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© Borgis - Postępy Nauk Medycznych 7/2016, s. 456-461
*Marzena Dębska
Modern possibilities of prenatal therapy
Współczesne możliwości terapii prenatalnej
2nd Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, Father Jerzy Popiełuszko “Bielański” Hospital, Independent Public Health Care Institution in Warsaw
Head of Department: Associate Professor Romuald Dębski, MD, PhD
Streszczenie
Dzięki powszechnemu wykonywaniu u kobiet ciężarnych badań ultrasonograficznych i prowadzeniu systematycznej diagnostyki prenatalnej, możliwe jest obecnie wykrywanie wielu chorób i wad wrodzonych na etapie życia płodowego. Coraz więcej nieprawidłowości może być leczonych już w okresie ciąży, na coraz wcześniejszym jej etapie, często na długo przed urodzeniem dziecka. Ponieważ leczenie prenatalne jest obarczone ryzykiem powikłań, które w rezultacie mogą prowadzić nawet do utraty ciąży, dlatego rekomendowane jest jedynie w przypadku najcięższych patologii. Umożliwia ono całkowite wyleczenie, jak w przypadku choroby hemolitycznej, lub, częściej, przeżycie chorego dziecka do okresu porodu i dalsze jego leczenie po porodzie, jak to ma miejsce w przypadkach przepukliny przeponowej czy uropatii zaporowych. Coraz częściej leczenie wewnątrzmaciczne podejmuje się również w wadach, które nie stanowią bezpośredniego zagrożenia życia dziecka, takich jak przepuklina oponowo-rdzeniowa czy większość przypadków stenozy aortalnej, a głównym jego celem jest zmniejszenie konsekwencji choroby i poprawienie rozwoju dziecka w późniejszym okresie życia.
Summary
Many diseases and congenital defects can be detected already during foetal life due to the widespread use of prenatal ultrasonography and the implementation of routine prenatal diagnostics. An increasing number of abnormalities can be treated in utero, at early stages of pregnancy, long before birth. Since prenatal treatment involves some risk of complications that may even result in the loss of pregnancy, it is recommended only in the most severe pathologies. The therapy allows for a complete recovery (for example in foetal haemolytic disease) or, more frequently, is aimed at prolonging survival of the foetus until birth to enable its further postnatal treatment (e.g. diaphragmatic hernia and obstructive uropathies). Prenatal interventions are also increasingly implemented in defects that do not pose a direct threat to the life of the foetus, such as myelomeningocele and most cases of critical aortic stenosis, in order to minimise the consequences of the disease and improve further development of the child.



Introduction
The beginnings of intrauterine treatment date back to the 1960s, when the global scientific environment focused on researching the issue of foetal haemolytic disease. However, the real development of prenatal therapy has been observed since the 1980s, which we owe to ultrasonography, which enabled real-time foetal imaging and intrauterine treatment monitoring. Prenatal treatment is used in a variety of diseases – from anaemia, through diaphragmatic hernia, spina bifida, to heart defects. The current intrauterine therapies can be classified into “needle” treatments, such as foetal transfusions, paracentesis, inserting shunt catheters, foetoscopy and open uterus surgeries. The last achivement in prenatal therapy are foetal cardiac interventions. This paper presents the selected types of pathologies observed at a prenatal stage as well as prenatal treatment strategies.
foetal haemolytic disease
Rh incompatibility
Red blood cell incompatibility still remains one of the main causes of foetal anaemia despite widespread prophylaxis with anti-Rh immunoglobulin. Prenatal therapy in foetal haemolytic disease involves repeated foetal RBC transfusions. The treatment is very effective and has remained relatively unchanged throughout the last decades. Although foetal transfusion belongs to routine procedures in fetal therapy centers, the therapy still requires much experience and precision (1). In recent years, much concern has been given to the fact that foetal transfusions should use maternal red blood cell preparations, if only possible, as mothers are safe RBC donors for their foetuses. Currently, we observe a huge breakthrough in the management of foetal haemolytic disease, which is possible due to the advances in both laboratory and ultrasonography diagnostics. At present, foetal anaemia, regardless of its cause, can be detected by Doppler assessment of peak systolic velocity in the middle cerebral artery (MCA PSV). This method, based on the use of hyperdynamic circulation in foetuses with anaemia, is characterised by almost 100% sensitivity in detecting at least moderate to severe anaemia (2). Its implementation at the beginning of the year 2000 considerably reduced the frequency of invasive diagnostic procedures (umbilical puncture-cordocentesis) aimed at the assessment of foetal blood count, and thus reduced the incidence of complications and intensification of immunisation in a pregnant woman (3). Similarly, a non-invasive determination of the foetal blood group is possible based on the assessment of foetal DNA (cfDNA) in the mother’s bloodstream. It is particularly useful in immunised women with antibodies from previous pregnancies. Blood type assay for some of the most common antigens causing foetal haemolytic disease (in Poland the assayed genes are RhD, c E, K; the tests are performed at the Institute of Haematology and Transfusion Medicine in Warsaw) allows for determining the risk for the foetuses in subsequent (current) pregnancies. This test is characterised by very high sensitivity and specificity. In the case of results indicating the absence of risk for the foetus (if the foetus lacks the antigen against which the antibodies are directed), further monitoring of the patient can be discontinued.
Foeto-neonatal alloimmune thrombocytopenia (FNAIT)
Foeto-neonatal alloimmune thrombocytopenia, which is associated with the presence of maternal antibodies against foetal platelets, is the most common cause of deep thrombocytopenia in foetuses and infants. Deep thrombocytopenia (platelet count below 50,000/mm3) is dangerous for foetuses since it may cause spontaneous bleedings. Intracranial haemorrhages (ICH), which may lead to the infant’s death or neurological complications of varying severity, are one of the most severe complications of foeto-neonatal alloimmune thrombocytopenia. Prenatal diagnosis of foetal thrombocytopenia is difficult as the disease shows no symptoms in ultrasonography. Unfortunately, the platelet antibody titres seem not be as helpful in assessing the severity of the disease as in RBC incompatibility. In some cases, in order to confirm or exclude foetal thrombocytopenia, diagnostic umbilical vessel puncture with complete blood count is performed. Foeto-neonatal alloimmune thrombocytopaenia (FNAIT) still is unlike the Rh-Disease, a not fully known and underdiagnosed disease. Its diagnosis is usually based on the analysis of complications that occurred in already born infants and the ex post search for thrombocytopenia. The implementation of Polish screening program (PREVFNAIT) (4) targeted at the most common cause of FNAIT – presence of anti-HPA-1a antibodies, has allowed to diagnose pregnant women who are at risk of foetal thrombocytopenia before the symptoms occur in the fetus or newborn. This allows for implementing a therapy, whose principles usually differ between different centres, but which is currently considered the primary non-invasive therapy. So far, no uniform management strategy for the disease has been developed. However, contrary to RBC incompatibility, where the main therapeutic management involves RBC transfusion, foetal platelet transfusions in foeto-neonatal alloimmune thrombocytopenia (FNAIT) are sporadic. The therapy is based on regular, usually weekly, administration of human immunoglobulin infusions (IVIG) in a pregnant woman, combined with steroids in some cases (5).
Multiple gestation complications
The common placenta in monochorionic pregnancy can involve typical complications, like twin-to-twin transfusion syndrome (TTTS) and twin reversed arterial perfusion (TRAP), which often require prenatal treatment.
Twin-to-twin transfusion syndrome (TTTS)
Monochorionic placenta contains, under physiological conditions, balanced vessel connections (anastomoses) which bind circulatory systems of both foetuses. Transfusion syndrome, which involves disproportionate blood flow between foetuses, occurs in approximately 15% of monochorionic diamniotic pregnancies. It involves a disproportionate blood flow from one foetus (donor) to the other (recipient) through abnormal, mostly arteriovenous, connections in the placenta. As a result, anaemia, hypovolaemia and oligohydramnios/anhydramnion develop in the donor foetus who ceases to grow and becomes hypotrophic. The recipient foetus, in turn, develops hypervolaemia, polycythaemia, polyhydramnios and is usually much larger than the donor. Both foetuses are at risk of severe complications, including intrauterine death (mostly the donor), heart failure (the recipient), preterm delivery and other. The therapy of the twin-to-twin transfusion syndrome has evolved from purely symptomatic methods – drainage of polyhydramnios in the recipient foetus (serial amnioreduction), septostomy (creating an artificial connection between amniotic sacs of the twins), foetal transfusions into the donor foetus – to causal treatment which currently involves foetoscopic laser ablation of vascular connections (6). Initially, vascular ablation was performed in a non-selective manner, coagulating all visible vessels connecting two placental poles along the amniotic septum. Nowadays, selective ablation of abnormal connections, which seem to be responsible for the complications, is preferred (7). Many studies have demonstrated the advantage of laser vascular ablation over other therapeutic methods in TTTS. Laser therapy, in comparison to amnioreduction, considerably reduces the number of distant complications in foetuses and infants, and it particularly improves their neurological condition. The main effect of amnioreduction, though, is to lengthen the duration of pregnancy in the absence of therapeutic effects on the increasing foetal hemodynamic disorders.
Twin reversed arterial perfusion (TRAP)
In the TRAP syndrome, one of the foetuses ceases to grow at a very early stage. Often, only the lower part of the body develops, while the heart does not in most cases. This is caused by the presence of arterial anastomosis (usually at the level of umbilical arteries), through which deoxygenated blood flows from very early stages of gestation from one foetus to the other, thus disturbing the development of the circulatory system. The affected foetus, referred to as the acardiac twin, is completely dependent on the circulation of the healthy foetus (pumping twin), and often comprises a considerable burden to the circulatory system of the latter. In extreme cases, when the size of the acardiac twin is large, heart failure and oedema occur in the pumping twin. Such a condition is a direct threat to its life and if this situation occurs before it is possible to safely deliver the pumping twin, then it is an indication for closing the umbilical cord of the acardiac twin. The procedure is usually performed by means of foetoscopic laser coagulation of the umbilical cord. This allows for further continuation of the pregnancy and the development of a healthy foetus.
Congenital diaphragmatic hernia (CDH)

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Piśmiennictwo
Van Kamp IL, Klumper FJ, Oepkes D et al.: Complications of intrauterine intravascular transfusion for fetal anemia due to maternal red-cell alloimmunization. Am J Obstet Gynecol 2005; 192(1): 171-177.
Mari G, Deter RL, Carpenter RL et al.: Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med 2000; 342: 9-14.
Society for Maternal-Fetal Medicine (SMFM), Mari G, Norton ME et al.: Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: the fetus at risk for anemia – diagnosis and management. Am J Obstet Gynecol 2015; 212: 697-710.
Uhrynowska M, Dębska M, Orzińska A, Brojer E: Zapobieganie alloimmunologicznej małopłytkowości płodów i noworodków (AIMPN) w Polsce – program PREVFNAIT. Gin Pol 2015; 1(86): 62-67.
Pacheco LD, Berkowitz RL, Moise KJ Jr et al.: Fetal and neonatal alloimmune thrombocytopenia: a management algorithm based on risk stratification. Obstet Gynecol 2011; 118: 1157-1163.
Roberts D, Neilson JP, Kilby MD, Gates S: Interventions for the treatment of twin-twin transfusion syndrome. Cochrane Database Syst Rev 2014; 1: CD002073.
Quintero RA, Ishii K, Chmait RH et al.: Sequential selective laser photocoagulation of communicating vessels in twin-twin transfusion syndrome. J Matern Fetal Neonatal Med 2007; 20: 763-768.
Deprest J, Brady P, Nicolaides K et al.: Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial. Semin Fetal Neonatal Med 2014; 19: 338-348.
Deprest J, Gratacos E, Nicolaides KH; FETO Task Group: Fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia: evolution of a technique and preliminary results. Ultrasound Obstet Gynecol 2004; 24: 121-126.
Sutton LN: Fetal surgery for neural tube defects. Best Pract Res Clin Obstet Gynaecol 2008; 22: 175-188.
Adzick NS, Thom EA, Spong CY et al.: A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 2011; 364: 993-1004.
Sarhan O, Zaccaria I, Macher MA et al.: Long-term outcome of prenatally detected posterior urethral valves: single center study of 65 cases managed by primary valve ablation. J Urol 2008; 179: 307-312.
Nicolaides KH, Cheng HH, Snijders RJ, Moniz CF: Fetal urine biochemistry in the assessment of obstructive uropathy. Am J Obstet Gynecol 1992; 166(3): 932-937.
DeFoor W, Clark C, Jackson E et al.: Risk factors for end stage renal disease in children with posterior urethral valves. J Urol 2008; 180 (4 suppl.): 1705-1708.
Sananes N, Favre R, Koh CJ et al.: Urological fistulas after fetal cystoscopic laser ablation of posterior urethral valves: surgical technical aspects. Ultrasound Obstet Gynecol 2015; 45(2): 183-189.
Moon-Grady AJ, Morris SA, Belfort M et al.: International Fetal Cardiac Intervention Registry: A Worldwide Collaborative Description and Preliminary Outcomes. J Am Coll Cardiol 2015 Jul 28; 66(4): 388-399. DOI: 10.1016/j.jacc.2015.05.037.
Dangel J, Dębska M, Koleśnik A et al.: Skuteczne walwuloplastyki aortalne u płodów – nowa era i nowe wyzwanie dla polskiej kardiologii perinatalnej. Echo Płodu 2012; 2(4): 16-20.
Dangel J, Dębska M, Koleśnik A et al.: Pierwsza w Polsce skuteczna przezskórna plastyka balonowa zastawki aortalnej u płodu. Gin Pol 2011; 82(8): 632-636.
Dębska M, Szymkiewicz-Dangel J, Koleśnik A et al.: Interwencyjne zabiegi kardiologiczne u płodów – czy jesteśmy do nich przygotowani? Gin Pol 2015; 86(4): 280-286.
otrzymano: 2016-06-03
zaakceptowano do druku: 2016-06-24

Adres do korespondencji:
*Marzena Dębska
2nd Department of Obstetrics and Gynecology Centre of Postgraduate Medical Education Father Jerzy Popiełuszko “Bielański” Hospital, Independent Public Health Care Institution in Warsaw
ul. Cegłowska 80, 01-809 Warszawa
tel. +48 (22) 569-02-74
marzena@debska.me

Postępy Nauk Medycznych 7/2016
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