Table 1 Published studies on the use of TNF-α blockers in IBD pregnancies
From: Safety of TNF-α inhibitors during IBD pregnancy: a systematic review
Author | Year | Anti-TNF | Stage of pregnancy | Study type | Mode of delivery | Outcome of pregnancies |
|---|---|---|---|---|---|---|
James [25] | 2001 | IFX | P(T2) | Case report | Unknown | Normal, healthy, full term |
Srinivasan [21] | 2001 | IFX | PC/P(T1) | Case report | Unknown | Premature, preterm, LBW. Adverse outcome: intracerebral and intrapulmonary bleeding followed by death 3 days later (metronidazole + azathioprine + 5-ASA was also administered in pregnancy for treatment of flare and fistulae) |
Bank et al. [24] | 2002 | IFX | P(T1-T2) | Case report | Unknown | Normal, healthy, full term (correspondence with authors) |
Burt et al. [27] | 2003 | IFX | PC | Case report | C-section | Normal, healthy, preterm (36 weeks) |
Katz et al. [49] | 2004 | IFX | 53/96 PC; 58/96 P(T1); 6/96 unknown | Case series from Infliximab Safety Database (82 CD, one UC, 10 RA, 3 unknown); 96 women, 72 births | Unknown | 64/96 were live births (1 preterm death at 24 week, 1 full-term with tetralogy of Fallot, 1 perinatal sepsis, 1 intestinal malrotation, 1 developmental delay); 4 pregnancies ended with twins. 14/96 were miscarriages, 18/96 were therapeutic terminations |
Mahadevan et al.[32] | 2005 | IFX | 9/10 PC; 8/10 P(T2); 8/10 P(T3); 7/10 PP | Case series (n = 10 women) | 8/10 C-section, 2/10 Vaginal | 3/10 were preterm, 1/10 were LBW, 2/10 were neonatal illnesses, which resolved. All normal at follow-up |
Tursi [34] | 2006 | IFX | PC/P(T1-T3)/PP | Case report | Unknown | Normal, healthy, preterm (36 weeks) |
Xirouchakis et al. [64] | 2006 | IFX | PC/P(T1) | Case report | Vaginal | Normal, healthy, full term |
Vasiliauskas et al. [16] | 2006 | IFX (10 mg/kg body weight) | PC/P(T1-T3) | Case report | Vaginal | Normal, healthy, full term |
Mahadevan et al. [28] | 2007 | IFX | P(T1-T3) | Case series (n = 5) | 4 vaginal/1 C-section | Normal, healthy, full term |
Malgarinos et al. [29] | 2007 | IFX | PC/P(T1-T3) | Case report | Unknown | Normal, healthy, preterm |
Angelucci et al. [26] | 2008 | IFX | P(T1) | Case report | C-section | Normal, healthy, full term |
Palmer et al. [20] | 2008 | IFX | P(T2-T3) | Case report | Unknown | Intra-uterine fetal death due to placental abruption or intra-uterine infection |
Stengel et al. [33] | 2008 | IFX | PC/P(T1-T3) | Case report | C-section | Normal, healthy, full term |
Kane et al. [68] | 2009 | IFX | 2 PC/P(T1-T3), 1 P(T2) | Case series (3 women) | 2 vaginal, 1 C-section | 3 normal, healthy, full term |
Hou et al. [14] | 2009 | IFX | PC/p(T1-T3) | Case report | Vaginal | Normal, healthy, full term |
Arai et al. [23] | 2010 | IFX | P(T2-T3) | Case report | Unknown | Normal, healthy, full term |
Epping et al. [66] | 2010 | IFX | PC/P(T1-T3) | Case report | Unknown | Normal, healthy, full term |
Angelucci et al. [65] | 2010 | IFX | PC/P(T1) | Case report | C-section | Normal, healthy, preterm (31 weeks) |
Correia et al. [30] | 2010 | IFX | PC/P(T1-T3) | 2 case reports | C-section | Normal, healthy; 1 preterm (31 weeks) |
Molnár et al. [47] | 2010 | IFX | PC/P(T1-T3) | Case report | Unknown | Normal, healthy, full term |
Cheent et al. [63] | 2010 | IFX (10 mg/kg body weight) | PC/P(T1-T3) | Case report | Vaginal | Healthy, full term, no malformations |
Aratari et al. [44] | 2011 | IFX | P(T2) | Case report | C-section | Healthy, preterm (37 weeks) |
Abdul Wahab et al. [40] | 2011 | IFX | P(T2-T3) | Case report | Unknown | Normal, healthy, full term |
Kozeluhova [41] | 2011 | IFX | PC/P(T1-T3) | Case report | Unknown | Normal, healthy, full term |
Chaparro et al. [45] | 2011 | IFX | PC/P(T1-T3) | Case report | C-section | Normal, healthy, full term |
Naganuma et al. [67] | 2011 | IFX | PC/P(T1-3) | Case series (3 women) | Unknown | All healthy, full term, 1 low birth weight, no malformations |
Steenholdt et al. [22] | 2012 | IFX | PC/P(T1-T2) | Case report | Unknown | Normal, healthy, full term |
Arguelles-Arias et al. [42] | 2012 | IFX | PC/P(T1-T3) | Case series (12 women) | 8 vaginal, 4 C-sections | 12 healthy children |
Lichtenstein et al. [36] | 2012 | IFX | 142 reported pregnancies | Case series (analysis of data from TREAT registry) | Unknown | The vast majority of babies (92.4%) were healthy with no defects or other adverse events |
Snoeckx et al. [38] | 2013 | IFX | PC/P(T1-T3) | Case series (556 pregnancies) | Unknown | There were 58 miscarriages, 38 elective abortions, 7 stillbirths, and 453 live births |
Vesga et al. [80] | 2005 | ADA | PC/P(T1-T3)/PP | Case report | C-section | Normal, healthy, full term |
Coburn et al. [77] | 2006 | ADA | P(T2; T3) | Case report | Unknown | Normal, healthy, full term |
Mishkin et al. [79] | 2006 | ADA | PC/P(T1-T3) | Case report | Vaginal | Normal, healthy, full term |
Chambers et al. [75] | 2006 | ADA | PC/P(T1) | Case series (5 women) | Unknown | All full-term live births. No malformations |
Bosworth et al. [71] | 2007 | ADA | PC/P(T1-T3) | Case report | C-section | Normal, healthy, full term |
Johnson et al. [72] | 2009 | ADA | PC/P(T1-T3) | Case-controlled study 34 women and 45 controls (OTIS) | Unknown | 29 live-born (1 with undescended testicle + 1 with microencephaly); 5 spontaneous abortions. Two major structural defects in control group |
Jürgens et al. [78] | 2010 | ADA | PC/P(T1) | Case report | Vaginal | Healthy, full term |
Ben-Horin et al. [74] | 2010 | ADA | PC/P(T1-3) | Case report | Vaginal | Healthy, full term |
Abdul Wahab et al. [73] | 2011 | ADA | PC/P(T1-T3) | Case report | C-section | Twins, normal, healthy, full term |
Mahadevan et al. [76] | 2011 | ADA | PC/P(T1-T3) | Case series (5 women) | 2 vaginal 3 C-sections | Healthy (one infant developed pulmonary edema, but recovered fully) |
Kane et al. [31] | 2009 | CZP | Unknown (UCB data on file) | Case series (16 women) | Unknown | 4 healthy, full term; 1 small for gestational age; and 2 lost to follow-up. 8 induced abortions amd 1 spontaneous abortion |
Mahadevan et al. [85] | 2009 | CZP | P(T2; T3)/PP | Case report | Unknown | Healthy, full term, no malformations |
Oussalah et al. [86] | 2009 | CZP | PC/P(T1; T3) | Case report | Vaginal | Normal, healthy, full term. Adverse outcome in 1 case: bleeding 7 days post-partum, secondary to cotyledon retention |
Steinberg et al. [84] | 2010 | CZP | P(T2-T3) | Case report | C-section | Healthy, full term, no malformations |
Mahadevan et al. [87] | 2012 | CZP | PC/P(T1-T3) | Case series (139 pregnancies including 17 with rheumatoid arthritis) | Unknown | 21 miscarriages, 15 elective abortions, and 103 live births (2 with congenital abnormalities: 1 with mild unilateral hydronephrosis and 1 with vesicouretic reflux) |
Slama et al. [19] | 2010 | IFX/ADA | PC/P(T1-T3) | Case series (289 pregnancies including other diseases than IBD) | Unknown | No increased risk of adverse pregnancy outcome compared with unexposed IBD pregnancies |
Dunne et al. [46] | 2011 | IFX/ADA | PC/P(T1-T3) | 15 case series (15 women) | Unknown | 9 terminated pregnancies at study end. All live births were healthy, with two sets of twins |
Schnitzler et al. [54] | 2011 | IFX/ADA | PC and/or P(T1) and/or P(T2) | Case-controlled study (35 women with 42 pregnancies (35 IFX + 7 ADA) versus 101 pregnancies before IBD/treatment and 56 matched pregnancies in healthy controls) | Unknown | 10 abortions (1 trisomy 18, 1 elective), 1 stillbirth (umbilical strangulation), 32 live births: 8/32 premature, 6/32 low birth weight. All children were born healthy but one child with necrotizing enterocolitis died at 13 days of age (mother required treatment for severe asthma and CD during T3) |
Machková et al. [43] | 2012 | IFX/ADA | PC/P(T1-T3) | Case series (33 pregnancies in 31 women) | Unknown | 5/33 pregnancies ongoing. 24/28 healthy children (4/24 preterm), 3/24 spontaneous abortions, and 1/24 provoked abortion |
Habal et al. [37] | 2013 | IFX/ADA | PC/P(T1-T3) | Case series (29 pregnancies in 21 women) | Unknown | 27 normal, healthy, full term; 2 miscarriages |
Traussnigg et al. [39] | 2013 | IFX/ADA | PC/P(T1-T3) | Case series (14 pregnancies in 13 women) | Unknown | 13 normal, healthy, full term; 1 miscarriage |
Zelinkova Z et al. [12] | 2013 | IFX/ADA | PC/P(T1-T3) (T1-T2 ADA only) | Case series (31 pregnancies in 28 women) | Unknown | 28 live births (27 normal, healthy, full term; 1 child born to a mother treated with concomitant methotrexate periconceptually had polydactyly); 3 miscarriages |
Casanova et al. [48] | 2011 | IFX/ADA/CZP | PC/P(T1-T3) | Case-controlled retrospective study (30 pregnancies in treated mothers versus 110 unexposed IBD pregnancies) | Unknown | Prevalence of unfavorable delivery outcome (spontaneous abortion, preterm delivery, low birth weight and malformations) were higher in the control group |
Seirafi et al. [52] | 2011 | IFX/ADA/CZP | PC/P(T1-T3) | Case series (85 women) | Unknown | 6/85 were miscarriages, 47/85 were live births (30/85 ongoing), 8/49 were preterm, 3/49 were deaths (two in utero/one very premature),7/46 live births had neonatal complications (1 infection, 3 respiratory distress syndrome, 6 LBW <2500 g, 1 HELLP syndrome |
Mahadevan et al. [51] | 2012 | IFX/ADA/CZP | PC/P(T1-T3) | Case-controlled study (291 women without, and 79 with immunomodulators) | Unknown | No increased risk apart from higher risk of spontaneous abortion and C-section in group treated with biologics alone, and higher risk of preterm birth and infections int offspring at 12 months in combined thiopurine group verus biologics-alone group or unexposed IBD pregnancies |
Casanova et al. [35] | 2013 | IFX/ADA/CZP | PC/P(T1-T3) | Case series (66 pregnancies) | Unknown | 55 normal, healthy full term;, 4 preterm; 6 miscarriages; 1 congenital abnormality (several cardiac malformations) |
Mahadevan et al. [17] | 2013 | IFX/ADA/CZP | PC/P(T1-T3) | Case series (31 women) | 15 vaginal, 16 C-section | All 33 children (2 sets of twins) were normal, healthy, full term |