Development of a dietary screening questionnaire to predict excessive weight gain in pregnancy

Excessive gestational weight gain (GWG) is a risk factor for several adverse pregnancy outcomes, including macrosomia. Diet is one of the few modifiable risk factors identified. However, most dietary assessment methods are impractical for use in maternal care. This study evaluated whether a short dietary screening questionnaire could be used as a predictor of excessive GWG in a cohort of Icelandic women. The dietary data were collected in gestational weeks 11–14, using a 40‐item food frequency screening questionnaire. The dietary data were transformed into 13 predefined dietary risk factors for an inadequate diet. Stepwise backward elimination was used to identify a reduced set of factors that best predicted excessive GWG. This set of variables was then used to calculate a combined dietary risk score (range 0–5). Information regarding outcomes, GWG (n = 1,326) and birth weight (n = 1,651), was extracted from maternal hospital records. In total, 36% had excessive GWG (Icelandic criteria), and 5% of infants were macrosomic (≥4,500 g). A high dietary risk score (characterized by a nonvaried diet, nonadequate frequency of consumption of fruits/vegetables, dairy, and whole grain intake, and excessive intake of sugar/artificially sweetened beverages and dairy) was associated with a higher risk of excessive GWG. Women with a high (≥4) versus low (≤2) risk score had higher risk of excessive GWG (relative risk = 1.23, 95% confidence interval, CI [1.002, 1.50]) and higher odds of delivering a macrosomic offspring (odds ratio = 2.20, 95% CI [1.14, 4.25]). The results indicate that asking simple questions about women's dietary intake early in pregnancy could identify women who should be prioritized for further dietary counselling and support.     

Optimal Positive end-expiratory pressure (PEEP) settings indifferential lung ventilation during simultaneous unilateral pneumothoraxand laparoscopy.

BACKGROUND: A combined thoraco-laparoscopic technique for esophageal resection is technically possible, but it requires special attention to ventilation. The positive insufflation pressure normally used in laparoscopy will, when communication between thorax and abdomen is established, create a pneumothorax. METHODS: We performed an experimental study of differential lung ventilation with different levels of positive end-expiratory pressure (PEEP) settings during thoraco-laparoscopy in anesthetized pigs. RESULTS: Positive pressure insufflation of carbon dioxide (CO2) resulted in elevated pulmonary capillary wedge pressure, hypercarbia, and respiratory acidosis. Hypoxemia, however, developed only at lower settings of PEEP. Heart rate, mean arterial pressure, and cardiac output remained relatively stable. CONCLUSION: Pneumopleuroperitoneum under positive CO2 insufflation pressure had adverse effects on blood gases. Hypercarbia, respiratory acidosis, and hypoxemia were early manifestations that occurred even in the presence of hemodynamic stability. The application of PEEP equal to or above CO2 insufflation pressure improved blood gases; in particular, the hypoxia could be avoided. No beneficial effects of differential lung ventilation were documented.     

Size at birth and glucose intolerance in a relatively genetically homogeneous,high-birth weight population

BACKGROUND: The results of epidemiologic studies have linked birth size to adult glucose intolerance. OBJECTIVE: We investigated this association in a genetically homogeneous population with higher birth weights and a lower prevalence of type 2 diabetes than previously studied. DESIGN: The subjects were 2362 men and 2286 women aged 33-65 y. Size at birth was obtained from the National Archives of Iceland. Data for adult anthropometry, fasting blood glucose, and blood glucose after an oral glucose load came from the randomized prospective Reykjavík Study. RESULTS: Postchallenge glucose concentrations were inversely related to birth weight and length in men and inversely related to birth weight and ponderal index in women (P < 0.001). This association was mainly found among those within the highest one-third of adult body mass index values. In men, the prevalence of dysglycemia was lower with increasing weight (P = 0.04) and length (P = 0.003) at birth but there was no relation of dysglycemia to ponderal index. For women, there was no linear trend for dysglycemia in relation to size at birth but the relation with birth length was U shaped. CONCLUSIONS: Greater birth weight and length appear to offer a protective effect against glucose intolerance. Adult overweight or obesity enhances the risk associated with low birth weight and length. Because the population studied has higher birth weights and a lower prevalence of type 2 diabetes than are found in neighboring countries, it is possible that decreasing the number of low-birth weight infants might help to stem the increasing prevalence of type 2 diabetes worldwide.     

Relationship between size at birth and hypertension in a genetically homogeneous population of high birth weight

OBJECTIVE: To investigate the association between birth size and hypertension within a genetically homogeneous population of high birth weight. DESIGN: Cohort-study with retrospectively collected data on size at birth. SUBJECTS AND SETTING: The study included 4601 men and women born 1914-1935 in Reykjavik, Iceland, who participated in the Reykjavik Study of the Icelandic Heart Association. MAIN OUTCOME MEASURES: Birth size measurements, adult blood pressure (BP) and body mass index (BMI), and family history of hypertension. RESULTS: Birth weight was inversely related to hypertension in adulthood in women (P for trend < 0.001). The relationship was of borderline significance in men (P for trend = 0.051). A low ponderal index was significantly associated with high BP in women (P for trend = 0.025) but not men (P > 0.05). For women with an adult BMI > 26 kg/m2, the odds ratio for hypertension for those born weighing < 3.45 kg was 2.1 [95% confidence interval, 1.3-3.3, compared with women born weighing > 3.75 kg. The association was only significant in women without a family history of hypertension. CONCLUSIONS: An inverse association between size at birth and adult hypertension was seen in a population of greater birth size than has previously been investigated. The relation was strongest among women born small who were overweight in adulthood, and for those without a family history of hypertension. The results support the hypothesis that the association between birth weight and hypertension is not of genetic origin only. The large birth size of Icelanders might be protective and partly explain the lower mean systolic blood pressure in Iceland than in related nations.     

Immunization of female mice with glycoconjugates protects their offspring against encapsulated bacteria

The immune system of the newborn is immature, and therefore it is difficult to induce protective immunity by vaccination in the neonatal period. Immunization of mothers during pregnancy against infections caused by encapsulated bacteria could thus be particularly attractive, as infants do not respond to polysaccharide (PS) antigens. Transmission of maternal vaccine-specific antibodies and protection of offspring against pneumococcal bacteremia and/or lung infection were studied in a neonatal murine model of pneumococcal immunization and infections. Adult female mice were immunized with native pneumococcal PS (PPS) of serotypes 1, 6B, and 19F or PPS conjugated to tetanus protein (Pnc-TT), and PPS-specific antibodies were measured in sera of mothers and their offspring. Effective transmission of maternal antibodies was observed, as PPS-specific immunoglobulin G levels in 3-week-old offspring of immunized mothers were 37 to 322% of maternal titers, and a significant correlation between maternal and offspring antibody levels was observed. The PPS-specific antibodies persisted for several weeks but slowly decreased over time. Offspring of Pnc-TT-immunized mothers were protected against pneumococcal infections with homologous serotypes, whereas PPS immunization of mothers did not protect their offspring, in agreement with the low titer of maternal PPS specific antibodies. When adult female mice were immunized with a meningococcal serogroup C conjugate vaccine (MenC-CRM), antibody response and transmission were similar to those observed for pneumococcal antibodies. Importantly, bactericidal activity was demonstrated in offspring of MenC-CRM-immunized mothers. These results demonstrate that this murine model of pneumococcal immunization and infections is suitable to study maternal immunization strategies for protection of offspring against encapsulated bacteria.     

Infant feeding patterns and midlife erythrocyte sedimentation rate

AIM: To assess the erythrocyte sedimentation rate (ESR), and other coronary heart disease (CHD) risk factors in adults who were either breast- or bottle-fed in early infancy. METHODS: Subjects were 3614 men and women born 1914-1935. Information on infant feeding patterns was gathered from original midwife's birth records. Adult ESR, triglycerides, total cholesterol, blood pressure, fasting glucose, weight and height were measured. RESULTS: The number of subjects bottle-fed in early infancy was 186 (5.2%). The geometric mean of ESR was 15.9% (95% CI 1.8%-31.8%) higher in those who were bottle-fed compared with those breastfed, p = 0.026, when adjusting for age and gender. Those who had been breastfed in early infancy had on average 2.9% higher BMI in adulthood (p = 0.012). The hazard ratio for event of CHD for bottle-fed persons versus breastfed was 1.18 (95% CI 0.88-1.57), adjusting for potential confounding factors. CONCLUSIONS: Higher adult ESR, a moderate risk factor for CHD, among those bottle-fed compared to those breastfed in early infancy might indicate a long term anti-inflammatory influence of breast milk.     

Childhood growth and adult hypertension in a population of high birth weight

Low birth weight has consistently been associated with increased adult blood pressure. The relative importance of childhood growth is, however, less well established. This study examined sex-specific associations between childhood growth and adult blood pressure in 2120 subjects born from 1921 to 1935 in Reykjavik who were recruited into a longitudinal study in 1967-1991. Size at birth and growth at regular intervals between 8 and 13 years were collected from national archives. Hypertensive males did not differ from normotensive males at birth but were increasingly taller and of higher body mass index between 8 and 13 years. No differences in adult height were observed between hypertensive and normotensive males. For boys, growth-velocity (change in growth per year) for body mass index and height between 8 to 13 years was positively associated (P<0.05) with adult blood pressure. The association for body mass index-velocity was fully accounted for by concurrent body size, whereas height-velocity was independent of birth weight and concurrent body size. Males in the highest compared with the lowest tertile in the height-velocity distribution had 66% increased risks of hypertension (95% CI: 15% to 139% increased risks of hypertension) corresponding with 5.0 mm Hg increase (95% CI: 1.5 to 8.5 mm Hg increase) and 3.1 mm Hg increase (95% CI: 1.1 to 5.0 mm Hg increase) in systolic and diastolic blood pressures, respectively. Hypertensive females weighed less at birth but did not differ markedly from normotensive girls between 8 and 13 years, and no association was observed for growth-velocity. In conclusion, rapid linear growth between 8 and 13 years predicts elevated adult blood pressure in boys. This association is likely to reflect relatively early onset of puberty among hypertensive males.     

Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer

Introduction  

BRCA1 or BRCA2 germline mutations increase the risk of developing breast cancer. Tumour cells from germline mutation carriers have frequently lost the wild-type allele. This is predicted to result in genomic instability where cell survival depends upon dysfunctional checkpoint mechanisms. Tumorigenic potential could then be acquired through further genomic alterations. Surprisingly, somatic BRCA mutations are not found in sporadic breast tumours. BRCA1 methylation has been shown to occur in sporadic breast tumours and to be associated with reduced gene expression. We examined the frequency of BRCA1 methylation in 143 primary sporadic breast tumours along with BRCA1 copy number alterations and tumour phenotype.     

Old Question Revisited: Are High-Protein Diets Safe in Pregnancy?

Background: A previous randomized dietary intervention in pregnant women from the 1970s, the Harlem Trial, reported retarded fetal growth and excesses of very early preterm births and neonatal deaths among those receiving high-protein supplementation. Due to ethical challenges, these findings have not been addressed in intervention settings. Exploring these findings in an observational setting requires large statistical power due to the low prevalence of these outcomes. The aim of this study was to investigate if the findings on high protein intake could be replicated in an observational setting by combining data from two large birth cohorts. Methods: Individual participant data on singleton pregnancies from the Danish National Birth Cohort (DNBC) (n = 60,141) and the Norwegian Mother, Father and Child Cohort Study (MoBa) (n = 66,302) were merged after a thorough harmonization process. Diet was recorded in mid-pregnancy and information on birth outcomes was extracted from national birth registries. Results: The prevalence of preterm delivery, low birth weight and fetal and neonatal deaths was 4.77%, 2.93%, 0.28% and 0.17%, respectively. Mean protein intake (standard deviation) was 89 g/day (23). Overall high protein intake (>100 g/day) was neither associated with low birth weight nor fetal or neonatal death. Mean birth weight was essentially unchanged at high protein intakes. A modest increased risk of preterm delivery [odds ratio (OR): 1.10 (95% confidence interval (CI): 1.01, 1.19)] was observed for high (>100 g/day) compared to moderate protein intake (80–90 g/day). This estimate was driven by late preterm deliveries (weeks 34 to <37) and greater risk was not observed at more extreme intakes. Very low (<60 g/day) compared to moderate protein intake was associated with higher risk of having low-birth weight infants [OR: 1.59 (95%CI: 1.25, 2.03)]. Conclusions: High protein intake was weakly associated with preterm delivery. Contrary to the results from the Harlem Trial, no indications of deleterious effects on fetal growth or perinatal mortality were observed.     

Clinical phenotype in heterozygote and biallelic Bernard‐Soulier syndrome—A case control study

Bernard‐Soulier syndrome (BSS) is a rare severe autosomal recessive bleeding disorder. To date heterozygous carriers of BSS mutations have not been shown to have bleeding symptoms. We assessed bleeding using a semi‐quantitative questionnaire, platelet parameters, PFA‐100 closure times, ristocetin response, GP Ib/IX expression and VWF antigen in 14 BSS patients, 30 heterozygote carriers for related mutations and 29 controls. Eight mutations in GP1BA, GP1BB or GP9 were identified including four previously unknown pathogenic mutations. Subjects with BSS reported markedly more mucocutaneous bleeding than controls. Increased bleeding was also observed in heterozygotes. Compared to controls, patients with BSS had lower optical platelet counts (P < 0.001), CD61‐platelet counts (P < 0.001) and higher mean platelet volume (17.7 vs. 7.8 fL, P < 0.001) and ristocetin response and closure times were unmeasurable. Heterozygotes had higher MPV (9.7 fL, P < 0.001) and lower platelet counts (P < 0.001) than controls but response to ristocetin and closure times were normal. The VWF was elevated in both BSS and in heterozygotes (P = 0.005). We conclude that heterozygotes for BSS mutations have lower platelet counts than controls and show a bleeding phenotype albeit much milder than in BSS. Both patients with BSS and heterozygote carriers of pathogenic mutations have raised VWF. Am. J. Hematol. 90:149–155, 2015. © 2014 Wiley Periodicals, Inc.