First-trimester combined screening for Down syndrome: prediction of low birth weight, small for gestational age and pre-term delivery in a cohort of non-selected women

OBJECTIVE: To establish the relationship between the first-trimester screening markers [pregnancy-associated plasma protein A (PAPP-A), free human chorionic gonadotrophin-beta (beta-hCG), nuchal translucency (NT)], the Down syndrome (DS) risk estimate, and the adverse outcomes such as low birth weight, small for gestational age (SGA) and pre-term delivery. METHODS: A retrospective cohort study including 1,734 non-selected singleton pregnancies consecutively enrolled into the programme of first-trimester combined screening for DS in a 12-month period at a single centre. Data from the Prenatal Patient Registry in ASTRAIA were combined with the Danish National Newborn Screening Registry and Danish Birth Registry. RESULTS: There was a significant relation between low PAPP-A MoM, low beta-hCG MoM, increased risk estimate for DS and low birth weight and SGA. Low PAPP-A MoM and increased NT showed a significant relation to pre-term and spontaneous pre-term delivery. Low PAPP-A MoM showed a significant relation to early pre-term delivery. CONCLUSION: First-trimester screening markers exhibited a significant relation to low birth weight, SGA and to some extent, to pre-term and early pre-term delivery. The screening performance of individual markers was poor.     

First-trimester maternal serum progesterone in aneuploid pregnancies

BACKGROUND: First-trimester maternal serum screening for Down syndrome (DS) can be improved by the use of additional serum markers. We examined whether progesterone (P), synthesized by placenta, might be a first-trimester maternal serum marker for fetal DS. MATERIALS AND METHODS: P was quantified in first-trimester maternal serum from 42 DS, six trisomy 18 and two trisomy 13 pregnancies and 115 controls. Log-regression of P versus gestational age in days was used to convert P concentrations into multiples of the median (MoM). RESULTS: The P concentrations in controls increased with gestational age (p = 9.5 x 10(-7)). The log10MoM P distribution in DS pregnancies was not significantly different from that in controls. However, from day 58-67, the log10MoM P was elevated in DS pregnancies (n = 10) with a mean (SD) of 0.1040 (0.0956), compared to a mean (SD) of - 0.0109 (0.1661) in controls (n = 24) (p = 0.05). Five out of six trisomy 18 and both trisomy 13 pregnancies had a P MoM < 1. CONCLUSION: P is not a useful marker for DS in first trimester, except perhaps in a narrow gestational age window from day 58 to 67. P is a trisomy 18/13 marker.     

Association between maternal weight gain and birth weight

OBJECTIVE: To investigate the association between maternal weight gain and birth weight less than 3,000 g and greater than or equal to 4,000 g in underweight (body mass index [BMI] less than 19.8 kg/m(2)), normal weight (BMI 19.8-26.0 kg/m(2)), overweight (BMI 26.1-29.0 kg/m(2)), and obese (BMI greater than 29.0 kg/m(2)) women, with emphasis on the use of the American Institute of Medicine (IOM) recommendations in Denmark. METHODS: We analyzed data from 2,248 women with singleton, term pregnancies. The relationship between weight gain and risk of birth weight less than 3,000 g and greater than or equal to 4,000 g was examined in the four BMI groups, and use of IOM recommendations was tested by logistic regression analyses. RESULTS: We found an inverse relationship between maternal weight gain and the proportion of infants with a birth weight less than 3,000 g. Birth weight greater than or equal to 4,000 g increased with an increasing weight gain in underweight and normal-weight women, but the association was less apparent in overweight and obese women. Underweight women seemed to benefit from gaining more weight than recommended by the IOM, because the odds ratio (OR) of birth weight less than 3,000 g was 0.3 (95% confidence interval [CI] 0.1-0.9) and the OR was 1.7 for birthweight greater than or equal to 4,000 g (95% CI 0.8-3.6). The normal-weight women had an increased risk of birth weight less than 3,000 g (OR 2.4, 95% CI 1.5-3.7) if weight gain was below the recommended range, and the OR of birth weight greater than or equal to 4,000 g was 1.9 (95% CI 1.5-2.5) when the women gained more than recommended. CONCLUSION: The IOM recommendations may provide a basis for Danish recommendations to pregnant women, although the upper recommended limit for underweight women may have to be increased.     

Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

OBJECTIVES: To evaluate the effect of estrogen replacement therapy or soy isoflavones supplement on endothelium-dependent relaxation in vitro and gene expression of endothelial nitric oxide synthase (eNOS) in cerebral arteries in a rabbit model of human hypercholesterolemia. STUDY DESIGN: Thirty-six female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomised to treatment with 17beta-estradiol (17beta-E(2)), SoyLife 150 or control for 16 weeks. Ring segments of basilar artery (BA) and posterior cerebral artery (PCA) were mounted in myographs for isometric tension recordings. Concentration response curves to carbamylcholine chloride, sodium nitroprusside (SNP) and l-NAME were evaluated after precontraction with potassium. Total RNA was extracted, reverse transcribed and eNOS quantitated by real-time polymerase chain reaction (real-time PCR). RESULTS: Plasma cholesterol was significantly higher at termination in the SoyLife group (P<0.0001), whereas low-density lipoprotein (LDL) cholesterol was comparable in all treatment groups. Neither treatment influenced the endothelium-dependent responses to carbamylcholine chloride or l-NAME or the endothelium-independent response to SNP in any of the arteries. Correspondingly, eNOS mRNA was similarly expressed in all treatment groups in both arteries. CONCLUSIONS: Improvement of cerebral endothelial function by estrogen or soy isoflavones in ovariectomized WHHL rabbits is not supported by the present data. The findings may be unique to the WHHL rabbit in which the hypocholesterolemic effect of estrogens mediated by upregulation of liver LDL receptors is excluded.     

Percutaneous endovascular occlusion of symptomatic coronary arteriovenous fistulas with cyanoacrylate

We describe four cases with symptomatic coronary artery fistulas that were treated primarily with endovascular cyanoacrylate embolization. Coils were also used as adjunctive embolic agents in two of these cases. All four cases showed symptomatic improvement after closure of the fistulas. Complications occurred in three cases including transient ST-segment elevation in one, symptomatic pulmonary embolization in a second, and transient pleuritic chest pain, pericarditis and acute renal failure in a third. The technical aspects of all four cases are given together with a review of the use of cyanoacrylate as an embolic material. We conclude that cyanoacrylate embolization could be considered as an alternative technique for the endovascular closure of coronary artery fistulas but must also caution that the use of this embolic agent is hazardous and should be restricted to practitioners experienced in its usage.     

A multimer model for P680, the primary electron donor of photosystem II

We consider a model of the photosystem II (PS II) reaction center in which its spectral properties result from weak (approximately 100 cm-1) excitonic interactions between the majority of reaction center chlorins. Such a model is consistent with a structure similar to that of the reaction center of purple bacteria but with a reduced coupling of the chlorophyll special pair. We find that this model is consistent with many experimental studies of PS II. The similarity in magnitude of the exciton coupling and energetic disorder in PS II results in the exciton states being structurally highly heterogeneous. This model suggests that P680, the primary electron donor of PS II, should not be considered a dimer but a multimer of several weakly coupled pigments, including the pheophytin electron acceptor. We thus conclude that even if the reaction center of PS II is structurally similar to that of purple bacteria, its spectroscopy and primary photochemistry may be very different.     

The ETO domain is necessary for the developmental abnormalities associated with AML1-ETO expression in the hematopoietic stem cell compartment in vivo

Translocation of the ETO gene on human chromosome 8 with the AML1 gene on chromosome 21 (AML1-ETO) is a recurrent cytogenetic abnormality associated with approximately 12% of acute myelogenous leukemia (AML) cases. To understand the contribution of the t(8;21) to AML, we transduced purified hematopoietic stem cells (HSC) with a retroviral vector that coexpressed AML1-ETO or just the AML1 portion (AML1d) of the translocation along with a green fluorescent protein reporter gene. Animals reconstituted with AML1-ETO-expressing cells exhibited many of the hematopoietic developmental abnormalities seen in the bone marrow of human patients with the t(8;21), although the animals did not develop acute leukemia. We noted a gradual increase in primitive myeloblasts that accounted for approximately 10% of bone marrow by 10 months posttransplant. Consistent with this observation was a 50-fold increase in myeloid colony-forming cells in vitro. In addition, accumulation of late stage metamyelocytes was observed in bone marrow along with an increase in immature eosinophil myelocytes that showed abnormal basophilic granulation. There was also a gradual increase in both the frequency and absolute number of AML1-ETO-expressing HSC so that by 10 months posttransplant, there were 29-fold greater HSC numbers than in transplant-matched control mice. These phenotypes were not observed in animals reconstituted with cells expressing only the DNA-binding domain of AML1, suggesting that the ETO domain is necessary to establish the developmental abnormalities associated with AML1-ETO expression in HSC.