Editors

HeliMalm

LeeaKeski-Nisula

Chronic Diseases and Pregnancy

Essentials

Chronic diseases, when untreated, impair fertility; adequate management effectively restores fertility.
Already before conception, the treating physician should confirm the control of the disease, and an obstetrician the health of the reproductive system. In that process, also individual risks of pregnancy and changes of success are assessed.
The pregnancy must be monitored closely throughout gestation according to the principles of monitoring high-risk pregnancy and in good collaboration between the prenatal clinic and maternity hospital Antenatal Clinics and Specialist Care: Consultations, Referrals, Treatment Guidelines.
The increasing average age of parturients increases the prevalence of chronic diseases among pregnant women.
See also Use of Medication during Pregnancy.

Heart and vascular diseases

Cardiac output begins to rise during the first trimester of pregnancy and increases by 30-50%. This means an increased circulatory burden for the heart. Both heart rate and stroke volume increase, and peripheral vascular resistance decreases.
Towards the end of pregnancy, the ability of the cardiovascular system to react to physical strain becomes more limited.
The axis of the heart shifts horizontally because of the rise of the diaphragm, increasing the tendency of ectopic beats.
In the supine position, the uterus causes obstruction of the inferior vena cava and diminishes venous return. Therefore, a pregnant woman must be placed in a left lateral recumbent position for every examination or treatment that lasts for long.

Hypertension Bed Rest for Hypertension during Pregnancy, Calcium Supplementation during Pregnancy for Preventing Hypertensive Disorders, Planned Early Delivery Versus Expectant Management for Hypertensive Disorders from 34 Weeks Gestation to Term, Drugs for Rapid Treatment of Very High Blood Pressure during Pregnancy, Adverse Effects of Hypertension Treatment during Pregnancy, Beta-Blockers for Mild to Moderate Hypertension in Pregnancy, Antihypertensive Drug Therapy for Mild to Moderate Hypertension during Pregnancy

See Elevated Blood Pressure in Pregnancy (Gestational Hypertension, Pre-Eclampsia) and Antenatal Clinics and Specialist Care: Consultations, Referrals, Treatment Guidelines.
The limit for normal arterial blood pressure in a fertile-aged woman is 130/80 mmHg. The action limit during pregnancy is 140/90 mmHg.
Hypertension during pregnancy is associated with pre-eclampsia in 70% of patients, and chronic hypertension in 30% of patients.
The incidence of chronic hypertension is about 2-5% http://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.113.003904 http://www.cdc.gov/mmwr/volumes/71/wr/mm7117a1.htm. The risk of hypertension increases after the age of 30 years.
Foetal risks are connected with chronic placental insufficiency, e.g. small-for-gestational-age newborn and foetal hypoxia. The maternal risks in severe hypertension are circulatory brain disturbances, heart failure and complications resulting from the often associated superimposed pre-eclampsia.
If increased blood pressure is associated with evident proteinuria, hospital care is considered necessary. A slight or moderate rise in blood pressure without albuminuria is a small risk for the mother and foetus, but requires close monitoring of the pregnancy in the maternity outpatient clinic and, if the situation gets worse, on a hospital ward.
The patient's existing antihypertensive medication can often be continued unchanged also during pregnancy. The drug of choice is labetolol (combined alpha-beta-receptor blocker). Its haemodynamic effects on placental blood circulation are more favourable than those of mere beta-receptor blocking agents Beta-Blockers for Mild to Moderate Hypertension in Pregnancy. Use of beta-receptor blockers during pregnancy has been connected to foetal growth retardation. Of beta-blockers, use of metoprolol or bisoprolol, for example, is possible, but the use of atenolol should be avoided. Of calcium channel blockers, the most experience exists on nifedipine Drugs for Rapid Treatment of Very High Blood Pressure during Pregnancy.
Pharmacotherapy is initiated when the diastolic pressure reaches or exceeds 100 mmHg. Usually pharmacotherapy is started within specialized care.
The treatment decreases the risks of the mother in particular. There is no undisputed evidence on the benefits of drug therapy of mildly or moderately elevated blood pressure either to the mother or the child Antihypertensive Drug Therapy for Mild to Moderate Hypertension during Pregnancy.
Drugs affecting the renin-angiotensin system, ACE inhibitors and ARBs is contraindicated, and the medication must be changed to some other medication already when planning pregnancy or, the latest, when pregnancy is confirmed. The use of these drugs during the second or third trimester may cause permanent renal injury in the foetus which may manifest as anuria in the newborn.
Diuretic drugs are not recommended because those with chronic hypertension or pre-eclampsia often have decreased blood volume.

Heart diseases

The increased load of pregnancy is most serious in connection with a pressure load, for example in mitral stenosis and cyanotic heart disease. Mothers with mitral stenosis have an increased risk for atrial flimmer or pulmonary oedema.
The probability of maternal death due to the aortic root enlargement associated with Marfan's syndrome is up to 50%. The risk increases when the aortic root enlargement is over 4.5 cm in size. Pulmonary hypertension entails more or less similar risks. Eisenmenger's syndrome and severe cardiomyopathies also belong to the same risk group.
If the mother is in the class I or II on the NYHA scale measuring physical capacity Chronic Heart Failure, or in the same class on the CSS scale measuring the intensity of angina pain, pregnancy does not pose any significant risk to her. However, maternal mortality in NYHA/CSS class III-IV heart disease is about 10%, especially if a good control of the disease has not been reached prior to the pregnancy. The risk level is about the same in pregnancy after myocardial infarction.
Medical treatment is chosen according to the cardiac disease, often in co-operation with specialized care in internal medicine.

Thrombotic complications

The risk of recurrence of earlier deep vein thrombosis or pulmonary embolism increases up to 40-fold during pregnancy.
As basic laboratory tests, APTT to detect possible lupus anticoagulant syndrome, as well as AT_III, protein-C and protein-S
When earlier deep vein thrombosis or pulmonary embolism was associated with a lack of AT_III, protein-C or protein-S, thrombosis prophylaxis with low molecular weight heparin has to be started already on gestational week 6, and continued throughout pregnancy until 3 months since delivery. In the case of AT_III deficiency, AT_III concentrate is possibly administered during labour.
If an earlier thrombosis has occurred without a lack of AT_III, protein-C or protein-S, the prophylactic treatment can be started on gestational weeks 20-24 and ended 6-12 weeks after delivery.
The drug of choice is low molecular weight heparin (LMWH) administered once daily. A double dose is used if the mother weighs more than 75 kg and also after the 24th week of gestation. The treatment has to be stopped for the time of labour, 12 hours before induction of labour.
Warfarin is not used due to the associated teratogenic risk, except in patients with a cardiac prosthetic valve. The mother's warfarin therapy should be replaced by a low molecular weight heparin as soon as menstruation has stopped and, the latest, by the beginning of week 6 of pregnancy. LMWHs do not cross the placenta.
See also Evaluation of Thrombophilia.

Metabolic disorders

Diabetes Different Intensities of Glycaemic Control for Pregnant Women with Pre-Existing Diabetes, Continuous Subcutaneous Insulin Infusion for Pregnant Women with Diabetes, Treatments for Gestational Diabetes, Gestational Diabetes Mellitus and Pregnancy Outcomes, Maternal Obesity and Infant Outcomes

It is important to distinguish between pregnancy in a mother with diabetes and a pregnancy associated with gestational diabetes Gestational Diabetes Mellitus (Gdm).
Diabetic control is often concentrated at larger hospitals in order to maintain sufficient experience and routine required for the monitoring. Find out about local practices.
Achieving good control of diabetes is necessary already before conception, because only then the rate of foetal malformations can be effectively reduced. An obstetrician, a diabetes nurse, a therapeutic dietitian, pediatrician and an internist take part in the care throughout pregnancy.
Careful monitoring at the prenatal clinic takes place at 1-4 week intervals and at an obstetric ward only if needed.
The maternal risks associated with pregnancy include impairment of renal problems, disturbances in glucose balance, aggravation of diabetic retinopathy, increased risk of pre-eclampsia and polyhydramnios. The foetal risks include congenital malformations, spontaneous abortion and premature labour, intrauterine death, macrosomia, birth injuries due to, for example, shoulder dystocia, low birth weight if there are maternal vascular changes, as well as neonatal hypoglycaemia, hypocalcaemia, hyperbilirubinaemia and lung immaturity Gestational Diabetes Mellitus and Pregnancy Outcomes, Maternal Obesity and Infant Outcomes, Treatments for Gestational Diabetes.
Insulin therapy is given as a multi-injection or insulin pump treatment with normoglycaemia as the goal. If the frequency of control visits is sufficiently tight (at 1-4-week intervals) the treatment can be carried out on outpatient basis throughout pregnancy. Short hospitalization periods are planned individually as needed. Continuous surveillance is indicated if there are complications.
Oral antidiabetic drugs (particularly metformin Metformin for Gestational Diabetes) are sometimes used together with insulin therapy or as the only medication, especially in mothers with type 2 diabetes. The experiences are primarily favourable, but in the most recent studies, metformin use has been associated with increased risk of foetal growth retardation.
Labour induction is often needed before the term and sometimes also prematurely. If there are no problems during pregnancy, labour can also take place close to the term and vaginally, if possible. Indications for Caesarean section include common obstetric indications, such as pelvic disproportion, imminent asphyxia, worsening pre-eclampsia, and abnormal foetal presentation. Maternal proliferative retinopathy and renal complications may also lead to Caesarean section.

Hypothyroidism Thyroxine Replacement for Subfertile Women with Subclinical Hypothyroidism

Untreated hypothyroidism increases the risk of infertility and miscarriage.
Thyroxine dosage needs to be increased by 25-50 µg per day during pregnancy. The dosage is increased by 25 µg per day as soon as the pregnancy begins; it is further adjusted according to the TSH concentration so that this is maintained below 2-3 mU/l.
Therapeutic balance is determined before conception, during the first prenatal visit and in gestational weeks 20-24 and 28-32. Slight hyperthyroidism is not dangerous for the foetus or the mother. After an operation for thyroid gland cancer, TSH concentrations must remain undetectable.
Certain drugs, especially iron, disturb the absorption of thyroxine; these medications should be taken at different times.
After delivery, thyroid substitution therapy can be reduced into the pregestational level.

Hyperthyroidism

Untreated hyperthyroidism may cause a spontaneous abortion or premature labour.
The clinical symptoms and signs are often mixed up with the normal changes caused by pregnancy (increased pulse rate and tachycardia, mild thyroid enlargement, slight exophthalmus).
Biochemical monitoring as in hypothyroidism: TSH and free thyroid hormones, plus the level of serum thyroid-stimulating antibodies. Those antibodies can cross the placenta, and increase the risk of hypothyroidism of the newborn.
Pharmacological treatment consists of a thyrostatic drug (carbimazole). The dosage is adjusted so that the laboratory tests may show slight thyroid overactivity. The risk of foetal hypothyroidism is only 1% in such cases.
The use of carbimazole during the first trimester has been associated with slightly increased malformation risk. It is important to assess whether the use of the medication is necessary at this phase of pregnancy. Based on such consideration, the drug may be replaced by propylthiouracil for the period of the first trimester (PTU, may require special permit).
Sometimes surgery is used. Radioiodine therapy is not possible.

Obesity

A maternal pregestational body weight of more than 90 kg is associated with a 4-fold risk of gestational hypertension and a 1.5-fold risk of gestational diabetes compared with normal-weight women.
Obesity also increases the risk of thromboembolic complications, especially if bed rest is needed.
Foetal risk for macrosomia increases Maternal Obesity and Infant Outcomes, which in turn is associated with prolonged labour, increased need for Caesarean section Maternal Obesity as a Risk Factor for Complications in Pregnancy, as well as shoulder dystocia and risk of injury.
Considerable slimming during pregnancy is not recommended, but the targeted weight gain is limited to not more than 4-9 kg. At the prenatal clinic, the mother should be encouraged to weight management and physical exercise.

Neurological diseases

Epilepsy

Good preconceptional control of the antiepileptic medication is important.
The general principle in antiepileptic medication is monotherapy, as far as possible, using the drug that best keeps the seizures away.
A grand mal seizure causes foetal hypoxia, as the maternal oxygenation is disturbed, and may be dangerous for the foetus.
Epilepsy in itself is probably associated with a slightly increased risk of malformations. Many antiepileptic drugs increase this risk. The risk increases further with dose and when two or more antiepileptic drugs are used simultaneously.
The use of valproic acid during pregnancy leads to manyfold increase in the risk of foetal malformations. The risk increases with dose and is over 20% when the daily dose exceeds 1 450 mg. Mother's use of valproic acid during pregnancy also increases considerably the child's risk of autism and developmental delay. A woman in fertile age using valproic acid should follow a pregnancy prevention programme associated with valproic acid use. Use of valproic acid during pregnancy should be limited to treatment of epilepsy in cases where no other effective medication can be found.
Of the antiepileptic drugs that have been in use for a long time, also carbamazepine and phenytoin increase the risk of malformations.
Of the newer antiepileptic drugs, use of topiramate has been associated with an increased risk of malformations (especially risk of cleft lip and palate) and its use during pregnancy should be limited to the treatment of epilepsy and only to situations where medication is essential and no alternative drugs can be used.
Experiences concerning lamotrigine and levetiracetam are not suggestive of any particular foetal risk.
During pregnancy, regular monitoring of drug concentrations and, as necessary, increase of dosage is important. The concentration of especially lamotrigine, but also of oxcarbazepine and levetiracetam, may significantly decrease with the progress of pregnancy, and this may predispose to seizures. Respectively, after delivery the dosage is gradually returned, as guided by drug concentration measurements, to the level where it was before the pregnancy. A mother with epilepsy should be monitored by a maternity outpatient clinic.

Migraine

The incidence of a migraine attack is highest during the first trimester and during the last month of pregnancy, lowest during the second trimester.
Close to the delivery pre-eclampsia-like symptoms (vision disturbances, high blood pressure, headache and upper abdominal pain) cause differential diagnostic problems.
NSAIDs can be used for migraine attacks during the first trimester of pregnancy (primary alternatives are ibuprofen or diclofenac), as well as prochlorperazine, and in addition metoclopramide for nausea. Targeted drugs (5-HT₁ agonists, primarily sumatriptan) should be used only occasionally. Ergotamine derivatives are prohibited.
After week 28 of gestation the foetal ductus arteriosus starts to react more readily to NSAIDs. Therefore drugs from this group are only used after very careful consideration. During prolonged treatment the ductus may close intrauterinally and cause a problem of the circulatory regulation in the newborn.
If attacks are recurrent, beta blocker medication (metoprolol) or tricyclic antidepressants (amitriptyline) may be used as prophylactic medication.
Of targeted drugs, sumatriptan,rizatriptan, zolmitriptan or eletriptan may be used in the treatment of acute migraine attacks during lactation.

Disturbances of cerebral circulation

Risk of thrombotic stroke is increased about tenfold during pregnancy. The rupture risk of cerebral aneurysms and arteriovenous anomalies is increased as well.
Principles of treatment are the same as with non-pregnant patients. If it has been possible to treat an aneurysm by operation, a subsequent pregnancy does not cause any additional risk. Non-operated conditions, by contrast, are relative contraindications for pregnancy and delivery. The delivery should be managed so that the mother has no need to strain or push.

Renal diseases

Glomerular filtration increases by 30-50% during gestation. This leads to a decrease in the plasma creatinine concentration; the level < 80 µmol/l is regarded as normal. A degree of hydronephrosis and hydroureter also occurs, especially on the right side.
The prognosis of the pregnancy is highly worsened, if the mother has hypertension or increased plasma creatinine concentration and proteinuria already before the pregnancy. The limit of diastolic blood pressure is considered to be at 90 mmHg and of plasma creatinine concentration at 125-175 µmol/l. If creatinine levels exceed this, pregnancy is not recommended. Already a moderate renal failure (creatinine clearance 30-50 ml/min/1.73 m² ) significantly worsens the prognosis of pregnancy.
The pregnancy must be observed very closely and this should take place in a hospital specializing in such issues.
Even mild renal insufficiency is associated with hypertension and pre-eclampsia in over 50% of patients, leading to placental insufficiency, foetal growth retardation and premature labour.
Lupus nephropathy, membranous glomerulonephritis, scleroderma and polyarteritis nodosa affect the prognosis of pregnancy exceptionally much, even if the renal function test results are not yet markedly abnormal. Therefore, these conditions are considered as relative contraindications for pregnancy.
Asymptomatic bacteriuria Urinary Tract Infections should be treated by e.g. nitrofurantoin, cephalosporin or mecillinam already during the first trimester of pregnancy Antibiotics Vs. No Treatment for Asymptomatic Bacteriuria in Pregnancy. If left untreated, the risk of pyelonephritis is about 30-40%.
A patient with feverish pyelonephritis Urinary Tract Infections should be treated in a hospital. The antimicrobial therapy is started parenterally, e.g. with a cephalosporin, and continued according to sensitivity testing. Peroral antimicrobial therapy is continued for 10 days. If the infection recurs during pregnancy, a prophylactic medication for the duration of pregnancy is indicated. The most common medications are nitrofurantoin 50-75 mg, cephalexin 250 mg or pivmecillanam 200 mg in the evening.
Pregnancy is recommended at the earliest 1-2 years after renal transplantation, provided that there are no problems with renal function or immunosupressive therapy. Such pregnancies succeed well under close follow-up, when these prerequisites are fulfilled.

Rheumatic disorders

The most problematic rheumatic disorders during pregnancy are rheumatoid arthritis and systemic lupus erythematosus, SLE.
75% of women with rheumatoid arthritis feel better during pregnancy than at other times. The symptoms become less already at the end of the first trimester. Following delivery, the symptoms recur in 90% of cases and are usually more severe.
Drugs contraindicated during pregnancy include leflunomide, methotrexate, mycofenolate and cyclophosphamide. Use of these drugs must be discontinued already when planning pregnancy. The length of the safety period depends on the drug and varies between 6 weeks (mycofenolate) and 2 years (leflunomide).
D-penicillamine and acetylsalicylic acid at a dosage used to treat pain should not be used for rheumatic disorders during pregnancy.
Traditional drugs suitable for treatment of rheumatic disorders during pregnancy include hydroxychloroquine, sulphasalazine, glucocorticoids, azathioprine and cyclosporin. Of the biological drugs used for treating rheumatoid disorders, there is most experience on TNF alpha inhibitors. Use of adalimumab and infliximab should be discontinued, so far as possible, in the middle of pregnancy and of etanercept at the week 32 of pregnancy. In the most severe cases, drug therapy is continued throughout the whole pregnancy. Certilizumab may be continued throughout the whole pregnancy. JAK inhibitors should not be used during pregnancy because there is little experience on them.
Use of NSAIDs should be kept primarily short-term. Regular use before the time of ovulation may prevent the release of the egg from the ovary and use of NSAIDs close to the time of fertilization may possibly increase the risk of miscarriage. Regular and recurrent use of NSAIDs from the middle of pregnancy onwards may affect negatively the foetal kidney function and, during the third trimester, circulation and is consequently contraindicated. Use of COX-2 selective anti-inflammatory drugs is contraindicated throughout the whole pregnancy.
See also table T1.
SLE is always a threat to pregnancy. The clinical picture exacerbates in about every third patient and usually does not alleviate in any patient. The prognosis is especially poor in cases with circulatory antibodies to phospholipids (e.g. cardiolipin or lupus anticoagulant antibodies). These are associated with an increased risk of thrombotic disorders: arterial thrombosis, early fibrosis of the placenta, placental infarction, spontaneous abortion, foetal growth disturbances, atrioventricular block and intrauterine foetal death. When SLE is in an active phase, results of any treatment are poor.
- Recommended treatment includes aspirin at a dose of 100 mg daily and LMWH at a prophylactic or increased prophylactic dose starting immediately at the beginning of pregnancy. SLE is so rare that the efficacy of therapies has been difficult to prove.

Recommendation regarding use of antirheumatic drugs during pregnancy and breastfeeding. Source: Reumataudit ja raskaus [Rheumatic diseases and pregnancy]. The Finnish Rheumatism Association http://www.reumaliitto.fi/fi/reuma-aapinen/hyva-tietaa/reumataudit-ja-raskaus (updated by Heli Malm April 2021).

Drug	Recommendation on use during pregnancy	Recommendation on use during breastfeeding
Acetylsalicylic acid(at a dosage used to treat pain)	Should not be used	Should not be used
Indomethasin	Should not be used	Should not be used
Other NSAIDs	May be used, short-acting preparations preferred^* (first choice is ibuprofen)	May be used, short-acting preparations preferred^* (first choice is ibuprofen)
Hydroxychloroquine	May be used	May be used
Azathioprine	May be used ^*******	May be used ^*******
Methotrexate	Must be discontinued 3 months before pregnancy	Should not be used
Cyclophosphamide	Must be discontinued 3 months before pregnancy	Prohibited
Sulphasalazine^**	May be used	May be used
Cyclosporine	May be used	May be used^***
Podophyllotoxin	Must be discontinued 3 months before pregnancy	Prohibited
Mycophenolate	Must be discontinued 3 months before pregnancy	Prohibited
Leflunomide	Must be discontinued before pregnancy^****	Prohibited
TNF alpha inhibitors (infliximab, etanercept, adalimumab, certolizumab, golimumab)	If required, use may be continued until the middle of pregnancy or, in severe situations, throughout the whole pregnancy^*****	May be used Limited experience on golimumab
Anakinra	Discontinue when pregnancy is detected	Not recommended, little experience
Abatacept	Recommended to be discontinued 3 months before pregnancy	Not recommended, little experience
Rituximab	Recommended to be discontinued 12 months before pregnancy	Not recommended, little experience
Tocilizumab	Recommended to be discontinued 3 months before pregnancy	Not recommended, little experience
Glucocorticoids	May be used	May be used^******

^* Regular and recurrent use of NSAIDs should be avoided from week 20 of pregnancy onwards. COX-2 selective anti-inflammatory drugs are contraindicated during pregnancy. Use of celecoxib as a limited course of treatment is possible during breastfeeding.

^** Folic acid supplementation 0.8 mg is recommended starting when pregnancy is planned and continuing until the end of first trimester.

^*** Great variation in excretion into breast milk; monitoring of the child is necessary and the drug concentration in the child should be determined, as required.

^**** Recommended to be discontinued 2 years before pregnancy. Blood concentration of the drug can be reduced by treatment with cholestyramine (8 g three times daily for 11 days) or activated charcoal (50 g four times daily for 11 days). Pregnancy is possible 2 months after the aforementioned medications.

^***** Recommendations regarding discontinuation are drug-specific and case-specific. The ability of certolizumab to cross the placenta is poor late in pregnancy and its use may be continued, if required, throughout the pregnancy.

^****** When using the dose 40 mg/day or more, a 4-hour break between the administration of the drug and the next breastfeeding session is recommended.

^******* When starting the medication, determining the activity of the thiopurine methyltransferase (TPMT) gene and, as necessary, also the NUDT15 gene is recommended.

Psychiatric problems

Especially traditional neuroleptics (phenothiazine derivatives) may cause ovulation disorders by increasing prolactin production. Impairment of fertility may also be caused by sexual problems.
Pregnancy may be a time of considerable psychological stress. Earlier psychiatric disorders present a clear risk factor already during pregnancy, but also during puerperium, with regard to postpartum depression and puerperal psychosis. The risk is also increased when the partner has a history of psychopathology.
Pharmacotherapy that is important for the mother is continued during pregnancy and after labour. Of the new antipsychotic drugs, first choices include aripiprazole or quetiapine. Scientific knowledge on the possible foetal harms of olanzapine is contradictory. Since new antipsychotic drugs may affect glucose balance, blood glucose monitoring is important already before the pregnancy. Of the traditional antipsychotic drugs, the use of phenothiazine derivatives and thioxanthine derivatives, as well as haloperidol is possible.
Use of lithium is usually continued if treatment response has been good. Lithium therapy requires careful monitoring of the drug concentration. After exposure during the first trimester of pregnancy, foetal echocardiography is recommended at about week 20 of pregnancy.
Usable antidepressant drugs include SSRIs (primarily sertraline, citalopram and escitalopram), as well as venlaflaxine and mirtazapine, and also, if necessary, bupropion or duloxetine. Of tricyclic antidepressants, amitriptyline and nortriptyline are possible to use.
Use of benzodiazepines does not increase the risk of malformations. The primary choice during pregnancy is oxazepam. Regular use, however, should be avoided.
Of mood stabilizers, lamotrigine seems to be safe. The metabolism of lamotrigine accelerates during pregnancy, and hence it is important to monitor the clinical response and, as necessary, drug concentration. Use of valproic acid as mood stabilizer is contraindicated during pregnancy and the medication must be changed to something else already when planning pregnancy.
All drugs that affect the central nervous system may cause symptoms to the newborn. Use of SSRIs during the second half of the pregnancy entails an about 2-fold risk of the infant requiring treatment in a neonatal monitoring unit. Symptoms usually resolve rapidly.
Tranquillizers taken in large doses close to the birth depress the newborn and may cause somnolence and muscular hypotonia, as well as respiratory difficulties.
Maintaining the mother's mental well-being through pregnancy and after delivery is crucially important also with regard to the child's safety and development. Medication important for the mother must not be discontinued. Discontinuing medication may predispose the mother to worsening of the symptoms of the disease after delivery. The situation must always be individually assessed.
- In discontinuing, for example, SSRI drugs after the middle of pregnancy, one cannot necessarily even prevent drug symptoms in the newborn, since the drug-induced increase in the foetal serotonergic tonus may last for a long time even after the medication is discontinued.

Asthma

Asthma is worsened in about every third woman during pregnancy, but improves in the same proportion of cases. Asthma usually causes no major problems.
Good treatment of asthma is important during pregnancy. Poor control of asthma increases, in particular, the risk of premature labour.
The following drugs are safe for the foetus: inhaled glucocorticoids, beta₂-agonists, theophylline derivatives, as well as many antihistamines (most experience exists on loradatine, cetirizine, fexofenadine). Leukotriene receptor antagonist therapy is possible, if, from the viewpoint of asthma control, it has been important already before the pregancy.
Status asthmaticus during labour is a real problem, as poor maternal oxygenation can result in foetal hypoxia. The treatment is similar to that in non-pregnant patients. The risk of Caesarean section due to foetal emergency is increased.

Cancers

The prevalence of carcinoma during pregnancy is about 1:1 000-2 000 deliveries.
The most common type of cancer during pregnancy is breast cancer. More rare cancer types include leukaemias, uterine cervical, ovarian and intestinal cancer as well as melanomas.
Cancer is usually not spread to the foetus. Malignant melanoma is an exception.
Cytostatic drugs are teratogenic and exposure during the first trimester increases the risk of malformations. Starting cytostatic therapy during the second trimester (week 14-16 of pregnancy onwards) may be considered case by case. Radiotherapy treatment from week 10 of pregnancy onwards increases, depending on the dose, the risk of microcephaly and severe mental retardation.
It is important to treat every case individually, carefully negotiating with the patient.
The prognostic trend is mainly seen within 2 years after the treatment: if the prognosis is good no signs of recurrence of the cancer are seen; if it is poor, symptoms and signs of cancer recur. For example, the earlier recommendation was to avoid pregnancy after breast cancer treatment for 5 years, but nowadays it is for 2 years. There is no clear evidence that pregnancy itself would negatively affect the prognosis of breast cancer. Follow-up, however, becomes more difficult due to changes in pregnancy.

Find out about national or regional teratological information services and consult them, as necessary.

References

Iezzoni LI, Yu J, Wint AJ et al. Prevalence of current pregnancy among US women with and without chronic physical disabilities. Med Care 2013;51(6):555-62. [PubMed]
Weihua L, Qing G, Xiaoyan Y et al. Antihypertensive drug therapy for mild-to-moderate hypertension during pregnancy: summaries of nursing care-related systematic reviews from the Cochrane Library. J Cardiovasc Nurs 2015;30(1):13-4. [PubMed].
Zhu B, Zhang L, Fan YY et al. Metformin versus insulin in gestational diabetes mellitus: a meta-analysis of randomized clinical trials. Ir J Med Sci 2016;185(2):371-81. [PubMed]
Marchenko A, Etwel F, Olutunfese O et al. Pregnancy outcome following prenatal exposure to triptan medications: a meta-analysis. Headache 2015;55(4):490-501. [PubMed]
Diav-Citrin O, Shechtman S, Tahover E et al. Pregnancy outcome following in utero exposure to lithium: a prospective, comparative, observational study. Am J Psychiatry 2014;171(7):785-94. [PubMed]
Tomson T, Battino D, Bonizzoni E ym. Dose-dependent teratogenicity of valproate in mono- and polytherapy: an observational study. Neurology 2015;85(10):866-72. [PubMed]
Bromley R. The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs. Reprod Toxicol 2016;64():203-10. [PubMed]
European Medicines Agency http://www.ema.europa.eu
Østensen M. The use of biologics in pregnant patients with rheumatic disease. Expert Rev Clin Pharmacol 2017;10(6):661-669. [PubMed]
Förger F, Villiger PM. Treatment of rheumatoid arthritis during pregnancy: present and future. Expert Rev Clin Immunol 2016;12(9):937-44. [PubMed].
Huybrechts KF, Hernández-Díaz S, Patorno E ym. Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations. JAMA Psychiatry 2016;73(9):938-46. [PubMed]
Damkier P, Videbech P. The Safety of Second-Generation Antipsychotics During Pregnancy: A Clinically Focused Review. CNS Drugs 2018;32(4):351-366. [PubMed]
Malm H, Artama M, Gissler M ym. Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstet Gynecol 2011;118(1):111-20. [PubMed]
Furu K, Kieler H, Haglund B ym. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design. BMJ 2015;350():h1798. [PubMed]
Feig DS, Donovan LE, Zinman B ym. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2020;8(10):834-844. [PubMed]
Betcher HK, Wisner KL. Psychotropic Treatment During Pregnancy: Research Synthesis and Clinical Care Principles. J Womens Health (Larchmt) 2020;29(3):310-318. [PubMed]
Clark CT. Psychotropic drug use in perinatal women with bipolar disorder. Semin Perinatol 2020;44(3):151230. [PubMed]
Ellfolk M, Leinonen MK, Gissler M ym. Second-generation antipsychotic use during pregnancy and risk of congenital malformations. Eur J Clin Pharmacol 2021;77(11):1737-1745. [PubMed]
Ellfolk M, Leinonen MK, Gissler M ym. Second-generation antipsychotics and pregnancy complications. Eur J Clin Pharmacol 2020;76(1):107-115. [PubMed]
Flint J, Panchal S, Hurrell A ym. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2016;55(9):1693-7. [PubMed]
Tomson T, Battino D, Perucca E. Teratogenicity of antiepileptic drugs. Curr Opin Neurol 2019;32(2):246-252. [PubMed]
Malm H, Sourander A, Gissler M ym. Pregnancy Complications Following Prenatal Exposure to SSRIs or Maternal Psychiatric Disorders: Results From Population-Based National Register Data. Am J Psychiatry 2015;172(12):1224-32. [PubMed]
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Drug Safety Communication - Avoid Use of NSAIDs in Pregnancy at 20 Weeks or Later (19.10.2020) http://www.fda.gov/

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