

The oral glucose tolerance test remains the investigation of choice for gestational diabetes

NICE have recently updated their guidelines. Women who are at risk of gestational diabetes
should have an oral glucose tolerance test as soon as possible after booking, rather than waiting
to 16-18 weeks as was previously advocated.
Insulin should be started straight away given the blood glucose levels and evidence of
macrosomia. Aspirin should also be considered as she is at increased risk of pre-eclampsia.
Diabetes mellitus may be a pre-existing problem or develop during pregnancy, gestational
diabetes. It complicates around 1 in 40 pregnancies. NICE updated the guidance in 2015

Risk factors for gestational diabetes

 BMI of > 30 kg/m²

 previous macrosomic baby weighing 4.5 kg or above
 previous gestational diabetes
 first-degree relative with diabetes
 family origin with a high prevalence of diabetes (South Asian, black Caribbean and
Middle Eastern)

14
Screening for gestational diabetes

 women who've previously had gestational diabetes: oral glucose tolerance test (OGTT)
should be performed as soon as possible after booking and at 24-28 weeks if the first
test is normal. NICE also recommend that early self-monitoring of blood glucose is an
alternative to the OGTTs
 women with any of the other risk factors should be offered an OGTT at 24-28 weeks

Diagnostic thresholds for gestational diabetes

 these have recently been updated by NICE, gestational diabetes is diagnosed if either:
 fasting glucose is >= 5.6 mmol/l
 2-hour glucose is >= 7.8 mmol/l

Management of gestational diabetes

 newly diagnosed women should be seen in a joint diabetes and antenatal clinic within a
week
 women should be taught about selfmonitoring of blood glucose
 advice about diet (including eating foods with a low glycaemic index) and exercise
should be given
 if the fasting plasma glucose level is < 7 mmol//l a trial of diet and exercise should be
offered
 if glucose targets are not met within 1-2 weeks of altering diet/exercise metformin
should be started
 if glucose targets are still not met insulin should be added to diet/exercise/metformin
 if at the time of diagnosis the fasting glucose level is >= 7 mmol/l insulin should be
started
 if the plasma glucose level is between 6-6.9 mmol/l, and there is evidence of
complications such as macrosomia or hydramnios, insulin should be offered
 glibenclamide should only be offered for women who cannot tolerate metformin or
those who fail to meet the glucose targets with metformin but decline insulin treatment

NICE have recently changed their gestational diabetes guidelines. Insulin should be started in
the fasting glucose is >= 7 mmol/l. Aspirin should also be considered given the increased risk of
pre-eclampsia.

Management of pre-existing diabetes

 weight loss for women with BMI of > 27 kg/m^2

 stop oral hypoglycaemic agents, apart from metformin, and commence insulin

15
  folic acid 5 mg/day from pre-conception to 12 weeks gestation
 detailed anomaly scan at 20 weeks including four-chamber view of the heart and
outflow tracts
 tight glycaemic control reduces complication rates
 treat retinopathy as can worsen during pregnancy

Diabetes in pregnancy: detailed heart scan at 18-20 weeks

Targets for self monitoring of pregnant women (pre-existing and gestational diabetes)

Time Target

Fasting 5.3 mmol/l

1 hour after meals 7.8 mmol/l, or:

2 hour after meals 6.4 mmol/l

Patients with diabetes (type 1 and 2) should take aspirin 75mg daily from 12 weeks gestation to
reduce the risk of pre-eclampsia. They are also at higher risk of neural tube defects, therefore
should take the higher dose of folic acid, 5mg daily, whilst trying to conceive until 12 weeks
gestation. Pregnant women who have risk factors such as this should be referred at booking to
Consultant lead antenatal care. 

All pregnant and breastfeeding women are advised to take vitamin D 10mcg daily.

A vitamin B12 supplement may be advised for pregnant women who eat a vegan diet. 

Pregnancy: diabetes - complications

Maternal complications

 polyhydramnios - 25%, possibly due to fetal polyuria

 preterm labour - 15%, associated with polyhydramnios

Neonatal complications

 macrosomia (although diabetes may also cause small for gestational age babies)
 hypoglycaemia (secondary to beta cell hyperplasia)

16
  respiratory distress syndrome: surfactant production is delayed
 polycythaemia: therefore more neonatal jaundice
 malformation rates increase 3-4 fold e.g. sacral agenesis, CNS and CVS malformations
(hypertrophic cardiomyopathy)
 stillbirth
 hypomagnesaemia
 hypocalcaemia
 shoulder dystocia (may cause Erb's palsy)

Bacterial vaginosis ( see in Gyne )

This history and presence of clue cells suggests a diagnosis of bacterial vaginosis. The BNF
suggests topical clindamycin as an alternative treatment for patients who are allergic to
metronidazole.
Bacterial vaginosis increases the risk of miscarriage and premature birth. There is increasing
evidence that metronidazole is safe in pregnancy. Of note there is no evidence of teratogenicity
with its use in the first trimester of pregnancy. The guidelines recommend the treatment of
symptomatic patients at all stages of pregnancy. Metronidazole and oral clindamycin enter
breast milk. Clindamycin intravaginal gel is recommended for breast feeding women.

Chickenpox exposure in pregnancy

If a non-immune pregnant patient is exposed to chicken pox she sould be offered VZIG as soon
as possible. VZIG is effective when given up to 10 days after contact (in the case of continuous
exposures, this is defined as 10 days from the appearance of the rash in the index case).

A second dose of VZIG may be required if a further exposure is reported and 3 weeks have
elapsed since the last dose. 

Chickenpox exposure in pregnancy - if not immune give VZIG

The negative IgG indicates no previous exposure to chickenpox

Chickenpox is caused by primary infection with varicella zoster virus. Shingles is reactivation of
dormant virus in dorsal root ganglion. In pregnancy there is a risk to both the mother and also
the fetus, a syndrome now termed fetal varicella syndrome.

Risks to the mother

 5 times greater risk of pneumonitis

17
Fetal varicella syndrome (FVS)

 risk of FVS following maternal varicella exposure is around 1% if occurs before 20 weeks
gestation
 studies have shown a very small number of cases occurring between 20-28 weeks
gestation and none following 28 weeks
 features of FVS include skin scarring, eye defects (microphthalmia), limb hypoplasia,
microcephaly and learning disabilities

Other risks to the fetus

 shingles in infancy: 1-2% risk if maternal exposure in the second or third trimester
 severe neonatal varicella: if mother develops rash between 5 days before and 2 days
after birth there is a risk of neonatal varicella, which may be fatal to the newborn child
in around 20% of cases

Management of chickenpox exposure

 if there is any doubt about the mother previously having chickenpox maternal blood
should be urgently checked for varicella antibodies
 if the pregnant women is not immune to varicella she should be given varicella zoster
immunoglobulin (VZIG) as soon as possible. RCOG and Greenbook guidelines suggest
VZIG is effective up to 10 days post exposure
 consensus guidelines suggest oral aciclovir should be given if pregnant women with
chickenpox present within 24 hours of onset of the rash
 Chickenpox exposure in pregnancy - first step is to check antibodies

If there is any doubt about the mother previously having chickenpox maternal blood should
be checked for varicella antibodies

Urinary tract infection in adults: management

A test of cure MSU should be sent in pregnant women treated for a UTI

Pregnant women should be prescribed a 7 day course of antibiotics. Nitrofurantoin should only
be avoided in the third trimester
Amoxicillin is also recommended in this situation ( 38 wks preg ). Nitrofurantoin should be
avoided near term as it may cause neonatal haemolysis but it may be used earlier in the
pregnancy.

18
This lady is highly likely to have a urinary tract infection so advising her just to use cranberry
juice is inappropriate

Asymptomatic bacteriuria in pregnant women

 1. repeat MSU
 2. if confirmed treat with amoxicillin or a cephalosporin

SIGN advise that pregnant women with asymptomatic bacteriuria should have a second urine
culture to confirm the result.
Lower urinary tract infections in non-pregnant women

 local antibiotic guidelines should be followed if available

 2012 SIGN guidelines recommend trimethoprim or nitrofurantoin for 3 days

Pregnant women with symptomatic bacteriuria should be treated with an antibiotic for
7 days. A urine culture should be sent. For asymptomatic pregnant women:

 a urine culture should be performed routinely at the first antenatal visit

 if positive, a second urine culture should be sent to confirm the presence of bacteriuria
 SIGN recommend to treat asymptomatic bacteriuria detected during pregnancy with an
antibiotic
 a 7 day course of antibiotics should be given
 a further urine culture should be sent following completion of treatment as a test of
cure

For patients with sign of acute pyelonephritis hospital admission should be considered

 local antibiotic guidelines should be followed if available

 the BNF currently recommends a broad-spectrum cephalosporin or a quinolone for 10-
14 days

Hyperemesis gravidarum

Smoking is associated with a decreased incidence of hyperemesis gravidarum

Hyperemesis gravidarum describes excessive vomiting during pregnancy. It occurs in around 1%

of pregnancies and is thought to be related to raised beta hCG levels. Hyperemesis gravidarum
is most common between 8 and 12 weeks but may persist up to 20 weeks*.

19
Associations

 multiple pregnancies
 trophoblastic disease
 hyperthyroidism
 nulliparity
 obesity

Smoking is associated with a decreased incidence of hyperemesis

Management

 antihistamines should be used first-line (BNF suggests promethazine as first-line)

 ginger and P6 (wrist) acupressure: NICE Clinical Knowledge Summaries suggest these
can be tried but there is little evidence of benefit
 admission may be needed for IV hydration

Complications

 Wernicke's encephalopathy
 Mallory-Weiss tear
 central pontine myelinolysis
 acute tubular necrosis
 fetal: small for gestational age, pre-term birth

*and in very rare cases beyond 20 weeks

Puerperal pyrexia

Puerperal pyrexia may be defined as a temperature of > 38ºC in the first 14 days following
delivery.

Causes:

 endometritis: most common cause

 urinary tract infection
 wound infections (perineal tears + caesarean section)
 mastitis
 venous thromboembolism

20
Management

 if endometritis is suspected the patient should be referred to hospital for intravenous

antibiotics (clindamycin and gentamicin until afebrile for greater than 24 hours)

Alpha feto-protein

AFP 

 raised in neural tubes defects

 decreased in Down's syndrome

Alpha-fetoprotein (AFP) is a protein produced by the developing fetus

Increased AFP Decreased AFP

Neural tube defects (meningocele, myelomeningocele Down's syndrome

and anencephaly) Trisomy 18
Abdominal wall defects (omphalocele and gastroschisis) Maternal diabetes
Multiple pregnancy mellitus

Prescribing in pregnant patients

orlistat is not a known teratogen it should be used with 'caution' in pregnancy according to the
BNF and the benefits are very likely outweighed by risks.
Very few drugs are known to be completely safe in pregnancy. The list below largely comprises
of those known to be harmful. Some countries have developed a grading system - see the link.

Antibiotics

 tetracyclines
 aminoglycosides
 sulphonamides and trimethoprim
 quinolones: e.g ciprofloxacin the BNF advises to avoid due to arthropathy in some
animal studies

21
Other drugs

 ACE inhibitors, angiotensin II receptor antagonists

 statins
 warfarin
 sulfonylureas
 retinoids (including topical)
 cytotoxic agents

The majority of antiepileptics including valproate, carbamazepine and phenytoin are known to
be potentially harmful. The decision to stop such treatments however is difficult as
uncontrolled epilepsy is also a risk
Warfarin is contraindicated in pregnancy. Most women are switched to low-molecular weight
heparin for the duration of the pregnancy.
The BNF advises avoiding quinolones in pregnancy due to arthropathy in animal studies.

There have been some reports of an increased risk of necrotizing enterocolitis following the use
of co-amoxiclav in pregnancy. The evidence is however inconclusive and the BNF states that co-
amoxiclav is 'not known to be harmful'. A link is provided both to the BNF and the UK teratology
information service.
Folic acid

Folic acid is converted to tetrahydrofolate (THF). Green, leafy vegetables are a good source of
folic acid.

Functions

 THF plays a key role in the transfer of 1-carbon units (e.g. methyl, methylene, and
formyl groups) to the essential substrates involved in the synthesis of DNA & RNA

Causes of folic acid deficiency:

 phenytoin
 methotrexate
 pregnancy
 alcohol excess

Consequences of folic acid deficiency:

 macrocytic, megaloblastic anaemia

22
  neural tube defects

Women are advised to take folic acid 400mcg when trying to conceive through to 12 weeks
gestation to reduce the incidence of neural tube defects. A higher dose of 5mg is indicated if
there are additional risk factors eg. diabetes or personal or family history of neural tube
defects. A daily supplement of vitamin D 10mcg is also advised throughout pregnancy for bone
health, and should be continued for the duration of breastfeeding. If a woman chooses to take
a multivitamin in pregnancy, she should be advised to ensure it does not contain vitamin A
(retinol) as it is teratogenic in high doses.

Breast feeding: contraindications

Ovarian cancer, rather than endometrial, is associated with familial breast cancer.

The major breastfeeding contraindications tested in exams relate to drugs (see below). Other
contraindications of note include:

 galactosaemia
 viral infections - this is controversial with respect to HIV in the developing world. This is
because there is such an increased infant mortality and morbidity associated with bottle
feeding that some doctors think the benefits outweigh the risk of HIV transmission

The following drugs can be given to mothers who are breast feeding:

Breast feeding is acceptable with nearly all anti-epileptic drugs

The BNF states 'breast-feeding is acceptable with all antiepileptic drugs, taken in normal doses,
with the possible exception of barbiturates.

 antibiotics: penicillins, cephalosporins, trimethoprim

 endocrine: glucocorticoids (avoid high doses), levothyroxine*
 epilepsy: sodium valproate, carbamazepine , lamotrigine , phenytoin .
 asthma: salbutamol, theophyllines
 psychiatric drugs: tricyclic antidepressants, antipsychotics**
 hypertension: beta-blockers, hydralazine, methyldopa
 anticoagulants: warfarin, heparin
 digoxin

The following drugs should be avoided:

 antibiotics: ciprofloxacin, tetracycline, chloramphenicol, sulphonamides

 psychiatric drugs: lithium, benzodiazepines
 aspirin

23
  carbimazole
 sulphonylureas
 cytotoxic drugs
 amiodarone

*the BNF advises that the amount is too small to affect neonatal hypothyroidism screening

**clozapine should be avoided.

Breastfeeding problems

Mastitis

Mastitis affects around 1 in 10 breast feeding women. The BNF advises to treat 'if systemically
unwell, if nipple fissure present, if symptoms do not improve after 12-24 hours of effective milk
removal of if culture indicates infection'. The first-line antibiotic is flucloxacillin for 10-14 days.
Breast feeding or expressing should continue during treatment.

If left untreated, mastitis may develop into a breast abscess. This generally requires incision and
drainage.
Lactation mastitis is inflammation in the interlobular connective tissue of the breast, which may
or may not be associated with infection. It occurs in around 10% on breast feeding women and
is most common six weeks post-partum.

Distinguishing between an engorged breast, blocked duct, non-infectious mastitis, and infected
mastitis can be challenging. Accumulation of milk in breast tissue causes an inflammatory
response (non-infectious mastitis) with inadequate milk removal predisposing to bacterial
growth (infectious mastitis). Clinically this presents as a painful breast, with fever, malaise and a
tender, red, swollen and hard area of the breast, usually in a wedge-shaped distribution.

Infectious mastitis should be suspected if:

 Symptoms do not improve or are worsening after 12-24 hours despite effective milk
removal.
 The woman has a nipple fissure that is infected.
 Bacterial culture is positive (breast milk culture is not routinely required unless mastitis
is severe, there has been no response to antibiotics, or this is recurrent mastitis).

Management of mastitis focuses on relieving pain with simple analgesia and warm compresses,
and encouraging complete emptying of the breast after feeding (this may require the woman to
express the remaining milk by hand or by using a breast pump). 

24
The woman should be encouraged to continue breast feeding as this improves milk removal
and prevent nipple damage. If pain prevents the woman from breast feeding she should be
encouraged to express breast milk by hand or pump until breastfeeding can be resumed.

Antibiotics are only recommended if the lady has an infected nipple fissure, symptoms do not
improve or are worsening after 12-24 hours despite effective milk removal, or bacterial culture
is positive. The first line antibiotic is flucloxacillin 500 mg qds for 14 days (erythromycin 250 mg
to 500 mg qds for 14 days if penicillin allergic) and the woman should be reassured that only
small amount of these are excreted in milk and the infant is not usually affected. 

Intravenous antibiotics are rarely indicated for mastitis. If a breast abscess is suspected (a
history of recent mastitis, painful, swollen lump in the breast with redness, heat, and swelling
of the overlying skin) then urgent referral to breast surgeons for drainage is warranted.

Vitamin A (retinol)

Vitamin A is a fat soluble vitamin. 

Functions

 converted into retinal, an important visual pigment

 important in epithelial cell differentiation
 antioxidant

Consequences of vitamin A deficiency

 night blindness

Vitamin A is teratogenic in high doses, and pregnant women should not exceed a daily
intake of >10,000IU. Women are therefore advised to avoid any supplements containing
vitamin A, such as normal multivitamin tablets, in pregnancy (NHS Choices). However, as
supplements in the UK are now limited to a maximum vitamin A content of 6,000IU, if
they have been taking one it should not be cause for concern. Pregnant women are also
advised to avoid eating liver, as it has high levels of vitamin A. 

Pregnancy: anaemia

Pregnant women are screened for anaemia at:

 the booking visit (often done at 8-10 weeks), and at

 28 weeks

25
NICE use the following cut-offs to determine whether a woman should receive oral iron
therapy:

Gestation Cut-off

Booking visit < 11 g/dl

28 weeks < 10.5 g/dl

Malaria: prophylaxis

Folic acid should be prescribed for pregnant patients taking proguanil

There are around 1,500-2,000 cases each year of malaria in patients returning from endemic
countries. The majority of these cases (around 75%) are caused by the potentially
fatal Plasmodiumfalciparum protozoa. The majority of patients who develop malaria did not
take prophylaxis. It should also be remembered that UK citizens who originate from malaria
endemic areas quickly lose their innate immunity.
Up-to-date charts with recommended regimes for malarial zones should be consulted prior to
prescribing.

Time to begin Time to end

Drug Side-effects + notes before travel after travel

Atovaquone + proguanil GI upset 1 - 2 days 7 days

(Malarone)

Chloroquine Headache 1 week 4 weeks

Contraindicated in
epilepsy
Taken weekly

Doxycycline Photosensitivity 1 - 2 days 4 weeks

26
 Time to begin Time to end
Drug Side-effects + notes before travel after travel

Oesophagitis

Mefloquine (Lariam) Dizziness 2 - 3 weeks 4 weeks

Neuropsychiatric
disturbance

Contraindicated in
epilepsy
Taken weekly

Proguanil (Paludrine) 1 week 4 weeks

Proguanil + chloroquine See above 1 week 4 weeks

Pregnant women should be advised to avoid travelling to regions where malaria is endemic.
Diagnosis can also be difficult as parasites may not be detectable in the blood film due to
placental sequestration. However, if travel cannot be avoided:

 chloroquine can be taken

 proguanil: folate supplementation (5mg od) should be given
 Malarone (atovaquone + proguanil): the BNF advises to avoid these drugs unless
essential. If taken then folate supplementation should be given
 mefloquine: caution advised
 doxycycline is contraindicated

It is again advisable to avoid travel to malaria endemic regions with children if avoidable.
However, if travel is essential then children should take malarial prophylaxis as they are more at
risk of serious complications.

 diethyltoluamide (DEET) 20-50% can be used in children over 2 months of age

 doxycycline is only licensed in the UK for children over the age of 12 years.

HIV and pregnancy

With the increased incidence of HIV infection amongst the heterosexual population there are
an increasing number of HIV positive women giving birth in the UK. In London the incidence
may be as high as 0.4% of pregnant women. The aim of treating HIV positive women during
pregnancy is to minimise harm to both the mother and fetus, and to reduce the chance of
27
vertical transmission. 

Factors which reduce vertical transmission (from 25-30% to 2%)

 maternal antiretroviral therapy

 mode of delivery (caesarean section)
 neonatal antiretroviral therapy
 infant feeding (bottle feeding)

Screening

 NICE guidelines recommend offering HIV screening to all pregnant women

Antiretroviral therapy

 all pregnant women should be offered antiretroviral therapy regardless of whether they
were taking it previously
 if women are not currently taking antiretroviral therapy the RCOG recommend that it is
commenced between 28 and 32 weeks of gestation and should be continued
intrapartum. BHIVA recommend that antiretroviral therapy may be started at an earlier
gestation depending upon the individual situation

Mode of delivery

 vaginal delivery is recommended if viral load is less than 50 copies/ml at 36 weeks,

otherwise caesarian section is recommended
 a zidovudine infusion should be started four hours before beginning the caesarean
section

Neonatal antiretroviral therapy

 zidovudine is usually administered orally to the neonate if maternal viral load is <50
copies/ml. Otherwise triple ART should be used. Therapy should be continued for 4-6
weeks.

Infant feeding

 in the UK all women should be advised not to breast feed

28
  The 2008 BHIVA guidelines suggest vaginal delivery may be an option for women on
HAART who have an undetectable viral load but whether this will translate into clinical
practice remains to be seen

Vitamin B12 (cobalamin)

A B12 supplement may be indicated for breastfeeding women who eat a vegan diet. This is
because vitamin B12 is mainly found in meat and dairy products. Dietary sources of vitamin B12
suitable for vegans may include fortified breakfast cereals, and yeast extracts (eg. Marmite).
The NHS also advises that all breastfeeding women - whatever their diet - should take a daily
supplement of vitamin D 10mcg for the bone health of themselves and their baby. Some
women may be eligible for free supplements, if they qualify for Healthy Start vouchers; the
Health Visitor can advise.

Vitamin B12 is a water soluble vitamin of the B complex group. Typically humans have enough
reserves of vitamin B12 to last 5 years. Vitamin B12 It is unusual in only being found in animal
products.

Functions

 cofactor for the conversion of homocysteine into methionine via the enzyme
homocysteine methyltransferase
 cofactor for the isomerization of methylmalonyl CoA to Succinyl Co A via the enzyme
methylmalonyl mutase
 used to regenerate folic acid in the body

Causes of vitamin B12 deficiency:

 pernicious anaemia
 Diphyllobothrium latum infection
 Crohn's disease

Consequences of vitamin B12 deficiency:

 macrocytic, megaloblastic anaemia

 peripheral neuropathy

Epilepsy: pregnancy and breast feeding

Epilepsy + pregnancy = 5mg folic acid

29
The risks of uncontrolled epilepsy during pregnancy generally outweigh the risks of medication
to the fetus. All women thinking about becoming pregnant should be advised to take folic acid
5mg per day well before pregnancy to minimise the risk of neural tube defects. Around 1-2% of
newborns born to non-epileptic mothers have congenital defects. This rises to 3-4% if the
mother takes antiepileptic medication.

Other points

 aim for monotherapy

 there is no indication to monitor antiepileptic drug levels
 sodium valproate: associated with neural tube defects
 carbamazepine: often considered the least teratogenic of the older antiepileptics
 phenytoin: associated with cleft palate
 lamotrigine: studies to date suggest the rate of congenital malformations may be low.
The dose of lamotrigine may need to be increased in pregnancy

Breast feeding is generally considered safe for mothers taking antiepileptics with the possible
exception of the barbiturates
It is advised that pregnant women taking phenytoin are given vitamin K in the last month of
pregnancy to prevent clotting disorders in the newborn

Sodium valproate

The November 2013 issue of the Drug Safety Update also carried a warning about new evidence
showing a significant risk of neurodevelopmental delay in children following maternal use of
sodium valproate.

The update concludes that sodium valproate should not be used during pregnancy and in
women of childbearing age unless clearly necessary. Women of childbearing age should not
start treatment without specialist neurological or psychiatric advice.
Bleeding in pregnancy

The table below outlines the major causes of bleeding during pregnancy. Antepartum
haemorrhage is defined as bleeding after 24 weeks

1st trimester 2nd trimester 3rd trimester

Spontaneous abortion Spontaneous abortion Bloody show

Ectopic pregnancy Hydatidiform mole Placental abruption
Hydatidiform mole Placental abruption Placenta praevia

30
 1st trimester 2nd trimester 3rd trimester

Vasa praevia

Alongside the pregnancy related causes, conditions such as sexually transmitted infections and
cervical polyps should be excluded. 

The table below outlines the key features of each condition:

Threatened miscarriage - painless vaginal bleeding typically around

6-9 weeks
Missed (delayed) miscarriage - light vaginal bleeding and symptoms
of pregnancy disappear
Inevitable miscarriage - complete or incomplete depending or
whether all fetal and placental tissue has been
Spontaneous expelled. Incomplete miscarriage - heavy bleeding and crampy,
abortion lower abdo pain. Complete miscarriage - little bleeding

Ectopic Typically history of 6-8 weeks amenorrhoea with lower abdominal

pregnancy pain (usually unilateral) initially and vaginal bleeding later. Shoulder
tip pain and cervical excitation may be present

Hydatidiform Typically bleeding in first or early second trimester associated with

mole exaggerated symptoms of pregnancy e.g. hyperemesis. The uterus
may be large for dates and serum hCG is very high

Placental Constant lower abdominal pain and, woman may be more shocked
abruption than is expected by visible blood loss. Tender, tense uterus* with
normal lie and presentation. Fetal heart may be distressed

Placental Vaginal bleeding, no pain. Non-tender uterus* but lie and

praevia presentation may be abnormal

Vasa praevia Rupture of membranes followed immediately by vaginal bleeding.

Fetal bradycardia is classically seen

31
*vaginal examination should not be performed in primary care for suspected antepartum
haemorrhage - women with placenta praevia may haemorrhage

Antepartum haemorrhage: determining cause

Antepartum haemorrhage is defined as bleeding from the genital tract after 24 weeks
pregnancy, prior to delivery of the fetus

Distinguishing placental abruption from praevia

Placental abruption Placenta praevia

 shock out of keeping with visible loss
 pain constant
 tender, tense uterus*
 normal lie and presentation
 fetal heart: absent/distressed
 coagulation problems
 beware pre-eclampsia, DIC, anuria
 shock in proportion to visible loss
 no pain
 uterus not tender*
 lie and presentation may be abnormal
 fetal heart usually normal
 coagulation problems rare
 small bleeds before large

*vaginal examination should not be performed in primary care for suspected antepartum
haemorrhage - women with placenta praevia may haemorrhage

Post-partum haemorrhage
Post-partum haemorrhage (PPH) is defined as blood loss of > 500mls and may be primary or
secondary

Primary PPH

 occurs within 24 hours

 affects around 5-7% of deliveries
 most common cause of PPH is uterine atony (90% of cases). Other causes include genital
trauma and clotting factors

Risk factors for primary PPH include*:

 previous PPH

32
  prolonged labour
 pre-eclampsia
 increased maternal age
 polyhydramnios
 emergency Caesarean section
 placenta praevia
 macrosomia
 ritodrine (a beta-2 adrenergic receptor agonist used for tocolysis)

Management

 ABC
 IV syntocinon (oxytocin) 10 units or IV ergometrine 500 micrograms
 IM carboprost
 other options include: B-Lynch suture, ligation of the uterine arteries or internal iliac
arteries
 if severe, uncontrolled haemorrhage then a hysterectomy is sometimes performed as a
life-saving procedure

Secondary PPH

 occurs between 24 hours - 12 weeks**

 due to retained placental tissue or endometritis

*the effect of parity on the risk of PPH is complicated. It was previously though multiparity was
a risk factor but more modern studies suggest nulliparity is actually a risk factor

**previously the definition of secondary PPH was 24 hours - 6 weeks. Please see the RCOG
guidelines for more details

Rhesus negative pregnancy

Anti-D is still required following delivery even if the mother received routine
antenatal anti-D prophylaxis

Subsequent pregnancies are most at risk following the sensitising event of the first childbirth.

A basic understanding of the pathophysiology is essential to understand the management of

Rhesus negative pregnancies

33
  along with the ABO system the Rhesus system is the most important antigen found on
red blood cells. The D antigen is the most important antigen of the rhesus system
 around 15% of mothers are rhesus negative (Rh -ve)
 if a Rh -ve mother delivers a Rh +ve child a leak of fetal red blood cells may occur
 this causes anti-D IgG antibodies to form in mother
 in later pregnancies these can cross placenta and cause haemolysis in fetus
 this can also occur in the first pregnancy due to leaks

Prevention

 test for D antibodies in all Rh -ve mothers at booking

 NICE (2008) advise giving anti-D to non-sensitised Rh -ve mothers at 28 and 34 weeks
 the evidence base suggests that there is little difference in the efficacy of single-dose (at
28 weeks) and double-dose regimes (at 28 & 34 weeks). For this reason the RCOG in
2011 advised that either regime could be used 'depending on local factors'
 anti-D is prophylaxis - once sensitization has occurred it is irreversible
 if event is in 2nd/3rd trimester give large dose of anti-D and perform Kleihauer test -
determines proportion of fetal RBCs present

Anti-D immunoglobulin should be given as soon as possible (but always within 72 hours) in the
following situations:

 delivery of a Rh +ve infant, whether live or stillborn

 any termination of pregnancy
 miscarriage if gestation is > 12 weeks
 ectopic pregnancy
 external cephalic version
 antepartum haemorrhage
 amniocentesis, chorionic villus sampling, fetal blood sampling

Tests

 all babies born to Rh -ve mother should have cord blood taken at delivery for FBC, blood
group & direct Coombs test
 Coombs test: direct antiglobulin, will demonstrate antibodies on RBCs of baby
 Kleihauer test: add acid to maternal blood, fetal cells are resistant

Affected fetus

34
  oedematous (hydrops fetalis, as liver devoted to RBC production albumin falls)
 jaundice, anaemia, hepatosplenomegaly
 heart failure
 kernicterus
 treatment: transfusions, UV phototherapy

Smoking cessation

NRT patches should be removed before going to bed

Smoking cessation in pregnancy

 check all women with a carbon monoxide monitor

 CBT/motivational interviewing before NRT

Smoking cessation in pregnancy

 check all women with a carbon monoxide monitor

 CBT/motivational interviewing before NRT.

NICE released guidance in 2008 on the management of smoking cessation. General points
include:

 patients should be offered nicotine replacement therapy (NRT), varenicline or

bupropion - NICE state that clinicians should not favour one medication over another
 NRT, varenicline or bupropion should normally be prescribed as part of a commitment
to stop smoking on or before a particular date (target stop date)
 prescription of NRT, varenicline or bupropion should be sufficient to last only until 2
weeks after the target stop date. Normally, this will be after 2 weeks of NRT therapy,
and 3-4 weeks for varenicline and bupropion, to allow for the different methods of
administration and mode of action. Further prescriptions should be given only to people
who have demonstrated that their quit attempt is continuing
 if unsuccessful using NRT, varenicline or bupropion, do not offer a repeat prescription
within 6 months unless special circumstances have intervened
 do not offer NRT, varenicline or bupropion in any combination

Nicotine replacement therapy

35
  adverse effects include nausea & vomiting, headaches and flu-like symptoms
 NICE recommend offering a combination of nicotine patches and another form of NRT
(such as gum, inhalator, lozenge or nasal spray) to people who show a high level of
dependence on nicotine or who have found single forms of NRT inadequate in the past

Varenicline

 a nicotinic receptor partial agonist

 should be started 1 week before the patients target date to stop
 the recommended course of treatment is 12 weeks (but patients should be monitored
regularly and treatment only continued if not smoking)
 has been shown in studies to be more effective than bupropion
 nausea is the most common adverse effect. Other common problems include headache,
insomnia, abnormal dreams
 varenicline should be used with caution in patients with a history of depression or self-
harm. There are ongoing studies looking at the risk of suicidal behaviour in patients
taking varenicline
 contraindicated in pregnancy and breast feeding

Bupropion

 a norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist

 should be started 1 to 2 weeks before the patients target date to stop
 small risk of seizures (1 in 1,000)
 contraindicated in epilepsy, pregnancy and breast feeding. Having an eating disorder is a
relative contraindication

Pregnant women

NICE recommended in 2010 that all pregnant women should be tested for smoking using
carbon monoxide detectors, partly because 'some women find it difficult to say that they smoke
because the pressure not to smoke during pregnancy is so intense.'. All women who smoke, or
have stopped smoking within the last 2 weeks, or those with a CO reading of 7 ppm or above
should be referred to NHS Stop Smoking Services.

Interventions

 the first-line interventions in pregnancy should be cognitive behaviour therapy,

motivational interviewing or structured self-help and support from NHS Stop Smoking
Services
 the evidence for the use of NRT in pregnancy is mixed but it is often used if the above
measures failure. There is no evidence that it affects the child's birthweight. Pregnant
women should remove the patches before going to bed

36
  as mentioned above, varenicline and bupropion are contraindicated

Semen analysis

Semen analysis should be performed after a minimum of 3 days and a maximum of 5 days
abstinence. The sample needs to be delivered to the lab within 1 hour

Normal semen results*

 volume > 1.5 ml

 pH > 7.2
 sperm concentration > 15 million / ml
 morphology > 4% normal forms
 motility > 32% progressive motility
 vitality > 58% live spermatozoa

*many different reference ranges exist. These are based on the NICE 2013 values

Preterm birth
Preterm birth is defined as delivery of an infant before 37 weeks gestation. It occurs in around
5-10% of pregnancies (6% of singletons, 45% of twins)

Causes

 unexplained (30-40%)
 multiple pregnancies (20-30%)
 congenital abnormalities
 antepartum haemorrhage
 pre-eclampsia
 cervical incompetence
 diabetes mellitus
 polyhydramnios
 uterine abnormalities
 infections e.g. Pyelonephritis

Antiphospholipid syndrome
Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both
venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a
primary disorder or secondary to other conditions, most commonly systemic lupus
37
erythematosus (SLE)

A key point for the exam is to appreciate that antiphospholipid syndrome causes a paradoxical
rise in the APTT. This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies
with phospholipids involved in the coagulation cascade

Features

 venous/arterial thrombosis
 recurrent fetal loss
 livedo reticularis
 thrombocytopenia
 prolonged APTT
 other features: pre-eclampsia, pulmonary hypertension

Associations other than SLE

 other autoimmune disorders

 lymphoproliferative disorders
 phenothiazines (rare)

Management - based on BCSH guidelines

 initial venous thromboembolic events: evidence currently supports use of warfarin with
a target INR of 2-3 for 6 months
 recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking
warfarin then increase target INR to 3-4
 arterial thrombosis should be treated with lifelong warfarin with target INR 2-3

Antiphospholipid syndrome: pregnancy

Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both
venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a
primary disorder or secondary to other conditions, most commonly systemic lupus
erythematosus (SLE)

In pregnancy the following complications may occur:

 recurrent miscarriage
 IUGR
 pre-eclampsia

38
  placental abruption
 pre-term delivery
 venous thromboembolism

Management

 low-dose aspirin should be commenced once the pregnancy is confirmed on urine

testing
 low molecular weight heparin once a fetal heart is seen on ultrasound. This is usually
discontinued at 34 weeks gestation
 these interventions increase the live birth rate seven fold .
 Antiphospholipid syndrome in pregnancy: aspirin + LMWH

The ultrasound at 11 weeks gestation would show a fetal heart if the pregnancy was
viable. This patient should therefore be taking both aspirin and low-molecular weight
heparin.

Pregnancy: jaundice
Intrahepatic cholestasis of pregnancy

 pruritus
 bilirubin < 100
 occurs in 2nd and 3rd trimester

Acute fatty liver of pregnancy

Acute fatty liver of pregnancy is rare complication which may occur in the third trimester or the
period immediately following delivery.

Features

 abdominal pain
 nausea & vomiting
 headache
 jaundice
 hypoglycaemia
 severe disease may result in pre-eclampsia

Investigations

 ALT is typically elevated e.g. 500 u/l

39
Management

 support care
 once stabilised delivery is the definitive management

Gilbert's, Dubin-Johnson syndrome, may be exacerbated during pregnancy

HELLP

 Haemolysis, Elevated Liver enzymes, Low Platelets.

Gilbert's syndrome

Gilbert's syndrome is an autosomal recessive* condition of defective bilirubin conjugation due

to a deficiency of UDP glucuronyl transferase. The prevalence is approximately 1-2% in the
general population

Features

 unconjugated hyperbilinaemia (i.e. not in urine)

 jaundice may only be seen during an intercurrent illness

Investigation and management

 investigation: rise in bilirubin following prolonged fasting or IV nicotinic acid

 no treatment required

*the exact mode of inheritance is still a matter of debate

Bilirubin 42 µmol/L

ALP 160 U/L

ALT 25 U/L

Albumin 34 g/L
Morning sickness and pruritus are common in pregnant women. Intrahepatic cholestasis of
pregnancy would not occur in the first trimester. An ALP of 160 U/l is normal in a pregnant
woman leaving the only abnormal result being the raised bilirubin (which usually falls in
pregnancy). The most likely diagnosis is therefore Gilbert's syndrome.

40
Herpes simplex virus

This patient has genital herpes simplex virus (HSV). The guidelines recommend treatment with
oral (or intravenous) aciclovir at any stage in pregnancy. Aciclovir is not licensed in pregnancy
but is considered safe and not associated with birth defects. It is well tolerated in pregnancy.
Paracetamol and topical lidocaine 2% gel can be used for symptomatic relief.

The primary purpose of treatment is to reduce the risk of transmission to the neonate at birth.
The risk is much more considerable with primary genital herpes simplex within the final six
weeks of pregnancy. Caesarian section should be the recommended mode of delivery for all
women developing the first episode of genital HSV in the third trimester.

There are two strains of the herpes simplex virus (HSV) in humans: HSV-1 and HSV-2. Whilst it
was previously thought HSV-1 accounted for oral lesions (cold sores) and HSV-2 for genital
herpes it is now known there is considerable overlap

Features

 primary infection: may present with a severe gingivostomatitis

 cold sores
 painful genital ulceration

Management

 gingivostomatitis: oral aciclovir, chlorhexidine mouthwash

 cold sores: topical aciclovir although the evidence base for this is modest
 genital herpes: oral aciclovir. Some patients with frequent exacerbations may benefit
from longer term aciclovir

Ectopic pregnancy
Implantation of a fertilized ovum outside the uterus results in an ectopic pregnancy

A typical history is a female with a history of 6-8 weeks amenorrhoea who presents with lower
abdominal pain and later develops vaginal bleeding

 lower abdominal pain: typically the first symptom. Pain is usually constant and may be
unilateral. Due to tubal spasm
 vaginal bleeding: usually less than a normal period, may be dark brown in colour
 history of recent amenorrhoea: typically 6-8 weeks from start of last period; if longer
(e.g. 10 wks) this suggest another causes e.g. inevitable abortion

 peritoneal bleeding can cause shoulder tip pain and pain on defecation / urination

41
Examination findings

 abdominal tenderness
 cervical excitation (also known as cervical motion tenderness)
 adnexal mass: NICE advise NOT to examine for an adnexal mass due to an increased risk
of rupturing the pregnancy. A pelvic examination to check for cervical excitation is
however recommended

Migraine: pregnancy, contraception and other hormonal factors

SIGN produced guidelines in 2008 on the management of migraine, the following is selected
highlights:

Migraine during pregnancy

 paracetamol 1g is first-line
 aspirin 300mg or ibuprofen 400mg can be used second-line in the first and second
trimester

Migraine and the combined oral contraceptive (COC) pill

 if patients have migraine with aura then the COC is absolutely contraindicated due to an
increased risk of stroke (relative risk 8.72)

Migraine and menstruation

 many women find that the frequency and severity of migraines increase around the
time of menstruation
 SIGN recommends that women are treated with mefanamic acid or a combination of
aspirin, paracetamol and caffeine. Triptans are also recommended in the acute situation

Migraine and hormone replacement therapy (HRT)

 safe to prescribe HRT for patients with a history of migraine but it may make migraines
worse

Hepatitis B and pregnancy

Without intervention the vertical transmission rate is around 20%, which increases to 90% if the
woman is positive for HBeAg.

42
HBeAg is a marker of infectivity. The Green Book guidelines advise giving both the vaccine and
immunoglobulin in this situation. If the patient had antibodies against HBe (anti-HBe), rather
than the HBe antigen , then only the vaccine would need to be given.

Basics

 all pregnant women are offered screening for hepatitis B

 babies born to mothers who are chronically infected with hepatitis B or to mothers
who've had acute hepatitis B during pregnancy should receive a complete course of
vaccination + hepatitis B immunoglobulin
 studies are currently evaluating the role of oral antiviral treatment (e.g. Lamivudine) in
the latter part of pregnancy
 there is little evidence to suggest caesarean section reduces vertical transmission rates
 hepatitis B cannot be transmitted via breastfeeding (in contrast to HIV).

Rheumatoid arthritis: pregnancy

Rheumatoid arthritis (RA) typically develops in women of a reproductive age. Issues
surrounding conception are therefore commonly encountered. There are no current published
guidelines regarding how patients considering conception should be managed although expert
reviews are largely in agreement.

Key points

 patients with early or poorly controlled RA should be advised to defer conception until
their disease is more stable
 RA symptoms tend to improve in pregnancy but only resolve in a small minority.
Patients tend to have a flare following delivery
 methotrexate is not safe in pregnancy and needs to be stopped at least 3 months before
conception
 leflunomide is not safe in pregnancy
 sulfasalazine and hydroxychloroquine are considered safe in pregnancy
 interestingly studies looking at pregnancy outcomes in patients treated 
 with TNF-α blockers do not show any significant increase in adverse outcomes. It should
be noted however that many of the patients included in the study stopped taking TNF-α
blockers when they found out they were pregnant
 low-dose corticosteroids may be used in pregnancy to control symptoms
 NSAIDs may be used until 32 weeks but after this time should be withdrawn due to the
risk of early close of the ductus arteriosus
 patients should be referred to an obstetric anaesthetist due to the risk of atlanto-axial
subluxation

Breast cancer: screening

43
The NHS Breast Screening Programme is being expanded to include women aged 47-73 years
from the previous parameter of 50-70 years. Women are offered a mammogram every 3 years.
After the age of 70 years women may still have mammograms but are 'encouraged to make
their own appointments'.

The effectiveness of breast screening is regularly debated although it is currently thought that
the NHS Breast Screening Programme may save around 1,400 lives per year.

Familial breast cancer

NICE published guidelines on the management of familial breast cancer in 2013, giving
guidelines on who needs referral.

If the person concerned only has one first-degree or second-degree relative diagnosed with
breast cancer they do NOT need to be referred unless any of the following are present in the
family history:

 age of diagnosis < 40 years

 bilateral breast cancer
 male breast cancer
 ovarian cancer
 Jewish ancestry
 sarcoma in a relative younger than age 45 years
 glioma or childhood adrenal cortical carcinomas
 complicated patterns of multiple cancers at a young age
 paternal history of breast cancer (two or more relatives on the father's side of the
family)

Women who are at an increased risk of breast cancer due to their family history may be offered
screening from a younger age. The following patients should be referred to the breast clinic for
further assessment:

 one first-degree female relative diagnosed with breast cancer at younger than age 40
years, or
 one first-degree male relative diagnosed with breast cancer at any age, or
 one first-degree relative with bilateral breast cancer where the first primary was
diagnosed at younger than age 50 years, or
 two first-degree relatives, or one first-degree and one second-degree relative,
diagnosed with breast cancer at any age, or
 one first-degree or second-degree relative diagnosed with breast cancer at any age and
one first-degree or second-degree relative diagnosed with ovarian cancer at any age
(one of these should be a first-degree relative), or

44
  three first-degree or second-degree relatives diagnosed with breast cancer at any age

Management & Referral in Surgery.

Tamoxifen

Alopecia and cataracts are listed in the BNF as possible side-effects. They are however not as
prevalent as hot flushes, which are very common in pre-menopausal women

Tamoxifen is a selective estrogen receptor modulator (SERM) which acts as an oestrogen

receptor antagonist and partial agonist. It is used in the management of oestrogen receptor
positive breast cancer

Adverse effects

 menstrual disturbance: vaginal bleeding, amenorrhoea

 hot flushes
 venous thromboembolism
 endometrial cancer

Tamoxifen is typically used for 5 years following removal of the tumour.

Raloxifene is a pure oestrogen receptor antagonist, and carries a lower risk of

endometrial cancer

45
Gynecology cont.

Urinary incontinence

Urinary incontinence (UI) is a common problem, affecting around 4-5% of the population. It is
more common in elderly females. 

Causes

 overactive bladder (OAB)/urge incontinence: due to detrusor over activity

 stress incontinence: leaking small amounts when coughing or laughing
 mixed incontinence: both urge and stress
 overflow incontinence: due to bladder outlet obstruction, e.g. due to prostate
enlargement

Initial investigation

 bladder diaries should be completed for a minimum of 3 days

 vaginal examination to exclude cystocele
 urine dipstick and culture

Management depends on whether urge or stress UI is the predominant picture. If urge

incontinence is predominant:

 bladder retraining (lasts for a minimum of 6 weeks, the idea is to gradually increase the
intervals between voiding)
 bladder stabilising drugs: antimuscarinic is first-line >> examples of muscarinic
antagonists used in urinary incontinence include Tolterodene , oxybutynin and
solifenacin. Examples of muscarinic antagonists used in different conditions include
ipratropium (chronic obstructive pulmonary disease) and procyclidine (Parkinson's
disease).
Tamsulosin is an alpha blocker/

46
  surgical management: e.g. sacral nerve stimulation

If stress incontinence is predominant:

 pelvic floor muscle training (for a minimum of 3 months)

 surgical procedures: e.g. retropubic mid-urethral tape procedures

Contraception Continued

Implanon/Nexplanon – subdermal

Previous ectopic pregnancy is not a contraindication to intrauterine device insertion.

Intrauterine systems (Mirena) cannot be used for emergency contraception.

Consent: children

The General Medical Council have produced guidelines on obtaining consent in children:

 at 16 years or older a young person can be treated as an adult and can be presumed to
have capacity to decide
 under the age of 16 years children may have capacity to decide, depending on their
ability to understand what is involved
 where a competent child refuses treatment, a person with parental responsibility or the
court may authorise investigation or treatment which is in the child's best interests*

With regards to the provision of contraceptives to patients under 16 years of age the Fraser
Guidelines state that all the following requirements should be fulfilled:

 the young person understands the professional's advice

 the young person cannot be persuaded to inform their parents
 the young person is likely to begin, or to continue having, sexual intercourse with or
without contraceptive treatment
 unless the young person receives contraceptive treatment, their physical or mental
health, or both, are likely to suffer
 the young person's best interests require them to receive contraceptive advice or
treatment with or without parental consent

Gillick or Fraser?

47
 Some doctors use the term Fraser competency when referring to contraception and
Gillick competency when referring to general issues of consent in children. The
(widespread) rumours that Victoria Gillick removed her permission to use her name or
applied copyright have recently been debunked.

More information can be found in the following article:

Wheeler R. Gillick or Fraser? A plea for consistency over competence in children BMJ
2006;332:807

*in Scotland those with parental responsibility cannot authorise procedures a

competent child has refused

**Emergency IUD :

Must be inserted within 5 days of UPSI OR up to 5 days after the likely ovulation
date

Combined vaginal ring

The Nuvaring is a relatively new method of contraception, licensed in 2001. You may not need
to memorise the method failure rules as they can be easily looked up. However it's worth
having a read of the following advice taken from the BNF:

Expulsion, delayed insertion or removal, or broken vaginal ring

If the vaginal ring is expelled for less than 3 hours, rinse the ring with cool water and
reinsert immediately; no additional contraception is needed.

If the ring remains outside the vagina for more than 3 hours or if the user does not know
when the ring was expelled, contraceptive protection may be reduced:

If ring expelled during week 1 or 2 of cycle, rinse ring with cool water and reinsert; use
additional precautions (barrier methods) for next 7 days;

 If ring expelled during week 3 of cycle, either insert a new ring to start a new cycle or
allow a withdrawal bleed and insert a new ring no later than 7 days after ring was

48
 expelled; latter option only available if ring was used continuously for at least 7 days
before expulsion.
 If insertion of a new ring at the start of a new cycle is delayed, contraceptive protection
is lost. A new ring should be inserted as soon as possible; additional precautions (barrier
methods) should be used for the first 7 days of the new cycle. If intercourse occurred
during the extended ring-free interval, pregnancy should be considered
 No additional contraception is required if removal of the ring is delayed by up to 1 week
(4 weeks of continuous use). The 7-day ring-free interval should be observed and
subsequently a new ring should be inserted. Contraceptive protection may be reduced
with continuous use of the ring for more than 4 weekspregnancy should be ruled out
before inserting a new ring.
 If the ring breaks during use, remove it and insert a new ring immediately; additional
precautions (barrier methods) should be used for the first 7 days of the new cycle.

The Nuvaring is a relatively new method of contraception, licensed in 2001. You may not need
to memorise the method failure rules as they can be easily looked up. However it's worth
having a read of the following advice taken from the BNF:

Expulsion, delayed insertion or removal, or broken vaginal ring

 If the vaginal ring is expelled for less than 3 hours, rinse the ring with cool water and
reinsert immediately; no additional contraception is needed.
 If the ring remains outside the vagina for more than 3 hours or if the user does not know
when the ring was expelled, contraceptive protection may be reduced:
 If ring expelled during week 1 or 2 of cycle, rinse ring with cool water and reinsert; use
additional precautions (barrier methods) for next 7 days;
 If ring expelled during week 3 of cycle, either insert a new ring to start a new cycle or
allow a withdrawal bleed and insert a new ring no later than 7 days after ring was
expelled; latter option only available if ring was used continuously for at least 7 days
before expulsion.
 If insertion of a new ring at the start of a new cycle is delayed, contraceptive protection
is lost. A new ring should be inserted as soon as possible; additional precautions (barrier
methods) should be used for the first 7 days of the new cycle. If intercourse occurred
during the extended ring-free interval, pregnancy should be considered.
 No additional contraception is required if removal of the ring is delayed by up to 1 week
(4 weeks of continuous use). The 7-day ring-free interval should be observed and
subsequently a new ring should be inserted. Contraceptive protection may be reduced
with continuous use of the ring for more than 4 weekspregnancy should be ruled out
before inserting a new ring.
 If the ring breaks during use, remove it and insert a new ring immediately; additional
precautions (barrier methods) should be used for the first 7 days of the new cycle.

49