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Use of Medication during Pregnancy

Essentials

  • Any medication used during pregnancy should always have a clear indication. On the other hand, any medication that is important for the mother should not be left unprescribed.
  • The same principles apply for breastfeeding.
  • Medication should be planned before pregnancy already, and drugs for which there is experience of use during pregnancy should be preferred.
  • Susceptibility to malformations is at its highest from the beginning of the 5th to the end of the 10th week of pregnancy, counting from the last menstruation, i.e. from the 3rd to the 8th foetal week from conception.
  • At later stages of pregnancy, adverse drug effects may manifest in other ways, such as delayed growth, disturbed organ maturation or, for instance, cognitive problems appearing later.
  • The minimum dose that is sufficient for the treatment of the mother's symptoms should be used..
  • The metabolism and excretion of drugs may change due to the physiological changes related to pregnancy, and the dosage may need to be altered.

Folic acid

  • Sufficient intake of folate, a group B vitamin (dietary form), and folic acid (found in vitamin preparations) is important for normal foetal development.
  • Sufficient intake of folate / folic acid reduces the risk of congenital malformations, particularly neural tube defects. In Finnish women of fertile age, dietary intake of folate is low.
  • Daily doses of 0.4 mg folic acid to complement a balanced diet are recommended for all women who are planning to become pregnant, starting at the latest 2 months before stopping contraception.
    • It is well justified to start this early to guarantee sufficient folate levels in the first weeks of pregnancy when the foetal organs are forming.
  • If a neural tube defect has been detected in a previous pregnancy or has occurred in the close family, the recommended dose is increased to 4.0 mg daily.
  • Folic acid supplementation is recommended until the 12th week of pregnancy. After that time, the daily dose exceeding 0.4 mg is not recommended.
  • The pharmacy's pregnancy multivitamin preparation is a good choice. Multivitamin preparations contain also other group B vitamins, of which especially vitamin B12 intake is important for the utilization of folic acid. Furthermore, multivitamin preparations include iodine, and its sufficient intake is also important.
  • Table T1 lists the most common diseases and symptoms and the medications that are best suited for their treatment during pregnancy. The recommendations also apply for medication used during breastfeeding.
  • Table T2 lists medicines and other chemical agents known to be detrimental to pregnancy.

Common symptoms and conditions and medications used in their treatment

Disease or conditionSuitable medication during pregnancyNote
Acne
Preparations containing isotretinoin must be stopped at least one month before reliable contraception is discontinued.
Topical retinoids should not be used during pregnancy, and it is recommended to stop using them already when planning pregnancy.
Allergy
Primarily topical medication (cromoglycate, glucocorticoids)
Of antihistamines (des)loratadine, (levo)cetirizine or fexofenadine.
Preparations containing pseudoephedrine to be avoided. Hyposensitization therapy that has been started before pregnancy may be continued during pregnancy.
Asthma
If a good therapeutic response has previously been obtained with long-acting beta2-agonists or leukotriene receptor antagonists, there is no obstacle to their use during pregnancy
Systemic glucocorticoids, as necessary
Proper management of asthma during pregnancy is important.
In general, the same basic principles in the management of asthma apply for both pregnant and non-pregnant women.
Systemic glucocorticoid therapy:
  • increased risk of cleft lip and palate not confirmed
  • therapy important for the mother may be carried out at any phase of pregnancy.
Bacterial infections Treatments for Symptomatic Urinary Tract Infections during Pregnancy
Penicillins, penicillin derivatives and cephalosporins
Nitrofurantoin (must not be used if G6FD deficiency)
Macrolides (azithromycin, roxithromycin are the first choices)
Metronidazole (primarily topical treatment)
Trimethoprim and sulpha-trimethoprim products should be avoided when planning pregnancy and in early pregnancy.
Tetracyclines should be avoided (risks are highest during 2nd and 3rd trimester).
Fluoroquinolones should be restricted to special situations (clear indications, short-term use).
In sporadic studies, the use of macrolide group antibiotics in early pregnancy has been associated with an increased risk of a congenital heart disease, but the association has not come up in all studies, nor has the causal connection been confirmed.
Crohn's disease, ulcerative colitis
Of TNF-alpha inhibitors infliximab and adalimumab
It is important to have the disease in remission during pregnancy.
Contraindicated: methotrexate and mycophenolic acid
The placental penetration of infliximab and adalimumab increases from the second trimester onwards, and the neonate's medication concentration may be higher than the mother's.
Azathioprine, mercaptopurine (6MP): Examination of the TPMT and, when considered necessary, NUDT15 gene activity before the start of the treatment
Lipid-lowering drugs
Not to be used during pregnancy or breastfeeding
(Cholestyramine treatment possible; intake of fat-soluble vitamins should be ensured)
HMG CoA reductase inhibitors (statins) are discontinued at the latest when the pregnancy is confirmed.
Analgesics and antipyretics
Paracetamol is the first choice and usable during the whole pregnancy, but unnecessary use should be avoided.
Regular, long-term use should always be discussed with a physician.
Non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen is the first choice (see "Note").
Use of paracetamol during pregnancy has been associated with the increased risk of cryptorchidism, ADHD and autism, the association has not been confirmed.
Excessive use of NSAIDs when planning a pregnancy may decrease fertility, and excessive use during early pregnancy may possibly increase the risk of miscarriage.
Repeated use of NSAIDs from the 20th week of pregnancy onwards should be avoided (adverse effect on the maturation of foetal renal function from the 20th week of pregnancy onwards and on the premature closure of the ductus arteriosus from the 28th week of pregnancy onwards).
COX-2 selective NSAIDs are contraindicated during all phases of pregnancy.
Malaria prophylaxis The Safety of Antimalarial Drugs in Pregnancy, Drugs for Malaria in Pregnant Women
Consider drug resistance status of the geographical area.
Doxycycline (not after 14 weeks of pregnancy)
Atovaquone and proguanil on serious grounds during the 2nd and 3rd trimesters
Travelling in malaria-endemic areas should be avoided during pregnancy.
Protective clothing is important
There is little experience with the use of atovaquone during early pregnancy.
Depression
Other possible drugs: bupropion, duloxetine, mirtazapine, venlafaxine, out of tricyclic antidepressants amitriptyline, nortriptyline
Use of antidepressive medication must be clearly indicated - good treatment of mother's depression is essential.
May cause in the newborn drug-induced symptoms which usually resolve rapidly but may also be severe.
Routine discontinuation of a drug important for the mother is not recommended late in pregnancy.
Breastfeeding is usually possible (doxepin contraindicated).
Anthelmintics (pinworm)
No significant systemic absorption
Migraine attack
NSAIDs (see also Analgesics and antipyretics)
Sumatriptanonly for occasional use
There is little experience of repeated use of highly specific drugs.
Ergotamine derivatives are contraindicated.
Migraine prophylaxis
Tricyclic antidepressants (amitriptyline; beta blockers (metoprolol, propranolol)
Heartburn and hyperacidity
Proton pump inhibitors: omeprazole, esomeprazole (lansoprazole, pantoprazole also possible)
Famotidinefor short-time use (less experience)
Misoprostol is contraindicated.
Pregnancy nausea
Non-pharmacological treatments are preferable in the treatment of pregnancy nausea.
Use of metoclopramide should generally be limited to 5 days in order to minimize neurological adverse effects (extrapyramidal symptoms).
In pregnancy nausea the need for medication may be more long-term and assessed at physician's discretion.
There is conflicting evidence on the safety of ondansetron; if possible start only after the 10th week of pregnancy.
Fungal infections Topical Treatment for Vaginal Candidiasis in Pregnancy
Vaginally administered yeast fungus medication (clotrimazole, miconazole)
Antifungal medicines applied to the skin (e.g. clotrimazole, miconazole, terbinafine on a limited area)
For oral fungal infections nystatin
Oral fluconazole (single dose 150 mg) has in sporadic studies been associated with an increased risk of miscarriage / foetal death. The use to be limited on the basis of a physician's opinion and to situations where treatment response is not reached with a vaginally administered preparation.
Repeated use of systemically administered antifungal drugs should be restricted to severe situations only.
Scabies, head lice
Systemic absorption marginal
Insomnia
Preferably non-pharmacological management
Of benzodiazepines oxazepam
Of short-acting hypnotics zopiclone, zolpidem only for short-term use
Repeated use of tranquilizers or hypnotics should be avoided.
Regular use during late pregnancy may cause drug-related symptoms in the newborn.
Use of melatonin is not recommended during pregnancy and breastfeeding.
Hypertension Antihypertensive Drug Therapy for Mild to Moderate Hypertension during Pregnancy, Drugs for Rapid Treatment of Very High Blood Pressure during Pregnancy, Beta-Blockers for Mild to Moderate Hypertension in Pregnancy
Calcium-channel blockers (nifedipine, verapamil)
Drugs affecting the renin-angiotensin system (ACE inhibitors, angiotensin receptor blockers) are contraindicated; the medication should be discontinued when pregnancy is planned, and at the latest when the pregnancy is confirmed.

Medicines and other chemical agents with known or possible adverse foetal effects

DrugAdverse foetal effectNote
Vitamin A derivatives; isotretinoin, acitretin, alitretinoin, tretinoin
Significant risk (25%) of severe malformation (particularly heart, CNS, facial and cranial bones) related to exposure in early pregnancy
Possible risk of developmental delay
Restriction and supervision of the use of medication
Reliable contraception should be taken care of before starting to use the medication.
The following withdrawal periods should be observed before stopping reliable contraception:
acitretin 3 years.
Hyperplasia of the clitoris
Risk from the 10th week of pregnancy onward
Possible increased risk of failure of neural tube closure
-
Antiepileptic drugs
The regular follow-up of drug concentrations during pregnancy and, if necessary, a dose increase are important. Especially lamotrigine but also oxcarbazepine and levetiracetam concentration can decrease considerably as pregnancy advances, and may predispose to seizures. Similarly, in accordance with concentration determination the dose is restored after delivery gradually to the antepartum level. A mother with epilepsy should be followed-up at a maternity outpatient department.
Valproate (valproic acid)
Risk of significant malformation is 3- to 8-fold (10-24%) compared to "background risk" (3%)
  • The absolute risk of neural tube defects 1-2%
  • Cheilopalatoschisis, cardiac and urogenital malformations
  • Developmental delay
Use of valproate during pregnancy contraindicated without compelling reason (epilepsy that requires pharmacotherapy and no other drug options)
Start folic acid supplementation 0.4-4 mg already when planning pregnancy. From week 12 of pregnancy onwards the daily dose should not exceed 0.4 mg.
Structural ultrasound examination at week 19-21 of pregnancy
Carbamazepine
Risk of significant malformation is about 2-fold (6%) compared to "background risk" (3%)
The risk of neural tube defects is 0.5%.
Use must be based on a serious indication (epilepsy).
Start folic acid supplementation 0.4-4 mg already when planning pregnancy. From week 12 of pregnancy onwards the daily dose should not exceed 0.4 mg.
Structural ultrasound examination at week 19-21 of pregnancy
Phenytoin
Risk of significant malformation is about 2-fold (6%) compared to "background risk" (3%).
Hypoplasia of distal phalanges, possibly cheilopalatoschisis, cardiac malformations
Use must be based on a serious indication
Start folic acid supplementation 0.4-4 mg already when planning pregnancy. From week 12 of pregnancy onwards the daily dose should not exceed 0.4 mg.
Structural ultrasound examination at week 19-21 of pregnancy
Topiramate
Increased risk of malformations, especially with regard to cheilopalatoschisis
Concomitant use with other antiepileptic drugs further increases the risk.
Use must be based on a serious indication
Start folic acid supplementation 0.4-4 mg already when planning pregnancy. From week 12 of pregnancy onwards the daily dose should not exceed 0.4 mg.
Structural ultrasound examination at week 19-21 of pregnancy
Miscarriage, foetal death
Detrimental at every stage of pregnancy
Others
Ethanol
Miscarriage, malformations, delayed growth, developmental delay
Detrimental at every stage of pregnancy
Doses used for the treatment of systemic mycosis: aberrant skeletal development, cheilopalatoschisis, cardiac defects
Single dose used to treat vaginal candidiasis (150 mg) associated with an increased risk of miscarriage / foetal death.
Genotoxic potential
Clearly teratogenic in animal tests
Reliable contraceptive precautions must be taken.
Men: a withdrawal period of 3 months is recommended before attempting pregnancy.
Narcotics
Malformations, prematurity, bleeding, infections, withdrawal symptoms in the neonate
Detrimental at every stage of pregnancy
Teratogenic in animal tests
2-year withdrawal period before stopping reliable contraception
Acceleration of elimination by cholestyramine or medicinal charcoal
A thalidomide analogue
Teratogenic in animal tests (primates)
Restrictions and precautions as for thalidomide
Low risk of aberrant cardiac development (risk of Ebstein's anomaly < 0.1%)
May be used with clear indications during pregnancy
After exposure in early pregnancy foetal cardiac ultrasonography at about the 20th week of pregnancy
Drug concentration to be monitored
Methimazole embryopathy: absence of nostrils, oesophageal atresia, congenital local aplasia cutis
Possible risk is low
In early pregnancy, consider carefully the necessity of the medication.
Changing to propylthiouracil (PTU) may be considered case by case if possible from the therapeutic viewpoint. Change back to carbimazole at the beginning of the second trimester.
Optimal treatment of hyperthyroidism is important.
Folate antagonist
Miscarriage, malformations of multiple organs (CNS, cranium and other bones, heart)
Malformation risk associated with low-dose therapy about 2-fold compared to "background risk" (absolute risk 6-7%)
Contraindicated during pregnancy.
Withdrawal periods: after a single dose no clear justification for any specific withdrawal period;
after repeated dosage for the treatment of chronic diseases withdrawal period 3 months before the beginning of pregnancy; folic acid prophylaxis important
Men:
In low-dose treatment risk through the man theoretical, not confirmed.
For doses used for the treatment of cancer: see Cytotoxic drugs
Folic acid prophylaxis important also for men
Misoprostol (for gastric ulcer, also used for medical abortion)
Miscarriage
Aberrant limb development, ankylosis, damage to cranial nerve nuclei (Möbius syndrome)
There is an NSAID preparation available that contains misoprostol to prevent gastric symptoms
Initiated medical abortion should be completed.
Risk of significant malformation is about 20-25%.
Risk of miscarriage is 40%.
Malformations in the ear area, eyes and heart, cheilopalatoschisis
Reliable contraceptive precautions should be taken during the treatment and for 6 weeks after withdrawing the medication.
Risk through the man is theoretical, not confirmed.
In single studies an association with cardiac defects has been found, but the connection has not been confirmed.
Withdrawal symptoms of the newborn infant
The time between birth and the occurrence of withdrawal symptoms may be several days/weeks.
Pharmaceutical agents affecting the renin-angiotensin system (ACE inhibitors, ATR blockers, renin inhibitors)
Risk of foetal kidney damage
The risk is related to use in 2nd and 3rd trimesters.
Medication must be changed when planning pregnancy or no later than when pregnancy is confirmed.
Teratogenic in animal tests
A withdrawal period of at least 4 months before stopping reliable contraception
Manufacturer recommends for male patients a withdrawal period of at least 7 months. The risk through a man is theoretical, not confirmed.
Malformations, miscarriage, delayed growth
Women:
After stopping the medication, a withdrawal period is needed before pregnancy begins.
The length of the withdrawal period depends on the underlying disease and on the pharmacokinetics of the drug.
Cytotoxic treatment possible from the 16th week of pregnancy onward if clearly indicated.
Men:
For cancer treatments, a withdrawal period of at least 1.5 years is recommended; in case of a low-dose treatment, as far as possible, a 3- to 6-month withdrawal period
The limited experience has not, however, shown a significant risk in pregnancies that have started during the father's treament or within the withdrawal period.
No effect on the total incidence of malformations
Cardiac malformations somewhat more common in pregnancies in fluoxetine (ventricular septal defects) and paroxetine users (right ventricular outflow tract obstruction defects)
Adaptation problems in the neonate (breathing difficulty, increased tonus)
Pulmonary hypertension more common in neonates born to mothers who have taken SSRIs (3:1 000) than in unexposed neonates (1-2:1 000)
The absolute increase in the risk of specific cardiac malformations is small (< 1%) and no causal connection has been confirmed.
Medication should not be routinely stopped in late pregnancy if it is important for the mother.
The neonate should be monitored at least up to the age of 2 days.
There is contradictory information on the possible long-term effects on children's neurocognitive and neuropsychiatric development.
Risk of severe malformation > 50%
Risk of miscarriage 40-50%
Multiple organ malformations: partial or complete symmetric lack of limbs, eye and ear anomalies, renal and urinary tract anomalies.
New indications (leprosy, autoimmune diseases, metastatic cancers, secondary symptoms associated with AIDS)
Close supervision of the use of the drug is necessary.
Reliable contraception is necessary.
Men: thalidomide is excreted in sperm; the manufacturer recommends the use of condoms.
Enamel damage of deciduous teeth, accumulation in the skeleton
Risk of enamel damage of deciduous teeth from the 16th week of pregnancy onward
Folate antagonist
Use should be avoided when planning pregnancy and during the first trimester.
Possible adverse effect on fertility during course of medication
Adverse effect on the renal function of the foetus from week 20 of the pregnancy onwards and on the circulatory system (premature closure of the ductus arteriosus) of the foetus from the week 28 of the pregnancy onwards
Rupture of the ovarian follicle and implantation of the embryo in the uterus are events depending on prostaglandin synthesis.
Repeated and regular use should be avoided from the 20th week of pregnancy onward.
COX-2 inhibitors should not be used during pregnancy.
Acetylsalicylic acid (ASA), analgesic doses: in addition to the above, risk of peripartal bleeding (mother and child)
There are no special risks associated with low dose ASA.
Aberrant bone and cartilage development, foetal bleedings
Medication must be changed by no later than the beginning of the 6th week of pregnancy (4th foetal week).
  • For more information, consult local teratological information services regarding the safe use of medication during pregnancy and breastfeeding.

References

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Evidence Summaries