Clinical Topic A-Z Clinical Speciality

Pre-conception - advice and management

Pre-conception - advice and management
D016742Preconception Care
PregnancyPreventative medicineWomen's health
2012-06-01Last revised in June 2012

Pre-conception - advice and management - Summary

Pre-conception advice should not be confused with antenatal care.

Pre-conception advice provides advice about what can be done to have the best chance of having a healthy pregnancy and a healthy baby.

Pre-conception care can achieve this by:

Optimizing the management of chronic maternal health problems.

Providing lifestyle advice to avoid behaviours hazardous to a pregnancy, such as smoking, drinking excessive alcohol, or taking drugs.

Providing advice to optimize the health of the mother and baby, such as guidance on taking folic acid supplements.

Identifying couples who are at increased risk of having a baby with a genetic or chromosomal malformation, and providing them with sufficient knowledge to make informed decisions.

A detailed assessment should be carried out. Each part of the assessment identifies a specific management requirement. The following should be assessed in a woman who is planning to become pregnant:

When is she planning pregnancy?

Is she currently taking folic acid and if so, is she taking an appropriate dose for her risk of a neural tube defect?

Is she up to date with her cervical smear?

Is she a smoker?

How many units of alcohol does she drink each week?

Does she use illicit drugs?

Does she have immunity to rubella?

Does she have a definite history of chickenpox or shingles?

Is she at high risk of hepatitis B?

Does she have any concerns about work exposure to hazardous substances or radiation?

Is she taking over-the-counter medicines, vitamins, or herbal remedies?

Is she overweight or obese?

If the woman has a chronic health problem there is specific pre-conception management advice including specialist referral where appropriate for women with:

Depression.

Bipolar disorder.

Schizophrenia.

Epilepsy.

Diabetes.

Thyroid disease.

Chronic hypertension.

Chronic cardiac disease.

Renal disease.

Asthma.

Thalassaemia.

Sickle-cell disease.

Previous thromboembolism.

Rheumatoid arthritis.

History of previous miscarriage should be determined.

If she has any concerns about the risk of having a baby with a chromosomal abnormality such as Down's syndrome, this should be discussed.

A history should be taken to find out whether she or her partner are at increased risk of having a baby with an inherited genetic disorder and screening and counselling should be offered where appropriate.

Advice should be offered on:

Time it may take to become pregnant.

Folic acid.

Smoking.

Alcohol consumption.

Illicit drug use.

Hazardous substances or radiation.

Vitamin A and over-the-counter or herbal medicines.

Being overweight or obese.

Cervical screening.

Immunizations.

Previous miscarriage(s).

The risk to older women of chromosome abnormalities.

Have I got the right topic?

192months540monthsBoth

This CKS topic covers advice and information for women who are not pregnant but are planning a pregnancy.

This CKS topic does not cover antenatal or postnatal care. There are separate CKS topics on Antenatal care - uncomplicated pregnancy and Hypertension in pregnancy.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in June 2012

March 2012 — revised. A literature search was conducted in January 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. Minor changes to clinical recommendations have been made.

Previous changes

January 2012 — minor update. Reference to the 2004 National Institute for Health and Care Excellence (NICE) guideline The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care has been changed to reflect the updated NICE guideline [National Clinical Guideline Centre, 2012].

March 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

March 2011 — minor update. Text added regarding the small increased risk of cardiovascular malformation associated with first trimester maternal exposure to fluoxetine [MHRA, 2010]. Issued in June 2011.

September 2010 — minor update. Text amended to include recommendations from the National Institute for Health and Care Excellence (NICE) public health guidance 27 about preparing for pregnancy for women with a body mass index (BMI) of 30 kg/m2 or more [NICE, 2010b]. Issued September 2010.

January 2009 — minor update to clarify the advice for folic acid supplementation in women with sickle-cell anaemia and thalassaemia. Issued in February 2009.

August 2007 — minor typographical updates to the Clinical Summaries (Advice for all women, Women with chronic medical conditions, Women with mental health issues, and Women with metabolic disorders). Issued in August 2007.

April to July 2007 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

Updated alcohol advice for pregnant women issued by the Department of Health has been included.

March 2007 — minor update to include recent national guideline advice regarding the management of women with hypothyroidism and sub-clinical hypothyroidism who are planning a pregnancy or have pregnancy confirmed [BTA et al, 2006]. Issued in March 2007.

January 2007 — minor update to include advice to screen women for hepatitis B, syphilis, and HIV (in line with standard UK antenatal care). Issued in January 2007.

October 2006 — minor update to include recent advice form CEMACH, recommending folic acid 5 mg for diabetic women who wish to become pregnant. Minor update to include Department of Health advice regarding immunization with varicella vaccine for health care workers. Issued in October 2006.

January 2006 — minor update to include recent advice from the MHRA regarding the safety of paroxetine in pregnancy. Issued in February 2006.

December 2003 — written. Validated in March 2004 and issued in June 2004.

Update

New evidence

Evidence-based guidelines

Guidelines published since the last revision of this topic:

SIGN (2012) Antithrombotics: indications and management. Scottish Intercollegiate Guidelines Network www.sign.ac.uk [Free Full-text]

HTAs (Health Technology Assessments)

No new HTAs since 1 January 2012.

Economic appraisals

No new economic appraisals relevant to England since 1 January 2012.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analyses since 1 January 2012.

Primary evidence

No new randomized controlled trials published in the major journals since 1 January 2012.

New policies

No new national policies or guidelines since 1 January 2012.

New safety alerts

No new safety alerts since 1 January 2012.

Changes in product availability

No changes in product availability since 1 January 2012.

Goals and outcome measures

Goals

To provide the information that a woman and her partner need in order to make informed choices about planning a pregnancy

To ensure the best possible outcome for the couple and the baby

Background information

Definition

What is it?

Pre-conception advice should not be confused with antenatal care.

Pre-conception advice provides advice about what can be done to have the best chance of having a healthy pregnancy and a healthy baby, by making informed choices about planning a pregnancy.

Pre-conception care can achieve this by:

Optimizing the management of chronic maternal health problems.

Providing lifestyle advice to avoid behaviours hazardous to a pregnancy, such as smoking, drinking excessive alcohol, or taking illicit drugs.

Providing advice to optimize the health of the mother and baby, such as guidance on taking folic acid supplements, and vitamin D supplements once pregnant.

Identifying couples who are at increased risk of having a baby with a genetic or chromosomal malformation, and providing them with sufficient knowledge to make informed decisions.

[Health Canada, 2000]

Raising the issue of pre-conception care

When should I raise the issue of pre-conception care?

In reality, not all pregnancies are planned, and many women will not consult specifically for pre-conception advice.

Consider raising the issue of pre-conception care for women (and their partners) who present for:

New registration checks

Well woman consultations

Contraceptive advice and reviews

Medication review

The Family Planning Association (FPA) produces a leaflet, Planning a Pregnancy, for use by health professionals to explain how a woman can prepare for a pregnancy, how conception occurs, and how she and her partner can improve her chances of getting pregnant (see www.fpa.org.uk).

Management

Management

Scenario: Assessment : covers the assessment of a woman and her partner who are planning a pregnancy.

Scenario: Advice for all women : covers general advice on pre-conception care that is applicable to all women who are planning a pregnancy.

Scenario: Mental health issues : covers specific issues to be considered in a woman with depression, bipolar disorder, or schizophrenia who is planning a pregnancy.

Scenario: Metabolic disorders : covers specific issues to be considered in a woman with thyroid disease or diabetes who is planning a pregnancy.

Scenario: Chronic medical conditions : covers specific issues to be considered in a woman with epilepsy, chronic cardiac disease, chronic hypertension, renal disease, venous thromboembolism, asthma, or rheumatoid arthritis who is planning a pregnancy.

Scenario: Genetic haemoglobinopathies : covers specific issues to be considered in a woman with sickle-cell disease or thalassemia who is planning a pregnancy.

Scenario: Advice for older women : covers the provision of information about the risks of Down's syndrome with increasing maternal age, as well as advice about antenatal screening and diagnostic tests for Down's syndrome.

Scenario: Advice about genetic screening : covers the provision of advice about screening for haemoglobinopathies in general practice, and information regarding who should be referred for genetic screening.

Scenario: Assessment

Scenario: Assessment - pre-conception - advice and management

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Assessment

What do I need to assess in a woman planning a pregnancy?

Each part of the assessment identifies a specific management requirement. Further information about how to assess and manage individual components is provided by following the hyperlinks.

Assess the following in a woman who is planning to become pregnant:

When is she planning a pregnancy?

Is she currently taking folic acid and if so, is she taking an appropriate dose for her risk of a neural tube defect?

Is she up to date with her cervical smear?

Is she a smoker?

How many units of alcohol does she drink each week?

Does she use illicit drugs?

Does she have immunity to rubella?

Does she have a definite history of chickenpox or shingles?

Is she at high risk of hepatitis B?

Does she have any concerns about work exposure to hazardous substances or radiation?

Is she taking over-the-counter medicines, vitamins, or herbal remedies?

Is she overweight or obese?

Does she have a chronic health problem? Pre-conception management advice is provided for:

Depression

Bipolar affective disorder

Schizophrenia

Epilepsy

Diabetes mellitus

Thyroid disease

Chronic hypertension

Chronic cardiac disease

Renal disease

Asthma

Thalassaemia

Sickle-cell disease

Previous thromboembolism

Rheumatoid arthritis

Has she had a previous miscarriage?

Has she or her partner expressed concerns about their risk of having a baby with a chromosomal abnormality such as Down's syndrome?

Is she or her partner at increased risk of having a baby with an inherited genetic disorder?

Basis for recommendation

Basis for recommendation

This recommendation is based on what CKS considers to be good clinical practice. Details about specific recommendations can be found in the individual scenarios.

Scenario: Advice for all women

Scenario: Pre-conception advice for all women

192months540monthsFemale

Advice on time to become pregnant

What advice can I give a woman planning pregnancy about how long it is likely to take to become pregnant?

Of 100 couples having regular sexual intercourse every two or three days and who are not using contraception:

84 will conceive within 1 year.

92 will conceive within 2 years.

The remainder will take longer and some of these may need help for them to conceive.

Advise women planning pregnancy who have been using the progestogen-only injection for contraception that normal fertility may be delayed for up to 1 year after the last injection. Other methods of contraception are not known to have any effect on fertility once they have been discontinued.

For further information about what to do if a couple is having difficulty conceiving see the CKS topic on Infertility.

Basis for recommendation

Basis for recommendation

The figures about the time taken for 100 couples to conceive are derived from statistics quoted by the Human Fertilisation and Embryology Authority [HFEA, 2010].

The advice about the delay to normal fertility with injected progestogen only contraception is derived from evidence reported by the National Institute for Health and Care Excellence [NICE, 2005].

Advice on folic acid

What advice should I give a woman planning pregnancy regarding folic acid?

Assess the couple's risk of a neural tube defect (NTD).

Couples are at high risk of conceiving a child with a NTD if:

Either partner has a NTD, they have had a previous pregnancy affected by a NTD, or they have a family history of a NTD.

The woman is taking anti–epileptic drugs or has coeliac disease, diabetes, or thalassaemia trait.

The woman is obese (defined as a body mass index [BMI] of 30 kg/m2 or more).

All other people have a normal risk of conceiving a child with a NTD.

Advise women who are at normal risk for a NTD to take folic 400 micrograms daily, and once pregnant, to continue this until the twelfth week of pregnancy.

Advise women at high risk of a NTD to take folic acid 5 mg daily and, once pregnant, to continue this until the twelfth week of pregnancy.

Women with thalassaemia trait should continue taking folic acid 5 mg daily until the birth of the baby.

Advise women with a haemolytic anaemia particularly a haemoglobinopathy such as thalassaemia or sickle cell anaemia to take folic acid 5 mg to 10 mg daily throughout pregnancy.

Basis for recommendation

Basis for recommendation

Basis for recommending folic acid supplements to all women:

There is compelling evidence in a Cochrane systematic review that examined the effect of folic acid on the incidence of neural tube defects (NTDs). The study included 6105 women with and without pregnancies previously affected by an NTD, and who were given either periconceptional folate supplementation in doses ranging from 0.36–4.0 mg daily or a placebo. It found that periconceptional folic acid supplementation (alone or in combination with vitamins and minerals) reduced the incidence of NTDs (RR 0.28, 95% CI 0.15 to 0.52), and also recurrence (RR 0.32, 95% CI 0.17 to 0.60). No significant harms were detected from folic acid supplementation, and it did not significantly increase the risk of miscarriage, ectopic pregnancy, or stillbirth. The authors concluded that 'folic acid, alone or in combination with vitamins and minerals, prevents NTDs but does not have a clear effect on other birth defects' [De-Regil et al, 2010].

Basis for recommending high dose folate supplementation to women at high risk of an NTD:

The recommendation to prescribe folic acid 5 mg daily to people at higher risk of a NTD and 400 micrograms to people at normal risk of NTD is based on the recommendations of an expert advisory group in 1992, and reiterated by the National Institute for Health and Care Excellence in their antenatal guideline [Expert Advisory Group et al, 1992; NICE, 2008b]. A woman is considered to be at high risk of conceiving a child with an NTD if:

Either she or her partner (or a first-degree relative) have had a previous pregnancy affected by a NTD, or if either suffers from the condition themselves (the risk is increased about ten-fold) [MRC Vitamin Study Research Group, 1991; Expert Advisory Group et al, 1992].

She has coeliac disease (when dietary intake of folate is likely to be compromised due to inability to digest wheat products) [DH, 2000; BNF 63, 2012].

She has type 1 or type 2 diabetes [CEMACH, 2006].

She is taking an anti-epileptic medication. The Guideline Development Group commissioned by the National Institute for Health and Care Excellence reviewed the evidence and recommended a higher dose of folic acid in the guideline 'The epilepsies. The diagnosis and management of the epilepsies in adults and children in primary and secondary care'. They quoted the conclusions of a narrative review: ‘The value of periconceptional folic acid supplementation for women in the general population is accepted. However, it is unclear whether folic acid supplementation protects against the embryotoxic and teratogenic effects of anti-epileptic drugs because animal and human studies and case reports have shown variable results. Nevertheless, folic acid supplementation is recommended for women with epilepsy as it is for other women of childbearing age. However, the dose of 400 micrograms per day may not be high enough for many women who do not metabolize folate effectively.’ [National Clinical Guideline Centre, 2012].

She or her partner have a family history of a child with a neural tube defect [BNF 63, 2012].

She has pre-pregnancy obesity [CMACE and RCOG, 2010; UKTIS, 2011d].

Inconclusive data suggest that there is a higher prevalence of NTD among women who have thalassaemia trait:

In one study, women were referred to a tertiary centre for prenatal diagnosis [Lam and Tang, 1999]. Of the 1961 women referred, 206 women were alpha-thalassaemia heterozygotes and 102 women were beta-thalassaemia heterozygotes. Three alpha-thalassaemia carriers and one beta-thalassaemia carrier had a pregnancy affected by anencephaly compared with five of the 1523 non-carrier pregnancies available for follow-up, which were affected by spina bifida (OR 3.99, 95% CI 1.07 to 14.94; p < 0.05).

A second study (n = 75 women with a pregnancy affected by a NTD) found that the prevalence of thalassaemia carriers who had a pregnancy affected by a NTD was significantly higher than in the general population (22.5% versus 14%; p < 0.05) [Ibba et al, 2003].

Basis for recommending high dose folic acid supplements in women with thalassaemia trait

Women with thalassemia trait are anaemic because erythropoiesis is ineffective. The increased turnover in the bone marrow results in folate depletion. Expert advice in a text book is that these women will probably benefit from taking 5 mg of folic acid daily throughout pregnancy [Strong and Rutherford, 2011].

Basis for recommending high dose folic acid supplements in women with haemolytic anaemias including haemoglobinopathies.

Expert advice in a textbook is that women with haemolytic anaemia including haemoglobinopathies need extra folate supplementation from early pregnancy. Experts advise that women should continue taking folic acid at a dose of 5 mg to 10 mg daily throughout their pregnancy [Strong and Rutherford, 2011].

Women with sickle-cell anaemia have an increased requirement for folic acid, due to the increased production of red blood cells, and are advised to take lifelong folic acid supplements. [Oteng-Ntim et al, 2003; Oteng-Ntim et al, 2006].

Advice on smoking

What advice should I give to a woman planning pregnancy who smokes?

Advise all women planning pregnancy who smoke to stop smoking:

Offer women who wish to stop smoking referral to a smoking-cessation service.

Advise women who may become pregnant to initially try to stop smoking without using nicotine replacement therapy (NRT).

Offer NRT to women who are planning pregnancy, and who have tried and failed to stop smoking without using NRT.

Do not prescribe bupropion or varenicline to women who may become pregnant.

For further information about how to manage a woman who wishes to stop smoking see the CKS topic on Smoking cessation.

Basis for recommendation

Basis for recommendation

Why advise women who smoke and wish to become pregnant to stop smoking?

Smoking in pregnancy increases the risk of miscarriage, preterm delivery, reduced birthweight, and perinatal death [Dobson et al, 1998].

Why offer referral to a smoking-cessation service?

There is evidence from a Cochrane systematic review of the effectiveness of these interventions at reducing the number of women who are pregnant and smoke [Lumley et al, 2009].

Why advise women who may become pregnant to initially try to stop smoking without using NRT?

In the early stages of pregnancy a woman may not be aware that she is pregnant. For women using NRT this exposes the fetus to nicotine. The risk of this exposure to the fetus has not been established, and is avoided if the woman can stop smoking without using NRT.

Why offer NRT to women who have tried and failed to stop smoking without using NRT?

Cigarette smoking, in general, delivers more nicotine than NRT, and also exposes the mother and fetus to many other toxins. NRT is likely to be appreciably safer than continued smoking, and can theoretically be justified in pregnant women in whom non-pharmacological interventions have failed [Dempsey and Benowitz, 2001; NHS Northern & Yorkshire Regional Drug & Therapeutics Centre, 2008; NICE, 2008a].

Why is bupropion or varenicline not recommended to women who may become pregnant?

There are a lack of data available on the safety of these drugs during pregnancy. If bupropion or varenicline is prescribed, the course should be completed before the woman tries to conceive as they should not be offered to pregnant women [NICE, 2008a; BNF 63, 2012].

Advice about alcohol consumption

What advice should I give to a women planning pregnancy, regarding alcohol consumption?

Advise women planning pregnancy (or who are at any stage of pregnancy) to avoid drinking alcohol. If women do choose to drink, to minimize the risk to the baby, they should not drink more than one to two units of alcohol once or twice a week and should not binge drink (defined as more than five standard drinks or 7.5 UK units on a single occasion).

Offer support to women who wish to reduce their drinking to within recommended levels but feel unable to do so alone.

Offer specialist referral if a women is unable to reduce her drinking with support in primary care.

Additional information

Additional information

One unit of alcohol:

In the UK one unit is defined as a drink containing 8 g of ethanol. This is equivalent to:

Half a pint of average strength beer, lager, or cider (3–4% alcohol by volume [ABV]).

Small pub measure (25 mL) of spirits (40% ABV).

Standard pub measure (50 mL) of fortified wine, for example sherry, or port (20% ABV).

A small glass (125 mL) of average strength wine (12% ABV) contains 1.5 units of alcohol.

A standard pub measure (35 mL) of spirits (40% ABV) contains 1.5 units of alcohol.

Specialist referral for people who are unable to reduce their drinking:

A fetus is at risk of harm from levels of alcohol consumption that are unlikely to have any long term risks to the health of the mother. Levels of drinking that are considered harmful to a woman's health should not be used as a guide for when to refer a women who may become pregnant.

For further information on how to provide advice and support for a person who wishes to reduce their drinking, see the CKS topic on Alcohol - problem drinking.

Basis for recommendation

Basis for recommendation

The recommendation for women to avoid alcohol if they are pregnant or trying to conceive comes from the Department of Health [DH, 2012]. This updated advice is not a result of new scientific evidence, but is consistent with the current evidence. The advice has been revised to make it easier to understand and to provide consistent advice across the UK.

Guidelines from the National Institute for Health and Care Excellence advise women planning a pregnancy to avoid drinking alcohol [NICE, 2008b]:

Alcohol consumption in the first 3 months of pregnancy may be associated with an increased risk of miscarriage.

Getting drunk and binge drinking may be harmful to the unborn infant.

There is uncertainty about a safe level of alcohol consumption although there is no evidence of harm to the infant when mothers have drunk 1–2 UK units a week.

Women who are planning pregnancy may become pregnant at any time, and in the early stages of pregnancy may be unaware that they are pregnant. Therefore, the recommendations for safe drinking levels for pregnant women should also be applied to women planning pregnancy.

Advice on illicit drug use

What advice should I give to a woman planning pregnancy, who uses illicit drugs?

Advise women planning pregnancy who use illicit drugs to stop using drugs, if they are able to do so.

Offer people injecting illicit drugs testing for hepatitis C, hepatitis B, and HIV and refer if tests are positive.

Offer referral to women planning pregnancy who use illicit drugs and are unable to stop with support in primary care.

Offer contraceptive advice to women using illicit drugs who may become pregnant before illicit drug use has stopped.

Additional information

Additional information

Referring women who are using illicit drugs to specialist drugs and alcohol services:

Refer women who are unable to stop using illicit drugs without specialist help.

Women using opioids may be offered stabilization and maintenance on methadone in place of complete withdrawal from opioids.

For further information about managing pregnant women who are dependant on opioids, see the CKS topic on Opioid dependence.

Offering contraceptive advice to women who may become pregnant before stopping illicit drug use:

Women may become pregnant when there is a delay in stopping illicit drug use. This delay may occur because:

They may not be motivated to stop their drug use.

Referral to specialist drugs and alcohol services takes time.

Treatment and withdrawal from illicit drugs may take time to complete.

For further information see the CKS topic on Contraception - assessment.

Basis for recommendation

Basis for recommendation

Basis for advice to stop any illicit drug use before conception:

The fetus is particularly vulnerable to the harmful effects of drugs. No illicit drugs have definitely been established as safe during pregnancy.

It is therefore widely recommended by experts that all illicit drugs should be avoided during pregnancy.

Evidence from a number of studies have reported an increased risk of fetal harms from cocaine use during pregnancy, including [Shankaran et al, 2007]:

Higher rate of premature birth.

Lower birth weight.

Smaller head circumference.

Intracerebral haemorrhage.

Behavioural problems that persist until at least 7 years old in children born to mothers that were heavy cocaine users during pregnancy.

A number of studies have reported harms to the fetus from illicit opioid use (such as heroin) during pregnancy. However, confounding factors, such as high rates of smoking and poor diet in this population, mean that it is difficult to determine the size of the effect directly caused by opioid use. Harms reported include [Shankaran et al, 2007]:

Low birth weight.

Intrauterine growth retardation.

Infant distress due to acute drug withdrawal after delivery.

Basis for hepatitis C, hepatitis B, and HIV testing [RCGP, 2007]:

Hepatitis C is transmitted to the fetus in up to 6% of people with chronic infection. It is not thought to occur in people who have been infected but have cleared the virus, either naturally or following treatment.

Treatment with ribavirin and interferon is successful in clearing the virus in between 40 to 60% of people. Treatment prior to conception can prevent fetal infection.

There are no pre-conception treatments to prevent transmission of HIV or hepatitis B to the fetus, but it is sensible to test for these conditions at the same time when there is a clear risk factor.

Advice on hazardous substances or radiation

What advice should I give to women who are planning pregnancy who may be exposed to hazardous substances or radiation?

Advise women planning pregnancy to read product warning labels before using chemicals.

Advise a woman who is planning pregnancy and is concerned about work exposure to hazardous substances, infections, or radiation, to discuss her intention of becoming pregnant to her employer, if possible.

Advise a woman planning pregnancy, who does not wish to discuss her intention to become pregnant to her employer, that information about the risk of exposure to specific substances can be obtained by telephoning an expert at the Health and Safety Executive.

Further information is available on the Health and Safety Executive website at www.hse.gov.uk. This includes:

The health and safety obligations of employees and employers with regards to hazardous substances and radiation.

Information about the risks of specific substances.

The telephone number of an expert for discussion of the risks of specific substances.

Basis for recommendation

Basis for recommendation

Basis for recommending a woman discusses her intention to become pregnant with her employer:

An employer is legally obliged to [UK Parliament, 1999]:

Ensure that employees are informed of all potential risks to their health and safety.

Assess the health and safety risks for different groups of employees, including the risks to women of childbearing age who could be in the early stages of pregnancy but unaware that they are pregnant.

Inform all women of childbearing age of potential hazards in their workplace.

Implement all reasonable health and safety measures identified by the assessment as being necessary, to remove or reduce the risk to women of childbearing age.

By discussing her intention to become pregnant with her employer, a woman has the opportunity to discuss any concerns she may have about her exposure to hazardous substances.

Knowing that she intends to become pregnant, her employer may need to take reasonable measures to reduce or remove any potential risks to the woman.

Advice on vitamin A and OTC or herbal medicines

What advice should I give to women planning pregnancy regarding vitamin A, and over-the-counter or herbal medicines?

Advise women planning pregnancy not to take any over-the-counter medicines without consulting a pharmacist to ensure that these products are safe to take if she were to become pregnant.

Advise women planning pregnancy not to take any herbal remedies.

Advise women planning pregnancy not to exceed 10,000 IU of vitamin A (from supplementation), either before becoming pregnant or at any time during pregnancy.

Vitamin A supplements

Vitamin A supplements

Vitamin A can be obtained in two forms, vitamin A (retinol) and pro-vitamin A (beta-carotene).

Beta-carotene is converted to vitamin A as needed by the body and therefore, there are no concerns over the safety of beta-carotene supplementation.

The composition of a daily vitamin supplements is now limited to a maximum of 6000 IU of vitamin A. As long as a person does not exceed the recommended daily intake of vitamins they will remain well within the safe daily dose for vitamin A.

[Schaefer et al, 2007]

Basis for recommendation

Basis for recommendation

Basis for recommending that women seek advice from a pharmacist about the safety of over-the-counter medicines:

Some over-the-counter medicines, such as ibuprofen, are not recommended during pregnancy because of their potential to harm the fetus.

Women who are trying to become pregnant may not be aware they are pregnant in the early stages, when the fetus is at its most vulnerable to the harmful effects of certain drugs.

Basis for recommending that women planning pregnancy do not to take any herbal remedies:

Herbal remedies are unlicensed products and there is little or no information on their safety immediately before or during pregnancy.

Basis for recommending limiting vitamin A supplementation in pregnancy:

There is evidence that taking more than 10,000 IU of vitamin A daily from supplementation may result in an increased incidence of birth defects [WHO, 1998].

Advice on being overweight or obese

What advice should I give women planning pregnancy who are overweight or obese?

Advise the woman of the potential health risks of being obese:

Pre-pregnancy obesity is associated with an increased risk of the infant developing:

Neural tube defects.

Heart defects.

Cleft palate and/ or cleft lip.

Anorectal atresia.

Hydrocephaly.

Limb reduction abnormalities.

Increasing obesity (higher body mass index [BMI]) is associated with a proportionally increased risk of adverse pregnancy outcomes. There is an increased risk of impaired glucose tolerance, gestational diabetes, miscarriage, and maternal death. A small increase in body mass index (BMI) such as 1–2 BMI units (kg/m2) between pregnancies increases the risk of developing gestational hypertension and gestational diabetes even if the woman is not overweight or obese, and increases the risk of having a large baby [NICE, 2010a].

Advise women who are overweight or obese to lose weight before becoming pregnant.

Overweight is defined as a BMI between 25 kg/m2 and 29.9 kg/m2.

Obesity is defined as a BMI of 30 kg/m2 or more.

Target weight for a person who is overweight or obese:

Women should be informed of the increased health risks their weight poses to themselves and would pose to their unborn child.

Women should be informed that losing 5–10% of their weight (a realistic target) would have significant health benefits and could increase their chances of becoming pregnant.

Women should be encouraged to check their weight and waist measurement periodically, or as an alternative, check the fit of their clothes.

Offer a weight loss support programme that includes advice about diet and physical activity.

Women should be aware that if they do fall pregnant, there is no need to 'eat for two' or to drink full-fat milk.

Advise women who are obese (BMI of 30 kg/m2 or more) to take folic acid 5 mg daily starting at least one month before conception and continuing during the first trimester.

Additional information

Additional information

Body mass index (BMI):

The body mass index (BMI) is calculated by dividing the body weight in kilograms by the square of the height in metres.

For further information on managing people who are overweight or obese, see the CKS topic on Obesity.

Target weight for a person who is overweight or obese:

People that are overweight or obese are at an increased risk of adverse pregnancy outcomes compared to people who are not overweight. This risk is proportional to a person's BMI, with the increased risk being modest in a person who is overweight but significant in people who are obese, particularly people with a BMI of over 40 kg/m2.

It is impractical to expect most people who are overweight or obese to reduce their weight to their ideal body weight. However, they should be informed of their increased risk of adverse pregnancy outcomes caused by their excess weight and supported in their efforts to reduce weight as much as possible before becoming pregnant.

Weight loss programmes are not recommended during pregnancy as they may harm the health of the unborn child. There are no evidence-based UK guidelines on recommended weight-gain ranges during pregnancy, and there is great variability in the amount of weight pregnant women can gain during pregnancy.

Basis for recommendation

Basis for recommendation

Risks of being obese during pregnancy

The recommendation to advise women of the potential health risks of obesity is based on the National Institute for Health and Care Excellence (NICE) public health guidance Dietary interventions and physical activity interventions for weight management before, during and after pregnancy [NICE, 2010a].

Risk to the fetus

This information is from the UK teratology information service [UKTIS, 2011d].

Health risks of obesity for mother and child during pregnancy

This information is based on expert opinion in the NICE guideline Dietary interventions and physical activity interventions for weight management before, during and after pregnancy [NICE, 2010a].

Studies demonstrate that women who are overweight or obese have a greater risk of an adverse pregnancy outcome compared with women who are not overweight. These adverse pregnancy outcomes include [Cedergren, 2004; Villamor and Cnattingius, 2006]:

Pre-eclampsia.

Antepartum stillbirth.

Caesarean section.

Instrumental delivery.

Shoulder dystocia.

Fetal distress.

Early neonatal death.

Weight loss and target weight

The recommendation to advise women to lose weight if obese or overweight and the target weight loss suggested, are based on the National Institute for Health and Care Excellence (NICE) public health guidances: Weight management before, during and after pregnancy [NICE, 2010b], and Dietary interventions and physical activity interventions for weight management before, during and after pregnancy [NICE, 2010a].

Weight loss support programme

This information is based on expert opinion in the NICE guideline Dietary interventions and physical activity interventions for weight management before, during and after pregnancy [NICE, 2010a].

Dietary advice if a woman falls pregnant

This recommendation is based on the fact that energy needs do not change in the first 6 months of pregnancy, and in the last 3 months of pregnancy they increase slightly by approximately 200 calories per day [NICE, 2010b].

Dose of folic acid

A dose of 5 mg daily is advised by the UK teratology information service [UKTIS, 2011d].

Expert opinion in the guideline Management of women with obesity in pregnancy produced by the Royal College of Obstetricians and Gynaecologists and the Centre for Maternal and Child Enquiries advises starting folic acid 5 mg daily at least one month before conception and continuing throughout the first trimester [CMACE and RCOG, 2010]. They base their advice on the results of a meta-analysis of 12 cohort studies that reported the following odds ratios (OR) for neural tube defects:

Overweight women: OR 1.22, (95% CI 0.99 to 1.49).

Obese women: OR 1.70, (95% CI 1.34 to 2.15).

Severely obese women: OR 3.11, (95% CI 0.1.75 to 5.46).

Advice on cervical screening

What advice should I give a woman who wishes to become pregnant regarding cervical screening?

Advise all women planning pregnancy who are due a cervical smear test to have the test as soon as possible, before becoming pregnant.

Basis for recommendation

Basis for recommendation

Cervical smears are not routinely taken during pregnancy as pregnancy-related inflammatory changes make them difficult to interpret.

Guidelines from the NHS cancer screening programme recommend deferring a routine cervical screening test if the woman is pregnant [NHS Cancer Screening Programmes, 2006; NHS Cancer Screening Programmes, 2010].

Advice on immunizations

What advice should I give women planning pregnancy regarding immunizations?

Test women planning pregnancy for immunity to rubella if they do not have documented immunity, and vaccinate if the test is negative.

Test women planning pregnancy for immunity to varicella if they do not have a definite history of chickenpox or shingles, and vaccinate if the test is negative and they are eligible for the vaccine. Women eligible for varicella vaccine include healthcare workers who may come into direct contact with infected patients and healthy, susceptible close contacts of immunocompromised patients.

Vaccinate women planning pregnancy against hepatitis B if they are at high risk of contracting the disease.

People at risk include intravenous drug users, those who change sexual partners frequently, those with chronic renal or liver disease, and those who are in close contact with people with hepatitis B.

Additional information

Additional information

Rubella:

Women are considered immune to rubella when [DH, 2010]:

A rubella antibody screening test has detected antibodies.

At least two documented doses of rubella vaccine have been given.

Vaccinating against rubella [DH, 2010]:

The measles, mumps, and rubella (MMR) combined vaccine is now used for immunization of unprotected women of childbearing age, due to the non-availability of single rubella vaccine.

Women should be advised to use effective contraception to avoid becoming pregnant for 1 month after receiving rubella-containing vaccine, although surveillance of women immunized during pregnancy, including 293 immunized during the high-risk period 6 weeks after the last menstrual period, failed to detect any significant problems.

Varicella:

Women are eligible for varicella vaccination when they are [DH, 2011]:

Healthcare workers who come into direct contact with patients.

Healthy, susceptible close contacts of immunocompromised patients.

Women are considered immune to varicella when [DH, 2011]:

They have a definite history of chickenpox or Herpes zoster.

They do not have a definite history of chickenpox or Herpes zoster, but testing has demonstrated varicella immunity.

Hepatitis B:

People are considered at risk of hepatitis B if they [DH, 2009]:

Are intravenous drug users or at risk of starting to inject, such as people that presently smoke heroin or crack cocaine.

Change partners frequently, particularly commercial sex workers and men who have sex with men.

Are in close contact with people with acute or chronic hepatitis B or in close contact with people at risk of developing hepatitis B. This includes:

Health workers.

Close family contacts of someone with the disease, or at risk of developing the disease.

People travelling to, or going to reside in, areas of high or intermediate prevalence of the disease.

People in prison.

Individuals with learning difficulties in residential accommodation.

Have chronic renal failure.

Have chronic liver disease.

Basis for recommendation

Basis for recommendation

Basis for recommending immunization against rubella for non-immune women who are planning pregnancy

Maternal immunity to rubella prevents infection which can cause fetal death or congenital rubella syndrome. This syndrome is most likely when infection occurs in the first 8–10 weeks of pregnancy and includes [DH, 2010]:

Cataracts and other eye defects.

Deafness.

Cardiac abnormalities.

Microcephaly.

Intrauterine growth retardation.

Inflammatory lesions of brain, liver, lungs, and bone marrow.

Basis for recommending the restricted use of varicella immunization

It is recommended that varicella immunization is restricted to healthcare workers who come into direct contact with patients and healthy, susceptible close household contacts of immunocompromised patients because [DH, 2011]:

Although there would be benefit from immunizing the general population against varicella, the supply of vaccine is limited. Therefore, the Department of Health recommends restricting its use to those at greatest risk and for whom there is evidence that it is likely to be effective.

Basis for recommending immunization against varicella for non-immune women planning pregnancy who are eligible for the vaccine

To prevent fetal harm following maternal varicella infection. These harms include [DH, 2011]:

In the first 20 weeks of pregnancy, congenital (fetal) varicella syndrome which includes limb hypoplasia, microcephaly, cataracts, growth retardation, and skin scarring.

In the second and third trimesters of pregnancy, herpes zoster may result in an otherwise healthy infant. Occasional cases of fetal damage comprising chorioretinal damage, microcephaly, and skin scarring may result.

In the last 7 days before, to a week after, delivery, severe and even fatal disease in the neonate.

To prevent maternal harm in the second and third trimester of pregnancy. Maternal deaths have been reported due to varicella infections between 27 and 32 weeks gestation.

Basis for recommending immunization against hepatitis B for women planning pregnancy who are at risk of contracting hepatitis B

Maternal immunization against hepatitis B prevents infection that can be transmitted to the baby perinatally [DH, 2009].

Previous miscarriage(s)

How do I manage a woman with previous miscarriage(s)?

Reassure the woman that she still has a good chance of a subsequent successful pregnancy.

Refer women who have had three or more consecutive miscarriages to a gynaecologist for identification and management of any treatable cause.

For more information see the CKS guidance on Miscarriage.

Basis for recommendation

Basis for recommendation

Miscarriage is relatively common, occurring in 20% of all clinically-recognized pregnancies [RCOG, 2008].

If the last pregnancy ended normally, the risk of miscarriage in the next pregnancy is reduced to about 5% [Regan et al, 1989].

If the last pregnancy ended in miscarriage, the risk of miscarriage in the next pregnancy is increased to about 20% [Regan et al, 1989].

Around 1% of women have recurrent miscarriages [RCOG, 2011].

A woman who has had three consecutive miscarriages still has a 60–75% chance of a successful fourth pregnancy [Drife and Magowan, 2004].

It is recommended that a woman with recurrent miscarriages is referred to a gynaecologist for identification and management of any treatable cause [RCOG, 2011]. Conditions associated with recurrent miscarriage include [RCOG, 2011]:

Antiphospholipid syndrome

Genetic factors

Thrombophilia

Incompetent cervix

In a significant proportion of women who have recurrent miscarriages, the cause remains unexplained despite investigation. In these women the prognosis for a successful future pregnancy with supportive care alone is about 75% [Drife and Magowan, 2004; RCOG, 2011].

Scenario: Mental health issues

Scenario: Pre-conception advice - women with mental health issues

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Depression

How do I manage a woman with depression who wishes to become pregnant?

In women with depression assess:

The risks of stopping any current antidepressant medication in relation to the woman's current mental state, her previous history of depression, and duration of current antidepressant medication.

The safety during pregnancy of the current antidepressant medication, and the possibility of switching to an antidepressant more appropriate for use during pregnancy.

Seek specialist advice in women with severe depression, or if unsure whether to try withdrawing or switching an antidepressant.

Advise the woman not to stop taking her medication unless otherwise directed by the psychiatrist or the primary care practitioner.

For further information, see What are the risks of taking antidepressant drugs in pregnancy?

Offer general pre-pregnancy advice (see Advice for all women).

What are the risks of taking antidepressant drugs in pregnancy?

What are the risks of taking antidepressant drugs during pregnancy?

Tricyclic antidepressants (TCAs)

Extensive epidemiological studies have shown no evidence that therapeutic doses of TCAs are associated with an increased incidence of congenital malformations or other adverse pregnancy outcomes [NTIS, 2005].

Selective serotonin reuptake inhibitors (SSRIs)

First trimester exposure to SSRIs.

Some studies have reported an increased risk of cardiovascular malformations with SSRIs but a causal relationship has not been demonstrated [UKTIS, 2011j]. The risk has been demonstrated most consistently with paroxetine [UKTIS, 2011j; UKTIS, 2011g]. The possibility of a class effect cannot be excluded [MHRA, 2010].

Recent evidence also suggests that there may be a small increased risk of cardiovascular malformations with fluoxetine (ranging in severity from reversible ventricular septal defects to transposition of the great vessels). Meta-analysis of data from seven cohort studies suggest that the risk of having an infant with a cardiovascular defect following maternal fluoxetine exposure is less than 2 in 100 [MHRA, 2010; UKTIS, 2011h].

Evidence is contradictory but an increased risk of cardiovascular malformations with sertraline and citalopram has been suggested. If true, the risk appears to be small [UKTIS, 2011l; UKTIS, 2011k].

Data on the safety of escitalopram are extremely limited [UKTIS, 2011i].

Data on fluvoxamine are limited but it is probably safe [Schaefer et al, 2007]. The Summary of Product Characteristics from the manufacturer does not report any teratogenic effects [ABPI Medicines Compendium, 2011].

Use of SSRIs later in pregnancy may be associated with [UKTIS, 2011j]:

A mild transient neonatal withdrawal syndrome.

Probably a very small increased risk of persistent pulmonary hypertension of the newborn if there is exposure to SSRIs beyond 20 weeks. There are no data to quantify the risk with a specific SSRI or to know if the effect is dose related.

Monoaminoxidase inhibitors (MAOIs)

MAOIs are not recommended for use in pregnancy and there are limited data available on their safety in pregnancy. They can exacerbate pregnancy-associated hypertension, with consequences for fetal growth and development, and they have the potential to interact with other medication and certain food substances, which may produce a hypertensive crisis [Schaefer et al, 2007].

Other antidepressants

Other antidepressants such as duloxetine, mianserin, reboxetine, and trazadone should be avoided if possible as there is limited information about their use and safety [Schaefer et al, 2007]. Mirtazapine and venlafaxine are drugs of second choice [Schaefer et al, 2007]. Limited data on mirtazepine and venlafaxine do not suggest an increase in the risk of congenital malformations. Neonatal withdrawal symptoms would be expected with mirtazepine and venlafaxine and there are theoretical concerns that neonatal exposure to venlafaxine could result in persistent pulmonary hypertension of the newborn [NTIS, 2010; UKTIS, 2011f].

Basis for recommendation

Basis for recommendation

These recommendations are based on advice from the UK teratology information service [UKTIS, 2011j] and accepted good clinical practice.

Bipolar affective disorder

How should I manage a woman with bipolar affective disorder who wishes to become pregnant?

Refer all women with bipolar affective disorder who wish to become pregnant to a psychiatrist for assessment and review of current medication.

Advise the woman to continue using effective contraception until she has been fully reviewed by the psychiatrist.

Advise the woman not to stop taking her medication unless otherwise directed by the psychiatrist.

For more information see the section on Planning a pregnancy in the CKS topic on Bipolar affective disorder.

Offer general pre-pregnancy advice (see Advice for all women).

Women taking anti-epileptic drugs for treatment of their bipolar disorder are considered to be at high risk of conceiving a child with a neural tube defect, and should be prescribed folic acid 5 mg daily until the twelfth week of pregnancy.

Basis for recommendation

Basis for recommendation

Referral to a psychiatrist is recommended to assess and manage the potential risks to both mother and fetus.

The potential for medication to cause adverse obstetric and neonatal outcomes — the National Institute for Health and Care Excellence (NICE) recommends that women with bipolar affective disorder who are considering pregnancy should normally be advised to stop taking valproate, carbamazepine, lithium, and lamotrigine, and that alternative prophylactic drugs (such as an antipsychotic) should be considered.

The effect of pregnancy and childbirth on the natural course of bipolar affective disorder — in women with a diagnosis of bipolar affective disorder there is approximately a 50% chance of an episode of psychosis in the postnatal period.

The effect of medication on fertility — conventional antipsychotics and some atypical antipsychotics can reduce fertility by causing hyperprolactinaemia.

[NICE, 2006]

Schizophrenia

How do I manage a woman with schizophrenia who wishes to become pregnant?

Refer all women with schizophrenia who wish to become pregnant to a psychiatrist for assessment and review of current medication.

Advise the woman to continue using effective contraception until a full assessment by the psychiatrist has taken place.

Advise the woman not to stop taking her medication unless otherwise directed by the psychiatrist.

For more information see the scenario Scenario: Women of childbearing age in the CKS topic on Schizophrenia.

Offer general pre-pregnancy advice (see Advice for all women).

Basis for recommendation

Basis for recommendation

CKS recommends referral to a psychiatrist to assess the potential risk to the fetus of current medication, and the likelihood of maternal relapse.

Scenario: Metabolic disorders

Scenario: Pre-conception advice - women with metabolic disorders

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Thyroid disease

How do I manage a woman with thyroid disease who wishes to become pregnant?

Subclinical hypothyroidism:

Perform thyroid function tests (TFTs) before conception if they have not been done in the past 6 months. For more information see Pre-existing subclinical hypothyroidism in the CKS topic on Hypothyroidism.

If the woman has subclinical hypothyroidism and is not receiving levothyroxine treatment, start this whilst waiting for specialist referral. Follow local specialist advice regarding an appropriate starting dose.

Advise women who are planning a pregnancy to consult their GP as soon as they think they may be pregnant as dosage adjustment may be needed, together with regular monitoring of thyroid function.

Hypothyroidism:

Ensure optimum control before pregnancy. For more information see Pre-existing overt hypothyroidism in the CKS topic on Hypothyroidism.

Perform TFTs before conception to check adequacy of treatment and to make sure the woman is stable. Ensure she understands the importance of compliance with levothyroxine therapy.

Advise women who are planning a pregnancy to consult their GP as soon as they think they may be pregnant as dosage adjustment may be needed, together with regular monitoring of thyroid function.

Hyperthyroidism:

Refer women who are not already under consultant care, or inform the specialist responsible for the woman's care that she wishes to conceive.

Advise the woman that frequent monitoring of thyroid function during pregnancy will be required.

Deferring pregnancy until the course of treatment has been completed may be a better option, if practical.

For women planning pregnancy within the next 2–3 years, initial treatment with radioactive iodine or surgery may be best. Radioactive iodine is contraindicated in pregnancy and during breastfeeding — women should avoid becoming pregnant and men should not father children for at least 4 months following treatment.

Discuss the standard pre-conception measures (see Advice for all women).

For further details, see the CKS topics on Hyperthyroidism and Hypothyroidism.

Basis for recommendation

Basis for recommendation

Subclinical hypothyroidism

These recommendations are based on expert opinion [Edwards and Vanderpump, 2007]. Some of the evidence to support these recommendations is based on observational studies.

There is evidence that subclinical hypothyroidism can progress to overt hypothyroidism, particularly in people who are antithyroid-antibody positive [Vanderpump et al, 1995; Surks et al, 2004].

The need for levothyroxine is increased in pregnancy in women with hypothyroidism, and absorption of levothyroxine may be diminished. It is important to intervene quickly as soon as pregnancy has been diagnosed [BTA et al, 2006].

There is evidence of increased fetal loss, and intelligence quotient (IQ) and psychomotor deficits, in infants born to mothers with undiagnosed or inadequately treated hypothyroidism (including subclinical hypothyroidism) [Haddow et al, 1999; Pop et al, 1999; Casey et al, 2005].

The increase in the levothyroxine dose is necessary to maintain normal serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) for the gestational age [BTA et al, 2006].

Hypothyroidism

These recommendations are based on a UK consensus guideline produced by the Association for Clinical Biochemistry, British Thyroid Association, and the British Thyroid Foundation [BTA et al, 2006].

The need for levothyroxine increases in pregnancy in women with hypothyroidism, and absorption of levothyroxine may be diminished. It is therefore important to intervene quickly as soon as pregnancy has been diagnosed [BTA et al, 2006].

The increase in the levothyroxine dose is necessary to maintain normal serum TSH and FT4 for the gestational age. A TSH concentration of 0.4–2.0 mU/L is normal for pregnancy [BTA et al, 2006].

There is evidence of increased fetal death, and intelligence quotient (IQ) and psychomotor deficits, in infants born to mothers with undiagnosed or inadequately treated hypothyroidism [Haddow et al, 1999; Pop et al, 1999; Casey et al, 2005].

Other risks if untreated include a higher incidence of stillbirth, congenital abnormalities and obstetric complications [Lazarus, 2010].

If inadequately treated, hypothyroidism is associated with anovulation. However, with adequate replacement, ovulation is normal [Chamberlain and Morgan, 2002].

Hyperthyroidism

A consensus statement for good practice and audit measures in the management of hypo- and hyperthyroidism recommends that anyone with hyperthyroidism can expect referral to a specialist at diagnosis of hyperthyroidism [Vanderpump et al, 1996]. As hyperthyroidism in pregnancy can present special concerns, the recommendation to inform the woman's specialist is a pragmatic one, in order to address any specific concerns as soon as possible.

Use of radioactive iodine is contraindicated during pregnancy. Consensus recommends that women of childbearing age should wait at least 4 months after radioiodine treatment before trying to conceive [Vanderpump et al, 1996; O'Doherty et al, 1999].

Diabetes mellitus

How do I manage a woman with diabetes mellitus who wishes to become pregnant?

Refer all women with diabetes mellitus who wish to become pregnant to a pre-conception diabetes clinic (if available) or to their diabetes care team, as soon as possible.

Advise women with type 2 diabetes that their current medication for diabetes will need to be reviewed, and that they will probably be advised to switch to insulin therapy for the duration of their pregnancy.

Discuss the importance of optimal blood glucose control with the woman.

Women planning pregnancy should ideally aim to achieve a pre-conception glycosylated haemoglobin (HbA1C) value of less than 42 mmol/mol (< 6.1%) if this can be achieved safely. Reassure the woman that any reduction in HbA1C towards the normal HbA1C value of less than 42 mmol/mol (< 6.1%) is likely to reduce the risk of congenital malformations. However if a normal HbA1C cannot be achieved then the woman should aim for a target of less than 53 mmol/mol (< 7%) if this target is safely achievable, but hypoglycaemic risk should be considered when trying to achieve this target.

Advise the woman to avoid pregnancy if the HbA1C is above 86 mmol/mol (10%).

Advise the woman to continue using effective contraception methods until her individualized target has been achieved.

Offer monthly monitoring of HbA1C.

Ensure that complications of diabetes are reviewed.

Ensure that concurrent medication is reviewed.

Measure thyroid stimulating hormone (TSH), free thyroxine, and thyroid peroxidase antibodies in women with type 1 diabetes.

Discuss the standard pre-conception measures (see Advice for all women).

Women with diabetes are considered to be at high risk of conceiving a child with a neural tube defect and should be prescribed folic acid 5 mg daily until week 12 of pregnancy.

Additional information

Additional information

Optimal blood glucose control

Explain that establishing good glycaemic control before conception and maintaining good glycaemic control throughout pregnancy will reduce but not eliminate the risk of miscarriage, congenital malformation, stillbirth, and neonatal death [NICE, 2008c].

Women planning pregnancy should aim to move towards a normal HbA1C value of less than 42 mmol/mol (< 6.1%). Women should aim to achieve HbA1C levels as close to the normal range as possible (where the upper limit of normal in people without diabetes is 6%), whilst avoiding the risk of hypoglycaemia. Diabetes UK suggest a value of 53 mmol/mol (<7%). Monthly monitoring of HbA1C is advised in guidelines from the National Institute for Health and Care Excellence [Canadian Diabetes Association, 2008; NICE, 2008c; Diabetes UK, 2011].

Home blood-glucose test results should not be higher than 5.5 mmol/L before meals, and 7.7 mmol/L 2 hours after meals [CEMACH, 2006; Diabetes UK, 2011].

Review complications of diabetes

Arrange screening for retinopathy, nephropathy, and neuropathy [International Diabetes Federation, 2005; American Diabetes Association, 2007; Canadian Diabetes Association, 2008] (see the section Surveillance for complications in the CKS topic Diabetes - type 1, and the section Initial assessment and review in the CKS topic on Diabetes - type 2). Assess renal function pre-conceptually and refer to a nephrologist before discontinuing contraception if [NICE, 2008c]:

Serum creatinine is 120 micromol/L or above.

Estimated glomerular filtration rate (eGFR) is less than 45 mL/minute/1.73m2.

Evaluate cardiovascular disease risk and ensure optimal blood pressure control [International Diabetes Federation, 2005; American Diabetes Association, 2007] (see the CKS topics on CVD risk assessment and management, and Hypertension in pregnancy. Also see the section Managing cardiovascular risk in the CKS topic Diabetes - type 1, and the scenarios Managing blood pressure and Managing lipids in the CKS topic Diabetes - type 2.

Review concurrent medication

Stop angiotensin converting enzyme (ACE) inhibitors and angiotensin-II receptor antagonists (AIIRAs) [International Diabetes Federation, 2005; CEMACH, 2006; American Diabetes Association, 2007]. For more information about managing hypertension in pregnancy see the CKS topic on Hypertension in pregnancy.

Stop statins and fibrates [International Diabetes Federation, 2005; CEMACH, 2006].

Basis for recommendation

Basis for recommendation

Referral:

The recommendation to refer all women with diabetes mellitus is based on the Confidential Enquiry into Maternal and Child Health [CEMACH, 2006]. Referral is recommended to explain the risks associated with pregnancy, to ensure that optimal blood glucose control is achieved, and to review any medication that may be harmful to the fetus.

Women with type 2 diabetes who are planning a pregnancy should discontinue oral hypoglycaemics prior to conception (metformin is occasionally indicated) and attain glycaemic targets using insulin, if indicated. This should be done under specialist supervision.

There is no evidence that metformin or the sulphonylureas are teratogenic. However, metformin may be associated with growth retardation and hyperbilirubinaemia. Sulphonylureas cross the placenta and may cause hyperinsulinaemia and macrosomia in the fetus [Seymour and Pugh, 2000; American Diabetes Association, 2003].

Insulin allows a better degree of metabolic control during pregnancy than oral hypoglycaemics.

Human insulin does not cross the placenta, and there is no indication that it is associated with an increased risk of fetal or neonatal toxicity. Insulin glargine is not recommended for use during pregnancy as there are currently a lack of data to support its safety [UKTIS, 2011e].

Optimal blood glucose control:

The recommendation to improve a pre-conception HbA1C towards a normal value of less than 42 mmol/mol (<6.1%) is based on recommendations from the guideline development group in the guideline Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period commissioned by the National Institute for Health and Care Excellence [NICE, 2008c]. Expert opinion from Diabetes UK suggests that if possible HbA1C should be less than 53 mmol/mol (<7%) taking hypoglycaemic risk into account [Diabetes UK, 2011].

Poor control of diabetes increases the risks of major congenital abnormality and spontaneous abortion. Studies have identified an association between raised maternal glucose levels during embryogenesis and high rates of spontaneous abortion and major malformation [American Diabetes Association, 2003].

Observational studies indicate that the risk of malformations increases continuously with increasing maternal glycaemia during the first 6–8 weeks of gestation [American Diabetes Association, 2007].

Epidemiological studies indicate that HbA1C values less than 1% above normal are associated with rates of congenital malformations and spontaneous abortions similar to those in non-diabetic pregnancies [American Diabetes Association, 2003].

Studies have shown that providing pre-conception care to promote the achievement of tight blood glucose control during the pre-conception period and the first trimester reduces rates of malformation [American Diabetes Association, 2003].

Pre-conception care appears to reduce the risk of congenital malformations (five non-randomized studies; incidence = 1.0–1.7% in infants of mothers receiving care versus 1.4–10.9% in women who did not participate) [American Diabetes Association, 2007].

Pregnancy may affect glycaemic control, increasing the risk of hypoglycaemia, and decreasing the ability to be aware that hypoglycaemia is occurring [NICE, 2008c].

Review complications of diabetes:

Diabetic retinopathy, if present, can accelerate during pregnancy [Diabetes UK, 2011]. Rapid reduction of blood glucose concentrations has been shown to accelerate diabetic retinopathy in both pregnant and non-pregnant women. There is also evidence that pregnancy, and hypertension complicating pregnancy, may act as independent risk factors for the progression of diabetic retinopathy. Formal retinal assessment should therefore be performed before pregnancy so that improved diabetic control can be achieved in the 3–9 months before a planned conception. This should avoid the need for acute improvement of the blood glucose concentrations in early pregnancy and thus minimize the risk of exacerbating proliferative retinopathy [NICE, 2008c; Hod and Yogev, 2010].

The guideline development group in the guideline Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period commissioned by the National Institute for Health and Care Excellence recommend monitoring renal function pre-conceptually and referring to a renal physician if appropriate [NICE, 2008c].

Autonomic neuropathy may complicate the management of diabetes during pregnancy, and these complications should ideally be identified and managed before conception [American Diabetes Association, 2003].

Aggressive monitoring and control of hypertension in the pre-conception period is necessary to reduce the risk of further diabetic complications, and to stabilize the woman's blood pressure on drugs that are safe during pregnancy [American Diabetes Association, 2003].

Review concurrent medication:

Women should be referred to a diabetic specialist and may be advised to use metformin either with or as an alternative to insulin. All other oral hypoglycaemic medications should be stopped and insulin substituted [NICE, 2008c].

Available data do not show an increased risk of congenital malformations or adverse pregnancy outcomes in women taking metformin [UKTIS, 2011b].

Insulin does not cross the placenta and adverse outcomes in pregnancy in women taking insulin are believed to be due to glycaemic control rather than exposure to insulin [UKTIS, 2011e]. Data about insulin glargine are lacking but there is no indication of an increased risk of congenital malformations [UKTIS, 2011c].

Studies suggest that angiotensin-converting enzyme inhibitors (ACE inhibitors) are associated with congenital malformations, intrauterine growth retardation, hypoglycaemia, kidney disease, and premature delivery, and that angiotensin II receptor antagonists (AIIRAs) are associated with congenital malformations. The National Teratology Information Service state that they are contraindicated at all stages of pregnancy, and the National Institute for Health and Care Excellence state that there is sufficient concern, despite the relatively poor quality of the studies, to recommend avoiding ACE inhibitors and AIIRAs both in women planning pregnancy and during pregnancy [NTIS, 2007; NTIS, 2009; National Collaborating Centre for Women's and Children's Health, 2010].

Statins and fibrates should be stopped prior to pregnancy. The long-term treatment of hyperlipidaemia is not likely to be significantly impaired by temporarily stopping these drugs, and their safety during pregnancy has not been proven [Schaefer et al, 2007].

Measure thyroid function:

The recommendations to test thyroid function is based on a UK consensus guideline produced by the Association for Clinical Biochemistry, British Thyroid Association, and the British Thyroid Foundation [BTA et al, 2006]. The strength of evidence supporting this recommendation is expert opinion alone.

The guideline recommends carrying out thyroid function tests (TFTs) in asymptomatic people only if they are at high risk of having or developing hypothyroidism. In women with type 1 diabetes there is a 5–10% coincidence of hyper- or hypothyroidism [American Diabetes Association, 2003].

Prescribe folic acid 5 mg daily

This recommendation is based on expert advice from the UK Teratology Information Service and the British National Formulary [UKTIS, 2011a; BNF 63, 2012].

Scenario: Chronic medical conditions

Scenario: Pre-conception advice - women with chronic medical conditions

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Epilepsy

How do I manage a woman with epilepsy who wishes to become pregnant?

Reassure the woman that, even on anti-epileptic medication, they are likely to have a healthy pregnancy although the risk of complications during pregnancy and labour is higher than for a women who does not have epilepsy.

Refer all women taking anti-epileptic drugs (AEDs) to a specialist for review of epilepsy treatment before the woman becomes pregnant, to discuss the relative risks and benefits of adjusting their medication.

Advise the woman to continue using effective contraception until a full assessment by the specialist has taken place.

Advise the woman not to stop taking her medication unless otherwise directed by the specialist.

Discuss the standard pre-conception measures (see Advice for all women).

Women taking AEDs are considered to be at high risk of conceiving a child with a neural tube defect, and should be prescribed folic acid 5 mg daily until the twelfth week of pregnancy.

Basis for recommendation

Basis for recommendation

These recommendations are consistent with recommendations from the National Institute for Health and Care Excellence (NICE) clinical guideline on epilepsy [National Clinical Guideline Centre, 2012].

Referral is important to assess the risk to the fetus of current medication, and the risk to the mother and fetus of uncontrolled seizures during pregnancy.

NICE identified five prospective studies that measured changes in the frequency of seizures during pregnancy in women with epilepsy. They concluded that:

Generally, seizure frequency does not increase during pregnancy or in the early puerperium in women with epilepsy.

In a minority of women with epilepsy there may be an increase in the frequency of seizures (between 15% and 37%).

1–2% of women with epilepsy will have a tonic-clonic seizure during labour, and a further 1–2% within the following 24 hours.

Pregnancy in women with epilepsy is associated with a higher risk of congenital abnormalities compared with women who do not have epilepsy. However, these malformations are associated with the use of AEDs rather than epilepsy itself [SIGN, 2003].

The most common major malformations associated with AEDs include neural tube defects, orofacial defects, congenital heart abnormalities, and hypospadias.

Minor malformations include hypertelorism, epicanthic folds, and digital hypoplasia.

The risk of a major fetal malformation in pregnancy is 2%. This risk increases up to three fold in a woman who is taking one anti-epileptic drug [SIGN, 2003].

Sodium valproate has been associated with a significantly higher risk of malformations than carbamazepine or lamotrigine [SIGN, 2005].

Dose of folic acid

This is based on recommendations in the guideline The epilepsies. The diagnosis and management of the epilepsies in adults and children in primary and secondary care commissioned by the National Institute for Health and Care Excellence (NICE) and the British National Formulary [BNF 63, 2012; National Clinical Guideline Centre, 2012].

Chronic cardiac disease

How do I manage a woman with chronic cardiac disease who wishes to become pregnant?

Refer all women with cardiac disease who wish to become pregnant to a cardiologist for accurate diagnosis and functional assessment so that maternal and fetal risk can be assessed.

Advise the woman to continue using effective contraception until a full assessment by the cardiologist has taken place.

Advise the woman not to stop taking her medication unless otherwise directed by the cardiologist.

Discuss the standard pre-conception measures (see Advice for all women).

Basis for recommendation

Basis for recommendation

Heart disease is the commonest cause of maternal death in the UK.

All women with chronic cardiac disease should undergo accurate diagnostic and functional evaluation prior to pregnancy, in order to predict maternal and fetal risk as far as possible:

A woman's functional capacity preconception is an important predictor of her ability to tolerate pregnancy.

Women with heart disease and no symptoms (or minimal symptoms) prior to pregnancy will have a relatively low risk of complications during pregnancy and the peripartum period.

Women with pulmonary hypertension, an aortic aneurysm, severe aortic stenosis, or symptomatic ventricular dysfunction should be advised against becoming pregnant.

[Head, 2010]

Chronic hypertension

How do I manage a woman with chronic hypertension who wishes to become pregnant?

Refer all women with a history of hypertension who wish to become pregnant to a cardiac specialist prior to becoming pregnant.

Advise the woman that she will be at increased risk of pre-eclampsia during pregnancy, and that she will require careful monitoring.

Advise the woman to continue using effective contraception until she has been fully assessed.

Advise the woman not to stop taking her current medication unless otherwise directed by the specialist.

Discuss the standard pre-conception measures (see Advice for all women).

Basis for recommendation

Basis for recommendation

Chronic hypertension is associated with an increased risk of pre-eclampsia, placental abruption, and increased neonatal morbidity and mortality [Sibai et al, 1998].

The Working Group on High Blood Pressure in Pregnancy recommends that, prior to becoming pregnant, women with a history of hypertension should be reviewed by a cardiac specialist [Working Group on High Blood Pressure in Pregnancy, 2000; NICE, 2010c]. This is in order to:

Arrange shared care.

Review the diagnosis — although most women will have essential hypertension, some may have undiagnosed secondary hypertension, which can deteriorate rapidly during pregnancy.

Discuss lifestyle factors.

Review the woman's current medication:

If the hypertension is mild and well controlled, some specialists may attempt to stop or reduce treatment under close observation.

If treatment is to be continued, switching to an antihypertensive drug that is thought to be safer during pregnancy might be considered.

Studies suggest that angiotensin-converting enzyme inhibitors (ACE inhibitors) are associated with congenital malformations, intrauterine growth retardation, hypoglycaemia, kidney disease, and premature delivery, and that angiotensin II receptor antagonists (AIIRAs) are associated with congenital malformations. The National Teratology Information Service state that they are contraindicated at all stages of pregnancy, and the National Institute for Health and Care Excellence state that there is sufficient concern, despite the relatively poor quality of the studies, to recommend avoiding ACE inhibitors and AIIRAs both in women planing pregnancy and during pregnancy [NTIS, 2007; NTIS, 2009; National Collaborating Centre for Women's and Children's Health, 2010].

The drugs with most safety data are methyldopa, beta-blockers (labetalol, metoprolol, propranolol), and hydralazine. If these drugs are ineffective, a modified-release preparation of nifedipine may be considered as a second-line alternative. However the manufacturer recommends that it should not be used before the 20th week of pregnancy [NHS Northern & Yorkshire Regional Drug & Therapeutics Centre, 2006; NTIS, 2006; ABPI Medicines Compendium, 2012].

Pre-eclampsia complicates 25% of pregnancies in women with pre-existing hypertension. The incidence is higher if there is associated renal insufficiency, longer duration (hypertension for 4 years or more), and a history of hypertension in previous pregnancies [Working Group on High Blood Pressure in Pregnancy, 2000].

For further details, see the CKS topic on Hypertension in pregnancy.

Renal disease

How do I manage a woman with renal disease who wishes to become pregnant?

Refer women who have renal disease and are planning a pregnancy to a specialist for assessment.

Advise the woman to continue using effective contraception until she has been fully assessed.

Advise the woman not to stop taking her current medication unless otherwise directed by the specialist.

Discuss the standard pre-conception measures (see Advice for all women).

Basis for recommendation

Basis for recommendation

Renal disease during pregnancy is associated with risk of prematurity, intrauterine growth retardation, and accelerated deterioration in maternal renal function [Jungers and Chauveau, 1997].

Mild renal disease (CKD stages, 1, 2 and 3A, serum creatinine < 125 micromol/L) does not usually worsen during pregnancy, but fetal survival may be moderately reduced.

Moderate renal disease (CKD stages 3B and 4, serum creatinine 125 micromol/L to 250 micromol/L) may accelerate during pregnancy and jeopardize fetal survival.

Most women with severe renal disease (severe CKD stage 4 or CKD stage 5 [serum creatinine greater than 250 micromol/L]) are infertile. If they do conceive their chances of a normal pregnancy and a healthy child are low, and the risks to maternal health are high.

Women with renal diseases that tend to progress should be encouraged to complete childbearing whilst renal function is preserved.

If the woman also has co-existent hypertension then the risk of fetal death is 12% compared to 6% for a women with renal disease but no hypertension.

Women who have had a renal transplant should be advised to wait 1.5–2 years after the transplant and only attempt pregnancy if creatinine is stable at or below 200 micromol/L. The specialist may also need to change the immunosuppressant medication (tacrolimus and mycophenolate are contraindicated in pregnancy).

[Firth, 2010]

Venous thromboembolism

How do I manage a woman with venous thromboembolism who wishes to become pregnant?

Screen all women with a personal or immediate family history of venous thromboembolism (VTE) for both inherited and acquired thrombophilia. Thromboprophylaxis, either in the first trimester or post-partum, may be required.

Seek specialist advice for women who have a past history of deep vein thrombosis or pulmonary embolism, and for those with an abnormal thrombophilia screen.

Refer all women receiving warfarin therapy who are planning a pregnancy to a specialist for advice, as warfarin will need to be stopped or replaced by heparin, depending on the woman's degree of risk of VTE.

Discuss the standard pre-conception measures (see Advice for all women).

Basis for recommendation

Basis for recommendation

Pulmonary embolism is the leading cause of maternal death in the UK, accounting for one third of all maternal deaths [Bonnar, 2001]. Women with a history of deep vein thrombosis or pulmonary embolism in association with pregnancy, surgery, or the combined contraceptive pill should be considered especially at risk of recurrence during pregnancy, whether or not an underlying thrombophilia has been detected [Bonnar, 2001].

There is some evidence that pregnancy leads to an increase in the risk of venous thromboembolism in women with a previous thrombosis. One retrospective study of women with a history of previous thromboembolism found a recurrence rate of 10.9% per 100 patient-years during pregnancy, compared with a rate of 3.7% in women who were not pregnant [Pabinger et al, 2002].

Inherited and acquired thrombophilia not only increase the risk of venous thrombosis in pregnancy, but may also be partly responsible for recurrent fetal death and intrauterine growth retardation [Bonnar, 2001].

Warfarin is teratogenic and should ideally be stopped before conception and therapy switched to heparin or low-dose aspirin as appropriate. If this is not possible, stopping anticoagulation before the sixth week after conception may minimize the risk to the fetus. If the woman continues to take warfarin in the pre-conception period, adequate pregnancy testing must be undertaken so that warfarin can be stopped prior to the sixth week [Schaefer et al, 2007].

Asthma

How do I manage a woman with asthma who wishes to become pregnant?

In women with mild-to-moderate asthma, ensure that asthma is well controlled.

For women with severe asthma and those in whom asthma is poorly controlled, refer to a chest physician to ensure adequate control and monitoring.

Discuss the importance of continuing to take asthma medication as prescribed, both before conception and throughout the pregnancy, to maintain good asthma control.

Treatment of controlled asthma requires little modification in pregnancy. The risks from uncontrolled asthma are much greater than the risk from asthma treatment during pregnancy.

Steroid tablets should be used as normal in the pre-conception period and during pregnancy and never withheld because of pregnancy.

Discuss the standard pre-conception measures (see Advice for all women).

For further details of asthma management see the CKS topic on Asthma.

Basis for recommendation

Basis for recommendation

There is little evidence that pregnancy consistently affects the clinical course of asthma.

Large epidemiological studies suggest increased risks of pre-term delivery, low birthweight, and congenital malformations in women with asthma compared to those without. These risks are generally considered to relate to poor control of asthma — studies have shown that when asthma in pregnancy is managed by a respiratory specialist, and good control achieved, there are no additional fetal risks.

There is sufficient experience with long-acting and short-acting beta2-agonists, inhaled corticosteroids, antimuscarinic bronchodilators, cromones, and theophylline to recommend their use as normal during pregnancy [SIGN and BTS, 2011].

There is less experience with leukotriene receptor antagonists during pregnancy, but the Scottish Intercollegiate Guidelines Network and British Thoracic Society (SIGN and BTS) guidelines recommend that they may be continued during pregnancy if they have produced a good response and are considered essential [SIGN and BTS, 2011].

There are concerns that oral corticosteroids taken in the first trimester of pregnancy may be associated with oral clefts. Data from several studies has failed to show this association. A recent population-based case control study of women who had taken corticosteroids from 4 weeks before pregnancy to 12 weeks post-conception demonstrated an odds ratio of 1.7 (95% CI 1.1 to 2.6) for cleft lip. Even if this association is real it is important to treat exacerbations of acute asthma in pregnancy as the benefits outweigh the risks to the mother and the fetus [SIGN and BTS, 2011].

Prednisolone is the preferred oral corticosteroid as it is extensively metabolized by placental enzymes and little crosses the placenta [SIGN and BTS, 2011].

Prolonged exposure to prednisolone increases the risk of intrauterine growth retardation, although it is not clear whether these effects are associated with the maternal illness or are directly related to corticosteroid use [Schaefer et al, 2007].

Rheumatoid arthritis

How do I manage a woman with rheumatoid arthritis who wishes to become pregnant?

Refer all women with rheumatoid arthritis who wish to become pregnant to a rheumatologist, especially if they are taking nonsteroidal anti-inflammatory drugs (NSAIDs) or disease-modifying anti-rheumatic drugs (DMARDs).

Ensure the use of effective contraception whilst taking DMARDs. Because of their long half-life, some DMARDs may need to be discontinued several months before a planned conception.

Discuss the standard pre-conception measures (see Advice for all women).

Basis for recommendation

Basis for recommendation

Referral to a rheumatologist is recommended for a review of the woman's medication. The main concerns relate to the safety during pregnancy of some drugs used to control rheumatoid arthritis.

Because of the teratogenic and fetotoxic effects of many DMARDs, women should be advised to continue using effective contraception until their medication has been reviewed, and in some cases for several months after stopping medication.

[Schaefer et al, 2007]

Scenario: Genetic haemoglobinopathies

Scenario: Pre-conception advice - women with genetic haemoglobinopathies

192months540monthsFemale

Thalassaemia

How do I manage a woman with thalassaemia who wishes to become pregnant?

Discuss the standard pre-conception measures (see Advice for all women).

Women with thalassaemia:

Refer all women with thalassaemia to a haematologist for assessment.

Women with thalassaemia should receive folic acid 5 mg daily throughout the pregnancy.

Women who are carriers (thalassaemia trait):

Seek advice from a haematologist or haemoglobinopathy counsellor (if available) for women who are carriers and have an unusual variant or need further investigation.

Ensure that the woman's partner has been tested (see Advice about genetic screening).

Women with thalassaemia trait should receive folic acid 5 mg daily throughout the pregnancy.

Basis for recommendation

Basis for recommendation

Alpha-thalassaemia carriers (alpha-thalassaemia trait): the woman may become anaemic particularly if she is a carrier of two defective genes [Letsky, 1999].

3-alpha-thalassaemia (HbH disease): the woman will have chronic haemolytic anaemia and may require transfusion [Letsky, 1999].

Homozygous alpha-thalassaemia (Bart's haemoglobin hydrops syndrome): pregnancy is associated with severe, sometimes life-threatening pre-eclampsia. Vaginal deliveries are often associated with obstetric complications resulting from the large fetus, bulky placenta, and often the small stature of the mother (usually of Far Eastern origin) [Letsky, 1999].

Beta-thalassaemia minor (beta-thalassaemia trait) (symptomless carriers):

If iron stores are depleted, the woman may need oral iron supplements during pregnancy. Before giving iron supplements it is important to confirm with the local haematologist that the woman is truly iron deficient. A low mean cell volume (which is a feature of beta-thalassaemia) does not usually mean the woman is iron deficient [Letsky, 1999]. Primary care practitioners should request a serum ferritin for these women.[Letsky, 1999].

Beta-thalassaemia major (homozygous beta-thalassaemia): pregnancy is rare in these women and is likely to have serious complications [Letsky, 1999]. These women need specialist reproductive endocrinological referral if they wish to become pregnant.

Folic acid supplementation

Women with haemolytic anaemia, including those with haemoglobinopathies, need extra folate supplementation from early pregnancy [Strong and Rutherford, 2011].

Women with thalassemia trait are anaemic because erythropoiesis is ineffective. The increased turnover in the bone marrow results in folate depletion. Expert advice in a text book is that these women will probably benefit from taking 5 mg of folic acid daily throughout pregnancy [Strong and Rutherford, 2011].

Sickle-cell disease

How do I manage a woman with sickle-cell disease who wishes to become pregnant?

Refer all women with a sickle-cell disease to a haematologist for assessment and monitoring.

Advise the woman to continue using adequate contraception until she has been fully assessed by a haematologist.

Women who are carriers should be treated as for a normal pregnancy.

Discuss the standard pre-conception measures (see Advice for all women).

Ensure women with HbS/S or HbS/C disease are taking folic acid 5 mg for life.

Women who are carriers should receive folic acid 400 micrograms daily.

Basis for recommendation

Basis for recommendation

Pregnant women with sickle cell disease are more likely to have sickle cell crises and an increased risk of complications including life-threatening acute chest syndrome. There is also an increased risk of intrauterine growth retardation, premature delivery and miscarriage.

Sickle-cell carriers (HbA/S): women have no problems from overt sickling during pregnancy, but care is needed to avoid hypoxia if a general anaesthetic is required.

[NHS Antenatal and Newborn Screening Programmes, 2010; Perry and Lowndes, 2010; NHS Screening Programmes, 2011]

Scenario: Advice for older women

Scenario: Advice for older women regarding their risk of having a Down's syndrome baby

360months540monthsFemale

Advice for older women on risks of chromosomal abnormality

What advice can I give older women who are planning a pregnancy about their risks of having a baby with a chromosomal abnormality such as Down's syndrome?

Discuss the standard pre-conception measures (see Advice for all women).

Advise women planning pregnancy who are concerned about the risks of chromosomal abnormalities, such as Down's syndrome, that the risk increases with maternal age and after a previously-affected pregnancy. The risk of Down's syndrome is given in Table 1.

Advise that there is no pre-conception test that can predict whether a couple will conceive a baby with a chromosomal abnormality such as Down's syndrome.

Advise that antenatal screening tests can estimate the likelihood of a pregnant woman carrying a baby with Down's syndrome.

Advise that a definitive diagnostic test for Down's syndrome is offered to pregnant women at high risk. This can be established by amniocentesis, chorionic villus sampling, or fetal blood sampling. It is important that they are aware that testing carries a risk of fetal death but this occurs in less than 1% of cases.

Table 1 . Risk of Down's syndrome with increasing maternal age.
Age of mother Risk
20 years 1:1500
30 years 1:800
35 years 1:270
40 years 1:100
45 years and over 1:50 and greater

Basis for recommendation

Basis for recommendation

Basis for advice about risk of Down's syndrome and maternal age:

There is well-established evidence from large epidemiological studies of the relationship between maternal age and the risk of Down's syndrome [Cuckle et al, 1987].

Basis for advice about antenatal screening and diagnosis of Down's syndrome:

These recommendations are derived from a national guideline Antenatal care: routine care for the healthy pregnant woman published by the National Institute for Health and Care Excellence [NICE, 2008b].

Scenario: Advice about genetic screening

Scenario: Advice regarding when to refer for genetic screening

192months540monthsBoth

Advice when risk of genetic disorder

What pre-conception advice can I give to a couple who are at a higher risk of having a baby with an inherited genetic disorder including haemoglobinopathies?

Discuss the standard pre-conception measures (see Advice for all women).

Identify women who are at higher risk of haemoglobinopathies by asking them to complete a family of origin questionnaire, available at sct.screening.nhs.uk (pdf):

Take blood for full blood count and electrophoresis:

From all women from high prevalence areas.

From all women from low prevalence areas if they or their partner come from a population (identified by the questionnaire) at increased risk of haemoglobinopathies.

Take blood for full blood count alone:

From women from low prevalence areas who come from a population (identified by the questionnaire) at low risk of haemoglobinopathies.

Screen men for haemoglobinopathies only if the women is identified as a carrier.

Offer referral for genetic screening and counselling to couples that are planning pregnancy who:

Have a personal or family history of an inherited genetic disorder (see Table 1).

Have had a previous pregnancy affected by an inherited genetic disorder.

Are Ashkenazi Jews (for Tay–Sachs disease).

Offer referral for pre-natal diagnosis testing to women who would consider termination of an effected pregnancy when they are known to be a carrier of a recessively inherited genetic disorder and:

The father of the baby is known to be a carrier for the same disorder or,

The carrier status of the father is unknown and cannot be established.

Advise women who would consider termination of an affected pregnancy that it is important that they present early in pregnancy, ideally, if they want to avoid a termination after the first trimester.

Table 1 . Most common genetic disorders requiring referral for testing.
Genetic disorder Condition
Dominantly-inherited disorders Neurofibromatosis
Tuberous sclerosis
Huntington's disease
Adult polycystic disease
Marfan's syndrome
Achondroplasia
Recessively-inherited disorders Haemoglobinopathies
Cystic fibrosis
Tay–Sachs disease
Gaucher's disease
Congenital adrenal hyperplasia
Friedrich's ataxia
Spinal muscular atrophy
X-linked disorders Duchenne's muscular dystrophy
Fragile X syndrome
Haemophilias A and B
Glucose-6-phosphate dehydrogenase deficiency
[Farndon and Kilby, 1999]

Additional information

Additional information

Cousin marriage:

The indications for screening for a specific genetic disorder are determined by the population a couple comes from and their personal and family history.

Cousin marriage increases the risk of a couple having a child with a genetic disorder but it does not alter the indications for screening.

Haemoglobinopathy screening:

The family of origin questionnaire should be sent off with blood samples to aid in interpretation of results for all people.

High and low prevalence areas — a general practice should be informed by their hospital trust if they have a population that is at high risk or low risk of haemoglobinopathies.

Further information about haemoglobinopathy screening is available on the website for the NHS sickle cell and thalassaemia screening programme.

Pre–natal diagnosis:

Pre–natal diagnosis is considered appropriate when the risk of a baby being affected by the disorder is high and the women would consider termination of an affected pregnancy.

For a couple who are both carriers of a recessively inherited genetic disorder the chances of having an affected pregnancy are one in four.

When only the carrier status of the women can be established the risk of an affected pregnancy will depend on the prevalence of the disorder in a population. For certain high prevalence disorders the risk of an affected pregnancy may be high enough to justify offering pre–natal diagnosis even when the carrier status of the man cannot be established.

For people who would not find late termination of pregnancy acceptable it is important that they are referred to a fetal medicine specialist early in pregnancy, ideally by 10 weeks, to allow time for testing of the father of the baby (if necessary) and pre–natal diagnosis testing prior to termination.

Pre–natal diagnosis can be carried out from twelve weeks of pregnancy onwards.

Basis for recommendation

Basis for recommendation

Screening for haemoglobinopathies

Antenatal guidelines from the National Institute of Health and Clinical Excellence recommend that the Family Origin Questionnaire from the NHS Antenatal and Newborn Screening Programme should be used to identify women identified as being at a higher risk of haemoglobinopathies. These women should be offered preconception counselling (supportive listening, advice giving and information) and carrier testing [NICE, 2008b].

The NHS Sickle Cell and Thalassaemia Screening Programme indicate that screening for haemoglobinopathy carrier status may also be considered pre-conception [NHS Screening, 2006].

People who have a personal or family history of an inherited genetic disorder and people who have previously had an affected pregnancy are at high risk of having a baby with an inherited genetic disorder. Screening people at high risk is a common sense recommendation supported by experts [Cunniff and American Academy of Pediatrics Committee on Genetics, 2004].

Evidence

Evidence

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of pre-conception - advice and management.

Search dates

2007 - January 2012.

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.

exp Preconception Care/, preconcept$.tw.

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSh subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Bandolier

Drug & Therapeutics Bulletin

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

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