Twin pregnancies in Cardiff and Vale of Glamorgan over four decades: natural twinning is on the increase

Objective

To assess trends in twinning over four decades using a population-based registry.

Design

Ecological study to conduct trend analysis of twin pregnancies in a geographically defined area over 40 years.

Setting

All pregnancies in the Cardiff and Vale of Glamorgan area of South Wales from 1965 to 2004, as recorded in the Cardiff Birth Survey (CBS) database.

Methods

Trends of the incidence of all twin pregnancies (≥18 weeks of gestation) were calculated in 5-year increments, beginning with 1965–1969 and ending in 2000–2004. Natural twinning rates could only be calculated for the terminal five time periods (i.e., 1980–1984, 1985–1989, 1990–1994, 1995–1999, and 2000–2004), when information regarding non-spontaneous (iatrogenic) twinning was first collected in the database. All results were adjusted for maternal age.

Results

The total twinning rate was 13.1 per 1000 pregnancies in the 1st time period (1965–1969). Subsequently, there was a gradual reduction in twinning, reaching a nadir of 10.3 per 1000 for the time period 1980–1985 (Z = 3.15, P value < 0.001). This was followed by a gradual increase in twinning, reaching a maximum of 15.7 per 1000 for both 1995–1999 and 2000–2004 (Z = −5.18, P value < 0.0001). After exclusion of the cases of iatrogenic pregnancies, the natural twinning rate showed a continuous and gradual increase from 10 per 1000 spontaneous pregnancies in 1980–1984 to 13.3 per 1000 in 2000–2004 (Z = −5.08, P value < 0.0001).

Conclusion

The data showed a gradual, continuous increase in natural twinning rates over the last two decades. Such an increase cannot be attributed to the rise in maternal age alone.     

Protease inhibitor therapy and fetal growth potential in HIV-positive women

Our objective was to test if protease inhibitors (PIs) increase the incidence of fetal growth restriction (FGR). Human immunodeficiency (HIV)-seropositive women were studied. At birth the neonatal weight percentile was assigned by predicted growth potential (GP), accounting for race, parity, weight, height, gestational age, birthweight, and gender (Gardosi, 1992). FGR was defined as GP < 10% percentile. Maternal age, CD4 count, viral load, weight gain, prenatal care, tobacco, alcohol, substance abuse, and PI use were related to FGR using chi-square and multiple regression analysis. Ninety-three of 191 women received PI. In these, FGR occurred in 27 (29%) compared with 15 (15.3%) in the non-PI group ( P = 0.02). Maternal CD4 count ( P < 0.0001) was the primary determinant, and smoking ( P = 0.037) was an independent cofactor for FGR (Nagelkerke r2 = 0.24). Twenty-six of 82 (31.7%) smokers had FGR, versus 16 of 109 (14.7%) of nonsmokers (odds ratio, 2.69; 95% confidence interval, 1.33 to 5.46; P = 0.005). After exclusion of the CD4 count, PI became a cofactor for FGR ( P = 0.021 and Nagelkerke r2 = 0.104). We concluded that maternal HIV status and smoking determine the risk for FGR. Although PIs increase the risk for FGR, this effect appears to depend on maternal disease severity.     

Targeting access to reproductive health: giving contraception more prominence and using indicators to monitor progress

Unmet need for contraception represents a major failure in the provision of reproductive health services and reflects the extent of access to services for spacing and limiting births, which are also affected by personal, partner, community and health system factors. In the context of the Millennium Development Goals, family planning has been given insufficient attention compared to maternal health and the control of sexually transmitted infections. As this omission is being redressed, efforts should be directed towards ensuring that an indicator of unmet need is used as a measure of access to services. The availability of data on unmet need must also be increased to enable national comparisons and facilitate resource mobilisation. Unmet need is a vital component in monitoring the proportion of women able to space and limit births. Unmet need for contraception is a measure conditioned by people's preferences and choices and therefore firmly introduces a rights perspective into development discourse and serves as an important instrument to improve the sensitivity of policy dialogue. The new reproductive health target and the opportunity it offers to give appropriate attention to unmet need for contraception will allow the entry of other considerations vital to ensuring universal access to reproductive health.     

Magnesium metabolism in blood and the whole body in man using 28magnesium.

Studies of magnesium kinetics in plasma, red cells, and the whole-body with ²⁸Mg are described. The observations in plasma were analyzed with a three-compartment model and those in red cells with a two-compartment model. An integral approach, using the occupancy principle, was used in the analysis of the whole-body observations. At 120 hr after intravenous administration of ²⁸Mg, exchangeable magnesium calculated by the dilution principle was only 23% of total body magnesium. There was good agreement between the estimates of exchangeable magnesium based on plasma and “spot” urine ²⁸Mg activity. Exchangeable magnesium, as estimated by compartmental analysis and the occupancy principle, was only 12.5%–15% of total body magnesium. These results suggest the existence of magnesium compartments in the body with turnover half-periods of at least 63–181 days that cannot be investigated adequately with the short-lived tracer, ²⁸Mg. A possible mechanism for the observed pattern of red cell uptake of ²⁸Mg in vivo is suggested in which magnesium enters these cells only during erythropoiesis and is then lost progressively from circulating red cells during the aging process. Present results suggest that the concentration of magnesium in reticulocytes may be 3.9 times greater than the mean red cell concentration. Magnesium may leave red cells exponentially with age; a half-period of 22.4 days is suggested.     

Evidence of depot‐specific regulation of all‐trans‐retinoic acid biosynthesis in human adipose tissue

The prevalence of obesity continues to rise, underscoring the need to better understand the pathways mediating adipose tissue (AT) expansion. All‐trans‐retinoic acid (atRA), a bioactive vitamin A metabolite, regulates adipogenesis and energy metabolism, and, in rodent studies, aberrant vitamin A metabolism appears a key facet of metabolic dysregulation. The relevance of these findings to human disease is unknown, as are the specific enzymes implicated in vitamin A metabolism within human AT. We hypothesized that in human AT, family 1A aldehyde dehydrogenase (ALDH1A) enzymes contribute to atRA biosynthesis in a depot‐specific manner. To test this hypothesis, parallel samples of subcutaneous and omental AT from participants (n = 15) were collected during elective abdominal surgeries to quantify atRA biosynthesis and key atRA synthesizing enzymes. ALDH1A1 was the most abundant ALDH1A isoform in both AT depots with expression approximately twofold higher in omental than subcutaneous AT. ALDH1A2 was detected only in omental AT. Formation velocity of atRA was approximately threefold higher (p = 0.0001) in omental AT (9.8 [7.6, 11.2]) pmol/min/mg) than subcutaneous AT (3.2 [2.1, 4.0] pmol/min/mg) and correlated with ALDH1A2 expression in omental AT (β‐coefficient = 3.07, p = 0.0007) and with ALDH1A1 expression in subcutaneous AT (β‐coefficient = 0.13, p = 0.003). Despite a positive correlation between body mass index (BMI) and omental ALDH1A1 protein expression (Spearman r = 0.65, p = 0.01), BMI did not correlate with atRA formation. Our findings suggest that ALDH1A2 is the primary mediator of atRA formation in omental AT, whereas ALDH1A1 is the principal atRA‐synthesizing enzyme in subcutaneous AT. These data highlight AT depot as a critical variable for defining the roles of retinoids in human AT biology.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Rodent data suggest that dysregulated production of all‐trans‐retinoic acid (atRA), the primary bioactive metabolite of vitamin A, may contribute to body weight gain and its complications. However, the key enzymes responsible for atRA biosynthesis in human adipose tissue have not been identified, nor has the relationship between body weight and adipose tissue atRA biosynthesis been evaluated in humans.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study sought to identify the key enzymes involved in atRA biosynthesis in human omental and subcutaneous adipose tissue. This study also quantified atRA formation velocity and explored the potential relationship between body mass index (BMI) and atRA biosynthesis in both adipose tissue depots.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study establishes that among the aldehyde dehydrogenase (ALDH) isoforms, ALDH1A1 and ALDH1A2 both contribute to atRA biosynthesis in human omental adipose tissue, whereas only ALDH1A1 contributes to atRA biosynthesis in subcutaneous adipose tissue. Both ALDH1A1 expression and atRA formation velocity are substantially higher in omental than subcutaneous adipose tissue. Omental ALDH1A1 protein expression exhibits a positive correlation with BMI, but atRA formation velocity in both omental and subcutaneous adipose tissue shows no correlation with BMI. Thus, these findings highlight discrepancies between human and rodent adipose tissue biology and, moreover, reveal depot‐specific regulation of vitamin A metabolism in human adipose tissue.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This line of research ultimately is intended to define the roles of vitamin A metabolites in the regulation of tissue remodeling and energy partitioning in human adipose tissue. This knowledge could contribute to the delineation of mechanisms underlying progressive obesity and its complications.     

The effect of oral contraceptive use on vertebral bone mass in pre- and post-menopausal women

The effects of oral contraceptive use on bone mineral density in pre- and post-menopausal women were evaluated in two separate studies. First, in a population of young women carefully controlled for all risk factors known to be associated with osteoporosis, it was determined that vertebral bone mineral was increased by about 1% for each year of exposure to oral contraceptives. A similar result was obtained by examining vertebral mineral content of an unselected, but healthy premenopausal population. Effects of oral contraceptives on bone mass could not be found among postmenopausal women, unless perhaps in the initial year or two after loss of ovarian function.     

Conditioned responses in a methadone population. A comparison of laboratory, clinic, and natural settings

The incidence of conditioned high, craving, and withdrawal in methadone-maintained patients was compared across three settings: an artificial laboratory setting, clinic extinction sessions, and in self-reports from the natural home environment. A significant proportion of methadone patients showed increased craving and withdrawal in response to drug-related stimuli, even in the artificial laboratory setting. As stimulus opportunities became more varied (clinic extinction sessions) and closer to those in the patient's own home environment, the proportion of patients experiencing subjective craving and withdrawal increased. These results are discussed in terms of the nature of, and inter-relationships among, the conditioned responses found in opiate abusers and the potential role of these responses in relapse to drug use in the abstinent patient.     

Foot shock induces time and region specific adrenergic receptor changes in rat brain

Rats were subjected to 1 hr or 2 hr of electric foot shock for 1 day or 7 days and adrenergic receptor binding was evaluated in the hypothalamus, brainstem and cortex. beta-Adrenergic receptor density in the hypothalamus was dramatically reduced following 1 hr of shock. Following repeated shock, alpha 2-adrenergic receptors in the cortex and brainstem were observed to increase. Cortical alpha 2-adrenergic receptors were more sensitive to stress than the alpha 2-adrenergic receptors of the brainstem, alterations in the latter only reaching statistical significance following 7 days of shock and 24 hr of recovery. alpha 1- and beta-adrenergic receptors in the brainstem and cortex were relatively resistant to stress induced changes. The significance of type of stress, duration of stress, and strain of rat for understanding the current data are discussed in the context of prior reports of stress induced receptor changes.