In-utero exposure to antihypertensive medication and neonatal and child health outcomes

a systematic review

Catherine A Fitton, Markus F C Steiner, Lorna Aucott, J. P. Pell, Daniel F Mackay, Michael Fleming, James S McLay

Research output: Contribution to journalArticle

8 Citations (Scopus)
5 Downloads (Pure)

Abstract

BACKGROUND: Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which remains a leading cause of maternal and fetal morbidity and mortality. The long-term effects to the child of in-utero exposure to antihypertensive agents remains largely unknown.

OBJECTIVE: The aim of this study was to systematically review published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications.

METHODS: OVID, Scopus, EBSCO Collections, the Cochrane Library, and Web of Science databases were searched for relevant publications published between January 1950 and October 2016 and a total of 688 potentially eligible studies were identified.

RESULTS: Following review, 47 primary studies were eligible for inclusion. The Critical Appraisal Skills Programme checklist was used to assess study quality. Five studies were of excellent quality; the remainder were either mediocre or poor. Increased risk of low birth weight, low size for gestational age, preterm birth, and congenital defects following in-utero exposure to all antihypertensive agents were identified. Two studies reported an increased risk of attention deficit hyperactivity disorder following exposure to labetalol, and an increased risk of sleep disorders following exposure to methyldopa and clonidine.

CONCLUSION: The current systematic review demonstrates a paucity of relevant published high-quality studies. A small number of studies suggest possible increased risk of adverse child health outcomes; however, most published studies have methodological weaknesses and/or lacked statistical power thus preventing any firm conclusions being drawn.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.

Original languageEnglish
Pages (from-to)2123-2137
Number of pages15
JournalJournal of Hypertension
Volume35
Issue number11
Early online date11 Jul 2017
DOIs
Publication statusPublished - Nov 2017

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Antihypertensive Agents
Licensure
Library Science
Labetalol
Fetal Mortality
Methyldopa
Pregnancy
Premature Birth
Clonidine
Low Birth Weight Infant
Attention Deficit Disorder with Hyperactivity
Checklist
Gestational Age
Reproduction
Publications
Mothers
Databases
Hypertension
Morbidity
Drug Therapy

Keywords

  • adverse drug event
  • antihypertensive agents
  • child health
  • drug exposure in pregnancy
  • female
  • hypertension
  • in-utero exposure
  • pharmacovigilance
  • preeclampsia
  • pregnancy-induced hypertension

Cite this

In-utero exposure to antihypertensive medication and neonatal and child health outcomes : a systematic review. / Fitton, Catherine A; Steiner, Markus F C; Aucott, Lorna; Pell, J. P.; Mackay, Daniel F; Fleming, Michael; McLay, James S.

In: Journal of Hypertension, Vol. 35, No. 11, 11.2017, p. 2123-2137.

Research output: Contribution to journalArticle

Fitton, Catherine A ; Steiner, Markus F C ; Aucott, Lorna ; Pell, J. P. ; Mackay, Daniel F ; Fleming, Michael ; McLay, James S. / In-utero exposure to antihypertensive medication and neonatal and child health outcomes : a systematic review. In: Journal of Hypertension. 2017 ; Vol. 35, No. 11. pp. 2123-2137.
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abstract = "BACKGROUND: Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which remains a leading cause of maternal and fetal morbidity and mortality. The long-term effects to the child of in-utero exposure to antihypertensive agents remains largely unknown.OBJECTIVE: The aim of this study was to systematically review published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications.METHODS: OVID, Scopus, EBSCO Collections, the Cochrane Library, and Web of Science databases were searched for relevant publications published between January 1950 and October 2016 and a total of 688 potentially eligible studies were identified.RESULTS: Following review, 47 primary studies were eligible for inclusion. The Critical Appraisal Skills Programme checklist was used to assess study quality. Five studies were of excellent quality; the remainder were either mediocre or poor. Increased risk of low birth weight, low size for gestational age, preterm birth, and congenital defects following in-utero exposure to all antihypertensive agents were identified. Two studies reported an increased risk of attention deficit hyperactivity disorder following exposure to labetalol, and an increased risk of sleep disorders following exposure to methyldopa and clonidine.CONCLUSION: The current systematic review demonstrates a paucity of relevant published high-quality studies. A small number of studies suggest possible increased risk of adverse child health outcomes; however, most published studies have methodological weaknesses and/or lacked statistical power thus preventing any firm conclusions being drawn.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.",
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note = "ACKNOWLEDGEMENTS We acknowledge the support from the Farr Institute at Scotland. The Farr Institute at Scotland is supported by a 10-funder consortium: Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates), the Wellcome Trust, (MRC Grant No: MR/K007017/1).",
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AU - Fitton, Catherine A

AU - Steiner, Markus F C

AU - Aucott, Lorna

AU - Pell, J. P.

AU - Mackay, Daniel F

AU - Fleming, Michael

AU - McLay, James S

N1 - ACKNOWLEDGEMENTS We acknowledge the support from the Farr Institute at Scotland. The Farr Institute at Scotland is supported by a 10-funder consortium: Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates), the Wellcome Trust, (MRC Grant No: MR/K007017/1).

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N2 - BACKGROUND: Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which remains a leading cause of maternal and fetal morbidity and mortality. The long-term effects to the child of in-utero exposure to antihypertensive agents remains largely unknown.OBJECTIVE: The aim of this study was to systematically review published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications.METHODS: OVID, Scopus, EBSCO Collections, the Cochrane Library, and Web of Science databases were searched for relevant publications published between January 1950 and October 2016 and a total of 688 potentially eligible studies were identified.RESULTS: Following review, 47 primary studies were eligible for inclusion. The Critical Appraisal Skills Programme checklist was used to assess study quality. Five studies were of excellent quality; the remainder were either mediocre or poor. Increased risk of low birth weight, low size for gestational age, preterm birth, and congenital defects following in-utero exposure to all antihypertensive agents were identified. Two studies reported an increased risk of attention deficit hyperactivity disorder following exposure to labetalol, and an increased risk of sleep disorders following exposure to methyldopa and clonidine.CONCLUSION: The current systematic review demonstrates a paucity of relevant published high-quality studies. A small number of studies suggest possible increased risk of adverse child health outcomes; however, most published studies have methodological weaknesses and/or lacked statistical power thus preventing any firm conclusions being drawn.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.

AB - BACKGROUND: Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which remains a leading cause of maternal and fetal morbidity and mortality. The long-term effects to the child of in-utero exposure to antihypertensive agents remains largely unknown.OBJECTIVE: The aim of this study was to systematically review published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications.METHODS: OVID, Scopus, EBSCO Collections, the Cochrane Library, and Web of Science databases were searched for relevant publications published between January 1950 and October 2016 and a total of 688 potentially eligible studies were identified.RESULTS: Following review, 47 primary studies were eligible for inclusion. The Critical Appraisal Skills Programme checklist was used to assess study quality. Five studies were of excellent quality; the remainder were either mediocre or poor. Increased risk of low birth weight, low size for gestational age, preterm birth, and congenital defects following in-utero exposure to all antihypertensive agents were identified. Two studies reported an increased risk of attention deficit hyperactivity disorder following exposure to labetalol, and an increased risk of sleep disorders following exposure to methyldopa and clonidine.CONCLUSION: The current systematic review demonstrates a paucity of relevant published high-quality studies. A small number of studies suggest possible increased risk of adverse child health outcomes; however, most published studies have methodological weaknesses and/or lacked statistical power thus preventing any firm conclusions being drawn.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.

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KW - pharmacovigilance

KW - preeclampsia

KW - pregnancy-induced hypertension

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