Keld-Erik Byg

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

Aim:u2002 To report reference intervals for haematological variables during normal pregnancy and postpartum.

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 20xa0mg (n=74), 40xa0mg (n=76), 60xa0mg (n=77) and 80xa0mg (n=75) from 18xa0weeks gestation (inclusion) to 8xa0weeks postpartum. Iron status markers [serum ferritin, serum soluble transferrin receptor (sTfR), haemoglobin] were recorded at 18, 32 and 39xa0weeks gestation and 8xa0weeks postpartum. Body iron was calculated using the serum sTfR/serum ferritin ratio. ID was defined by serum ferritin <12xa0μg/l in pregnancy and <15xa0μg/l postpartum; IDA as serum ferritin <12xa0μg/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 ≤30xa0μg/l, 37.7% ferritin 30–70xa0μg/l and 11.6% ferritin >70xa0μg/l. At 32xa0weeks, women with ferritin ≤30xa0μg/l had an ID frequency of: 20-mg group 54.1%, 40xa0mg 29.7%, 60xa0mg 24.4%, 80xa0mg 20.6% (p<0.001); women with ferritin >30xa0μg/l had an ID frequency of: 20-mg group 20.0%, 40xa0mg 13.9%, 60xa0mg 5.7%, 80xa0mg 5.1% (p<0.001). Women with ferritin >70xa0μg/l had no ID. Postpartum, ID was found in 4.7% in 20-mg group, 2.9% in group 40xa0mg and 0% in group 60 and 80xa0mg. IDA: At 32xa0weeks, women with ferritin ≤30xa0μg/l had an IDA frequency of: 20-mg group 2.7%, 40xa0mg 2.7%, 60 and 80xa0mg 0%; none of the women with ferritin >30xa0μg/l displayed IDA. Body iron at 18xa0weeks was 10.4xa0mg/kg, similar in the four iron groups. Later in pregnancy body iron declined significantly, being lower the 20xa0mg group, and similar in the 40, 60 and 80-mg groups. Postpartum body iron rose to inclusion levels being 9.3xa0mg/kg in the 20-mg group and 10.5xa0mg/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 80–100xa0mg ferrous iron/day to women having ferritin ≤30xa0μg/l and 40xa0mg ferrous iron/day to women having ferritin 31–70xa0μg/l. In the prevention of IDA, we suggest 40xa0mg ferrous iron/day to women having ferritin ≤70xa0μg/l. Women with ferritin >70xa0μg/l have no need for iron supplement.

Iron status in Danes 1994. II: Prevalence of iron deficiency and iron overload in 1319 Danish women aged 40-70 years. Influence of blood donation, alcohol intake and iron supplementation.

Abstractu2002Iron status, i.e. serum ferritin and haemoglobin (Hb) levels, was assessed in a population survey in 1994 (Dan-Monica 10) comprising 1319 Caucasian Danish women in age cohorts of 40, 50, 60 and 70u2009years. In the entire series, ferritin levels increased significantly from 40u2009years to 60u2009years of age. The prevalence of small iron stores (ferritin 16–32u2009μg/l), depleted iron stores (ferritin <16u2009μg/l) and of iron deficiency anaemia (ferritin <13u2009μg/l and Hb <121u2009g/l) decreased steadily with age. Blood donors (n=109) had lower ferritin levels than non-donors (P<0.0001). Ferritin levels in donors were inversely correlated with the cumulated number of lifetime phlebotomies (rs=–0.25, P<0.01). Ferritin levels in non-donors (n=1208) were low in 40-year-old women (median 40u2009μg/l) and increased to a median of 95u2009μg/l in 60- and 70-year-old women (P<0.0001). In non-donors 40u2009years of age, the prevalence of small iron stores was 40.4%, the prevalence of depleted iron stores 10.8% and the prevalence of iron deficiency anaemia 2.16%. The prevalence of iron overload (ferritin >300u2009μg/l) was 1.54%. Ferritin levels in 60- and 70-year-old non-donors were correlated with the body mass index (rs=0.11, P=0.01). Ferritin levels in 50- to 60-year-old non-donors were correlated with alcohol intake (rs=0.23, P<0.0001). In the entire series, 37.5% of non-donors took supplemental ferrous iron (median 14u2009mg iron per day). Iron supplements had a significant positive influence on iron status in 40-year-old premenopausal non-donors but no effect in postmenopausal women or in donors. Non-donors (n=170) treated with acetylsalicylic acid had lower ferritin levels (median 55u2009μg/l) than non-treated (n=1038; median 75u2009μg/l) (P<0.0001). Compared with the Dan-Monica 1 iron status survey in 1984, the prevalence of iron deficiency and iron deficiency anaemia was unchanged, whereas the prevalence of iron overload displayed a slight increase. The 1987 abolition of the mandatory iron fortification of flour apparently had no negative effect on iron status.

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

Abstract:u2002 Objectives:u2002To assess cobalamin (vitamin B12) status during normal pregnancy and postpartum in a longitudinal setting. Methods:u2002This 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 39u2003wk gestation and 8u2003wk postpartum during lactation. Results:u2002P‐cobalamin showed a gradual, significant decline during pregnancy (Pu2003<u20030.0001) followed by a significant increase postpartum (Pu2003<u20030.0001); at 18, 32, 39u2003wk gestation and 8u2003wk postpartum median values were 225, 172, 161 and 319u2003pmol/L, respectively. P‐methylmalonic displayed a gradual, significant increase during pregnancy as well as postpartum (Pu2003<u20030.001) with median values of 0.11, 0.13, 0.14, and 0.16u2003μmol/L, respectively. P‐homocysteine demonstrated a significant increase during pregnancy and postpartum (Pu2003<u20030.001). The frequency of P‐cobalamin values <150u2003pmol/L increased during pregnancy from 15% at 18u2003wk to 43% at 39u2003wk gestation and subsequently declined to 3% postpartum. Conclusion:u2002Low cobalamin status may occur among pregnant women, especially in late pregnancy. The recommendations for periconceptional vitamin B12 supplementation should be reconsidered.

Iron status in Danes updated 1994. I: Prevalence of iron deficiency and iron overload in 1332 men aged 40–70 years. Influence of blood donation, alcohol intake, and iron supplementation

Abstractu2002Iron status, S-ferritin, and hemoglobin (Hb) were assessed in a population survey in 1994 (DAN-MONICA 10) comprising 1332 Caucasian Danish men equally distributed in age cohorts of 40, 50, 60 and 70u2009years. Blood donors (n=186) had lower S-ferritin, median 76u2009μg/l, than nondonors, median 169u2009μg/l (p<0.0001). S-ferritin in donors was inversely correlated with the number of phlebotomies (rs=–0.57, p<0.0001). S-ferritin in nondonors (n=1146) was similar in men 40–60u2009years of age, median 176u2009μg/l, and subsequently decreased at 70u2009years of age to a median of 146u2009μg/l (p=0.01). In the entire series, the prevalence of small iron stores (S-ferritin 16–32u2009μg/l) was 2.7%, that of depleted iron stores (S-ferritin <16u2009μg/l) 0.45%, and that of iron deficiency anemia (S-ferritin <13u2009μg/l and Hb <129u2009g/l) 0.15%. Among nondonors, the prevalence of iron overload (S-ferritin >300u2009μg/l) was 20%. S-ferritin in nondonors correlated with body mass index (rs=0.19, p=0.0001) and with alcohol intake (rs=0.26, p=0.0001). In the entire series, 28% of the subjects took supplemental iron (median 14u2009mg ferrous iron daily). Iron supplements had no influence on iron status. Nondonors (n=170) treated with acetylsalicylic acid had lower S-ferritin, median 136u2009μg/l, than nontreated, median 169u2009μg/l (p<0.001) and those treated with H2-receptor antagonists (n=30) had lower S-ferritin, median 142u2009μg/l, than nontreated, median 171u2009μg/l (p<0.04). Compared with the DAN-MONICA 1 iron status survey of Danish men in 1984, the prevalences of iron depletion and iron deficiency anemia are unchanged whereas the prevalence of iron overload has increased significantly. In Denmark, iron fortification of flour was abolished in 1987. This apparently had no negative effect on iron status in men.

Erythrocyte folate, plasma folate and plasma homocysteine during normal pregnancy and postpartum: a longitudinal study comprising 404 Danish women

Abstract:u2002 Objective:u2002To assess folate and homocysteine status during normal pregnancy and postpartum in a longitudinal setting. Methods:u2002This study, performed in 1995–1996, comprised 404 healthy pregnant Danish Caucasian women residential in Copenhagen County. Women taking folic acid tablets or vitamin B12 injections were not included. Dietary multivitamin supplements containing folic acid 100u2003μg or vitamin B12 1u2003μg, taken by 34%, were discontinued at inclusion. Participants had normal renal function. Folate status [erythrocyte (Ery‐) folate, plasma (P‐) folate, P‐homocysteine] was measured at 18, 32 and 39u2003wk of gestation and 8u2003wk postpartum when the women were lactating. Results:u2002Through 18, 32 and 39u2003wk of gestation and postpartum, P‐folate demonstrated a significant fall: median values were 14.4, 10.2, 9.3 and 8.9u2003nmol/L, respectively (Pu2003<u20030.0001). The prevalence of low P‐folate <6u2003nmol/L increased during pregnancy from 0.7% to 19.0% postpartum (Pu2003<u20030.0001). Ery‐folate displayed a similar, significant fall: median value was 0.84, 0.75, 0.65 and 0.55u2003μmol/L, respectively (Pu2003<u20030.0001). The prevalence of low Ery‐folate <0.40u2003μmol/L increased during pregnancy from 0.5% to 17.2% postpartum (Pu2003<u20030.0001). P‐homocysteine demonstrated a significant increase: median value was 6.4, 7.0, 7.7 and 10.8u2003μmol/L, respectively (Pu2003<u20030.0001). The prevalence of P‐homocysteine >13u2003μmol/L increased during pregnancy from 0.7% to 20.8% postpartum (Pu2003<u20030.0001). The prevalence of low folate status (defined as P‐folate <6u2003nmol/L and P‐homocysteine >13u2003μmol/L) was 0%, 0%, 1.2%, and 8.4% at 18, 32 and 39u2003wk of gestation and 8u2003wk postpartum, respectively. Conclusion:u2002Low folate status occurs among Danish pregnant women, especially in late pregnancy and postpartum during lactation. Despite new guidelines for folic acid supplement since 1997, only 13% of pregnant women followed the guidelines in 2003. The official recommendations for periconceptional folic acid supplement should be reconsidered and reinforced.

Side Effects of Oral Iron Prophylaxis in Pregnancy – Myth or Reality?

Background: It is a common belief among women that iron compounds have unpleasant gastrointestinal side effects. Objective: To assess the gastrointestinal side effects of iron prophylaxis in pregnancy. Methods: A randomized, double-blind study comprising 404 healthy pregnant women allocated to four groups taking ferrous iron supplement (as fumarate) in doses of 20 (n = 99), 40 (n = 100), 60 (n = 102) and 80 mg (n = 103) daily from 18 weeks of gestation to delivery. Iron supplement was predominantly taken at bedtime. Gastrointestinal symptoms (nausea, vomiting, epigastric pain, eructation, pyrosis, meteorism, borborygmi, colic pain, flatulence, constipation, thin feces, diarrhea), black feces, and use of laxatives were recorded by interview at 18, 32 and 39 weeks of gestation. Results: The frequencies of gastrointestinal symptoms were not significantly different in the four iron supplement groups either at inclusion or at 32 and 39 weeks of gestation and thus not related to the iron dose. Conclusion: This study shows that a supplement of 20–80 mg ferrous iron (as fumarate), taken between meals, has no clinically significant gastrointestinal side effects. The implementation of iron prophylaxis to pregnant women should not be compromised by undue concern of non-existing side effects.

Lead content in autopsy liver tissue in samples from Greenlandic Inuit and Danes

Objectives. To measure the quantity of lead (Pb) in liver tissue samples from Greenlandic Inuit, and compare the results with those obtained in Caucasian 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. Participants were 50 Greenlandic Inuit (27 men) with a median age of 61 years (range 23–83) and 74 Danes (44 men) with a median age of 60 years (range 15–87). Liver tissue samples (normal by macroscopic and microscopic examination) were obtained at autopsy. Total liver lead content was measured by X-ray fluorescence spectrometry with a detection limit of 0.05 μmol/kg dry weight. Results. In the entire series, Inuit had higher liver lead contents than Danes (p < 0.0001). Inuit men had higher liver lead content than Inuit women (p = 0.02). In Danes, men tended to have higher liver lead contents than women, but the difference was insignificant. The median (5–95 percentile) lead content was 14.96 μmol/kg dry liver (4.83–74.80) in Inuit, and < 0.05 μmol/kg dry liver (< 0.05–29.44) in Danes. All Inuit had liver lead contents above the detection limit, whereas 60 Danes (81%) had liver lead content below the detection limit. There was a positive correlation between liver lead content and age in both Inuit (rs = 0.46, p = 0.002) and Danes (n = 14; rs = 0.71, p = 0.01). Inuit had higher hepatic lead indices (liver lead content divided by age) than Danes (p < 0.0001). In Inuit, median hepatic lead index was 0.258, being higher in men than in women (p = 0.02). In Danes, the median hepatic lead index was 0.001, again higher in men than in women (p = 0.03). Conclusions. Our results show a gender-related difference in hepatic lead content, i.e. Inuit men have higher liver lead contents than women. Furthermore, Inuit men and women have higher hepatic lead contents than Danish men and women. In both Inuit and Danes, the liver lead content increases with age. One reason for thehigh lead levels in Inuit may be ingestion of seabirds contaminated by lead shot.

Broncho-fibroscopie de lésions pulmonaires circonscrites sans anomalies endobronchiques : rendement diagnostique en fonction de leur taille, de l'aspect de leurs bords et de leur localisation sur la radiographie du thorax

RésuméLe but de cette étude rétrospective était d’évaluer la relation entre le rendement diagnostique global de la broncho-fibroscopie (BF) et la taille, l’aspect des bords et la localisation de lésions pulmonaires circonscrites sur des radiographies thoraciques standard. Cent neuf patients consécutifs, 69 hommes et 40 femmes, d’âge moyen 63 ans, avec des lésions pulmonaires circonscrites sans anomalies endobronchiques ont été examinés par BF en utilisant un guidage fluoroscopique et ont été inclus dans l’étude. Des biopsies transbronchiques à la pince et un lavage bronchique ont été réalisés sur chaque patient. Le plus grand diamètre — c’est-à-dire la taille de la lésion sur la radiographie thoracique postérieure-antérieure — a été mesurée, ainsi que la distance entre la lésion et la ligne médiane du thorax et la carina principale. Le meilleur facteur radiographique prédictif pour une valeur diagnostique de la BF chez ces patients était la taille de la lésion. Le rendement augmentait proportionnellement à la taille, et une valeur maximum était atteinte pour des lésions d’un diamètre supérieur à 50 mm. Ceci implique que la BF a un rendement diagnostique meilleur pour les lésions de masse que pour les lésions nodulaires. Des facteurs prédictifs — de manière moins significative — étaient: les bords de la lésion (un meilleur rendement pour les lésions avec des bords flous que pour les lésions avec des bords nets); la localisation de la lésion dans la cage thoracique (un meilleur rendement pour les lésions centrales par rapport’ aux lésions périphériques); et enfin la localisation dans les lobes pulmonaires (un meilleur rendement pour les lobes moyens et inférieurs que pour les lobes supérieurs). La connaissance de ces facteurs radiographiques permet à l’opérateur réalisant une BF de donner une estimation fiable de la probabilité d’obtenir un diagnostic par broncho-fibroscopie pour une lésion donnée.SummaryThe aim of this retrospective study was to evaluate the relationship between the overall diagnostic yield of fiberoptic bronchoscopy (FOB) and the size, border and location of circumscribed pulmonary lesions on standard chest X-ray. One-hundred-nine consecutive patients, 69 men, 40 women, with a median age of 63 years, with circumscribed pulmonary lesions and without endobronchial abonormalities, were examined with FOB using fluoroscopic guidance, and were eligible for the study. Transbronchial forceps biopsies and bronchial washing were performed in all patients. The largest diameter, i.e. the size, of the lesion on posterior-anterior chest X-ray was measured as well as the distance of the lesion from the thoracic midline and the main carina. The best predictive radiographic factor for the diagnostic yield of FOB in these patients was the size of the lesion. The yield increased in parallel with the size and maximum yield was obtained in lesions with a diameter greater than 50 mm. This implies that FOB has a higher diagnostic yield in mass lesions than in nodular lesions. Factors of secondary predictive significance for the diagnostic yield were the border of the lesion (higher yield in lesions with fuzzy borders than in lesions with sharp borders); the location of the lesion in the thoracic cage (higher yield in centrally located lesions than in peripherally located lesions); and the location in the lung lobes (higher yield in the middle and lower lobes than in the upper lobes). Knowledge concerning these radiographic factors enables the FOB operator to give a reliable estimate of the chance of obtaining the diagnosis at fiberoptic bronchoscopy in a particular lesion.