Table 4.
Description of major birth defects in the TNF-α inhibitor cohort (n = 21)
| Substance and exposure time (after LMP) | Treatment indication | Co-medication (trimester or exact gestational period) | Gestational age at birth/elective termination (in weeks after LMP) and birth weight, sex | Birth defects |
|---|---|---|---|---|
| ADA from before pregnancy until week 5 + 6 days | Psoriatic arthritis | None | Week 38 + 5 days, 2770 g, female | Hexadactyly both feet, atrial septal defect |
| ADA from before pregnancy until week 38 + 5 days | Crohn’s disease | Prednisolone (1–3), ASS low-dose (1–3), omeprazole (1–3), lansoprazole (1), enoxaparin (1–3) | Week 38 + 5 days, 2540 g, male | Oesophageal atresia type IIIb (Vogt) with tracheo-oesophageal fistula; ventricular septal defect, syndactyly D2/3 both feet, peripheral pulmonary stenosis, PFO |
| ADA from before pregnancy until week 2 + 1 day | Ankylosing spondylitis | Amoxicillin (3), betamethasone (lung maturation, 3) | Week 32 + 3 days, 1840 g, female | Atrial septal defect with left-right shunt and aneurysm, cavum septum pellucidum on both sides, haemangioma at left flank |
| ADA only once in week 3 | Rheumatoid arthritis | Prednisone (1–3), levothyroxine (1–3) | Week 39 + 4 days, 3330 g, female | Ventricular septal defect, hip dysplasia type 2c (Graf) |
| ADA only once in week 1 + 5 days | Psoriasis | Ciclosporin (1), insulin (3) | Week 39 + 3 days, 3490 g, male | Hexadactyly |
| ADA from before pregnancy until week 7 | Ankylosing spondylitis | Ethinylestradiol/chlormadinone (1) | Week 34 + 3 days, 1990 g, male | Haemangioma right temple, (umbilical hernia) |
| ADA started during week 12 until week 14 (two injections) | Crohn’s disease | Prednisolone (1) | Spontaneous abortion in week 15 | Imperforate anus |
| ADA from before pregnancy until week 40 + 5 days | Ankylosing spondylitis | Sulfasalazine (1), fluoxetine(1), alprazolam (1) | Week 40, 3750 g, male | Amniotic band sequence: talipes and amputation of four fingers of the right hand |
| ADA and ETA from before pregnancy until week 2 + 2 days | Rheumatoid arthritis | Low dose methotrexate (from before pregnancy until week 2 + 2 days), prednisolone (1–3), omeprazole (1–3), ibuprofen (1–2). | Week 40 + 2 days, 2520 g, male | Cystic adenomatoid malformation of the right lung dorsobasal (multiple cysts of different sizes, totally 2.3 cm x 4.2 cm, surgery done), incomplete right bundle branch block, pericardial effusion, PFO and PDA, slight persistent pulmonary hypertension |
| ETA from before pregnancy until week 8 | Rheumatoid arthritis | Prednisone (1–3), fluconazole (1) | Week 35 + 3 days, 2200 g, male | Hypoplastic left heart, hypospadias glandis |
| ETA from before pregnancy until week 3 + 5 days | Rheumatoid arthritis | Prednisolone (1–3), thyroxine, ibuprofen (as needed) | Week 37 + 3 days, 2860 g, male | Agenesis of left kidney |
| ETA from before pregnancy until week 4 | Ankylosing spondylitis, Crohn’s disease | Prednisolone (1–3) | Week 36, 2920 g, female | WPW-syndrome with heart failure |
| ETA from before pregnancy until week 5 | Rheumatoid arthritis | None | Week 36 + 4 days, 3200 g, male | Bilateral hydronephrosis |
| ETA from before pregnancy until week 32 + 6 days | Behcet’s disease | Dalteparin (1–3) | Week 32 + 6 days, 2260 g, female | Atrial septal defect, (inguinal hernia) |
| IFX from before pregnancy until week 36 + 4 days | Crohn’s disease | None | Week 38; 2450 g, female | Aneurysmatic subaortic ventricular septal defect |
| IFX from before pregnancy until week 27 + 5 days | Crohn’s disease | Prednisolone (1–3), methylprednisolone (2–3), azathioprine (2–3), corticoid for lung maturation (2–3), antibiotics (2–3) | Week 27 + 5 days, 860 g, female | Two rapidly growing facial haemangiomata (propranolol therapy), (left inguinal hernia, PFO spontaneously closed) |
| IFX from before pregnancy until week 34 + 4 days | Crohn’s disease | Azathioprine (1–3), acyclovir (1), anti-D-immunoglobulins, human insulin (2–3), cefuroxime | Week 40 + 4 days, 3950 g, male | Hydronephrosis and obstructive megaureter right at birth. (Later silent kidney right and hypertrophy of left kidney) |
| IFX only once in week 3 + 6 days | Crohn’s disease | Low dose methotrexate (from before pregnancy until week 4 + 4 days) | Week 38 + 6 days, 2590 g, male | Pelviureteric junction obstruction (surgery required) |
| IFX from before pregnancy until week 25 (weeks 1, 9, 17, 25) | Crohn’s disease | Hydrocortisone rect. (1–2), azathioprine (1–3), mesalazine (1–3), pantoprazole (1–2), isoniazid and pyridoxine (1–2), betamethasone (lung maturation; 3), ibuprofen (1), citalopram (1) | Week 33 + 4 days, 2400 g, male | Hypospadias glandis, hepatic cyst; small aortic-pulmonary collateral |
| IFX from before pregnancy until week 5 + 2 days | Crohn’s disease | Contraceptive pill (until week 5 + 3 days) | Spontaneous abortion week 13 + 5 days (pericentric inversion of chromosome 9). | Megacystis, bilateral talipes |
| IFX from before pregnancy until week 23 + 5 days | Ulcerative colitis | None | Week 33 + 1 day, 1985 g, male (twin pregnancy, other twin healthy) | Facial haemangioma (cryo-therapy) |
LMP last menstrual period; PFO persistent foramen ovale; PDA persistent ductus arteriosus; WPW-syndrome:Wolf Parkinson White syndrome