Table-2-for-Medication-use-during-pregnancy-and-lactation (ELearningPage)

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 <HtmlField Name="References"><![CDATA[<ol>
 <li>Stockholm County Council. Janusmed Drugs and Birth Defects (Janusmed fosterp&aring;verkan). Available at:&nbsp;<a href="www.janusinfo.se/fosterpaverkan">www.janusinfo.se/fosterpaverkan</a>. Accessed January 2018.</li>
 <li>Briggs GG, Freeman RK. Drugs in Pregnancy and Lactation. A reference guide to fetal and neonatal risk. 11th ed: Wolters Kluwer Health; 2017.</li>
 <li>Schaefer C, Peters P, Miller RK. Drugs During Pregnancy and Lactation. Treatment Options and Risk Assessment: Academic Press, Elsevier; 2015.</li>
 <li>The United Kingdom Teratology Information Service (UKTIS). Exposure in pregnancy. Available at:&nbsp;<a href="www.toxbase.org/Exposure-in-pregnancy">www.toxbase.org/Exposure-in-pregnancy</a>. Accessed January 2018.</li>
 <li>Thomson Reuters. Micromedex: Reprorisk. Available at:&nbsp;<a href="www.micromedexsolutions.com">www.micromedexsolutions.com</a>. Accessed January 2018.</li>
 <li>Hassouna A, Allam H. Limited dose warfarin throughout pregnancy in patients with mechanical heart valve prosthesis: a meta-analysis. Interact Cardiovasc Thorac Surg. 2014;18(6):797-806.</li>
 <li>Cotrufo M, De Feo M, De Santo LS, Romano G, Della Corte A, Renzulli A, et al. Risk of warfarin during pregnancy with mechanical valve prostheses. Obstet Gynecol. 2002;99(1):35-40.</li>
 <li>Orbach H, Matok I, Gorodischer R, Sheiner E, Daniel S, Wiznitzer A, et al. Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes. Am J Obstet Gynecol. 2013;208(4):301 e1-6.</li>
 <li>Lennestal R, Otterblad Olausson P, Kallen B. Maternal use of antihypertensive drugs in early pregnancy and delivery outcome, notably the presence of congenital heart defects in the infants. Eur J Clin Pharmacol. 2009;65(6):615-25.</li>
 <li>Li DK, Yang C, Andrade S, Tavares V, Ferber JR. Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study. BMJ. 2011;343:d5931.</li>
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 <li>Walfisch A, Al-maawali A, Moretti ME, Nickel C, Koren G. Teratogenicity of angiotensin converting enzyme inhibitors or receptor blockers. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2011;31(6):465-72.</li>
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 <li>Brent RL. Nongenital malformations following exposure to progestational drugs: the last chapter of an erroneous allegation. Birth Defects Res A Clin Mol Teratol. 2005;73(11):906-18.</li>
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 <li>Li H, Zheng J, Luo J, Zeng R, Feng N, Zhu N, et al. Congenital anomalies in children exposed to antithyroid drugs in-utero: a meta-analysis of cohort studies. PLoS One. 2015;10(5):e0126610.</li>
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 <li>Nurmohamed L, Moretti ME, Schechter T, Einarson A, Johnson D, Lavigne SV, et al. Outcome following high-dose methotrexate in pregnancies misdiagnosed as ectopic. Am J Obstet Gynecol. 2011;205(6):533 e1-3.</li>
 <li>Weber-Schoendorfer C, Chambers C, Wacker E, Beghin D, Bernard N, Network of French Pharmacovigilance C, et al. Pregnancy outcome after methotrexate treatment for rheumatic disease prior to or during early pregnancy: a prospective multicenter cohort study. Arthritis Rheumatol. 2014;66(5):1101-10.</li>
 <li>Lambertini M, Peccatori FA, Azim HA, Jr. Targeted agents for cancer treatment during pregnancy. Cancer Treat Rev. 2015;41(4):301-9.</li>
 <li>Moritz MJ et al. Transplant Pregnancy Register International. 2016 Annual Report.</li>
 <li>Hoeltzenbein M, Elefant E, Vial T, Finkel-Pekarsky V, Stephens S, Clementi M, et al. Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services. American journal of medical genetics Part A. 2012;158A(3):588-96.</li>
 <li>EMA recommends additional measures to prevent use of mycophenolate in pregnancy. Pregnant women must not be exposed unless there is no suitable alternative to prevent transplant rejection. 2015. Available at:&nbsp;<a href="http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2015/10/WC500195985.pdf">http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2015/10/WC500195985.pdf</a></li>
 <li>Cheent K, Nolan J, Shariq S, Kiho L, Pal A, Arnold J. Case Report: Fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn's disease. J Crohns Colitis. 2010;4(5):603-5.</li>
 <li>Broms G, Granath F, Ekbom A, Hellgren K, Pedersen L, Sorensen HT, et al. Low Risk of Birth Defects for Infants Whose Mothers Are Treated With Anti-Tumor Necrosis Factor Agents During Pregnancy. Clin Gastroenterol Hepatol. 2016;14(2):234-41 e1-5.</li>
 <li>Weber-Schoendorfer C, Oppermann M, Wacker E, Bernard N, network of French pharmacovigilance c, Beghin D, et al. Pregnancy outcome after TNF-alpha inhibitor therapy during the first trimester: a prospective multicentre cohort study. Br J Clin Pharmacol. 2015;80(4):727-39.</li>
 <li>Svensk reumatologisk f&ouml;rening. Riktlinjer f&ouml;r l&auml;kemedelsbehandling i samband med graviditet och amning hos patienter med reumatisk sjukdom. Uppdaterat 2019. Available at:&nbsp;<a href="http://svenskreumatologi.se/wp-content/uploads/2019/03/graviditet-och-amning_riktlinjedokument-graviditet-_amning-2019.pdf">http://svenskreumatologi.se/wp-content/uploads/2019/03/graviditet-och-amning_riktlinjedokument-graviditet-_amning-2019.pdf</a>&nbsp;Accessed May 2019. 2017.</li>
 <li>Akbari M, Shah S, Velayos FS, Mahadevan U, Cheifetz AS. Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(1):15-22.</li>
 <li>Mozaffari S, Abdolghaffari AH, Nikfar S, Abdollahi M. Pregnancy outcomes in women with inflammatory bowel disease following exposure to thiopurines and antitumor necrosis factor drugs: a systematic review with meta-analysis. Hum Exp Toxicol. 2015;34(5):445-59.</li>
 <li>Davison JM, Dellagrammatikas H, Parkin JM. Maternal azathioprine therapy and depressed haemopoiesis in the babies of renal allograft patients. Br J Obstet Gynaecol. 1985;92(3):233-9.</li>
 <li>Moore KL. The developing human. Clinically oriented embryology. 10th ed: Elsevier; 2016.</li>
 <li>Vargesson N. Thalidomide-induced teratogenesis: history and mechanisms. Birth defects research Part C, Embryo today : reviews. 2015;105(2):140-56.</li>
 <li>European Medicines Agency (EMA). Assessment report for Thalidomide Pharmion. 2008. Available at:&nbsp;<a href="http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000823/WC500037054.pdf">http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000823/WC500037054.pdf</a>&nbsp;Accessed March 12, 2017.</li>
 <li>Koren G, Florescu A, Costei AM, Boskovic R, Moretti ME. Nonsteroidal antiinflammatory drugs during third trimester and the risk of premature closure of the ductus arteriosus: a meta-analysis. Ann Pharmacother. 2006;40(5):824-9.</li>
 <li>Ostensen M, Khamashta M, Lockshin M, Parke A, Brucato A, Carp H, et al. Anti-inflammatory and immunosuppressive drugs and reproduction. Arthritis Res Ther. 2006;8(3):209.</li>
 <li>Reinebrant HE, Pileggi-Castro C, Romero CL, Dos Santos RA, Kumar S, Souza JP, et al. Cyclo-oxygenase (COX) inhibitors for treating preterm labour. Cochrane Database Syst Rev. 2015(6):CD001992.</li>
 <li>Desai RJ, Huybrechts KF, Hernandez-Diaz S, Mogun H, Patorno E, Kaltenbach K, et al. Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study. BMJ. 2015;350:h2102.</li>
 <li>Kallen B, Borg N, Reis M. The use of central nervous system active drugs during pregnancy. Pharmaceuticals. 2013;6(10):1221-86.</li>
 <li>Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Sabers A, et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. The Lancet Neurology. 2011;10(7):609-17.</li>
 <li>Tomson T, Xue H, Battino D. Major congenital malformations in children of women with epilepsy. Seizure. 2015;28:46-50.</li>
 <li>Bromley R, Weston J, Adab N, Greenhalgh J, Sanniti A, McKay AJ, et al. Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child. Cochrane Database Syst Rev. 2014(10):CD010236.</li>
 <li>EMA. CMDh agrees to strengthen warnings on the use of valproate medicines in women and girls. Women to be better informed of risks of valproate use in pregnancy and need for contraception. Available at:&nbsp;<a href="http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Valproate_and_related_substances_31/Position_provided_by_CMDh/WC500177637.pdf">http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Valproate_and_related_substances_31/Position_provided_by_CMDh/WC500177637.pdf</a></li>
 <li>Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Perucca E, et al. Dose-dependent teratogenicity of valproate in mono- and polytherapy: an observational study. Neurology. 2015;85(10):866-72.</li>
 <li>Ennis ZN, Damkier P. Pregnancy exposure to olanzapine, quetiapine, risperidone, aripiprazole and risk of congenital malformations. A systematic review. Basic Clin Pharmacol Toxicol. 2015;116(4):315-20.</li>
 <li>Habermann F, Fritzsche J, Fuhlbruck F, Wacker E, Allignol A, Weber-Schoendorfer C, et al. Atypical antipsychotic drugs and pregnancy outcome: a prospective, cohort study. Journal of clinical psychopharmacology. 2013;33(4):453-62.</li>
 <li>EMA. Pharmacovigilance Working Party (PhVWP). Antipsychotics &ndash; Risk of extrapyramidal effects and withdrawal symptoms in newborns after exposure during pregnancy. 2011. Available at:<a href="http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/07/WC500109581.pdf">&nbsp;http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/07/WC500109581.pdf</a></li>
 <li>Huybrechts KF, Hernandez-Diaz S, Patorno E, Desai RJ, Mogun H, Dejene SZ, et al. Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations. JAMA psychiatry. 2016;73(9):938-46.</li>
 <li>Patorno E, Huybrechts KF, Bateman BT, Cohen JM, Desai RJ, Mogun H, et al. Lithium Use in Pregnancy and the Risk of Cardiac Malformations. N Engl J Med. 2017;376(23):2245-54.</li>
 <li>Diav-Citrin O, Shechtman S, Tahover E, Finkel-Pekarsky V, Arnon J, Kennedy D, et al. Pregnancy outcome following in utero exposure to lithium: a prospective, comparative, observational study. The American journal of psychiatry. 2014;171(7):785-94.</li>
 <li>Kozma C. Neonatal toxicity and transient neurodevelopmental deficits following prenatal exposure to lithium: Another clinical report and a review of the literature. American journal of medical genetics Part A. 2005;132A(4):441-4.</li>
 <li>Ban L, West J, Gibson JE, Fiaschi L, Sokal R, Doyle P, et al. First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study. PLoS One. 2014;9(6):e100996.</li>
 <li>Laegreid L, Olegard R, Wahlstrom J, Conradi N. Abnormalities in children exposed to benzodiazepines in utero. Lancet. 1987;1(8524):108-9.</li>
 <li>Norby U, Forsberg L, Wide K, Sjors G, Winbladh B, Kallen K. Neonatal Morbidity After Maternal Use of Antidepressant Drugs During Pregnancy. Pediatrics. 2016;138(5).</li>
 <li>Malm H, Sourander A, Gissler M, Gyllenberg D, Hinkka-Yli-Salomaki S, McKeague IW, et al. Pregnancy Complications Following Prenatal Exposure to SSRIs or Maternal Psychiatric Disorders: Results From Population-Based National Register Data. The American journal of psychiatry. 2015:appiajp201514121575.</li>
 <li>Grigoriadis S, VonderPorten EH, Mamisashvili L, Eady A, Tomlinson G, Dennis CL, et al. The effect of prenatal antidepressant exposure on neonatal adaptation: a systematic review and meta-analysis. J Clin Psychiatry. 2013;74(4):e309-20.</li>
 <li>Grigoriadis S, VonderPorten EH, Mamisashvili L, Roerecke M, Rehm J, Dennis CL, et al. Antidepressant exposure during pregnancy and congenital malformations: is there an association? A systematic review and meta-analysis of the best evidence. J Clin Psychiatry. 2013;74(4):e293-308.</li>
 <li>Kieler H, Artama M, Engeland A, Ericsson O, Furu K, Gissler M, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries. BMJ. 2011;344:d8012.</li>
 <li>Grzeskowiak LE, Morrison JL, Henriksen TB, Bech BH, Obel C, Olsen J, et al. Prenatal antidepressant exposure and child behavioural outcomes at 7 years of age: a study within the Danish National Birth Cohort. BJOG. 2016;123(12):1919-28.</li>
 <li>Lund N, Pedersen LH, Henriksen TB. Selective serotonin reuptake inhibitor exposure in utero and pregnancy outcomes. Arch Pediatr Adolesc Med. 2009;163(10):949-54.</li>
 <li>Sujan AC, Rickert ME, Oberg AS, Quinn PD, Hernandez-Diaz S, Almqvist C, et al. Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring. JAMA. 2017;317(15):1553-62.</li>
 <li>Brown HK, Ray JG, Wilton AS, Lunsky Y, Gomes T, Vigod SN. Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children. JAMA. 2017;317(15):1544-52.</li>
 <li>Brandlistuen RE, Ystrom E, Eberhard-Gran M, Nulman I, Koren G, Nordeng H. Behavioural effects of fetal antidepressant exposure in a Norwegian cohort of discordant siblings. International journal of epidemiology. 2015;44(4):1397-407.</li>
 <li>Deligiannidis KM, Byatt N, Freeman MP. Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Journal of clinical psychopharmacology. 2014;34(2):244-55.</li>
 <li>Norby U, Winbladh B, Kallen K. Perinatal Outcomes After Treatment With ADHD Medication During Pregnancy. Pediatrics. 2017;140(6).</li>
 <li>Bro SP, Kjaersgaard MI, Parner ET, Sorensen MJ, Olsen J, Bech BH, et al. Adverse pregnancy outcomes after exposure to methylphenidate or atomoxetine during pregnancy. Clin Epidemiol. 2015;7:139-47.</li>
 <li>Haervig KB, Mortensen LH, Hansen AV, Strandberg-Larsen K. Use of ADHD medication during pregnancy from 1999 to 2010: a Danish register-based study. Pharmacoepidemiol Drug Saf. 2014;23(5):526-33.</li>
 <li>Huybrechts KF, Broms G, Christensen LB, Einarsdottir K, Engeland A, Furu K, et al. Association Between Methylphenidate and Amphetamine Use in Pregnancy and Risk of Congenital Malformations: A Cohort Study From the International Pregnancy Safety Study Consortium. JAMA psychiatry. 2017.</li>
 <li>Diav-Citrin O, Shechtman S, Arnon J, Wajnberg R, Borisch C, Beck E, et al. Methylphenidate in Pregnancy: A Multicenter, Prospective, Comparative, Observational Study. J Clin Psychiatry. 2016;77(9):1176-81.</li>
 <li>Ray JG, Vermeulen MJ, Bharatha A, Montanera WJ, Park AL. Association Between MRI Exposure During Pregnancy and Fetal and Childhood Outcomes. JAMA. 2016;316(9):952-61.</li>
</ol>]]></HtmlField>
 <HtmlField Name="PageContent"><![CDATA[The drugs included in the table are either well-known for their teratogenic effects or substances with wide-spread use for which there might be fetal effects to consider. The details in the table are considered as extra reading for those specially interested. Please observe that the table is not fully comprehensive. There are more substances that might harm fetal development both within the listed and other therapeutic areas. In many cases, the fetal effects are summarized on a group level in the table. For individual substances within the respective group, there are often still insufficient data to assess for example the risk of specific birth defects. For a complete picture and extensive information, we refer to the resources listed under useful links and literature. The drugs in the table are listed according to the ATC-code system.
<table class="vandret-layout">
 <thead>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="col">Medicinal drugs</th>
 <th class="vandret-layoutTableOddCol" scope="col">Fetal effects</th>
 <th class="vandret-layoutTableEvenCol" scope="col">Comment </th>
 <th class="vandret-layoutTableOddCol" scope="col">References</th>
 </tr>
 </thead>
 <tbody>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Anticoagulants</th>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 <td class="vandret-layoutTableEvenCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Anticoagulants in general </th>
 <td class="vandret-layoutTableOddCol">Increased risk of bleeding complications, especially when used during late pregnancy, due to the pharmacodynamic effects of the drugs.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">In contrast to other anticoagulants, low molecular heparins are considered safe during pregnancy. There are substantial data concerning especially dalteparin, without any negative fetal impact.</td>
 <td class="vandret-layoutTableOddCol">[1-7]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Vitamin K antagonists,
 
 e.g. warfarin
 
 </th>
 <td class="vandret-layoutTableOddCol">Fetal warfarin syndrome: hypoplasia of the nasal cartilage and extremities, eye defects and CNS impairment including intellectual disability. The syndrome is linked to exposure primarily during pregnancy week 6 to 9 with a risk of ~ 20%. Exposure after the first trimester has been connected to hydrocephaly, microcephaly, CNS defects, stillbirth and neonatal death, probably because of bleeding complications.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Vitamin K antagonists are contraindicated during pregnancy and should be replaced with low molecular heparin, preferentially before the pregnancy. In rare cases, the woman&rsquo;s condition requires treatment with a vitamin K antagonist throughout pregnancy. </td>
 <td class="vandret-layoutTableOddCol">[1-7]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Cardiovascular drugs</th>
 <td class="vandret-layoutTableOddCol"></td>
 <td class="vandret-layoutTableEvenCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Antihypertensive drugs
 
 in general
 
 </th>
 <td class="vandret-layoutTableOddCol">Neonatal complications like hypotension, hypoglycemia, intrauterine growth restriction and premature birth are linked to treatment with antihypertensives in general. These effects are to a large extent probably caused by the underlying maternal condition. Several antihypertensive drugs are further associated with an increased risk for cardiac malformations. Since this seems to be a common effect of these drugs, it is possibly also linked to the disease per se or to changes in the fetal blood pressure.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">It is important that hypertension and preeclampsia are adequately treated during pregnancy. Labetalol (an alpha-beta blocker), beta blocking agents, calcium antagonists, hydralazine and methyldopa are considered medications of choice to pregnant women. Recommendations vary between countries. ACE-inhibitors, AT-II-antagonists and renin inhibitors are contraindicated during pregnancy.</td>
 <td class="vandret-layoutTableOddCol">[1, 2, 4, 5, 8-10]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Diuretics</th>
 <td class="vandret-layoutTableOddCol">Electrolyte disturbances, hypotension, hypoglycemia and intrauterine growth restriction. Thiazide diuretics are also associated with thrombocytopenia.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Use not recommended unless required by mother&rsquo;s cardiovascular condition.</td>
 <td class="vandret-layoutTableOddCol">[1-3, 5]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Beta blocking agents</th>
 <td class="vandret-layoutTableOddCol">Neonatal bradycardia. Other effects like hypotension, hypoglycemia, intrauterine growth restriction and a slight increased risk for cardiac malformations, are probably attributed primarily to the mother&rsquo;s disease.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableOddCol">[1-5, 9, 11]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">ACE inhibitors</th>
 <td class="vandret-layoutTableOddCol">Treatment during the second and third trimester can cause oligohydramnios, pulmonary hypoplasia, oligouria/anuria, fetal growth retardation, hypocalvaria, hypotension and fetal or neonatal death. There is some evidence for an increased risk of cardiac malformations after exposure during early pregnancy, but available data are conflicting. Probably, ACE inhibitors do not differ from other antihypertensives in this respect.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">ACE-inhibitors should not be used during pregnancy, especially not during the second and third trimester. Women treated with these drugs should be switched to other antihypertensive therapy. A targeted ultrasound can be considered to assess amniotic fluid volume and detect fetal lung hypoplasia, if exposure took place during the second or third trimester.</td>
 <td class="vandret-layoutTableOddCol">[1-4, 9, 10, 12-14]</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Angiotensin II antagonists</th>
 <td class="vandret-layoutTableOddCol">Similar effects as for ACE inhibitors are expected, but data are so far limited.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Same recommendations as for ACE inhibitors.</td>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Renin-inhibitors</th>
 <td class="vandret-layoutTableOddCol">Similar effects as for ACE inhibitors and angiotensin II antagonists are expected, but data are so far limited.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Same recommendations as for ACE inhibitors and angiotensin II antagonists.</td>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Retinoids </th>
 <td class="vandret-layoutTableOddCol"></td>
 <td class="vandret-layoutTableEvenCol">&nbsp;</td>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Systemic use: Isotretinoin and related substances </th>
 <td class="vandret-layoutTableOddCol">Retinoids are powerful teratogens; at least 20% of infants exposed to isotretinoin during early pregnancy are affected. Typically, retinoids cause a pattern of defects involving craniofacial, cardiac, thymic and central nervous system structures. There is also an increased risk of spontaneous abortions and impaired central nervous system development.</td>
 <td class="vandret-layoutTableEvenCol">Strictly contraindicated during pregnancy. The use is firmly regulated and a risk management plan must be followed to avoid pregnancy during treatment. Reliable contraception must be used before, during and a given time period after treatment cessation. The length of necessary contraception use after treatment discontinuation depends on the substance. For isotretinoin, it is at least 30 days. If exposure took place during the first trimester, a detailed fetal anomaly scan is recommended.&nbsp;</td>
 <td class="vandret-layoutTableOddCol">[3, 15, 16]</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Topical use</th>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Topical use of retinoids carries less risk than systemic treatment, but should nevertheless be strictly avoided during pregnancy and already when planning pregnancy.&nbsp;</td>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Prostaglandins</th>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 <td class="vandret-layoutTableEvenCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Misoprostol</th>
 <td class="vandret-layoutTableOddCol">Spontaneous abortion and a spectrum of abnormalities, especially different skull defects, cranial nerve palsies (M&ouml;bius syndrome), arthrogryposis, transverse limb reduction defects and equinovarus.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Contraindicated during pregnancy. An ultrasound scan 2&ndash;3 weeks after inadvertent exposure to misoprostol is suggested to exclude partial placental abruption. A targeted ultrasound is recommended during pregnancy week 16&ndash;18 besides monitoring the fetal growth.
 
 It is important to counsel women regarding the risks, before medical termination of pregnancy.
 
 </td>
 <td class="vandret-layoutTableOddCol">[1, 2, 4, 17]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Sex hormones</th>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">&nbsp;</td>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Androgens</th>
 <td class="vandret-layoutTableOddCol">Masculinization of the female external genitalia. The most sensitive period being week 8-10 post-conception. Exposure later during pregnancy might cause clitoral hypertrophy.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Contraindicated during pregnancy.</td>
 <td class="vandret-layoutTableOddCol">[1, 2, 18]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Progestogens (gestagens)</th>
 <td class="vandret-layoutTableOddCol">Masculinization of the female external genitalia might occur if exposure to high doses of progestogens &ndash; especially androgenic progestogens &ndash; takes place during early pregnancy. The risk is however small to modest. Progestogens in doses used for contraception are most likely harmless to the fetus.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Progestogens should be avoided during pregnancy, unless clearly indicated in special situations.</td>
 <td class="vandret-layoutTableOddCol">[1, 2, 5, 19]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Corticosteroids </th>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">&nbsp;</td>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Glucocorticoids</th>
 <td class="vandret-layoutTableOddCol">Decreased placental and birth weight are plausible effects of systemic treatment with glucocorticoids. Available data are however limited and confounded by the mother&rsquo;s disease. There might also be a slightly increased risk for orofacial clefts when used during early pregnancy. Overall the risk for the developing fetus is small, if any.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">If the pregnant woman&rsquo;s condition requires systemic treatment, the dose should be kept as low and the duration of therapy as short as possible. Prednisone and prednisolone are the primary choices as their passage to the fetus is limited. Glucocorticoids for inhalation are safe during pregnancy. The same goes for dermatological use, even though extensive topical administration with strong corticosteroids, should be avoided, especially under occlusion,
 
 Betamethasone and dexamethasone pass the placenta and are used to speed up lung development in preterm fetuses.
 
 </td>
 <td class="vandret-layoutTableOddCol">[1, 3-5, 20]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Thyroid therapy</th>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">&nbsp;</td>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Antithyroid preparations
 
 (thyrostatics)
 
 </th>
 <td class="vandret-layoutTableOddCol">Treatment with antithyroids (thiamazole, methimazole, propylthiouracil) has been associated with an increased risk of various birth defects, e.g. scalp defects and esophagus atresia. The absolute risk seems however low. Treatment with antithyroid drugs after pregnancy week 15 might induce fetal hypothyroidism and goiter. </td>
 <td class="vandret-layoutTableEvenCol">Antithyroid treatment should only be undertaken on a strict indication. It is crucial to keep the pregnant woman in a euthyroid state to minimize the risk for fetal goiter or hypothyroidism. Careful monitoring of therapy is necessary.
 
 Substitution therapy with levothyroxine is safe during pregnancy and treatment of hypothyroidism important.
 &nbsp;</td>
 <td class="vandret-layoutTableOddCol">[1, 3-5, 21, 22]</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Antiinfectives for systemic use</th>
 <td class="vandret-layoutTableOddCol"></td>
 <td class="vandret-layoutTableEvenCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Tetracyclines</th>
 <td class="vandret-layoutTableOddCol">Potential risk of discoloration of deciduous teeth when used from the 4th pregnancy month and onwards.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Tetracyclines should only be used in the second half of the pregnancy if no other adequate antibiotic is available. There is evidence that the risk for dental staining is less for doxycycline than for older substances like tetracycline. The enamel of permanent teeth does not start to develop until after birth. </td>
 <td class="vandret-layoutTableOddCol">[1, 23, 24]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Trimethoprim</th>
 <td class="vandret-layoutTableOddCol">Potentially an increased risk of birth defects, e.g. neural tube defects, cardiac malformations and orofacial clefts. Trimethoprim is an inhibitor of folic acid synthesis and folic acid is required for normal fetal development. Results from available human studies are however conflicting and the risk with trimethoprim is most likely low. There are also indications that trimethoprim is linked to an increased risk of spontaneous abortion, but it is unclear whether the association is causal.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Supplementation with a higher dose (0.8&ndash;5 mg) folic acid has been suggested during preconception and the first trimester.</td>
 <td class="vandret-layoutTableOddCol">[1, 2, 4, 25, 26]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Sulfonamides</th>
 <td class="vandret-layoutTableOddCol">Competes with bilirubin for binding sites at plasma proteins and might induce hyperbilirubinemia and theoretically kernicterus. The risk is however, extremely low, but should be taken into consideration if the neonate is very premature or G6PD (Glucose-6-phosphate dehydrogenase) deficient.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Avoid during late pregnancy if premature birth is threatening.</td>
 <td class="vandret-layoutTableOddCol">[2, 3]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Aminoglycosides</th>
 <td class="vandret-layoutTableOddCol">Fetal ototoxicity after treatment during the second and third trimester. This is documented for streptomycin but there might be some risk with more modern aminoglycosides as well.</td>
 <td class="vandret-layoutTableEvenCol">If possible, treatment with aminoglycosides should not be carried out during the second and third trimester. When therapy is necessary, the dose should be kept as low and the duration of treatment as limited as possible. Streptomycin should be avoided.</td>
 <td class="vandret-layoutTableOddCol">[1, 2, 4, 27]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Fluconazole</th>
 <td class="vandret-layoutTableOddCol">High doses (400&ndash;800 mg/day) have been linked to a distinct pattern of birth defects including multiple synostosis, heart defects, skeletal anomalies and dysmorphic facial features. Low dose of fluconazole (150 mg/day) carries a very low risk, if any, but a slight increased risk for cardiac malformations and spontaneous abortion cannot be excluded. &nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Fluconazole in high dose should preferentially not be administered during early pregnancy. If the fetus is exposed during this period, a targeted ultrasound is recommended. Low dose fluconazole should be used with some caution during the first and early second trimester. </td>
 <td class="vandret-layoutTableOddCol">[1, 2, 4, 28-30]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Antineoplastic drugs</th>
 <td class="vandret-layoutTableOddCol"></td>
 <td class="vandret-layoutTableEvenCol">&nbsp;</td>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Chemotherapy in general</th>
 <td class="vandret-layoutTableOddCol">Antineoplastic agents interrupt vital cell functions and may have significant teratogenic effects. Exposure during the first trimester might cause major malformations, fetal death and miscarriage. Treatment during the second and third trimesters is associated with intrauterine growth restriction, low birth weight, still birth, neonatal neutropenia and sepsis.
 
 Yet, follow-up data after cancer treatment indicate that most children exposed to chemotherapy during the second and/or third trimester in utero are doing well. It is difficult to assess differences between individual substances since cancer therapy usually involves several drugs simultaneously.
 
 Some antineoplastic agents might cause mutations of the germ cells, which theoretically could impair the embryo if exposure occurs before conception. An increased risk of birth defects due to chromosomal changes has however not been confirmed in human studies. The risk is thereby probably very low.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">The benefit for the mother must be carefully weighed against the risk for the fetus. If possible, treatment is postponed until after the first trimester. If the situation is life-threating for the woman, it might be necessary to consider termination of pregnancy and initiate treatment promptly.
 
 In case the malignancy is diagnosed after &gt;32 pregnancy weeks, it is usually reasonable to deliver the infant before treatment. Non-pregnant women treated with antineoplastic agents should use effective contraception during treatment to avoid pregnancy.
 
 </td>
 <td class="vandret-layoutTableOddCol">[31-35]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">&nbsp;</th>
 <td class="vandret-layoutTableOddCol">Below, a few antineoplastic agents are described in more detail. For other antineoplastic drugs, see&nbsp;www.janusinfo/fosterpaverkan and other recommended resources.</td>
 <td class="vandret-layoutTableEvenCol">&nbsp;</td>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Alkylating agents</th>
 <td class="vandret-layoutTableOddCol">Major malformations are described in the literature after exposure to e.g. cyclophosphamide and busulfan in early pregnancy. Additionally, alkylating agents are associated with intrauterine growth restriction, bone marrow suppression and potentially mutagenic effects. &nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Treatment should preferentially not be undertaken during early pregnancy. If exposure occurred during this time and the woman wishes to continue the pregnancy, detailed fetal anomaly scans are advised. </td>
 <td class="vandret-layoutTableOddCol">[1, 2, 31]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Methotrexate</th>
 <td class="vandret-layoutTableOddCol">Methotrexate is a folic acid antagonist. Low doses (~ &lt;=30 mg/week) used for immunosuppression have been associated with a moderate risk increase for birth defects and spontaneous abortion. Available data are however limited. Higher doses carry a higher risk for both spontaneous abortion and birth defects, for example a special embryopathy characterized by craniofacial defects, malformations of the digits, and defects of the spine and ribs. Methotrexate is further linked to intrauterine growth restriction and has mutagenic effects.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Treatment during pregnancy is contraindicated. A three months&rsquo; drug-free period is recommended after repeated doses before giving up efficient contraception. Detailed prenatal diagnosis is warranted after inadvertent exposure during the first trimester or before conception. Women should be supplemented with high dose folic acid (1-5 mg/day, according to local guidelines). </td>
 <td class="vandret-layoutTableOddCol">[1, 2, 4, 36, 37]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Molecularly targeted anticancer therapies</th>
 <td class="vandret-layoutTableOddCol">Modern targeted therapy includes many different substances with quite specific indications and fetal effects. Some of them are monoclonal antibodies that cross the placenta to a significant extent during the second and third trimester but to a lesser degree during early pregnancy. Thereby, they may be expected to affect the fetus mainly during late pregnancy. Trastuzumab for example blocks the fetal kidney function and can induce oligohydramnios. Rituximab may cause fetal B-cell depletion.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Examples of targeted therapy:
 
 Trastuzumab: Treatment should only be undertaken during the second and third trimester after special consideration. Careful monitoring of amniotic fluid volume is recommended.
 
 Rituximab: The potentially impaired immune system of exposed infants should be reckoned, for example before administration of live vaccines.
 
 </td>
 <td class="vandret-layoutTableOddCol">[1, 2, 4, 31, 32, 38]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Immunosuppressants</th>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">&nbsp;</td>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Mycophenolic acid</th>
 <td class="vandret-layoutTableOddCol">Increased risk of spontaneous abortions and birth defects, some with a characteristic pattern involving external ears, face, distal limbs, heart and kidney after exposure in early pregnancy. The European Medicines Agency (EMA) issued a special warning in 2015 concerning the fetal impact.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Contraindicated during pregnancy. Women exposed during early pregnancy should be offered detailed fetal anomaly scans. Non-pregnant women treated with mycophenolate must use effective contraception to avoid pregnancy.</td>
 <td class="vandret-layoutTableOddCol">[1, 2, 5, 39-41]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Tumor necrosis factor alpha (TNF-&alpha;) inhibitors </th>
 <td class="vandret-layoutTableOddCol">There is a theoretical risk that treatment will compromise the immune system of the newborn resulting in an increased risk of infection. This effect is mainly thought to be linked to TNF-&alpha; inhibitors that are IgG-antibodies with intact Fc-part, since they cross the placenta via active transport from the second trimester and onwards. Some placental transfer during the first trimester cannot, however, be ruled out. Available data concerning birth defects are relatively limited but TNF-&alpha; inhibitors do not seem to, or only slightly, increase the risk of malformations. &nbsp;</td>
 <td class="vandret-layoutTableEvenCol">TNF-&alpha;-inhibitors should be used cautiously during pregnancy and only if treatment is essential for the pregnant woman. Depending on the agent and the indication, it should be considered to pause treatment during the second or early third trimester to reduce fetal exposure. Live vaccines should be avoided to exposed infants during their first 6-12 months of life. </td>
 <td class="vandret-layoutTableOddCol">[1, 4, 42-45]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Interleukin inhibitors</th>
 <td class="vandret-layoutTableOddCol">The same concerns regarding the immune system of the neonate as for TNF-&alpha; inhibitors. There are not enough data to assess the risk for birth defects.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Same as for TNF-&alpha; inhibitors.</td>
 <td class="vandret-layoutTableOddCol">&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Azathioprine</th>
 <td class="vandret-layoutTableOddCol">A few reports of neonatal complications like neutropenia and thrombocytopenia probably due to the immunosuppression, have been published. No increased risk of birth defects.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Treatment can be continued during pregnancy.
 
 Measurement of thiopurine S-methyltransferase gene (TPMT) activity is encouraged prior to commencing treatment.
 
 </td>
 <td class="vandret-layoutTableOddCol">[1, 2, 4, 46-48]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Thalidomide and related drugs</th>
 <td class="vandret-layoutTableOddCol">Thalidomide is the most infamous teratogen in history. It has been estimated that around 10 000 children were born with thalidomide induced birth defects worldwide in the end of the 1950s and beginning of the 1960s before the drug was withdrawn from the market. Examples of malformations were phocomelia, heart defects, anomalies of the urinary and alimentary systems, absence of the external and internal ears and hemangioma of the face. The damage occurred mainly after exposure during day 34-50 after the last menstrual period. The risk of embryopathy during this period is 20-50%.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Thalidomide and closely related substances have been reinstated for treatment of multiple myeloma and leprosy. The use is strictly regulated and a risk management plan must be followed to avoid pregnancy during treatment. </td>
 <td class="vandret-layoutTableOddCol">[1, 2, 49-51]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">
 Musculo-skeletal system
 
 </th>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">&nbsp;</td>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Antiinflammatory and antirheumatic products, non-steroids (NSAIDs)</th>
 <td class="vandret-layoutTableOddCol">Exposure to NSAIDs in late pregnancy is linked to premature closure of ductus arteriosus. The risk appears to be apparent at approximately pregnancy week 27 and increases with advancing gestation. Closure of ductus arteriosus can result in pulmonary hypertension, respiratory disorders in the newborn and in severe cases, fetal death.
 
 Additionally, NSAIDs can cause impaired renal function of the fetus with oligohydramnios and anuria. Bleeding complications and prolongation of the delivery are other effects due to the inhibition of prostaglandins.
 
 There is no overall risk increase of malformations with NSAIDs, but a higher frequency of cardiac malformations has been associated with NSAIDs as a group. The risk is nevertheless low.
 
 A couple of studies have also linked first trimester use of NSAIDs to an increased prevalence of miscarriage, but available data are conflicting.
 &nbsp;</td>
 <td class="vandret-layoutTableEvenCol">NSAIDs should not be used during the third trimester, as far as possible. If repeated dosing of NSAIDs is necessary from ca week 27 and onwards, meticulous fetal monitoring regarding ductus arteriosus patency and oligohydramnios must be undertaken.
 
 Use of selective COX-2 inhibitors is contraindicated throughout pregnancy, due to lack of experience and the effects connected with other NSAIDs.
 
 </td>
 <td class="vandret-layoutTableOddCol">[3, 52-54]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Acetylsalicylic acid (ASA) in antiphlogistic doses </th>
 <td class="vandret-layoutTableOddCol">Risk of bleeding in the mother and the newborn infant if used close to delivery. &nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Same as NSAIDs. Antiphlogistic doses are not recommended during pregnancy.
 
 Low dose ASA (&lt;=150mg/ day) can be used during pregnancy and is not associated with specific risks.
 
 </td>
 <td class="vandret-layoutTableOddCol">[1, 4]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">
 Nervous system 
 </th>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">&nbsp;</td>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Opioids</th>
 <td class="vandret-layoutTableOddCol">Withdrawal symptoms in the newborn after long term treatment. Respiratory depression in the neonate if treatment takes place close to the delivery. Low or no increased risk for birth defects.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Sporadic short term use of opioids can be used during pregnancy, while long term treatment and use near term should be avoided.
 
 Buprenorphine or methadone can be used during pregnancy in opioid-dependent women.
 
 If treatment is undertaken, responsible pediatrician should be informed when examining the newborn child.
 
 </td>
 <td class="vandret-layoutTableOddCol">[1, 2, 4, 55, 56]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Antiepileptics</th>
 <td class="vandret-layoutTableOddCol">Most well-documented antiepileptic drugs increase the risk of birth defects. The substance being most harmful is valproic acid that is clearly linked to a high frequency of malformations, (e.g. spina bifida, absolute risk 1-2%; orofacial clefts; microcephaly; hypospadias and cardiovascular defects) as well as cognitive impairment, developmental delay and autistic disorders. The risk is higher with higher doses and combination therapy.
 
 Neonatal withdrawal symptoms are reported after treatment with antiepileptics during late pregnancy. For the more recently introduced drugs, there are not yet enough data for reliable risk assessment.
 
 &nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Antiepileptic drugs should only be used during pregnancy on a strict indication. The dose should be kept as low as possible but keep the woman free from seizures. Supplementation with folic acid already from preconception is recommended according to local guidelines and antiepileptic drug plasma concentrations should be monitored during treatment. The same considerations apply when antiepileptics are used for bipolar disease or other indications. If the woman is treated with antiepileptics during early pregnancy, fetal anomaly scans are advocated.
 
 Valproic acid is contraindicated during pregnancy and women with child bearing potential must be on a special pregnancy prevention program during treatment. There is however a small number of women whose epilepsy cannot be controlled without this drug and that might have to continue therapy during pregnancy. It is important to follow up the neurodevelopment of infants and children exposed prenatally to valproic acid.
 
 </td>
 <td class="vandret-layoutTableOddCol">[1, 4, 57-61]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Antipsychotics</th>
 <td class="vandret-layoutTableOddCol">Transient withdrawal symptoms in the neonate with e.g. agitation, hyper- or hypotension and feeding difficulties as symptoms. The drug authorities have also issued warnings for extrapyramidal symptoms in the neonate but the documentation for this adverse effect is sparse. There does not seem to be a substantial increased risk of birth defects, but data are limited for many individual drugs. Second-generation antipsychotics may increase glucose intolerance and have been associated with gestational diabetes and large for gestational age. Risperidone has though been associated with an increased risk of cardiac anomalies, but this finding needs to be confirmed. Until now, there are also not enough data to assess an impact on long term neurodevelopment or whether there are differences in fetal effects between atypical and typical antipsychotics.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">If antipsychotic treatment is necessary, the dose should be kept as low as possible but at the same time it is crucial to prevent relapse of the maternal condition.
 
 Regular control of blood sugar levels recommended.
 
 Responsible pediatrician should be informed about the medication, when examining the newborn child.
 
 </td>
 <td class="vandret-layoutTableOddCol">[1, 4, 62-65]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Lithium</th>
 <td class="vandret-layoutTableOddCol">A small increased prevalence of cardiac malformations (1&ndash;2% risk compared to 0.8% background risk). A probably increased risk of Ebstein&rsquo;s anomaly (right ventricular hypoplasia, malformed tricuspid valve). The literature is however conflicting, and the magnitude of the risk has not been established. Infants exposed during late pregnancy may exhibit several neonatal symptoms, for example hypotonia, respiratory disorders, depressed neurological status, kidney malfunction and diabetes insipidus, heart disturbances, hypothyreosis and fetal goiter. The effects seem to be transient. The limited available data concerning long term impact do not suggest impaired cognitive development.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Folic acid supplementation according to local guidelines should be considered. S-lithium concentration must be regularly monitored during treatment A targeted ultrasound to exclude cardiac maldevelopment is recommended after exposure during early pregnancy. The pediatrician should be informed about exposure to lithium during late pregnancy, when examining the newborn child. </td>
 <td class="vandret-layoutTableOddCol">[1, 3, 4, 66-68]</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Benzodiazepine derivatives</th>
 <td class="vandret-layoutTableOddCol">Treatment during late pregnancy can induce neonatal symptoms like hypotonia, hypothermia, respiratory disorders and withdrawal symptoms. An increased risk of birth defects has not been confirmed. &nbsp;</td>
 <td class="vandret-layoutTableEvenCol">If possible, benzodiazepines should be avoided during pregnancy.
 
 Occasional use is possible (primarily with short-acting agents such as oxazepam). The pediatrician should be informed about the treatment with benzodiazepines, when examining the newborn child.
 
 </td>
 <td class="vandret-layoutTableOddCol">[1, 2, 4, 69, 70]&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Antidepressants</th>
 <td class="vandret-layoutTableOddCol">Infants exposed to antidepressant drugs during late pregnancy have more often neonatal complications like respiratory disorders, hypoglycemia, CNS effects and feeding difficulties. The symptoms are transient but might necessitate admission to a neonatal care unit. It is also more common with premature birth, low birth weight and low Apgar scores in this group. The risk for severe adverse effects is low.
 
 Among the different antidepressant groups, selective serotonin reuptake inhibitors (SSRIs) are specifically linked to an increased frequency of persistent pulmonary hypertension of the newborn (PPHN). The absolute risk of PPHN is however very low also after treatment with SSRIs, approximately 0.3&ndash;0.7% vs. 0.1&ndash;0.2% in the general population.
 
 There does not seem to exist a substantial risk increase of birth defects with antidepressant drugs, even though fluoxetine, paroxetine and clomipramine have been associated with a higher prevalence of cardiac malformations.
 
 Studies of long-term outcome among children exposed to antidepressant drugs in utero are limited. Antidepressant treatment during pregnancy have in some studies been associated with an increased risk for autism in the offspring. The results are however conflicting and most likely; the higher prevalence of autism is caused by other factors than the antidepressant treatment. Studies that used sibling analyses to adjust for the genetic disposition of autism, did for example not confirm the association. Studies have also suggested an increased risk of internalizing behavior and depression, but a causal association has not been established.
 &nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Treatment of moderate to severe depression may require use of antidepressants during pregnancy. If treatment is crucial for the pregnant woman, the benefits outweighs the potential fetal effects. SSRIs are first line options, serotonin and noradrenaline reuptake inhibitors (SNRIs), mirtazapine and tricyclic antidepressants are considered second line choices. Dose adjustments may be warranted. To optimize treatment, plasma concentration measurements before and during pregnancy could be valuable. The health care staff at the delivery unit should be aware of the risk for neonatal complications.
 
 
 </td>
 <td class="vandret-layoutTableOddCol">[1, 71-81]</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row"> Centrally acting sympathomimetics&nbsp;&nbsp;&nbsp;&nbsp;</th>
 <td class="vandret-layoutTableOddCol">Infants whose mothers used drugs for attention deficit hyperactivity disorder (ADHD) during pregnancy have an increased risk for neonatal morbidity, especially CNS-related symptoms. They are more often admitted to a neonatal care unit and are more frequently born moderately preterm and with low Apgar scores. It is however not possible to ascertain to what extent these findings are caused by the medication or confounding factors like the ADHD condition per se or life style aspects.
 
 Regarding birth defects, there might be a slight risk increase for cardiac malformations, but more data are needed. There are no studies concerning long-term effects and it is also not possible to distinguish between different ADHD medications.
 
 </td>
 <td class="vandret-layoutTableEvenCol">Risk and benefits must be carefully assessed in each individual case. Abstaining from ADHD treatment might result in for example increased maternal stress and use of alcohol or illegal drugs that in turn might affect the fetus negatively.&nbsp;</td>
 <td class="vandret-layoutTableOddCol">[1, 82-86]</td>
 </tr>
 <tr class="vandret-layoutTableEvenRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Contrast media</th>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">&nbsp;</td>
 <td class="vandret-layoutTableOddCol"> &nbsp;&nbsp;&nbsp;&nbsp;</td>
 </tr>
 <tr class="vandret-layoutTableOddRow">
 <th class="vandret-layoutTableEvenCol" scope="row">Gadolinum</th>
 <td class="vandret-layoutTableOddCol">Use of gadolinium agents in connection with magnetic resonance imaging (MRI) has been associated with an increased risk of a broad set of rheumatological, inflammatory, or infiltrative skin conditions and for stillbirth or neonatal death.&nbsp;</td>
 <td class="vandret-layoutTableEvenCol">Gadolinium contrast agents should, as far as possible, be avoided during pregnancy.</td>
 <td class="vandret-layoutTableOddCol">[87]&nbsp;</td>
 </tr>
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