Elevated amniotic fluid ferritin levels are associated with inflammation-related pregnancy loss following mid-trimester amniocentesis.

OBJECTIVE: Occult infection accounts for up to 12% of pregnancy losses following genetic amniocentesis. Elevated serum and cervical fluid levels of ferritin, an acute-phase reactant, have been associated with spontaneous preterm delivery. We determined the association between amniotic fluid (AF) ferritin levels and post-amniocentesis pregnancy loss. METHODS: We performed a case-control study involving 66 women with a non-anomalous fetus who had a spontaneous pregnancy loss within 30 days following genetic amniocentesis and 66 term controls matched for maternal age, gestational age, time of test and indication for amniocentesis. Amniotic fluid ferritin and interleukin-6 (IL-6) levels were measured using commercially available kits. RESULTS: Mean (+/- SD) AF ferritin levels were similar between the cases (19.3 +/- 21.4 ng/ml) and the controls (19.8 +/- 22.7ng/ml) (p = 0.9). Mean (+/- SD) AF IL-6 levels were significantly higher in the women with post-amniocentesis pregnancy loss (4.0 +/- 13.1 ng/ml) than in controls (0.5 +/- 0.7 ng/ml) (p = 0.04). A significant proportion (12.1%, 8/66) of the women with post-amniocentesis pregnancy loss had elevated amniotic fluid IL-6 levels (> 3 SD, 2.5 ng/ml) indicating inflammation, as compared to none in the control group (p = 0.01). In this subgroup of women with pregnancy loss and elevated IL-6 levels, AF ferritin levels were significantly elevated (52.0 +/- 45.5 ng/ml) compared to the level in women who had a term delivery (19.8 +/- 22.7 ng/ml) (p = 0.002), and were strongly correlated with IL-6 levels among the cases (r = 0.67, p < 0.001). CONCLUSION: The strong correlation of AF ferritin with IL-6 levels, along with the high ferritin values in cases with high AF IL-6, indicates that ferritin is a marker of inflammation in asymptomatic women destined to have an early pregnancy loss.

Plasma extracellular superoxide dismutase activity in healthy pregnant women is not influenced by zinc supplementation.

We hypothesized that plasma extracellular superoxide dismutase (EC-SOD) activity reflects the zinc nutriture of healthy pregnant women. Sixty-three women were selected from 580 African-American women who participated in a clinical trial to evaluate the effect of prenatal zinc supplementation on pregnancy outcome. Half of the women received zinc (25 mg/d) and the other half was given a placebo from about 19 wk gestation to delivery. In the trial, a positive effect of zinc supplementation on birthweight was observed, indicating that the population as a whole had suboptimal zinc nutriture. Using plasma samples obtained during the trial, EC-SOD activities were measured and the values were compared with plasma zinc concentrations and plasma alkaline phosphatase activities. Plasma EC-SOD activities in our subjects were lower than previously published values for healthy adults in Korea. Although plasma EC-SOD activity may reflect severe zinc deficiency, it is not a sensitive marker for marginal deficiency status. Plasma EC-SOD activities did not prove to be a better indicator of zinc nutriture of pregnant women than either plasma zinc or plasma alkaline phosphatase activities.

Effect of feeding on circulating micronutrient concentrations in the Burmese python (Python molurus).

Burmese pythons (Python molurus) regulate digestive performance and metabolism with the ingestion of each meal. To explore the python's postprandial responses, we monitored the concentrations of blood micronutrients and homocysteine during fasting and for 15 days after feeding. Plasma folate concentrations peaked with a 270% increase over fasting levels 3 days after feeding, whereas plasma B-12 peaked with a 66% increase within 1 day. Erythrocyte folate concentrations were highest 15 days after feeding with a 44% increase. The major plasma folate was 5-methyltetrahydrofolate during fasting and was non-5-methyltetrahydrofolate during digestion, whereas erythrocytes contained polyglutamyl forms of non-5-methyltetrahydrofolate. Plasma homocysteine concentrations peaked with a 56% increase 3 days after feeding, and were markedly greater than those of mammals. Plasma zinc and copper did not change significantly. Plasma zinc concentrations were 20 times greater than plasma copper and approximately 30 times higher than those of mammals. Pythons showed a significant postprandial decline of 25% in hematocrit. Plasma pyridoxal 5'-phosphate (coenzyme form of vitamin B-6) was not detected probably due to its tight protein binding. Most micronutrient concentrations appear to plateau 3 days after feeding, suggesting that pythons have relatively rapid homeostasis of micronutrients despite the ingestion of large meals.

Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malformations.

OBJECTIVE: The aim of this study was determine whether the cytosine-to-thymine mutation at base 677 of the gene for methylenetetrahydrofolate reductase (C677T MTHFR ), which has been associated with neural tube defects, is also associated with congenital cardiac malformations. STUDY DESIGN: Amniotic fluid homocysteine levels were measured and the presence or absence of the C677T MTHFR mutation in amniocytes was determined in stored amniotic fluid obtained from 26 pregnancies complicated by isolated (presumed multifactorial) fetal cardiac defects and from 116 normal pregnancies. RESULTS: The pregnancies affected by fetal cardiac defects had higher amniotic fluid homocysteine levels (1.7 +/- 1.7 vs 1.0 +/- 0.7 micromol/L; P =.07) and included more samples with homocysteine levels >90th percentile (27% vs 9%; P =.02) and more cases with the C677T MTHFR mutation (35% vs 13%; P =.01). Fifty percent of cases had either a high homocysteine level or the C677T MTHFR mutation (50% vs 20%; P =.003) and 12% had both (12% vs 0%; P =.0006). CONCLUSION: Fifty percent of these isolated congenital cardiac defects were associated with either the C677T MTHFR mutation or elevated amniotic fluid homocysteine levels, or both. This finding adds to what is already known about the multiple and complex biochemical and developmental functions of the homocysteine pathway.

Low seminal plasma folate concentrations are associated with low sperm density and count in male smokers and nonsmokers.

OBJECTIVE: To measure folate levels in seminal plasma from smokers and nonsmokers and to evaluate relationships between seminal plasma folate levels and both folate nutriture and semen quality measures. DESIGN: Observational study. SETTING: United States Department of Agriculture, Western Human Nutrition Research Center, Presidio of San Francisco, San Francisco, California. PATIENT(S): Healthy male smokers (n=24) and nonsmokers (n=24). MAIN OUTCOME MEASURE(S): Blood levels of plasma folate and homocysteine, seminal plasma total, non-methyl- and 5-methyltetrahydrofolate concentrations, and total sperm count and density. RESULTS: Total seminal plasma folate concentrations were on average 1.5 times higher than blood plasma folate concentrations in all men. Seminal plasma folates contained 5-methyltetrahyrdofolate (74% of total) and non-methyltetrahydrofolates (26% of total); all samples had less than four glutamyl residues. Total and 5-methyltetrahydrofolate concentrations correlated significantly with blood plasma folate and homocysteine concentrations. Seminal plasma non-methyltetrahydrofolate levels correlated significantly with sperm density and total sperm count. Seminal plasma of smokers contained a proportionally lower concentration of non-methyltetrahydrofolates compared with nonsmokers. CONCLUSION(S): Seminal plasma total folate and 5-methyltetrahydrofolate concentrations reflect folate nutriture. The non-methyltetrahydrofolate fraction of seminal plasma may be important for male reproductive function.

Bioactivity of [6R]-5-formyltetrahydrofolate, an unusual isomer, in humans and Enterococcus hirae, and cytochrome c oxidation of 10-formytetrahydrofolate to 10-formyldihydrofolate.

The bio-inactive C-6 isomer, [6R]-5-formyl-tetrahydrofolate (5-HCO-H(4)F), is not found in Nature. An oral dose of 13.5 micromol of [6R]-5-HCO-H(4)F in humans results in the appearance of the naturally occurring [6S]-5-methyl-tetrahydrofolate and relatively large amounts of other bioactive folates in plasma. The removal of the asymmetry at C-6 could account for these results. Two oxidized cytochrome c [cyt c (Fe3+)] molecules oxidize one 10-formyl-tetrahydrofolate (10-HCO-H(4)F) with second-order kinetics and a rate constant of 1.3 x 10(4) M(-1) x s(-1). The folate product of this oxidation reaction is 10-formyl-dihydrofolate (10-HCO-H(2)F), which has no C-6 asymmetric centre and is therefore bioactive. The folate-requiring bacterium, Enterococcus hirae, does not normally biosynthesize cytochromes but does so when given an exogenous source of haem (e.g. haemin). E. hirae grown in haemin-supplemented media for 3 days utilizes both [6R]- and [6S]-5-HCO-H(4)F in contrast to that grown in control medium, which utilizes only the [6S] isomer. Since known chemical reactions form 10-HCO-H(4)F from 5-HCO-H(4)F, the unusually large rate constant for the oxidation of 10-HCO-H(4)F by cyt c (Fe3+) may account for the unexpected bioactivity of [6R]-5-HCO-H(4)F in humans and in E. hirae grown in haemin-containing media. We used an unnatural C-6 folate isomer as a tool to reveal the possible in vivo oxidation of 10-HCO-H(4)F to 10-HCO-H(2)F; however, nothing precludes this oxidation from occurring in vivo with the natural C-6 isomer.

Second-trimester plasma homocysteine levels and pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction.

OBJECTIVE: The purpose of this study was to determine whether second-trimester plasma homocysteine levels are elevated among women whose pregnancies are subsequently complicated by pregnancy-induced hypertension, preeclampsia, or intrauterine growth restriction. STUDY DESIGN: Women with normal but relatively low plasma zinc levels were randomly assigned to receive zinc supplementation or placebo from 19 weeks' gestation until delivery. Plasma homocysteine concentration and plasma and erythrocyte folate levels were determined for all available stored samples (zinc group, 231/294; placebo group, 206/286) at 26 and 37 weeks' gestation. Among all women with available samples, pregnancy-induced hypertension (n = 12) or preeclampsia (n = 4) developed in 16 women, and 22 pregnancies were complicated by intrauterine growth restriction. RESULTS: Mean homocysteine levels in women with pregnancy-induced hypertension and preeclampsia were similar to those of control subjects at 26 weeks' gestation but were significantly higher at 37 weeks' gestation. Homocysteine levels were similar between women with pregnancies complicated by intrauterine growth restriction and control subjects at both time points. CONCLUSION: Second-trimester plasma homocysteine concentrations do not predict the subsequent development of pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction.

Homocysteine, folate, vitamin B-12 and vitamin B-6 in patients receiving antiepileptic drug monotherapy.

We hypothesized that elevated plasma homocysteine concentrations (hyperhomocysteinemia) exist in patients receiving antiepileptic drugs (AED), and a long-term administration of AED may result in an increased risk of occlusive vascular disease in these patients. A total of 62 patients who received AED monotherapy (phenytoin, lamotrigine, carbamazepine or valproate) participated in this study. Blood concentrations of homocysteine, folate, vitamin B-12 and pyridoxal-5'-phosphate (PLP, a coenzyme form of vitamin B-6) were measured, and thermolabile genotypes of 5, 10-methylenetetrahydrofolate reductase (MTHFR) were also determined. Of 62 patients, only seven (11.4%) had hyperhomocysteinemia. Of 20 patients who received phenytoin, three (15.0%) had hyperhomocysteinemia, whereas 85% of these had plasma folate concentrations below the normal range. However, erythrocyte folate concentrations were abnormally low in only 25% of the patients who received phenytoin. Valproate administration increased serum vitamin B-12 concentrations. Over 55% of the entire patients had PLP concentrations below the normal range, although the reason is unknown. Only three patients had the homozygous thermolabile genotype of MTHFR; therefore, meaningful statistical analysis was not possible in this study. However, one patient with homozygous genotype who received phenytoin therapy had hyperhomocysteinemia with poor folate nutritional status, and the other two had normal homocysteine concentrations with normal folate status. Our data suggest that hyperhomocysteinemia is not a serious clinical concern in epileptic patients when folate nutriture is adequate.

Effects of dietary zinc deficiency on homocysteine and folate metabolism in rats.

In rats, zinc deficiency has been reported to result in elevated hepatic methionine synthase activity and alterations in folate metabolism. We investigated the effect of zinc deficiency on plasma homocysteine concentrations and the distribution of hepatic folates. Weanling male rats were fed ad libitum a zinc-sufficient control diet (382.0 nmol zinc/g diet), a low-zinc diet (7.5 nmol zinc/g diet), or a control diet pair-fed to the intake of the zinc-deficient rats. After 6 weeks, the body weights of the zinc-deficient and pair-fed control groups were lower than those of controls, and plasma zinc concentrations were lowest in the zinc-deficient group. Plasma homocysteine concentrations in the zinc-deficient group (2.3 +/- 0.2 micromol/L) were significantly lower than those in the ad libitum-fed and pair-fed control groups (6.7 +/- 0.5 and 3.2 +/- 0.4 micromol/L, respectively). Hepatic methionine synthase activity in the zinc-deficient group was higher than in the other two groups. Low mean percentage of 5-methyltetrahydrofolate in total hepatic folates and low plasma folate concentration were observed in the zinc-deficient group compared with the ad libitum-fed and pair-fed control groups. The reduced plasma homocysteine and folate concentrations and reduced percentage of hepatic 5-methyltetrahydrofolate are probably secondary to the increased activity of hepatic methionine synthase in zinc deficiency.

Maternal serum ferritin and fetal growth.

OBJECTIVE: To determine the relationship between maternal serum ferritin and concentrations and specific types of fetal growth restriction (FGR). METHODS: Serum ferritin concentrations were measured at approximately 25 and 36 weeks' gestation in 480 multiparas with singleton fetuses who participated in a study of risk factors for repeated FGR. Asymmetric FGR was defined by low birth weight for gestational age criteria and a ponderal index less than 2.32, and symmetric FGR was defined by the same birth weight for gestational age criteria and a ponderal index of at least 2.32. RESULTS: Among 480 infants, 370 were appropriate for gestational age (AGA), 58 had asymmetric FGR, and 52 had symmetric FGR. Higher ferritin concentrations were associated with black race, maternal age 25 years or older, and smoking. Mothers of asymmetric-FGR infants had higher mean ferritin levels than mothers of AGA infants at 25 weeks' (38.0 versus 20.2 microg/L, P < .01) and 36 weeks' gestation (21.0 versus 13.3 microg/L, P < .01), whereas mothers of symmetric-FGR infants had significantly lower ferritin levels at 36 weeks (8.3 microg/L). For mothers with serum ferritin levels of at least 26 microg/L (highest quartile at 25 weeks), the adjusted odds ratio (OR) for asymmetric-FGR infants was 3.4, 95% confidence interval (CI) 1.6, 7.2. There was a similar association between the highest quartile of serum ferritin at 36 weeks (at least 20 microg/L) and asymmetric FGR (adjusted OR 2.7, 95% CI 1.3, 5.8). Women with serum ferritin levels less than 3 microg/L (lowest quartile at 36 weeks) had an adjusted OR for symmetric-FGR infants of 2.2, 95% CI 1.01, 4.6. CONCLUSION: High maternal serum ferritin levels are associated with asymmetric FGR, whereas low serum ferritin levels are associated with symmetric FGR.

Maternal plasma zinc concentrations and pregnancy outcome.

BACKGROUND: There is no consensus in the literature as to whether maternal zinc nutriture is associated with pregnancy outcome or fetal growth. OBJECTIVE: We evaluated the associations between plasma zinc concentrations during pregnancy and various measures of pregnancy outcome and neonatal conditions at birth. DESIGN: We measured zinc concentrations in plasma samples obtained at a mean of 16 wk of gestation (range: 6-34 wk) from 3448 women who were screened for a trial designed to evaluate the effect of zinc supplementation on fetal growth. Subjects were from low socioeconomic backgrounds and attended a public health clinic for their prenatal care. Plasma zinc concentrations were compared with pregnancy outcome, including complications during pregnancy and delivery, and anthropometric measures and Apgar scores of neonates. RESULTS: Plasma zinc concentrations declined as gestation progressed. After plasma zinc concentrations were adjusted for gestational age, they were not significantly associated with any measure of pregnancy outcome or neonatal condition. CONCLUSION: We conclude that plasma zinc concentrations during the late first trimester to the early third trimester do not predict pregnancy outcomes in women of a low socioeconomic background.

Amniotic fluid homocysteine levels, 5,10-methylenetetrahydrafolate reductase genotypes, and neural tube closure sites.

A specific gene mutation leading to altered homocysteine metabolism has been identified in parents and fetuses with neural tube defects (NTDs). In addition, current animal and human data indicate that spine closure occurs simultaneously in five separate sites that then fuse. We sought to determine whether either this mutation or abnormal amniotic fluid homocysteine levels are associated with all five neural tube closure sites. We retrieved stored amniotic fluid from cases of isolated fetal neural tube defect diagnosed from 1988 to 1998 (n = 80) and from normal controls matched for race, month and year of amniocentesis, and maternal age. Cases were categorized according to defect site by using all available medical records. The presence or absence of the 677C-->T mutation of 5, 10-methylenetetrahydrafolate reductase (MTHFR) gene was determined, and homocysteine levels were measured; case and controls were compared. Significantly more cases than controls were heterozygous or homozygous for the 677C-->T MTHFR mutation (44% vs. 17%, P < or = 0. 001). Likewise, cases were significantly more likely than controls to have amniotic fluid homocysteine levels >90th centile (>1.85 micromol/L), 27% vs. 10%, P = 0.02. Most (83%) of control cases had both normal MTHFR alleles and normal amniotic fluid homocysteine levels (normal/normal), whereas only 56% of NTD case were normal/normal (P = 0.001). When evaluated by defect site, only defects involving the cervical-lumbar spine, lumbosacral spine, and occipital encephalocele were significantly less likely to be normal/normal than controls (P = 0.007, 0.0003, and 0.007, respectively), suggesting a strong association with the 677C-->T allele. In contrast, anencephaly, exencephaly, and defects confined to the sacrum included many cases that had both normal MTHFR alleles and normal homocysteine and were not significantly different from controls. The 677C-->T MTHFR mutation and elevated homocysteine levels appear to be disproportionately associated with defects spanning the cervical-lumbar spine, lumbosacral spine, and occipital encephalocele. In contrast, anencephaly, exencephaly, and defects confined to the sacrum may not be related to altered homocysteine metabolism.

Role of amniotic fluid homocysteine level and of fetal 5, 10-methylenetetrahydrafolate reductase genotype in the etiology of neural tube defects.

A mutation in the gene 5,10-methylenetetrahydrofolate reductase (MTHFR), leading to altered homocysteine metabolism, has been identified in parents and fetuses with fetal neural tube defects. We sought to determine which is of greater importance in fetal neural tube defect formation: the fetal MTHFR mutation or elevated amniotic fluid homocysteine level. We retrieved stored amniotic fluid from cases of isolated fetal neural tube defect diagnosed from 1988 to 1998 (n = 80), and from normal controls matched for race, month and year of amniocentesis, and maternal age. The presence or absence of the 677C-->T mutation of MTHFR was determined and homocysteine levels were measured; cases and controls were compared. Significantly more cases than controls were heterozygous or homozygous for the 677C-->T MTHFR mutation (44% vs 17%, P < or = 0.001). Cases were also significantly more likely than controls to have an amniotic fluid homocysteine level above the 90th centile (>1.85 micromol per liter); 27% vs 10%, P = 0.02. Thirty one cases and 12 controls had an abnormal genotype; however, amniotic fluid homocysteine levels were not significantly different between these two groups (6/31, or 19% of cases had an elevated homocysteine compared to 1/12, or 8% of controls; P = 0.65). In contrast, 40 cases and 60 controls had a normal genotype; the neural tube defect cases had significantly higher homocysteine levels (13/40, or 32% of cases had an elevated homocysteine level compared to only 6/60, or 10% of controls; P = 0.008). Although both abnormal fetal MTHFR genotype and abnormal amniotic fluid homocysteine concentration are significantly associated with neural tube defects, the association with amniotic fluid homocysteine concentration is significant regardless of the fetal MTHFR genotype. The relationship between maternal and fetal homocysteine metabolism is complex.

Folate and homocysteine metabolism in copper-deficient rats.

To investigate the effect of copper deficiency on folate and homocysteine metabolism, we measured plasma, red-cell and hepatic folate, plasma homocysteine and vitamin B-12 concentrations, and hepatic methionine synthase activities in rats. Two groups of male Sprague-Dawley rats were fed semi-purified diets containing either 0. 1 mg (copper-deficient group) or 9.2 mg (control group) of copper per kg. After 6 weeks of dietary treatment, copper deficiency was established as evidenced by markedly decreased plasma and hepatic copper concentrations in rats fed the low-copper diet. Plasma, red-cell, hepatic folate, and plasma vitamin B-12 concentrations were similar in both groups, whereas plasma homocysteine concentrations in the copper-deficient group were significantly higher than in the control group (P<0.05). Copper deficiency resulted in a 21% reduction in hepatic methionine synthase activity as compared to the control group (P<0.01). This change most likely caused the increased hepatic 5-methyltetrahydrofolate and plasma homocysteine concentrations in the copper-deficient group. Our results indicate that hepatic methionine synthase may be a cuproenzyme, and plasma homocysteine concentrations are influenced by copper nutriture in rats. These data support the concept that copper deficiency can be a risk factor for cardiovascular disease.

Gender difference in cord serum ferritin concentrations.

We measured cord serum ferritin concentrations in a total of 255 infants (116 females and 139 males), and evaluated the association between these values and various neonatal as well as maternal characteristics. The mean ferritin concentration in females (166 +/- 110 microg/l) was significantly higher than that in male infants (123 +/- 77 microg/l). The gender differences in ferritin were significant within groups of infants with fetal growth restriction, those who weighed <3,000 g, those whose mothers were African Americans or <25 years old. Maternal serum ferritin concentrations at 36 weeks of gestation significantly correlated with cord serum ferritin of male infants (r = 0.32, p < 0.001), whereas the association was not significant for females (r = 0.09, p > 0.41). Although the mechanism of the gender difference is unknown, it may be important to consider the sex of neonates when evaluating their iron nutriture immediately after birth.

Serum leptin concentrations during pregnancy and their relationship to fetal growth.

OBJECTIVE: To test the hypothesis that maternal and cord serum leptin concentrations correlate with birth weight of infants. METHODS: Pregnant women (n = 135) of low socioeconomic status who delivered full-term infants were selected from more than 1500 women who participated in a study to identify factors related to fetal growth restriction (FGR). They were divided into two groups based on their infants being classified as having FGR (n = 66) or not (n = 69), and each group was divided further into three subgroups based on prepregnancy body mass index (BMI): less than 19.8, 19.8-28.9, and 29 or more. Sample estimations indicated that 20 subjects per subgroup would be adequate to detect 50% difference in leptin concentrations. RESULTS: Mean maternal serum leptin concentrations adjusted for BMI were highest at approximately 22-27 weeks' gestation (29.8 ng/mL) and declined thereafter until term (25.2 ng/mL). Leptin concentration and prepregnancy BMI correlated significantly. We found neither significant difference in leptin concentrations between the subjects with and without FGR infants nor significant correlation between maternal leptin concentrations and birth weight of infants. Mean cord serum leptin concentration (10.8 ng/mL) was lower than maternal concentrations and correlated significantly with birth weight (r = .61, P < .001). CONCLUSION: Our findings suggest that maternal leptin concentration during pregnancy is not an accurate indicator of fetal growth. Cord serum leptin concentrations were lower than maternal serum concentrations and correlated significantly with birth weight.

Plasma and erythrocyte zinc concentrations and their relationship to dietary zinc intake and zinc supplementation during pregnancy in low-income African-American women.

OBJECTIVE: To evaluate the effects of usual dietary intake of zinc and of zinc supplementation during pregnancy on plasma and erythrocyte zinc concentrations. DESIGN: A randomized, double-blind, placebo-controlled trial. SUBJECTS: Low-income African-American women (n = 580) assigned randomly to groups at 19 weeks of gestation. INTERVENTION: A daily dose of zinc (25 mg) or a placebo until delivery. MAIN OUTCOME MEASURES: Plasma, erythrocyte, and dietary zinc levels. STATISTICAL ANALYSES: Multiple regression and repeated measures analysis of variance. RESULTS: In both the placebo and the supplemented groups, when all subjects were grouped by usual dietary zinc intake above or below the median (12 mg/day), results were the same: Women with high dietary zinc intake had higher erythrocyte zinc levels at the time of randomization and at all subsequent measurements during pregnancy than those who had low dietary zinc intake (P < or = .06; difference not significant for zinc-supplemented group); no difference was observed for plasma zinc levels. On the other hand, when the subjects were stratified at the median by total daily zinc intake (usual dietary zinc + 25 mg zinc supplement) during pregnancy, a significant difference in plasma zinc levels (P < .005) was found between women with high total zinc intake (mean = 38 mg/day) and low total intake (mean = 13 mg/day) at 26, 32, and 38 weeks of gestation; however, no such differences were found in erythrocyte zinc levels. APPLICATIONS: These results should help dietitians and other health professionals better understand the expected changes in plasma and erythrocyte zinc levels during pregnancy, and the relationship between dietary and supplemental zinc and zinc nutriture.

Plasma alkaline phosphatase and pregnancy outcome.

The objective was to determine the relationship between plasma alkaline phosphatase (AP) activity and birthweight (BWT) and preterm delivery (PTD). Five hundred eighty African-American women had plasma AP activities measured at various gestational ages (GA) with the results compared to a number of pregnancy outcomes. Plasma AP activity rose linearly during pregnancy from a mean of 39 U/L at 19 weeks to 130 U/L at delivery. In individual women, AP activities were consistently high or low as confirmed by correlation coefficients in adjacent time periods ranging from 0.63 to 0.87. AP at 19 weeks was not significantly associated with any outcome measure. However, at 26 weeks, AP in the highest quartile was associated with a 15.0% incidence of PTD < 37 weeks compared to 6.8% in the lower three quartiles (P = .004). For PTD < or = 32 weeks, the difference of PTD was 6.8 vs. 1.6% (P < .003). When women in the highest quartile of increase in AP from 19 to 26 weeks were compared to those in the lower quartiles, the rate of PTD < 37 weeks was 15.2 vs. 6.4% (P = .002), and the rate of PTD < or = 32 weeks was 6.1 vs. 1.7%, (P = .01). The mean BWT for the highest vs. the lower three quartiles in rate of increase was 3,058 vs. 3,288 g (P = .0005) and the mean GA was 38.1 vs. 39.2 weeks (P = .0001). Regression analyses adjusting for multiple confounders confirmed the association between high AP at 26 weeks and PTD < 37 weeks [OR (95% C.I.), 2.4 (1.2-4.8)] and PTD < or = 32 weeks [OR (95% C.I.), 3.7 (1.2-11.7)]. Similar results were found among women with a large increase in AP between 19 and 26 weeks. From these results we conclude that high or increasing AP activity at 26 weeks, but not 19 weeks, was significantly associated with subsequent PTD and a lower BWT.