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This study aimed to investigate the serum biochemical markers' propensity associated with sex chromosome abnormalities (SCAs) and assess the clinical efficacy of SCAs in serum biochemical screening during the second trimester. A retrospective case-control analysis was conducted on pregnant women who underwent serum biochemical screening during the second trimester. The study compared groups of women with SCAs to those with normal chromosome karyotypes to assess changes in biochemical markers. We analysed and compared the performance of serum biochemical screening in each SCA group. The results showed that the alterations in serum biochemical markers varied among the different SCA groups. Typically, the serum biochemical markers of fetal SCAs were either above the 95th percentile or below the 5th percentile. The proportions of high- and intermediate-risk findings for 45,X, 47,XXX, 47,XXY, 47,XYY, and mosaic sex chromosomal abnormalities were 43.48%, 78.95%, 63.89%, 70.59%, and 78.13%, respectively. Besides detecting fetal trisomy 21 and trisomy 18, the current contingent screening procedures may also accidentally identify various fetal SCAs at a rate of 69.18%., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Approval was granted by Sichuan University’s Institutional Ethics Committee (No.2024(073)). Consent to participate: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s).)

Early gestational diabetes mellitus (eGDM) is diagnosed when fasting plasma glucose before 24 weeks of gestation (WG) is ≥ 5.1 mmol/L, whilst standard GDM is diagnosed between 24 and 28 WG by oral glucose tolerance test (OGTT). eGDM seems to have worse obstetric outcomes than standard GDM. We compared the rates of postpartum glucose metabolism disorders between women with early versus standard GDM in this prospective study on women with GDM from three university hospitals between 2014 and 2016. Patients were included if they were < 24 WG with at least one risk factor for GDM and excluded if they had type 2 diabetes. Patients were assigned to Group 1 (G1) for eGDM according to IADPSG: fasting blood glucose < 24 WG between 5.1 and 7 mmol/L. Group 2 (G2) consisted of patients presenting a standard GDM at 24-28 WG on OGTT results according to IADPSG: T0 ≥ 5.1 mmol/L or T60 ≥ 10.0 mmol g/L or T120 ≥ 8.5 mmol/L. The primary outcome was postpartum OGTT result. Five hundred patients were analysed, with 273 patients undergoing OGTT at 4-18 weeks postpartum: 192 patients in G1 (early) and 81 in G2 (standard). Patients in G1 experienced more insulin therapy during pregnancy than G2 (52.2% versus 32.5%, p < 0.001), but no patients were taking insulin postpartum in either group. G1 patients experienced less preterm labour (2.6% versus 9.1%, p = 0.043), more induced deliveries (38% versus 25%, p = 0.049) and reduced foetal complications (29.2% versus 42.0%, p = 0.048). There was no significant difference in the rate of postpartum glucose metabolism disorders (type 2 diabetes, impaired glucose tolerance, impaired fasting glycaemia) between groups: 48/192 (25%) in G1 and 17/81 (21%) in G2, p = 0.58. Thus the frequency of early postpartum glucose metabolism disorders is high, without difference between eGDM and standard GDM. This supports measurement of fasting plasma glucose before 24 WG and the threshold of 5.1 mmol/L seems appropriate until verification in future studies.Trial registration: NCT01839448, ClinicalTrials.gov on 22/04/2013.

Dyslipidemia in pregnancy are associated with risk of adverse outcomes. As an adverse pregnancy outcome, small-for-gestational-age has been extensively studied in Western countries. However, similar studies have rarely been conducted in Asian countries. Data were derived from 5695 pairs of non-diabetic mothers and neonates between 1 Jan 2014 and 31 Dec 2014. 5.6% neonates in our study were SGA. Serum samples were collected during second and third trimesters for evaluation on fasting lipids levels. The present study intended to explore the associations between maternal lipid profile and small-for-gestational-age neonates. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and adjusted via logistic regression analysis. After adjustments for confounders, third-trimester total cholesterol levels were associated with a decreased risk for small-for-gestational-age (aOR = 0.622, 95% CI 0.458-0.848, P = 0.002), and third-trimester high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were associated with an increased risk for small-for-gestational-age (aOR = 1.955, 95% CI 1.465-2.578, P < 0.001; aOR = 1.403, 95% CI 1.014-1.944, P = 0.041).In the highest gestational weight gain strata, especially the third-trimester, the effect of high-density lipoprotein cholesterol levels on the risk for small-for-gestational-age is larger. High high-density lipoprotein cholesterol level during third trimester could be considered as indicators of a high-risk of small-for-gestational-age, regardless of gestational weight gain.

Early identification of patients at risk of developing preeclampsia (PE) would allow providers to tailor their prenatal management and adopt preventive strategies, such as low-dose aspirin. Nevertheless, no mid-trimester biomarkers have as yet been proven useful for prediction of PE. This study investigates the ability of metabolomic biomarkers in mid-trimester maternal plasma to predict PE. A case-control study was conducted including 33 pregnant women with mid-trimester maternal plasma (gestational age [GA], 16-24 weeks) who subsequently developed PE and 66 GA-matched controls with normal outcomes (mid-trimester cohort). Plasma samples were comprehensively profiled for primary metabolic and lipidomic signatures based on gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and liquid chromatography Orbitrap mass spectrometry (LC-Orbitrap MS). A potential biomarker panel was computed based on binary logistic regression and evaluated using receiver operating characteristic (ROC) analysis. To evaluate whether this panel can be also used in late pregnancy, a retrospective cohort study was conducted using plasma collected from women who delivered in the late preterm period because of PE (n = 13) or other causes (n = 21) (at-delivery cohort). Metabolomic biomarkers were compared according to the indication for delivery. Performance of the metabolomic panel to identify patients with PE was compared also to a commonly used standard, the plasma soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio. In the mid-trimester cohort, a total of 329 metabolites were identified and semi-quantified in maternal plasma using GC-TOF MS and LC-Orbitrap-MS. Binary logistic regression analysis proposed a mid-trimester biomarker panel for the prediction of PE with five metabolites (SM C28:1, SM C30:1, LysoPC C19:0, LysoPE C20:0, propane-1,3-diol). This metabolomic model predicted PE better than PlGF (AUC [95% CI]: 0.868 [0.844-0.891] vs 0.604 [0.485-0.723]) and sFlt-1/PlGF ratio. Analysis of plasma from the at-delivery cohort confirmed the ability of this biomarker panel to distinguish PE from non-PE, with comparable discrimination power to that of the sFlt-1/PlGF ratio. In conclusion, an integrative metabolomic biomarker panel in mid-trimester maternal plasma can accurately predict the development of PE and showed good discriminatory power in patients with PE at delivery.

Elevation of total cell-free DNA (cfDNA) in patients with preeclampsia is well-known; however, whether this change precedes the onset of symptoms remains inconclusive. Here, we conducted a nested case-control study to determine the elevation of cfDNA levels in women who subsequently developed preeclampsia. Methylated HYP2 (m-HYP2) levels were determined in 68 blood samples collected from women with hypertensive disorders of pregnancy, along with 136 control samples, using real-time quantitative PCR. The measured m-HYP2 levels were converted to multiples of the median (MoM) values for correction of maternal characteristics. The m-HYP2 levels and MoM values in patients with preeclampsia were significantly higher than in controls during the third trimester (P < 0.001, both), whereas those for women who subsequently developed preeclampsia did not differ during the second trimester. However, when patients with preeclampsia were divided based on the onset-time of preeclampsia or 10th percentile birth weight, both values were significantly higher in women who subsequently developed early-onset preeclampsia (P < 0.05, both) and preeclampsia with small-for-gestational-age (SGA) neonate (P < 0.01, both) than controls. These results suggested that total cfDNA levels could be used to predict early-onset preeclampsia or preeclampsia with SGA neonate.

Objective: To examine the association between maternal erythrocyte long-chain omega-3 PUFA (n-3 LCPUFA), measured in early pregnancy, and pregnancy and birth outcomes., Study Design: One hundred and eight healthy women with a singleton pregnancy were included. Erythrocyte fatty acids were analyzed using gas chromatography. Gestational length, birth anthropometric measures, and pregnancy-associated complications were collected from hospital medical records., Results: We observed significant positive associations between maternal docosahexaenoic acid (DHA) levels (p = 0.024) and omega-3 index values (p = 0.021) and gestational length in adjusted linear regression models. Each point in maternal DHA level was associated with 2.19 days longer gestational duration (β = 2.19; 95% CI 0.29-4.09). No consistent associations were found between n-3 PUFA levels and composite pregnancy outcome., Conclusion: These findings suggest that the gestational length is positively affected by maternal n-3 LCPUFA status as soon as the early stages of pregnancy.

Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcome (APO). Accurate prediction of APO is critical to identify, counsel, and manage these high-risk patients. We undertook this study to identify novel biomarkers in mid-trimester maternal plasma to identify pregnant patients with SLE at increased risk of APOs. The study population consisted of pregnant women whose plasma was taken in mid-trimester and available for metabolic signature: (1) SLE and normal pregnancy outcome (Group 1, n = 21); (2) SLE with APO (Group 2, n = 12); and (3) healthy pregnant controls (Group 3, n = 10). Mid-trimester maternal plasma was analyzed for integrative profiles of primary metabolite and phospholipid using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and liquid chromatography Orbitrap mass spectrometry (LC-Orbitrap MS). For performance comparison and validation, plasma samples were analyzed for sFlt-1/PlGF ratio. In the study population, APO developed in 12 of 33 women with SLE (36%). Metabolite profiling of mid-trimester maternal plasma samples identified a total of 327 metabolites using GC-TOF MS and LC-Orbitrap MS. Partial least squares discriminant analysis (PLS-DA) showed clear discrimination among the profiles of SLE groups and healthy pregnant controls (Groups 1/2 vs. 3). Moreover, direct comparison between Groups 1 and 2 demonstrated that 4 primary metabolites and 13 lipid molecules were significantly different. Binary logistic regression analysis suggested a potential metabolic biomarker model that could discriminate Groups 1 and 2. Receiver operating characteristic (ROC) analysis revealed the best predictability for APO with the combination model of two metabolites (LysoPC C22:5 and tryptophan) with AUC of 0.944, comparable to the AUC of sFlt-1/PlGF (AUC 0.857). In conclusion, metabolic biomarkers in mid-trimester maternal plasma can accurately predict APO in patients with SLE.

High sensitivity C-reactive protein (hs-CRP) is a marker of systemic low-grade inflammation and associated with chronic inflammatory diseases. It is unknown whether maternal and infant hs-CRP levels are correlated and little is known about risk factors in early childhood. Hs-CRP were measured in mothers during pregnancy week 24 (N = 690), and one-week postpartum (N = 675) and in their children age 6 mo (N = 640) enrolled in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC 2010 ) cohort. The risk factor analysis included anthropometrics, environmental exposures and CRP-Genetic Risk Score (GRS). Mother's body mass index (BMI), use of antibiotics, smoking, cesarean delivery and season were associated with higher maternal hs-CRP level, whereas higher social circumstances were associated with lower hs-CRP level (p < 0.05). Child's BMI, siblings, bacterial airway colonization, current infection, CRP-genetic risk score and season were associated with higher hs-CRP at age 6 mo (all p < 0.05). Mother's hs-CRP level in pregnancy week 24 was associated with hs-CRP level in the child at 6 mo: β-coefficient = 0.11 [95% CI: 0.01-0.20], R 2  = 0.22, p = 0.03. The association was unchanged adjusted for all significant risk factors. Systemic low-grade inflammation in pregnant mothers and their offspring is correlated independently of BMI, environmental exposures and genetic risk factors.

Objective: Inflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia., Study Design: A sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios., Results: Higher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia., Conclusions: Among women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth.

Objective: We hypothesized second trimester serum cortisol would be higher in spontaneous preterm births compared to provider-initiated (previously termed 'medically indicated') preterm births., Study Design: We used a nested case-control design with a sample of 993 women with live births. Cortisol was measured from serum samples collected as part of routine prenatal screening. We tested whether mean-adjusted cortisol fold-change differed by gestational age at delivery or preterm birth subtype using multivariable linear regression., Result: An inverse association between cortisol and gestational age category (trend p = 0.09) was observed. Among deliveries prior to 37 weeks, the mean-adjusted cortisol fold-change values were highest for preterm premature rupture of the membranes (1.10), followed by premature labor (1.03) and provider-initiated preterm birth (1.01), although they did not differ statistically., Conclusion: Cortisol continues to be of interest as a marker of future preterm birth. Augmentation with additional biomarkers should be explored.

Objective: To evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (±) preeclampsia., Study Design: Included were 400 women with singleton deliveries in California in 2009-2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15-20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC)., Results: Twenty-five serum biomarkers along with maternal age <34 years and poverty status identified >80% of women with PTB ± preeclampsia with best performance in women with preterm preeclampsia (AUC = 0.889, 95% confidence interval (0.822-0.959) training; 0.883 (0.804-0.963) testing)., Conclusion: Together with maternal age and poverty status, mid-pregnancy immune and growth factors reliably identified most women who went on to have a PTB ± preeclampsia.

Objective: To assess the effect of infant size as a marker of placental function on the association between preeclampsia and the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF)., Study Design: The angiogenic factors sFlt-1 and PlGF were measured prospectively at 26 weeks gestation in 2322 women. Pregnancies were stratified by whether or not they were complicated by preeclampsia, the timing of delivery, and birthweight Z-score., Result: Independent of preeclampsia status, women with small infants (Z < -1.0) have an increased sFlt-1/PlGF ratio, and women with large infants (Z > 1.0) have a decreased ratio. Among pregnancies yielding small infants, the sFlt-1/PlGF ratio is markedly elevated in preeclamptic pregnancies requiring delivery before 37 weeks (110.0 vs. 17.9, p < 0.0001) but not in preeclamptic pregnancies delivered at term. The strength of the association between preeclampsia and the sFlt-1/PlGF ratio is increased for small infants compared to normal-sized or large infants., Conclusion: The sFlt-1/PlGF ratio in the late second trimester is similarly elevated in women with preeclampsia and in women with small infant size and more markedly elevated in a syndrome of placental dysfunction characterized by preeclampsia, preterm delivery, and growth restriction.

Whether the maternal vitamin D deficiency is associated with infant birth weight is still an argument. Here, we performed a nested case-control study (545 women who subsequently delivered infant with macrosomia and 1090 controls) to evaluate the association of the maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations with risk of macrosomia. We measured the serum 25(OH)D concentrations by enzyme immunoassays. Logistic regression analysis, receiver-operator characteristic curve analysis and graphical nomogram were used for the statistical analyses. Among women who delivered infant with macrosomia, 71.2% of the women had serum 25(OH)D concentrations <50.0 nmol/L compared with 61.1% of the control women (P < 0.001). For women with concentrations <50.0 nmol/L, they had a 33% increased risk of macrosomia compared with women whose 25(OH)D ranged from 50.0 to 74.9 nmol/L. The risk of macrosomia was significantly increased with the decreasing concentrations of serum 25(OH)D in a dose-dependent manner (P for trend = 0.001). We also observed a threshold for 25(OH)D of 50.0 nmol/L for delivering infant with macrosomia and a predictive accuracy of the 25(OH)D concentrations included panel, with an area under the ROC curve of 0.712 for delivering infant with macrosomia. In conclusion, maternal serum 25(OH)D <50.0 nmol/L is associated with delivering a macrosomic infant, and vitamin D deficiency should be monitored in pregnant women.

Preeclampsia is one of the most dangerous pregnancy complications, and the leading cause of maternal and perinatal mortality and morbidity. Although the clinical symptoms appear late, its origin is early, and hence detection is feasible already at the first trimester. In the current study, we investigated the abundance of circulating small non-coding RNAs in the plasma of pregnant women in their first trimester, seeking transcripts that best separate the preeclampsia samples from those of healthy pregnant women. To this end, we performed small non-coding RNAs sequencing of 75 preeclampsia and control samples, and identified 25 transcripts that were differentially expressed between preeclampsia and the control groups. Furthermore, we utilized those transcripts and created a pipeline for a supervised classification of preeclampsia. Our pipeline generates a logistic regression model using a 5-fold cross validation on numerous random partitions into training and blind test sets. Using this classification procedure, we achieved an average AUC value of 0.86. These findings suggest the predictive value of circulating small non-coding RNA in the first trimester, warranting further examination, and lay the foundation for producing a novel early non-invasive diagnostic tool for preeclampsia, which could reduce the life-threatening risk for both the mother and fetus.

Our aim was to evaluate whether the serum level of galectin-1 (Gal-1) at 18-24 and 27-31 weeks of gestation is a risk factor for predicting the later occurrence of not only preeclampsia (PE) but also gestational hypertension (GH). We measured serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and Gal-1 using an enzyme-linked immunosorbent assay in 81 and 73 normal pregnant women, 22 and 16 women with a later onset of GH, and 37 and 29 women with a later onset of PE at 18-24 and 27-31 weeks, respectively. We also measured Gal-1 in 33 women with GH and 78 women with PE after the onset. The levels of Gal-1 after the onset of GH, late-onset PE (onset at ⩾34 weeks), and early-onset PE (onset at <34 weeks) were significantly higher than those in normal pregnant women at 27-31 weeks. However, the low levels of Gal-1 (<8.1 ng ml -1 ) at 18-24 weeks, but not at 27-31 weeks, predicted the later occurrence of not only early-onset PE and late-onset PE but also GH. The low level of Gal-1 at 18-24 weeks was an independent risk factor for the later occurrence of GH and PE, after adjusting for the effects of a high BP and increased sFlt-1/PlGF ratio at 18-24 weeks. In conclusion, the serum level of Gal-1 is a novel risk factor for both GH and PE, specifically its expression at a low level in the second trimester and a high level after onset.

Objective: Racial differences in chronic maternal stress may contribute to disparities in pregnancy outcomes. The objective is to identify racial and ethnic differences in self-reported and biologic measures of stress between non-Hispanic black (NHB) and non-Hispanic white (NHW) pregnant women., Study Design: NHB and NHW pregnant women were enrolled before 23 weeks of gestation in this prospective cohort study. Equal numbers of women were recruited with public vs private insurance in each racial group. Self-reported stress was measured and blood samples collected in the second and third trimesters were analyzed for serum Epstein-Barr virus antibody, C-reactive protein (CRP), corticotropin-releasing hormone (CRH) and adenocorticotropic hormone (ACTH)., Results: One hundred and twelve women were enrolled. NHW women reported more buffers against stress (P=0.04) and neighborhood satisfaction (P=0.02). NHB women reported more discrimination (P<0.001), food insecurity (P=0.04) and had significantly higher mean CRP levels and mean ACTH levels in the second and third trimesters., Conclusion: Significant differences in self-reported and biologic measures of chronic stress were identified between NHB and NHW pregnant women with similar economic characteristics. Future studies should investigate mechanisms underlying these differences and their relationship to pregnancy outcomes.

Our aim was to develop a novel screening method to detect the imminent onset of preeclampsia (PE) within 4 weeks after blood sampling. We prospectively collected data regarding past history of PE/gestational hypertension (GH), blood pressure levels at 16-23 weeks and plasma levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) twice at 19-31 weeks, which were measured using an automated electrochemiluminescence immunoassay. We found that a three-step approach by sequential selection using maternal factors, including a past history of PE/GH or blood pressure levels ≥120/80 mm Hg at 16-23 weeks (first step), followed by plasma levels of PlGF in the <5th percentile (second step) and plasma levels of sFlt-1 in the ≥95th percentile (third step) yielded both high sensitivity and specificity. The imminent onset of PE occurred in 2 of 1199 (0.2%) women recruited at 19-25 weeks and in 6 of 798 (0.8%) women recruited at 26-31 weeks. The sensitivity, specificity, positive likelihood ratio (95% confidence interval), negative likelihood ratio (95% confidence interval), positive predictive value and negative predictive value of the three-step approach for predicting the imminent onset of PE at 19-25 weeks were 100%, 99.8%, 599 (150-2390), 0%, 50% and 100%, respectively; and those at 26-31 weeks were 83%, 99.1%, 94 (42-214), 0.17 (0.03-1.01), 42% and 99.9%, respectively. In conclusion, the three-step approach is a highly sensitive and specific screening method for detecting the imminent onset of PE within 4 weeks after blood sampling at 19-31 weeks of gestation.

The aim of this study was to determine the predictive value of the combination of plasma-soluble fms-like tyrosine kinase 1 (sFlt-1) and uterine artery Doppler for the detection of preeclampsia in women of advanced age at 16-18 weeks of gestation and to identify associations between other pregnancy complications and abnormalities of these combined tests. The maternal plasma sFlt-1 level was measured, and uterine artery Doppler was performed at 16-18 weeks of gestation in 314 cases of elderly gravida. The main outcome was preeclampsia. Fourteen women (4.46%) developed preeclampsia. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of uterine artery Doppler combined with plasma sFlt-1 for preeclampsia prediction were 28.6, 95.7, 23.5 and 96.6%, respectively. For the prediction of early-onset preeclampsia, the sensitivity, specificity, PPV and NPV were 80, 95.8, 23.5 and 99.7%, respectively. Patients with abnormal uterine artery Doppler findings and an abnormal plasma s Flt-1 level (greater than 1724.5 pg ml(-1)) had a higher risk of preterm delivery (relative risk (RR)=3.38, 95% confidence interval (CI) 1.47-7.59), neonatal respiratory distress syndrome (RR=52.06, 95% CI 5.71-474.45) and perinatal death (RR=17.35, 95% CI 1.13-265.64). Our findings indicate that the combination of uterine artery Doppler and sFlt-1 level at 16-18 weeks of gestation in cases of elderly gravida has a high predictive value for early-onset preeclampsia, but not for overall preeclampsia. This combination test may be a useful early second trimester screening test for the prediction of early-onset preeclampsia in cases of elderly gravida.

Background/objectives: C-reactive protein (CRP) is the most extensively studied inflammatory risk marker, and elevated serum CRP concentrations in pregnant women are known to be associated with subsequent development of preeclampsia and preterm delivery. Researchers have suggested that folate intake may help to control the inflammation process. We examined whether folate nutrition modifies the relationship between serum CRP concentration and gestational age at delivery., Subjects/methods: Serum CRP concentrations were analyzed in 815 pregnant women between 12 and 28 weeks of gestation. Dietary intakes were assessed using a 24-h dietary recall. The serum folate and high-sensitivity CRP concentrations were analyzed by radioassay and latex agglutination tests, respectively., Results: Serum CRP concentration was negatively correlated (P < 0.001) with gestational age at delivery. Serum folate concentration was negatively correlated (P < 0.01) with serum CRP concentration, and total dietary folate intake was positively correlated (P < 0.001) with serum folate concentration. Multiple regression analysis after adjustment for covariates revealed that maternal CRP concentrations were negatively associated with gestational age at delivery; these negative associations existed only when folate intake during pregnancy was below the Korean estimated average requirements (520 μg dietary folate equivalent per day), and serum folate concentrations were above the normal (6 ng/ml)., Conclusions: We found that adequate maternal folate intake during pregnancy may have a beneficial role against shorter gestational age at delivery, which is associated with higher serum CRP concentrations in pregnant women.

Background/objectives: Nitric oxide (NO) has been proposed as a mediator of vascular expansion during pregnancy. Inability to increase NO synthesis and/or production of its precursor, arginine, may be a contributor to pregnancy-induced hypertension or preeclampsia. Because maternal weight is associated with blood pressure and risk of preeclampsia during pregnancy, it may also influence arginine and/or NO production. The purpose of this study was to determine the in vivo arginine production and NO synthesis rate in pregnant women with normal (n=10) and low (n=10) body mass indices (BMIs)., Subjects/methods: Arginine flux and NO synthesis rate were measured in the postabsorptive state with constant infusions of 15N2-arginine and 13C,2H4-citrulline. Plasma concentrations of arginine and NO metabolites were also measured. Kinetic parameters were correlated to maternal variables, gestational age, birth weight and blood pressure., Results: Endogenous arginine flux was significantly faster in the low-BMI compared with normal-BMI women in the first trimester (63.1+/-3.4 vs 50.2+/-2.0 micromol/kg per h, P<0.01), but not in the second. Plasma NO concentration was higher (44.7+/-5.3 vs 30.4+/-1.9 micromol/l, P=0.03) and its rate of synthesis trended faster in the low-BMI compared with normal-BMI group in the second trimester. Maternal weight and BMI were negatively correlated with arginine flux in both trimesters and NO synthesis in the second trimester., Conclusions: These findings suggest, but do not prove, that maternal BMI may be a factor in the ability to produce NO during pregnancy and may be one way by which BMI influences blood pressure during pregnancy.

It has been established that serum soluble endoglin (sEng) increases in women with preeclampsia. However, sEng levels have not been evaluated using a normal reference value specific to each gestational age. First, we established the normal reference value for sEng using 85 pregnant controls without preeclampsia, from whom serum samples were collected three times at 20-23, 27-30, and 36-38 weeks of gestation. Second, we evaluated the serum sEng levels after the onset of preeclampsia in 56 preeclamptic patients. In three women (3.5%) with normal pregnancies, sustained high sEng levels (>15 ng/mL) were observed. We calculated the reference value for sEng using the remaining 82 normal controls. The log10sEng was almost normally distributed at each gestational week during 20-38 weeks, and the mean log10sEng was represented as a quadratic curve of gestational week. The SD of log10sEng was represented as a linear equation of gestational week. The mean log10sEng significantly and gradually increased from 20-23 weeks to 27-30 weeks of gestation and then rapidly increased at 36-38 weeks of gestation. Ninety-three percent of preeclamptic women showed sEng>or=95th percentile of the reference value. The log10sEng levels and the SD score (SDS) of log10sEng in women with early-onset preeclampsia (onset<32 weeks of gestation) were significantly higher than those in women with late-onset preeclampsia (onset>or=32 weeks of gestation) (1.97+/-0.23 vs. 1.78+/-0.28, 9.94+/-2.61 vs. 4.47+/-2.06, respectively). In conclusion, alteration of serum sEng levels after the onset of preeclampsia was more pronounced in women with early-onset preeclampsia compared to those with late onset.

Objective: Pregnancy is a unique situation characterized by insulin resistance. The role of adiponectin, an insulin-sensitizing hormone, has not been completely clarified during pregnancy. The aim of this cross-sectional study was to evaluate adiponectin levels during pregnancy and postpartum., Study Design: Adiponectin and leptin levels were tested in 80 pregnant women, 20 in each trimester (mean gestational age 10.5+/-1.9; 19.3+/-4.9; 39.3+/-0.8 weeks,) as well as 4 days postpartum., Results: Adiponectin levels during first (13.3+/-3.6 micro g/ml), second (12.6+/-4.4 micro g/ml) and third trimester (11.2+/-3.7 micro g/ml) did not differ and were significantly higher than postpartum levels (8.8+/-2.1 micro g/ml; P<0.0001, P<0.004 and P<0.02, respectively)., Conclusion: Despite increased insulin resistance during pregnancy, no significant alterations in adiponectin levels were observed. This may imply that the regulation of adiponectin during gestation is altered. The elevated gestational adiponectin levels are consistent with increased 'adiponectin resistance' during pregnancy.

Objective: It has been known that maternal oxidative stress during pregnancy plays an important role in fetal growth. However, the association between antioxidant vitamin levels and birth outcomes is not conclusive. We investigated the relationship between maternal serum levels of vitamins C and E during the second trimester and birth weight and length., Design: Prospective cohort study., Setting: Outpatient-clinic of obstetrics, Ewha Womans University Hospital, South Korea., Subjects and Methods: The study subjects were 239 healthy, pregnant women who visited an obstetric clinic for antenatal care, and their singleton live births, in Seoul, Korea, between August 2001 and March 2003. We measured the levels of vitamins C and E in maternal serum during the period 24-28 gestational weeks. Each woman was interviewed for dietary intake by trained interviewers during the second trimester., Results: The serum concentration of maternal vitamin C during the second trimester was significantly associated with birth weight and length in the group of full-term deliveries. An increase of 1 microg/ml in the serum vitamin C level increased the birth weight by 27.2 g and the birth length by 0.17 cm. When we considered the levels of vitamins C and E together in the relationship with birth weight and length, we found that the heaviest birth weight and the longest birth length belonged to the group of upper vitamin C/upper vitamin E. However, dietary intake estimated by 24-h recall method was not a predictor of the levels of serum vitamins C and E., Conclusion: We found that maternal serum vitamin C levels during the second trimester were positively correlated with birth weight and length in full-term babies. We also found that birth weight and length were highest when the levels of both vitamins C and E were high. Our results indicate the importance of antioxidant nutrient balance for pregnant women who are exposed to various oxidants through food, drinking water, or inhaled air.

Objective: The aim of this study was to assess the effects of fish oil supplementation in pregnancy on maternal erythrocyte fatty acid composition at different stages of pregnancy and in the post-partum period, and on neonatal erythrocyte fatty acid composition., Design: A double-blind, randomised, placebo-controlled study., Setting: : Subiaco, Western Australia., Subjects: In all, 98 women booked for delivery at St John of God Hospital, Subiaco, were recruited from private rooms of obstetricians. In total, 83 women and their healthy full-term babies completed the study., Intervention: Women received either 4 g of fish oil (n=52) (56% docosahexaenoic acid (DHA) and 28% eicosapentaenoic acid (EPA) or placebo (olive oil) (n=46) per day from 20 weeks gestation until delivery., Main Outcome Measures: Erythrocyte phospholipid fatty acids were measured in maternal peripheral blood at 20, 30 and 37 weeks of pregnancy and at 6 weeks post partum, and from cord blood collected at birth., Results: Compared to the control group, maternal EPA and DHA were significantly higher in the fish oil group at 30 and 37 weeks gestation, and remained elevated at 6 weeks post partum (P<0.001). The proportions of n-6 polyunsaturated (arachidonic acid, 22:3n-6 and 22:4n-6) were significantly lower in the fish oil supplemented group at the same time periods (P<0.001). Similarly, the proportions of EPA and DHA were significantly higher (P<0.001), and those of n-6 polyunsaturated fatty acids arachidonic acid, 20:3n-6, 22:3n-6 and 22:4n-6 were significantly lower (P<0.001), in erythrocytes from neonates in the fish oil group, compared to those in the control group., Conclusion: Fish oil supplementation from 20 weeks of pregnancy until birth is an effective means of enhancing n-3 fatty acid status of both mothers and neonates. Furthermore, the changes in maternal erythrocyte fatty acid composition are retained until at least 6 weeks post partum. It is essential to assess the effects of concomitant decreases in arachidonic acid status before any dietary recommendations can be made., Sponsorship: The study was supported by grants from the NH & MRC and Raine Medical Research Foundation, Australia.

The possibility of using umbilical cord blood for transplantation in several enzyme deficiencies has received increasing attention because of the availability of cord blood, the reduced incidence of post-transplantation complications, such as graft-versus-host disease and the possible accomplishment of good corrective results following transplantation, even in cases of greater HLA disparity. The use of hematopoietic stem cells from unrelated donors is even more highly recommended for the treatment of inherited enzyme deficiencies, because it might reduce the risk of the transplanted cells originating from a carrier of the defect, which might have an inadequate corrective ability. Our study was designed to elucidate whether the gestational age and mode of delivery influences the arylsulfatase-A activity in the umbilical cord blood. Enzyme activities proved to be similar in the four populations studied (full-term normal spontaneous vaginal delivery, full-term caesarean section, preterm normal spontaneous vaginal delivery and preterm caesarean section). Therefore, umbilical cord blood samples seem to be suitable for transplantation in metachromatic leukodystrophy, regardless of gestational age and mode of delivery. Moreover, our results are the first published data on normal values for arylsulfatase-A activity in human umbilical cord blood.