Skip to main content

Fetal Medicine and Treatment

  • Chapter
  • First Online:
Pediatric Clinical Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 205))

Abstract

Fetal medicine covers a broad spectrum of conditions that can be diagnosed before birth. Different disorders will require different treatment strategies and there is often an important ontogenetic aspect on how and when treatment can be implemented. Due to the limited availability there is a general lack of knowledge on how pharmacotherapy can be provided in the most efficient way. Until recently most knowledge about how different drugs are transferred and metabolized in the human fetus is based on very limited observational studies on concentrations of drugs in fetal blood and other fetal compartments. It might be that the rapid development of other non-invasive methods for fetal diagnostics such as isolation of fetal DNA and RNA in maternal serum, NMR imaging and other techniques could in the future be explored in fetal pharmacotherapy. Introduction of new treatment strategies are often based on extrapolation from experience in neonates and adults. However some fetal conditions are very specific for this time period in life. This especially entails disturbances in development as malformations, early growth restriction and several congenital disorders. Here it might be required to introduce new treatment strategies without any previous experience in humans. Example of this ethical dilemma is gene therapy for lung growth in severe cases of diaphragmatic hernia and early growth restriction. The risk–benefit issues need to be discussed in all these alternatives. However, it is likely that the concept of the human fetus as a potential patient is still in its infancy and with an improved understanding about fetal patho-physiology there will be a continued need for better knowledge of pharmacotherapy during this crucial time period in life.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 389.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 499.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adler SP, Nigro G (2009) Findings and conclusions from CMV hyperimmune globulin treatment trials. J Clin Virol 46(Suppl 4):S54–S57

    Article  PubMed  Google Scholar 

  • Ballabio M, Nicolini U, Jowette T, Ruiz de Elvira MC, Ekins RP, Rodeck CH (1989) Maturation of thyroid function in normal human foetuses. Clin Endocrinol 31(5):565–571

    Article  CAS  Google Scholar 

  • Bang J, Bock JE, Trolle D (1982) Ultrasound guided fetal intravenous transfusion for severe rhesus haemolytic disease. Br Med J 284:373–374

    Article  CAS  Google Scholar 

  • Bergman G, Eliasson H, Bremme K, Wahren-Herlenius M, Sonesson SE (2009) Anti-Ro52/SSA antibody-exposed fetuses with prolonged atrioventricular time intervals show signs of decreased cardiac performance. Ultrasound Obstet Gynecol 34(5):543–549

    Article  PubMed  CAS  Google Scholar 

  • Blakemore K, Hattenburg C, Stetten G et al (2004) In utero hematopoietic stem cell transplantation with haploidentical donor adult bone marrow in a canine model. Am J Obstet Gynecol 190:960–973

    Article  PubMed  Google Scholar 

  • Boreus LO (1967) Pharmacology of the human fetus: dose-effect relationship for acetylcholine during ontogenesis. Biol Neonat 11:328–337

    Article  Google Scholar 

  • Carvalho JS, Prefumo F, Ciardelli V et al (2007) Evaluation of fetal arrhythmias from simultaneous pulsed wave Doppler in pulmonary artery and vein. Heart 93:1448–1453

    Article  PubMed  Google Scholar 

  • Dalziel RD (2008) Antenatal corticosteroids for accelerating fetalö lung maturation for women at risk of preterm birth. The Cochrane collaboration. Cochrane Library 4:1–166

    Google Scholar 

  • Derbyshire WGS (2006) Can fetuses feel pain? BMJ 332(7546):909–912

    Article  PubMed  Google Scholar 

  • Fisk NM, Gitau R, Teixeira JM, Giannakoulopoulos X, Cameron AD, Glover VA (2001) Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling. Anesthesiology 95:828–835

    Article  PubMed  CAS  Google Scholar 

  • Flake AW, Zanjani ED (1999) In utero hematopoietic stem cell transplantation: ontogenic opportunities and biologic barriers. Blood 94:2179–2191

    PubMed  CAS  Google Scholar 

  • Flake AW, Roncarolo MG, Puck JM et al (1996) Treatment of x-linked severe combined immunodeficiency by in utero transplantation of paternal bone marrow. N Engl J Med 335:1806–1810

    Article  PubMed  CAS  Google Scholar 

  • Frenkel LM, Brown ZA, Bryson YJ, Corey L, Unadkat JD, Hensleigh PA, Arvin AM, Prober CG, Connor JD (1991) Pharmacokinetics of acyclovir in the term human pregnancy and neonate. Am J Obstet Gynecol 164(2):569–576

    PubMed  CAS  Google Scholar 

  • Giannakoulopoulos X, Sepulveda W, Kourtis P, Glover V, Fisk NM (1994) Fetal plasma cortisol and beta-endorphin response to intrauterine needling. Lancet 344:77–81

    Article  PubMed  CAS  Google Scholar 

  • Harrison MR, Slotnick RN, Crombleholme TM et al (1989) In-utero transplantation of fetal liver haemopoietic stem cells in monkeys. Lancet 2:1425–1427

    Article  PubMed  CAS  Google Scholar 

  • Jacquemard F, Yamamoto M, Costa J-M, Romand S, Jaqz-Aigrain E, Dejean A, Daffos F, Ville Y (2007) Maternal administration of valaciclovir in symptomatic intrauterine cytomegalovirus infection. BJOG 114(9):1113–1121

    Article  PubMed  CAS  Google Scholar 

  • Jaeggi ET, Fouron JC, Silverman ED et al (2004) Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation 110:1542–1548

    Article  PubMed  Google Scholar 

  • Juchau MR, Dyer DC (1972) Pharmacology of the placenta. Pediatr Clin North Am 19:65–69

    PubMed  CAS  Google Scholar 

  • Krapp M, Kohl T, Simpson JM et al (2003) Review of diagnosis, treatment, and outcome of fetal artrial flutter compared with supraventricular tachycardia. Heart 89:913–917

    Article  PubMed  CAS  Google Scholar 

  • Lagercrantz H, Changeux J-P (2009) The emergence of human consciousness: from fetal to neonatal life. Pediatr Res 65(3):255–260

    Article  PubMed  Google Scholar 

  • Lanari M, Lazzarotto T, Venturi V, Papa I, Gabrielli L, Guerra B et al (2006) Neonatal cytomegalovirus blood load and risk of sequelae in symptomatic and asymptomatic congenitally infected newborns. Pediatrics 117:76–83

    Article  Google Scholar 

  • Lazzarotto T, Varani S, Guerra B, Nicolosi A, Lanari M, Landini MP (2000) Prenatal indicators of congenital cytomegalovirus infection. J Pediatr 137:90–95

    Article  PubMed  CAS  Google Scholar 

  • Le Blanc K, Gotherstrom C, Ringden O et al (2005) Fetal mesenchymal stem-cell engrafment in bone after in utero transplantation in a patient with severe osteogenesis imperfect. Transplantation 79:1607–1614

    Article  PubMed  Google Scholar 

  • Leeder JS (2009) Developmental pharmacogenetics a general paradigm for application to neonatal pharmacology and toxicology. Clin Pharmacol Ther 86(6):678–682

    Article  PubMed  CAS  Google Scholar 

  • Liggins GC (1969) Premature delivery of fetal lambs infused with glucocorticoids. J Endocrinol 45:515–523

    Article  PubMed  CAS  Google Scholar 

  • Liggins GC, Howie RN (1972) A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome. Pediatrics 50:515–525

    PubMed  CAS  Google Scholar 

  • Liley AW (1963) Intrauterine transfusion of foetus in haemolytic disease. Br Med J ii:1107–1109

    Article  Google Scholar 

  • Mitsuda N, Tamaki H, Amino N, Hosono T, Miyai K, Tanizawa O (1992) Risk factors for developmental disorders in infants born to women with Graves’ disease. Obstet Gynecol 80(3 Pt 1):359–364

    PubMed  CAS  Google Scholar 

  • Myllynen P, Immonen E, Kummu M, Vähäkangas K (2009) Developmental expression of drug metabolizing enzymes and transporter proteins in human placenta and fetal tissues. Expert Opin Drug Metab Toxicol 5(12):1483–1499

    Article  PubMed  CAS  Google Scholar 

  • Nigro G, Stuart P, La Torre R, Best A (2005) Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 353:13–21

    Article  Google Scholar 

  • Oudijk MA, Michon MM, Kleinman CS et al (2000) Sotalol in the treatment of fetal dysrhythmias. Circulation 101:2721–2726

    PubMed  CAS  Google Scholar 

  • Rodeck CH, Kemp JR, Holman CA, Whitmore DN, Karnicki J, Austin MA (1981) Direct intravascular fetal blood transfusion by fetoscopy in severe Rhesus isoimmunisation. Lancet 1:625–627

    Article  PubMed  CAS  Google Scholar 

  • Simpson JM, Sharland GK (1998) Fetal tachycardias: management and outcome of 127 consecutive cases. Heart 79:576–581

    PubMed  CAS  Google Scholar 

  • Söderberg-NauclĂ©r C (2008) HCMV microinfections in inflammatory diseases and cancer. J Clin Virol 41(3):218–223

    Article  PubMed  Google Scholar 

  • Stone KM, Reiff-Eldridge R, White AD, Cordero JF, Brown Z, Alexander ER, Andrews EB (2004) Pregnancy outcomes following systemic prenatal acyclovir exposure: conclusions from the international acyclovir pregnancy registry, 1984–1999. Birth Defects Res A Clin Mol Teratol 70(4):201–207

    Article  PubMed  CAS  Google Scholar 

  • Strandberg L, Winqvist O, Sonesson SE, Mohseni S, Salomonsson S, Bremme K, Buyon JP, Julkunen H, Wahren-Herlenius M (2008) Antibodies to amino acid 200–239 (p200) of Ro52 as serological markers for the risk of developing congenital heart block. Clin Exp Immunol 154(1):30–37

    Article  PubMed  CAS  Google Scholar 

  • Strumper D, Durieux ME, Gogarten W, Van Aken H, Hartleb K, Marcus MA (2003) Fetal plasma concentrations after intraamniotic sufentanil in chronically instrumented pregnant sheep. Anesthesiology 98:1400–1406

    Article  PubMed  Google Scholar 

  • Teixeira JM, Glover V, Fisk NM (1999) Acute cerebral redistribution in response to invasive procedures in the human fetus. Am J Obstet Gynecol 181:1018–1025

    Article  PubMed  CAS  Google Scholar 

  • Tiblad E, Westgren M (2008) Fetal stem-cell transplantation. Best Pract Res Clin Obstet Gynaecol 22(1):189–201

    Article  PubMed  Google Scholar 

  • Touraine JL, Raudrant D, Royo C et al (1989) In-utero transplantation of stem cells in bare lymphocyte syndrome. Lancet I:1382

    Article  Google Scholar 

  • Van de Velde M, Van Schoubroech D, Lewi LE, Marcus MAE, Jani JC, Missant C et al (2005) Remifentanil for fetal immobilization and maternal sedation during fetoscopic surgery: a randomized double blind comparison with diazepam. Anesth Analg 101:251–258

    Article  PubMed  Google Scholar 

  • Van de Velde M, Jani J, De Buck F, Deprest J (2006) Fetal pain preception and pain management. Semin Fetal Neonatal Med 11(4):232–236

    Article  PubMed  Google Scholar 

  • Weiner CP, Williamson RA, Wenstrom KD, Sipes SL, Widness JA, Grant SS et al (1991) Management of fetal hemolytic disease by cordocenteses. II. Outcome of treatment. Am J Obstet Gynecol 165:1302–1307

    PubMed  CAS  Google Scholar 

  • Westgren M (2009) Intrauterine transplantation. Blood 113(19):4484

    Article  PubMed  CAS  Google Scholar 

  • Westgren M, Jabbar F, Larsen JF, Rahman F, Selbing A, Stangeberg M (1988) Introduction of a programme for intravascular transfusions at severe rhesus isoimmunization. J Perinat Med 16:417–422

    Article  PubMed  CAS  Google Scholar 

  • Westgren M, Ringden O, Eik-Nes S et al (1996) Lack of evidence of permanent engraftment after in utero fetal stem cell transplantation in congenital hemoglobinopathies. Transplantation 61:1176–1179

    Article  PubMed  CAS  Google Scholar 

  • Westgren M, Ringden O, Bartmann P et al (2002) Prenatal t-cell reconstitution after in utero transplantation with fetal liver cells in a patient with x-linked severe combined immunodeficiency. Am J Obstet Gynecol 187:475–482

    Article  PubMed  Google Scholar 

  • Yaffe SJ (1980) Clinical implications of perinatal pharmacology. Eur J Clin Pharmacol 18(1):3–7

    Article  PubMed  CAS  Google Scholar 

  • Zanjani ED, Ascensao JL, Flake AW et al (1992) The fetus as an optimal donor and recipient of hemopoietic stem cells. Bone Marrow Transplant 10(Suppl 1):107–114

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Magnus Westgren .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Westgren, M. (2011). Fetal Medicine and Treatment. In: Seyberth, H., Rane, A., Schwab, M. (eds) Pediatric Clinical Pharmacology. Handbook of Experimental Pharmacology, vol 205. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-20195-0_13

Download citation

Publish with us

Policies and ethics