The impact of an ultrasound atlas for scoring salivary glands in primary Sjögren's syndrome: a pilot study.

The objective of this pilot study was to assess the impact of a salivary gland ultrasound (SGUS) atlas for scoring parenchymal changes in Sjögren's syndrome by assessing the reliability of the scoring system (0-3), without and with the use of the SGUS atlas. Ten participants with varying experience in SGUS contributed to the reliability exercise. Thirty SGUS images of the submandibular and parotid gland with abnormalities ranging from 0 to 3 were scored using the written definitions of the OMERACT SGUS scoring system and using the SGUS atlas based on the OMERACT scoring system. For intra-reader reliability, two rounds were performed without and with the atlas-in the 2nd round the 30 images were rearranged in random order by a physician not included in the scoring. Inter-reader reliability was also determined in both rounds. Without using the atlas, the SGUS OMERACT scoring system showed fair inter-reader reliability in round 1 (mean kappa 0.36; range 0.06-0.69) and moderate intra-reader reliability (mean kappa 0.55; range 0.28-0.81). With the atlas, inter-reader reliability improved in round 1 to moderate (mean kappa 0.52; range 0.31-0.77) and intra-reader reliability to good (mean kappa 0.69; range 0.46-0.86). Higher intra-reader reliability was noted in participants with previous SGUS experience. The SGUS atlas increased both intra- and inter-reader reliability for scoring gland pathology in participants with varying SGUS experience suggesting a possible future role in clinical practice and trials. Key Points • Ultrasonography can detect parenchymal changes in salivary glands in patients with Sjögren's disease. • An ultrasound atlas may improve reliability of scoring parenchymal changes in salivary glands.

Low protection from breakthrough SARS-CoV-2 infection and mild disease course in ocrelizumab-treated patients with multiple sclerosis after three mRNA vaccine doses.

BACKGROUND: Our study investigated the rate of breakthrough SARS-CoV-2 infection and clinical outcomes in a cohort of multiple sclerosis (MS) patients who were treated with the anti-CD20 monoclonal antibody (Ab), ocrelizumab, before first, second and third BNT162b2 mRNA vaccinations. To correlate clinical outcomes with the humoral and cellular response. METHODS: The study was a prospective non-randomised controlled multicentre trial observational study. Participants with a diagnosis of MS who were treated for at least 12 months with ocrelizumab prior to the first BNT162b2 mRNA vaccination were prospectively followed up from January 2021 to June 2022. RESULTS: Out of 54 participants, 32 (59.3%) developed a positive SARS-CoV-2 PCR test in the study period. Mild infection was observed in all infected participants. After the third vaccination, the non-infected participants had higher mean Ab levels compared to the infected participants (54.3 binding antibody unit (BAU)/mL vs 26.5 BAU/mL, p=0.030). The difference in reactivity between spike-specific CD4+ and CD8+ T lymphocytes in the two groups was not significant. CONCLUSION AND RELEVANCE: The study results demonstrate rates of 59% in breakthrough infections after the third SARS-CoV-2 mRNA vaccination in ocrelizumab-treated patients with MS, without resulting in critical disease courses. These findings suggest the need for continuous development of prophylactic treatments when proved important in the protection of severe breakthrough infection.

Non-Invasive Metabolic and Structural Retinal Markers in Patients with Giant Cell Arteritis and Polymyalgia Rheumatica: A Cross-Sectional Study.

Giant cell arteritis (GCA) is a potential sight-threatening disease. Although it is associated with polymyalgia rheumatica (PMR), visual loss is not common in PMR. A retinal oximeter can be used to conduct a direct, non-invasive, in vivo assessment of the vascular system. In a cross-sectional study, we measured the retinal oxygen saturation and retinal vessel calibers in GCA patients, PMR patients, and control participants. Twenty GCA patients (38 eyes), 19 PMR patients (33 eyes), and 12 controls (20 eyes) were investigated. Images were analyzed using Oxymap Analyzer software 2.5.0 (Oxymap ehf., Reykjavik, Iceland). Groups were compared using an age- and sex-adjusted linear mixed model regression. The median (IQR) age for GCA patients was 69.0 (66.5-76.5) years, for PMR 69.0 (67.0-72.0) years, and for the controls 75.5 (71.5-81.0) years, respectively. As compared to the controls (115.3 µm), the retinal arterioles were significantly wider in patients with GCA (124.4 µm; p = 0.023) and PMR (124.8 µm; p = 0.049). No difference was found in the retinal venular caliber or vascular oxygen saturation. These results indicate that GCA and PMR patients differ similarly in the retinal arteriolar diameter compared to controls. Further studies are needed in order to clarify the underlying inflammatory mechanisms in retinal arteriolar vessels and if these parameters can be used to predict clinical outcomes.

A prospective, one-year follow-up study of patients newly diagnosed with neurosarcoidosis.

METHODS: Twenty patients with newly diagnosed neurosarcoidosis were examined for multiple outcomes in an observational cohort study with 12-month follow-up. RESULTS: The patients' contrast-enhancing lesions on MRI scans reduced during treatment (p < 0.0001). The mean modified Rankin Score improved from 3.0 to 1.8 (p < 0.0001), and 75% of patients experienced clinically important improvement. Patients improved on the Symbol Digit Modalities Test (p < 0.0001) and on SF-36 Physical (p = 0.003) and Mental Component Summary scores (p = 0.03). Proportions of patients with substantial fatigue (75%) and high depression score (35%) were unchanged. CONCLUSIONS: 12-month immunosuppression improved several outcomes, and 75% of patients experienced clinically important improvement.

Inflammatory profiles in plasma and cerebrospinal fluid of patients with neurosarcoidosis.

METHODS: Cerebrospinal fluid (CSF) and plasma levels of 38 biomarkers from 20 neurosarcoidosis (NS) patients were compared to healthy controls (HC). RESULTS: In CSF, 25 biomarkers were significantly elevated compared to HC: IFNγ, TNFα, TNFß, IL-2, IL-6, IL-10, IL-12B, IL-15, IL-16, CCL2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26, CXCL8, CXCL10, TNFR2, VEGF-A, PIGF, SAA, VCAM1, and ICAM1. In plasma, 12 biomarkers were significantly elevated compared to HC: IFNγ, TNFα, CCL2, CCL3, CCL4, CCL17, CXCL10, VEGFR1, PIGF, SAA, VCAM1, and ICAM1. CONCLUSION: NS patients have profoundly elevated cytokines, chemokines, vascular angiogenesis, and vascular injury biomarkers in CSF and plasma.

Persistently reduced humoral and sustained cellular immune response from first to third SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients.

OBJECTIVE: To examine humoral and cellular response in multiple sclerosis patients on anti-CD20 therapy after third BNT162b2 mRNA SARS-CoV-2 vaccination. METHODS: A prospective longitudinal study design from first throughout third vaccination in Danish and American MS centers. All participants were treated with ocrelizumab. Antibody (Ab) levels were assessed before and after third vaccination using SARS-CoV-2 IgG II Quant assay (Abbott Laboratories). B- and T-lymphocytes enumeration was done with BD Multitest™6-color TBNK reagent. Spike-specific T-cell responses were measured through PBMC stimulation with spike peptide pools (JPT Peptide Technologies). RESULTS: We found that 14.0%, 37.7%, and 33.3% were seropositive after first, second and third vaccination. The median Ab-levels were 74.2 BAU/mL (range: 8.5-2427) after second vaccination, as well as 43.7 BAU/ml (range: 7.8-366.1) and 31.3 BAU/mL (range: 7.9-507.0) before and after third vaccination, respectively. No difference was found in levels after second and third vaccination (p = 0.1475). Seropositivity dropped to 25.0% of participants before the third vaccination, a relative reduction of 33.3% (p = 0.0020). No difference was found between frequencies of spike reactive CD4+and CD8+ T-cells after second (0.65 ± 0.08% and 0.95 ± 0.20%, respectively) and third vaccination (0.99 ± 0.22% and 1.3 ± 0.34%, respectively). CONCLUSION: In this longitudinal cohort we found no significant increased humoral or cellular response with administration of a third SARS-CoV-2 mRNA vaccination. These findings suggest the need for clinical strategies to include allowance of B cell reconstitution before repeat vaccination and/or provision of pre-exposure prophylactic monoclonal antibodies.

Humoral immune response following SARS-CoV-2 mRNA vaccination concomitant to anti-CD20 therapy in multiple sclerosis.

BACKGROUND: The immunogenicity of COVID-19 vaccine among patients receiving anti-CD20 monoclonal antibody (Ab) treatment has not been fully investigated. Detectable levels of SARS-CoV-2 immunoglobulin G (IgG) are believed to have a predictive value for immune protection against COVID-19 and is currently a surrogate indicator for vaccine efficacy. OBJECTIVE: To determine IgG Abs in anti-CD20 treated patients with multiple sclerosis (MS). METHOD: IgG Abs against SARS-CoV-2 spike receptor-binding domain were measured with the SARS-CoV-2 IgG II Quant assay (Abbott Laboratories) before and after vaccination (n = 60). RESULTS: 36.7% of patients mounted a positive SARS-CoV-2 spike Ab response after the second dose of vaccine. Five patients (8.3%) developed Abs >264 BAU/mL, another 12 patients (20%) developed intermediate Abs between 54 BAU/mL and 264 BAU/mL and five patients (8.3%) had low levels <54 BAU/mL. Of all seropositive patients, 63.6% converted from seronegative to seropositive after the 2nd vaccine. CONCLUSION: Our study demonstrates decreased humoral response after BNT162b2 mRNA SARS-CoV-2 vaccine in MS patients receiving B-cell depleting therapy. Clinicians should advise patients treated with anti-CD20 to avoid exposure to SARS-CoV-2. Future studies should investigate the implications of a third booster vaccine in patients with low or absent Abs after vaccination.

Nationwide study on trends in unplanned hospital attendance and deaths during the 7 weeks after the onset of the COVID-19 pandemic in Denmark.

BACKGROUND: The impact of a pandemic on unplanned hospital attendance has not been extensively examined. The aim of this study is to report the nationwide consequences of the COVID-19 pandemic on unplanned hospital attendances in Denmark for 7 weeks after a 'shelter at home' order was issued. METHODS: We merged data from national registries (Civil Registration System and Patient Registry) to conduct a study of unplanned (excluding outpatient visits and elective surgery) hospital-based healthcare and mortality of all Danes. Using data for 7 weeks after the 'shelter at home' order, the incidence rate of unplanned hospital attendances per week in 2020 was compared with corresponding weeks in 2017-2019. The main outcome was hospital attendances per week as incidence rate ratios. Secondary outcomes were general population mortality and risk of death in-hospital, reported as weekly mortality rate ratios (MRRs). RESULTS: From 2 438 286 attendances in the study period, overall unplanned attendances decreased by up to 21%; attendances excluding COVID-19 were reduced by 31%; non-psychiatric by 31% and psychiatric by 30%. Out of the five most common diagnoses expected to remain stable, only schizophrenia and myocardial infarction remained stable, while chronic obstructive pulmonary disease exacerbation, hip fracture and urinary tract infection fell significantly. The nationwide general population MRR rose in six of the recorded weeks, while MRR excluding patients who were COVID-19 positive only increased in two. CONCLUSION: The COVID-19 pandemic and a governmental national 'shelter at home' order was associated with a marked reduction in unplanned hospital attendances with an increase in MRR for the general population in two of 7 weeks, despite exclusion of patients with COVID-19. The findings should be taken into consideration when planning for public information campaigns.

Elevated Neurofilament Light Chain in Cerebrospinal Fluid and Plasma Reflect Inflammatory MRI Activity in Neurosarcoidosis.

BACKGROUND: Damage to axonal cells releases neurofilament light chain (NFL) into the cerebrospinal fluid and plasma. The objective of this study was to investigate NFL as a potential biomarker of disease activity in neurosarcoidosis. MRIs were graded according to enhancing lesions at different central nervous system (CNS) sites. RESULTS: In cerebrospinal fluid, levels of NFL were higher in neurosarcoidosis patients (n = 20) median 2304 pg/mL (interquartile range (IQR) 630-19,612) compared to 426 pg/mL (IQR 261-571) in extra-neurologic sarcoidosis patients (n = 20) and 336 pg/mL (IQR 194-402) in healthy controls (n = 11) (p = 0.0002). In plasma, levels of NFL were higher in neurosarcoidosis patients median 28.2 pg/mL (IQR 11.5-49.3) compared to 6.2 pg/mL (IQR 4.3-8.2) in extra-neurologic sarcoidosis patients and 7.1 pg/mL (IQR 6.2-9.0) in healthy controls (p = 0.0001). Levels in both cerebrospinal fluid and plasma were higher in neurosarcoidosis patients with moderate/severe enhancement than patients with mild enhancement on MRI (p = 0.009 and p = 0.005, respectively). To distinguish neurosarcoidosis patients from extra-neurologic patients and healthy controls, a cut-off level of 630 pg/mL in cerebrospinal fluid had 94% specificity and 79% sensitivity, while a cut-off level of 11.4 pg/mL in plasma had 97% specificity and 75% sensitivity. CONCLUSIONS: NFL levels in cerebrospinal fluid and plasma are significantly higher in neurosarcoidosis patients compared to extra-neurologic patients and healthy controls, and the levels correlate to the extent of inflammation on MRI.

The Role of Non-Selective TNF Inhibitors in Demyelinating Events.

The use of non-selective tumor necrosis factor (TNF) inhibitors is well known in the treatment of inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis. Its use in neurological disorders is limited however, due to rare adverse events of demyelination, even in patients without preceding demyelinating disease. We review here the molecular and cellular aspects of this neuroinflammatory process in light of a case of severe monophasic demyelination caused by treatment with infliximab. Focusing on the role of TNF, we review the links between CNS inflammation, demyelination, and neurodegenerative changes leading to permanent neurological deficits in a young woman, and we discuss the growing evidence for selective soluble TNF inhibitors as a new treatment approach in inflammatory and neurological diseases.

Altered retinal oxygen metabolism in patients with combined ocular and central nervous system sarcoidosis.

OBJECTIVE: To evaluate retinal oxygen metabolism by retinal oximetry for ocular and CNS diseases in a cross-sectional study of sarcoidosis. METHODS: Overall 201 eyes from 103 biopsy-verified sarcoidosis patients were included and divided into four groups depending on the organ affection: (i) sarcoidosis without ocular or CNS affection, (ii) ocular sarcoidosis, (iii) CNS sarcoidosis, and (iv) combined ocular and CNS sarcoidosis. Retinal oximetry was obtained and analysed, with the mean retinal arteriolar and venular saturation as well as arteriovenous difference as principal outcomes. Comparison between groups was done in a multi linear regression model adjusted for age, sex, duration of sarcoidosis, best corrected visual acuity and retinal oximetry quality. RESULTS: Mean (s.d.) age was 50.5 (13.4) (95% CI: 47.9, 53.1) years and 52.2% were males. Eyes of the combined Ocular/CNS group had a higher retinal arteriovenous difference than eyes of the Non-ocular/no-CNS group (42.1% vs 37.7%, P = 0.012) but did not differ between other groups. Eyes in the four groups (Non-ocular/no-CNS, Ocular, CNS and Ocular/CNS) did not differ according to retinal arterial (94.5%, 93.5%, 93.5% and 94.5%, respectively) or venular (57.5%, 56.4%, 55.0% and 52.5%, respectively) oxygen saturation. CONCLUSIONS: The results of this study suggest that eyes of sarcoidosis patients with combined ocular and CNS affection have an altered oxygen metabolism indicating a subclinical eye affection that is not recognized by conventional screening methods.

Use of Cerebrospinal Fluid Biomarkers in Diagnosis and Monitoring of Rheumatoid Meningitis.

Rheumatoid meningitis is a rare extra-articular manifestation of rheumatoid arthritis, often with non-specific symptoms. In most cases brain MRI shows a patchy lepto- and pachymeningeal enhancement, but the diagnosis currently relies on examination of a meningeal biopsy with presence of plasma cells and rheumatoid noduli. Presence of IgM rheumatic factor (RF) has been found in several cases and recently four cases have shown high titer anti-cyclic citrullinated peptide (anti-CCP) in CSF, suggesting this as a potential marker for rheumatoid meningitis. We present a 62 year-old woman with sero-positive (IgM RF and anti-CCP) rheumatoid arthritis, presenting with headache and gait impairment. Brain MRI revealed the classical patchy meningeal enhancement and the diagnosis of rheumatoid meningitis was confirmed by neuropathological examination of a meningeal biopsy. Analysis of the CSF revealed positive IgM RF (92.7 IU/mL) and strongly positive anti-CCP (19,600 IU/mL) and CXCL-13 (>500 ng/L). After treatment with high-dose steroid and Rituximab the clinical symptoms resolved. A 6 month follow-up analysis of CSF showed a dramatic decrease in all these markers with negative IgM RF and a decrease in both anti-CCP (64 IU/mL) and CXCL-13 (<10 ng/L). Our case further underlines the potential use of CSF anti-CCP and IgM RF in the diagnosis of RM and the use of these markers and CXCL-13 in evaluation of treatment response. A case review of 48 cases of rheumatoid meningitis published since 2010, including, symptoms, serum, and CSF findings, treatment, and outcome is provided.

[Cognitive dysfunction, loss of visual acuity and hearing can be symptoms of Susac syndrome].

This is a case report of a 56-year-old male patient with Susac syndrome. The syndrome is a rare immune-mediated, ischaemic, occlusive microvascular endotheliopathy affecting the brain, retina and inner ear. Diagnosis and treatment are challenging, since the presentation shows great variability. Brain MRI, fundoscopy and audiometry enable the diagnosis. Early treatment with immuno-suppressive medication is crucial and can reduce complications like dementia, loss of visual acuity and hearing. The treatment is empirical and based on the fact, that the histopathology of the syndrome is similar to juvenile dermatomyositis.

Non-parathyroid hypercalcemia associated with paraffin oil injection in 12 younger male bodybuilders: a case series.

INTRODUCTION: Injection of paraffin oil to augment muscles size is a troubling phenomenon known to cause a foreign body reaction with formation of granulomas. In a few case reports, long-term side effects have been reported in terms of hypercalcemia and renal failure. METHODS: We identified a case series of 12 male bodybuilders presenting with non-parathyroid hypercalcemia who previously had injected paraffin oil to increase muscles size. RESULTS: At admission, all patients had moderate-to-severe hypercalcemia with suppressed PTH levels and impaired renal function. Calcitriol levels were within the normal range or slightly elevated. Follow-up measurements showed marked hypercalciuria with nearly normal levels of bone turnover markers. A correlation was found between levels of peptidyl dipeptidase and calcitriol (R = 0.812, P = 0.050). Treatment with antiresorptive agents seemed less effective than glucocorticoids, which resulted in a significantly lowering of ionized calcium levels and improved renal function, although no patients were cured by this treatment. Immunosuppression with azathioprine or mycophenolate may have a glucocorticoid-saving effect. One patient had surgery with removal of affected muscle tissue, without any apparent effect on plasma calcium levels. CONCLUSION: The hypercalcemia and associated hypercalciuria seems to be due to an intestinal hyperabsorption of calcium. It remains to be elucidated, whether an increased calcitriol synthesis within granulomas is the only (main) mechanism by which intestinal calcium absorption is increased. Glucocorticoids seem most appropriate as the first choice for treatment. Bodybuilders should be warned against use of intramuscular oil injections (and other substances), as this may have severe adverse health consequences.

Reference intervals for haematological variables during normal pregnancy and postpartum in 434 healthy Danish women.

AIM: To report reference intervals for haematological variables during normal pregnancy and postpartum. MATERIAL AND METHODS: The series comprised 434 healthy ethnic Danish women with a normal pregnancy > or =37 wk duration and a normal delivery with newborns weight >2500 g. Blood samples were obtained at 18, 32 and 39 wk gestation and at 8 wk postpartum. The following variables were analysed: Haemoglobin (Hb), haematocrit (Hct), blood erythrocyte count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, white cell count, platelet count, erythrocyte folate, plasma folate, plasma cobalamin, plasma methylmalonic acid, plasma total homocysteine, serum ferritin, serum soluble transferrin receptor and plasma creatinine. Reference intervals were calculated using log(10)-transformed values (which showed normal distributions) as mean +/- 1.96 x SD. RESULTS: The lower reference value for Hb during pregnancy was 6.45 mmol/L (105 g/L) and 7.3 mmol/L (118 g/L) postpartum. The lower reference value for Hct was 0.31 in pregnancy and 0.35 postpartum. There was a gradual decline in the lower reference value for erythrocyte folate during pregnancy and postpartum from 0.46 to 0.29 micromol/L and in plasma folate from 6 to 4 nmol/L. Lower reference value for plasma cobalamin declined during pregnancy from 96 to 71 pmol/L, but increased postpartum to 148 pmol/L. Upper reference value for plasma homocysteine increased gradually during pregnancy and postpartum from 11.0 to 20.6 micromol/L. Geometric mean serum ferritin at 18 wk gestation was 32 microg/L. Plasma creatinine values were low during pregnancy and displayed a significant increase postpartum. CONCLUSION: The characteristic changes occurring in haematological indices during pregnancy and postpartum are described in this study. The results may be used as reference values in the assessment of health status of pregnant women with a similar socio-economic and racial background.

Rubidium content in autopsy liver tissue samples from Greenlandic Inuit and Danes measured by X-ray fluorescence spectrometry.

BACKGROUND: The biological function of rubidium (Rb) is unknown, but this alkali metal probably has a normal biologic role. OBJECTIVE: To measure the content of Rb in liver tissue samples from Greenlandic Inuit using X-ray fluorescence spectrometry, and compare the results with those obtained in liver samples from ethnic Danes. STUDY DESIGN: Observational, descriptive survey on environmental pathology. METHODS: The setting was related to forensic medicine and hospitalised care in Nuuk, Ilulissat and Copenhagen. Normal liver tissue was obtained at autopsy from 50 Greenlandic Inuit (27 men) with a median age of 61 years (range 23-83) and from 42 Danes (31 men) with a median age of 38 years (range 16-83). RESULTS: Liver Rb content in Inuit was not significantly different compared with Danes. There was no significant gender difference in liver Rb content either in Inuit or in Danes. The content of Rb given as median (5-95 percentile) was 0.1837mmol/kg dry liver (0.1041-0.3147) in Inuit, and 0.1965mmol/kg dry liver (0.0799-0.2815) in Danes (p=0.6). There was an inverse correlation between liver Rb content and age in Inuit (r(s)=-0.45, p=0.002) but not in Danes. Median hepatic Rb index (Rb content in micromol/kg dry weight divided by age in years) in Inuit was 3.05 and in Danes 4.21 (p=0.02). The correlations between liver Rb and liver potassium content were: Inuit r(s)=0.28, p=0.07; Danes r(s)=0.25, p=0.08; combined series r(s)=0.34, p=0.01. CONCLUSIONS: Inuit have liver Rb levels, which are quite similar to the levels found in Danes. In Inuit, liver Rb content appears to decrease with age.

[Blau syndrome--a chronic granulomatous, genetic disease]. / Blaus syndrom--en genetisk betinget, kronisk, granulomatøs sygdom.

Blau syndrome is a rare hereditary granulomatous disease presenting in patients of young age with exanthema, granulomatous arthritis and uveitis. Genetic analysis has shown an autosomal dominant inheritance and a number of specific mutations on chromosome 16q in codon 334, of which the most predominant are R334W and R334Q. Blau syndrome exists in Caucasian, Asian and Afro-American families, and de novo mutations have been reported. The estimated minimum incidence in Denmark is 0.05 per 100,000 person-years. Blau syndrome has pathological, clinical and therapeutic features in common with sarcoidosis but rarely involves the lungs or other parenchymatous organs. Discrimination between Blau syndrome and early-onset sarcoidosis should rely on chromosome analysis.

[Blau syndrome in monozygotic twins]. / Blaus syndrom hos enaeggede tvillinger.

This case report describes Blau syndrome in monozygotic twins. The disease ran an identical course in both patients, starting with a maculopapulous exanthema at one year of age. Skin biopsies showed epithelioid cell granulomas with multinucleated giant cells. Shortly after arthritis and periarticular swelling developed and uveitis appeared at 8 years of age. Treatment consisted of prednisolone and methotrexate, and from 18 years of age of infliximab, with good effect. DNA analysis showed de novo R334W mutation in the CARD15 gene. The patients have now been followed for 19 years and are in good clinical condition.

Body iron and individual iron prophylaxis in pregnancy--should the iron dose be adjusted according to serum ferritin?

This study aims to evaluate iron prophylaxis in pregnant women from the individual aspect, i.e. according to serum ferritin levels at the beginning of pregnancy, and to assess which dose of iron would be adequate to prevent iron deficiency (ID) and iron deficiency anaemia (IDA) during pregnancy and postpartum. A randomised, double-blind study comprising 301 healthy Danish pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n=74), 40 mg (n=76), 60 mg (n=77) and 80 mg (n=75) from 18 weeks gestation (inclusion) to 8 weeks postpartum. Iron status markers [serum ferritin, serum soluble transferrin receptor (sTfR), haemoglobin] were recorded at 18, 32 and 39 weeks gestation and 8 weeks postpartum. Body iron was calculated using the serum sTfR/serum ferritin ratio. ID was defined by serum ferritin <12 microg/l in pregnancy and <15 microg/l postpartum; IDA as serum ferritin <12 microg/l and haemoglobin <5th percentile in iron-replete pregnant women. Women in the iron supplement groups were stratified according to serum ferritin levels at inclusion; 50.7% had ferritin 70 microg/l. At 32 weeks, women with ferritin 30 microg/l had an ID frequency of: 20-mg group 20.0%, 40 mg 13.9%, 60 mg 5.7%, 80 mg 5.1% (p<0.001). Women with ferritin >70 microg/l had no ID. Postpartum, ID was found in 4.7% in 20-mg group, 2.9% in group 40 mg and 0% in group 60 and 80 mg. IDA: At 32 weeks, women with ferritin 30 microg/l displayed IDA. Body iron at 18 weeks was 10.4 mg/kg, similar in the four iron groups. Later in pregnancy body iron declined significantly, being lower the 20 mg group, and similar in the 40, 60 and 80-mg groups. Postpartum body iron rose to inclusion levels being 9.3 mg/kg in the 20-mg group and 10.5 mg/kg in the 40-, 60- and 80-mg groups. This study gives an estimate of iron dosage in individual iron prophylaxis adjusted to serum ferritin levels in early pregnancy. In the prevention of ID, we suggest 80-100 mg ferrous iron/day to women having ferritin 70 microg/l have no need for iron supplement.

Cobalamin status during normal pregnancy and postpartum: a longitudinal study comprising 406 Danish women.

OBJECTIVES: To assess cobalamin (vitamin B(12)) status during normal pregnancy and postpartum in a longitudinal setting. METHODS: This study was performed in 1995-1996. It comprised 406 healthy, pregnant Danish Caucasian women, living in Copenhagen County. Cobalamin status, i.e. plasma (P-) cobalamin, P-methylmalonic acid and P-homocysteine was measured at 18, 32 and 39 wk gestation and 8 wk postpartum during lactation. RESULTS: P-cobalamin showed a gradual, significant decline during pregnancy (P < 0.0001) followed by a significant increase postpartum (P < 0.0001); at 18, 32, 39 wk gestation and 8 wk postpartum median values were 225, 172, 161 and 319 pmol/L, respectively. P-methylmalonic displayed a gradual, significant increase during pregnancy as well as postpartum (P < 0.001) with median values of 0.11, 0.13, 0.14, and 0.16 micromol/L, respectively. P-homocysteine demonstrated a significant increase during pregnancy and postpartum (P < 0.001). The frequency of P-cobalamin values <150 pmol/L increased during pregnancy from 15% at 18 wk to 43% at 39 wk gestation and subsequently declined to 3% postpartum. CONCLUSION: Low cobalamin status may occur among pregnant women, especially in late pregnancy. The recommendations for periconceptional vitamin B(12) supplementation should be reconsidered.