Coumarins during pregnancy: long-term effects on growth and development of school-age children.
Anticoagulation during pregnancy is complicated because of potential risks for mother and foetus. Unfractionated or low-molecular-weight heparin is used for most anticoagulant indications. Its efficacy, however, in pregnant women with prosthetic heart valves is questioned, therefore coumarins are preferred for this indication. We studied long-term effects of prenatal coumarin-exposure on growth and on neurological, behavioural and cognitive development in 274 school-age children in comparison with 231 age-matched non-exposed controls. No major abnormalities were found. The exposed children had an increased risk for minor neurological dysfunction and for a low intelligence quotient (IQ below 80). The risk for a combination of two or more (minor) abnormalities was higher for the exposed children, RR = 7.6. We conclude that prenatal exposure to coumarins is associated with an increased risk for disturbances in development in school-age children. However, for the vast majority of children there is no clinical significant effect on growth and long-term development.
Wesseling
J
J
Department of Paediatrics, Beatrix Children's Hospital, University Hospital Groningen, The Netherlands.
Van Driel
D
D
Heymans
H S
HS
Rosendaal
F R
FR
Geven-Boere
L M
LM
Smrkovsky
M
M
Touwen
B C
BC
Sauer
P J
PJ
Van der Veer
E
E
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology*; D000015:Abnormalities, Multiple / Q000139:chemically induced* / Q000453:epidemiology; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002652:Child Behavior / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D015331:Cohort Studies; D003374:Coumarins / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D002658:Developmental Disabilities / Q000139:chemically induced* / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects; D005500:Follow-Up Studies; D005865:Gestational Age; D006130:Growth Disorders / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007360:Intelligence / Q000187:drug effects*; D007361:Intelligence Tests; D008297:Male; D008431:Maternal-Fetal Exchange; D009460:Neurologic Examination; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D011627:Puberty / Q000187:drug effects; D012306:Risk
D000925:Anticoagulants; D003374:Coumarins