title: Iron supplementation in pregnancy—does the preparation matter? Do side-effects reduce compliance to iron supplementation? A study of daily- and weekly-dose regimens in pregnancy. Safety and efficacy of lactoferrin versus ferrous sulphate in curing iron deficiency and iron deficiency anaemia in hereditary thrombophilia pregnant women: an interventional study Lactoferrin Efficacy versus Ferrous Sulfate in Curing Iron Disorders in Pregnant and Non-Pregnant Women Lactoferrin versus ferrous sulphate for the treatment of iron deficiency anemia during pregnancy: a randomized clinical trial Factors determining compliance to routine iron supplementation in pregnancy at the University of Portharcout Teaching Hospital. Influence of lactoferrin in preventing preterm delivery: a pilot study. Oral administration of lactoferrin increases hemoglobin and total serum iron in pregnant women. Determinants of compliance with iron supplementation among pregnant women in Senegal. Efficacy and tolerability of oral bovine lactoferrin compared to ferrous sulfate in pregnant women with iron deficiency anemia: A prospective controlled randomized study
abstract: Objective To assess the use , side effects and discontinuation rates of iron preparations during pregnancy . Design Six hundred and twelve r and omly selected postpartum women completed a question naire on iron supplement use in the second and third trimesters . Results Of the 517 women ( 84.5 % ) reported using iron supplements , 453 were eligible for the study . The most common preparation was ferrous fumarate ( 46.8 % , P < 0.01 ) , followed by ferrous sulfate ( 31.8 % ) , ferric polymaltose ( 12.4 % ) , and ferric bisglycinate ( 7.3 % ) . Almost half the participants ( 45 % ) reported at least one adverse effect , especially constipation ( 27.4 % , P < 0.01 ) , nausea ( 10.8 % ) . Multivitamin preparations and ferric bisglycinate were associated with the fewest side effects ( 23.7 , 21.2 % respectively , P < 0.01 ) , and ferrous fumarate and immediate-release ferrous sulfate with the most ( 56.3 , 53.7 % respectively ) . Eighty-three women discontinued their originally prescribed iron preparation , mainly ( 89 % ) due to side effects . Discontinuation rates were lowest for the multivitamin and ferric bisglycinate ( 10.5 , 9.1 % , respectively ) . In most cases , the specific preparation was recommended by the women ’s physician ( 76 % ) . Conclusion Ferrous fumarate-containing multivitamin preparations and ferric bisglycinate , although infrequently recommended as the first-line of iron supplementation , may be associated with less side effects and better compliance Side-effects of iron supplementation lead to poor compliance . A weekly-dose schedule of iron supplementation rather than a daily-dose regimen has been suggested to produce fewer side-effects , thereby achieving a higher compliance . This study compared side-effects of iron supplementation and their impact on compliance among pregnant women in Bangladesh . These women were assigned to receive either weekly doses of 2 x 60 mg iron ( one tablet each Friday morning and evening ) or a daily dose of 1 x 60 mg iron .  Fifty antenatal care centres were r and omly assigned to prescribe either a  weekly- or a daily-supplementation regimen ( 86 women in each group ) . Side-effects were assessed by recall after one month of supplementation and used for predicting compliance in the second and third months of supplementation . Compliance was monitored using a pill bottle equipped with an electronic counting device that recorded date and time whenever the pill bottle was opened . Of five gastrointestinal side-effects ( heartburn , nausea , vomiting , diarrhoea , or constipation ) assessed , vomiting occurred more frequently in the weekly group ( 21 % ) than in the daily group ( 11 % , p<0.05 ) . Compliance ( ratio between observed and recommended tablet intake ) was significantly higher in the weekly-supplementation regimen ( 93 % ) than in the daily-supplementation regimen ( 61 % , p<0.05 ) . Overall , gastrointestinal side-effects were not significantly associated with compliance . However , the presence of nausea and /or vomiting reduced compliance in both the regimens-but only among women from the lower socioeconomic group . In conclusion , weekly supplementation of iron in pregnancy had a higher compliance compared to daily supplementation of iron despite a higher frequency of side-effects . The findings support the view that gastrointestinal side-effects generally have a limited influence on compliance , at least in the dose ranges studied . Efforts to further reduce side-effects of iron supplementation may not be a successful strategy for improving compliance and effectiveness of antenatal iron supplementation Objective Evaluate the safety and efficacy of bovine lactoferrin ( bLf ) versus the ferrous sulphate st and ard intervention in curing iron deficiency ( ID ) and ID anaemia ( IDA ) in pregnant women affected by hereditary thrombophilia ( HT ) . Design Interventional study . Setting Secondary -level hospital for complicated pregnancies in Rome , Italy . Population 295 HT pregnant women ( ≥18 years ) suffering from ID/IDA . Methods Women were enrolled in Arm A or B in accordance with their personal choice . In Arm A , 156 women received oral administration of 100 mg of bLf twice a day ; in Arm B , 139 women received 520 mg of ferrous sulphate once a day . Therapies lasted until delivery . Main outcome measures Red blood cells , haemoglobin , total serum iron , serum ferritin ( haematological parameters ) were assayed before and every 30 days during therapy until delivery . Serum IL-6 , key factor in inflammatory and iron homeostasis disorders , was detected at enrolment and after therapy at delivery . Possible maternal , foetal , and neonatal adverse effects were assessed . Results Haematological parameters were significantly higher in Arm A than in Arm B pregnant women ( P ≤ 0.0001 ) . Serum IL-6 significantly decreased in bLf-treated women and increased in ferrous sulphate-treated women . BLf did not exert any adverse effect . Adverse effects in 16.5 % of ferrous sulphate-treated women were recorded . Arm A women experienced no miscarriage compared to five miscarriages in Arm B women . Conclusions Differently from ferrous sulphate , bLf is safe and effective in curing ID/IDA associated with a consistent decrease of serum IL-6 . The absence of miscarriage  among bLf-treated women provided an unexpected benefit . Trial registration : Clinical Trials.gov Identifier NCT01221844 Iron homeostasis in pregnancy compensates for increased iron requirements and in women of child-bearing age for iron loss in menses . Oral administration of ferrous sulfate , prescribed to cure iron deficiency ( ID ) and ID anemia ( IDA ) , often fails to increase hematological parameters and causes adverse effects . Recently , we demonstrated safety and efficacy of bovine lactoferrin ( bLf ) in pregnant women suffering from ID/IDA . Two clinical trials were conducted on pregnant and non-pregnant women of child-bearing age suffering from ID/IDA . In both trials , women received oral administration of bLf 100 mg/twice/day ( Arm A ) , or ferrous sulfate 520 mg/day ( Arm B ) . Hematological parameters , serum IL-6 and prohepcidin were assayed before and after therapy . Unlike ferrous sulfate , bLf  increased hematological parameters ( P<0.0001 ) . In pregnant women , bLf  decreased serum IL-6 ( P<0.0001 ) , and increased prohepcidin ( P=0.0007 ) . In non-pregnant women bLf did not change the low IL-6 levels while it increased prohepcidin ( P<0.0001 ) . Ferrous sulfate increased IL-6 ( P<0.0001 ) and decreased prohepcidin ( P=0.093 ) . bLf established iron homeostasis by modulating serum IL-6 and prohepcidin synthesis , whereas ferrous sulfate increased IL-6 and failed to increase hematological parameters and prohepcidin .  bLf is a more effective and safer alternative than ferrous sulfate for treating ID and IDA Abstract Objective : This study was conducted to evaluate the efficacy and safety of lactoferrin in comparison to ferrous sulphate for the treatment of iron deficiency anemia ( IDA ) during pregnancy . Material s and methods : This prospect i ve , r and omized , parallel-group , single-center study was conducted in the Department of Obstetrics and Gynecology at Menoufia University Hospital , Egypt and included a total of 200 pregnant women in the second trimester with IDA who were enrolled and r and omly assigned either to receive 150 mg of dried ferrous sulphate capsules or lactoferrin 250 mg capsules once daily for eight consecutive weeks . The primary efficacy parameter was the amount of increase in hemoglobin concentration by 4 and 8 weeks , the adverse effects related to iron therapy and the patient compliance to the treatment . Results : Total increase in Hb after 2 months with lactoferrin was higher ( 2.26 ± 0.51 g/dL ) compared to ferrous sulfate ( 1.11 ± 0.22 g/dL ) ( p < 0.001 ) . Gastrointestinal adverse events occurred more frequently with ferrous sulphate than the lactoferrin group ( p < 0.001 ) . The number of women requesting change the drug was higher in the ferrous sulphate group ( p < 0.001 ) . Conclusion : Lactoferrin was more effective than ferrous sulfate over a two-month period in pregnant women with IDA , with fewer gastrointestinal adverse events and better treatment acceptability BACKGROUND Routine intake of iron supplements during pregnancy improves maternal health and pregnancy outcomes . This is observed in a background of increased availability and compliance to routine antenatal iron supplements . Poor compliance arises not only because of patient behavior but also from factors that may be out of patient 's control . The aim of this study was to determine the proportion of patients who comply , the level of compliance with the iron prescription given at the antenatal clinic as well as propose interventions aim ed at increasing compliance amongst the antenatal population . METHODS A total of five hundred antenatal clients were recruited r and omly ( the 3rd of clients presenting to the clinic ) during their antenatal visits between 1st May and 30th June , 2009 at the UPTH .  Prescriptions for iron supplements and folic acid were given and they were interviewed using a st and ard structured question naire . Women with low or high compliance were asked to explain what influenced their adherence to iron supplementation . RESULTS Overall compliance in this study was 88.0 % . Women who complied fully were of the perception that good blood level and birth weight were beneficial effects of the routine iron supplement .  Gastrointestinal side effects and forgetfulness were the main reasons for low compliance Lactoferrin ( Lf ) is an approximately 80-kDa iron-binding glycoprotein , belonging to the transferrin family , with well-known bacteriostatic and bactericidal properties . It is produced and stored in specific ( secondary ) neutrophil granules and released during neutrophil activation and degranulation . Nowadays , Lf has a well-known therapeutic indication for combating iron deficiency anemia ( IDA ) in pregnant women . Studies suggest that Lf plays an important role against cervicovaginal infections by decreasing cytokines levels , such as interleukin (IL)-6 , in cervicovaginal fluid . The aim of this preliminary trial was to evaluate the effectiveness of Lf in preventing preterm delivery caused by cervical infections and ripening . From November 2009 to August 2010 , 21 pregnant women ( 26 - 32 weeks pregnant ) , aged between 22 and 36 years , suffering from IDA , at risk of preterm delivery , were prospect ively enrolled in the study . One group ( N=14 ) received 100 mg of recombinant human lactoferrin ( bLf ) [ corrected ] ( lattoferrina ; AG-pharma ) twice a day before meals , for one month . The other group ( N=7 ) received 520 mg of ferrous sulfate ( Ferro-Grad ; Abbott Laboratories , USA ) once a day . The patients underwent  transvaginal ultrasound  to evaluate cervical length and funneling , and vaginal swabs were used to detect infections and cervicovaginal fluid sample collection to determine IL-6 levels . The results showed a correlation between the oral administration of 200 mg of bLf [ corrected ] with both the normalization of vaginal flora ( vaginal infection disappearance ) and the decrease in IL-6 cervicovaginal fluid levels in women at risk of preterm delivery Iron deficiency anemia ( IDA ) during pregnancy continues to be of world-wide concern . IDA is a risk factor for preterm delivery and subsequent low birth weight , and possibly for poor neonatal health . Iron supplementation in pregnancy is a widely recommended practice , yet intervention programs have met with many controversies . In our study , 300 women at different trimesters of pregnancy were enrolled in a trial of oral administration of ferrous sulfate ( 520 mg once a day ) or 30 % iron-saturated bovine lactoferrin ( bLf ) ( 100 mg twice a day ) . Pregnant women refusing treatment represented the control group . In this group hemoglobin and total serum iron values measured after 30 d without treatment decreased significantly , especially in women at 18 - 31 weeks of pregnancy . In contrast , after 30 d of oral administration of bLf , hemoglobin and total serum iron values increased and to a greater extent than those observed in women treated orally for 30 d with ferrous sulfate , independently of the trimester of pregnancy . Unlike ferrous sulfate , bLf did not result in any side effects . These findings lead us to hypothesize that lactoferrin could influence iron homeostasis directly or through other proteins involved in iron transport out of the intestinal cells into the blood BACKGROUND Community iron supplementation programmes for pregnant women have lacked effectiveness , partly because of low compliance . OBJECTIVE To determine factors that influence compliance among pregnant women in Senegal . DESIGN Two hundred and twenty-one pregnant women , recruited from six health centres in Dakar during their first prenatal visit , were r and omly assigned to receive either a prescription to purchase iron/folic acid tablets ( control , n = 112 ) to be taken daily , according to official policy , or to receive free tablets ( treatment , n = 109 ) . Compliance was assessed 20 weeks after enrollment through interviews and pill count . Women with low or high compliance ( < 70 % or > or=70 % ) were asked to explain what influenced their adherence to supplementation . RESULTS Overall compliance was 69 % ; it was significantly higher in the treatment than in the control group ( 86 % vs. 48 % ; P < 0.0001 ) . Women with high compliance ( 58 % ) were motivated by : ( 1 ) the perception of improved health upon taking the tablets ( treatment = 24 % , control = 10 % ) ; ( 2 ) the insistence by midwives that they take the tablets ; and ( 3 ) the mention that the tablets would improve health . Women with low compliance ( 42 % ) reported : ( 1 ) the experience of side-effects that they associated with the tablets ( treatment = 13 % , control = 14 % ) ; ( 2 ) misunderst and ing that they needed to continue taking the tablets throughout pregnancy ( treatment = 0 % , control = 18 % ) ; and ( 3 ) forgetfulness . CONCLUSION Compliance with iron/folic acid supplementation in Senegal can be increased by providing women with clear instructions about tablet intake and educating them on the health benefits of the tablets Objective . To compare the effects of bovine lactoferrin with ferrous sulfate on iron nutritional status and to evaluate their tolerability in 100 pregnant women with iron deficiency anemia . Design . Prospect i ve , r and omized , controlled , double blind trial . Setting . Obstetrics clinic of a University Department of Obstetrics and Gynecology . Population . One‐hundred pregnant , healthy women to be treated either with one capsule of 100 mg bovine lactoferrin twice a day ( Group A ; n = 49 ) and 520 mg ferrous sulfate once a day ( Group B ; n = 48 ) . Methods . After 30 days , we evaluated hemoglobin ( Hb ) , serum ferritin , serum iron and total iron‐ binding capacity ( TIBC ) values . All women were asked to keep a diary of five potential gastrointestinal side effects ( abdominal pain , nausea , vomiting , diarrhea and constipation ) . For each symptom , patients had to rate its severity according to a scale ranging from 0 ( absent ) to 3 ( severe ) . Main outcome measures . Hb level before and after treatment . Secondary outcomes were serum ferritin , serum iron and TIBC levels and the difference in symptom scores between groups . Results . In Groups A and B , Hb , serum ferritin and iron were significantly increased while TIBC was significantly reduced in comparison with basal values . No significant differences were observed between Groups A and B. The median scores of abdominal pain and constipation were significantly higher in patients treated with ferrous sulfate in comparison with those treated with bovine lactoferrin . Conclusions . The results show that bovine lactoferrin has the same efficacy as ferrous sulfate in restoring iron deposits with significantly fewer gastrointestinal side effects
target: Significantly less gastrointestinal side effects were reported with lactoferrin treatment .
  No significant differences existed with regard to other outcomes .
  In conclusion , for pregnant women with IDA , daily oral bovine lactoferrin is just as good as ferrous sulfate in improving hematological parameters with fewer gastrointestinal side effects .
background: This systematic review and meta- analysis aim ed to evaluate the efficacy of daily oral bovine lactoferrin versus daily oral ferrous iron preparations for treatment of iron deficiency anemia ( IDA ) during pregnancy .