Beals syndrome (congenital contractural arachnodactyly): prenatal ultrasound findings and molecular analysis.

We report the prenatal findings in two cases of Beals syndrome. Both pregnancies presented with clinical features of arthrogryposis multiplex congenita/fetal akinesia syndrome (AMC/FAS), including clenched fists and multiple joint contractures on repeat prenatal ultrasound examinations. The first case was diagnosed as having Beals syndrome on physical examination shortly after birth and the diagnosis was confirmed by DNA analysis, shown as a point mutation in the fibrillin 2 (FBN2) gene. The second case was diagnosed with Beals syndrome following microarray analysis on amniocytes, which showed a deletion of the FBN2 gene. Although most cases with AMC/FAS carry a poor prognosis, Beals syndrome is consistent with normal cognitive development and a better prognosis. Thus, making the correct diagnosis is crucial, both pre- and postnatally, for accurate counseling and management.

The price of performance: a cost and performance analysis of the implementation of cell-free fetal DNA testing for Down syndrome in Ontario, Canada.

OBJECTIVE: To examine the cost and performance implications of introducing cell-free fetal DNA (cffDNA) testing within modeled scenarios in a publicly funded Canadian provincial Down syndrome (DS) prenatal screening program. METHOD: Two clinical algorithms were created: the first to represent the current screening program and the second to represent one that incorporates cffDNA testing. From these algorithms, eight distinct scenarios were modeled to examine: (1) the current program (no cffDNA), (2) the current program with first trimester screening (FTS) as the nuchal translucency-based primary screen (no cffDNA), (3) a program substituting current screening with primary cffDNA, (4) contingent cffDNA with current FTS performance, (5) contingent cffDNA at a fixed price to result in overall cost neutrality,(6) contingent cffDNA with an improved detection rate (DR) of FTS, (7) contingent cffDNA with higher uptake of FTS, and (8) contingent cffDNA with optimized FTS (higher uptake and improved DR). RESULTS: This modeling study demonstrates that introducing contingent cffDNA testing improves performance by increasing the number of cases of DS detected prenatally, and reducing the number of amniocenteses performed and concomitant iatrogenic pregnancy loss of pregnancies not affected by DS. Costs are modestly increased, although the cost per case of DS detected is decreased with contingent cffDNA testing. CONCLUSION: Contingent models of cffDNA testing can improve overall screening performance while maintaining the provision of an 11- to 13-week scan. Costs are modestly increased, but cost per prenatally detected case of DS is decreased.

The RNA helicase RHAU (DHX36) unwinds a G4-quadruplex in human telomerase RNA and promotes the formation of the P1 helix template boundary.

Human telomerase RNA (hTR) contains several guanine tracts at its 5'-end that can form a G4-quadruplex structure. Previous evidence suggests that a G4-quadruplex within this region disrupts the formation of an important structure within hTR known as the P1 helix, a critical element in defining the template boundary for reverse transcription. RNA associated with AU-rich element (RHAU) is an RNA helicase that has specificity for DNA and RNA G4-quadruplexes. Two recent studies identify a specific interaction between hTR and RHAU. Herein, we confirm this interaction and identify the minimally interacting RNA fragments. We demonstrate the existence of multiple quadruplex structures within the 5' region of hTR and find that these regions parallel the minimal sequences capable of RHAU interaction. We confirm the importance of the RHAU-specific motif in the interaction with hTR and demonstrate that the helicase activity of RHAU is sufficient to unwind the quadruplex and promote an interaction with 25 internal nucleotides to form a stable P1 helix. Furthermore, we have found that a 5'-terminal quadruplex persists following P1 helix formation that retains affinity for RHAU. Finally, we have investigated the functional implications of this interaction and demonstrated a reduction in average telomere length following RHAU knockdown by small interfering RNA (siRNA).

Retrospective review of diagnostic performance of intracranial translucency in detection of open spina bifida at the 11-13-week scan.

OBJECTIVES: To evaluate diagnostic performance of intracranial translucency (IT) for detection of open spina bifida and interobserver agreement for visualization of IT during the 11-13-week scan. METHODS: A retrospective study was undertaken in a tertiary referral center. Two hundred 11-13-week scans for nuchal translucency, performed by sonographers certified by The Fetal Medicine Foundation, U.K., were reviewed independently for IT by two expert observers. When IT was not seen, the observers determined whether this was due to poor IT image quality or the presence of spina bifida. Discordant cases were reviewed by a third observer and the majority decision was used for analysis. All observers were blinded to individual pregnancy outcome and the number of cases with spina bifida. RESULTS: There were 191 normal fetuses, eight fetuses with open spina bifida and one with closed spina bifida (this case was excluded from analysis). IT was seen in 150 fetuses and all were normal. In six of the 49 cases in which IT was not seen, IT non-visibility was attributed to open spina bifida; among these cases, four fetuses had open spina bifida and two were normal. In the remaining 43 cases (including 39 normal fetuses), IT non-visibility was attributed to inadequate image quality. Sensitivity was 50% (4/8) and specificity was 99% (150/152). Concordance between the two observers concerning IT visibility was 79%, (κ = 0.47, representing moderate agreement). CONCLUSION: There was moderate interobserver agreement for visualization of IT on images obtained for nuchal translucency measurement at 11-13 weeks. When IT was confidently seen, open spina bifida could be excluded. However, non-visibility of IT correctly diagnosed only 50% of fetuses with open spina bifida.

Placental size and the prediction of severe early-onset intrauterine growth restriction in women with low pregnancy-associated plasma protein-A.

OBJECTIVES: Screening studies for trisomy 21 demonstrate that low maternal serum pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation is associated with stillbirth, intrauterine growth restriction (IUGR) and pre-eclampsia in chromosomally normal fetuses. However, the strength of these associations is too weak to justify screening for these placental insufficiency syndromes. Our objective was to evaluate placental size and uterine artery (UtA) Doppler imaging as second-stage screening tests for women with low PAPP-A. METHODS: We prospectively studied 90 normal singleton pregnancies with first-trimester PAPP-A

Screening for placental insufficiency in high-risk pregnancies: is earlier better?

OBJECTIVE: To compare a profile of placental function between the first and second trimesters in pregnancies at high risk of adverse perinatal outcomes attributable to placental insufficiency. STUDY DESIGN: Prospective cohort study in 61 singleton pregnancies. Uterine artery Doppler and placental morphology (shape and texture) were determined at 11-13(+6) weeks and at 18-23(+6) weeks. First trimester (pregnancy-associated placental protein-A [PAPP-A]) and second trimester (total hCG and alpha fetoprotein [AFP]) serum biochemistry were determined. The two screening periods were compared for the prediction of a range of severe adverse perinatal outcomes (intrauterine growth restriction [IUGR], abruption, severe pre-eclampsia/HELLP syndrome, delivery<32 weeks, or stillbirth). RESULTS: Adverse perinatal outcomes occurred in 14 (23%) women; 3 (4.9%) losses<20 weeks, 2 (3.3%) stillbirths>20 weeks, 4 (6.6%) IUGR, 7 (11.5%) severe pre-eclampsia/HELLP syndrome, and 10 (16.4%) deliveries<32 weeks. Abnormal second trimester placental morphology was significantly associated with adverse outcome [+LR: 3.6, 95% CI: 1.3-8.5; -LR: 0.63, 95% CI: 0.36-0.93; p=0.025], as was > or = 1 abnormal second trimester tests [+LR: 5.9, 95% CI: 1.6-24; -LR: 0.68, 95% CI: 0.59-0.89; p=0.005] or > or = 2 abnormal second trimester tests [+LR: 3.6, 95% CI: 1.3-7.7; -LR: 0.58, 95% CI: 0.27-0.94; p=0.035]. No combination of first trimester tests significantly predicted severe adverse perinatal outcomes. A study sample size of 822 women with similar high-risk characteristics would be needed in order to refute the conclusion that present methods of first trimester screening are not inferior to second trimester screening for severe placental insufficiency (p=0.05, power 80%, z-test). CONCLUSIONS: In clinically high-risk pregnancies, prediction of adverse perinatal outcomes using placental function testing is more effective in the second compared with the first trimester.

Is maternal obesity a predictor of shoulder dystocia?

OBJECTIVE: To explore the relationship between maternal obesity and shoulder dystocia while controlling for the potential confounding effects of other variables associated with obesity. METHODS: We performed a case-control study of provincial delivery records audited by the Northern and Central Alberta Perinatal Outreach Program. Risk factors evaluated were selected based on previously published studies. Cases and controls were drawn from 45,877 live singleton cephalic vaginal deliveries weighing more than 2500 g between January 1995 and December 1997. There were 413 cases of shoulder dystocia (0.9% incidence). Controls (n = 845) were randomly chosen from the remainder of the target population to create a 1:2 case/control ratio. Univariate analysis with calculation of odds ratios (ORs) was used to determine which of the chosen risk factors were significantly related to the incidence of shoulder dystocia. Multivariable regression analyses were then used to determine the independently associated variables, and the adjusted ORs were obtained for each relevant risk factor. RESULTS: Maternal obesity was not significant as an independent risk factor for shoulder dystocia after adjusting for confounding variables (adjusted OR 0.9; 95% confidence interval [CI] 0.5, 1.6). Fetal macrosomia was the single most powerful predictor. The adjusted ORs were 39.5 (95% CI 19.1, 81.4) for birth weight greater than 4500 g and 9.0 (95% CI 6.5, 12.6) for birth weight between 4000 and 4499 g. CONCLUSION: The strongest predictors of shoulder dystocia are related to fetal macrosomia. For obese nondiabetic women carrying fetuses whose weights are estimated to be within normal limits, there is no increased risk of shoulder dystocia.

Asymmetric sandwich-type polyoxoanions. Synthesis, characterization, and x-ray crystal structures of diferric complexes [TM(II)Fe(III)(2)(P(2)W(15)O(56))(P(2)TM(II)(2)W(13)O(52))](16-), TM = Cu or Co.

Reaction of the diferric sandwich-type polyoxometalate (NaOH(2))(2)Fe(III)(2)(P(2)W(15)O(56))(2)(16-)(1) with excess aqueous Cu(II) or Co(II) yields a new type of d-electron-metal substituted polyoxometalate, [TM(II)Fe(III)(2)(P(2)W(15)O(56)) (P(2)TM(II)(2)W(13)O(52))](16-), TM = Cu (2), Co (3), respectively. The structure of the sodium salt of 2 (Na2), determined by single-crystal X-ray diffraction analysis (a = 13.4413(9) A, b = 21.2590(15) A, c = 25.5207(18) A, alpha = 80.475(2) degrees, beta = 85.555(2) degrees, gamma = 89.563(2) degrees, triclinic, P(-)1, R1 = 5.42%, based on 43097 independent reflections), consists of a defect Fe(2)Cu central unit sandwiched between two different trivacant Wells-Dawson-type units, P(2)W(15) and P(2)Cu(2)W(13), where the latter unit has two octahedral Cu(II) ions substituted for two adjacent belt W(VI) atoms. The CuO(5)OH(2) octahedron in the central unit shows pronounced Jahn-Teller distortion. A low-resolution X-ray structure of Na3 is included in the Supporting Information. UV-visible, infrared, (31)P NMR, cyclic voltammetric, and elemental analysis data are all consistent with the structure determined from the X-ray analysis. Cyclic voltammograms of 2 and 3 exhibit multiple electron-transfer processes under ambient conditions, and copper or cobalt incorporation into the framework of 1 results in a substantial pertubation of the electrochemical properties of the polyoxotungstate framework. The tetra-n-butylammonium salts of 2 and 3 (readily prepared by metathesis) are stable and effective catalysts for the oxidation of some alkenes with high yields based on H(2)O(2).

Crohn's disease, pregnancy, and birth weight.

OBJECTIVE: Although there is general agreement that conception should be avoided when Crohn's disease is active, many questions remain unanswered for the woman with Crohn's disease in remission who becomes pregnant. METHODS: Sixty-five charts of women with Crohn's disease quiescent at the start of pregnancy were identified between January 1993 and December 1997. Each pregnancy was matched to a healthy control pregnancy by date, age, parity, smoking status, and gestational age +/- 1 wk, and comparisons were carried out using matched analyses. RESULTS: The two groups were similar in terms of maternal height, weight, and body mass index (BMI), in addition to the matched variables. The incidence of pregnancy complications was similar for most of the complications examined, whereas the incidence of poor maternal weight gain differed significantly between the groups (17/65 vs 2/65, p < 0.001). Flare-up of the Crohn's disease was seen in 13/65 (20%) of pregnancies. The greatest differences in neonatal outcomes were in terms of birth weight (3150+/-80 g vs 3500+/-60 g) and birth weight percentile (36.7%+/-.6% vs 57.5%+/-3.4%). Overall, there were 16 (24.6%) small for gestational age (SGA) births in the Crohn's group, compared with only one (1.5%) in the control group (p = 0.0007). Multivariate analysis was performed to identify factors predictive of SGA births in the Crohn's group. Ileal Crohn's disease was a statistically significant predictor (p = 0.035), whereas previous bowel resection trended toward statistical significance (p = 0.065). CONCLUSIONS: In view of the risk of low birth weight, all women with Crohn's disease who become pregnant should be followed carefully during the pregnancy, particularly those who have ileal disease or who have previously undergone bowel resection. Furthermore, smoking cessation needs to be aggressively pursued in these patients.

Early motor development of breech- and cephalic-presenting infants.

OBJECTIVE: This study was conducted to determine whether breech-presenting infants have a different pattern of early neuromotor development than cephalic-presenting infants--regardless of mode of delivery-thus explaining both the failure to assume cephalic version at the end of gestation and the higher rates of childhood motor impairments associated with breech presentation. METHODS: Ninety morphologically normal, term, breech-presenting singletons with birthweights greater than 2,500 g were paired with a similar cephalic-presenting infant, matched for gender and mode of delivery (n = 180; 100 delivered abdominally and 80 delivered vaginally). Data on neurological status (Neurological Assessment of the Preterm and Full-term Newborn Infant) and motor performance (Alberta Infant Motor Scale, Peabody Developmental Motor Scales, and age of walking) were collected prospectively over the first 18 months of life. This study was designed with a power of .80 to detect a "medium" effect size for motor development using the Alberta Infant Motor Scale. The data were analyzed using analysis of variance techniques. RESULTS: Breech-presenting infants had minor transient differences compared with cephalic-presenting infants. First, they had more open popliteal angles at birth (P < .001). Second, they had significantly lower motor scores at 6 weeks than the normative sample (P < .001). At 18 months, three infants were diagnosed with neurological problems, all of whom were delivered electively in the cesarean-breech group. CONCLUSION: As a group, breech-presenting infants do not have a persistent, inherently different pattern of motor development than cephalic-presenting infants. Mode of delivery did not explain the excess neuromotor impairment detected in the subgroup of breech infants.

Polytopic anomalies with agenesis of the lower vertebral column.

We describe clinical, pathological and radiological findings in 15 cases of sporadic and familial lower spine agenesis with additional anomalies of the axial skeleton and internal organs and speculate about the cause and pathogenesis of this malformation complex. We show that all of these findings are defects of blastogenesis, originate in the primary developmental field and/or the progenitor fields, thus representing polytopic field defects. This concept appears applicable in our cases and makes such terms such as "caudal regression syndrome" or "axial mesodermal dysplasia spectrum" redundant.

Morbidity assessment index for newborns: a composite tool for measuring newborn health.

OBJECTIVE: The objective was to develop, validate, and recommend a scaling model for a discriminative obstetric outcome measure named the Morbidity Assessment Index for Newborns. The purpose of this tool is to allow comparison of obstetric therapeutic strategies on neonatal morbidity, particularly in the mild to moderate morbidity range. STUDY DESIGN: A list of 66 check-mark (yes or no) items of readily available clinical and laboratory data from the early neonatal period was compiled by a panel of obstetric and neonatal experts. These data were collected on 411 neonates born at >/=28 weeks' gestation and representing all grades of morbidity. Detailed psychometric testing included dimensionality testing and item analysis with the item response theory. The scores obtained with this new assessment tool were correlated with newborn and maternal disease conditions or events and with other measures of newborn morbidity. RESULTS: The Morbidity Assessment Index for Newborns is easy to apply in prospective or retrospective studies. Detailed psychometric evaluation resulted in modification of the list to 47 items, each item with a relative scale value according to severity of morbidity. The test was demonstrated to be a reliable and generalizable scaled index that performs optimally for the mild to moderate neonatal morbidity range. CONCLUSION: The Morbidity Assessment Index for Newborns is a validated outcome measurement scale of neonatal morbidity. This new tool may facilitate the conduct of obstetric clinical trials or epidemiologic population-based studies in obstetrics.

Technical factors in early amniocentesis predict adverse outcome. Results of the Canadian Early (EA) versus Mid-trimester (MA) Amniocentesis Trial.

The purpose of this study was to identify risk factors for fetal loss and other pregnancy complications associated with genetic amniocentesis. Data were acquired in the Canadian Early Amniocentesis Trial (CEMAT), a multicentered (12) prospective, randomized trial comparing continuous ultrasound-guided early amniocentesis (EA) and mid-trimester amniocentesis (MA) (CEMAT Group, 1998). Details of the procedure were recorded and analysed by allocation (EA versus MA), operator and centre, and correlated with pregnancy outcome. A total of 62 spontaneous pregnancy losses occurred between the procedure and 20 weeks' gestation among the 3691 patients who received their procedures within the allocated window (EA=53/1916, MA=9/1775). Technical factors correlating with these losses included procedures 'judged to be difficult' by the operator, and post-procedure amniotic fluid leakage or bleeding. Maternal risk factors included maternal hypertension (fetal loss 11. 1 per cent, compared with non-hypertensive women, 2.6 per cent) increased body mass index (BMI) and gravidity of three or greater. Allocation to EA was predictive of fetal loss, as well as failed procedure, multiple needle insertions, amniotic fluid leakage, failed culture and talipes equinovarus, in excess compared with MA. In conclusion, in this large prospective randomized trial evaluating amniocentesis, specific maternal, fetal and procedural variables were found to be predictive of fetal loss and adverse pregnancy outcome. Performing amniocentesis before 13 weeks' gestation (EA) was the major predictive factor for adverse outcome. These data suggest that first-trimester chorionic villus sampling (CVS) and MA will likely remain the invasive procedures of choice for evaluation of fetal karyotype.

Pregnancy in chronic dialysis: a review and analysis of the literature.

UNLABELLED: Pregnancy is uncommon in end-stage renal failure, particularly in patients requiring dialysis. We reviewed the literature from 1965 to date, seeking an optimal way of dialyzing pregnant women after encountering one such patient METHODS: We searched the English literature by cross-referencing "pregnancy" with "hemo-" or "peritoneal dialysis" and "renal failure". Eighty-six pregnancies worldwide were found to which we added one case of our own. Various independent factors were studied against gestational age at delivery using uni- and multivariate analysis. These factors included mother's age, previous delivery, diagnoses of renal disease, dialysis duration prior to pregnancy, gestational age at onset of dialysis, dialysis type, level of hemoglobin during pregnancy, BUN and creatinine targets, BUN/creatinine ratio, dialysis intensity at the beginning and end of pregnancy, influence of erythropoietin and dialysis complications. RESULTS: Of the 87 pregnancies, 12% resulted in stillbirths, 9% of neonates died prior to discharge. The mean gestational age at delivery was 32 +/- 5 weeks, and the mean birth weight 1604 +/- 652 g. Two congenital abnormalities and one twin pregnancy were reported. 48% of deliveries were premature. Pre-eclampsia was reported in 11%, and worsening hypertension in 17%. CAPD was used in 25 and hemodialysis in 62 patients. Fetal survival was similar in both cases (72% vs 82%), although incidence of various dialysis complications differed. The conventional dialysis goals of a low target BUN level and hemoglobin for pregnant patients were not factors in predicting fetal outcome. The number of hemodialyses/week were negatively correlated (R = -0.35, P = 0.061), but the hours of dialysis positively correlated (R = 0.42, p = 0.035) to gestational age. Fetal survival was independently influenced by creatinine level [564 micromol/L when baby survived vs 788 micromol/L when baby died (p = 0.021)], BUN/creatinine ratio (50 vs 30, p = 0.053), and hours of dialysis (5.6 hrs vs 3.6 hrs, p = 0.013). There was no relation of either frequency or volume of peritoneal dialysis exchanges to gestational age or fetal survival. CONCLUSIONS: Greater attention to a high intake of protein (>1.5 g/kg) and higher dose of hemodialysis, achieved by longer, every other day dialysis, may be the optimal approach to pregnant patients on hemodialysis. Our first attempt to define the goal of hemodialysis is to keep the predialysis creatinine below 600 mmol/L and the protein intake high enough so the predialysis BUN level is >25 mmol/L. There are no clear guidelines on how to best perform CAPD.

Relative importance of maternal constitutional factors and glucose intolerance of pregnancy in the development of newborn macrosomia.

The purpose of this case-control study was to determine the relative importance of various predictors of newborn macrosomia, with particular reference to maternal constitutional factors and glucose intolerance of pregnancy. Macrosomia was defined by both absolute birthweight > or = 4,000 g and birthweight > or = 90th centile for gestational age. One thousand mother/newborn pairs [209 macrosomic (cases) and 791 non-macrosomic newborns (controls)] were recruited. Mothers with pre-gestational diabetes mellitus were excluded. Data on pregnancy and pregnancy variables were collected by review of prenatal, labour, and delivery and newborn assessment records and interview with the mother. Predictors that entered the stepwise multiple regression model in order of significance were: previous history of macrosomia, increasing maternal weight, nonsmoking status, multiparity, male newborn gender, gestational age of 40-42 weeks, North American Aboriginal ethnicity, maternal birthweight > 4,000 g, maternal height and maternal age < 17 years. Glucose screen positive/100-g oral glucose tolerance test (GTT) negative status was a significant predictor for macrosomia as defined by birthweight greater than the 90th percentile for gestational age, but not for absolute birthweight over 4,000 g. It was the least significant of all the factors examined. Treated gestational diabetes was not a significant predictor. By multivariate analysis, maternal constitutional factors are more powerful predictors of newborn macrosomia than maternal mild glucose intolerance. Treatment of mothers with GDM may be masking the effect of more pronounced carbohydrate intolerance.

A randomized controlled trial of strict glycemic control and tertiary level obstetric care versus routine obstetric care in the management of gestational diabetes: a pilot study.

OBJECTIVES: The purpose of this study was to determine whether strict maternal glycemic control for the treatment of gestational diabetes lessened the risk of fetal macrosomia, birth trauma, neonatal hypoglycemia, and operative delivery. The aim of the pilot study was to prepare for a multicenter trial by assessing patient acceptance of the study, by determining realistic accrual rates, and by detecting any major adverse outcomes in the control group that received routine obstetric care. STUDY DESIGN: The study was a prospective randomized controlled trial comparing fetal-neonatal and maternal outcomes in 300 women with gestational diabetes. Women randomized to the treatment arm were managed by strict glycemic control and tertiary level obstetric care, and women in the control arm received routine obstetric care. RESULTS: Three hundred women with gestational diabetes mellitus were studied. There was no difference in maternal age, weight, or length of gestation between groups. The treatment mean birth weight was 3437 +/- 575 gm compared with 3544 +/- 601 gm in the control group, a difference of 107 gm (not significant). Macrosomia rates were similar. There was no birth trauma in either group. The frequency of neonatal hypoglycemia and other metabolic complications was the same. The mode of delivery also showed similar patterns. The treatment group had significantly lower preprandial and postprandial glucose levels by 32 weeks' gestation, which continued to term. CONCLUSION: This pilot study suggests that intensive treatment of gestational diabetes mellitus may have little effect on birth weight, birth trauma, operative delivery, or neonatal metabolic disorders. It has demonstrated the safety of proceeding to a multicenter trial of sufficient sample size to confirm these findings.

Relationship between plasma glucose levels in glucose-intolerant women and newborn macrosomia.

The purpose of this study was to examine the relationship between newborn macrosomia and plasma glucose profile in both a "glucose challenge test (GCT)-positive oral glucose tolerance test (OGTT)-negative" group (n = 113) and a gestational diabetes mellitus (GDM) group (n = 50). We examined 1) plasma glucose concentrations following a positive screen 50-g GCT (n = 163), 2) glucose concentrations following a 100-g OGTT (n = 163), and 3) the average fasting (AF) and 2-hour postprandial (APP) plasma glucose concentrations in the treated GDM group (n = 46). It was a case-control study with macrosomia vs. non-macrosomia in the ratio of 1:4. Macrosomia was analyzed by both birthweight > 4,000 g and gender-specific birthweight > 90th percentile for gestational age criteria. The GCT and the OGTT were performed between 26 and 30 weeks of pregnancy. The results demonstrated no significant impact of plasma glucose values from GCT, OGTT, AF, or APP on macrosomia in both "GCT-positive OGTT-negative" and GDM (treated) groups. Further, the screening and diagnostic plasma glucose concentrations were not related to macrosomia in both "GCT-positive OGTT-negative" and GDM groups. We found a difference of 0.6 mmol/liter in the maternal AF and APP glucose concentrations between mothers of macrosomic versus non-macrosomic newborns in the treated (diet or diet+insulin) GDM group. The clinical relevance of this difference remains to be explored. Our study provides a different methodological and analytic perspective in examining macrosomia versus non-macrosomia in the "GCT-positive OGTT-negative" and the GDM groups using univariate and multivariate analyses.

Primitive reflexes and the determination of fetal presentation at birth.

Ninety term breech-presenting singletons with birth weights greater than 2500 g and no congenital anomalies were matched with similar cephalic-presenting infants on gender and mode of delivery (n = 180). Thirteen primitive reflexes were examined at birth, 6 weeks and 3 and 5 months. No significant differences in the intensity of the asymmetrical tonic neck, symmetrical tonic neck, positive support tonic labyrinthine (prone and supine), segmental rolling (head-on-body and body-on-body), Galant, Moro, upper and lower extremity grasp, lower extremity placing and stepping reflexes were observed between these two groups of infants. Infants delivered vaginally, regardless of presentation, had weaker Moro reflexes at 5 months than infants delivered by cesarean section. The popular notion that precursors to early motor behaviors, such as the placing and stepping reflexes, are determinants of fetal presentation at the end of pregnancy is not supported by these results. Instead, spontaneously generated active whole body movements may be more significant influences of fetal orientation at the time of birth.

Gestational diabetes mellitus. Unresolved issues and future research directions.

OBJECTIVE: To summarize the controversial aspects of gestational diabetes (GDM) and introduce readers to possible relevant research questions that could be examined to provide clinicians with good-quality data on which to base decisions about this relatively common pregnancy-related issue. DATA SOURCES AND STUDY SELECTION: Ongoing review of the English literature related to GDM. Sources were not restricted to prospective, controlled trials, as these are severely limited in number. SYNTHESIS: Controversial issues include the relevance of GDM to clinically meaningful outcomes in the index pregnancy, the effectiveness of current therapy in altering these outcomes, and the resultant questionable relevance of routine screening and diagnosis of an entity with as yet uncertain significance in pregnancy. CONCLUSIONS: Suggested questions to be addressed in multicentre controlled trials include randomization with respect to screening and with respect to treatment. Until such trials are completed, continuing with a standard approach to screening, diagnosis, and treatment, such as that suggested by the third international workshop on GDM, is recommended.