An Evaluation of Oxidative Status in Serum and Breast Milk of Mothers Giving Birth Prematurely and at Full-Term

Background: Burning fat and carbohydrates to provide energy in biological systems causes the formation of free oxygen species. Objectives: This study aimed to evaluate the oxidative status of serum and breast milk of mothers giving birth prematurely and at full-term. Materials and Methods: The study comprised 50 mothers who gave birth at full-term at more than 38 weeks and 43 mothers who gave birth pre-term at below 32 weeks. On the postnatal 5th day, samples of the mother’s milk and serum were taken and stored at -80°C until the study day. On the study day, the total oxidant and total antioxidant levels were measured using the Erel method and the oxidative stress index (OSI) was calculated. Results: While the total oxidant level and total antioxidant level values of the milk of the premature birth mothers were found to be significantly high compared to those of the full-term birth mothers (P = 0.001), no statistically significant difference was found in the oxidative stress index values (P > 0.05). No statistically significant difference was found in the total oxidant level and oxidative stress index values of the serum of the premature birth mothers compared to those of the full-term birth mothers, while the total antioxidant level was found to be significantly low (P = 0.04). Conclusions: The oxidants and antioxidants in the milk of mothers giving birth prematurely were found to be significantly higher than those of full-term birth mothers. This can be evaluated as the milk of the premature birth mothers providing increased antioxidant defense to protect the infant.

Maternal Glucose at 28 Weeks of Gestation Is Not Associated With Obesity in 2-Year-Old Offspring:The Belfast Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Family Study

OBJECTIVE:Diabetes during pregnancy is a strong risk factor for obesity in the offspring, but the age at which this association becomes apparent is unknown. The purpose of this study was to examine the relation of glycemia during pregnancy with anthropometry in offspring of nondiabetic pregnant women from the Belfast U.K. center of the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.
RESEARCH DESIGN AND METHODS: Women from the HAPO Study were invited to participate in follow-up of their offspring aged 2 years. Measurements included height, weight, and thickness of triceps, subscapular, and suprailiac skinfolds. RESULTS: A total of 1,165 offspring (73% of eligible children; 598 boys and 567 girls) were seen from ages 22-30 completed months. The only association that reached statistical significance was between categories of maternal 1-h glucose and BMI Z score =85th percentile at 2 years (P = 0.017). Overall the correlations between maternal glucose during pregnancy and BMI Z score at age 2 years were weak (fasting glucose r = 0.05, P = 0.08; 1-h glucose r = 0.04, P = 0.22; 2-h glucose r = 0.03, P = 0.36; and area under the curve for glucose r = 0.04, P = 0.18).
CONCLUSIONS: This study found little association between maternal glucose during pregnancy and obesity in the offspring at this young age. These findings are not unexpected given that study results for young offspring whose mothers had diabetes during pregnancy were indistinguishable from those for normal offspring at this age. It will be interesting to see whether, as these children age, maternal glucose during pregnancy in the ranges included in the HAPO Study will be associated with obesity in their children. © 2010 by the American Diabetes Association.

BORN AT 27 WEEKS OF GESTATION WITH CLASSICAL PKU: CHALLENGES OF DIETETIC MANAGEMENT IN A VERY PRETERM INFANT

Only few cases of classical phenylketonuria (PKU) in premature infants have been reported. Treatment of these patients is challenging due to the lack of a phenylalanine-free amino acid solution for parenteral infusion. The boy was born at 27 weeks of gestation with a weight of 1000 g (P10). He received parenteral nutrition with a protein intake of 3 g/kg/day. On day 7 he was diagnosed with classical PKU (genotype IVS10-11G>A/IVS12+ 1G>A) due to highly elevated phenylalanine (Phe) level in newborn screening (2800 micromol/L). His maximum plasma Phe level reached 3696 micromol/L. Phe intake was stopped for 4 days. During this time the boy received intravenous glucose and lipids as well as little amounts of Phe-free formula by a nasogastric tube. Due to a deficit of essential amino acids and insufficient growth, a parenteral nutrition rich in branched-chain amino-acids and relatively poor in Phe was added, in order to promote protein synthesis without overloading in Phe. Under this regimen, Phe plasma levels normalized on day 19 when intake of natural protein was started. The boy has now a corrected age of 2 years. He shows normal growth parameters and psychomotor development. Despite a long period of highly elevated Phe levels in the postnatal period our patient shows good psychomotor development. The management of premature infants with PKU depends on the child's tolerance to enteral nutrition. It demands an intensive follow-up by an experienced team and dedicated dietician. Appropriate Phe-free parenteral nutrition would be necessary especially in case of gastro-intestinal complications of prematurity.

Quantitative Analysis of Placental Vasculature by Three-Dimensional Power Doppler Ultrasonography in Normal Pregnancies From 12 to 40 Weeks of Gestation

Evaluate the distribution and variation of placental vascular indices according to gestational age and placental volume. From March to November 2007, three-dimensional (3D)-power Doppler ultrasound was performed in 295 normal pregnancies from 12 to 40 weeks of gestation. Using the same preestablished settings for all patients, power Doppler was applied to the placenta and placental Volume was obtained by the rotational technique (VOCAL(TM)). The 3D-power histogram was used to determine the placental vascular indices: vascularization index (VI), flow index (FI) and vascularization-flow index (VFI). The placental vascular indices were then plotted against gestational age and placental volume. All placental vascular indices showed constant distribution throughout gestation. A tendency for a reduction in placental vascular indices with increased placental volume was observed, but was only statistically significant when placental FI was considered (p < 0.05). All placental vascular indices estimated by 3D-power Doppler ultrasonography presented constant distribution throughout gestation, despite the increase in placental volume according to gestational age. (C) 2008 Elsevier Ltd. All rights reserved.

Perinatal care at the limit of viability between 22 and 26 completed weeks of gestation in Switzerland. 2011 revision of the Swiss recommendations

Perinatal care of pregnant women at high risk for preterm delivery and of preterm infants born at the limit of viability (22-26 completed weeks of gestation) requires a multidisciplinary approach by an experienced perinatal team. Limited precision in the determination of both gestational age and foetal weight, as well as biological variability may significantly affect the course of action chosen in individual cases. The decisions that must be taken with the pregnant women and on behalf of the preterm infant in this context are complex and have far-reaching consequences. When counselling pregnant women and their partners, neonatologists and obstetricians should provide them with comprehensive information in a sensitive and supportive way to build a basis of trust. The decisions are developed in a continuing dialogue between all parties involved (physicians, midwives, nursing staff and parents) with the principal aim to find solutions that are in the infant's and pregnant woman's best interest. Knowledge of current gestational age-specific mortality and morbidity rates and how they are modified by prenatally known prognostic factors (estimated foetal weight, sex, exposure or nonexposure to antenatal corticosteroids, single or multiple births) as well as the application of accepted ethical principles form the basis for responsible decision-making. Communication between all parties involved plays a central role. The members of the interdisciplinary working group suggest that the care of preterm infants with a gestational age between 22 0/7 and 23 6/7 weeks should generally be limited to palliative care. Obstetric interventions for foetal indications such as Caesarean section delivery are usually not indicated. In selected cases, for example, after 23 weeks of pregnancy have been completed and several of the above mentioned prenatally known prognostic factors are favourable or well informed parents insist on the initiation of life-sustaining therapies, active obstetric interventions for foetal indications and provisional intensive care of the neonate may be reasonable. In preterm infants with a gestational age between 24 0/7 and 24 6/7 weeks, it can be difficult to determine whether the burden of obstetric interventions and neonatal intensive care is justified given the limited chances of success of such a therapy. In such cases, the individual constellation of prenatally known factors which impact on prognosis can be helpful in the decision making process with the parents. In preterm infants with a gestational age between 25 0/7 and 25 6/7 weeks, foetal surveillance, obstetric interventions for foetal indications and neonatal intensive care measures are generally indicated. However, if several prenatally known prognostic factors are unfavourable and the parents agree, primary non-intervention and neonatal palliative care can be considered. All pregnant women with threatening preterm delivery or premature rupture of membranes at the limit of viability must be transferred to a perinatal centre with a level III neonatal intensive care unit no later than 23 0/7 weeks of gestation, unless emergency delivery is indicated. An experienced neonatology team should be involved in all deliveries that take place after 23 0/7 weeks of gestation to help to decide together with the parents if the initiation of intensive care measures appears to be appropriate or if preference should be given to palliative care (i.e., primary non-intervention). In doubtful situations, it can be reasonable to initiate intensive care and to admit the preterm infant to a neonatal intensive care unit (i.e., provisional intensive care). The infant's clinical evolution and additional discussions with the parents will help to clarify whether the life-sustaining therapies should be continued or withdrawn. Life support is continued as long as there is reasonable hope for survival and the infant's burden of intensive care is acceptable. If, on the other hand, the health car...

Gestation-specific reference intervals for comprehensive spot urinary steroid hormone metabolite analysis in normal singleton pregnancy and 6 weeks postpartum

BACKGROUND: Normal pregnancy depends on pronounced adaptations in steroid hormone concentrations. Although in recent years, the understanding of these hormones in pregnancy has improved, the interpretation is hampered by insufficient reference values. Our aim was to establish gestation-specific reference intervals for spot urinary steroid hormone levels in normal singleton pregnancies and 6 weeks postpartum. METHODS: Cross-sectional multicentre observational study. Women recruited between 2008 and 2013 at 3 University Hospitals in Switzerland (Bern), Scotland (Glasgow) and Austria (Graz). Spot urine was collected from healthy women undergoing a normal pregnancy (age, 16-45 years; mean, 31 years) attending routine antenatal clinics at gestation weeks 11, 20, and 28 and approximately 6 weeks postpartum. Urine steroid hormone levels were analysed using gas-chromatography mass spectrometry. Creatinine was also measured by routine analysis and used for normalisation. RESULTS: From the results, a reference interval was calculated for each hormone metabolite at each trimester and 6 weeks postpartum. Changes in these concentrations between trimesters and postpartum were also observed for several steroid hormones and followed changes proposed for index steroid hormones. CONCLUSIONS: Normal gestation-specific reference values for spot urinary steroid hormones throughout pregnancy and early postpartum are now available to facilitate clinical management and research approaches to steroid hormone metabolism in pregnancy and the early postpartum period.

Ureaplasma parvum : understanding the complexities of intra-amniotic infection in an ovine model

The human Ureaplasma species are the most frequently isolated bacteria from the upper genital tract of pregnant women and can cause clinically asymptomatic, intra-uterine infections, which are difficult to treat with antimicrobials. Ureaplasma infection of the upper genital tract during pregnancy has been associated with numerous adverse outcomes including preterm birth, chorioamnionitis and neonatal respiratory diseases. The mechanisms by which ureaplasmas are able to chronically colonise the amniotic fluid and avoid eradication by (i) the host immune response and (ii) maternally-administered antimicrobials, remain virtually unexplored. To address this gap within the literature, this study investigated potential mechanisms by which ureaplasmas are able to cause chronic, intra-amniotic infections in an established ovine model. In this PhD program of research the effectiveness of standard, maternal erythromycin for the treatment of chronic, intra-amniotic ureaplasma infections was evaluated. At 55 days of gestation pregnant ewes received an intra-amniotic injection of either: a clinical Ureaplasma parvum serovar 3 isolate that was sensitive to macrolide antibiotics (n = 16); or 10B medium (n = 16). At 100 days of gestation, ewes were then randomised to receive either maternal erythromycin treatment (30 mg/kg/day for four days) or no treatment. Ureaplasmas were isolated from amniotic fluid, chorioamnion, umbilical cord and fetal lung specimens, which were collected at the time of preterm delivery of the fetus (125 days of gestation). Surprisingly, the numbers of ureaplasmas colonising the amniotic fluid and fetal tissues were not different between experimentally-infected animals that received erythromycin treatment or infected animals that did not receive treatment (p > 0.05), nor were there any differences in fetal inflammation and histological chorioamnionitis between these groups (p > 0.05). These data demonstrate the inability of maternal erythromycin to eradicate intra-uterine ureaplasma infections. Erythromycin was detected in the amniotic fluid of animals that received antimicrobial treatment (but not in those that did not receive treatment) by liquid chromatography-mass spectrometry; however, the concentrations were below therapeutic levels (<10 – 76 ng/mL). These findings indicate that the ineffectiveness of standard, maternal erythromycin treatment of intra-amniotic ureaplasma infections may be due to the poor placental transfer of this drug. Subsequently, the phenotypic and genotypic characteristics of ureaplasmas isolated from the amniotic fluid and chorioamnion of pregnant sheep after chronic, intra-amniotic infection and low-level exposure to erythromycin were investigated. At 55 days of gestation twelve pregnant ewes received an intra-amniotic injection of a clinical U. parvum serovar 3 isolate, which was sensitive to macrolide antibiotics. At 100 days of gestation, ewes received standard maternal erythromycin treatment (30 mg/kg/day for four days, n = 6) or saline (n = 6). Preterm fetuses were surgically delivered at 125 days of gestation and ureaplasmas were cultured from the amniotic fluid and the chorioamnion. The minimum inhibitory concentrations (MICs) of erythromycin, azithromycin and roxithromycin were determined for cultured ureaplasma isolates, and antimicrobial susceptibilities were different between ureaplasmas isolated from the amniotic fluid (MIC range = 0.08 – 1.0 mg/L) and chorioamnion (MIC range = 0.06 – 5.33 mg/L). However, the increased resistance to macrolide antibiotics observed in chorioamnion ureaplasma isolates occurred independently of exposure to erythromycin in vivo. Remarkably, domain V of the 23S ribosomal RNA gene (which is the target site of macrolide antimicrobials) of chorioamnion ureaplasmas demonstrated significant variability (125 polymorphisms out of 422 sequenced nucleotides, 29.6%) when compared to the amniotic fluid ureaplasma isolates and the inoculum strain. This sequence variability did not occur as a consequence of exposure to erythromycin, as the nucleotide substitutions were identical between chorioamnion ureaplasmas isolated from different animals, including those that did not receive erythromycin treatment. We propose that these mosaic-like 23S ribosomal RNA gene sequences may represent gene fragments transferred via horizontal gene transfer. The significant differences observed in (i) susceptibility to macrolide antimicrobials and (ii) 23S ribosomal RNA sequences of ureaplasmas isolated from the amniotic fluid and chorioamnion suggests that the anatomical site from which they were isolated may exert selective pressures that alter the socio-microbiological structure of the bacterial population, by selecting for genetic changes and altered antimicrobial susceptibility profiles. The final experiment for this PhD examined antigenic size variation of the multiple banded antigen (MBA, a surface-exposed lipoprotein and predicted ureaplasmal virulence factor) in chronic, intra-amniotic ureaplasma infections. Previously defined ‘virulent-derived’ and ‘avirulent-derived’ clonal U. parvum serovar 6 isolates (each expressing a single MBA protein) were injected into the amniotic fluid of pregnant ewes (n = 20) at 55 days of gestation, and amniotic fluid was collected by amniocentesis every two weeks until the time of near-term delivery of the fetus (at 140 days of gestation). Both the avirulent and virulent clonal ureaplasma strains generated MBA size variants (ranging in size from 32 – 170 kDa) within the amniotic fluid of pregnant ewes. The mean number of MBA size variants produced within the amniotic fluid was not different between the virulent (mean = 4.2 MBA variants) and avirulent (mean = 4.6 MBA variants) ureaplasma strains (p = 0.87). Intra-amniotic infection with the virulent strain was significantly associated with the presence of meconium-stained amniotic fluid (p = 0.01), which is an indicator of fetal distress in utero. However, the severity of histological chorioamnionitis was not different between the avirulent and virulent groups. We demonstrated that ureaplasmas were able to persist within the amniotic fluid of pregnant sheep for 85 days, despite the host mounting an innate and adaptive immune response. Pro-inflammatory cytokines (interleukin (IL)-1â, IL-6 and IL-8) were elevated within the chorioamnion tissue of pregnant sheep from both the avirulent and virulent treatment groups, and this was significantly associated with the production of anti-ureaplasma IgG antibodies within maternal sera (p < 0.05). These findings suggested that the inability of the host immune response to eradicate ureaplasmas from the amniotic cavity may be due to continual size variation of MBA surface-exposed epitopes. Taken together, these data confirm that ureaplasmas are able to cause long-term in utero infections in a sheep model, despite standard antimicrobial treatment and the development of a host immune response. The overall findings of this PhD project suggest that ureaplasmas are able to cause chronic, intra-amniotic infections due to (i) the limited placental transfer of erythromycin, which prevents the accumulation of therapeutic concentrations within the amniotic fluid; (ii) the ability of ureaplasmas to undergo rapid selection and genetic variation in vivo, resulting in ureaplasma isolates with variable MICs to macrolide antimicrobials colonising the amniotic fluid and chorioamnion; and (iii) antigenic size variation of the MBA, which may prevent eradication of ureaplasmas by the host immune response and account for differences in neonatal outcomes. The outcomes of this program of study have improved our understanding of the biology and pathogenesis of this highly adapted microorganism.

Homocysteine is lower in the Third Trimester of Pregnancy in Women with Enhanced Folate status from continued Folic Acid Supplementation.

Background: In many countries current recommendations are that women take a daily 400ug folic acid supplement, from before conception until the end of the 12th week of gestation, for the prevention of neural tube defects. Low folate status is associated with an elevated concentration of plasma total homocysteine (tHcy), a risk factor that is associated with pregnancy complications such as pre-eclampsia. Methods: In a longitudinal study, tHcy and corresponding folate status were determined in 101 pregnant women at 12, 20 and 35 weeks of gestation, in 35 non-pregnant control subjects sampled conconcurrently, and in a subgroup (n=21 pregnant, 19 non-pregnant women) at 3 days post-partum. Results: Plasma tHcy concentrations were significantly lower throughout pregnancy compared with control subjects, with values lowest in the 2nd trimester before increasing toward non-pregnant values in the 3rd trimester. Importantly, tHcy concentrations were lower in pregnant women taking folic acid supplements compared to those not, an effect which reached significance in the 3rd trimester (5.25 umol/l v 6.89 umol/l, P <0.05). Furthermore, during the 3rd trimester, tHcy concentrations were significantly higher in pregnant women with a history of miscarriage compared to those with no previous history (7.32 umol/l v 5.62 u­mol/l, P <0.01). Conclusion: This is the first longitudinal study to show that homocysteine levels rise in late pregnancy towards non-pregnant levels; a rise which can be limited by enhancing folate status through continued folic acid supplementation. These results indicate a potential role for continued folic acid supplementation in reducing pregnancy complications associated with hyperhomocysteinaemia.

Cord blood erythropoietin, pH, PaO2 and haematocrit following caesarean section before labour

We have investigated the relationship between erythropoietin (Epo) and pH, PaO2 and haematocrit in 100 cord blood samples obtained at Caesarean section prior to labour. Of 82 term (> 37 weeks) infants, 64 were appropriately grown (10th-90th centiles), and their mean cord serum Epo and cord blood Epo was 23 +/- 8 mU/ml (mean +/- SD). Strong inverse correlations were found between cord serum Epo and cord blood pH (r = -0.74; p <0.0001), and between cord serum Epo and cord blood PaO2 (r = -0.55; p <0.0001), but not between cord serum Epo and cord haematocrit (r = 0.02; p <0.9). For the 18 preterm babies (gestation 32.4 +/- 4.1 weeks, birth weight 1,820 +/- 476 g), the Epo level was 36 +/- 8 mU/ml, which was not significantly greater than for the term babies. Strong inverse correlations were again found between Epo and pH (r = -0.87; p <0.0001) and Epo and PaO2 (r = -0.69; p <0.002). Babies from complicated pregnancies (intra-uterine growth retardation, pre-eclampsia, antepartum haemorrhage, diabetes mellitus and fetal distress) tended to have higher Epo levels. Thirteen babies had Epo levels > 40 mU/ml, and 11 (85%) of these required neonatal intensive care. Cord serum Epo correlates better with oxygen tension and pH at birth than with fetal growth and haematocrit, which are measures of chronic stress to the fetus.

The neurodevelopmental progress of infants less than 33 weeks into adolescence

Background: Several studies have shown an increased incidence of neurodevelopmental impairment in very preterm survivors at school age compared with controls.

Aim: To compare findings in the same cohort at 8 years and 15 years.

Methods: A total of 151 of the 224 eligible infants born before 33 weeks of gestation from 1979 to 1982, and who were living in the UK, were assessed at 8 and 15 years. Items common to both assessments were compared to evaluate changes in neurodevelopmental function. The assessment included a structured neurological examination, psychometric tests using the WISC-R (in subjects born in 1981-82), a test of visuomotor integration (Beery), and a school questionnaire.

Results: There was a significant increase in the proportion of subjects classified as impaired with disability from 11% at 8 to 22% at 14-15 years of age. The proportion of subjects classified as impaired without disability increased from 16% at 8 to 26% at 14-15 years of age. Full scale IQ decreased from 104 to 95 from childhood to adolescence, and more adolescents (24%) were requiring extra educational provision than they had at the age of 8 years (15%).

Conclusion: Results indicate that between the ages of 8 and 15 years in this cohort of very preterm survivors there is an apparent deterioration in neurodevelopmental outcome category, cognitive function, and extra educational support. It is not clear whether this represents a genuine deterioration in neurocognitive function or whether it represents the expression of pre-existing cerebral pathology in an increasingly complex environment.

The Role of Growth Trajectories in Classifying Fetal Growth Restriction

OBJECTIVE: To examine the validity of a growth trajectory method to discriminate between pathologically and constitutionally undergrown fetuses using repeated measures of estimated fetal weight.

METHODS: In a prospective, observational, multicenter study in Ireland, 1,116 women with a growth-restricted fetus diagnosed participated with the objective of evaluating ultrasound findings as predictors of pediatric morbidity and mortality. Fetal growth trajectories were based on estimated fetal weight.

RESULTS: Between 22 weeks of gestation and term, two fetal growth trajectories were identified: normal (96.7%) and pathologic (3.3%). Compared with the normal trajectory, the pathologic trajectory was associated with an increased risk for preeclampsia (odds ratio [OR] 8.1, 95% confidence interval [CI] 2.6–23.4), increased umbilical artery resistance at 30 weeks of gestation (OR 12.6, 95% CI 4.6–34.1) or 34 weeks of gestation (OR 28.0, 95% CI 8.9–87.7), reduced middle cerebral artery resistance at 30 weeks of gestation (OR 0.33, 95% CI 0.12–0.96) or 34 weeks of gestation (OR 0.14, 95% CI 0.03–0.74), lower gestational age at delivery (mean 32.02 weeks of gestation compared with 38.02 weeks of gestation; P<.001), and higher perinatal complications (OR 21.5, 95% CI 10.5–44.2). In addition, 89.2% of newborns with pathologic fetal growth were admitted to neonatal intensive care units compared with 25.9% of those with normal growth.

CONCLUSIONS: Fetal growth trajectory analysis reliably differentiated fetuses with a pathologic growth pattern among a group of women with growth-restricted fetuses. With further development, this approach could provide clarity to how we define, identify, and ultimately manage pathologic fetal growth.

LEVEL OF EVIDENCE: II

Seasonal and gestation stage associated differences in aflatoxin exposure in pregnant Gambian women

Objective: Aflatoxin is known to cross the placental barrier and exposures in utero could influence genomic programming, foetal growth and development, resulting in long-term health effects. We aimed to determine aflatoxin exposure in Gambian women at two stages of pregnancy and during the rainy and dry seasons.

Methods: We examined aflatoxin exposure in pregnant Gambian women at early (<16 weeks) and later (16 weeks onward) stages of pregnancy and at different times of the year, during the rainy (June to October 2009) or dry (November to May 2010) season, using aflatoxin–albumin adducts (AF-alb).

Results: Mean AF-alb was higher during the dry season than in the rainy season, in both early and later pregnancy although the difference was strongest in later pregnancy. There was a modest increase in AF-alb in later than early pregnancy (geometric mean 41.8 vs. 34.5 pg/mg, P < 0.05), but this was restricted to the dry season when exposures were generally higher.

Conclusions: The study confirmed that Gambian pregnant women were exposed to aflatoxin throughout the pregnancy, with higher levels in the dry season. There was some evidence in the dry season that women in later pregnancy had higher AF-alb levels than those in earlier pregnancy. Further research on the effects of exposure to this potent mutagen and carcinogen throughout pregnancy, including the epigenetic modification of foetal gene expression and impact on pre- and post-natal growth and development, are merited.

Factor V Leiden and Prothrombin G20210A in Portuguese Women with Recurrent Miscarriage: Is it Worthwhile to Investigate?

OBJECTIVE: To compare the prevalence of factor V Leiden (FVL) and prothrombin (PT) G20210A mutations in Portuguese women with unexplained recurrent miscarriage (RM) and a control group of parous women. MATERIALS AND METHODS: FVL and PT G20210A analysis were carried out in 100 women with three or more consecutive miscarriages and 100 controls with no history of pregnancy losses. Secondary analysis was made regarding gestational age at miscarriage (embryonic and fetal losses). RESULTS: Overall, the prevalence of FVL and PT G20210A was similar in women with RM (5 and 3%) compared with controls (5 and 1%) OR 1.36 (CI 95% 0.45-4.08). In RM embryonic subgroup, PT G20210A was observed in 1.3% of women and FVL prevalence (2.6%) was inclusively lesser than that of controls. Both polymorphisms were more prevalent in women with fetal losses than in controls, although statistical significance was not reached due to the small size of the >10 weeks' subgroup. CONCLUSION: These data indicate that neither FVL nor PT G20210A is associated with RM prior to 10 weeks of gestation. Therefore, its screening is not indicated as an initial approach in Portuguese women with embryonic RM and negative personal thromboembolic history.