Similarities and Differences between Crystal and Enzyme Environmental Effects on the Electron Density of Drug Molecules.

The crystal interaction density is generally assumed to be a suitable measure of the polarization of a low-molecular weight ligand inside an enzyme, but this approximation has seldomly been tested and has never been quantified before. In this study, we compare the crystal interaction density and the interaction electrostatic potential for a model compound of loxistatin acid (E64c) with those inside cathepsin B, in solution, and in vacuum. We apply QM/MM calculations and experimental quantum crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density. Less than 0.1 e are shifted between these two environments in total. However, this difference has non-negligible consequences for derived properties.

A Prospective Evaluation of Point-of-Care Measurements of Maternal Glucose for the Diagnosis of Gestational Diabetes Mellitus.

BACKGROUND: Point-of-care (POC) measurement of glucose is currently recommended only for the monitoring of gestational diabetes mellitus (GDM). This prospective observational study evaluated the use of POC measurements of maternal glucose to diagnose GDM in women being screened selectively with a 1-step 75 g oral glucose tolerance test (OGTT). METHODS: The strictest preanalytic and analytic international laboratory standards were applied to measure maternal plasma glucose at fasting and at 1 and 2 h post glucose load. The recent International Association of Diabetes and Pregnancy Study Groups diagnostic criteria were used. At the same time, maternal capillary glucose was measured. Because of differences in plasma and capillary glucose measurements, regression analysis of POC capillary glucose results vs laboratory plasma glucose results was conducted. The regression equations for plasma glucose were derived in a derivation cohort (n = 102). These equations were applied in the validation cohort (n = 100). Predicted and actual plasma glucose values were compared. RESULTS: Of the 202 women screened, 36.6% were nulliparous, 56.4% were obese, and 81.2% were Irish-born. Two thirds had a single risk factor for GDM, and a third had multiple risk factors. Based on the plasma measurements, 53.5% had GDM. As a predictor of GDM, the diagnostic accuracy of POC measurement was 83.0% (95% confidence interval, 74.2-89.8). CONCLUSIONS: In high-resource settings where measures to inhibit glycolysis are implemented, the use of POC measurements for the diagnosis of GDM is not justified based on this study. In low- and medium-resource settings, where measures to inhibit glycolysis are not achievable, regression analysis using POC measurements may be acceptable compared with plasma samples subject to glycolysis.

Assessing maternal dietary quality in early pregnancy in the programming of intrauterine fetal growth.

INTRODUCTION: It is established globally that a healthy maternal diet during pregnancy is important in programming fetal growth and development. The assessment of maternal dietary intake, however, is challenging both in clinical practice and in research studies. The aim of this study was to compare three individual dietary quality scores in early pregnancy based on European, American and World Health Organization (WHO) nutrient recommendations for the identification of suboptimal fetal growth. MATERIAL AND METHODS: Women were recruited conveniently at their first antenatal hospital visit and completed a supervised 4-day diet history. The results were dichotomized into those women meeting and those not meeting macronutrient and micronutrient recommendations from the European Food Safety Authority (EFSA), WHO and the Institute of Medicine (USA). Composite nutrient scores were derived. The relation between the three individual dietary scores in early pregnancy and subsequent birthweight and small-for-gestational-age was compared using regression analyses. RESULTS: Of the 202 women, the mean age was 32.2 (SD 5.0) years and 44.6% were nulliparas. The mean dietary quality scores were: EFSA 9.4 (SD 3.1), WHO 8.5 (SD 3.7) and USA 9.6 (SD 3.6). On multivariable regression, there was a positive relationship between the EFSA (ß = 44.7, 95% CI 17.0-72.4, P = 0.002), WHO (ß = 39.2, 95% CI 17.2-61.1, P = 0.001), and USA (ß = 40.0 95% CI 17.6-62.3, P = 0.001) score and birthweight. All 3 scores were positively associated with birthweight centiles. However, only those in the lowest quartile of the EFSA score were more likely to be small-for-gestational-age (odds ratio 2.8, 95% CI 1.1-7.4, P = 0.03). CONCLUSIONS: This study found that a dietary quality score based on European nutrient recommendations was better than other international recommendations at identifying in early pregnancy those women at risk of suboptimal fetal growth.

Caesarean section rates in women in the Republic of Ireland who chose to attend their obstetrician privately: a retrospective observational study.

BACKGROUND: Caesarean section (CS) rates are increasing and there are wide variations in rates internationally and nationally. There is evidence that women who attend their obstetrician privately have a higher incidence of CS than those who attend publicly. The purpose of this observational study was to further investigate why CS rates may be higher in women who chose to attend their obstetrician privately. METHODS: This study analysed data collected as part of the clinical records by midwives at the woman's first antenatal appointment in a large European maternity hospital. All women who delivered between the years 2009 and 2017 were included. Data were analysed both cross-sectionally and longitudinally. RESULTS: Overall, 73,266 women had a singleton pregnancy and 1830 had a multiple pregnancy. Of the packages of maternity care, 75.2% chose public, 10.8% chose semiprivate and 14.0% chose private. During the study, 11,991 women attended the hospital for their first and second pregnancies. Overall, women who attended privately were older and had higher proportions of infertility treatment and history of miscarriage (all p < 0.001) compared to those publicly-funded. Private patients were more likely to have a history of infertility, a history of miscarriage, a multiple pregnancy and to be ≥35 yrs. They had lower rates of obesity, smoking and illicit drug use in pregnancy (all p < 0.001). In women who chose private care, the overall rate of CS was higher compared to women choosing publicly-funded (42.7% vs 25.3%, p < 0.001) The increase was due to an increase in elective rather than emergency CS. The increase in elective CS fell after adjustment for clinical risks. In the longitudinal analysis, 89.7% chose the same package second time around. Women who changed from public to private care for the second pregnancy were more likely to have had a previous emergency CS or admission to the Neonatal Unit. CONCLUSIONS: This study suggests that the increased CS rate in women privately insured may be attributed, in part, to the fact that women who can afford health insurance choose continuity of care from a senior obstetrician because they are risk adverse and wish to have the option of an elective CS.

The interaction between maternal smoking, illicit drug use and alcohol consumption associated with neonatal outcomes.

BACKGROUND: The adverse effects of smoking on neonatal outcomes, such as small-for-gestational-age (SGA), has been extensively studied however, the consequences of smoking combined with alcohol and/or drug use is less clear. METHODS: This retrospective observational study analyzed clinical and sociodemographic details of 40156 women who delivered a singleton baby between the years 2011 and 2015. RESULTS: Compared with women who had never smoked, smokers who did not engage in alcohol or drug use had an odds ratio (OR) of delivering a baby who was SGA of 3.2 (95% CI: 3.1-3.5). Smokers who used illicit drugs in isolation or in combination with alcohol during pregnancy had higher ORs for SGA (1.4, 95% CI: 1.1-1.7, P = 0.006 and 1.8, 95% CI: 1.2-2.7, P = 0.007) compared to women who smoked but did not engage in alcohol or drug use in pregnancy. These women also delivered babies with lower mean birthweights (125 g, P < 0.001 and 181.4 g, P = 0.003) and head circumferences (0.4 cm, P < 0.001 and 0.3 cm, P = 0.048). Women who smoked and used alcohol, but not illicit drugs were not associated adverse outcomes above that of smoking in isolation. CONCLUSION: Illicit drug use combined with maternal smoking during pregnancy increases the risk of adverse neonatal outcomes above that of smoking in isolation.

The impact of revised diagnostic criteria on hospital trends in gestational diabetes mellitus rates in a high income country.

OBJECTIVE: In 2010, national guidelines were published in Ireland recommending more sensitive criteria for the diagnosis of Gestational Diabetes Mellitus (GDM). The criteria were based on the 2008 Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study and were endorsed subsequently by the World Health Organization (WHO). Screening nationally is selective based on risk factors. We examined the impact of the new criteria on hospital trends nationally for GDM over the 10 years 2008-17. RESEARCH DESIGN AND METHODS: Data from three national databases, the Hospital Inpatient Enquiry System (HIPE), National Perinatal Reporting System (NPRS) and the Irish Maternity Indicator System (IMIS), were analyzed using descriptive statistics, analysis of variance, and Poisson loglinear modelling. RESULTS: The overall incidence of GDM nationally increased almost five-fold from 3.1% in 2008 to 14.8% in 2017 (p ≤ 0.001). The incidence varied widely across maternity units. In 2008, the incidence varied from 0.4 to 5.9% and in 2017 it varied from 1.9 to 29.4%. There were increased obstetric interventions among women with GDM over the decade, specifically women with GDM having increased cesarean sections (CS) and induction of labor (IOL) (p ≤ 0.001). These trends were significant in large and mid-sized maternity hospitals (p ≤ 0.001). The increase in GDM diagnosis could not be explained by an increase in maternal age nationally over the decade. The data did not include information on other risk factors such as obesity. The increased incidence in GDM diagnosis was accompanied by a decrease in high birthweight ≥ 4.5 kg nationally. CONCLUSIONS: We found adoption of the new criteria for diagnosis of GDM resulted in a major increase in the incidence of GDM rates. Inter-hospital variations increased over the decade, which may be explained by variations in the implementation of the new national guidelines in different maternity units. It is likely to escalate further as compliance with national guidelines improves at all maternity hospitals, with implications for provision and configuration of maternity services. We observed trends that may indicate improvements for women and their offspring, but more research is required to understand patterns of guideline implementation across hospitals and to demonstrate how increased GDM diagnosis will improve clinical outcomes.

A cross-sectional study of maternal-fetal attachment and perceived stress at the first antenatal visit.

BACKGROUND: Maternal-fetal attachment (MFA) psychologically is well described. Suboptimal attachment may have negative consequences particularly if it is associated with unhealthy maternal behaviour that may potentially increase the risk of adverse pregnancy outcomes. The perception of stress or anxiety is also associated with potential adverse outcomes including preterm birth. OBJECTIVE: This cross-sectional study examined MFA and perceived stress at the time of the first ultrasound examination in early pregnancy. METHODS: Convenience sampling was used to recruit women after they presented to the Ultrasound Department for a routine dating ultrasound at their first antenatal visit. Informed consent was obtained and clinical and sociodemographic details were recorded. Women were invited to complete validated Cranley MFA and Perceived Stress Scale (PSS) questionnaires. RESULTS: Of the 90 women recruited, 80 completed the questionnaires successfully. No association was found between the MFA score and maternal age, parity, education, marital status, previous pregnancy loss or smoking behaviour. An unplanned pregnancy was associated with a lower mean MFA score (p < 0.01) and a higher mean PSS score (p < 0.005). These relationships persisted in a multiple regression analysis controlling for maternal age and parity. CONCLUSION: In early pregnancy, an unplanned pregnancy is associated with a lower MFA and higher PSS score. Additional research is required to assess if this persists as pregnancy advances. ABBREVIATIONS: Maternal-Fetal Attachment (MFA), Maternal-Fetal Attachment Scale (MFAS), Perceived stress scale (PSS), Maternal Antenatal Attachment Scale (MAAS), Standard Deviation (SD), Central Statistics Office (CSO), Body Mass Index (BMI), Relative Risk (RR).

Feasibility of recruitment to a behavioural smoking cessation intervention combined with ongoing online support.

The aim of this randomized controlled trial was to determine whether a behavioural intervention in pregnancy supported by online information would improve smoking cessation rates. However, due to a number of challenges, recruitment to this trial was reluctantly halted. We aimed to recruit 220 maternal smokers within 2 years and after screening 1995 women, just 22 enrolled over a 8-month period. Only three women accessed the online element of the intervention and, at follow up, no women reported quitting. We report our findings as they may inform the design and powering of future smoking cessation interventions in pregnancy.

Knee Surgery Is Associated With Greater Odds of Knee Osteoarthritis Diagnosis.

CONTEXT: Knee osteoarthritis (OA) frequently develops following knee injury/surgery. It is accepted that knee injury/surgery precipitates OA with previous studies examining this link in terms of years after injury/surgery. However, postinjury OA prevalence has not been examined by decade of life; thereby, limiting our understanding of the age at which patients are diagnosed with posttraumatic knee OA. OBJECTIVE: Evaluate the association between the knee injury and/or surgical history, present age, and history of receiving a diagnosis of knee OA. DESIGN: Cross-sectional survey. SETTING: Online survey. PARTICIPANTS: A total of 3660 adults were recruited through ResearchMatch©. Of these, 1723 (47.1%) were included for analysis due to history of (1) knee surgery (SURG: n = 276; age = 53.8 [15.3] y; and body mass index [BMI] = 29.9 [8.0] kg/m2), (2) nonsurgical knee injury (INJ: n = 449; age = 46.0 [15.6] y; and BMI = 27.5 [6.9] kg/m2), or (3) no knee injury (CTRL: n = 998; age = 44.0 [25.2] y; and BMI = 26.9 [6.6] kg/m2). Respondents were subdivided by decade of life (20-29 through 70+). INTERVENTION: An electronic survey regarding knee injury history, treatment, and diagnosis of knee OA. MAIN OUTCOME MEASURES: Binary logistic regression determined the association between knee surgical status and OA by decade of life. Participants with no histories of OA or lower-extremity injury were the referent categories. BMI was a covariate in all analyses. RESULTS: SURG respondents were more likely to report having knee OA than CTRL for all age groups (odds ratios: 11.43-53.03; P < .001). INJ respondents aged 30 years and older were more likely to have OA than CTRL (odds ratios: 2.99-14.22; P < .04). BMI influenced associations for respondents in their 50s (P = .001) and 60s (P < .001) only. CONCLUSIONS: INJ increased the odds of reporting a physician diagnosis of knee OA in adults as young as 30 to 39 years. Importantly, SURG yielded 3 to 4 times greater odds of being diagnosed with knee OA compared with INJ in adults as young as 20 to 29 years. Delaying disease onset in these young adults is imperative to optimize the quality of life long term after surgery.

Tonic aortic depressor nerve stimulation does not impede baroreflex dynamic characteristics concomitantly mediated by the stimulated nerve.

Although electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) is being explored as a device therapy for resistant hypertension, possible effects on baroreflex dynamic characteristics of interaction between electrical stimulation and pressure inputs are not fully elucidated. To examine whether the electrical stimulation of the baroreceptor afferent nerve impedes normal short-term arterial pressure (AP) regulation mediated by the stimulated nerve, we electrically stimulated the right aortic depressor nerve (ADN) while estimating the baroreflex dynamic characteristics by imposing pressure inputs to the isolated baroreceptor region of the right ADN in nine anesthetized rats. A Gaussian white noise signal with a mean of 120 mmHg and standard deviation of 20 mmHg was used for the pressure perturbation. A tonic ADN stimulation (2 or 5 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (367.0 ± 70.9 vs. 247.3 ± 47.2 arbitrary units, P < 0.01) and mean AP (98.4 ± 7.8 vs. 89.2 ± 4.5 mmHg, P < 0.01) during dynamic pressure perturbation. The ADN stimulation did not affect the slope of dynamic gain in the neural arc transfer function from pressure perturbation to sympathetic nerve activity (16.9 ± 1.0 vs. 14.7 ± 1.6 dB/decade, not significant). These results indicate that electrical stimulation of the baroreceptor afferent nerve does not significantly impede the dynamic characteristics of the arterial baroreflex concomitantly mediated by the stimulated nerve. Short-term AP regulation by the arterial baroreflex may be preserved during the baroreflex activation therapy.

Mice lacking PKC-θ in skeletal muscle have reduced intramyocellular lipid accumulation and increased insulin responsiveness in skeletal muscle.

Protein kinase C-θ (PKC-θ) is a lipid-sensitive molecule associated with lipid-induced insulin resistance in skeletal muscle. Rodent models have not cohesively supported that PKC-θ impairs insulin responsiveness in skeletal muscle. The purpose of this study was to generate mice that lack PKC-θ in skeletal muscle and determine how lipid accumulation and insulin responsiveness are affected in that tissue. Mice lacking PKC-θ in skeletal muscle (SkMPKCθKO) and controls (SkMPKCθWT) were placed on a regular diet (RD) or high-fat diet (HFD) for 15 wk, followed by determination of food intake, fasting glucose levels, lipid accumulation, and insulin responsiveness. There were no differences between SkMPKCθWT and SkMPKCθKO mice on a RD. SkMPKCθKO mice on a HFD gained less weight from 10 through 15 wk of dietary intervention ( P < 0.05). This was likely due to less caloric consumption ( P = 0.0183) and fewer calories from fat ( P < 0.001) compared with SkMPKCθWT mice on a HFD. Intramyocellular lipid accumulation ( P < 0.0001), fatty acid binding protein 4, and TNF-α mRNA levels ( P < 0.05) were markedly reduced in SkMPKCθKO compared with SkMPKCθWT mice on a HFD. As a result, fasting hyperglycemia was mitigated and insulin responsiveness, as indicated by Akt phosphorylation, was maintained in SkMPKCθKO on a HFD. Liver lipid accumulation was not affected by genotype, suggesting the deletion of PKC-θ from skeletal muscle has a tissue-specific effect. PKC-θ is a regulator of lipid-induced insulin resistance in skeletal muscle. However, the effects of this mutation may be tissue specific. Further work is warranted to comprehensively evaluated whole body metabolic responses in this model.

Covalency and Ionicity Do Not Oppose Each Other-Relationship Between Si-O Bond Character and Basicity of Siloxanes.

Covalency and ionicity are orthogonal rather than antipodal concepts. We demonstrate for the case of siloxane systems [R3 Si-(O-SiR2 )n -O-SiR3 ] that both covalency and ionicity of the Si-O bonds impact on the basicity of the Si-O-Si linkage. The relationship between the siloxane basicity and the Si-O bond character has been under debate since previous studies have presented conflicting explanations. It has been shown with natural bond orbital methods that increased hyperconjugative interactions of LP(O)→σ*(Si-R) type, that is, increased orbital overlap and hence covalency, are responsible for the low siloxane basicity at large Si-O-Si angles. On the other hand, increased ionicity towards larger Si-O-Si angles has been revealed with real-space bonding indicators. To resolve this ostensible contradiction, we perform a complementary bonding analysis, which combines orbital-space, real-space, and bond-index considerations. We analyze the isolated disiloxane molecule H3 SiOSiH3 with varying Si-O-Si angles, and n-membered cyclic siloxane systems Si2 H4 O(CH2 )n-3 . All methods from quite different realms show that both covalent and ionic interactions increase simultaneously towards larger Si-O-Si angles. In addition, we present highly accurate absolute hydrogen-bond interaction energies of the investigated siloxane molecules with water and silanol as donors. It is found that intermolecular hydrogen bonding is significant at small Si-O-Si angles and weakens as the Si-O-Si angle increases until no stable hydrogen-bond complexes are obtained beyond φSiOSi =168°, angles typically displayed by minerals or polymers. The maximum hydrogen-bond interaction energy, which is obtained at an angle of 105°, is 11.05 kJ mol-1 for the siloxane-water complex and 18.40 kJ mol-1 for the siloxane-silanol complex.

Is birth weight the major confounding factor in the study of gestational weight gain?: an observational cohort study.

BACKGROUND: Much interest has been focussed on both maternal obesity and gestational weight gain (GWG), particularly on their role in influencing birth weight (BW). Several large reviews have reported that excessive GWG is associated with an increase in BW. However recent large, well-designed, randomized controlled trials studying interventions aimed at reducing GWG have all consistently failed to show a reduction in BW despite achieving a reduction in GWG. The aim of this longitudinal prospective study was to examine the relationship between GWG and birth weight in women where GWG and Body Mass Index (BMI) were measured accurately in a strictly standardized way. METHODS: Women were enrolled at their convenience before 18 weeks gestation. Height and weight were measured accurately at the first antenatal visit and BMI calculated. Maternal weight was measured again after 37 weeks gestation. The weight of the baby was measured at birth. Relationships were tested using linear regression analysis, chi-squared tests and t-tests as appropriate. RESULTS: Of the 522 women studied, the mean BMI was 25.3 kg/m2 and 15.7% were obese. The mean BW at term was 3576 g (2160-5120) and 2.7% (n = 14) weighed ≥4500 g. The mean GWG overall was 12.3 kg (4.6 to 28.4) and GWG decreased as BMI increased. The mean GWG was less in obese women, at 8.7 kg (- 4.6 to 23.4), compared to non-obese,13.0 kg (0.6-28.4) (p < 0.001). Mean BW in obese women was 3630 g vs 3565 g in non-obese (p = 0.27). The total GWG correlated positively with BW (p < 0.001). When BW was subtracted from total GWG, GWG no longer correlated with BW (p = 0.12). CONCLUSIONS: The positive correlation between GWG in pregnancy and BW can be accounted for by the contribution of fetal weight to GWG antenatally without a contribution from increased maternal adiposity. There was a wide range of BW irrespective of the degree of GWG and obese women had a lower GWG than non-obese women. These findings help explain why Randomized Controlled Trials (RCTs) designed to reduce GWG have failed to decrease BW and suggest there is no causative link between excessive GWG and increased BW.

Optimization of folic acid supplementation in the prevention of neural tube defects.

Background: We examined the relationship between timing and duration of folic acid (FA) supplementation in achieving red blood cell (RBC) folate levels in early pregnancy which are optimal (>906 nmol/l) for the prevention of neural tube defects (NTDs). Methods: Clinical, FA supplementation and dietary folate details were computerized at the first antenatal visit. Maternal blood samples were analysed for RBC and serum folate. Results: Of the 502 women, 98.2% (n = 493) reported taking FA. There was a positive correlation between duration of supplementation and both RBC folate (r = 0.43, P < 0.001) and serum folate (rho = 0.29, P < 0.001). The optimal RBC folate level was achieved in 80.4% (n = 46) of women who started FA 400 µg 4-8 weeks before their LMP compared with only 53.6% (n = 153) in women who started 4-8 weeks after their LMP (P < 0.001). Conclusions: This study provides, for the first time, information on both the timing and duration of FA that will achieve the optimum RBC folate levels associated with the prevention of NTDs. Women who are taking FA (400 µg) need to start before they conceive.

Aortic depressor nerve stimulation does not impede the dynamic characteristics of the carotid sinus baroreflex in normotensive or spontaneously hypertensive rats.

Recent clinical trials in patients with drug-resistant hypertension indicate that electrical activation of the carotid sinus baroreflex can reduce arterial pressure (AP) for more than a year. To examine whether the electrical stimulation from one baroreflex system impedes normal short-term AP regulation via another unstimulated baroreflex system, we electrically stimulated the left aortic depressor nerve (ADN) while estimating the dynamic characteristics of the carotid sinus baroreflex in anesthetized normotensive Wistar-Kyoto (WKY; n = 8) rats and spontaneously hypertensive rats (SHR; n = 7). Isolated carotid sinus regions were perturbed for 20 min using a Gaussian white noise signal with a mean of 120 mmHg for WKY and 160 mmHg for SHR. Tonic ADN stimulation (2 Hz, 10 V, and 0.1-ms pulse width) decreased mean sympathetic nerve activity (73.4 ± 14.0 vs. 51.6 ± 11.3 arbitrary units in WKY, P = 0.012; and 248.7 ± 33.9 vs. 181.1 ± 16.6 arbitrary units in SHR, P = 0.018) and mean AP (90.8 ± 6.6 vs. 81.2 ± 5.4 mmHg in WKY, P = 0.004; and 128.6 ± 9.8 vs. 114.7 ± 10.3 mmHg in SHR, P = 0.009). The slope of dynamic gain in the neural arc transfer function from carotid sinus pressure to sympathetic nerve activity was not different between trials with and without the ADN stimulation (12.55 ± 0.93 vs. 13.03 ± 1.28 dB/decade in WKY, P = 0.542; and 17.37 ± 1.01 vs. 17.47 ± 1.64 dB/decade in SHR, P = 0.946). These results indicate that the tonic ADN stimulation does not significantly modify the dynamic characteristics of the carotid sinus baroreflex.

Duration of periconceptional folic acid supplementation in women booking for antenatal care.

OBJECTIVE: To provide accurate estimates of the commencement time, duration and dosage of folic acid (FA) supplementation taken by Irish women in the periconceptional period. The study also aimed to establish the factors associated with optimal FA supplementation practices. DESIGN: Cross-sectional observational study. Women's clinical and sociodemographic details were computerised. Maternal weight and height were measured before calculating BMI. Detailed FA supplementation questionnaires were completed under the supervision of a trained researcher. SETTING: A large university maternity hospital, Republic of Ireland, January 2014-April 2016. SUBJECTS: Women (n 856) recruited at their convenience in the first trimester. RESULTS: While almost all of the women (97 %) were taking FA at enrolment, only one in four women took FA for at least 12 weeks preconceptionally (n 208). Among the 44 % of women who were supplementing with FA preconceptionally, 44 % (162/370) reported taking FA for less than the 12 weeks required to achieve optimal red-blood-cell folate levels for prevention of neural tube defects. On multivariate analysis, only planned pregnancy and nulliparity were associated with taking FA for at least 12 weeks preconceptionally. Among women who only took FA postconceptionally, almost two-thirds commenced it after day 28 of their pregnancy when the neural tube had already closed. CONCLUSIONS: As the timing of FA was suboptimal both before and after conception, we recommend that current national FA guidelines need to be reviewed.

Maternal nutrient intakes from food and drinks consumed in early pregnancy in Ireland.

Background: The aim of this observational study was to measure food, macronutrient and micronutrient intakes of women presenting for antenatal care and assess compliance with current nutritional recommendations. Methods: Women were recruited in the first trimester of pregnancy. Maternal weight and height were measured and body mass index (BMI) calculated. Body composition was measured using bioelectrical impedance analysis. Maternal energy and nutrient intakes were estimated using a validated Willett Food Frequency Questionnaire and misreporting of energy intakes (EI) determined. Results: Plausible EIs were reported in 402 women. Mean age, weight and BMI were 30.8 years, 67.1 kg and 24.6 kg/m2 respectively. Median EIs were 2111 kcal, and median protein, carbohydrate and fat intakes were 17.3, 48.1 and 36.2 g/MJ/day, respectively. More than 90% of women exceeded the recommended daily allowance for saturated fat. Nearly all of the women (99%) did not meet estimated average requirements (EAR) for vitamin D. One in three women failed to achieve a dietary folate intake of 400 µg/day. Over one in five women failed to meet the EAR for iron, and 14% failed to achieve the EAR for calcium. Conclusions: Our findings highlight concerning deficits in nutrient intakes among women and will help guide professional dietary advice to women attending for future obstetric care in Ireland.

The relationship between maternal body composition in early pregnancy and foetal mid-thigh soft-tissue thickness in the third trimester in a high-risk obstetric population.

Maternal obesity is an emerging challenge in contemporary obstetrics. To date there has been no study analysing the relationship between specific maternal body composition measurements and foetal soft-tissue measurements. The aim of this study was to determine whether measurement of maternal body composition at booking predicts foetal soft-tissue trajectories in the third trimester. We analysed the relationship between foetal thigh in the third trimester and both maternal BMI and body composition using the Tanita digital scales in the first trimester. Foetal subcutaneous thigh tissue measurements were obtained at intervals of 28, 32 and 36 weeks of gestation. A total of 160 women were identified. There was a direct correlation between MTST at 36 weeks and BMI (p = .002). There was a positive correlation between MTST at 36 weeks and leg fat mass (p = .13) and leg fat free mass (p = .013). There was a positive correlation between arm fat free mass and MTST at 36 weeks. We showed there is an association between maternal fat distribution and foetal subcutaneous thigh tissue measurements. MTST may be more useful in determining if a child is at risk of macrosomia. Impact statement Previous studies have suggested that maternal obesity programmes intrauterine foetal adiposity and growth. The aim of this study was to examine the relationship in a high-risk obstetric population between measurements of maternal body composition in early pregnancy and the assessment of foetal adiposity in the third trimester using serial ultrasound measurements of mid-thigh soft-tissue thickness. BMI is only a surrogate measurement of fat and does not measure fat distribution. Our study shows the distribution of both maternal fat and fat-free mass in early pregnancy may be positively associated with foetal soft-tissue measurements in the third trimester. Maternal arthropometric measurements other than BMI may help predict babies at risk of macrosomia and neonatal adiposity.

Development of a servo pump system for in vivo loading of pathological pulmonary artery impedance on the right ventricle of normal rats.

Pulmonary artery (PA) impedance provides detailed information on right ventricular (RV) afterload in pulmonary hypertension (PH). This study aimed to examine PA impedance in a rat model of monocrotaline-induced PH (MCT-PH) and to develop an experimental system for in vivo loading of pathological PA impedance on the RV of normal rats. PA impedance was quantified in normal (n= 10) and MCT-PH rats (n= 10) using a three-element Windkessel (3-WK) model. Compared with normal rats, MCT-PH rats had higher characteristic impedance (ZC) and peripheral pulmonary resistance (RP) (ZC: 0.121 ± 0.039 vs. 0.053 ± 0.017 mmHg·min·ml(-1), P< 0.001; RP: 0.581 ± 0.334 vs. 0.252 ± 0.105 mmHg·min·ml(-1), P= 0.013) and lower pulmonary artery compliance (CP) (0.242 ± 0.131 vs. 0.700 ± 0.186 ml/mmHg, P< 0.001). In another group of 10 normal rats, a computer-controlled servo pump was connected to the left PA for loading PA impedance with parameters in pathological ranges designed by the 3-WK model. Activation of the servo pump decreased the error of measured vs. target PA impedance (modulus: from 0.047 ± 0.020 without pump activation to 0.019 ± 0.007 with pump activation,P< 0.001; phase: 0.085 ± 0.028 to 0.043 ± 0.012 radians,P< 0.001). In conclusion, MCT-PH increases ZC and RP and decreases CP Our servo pump system, which is capable of imposing arbitrary PA impedance with pathological parameters, may offer a unique opportunity to delineate the pathological significance of PA impedance in PH.

Impact of Implementing Preanalytical Laboratory Standards on the Diagnosis of Gestational Diabetes Mellitus: A Prospective Observational Study.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes, but risk is reduced with identification and early treatment. Glucose measurements are affected by preanalytical sample handling, such as temperature of storage, phlebotomy-analysis interval, and use of a glycolysis inhibitor. We evaluated glucose concentrations and the incidence of GDM after strict implementation of the American Diabetes Association (ADA) preanalytical guidelines, compared with usual hospital conditions. METHODS: Women screened selectively for GDM at 24-32 weeks' gestation were recruited at their convenience before a 75-g oral glucose tolerance test. Paired samples were taken: the first sample followed ADA recommendations and was transferred to the laboratory on an iced slurry for immediate separation and analysis (research conditions), and the second sample was not placed on ice and was transferred according to hospital practice (usual conditions). RESULTS: Of samples from 155 women, the mean fasting, 1-h, and 2-h results were 90.0 (12.6) mg/dL [5.0 (0.7) mmol/L], 142.2 (43.2) mg/dL [7.9 (2.4) mmol/L], and 102.6 (32.4) mg/dL [5.7 (1.8) mmol/L], respectively, under research conditions, and 81 (12.6) mg/dL [4.5 (0.7) mmol/L], 133.2 (41.4) mg/dL [7.4 (2.3) mmol/L], and 99 (32.4) mg/dL [5.5 (1.8) mmol/L] under usual conditions (all P < 0.0001). GDM was diagnosed in 38.1% (n = 59) under research conditions and 14.2% (n = 22) under usual conditions (P < 0.0001). The phlebotomy-analysis interval for the fasting, 1-h, and 2-h samples was 20 (9), 17 (10), and 17 (9) min under research conditions and 162 (19), 95 (23), and 32 (19) min under usual conditions (all P < 0.0001). All cases of GDM were diagnosed on fasting or 1-h samples; the 2-h test diagnosed no additional cases. CONCLUSIONS: Implementation of ADA preanalytical glucose sample handling recommendations resulted in higher mean glucose concentrations and 2.7-fold increased detection of GDM compared with usual hospital practices.