Gripo infekcija nėštumo metu

Gripo infekcija nėštumo metu

Įvadas

Gripas yra ūminė virusinė kvėpavimo takų infekcija, pasižyminti sezoniškumu ir plintanti lašeliniu būdu per orą. Šiai infekcijai būdingas staigus simptomų pasireiškimas, ilga, sunki eiga ir dažnos komplikacijos. Gripą sukelia RNR virusai, kurie skirstomi į 4 gentis, iš kurių žmogui pavojingos 3 – A, B ir C tipo virusai. Virusas geba greitai mutuoti ir prisitaikyti. Pats pavojingiausias yra A tipo virusas, kurio atstovai (H1N1 – kiaulių gripas, H5N1 – paukščių gripas) pasaulyje sukelia pandemijas. Dauguma mokslinių tyrimų apie gripo virusinės infekcijos ir gydymo poveikį nėščiosioms ir vaisiui yra atlikta būtent šių pandemijų metu. Nėščiosios, vaikai ir senyvo amžiaus žmonės yra pati pažeidžiamiausia visuomenės dalis, todėl jų gydymui ir prevencijai turi būti skiriamas išskirtinis dėmesys.

 

Simptomai ir diagnostika

Nėščiųjų gripo simptomai nesiskiria nuo bendrosios populiacijos simptomų. Ligai būdinga >38 oC temperatūra, kosulys, šaltkrėtis, bendras silpnumas, raumenų, galvos ir gerklės skausmas. Tiesa, nėštumo metu ligos eiga būna sunkesnė, hospitalizavimo dažnis didesnis, o trukmė – ilgesnė [1, 2]. Dažnesnės letalinės išeitys, kurios susijusios su nėštumo metu pasikeitusiu moters kardiovaskuliniu krūviu, plaučių tūriu, metabolizmu ir hormonų pusiausvyra [1, 2].

Liga diagnozuojama įvertinus klinikinius požymius, epidemiologinius duomenis, anamnezę ir laboratorinius tyrimus. Tikslinga tirti ir tas nėščiąsias, kurios buvo paskiepytos sezonine vakcina nuo gripo, nes jos efektyvumas skiriasi priklausomai nuo gripo sezono (1 pav.).

1 pav. Sezoninės vakcinos nuo gripo efektyvumo palyginimas (Jungtinių Amerikos Valstijų ligų kontrolės ir prevencijos centro duomenys) [3]

*Vertintas periodas nuo 2016 metų balandžio 20 dienos iki 2017 metų balandžio 9 dienos.

**Duomenys dar gali keistis iki gripo sezono pabaigos.

Gripo poveikis vaisiui

Seroepidemiologinės studijos, atliktos 2000 metais, duomenimis, gripo virusas negali praeiti placentinio barjero ir užkrėsti vaisių antrame ir trečiame nėštumo trečdalyje [4]. Nėra įrodymų apie tiesioginį viruso teratogeninį ar toksinį poveikį vaisiui, tačiau gripo infekcija pirmame nėštumo trečdalyje siejama su didesne vaisiaus nechromosominių anomalijų rizika (galimybių santykis (GS) 2,0, 95 proc. intervale 1,62–2,48) [5]. 2013 metais atlikta sisteminė apžvalga ir metaanalizė nurodo šias dažniausias vaisiaus raidos anomalijas: lūpos ir gomurio defektai (GS 3,1, 2,20–4,42), nervinio vamzdelio defektai (GS 3,3, 2,05–5,40), hidrocefalija (GS 5,7, 1,1–30,0), įgimtosios širdies ydos (GS 1,6, 1,13–2,14), aortos vožtuvo atrezija / stenozė (GS 2,59, 1,21–5,54), skilvelių pertvaros defektai (GS 1,59, 1,24–2,14), virškinimo trakto defektai (GS 1,72, 1,09–2,68) ir galūnių redukcijos defektai (GS 2,03, 1,27–3,27) [5]. Atsakingas antipiretikų vartojimas labai sumažina hipertermijos sukeltų anomalijų dažnį.

Gripo infekcija didina savaiminio persileidimo, priešlaikinio gimdymo, vaisiaus augimo sulėtėjimo ir intrauterinės vaisiaus mirties riziką [1]. Diskutuojama, kas sukelia to priežastis – gripo sukeliama anoreksija, stiprus kosulys, o gal gydymas [1, 4].  

Gydymas

Empirinis gydymas turi būti skiriamas iš karto įtarus gripo virusinę infekciją, kai nėra galimybių greitai patvirtinti influenza viruso. Teigiama, kad ankstyvojo gydymo nauda yra didesnė už teorinę riziką. Ankstyvoji gydymo pradžia (per 48 val. nuo pirmųjų simptomų pasireiškimo) sutrumpina vidutinį gulėjimo ligoninėje laiką nuo 7,8 iki 2,2 dienų [6]. Gydymui rekomenduojami ir Lietuvoje yra prieinami yra 2 vaistai nuo gripo, priklausantys neuramidazių inhibitorių grupei – oseltamiviras ir zanamiviras (1 lentelė). Neetiška atlikti vaistų bandymus su nėščiosiomis, todėl oficialių tyrimų duomenų apie šių vaistų poveikį nėštumui nėra. Tačiau 3 moterys, iš dalyvavusiųjų klinikiniame oseltamiviro tyrime, pastojo. Vienai jų įvyko savaiminis persileidimas, viena nutraukė nėštumą savo noru ir viena pagimdė visiškai sveiką naujagimį. Kitose publikacijose nurodyta, kad oseltamiviras nedidina vaisiaus apsigimimų rizikos [7], todėl  vaistas gali būti pirmojo pasirinkimo.

Cheminis pavadinimas

Firminis pavadinimas

Dozė

Vaisto forma

Vartojimas

Gydymo trukmė

Oseltamiviras

Tamiflu®

75 mg

Peroralinės kapsulės

2 k./d. išgerti po 1 kapsulę

5 dienos

Zanamiviras*

Relenza®

10 mg

Inhaliuojamieji milteliai

2 k./d. inhaliuoti po 2 įkvėpimus

5 dienos

 1 lentelė. Vaistų nuo gripo viruso infekcijos gydymo rekomendacijos nėščiosioms

*Netinka nėščiosioms, sergančioms bronchų astma.

 

Be specifinio antivirusinio gydymo, labai svarbu gydyti karščiavimą ir simptomus. Antipiretikai ne tik sumažina įgimtųjų vaisiaus defektų riziką pirmuoju nėštumo trimestru, bet ir gimdymo metu karščiavimo sukeltų naujagimių traukulių, encefalopatijos, cerebrinio paralyžiaus ir naujagimių mirties riziką. Svarbu laiku pastebėti komplikacijas ir, jei reikia, skirti antibakterinį gydymą.

Gripu sergančios pacientės gydymo įstaigoje turėtų būti atskirtos nuo kitų ligonių tiek priėmimo skyriuje laukiant konsultacijos, tiek ir hospitalizacijos metu. Pacientės turėtų būti aprūpintos medicininėmis kaukėmis, laikytis rankų higienos, naudoti vienkartines nosines, dažnai vėdinti palatą ir mažiau kontaktuosi su kitais asmenimis.  

Gripo viruso infekcija, diagnozuota gimdymo metu ar po gimdymo, turėtų būti gydoma pagal jau nurodytas rekomendacijas. Oseltamiviro ir zanamiviro poveikis maitinamiems krūtimi kūdikiams neištirtas. Šie preparatai patenka į moters pieną, tačiau publikacijose neaprašyta jokių pasikartojančių naujagimių sveikatos sutrikimų [7, 8].

Amerikos ligų kontrolės ir prevencijos centras rekomenduoja atskirti sveiką naujagimį nuo gripu sergančios motinos. Jei atskyrimas nėra priimtinas, rekomenduojama laikytis asmens ir patalpų higienos, naujagimio lovytę statyti ne arčiau kaip 2 m nuo sergančios motinos lovos. Kai valdyti kosulį ir kvėpavimo takų sekreciją galimybių nėra, žindyti kūdikį nerekomenduojama, tačiau reikėtų tęsti laktacijos stimuliaciją, o naujagimį maitinti nutrauktu pienu.

 

Profilaktika

Pasaulio sveikatos organizacija rekomenduoja skiepyti visas nėščiąsias nepriklausomai nuo nėštumo trečdalio. Patariama skiepyti planuojančias pastoti moteris, kurių nėštumas tęsis gripo sezono metu. Tikslinga skiepyti ir žmogaus imunodeficito virusu sergančias moteris. Imunoprofilaktikai gali būti pasirenkama sezoninė trivalentė arba keturvalentė vakcina. Šios vakcinos vaisiui yra saugios [9]. Nėštumo metu nerekomenduojama tik gyvoji susilpninta vakcina (nosies purškalas), tačiau ji yra saugi po gimdymo.

Aktyvi nėščiųjų vakcinacija siejama su mažesne negyvagimio [10], priešlaikinio gimdymo [11, 12] rizika, didesniu vaisiaus svoriu [12], tačiau neturi įtakos persileidimų skaičiui [10].

Vakcinuotų nėščiųjų naujagimiams nustatytas imunitetas gripo virusui, kuris nežindant visiškai išnyksta tik kūdikiui sulaukus 3 mėnesių, o žindomiems išlieka žindymo laikotarpiu iki 6 mėnesių, priklausomai nuo žindyvės kraujyje esančių specifinių IgA koncentracijos [13, 14]. Tyrimų duomenimis, skiepytų moterų ir naujagimių sergamumas gripu bei į gripą panašia infekcija sumažėjo nuo 24 proc. iki 89 proc. [11, 15].

Kūdikius iki 6 mėnesių nerekomenduojama skiepyti gripo vakcina dėl abejotino imuninio atsako. Praktikoje naudojama kokono taktika, kai visi asmenys, kontaktuojantys su kūdikiu, yra skiepijami, imamasi kitų įmanomų profilaktikos priemonių. Taip sukuriama saugi aplinka [16].

Nėščiosioms, pajutusioms pirmuosius gripo viruso simptomus, gali būti skiriama chemoprofilaktika antivirusiniais vaistais (2 lentelė).

Cheminis pavadinimas

Firminis pavadinimas

Dozė

Vaisto forma

Vartojimas

Gydymo trukmė

Oseltamiviras

Tamiflu®

75 mg

Peroralinės kapsulės

1 kapsulę išgerti 1 k./d.

Iki 10 dienų

Zanamiviras*

Relenza®

10 mg

Inhaliuojamieji milteliai

Inhaliuoti po 2 įkvėpimus 1 k./d.

Iki 10 dienų

2 lentelė. Gripo viruso infekcijos profilaktikos rekomendacijos nėščiosioms

*Netinka nėščiosioms, sergančioms bronchų astma.

Apibendrinimas

  • Nėščiųjų gripo eiga yra sunkesnė, o komplikacijos dažnesnės.
  • Gripas pirmuoju nėštumo trečdaliu yra siejamas su didesne vaisiaus anomalijų rizika.
  • Nėščiųjų ir žindyvių gydymas antivirusiniais vaistais yra rekomenduojamas atsižvelgiant į naudos ir žalos santykį.
  • Vakcinacija mažina nėštumo komplikacijų dažnį ir didina naujagimių atsparumą gripo virusui.

 

Literatūra:

  1.  Centers for Disease Control and Prevention (CDC). Maternal and infant outcomes among severely ill pregnant and postpartum women with 2009 pandemic influenza A (H1N1)–United States, April 2009-August 2010. MMWR Morb Mortal Wkly Rep 2011; 60:1193.
  2. Siston AM, Rasmussen SA, Honein MA, et al. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 2010; 303:1517.
  3. https://www.cdc.gov/flu/professionals/vaccination/effectiveness-studies.htm.
  4. Irving WL, James DK, Stephenson T, et al. Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study. BJOG 2000; 107:1282.
  5. Luteijn JM, Brown MJ, Dolk H. Influenza and congenital anomalies: a systematic review and meta-analysis. Hum Reprod 2014; 29:809.
  6. Oboho IK, Reed C, Gargiullo P, et al. Benefit of Early Initiation of Influenza Antiviral Treatment to Pregnant Women Hospitalized With Laboratory-Confirmed Influenza. J Infect Dis 2016; 214:507.
  7. Greer LG, Leff RD, Rogers VL, et al. Pharmacokinetics of oseltamivir according to trimester of pregnancy. Am J Obstet Gynecol 2011; 204:S89.
  8. Wentges-van Holthe N, van Eijkeren M, van der Laan JW. Oseltamivir and breastfeeding. Int J Infect Dis 2008; 12:451.
  9. Tamma PD, Ault KA, del Rio C, et al. Safety of influenza vaccination during pregnancy. Am J Obstet Gynecol 2009; 201:547.
  10. Bratton KN, Wardle MT, Orenstein WA, Omer SB. Maternal influenza immunization and birth outcomes of stillbirth and spontaneous abortion: a systematic review and meta-analysis. Clin Infect Dis 2015; 60:e11.
  11. Thompson MG, Li DK, Shifflett P, et al. Effectiveness of seasonal trivalent influenza vaccine for preventing influenza virus illness among pregnant women: a population-based case-control study during the 2010-2011 and 2011-2012 influenza seasons. Clin Infect Dis 2014; 58:449.
  12. Steinhoff MC, Omer SB, Roy E, et al. Neonatal outcomes after influenza immunization during pregnancy: a randomized controlled trial. CMAJ 2012; 184:645.
  13. Nunes MC, Cutland CL, Jones S, et al. Duration of Infant Protection Against Influenza Illness Conferred by Maternal Immunization: Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr 2016; 170:840.
  14. Schlaudecker EP, Steinhoff MC, Omer SB, et al. IgA and neutralizing antibodies to influenza a virus in human milk: a randomized trial of antenatal influenza immunization. PLoS One 2013; 8:e70867.
  15. Demicheli V, Jefferson T, Al-Ansary LA, et al. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev 2014; :CD001269.
  16. https://www.cdc.gov/flu/protect/children.htm.

Gyd. Sandra Tumėnė

Vilniaus universiteto Medicinos fakulteto Klinikinės medicinos instituto Akušerijos ir ginekologijos klinika


137 mintys apie “Gripo infekcija nėštumo metu

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