Basis for recommendation

This recommendation is based on what CKS considers to be good clinical practice, taking into account information in UK guidelines [Expert Advisory Group et al, 1992; RCOG, 2018; PHE, 2019a; NICE, 2022a; UKHSA, 2022], UK recommendations [NIHR, 2017; POST, 2017], American guidance [ACOG, 2020; AAFP, 2022] and expert opinion in review articles [BMA, 2016; Chamberlain et al, 2017; BJGP, 2020; BMJ Best Practice, 2022]. 

• Details about specific recommendations can be found in the individual scenarios.

Basis for recommendation

Maternal age

• This recommendation is based on expert opinion in a review article [Callegari et al, 2015], and is extrapolated from the results of an analysis of prospective data from 36,056 women to identify effects of maternal age on obstetric outcomes. This mentioned the association between increasing maternal age and subfertility, and found an increased risk of miscarriage, chromosomal abnormalities, congenital abnormalities, gestational diabetes, placenta praevia, and caesarean delivery in women aged over 35 years, with women over 40 years experiencing an increased risk of abruption, preterm delivery, low birth weight, and perinatal mortality [Cleary-Goldman et al, 2005].
• A 2021 prospective study of approximately 421,000 pregnancies quantified the increased risk of miscarriage [BMJ, 2019]; the risk rose rapidly after 30 years of age and was 53% in those aged 45 years and over. The lowest risk of miscarriage was in those aged 25-29 years (10%).

Interpregnancy interval

• This recommendation is based on advice from the World Health Organisation [WHO, 2007] and the position statement from the American Academy of Family Physicians [AAFP, 2022]. The evidence comes from a meta-analysis of data from cohort, cross-sectional, and case-control studies looking at the association between birth spacing and adverse perinatal outcomes [Conde-Agudelo et al, 2006]. 
• A 2021 international longitudinal cohort study examined data from more than 5.5 million births in high-income countries (USA, Australia, Finland and Norway) [PLoS One, 2021]. Data showed that interpregnancy intervals (IPI) of >60 months were consistently associated with a greater risk of adverse events. However shorter IPI (<6 months) were associated only with an increased risk of spontaneous preterm birth, and there was insufficient evidence of other adverse outcomes at shorted intervals.
• Original data from the 2006 study mainly looked at outcomes in Latin-America and their findings may not be directly transferable to other settings.

Miscarriage

• This recommendation is based on patient information, produced by the Royal College of Obstetricians and Gynaecologists Patient Information Committee  [RCOG, 2016a] and the Miscarriage Association [Miscarriage Association, 2013].

Basis for recommendation

Conception statistics

• The figures about the time taken for 100 couples to conceive are derived from statistics quoted by the National Institute for Health and Care Excellence (NICE) in their guideline on Fertility problems: assessment and treatment [NICE, 2017].

Optimising the chances of pregnancy

• This recommendation is based on the NICE guideline Fertility problems: assessment and treatment [NICE, 2017]. Regular intercourse gives the best chance of conception. Awareness of the fertile window around ovulation has been shown to give similar overall conception rates (around 80%) but reduce the time taken to achieve pregnancy [Duane, 2022]. 

Delayed fertility with the progestogen-only injection

• 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 in the guideline Long-acting reversible contraception [NICE, 2019a].

Basis for recommendation

These recommendations are largely based on the NICE guideline Maternal and child nutrition: nutrition and weight management in pregnancy, and nutrition in children up to 5 years [NICE, 2025].  

Risk of neural tube defect

• Assessing the couple's risk of conceiving a child with a neural tube defect (NTD) allows an appropriate dose of folic acid to be given, depending on the level of risk. The information on factors and conditions increasing the risk of a neural tube defect is based on UK guidelines [RCOG, 2011a; RCOG, 2014; RCOG, 2018; SIGN, 2018; NICE, 2020a; NICE, 2022b], guidance from the US [ACOG, 2020; AAFP, 2022], reports [NIHR, 2017; POST, 2017] and a review article [Hussein, 2021].

Recommending folic acid supplements to all women

• A Cochrane systematic review examined the effect of folic acid on the incidence of NTDs. The meta-analysis of five good-quality studies included 6708 women and found that folic acid supplementation in women, who became pregnant or were less than 12 weeks pregnant at the time of the study, reduced the incidence of NTDs (RR 0.31, 95% CI 0.17 to 0.58) compared with no intervention, placebo, or other micronutrients without folate. 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, 2015].

Dose of folate supplementation depending on the risk of NTD

• The recommendation to prescribe folic acid 5 mg daily to people at higher risk of an NTD and 400 micrograms to people at normal risk of NTD is based on the recommendations of an expert advisory group in 1992 [Expert Advisory Group et al, 1992], and reports from the National Institute for Health Research (NIHR): Better beginnings [NIHR, 2017] and the Parliamentary Office of Science and Technology: Dietary advice, pregnancy and breastfeeding [POST, 2017] (which references [SACN, 2006]), and advice in the British National Formulary [BNF, 2022]. 

High dose folic acid supplements 

• The Royal College of Obstetricians and Gynaecologists (RCOG) guideline Management of sickle cell disease in pregnancy recommends that, to prevent neural tube defects, women with sickle cell disease should receive folic acid 5 mg once daily pre-conceptually and during pregnancy because of the increased demand for folate in pregnancy [RCOG, 2011a]. This is supported by advice in the British National Formulary [BNF, 2022].
• For women with thalassaemia, the RCOG guideline Management of beta thalassaemia in pregnancy recommends a dose of 5 mg folic acid daily, to start 3 months before conception. This dose reduces the risk of neural tube defects as the demand for folic acid is higher in women with thalassaemia [RCOG, 2014].
• The National Institute for Health and Care Excellence guideline Diabetes in pregnancy: from preconception to the postnatal period advises that women with diabetes who are planning to become pregnant should take 5 mg of folic acid until 12 weeks of gestation [NICE, 2020a].
• The Royal College of Obstetricians and Gynaecologists (RCOG) guideline Epilepsy in pregnancy advises that all women with epilepsy should take 5 mg folic acid prior to conception until at least the end of the first trimester, to reduce both the incidence of major congenital malformation and also the risk of possible anti-epilepsy drug related cognitive deficits [RCOG, 2016b].

Basis for recommendation

Advice to women planning pregnancy to eat a healthy, balanced diet

• CKS recommends a healthy, balanced diet for women planning to conceive based on expert opinion in reports from the National Institute for Health Research Dissemination Centre: Better beginnings, improving health for pregnancy [NIHR, 2017], the Parliamentary Office of Science and Technology: Dietary advice, pregnancy and breastfeeding [POST, 2017]. Expert opinion in review articles has also been taken into account [Ioannides, 2017]. 
  • Diet and nutrition before conception and during pregnancy are important as it can impact on pregnancy outcomes and the health of the mother and her baby [NIHR, 2017; POST, 2017].

Dietary advice to help maintain a healthy weight before pregnancy

• This recommendation is based on the National Institute for Health and Clinical Excellence public health guideline Weight management before, during and after pregnancy [NICE, 2010] and advice from the US [AAFP, 2022].

Using the Eatwell guide for information on achieving a balance of healthier food

• The report from the National Institute for Health Research Dissemination Centre: Better beginnings, improving health for pregnancy recommends the Eatwell guide for this purpose [NIHR, 2017].

Basis for recommendation

Advice on achieving a healthy weight before conception

• This recommendation is based on a National Institute for Health Research (NIHR) report: Better beginnings, improving health for pregnancy [NIHR, 2017], a Parliamentary Office of Science and Technology report: Dietary advice, pregnancy and breastfeeding [POST, 2017], and expert opinion in guidance [AAFP, 2022].

Risks of being overweight before conception

• The recommendation to advise women of the potential health risks of obesity is based on World Health Organisation guidance: Preconception care to reduce maternal and childhood mortality and morbidity [WHO, 2012] and the American Academy of Family Physicians (AAFP) guideline Preconception care (position paper) [AAFP, 2022], and expert opinion in a review article [BJGP, 2020]. 
• Examples of health risks from being obese have been collated from a number of sources: a NIHR report Better beginnings, improving health for pregnancy [NIHR, 2017]; reports on Dietary advice, pregnancy and breastfeeding from the Parliamentary Office of Science and Technology [POST, 2017], and obesity, reproduction and pregnancy outcomes from the Academy of Nutrition and Dietetics [Stang and Huffman, 2016]; an AAFP position statement on Preconception care [AAFP, 2022]; and a UKTIS monograph on Obesity in pregnancy [UKTIS, 2011].

Weight loss

• The recommendation to advise women to lose weight if obese, and the target weight loss suggested is based on the NICE public health guidance: Weight management before, during and after pregnancy [NICE, 2010]. 
• The recommendation to offer a weight loss support programme is based on expert opinion in the NICE public health guidance: Weight management before, during and after pregnancy [NICE, 2010] and the report obesity, reproduction and pregnancy outcomes from the Academy of Nutrition and Dietetics [Stang and Huffman, 2016].
  • Although a Cochrane systematic review (2015 but not yet updated) found no randomised controlled trials assessing the effect of preconception interventions on pregnancy outcomes for overweight or obese women [Opray et al, 2015], a NIHR report: Better beginnings, improving health for pregnancy was of the opinion that women in these groups could benefit from accessing general weight management services [NIHR, 2017]. 
• The dietary advice if a woman becomes pregnant 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, 2010].

Risk of being underweight before conception

• The recommendation to advise women of the potential risks of being underweight before conception, and the examples of health risks of being underweight, are based on the AAFP guideline Preconception care (position paper) [AAFP, 2022],  and a NIHR report Better beginnings, improving health for pregnancy [NIHR, 2017].

Suspected eating disorder

• The recommendation on suspected eating disorders is extrapolated from a NIHR report Better beginnings, improving health for pregnancy which suggests that specialist monitoring and support are required for women with eating disorders in pregnancy [NIHR, 2017].

Basis for recommendation

Advising women who smoke and wish to become pregnant to stop smoking

• CKS recommends women planning a pregnancy stop smoking, because smoking in pregnancy is harmful to the mother, fetus, and others at home [Schaefer, 2015]. Tobacco smoking in pregnancy has been linked with complications including spontaneous abortion, intrauterine growth retardation, cleft lip and palate, preterm birth, placental abruption, stillbirth, and sudden infant death syndrome (SIDS) [UKTIS, 2018; AAFP, 2022]. Completing smoking cessation before pregnancy reduces the greatest modifiable risk for adverse pregnancy outcomes [NIHR, 2017].
• This recommendation is supported by reports from the National Institute for Health Research (NIHR) Better beginnings, improving health for pregnancy [NIHR, 2017] and NHS Greater Glasgow and Clyde (public health) Prepared for pregnancy? Preconception health, education and care in Scotland [NHSGGC, 2016]; the American Academy of Family Physicians (AAFP) position paper Preconception care [AAFP, 2022] and a fact sheet from the US Centers for Disease Control and Prevention on Preconception clinical care for women: Exposures [CDC, 2014]. 

Referral to a smoking-cessation service

• The National Institute for Health and Care Excellence (NICE) public health guideline on Tobacco: Preventing uptake, promoting quitting and treating dependence [NICE, 2022a] recommends that:
  • At consultations, primary healthcare professionals should advise all smokers to quit. Those who want to quit should be referred to an intensive support service such as the NHS Stop Smoking Services, and those who are unwilling or unable to be referred should be offered drug treatment and additional support.
  • Smokers wishing to quit should receive behavioural therapy, advice, and support (with or without pharmacological treatment) from a healthcare professional trained to provide smoking cessation services.
• The US Centers for Disease Control and Prevention also recommend brief interventions for women of childbearing age who are smokers, followed by referral to a more intensive service if the woman wishes [CDC, 2014]. 
• A Cochrane systematic review (search date November 2015), found that psychosocial interventions such as counselling can increase the proportion of women stopping smoking in late pregnancy and low birthweight newborns, but the role of health education remains unclear [Chamberlain et al, 2017]. 

Initially trying to stop smoking without using NRT

• This recommendation for women planning a pregnancy is extrapolated from expert opinion that suggests that where possible, smoking cessation during pregnancy should use non-pharmacological methods such as counselling or behavioural therapies [UKTIS, 2018]. 

Offering NRT to women who have tried and failed to stop smoking without using NRT

• This recommendation is extrapolated from expert opinion for pregnant women that, if non-pharmacological measures for smoking cessation fail, nicotine replacement therapy can be considered, using professional judgement, if it will reduce the mother's tobacco use and therefore exposure to the fetus [UKTIS, 2018; NICE, 2022a]. With nicotine replacement therapy, the exposure is to nicotine alone, compared with the many chemicals found in tobacco smoke (for example carbon monoxide, hydrocarbons, and tar) [UKTIS, 2018; Claire, 2020].

Not prescribing bupropion or varenicline for women who may become pregnant

• This recommendation is taken from the National Institute for Health and Care Excellence (NICE) public health guideline on Tobacco: Preventing uptake, promoting quitting and treating dependence [NICE, 2022a]. 
  • There are a lack of data available on the safety of these drugs during pregnancy [Schaefer, 2015; Claire, 2020]. If bupropion or varenicline is prescribed, the course should be completed before the woman tries to conceive as these drugs should not be offered to pregnant women [BNF, 2022].

Basis for recommendation

Avoidance of alcohol if trying to conceive

• The recommendation for women to avoid alcohol if they are pregnant or trying to conceive is based on the Chief Medical Officers' Low risk drinking guidelines [DH, 2016]. The aim of this advice is to keep fetal risks to a minimum and is supported by a British Medical Association report Alcohol and pregnancy. Preventing and managing fetal alcohol spectrum disorders [BMA, 2016]; a National Institute for Health Research (NIHR) report: Better beginnings, improving health for pregnancy [NIHR, 2017]; a Parliamentary Office of Science and Technology report: Dietary advice, pregnancy and breastfeeding [POST, 2017]; a NHS Greater Glasgow and Clyde (public health) report Prepared for pregnancy? Preconception health, education and care in Scotland [NHSGGC, 2016]; and advice from the American Academy of Family Physicians on Preconception care [AAFP, 2022].
• Although the risk of harm to the baby is likely to be low if a woman has drunk only small amounts of alcohol before she was aware of her pregnancy, it is safest for a woman not to drink alcohol if she is pregnant or could become pregnant [DH, 2016].
  • Risks to a baby from alcohol use in pregnancy include fetal alcohol spectrum disorders (FASD) and fetal alcohol syndrome, characterised by reduced growth, facial abnormalities, and potentially long-term learning and behavioural difficulties [DH, 2016; NIHR, 2017].
  • Preterm birth and babies that are of low birth weight and small for gestational age, may also be more common in mothers drinking more than 1–2 units of alcohol per day during pregnancy [DH, 2016]. 

Referral

• The British Medical Association report on Alcohol and pregnancy. Preventing and managing fetal alcohol spectrum disorders gives referral to specialist alcohol services as an example of a specific prevention strategy for high-risk women [BMA, 2016].

Basis for recommendation

Stopping illicit drug use before conception

• Illicit drug use can be harmful to the health of the woman and her baby, and can co-exist with alcohol and smoking which also increase health risks [NIHR, 2017].
• A number of studies have reported harm to the fetus from illicit drug use during pregnancy, including [Callegari et al, 2015; Azuine, 2019; Roncero, 2020]:
  • Marijuana — possible childhood neurodevelopmental effects (although data are not conclusive).
  • Cocaine — low birth weight, small head circumference, premature birth, and perinatal death.
  • Heroin and other opiates — spontaneous abortion, intrauterine death, low birth weight, premature birth, and infant distress due to acute drug withdrawal after delivery.
• It is therefore widely recommended by experts that illicit drugs should be avoided by women considering pregnancy [ACOG, 2020].

Referral for women planning pregnancy who are unable to stop illicit drug use

• The recommendation to refer women having difficulties with misuse of drugs is based on a National Institute for Health Research report: Better beginnings, improving health for pregnancy, which infers that this group of women may require specialist support and care during pregnancy [NIHR, 2017].
• Other organisations supporting this recommendation include the American Academy of Family Physicians, whose position paper on Preconception care advises that family physicians provide women of childbearing age who misuse drugs brief interventions and refer as appropriate to a treatment centre or higher level care [AAFP, 2022]. The US Centers for Disease Control and Prevention also recommend, as part of a pre-conception risk assessment, referral to a programme providing abstinence support and rehabilitation for women using illicit substances [CDC, 2014].

Offering contraceptive advice

• This recommendation is based on expert opinion in a factsheet from the Centers for Disease Control and Prevention on Preconception clinical care for women: Exposures which indicates the importance of delaying pregnancy until a woman is free of illicit substances [CDC, 2014].

Hepatitis C, hepatitis B, and HIV testing 

• People who have ever injected drugs are at increased risk of hepatitis B and C. The National Institute for Health and Care Excellence (NICE) public health guideline Hepatitis B and C testing: people at risk of infection recommends that GPs and practice nurses should offer hepatitis B and C testing to people who currently inject, or have a history of injecting, drugs [NICE, 2013]. 
• UK National Guidelines for HIV testing state that HIV testing should also be offered to any person with a history of injecting drugs [BHIVA, 2020]. 

Basis for recommendation

Avoiding exposure to hazardous substances and radiation

• This recommendation is based on expert opinion that pre-conception care should include alerting women to potential hazards and, if possible, avoiding exposure to toxic substances in the home, environment, and workplace  [Di Renzo et al, 2015; NHSGGC, 2016; Bekkar, 2020]. Examples include pesticides, solvents, heavy metals, tobacco smoke, carbon monoxide; anaesthetic gases; and ionising radiation [CDC, 2014; Kumar, 2019]. 
• In their position paper: Preconception care, the American Academy of Family Physicians notes the importance of addressing occupational hazards and exposures [AAFP, 2022], some of which have been linked to adverse reproductive outcomes [CDC, 2014]. There is evidence to suggest that preconception and prenatal exposure to toxins in the environment can significantly affect reproductive health [ACOG, 2020].

Workplace exposure to hazardous substances and radiation

• CKS recommends discussing plans for pregnancy with an employer if possible as they are 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.
• The Health and Safety Executive (www.hse.gov.uk) is an alternative source of information — as an organisation its role is to prevent ill-health, injury, or death in Great Britain's workplaces.  
• The recommendation to discuss with an occupational medicine specialist, if available, is based on the Centers for Disease Control and Prevention factsheet Preconception clinical care for women: Exposures [CDC, 2014].

Basis for recommendation

Discussing changes to prescribed medication

• This recommendation is intended as a general guide and advice should be tailored to the individual circumstances of the woman. It is based on an American Academy of Family Physicians position paper: Preconception care [AAFP, 2022], and a US Centers for Disease Control and Prevention factsheet on Preconception clinical care for women: Exposures [CDC, 2014].
• Recommendations related to the management of chronic medical conditions are made in their individual sections.

Over-the-counter medication

• The US Centers for Disease Control and Prevention recommend that women of reproductive age should be encouraged to discuss the use of over-the-counter medication with the provider when planning a pregnancy [CDC, 2014].
  • This is because medication use is high during pregnancy; one study found 73.4% of the study cohort of pregnant women took medication (excluding supplements and vitamins) [Haas, 2018].
  • Some medications available over the counter (for example, ibuprofen and aspirin) should be avoided in pregnancy as they may be harmful to the fetus [BNF, 2022].

Herbal remedies

• CKS does not recommend the use of herbal medicines in women planning pregnancy because evidence on their efficacy, toxicity, and safety is limited [Muñoz Balbontín, 2019]. The US Centers for Disease Control and Prevention emphasises the importance of educating women about discussing the use of herbal dietary supplements before pregnancy, and making them aware of the unknown safety profile of many products [CDC, 2014].

Basis for recommendation

• This recommendation is based on guidelines from the NHS cervical screening programme which recommend deferring a routine cervical screening test if the woman is pregnant [PHE, 2021].

Basis for recommendation

Immunization against rubella for non-immune women planning pregnancy

• The recommendation to confirm protection against rubella is based on Immunisation against infectious disease (the 'Green book'), published by Public Health England, which advises offering MMR vaccine to all seronegative women of childbearing age who require protection against rubella [PHE, 2013a].
• Maternal immunity to rubella protects against 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 [PHE, 2013a]:
  • Cataracts and other eye defects.
  • Deafness.
  • Cardiac abnormalities.
  • Microcephaly.
  • Intrauterine growth retardation.
  • Inflammatory lesions of brain, liver, lungs, and bone marrow.

Immunization against varicella for non-immune women planning pregnancy who are eligible for the vaccine

• The recommendation on determining if a woman planning pregnancy has immunity to varicella is based on information in Immunisation against infectious disease (the 'Green book'), published by Public Health England.
• CKS recommends immunizing against varicella to prevent:
  • Fetal harms following maternal varicella infection, including [PHE, 2019b]:
    • In the first 20 weeks of pregnancy, congenital (fetal) varicella syndrome (including 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.
  • Maternal harm in the second and third trimester of pregnancy, for example from fulminating varicella pneumonia. Maternal deaths have been reported due to varicella infections between 27 and 32 weeks gestation [PHE, 2019b].
• Immunisation against infectious disease (the 'Green book') recommends that varicella immunization is restricted to certain groups including healthcare workers who come into direct contact with patients; laboratory staff where exposure to varicella virus is an occupational risk; and healthy, susceptible close household contacts of immunocompromised patients [PHE, 2019b].

Immunization against hepatitis B for women planning pregnancy who are at risk of contracting hepatitis B

• This recommendation is based on Immunisation against infectious disease (the 'Green book'), which recommends pre-exposure immunization for people at high risk of exposure to the virus because of lifestyle or occupational factors [UKHSA, 2022].
  • Maternal immunization against hepatitis B prevents infection that can be transmitted to the baby perinatally [UKHSA, 2022].

Basis for recommendation

Avoidance of pregnancy during a trip to an area with active Zika virus transmission

• These recommendations are based on guidelines from Public Health England on Zika virus (ZIKV): clinical and travel guidance [PHE, 2019c] and Zika virus: sexual transmission advice algorithm [PHE, 2019d].

Mosquito bite avoidance measures

• Public Health England recommends mosquito bite avoidance measures for travellers to countries with active Zika virus transmission in the guidance Zika virus: clinical and travel advice, because Zika is transmitted by Aedes mosquitoes which usually bite during the day (particularly mid-morning and late afternoon to dusk) [PHE, 2019c].

Advice on returning to the UK regarding delaying pregnancy

• These recommendations are based on guidelines from Public Health England on Zika virus: clinical and travel guidance [PHE, 2019c] and Zika virus: sexual transmission advice algorithm [PHE, 2019d].
  
  • Avoidance of pregnancy is recommended during, and for 2-3 months after, travel to a Zika-affected area, because although infection with Zika virus generally causes mild or no symptoms, it can have a severe effect on the developing fetus [PHE, 2019c]. There is a consensus that it can cause microcephaly and other congenital abnormalities (congenital Zika syndrome) [Freitas, 2020]. 

Basis for recommendation

Discussion of the woman's mental health problem and the impact of pregnancy and childbirth.

• This recommendation is based on the National Institute for Health and Care Excellence (NICE) guideline Antenatal and postnatal mental health: clinical management and service guidance [NICE, 2020b].

Referral of women with a current or past severe mental health problem who are planning a pregnancy

• This recommendation is based on the NICE guideline Antenatal and postnatal mental health: clinical management and service guidance [NICE, 2020b] and a British Association of Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum [McAllister-Williams, 2017].
  • Optimal management of a woman's mental health problem during pregnancy is important because there is an association between psychiatric disorders in pregnancy and adverse obstetric and infant outcomes [Lassi et al, 2014]. A position paper from the American Academy of Family Physicians on Preconception care is of the opinion that achieving control of depression and anxiety disorders before conception can help prevent negative outcomes for a woman and her family [AAFP, 2022]. 
  • Pre-conception advice is important when the woman's current medication is associated with risk of teratogenicity (for example anticonvulsant mood stabilisers such as valproate or carbamazepine) [McAllister-Williams, 2017]. Because of the risks of some drugs to a pregnancy, CKS recommends continuing effective contraception until a woman planning a pregnancy has been seen by a specialist. Even if the decision is made to discontinue treatment, for some drugs effective contraception may need to be continued for a period of time, depending on the half-life and teratogenicity of the drug [McAllister-Williams, 2017]. 
  • CKS advises not stopping medication unless otherwise directed by the psychiatrist because if the illness is untreated there may be an increased risk of relapse which can cause adverse effects for the woman and her pregnancy [McAllister-Williams, 2017].

Management of women who do not require referral

• These recommendations are pragmatic and take into account recommendations in the NICE guideline Antenatal and postnatal mental health: clinical management and service guidance [NICE, 2020b] and a British Association of Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum [McAllister-Williams, 2017]. 

Measurement of prolactin levels

• This recommendation is based on the NICE guideline Antenatal and postnatal mental health: clinical management and service guidance. Testing is advised because increased levels of prolactin can reduce a woman's chance of becoming pregnant [NICE, 2020b].

Offering written patient information

• This recommendation is pragmatic and is based on what CKS considers to be good clinical practice.

Basis for recommendation

The basis for the recommendations on pre-conception care for women with thyroid disease are discussed in the relevant sections in the CKS topics on Hyperthyroidism and Hypothyroidism.

Basis for recommendation

Referral

• This recommendation is based on expert opinion in a Diabetes UK position statement on Preconception care for women with diabetes. This states that a woman with diabetes should have access to members of the multidisciplinary team relevant to her needs (for example diabetologist, obstetrician, specialist diabetes dietitian, specialist diabetes nurse, and specialist diabetes midwife). The aim is to provide appropriate information to enable the woman to make informed decisions about her care [Diabetes UK, 2015]. Expert opinion in a review article also describes pre-conception diabetic care as a multidisciplinary approach [Lassi et al, 2014]. 

Reviewing blood glucose targets and concurrent medication

• This recommendation is extrapolated from a National Institute for Health and Care Excellence guideline on Diabetes in pregnancy: management from preconception to the postnatal period [NICE, 2020a], a Diabetes UK position statement on Preconception care for women with diabetes [Diabetes UK, 2015], and expert opinion in a review article [Callegari et al, 2015].
  • Data are extremely limited for the use of antidiabetic drugs other than metformin during pregnancy [UKTIS, 2021], therefore, oral blood glucose-lowering drugs (except metformin) should be stopped before pregnancy and replaced with insulin [NICE, 2020a]. There is no evidence that metformin is associated with an increased risk of congenital malformations or other adverse pregnancy outcomes [UKTIS, 2017]. 
  • Studies suggest that, in the second half of pregnancy, angiotensin-converting enzyme inhibitors (ACE inhibitors) are associated with reduced placental circulation, fetal hypotension, oligohydramnios, and anuria in the neonate, and that angiotensin II receptor antagonists (AIIRAs) have similar risks [Schaefer, 2015]. ACE inhibitors and AIIRAs should therefore be stopped both in women planning pregnancy and during pregnancy [NICE, 2020a; BNF, 2022].
  • Statins should be discontinued prior to pregnancy [ESC, 2018; NICE, 2020a]. The mother is unlikely to be harmed by temporarily stopping these drugs when used for primary prevention, and one study and an analysis of case reports suggest an association with statin use and fetal nervous system and limb defects, although the risk is unclear as a number of studies did not report an increase in malformations [Schaefer, 2015]. 
  • A 2020 systematic review and meta-analysis concluded that preconception care for women with diabetes probably lowers their HbA1c level by 1.27%, reduces the risk of premature delivery and reduces risk of perinatal mortality by 54% [PLoS One, 2020].

Discussing the effects of diabetes on pregnancy, and pregnancy on diabetes

• CKS recommends discussing with the woman the implications of her diabetes and her pregnancy based on the NICE guideline on Diabetes in pregnancy: management from preconception to the postnatal period [NICE, 2020a], expert opinion in a Diabetes UK position statement on Preconception care for women with diabetes [Diabetes UK, 2015], and expert opinion in a review article [Broughton, 2019].

Discussing the importance of optimal blood glucose control

• This recommendation is based on the NICE guideline on Diabetes in pregnancy: management from preconception to the postnatal period [NICE, 2020a] and a position paper from the American Academy of Family Physicians [AAFP, 2022].
  • There is a correlation between increasing maternal hyperglycaemia and maternal and fetal adverse outcomes. The risks of uncontrolled diabetes in pregnancy include progression of retinopathy or nephropathy, pre-eclampsia, congenital malformations, fetal macrosomia, preterm delivery, complications with delivery (for example shoulder dystocia), intrauterine death, and neonatal hypoglycaemia [Broughton, 2019; UKTIS, 2021]. 

HbA1c measurement and levels, and capillary plasma glucose target ranges

• The recommendations on HbA1c measurement, HbA1c levels, and capillary plasma glucose target ranges reflect those in the NICE guideline on Diabetes in pregnancy: management from preconception to the postnatal period [NICE, 2020a], information in a Diabetes UK position statement on Preconception care for women with diabetes [Diabetes UK, 2015] and expert opinion in a review article [Broughton, 2019].
  • UKTIS advises close monitoring of maternal glucose levels during pregnancy because of changing insulin requirements throughout pregnancy that need frequent assessment [UKTIS, 2021]. 

Advice on diet and weight

• This recommendation is based on the NICE guideline on Diabetes in pregnancy: management from preconception to the postnatal period [NICE, 2020a].

Folic acid

• NICE and the British National Formulary consider women with diabetes mellitus to be at high risk of conceiving a child with a neural tube defect. The recommended dose of folic acid for this group is 5 mg daily from before conception until 12 weeks of gestation [NICE, 2020a; BNF, 2022].

Offering retinal and renal assessment

• These recommendations on retinal and renal assessment in a woman with diabetes planning a pregnancy reflect the NICE guideline on Diabetes in pregnancy: management from preconception to the postnatal period [NICE, 2020a].
  • If a woman has diabetic retinopathy it can progress more quickly during pregnancy [Diabetes UK, 2015] and there is evidence to suggest that rapid optimisation of glycaemic control can cause deterioration of diabetic retinopathy [NICE, 2020a].

Measurement of thyroid function

• The recommendation to test thyroid function is based on expert opinion in a UK consensus guideline produced by the Association for Clinical Biochemistry, British Thyroid Association, and the British Thyroid Foundation [BTA, 2006]. 

Basis for recommendation

GLP-1 agonists and pregnancy

• These recommendations are based on the College of Sexual and Reproductive Healthcare statement Glucagon-like peptide-1 (GLP-1) agonists and oral contraception [CoSRH, 2025] and the Medicines and Healthcare products Regulatory Agency [MHRA, 2025]. 

Basis for recommendation

Reassurance

• This recommendation is based on guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG) on Epilepsy in pregnancy [RCOG, 2016b], and the Scottish Intercollegiate Guidelines Network (SIGN) on Diagnosis and management of epilepsy in adults [SIGN, 2018].
• There is evidence to suggest that most women with epilepsy will experience improved seizure frequency or no change during pregnancy, with around half having no seizures during pregnancy [SIGN, 2018]. 

Referral

• Referral is important to allow an epilepsy specialist to review the diagnosis, assess the risk to the fetus of current medication, ensure optimal seizure control before conception, and discuss any genetic factors. This recommendation is based on an RCOG guideline on Epilepsy in pregnancy [RCOG, 2016b], and a guideline from the Scottish Intercollegiate Guidelines Network (SIGN) on Diagnosis and management of epilepsy in adults that advises women should receive a review by specialist services before conceiving [SIGN, 2018].
  • Good seizure control before conception increases the likelihood of seizure control during pregnancy [SIGN, 2018]. 
• 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 antiepileptic drugs (AEDs) rather than epilepsy itself [Schaefer, 2015; SIGN, 2018; MHRA, 2021].
  • The most common major malformations associated with AEDs include neural tube defects, orofacial defects, congenital heart disorders, and urinary tract and skeletal abnormalities [Schaefer, 2015; MHRA, 2021], but the risk of neurodevelopmental disorders is also increased.
  •  The risk of fetal congenital abnormalities depends on the type, number, and dose of AEDs taken [RCOG, 2016b]. Sodium valproate has been associated with a significantly higher risk of malformations than other AEDs [MHRA, 2021]. 

Contraception

• This recommendation is based on expert opinion that contraception should be used by women with epilepsy prior to reviewing and optimising their medication in relation to fetal toxicity because of the potential teratogenic risks of AEDs [Parekh, 2022]. 

Advice not to stop medication unless advised by a specialist

• Expert opinion suggests that stable medication should not be quickly stopped or altered during pregnancy [Schaefer, 2015; NICE, 2022b]. A pregnant woman with epilepsy and her fetus are at risk from the effect of seizures as well as the teratogenic effects of AEDs [Lassi et al, 2014]. The SIGN guideline on Diagnosis and management of epilepsy in adults reflects this, stating that poor adherence with AED treatment during pregnancy may lead to problems with seizures [SIGN, 2018]. 

Dose of folic acid in women taking antiepileptic drugs

• This is based on recommendations in the guidelines Epilepsies: diagnosis and management commissioned by the National Institute for Health and Care Excellence (NICE) [NICE, 2022b] and Diagnosis and management of epilepsy in adults from the Scottish Intercollegiate Guidelines Network (SIGN), which states that a higher dose of folic acid is advisable for women with epilepsy needing AED treatment because several AEDs are folate antagonists [SIGN, 2018]. This is also supported by dosing recommendations in the British National Formulary [BNF, 2022].
• The RCOG guideline on Epilepsy in pregnancy advises that 'all' women with epilepsy, receive 5 mg of folic acid [RCOG, 2016b]. This is at variance with other guidelines that only advise the higher 5 mg folic acid dose for women on AEDs. 

Basis for recommendation

Referral to a cardiologist

• CKS recommends referral to a specialist for women with cardiac disease on the basis of European guidelines which consider specialist care to be essential for women with pre-existing heart disease planning a pregnancy [ESC, 2018; NICE, 2019b]. Heart disease is the most common cause of maternal death in the UK [MBRRACE-UK, 2021].
• 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 [ESC, 2018; Guimarães, 2019]:
  • A woman's functional capacity preconception is an important predictor of her ability to tolerate pregnancy.
  • Women with pulmonary hypertension, an aortic aneurysm, severe aortic stenosis, or symptomatic ventricular dysfunction should be advised against becoming pregnant.

Continuing with contraception until assessment by a cardiologist

• This recommendation is pragmatic and is extrapolated from expert opinion in a review article suggesting that the woman should have a pre-conception discussion with a cardiologist before becoming pregnant [Callegari et al, 2015]. 

Advice not to stop medication unless advised by a cardiologist

• CKS pragmatically advises not stopping medication unless advised by a cardiologist based on expert opinion in a review article suggesting that the woman should have a pre-conception discussion with a cardiologist before becoming pregnant [Callegari et al, 2015].

Basis for recommendation

Referral

• CKS recommends referral to a specialist in hypertensive disorders for women with chronic hypertension planning a pregnancy because hypertension during pregnancy increases the risks for the mother and baby, and adjustments to the woman's medication and assessment for end organ damage prior to pregnancy may be required [NICE, 2019c].
•  [Callegari et al, 2015]. 
  • If a woman has chronic hypertension, pregnancy is associated with an increased risk of hypertensive disorders of pregnancy (such as pre-eclampsia), placental abruption, intrauterine growth retardation, preterm birth, and fetal loss [Farahi and Zolotor, 2013; Lassi et al, 2014]. Hypertension in pregnancy is one of the most common causes of maternal death in the UK [MBRRACE-UK, 2021].
  • A National Institute for Health and Care Excellence guideline on Hypertension in pregnancy: diagnosis and management emphasises the need to discuss hypertensive treatment if planning a pregnancy. Angiotensin converting-enzyme inhibitors and angiotensin II receptor blockers increase the risk of congenital abnormalities if taken in pregnancy [NICE, 2019c], and expert opinion suggests they should be avoided in women planning pregnancy and during pregnancy [ESC, 2018; AAFP, 2022; BNF, 2022]. Safer alternative treatments should be discussed if pregnancy is being planned. For more information, see the CKS topic on Hypertension in pregnancy.
  • The American Academy of Family Physicians position paper on Preconception care notes the need for a pre-conception assessment for renal disease, retinopathy, and ventricular hypertrophy in women with chronic hypertension [AAFP, 2022]. This is supported by expert opinion in review articles [Guimarães, 2019; Sliwa, 2021]. 

Increased risk of pre-eclampsia

• This recommendation is based on an American Academy of Family Physicians position paper on Preconception care that advises counselling about pre-eclampsia for women with chronic hypertension [AAFP, 2022]. There is evidence that pre-eclampsia is more common in women with chronic hypertension [Bramham et al, 2014; NICE, 2019c]. 

Using effective contraception until fully assessed

• This recommendation is pragmatic and is based on what CKS considers to be good clinical practice. Avoiding pregnancy until a full assessment has taken place allows the risks of hypertension and medication to be evaluated and any necessary pre-conception adjustments to be made, with the aim of optimising the chance of a healthy pregnancy. 

Not stopping medication unless directed by a specialist

• CKS has extrapolated this recommendation from evidence on the risks of chronic hypertension in pregnancy, including preterm birth, placental abruption, intrauterine growth restriction, and fetal loss. The woman is also at increased risk of worsening hypertension, endorgan damage, and pre-eclampsia. Although there is no evidence that treating mild to moderate hypertension in pregnancy improves perinatal outcomes, it does reduce the risk of severe hypertension [Abalos, 2018].
• The NICE guideline Hypertension in pregnancy: diagnosis and management [NICE, 2019c] advises aiming to keep blood pressure lower than 135/85 mmHg in pregnant women with chronic hypertension.

Basis for recommendation

Ensuring that mild asthma is well controlled

• This recommendation is based on the British guideline on the management of asthma from the Scottish Intercollegiate Guidelines Network (SIGN) and British Thoracic Society (BTS) that advise if asthma is well controlled before pregnancy, there is little or no risk of adverse maternal or fetal complications [BTS/SIGN, 2019]. 

Referring women with moderate, severe or poorly-controlled asthma

• The British guideline on the management of asthma from the Scottish Intercollegiate Guidelines Network (SIGN) and British Thoracic Society (BTS) states that pregnant women with moderate to severe asthma should be closely monitored to attain good control and minimise problems for the woman and her baby [BTS/SIGN, 2019].
• Women with severe asthma are more likely than those with mild asthma to experience worsening of symptoms during pregnancy [BTS/SIGN, 2019]. 
• CKS also recommends referral of pregnant women with poorly-controlled asthma, as this group have an increased risk of complications for both the mother and the fetus, including hyperemesis, pre-eclampsia, fetal growth restriction, complicated labour, pre-term birth, low birth weight, and perinatal mortality. Prospective analyses show that for women with well-controlled asthma, there is only a small, or no, increase in risk for the mother and baby [BTS/SIGN, 2019; Couillard, 2021].

Continuing asthma medication

• This recommendation is based on the SIGN/BTS British guideline on the management of asthma which advises counselling women with asthma on the importance and safety of continuing their treatment during pregnancy [BTS/SIGN, 2019].
  • Generally, medicines used to treat asthma in pregnancy are considered to be safe and the risks of treatment are outweighed by the risk of harm from severe, uncontrolled, or chronically undertreated asthma [BTS/SIGN, 2019; BNF, 2022].
  • There is sufficient experience with long-acting and short-acting beta2-agonists, inhaled corticosteroids, sodium cromoglicate, nedocromil sodium, and theophylline (check blood levels) to recommend their use as normal during pregnancy [BTS/SIGN, 2019].
  • There is limited data on the use of leukotriene receptor antagonists during pregnancy, but the SIGN and BTS guidelines recommend that they may be continued during pregnancy if they are needed to achieve adequate control of asthma [BTS/SIGN, 2019].
  • There are concerns that oral corticosteroids taken in the first trimester of pregnancy may be associated with oral clefts, but data are conflicting. 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. Prednisolone is the preferred oral corticosteroid as little crosses the placenta [BTS/SIGN, 2019].

Basis for recommendation

Referral

• CKS has based this recommendation on findings from a 2020 retrospective cohort study of 178 pregnancies in women with CKD stage 3-5 where [Wiles, 2021]:
  • 26% of the cohort delivered before 34 weeks gestation.
  • 36% of the neonates were below the 10th centile for weight.
  • There was significant postpartum eGFR decline.
• Expert opinion suggests that a multidisciplinary team approach may be required to control disease activity prior to conception, optimise blood pressure, and ensure treatments are reviewed and are relatively safe for the mother and fetus [Gonzalez Suarez, 2019].
• A cross-sectional assessment of 72 women with chronic kidney disease attending a pre-pregnancy counselling clinic found that about 90% of women found it informative, and helped with their decision making about pregnancy [Wiles et al, 2015].

Contraception

• This recommendation is based on expert opinion that suggests planning pregnancy for the right time, when renal disease is stable and after a period of remission [Bramham and Lightstone, 2012; Smyth et al, 2013].
• Women may also be taking potentially teratogenic drugs (for example angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, some immunosuppressants, or warfarin), which need to be switched to safer alternatives prior to pregnancy [ESC, 2018; BNF, 2022].

Not stopping medication unless otherwise directed by a specialist

• This recommendation is based on what CKS considers to be good clinical practice. It takes into account the adverse outcomes associated with maternal renal disease in pregnancy, and expert opinion stating that the goal of treatment is to control disease activity [Smyth et al, 2013] and that features of renal disease such as hypertension and proteinuria should be optimised before pregnancy [Wiles et al, 2015].

Basis for recommendation

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

• This recommendation is based on the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Reducing the risk of venous thromboembolism during pregnancy and the puerperium [RCOG, 2015].
• Thrombophilia and a history of previous venous thromboembolism (VTE) are both significant risk factors for developing VTE in pregnancy [RCOG, 2015; ESC, 2018]. Thrombophilia can have adverse effects on the mother and fetus including pre-eclampsia, placental infarction or abruption, intrauterine growth restriction, and fetal death [Callegari et al, 2015]. The RCOG guideline recommends thrombophilia testing for certain groups of women with previous VTE and advises that interpretation of results should be done by clinicians with expertise in the area [RCOG, 2015].
• Pre-pregnancy counselling should be offered to women with a history of VTE to formulate a management plan for thromboprophylaxis in pregnancy as they have an increased risk of recurrence in pregnancy. Management will depend on the underlying cause of VTE and the RCOG recommends collaboration with a haematologist with expertise in thrombosis in pregnancy [RCOG, 2015]. 
  • For women with a previous history of recurrent VTE, specialist advice is required regarding dose of low molecular weight heparin in pregnancy as higher doses may be required [RCOG, 2015; ESC, 2018]. 

Refer all women receiving warfarin therapy who are planning a pregnancy

• The RCOG recommends counselling of all women taking warfarin or other oral anticoagulants about the associated fetal risks [RCOG, 2015]. 
  • Warfarin is teratogenic and should ideally be stopped before conception. This usually involves switching therapy to low-molecular-weight heparin or heparin [BNF, 2022].

Basis for recommendation

Referral to a rheumatologist

• CKS has based this recommendation on British Society for Rheumatology and British Health Professionals in Rheumatology (BSR/BHPR) guidelines on prescribing drugs in pregnancy and breastfeeding [Flint et al, 2016a; Flint et al, 2016b], and a European League Against Rheumatism consensus on the use of antirheumatic drugs before and during pregnancy and lactation [Gotestam Skorpen et al, 2016]. Referral enables discussion of:
  • Medication — may be reviewed to weigh the risk of drug treatment for the fetus against the risk to the mother and fetus of untreated disease. Some drugs used for rheumatic conditions should not be used when trying to conceive or during pregnancy due to teratogenic risks or lack of safety data, and may need to be stopped in advance of conception (examples include methotrexate, cyclophosphamide, and mycophenolate mofetil) [Flint et al, 2016a; Flint et al, 2016b; Gotestam Skorpen et al, 2016; Sammaritano, 2020].
  • Potential risks in pregnancy associated with the underlying rheumatic disease — women with rheumatic diseases are at increased risk of adverse pregnancy outcomes including pre-eclampsia, preterm delivery, and fetal growth restriction. They may also have co-morbidities (for example, renal disease or steroid-induced diabetes) that need to be considered [Sammaritano, 2020].

Use of effective contraception

• Because of the teratogenic and fetotoxic effects of some DMARDs [Arthritis Foundation, 2022; BNF, 2022], CKS recommends that 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.

Basis for recommendation

Reassurance

• This recommendation is based on the College of Sexual and Reproductive Healthcare (CoSRH) guideline on Sexual and reproductive health for individuals with inflammatory bowel disease [CoSRH, 2016]. However, there is some evidence to suggest that in women with active Crohn's disease or adhesions from surgery, fertility may be decreased [CoSRH, 2016].

Referral

• This recommendation is based on the British Society of Gastroenterology publication Guidelines for the management of inflammatory bowel disease in adults [BSG, 2021] and also on the College of Sexual and Reproductive Healthcare (CoSRH) guideline on Sexual and reproductive health for individuals with inflammatory bowel disease [CoSRH, 2016].
  • Referral for pre-pregnancy counselling ensures optimal management of IBD before the woman becomes pregnant because the best time to conceive is when IBD is controlled and the woman is well nourished [CoSRH, 2016; BSG, 2021]. Women with active disease at conception are more likely to experience active disease when they are pregnant [van der Woude, 2015; CoSRH, 2016].
  • Specialist involvement is beneficial because although most pregnancies in women with controlled IBD are uncomplicated [Kanis and van der Woude, 2016], women with active IBD are at increased risk of preterm labour, small for gestational age or low birthweight babies, and caesarean section [BSG, 2021], and pregnancy may affect the course of IBD [van der Woude, 2015]. 
  • Medication review prior to pregnancy is important because of the need for some drugs for IBD to be stopped before conception because of the risks of congenital abnormalities [CoSRH, 2016].

Continuing effective contraception until after a full specialist assessment

• CKS has made this recommendation because although most medications for IBD are not related to adverse outcomes in pregnancy [Kanis and van der Woude, 2016], some drugs used for its treatment can be harmful to the fetus and effective contraceptive use is necessary for some time after treatment has stopped (for example methotrexate, mercaptopurine, mycophenolate mofetil, and TNF-alpha inhibitors) [CoSRH, 2016; BNF, 2022].

Advising not to stop medication unless otherwise directed by the specialist

• The CoSRH guideline on Sexual and reproductive health for individuals with inflammatory bowel disease advises encouraging women to continue with medication [CoSRH, 2016]. Expert opinion in a review article comments on the possibility of relapse if maintenance treatment is stopped, and recommends counselling women wanting to conceive regarding this to reduce the risk of disease flares in pregnancy which are associated with adverse maternal and fetal outcomes [van der Woude, 2015]. Many adverse outcomes occur in relation to disease activity rather than the drugs taken to control IBD, and the benefits of disease control outweigh the fetal risks of medication [BSG, 2021].

Dose of folic acid

• FSRH guidelines recommend that the standard 400 microgram daily dose of folic acid is usually suitable for women with IBD, but some (for example women on sulfasalazine, or those who have malabsorption after surgery to resect the small bowel) may need a higher dose [CoSRH, 2016]. This is also supported by expert opinion in a review article [Kubota-Sjogren et al, 2014]. The British National Formulary considers the children of pregnant women with malabsorption states to be at high risk of neural tube defects, and recommends a folic acid dose of 5 mg daily to be taken before conception and until week 12 of pregnancy [BNF, 2022].

Basis for recommendation

Referral of women with sickle cell disease for assessment and monitoring

• This recommendation is based on the Royal College of Obstetricians and Gynaecologists guideline Management of Sickle cell disease in pregnancy [RCOG, 2011a] and expert Sickle Cell Society Standards for the Clinical Care of Adults with Sickle Cell disease [Sickle Cell Society, 2018] that state that despite the risk of complications for women with haemoglobinopathies, successful pregnancies are possible with close monitoring by experienced haematologists and obstetricians.
  • Expert opinion in the RCOG guideline recommends pre-conception counselling by a specialist to enable the woman to be informed about the effects of sickle cell disease on pregnancy, and vice versa. This also allows formulation of a management plan including [RCOG, 2011a]:
    • Information on factors increasing the risk of sickle cell crises, such as nausea and vomiting in pregnancy, cold, overexertion, and stress.
    • Explanation of increased risks of worsening anaemia, crises and acute chest syndrome, infections (especially of the urinary system), growth restriction of the baby, fetal distress, induction of labour, and caesarean section.
    • Discussion of the chance of the woman's baby having sickle cell disease.
    • Assessment of chronic disease complications such as pulmonary hypertension, hypertension, sickle nephropathy, proliferative retinopathy, and iron overload.
    • Review of antibiotic prophylaxis and vaccination status.
    • Review of medication — some drugs used for sickle cell disease and its complications, such as hydroxycarbamide, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers are not safe to use in pregnancy and need to be stopped before a woman conceives.
  • Complications affecting the mother and fetus associated with sickle cell disease include an increased risk of acute painful crises during pregnancy, pre-eclampsia, fetal growth restriction, perinatal mortality, premature labour, thromboembolic events, and antepartum haemorrhage [RCOG, 2011a; Sickle Cell Society, 2018].

Referral of women with thalassaemia for assessment and monitoring

• This recommendation is based on a Royal College of Obstetricians and Gynaecologists (RCOG) guideline on Management of beta thalassaemia in pregnancy [RCOG, 2014] and expert opinion in a review article that concludes that despite the risk of complications for women with haemoglobinopathies, successful pregnancies are possible with close monitoring by experienced haematologists and obstetricians [Naik and Lanzkron, 2012]
  • Risks to the mother and baby are increased in pregnancies affected by beta thalassaemia. Data are limited due to the geographical distribution of many people with the disease and the increased risk of hypogonadotrophic hypogonadism (related to transfusion iron overload) affecting fertility [Naik and Lanzkron, 2012]. Adverse outcomes include worsening of anaemia; maternal cardiomyopathy due to iron overload; the risk of a pregnant woman developing endocrinopathies such as diabetes mellitus, hypothyroidism and hypoparathyroidism; and fetal growth restriction [Naik and Lanzkron, 2012; RCOG, 2014].
  • The RCOG guideline states that women with beta thalassaemia are ideally looked after by a multidisciplinary team including a specialist obstetrician and haematologist which should provide pre-conception counselling. This allows the woman to receive information about the impact of thalassaemia on her pregnancy, how pregnancy affects thalassaemia, and enables the team to plan management. Iron chelation therapy may be required prior to pregnancy to control iron overload, so referral well in advance of pregnancy is important [RCOG, 2014].
• Women with haemoglobin H disease (three alpha globin genes are absent) may experience varying severity of anaemia, jaundice, and hepatosplenomegaly [Clark, 2012]. In pregnancy, severe anaemia may occur, and haemolytic crisis can result in oxidative stress or infection [Lao, 2017], therefore CKS recommends referral for women with haemoglobin H disease planning a pregnancy.
• Inheritance of one unusual haemoglobin gene from one parent (sickle cell or thalassaemia trait) does not usually cause health issues [PHE, 2013b] and limited evidence suggests women with thalassaemia trait have pregnancy outcomes similar to the general population [Lao, 2017]. The recommendations on advice to give women with sickle cell or thalassaemia trait are based on Public Health England's (PHE) Sickle cell and thalassaemia: programme overview [PHE, 2013b], and also information for adult haemoglobinopathy carriers from PHE for sickle cell carriers and beta thalassaemia carriers [PHE, 2018].
  • Women who have one or two gene deletion alpha thalassaemia are usually asymptomatic with normal pregnancy outcomes, although they may have a mild hypochromic microcytic anaemia [Clark, 2012].

Folic acid

• For women with sickle cell disease, the RCOG guideline Management of Sickle cell disease in pregnancy recommends that folic acid should be given at a dose of 5 mg daily pre-conceptually and during pregnancy. This is to reduce the risk of neural tube defects and address the increased need for folate during pregnancy. The haemolytic anaemia of sickle cell disease increases a woman's risk of folate deficiency [RCOG, 2011a].
• For women with thalassaemia and thalassaemia trait, the RCOG guideline Management of beta thalassaemia in pregnancy recommends a dose of 5 mg folic acid daily, to start 3 months before conception. This dose reduces the risk of neural tube defects as the demand for folic acid is higher in women with thalassaemia [RCOG, 2014]. Expert opinion in a review article also recommends folic acid supplementation before and during pregnancy for women with thalassaemia [Lao, 2017]. 

Basis for recommendation

Ideally carrier screening and counselling should be performed before pregnancy, so couples are aware of their reproductive risk and are able to consider a greater range of options than if the woman is already pregnant [ACOG, 2017a; Ioannides, 2017]. 

History

• This recommendation is based on, and extrapolated from, the American College of Obstetricians and Gynecologists (ACOG) Committee on Genetics opinion document on Carrier screening for genetic conditions [ACOG, 2017a], a Cochrane systematic review on Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease [Hussein, 2021], and expert opinion in a review article [Ioannides, 2017].

Seeking specialist advice or referring for risk assessment, evaluation, and consideration of diagnostic testing

• CKS found no guidelines specifically relating to a primary care setting, but have extrapolated these recommendations from information in the ACOG Committee on Genetics opinion document on Carrier screening for genetic conditions [ACOG, 2017a] that recommends referral to an obstetrician-gynaecologist or other healthcare provider with genetic expertise for risk assessment, evaluation, and consideration of diagnostic testing for people with a family history of a genetic condition, or for whom there is concern about a genetic diagnosis.
• Seeking specialist advice or considering referral is also recommended because careful counselling is needed before undertaking testing [Ioannides, 2017], and the resources and expertise to do this may not be available in primary care.
  • The ACOG also recommends genetic counselling for couples with consanguinity due to the increased risk of recessive conditions in their children [ACOG, 2017b].
  • The recommendation regarding couples with recurrent pregnancy losses is extrapolated from expert opinion in a review article [Ioannides, 2017]. The Royal College of Obstetricians and Gynaecologists guideline on The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage recommends women who have experienced recurrent first-trimester or second-trimester miscarriage should be managed by a person with the necessary skills and expertise, and offered referral to a specialist clinic. These women should have pre-conception screening for antiphospholipid antibodies (plus a screen for inherited thrombophilias for women with second-trimester miscarriage), but routine karyotyping of couples with recurrent miscarriage is not recommended [RCOG, 2011b].