Maternal origin of nucleated erythrocytes in peripheral venous blood of pregnant women

We studied the origin of nucleated red blood cells (NRBC) in peripheral venous blood samples from 40 pregnant women carrying a male fetus, using a technique that allows direct chromosomal analysis by in situ hybridisation on immunologically and morphologically classified cells. Samples from ten nulligravid women were studied as controls. NRBC were enriched by negative magnetic activated cell sorting (miniMACS) using anti-CD45 monoclonal antibody. NRBC were detected by alkaline phosphatase anti-alkaline phosphatase immunostaining using a monoclonal anti-glycophorin A antibody. The origin of the NRBC was determined by fluorescence in situ hybridisation using X and Y specific probes. NRBC were found in 37 of the 40 pregnant women at a range of 1 to 230 per 20 ml of venous blood and in 6 of the 10 controls at a range of 1 to 3 per 20 ml of venous blood. All NRBC detected in the pregnant women were evidently of maternal origin, and in the pregnant women the number of NRBC was significantly higher (P < 0.05) than in the controls. Pregnancy per se seems to induce the appearance of maternal NRBC in the circulation, and it cannot therefore be assumed that NRBC isolated from the maternal blood are of fetal origin on the basis of morphology alone. Discrimination of fetal NRBC must occur for prenatal diagnosis of fetal genetic disorders.     

Enrichment of fetal trophoblasts and nucleated erythrocytes from maternal blood by an immunomagnetic colloid system

The aim of this study was to isolate fetal trophoblasts and nucleated erythrocytes from maternal blood using the immunomagnetic colloid system. About 25 ml of maternal blood was collected from pregnant women between of 14 and 20 weeks gestation. Nucleated erythrocytes (NRBCs) were isolated from 5 ml of maternal blood and a nested polymerase chain reaction for the Y chromosome was used to determine fetal origin. The sensitivity of the fetal gender diagnosis was 80% and the specificity was 86%. Both fetal trophoblasts and NRBCs were isolated from the remaining 20 ml of maternal blood. The fetal gender of the trophoblast-enriched fraction was determined using fluorescence in situ hybridisation (FISH) with dual-colour XY-specific DNA probes. XY-specific signals were observed in 0.38% of cells sorted from all pregnant women carrying male fetuses (n = 10). Simultaneous immunophenotyping for the fetal haemoglobin and FISH using XY probes were used to evaluate the fetal origin of cells enriched with anti-CD71. The mean percentage of male fetal erythroblasts was 0.24% and the number of fetal erythroblasts was estimated to be about 672 in 20 ml of maternal blood. The number of fetal erythroblasts detected in our study was greater than that detected by most other separation techniques. Our study shows that it would be feasible to use the immunomagnetic colloid system for the isolation of both trophoblasts and NRBCs from the same maternal blood sample with relatively good efficiency. Received: 17 December 1998 / Accepted: 9 February 1999     

不同类型妊娠高血压疾病对产妇妊娠结局的影响

目的:探讨不同类型妊娠高血压疾病(PIH)对产妇妊娠结局的影响。方法:选取2011年1月~2013年12月我妇产科院收治的妊娠期出现高血压症状的产妇106例为观察组,并选取同期正常孕产妇100例为对照组,根据诊断标准将观察组患者再分为PIH组(75例)、子痫前期组(21例)以及子痫组(10例),对比4组产妇的胎儿窘迫、胎盘早剥、早产、剖宫产、产后出血以及新生儿窒息的发生率。结果:观察组产妇的胎儿窘迫、胎盘早剥、早产、剖宫产、产后出血以及新生儿窒息的发生率明显高于对照组,差异有统计学意义(P0.05);妊娠期高血压组、子痫前期组、子痫组的胎儿窘迫、胎盘早剥、早产、剖宫产、产后出血以及新生儿窒息的发生率,依次升高,差别有统计学意义(P0.05)。结论:应正确认识到不同类型PIH对妊娠结局的影响以及其并发症的规律,做好预防措施,以减少不良妊娠结局的发生。     

Search for the optimal fetal cell antibody: results of immunophenotyping studies using flow cytometry

Fetal nucleated cells circulating in maternal peripheral blood are a noninvasive source of fetal DNA for prenatal genetic diagnoses. The successful isolation of fetal cells from maternal blood depends upon identification of differences between fetal and maternal cell surface antigen expression. To our best knowledge, a monoclonal antibody that binds only fetal blood cells has not yet been identified. We studied antigens recognized by six different monoclonal antibodies for their biologic expression on fetal blood cells as a function of gestational age, and compared their ability to bind fetal but not maternal cells. The results suggest a relationship between gestational age and nucleated cell surface antigen expression. The monoclonal antibodies FB3-2, H3-3, CD71 and 2-6B/6 are suitable reagents for first or early second trimester fetal cell isolation, although FB3-2 and H3-3 are more specific for fetal cells due to significantly lower expression of these antigens on maternal mononuclear cells. The observation that samples from fetuses with chromosome abnormalities or multiple structural anomalies express higher levels of these antigens indicates that these reagents will potentiate the detection of abnormal fetal cells in maternal blood samples. Received: 23 November 1996 / Accepted: 13 February 1997     

First-trimester NRBC count in maternal circulation: correlation with doppler ultrasound studies.

This study aimed to determine whether the number of nucleated red blood cells (NRBCs) in maternal circulation during the first trimester of pregnancy could identify pregnancies that will have an anomalous Doppler in the second trimester. A total of 85 blood samples were obtained at 11-14 weeks of gestation with mean uterine arterial perfusion index >1.6, as noted by Doppler ultrasonography. NRBCs were enriched by magnetic automated cell sorting using anti-CD71 and were stained with May/Grunwald/Giemsa. A total of 4.8 NRBCs (range 1-75) were identified in 68 cases. Follow-up scans at 22-24 weeks were available in 46 cases. In 39 women, blood flow in the uterine arteries normalized, whereas in seven, high resistance was noted. One woman in the high-resistance group developed preeclampsia (PET; four NRBCs) and another delivered an intrauterine growth restriction (IUGR) baby (75 NRBCs). The number of NRBCs in women whose Doppler indices later normalized and in those who continued to have increased impedance was similar. The study indicates that NRBC number in maternal circulation during the first trimester cannot be used to screen pregnancies at high risk for developing preeclampsia (PET)/IUGR. High-impedance blood flow in the uterine arteries in the first trimester may be due to an unfinished process of trophoblastic invasion, most likely to be completed successfully by 22-24 weeks.     

The fetal erythroblast is not the optimal target for non-invasive prenatal diagnosis: preliminary results.

Fetal cells, present in the blood of pregnant women, are potential targets for non-invasive prenatal diagnosis. The fetal erythroblast has been the favorite target cell type. We investigated four methods of enrichment for fetal erythroblasts, identifying only three fetal erythroblasts in 573 ml of maternal blood. This is much less than the expected two to six fetal cells per ml of maternal blood. Hamada and Krabchi used a cell type-independent marker, i.e., the Y chromosome in maternal blood from male pregnancies after Carnoy fixation, leaving the nuclei for hybridization with X-and Y-chromosome-specific probes. We found with a similar technique 28 fetal cells in 15 ml of maternal blood. The fetal origin of cells was confirmed by hybridizing the nuclei with X- and Y-chromosome-specific probes, using two consecutive hybridizations with the two probes in opposite colors (reverse FISH). Candidate fetal cells were inspected after each hybridization. Only cells that were found to change the color of both probe signals from first to second hybridization were diagnosed as fetal. To reduce the labor-intensive slide screening load, we used semiautomated scanning microscopy to search for candidate cells. We conclude that erythroblasts form only a small fraction of fetal cells present in maternal blood.     

A noninvasive approach to studying fetal cells for prenatal diagnosis of chromosomal aneuploidies

Fetal cells isolated from maternal peripheral blood during the second trimester of pregnancy were analyzed. Blood samples were centrifuged in a Ficoll-Paque gradient, the mononuclear cell fraction was isolated and stained with fluorescent monoclonal antibodies against glycophorine A (GPA + PE), transferrin (CD71 + FITC), and Hoechst 33342. Fluorescence-activated cell sorting (FACS) was conducted on a Vantage flow cytofluorimeter (Becton Dickinson). Fluorescence in situ hybridization (FISH) with Y chromosome-specific DNA probe revealed fetal cells that exhibited Y signal in all 20 blood samples obtained from women pregnant with healthy male fetuses. The concentration of these fetal cells averaged about 1.34% and ranged from 0.1 to 4.2% in different blood samples. In six cases, blood samples were obtained from pregnant women, in which prenatal cytogenetic analysis revealed various fetal aneuploidies. Using FISH with DNA probes specific for chromosomes X, 18, and 13/21, Fetal cells with chromosomal aberrations were detected in these six maternal blood samples at a concentration from 1.5 to 5.6% (on average 3.7%). These results indicate the possibility of a new noninvasive approach, which is safe for both mother and fetus when used for isolation of fetal cells from pregnant women's blood samples and prenatal diagnosis of a broad spectrum of fetal cell chromosomal aberrations.     

应用胎儿特异性抗体HbF（γ链）标记法无创性 产前基因诊断DMD

以孕8~26周孕妇外周血为材料,经过Percoll密度梯度离心初步富集,胎儿细胞特异性抗体—HbF标记、识别胎儿有核红细胞,母体和胎儿有核红细胞的精确区分是以胎儿和成人血红蛋白的组成差异为基础的。胎儿细胞胞浆黄染,而具有成人血红蛋白的母体细胞没有颜色。显微操作法获取全部阳性细胞后,以其全基因组扩增（PEP）的产物为模板,进行性别检测、DMD基因的多重PCR检测和STR连锁分析。结果,20名孕妇外周血中均发现与HbF呈阳性反应的胎儿NRBC。并完成7例DMD的产前基因诊断。HbF抗体标记法能有效识别胎儿有核红细胞,是无创性产前基因诊断中很有应用前景的标记方法。 Abstract： Maternal blood was obtained at 8-26weeks of gestation.After discontinuous density gradient centrifugation with Percoll ,HbF antibody was used to identify fetal NRBC.The precise differentiation between fetal and maternal NRBC is based on the constitutional difference between fetal and adult hemoglobin (Hb).Fetal cells appear yellow cytoplasmic staining,while adult cells colorless. NRBCs were collected by micromanipulation andwhole genome amplification was performed. DMD was prenatally diagnosed by using the combination of sex determination,multiplex PCR and linkage analysis of several STR sites of dystrophin. NRBCs stained with HbF were found in all of 20 maternal blood samples with gestations, and 7 fetuses with risk of DMD were diagnosed. We concluded that HbF antibody could identify fetal NRBC efficaciously,and this is a kind of more prospective application method.     

Reassessing the Impact of Smoking on Preeclampsia/Eclampsia: Are There Age and Racial Differences?

Objective

To investigate the association between cigarette use during pregnancy and pregnancy-induced hypertension/preeclampsia/eclampsia (PIH) by maternal race/ethnicity and age.

Methods

This retrospective cohort study was based on the U.S. 2010 natality data. Our study sample included U.S. women who delivered singleton pregnancies between 20 and 44 weeks of gestation without major fetal anomalies in 2010 (n = 3,113,164). Multivariate logistic regression models were fit to estimate crude and adjusted odds ratios and the corresponding 95% confidence intervals.

Results

We observed that the association between maternal smoking and PIH varied by maternal race/ethnicity and age. Compared with non-smokers, reduced odds of PIH among pregnant smokers was only evident for non-Hispanic white and non-Hispanic American Indian women aged less than 35 years. Non-Hispanic Asian/Pacific Islander women who smoked during pregnancy had increased odds of PIH regardless of maternal age. Non-Hispanic white and non-Hispanic black women 35 years or older who smoked during pregnancy also had increased odds of PIH.

Conclusion

Our study findings suggest important differences by maternal race/ethnicity and age in the association between cigarette use during pregnancy and PIH. More research is needed to establish the biologic and social mechanisms that might explain the variations with maternal age and race/ethnicity that were observed in our study.     

Kleihauer抗酸染色法标记母血中的胎儿有核红细胞

以18例孕7~25周的孕妇外周血为材料, 经Percoll不连续密度梯度离心初步富集胎儿有核红细胞。然后用Kleihauer抗酸染色法进行标记, 结果阳性胎儿有核红细胞的胞浆呈深红色, 而母亲的有核红细胞胞浆无色。显微操作法获取单个胎儿有核红细胞, 经全基因组扩增后, 产物进行性别鉴定及STR连锁分析检测, 验证有核红细胞的来源, 并完成9例杜氏肌营养不良(Duchenne muscular dystrophy,DMD)的无创性产前基因诊断。应用Kleihauer抗酸染色法标记胎儿有核红细胞, 它是一种快速、简单、直接的化学染色方法, 更易于推广到临床应用。     

Detection and relocation of cord blood nucleated red blood cells by laser scanning cytometry

BACKGROUND: Fetal nucleated red blood cells (NRBC) present in the peripheral blood of pregnant women at low frequency are a potential target for noninvasive prenatal diagnostics. METHODS: CD71-enriched cells from male cord blood (CB) were stained for the gamma chain of HbF (Hb-gamma) and cytocentrifuged. Fluorescence in situ hybridization (FISH) was done for the Y chromosome. Following staining of the nucleus with TO-PRO-3, laser scanning cytometry was performed. Artificial mixtures of small volumes of male CB and blood drawn from nonpregnant females were analyzed. RESULTS: In CB, 59% of events double positive for Hb-gamma and TO-PRO-3 were identified as CB-NRBC. In contamination studies, male fetal CB-NRBC were identified perfectly on the basis of morphologic characteristics and FISH reactivity following relocation and visual assessment. Mean recovery was 8.7%. CONCLUSIONS: Laser scanning cytometry of preenriched fetal NRBC may offer a promising way for noninvasive prenatal diagnostics. This is because it provides a virtual enrichment step and the position on the slides of cells visually confirmed to correspond to fetal NRBC is known. Further experimental procedures on well-defined and located target cells may be feasible.     

Evaluation of a soybean lectin-based method for the enrichment of erythroblasts.

We performed a comparative study of the enrichment of erythroblasts by a soybean agglutinin galactose-specific lectin method and a standardized magnetic cell-sorting (MACS) protocol. Blood samples, obtained from 11 pregnant women at between 11 and 40 weeks of gestation, were split and examined by each method in parallel. The number of erythroblasts recovered by the lectin method was approximately eightfold higher than the number obtained by MACS. Our data suggest that the lectin-based method may provide a better approach for the enrichment of rare fetal erythroblasts from maternal blood.     

Evaluation of bidirectional transfer of plasma DNA through placenta

To clarify the origin of cell-free fetal DNA in maternal plasma, we analyzed bidirectional transfer of plasma DNA between fetus and mother. We analyzed maternal and fetal plasma DNA obtained from 15 pregnant women at the time of Cesarean section. The subjects were five patients with preeclampsia and 10 gestational-age-matched normal controls. DNA was extracted from 1.5-ml plasma samples and the cellular fraction of maternal and umbilical blood. Seven polymorphic marker genes were analyzed. The relative concentration of fetal DNA in maternal plasma and maternal DNA in cord blood were evaluated. The relative concentration of maternal DNA in fetal circulation (median, 0.9%; range, 0.2–8.4%) was significantly lower than that of fetal DNA in maternal blood (14.3%, 2.3–64%), with P=0.007. The relative concentration of maternal DNA in fetal blood was not affected by preeclampsia. These findings indicate that cell-free DNA is unequally transferred through the placenta. The structural characteristics of the placenta suggest that the majority of cell-free fetal DNA in maternal plasma is derived from villous trophoblasts.     

Circulating anti-heat-shock-protein antibodies in normal pregnancy and preeclampsia

It has been previously reported that circulating anti-heat-shock-protein (Hsp) antibody levels are elevated in cardiovascular disorders. The aim of the present study was to determine circulating antihuman Hsp60, antimycobacterial Hsp65, and antihuman Hsp70 antibody levels in healthy pregnant women and preeclamptic patients and to investigate their relationship to the clinical characteristics of the study subjects, as well as to the markers of inflammation (C-reactive protein (CRP)), endothelial activation (von Willebrand factor antigen), or endothelial injury (fibronectin), oxidative stress (malondialdehyde) and to serum Hsp70 levels. Ninety-three preeclamptic patients and 127 normotensive healthy pregnant women were involved in this case control study. Serum anti-Hsp60, anti-Hsp65, anti-Hsp70, and Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Serum CRP levels were determined by an autoanalyzer using the manufacturer’s kit. Plasma von Willebrand factor antigen levels were quantified by ELISA, while plasma fibronectin concentration by nephelometry. Plasma malondialdehyde levels were measured by the thiobarbituric-acid-based colorimetric assay. For statistical analyses, nonparametric methods were applied. Anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibodies were detected in all of our serum samples. There were no significant differences in serum anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibody levels between the control and preeclamptic groups. Serum levels of Hsp70 and CRP, as well as plasma levels of VWF antigen, fibronectin, and malondialdehyde, were significantly higher in preeclamptic patients than in normotensive healthy pregnant women. Serum anti-Hsp60 antibody levels showed significant correlations with serum anti-Hsp65 antibody levels both in the control and the preeclamptic groups (Spearman R = 0.55 and 0.59; p < 0.001, respectively). However, no other relationship was found between clinical features (maternal age, smoking status, parity, body mass index, gestational age at blood draw, systolic and diastolic blood pressure, gestational age at delivery, and fetal birth weight) and measured laboratory parameters of the study subjects and serum anti-Hsp antibody levels in either study group. In conclusion, anti-Hsp60 and anti-Hsp70 antibodies as naturally occurring autoantibodies are present in the peripheral circulation of healthy pregnant women. Nevertheless, humoral immunity against heat shock proteins was not associated with preeclampsia. Further studies are warranted to explore the role of heat shock proteins and immune reactivity to them in the immunobiology of normal pregnancy and preeclampsia.     

Maternal Cadmium Levels During Pregnancy and the Relationship with Preeclampsia and Fetal Biometric Parameters

Preeclampsia, which is caused by multiple factors, still remains one of the most serious complications of pregnancy. This study was designed to determine cadmium levels in women with preeclampsia compared to those of normotensive women. In this case-control study, maternal blood, umbilical cord blood, and placental cadmium levels were measured by an inductively coupled plasma mass spectrometry system in 51 women presenting consecutively with preeclampsia and 51 normotensive pregnant women. Groups were matched for maternal age, parity, and gestational age. Birth outcomes were recorded, such as gestational age at delivery, birth weight, and Apgar score. Median (interquartile range [IQR]) blood cadmium concentration was 1.21 μg/L (0.76–1.84 μg/L) and 1.09 μg/L (0.72–1.31 μg/L) in women with preeclampsia and normotensive, respectively; values for placental cadmium levels of women with preeclampsia and normotensive were 3.61 μg/kg (2.19–4.37 μg/kg) and 4.28 μg/kg (3.06–5.71 μg/kg), respectively. We observed a statistically significant increase in blood and placental cadmium levels in women with preeclampsia compared to healthy pregnant women. After adjusting for pre-pregnancy body mass index, maternal age, parity, gestational age at sample collection, and maternal calcium and magnesium levels, the odds ratio of having preeclampsia in the high tertile was markedly increased (odds ratio, 7.83 [95% CI, 1.64–37.26]) compared with the low tertile. Interestingly, there was no difference in the cadmium level in umbilical cord blood between the groups. Within the preeclamptic group, higher cadmium status was significantly associated with decreased birth weight. Our study suggested that elevated cadmium level in the maternal circulation could potentially increase the risk of preeclampsia. The results also demonstrate that higher cadmium status may contribute to fetal growth restriction in preeclamptic patients.     

Comparison of methods for erythroblast selection: application to selecting fetal erythroblasts from maternal blood.

BACKGROUND: Many methods have been employed to obtain fetal cells from maternal blood for prenatal diagnostics, but there has been little work done that compares the efficacy of different methods. This study presents a comparison of two commonly used methods for selecting erythroblasts with selection directly from whole blood. METHODS: Erythroblasts were isolated from maternal blood by either differential lysis or density separation, followed by selection with an antibody to the transferrin receptor. These methods were compared with antibody selection directly from whole blood. The total yield of erythroblasts was determined for each method. RESULTS: Red cell lysis is not recommended because the lysis step cannot be well controlled. Density separation followed by antibody selection works well. However, a faster and simpler method, antibody selection directly from whole blood using Immunicon Ferrofluid and magnetic separators, works as well and has the potential to yield even more cells. CONCLUSIONS: Considering the need for a simple and quick method for selecting fetal cells from maternal blood, we suggest selection directly from whole blood.     

Fetal erythroblast isolation up to purity from cord blood and their culture in vitro

BACKGROUND: Erythroblasts have been the most encouraging candidate cell type for noninvasive prenatal genetic investigation. We previously showed that human erythroblasts can be recovered from bone marrow and blood bank buffy coats by a physical cell separation. In the present study, we modified our previous methodology, taking into account the peculiar behavior of erythroblasts in response to modifications of pH and osmolality of the separation medium. METHODS: Twenty to forty milliters of cord blood were initially centrifuged on Ficoll/diatrizoate (1.085 g/ml). The interphase cells were further separated on a continuous density gradient (1.040-1.085 g/ml). Two different gradients were initially compared: the first was iso-osmolar and neutral, whereas the second also contained an ionic strength gradient and a pH gradient (triple gradient). A subsequent monocyte depletion was performed by using magnetic microbeads coated with anti-CD14 monoclonal antibody (mAb), and erythroblasts were purified by sedimentation velocity. Purified cells were investigated by analyses with fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization (FISH) and immunocytochemistry with mAb against fetal hemoglobin and were cultured in vitro. RESULTS: When nucleated cells were spun on an iso-osmolar and neutral continuous density gradient, two separated bands of nucleated red blood cells (NRBCs) were obtained: a light fraction banding at 1.062 g/ml and an heavy fraction banding at 1.078 g/ml. Conversely, when cells were spun in the triple gradient, NRBCs were shifted to the low-density region. Monocyte depletion by immunomagnetic microbeads and velocity sedimentation provided a pure erythroblast population. FACS and FISH analyses and immunocytochemistry substantiated the purity of the isolated cell fraction, which was successfully cultured in vitro. CONCLUSIONS: We have shown that fetal erythroblasts can be purified up to homogeneity from cord blood, but further refinements of the isolation procedure are necessary before the same results can be obtained from maternal peripheral blood.     

Frequency of nucleated red blood cells in maternal blood during the different gestational ages

We wished to determine the time of pregnancy at which optimal numbers of nucleated red blood cells (NRBC) are present in maternal blood. Because 30% of the NRBC in maternal blood are fetal, there are implications for prenatal screening and diagnosis. Samples of whole blood were collected from each of 225 women at various times during pregnancy. The samples were processed by charge flow separation (CFS), the NRBC enumerated, and the numbers compared on a week-to-week basis. To quantify the relationship between week of pregnancy and actual and log-transformed numbers of NRBC recovered, Pearson product moment and Spearman correlation coefficient were estimated for each of four CFS instruments and for the four instruments combined. When the data were analyzed, we found no relationship between stage of pregnancy and numbers of NRBC recovered. Even after logarithmic transformation, variability among the women, estimated by standard deviation, was large and relatively stable across the different stages of pregnancy. The number of NRBC recoverable by CFS appears to be constant between 7 and 25 weeks. Received: 26 August 1998 / Accepted: 26 October 1998     

Parent-Offspring Conflict and the Persistence of Pregnancy-Induced Hypertension in Modern Humans

Preeclampsia is a major cause of perinatal mortality and disease affecting 5–10% of all pregnancies worldwide, but its etiology remains poorly understood despite considerable research effort. Parent-offspring conflict theory suggests that such hypertensive disorders of pregnancy may have evolved through the ability of fetal genes to increase maternal blood pressure as this enhances general nutrient supply. However, such mechanisms for inducing hypertension in pregnancy would need to incur sufficient offspring health benefits to compensate for the obvious risks for maternal and fetal health towards the end of pregnancy in order to explain why these disorders have not been removed by natural selection in our hunter-gatherer ancestors. We analyzed >750,000 live births in the Danish National Patient Registry and all registered medical diagnoses for up to 30 years after birth. We show that offspring exposed to pregnancy-induced hypertension (PIH) in trimester 1 had significantly reduced overall later-life disease risks, but increased risks when PIH exposure started or developed as preeclampsia in later trimesters. Similar patterns were found for first-year mortality. These results suggest that early PIH leading to improved postpartum survival and health represents a balanced compromise between the reproductive interests of parents and offspring, whereas later onset of PIH may reflect an unbalanced parent-offspring conflict at the detriment of maternal and offspring health.     

Preventive Effects of Folic Acid Supplementation on Adverse Maternal and Fetal Outcomes

Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09–0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18–0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes.