Follow-up studies in prenatal medicine Nagel, H.T.C. Citation Nagel, H. T. C. (2007, February 14). Follow-up studies in prenatal medicine. Retrieved from https://hdl.handle.net/1887/9762 Version: Corrected Publisher’s Version Licence agreement concerning inclusion of doctoral thesis in the License: Institutional Repository of the University of Leiden Downloaded from: https://hdl.handle.net/1887/9762 Note: To cite this publication please use the final published version (if applicable). Proefschrift H. Nagel 11-01-2007 13:34 Pagina 11 C H ! T " # $ * eneral introduction 11 Proefschrift H. Nagel 11-01-2007 13:34 Pagina 12 C H ! T " # $ The %etus in prenatal m edicine ccording to M edline de-initions' a conce.tus is an em ,ryo until a .ostconce.tional age o- 9 1 ee2s (or a gestational age o- $* 1 ee2s) and 1 ill then ,e a -etus until ,irth. =- ,orn via,le' the .erson then ,ecom es an in-ant. The -etus is a uni>ue .atient -or several reasons. 6irst' there is a uni>ue relationshi. ,et1 een the m other and her un,orn child. lthough the -etus has his o1 n rights' he or she can only ,e treated via the m other. There-ore the .ur.orted rights o- $ the -etus can never ta2e .recedence over that o- the m other. ;econd' des.ite advances in m edical care there is stri2ing little 2no1 ledge a,out -etal live. ? uestions such as does the -etus [email protected] .ain' does it have a m em ory' are still unans1 ered. Third' the accessi,ility o- the -etus as a .atient is lim ited. 6inally' the ill -etus o-ten dis.lays a .aucity o- sym .tom s. The introduction o- real)tim e ultrasound and m olecular ,iology in m edicine' in the second .art o- the last century' has ushered a ne1 era in .renatal m edicine. :oth diagnostic and thera.eutic tools ,ecam e availa,le. 6etal m edicine has evolved -rom interventions aim ed at short term care in norm al develo.ing individuals to1 ards interventions aim ed at im .roving the starting).oint -or long)term .ostnatal thera.y. A hen as2ing a,out the .rognosis o- their -etus' .arents are thin2ing o- a -uture that lays t1 enty' thirty years ahead o- us' and are 1 ishing their children to ,e inde.endent individuals having their o1 n -am ily. They 2no1 ,ut not al1 ays realiBe that .renatal diagnosis m ay lead in som e cases to the initiation o- thera.y and in other cases to the a,stinence o- -urther diagnostic or thera.eutic interventions or even to -eticide or term ination o- .regnancy. =n order to .rovide e--ective counseling' centers -or -etal m edicine have an o,ligation to include long)term -ollo1 )u. o- the children that 1 ere the su,Cect o- -etal interventions -or diagnosis and/or thera.y. -ter all' there is a danger o- overenthusiastic doctors that value every im .rovem ent that -etal m edicine does accom .lish and -orget a,out the .arents that have to care -or a handica..ed child. ;uch DdedicatedD care 1 ill greatly in-luence the rest o- their lives and that o- other m em ,ers o- their -am ily. ,rie% histor) o% prenatal m edicine =n $9&&' Ea>ues) le@andre LeCum eau de Fergaradec 1 as the -irst to descri,e the detection o- the -etal heart ,eat ,y auscultation' in $(*8 Crem er -irst descri,ed &'/ the -etal electrocardiogram -rom the a,dom inal sur-ace o- a .regnant 1 om an. :y $(&*' the -irst success-ul -etal o.erations on guinea .ig -etuses had ,een .er-orm ed. =n the $(/*s and $(0*s' [email protected] ental -etal o,servations 1 ere done ,y .er-orm ing o.erations on -etal lam ,s 1 hile still in utero. This [email protected] ental -etal 1+ Proefschrift H. Nagel 11-01-2007 13:34 Pagina 13 G E N E R A L I N T R O D U C T I O N o,servations changed in the $(5*s into studying the causality o- -etal mal-ormations (i.e. ,y interru.ting the mesenteric ,lood su..ly' intestinal atresia occurred) and in the $(8*s and $(3*s into .er-orming -etal surgery to simulate a variety o- human congenital anomalies (congenital dia.hragmatic hernia in the lam,' 0)8 congenital hydrone.hrosis in the ra,,it and lam,). =n the $(5*s' ;myth descri,ed 3 invasive electrocardiogra.hic monitoring 1ith an intra)amniotic electrode. 6rom the $(8*s on1ard amniocentesis' -etosco.y' and ultrasonogra.hy' and conse>uently the .ossi,ility o- e@amining the -etus clinically' genetically and ,iochemically 1ere introduced. nalysis o- the contents o- amniotic -luid made .ossi,le the .renatal diagnosis o- many inherited meta,olic and chromosomal disorders and .ermitted assessment o- -etal .ulmonary maturity and the severity o- -etal hemolytic disease. The era o- -etal medicine had really ,egun. ;econd trimester amniocentesis is traditionally .er-ormed around $8 1ee2sG gestation. 4 ,servational data -rom the $(3*s suggested that' at this gestation' relatively large amounts o- amniotic -luid (u. to &* ml) could ,e as.irated 1ithout signi-icant technical di--iculties. This amount o- amniotic -luid 1as needed to yield a su--icient num,er o- via,le -etal cells to minimiBe the ris2 o- la,oratory -ailure. maCor disadvantage o- second trimester amniocentesis is that a -inal result is usually availa,le only a-ter $9 1ee2sG gestation. ;uch a long 1aiting .eriod -or a diagnosis can ,e very distressing -or cou.les. lternatively' earlier o.tions include chorionic villus sam.ling and early amniocentesis. Chorionic villus sam.ling 1as 9 -irst introduced in $(35. =t involves as.iration o- .lacental tissue rather than amniotic -luid. U ltrasound guided as.iration can ,e .er-ormed using either .ercutaneous transa,dominal or the transvaginal/transcervical a..roach. Currently the choice o- a..roach and the choice o- instruments tend to ,e ,ased on the o.eratorGs .ersonal .re-erence. There is an understanda,le desire to .er-orm chorionic villus sam.ling as early as .ossi,le. Technically' this can ,e done success-ully as early as 8 1ee2sG gestation. Ho1ever' a -e1 clusters o- lim, reduction de-ects have ,een re.orted -ollo1ing chorionic villus sam.ling 1ith a trend to1ard an increased incidence o- these de-ects 1hen chorionic villus ()&$ sam.ling 1as done ,e-ore ( 1ee2sG gestation. lthough large e.idemiological -ollo1)u. studies -ailed to con-irm this association' most clinicians delay this .rocedure until a-ter $* 1ee2sG gestation. "arly amniocentesis (()$0 1ee2sG gestation)' introduced in the late $(9*s' is technically the same as a HlateG && .rocedure [email protected] that less amniotic -luid is removed. U ltrasound needle guidance is considered to ,e an essential .art o- the .rocedure ,ecause o- the relatively small target area. The .resence o- t1o se.arate mem,ranes (amnion and chorion) until $5 1ee2sG gestation creates an additional technical di--iculty. 4 nly the amniotic (inner) sac should ,e as.irated' ,ecause the outer sac does not contain su--icient num,ers o- living -etal cells. The :ritish !ro-essor =an I onald ($($*)$(93) 1as the .ioneer -or the 1- Proefschrift H. Nagel 11-01-2007 13:34 Pagina 14 C H ! T " # $ utiliBation o- ultrasound in o,stetrics. :e-ore the discovery o- ultrasound' J)ray &/ 1as used -or -etal diagnosis. !lain J)rays yielded little in-ormation. The introduction o- li.o-.hyl/hydro.hyl radio.a>ue materials into the amniotic -luid (amniogram) -acilitated intra.eritoneal trans-usions ,ut 1as not suita,le -or -etal diagnosis. =n the N etherlands' o,stetric ultrasound 1as -irst develo.ed and introduced in the early 3*s in the Leiden and Utrecht University AomenGs Hos.itals. =m.ortant -or -etal diagnosis and thera.y 1as the introduction o- real)time ultrasound in the early $(9*s. milestone in .renatale medicine 1as achieved ,y Ailliam Liley. He demonstrated that severe red cell immuniBation' in-usion o- red cells in the intra).eritoneal cavity o- the -etus ameliorated severe &0 hydro.s. Iuring the $(8*s t1o clinical methods 1ere develo.ed to record -etal heart,eat .attern' one ,ased on -etal electrocardiogram (internal registration) and the other ,ased on ultrasound (e@ternal registration). =n ,oth methods' uterine contractions 1ere recorded simultaneously. Iuring the $(3*s' the use o- cardiotocogra.hy ,ecame common .ractice in Aestern la,or 1ards. =n $(8$' "rich ;aling introduced the conce.t o- ,lood .H measurements to -etal scal. ,lood &5 sam.led during la,or -or -etal surveillance. Three years later' ;aling .u,lished &8 normal values -or -etal .H and ,lood gas during la,or and at ,irth. :lood .H is .resently acce.ted ,y many as the ,iochemical gold standard in -etal monitoring during la,or. The advent o- echocardiogra.hy' and es.ecially M)mode and .ulsed 1ave Io..ler ushered the -ield o- -etal arrhythmia detection and di--erentiation. #o,inson and ;ha1)Iunn detailed the use o- M)mode in the evaluation o- -etal &3 arrhythmias during the early $(3*s. s ultrasound technology [email protected] to include t1o)dimensional and ,oth s.ectral and color Io..ler modes' additional echocardiogra.hic techni>ues -or the identi-ication and di--erentiation o- -etal arrhythmias 1ere descri,ed. The intravascular intrauterine -etal trans-usion .er-ormed ,y the use &9 o- -etosco.y 1as introduced ,y #odec2 in $(9$.