Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy

Lasse Karlsen Eck; Thomas Bo Jensen; Dimitrios Mastrogiannis; Arendse Torp-Pedersen; Bjarke Askaa; Torben Kjær Nielsen; Henrik Enghusen Poulsen; Espen Jimenez-Solem; Jon Trærup Andersen

doi:10.1097/AOG.0000000000001936

Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy

Lasse Karlsen Eck, Thomas Bo Jensen, Dimitrios Mastrogiannis, Arendse Torp-Pedersen, Bjarke Askaa, Torben Kjær Nielsen, Henrik Enghusen Poulsen, Espen Jimenez-Solem, Jon Trærup Andersen

Department of Clinical Medicine

19 Citations (Scopus)

Abstract

OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring.

METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997 and 2011 identified from the Medical Birth Registry. Methotrexate-exposed fathers were identified from the National Prescription Registry. From the national Hospital Registry we identified paternity, live births, and stillbirths as well as discharge diagnoses on congenital malformations.

RESULTS: We identified 849,676 live births with known paternity. There were 127 live births of methotrexate-exposed fathers. Of these, four (3.2%) had major malformations compared with 28,814 (3.4%) of the unexposed. The odds ratio (OR) for major congenital malformation among exposed fathers compared with unexposed was 0.93 (95% confidence interval [CI] 0.34-2.51) and when adjusted for year of birth, maternal age, educational length, household income, and parity, the adjusted OR was 1.01 (95% CI 0.37-2.74). There were no stillbirths in the methotrexate-exposed group compared with 2,541 (0.3%) in the unexposed group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers.

CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available data suggest that prepregnancy paternal methotrexate exposure should not be of major concern. Multinational recommendations should be changed accordingly.

Original language	English
Journal	Obstetrics and Gynecology
Volume	129
Issue number	4
Pages (from-to)	707-714
ISSN	0029-7844
DOIs	https://doi.org/10.1097/AOG.0000000000001936
Publication status	Published - 2017

Keywords

Adult
Cohort Studies
Congenital Abnormalities
Denmark
Female
Humans
Immunosuppressive Agents
Infant, Newborn
Male
Methotrexate
Paternal Exposure
Pregnancy
Premature Birth
Prescription Drugs
Registries
Risk Assessment
Statistics as Topic
Stillbirth
Journal Article

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10.1097/AOG.0000000000001936

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title = "Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy",

abstract = "OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring.METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997 and 2011 identified from the Medical Birth Registry. Methotrexate-exposed fathers were identified from the National Prescription Registry. From the national Hospital Registry we identified paternity, live births, and stillbirths as well as discharge diagnoses on congenital malformations.RESULTS: We identified 849,676 live births with known paternity. There were 127 live births of methotrexate-exposed fathers. Of these, four (3.2%) had major malformations compared with 28,814 (3.4%) of the unexposed. The odds ratio (OR) for major congenital malformation among exposed fathers compared with unexposed was 0.93 (95% confidence interval [CI] 0.34-2.51) and when adjusted for year of birth, maternal age, educational length, household income, and parity, the adjusted OR was 1.01 (95% CI 0.37-2.74). There were no stillbirths in the methotrexate-exposed group compared with 2,541 (0.3%) in the unexposed group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers.CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available data suggest that prepregnancy paternal methotrexate exposure should not be of major concern. Multinational recommendations should be changed accordingly.",

keywords = "Adult, Cohort Studies, Congenital Abnormalities, Denmark, Female, Humans, Immunosuppressive Agents, Infant, Newborn, Male, Methotrexate, Paternal Exposure, Pregnancy, Premature Birth, Prescription Drugs, Registries, Risk Assessment, Statistics as Topic, Stillbirth, Journal Article",

author = "Eck, {Lasse Karlsen} and Jensen, {Thomas Bo} and Dimitrios Mastrogiannis and Arendse Torp-Pedersen and Bjarke Askaa and Nielsen, {Torben Kj{\ae}r} and Poulsen, {Henrik Enghusen} and Espen Jimenez-Solem and Andersen, {Jon Tr{\ae}rup}",

year = "2017",

doi = "10.1097/AOG.0000000000001936",

language = "English",

volume = "129",

pages = "707--714",

journal = "Obstetrics and Gynecology",

issn = "0029-7844",

publisher = "Lippincott Williams & Wilkins",

number = "4",

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T1 - Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy

AU - Eck, Lasse Karlsen

AU - Jensen, Thomas Bo

AU - Mastrogiannis, Dimitrios

AU - Torp-Pedersen, Arendse

AU - Askaa, Bjarke

AU - Nielsen, Torben Kjær

AU - Poulsen, Henrik Enghusen

AU - Jimenez-Solem, Espen

AU - Andersen, Jon Trærup

PY - 2017

Y1 - 2017

N2 - OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring.METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997 and 2011 identified from the Medical Birth Registry. Methotrexate-exposed fathers were identified from the National Prescription Registry. From the national Hospital Registry we identified paternity, live births, and stillbirths as well as discharge diagnoses on congenital malformations.RESULTS: We identified 849,676 live births with known paternity. There were 127 live births of methotrexate-exposed fathers. Of these, four (3.2%) had major malformations compared with 28,814 (3.4%) of the unexposed. The odds ratio (OR) for major congenital malformation among exposed fathers compared with unexposed was 0.93 (95% confidence interval [CI] 0.34-2.51) and when adjusted for year of birth, maternal age, educational length, household income, and parity, the adjusted OR was 1.01 (95% CI 0.37-2.74). There were no stillbirths in the methotrexate-exposed group compared with 2,541 (0.3%) in the unexposed group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers.CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available data suggest that prepregnancy paternal methotrexate exposure should not be of major concern. Multinational recommendations should be changed accordingly.

AB - OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring.METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997 and 2011 identified from the Medical Birth Registry. Methotrexate-exposed fathers were identified from the National Prescription Registry. From the national Hospital Registry we identified paternity, live births, and stillbirths as well as discharge diagnoses on congenital malformations.RESULTS: We identified 849,676 live births with known paternity. There were 127 live births of methotrexate-exposed fathers. Of these, four (3.2%) had major malformations compared with 28,814 (3.4%) of the unexposed. The odds ratio (OR) for major congenital malformation among exposed fathers compared with unexposed was 0.93 (95% confidence interval [CI] 0.34-2.51) and when adjusted for year of birth, maternal age, educational length, household income, and parity, the adjusted OR was 1.01 (95% CI 0.37-2.74). There were no stillbirths in the methotrexate-exposed group compared with 2,541 (0.3%) in the unexposed group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers.CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available data suggest that prepregnancy paternal methotrexate exposure should not be of major concern. Multinational recommendations should be changed accordingly.

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KW - Cohort Studies

KW - Congenital Abnormalities

KW - Denmark

KW - Female

KW - Humans

KW - Immunosuppressive Agents

KW - Infant, Newborn

KW - Male

KW - Methotrexate

KW - Paternal Exposure

KW - Pregnancy

KW - Premature Birth

KW - Prescription Drugs

KW - Registries

KW - Risk Assessment

KW - Statistics as Topic

KW - Stillbirth

KW - Journal Article

U2 - 10.1097/AOG.0000000000001936

DO - 10.1097/AOG.0000000000001936

M3 - Journal article

C2 - 28277353

SN - 0029-7844

VL - 129

SP - 707

EP - 714

JO - Obstetrics and Gynecology

JF - Obstetrics and Gynecology

IS - 4

ER -

Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy

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Keywords

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