Myo-inositol, glucose and zinc concentrations determined in the preconceptional period, during and after pregnancy.

OBJECTIVE: To determine the blood concentrations of myo-inositol, glucose and zinc before, during and after normal pregnancy. STUDY DESIGN: Preconceptionally, at 6, 10, 20, 30 and 37 weeks amenorrhea, and 6 weeks after delivery, blood samples of 18 nulliparae and 19 multiparae were obtained and concentrations of serum inositol and glucose, and red blood cell zinc were determined. The data were analyzed using a linear mixed model. RESULTS: The preconceptional mean (S.E.M.) inositol concentration of 21.7 (1.03) micromol/L was comparable to the concentrations at 6 and 37 weeks amenorrhea, 22.2 (1.03) micromol/L, and 19.9 (1.10) micromol/L, respectively. However, the inositol concentrations at 10 and 20 weeks amenorrhea and post partum were significantly lower than the preconceptional inositol concentration, p<0.05. The preconceptional mean (S.E.M.) glucose concentration of 3.9 (1.03) mmol/L was comparable to the concentration at 6 and 10 weeks amenorrhea, 3.9 (1.04) mmol/L and 3.8 (1.04) mmol/L respectively. Also at 20, 30 and 37 weeks amenorrhea and after delivery the glucose concentration was significantly lower than the preconceptional glucose concentration, p<0.05. Preconceptional red blood cell zinc concentrations were comparable to concentrations at 6, 10 and 20 weeks amenorrhea. At 30 and 37 weeks amenorrhea and post partum the zinc concentrations were significantly higher than in the preconceptional period (p<0.01). CONCLUSION: The concentrations of inositol, glucose and zinc significantly change during pregnancy. However, the preconceptional blood concentrations reflect the concentrations determined in the first pregnancy trimester rather well, which is important information to be used in future studies into the role of inositol, glucose and zinc in reproductive disorders.

Marginal maternal vitamin B12 status increases the risk of offspring with spina bifida.

OBJECTIVE: The purpose of this study was to investigate B vitamins and homocysteine as risk factor for offspring with spina bifida. STUDY DESIGN: Blood samples from 45 mothers and their children with spina bifida and from 83 control mothers and their children were obtained to determine the levels of serum and red blood cell folate, serum vitamin B(12), whole blood vitamin B(6), and total plasma homocysteine. RESULTS: In the case mothers, the vitamin B(12) concentration was 21% lower (95% CI, 8%-33%) compared with control mothers. Unlike folate, vitamin B(6,) and homocysteine, a vitamin B(12) concentration of

Low maternal dietary intakes of iron, magnesium, and niacin are associated with spina bifida in the offspring.

Evidence about the preventive effects of nutrients other than folate on the occurrence of spina bifida is scarce. Therefore, the aim of this work was to investigate the role of maternal nutritional intake and the risk of spina bifida in the offspring. In 106 cases and 181 controls, the mothers' nutrient intakes were obtained by an FFQ approximately 24 mo after conception of the index pregnancy. Energy-adjusted mean nutrient intakes were compared, and odds ratios (OR) and 95% CI were calculated. Although mean nutrient intakes were comparable to the Dutch food consumption survey data, fat, cholesterol, iron, and folate intakes were below the 1998 Dutch Recommended Daily Allowances. Case mothers had significantly lower intakes of plant proteins (7%), polysaccharides (4%), fiber (7%), iron (6%), magnesium (6%), and niacin (4%) than control mothers. Mono- and disaccharide intakes were significantly higher (6%) in the case mothers than in control mothers. The adjusted OR (95% CI) in the lowest quartiles for plant proteins was 5.4 (2.3-12.4), for fiber 3.1 (1.5-6.8), for iron 3.5 (1.4-8.3), for magnesium 1.9 (0.9-4.1), and for niacin 2.5 (1.2-5.2). Mono- and disaccharide and polysaccharide intakes in the highest quartile had ORs (95% CI) of 2.9 (1.4-6.3) and 0.5 (0.3-1.0), respectively. The nutritional intake of Dutch women from food groups containing iron and folate seems to be compromised. Low preconceptional intakes of plant proteins, iron, magnesium, and niacin are associated with a 2- to 5-fold increased risk of spina bifida.

High-resolution 1H NMR spectroscopy of amniotic fluids from spina bifida fetuses and controls.

OBJECTIVE: To quantify proton containing metabolites by in vitro 1H NMR spectroscopy of amniotic fluids from fetuses with spina bifida and controls. STUDY DESIGN: Fourteen amniotic fluids from spina bifida fetuses and 18 controls were obtained. Concentrations of carbohydrates, organic acids and amino acids were determined. Multiple linear regression analysis was used to evaluate the data. RESULTS: At 15 and 39 weeks amenorrhea, the estimated median amniotic fluid concentrations of succinic acid and glutamine were significantly higher in the spina bifida group compared to controls, 37 and 64%, respectively. Whereas creatine and creatinine were significantly lower, 27 and 36%, respectively. Amenorrhea influenced the concentrations of most compounds with the exception of lactic acid. CONCLUSION: 1H NMR spectroscopy shows significantly higher succinic acid and glutamine concentrations in amniotic fluids derived from spina bifida fetuses compared with controls. A derangement in amino acid metabolism is suggested.

Are myo-inositol, glucose and zinc concentrations in amniotic fluid of fetuses with spina bifida different from controls?

OBJECTIVE: Associations are reported between myo-inositol, glucose, zinc and the occurrence of spina bifida. To gain more insight into the pathogenesis of spina bifida, the concentrations of myo-inositol, glucose and zinc were determined in amniotic fluids from pregnancies with a spina bifida or unaffected control fetus. METHODS: Amniotic fluids of 27 pregnancies complicated by spina bifida and 49 controls were collected at the Department of Obstetrics and Gynecology of the University Medical Center Nijmegen in the Netherlands. Myo-inositol, glucose and zinc concentrations were determined. By indication, the samples were taken at different gestational ages. Therefore, the data were evaluated using multiple linear regression analysis to adjust for gestational age. RESULTS: Amniocentesis was performed at a more advanced gestational age in the spina bifida group than in controls. In the spina bifida group, amniotic fluid myo-inositol, glucose and zinc concentrations gradually declined throughout pregnancy. At a gestational age of 15 weeks, the estimated mean amniotic fluid glucose and zinc concentrations in the spina bifida group were, respectively, significantly lower (p< or =0.5) and higher (p< or =0.5) compared with the control group. At the same gestational age, the estimated mean myo-inositol concentrations were comparable in both groups. At a gestational age of 38 weeks, the estimated mean myo-inositol, glucose and zinc concentrations were not significantly different in the spina bifida compared with the control group. CONCLUSION: This study may suggest that a derangement in zinc and glucose transfer or metabolism is associated with spina bifida. Since compounds in amniotic fluid are only a very crude marker of the actual fetal condition, studies that focus on the metabolism of these compounds on tissue or even cellular level should be performed to clarify their role in the pathogenesis and future prevention of spina bifida.

Kinetics of myo-inositol loading in women of reproductive age.

BACKGROUND: Myo-inositol plays a key role in an important intracellular signalling pathway. A deranged myo-inositol metabolism has been associated with neural tube defects. A myo-inositol loading test was performed to investigate the kinetics in healthy women of reproductive age. METHODS: Five healthy non-obese females [mean age (standard deviation: SD) 22.8 (2.2) years] were recruited at the University Medical Center Nijmegen. Blood samples were drawn fasting and at 20, 40, 60, 90, 180 and 270 min after ingestion of 100 mg/kg body weight of myo-inositol. Urine samples were collected before myo-inositol loading and at 180 and 270 min post-loading. Samples were analysed for serum myo-, epi- and scyllo-inositol and glucose concentrations by gas chromatography. Plasma insulin concentrations were determined by radio-immunoassay. Random intercept models were fitted to evaluate the data. RESULTS: The estimated myo-inositol and scyllo-inositol concentrations both reached maximum values at 180 min post-loading, respectively: mean (SD) 101.5 (9.2) micro mol/L and 1.09 (0.11) micro mol/L. The estimated plasma insulin and serum glucose concentrations decreased slightly but significantly during the experiment: P < 0.0001 and P < 0.05, respectively. At 180 and 270 min post-loading, urinary myo-inositol concentrations were increased and urinary glucose concentrations were unchanged. CONCLUSIONS: Myo-inositol enters the bloodstream quickly after oral ingestion and a small amount of myo-inositol is converted to scyllo-inositol. The synthesis of glucose from myo-inositol could not be detected by serum measurements. These data can be used in further research into the association between myo-inositol and neural tube defects.

Orofacial clefts and spina bifida: N-acetyltransferase phenotype, maternal smoking, and medication use.

BACKGROUND: Orofacial clefts and spina bifida are midline defects with a multifactorial etiology. Maternal smoking and medication use periconceptionally have been studied as risk factors for these malformations. The biotransformation enzyme N-acetyltransferase 2 (NAT2), plays a part in the inactivation of toxic compounds in cigarette smoke and medication. We investigated maternal NAT2 phenotype and the interaction with smoking and medication use periconceptionally on orofacial cleft and spina bifida risk in offspring. METHODS: In this case-control study of 45 mothers of orofacial cleft children, 39 mothers of spina bifida children and 73 control mothers, NAT2 acetylator status was determined by measuring urinary caffeine metabolites. RESULTS: Slow NAT2 acetylators showed no increased risk for orofacial cleft (OR = 1.0, 95% CI: 0.4-2.3) or spina bifida offspring (OR = 0.7, 95% CI: 0.3-1.7) compared to fast NAT2 acetylators. More mothers with orofacial cleft and spina bifida offspring smoked cigarettes (36% and 23% respectively) and used medication periconceptionally (38% and 44% respectively) compared to control mothers (smoking:18%, medication use:19%). No interaction between maternal NAT2 acetylator status and smoking or medication use was observed for orofacial cleft and spina bifida risk. CONCLUSIONS: Maternal smoking and medication use is associated with orofacial cleft risk as well as medication use is with spina bifida. The maternal NAT2 acetylator status, however, was not associated with an increased risk for orofacial cleft or spina bifida offspring, nor in combination with periconceptional smoking or medication use.