A 28-day repeated dose study in rats (OECD407) enhanced for endocrine and immune parameters was performed with hexabromocyclododecane (HBCD). Rats were exposed by daily gavage to HBCD dissolved in corn oil in 8 dose groups with doses ranging between 0 and 200 mg/kg bw per day (mkd). Evaluation consisted of dose-response analysis with calculation of a benchmark dose at the lower 95% one-sided confidence bound (BMDL) at predefined critical effect sizes (CESs) of 10-20%. The most remarkable findings were dose-related effects on the thyroid hormone axis, that is, decreased total thyroxin (TT4, BMDL 55.5 mkd at CES--10%), increased pituitary weight (29 mkd at 10%) and increased immunostaining of TSH in the pituitary, increased thyroid weight (1.6 mkd at 10%), and thyroid follicle cell activation. These effects were restricted to females. Female rats also showed increased absolute liver weights (22.9 mkd at 20%) and induction of T4-glucuronyl transferase (4.1 mkd at 10%), suggesting that aberrant metabolization of T4 triggers feedback activation of the thyroid hormone system. These effects were accompanied by possibly secondary effects, including increased cholesterol (7.4 mkd at 10%), increased tibial bone mineral density (> 49 mkd at 10%), both in females, and decreased splenocyte counts (0.3-6.3 mkd at 20%; only evaluated in males). Overall, female rats appeared to be more sensitive to HBCD than male rats, and an overall BMDL is proposed at 1.6 mkd, based on a 10% increase of the thyroid weight, which was the most sensitive parameter in the sequence of events.

Pregnancy and lactation are times of additional demand for Ca. Ca is transferred across the placenta for fetal skeletal mineralisation, and supplied to the mammary gland for secretion into breast milk. In theory, these additional maternal requirements could be met through mobilisation of Ca from the skeleton, increased intestinal Ca absorption efficiency, enhanced renal Ca retention or greater dietary Ca intake. The extent to which any or all of these apply, the underpinning biological mechanisms and the possible consequences for maternal and infant bone health in the short and long term are the focus of the present review. The complexities in the methodological aspects of interpreting the literature in this area are highlighted and the inter-individual variation in the response to pregnancy and lactation is reviewed. In summary, human pregnancy and lactation are associated with changes in Ca and bone metabolism that support the transfer of Ca between mother and child. The changes generally appear to be independent of maternal Ca supply in populations where Ca intakes are close to current recommendations. Evidence suggests that the processes are physiological in humans and that they provide sufficient Ca for fetal growth and breast-milk production, without relying on an increase in dietary Ca intake or compromising long-term maternal bone health. Further research is needed to determine the limitations of the maternal response to the Ca demands of pregnancy and lactation, especially among mothers with marginal and low dietary Ca intake, and to define vitamin D adequacy for reproductive women.

Weight gain and the prepregnancy percentage of TBF-ie, factors related to the maternal nutritional situation-are important factors with regard to the variability in the BMR response to pregnancy. Thus, it is important to consider the nutritional situation before and during gestation when assessing pregnancy energy requirements.

Low maternal vitamin D status during pregnancy may have negative consequences for both mother and child. There are few studies of vitamin D status and its determinants in pregnant women living at northern latitudes. Thus, the present study investigates vitamin D status and its determinants during the third trimester of women living in Sweden (latitudes 57-58°N). A total of ninety-five fair-skinned pregnant women had blood taken between gestational weeks 35 and 37. The study included a 4 d food diary and questionnaires on dietary intake, supplement use, sun exposure, skin type, travels to southern latitudes and measure of BMI. Serum 25-hydroxyvitamin D (25(OH)D) was analysed using the chemiluminescence immunoassay. In the third trimester of pregnancy, mean serum concentration of 25(OH)D was 47.4 (sd 18.1) nmol/l (range 10-93 nmol/l). In total, 65% of women had serum 25(OH)D < 50 nmol/l and 17 % < 30 nmol/l. During the winter, 85% of the pregnant women had serum 25(OH)D < 50 nmol/l and 28 % < 30 nmol/l. The main determinants of vitamin D status were as follows: season; use of vitamin D supplements; travels to southern latitudes. Together, these explained 51% of the variation in 25(OH)D. In conclusion, during the winter, the majority of fair-skinned pregnant women had serum 25(OH)D < 50 nmol/l in their third trimester and more than every fourth woman < 30 nmol/l. Higher vitamin D intake may therefore be needed during the winter for fair-skinned pregnant women at northern latitudes to avoid vitamin D deficiency.

Previous studies have found a significantly increased risk of preterm delivery and low birth weight after cervical conization. Most of these studies were case-control studies or were small, hampering the ability to detect significant differences between gestational age groups. This population-based cohort study evaluated the adverse consequences of cervical conization on subsequent pregnancies. The investigators linked data from the Medical Birth Registry of Norway and the Cancer Registry of Norway for the years 1967 to 2003 on 15,108 births occurring in women who had previously had cervical conization and 57,136 who subsequently had the procedure. The 2,164,006 births during the study period by women who had never had cervical conization served as controls.The proportion of preterm birth (delivery before 37 weeks of gestation) was 17.2% [95% confidence interval (CI); 16.6%-17.8%] among women who gave birth after cervical conization; 6.7% (95% CI, 6.5%-6.9%) in women who gave birth before cervical conization; and 6.2% (95% CI, 6.2%-6.3%) in women who never had the procedure. The relative risk (RR) of premature delivery after cervical conization compared with women who never had cervical conization increased with decreasing gestational age: RR 2.5 (95% CI, 2.4-2.6) at 33 to 36 weeks; RR 3.4 (95% CI, 3.1-3.7) at 28 to 32 weeks; and RR 4.4 (95% CI, 3.8-5.0) at 24 to 27 weeks. The risk of a late abortion (Ͻ24 weeks of gestation) was higher after cervical conization compared with no conization; the RR was 4.0 with a 95% CI of 3.3 to 4.8. During the study period, the RR of preterm delivery declined, particularly for delivery before 28 weeks of gestation. These findings show that cervical conization increases the risk of preterm delivery in subsequent pregnancies, especially early in pregnancy when the clinical significance is highest. EDITORIAL COMMENT(As one would expect, the data that we have relating ablative and excisional procedures for cervical dysplasia to late abortion and prematurity were not derived from randomized studies. That is to say, reproductive age women with cervical dysplasia deemed to require cervical ablation or excision have not been randomized to therapy or to expectant management for the purposes of evaluating their subsequent preg-nancy performance. Nor has a study been done wherein women have been randomized to different methods of cervical ablation or excision for the purposes of comparing subsequent pregnancy outcomes. Clearly, randomized trials of this nature would be logistically extremely difficult to do, and, in some situations, ethically problematic. But they would be the best way to overcome the major problem in evaluating the OBSTETRICS Volume 64 Number 2 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACTPrevious studies have shown that during cesarean section, the concentration of lactate in myometrial capillary blood is higher among women with dysfunctional labor compared with normal labor. Small increases in lactate concentrations have been associated with impairment in the strength an...