Literature Report Summaries of recent studies
The nutritional relevance of micronutrients, omega-3 fatty acids and probiotics to women with the desire to have a baby, to pregnancy and the breastfeeding period
Preface During pregnancy and breastfeeding women have increased micronutrient requirements. The adequate supply of essential vitamins, minerals and unsaturated fatty acids is an important prerequisite for a healthy pregnancy and the development of embryo, fetus and infant. Current scientific studies show that, in a nutritional approach, the regular intake of probiotics can contribute to the buildup and enhancement of the immune system and strengthen the normal functions of the gut microflora. Just with a well-balanced diet alone it will be difficult to ensure a micronutrient intake fully covering the need of the future mother. Numerous trials have evaluated the effect of the supplementation of single or combinations of micronutrients related to specific pregnancy complications, such as pre-eclampsia, perinatal mortality and preterm births.
Probiotics
Omega-3 Fatty Acids
Micronutrients
1 2 3
Probiotics
1
Probiotics in primary prevention of atopic disease Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Kalliom채ki M, Salminen S, Arvilommi H, et al. Lancet 2001;357(9262):1076-79. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Kalliom채ki M, Salminen S, Poussa T, et al. Lancet 2003;361(9372):1869-71.
Summary Many studies on the development of allergic diseases start from the hygiene hypothesis which attributes the increased frequency of atopic dermatitis or other allergies in children to a relatively reduced microbial exposure in the early months of life. Since, however, the bacterial microflora of the gut belongs to the earliest and most essential stimulators of the mucosa-associated lymphatic tissue (immune system), Kaliom채ki et al. examined whether the development of atopic diseases could be influenced by probiotics. In this study more than 100 pregnant women with a positive family history of atopies (including having atopic parents) received daily either probiotic cultures (1 x 1010 CFU Lactobacillus GG) or placebo two to four weeks prenatally, and breastfeeding mothers for 6 months postnatally. Infants who were not breastfed, postnatally received probiotics in the first 6 months of life. Perinatal supplementation of probiotics and occurrence of an atopic dermatitis in children %
40
46 %
Pl a ce b o Probiotics
46 %
30 20
23 %
26 %
10
Comparison of the frequency of atopic diseases in children aged 2 or 4 years whose mothers had taken during pregnancy and 6 months after delivery placebo or probiotics.
After 2 years
After 4 years
Results After 24 months, only 23% of the children in the probiotic group developed an atopic eczema, whereas in the placebo group 46% of the children developed this atopic disease. In the follow-up evaluation after 4 years these results were confirmed. Compared with the placebo group, in the probiotic group an atopic eczema was diagnosed in about half as many children. Conclusion The supplementation of probiotics during and after pregnancy can prevent early atopic disease in children at high risk.
Probiotics
1
Effects of probiotics on immunity Probiotics: effects on immunity Isolauri E, Sütas Y, Kankaanpää P, et al. Am J Clin Nutr 2001;73(2 Suppl.):444S-50S.
Summary The gastrointestinal tract with a total surface area of approx. 400 m² is the largest organ of the human immune system. Numerous current studies on the effects and functions of the gut-associated immune system underline the relevance of the intestines to human health. In this context a rising number of articles focus on the potentially beneficial effects of probiotics on the gut defence barrier and immunoregulation. Thus, for instance, probiotic cultures can contribute to the regulation of an increased intestinal permeability in specific intestinal dysfunctions, e.g. gastroenteritis, food allergies and inflammatory bowel diseases. The immunological efficacy of probiotics is shown, among other things, by the stronger immune response to microbial pathogens. In fact, in several studies phagocytosis could be stimulated or an increased IgA release could be observed under the dietary effect of probiotic cultures. The immunomodulating effect of a diet including probiotics plays an especially important role in allergic diseases. In infants with cow’s milk allergy a probiotic diet led to a significant improvement of atopic dermatitis. Further studies with probiotic bacteria and their fermentation products demonstrate a reduced formation of TNF-alpha (tumor necrosis factor alpha) and increased formation of interferon gamma during oral ingestion. The effect of probiotics could also reduce inflammatory responses, enhance the intestinal integrity and stabilize gut microecology. Conclusion Probiotic cultures support the physiological intestinal functions. Furthermore they are able to protect against microbial pathogens and modulate the immune system, thus reducing the risk of atopic disease.
Probiotics
1
Probiotics: treatment option of bacterial vaginosis in pregnancy Ingestion of probiotics: optional treatment of bacterial vaginosis in pregnancy Shalev E. Isr Med Assoc J 2002;4(5):357-60.
Summary During pregnancy, bacterial vaginosis is diagnosed in 15 to 23% of women with the course of the disease being asymptomatic in up to 50% of cases. The presence of potentially pathogenic microorganisms in the vaginal microflora frequently remains undiscovered. Treatment of this infection, however, is indicated as women with bacterial vaginosis are at an increased risk of premature rupture of the membranes, preterm labor and preterm delivery. Moreover, fever during or after delivery (postpartum endometritis and wound infections) was observed more frequently in women with bacterial vaginosis. The therapeutic standard of bacterial vaginosis is the oral administration or topical application of antibiotics (metronidazol, clindamycin). But antibiotic therapy usually is not started before the second trimester in order to avoid possible risks to the fetus which can develop even at a low dose. Recent studies point out an extended and well-tolerated treatment option with probiotics. Thus, for instance, the dietary intake of specific probiotic cultures may have a favorable effect on the stabilization of the normal vaginal microflora. In a double-blind, randomized study including 46 women investigators could achieve a beneficial effect on the vaginal microflora with a dietary probiotic supplement (Lactobacillus acidophilus). During the study period, the women consuming the yoghurt that contained L. acidophilus (n=23) had a significantly increased number of positive vaginal cultures with L. acidophilus and a significant reduction of episodes of bacterial vaginosis. In the control group (n=23, eating pasteurized yoghurt) no such effects could be observed. Results Probiotic cultures are a well-tolerated, safe treatment option for bacterial vaginosis in pregnant women. They are promising as an adjunct to therapy contributing to a healthy vaginal microflora, especially before pregnancy or during the first trimester of pregnancy. Conclusion Probiotic microorganisms stabilize the vaginal microflora and may contribute to the prevention and treatment of bacterial vaginosis.
Probiotics Omega-3 Fatty Acids
12
Therapeutic measures for the prevention of allergic diseases Therapeutic measures for prevention of allergic rhinitis/asthma development. Stanaland BE. Allergy Asthma Proc 2004;25(1):11-5.
Summary The development of asthma and allergic disease involves not only genetic but also external factors. Such factors include, among other things, diet and environmental conditions. At a meeting on the occasion of the Eastern Allergy Conference in Palm Beach (Florida) in May 2003, the therapeutic measures for prevention of allergic disease were presented by Dr. Brett E. Stanaland from the University of South Florida. Therapeutic measures during pregnancy and breastfeeding according to Brett E. Stanaland Avoidance of the early feeding of dairy products and highly allergenic foods (e.g. nuts) Avoidance of nicotine and/or tobacco smoke exposure Ingestion of probiotics during pregnancy and breastfeeding
Avoidance of dust-mite exposure
Breastfeeding during the first 4 months of life
Diet rich in antioxidants and omega-3 fatty acids
An important measure, already in pregnancy, is the supplementation of the maternal diet with probiotics. Also during the breastfeeding phase which should last at least 4 to 6 months, the supplementation of the diet with probiotics is to be recommended to breastfeeding mothers. Another nutritional measure includes a diet for mother and child which is rich in antioxidants and omega-3 fatty acids. A sufficient supply can beneficially influence the modulation of the immune system. Moreover, during the first months of life cow’s milk and other highly allergenic foods should not be components of the child’s menu. Also the avoidance of dust-mite exposure and nicotine as well as a smokefree environment are essential measures of prevention. Conclusion Therapeutic measure for the prevention of allergic disease should already be taken during the prenatal and early infantile phase. An adequate supply of probiotics, antioxidants and omega-3 fatty acids is essential as these nutritional substances influence the early modulation of the immune system.
Probiotics Omega-3 Fatty Acids
12
Essential fatty acids are enhancers of the beneficial effects of probiotics Essential fatty acids as possible enhancers of the beneficial actions of probiotics. Das UN. Nutrition 2002;18(9):786-9. The influence of polyunsaturated fatty acids on probiotic growth and adhesion. Kankaanpää PE, Salminen SJ, Isolauri E, et al. FEMS Microbiol Lett 2001;194(2):149-53.
Summary The favorable effect of probiotics on the modulation of the immune system has been documented in many studies. For example, probiotics are able to reduce the release of inflammatory signal substances as a response to allergens. This feature is relevant to the development and severity of atopic conditions. Since polyunsaturated fatty acids also play a major role as immune modulators, Kankaanpää and colleagues examined the potential interaction between probiotics and fatty acids. In their study it was demonstrated that polyunsaturated fatty acids, such as omega-3 fatty acids, may promote the mucus adhesion of probiotics. The authors therefore conclude that the combination of long-chain polyunsaturated fatty acids and probiotics represents a protective barrier against atopic diseases. Fazit Omega-3 fatty acids support the adhesion and beneficial health-enhancing effects of probiotics. Supplementing the diet with omega-3 fatty acids and probiotics in pregnancy and the breastfeeding period can substantially contribute to the modulation of the infant’s immune system and thus reduce the allergy risk.
Omega-3 Fatty Acids
2
Fish oil supplementation in pregnancy and neonatal allergen-specific immune responses in infants at high risk of atopy Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial Dunstan JA, Mori TA, Barden A, et al. J Allergy Clin Immunol 2003;112(6):1178-84. Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy Dunstan JA, Mori TA, Barden A, et al. Clin Exp Allergy 2003;33(4):442-8.
Summary The dramatic increase in asthmatic and allergic diseases in the past 20 to 30 years is an important reason for the intensive research on potential factors which may help prevent allergies. It is striking to see that within this period the amount of antiinflammatory omega-3 fatty acids taken in with the food has dropped, whereas the percentage of omega-6 fatty acids in the diet has increased. Theoretically, the supplemental intake of omega-3 fatty acids should lead to a reduction in allergy frequency. As the predisposition towards allergic immune responses already exists before birth, it seems sensible to initiate immune modulation using omega-3 fatty acids during pregnancy. In this randomized, placebo-controlled study 98 atopic, pregnant women were included. From the 20th week of gestation until delivery 52 women received fish oil (3.7 g omega-3 PUFAs per day), 46 received placebo. In the group with fish oil supplementation the examination of the newborn babies showed significantly higher proportions of omega-3 PUFAs in neonatal erythrocyte membranes. All neonatal cytokine responses to all allergens tended to be lower in the fish oil group. At 1 year of age infants in the fish oil group (n=40) were significantly less likely to have an allergic response to specific allergens, e.g. to egg, compared with the placebo group. Conclusion The adequate dietary supply of pregnant women with omega-3 fatty acids can significantly reduce the risk of the development and the severity of infant allergy. The modulation of the immune system is beneficially influenced already in the prenatal phase.
Omega-3 Fatty Acids
2
High maternal plasma DHA during pregnancy is directly associated with neonatal sleep-state patterning Higher maternal plasma docosahexaenoic acid during pregnancy is associated with more mature neonatal sleep-state patterning Cheruku SR, Montgomery-Downs HE, Farkas SL. Am J Clin Nutr 2002;76(3):608-13.
Summary The role of omega-3 fatty acids for metabolism and cell growth has been impressively reported in numerous studies. The polyunsaturated fatty acids have an effect on many physiological processes and are essential building-blocks of the membranes of all body cells. In particular the phospholipid composition of the brain and the retina is characterized by a high content of omega-6 and omega-3 fatty acids, especially of docosahexaenoic acid (DHA). A sufficient supply of these fatty acis according to the special requirements is important for the functional maturation of tissues during the embryonic and neonatal period. However, the fetus is to a great extent depending on the placental supply. This is why in pregnancy, above all in the last trimester, long-chain fatty acids are selectively transferred from the maternal circulation to the fetus. In the study by Cheruku and colleagues the association between materal plasma DHA concentration and the neonatal sleep pattern as a marker for functional integrity of the central nervous system was determined. On the basis of the median plasma DHA level (by weight of total fatty acids) on the day of delivery, the study participants were divided into 2 groups: one group with high DHA levels (>3% DHA by weight of total fatty acids) and one group with low DHA (≤3% DHA by weight of total fatty acids). On the first and second day after delivery, the neonatal sleep-state patterns were assessed by means of the Motility Monitoring System (MMS) using a sensor pad recording the infant’s respiration and body movements. Results The investigators found a significant correlation between maternal DHA plasma levels and the sleep patterns of the newborns. Children whose mother had a high plasma DHA concentration had less active sleep and a more favorable relation between active sleep and quiet sleep. Also, and especially on the second day after birth, the neonates of mothers with high DHA levels showed markedly longer periods of wakefulness (48.2%) compared to neonates of mothers with low DHA levels (28.33%). Conclusion An adequate supply of docosahexaenoic acid to pregnant and breastfeeding women has a substantial effect on the nature of neonatal sleep patterns which may be interpreted as a sign for CNS maturity.
Omega-3 Fatty Acids
2
Relationship between diet, DHA content in mother’s milk and postpartum depression Seafood consumption, the DHA content of mothers’ milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. Hibbeln JR. J Affect Disord 2002;69(1-3):15-29.
Summary In pregnancy, nutrients for the fetus are all transferred from the maternal organism. This is also true of docosahexaenoic acid (DHA), an omega-3 fatty acid which is essential for neurological development. Since the DHA requirements of both the fetus and the neonate are very high, a DHA deficiency may occur during pregnancy or shortly after delivery in the maternal body. Several studies indicate that an inadequate dietary supply of DHA to the mother may increase the risk of postpartum depression. DHA is the omega-3 fatty acid which is especially abundant in fish oil. Therefore it is assumed that in countries with a high consumption of seafood the incidence of postpartum depression may be clearly reduced. In order to examine on a broad basis the association between diet during pregnancy and the prevalence of postpartum depression, 41 studies on this subject from 23 countries including 14,542 women were evaluated. All studies used the Edinburgh Postpartum Depression Scale (EPDS) for the subjects’ assessment. This scale was developed especially to estimate and compare the frequency and severity of postpartum depression. Results The prevalence rate of postpartum depression varied between 0.5% in Singapore and 24.5% in South Africa. The mean prevalence rate amounts to 12.4%. Basically authors noted that a high national consumption of seafood was strongly associated with low prevalence rates. Similarly they found that a high DHA content in mother’s milk predicts a low frequency of postpartum depression. The DHA content in mother’s milk again is closely related to the seafood consumption and is a marker for the maternal omega-3 fatty acid status. Due to current study results therefore the intake of at least 300 mg DHA daily is recommended for pregnant women. Conclusion The adequate dietary supply of omega-3 fatty acids, above all of DHA, to pregnant women can significantly lower the risk of developing postpartum depression.
Omega-3 Fatty Acids
2
Supplementation of long-chain unsaturated fatty acids in pregnancy and lactation Perinatal supply and metabolism of long-chain polyunsaturated fatty acids: importance for the early development of the nervous system Larque E, Demmelmair H, Koletzko B. Ann N Y Acad Sci 2002;967:299-310. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children‘s IQ at 4 years of age Helland IB, Smith L, Saarem K, et al. Pediatrics 2003;111(1):e39-44.
Summary Long-chain polyunsaturated fatty acids (PUFA), such as arachidonic acid (AA) and docosahexaenoic acid (DHA), are essential structural lipid components of biomembranes. In particular during the last trimester of pregnancy and in the first months of the prenatal period, the need for these fatty acids is very high, as in these periods major growth and developmental processes take place. In pregnancy long-chain PUFAs (polyunsaturated fatty acids) are preferentially transferred from mother to fetus across the placenta. Breastfed children receive long-chain fatty acids through the breast milk. Aiming to confirm the role of the prenatal supply of PUFAs, a number of double-blind randomized studies with PUFA-enriched infant formula were made. In detail, the effect on the development of vision and cognitive performance was assessed. On the basis of the data evaluated, it may be concluded that long-chain PUFAs in the early prenatal period are potentially to be considered essential micronutrients and are able to favorably influence the development. An expert panel of the Child Health Foundation recommend the supplementation of maternal diet with long-chain PUFAs during pregnancy and lactation. The sufficient dietary supply with omega-3 fatty acids, above all DHA, has beneficial effects on the cognitive functions of the growing child lasting long beyond the actual supplementation period. In a randomized double-blind study by Helland and colleagues (2003), 84 children at four years of age were tested with the Kaufman Assessment Battery for Children (K-ABC) for intelligence and cognitive performance. The mothers of the intervention group had received cod liver oil with a high content of omega-3 fatty acids and DHA from the 18th gestational week until three months after delivery. Mothers in the control group had received corn oil during the same period of time. Results The children of mothers who had taken cod liver oil in pregnancy showed markedly superior scores in all subscales of the test. The superiority in the Mental Processing Composite (a measure for the child’s intelligence) was significant. Conclusion Omega-3 fatty acids, especially DHA, have a sustained influence on the cognitive performance of the child. The Child Health Foundation recommends the supplementation of long-chain unsaturated fatty acids in pregnancy and lactation.
Omega-3 Fatty Acids
2
Fish oil supplementation in high risk pregnancies Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. Olsen SF, Secher NJ, Tabor A, et al. BJOG 2000;107(3):382-95.
Summary Numerous trials report that the dietary supply of omega-3 fatty acids may favorably influence the course of pregnancy. Therefore it is strongly assumed that also in high risk pregnancies the sufficient supply of omega-3 fatty acids may reduce the frequency of potential complications. The authors of this multicenter trial tested whether the early supplementation of fish oil reduces the risk of preterm delivery, intrauterine growth retardation, pre-eclampsia and pregnancy-induced hypertension. In total, 1,647 pregnant women at 19 European research sites who had a known history of the pregnancy-associated complications mentioned or of twin pregnancies, participated in this project. The women were divided into 6 subgroups, 4 prophylactic and 2 therapeutic groups. The subjects of the prophylactic groups (n=724) received from the 20th gestational week 2.7 g fish oil (1.3 g eicosapentaenoic acid, 0.9 g docosahexaenoic acid) daily. In the control group 753 women received daily olive oil. In the subgroups for the assessment of therapeutic effects, all 142 women ingested daily 6.1 g fish oil (2.9 g eicosapentaenoic acid, 2.1 g docosahexaenoic acid) or olive oil from the 33rd gestational week. Results The intake of fish oil reduced the risk of recurrent preterm deliveries in the prophylactic trial groups from 33% to 21%. The mean pregnancy duration was 269 days with the prophylactic administration of fish oil. In the women of the therapeutic groups who had received olive oil, investigators observed a mean pregnancy duration of 260 days. There were no significant effects on the other study parameters. Conclusion In high risk pregnancies the early dietary supplementation of omega-3 fatty acids can significantly reduce the recurrent risk of preterm delivery.
Micronutrients
3
Occurrence of congenital heart defects and maternal multivitamin use Occurrence of congenital heart defects in relation to maternal multivitamin use Botto LD, Mulinare J, Erickson JD. Am J Epidemiol 2000;151(9):878-84.
Summary Cardiac defects occurring in at least one in 150 newborns are the most common group of major congenital anomalies. The factors increasing the risk of an anomaly are known for few defects only. Known risk factors include rubella infection or maternal diabetes mellitus. Also the maternal multivitamin status seems to influence the occurrence of heart anomalies. This was suggested by the results of current population-based studies. However, in many cases not only the periconceptional supplementation but also the early preconceptional dietary supplementation with micronutrients should be recommended because many developmental processes in which a congenital defect may occur take place in a very early stage of pregnancy. Therefore, already at the start of pregnancy vitamins, minerals and trace elements should be administered at sufficient doses. The association between the early supply of micronutrients based on the actual need and the risk of congenital anomalies was determined in several studies, including the Atlanta Birth Defect Case-Control study. In this population-based case-control study including 3,987 pregnant women, the incidence of congenital heart defects in children was analyzed in relation to the maternal use of multivitamin combinations. Women who had supplemented their diet 3 months before and after conception on a regular basis with a multivitamin combination were assigned to a subgroup and compared to women who had not taken any supplemental vitamins in this period. Results In the group of early multivitamin users the risk of the occurrence of congenital heart defects could be reduced by 24%. In particular a significant risk reduction was found for common outflow tract defects (-54%) and for ventricular septal defects (-39%). Conclusion With the intake of a combination of micronutrients before and during pregnancy the incidence of heart anomalies can be reduced.
Micronutrients
3
Effect of vitamins E and C on oxidative stress and placental function in women at risk of pre-eclampsia Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial Chappell LC, Seed PT, Briley AL, et al. Lancet 1999;354(9181):810-6. Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function Chappell LC, Seed PT, Kelly FJ, et al. Am J Obstet Gynecol 2002;187(3):777-84.
Summary Pre-eclampsia is a relatively frequent complication of pregnancy characterized by symptoms including proteinuria, hypertension and edema. It is a common cause of maternal mortality and morbidity and may lead to preterm birth or still birth. The disorder occurs due to a disturbance of microcirculation which, among other factors, results in an impaired placental perfusion. The causes of pre-eclampsia have not yet been ultimately identified, as one major factor of pathophysiology oxidative stress is discussed. The plasma concentration of ascorbic acid is low, and the formation of reactive oxygen species in the placenta is increased. In a previous publication, Chappel and colleagues reported on a highly significant reduction of pre-eclampsia risk by supplementing 1,000 mg vitamin C and 400 IU vitamin E per day (Chappel et al. 1999). In an additional evaluation of the study mentioned, the authors determined whether and how vitamin supplementation influences indices of placental dysfunction. Before the start of the study pregnant women were examined for any risk factors. These comprised pre-eclampsia in previous pregnancies and abnormal Doppler ultrasound findings in uterine arteries. In total, 79 pregnant women at high pre-eclampsia risk received daily 1,000 mg vitamin C and 400 IU vitamin E (from gestational week 16 women with a previous history, and from gestational week 20-22 women with normal test results). They were compared to 81 pregnant women at high risk who received a placebo; 32 pregnant women at low risk served as controls. Results In the placebo group at high pre-eclampsia risk, clear signs of oxidative stress and placental dysfunction were observed. In the high-risk group with vitamin supplementation, risk markers of pre-eclampsia improved significantly: The ascorbic acid plasma levels as well as the markers of oxidative stress and placental function reached almost the values of the low-risk group. Plasma levels of vitamin E in the intervention group were 30% above the levels of the group that had not taken any vitamin supplement. Conclusion Antioxidant supplementation in women at risk of pre-eclampsia reduced this risk as well as the oxidative stress, and improved placental function.
Micronutrients
3
Effects of periconceptional multivitamin supplementation on pregnancy outcomes Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report. Czeizel AE, DudĂĄs I, MĂŠtneki J. Arch Gynecol Obstet 1994;255(3):131-9.
Summary Numerous studies confirm that the periconceptional supplementation of a multivitaminfolic acid combination may reduce the occurrence of neural tube defects. But beside the preventive effect on the development of fetal diseases, also other beneficial impacts are possible. There is some evidence for the fact that an optimal vitamin supply is not only critical to a healthy course, but also to the very occurrence of pregnancy itself. In the present study, the effects of a periconceptional supplementation of a combination of trace elements, compared to a multivitamin-folic acid combination, on the desired occurrence of pregnancy were assessed. In total, 3.953 subjects received a daily multivitamin combination containing 0.8 mg folic acid from the 28th day before the expected fertile days until the timepoint of the second missed menstrual period. In the control group, 3,952 study participants received a dietary supplement of trace elements during the same period of time. The series of study examinations included the recording of the number of pregnancies and the occurrence of neural tube defects. Results Multivitamin-folic acid supplementation significantly increased the rate of conceptions amounting to 71.3% compared to 67.9% in the group who had received only trace elements. Furthermore, the occurrence of neural tube defects was reduced in the multivitamin group. Conclusion The periconceptional supplementation of a multivitamin-folic acid combination improved fertility. The occurrence of neural tube defects was reduced at the same time.
Micronutrients
3
Correlation between plasma homocysteine levels, folate status and MTHFR gene mutation in women with recurrent spontaneous abortion Plasma homocysteine levels correlated to interactions between folate status and methylene tetrahydrofolate reductase gene mutation in women with unexplained recurrent pregnancy loss Kumar KS, Govindaiah V, Naushad SE, et al. J Obstet Gynaecol. 2003;23(1):55-8.
Summary Hyperhomocysteinemia is a risk factor for recurrent spontaneous abortion. This disorder is related either to a hereditary defect in the methionine-homocysteine pathway or it might be acquired as a result of deficiencies of vitamin B12 and folic acid. The genetic predisposition as well as the dietary supply of the micronutrients mentioned seem to have an equal impact on pathogenesis. The reasons are that, on the one hand, both vitamins contribute to the conversion of homocysteine to methionine, and, on the other, the metabolic reaction is catalyzed by the methylene tetrahydrofolate reductase (MTHFR) enzyme. This study aimed to assess the correlation between folate level and homocysteine concentration as well as the effects of hereditary MTHFR defects on the development of hyperhomocysteinemia. Study participants were 24 women who in their history had three or more consecutive recurrent pregnancy losses prior to the 22nd week of gestation. Before start of the study, all subjects and their partners had been screened for chromosomal anomalies, and the female subjects additionally underwent ultrasound and hormonal status tests. Another group including 24 females who had already completed one successful pregnancy and did not have any early abortion in their history served as control. Results In a total of 37.5% of the women with previous recurrent spontaneous abortions significantly lower folate levels were measured, while in the control group only 20.8% of women had a folate deficiency. The highest values of homocysteine concentration were found in women experiencing recurrent pregnancy loss with both the hereditary enzyme defect and folate deficiency. Conclusion The early diagnosis of hyperhomocysteinemia may contribute to initiating treatment, e.g. with folic acid supplementation, to ensure a healthy course of pregnancy.
Micronutrients
3
Folic acid supply and occurrence of neural tube defects in the infant Folate intake and the risk of neural tube defects: an estimation of dose-response Moore LL, Bradlee ML, Singer MR, et al. Epidemiology 2003;14(2):200-5.
Summary Several trials could show that with the supplementation of multivitamin-folic acid combinations in the periconceptional period and in early pregnancy, the risk of neural tube defects could be reduced significantly. However, study results do not provide any clear data concerning the optimal folic acid dose and the proper time point for the start of such supplementation. Therefore, in 23,228 pregnant women data on diet and vitamin intake in the early second trimester of pregnancy were collected during the course of pregnancy. The case-related endpoint of each survey was the prenatal diagnosis of a neural tube defect or birth. The daily total folic acid intake (from diet plus supplements) was measured as DFE (dietary folate equivalents) units. Here 1 DFE means 1 µg folic acid from the diet or 0.5 µg folic acid from supplements or 0.6 µg from folate-enriched foods. Prevalence rate of neural tube defects Prevalence rate 1st to 5th week of gestation 0.8
Conception
0.6 0.4 0.2
0
200
400
600
800
1000 1200
Folic acid intake per day expressed in μg
Results For each additional folic acid intake, i.e. each additional 500 DFE consumed per day, the prevalence of neural tube defect decreased by 22% (95% confidence internal [CI] 0.47-1.09) per 1,000 pregnancies. Conclusion The risk of fetal neural tube defects declines markedly with modest increased total folic acid consumption in early pregnancy. Risk reduction is clearly correlated with the total dose of additional folic acid consumed.
Micronutrients
3
Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Javaid MK, Crozier SR, Harvey NC, et al. Lancet 2006; 367: 36-43
Summary Vitamin D deficiency during pregnancy may lead to a reduced bone mineral content of the child. This deficiency still exists years later and is likely to have an effect on the risk of osteoporosis in future years of life. In this retrospective cohort study investigators examined the maternal vitamin D status during pregnancy and the later bone mass of the child. For the longitudinal study, data of 198 children were evaluated who were born in 1991 and 1992. The maternal body build, nutrition and vitamin D status during pregnancy were assessed in relation to the children’s bone mass and body size at the age of 9 years. Vitamin D deficiency of the mother during pregnancy was proven: 18% of them had a deficient (<11 μg/l 25(OH)-vitamin D) and 31% an insufficient vitamin D status (11 µg/l to 20 μg/l 25(OH)-vitamin D). A low maternal vitamin D concentration (<20 μg/l 25(OH)-vitamin D), especially during the late months of pregnancy, was associated with a reduced childhood whole-body bone mineral content (BMC) also beyond the 9th year of life. When mothers had a deficient vitamin D status (<11 μg/l 25(OH)-vitamin D), their children showed a statistically significant decrease of bone mass.
1
Maternal serum vitamin D levels during pregnancy
Childhood whole-body BMC1 at the age of 8-9 years
< 11 µg / l
1.04 kg
1 1-20 µg / l
1.14 kg
> 20 µg / l
1.16 kg
BMC = Bone mineral content
Conclusion The study results show that the maternal vitamin D status during pregnancy is associated with a sustained reduction of bone mineral content in the offspring during childhood. Vitamin D supplementation of pregnant women could lead to enhanced bone-mineral accrual and reduce the risk of osteoporotic fracture in their children.
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