Raskausajan lääkkeiden käyttö ja syntyneiden lasten terveys 1996−2019

Raskaudenaikaisen lääkkeiden käytön vaikutuksista sikiöön tiedetään vähän. Vain muutaman kymmenen lääkkeen tiedetään varmasti aiheuttavan sikiövaurioita. Toisaalta vain harvan lääkkeen tiedetään olevan turvallisia raskausaikana käytettynä. Käyttöön tulee jatkuvasti uusia lääkkeitä, joilla tieto raskaudenaikaisen käytön turvallisuudesta perustuu vain prekliinisiin tutkimuksiin. Tietoa raskaudenaikaisen lääkityksen mahdollisista sikiövaikutuksista kertyy vähitellen tilanteissa, joissa lääkehoito on välttämätöntä, tai kun altistuminen on tapahtunut aikana, jolloin raskaus ei ole vielä tiedossa. Tässä raportissa kuvataan Lääkealan turvallisuus- ja kehittämiskeskus Fimean, Kelan ja Terveyden ja hyvinvoinnin laitoksen (THL) tutkimusyhteistyön keskeiset tulokset raskaudenaikaisesta lääkkeiden käytöstä ja sen vaikutuksista vastasyntyneiden terveyteen ja epämuodostumien kokonaisesiintyvyyteen syntyneillä lapsilla tai raskauden-keskeytyksissä Suomessa vuosina 1996−2019. Raportti perustuu kansallisiin terveysrekistereihin: THL:n ylläpitämien syntyneiden lasten rekisterin, raskaudenkeskeyttämis- ja epämuodostumarekisterien sekä Kelan reseptitiedoston ja lääkekorvausoikeuksien tiedoston tietoihin

Second-generation antipsychotic use during pregnancy and risk of congenital malformations

Purpose To study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM). Methods A population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996-2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models. Results Use of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72-1.19) or to F-GA users (OR 0.82; 95% CI 0.56-1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19-3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35-10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results. Conclusions Olanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.</p

Ethics and legal requirements for data linkage in 14 European countries for children with congenital anomalies

INTRODUCTION: Linking healthcare data sets can create valuable resources for research, particularly when investigating rare exposures or outcomes. However, across Europe, the permissions processes required to access data can be complex. This paper documents the processes required by the EUROlinkCAT study investigators to research the health and survival of children with congenital anomalies in Europe. METHODS: Eighteen congenital anomaly registries in 14 countries provided information on all the permissions required to perform surveillance of congenital anomalies and to link their data on live births with available vital statistics and healthcare databases for research. Small number restrictions imposed by data providers were also documented. RESULTS: The permissions requirements varied substantially, with certain registries able to conduct congenital anomaly surveillance as part of national or regional healthcare provision, while others were required to obtain ethics approvals or informed consent. Data linkage and analysis for research purposes added additional layers of complexity for registries, with some required to obtain several permissions, including ethics approvals to link the data. Restrictions relating to small numbers often resulted in a registry’s data on specific congenital anomalies being unusable. CONCLUSION: The permissions required to obtain and link data on children with congenital anomalies varied greatly across Europe. The variation and complexity present a significant obstacle to the use of such data, especially in large data linkage projects. Furthermore, small number restrictions severely limited the research that could be performed for children with specific rare congenital anomalies

DNA Copy Number Losses in Human Neoplasms

This review summarizes reports of recurrent DNA sequence copy number losses in human neoplasms detected by comparative genomic hybridization. Recurrent losses that affect each of the chromosome arms in 73 tumor types are tabulated from 169 reports. The tables are available online at http://www.amjpathol.org and http://www.helsinki.fi/∼lgl_www/CMG.html. The genes relevant to the lost regions are discussed for each of the chromosomes. The review is supplemented also by a list of known and putative tumor suppressor genes and DNA repair genes (see Table 1, online). Losses are found in all chromosome arms, but they seem to be relatively rare at 1q, 2p, 3q, 5p, 6p, 7p, 7q, 8q, 12p, and 20q. Losses and their minimal common overlapping areas that were present in a great proportion of the 73 tumor entities reported in Table 2 (see online) are (in descending order of frequency): 9p23-p24 (48%), 13q21 (47%), 6q16 (44%), 6q26-q27 (44%), 8p23 (37%), 18q22-q23 (37%), 17p12-p13 (34%), 1p36.1 (34%), 11q23 (33%), 1p22 (32%), 4q32-qter (31%), 14q22-q23 (25%), 10q23 (25%), 10q25-qter (25%),15q21 (23%), 16q22 (23%), 5q21 (23%), 3p12-p14 (22%), 22q12 (22%), Xp21 (21%), Xq21 (21%), and 10p12 (20%). The frequency of losses at chromosomes 7 and 20 was less than 10% in all tumors. The chromosomal regions in which the most frequent losses are found implicate locations of essential tumor suppressor genes and DNA repair genes that may be involved in the pathogenesis of several tumor types