BLUK112-Rubin October 10, 2007 10:41Prescribing in PregnancyBLUK112-Rubin October 10, 2007 10:41Prescribingin PregnancyFourth editionEdited byPeter RubinNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKMargaret RamsayNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKBLUK112-Rubin October 10, 2007 10:41C 2000 BMJ Publishing GroupC 2008 by Blackwell PublishingBMJ Books is an imprint of the BMJ Publishing Group Limited, used under licenceBlackwell Publishing, Inc., 350 Main Street, Malden, Massachusetts 02148-5020, USABlackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UKBlackwell Publishing Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, AustraliaThe right of the Author to be identified as the Author of this Work has been asserted inaccordance with the Copyright, Designs and Patents Act 1988.All rights reserved. No part of this publication may be reproduced, stored in a retrievalsystem, or transmitted, in any form or by any means, electronic, mechanical,photocopying, recording or otherwise, except as permitted by the UK Copyright,Designs and Patents Act 1988, without the prior permission of the publisher.First published 1987Second Edition 1995Third Edition 2000Fourth Edition 20081 2008Library of Congress Cataloging-in-Publication DataPrescribing in pregnancy / edited by Peter Rubin, Margaret Ramsay. – 4th ed.p. ; cm.ISBN 978-1-4051-4712-5 (pbk.)1. Obstetrical pharmacology. I. Rubin, Peter C. II. Ramsay, M. M., M.D.[DNLM: 1. Drug Therapy. 2. Pregnancy. 3. PharmaceuticalPreparations–administration & dosage. 4. Pregnancy Complications–drug therapy.WQ 200 P932 2007]RG528.P74 2007618.2’061–dc222007017554ISBN: 978-1-4051-4712-5A catalogue record for this title is available from the British LibrarySet in 9.5/12pt Meridien by Aptara Inc., New Delhi, IndiaPrinted and bound in Singapore by Markono Print Media Pte LtdCommissioning Editor: Mary BanksEditorial Assistant: Victoria PittmanDevelopment Editor: Simone DudziakProduction Controller: Rachel EdwardsFor further information on Blackwell Publishing, visit our website:http://www.blackwellpublishing.comThe publisher’s policy is to use permanent paper from mills that operate a sustainableforestry policy, and which has been manufactured from pulp processed using acid-freeand elementary chlorine-free practices. Furthermore, the publisher ensures that the textpaper and cover board used have met acceptable environmental accreditation standards.Blackwell Publishing makes no representation, express or implied, that the drug dosagesin this book are correct. Readers must therefore always check that any productmentioned in this publication is used in accordance with the prescribing informationprepared by the manufacturers. The author and the publishers do not acceptresponsibility or legal liability for any errors in the text or for the misuse ormisapplication of material in this book.BLUK112-Rubin October 10, 2007 10:41ContentsContributors, viiPreface, xi1 Identifying fetal abnormalities, 1Lena M. Macara2 Treatment of common, minor and self-limitingconditions, 16Anthony J. Avery, Susan L. Brent3 Antibiotics in pregnancy, 36Tim Weller, Conor Jamieson4 Anticoagulants in pregnancy, 56Bethan Myers5 Treatment of cardiovascular diseases, 77Asma Khalil, Pat O’Brien6 Treatment of endocrine diseases, 89Anastasios Gazis7 Drugs in rheumatic disease during pregnancy, 98Mary Gayed, Caroline Gordon8 Psychotropic drugs in pregnancy, 114Neelam Sisodia9 Managing epilepsy and anti-epileptic drugs duringpregnancy, 126Michael F. O’Donoghue, Christine P. Hayes10 Treatment of diabetes in pregnancy, 150Nick Vaughan, Kate Morel, Louise Walker11 Treatment of asthma, 168Catherine Williamson, Anita Banerjee12 Drugs of misuse, 187Mary HepburnvBLUK112-Rubin October 10, 2007 10:41vi Contents13 Prescribing for the pregnant traveller, 205Pauline A. Hurley14 Drugs in breastfeeding, 216Jane M. RutherfordIndex, 231BLUK112-Rubin October 10, 2007 10:41ContributorsAnthony J. Avery, DM, FRCGPProfessor of Primary Health CareDivision of Primary CareSchool of Community HealthSciencesNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKAnita Banerjee, BSc, MBBS, MRCPSpR Endocrinology and DiabetesMellitusEndocrinology DepartmentHammersmith HospitalLondon, UKSusan L. Brent, BSc (Hons),MRPharmSDirector of PharmacyRegional Drug and TherapeuticsCentreWolfson UnitNewcastle upon Tyne, UKMary Gayed, MBChBAcademic Foundation Year TwoDoctorCity HospitalSandwell and West BirminghamHospitals NHS TrustBirmingham, UKAnastasios Gazis, DM, MRCPConsultant PhysicianDepartment of Endocrinology andDiabetesNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKCaroline Gordon, MRCPReader and Consultant inRheumatologyDepartment of RheumatologyDivision of Immunity andInfectionMedical SchoolUniversity of BirminghamBirmingham, UKChristine P. Hayes, MPhil,BSc (Hons)Epilepsy Specialist NurseNeurosciencesNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKMary Hepburn, BSc, MD, MRCGP,FRCOGConsultant ObstetricianPrincess Royal MaternityGlasgow, UKPauline A. Hurley, FRCOGConsultant Obstetrics, FetalMedicineThe Women’s CentreJohn Radcliffe HospitalOxford, UKviiBLUK112-Rubin October 10, 2007 10:41viii ContributorsConor Jamieson, BSc, PhD,MRPharmSPrincipal Pharmacist –Anti-infectivesHeart of England NHS FoundationTrustBirmingham, UKAsma Khalil, MB, BChSenior Research FellowHomerton University HospitalLondon, UKLena Macara, MD, FRCOGConsultant ObstetricianThe Queen Mother’s HospitalGlasgow, UKKate MorelDiabetes Nurse Specialist ManagerBrighton and Sussex UniversityHospitals NHS TurstBrighton, UKBethan Myers, MA, MRCP,FRCPath, DTM & HConsultant HaematologistDepartment of HaematologyNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKPat O’Brien, MRCOGObstetric LeadUniversity College LondonHospitalsLondon, UKMichael F. O’Donoghue, BSc, MBBS, MD, MRCP (UK)Consultant NeurologistNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKMargaret M. Ramsay, MA, MD,MRCP, FRCOGConsultant in FetomaternalMedicineNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKPeter C. Rubin, MA, DM, FRCPProfessor of TherapeuticsNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKJane M. Rutherford, DM, MRCOGConsultant in FetomaternalMedicineDepartment of ObstetricsNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKNeelam Sisodia, MBBS, MA,MRCPsychConsultant in Perinatal PsychiatryPerinatal Psychiatric ServiceMother and Baby UnitNottingham University HospitalsQueen’s Medical Centre CampusNottingham, UKN.J.A. Vaughan MA, MD, FRCPConsultant EndocrinologistBrighton and Sussex UniversityHospitals TrustRoyal Sussex County HospitalBrighton, UKLouise Walker, RDSpecialist Diabetes DieticianDiabetes CentreBrighton and Sussex UniversityHospitalsRoyal Sussex County HospitalBrighton, UKBLUK112-Rubin October 10, 2007 10:41Contributors ix
Tim Weller, MBChB, MD,
FRCPath (deceased)
Previously Consultant
Microbiologist
Department of Microbiology
City Hospital
Birmingham, UK
Catherine Williamson,
MD, MRCP
Senior Lecturer in Obstetric
Medicine
Hammersmith Hospital
Imperial College
London, UK
BLUK112-Rubin October 10, 2007 10:41
Preface
The use of drugs in women who are pregnant or breast feeding is
a question of fine balance. Harm may befall a baby because a drug
has been used, but mother and baby could suffer if a disease goes
untreated. Information about the safe and effective use of drugs
in pregnancy has not kept pace with the advances in other areas
of therapeutics. Systematic research involving drugs in pregnancy
is fraught with ethical, legal, emotional and practical difficulties
and in many cases our knowledge is based on anecdote or small
studies.
The purpose of this book is to bring together what is known
about prescribing in pregnancy and to put that information in a
clinical context. The first three editions were well received and this
has encouraged us to produce a fourth edition. All chapters have
been extensively revised or rewritten, with several new authors
bringing their clinical experience of this challenging subject.
We would like to thank Louise Sabir who once again has done
much behind-the-scenes work in contacting authors.
Acknowledgement
Dr Weller died suddenly while training for the London Marathon
shortly after submitting his chapter. He had also contributed to
the third edition and we gratefully acknowledge the professional
manner in which he approached these tasks.
Peter Rubin
Margaret Ramsay
Nottingham
xi
BLUK112-Rubin October 9, 2007 10:34
CHAPTER 1
Identifying fetal
abnormalities
Lena M. Macara
Key points
Days 18–55 postconception is the time of maximal teratogenic
potential when most organs are differentiating
Teratogenic effects of medications may affect both organ structure
and organ function
Detailed ultrasound assessment of the fetus by trained personnel
should detect most major structural abnormalities, but minor
abnormalities are often undetected
Patients at risk of neural tube defects (NTDs) should have 5 mg of
folic acid daily for a minimum of 6 wk prior to conception
Introduction
It is estimated that 2–3% of all pregnancies in the United King-
dom are affected by congenital abnormality. Almost half of these
abnormalities remain of uncertain aetiology, a further 25% may
be linked to a variety of genetic problems and only 2% are likely
to be associated with environmental factors that inc
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