Immunization in pregnancy and breastfeeding: Canadian Immunization Guide
- This chapter has not yet been updated with the following statement from the National Advisory Committee on Immunization (NACI):
- This CIG chapter has not been updated to contain any information regarding COVID-19 vaccines, refer to the COVID-19 vaccine chapter.
Last complete chapter revision (see Table of updates): April 2018
April 2018 - The chapter has been reviewed and updated to align with the updated National Advisory Committee on Immunization (NACI) Statement on immunization in pregnancy with acellular pertussis (Tdap) vaccine.
- New recommendation: One dose of Tdap vaccine should be administered in every pregnancy. Rationale: Transplacental antibody transfer to newborns provides protection during the 2 first months of life where morbidity and mortality is highest, ideally between 27 and 32 weeks of gestation.
Additional updates include:
- Considerations regarding the administration of immunoglobulin and of the following vaccines: conjugate quadrivalent meningococcal, meningococcus B vaccine, yellow fever, Japanese encephalitis.
- Data on the efficacy and safety of Human papillomavirus (HPV) vaccination in pregnancy is limited. Consider reporting exposure to HPV vaccine during pregnancy to the vaccine manufacturer.
- Vaccines containing thimerosal are safe in pregnancy and should be used if indicated.
- When available and indicated, inactivated vaccines are preferred to live attenuated vaccines.
Live herpes zoster vaccine is contraindicated during pregnancy. It is unknown whether it is secreted in human milk.
On this page
- Benefits of immunization in pregnancy for the mother
- Safety of immunization in pregnancy for the mother
- Benefits of immunization in pregnancy for the fetus and infant
- Safety of immunization in pregnancy for the fetus and infant
- Immunization during pregnancy
- Immunization of household contacts of pregnant women
- Immunization during breastfeeding
- Selected references
Please note: The National Advisory Committee on Immunization (NACI) recognizes that not all people giving birth or breastfeeding will identify as women or mothers. For the purposes of this chapter, the terms "woman", "women", "mother" and "maternal" are used, but should be considered to also apply to those individuals who do not specifically identify as female gender but are the parent gestating the fetus or breastfeeding the infant.
Pregnancy provides an opportunity for health care providers to evaluate immunization status. Pregnancy is associated with an altered immune response and, for some infectious diseases, an increased risk of infection and an increased risk of severe outcomes once infected. The fetus, neonate and young infant can also be affected by infections that can result in congenital abnormalities, impaired fetal growth or severe neonatal illness.
One of the challenges of developing guidelines for immunization during pregnancy and breastfeeding is the scarcity of studies to support evidence-based recommendations. Only a few methodologically robust studies of vaccine administration in pregnancy and breastfeeding exist; most safety data available are derived from active surveillance or from registries where outcomes are passively reported.
When considering vaccination in pregnancy, it is important to distinguish between live and inactivated vaccines. There is no theoretical reason to suspect that inactivated vaccines are associated with an increased risk of adverse events when administered during pregnancy and data from active and passive surveillance systems confirm safety for several vaccines. Live vaccines should generally not be given during pregnancy because of the theoretical risk of harm to the fetus if transmission of the vaccine strain to the fetus occurs.
The objective of vaccination during pregnancy is to protect the mother and the fetus and newborn. Even though pregnancy is an immunologically altered state, response to vaccines is adequate. Clinical trials of pertussis, tetanus toxoid, and inactivated polio vaccine administered during pregnancy have demonstrated normal adult immunologic responses.
Ideally, the immunization status of individuals of child-bearing age should be reviewed regularly and vaccines updated as needed. Live vaccines, for example, can be given during reproductive planning, prior to conception, with the advice to avoid pregnancy for at least 28 days following immunization.
Benefits of immunization in pregnancy for the mother
Vaccines recommended for the protection of a pregnant woman's health include:
- inactivated influenza vaccine
- acellular pertussis vaccine (given as tetanus toxoid, diphtheria toxoid, acellular pertussis vaccine)
- hepatitis B vaccine if susceptible and with ongoing exposure risks
- hepatitis A vaccine if a close contact of a person with hepatitis A or if travelling to an endemic area
- meningococcal vaccine in an outbreak setting or post-exposure, or if indicated by medical condition
- pneumococcal polysaccharide vaccine with or without conjugate vaccine if indicated by medical condition
- any other inactivated vaccine if indicated by exposure (e.g. rabies), travel (e.g. inactivated typhoid vaccine) or by medical condition (e.g. asplenia).
Safety of immunization in pregnancy for the mother
Inactivated vaccines are considered to be safe when administered in pregnancy. Reactions following vaccination with inactivated vaccines are usually limited to the injection site. No increase in anaphylactic reactions or events that might induce preterm labour has been observed following immunization with inactivated vaccines.
Benefits of immunization in pregnancy for the fetus and infant
The beneficial effects of immunization during pregnancy for the fetus as well as the newborn infant have been well documented. Vaccination during pregnancy protects the mother from vaccine-preventable diseases that may otherwise be acquired and be transmitted to the fetus or infant. In addition, protective concentrations of antibodies are transferred to the fetus transplacentally, resulting in increased infant protection in the early postnatal period. The majority of transplacental antibody transfer occurs during the third trimester and the half-life of these antibodies in the newborn is typically 4 to 6 weeks. Transplacentally acquired antibody concentrations progressively decrease during the first year of life.
Safety of immunization in pregnancy for the fetus and infant
There is no theoretical reason to anticipate adverse events in the fetus or infant following vaccination with inactivated vaccines during pregnancy. There are no published data indicating that currently authorized inactivated vaccines are teratogenic or embryotoxic or have resulted in specific adverse pregnancy outcomes.
The National Advisory Committee on Immunization (NACI) has concluded that vaccines that contain thimerosal (now only in multi-dose vials of influenza vaccine and hepatitis B vaccine) are safe in pregnancy and should be used if indicated.
In general, live attenuated viral or bacterial vaccines are contraindicated in pregnancy, as there is a theoretical risk to the fetus; however, when benefits outweigh this theoretical risk, vaccination with a live attenuated vaccine may be considered (e.g. during a rubella outbreak).
Immunization during pregnancy
Inactivated influenza vaccine
All pregnant women, at any stage of pregnancy, should receive inactivated influenza vaccine during each pregnancy, because of their increased risk of influenza-associated morbidity; evidence of adverse neonatal outcomes associated with maternal influenza; evidence that vaccination in pregnancy decreases risk of stillbirth and protects newborns from influenza and influenza-related hospitalization; and evidence that infants born during the influenza season to recipients of influenza vaccine are less likely to be premature, small for gestational age, or of low birth weight.
There is good evidence demonstrating the safety of inactivated influenza vaccine during pregnancy. Active surveillance following influenza vaccination during pregnancy has not shown evidence of harm to the mother or fetus associated with influenza immunization. Although the cumulative sample size of these studies is relatively small, particularly for immunization in the first trimester, passive surveillance has not raised any safety concerns, despite widespread use of influenza vaccine in pregnancy over several decades. Surveillance following the use of both adjuvanted and unadjuvanted pandemic H1N1 influenza (pH1N1) vaccine in more than 100,000 pregnant women in Canada and almost 500,000 pregnant women in Europe did not reveal any safety concerns.
During the influenza season, if influenza vaccine was not received during pregnancy it should be given as early as possible post-partum, preferably before discharge from hospital.
Refer to the Canadian Immunization Guide chapter on influenza and Statement on seasonal influenza vaccine for additional information.
Pertussis vaccine (given as tetanus toxoid, diphtheria toxoid, acellular pertussis vaccine)
All pregnant women should be given tetanus toxoid, diphtheria toxoid, acellular pertussis (Tdap) vaccine during every pregnancy, irrespective of their Tdap immunization history. Immunization with Tdap in pregnancy has been shown to be safe and effective in preventing neonatal and infant pertussis infection. High levels of antibody are transferred to the fetus, protecting the newborn from pertussis during the first two months of life when the morbidity and mortality from pertussis infection is highest. The vaccine should ideally be provided between 27 and 32 weeks of gestation. Immunization between 13 and 26 weeks of gestation may be considered in situations where there may be an increased risk of preterm delivery. Although it is preferable that immunization is administered in sufficient time before birth (i.e. 4 weeks) to allow optimal transfer of maternal antibodies, if not given earlier it should be given at any time until delivery, to provide partial protection and prevent maternal pertussis infection and subsequent transmission to the newborn.
Administration of tetanus toxoid in pregnancy has been shown to prevent neonatal tetanus infection and death in countries with high rates of neonatal tetanus.
Hepatitis B (HB) vaccine
All pregnant women should be routinely tested for hepatitis B surface antigen (HBsAg) in each pregnancy (unless they are already known to be hepatitis B virus (HBV) immune or carriers of HBV), so that the newborn can be given HB prophylaxis if indicated.
Acute HB infection in a pregnant woman may result in severe disease for the mother and chronic infection in the infant. A pregnant woman who has no markers of HB infection (HB antibody and HbsAg negative) but who is at high risk of HB acquisition should be offered a complete HB vaccine series at the first opportunity during the pregnancy and should be tested for antibody response. Immunization with HB vaccine in pregnancy has been shown to be safe.
Refer to Hepatitis B vaccine in Part 4 for additional information.
Vaccines that may be indicated
Haemophilus influenzae type b (Hib) vaccine
Hib vaccine should be considered in pregnancy if indicated for a medical condition at high risk for Hib disease. Although Hib vaccine has not been studied in pregnancy, there is no theoretical reason to suspect that adverse events to mother or infant will occur. Refer to Haemophilus influenzae type b vaccine in Part 4 and Immunization of immunocompromised persons and Immunization of persons with chronic diseases in Part 3 for additional information.
Hepatitis A (HA) vaccine
Hepatitis A can cause severe disease in pregnancy, and the vaccine should be considered for pregnant women when indicated for post-exposure prophylaxis, for travel to endemic areas or for other exposure risks. The efficacy and safety of hepatitis A vaccines given during pregnancy has not been studied in clinical trials, but there is no evidence of, or theoretical reason to suspect an increased risk of adverse events to the mother or the infant. Refer to Hepatitis A vaccine in Part 4 for additional information.
Conjugate quadrivalent meningococcal vaccine and meningococcus B vaccine should be considered in pregnancy, if indicated in circumstances such as a medical condition at high risk for meningococcal disease; travel to a high risk area; post-exposure prophylaxis; or during an outbreak. Although these vaccines have not been studied in pregnancy, there is no theoretical reason to suspect that adverse events to mother or infant will occur.
Pregnant women at high risk of invasive pneumococcal disease can, if indicated, be vaccinated with the appropriate pneumococcal vaccines. There is no evidence to suggest a risk of adverse events from immunization with pneumococcal conjugate or polysaccharide vaccine in pregnancy.
Inactivated poliomyelitis vaccine (IPV) may be considered for non-immune pregnant women who are at increased risk of exposure to wild poliovirus. Limited data have not revealed an increased risk of adverse events associated with IPV vaccine administered in pregnancy and there is no theoretical reason to suspect an increased risk of adverse events.
Refer to Poliomyelitis vaccine in Part 4 for additional information.
If a pregnant woman has had a potential exposure to rabies, since rabies is invariably fatal, post-exposure prophylaxis should be provided.
If pre-exposure prophylaxis is indicated, it is prudent to delay immunization until after pregnancy unless there is an increased risk of rabies exposure during the pregnancy, in which case the vaccine should be given. Limited data have not shown an increased risk of adverse events in pregnancy, and there is no theoretical reason to suspect that adverse events will occur.
Refer to Rabies vaccine in Part 4 for additional information.
Japanese encephalitis (JE) acquired during pregnancy carries the risk of intrauterine infection and miscarriage. Pregnant women who must travel to areas where the risk of JE infection is high should be immunized as the risk of disease outweighs the unknown risk of vaccination. Inactivated typhoid vaccine should be considered when indicated for travel to endemic areas if risk factors for severe disease are present. Cholera and enterotoxigenic Escherichia coli (ETEC) travellers' diarrhea vaccine should be considered for those at risk of severe disease if infection occurs.
These are inactivated vaccines and there is no theoretical reason to suspect increased risk of post-immunization adverse effects in the mother or fetus. However, because these vaccines have not been studied in pregnancy, administration should be considered only in high risk situations after evaluation of the benefits and risks. Live typhoid vaccine should not be used in pregnancy.
Refer to vaccine-specific chapters in Part 4 for additional information.
Immunoglobulin products may be administered in pregnancy as required for pre- or post-exposure prophylaxis (measles, varicella, HA, HB, tetanus, rabies) or as replacement therapy. There is no known or theoretical risk to the fetus or to a pregnant woman from their administration.
Vaccines not recommended
Human papillomavirus vaccine (HPV)
HPV vaccines are not currently recommended for use in pregnancy. Although HPV vaccine has not been causally associated with adverse outcomes of pregnancy or adverse events to the developing fetus, data on efficacy and safety of HPV vaccination in pregnancy are limited. It is recommended that initiation of the HPV vaccine series be delayed until after completion of pregnancy. If a vaccine dose has inadvertently been administered during pregnancy, no intervention is indicated, but completion of the series should be delayed until after pregnancy.
Vaccine recipients and health care providers are encouraged to report any exposure to HPV4 or HPV9 vaccine during pregnancy to the vaccine manufacturer (Merck Canada Inc.) at 1-800-567-2594. Exposure to HPV2 vaccine during pregnancy should be reported to the vaccine manufacturer (GlaxoSmithKline Inc.) at 1-800-387-7374.
Refer to Human papillomavirus vaccine in Part 4 for additional information.
Recombinant herpes zoster vaccine (RZV)
This vaccine should be used with precaution in those who are pregnant (as there are no data on its use in this population), or breastfeeding (as the effect on breast-fed infants of vaccination in those who are breastfeeding has not been studied). The safety and efficacy in individuals younger than 18 years of age has not been studied, and there are limited data on its use in immunocompromised individuals 50 years of age and older.
Refer to Herpes zoster (shingles) vaccine in Part 4 for additional information.
Generally contraindicated vaccines
Administration of live attenuated vaccines is generally contraindicated in pregnancy because there is a theoretical risk of infection of the fetus.
Measles-mumps-rubella (MMR) vaccine
Although MMR vaccine is generally contraindicated in pregnancy, in situations when potential benefits may outweigh risks, such as during measles or rubella outbreaks, vaccination may be considered. Rubella infection during pregnancy frequently gives rise to congenital rubella syndrome which can result in miscarriage, stillbirth or fetal malformations. Measles during pregnancy results in a higher risk of premature labour, spontaneous abortion and low birth weight infants. To date, there is no evidence demonstrating a teratogenic or other adverse effect from MMR vaccine given during pregnancy. Inadvertent immunization with MMR vaccine is therefore not a reason for pregnancy termination.
Pregnant women without documented laboratory evidence of rubella immunity or prior immunization with a rubella-containing vaccine should be serologically screened for rubella antibodies. Those who are seronegative should receive MMR vaccine, with the first dose given in the immediate post-partum period before discharge from hospital (unless they have received Rh immunoglobulin (RhIg) or other blood products recently). If indicated for measles or mumps protection, a second dose of MMR should be given 4 weeks or more after the first. For post-partum MMR immunization of women who received RhIg or other blood products, refer to Blood products, human immunoglobulin and timing of immunization in Part 1.
Refer to Measles vaccine, Mumps vaccine, and Rubella vaccine in Part 4 for additional information including guidance on post-exposure prophylaxis with measles immunoglobulin for susceptible pregnant women exposed to measles.
Monovalent varicella vaccine
Monovalent varicella vaccine, a live attenuated vaccine, is contraindicated in pregnancy because there is a theoretical risk to the fetus; however, there is no evidence to demonstrate a teratogenic or other adverse event from varicella vaccination in pregnancy. Inadvertent immunization with varicella vaccine is not a reason for pregnancy termination.
Pregnant women without documented laboratory evidence of varicella immunity or prior immunization with 2 doses of varicella vaccine should be serologically screened for varicella antibodies. Those who are seronegative should receive univalent varicella vaccine in the immediate post-partum period prior to hospital discharge unless they have received Rh immunoglobulin (RhIg). A second dose should be given 4 weeks or more after the first. For additional information regarding post-partum MMR immunization of women who received RhIg or other blood products, refer to Table 1 in Blood products, human immunoglobulin and timing of immunization in Part 1.
Refer to Varicella (chickenpox) vaccine in Part 4 for additional information, including post-exposure prophylaxis with varicella zoster immunoglobulin for pregnant women exposed to varicella.
Live herpes zoster vaccine (LZV)
LZV is contraindicated in pregnancy, and pregnancy should be avoided for three months after vaccine administration. While no studies have been conducted in this population, naturally occurring VZV infection is known to cause fetal harm in some cases. Given the age indication for LZV (≥ 50 years), it is unlikely to be inadvertently given in pregnancy.
Refer to Herpes zoster (shingles) vaccine in Part 4 for additional information.
Yellow fever (YF) vaccine
Yellow fever virus can cause severe infection in pregnancy and transmission to the fetus has been reported. YF vaccine should be avoided in pregnancy unless benefit outweighs risk. Pregnant women should be considered for YF immunization only if they are travelling to an area at high risk of YF transmission, travel cannot be postponed and a high level of protection against mosquito exposure is not feasible. Since seroconversion rates following YF vaccine are lower during pregnancy, post-immunization serology should be considered. Studies including several hundred women who received YF vaccine during pregnancy, using both active and passive surveillance methods, have not shown significant adverse events. Inadvertent immunization with YF vaccine is therefore not a reason for pregnancy termination.
A waiver or Certificate of Medical Contraindication to Vaccination should be provided if a pregnant woman travels to a country that is not an area of high risk but requires documentation of YF vaccination. Refer to Yellow fever vaccine in Part 4 and to CATMAT's Statement on pregnancy and travel for additional information.
Other live attenuated vaccines
The use of other live attenuated vaccines during pregnancy must be evaluated on the basis of the individual risk and benefit. If an alternative inactivated vaccine is available, such as in the case of influenza or typhoid vaccine, it should be used instead of a live attenuated vaccine.
Bacille Calmette-Guérin (BCG) vaccine has not been studied in pregnant women and should not be given during pregnancy, although no harmful effects of BCG vaccination on the fetus have been observed.
Live replicating Smallpox vaccine is contraindicated during pregnancy in non-emergency situations. It may be considered for a pregnant woman in the highly unlikely event of a high-risk exposure. Smallpox vaccine can very rarely lead to fetal vaccinia resulting in stillbirth or neonatal death. If a woman becomes pregnant within 4 weeks after smallpox vaccination she should be counselled regarding possible risk to the fetus.
Refer to vaccine-specific chapters in Part 4 for additional information.
Immunization of household contacts of pregnant women
Pregnancy in a household does not affect immunization indications for any other members of the household. Indeed, pregnancy should be used as an opportunity to update immunization of susceptible household contacts, including live vaccines such as rotavirus, MMR, MMRV, varicella, zoster and LAIV.
In the unlikely event of a household contact being vaccinated against smallpox, extreme precautions should be taken to prevent transfer of the vaccinia virus to unvaccinated household and other close contacts, pregnant or not. Such precautions can include isolation of the vaccinee from pregnant household contacts until the vaccine scab falls off.
Immunization during breastfeeding
Immunization of breastfeeding women
In general, routinely recommended vaccines can be safely administered to breastfeeding women. There are limited data available regarding the effects of immunization of breastfeeding women on their infants; however, there have been no reported adverse events related to administration of routine vaccines. There is no evidence that immunization during breastfeeding will adversely influence the maternal or infant immune response.
Annual influenza vaccination is recommended during breastfeeding if not given during that pregnancy. Women who are breastfeeding should be vaccinated with Tdap, Td, hepatitis B, hepatitis A, HPV, pneumococcal, meningococcal, Hib, IPV, rabies, inactivated typhoid, MMR, varicella and cholera-traveler's diarrhea vaccines if indicated.
It is not known whether LZV virus is secreted in human milk. Given the age indication for HZ vaccines (≥ 50 yr), breastfeeding women are unlikely to be among the target population.
Japanese encephalitis (JE) vaccine has not been studied in breastfeeding. It is an inactivated vaccine and there is no theoretical reason to suspect increased risk of adverse effects in the mother or infants. Breastfeeding women who must travel to areas where the risk of JE infection is high should be immunized if the risk of disease outweighs the unknown risk of vaccination to the woman and her breastfeeding infant.
Vaccines not recommended during breastfeeding
There are a few instances when vaccination is not recommended during breastfeeding. There have been three reported cases of probable transmission of YF vaccine strain virus from mothers to their infants through breastfeeding, resulting in meningoencephalitis in the infants. Therefore, in general, breastfeeding mothers should not be vaccinated. If, for entry to a country, a yellow fever vaccination certificate is required and there is no risk of acquiring yellow fever in the regions to be visited, a waiver or Certificate of Medical Contraindication to Vaccination should be sought. If travelling is to a highly endemic area and travel cannot be postponed, then the risk of vaccination causing disease in the breastfeeding infant should be weighed against the risk of yellow fever infection in the mother and the parents counselled about these risks.
Safety of oral typhoid vaccine in breastfeeding women is not known. Inactivated typhoid vaccine should be used.
Caution should also be exercised when considering BCG vaccine because it is a live vaccine and it is not known whether BCG vaccine is excreted in human milk.
Breastfeeding mothers should not receive live replicating smallpox vaccine in non-emergency situations. It is not known whether the vaccine virus (vaccinia) is excreted in human milk. If smallpox vaccine must be given as post-exposure prophylaxis to a breastfeeding woman, breastfeeding and other close contact with the baby should be avoided until the scab has separated from the vaccination site.
Immunization of breastfed infants
Infants who are breastfed should receive all recommended vaccines according to the routine immunization schedule. There is no evidence that the transfer of antibodies in human milk affects the efficacy of live attenuated vaccines in breastfed infants if these are given at the appropriate age.
Infants of breastfeeding women initiating monoclonal antibody treatment after delivery should be immunized according to routinely recommended schedules. Transfer of monoclonal antibodies through breast milk is limited, and the minimal quantities that are ingested are likely to be broken down in the infant's gastrointestinal tract.
For information on the immunization of infants exposed to immunosuppressive therapy in the womb, whether breastfeeding or not, refer to Immunization of immunocompromised persons in Part 3.
|Vaccine||Use in pregnancy||Use in breastfeeding||Comments|
|Cholera and travellers' diarrhea||Use if indicated if risk of severe disease is high||Use if indicated||
|Haemophilus influenzae b (Hib)||Recommended for those with health conditions predisposing to severe Hib disease||Recommended for with health conditions predisposing to severe Hib disease||
|Hepatitis A||Use if indicated||Use if indicated||
|Hepatitis B||Recommended for seronegative pregnant women at high risk of exposure to hepatitis B||Use if indicated||
|Herpes zoster (recombinant)||Currently not recommended||Use if indicated||
|Human papillomavirus (HPV)||Currently not recommended||Use if indicated||
|Influenza (inactivated)||Recommended in every pregnancy||Recommended if not vaccinated during that pregnancy||
|Japanese encephalitis||Use if indicated (for high-risk situations)||Use if indicated (for high-risk situations)||
Meningococcus quadrivalent conjugate
|Recommended for those with health conditions predisposing to meningococcal disease; travel to a high-risk area; post-exposure prophylaxis; during an outbreak||Recommended for those with health conditions predisposing to meningococcal disease; travel to a high-risk area; post-exposure prophylaxis; during an outbreak||
(given as Tetanus- diphtheria-acellular pertussis- Tdap)
|Recommended in every pregnancy, irrespective of immunization history||Recommended if no dose yet received in adulthood||
|Pneumococcal conjugate 13-valent (Pneu-C-13)||Recommended for those with immunocompromising conditions predisposing to invasive pneumococcal disease||Recommended for those with immunocompromising conditions predisposing to invasive pneumococcal disease||
|Pneumococcal polysaccharide (Pneu-P-23)||Recommended for those with health conditions predisposing to invasive pneumococcal disease||Recommended for those with health conditions predisposing to invasive pneumococcal disease||
|Polio (inactivated)||Use if indicated||Use if indicated||
|Rabies||Use if indicated for post-exposure prophylaxis||Use if indicated||
|Typhoid (inactivated)||Use if indicated||Use if indicated||
|Vaccine||Use in pregnancy||Use in breastfeeding||Comments|
|Bacille Calmette-Guérin||Contraindicated||Generally, should not be used||
|Herpes zoster (live)||Contraindicated||Contraindicated||
|Influenza (live attenuated)||Contraindicated||Use if indicated||
|Measles-mumps-rubella||Generally contraindicated||Recommended if not immune||
|Smallpox (live replicating)||
Consider in high risk situation such as post- exposure
Consider in high risk situations (e.g., post-exposure, outbreak)
|Typhoid (oral)||Contraindicated||Not recommended||
|Varicella||Contraindicated||Recommended if not immune||
|Yellow fever||Generally contraindicated||Generally contraindicated||
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