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Prescribing for pregnancy: general prepregnancy care
  1. Joanna Girling
  1. Dept Obstetrics and Gynaecology, West Middlesex University Hospital, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
  1. Correspondence to Joanna.Girling{at}chelwest.nhs.uk

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Introduction

Outcomes for mother and baby are better when the pregnancy has been planned. Supporting women to use contraception effectively when they do not wish to be pregnant, and helping them to prepare for pregnancy before they do conceive are both important. National data show that over 20% of all pregnancies ended as a legal termination in 2016, ranging from 6% in women in stable relationships in their 20s and 30s to more than 50% in single women aged under 18 years.1 Among women who had term pregnancies, only 66% were described as planned.2

This article covers some of the key issues that should be considered for all women as part of prepregnancy care.

Background

Ideally, women should be in the best physical and mental health before they conceive and be aware of lifestyle and medical adjustments required before and during pregnancy. Healthcare professionals should opportunistically enquire about pregnancy knowledge, use of contraception and plans to conceive; this might include at new patient, family planning, cervical smear, sexual health, medication review and vaccination appointments. For women with long-term medical disorders, routine consultations are also an important chance to discuss prepregnancy care.

Long-term conditions

Women with long-term conditions such as diabetes, epilepsy, hypertension, rheumatological disorders and mental health diagnoses need targeted preconception guidance about the impact of their health on pregnancy outcome, the potential impact of pregnancy on their medical or mental health disorder and use of their medication in pregnancy and breastfeeding. Some of these conditions will be covered in future articles in this series. For women with pre-existing medical conditions, the use of effective non-pharmacological options should be maximised, and the smallest number of the safest medicines at the lowest effective doses should be used while preparing for pregnancy and during pregnancy. In particular, it is important that consideration is given to those drugs that are most likely to be problematic during pregnancy because of potential harmful effects to the fetus if use is continued, and the possible negative impact on the woman’s health and the pregnancy from discontinuation or switching to less effective alternatives. Drugs that have been extensively used in pregnancy and appear to be usually safe should be prescribed in preference to new or untried drugs.3 Women should be closely involved in all discussions.

Optimising medicines

Continuing medication may be the best way to keep mother and baby healthy, and this may require specialist advice and should be supported by high-quality information (see box 1).4 For some women there will be effective alternatives with a good safety record, and discussion can focus on the optimal timing to switch, usually either before or very soon after conception. It is rarely right to abruptly stop and not replace long-term medication. Cessation of treatment increases the risk of acute exacerbations of the underlying condition, which may require higher doses or more potent agents to regain control. Women for whom there is not a safe or safer option should be given ample opportunity before conception (and while using reliable contraception) to consider the issues. These might include:

Box 1:

Sources of information

UK National Poisons Information Service Toxbase: https://www.toxbase.org/ (registration required)

UK Teratology Information Service: http://www.uktis.org/

UK Best Use of Medicines in Pregnancy: http://www.medicinesinpregnancy.org/

USA Toxicology Data Network Lactmed database: https://www.toxnet.nlm.nih.gov/newtoxnet/lactmed.htm

UK Breastfeeding Network: https://www.breastfeedingnetwork.org.uk/drugs-factsheets (information for the public)

  • likelihood of disease relapse or deterioration, time frame in which this might happen and impact on her short-term or long-term well-being;

  • likelihood of and gestational age of fetal adverse effects from all medication being considered;

  • potential adverse effects from alternative medication; and

  • anticipated time frame for conception, including any reasons for delayed conception such as oligo- or amenorrhoea, previous subfertility and infrequent coitus.

The Medicines and Healthcare products Regulatory Agency has published guidance on contraceptive methods and frequency of pregnancy testing to reduce inadvertent exposure during pregnancy in a woman taking a medicine of teratogenic potential.5

Two key publications, Better Beginnings, Improving Health for Pregnancy and Pre-conception—Advice and Management provide an overview of important aspects of prepregnancy care.6 7

Key considerations

Folic acid

The correct dose of folic acid should be started at least 3 months before conception and continued until at least 12 weeks’ gestation.

Neural tube defects (NTD) affect around 2.5 per 1000 pregnancies in populations that do not use folate supplementation.8 A folic acid supplement taken daily from 3 months prior to conception until 12 weeks’ gestation reduces the number of birth defects, including NTD such as spina bifida and anencephaly by up to 70% (risk ratio [RR] 0.31, 95% CI 0.17 to 0.58). As the spinal column and brain are forming within 1 week of a missed menses, it is important to start folic acid before conception.9

The standard dose of folic acid is 400 µg daily.3 Women with a higher likelihood of having a baby with NTD are recommended to take 5 mg daily. These include women who themselves or their partner have an NTD, or who have had a previous affected pregnancy or who have a first degree family member affected by NTD; women with established diabetes; those taking antiepileptic drugs; women with a body mass index (BMI) >30 kg/m2; women with potential malabsorption including conditions such as Coeliac disease; and those with sickle cell or thalassaemia trait or disease.

Optimising BMI

Raised BMI

Compared with women who have a normal BMI (18.5–24.9 kg/m2), those who have a BMI >30 kg/m2 have an increased likelihood of miscarriage, gestational diabetes (odds ratio [OR] 3.6, 95% CI 3.3 to 4.0), pre-eclampsia (OR 2.4, 95% CI 2.2 to 2.7), venous thromboembolism (OR 9.7, 95% CI 3.1 to 30.8), Caesarean section (OR 2.1, 95% CI 1.9 to 2.3), postpartum haemorrhage (OR 1.4, 95% CI 1.2 to 1.6) and maternal mortality.10–12 Infants of obese women are at increased risk of congenital abnormality (spina bifida OR 2.24, 95% CI 1.86 to 2.69; cardiovascular anomalies OR 1.3, 95% CI 1.12 to 1.51), stillbirth (OR 2.1, 95% CI 1.5 to 2.7), premature birth (OR 1.2, 95% CI 1.1 to 1.4), accelerated fetal growth (OR 2.4, 95% CI 2.2 to 2.5) and neonatal death (OR 2.6, 95% CI 1.2 to 5.8).10 13 14

Weight loss prior to conception helps to reduce the likelihood of stillbirth, pre-eclampsia and accelerated fetal growth, and may increase the success of vaginal birth after Caesarean.15 There are no high quality studies reporting impact of specific programmes aimed at preconception weight loss. Women should be encouraged and supported to lose weight before conception, by setting initial realistic goals such as a 5%–10% wt loss. Weight loss support programmes involving diet and physical activity should include evidence-based behaviour change techniques as outlined in national guidelines.16 If bariatric surgery is considered, women should use reliable contraception until weight loss has plateaued and usually until at least 12 months after the procedure.17

Low BMI

Women with a low BMI should be informed that the potential health risks include reduced fertility (through anovulation), increased miscarriage rate, preterm birth (adjusted RR 1.29, 95% CI 1.15 to 1.46), low birth weight (adjusted RR 1.64, 95% CI 1.38 to 1.94) and gastroschisis.18 Possible underlying causes for low BMI should be considered such as an eating disorder or malabsorption.

Smoking

In England, figures for 2017 show that 11% women smoked through pregnancy.19 The UK Government Tobacco Control Plan includes a target to reduce the prevalence of smoking in pregnancy to 6% or less by the end of 2022.20

Stopping smoking represents the biggest modifiable risk factor for adverse pregnancy outcome, and women should be strongly encouraged and supported to stop before they conceive; for women who are still smoking at conception, stopping as soon as possible can reduce preterm birth and growth restriction. Women who smoke during pregnancy have a higher likelihood of miscarriage (relative risk of miscarriage with any active smoking 1.23, 95% CI 1.16 to 1.30), which increases with number of cigarettes smoked; former smokers were no more likely to have a miscarriage than never smokers (summary relative risk ratio 0.90, 95% CI 0.69 to 1.16).21

Women who smoke also have an increased risk of stillbirth (summary relative risk [sRR] 1.46, 95% CI 1.38, 1.54), neonatal death (sRR 1.22, 95% CI 1.14, 1.30) and perinatal death (sRR 1.33, 95% CI 1.25 to 1.41), and these risks all increase with the number of cigarettes smoked.22 Smoking doubles the chance of preterm birth and of fetal growth restriction. There is also an increased likelihood of congenital abnormalities affecting the cardiovascular system (OR 1.09, 95% CI 1.02 to 1.17) and gastrointestinal system (eg, gastroschisis OR 1.50, 95% CI 1.28 to 1.76), and the face (eg, cleft palate OR 1.28, CI 1.20 to 1.36) and limbs (limb reduction defects OR 1.26, 95% CI 1.15 to 1.29).23 The likelihood of venous thromboembolism is also increased (adjusted OR 2.7, 95% CI 1.5 to 4.9).24

The National Institute for Health and Clinical Excellence’s (NICE) public health guideline does not specifically cover the approaches to women who are planning a pregnancy, as there are limited data on this.25 The guideline focuses on midwifery delivered support programmes for women who have already conceived. A separate NICE guideline applies to all who smoke and is for use in primary care and community settings.26

Local stop smoking support programmes should be offered to women wishing to stop smoking before they conceive, including behavioural options and nicotine replacement therapy (NRT). There are no published data about e-cigarettes in pregnancy and limited evidence about NRT use, so if women conceive using these interventions there should be a balanced discussion about the likelihood of resuming or increasing smoking cigarettes if they discontinue; compared with continuing smoking, they may improve pregnancy outcome, although it is likely that the best outcome is with complete cessation.27 28

The NICE guideline advises that neither varenicline nor bupropion should be offered to pregnant or breastfeeding women.25 Data about effects of fetal exposure to varenicline in pregnancy are limited to only 367 cases in prospective series, with no apparent increase in miscarriage, teratogenicity or intrauterine death, and thus ideally women who are trying to stop smoking as part of their prepregnancy planning should use effective contraception while taking varenicline.29 Given the lack of data concerning safety of varenicline use during pregnancy, a detailed fetal anomaly scan is recommended where exposure has occurred during the first trimester.30 Pregnancy exposure data for bupropion do not suggest an increased risk of spontaneous abortion, major congenital malformation overall, cardiac malformation, intrauterine death, low birth weight or preterm delivery following use in pregnancy.31 Single case-control studies have suggested possible associations with specific cardiac malformations that have not been replicated in other studies. Exposure to bupropion during pregnancy would not usually be regarded as medical grounds for termination of pregnancy.

Alcohol

The Department of Health recommends that women who are planning pregnancy as well as those already pregnant do not drink any alcohol at all. This is because there is insufficient evidence to know if low level alcohol use affects a baby, and because it is easy to inadvertently misjudge intake and consume more than intended.32 Alcohol is the most common teratogen that women are exposed to during pregnancy, with estimates that 3.2% of babies born in UK are affected by fetal alcohol spectrum disorders.33 These comprise a wide range of adverse effects on the baby, depending on the amount of alcohol consumed, the gestation and a variety of other less well defined factors including genetic predisposition, gestation of exposure and use of other toxins such as smoking or street drugs. Alcohol crosses directly and freely through the placenta; it has the potential to be toxic because the immature fetal liver cannot metabolise it and thus it can cross the fetal blood brain barrier and cause direct neurological damage. This can happen at any gestation and seems to be dose related with both binge drinking and number of units daily being important. As well as causing a typical facial appearance and neurocognitive disturbances, congenital malformations, preterm birth and fetal growth restriction are increased.

Screening for rubella susceptibility

Routine screening for rubella immunity in the first trimester of pregnancy was discontinued in England in 2016, as congenital rubella syndrome is considered to have been eradicated, due to the success of the childhood vaccination programme; it also recognised that screening during pregnancy cannot prevent congenital rubella from developing in the index pregnancy.34 35

It is now recommended by Public Health England (PHE) that a woman’s mumps, measles and rubella (MMR) status is checked at appropriate and often opportunistic opportunities such as at family planning clinics, when travelling abroad or during registration with a new GP), especially if she has arrived from Africa, Asia or other parts of the world where the prevalence of rubella remains high.36 PHE does not define the precise nature of this check; pragmatically, if a non-pregnant woman can answer positively to a question about previous MMR vaccination she can assume she is immune; if she cannot and does not have access to her childhood vaccine record, then she needs a blood test for rubella IgG followed by vaccination if the result is negative, or empirical vaccination. If a woman is uncertain of her MMR status, a further MMR vaccination prior to conception will not cause harm. Contraception should be used for at least 1 month after the last MMR vaccination. Rubella vaccination is not recommended during pregnancy, and should be deferred until after birth if conception has already occurred; it can be given during breast feeding. Inadvertent vaccination in pregnancy has not be shown to harm the fetus and is not considered an indication for termination of pregnancy. It should, however, be reported to PHE as should MMR vaccination within 30 days of last menstrual period (https://bit.ly/2ZpdYCY). Chickenpox, shingles or human papillomavirus vaccine given to women who are pregnant or in the weeks prior to becoming pregnant should also be reported.

Screening for thalassaemia and sickle cell

Beta thalassaemia and sickle cell disorders are common autosomal recessive single gene disorders which form part of the national antenatal screening programme; they can be diagnosed in utero in women at risk of having an affected fetus giving her the possibility to terminate the pregnancy.37 In women planning pregnancy, consideration of their haemoglobin electrophoresis status and if required subsequent partner testing allows time for a couple at risk of having an affected fetus to understand the implications and options that will be available to them after conception. This is particularly important for women who originate from countries with high prevalence of haemoglobinopathies including those bordering the Mediterranean, Middle Eastern, Asia and sub-Saharan Africa (eg, Nigeria and Democratic Republic Congo), where prevalence of sickle carrier status is up to 30%.

Over-the-counter medicines and other products

Significant numbers of women take over-the-counter (OTC) medicines including herbal and homeopathic products before and during pregnancy.38 39 Women should not assume that because a medicine is available without prescription that it is safe to use during pregnancy. The Best Use of Medicines in Pregnancy website (see box 1) provides a useful resource that women can access to get information about many commonly taken medicines. Healthcare professionals should enquire about the use of OTC medicines in women planning pregnancy. The potential harms and benefits of such products used during pregnancy should be discussed and advice on alternative options given. In the absence of robust evidence of safety, it is suggested that herbal medicinal products should be avoided during pregnancy and the postnatal period.40 41

Women planning pregnancy should not take products containing vitamin A. Preformed vitamin A as retinol in meat and dairy products or vitamin supplements is teratogenic especially if taken in early pregnancy at doses of 10 000 international units daily.40

Travel

Women who are considering pregnancy should use barrier contraception while travelling and for 2 or 3 months after returning from an area with a risk of zika infection.42 43 The likelihood of birth defects is low compared with other viruses such as rubella, but the incidence of zika infection can be high during an outbreak. Fetuses exposed in very early pregnancy may be at greatest risk of congenital zika virus syndrome which includes a range of issues including microcephaly. If women do travel to areas at risk, they should also take usual measures to minimise bites from the vector Aedes mosquito, a daytime mosquito, by wearing long-sleeved and long-legged clothing, by using insect repellents and mosquito nets when resting. The countries considered to be a risk for zika infection are listed on the PHE website (https://www.gov.uk/guidance/zika-virus-country-specific-risk%23atoz). More detailed guidance for couples considering travel prior to pregnancy to a country where zika transmission is reported is available from PHE, the Royal College of Obstetricians and Gynaecologists (https://www.rcog.org.uk/en/guidelines-research-services/guidelines/zika-virus-infection-and-pregnancy/) and the National Travel Health Network and Centre (https://travelhealthpro.org.uk/news/394/zika-virus-zikv-update-to-guidance).

Summary

Providing prepregnancy information for women is an important way to improve pregnancy outcome for them and the baby. Healthcare practitioners should consider ways to maximise the opportunities for women to access this advice. All prescribers should discuss the pros and cons of medication use on pregnancy, so that women can plan according to disease activity and its treatment, and know what medication changes to make once conception has occurred.44 Important considerations include:

  1. Using effective contraception so that pregnancy can be planned.

  2. Optimising medicines for women with chronic conditions to maximise disease control, decrease adverse effects and minimise fetal risks.

  3. Starting folic acid 3 months prior to conception and continuing until 12 weeks’ gestation.

  4. Achieving the most normal BMI possible before conceiving.

  5. Stopping smoking before conception, or if this is not possible, cutting down as much as possible as early as possible.

  6. Stopping drinking alcohol before conception, or if this is not possible, stopping binge drinking and reducing total input as far as possible.

  7. Before pregnancy, having rubella vaccination if susceptible.

  8. Haemoglobin electrophoresis screening for women at risk of sickling and thalassaemia disorders.

  9. Discussing use of OTC medicines, herbal and homeopathic products.

  10. Using barrier contraception if travelling to an area with a risk of zika infection and for 2–3 months after returning.­

Future articles in this series will consider the impact of long-term conditions on pregnancy outcome, the potential impact of pregnancy on the long-term condition and the need to optimise prescribing for women with long-term conditions who are planning pregnancy.

Supplemental material

References

Footnotes

  • Competing interests None declared. Disclosure of conflicts of interest form(s) are published online as supplementary files.

  • Provenance and peer review Commissioned; externally peer reviewed.