Pregnancy complications and birth outcome in patients with osteogenesis imperfecta - A population-based register study.

OBJECTIVE: Patients with Osteogenesis Imperfecta (OI) have varying degrees of bone fragility and increased fracture rates. There is a paucity of data related to complications to pregnancies in patients with OI and to their offspring. With this study we aim to evaluate the risk of complications to pregnancies, delivery, and offspring in pregnancies where the mother or father have OI. DESIGN: Nationwide, register-based, cohort study. SETTING: Danish health register-based data. POPULATION: All pregnancies registered in the Danish health registers where one parent has OI and a reference population of all other pregnancies in the general population from 1997 to 2018. METHODS: Descriptive epidemiology MAIN OUTCOME MEASURES: Pregnancy and delivery complications (e.g. prevalence of pre-eclampsia, eclampsia and perinatal haemorrhage), and complications in the offspring (e.g. prevalence of low birth weight, low Apgar Score, need of CPAP or NICU, prevalence of congenital malformations (using the EUROCAT classification), incidence of osteogenesis imperfecta, prevalence of birth related fractures and hospital contacts during the first year of life) from pregnancies with parental OI. RESULTS: We identified 433 OI related pregnancies among 134 mothers with OI and 73 fathers with OI. The rates of pregnancy and delivery complications were similar between the OI cohorts and the reference population. More (31 % vs 19 %) children were delivered by caesarean section in the OI cohort than in the reference population. CONCLUSION: Pregnancies, where one parent have OI, result in live births to term with very few complications.

Fractures following pregnancy in Osteogenesis imperfecta - A self-controlled case series using Danish Health Registers.

Osteogenesis imperfecta (OI) is a rare inherited connective tissue disorder with considerable clinical and genetic heterogeneity. The clinical hallmark of OI is liability to fractures due to reduced bone strength. Pregnancy and lactation are periods of increased calcium demand resulting in a decrease in maternal bone mineral density (BMD). This self-controlled case series evaluates fracture risk 12- and 19-months prior to conception compared to a period of 12- and 19 months following childbirth in women with OI. This study is based on data from the Danish National Patient Register collected between 1995 and 2018. Modified Poisson models were fitted to estimate Incidence Rate Ratio in the post/pre-pregnancy period/s, adjusted by parity and age. The 12-month observation group included 111 women with 205 pregnancies, and the 19-month observation 108 women with 197 pregnancies. We calculated fracture rates (IR) of 48.78 [95%CI 18.55-79.01] per 1000 person years 12 months prior to conception, and of 27.87 [95%CI 10.60-45.14] in the 12 months post-delivery. Comparing pre- and post-pregnancy period we found an incidence rate ratio (IRR) of 1.00 [95%CI 0.42-2.40]. When adjusting for parity and age at delivery no significant change in the IRR was noted. In the 19 months observation-period, the IR per 1000 person years prior to conception was 74.84 [95%CI 44.25-105.43] and the IR postpartum was 36.86 [95%CI 17.55-56.17], leading to an IRR of 0.61 [95%CI 0.31-1.18]. We could not identify any increased risk of fractures when comparing fracture rates during pregnancy and 12 or 19 months postpartum to fracture rates 12 or 19 months prior to conception.

Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes.

BACKGROUND: Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling. METHODS: Pregnant women with IBD receiving anti-TNF treatment were prospectively invited to participate in an electronic questionnaire carried out in 22 hospitals in Denmark, Australia, and New Zealand from 2011 to 2015. Risk estimates were calculated, and birth weight was investigated using t tests and linear regression. RESULTS: Of 175 women invited, 153 (87%) responded. In women in remission, the relapse rate did not differ significantly between those who discontinued anti-TNF before GW 30 (1/46, 2%) compared with those who continued treatment (8/74, 11%; relative risk, 0.20; 95% confidence interval [CI], 0.02 to 1.56; P = 0.08). Relapse (P = 0.001) and continuation of anti-TNF therapy after GW 30 (P = 0.007) were independently associated with reduced mean birth weight by 367 g (95% CI, 145 to 589 g; relapse) and 274 g (95% CI, 77 to 471 g; anti-TNF exposure after GW 30). Of 134 (88%) women who received counseling, 116 (87%) were satisfied with the information provided. CONCLUSIONS: To minimize fetal exposure in women in remission, discontinuation of anti-TNF before GW 30 seems safe. Relapse and continuation of anti-TNF therapy after GW 30 were each independently associated with lower birth weight, although without an increased risk for birth weight <2500 g. Most women received and were satisfied with counseling.

Fecal Calprotectin During Pregnancy in Women With Moderate-Severe Inflammatory Bowel Disease.

Background: Fecal calprotectin (FC) is a biomarker used for assessing disease activity among IBD patients. Sparse knowledge exists as to whether FC correlates with clinical disease activity during pregnancy. Our aim was to assess FC and selected biomarkers in women with moderate-severe IBD and correlate them with clinical disease activity scores in pregnant women. Methods: We identified a nationwide cohort of 219 singleton pregnancies in women with moderate-severe disease (all treated with anti-tumor recrosis factor-α [anti-TNF-α] therapy during pregnancy), and we reviewed the medical records to extract clinical details and information on biomarkers. FC, C-reactive protein (CRP), hemoglobin, and albumin were collected according to each trimester. Results: A total of 346 FC measurements were obtained throughout the gestational periods. FC values were between 80-120, 259-349, and 778-1277 mg/kg in women with clinically inactive, mild, and moderate-severe disease activity, respectively, and were significantly higher among the women with clinical disease activity. ROC curves for disease activity were computed according to the preconception period: 0.81 (95% confidence interval [CI], 0.69-0.93), first trimester: 0.73 (95% CI, 0.60-0.86), second trimester: 0.74 (95% CI, 0.62-0.86), and third trimester: 0.76 (95% CI, 0.64-0.88), respectively. We found a sensitivity of 69.7%-80.0%, a specificity of 66.7%-73.3%, and a positive predictive value of 66.7%-74.4% over the 4 gestational periods when a cutoff of 200 mg/kg was used. We found no clinically significant differences in CRP, albumin, or hemoglobin. Conclusions: FC in pregnant women with moderate-severe IBD treated with anti-TNF-α therapy was significantly higher in women with clinical disease activity compared with the women without. FC correlated with the level of clinical disease activity in all gestational periods.

Birth outcomes after preconception paternal exposure to methotrexate: A nationwide cohort study.

BACKGROUND: Methotrexate (MTX), a folic acid antagonist, is often prescribed for moderate to severe inflammatory related diseases. The safety of paternal MTX use prior to conception is unknown. This study, using the National Danish Registries, aimed to examine the association between paternal MTX use three months before conception and adverse birth outcomes. RESULTS: Children fathered by men treated with MTX within three months before conception constituted the exposed cohort (N=193), and children fathered by men not treated with MTX constituted the unexposed cohort (N=1,013,801). The adjusted odds ratio (OR) for preterm birth was 1.38 (95% CI:0.68-2.81). The adjusted ORs of congenital anomalies (CAs) and small for gestational age (SGA) were 1.10 (95% CI:0.57-2.13) and 0.98 (95% CI:0.39-2.50), respectively. CONCLUSION: Our results regarding the effect of paternal use of MTX within 3 months before conception on birth outcomes of CAs, preterm birth and SGA are overall reassuring.

Anti-TNF-α Use During the Third Trimester of Pregnancy in Women with Moderate-severe Inflammatory Bowel Disease and the Risk of Preterm Birth and Low Birth Weight.

BACKGROUND: Little knowledge exists about the association between anti-tumor necrosis factor-alpha (anti-TNF-α) therapy for inflammatory bowel disease during late pregnancy and adverse birth outcomes. We aimed to examine whether treatment with anti-TNF-α during the third trimester affected preterm birth and low birth weight (LBW), compared with women who discontinued anti-TNF-α therapy before the third trimester. METHODS: We identified a nationwide cohort of 219 women treated with anti-TNF-α during the pregnancy period and reviewed the medical records to extract clinical details. The exposed cohort (n = 113, 51.6%) constituted pregnancies exposed to anti-TNF-α during the third trimester, and the unexposed cohort (n = 106, 48.4%) constituted pregnancies with no anti-TNF-α during the third trimester. The association between anti-TNF-α therapy in the third trimester and adverse birth outcomes was studied (1) in those women who had clinical disease activity during pregnancy and (2) in women who had no clinical disease activity during pregnancy. RESULTS: In women with disease activity, treated with anti-TNF-α during the third trimester, we found an adjusted odds ratio of 2.23 (95% confidence interval [CI], 0.80-6.20) for preterm birth and 1.16 (95% CI, 0.26-5.23) for LBW. Among women without disease activity, treated with anti-TNF-α therapy during the third trimester, we found an adjusted odds ratio of 3.36 (95% CI, 0.31-36.46) for preterm birth and 0.86 (95% CI, 0.05-14.95) for LBW. CONCLUSIONS: For anti-TNF-α therapy in the third trimester, we found no statistically significant increased risk of either LBW or preterm birth.

The Effect of Disease Activity on Birth Outcomes in a Nationwide Cohort of Women with Moderate to Severe Inflammatory Bowel Disease.

BACKGROUND: Active inflammatory bowel disease (IBD) during conception and pregnancy may increase the risk of adverse birth outcomes. Former studies have examined heterogeneous groups of women with varying degrees of IBD severity. We aimed to examine the effect of active IBD on birth outcomes in a more homogeneous group of women with a moderate to severe disease course. Since in Denmark, moderate to severe IBD is an indication for use of anti-tumor necrosis factor-α therapy, we examined all women who used anti-tumor necrosis factor therapy during pregnancy. METHODS: We identified a nationwide cohort of 219 singleton pregnancies in women treated with anti-tumor necrosis factor-α therapy during pregnancy (2005-2014). Pregnancies with clinical disease activity (65.8%) constituted the exposed cohort and pregnancies without disease activity constituted the unexposed (34.2%). Disease activity scores were supported by levels of fecal calprotectin. Outcomes included low birth weight, preterm birth, and congenital anomalies. RESULTS: In women with IBD, disease activity was associated with adjusted odds ratio of low birth weight and preterm birth; 2.05 (95% confidence interval, 0.37-11.35) and 2.64 (95% confidence interval, 0.85-8.17), respectively. In those with clinical moderate to severe disease activity, the odds ratio for preterm birth was 3.60 (95% confidence interval, 1.14-11.36). In women with ulcerative colitis and disease activity, 19.5% had a child with low birth weight and 29.3% gave birth preterm. CONCLUSION: In women with moderate to severe IBD, 66% experienced disease activity during pregnancy. In those with the highest degree of disease activity, the risk of preterm birth was increased 3 to 4 folds. The proportion of adverse birth outcomes was high, particularly among women with ulcerative colitis and disease activity.

[Chronic intestinal ischaemia in a younger patient]. / Kronisk tarmiskæmi hos en yngre patient.

A 46-year-old woman presented with classic symptoms. Computed tomography-angiography and duplex ultrasonography showed stenosis of the aa. mesenteria superior et inferior. The patient was moved to a university hospital and a percutaneous transluminal angioplasty with insertion of stents was performed. She was discharged shortly after feeling well.