Temporal trends in multiple births after in vitro fertilisation in

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                       7  Albaum MN, Hill LC, Murphy M, Li YH, Fuhrman CR, Britton CA, et al.        11 Tudor GR, Finlay DB. Error review: can this improve reporting perform-
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                       10 Du Toit G, Swingler G, Iloni K. Observer variation in detecting lymphad-
                          enopathy on chest radiography. Int J Tuberc Lung Dis 2002;6:814-7.            (Accepted 22 June 2005)




                       Temporal trends in multiple births after in vitro
                       fertilisation in Sweden, 1982-2001: a register study
                       Bengt Källén, Orvar Finnström, Karl Gösta Nygren, Petra Otterblad Olausson


Centre for             During the 20 years since the first child was born in
Reproduction
                       Sweden after in vitro fertilisation, clinical policy has
                                                                                                           What is already known on this topic
Epidemiology,
Tornblad Institute,    changed. During the early 1990s, the clinics perform-                               Pregnancies occurring after in vitro fertilisation
University of Lund,    ing in vitro fertilisation and the National Board of
Biskopsgatan 7,
                                                                                                           are characterised by high rates of multiple births
S-223 62 Lund,         Health and Welfare agreed to reduce the number of                                   and, as a consequence, high rates of preterm
Sweden                 embryos transferred to the uterus during in vitro ferti-                            births
Bengt Källén           lisation from three to two. Here, we describe the
professor
                       changes in multiple birth rates that have resulted from                             During the 1990s Swedish fertility clinics agreed
Department of          this change and their impact on the rate of preterm                                 to reduce from three to two the number of
Paediatrics,
University Hospital,   birth. In future papers we intend to describe maternal                              embryos transferred to the uterus during in vitro
S-581 85               and child characteristics in greater detail.                                        fertilisation
Linköping, Sweden
Orvar Finnström                                                                                            What this study adds
professor              Participants, methods, and results
IVF Clinic,
                                                                                                           The rate of multiple births after in vitro
Sophiahemmet,
                       In Sweden 17 hospitals or private clinics perform in                                fertilisation increased to a maximum of 29% in
S-114 86               vitro fertilisation. The National Board of Health and                               1991 but fell to 18.5% by 2001, resulting in a 70%
Stockholm, Sweden      Welfare requested information from these laboratories                               reduction of preterm births
Karl Gösta Nygren      on all women who had undergone in vitro fertilisation
associate professor
                       and who had had a baby or whose pregnancy outcome
Centre for
Epidemiology,
                       was not known. By linking these data with the Swedish                         born in Sweden and recorded in that registry
National Board of      medical birth register, we identified infants born from                       (2 039 943 during 1982-2001). We performed statisti-
Health and Welfare,    1982 to 2001.1 2 This register covers nearly all deliver-                     cal analyses using the Mantel-Haenszel technique, with
Stockholm, Sweden
                       ies in Sweden and is based on copies of medical docu-                         adjustment for various putative confounders. We
Petra Otterblad
Olausson               ments from the antenatal care, the delivery, and the                          expressed risks as odds ratios and calculated 95% con-
head of register       paediatric examination of newborn infants.                                    fidence intervals with a test-based method (according
Correspondence to:          We compared the infants born after in vitro fertili-                     to Miettinen).
Bengt Källén           sation and identified in the registry with all infants
embryol@                                                                                                  We studied a total of 13 261 births after in vitro fer-
embryol.lu.se                                                                                        tilisation, which resulted in 16 280 infants registered.
                                              35
                        Twin deliveries (%)




                                                                                                     The figure shows the changes in percentage of twin
BMJ 2005;331:382–3
                                              30
                                                                                                     deliveries according to year of birth, with the first seven
                                                                                                     years added because of low numbers. The twinning
                                              25                                                     rate increased to a maximum of 29% in 1991 and then
                                              20
                                                                                                     decreased steadily to 18.5% in 2001. The annual
                                                                                                     number of triplet deliveries after in vitro fertilisation
                                              15                                                     varied between 11 and 32 during 1992-6, and between
                                              10
                                                                                                     three and seven after 1997. All seven sets of
                                                                                                     quadruplets were born before 1994.
                                               5                                                          The impact of the reduction of multiple births on
                                               0                                                     the rate of preterm births is marked. In 1991, the crude
                                                1988 89 90 91 92 93 94 95 96 97 98 99 2000 01        odds ratio for preterm birth was 9.41 (95% confidence
                                                                                     Year of birth   interval 7.58 to 11.67) and the odds ratio adjusted for
                                                                                                     maternal age (in 5 year groups, < 20, 20-24, etc), parity
                       Changes in percentage of deliveries after in vitro fertilisation that
                       resulted in birth of twins, by year of birth (vertical bars are 95%
                       confidence intervals)                                                         This article was posted on bmj.com on 13 May 2005: http://bmj.com/cgi/
                                                                                                     doi/10.1136/bmj.38443.595046.E0


382                                                                                                                       BMJ VOLUME 331          13 AUGUST 2005       bmj.com
                                                                                                                                                      Papers

(1- ≥ 4), smoking (none, < 10, ≥ 10 cigarettes/day), and            to one, and a further reduction in multiple births is to
years of involuntary childlessness was 4.63 (3.62 to                be expected whereas the pregnancy rate seems to be
5.92). The corresponding odds ratios in 2001 were 2.15              little affected.4 5
(1.76 to 2.62) and 1.33 (1.12 to 1.57). The risk for pre-
                                                                    Contributors: BK planned the study, analysed the data, and
term birth after in vitro fertilisation was thus reduced            wrote the first manuscript draft. OF and KGN planned the
by 77% (crude odds ratio) and 72% (adjusted odds                    study, helped in interpreting the data, and helped finalise the
ratio).                                                             manuscript. POO planned the study, collected data, helped in
                                                                    interpreting the data, and helped finalise the manuscript. BK is
                                                                    guarantor for the study.
Comment                                                             Funding: Grant from K and A Wallenberg Foundation (BK).
                                                                    Competing interests: None declared.
The rate of high order multiple births after in vitro fer-
                                                                    Ethical approval: Not required.
tilisation declined markedly during the 1991-2001, and
the twinning rate decreased by about 40% from a                     1   Cnattingius S, Ericson A, Gunnarskog J, Källén B. A quality study of a
maximum of 29% in 1991 to 18.5% in 2001. At the                         medical birth registry. Scand J Soc Med 1990;18:143-8.
                                                                    2   Centre for Epidemiology, Swedish National Board of Health and Welfare.
same time, the population twinning rate increased. The                  The Swedish Medical Birth Registry—a summary of content and quality. Stock-
European twinning rate after in vitro fertilisation was                 holm: Swedish National Board of Health and Welfare, 2003. (www.sos.se/
                                                                        FULLTEXT/112/2003-112-3/2003-112-3.pdf)
24.4% in 2000.3 The declining rate of multiple births               3   Assisted reproductive technology in Europe, 2000. Results generated
affected the risk of preterm infants, which declined by                 from European registers by ESHRE. Hum Reprod 2004;19:490-503.
                                                                    4   Tiitinen A, Unkilakallio L, Halttunen M, Hydén-Granskog C. Impact of
over 70%, and improved neonatal outcome.                                elective single embryo transfer on the twin pregnancy rate. Hum Reprod
     The change in clinical policy in the early 1990s that              2003;18:1449-53.
                                                                    5   Thurin A, Hausken J, Hillensjö T, Jablonowska B, Pinborg A, Strandell A,
initiated these changes was reducing from three to two                  et al. Elective single-embryo transfer versus double-embryo transfer in in
the number of embryos transferred to the uterus dur-                    vitro fertilization. N Engl J Med 2004;351:2392-402.
ing in vitro fertilisation. At present, the number of                   (Accepted 31 March 2005)
embryos transferred is being reduced further, from two              doi 10.1136/bmj.38443.595046.E0




   When I use a word . . .
   Rabid responses

    At last the BMJ has realised that too many rapid                LABH, by another consonantal shift, became RABH,
    responses are actually rabid responses (BMJ                     which gave the Greek word ereptomai, “to feed,”
    2005;330:1284). But Grimm’s law predicts it.                    related to ereptein (Latin eripere), “to pluck.” Erepsin
       The brothers Grimm, Jakob Ludwig and Wilhelm                 was the name that Otto Cohnheim used in 1901,
    Karl, are best known for the collection of fairy tales          presumably surreptitiously, to describe a group of
    that bears their name, first published in two volumes in        polypeptidases found in the small intestine. The name
    1812 and 1814 under the title Kinder- und                       came from ereptomai plus pepsin.
    Hausmärchen, with a third volume added in 1822. The                RABH also gave the Latin word rabere or, by
    tales have enthralled children ever since, but the              Grimm’s law, rapere, “to seize.” Whence the English
    brothers collected them as an act of serious                    words rabies, rabid, rape, raptor, rapture, and rapid.
    scholarship, consulting mediaeval manuscripts and
                                                                    Rabies is the Latin word for fury or madness, because
    talking to villagers and peasants in the districts of
                                                                    it seizes your mind. In France, by another consonantal
    Hesse and Hanau and transcribing their tales.
                                                                    shift, it is called la rage. The disease has also been
       The brothers were also eminent philologists, and
                                                                    called lyssa, the Greek word for madness, which
    Jakob’s work is commemorated in Grimm’s law. That it
    is called Grimm’s law confirms another law, that of             Homer used to describe battle rage, but which later
    Non-Original Malappropriate Eponymous                           authors used to refer to other forms, such as Bacchic
    Nomenclature (NOMEN), which states that no                      frenzy, the frenzy of the Furies, and even passionate
    phenomenon is named after its discoverer. The                   love, before applying it to rabies in dogs.
    principles of Grimm’s law were first described by                  Ravenous, ravish, and reverie (which originally
    Friedrich von Schlegel in 1806 and the Danish                   meant delirium) also come from RABH, via yet
    philologist Rasmus Kristian Rask in 1818; Jakob                 another consonantal shift, this time Verner’s law, after
    Grimm discussed them in detail in 1822 in his book              the Danish philologist who described it (preceded by
    Deutsche Grammatik.                                             Grassman). Henry Fielding well understood how rapid
       Grimm’s law is complicated, but it governs the ways          ravishment could be. “Fireblood,” he wrote in Jonathan
    in which particular sets of consonants change from              Wild (1743), “who was no backward Youth, began to
    one to another as languages develop. The relevant               take [Loetitia] by the Hand, and proceeded so warmly,
    letter sets are the labials p, b, and f; the velars k, g, and   that, to imitate his Actions with the Rapidity of our
    h; and the dentals t, d, and th. This explains the              Narration, he in a few Minutes ravished this fair
    Latin-English and Greek-English correspondences of              Creature, or at least would have ravished her, if she had
    pes-foot, labia-lip, and fundamentum-bottom (labials);          not, by a timely Compliance, prevented him.”
    cardia-heart, genu-knee, and hostis-guest (velars); and            So, the next time you are moved to write a rapid
    tres-three, duo-two, and thyroid-door (dentals). It also        response, make sure that it’s not so rapid that it
    explains the association between rapid and rabid.               becomes a rabid response instead and gets turned
       The Indo-European root LABH gave the Greeks
                                                                    down by the editors.
    lambanein (future lçpsomai), “to seize,” from which we
    get analeptic, cataleptic, epileptic, narcoleptic, and          Jeff Aronson clinical pharmacologist, Oxford
    nympholeptic. And a syllable is letters taken together.         (jeffrey.aronson@clinpharm.ox.ac.uk)



BMJ VOLUME 331     13 AUGUST 2005     bmj.com                                                                                                            383

				
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