Maternal drug histories and central nervous system anomalies.

Abstract

SUMMARY Prescription data for the three months before the last menstrual period and for the first trimester of pregnancy were obtained for 764 mothers whose children had a defect of the central nervous system and for an equal number of mothers of control babies born from the same doctors' practices. There was a statistically significant difference overall between the numbers of mothers who were prescribed drugs in the study and control groups during the trimester before the last menstrual period but no such difference was found for the first pregnancy trimester, nor was there a significant difference for any specific group of drugs. For a composite group of non-steroid anti-inflammatory drugs, salicylates, and sulphasalazine there was a significant difference for the trimester before the last menstrual period. There are arguments against such an artificial grouping, however, and when the individual drugs were considered the comparisons were no longer significant. The odds ratios for all medicines containing folic acid taken in the trimester before the last menstural period were considerably less than unity, in contrast with nearly all other comparisons. This supports a suggested protective effect against neural tube defects of folic acid supplements begun before the onset of pregnancy but the odds ratios of these comparisons were not statistically significant. The present study was designed to cover notifications of central nervous system defects for one year, 1981. A total of 1078 notifications of actual or suspected defects were sent to the Committee on Safety of Medicines (CSM) by the Office of Population Censuses and Surveys (OPCS). These study children were paired with control children and analysis of maternal drug histories in the trimester (three calendar months) before the last menstrual period as well as in the first trimester of pregnancy was undertaken. Patients and methodsThe method of selection of patients and the study procedures were similar to those of the previous investigations. Each malformed (study) child was paired with a normal liveborn child without a congenital abnormality from the same medical practice. The control child was the nearest normal birth in the practice within three months after the birth of the study child, and if such a child was not available then the last normal child born within the practice before the birth of the study child was taken, provided that the interval did not exceed 12 months.Method. Information on each study and control 1052 copyright.

Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): Childhood cancer and the consumption of Debendox and related drugs in pregnancy

“…Congenital malformations of various types have been associated with DB ingestion in early pregnancy (Donnai & Harris, 1978;Rothman et al, 1979) but the results of large prospective cohort studies have failed to produce any evidence that DB is teratogenic in humans (Correy & Newman, 1971;Milkovich & van den Berg, 1976;Shapiro et al, 1977;Smithells & Sheppard, 1978;Harron et al, 1980;Gibson et al, 1981;Jick et al, 1981). Case control studies have supported these findings (Winship et al, 1984). A literature review by MacMahon (MacMahon, 1981) suggests that although a causal association of DB and malformations can never be absolutely denied, evidence indicates that any teratogenic potential is only rarely expressed.…”

Folate intake in Europe: recommended, actual and desired intake

“…Furthermore, women who started the use of supplements after conception seem to be classi®ed as`non-users' (Mills et al, 1989), whereas other observational studies have indicated that folic acid can also be protective in this period (Milunsky et al, 1989;Bower & Stanley, 1989;Shaw et al, 1995). Other reasons could be the broad range of central nervous system defects that were included as cases in both studies (Winship et al, 1984;Mills et al, 1989).…”

“…In two case-control studies the reduction in the risk of an NTD-affected birth was not signi®cant (Winship et al, 1984;Mills et al, 1989). The study of Winship et al, (1984) lacked information on the use of non-prescribed drugs (of which folic acid is a common one) and on the use of drugs prescribed by hospital physicians.…”

“…The study of Winship et al, (1984) lacked information on the use of non-prescribed drugs (of which folic acid is a common one) and on the use of drugs prescribed by hospital physicians. The zero ®nding in the study of Mills et al (1989) may be caused by the low prevalence of NTDs in the geographic area.…”

Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and case-control studies

“…A complete list of excluded studies is available from the authors. Thirteen studies that examined major malformations, 11 13 14 23 – 32 11 studies that examined oral cleft alone, 1 7 10 13 27 30 31 33 – 36 and three studies that examined other specific malformations37 – 39 were included (some providing information for more than one evaluation). One study unpublished at the time of consideration has since been published 26…”