Pregnancy-induced hypertension, preterm birth, and cord blood adipokine levels.

Maternal hypertension may alter physiological parameters, dysregulating the release of hormones such as adipokines, thus influencing the fetal growth course. This study investigated whether hypertensive disorders of pregnancy alter cord blood adipokine levels and correlate these with anthropometric parameters in preterm infants. This is a prospective cohort study with pregnant women < 37-week gestation with and without hypertension and their offspring. Cord blood leptin, adiponectin, and ghrelin were analyzed by LUMINEX®. These adipokines were compared between the groups exposed or not to gestational hypertension using non-parametric statistical tests. The hypertensive pregnancies had significantly higher cord blood leptin (1.00 (IQR 0.67-1.20 ng/mL)) and adiponectin (18.52 (IQR 17.52-25.13 µg/mL)) levels than those without hypertension (0.07 (IQR 0.06-0.08 ng/mL) and 8.13 (IQR 6.50-8.68 µg/mL), respectively, p < 0.0001). The adipokine levels were higher in AGA and SGA infants in the exposed group for both moderate and late preterm. SGA had significantly higher ghrelin levels than the AGA infants. Ghrelin levels were negatively correlated with birth weight (r = - 0.613, p < 0.001), birth length (r = - 0.510, p < 0.001), head circumference (- 0.346, p < 0.002), and gestational age (r = - 0.612, p < 0.001).Conclusions: Our findings demonstrate an increase in adipokine levels in the cord blood of preterm newborn infants exposed to maternal hypertension. What is Known: • Clinical evidence suggests that concentration of the serum adipokines may be affected by risk of hypertension in both adults and pregnant women. • Maternal profile as hypertension alters intrauterine environment and could affect the function of fetal metabolism, impairing fetal growth. What is New: • Gestational hypertension modifies the adipokine profile, with higher rates already present at birth in cord blood samples. • Within the hypertensive group and stratifying for gestation age, ghrelin concentrations were higher in SGA newborns, both in the moderate and late preterm, compared with AGA newborns.

The enrichment of maternal environment prevents pre-term birth in a mice model.

Maternal lifestyle affects both mother health and pregnancy outcome in humans. Several studies have demonstrated that interventions oriented toward reducing stress and anxiety have positive effects on pregnancy complications such as preeclampsia, excessive gestational weight, gestational diabetes and preterm birth. In this work, we showed that the environmental enrichment (EE), defined as a noninvasive and biologically significant stimulus of the sensory pathway combined with voluntary physical activity, prevented preterm birth (PTB) rate by 40% in an inflammatory mouse model induced by the systemic administration of bacterial lipopolysaccharide (LPS). Furthermore, we found that EE modulates maternal metabolism and produces an anti-inflammatory environment that contributes to pregnancy maintenance. In pregnant mice uterus, EE reduces the expression of TLR4 and CD14 (the LPS receptor and its coactivator protein), preventing the LPS-induced increase in PGE2 and PGF2α release and nitric oxide synthase (NOS) activity. In cervical tissue, EE inhibits cervical ripening events, such as PGE2 release, matrix metalloproteinase (MMP)-9 increased activity and neutrophil recruitment, therefore conserving cervical function. It seems that EE exposure could mimic the stress and anxiety-reducing techniques mentioned above, explaining, at least partially, the beneficial effects of having a healthy lifestyle before and during gestation. Furthermore, we propose that designing an EE protocol for humans could be a noninvasive and preventive therapy for pregnancy complications, averting pre-term birth occurrence and dreaded sequelae that are present in the offspring born too soon.

Trace biomarkers associated with spontaneous preterm birth from the maternal serum metabolome of asymptomatic nulliparous women - parallel case-control studies from the SCOPE cohort.

Prediction of spontaneous preterm birth (sPTB) in asymptomatic women remains a great challenge; accurate and reproducible screening tools are still not available in clinical practice. We aimed to investigate whether the maternal serum metabolome together with clinical factors could be used to identify asymptomatic women at risk of sPTB. We conducted two case-control studies using gas chromatography-mass spectrometry to analyse maternal serum samples collected at 15- and 20-weeks' gestation from 164 nulliparous women from Cork, and 157 from Auckland. Smoking and vaginal bleeding before 15 weeks were the only significant clinical predictors of sPTB for Auckland and Cork subsets, respectively. Decane, undecane, and dodecane were significantly associated with sPTB (FDR < 0.05) in the Cork subset. An odds ratio of 1.9 was associated with a one standard deviation increase in log (undecane) in a multiple logistic regression which also included vaginal bleeding as a predictor. In summary, elevated serum levels of the alkanes decane, undecane, and dodecane were associated with sPTB in asymptomatic nulliparous women from Cork, but not in the Auckland cohort. The association is not strong enough to be a useful clinical predictor, but suggests that further investigation of the association between oxidative stress processes and sPTB risk is warranted.

Periodontal Disease, Inflammatory Cytokines, and PGE2 in Pregnant Patients at Risk of Preterm Delivery: A Pilot Study.

Periodontal disease is an infection that, in pregnant women, can act as a risk factor for preterm delivery by increasing local and systemic inflammatory responses. Objective. To analyze the presence of periodontal disease, proinflammatory cytokines, and prostaglandin E 2 (PGE2) in pregnant patients at high risk for preterm delivery. Materials and Methods. Pilot study for a case-control study. We included 46 pregnant patients (23 patients at risk of preterm delivery as cases and 23 patients without risk of preterm delivery as controls). We excluded patients who received periodontal treatment, antibiotics, or antimicrobials over the last 3 months as well as those with infections or diseases such as diabetes or hypercholesterolemia. The patients underwent a periodontal assessment, and their levels of cytokines (interleukin- [IL-] 2, IL-6, IL-10, and tumor necrosis factor- [TNF-] α) and prostaglandin E2 (PGE2) were quantified. Results. Patients with periodontal disease showed higher levels of cytokines (IL-2, IL-6, IL-10, and TNF-α) and PGE 2 . Patients at high risk for preterm birth showed higher IL levels compared with patients at low risk for preterm delivery. PGE 2 increased with the severity of periodontal disease. PGE 2 was higher in patients at low risk for preterm delivery, although this difference was not significant. Conclusion. Periodontal disease can increase the systemic inflammatory response as well as the levels of PGE 2 and inflammatory cytokines in pregnant patients.

The association among cytochrome P450 3A, progesterone receptor polymorphisms, plasma 17-alpha hydroxyprogesterone caproate concentrations, and spontaneous preterm birth.

BACKGROUND: Infants born <37 weeks' gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children <5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-alpha hydroxyprogesterone caproate reduces preterm birth by 33% in women with history of spontaneous preterm birth. We demonstrated previously that plasma concentrations of 17-alpha hydroxyprogesterone caproate vary widely among pregnant women and that women with 17-alpha hydroxyprogesterone caproate plasma concentrations in the lowest quartile had spontaneous preterm birth rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-alpha hydroxyprogesterone caproate plasma concentrations vary so much is unclear. Predominantly, 17-alpha hydroxyprogesterone caproate is metabolized by CYP3A4 and CYP3A5 enzymes. OBJECTIVE: We sought to: (1) determine the relation between 17-alpha hydroxyprogesterone caproate plasma concentrations and single nucleotide polymorphisms in CYP3A4 and CYP3A5; (2) test the association between progesterone receptor single nucleotide polymorphisms and spontaneous preterm birth; and (3) test whether the association between plasma concentrations of 17-alpha hydroxyprogesterone caproate and spontaneous preterm birth varied by progesterone receptor single nucleotide polymorphisms. STUDY DESIGN: In this secondary analysis, we evaluated genetic polymorphism in 268 pregnant women treated with 17-alpha hydroxyprogesterone caproate, who participated in a placebo-controlled trial to evaluate the benefit of omega-3 supplementation in women with history of spontaneous preterm birth. Trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were measured between 25-28 weeks of gestation after a minimum of 5 injections of 17-alpha hydroxyprogesterone caproate. We extracted DNA from maternal blood samples and genotyped the samples using TaqMan (Applied Biosystems, Foster City, CA) single nucleotide polymorphism genotyping assays for the following single nucleotide polymorphisms: CYP3A4*1B, CYP3A4*1G, CYP3A4*22, and CYP3A5*3; and rs578029, rs471767, rs666553, rs503362, and rs500760 for progesteronereceptor. We adjusted for prepregnancy body mass index, race, and treatment group in a multivariable analysis. Differences in the plasma concentrations of 17-alpha hydroxyprogesterone caproate by genotype were evaluated for each CYP single nucleotide polymorphism using general linear models. The association between progesterone receptor single nucleotide polymorphisms and frequency of spontaneous preterm birth was tested using logistic regression. A logistic model also tested interaction between 17-alpha hydroxyprogesterone caproate concentrations with each progesterone receptor single nucleotide polymorphism for the outcome of spontaneous preterm birth. RESULTS: The association between CYP single nucleotide polymorphisms *22, *1G, *1B, and *3 and trough plasma concentrations of 17-alpha hydroxyprogesterone caproate was not statistically significant (P = .68, .44, .08, and .44, respectively). In an adjusted logistic regression model, progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 were not associated with the frequency of spontaneous preterm birth (P = .29, .10, .76, .09, and .43, respectively). Low trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were statistically associated with a higher frequency of spontaneous preterm birth (odds ratio, 0.78; 95% confidence ratio, 0.61-0.99; P = .04 for trend across quartiles), however no significant interaction with the progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 was observed (P = .13, .08, .10, .08, and .13, respectively). CONCLUSION: The frequency of recurrent spontaneous preterm birth appears to be associated with trough 17-alpha hydroxyprogesterone caproate plasma concentrations. However, the wide variation in trough 17-alpha hydroxyprogesterone caproate plasma concentrations is not attributable to polymorphisms in CYP3A4 and CYP3A5 genes. Progesterone receptor polymorphisms do not predict efficacy of 17-alpha hydroxyprogesterone caproate. The limitations of this secondary analysis include that we had a relative small sample size (n = 268) and race was self-reported by the patients.

Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels.

Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of specific folate transporters: RFC, PCFT/HCP1 and FOLR1 in chorionic (fetal) and basal (maternal) plates of placentas of PT pregnancies (PT, 32-36 weeks, n = 51). Term placentas were used as controls (T, 37-41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns. FOLR1 mRNA expression was lower and protein concentration higher in PT placentas (both plates) relative to the control group (p <0.05). In addition, gestational age was positively correlated with mRNA expression (Rho = 0.7), and negatively with protein concentration (Rho = -0.7 for chorionic and -0.43 for basal plate). PCFT/HCP1 mRNA was lower in PT placentas, without changes in protein levels. RFC did not differ in PT placentas compared to controls. PT newborns presented higher cord blood folate level (p = 0.049) along with lower vitamin B12 concentration compared to controls (p = 0.037).In conclusion, placental FOLR1 mRNA was positively associated with gestational age. Conversely, FOLR1 protein concentrations along with folate/vitamin B12 ratio in cord blood were negatively associated with gestational age. Placental FOLR1 is likely the main placental folate transporter to the fetus in newborns.

Relationship between 17-alpha hydroxyprogesterone caproate concentration and spontaneous preterm birth.

OBJECTIVE: 17-alpha hydroxyprogesterone caproate 250 mg weekly reduces recurrent spontaneous preterm birth in women with a prior spontaneous preterm birth by 33%. The dose is not based on pharmacologic considerations. A therapeutic concentration has not been determined hampering any attempt to optimize treatment. This study evaluated the relationship between 17-alpha hydroxyprogesterone caproate plasma concentrations and the rate of spontaneous preterm birth in women with singleton gestation. STUDY DESIGN: A single blood sample was obtained between 25 and 28 weeks' gestation from 315 women with a spontaneous preterm birth who participated in a placebo-controlled, prospective, randomized clinical trial evaluating the benefit of omega-3 supplementation in reducing preterm birth. All women in the parent study received 17-alpha hydroxyprogesterone caproate and 434 received omega-3 supplementation and 418 received a placebo. Plasma from 315 consenting women was analyzed for 17-alpha hydroxyprogesterone caproate concentration. RESULTS: There were no differences between placebo and omega-3 supplemented groups in demographic variables, outcomes or in mean 17-alpha hydroxyprogesterone caproate concentration. Plasma concentrations of 17-alpha hydroxyprogesterone caproate ranged from 3.7-56 ng/mL. Women with plasma concentrations of 17-alpha hydroxyprogesterone caproate in the lowest quartile had a significantly higher risk of spontaneous preterm birth (P = .03) and delivered at significantly earlier gestational ages (P = .002) than did women in the second to fourth quartiles. The lowest preterm birth rates were seen when median 17-alpha hydroxyprogesterone caproate concentrations exceeded 6.4 ng/mL. CONCLUSION: Low plasma 17-alpha hydroxyprogesterone caproate concentration is associated with an increased risk of spontaneous preterm birth. This finding validates efficacy of this treatment but suggests that additional studies are needed to determine the optimal dosage.

Maternal body-mass index and cord blood circulating endothelial colony-forming cells.

OBJECTIVE: Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that are particularly abundant in umbilical cord blood. We sought to determine whether ECFC abundance in cord blood is associated with maternal body-mass index (BMI) in nonpathologic pregnancies. STUDY DESIGN: We measured the level of ECFCs in the cord blood of neonates (n = 27) born from non-obese healthy mothers with nonpathologic pregnancies and examined whether ECFC abundance correlated with maternal BMI. We also examined the effect of maternal BMI on ECFC phenotype and function using angiogenic and vasculogenic assays. RESULTS: We observed variation in ECFC abundance among subjects and found a positive correlation between prepregnancy maternal BMI and ECFC content (r = 0.51, P = .007), which was independent of other obstetric factors. Despite this variation, ECFC phenotype and functionality were deemed normal and highly similar between subjects with maternal BMI <25 kg/m(2) and BMI between 25-30 kg/m(2), including the ability to form vascular networks in vivo. CONCLUSIONS: This study underlines the need to consider maternal BMI as a potential confounding factor for cord blood levels of ECFCs in future comparative studies between healthy and pathologic pregnancies.

Role of TNF-α in the mechanisms responsible for preterm delivery induced by Stx2 in rats.

BACKGROUND AND PURPOSE: Infections with a strain of Escherichia coli producing Shiga toxins could be one of the causes of fetal morbidity and mortality in pregnant women. We have previously reported that Shiga toxin type 2 (Stx2) induces preterm delivery in pregnant rats. In this study, we evaluate the role of TNF-α, PGs and NO in the Stx2-induced preterm delivery. EXPERIMENTAL APPROACH: Pregnant rats were treated with Stx2 (0.7 ng g(-1)) and killed at different times after treatment. Placenta and decidua were used to analyse NOS activity by the conversion of L-[(14)C]arginine into L-[(14)C]citrulline, levels of PGE(2) and PGF(2α) assessed by radioimmunoassay, and cyclooxygenase (COX) proteins by Western blot. TNF-α level was analysed in serum by ELISA and by cytotoxicity in L929 cells. The inhibitor of inducible NOS, aminoguanidine, the COX-2 inhibitor, meloxicam, and the competitive inhibitor of TNF-α, etanercept, were used alone or combined to inhibit NO, PGs and TNF-α production respectively, to prevent Stx2-induced preterm delivery. KEY RESULTS: Stx2 increased placental PGE(2) and decidual PGF(2α) levels as well as COX-2 expression in both tissues. Aminoguanidine and meloxicam delayed the preterm delivery time but did not prevent it. Etanercept blocked the TNF-α increase after Stx2 treatment and reduced the preterm delivery by approximately 30%. The combined action of aminoguanidine and etanercept prevented Stx2-induced preterm delivery by roughly 70%. CONCLUSION AND IMPLICATIONS: Our results demonstrate that the increased TNF-α and NO induced by Stx2 were the predominant factors responsible for preterm delivery in rats.

Effect of nonsurgical periodontal therapy on serum and gingival crevicular fluid cytokine levels during pregnancy and postpartum.

BACKGROUND AND OBJECTIVE: A low-grade systemic inflammatory status originating from periodontal infection has been proposed to explain the association between periodontal disease and systemic conditions, including adverse obstetric outcomes. The aim of this study was to evaluate the effect of periodontal therapy during pregnancy on the gingival crevicular fluid and serum levels of six cytokines associated with periodontal disease and preterm birth. MATERIAL AND METHODS: A subsample of 60 women (18-35 years of age) up to 20 gestational weeks, previously enrolled in a larger randomized clinical trial, was recruited for the present study. Participants were randomly allocated to receive either comprehensive nonsurgical periodontal therapy before 24 gestational weeks (n = 30, test group) or only one appointment for supragingival calculus removal (n = 30, control group). Clinical data, and samples of blood and gingival crevicular fluid, were collected at baseline, at 26-28 gestational weeks and 30 d after delivery. The levels of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70 and tumor necrosis factor-α were analyzed by flow cytometry. RESULTS: After treatment, a major reduction in periodontal inflammation was observed in the test group, with bleeding on probing decreasing from 49.62% of sites to 11.66% of sites (p < 0.001). Periodontal therapy significantly reduced the levels of IL-1ß and IL-8 in gingival crevicular fluid (p < 0.001). However, no significant effect of therapy was observed on serum cytokine levels. After delivery, the levels of IL-1ß in the gingival crevicular fluid of the test group were significantly lower than were those in the control group (p < 0.001), but there were no significant differences between test and control groups regarding serum cytokine levels. CONCLUSION: Although periodontal therapy during pregnancy successfully reduced periodontal inflammation and gingival crevicular fluid cytokine levels, it did not have a significant impact on serum biomarkers.

Micronucleated erythrocytes in preterm newborns exposed to phototherapy and/or oxygentherapy.

Preterm newborns (PNBs) have an immature antioxidant defense system, and this makes them more susceptible to oxidative stress generated by postnatal treatments. The objective was to determine whether micronucleated erythrocytes increase in PNB by postnatal treatments such as oxygentherapy and phototherapy. We counted micronucleated erythrocytes and micronucleated polychromatic erythrocytes as DNA damage in 72 blood samples of PNB at 26-36 weeks of gestation, taken between 1 and 84 h after birth. We assume that more time passed between sampling and birth would correspond to greater time of exposure to oxygen (37 cases) and phototherapy plus oxygen (35 cases). In the PNB only exposed to oxygen, the differences were not significant, while there was a significant increase in micronucleated polychromatic erythrocytes with increasing exposure time in those treated with phototherapy plus oxygen. In conclusion, our results suggest that the MN increase from phototherapy can be observed in peripheral blood erythrocytes of PNB.

Free fetal DNA levels in patients at risk of preterm labour.

OBJECTIVES: Our main goals were to evaluate the capability of ffDNA to increase the accuracy in prediction of preterm labour by cervical length and to explore potential mechanisms of disease associated with this pathology. METHODS: Fifty-six women, with male fetus, with cervical length assessment at between 22 and 24 weeks were included in the study and divided in 1) Short cervix (<15 mm) delivered at term (T = 20); 2) Short cervix delivered before 37 weeks (PT = 14); and 3) Patients who delivered at term with normal cervical length (N = 22). Maternal plasma samples were collected between 22 and 24 weeks of gestational age. PCR using primers against DYS14 gene were used to quantified ffDNA in plasma samples. Statistical analysis was done using ANOVA test and spearman´s correlation. RESULTS: The median gestational age at delivery for short cervix groups was 26 + 1 for PT and 39 + 3 for T. The control group delivered at a median gestational age of 39 + 6 weeks. ffDNA was detectable in all cases. There was no significant difference between the 3 groups. Similarly, no significant correlation was observed between ffDNA and gestational age at delivery (r = -0.23; p = 0.07). CONCLUSIONS: ffDNA does not increase the accuracy of short cervix at between 22 and 24 weeks for the prediction of preterm labour.

Fetal endothelium dysfunction is associated with circulating maternal levels of sE-selectin, sVCAM1, and sFlt-1 during pre-eclampsia.

OBJECTIVES: To evaluate the association between endothelial activation markers in the maternal circulation with nitric oxide (NO) synthesis in human umbilical endothelial cells. STUDY DESIGN: This is a case-control study of normal and pre-eclamptic pregnancies. The levels of sE-selectin, soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble fms-like tyrosine kinase 1 (sFlt-1) were measured by enzyme-linked immunosorbent assay, and histamine-induced NO synthesis was detected by fluorometric examination of the human umbilical vein endothelial cells (HUVECs) isolated from normal and pathological pregnancies. RESULTS: Mothers with severe pre-eclamptic pregnancies have premature and smaller babies than mothers with normal pregnancies (P < 0.05); they also have high maternal plasma levels of sVCAM-1 (∼2-fold), sFlt-1 (∼2.5-fold), and lower (∼70%) histamine-stimulated NO synthesis in HUVECs. A positive relationship between systolic blood pressure (SBP) and plasma levels of sE-selectin, sVCAM-1, and sFlt-1 was demonstrated. Moreover, levels of sE-selectin, sVCAM-1, and sFlt-1 were negatively associated with newborn weight (NBW), gestational age at delivery, and NO synthesis. Women with high E-selectin (>63 ng/ml), VCAM-1 (>752 ng/ml), and sFlt-1 (>15204 pg/ml) showed high risk (∼2-fold) for preterm delivery and very preterm delivery, or fetal weight <1500 g (∼1.5-fold) compared with women with low levels. CONCLUSIONS: High circulating levels of maternal endothelial dysfunction markers present in pre-eclampsia are associated with decreased NO synthesis in fetal endothelium.

Increased free fetal DNA levels in early pregnancy plasma of women who subsequently develop preeclampsia and intrauterine growth restriction.

OBJECTIVE: To determine if maternal plasma ffDNA is increased early in pregnancies which subsequently develop preeclampsia (PE) and intrauterine growth restriction (IUGR). METHODS: Blood was obtained at 11-14 weeks and plasma stored. Among those who delivered a male infant and had a birth weight under the tenth centile and/or PE, we divided them into those who delivered before 35 weeks (9) and those who delivered after this gestation (15). A third group with uncomplicated pregnancies was used as controls (24). Real time-polymerase chain reaction (RT-PCR) was carried out to detect the multi-copy Y chromosome associated DSY14 gene. RESULTS: There were no differences between the ffDNA levels in the group delivered after 35 weeks and the control group (2.23ge/mL-1.61ge/mL p = 0.39). However, the levels of ffDNA at 11-14 weeks were statistically, significantly higher in patients that delivered before 35 weeks (4.34ge/mL-1.61ge/mL p = 0.0018). A logistic regression analysis shows that for every unit (1ge/mL) in which ffDNA increases, the likelihood of having PE or a fetus growing under the tenth centile delivered before 35 weeks increases by 1.67 times (CI 1.13-2.47). CONCLUSION: The concentration of ffDNA is significantly higher even during early pregnancy, in patients who subsequently develop PE and/or IUGR and are delivered before 35 weeks.

Does uric acid provide information about maternal condition and fetal outcome in pregnant women with hypertension?

OBJECTIVE: To evaluate associations between maternal serum uric acid (UA) levels, maternal status, and fetal outcome. METHODS: Maternal UA, urinary protein-creatinine ratio (P/C), blood pressure (BP), gestational age at delivery, and birth weight were evaluated in hypertensive pregnant women (n = 58). These were divided into two groups: high UA (> or =357 micromol/L) or normal UA (<357 micromol/L). RESULTS: Maternal diastolic BP and P/C ratio were higher in pregnant women with elevated UA levels. Systolic BP, gestational age and birth weight were not significantly different. CONCLUSION: UA equal or above 357 micromol/L in pregnant hypertensive women was associated with proteinuria and diastolic BP, but not with fetal outcome.

Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant women.

BACKGROUND: We undertook this study to compare the effectiveness and safety of antenatal daily and weekly supplementation with iron, folic acid, and vitamin B(12) in healthy, pregnant women who were not anemic at gestational week 20. METHODS: Women with singleton pregnancies and blood hemoglobin (Hb) >115 g/L at gestational week 20 (equivalent to 105 g/L at sea level) were randomly assigned to two groups, one consuming one tablet containing 60 mg iron, 200 mug folic acid and 1 mug vitamin B(12) daily (DS, n = 56); the other consuming two tablets once weekly (WS, n = 60). Blood Hb and serum ferritin concentrations were measured every 4 weeks from weeks 20 to 36, and pregnancy outcomes were evaluated. RESULTS: Mild anemia and hypoferritinemia throughout pregnancy occurred less frequently in DS than WS. None of the 116 women had Hb concentrations <103 g/L at any evaluation point. In contrast, hemoconcentration (Hb >145 g/L) from gestational week 28 onwards occurred in 11% in DS and 2% in WS. We observed ex post facto that hemoconcentration at gestational week 28 was associated with a significantly higher relative risk of low birth weight (RR 6.23, 95% CI 1.46-26.57) and premature delivery (RR 7.78, 95% CI 1.45-24.74). CONCLUSIONS: In women who were nonanemic at gestational week 20, both schemes (DS and WS) prevented the occurrence of Hb levels <100 g/L. DS women had a higher incidence of hemoconcentration. Hemoconcentration was associated with increased risk of low birth weight and premature delivery.

Predictors of preterm birth.

OBJECTIVE: This is a systematic review to assess published scientific evidence on preterm birth predictors. METHODS: An Internet search for predictors of preterm birth was performed and the evidence level of each method was evaluated. RESULTS: There is strong evidence that preterm birth can be predicted using vaginal sonography to evaluate cervical characteristics, fetal fibronectin in cervicovaginal secretions and interleukin-6 in amniotic fluid. There is consistent evidence that digital cervical examination is a weak predictor, and controversy regarding home uterine activity monitoring. There is scanty evidence about the predictive ability of maternal history and perceptions of symptoms since the study design fails to provide high evidence level. CONCLUSION: Cervical evaluation by vaginal sonography, fetal fibronectin and interleukin-6 are the best methods for predicting preterm birth.

Strict red blood cell transfusion guideline reduces the need for transfusions in very-low-birthweight infants in the first 4 weeks of life: a multicentre trial.

BACKGROUND AND OBJECTIVES: Very-low-birthweight infants are among the most heavily transfused patients. The objective of this study was to verify if the introduction of a strict guideline would reduce the need for red blood cell transfusions in the first 4 weeks of life in these neonates. MATERIALS AND METHODS: This was a multicentre prospective study of two cohorts of very-low-birthweight infants transfused in accordance with the recommendations of a neonatologist (Phase 1) or according to previously published guidelines (Phase 2). RESULTS: In the first 28 days of life, 102 patients (68.5%) in Phase 1 and 117 (59.7%) in Phase 2 were transfused. The number of transfusions was 1.9 +/- 2.0 in Phase 1 and 1.4 +/- 1.6 in Phase 2 (P = 0.01). After adjusting for gestational age, blood loss and the presence of respiratory distress syndrome, the strict guideline reduced the number of transfusions in 17.6% (IC 95%-30.5% to -2.6%). CONCLUSIONS: The strict guideline was effective in reducing erythrocyte transfusions in very-low-birthweight infants.