medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2018-7-64-73medsovet-2409Research ArticleБеременность и родыPregnancy and childbirth«Сладж» в околоплодных водахAmniotic fluid sludgeПустотинаО. А.PustotinaO. A.

д.м.н.

MD

Российский университет дружбы народовРоссияPeoples’ Friendship University of RussiaRussian Federation201818042018076473Copyright © Пустотина О.А., 20182018Пустотина О.А.Pustotina O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/2409Цель

Цель: оценка эффективности комплексной терапии в профилактике акушерских и перинатальных осложнений у женщин со «сладжем» в околоплодных водах (ОВ). Дизайн исследования: 29 женщин (из них 8 – с длиной шейки матки (ШМ) > 25 мм, 21 – с ШМ ≤ 25 мм) со «сладжем» в  ОВ  по данным трансвагинального ультразвукового исследования (ТВ-УЗИ) в  15–24   нед. беременности получали антибактериальную терапию, дополнительно назначался индометацин и/или вагинальный прогестерон (ВП). Проводился динамический контроль ШМ, количества «сладжа» в ОВ, течения беременности, послеродового и раннего неонатального периода. У женщин с преждевременными родами (ПР) проводилось гистологическое исследование последа. Результаты: появление «сладжа» в ОВ ассоциировано с длительным течением инфекционно-воспалительных заболеваний во время беременности. Исход беременности и прогноз развития инфекционных осложнений в послеродовом и раннем неонатальном периоде напрямую определялись наличием дополнительных факторов риска и характером антибактериальной терапии в составе комплексного лечения. Так, проведение антибактериальной терапии при длине ШМ > 25 мм ассоциировалось с доношенной беременностью и  отсутствием инфекционных осложнений в послеродовом и раннем неонатальном периоде у 62,5% женщин, тогда как при длине ШМ ≤ 25мм – у 52,3%. Наиболее неблагоприятный прогноз отмечался у женщин с угрожающими ПР и «сладжем» в ОВ. Внутривенный курс антибактериальных средств значительно эффективнее их перорального/вагинального применения в составе комплексной терапии для предупреждения неблагоприятных исходов беременности и  предотвращения манифестации внутриутробного инфицирования (ВУИ) у новорожденного.

 

 

Objective: Evaluate the efficacy of combination therapy for the prevention of obstetric and perinatal complications in women with amniotic fluid (AF) ‘sludge’. Study Design: 29 women (of which 8 with the length of the cervix (LC) > 25 mm, 21 with the LC ≤ 25 mm) with AF ‘sludge’ detected by transvaginal ultrasound (TV-US) at 15-24 weeks of gestation received antibacterial therapy, additionally prescribed Indometacin and/or vaginal progesterone (VP). The women underwent the dynamic monitoring of the LC, the amount of AF ‘sludge’, the course of pregnancy, the postnatal and early neonatal period. A histological study of the secundines was conducted in women with preterm labor (PL). Results: the presence of AF ‘sludge’ is associated with the longterm infectious-inflammatory diseases during pregnancy. The outcomes of pregnancy and the probability of the development of infectious complications in the postpartum and early neonatal period were directly determined by the presence of additional risk factors and the antibiotic therapy regimen as part of the combination treatment. Thus, the antibacterial therapy in women with the LC> 25 mm was associated with congenital pregnancy and the absence of infectious complications in the postnatal and early neonatal period in 62.5% of women, whereas in women with the LC ≤ 25 mm in 52.3% of women. The most unfavorable prognosis was identified in women with threatening PL and AF ‘sludge’. The intravenous antibacterial therapy is much more efficient than oral /vaginal one as part of the combination therapy to prevent adverse pregnancy outcomes and the manifestation of intrauterine infection (IUI) in the newborns.

«сладж» в околоплодных водахВУИпреждевременные родыхориоамнионитцитозантибактериальная терапиявагинальный прогестерониндометацинкороткая шейка маткиAF ‘sludge’IUIpreterm laborchorioamnionitiscytosisantibacterial therapyvaginal progesteroneIndometacinshort cervixReferencesPustotina OA. Urogenital infection in pregnant women: clinical signs and outcome. J. Perinat. Med., 2013, 41: 135.Pustotina OA. Urogenital infection in pregnant women: clinical signs and outcome. J. Perinat. Med., 2013, 41: 135.Pustotina OA, Bubnova NI, Yezhova LS. Pathogenesis of hydramnios and oligohydramnios in placental infection and neonatal prognosis. The J Maternal-fetal & neonat medi, 2008, 21(1): 267-271.Pustotina OA, Bubnova NI, Yezhova LS. Pathogenesis of hydramnios and oligohydramnios in placental infection and neonatal prognosis. The J Maternal-fetal & neonat medi, 2008, 21(1): 267-271.Пустотина О.А., Бубнова Н.И., Ежова Л.С., Младковская Т.Б. Клинико-морфологическая оценка фетоплацентарного комплекса при много- и маловодии инфекционного генеза. Акушерство и гинекология, 2008, 2: 19-22.Pustomina OA, Bubnova NI, Yezhova LS, Mladkovskaya TB. Clinico-morphological evaluation of the fetoplacental complex in hydramnios and oligoamnios of the infectious genesis. Akusherstvo i Ginekologiya, 2008, 2: 19-22.Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science, 2014, 345(6198): 760–765.Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science, 2014, 345(6198): 760–765.Romero R, Miranda J, Chaiworapongsa T, Chaemsaithong P, Gotsch F, Dong Z, et al. A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes. Am J Reprod Immunol, 2014, 71(4): 330–358.Romero R, Miranda J, Chaiworapongsa T, Chaemsaithong P, Gotsch F, Dong Z, et al. A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes. Am J Reprod Immunol, 2014, 71(4): 330–358.Kim CJ, Romero R, Chaemsaithong P et al. Acute Chorioamnionitis and Funisitis: Definition, Pathologic Features, and Clinical Significance. Am J Obstet Gynecol, 2015 October, 213(4 0): 29–52.Kim CJ, Romero R, Chaemsaithong P et al. Acute Chorioamnionitis and Funisitis: Definition, Pathologic Features, and Clinical Significance. Am J Obstet Gynecol, 2015 October, 213(4 0): 29–52.Gomez-Lopez N, Romero R, Xu Y et al. Neutrophil Extracellular Traps in the Amniotic Cavity of Women with Intra-Amniotic Infection: A New Mechanism of Host Defense. Reprod Sci, 2017, 24(8): 1139-1153.Gomez-Lopez N, Romero R, Xu Y et al. Neutrophil Extracellular Traps in the Amniotic Cavity of Women with Intra-Amniotic Infection: A New Mechanism of Host Defense. Reprod Sci, 2017, 24(8): 1139-1153.Gomez-Lopez N, Romero R, Garsia-Flores V et al. Amniotic fluid neutrophils can phagocytize bacteria: A mechanism for microbial killing in the amniotic cavity. Am J Reprod Immunol, 2017, 78(4). doi: 10.1111/aji.12723.Gomez-Lopez N, Romero R, Garsia-Flores V et al. Amniotic fluid neutrophils can phagocytize bacteria: A mechanism for microbial killing in the amniotic cavity. Am J Reprod Immunol, 2017, 78(4). doi: 10.1111/aji.12723.Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel L, Hassan S. The role of inflammation and infection in preterm birth. Semin Reprod Med, 2007, 25(1): 21–39.Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel L, Hassan S. The role of inflammation and infection in preterm birth. Semin Reprod Med, 2007, 25(1): 21–39.Romero R, Miranda J, Chaiworapongsa T, Chaemsaithong P, Gotsch F, Dong Z et al. A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes. Am J Reprod Immunol, 2014, 71(4): 330–358.Romero R, Miranda J, Chaiworapongsa T, Chaemsaithong P, Gotsch F, Dong Z et al. A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes. Am J Reprod Immunol, 2014, 71(4): 330–358.Romero R, Miranda J, Kusanovic JP, Chaiworapongsa T, Chaemsaithong P, Martinez A et al. Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques. J Perinat Med, 2015, 43(1): 19–36.Romero R, Miranda J, Kusanovic JP, Chaiworapongsa T, Chaemsaithong P, Martinez A et al. Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques. J Perinat Med, 2015, 43(1): 19–36.Madan I, Romero R, Kusanovic JP, Mittal P, Chaiworapongsa T, Dong Z et al. The frequency and clinical significance of intra-amniotic infection and/or inflammation in women with placenta previa and vaginal bleeding: an unexpected observation. J Perinat Med, 2010, 38(3): 275–279.Madan I, Romero R, Kusanovic JP, Mittal P, Chaiworapongsa T, Dong Z et al. The frequency and clinical significance of intra-amniotic infection and/or inflammation in women with placenta previa and vaginal bleeding: an unexpected observation. J Perinat Med, 2010, 38(3): 275–279.Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med, 2001, 29(7): 1303–1310.Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med, 2001, 29(7): 1303–1310.Oh KJ, Kim SM, Hong JS et al. Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation. Am J Obstet Gynecol, 2017, 216(6): 604.e1-604.Oh KJ, Kim SM, Hong JS et al. Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation. Am J Obstet Gynecol, 2017, 216(6): 604.e1-604.Roberts DJ, Celi AC, Riley LE, Onderdonk AB, Boyd TK, Johnson LC et al. Acute histologic chorioamnionitis at term: nearly always noninfectious. PLoS One, 2012, 7(3): e31819.Roberts DJ, Celi AC, Riley LE, Onderdonk AB, Boyd TK, Johnson LC et al. Acute histologic chorioamnionitis at term: nearly always noninfectious. PLoS One, 2012, 7(3): e31819.Пустотина О.А. Клинические, морфологические и цитологические критерии диагностики внутриутробной инфекции и прогнозирования инфекционных осложнений у матери и новорожденного. М., 1999. Дисс. на соискание ученой степени кандидата медицинских наук, 143 с.Pustotina OA. Clinical, morphological and cytological criteria for diagnosing intrauterine infection and predicting infectious complications in the mother and the newborn. M., 1999. Thesis for a PhD in medical sciences, 143 p.Пустотина О.А. Клинико-патогенетическое обоснование акушерской тактики при патологии объема околоплодных вод. М. 2006. Дисс. на соискание ученой степени доктора медицинских наук, 237 с.Pustotina OA. Clinical and pathogenetic substantiation of obstetric tactics in the amniotic fluid volume pathology. M. 2006. Thesis for MD in medical sciences, 237 p.Chen GY, Nunez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol, 2010, 10(12): 826–37.Chen GY, Nunez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol, 2010, 10(12): 826–37.Romero R, Miranda J, Chaiworapongsa T, Korzeniewski SJ, Chaemsaithong P, Gotsch F et al. Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Reprod Immunol, 2014, 72(5): 458–474.Romero R, Miranda J, Chaiworapongsa T, Korzeniewski SJ, Chaemsaithong P, Gotsch F et al. Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Reprod Immunol, 2014, 72(5): 458–474.Romero R, Miranda J, Chaemsaithong P, Chaiworapongsa T, Kusanovic JP, Dong Z et al. Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med, 2014: 1–16.Romero R, Miranda J, Chaemsaithong P, Chaiworapongsa T, Kusanovic JP, Dong Z et al. Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med, 2014: 1–16.Romero R, Miranda J, Chaiworapongsa T, Chaemsaithong P, Gotsch F, Dong Z et al. Sterile intra- amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance. J Matern Fetal Neonatal Med, 2014: 1–17.Romero R, Miranda J, Chaiworapongsa T, Chaemsaithong P, Gotsch F, Dong Z et al. Sterile intra- amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance. J Matern Fetal Neonatal Med, 2014: 1–17.Gardella C, Riley DE, Hitti J, Agnew K, Krieger JN, Eschenbach D. Identification and sequencing of bacterial rDNAs in culture-negative amniotic fluid from women in premature labor. Am J Perinatol, 2004, 21: 319–323.Gardella C, Riley DE, Hitti J, Agnew K, Krieger JN, Eschenbach D. Identification and sequencing of bacterial rDNAs in culture-negative amniotic fluid from women in premature labor. Am J Perinatol, 2004, 21: 319–323.Davies D. Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov, 2003, 2: 114–122.Davies D. Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov, 2003, 2: 114–122.Espinoza J, Goncalves LF, Romero R, Nien JK, Stites S, Kim YM et al. The prevalence and clinical significance of amniotic fluid ‘sludge’ in patients with preterm labor and intact membranes. Ultrasound Obstet Gynecol, 2005, 25: 346–352.Espinoza J, Goncalves LF, Romero R, Nien JK, Stites S, Kim YM et al. The prevalence and clinical significance of amniotic fluid ‘sludge’ in patients with preterm labor and intact membranes. Ultrasound Obstet Gynecol, 2005, 25: 346–352.Romero R, Kusanovic JP, Espinoza J, Gotsch F, Nhan-Chang CL, Erez O et al. What is amniotic fluid ‘sludge’? Ultrasound Obstet Gynecol, 2007, 30: 793–798.Romero R, Kusanovic JP, Espinoza J, Gotsch F, Nhan-Chang CL, Erez O et al. What is amniotic fluid ‘sludge’? Ultrasound Obstet Gynecol, 2007, 30: 793–798.Nakayama T, Kikuchi A, Okuno T et al. Enlarging amniotic fluid ‘sludge’ in preterm labor associated with severe course of sepsis and recurrent tension pneumothorax in the infant. J Med Ultrason, 2012, 3993: 187-192.Nakayama T, Kikuchi A, Okuno T et al. Enlarging amniotic fluid ‘sludge’ in preterm labor associated with severe course of sepsis and recurrent tension pneumothorax in the infant. J Med Ultrason, 2012, 3993: 187-192.Kusanovic JP, Espinoza J, Romero R, Goncalves LF, Nien JK, Soto E et al. Clinical significance of the presence of amniotic fluid ‘sludge’ in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol, 2007 Jan, 27(1): 12-15.Kusanovic JP, Espinoza J, Romero R, Goncalves LF, Nien JK, Soto E et al. Clinical significance of the presence of amniotic fluid ‘sludge’ in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol, 2007 Jan, 27(1): 12-15.Kusanovic JP, Romero R, Espinoza J, Goncalves LF, Gotsch F, Camacho N, Lee W, Erez O, Schoen ML, Hassan S. Clinical significance of the presence of amniotic fluid ‘sludge’ in patients with cervical cerclage. Ultrasound Obstet Gynecol, 2007, 30(4): 411.Kusanovic JP, Romero R, Espinoza J, Goncalves LF, Gotsch F, Camacho N, Lee W, Erez O, Schoen ML, Hassan S. Clinical significance of the presence of amniotic fluid ‘sludge’ in patients with cervical cerclage. Ultrasound Obstet Gynecol, 2007, 30(4): 411.Romero R, Schaudinn C, Kusanovic JP et al. Detection of a microbial biofilm in intraamniotic infection. Am J Obstet Gynecol, 2008, 198: 135. e1-135.e5.Romero R, Schaudinn C, Kusanovic JP et al. Detection of a microbial biofilm in intraamniotic infection. Am J Obstet Gynecol, 2008, 198: 135. e1-135.e5.Paules C, Moreno E, Gonzales A et al. Amniotic fluid sludge as a marker of intra-amniotic infection and histological chorioamnionitis in cervical insufficiency: a report of four cases and literature review. J Matern Fetal Neonatal Med, 2016, 29(16): 2681-2684.Paules C, Moreno E, Gonzales A et al. Amniotic fluid sludge as a marker of intra-amniotic infection and histological chorioamnionitis in cervical insufficiency: a report of four cases and literature review. J Matern Fetal Neonatal Med, 2016, 29(16): 2681-2684.Fuchs F, Boucoiran I, Picard A et al. Impact of amniotic fluid “sludge” on the risk of preterm delivery. J Matern Fetal Neonatal Med. 2015, 28(10): 1176-1180.Fuchs F, Boucoiran I, Picard A et al. Impact of amniotic fluid “sludge” on the risk of preterm delivery. J Matern Fetal Neonatal Med. 2015, 28(10): 1176-1180.Hatanaka AR, Mattar R, Kawanami TEN et al. Amniotic fluid “sludge” is an independent risk factor for preterm delivery. J Matern Fetal Neonatal Med, 2016, 29(1): 120-125.Hatanaka AR, Mattar R, Kawanami TEN et al. Amniotic fluid “sludge” is an independent risk factor for preterm delivery. J Matern Fetal Neonatal Med, 2016, 29(1): 120-125.Adanir I, Ozyuncu O, Gokmen Karasu AF, Ongeroglu L. Amniotic fluid “sludge”, prevalence and clinical significance of it in asymptomatic patients at high risk for spontaneous preterm delivery. J Matern Fetal Neonatal Med, 2018, 31(2): 135-140.Adanir I, Ozyuncu O, Gokmen Karasu AF, Ongeroglu L. Amniotic fluid “sludge”, prevalence and clinical significance of it in asymptomatic patients at high risk for spontaneous preterm delivery. J Matern Fetal Neonatal Med, 2018, 31(2): 135-140.Kusanovic JP, Romero R, Martinovic C et al. Transabdominal collection of amniotic fluid “sludge” and identification of Candida albicans intra-amniotic infection. J Matern Fetal Neonatal Med, 2018, 31(10): 1279-1284.Kusanovic JP, Romero R, Martinovic C et al. Transabdominal collection of amniotic fluid “sludge” and identification of Candida albicans intra-amniotic infection. J Matern Fetal Neonatal Med, 2018, 31(10): 1279-1284.Kim SK, Romero R, Kusanovic JP, Erez O, Vaisbuch E, Mazaki-Tovi S et al. The prognosis of pregnancy conceived despite the presence of an intrauterine device (IUD). J Perinat Med, 2010, 38(1): 45–53.Kim SK, Romero R, Kusanovic JP, Erez O, Vaisbuch E, Mazaki-Tovi S et al. The prognosis of pregnancy conceived despite the presence of an intrauterine device (IUD). J Perinat Med, 2010, 38(1): 45–53.Lee JH, Romero R, Kim SM, Chaemsaithong P, Park CW, Park JS et al. A new antibiotic regimen treats and prevents intra-amniotic infection/inflammation in patients with preterm PROM. J Matern Fetal Neonatal Med, 2016, 29(17): 2727-2737.Lee JH, Romero R, Kim SM, Chaemsaithong P, Park CW, Park JS et al. A new antibiotic regimen treats and prevents intra-amniotic infection/inflammation in patients with preterm PROM. J Matern Fetal Neonatal Med, 2016, 29(17): 2727-2737.Hassan S, Romero R, Hendler I, Gomez R, Khalek N, Espinoza J, et al. A sonographic short cervix as the only clinical manifestation of intra-amniotic infection. J Perinat Med, 2006, 34(1): 13–19.Hassan S, Romero R, Hendler I, Gomez R, Khalek N, Espinoza J, et al. A sonographic short cervix as the only clinical manifestation of intra-amniotic infection. J Perinat Med, 2006, 34(1): 13–19.Hassan SS, Romero R, Vidyadhari D et al. PREGNANT trial. Vaginal progesterone reduces the rate of preterm birth in women with a sono-graphic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol, 2011, 38: 18–31.Hassan SS, Romero R, Vidyadhari D et al. PREGNANT trial. Vaginal progesterone reduces the rate of preterm birth in women with a sono-graphic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol, 2011, 38: 18–31.Myers KM, Fetlovich H, Mazza E et al. The mechanical role of the cervix in pregnancy. J Biomech, 2015, 48(9): 1511-1523.Myers KM, Fetlovich H, Mazza E et al. The mechanical role of the cervix in pregnancy. J Biomech, 2015, 48(9): 1511-1523.Romero R, Nicolaides KH, Conde-Agudelo A et al. Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study. Ultrasound Obstet Gynecol, 2016, 48(3): 308-317.Romero R, Nicolaides KH, Conde-Agudelo A et al. Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study. Ultrasound Obstet Gynecol, 2016, 48(3): 308-317.Kuon RJ, Garfield RE. Actions of progestins for the inhibition of cervical ripening and uterine contractions to prevent preterm birth. Facts Views Vis Obgyn, 2012, 4(2): 110-119.Kuon RJ, Garfield RE. Actions of progestins for the inhibition of cervical ripening and uterine contractions to prevent preterm birth. Facts Views Vis Obgyn, 2012, 4(2): 110-119.Baumbach J, Shi S, Shi L et al. Inhibition of uterine contractility with various tocolytics with and without progesterone: in vitro studies. Am J Obstet Gynecol, 2012, 206: 254.e1-5.Baumbach J, Shi S, Shi L et al. Inhibition of uterine contractility with various tocolytics with and without progesterone: in vitro studies. Am J Obstet Gynecol, 2012, 206: 254.e1-5.Pustotina OA. Effectiveness of dydrogesterone, 17-OH progesterone and micronized progesterone in prevention of preterm birth in women with a short cervix. J Matern Fetal Neonat Med, 2017, 1-9.Pustotina OA. Effectiveness of dydrogesterone, 17-OH progesterone and micronized progesterone in prevention of preterm birth in women with a short cervix. J Matern Fetal Neonat Med, 2017, 1-9.Rakoff-Nahoum S, Kong Y, Kleinstein SH, Subramanian S, Ahern PP, Gordon JI, Medzhitov R. Analysis of gene-environment interactions in postnatal development of the mammalian intestine. Proc Natl Acad Sci U S A, 2015, 112(7): 1929– 1936.Rakoff-Nahoum S, Kong Y, Kleinstein SH, Subramanian S, Ahern PP, Gordon JI, Medzhitov R. Analysis of gene-environment interactions in postnatal development of the mammalian intestine. Proc Natl Acad Sci U S A, 2015, 112(7): 1929– 1936.Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y, Li H, Steinert A, Heikenwalder M, Hapfelmeier S, Sauer U et al. The maternal microbiota drives early postnatal innate immune development. Science, 2016, 351(6279): 1296–1302.Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y, Li H, Steinert A, Heikenwalder M, Hapfelmeier S, Sauer U et al. The maternal microbiota drives early postnatal innate immune development. Science, 2016, 351(6279): 1296–1302.De La Cochetiere MF, Durand T, Lepage P, Bourreille A, Galmiche JP, Dore J. Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. J Clin Microbiol, 2005, 43(11): 5588–5592.De La Cochetiere MF, Durand T, Lepage P, Bourreille A, Galmiche JP, Dore J. Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. J Clin Microbiol, 2005, 43(11): 5588–5592.Акушерство и гинекология. Клинические рекомендации РОАГ. Под ред. Сухих Г.Т., Серова В.Н. 2016.Obstetrics and gynecology. Clinical guidelines of Russian Society of Obstetricians and Gynecologists. Edited by Sukhikh GT, Serov VN. 2016.

The authors declare that there are no conflicts of interest present.