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.

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.

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.

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

OBJECTIVE: To assess folate and homocysteine status during normal pregnancy and postpartum in a longitudinal setting. METHODS: This 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 100 microg or vitamin B12 1 microg, 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 39 wk of gestation and 8 wk postpartum when the women were lactating. RESULTS: Through 18, 32 and 39 wk of gestation and postpartum, P-folate demonstrated a significant fall: median values were 14.4, 10.2, 9.3 and 8.9 nmol/L, respectively (P < 0.0001). The prevalence of low P-folate <6 nmol/L increased during pregnancy from 0.7% to 19.0% postpartum (P < 0.0001). Ery-folate displayed a similar, significant fall: median value was 0.84, 0.75, 0.65 and 0.55 micromol/L, respectively (P < 0.0001). The prevalence of low Ery-folate <0.40 micromol/L increased during pregnancy from 0.5% to 17.2% postpartum (P < 0.0001). P-homocysteine demonstrated a significant increase: median value was 6.4, 7.0, 7.7 and 10.8 micromol/L, respectively (P < 0.0001). The prevalence of P-homocysteine >13 micromol/L increased during pregnancy from 0.7% to 20.8% postpartum (P < 0.0001). The prevalence of low folate status (defined as P-folate <6 nmol/L and P-homocysteine >13 micromol/L) was 0%, 0%, 1.2%, and 8.4% at 18, 32 and 39 wk of gestation and 8 wk postpartum, respectively. CONCLUSION: Low 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.

Iron prophylaxis during pregnancy -- how much iron is needed? A randomized dose- response study of 20-80 mg ferrous iron daily in pregnant women.

OBJECTIVE: To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy. METHODS: A randomized, double-blind intention-to-treat study comprising 427 healthy pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n = 105), 40 mg (n = 108), 60 mg (n = 106), and 80 mg (n = 108) from 18 weeks of gestation. Iron status markers [hemoglobin (Hb), serum ferritin, and serum soluble transferrin receptor (sTfR)] were measured at 18 weeks (inclusion), 32 weeks, and 39 weeks of gestation and 8 weeks postpartum. Side effects of iron supplements were recorded. Iron deficiency was defined as serum ferritin <13 microg/l and iron deficiency anemia as serum ferritin <13 microg/l and Hb <5th percentile in iron replete pregnant women. RESULTS: There were no significant differences between variables in the four groups at inclusion. At 32 and 39 weeks of gestation, group 20 mg had significantly lower median serum ferritin (13 and 16 microg/l) than group 40 mg (17 and 21 microg/l), group 60 mg (18 and 23 microg/l), and group 80 mg (21 and 24 microg/l) (p < 0.0001). At 32 and 39 weeks of gestation, group 20 mg had a significantly higher prevalence of iron deficiency (50 and 29%) than group 40 mg (26 and 11%), group 60 mg (17 and 10%), and group 80 mg (13 and 9%) (p < 0.001). The prevalence of iron deficiency anemia at 39 weeks of gestation was significantly higher in group 20 mg (10%) than in group 40 mg (4.5%), group 60 mg (0%), and group 80 mg (1.5%) (p = 0.02). At 32 weeks of gestation, mean Hb in group 20 mg was lower than in group 80 mg (p = 0.06). There were no significant differences in iron status (ferritin, sTfR, and Hb) between group 40, 60, and 80 mg. Postpartum, group 20 mg had significantly lower median serum ferritin than group 40, 60, and 80 mg (p < 0.01). The prevalence of postpartum iron deficiency anemia was low and similar in the four groups. The frequency of gastrointestinal symptoms was not significantly different in the four iron supplement groups and thus not related to the iron dose. CONCLUSION: In Danish women, a supplement of 40 mg ferrous iron/day from 18 weeks of gestation appears adequate to prevent iron deficiency in 90% of the women and iron deficiency anemia in at least 95% of the women during pregnancy and postpartum.