(Date of issue: August 2013. Version: 2)
This factsheet has been written for members of the public by the UK Teratology Information Service (UKTIS). UKTIS is a not-for-profit organisation funded by Public Health England on behalf of UK Health Departments. UKTIS has been providing scientific information to health care providers since 1983 on the effects that medicines, recreational drugs and chemicals may have on the developing baby during pregnancy.
What are ACE inhibitors?
ACE inhibitors are medicines that are prescribed to treat high blood pressure, heart failure, and diabetic nephropathy (a kidney disease that can affect people with diabetes). Some products (marked in the list below with*) combine an ACE inhibitor with another type of medicine (either a diuretic or a calcium channel blocker). This leaflet summarises the scientific studies relating to the effects that ACE inhibitors may have on a baby when taken by the mother in pregnancy. Any potential effects of the additional components in the combination medicines are not discussed in this leaflet.
ACE inhibitors available in the UK include; captopril [Capoten®,Co-zidocapt®*,Capozide®*], cilazapril [Vascace®], enalapril maleate [Innovace®, Innozide®*], fosinopril sodium, imidapril hydrochloride [Tanatril®], lisinopril [Zestril®, Carace Plus®*, Zestoretic®*], moexipril hydrochloride [Perdix®], perindopril erbumine, perindopril arginine [Coversyl® Arginine, Coversyl® Arginine Plus*], quinapril [Accupro®, Accuretic®*], ramipril [Tritace®, Triapin®*], trandolapril [Gopten®, Tarka®*].
Is it safe to take an ACE inhibitor in pregnancy?
Any woman who is taking an ACE inhibitor and is planning a pregnancy should speak to her doctor to discuss the possibility of switching to a different medicine before she conceives. Some women with certain illnesses may need to take an ACE inhibitor during the first trimester of pregnancy. Use of ACE inhibitors in the second and third trimesters is not generally advised but may occasionally be considered necessary for the treatment of very serious illnesses if other treatments have not worked. Your doctor will be able to help you to weigh up how necessary an ACE inhibitor is to your health against the possible risks to you or your baby, which will depend on how many weeks pregnant you are.
This leaflet summarises the scientific studies relating to the effects of ACE inhibitors on a baby in the womb.
What if I have already taken an ACE inhibitor during pregnancy?
If you have taken an ACE inhibitor in the second or third trimester of pregnancy without medical supervision, it is important to let your doctor or midwife know straight away as your baby may need extra monitoring for the effects described below.
There is no strong scientific proof that taking ACE inhibitors during the first trimester will harm a baby in the womb. However, you should let your doctor know that you are pregnant so that you can decide together whether you should change to another safer medicine for the remainder of your pregnancy. It is important that your doctor reviews all medicines that you are taking if you become pregnant to assess whether you still need them and, if so, to make sure that you are taking the lowest dose that works.
Can taking ACE inhibitors in pregnancy cause miscarriage?
It is unclear whether taking ACE inhibitors in early pregnancy increases the chance of having a miscarriage. Two small studies both showed that women who take ACE inhibitors or a related type of medicine during early pregnancy may be more likely to have a miscarriage than women who have not taken any medicines. However, only 350 pregnancies were studied in total and women taking ACE inhibitors were not studied separately from women taking other related medicines for high blood pressure. More research into the specific effects of ACE inhibitors is therefore required to answer this question.
ACE inhibitors are used to treat high blood pressure and diabetes, both of which are more common in people with obesity. High blood pressure, diabetes and obesity are all thought to increase a woman’s chance of having a miscarriage. More research is also therefore needed to understand whether the increased risk of miscarriage reported in the above studies is due to the medicines the pregnant women were taking, their health problems, or a combination of both factors.
Can taking ACE inhibitors in pregnancy cause my baby to be born with birth defects?
A baby’s body and most internal organs are formed during the first 12 weeks of pregnancy. It is mainly during this time that some medicines are known to cause birth defects.
There is no convincing scientific evidence that taking ACE inhibitors during early pregnancy causes birth defects.
Although two studies have shown that women who took ACE inhibitors during the first three months of pregnancy were more likely to have a baby with a birth defect than women who didn’t take any medicines, a further five studies have not agreed with this finding. In the two studies that showed a link, the researchers thought that the birth defects may have been due to the illnesses that the mothers were taking ACE inhibitors to treat (e.g. high blood pressure, diabetes), rather than the ACE inhibitors themselves.
A small number of studies have investigated possible links between taking ACE inhibitors in early pregnancy and specific birth defects:
• Two studies suggested that ACE inhibitor use in early pregnancy may increase the likelihood of having a baby with a heart malformation, but another three studies have not shown this. In one of the studies that showed a link, the researchers thought that this was more likely to have been due to the fact that a large number of women in the study had diabetes (which is known to increase the risk of heart malformations in the baby) and not to the ACE inhibitors.
• One study indicated that babies born to women who took ACE inhibitors in early pregnancy were more likely to have defects of the central nervous system. Another study which investigated the risk of a specific type of nervous system defect called a neural tube defect found no link with ACE inhibitors.
• One study suggested that babies whose mothers had taken ACE inhibitors during early pregnancy were more likely to have a kidney defect. However, no other studies have investigated any possible link between ACE inhibitor use in early pregnancy and kidney defects and it is therefore not possible to say that there is a link based on only one study.
Taken together, these studies do not provide definite evidence that taking ACE inhibitors during early pregnancy causes any of the defects listed above. However, a link cannot yet be ruled out and women who take ACE inhibitors in early pregnancy need to continue to be studied.
What problems can taking ACE inhibitors after the first trimester of pregnancy cause in my baby?
Taking ACE inhibitors during the second and third trimesters can cause a number of problems in the baby including:
• Reduced levels of amniotic fluid around the baby in the womb (oligohydramnios). Many of the problems described below are thought to occur as a result of very low amniotic fluid levels.
• Kidney damage (renal tubular dysgenesis) which can lead to long-term kidney problems after birth.
• Under-development of the baby’s skull bones.
• Reduced growth of the baby in the womb.
• Poor development of the baby’s lungs (because inhaling amniotic fluid while in the womb helps to expand and develop the lungs).
• The baby’s bladder being under-developed (because urine expands and develops the bladder).
• The baby’s skull and leg bones being misshapen and the baby having ‘flattened’ facial features (as a result of there not being enough amniotic fluid to ‘cushion’ the baby in the womb).
• Compression (squashing) of the umbilical cord, which may result in reduced blood flow from the mother to the baby in the womb.
• A blood vessel in the baby called the ductus arteriosus not closing at birth to allow the baby’s blood to flow through its lungs once it starts breathing. Patent ductus arteriosus is the medical term used to describe this blood vessel staying open after birth.
Because very few women take ACE inhibitors during the second and third trimesters of pregnancy, no large studies have been carried out that might tell us what the chances are of a baby exposed to ACE inhibitors during this period developing the above problems.
Some of the complications described above can be serious, which explains why there are reports of babies exposed to ACE inhibitors during the second or third trimesters being stillborn and dying after birth. However, it is also possible that the serious illnesses for which pregnant women take ACE-inhibitors during late pregnancy may also contribute to the risks of stillbirth and the baby dying after birth.
ACE inhibitors should only be taken after the first trimester of pregnancy under strict medical supervision. If your doctor has advised that you take an ACE inhibitor during the second or third trimester, this is likely because you have a serious illness that cannot be treated any other way. Some of the pregnancy problems discussed above (e.g. low levels of amniotic fluid) can be detected by ultrasound scans. If low amniotic fluid levels are identified early enough and treatment with an ACE inhibitor is stopped in time, many of these effects will be prevented and some may be reversible. Regular monitoring of your baby will therefore be required to allow ongoing decisions to be made about the best treatment for your and your baby’s health. Please discuss any concerns that you may have with your doctor.
Can taking ACE inhibitors in pregnancy cause preterm birth or my baby to be small at birth (low birth weight)?
Two studies have both shown that women who took ACE inhibitors during pregnancy were more likely to give birth early (before 37 weeks of pregnancy) or to have a low birth weight baby (<2500g). However, more research is required before we can say whether preterm birth and low birth weight is caused by ACE inhibitors as it is possible that these outcomes are linked to the illness for which the mother was taking ACE inhibitors (e.g. high blood pressure in the mother is thought to affect the way that a baby grows in the womb).
Can taking ACE inhibitors in pregnancy cause learning or behavioural problems in the child?
A baby’s brain continues to develop right up until the end of pregnancy. It is therefore possible that taking certain medicines at any stage of pregnancy could have a lasting effect on a child’s learning or behaviour.
There is no known link between taking ACE inhibitors in pregnancy and learning or behavioural problems such as attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder in the child. There are, however, no scientific studies that have specifically investigated a link with these problems.
Will my baby need extra monitoring during pregnancy?
Most women will be offered a scan at around 20 weeks of pregnancy to look for birth defects as part of their routine antenatal care. Although there is no strong evidence that taking ACE inhibitors during the first trimester increases the risk of birth defects in the baby, the illnesses that ACE inhibitors are used to treat (e.g. high blood pressure, diabetes) are themselves linked to an increased risk of birth defects in the baby. In these cases your doctor may wish to monitor your pregnancy more closely.
If you have taken ACE inhibitors during the second or third trimesters, extra scans or monitoring of your baby will be required.
Are there any risks to my baby if the father has taken ACE inhibitors?
We would not expect any increased risk to your baby if the father took ACE inhibitors before or around the time your baby was conceived.
Who can I talk to if I have questions?
If you have any questions regarding the information in this leaflet please discuss them with your health care provider. They can access more detailed medical and scientific information from www.uktis.org.