Vitamin D receptor genotype and risk of osteoporotic hip fracture in elderly women of Utah: an effect modified by parity

Introduction The associations between vitamin D receptor (VDR) Bsm I and Fok I genotypes, parity, and risk of osteoporotic hip fracture were evaluated in a statewide population-based case-control study in Utah.Methods Women age 50–89 years with hip fracture (n=882) were ascertained via surveillance of 18 Utah hospitals from 1997 to 2001. Age-matched controls were randomly selected (n=897). Participants were interviewed in their homes, and blood samples were collected for genotyping.Results In logistic regression analyses that controlled for multiple confounders, Bsm I VDR genotype but not Fok I genotype was associated with risk of osteoporotic hip fracture (OR bb vs. BB genotype: 0.68; 95% CI: 0.50, 0.95). In similar analyses, no overall association was observed between parity status and risk of osteoporotic hip fracture. However, the effect of VDR genotype was modified by parity status. Among nulliparous women (n=140), Bsm I genotype was not associated with risk of hip fracture (OR bb vs. BB: 0.82; 95% CI: 0.28, 2.4); among primiparous women (n=133), bb genotype was associated with increased risk of hip fracture (OR bb vs. BB: 3.30; 95% CI: 0.96, 11.29); among multiparous women (n=1,400), bb genotype was associated with decreased risk of hip fracture (OR bb vs. BB: 0.59; 95% CI: 0.42, 0.84).Conclusion VDR Bsm I genotype was associated with risk of hip fracture in Utah women, and this effect was modified by parity status. Hormonal or lifestyle factors related to parity may underlie this interaction.     

Reproductive risk factors associated with breast cancer in young women by molecular subtype

BackgroundFew studies have examined detailed features of pregnancy and the postpartum period as potential risk factors for early onset breast cancer (BC) by molecular subtype. These data may have value for improving risk assessment and prevention.MethodsWe surveyed parous enrollees in the prospective Mayo Clinic Breast Disease Registry (MCBDR) who had been diagnosed with BC at age <55 years between 2015 and 2020. Summary statistics were used to describe survey responses and reproductive risk factors by BC subtype (defined by estrogen/progesterone receptors and human epidermal growth factor receptor expression, nurse-abstracted from the medical record). Associations were assessed with Kruskal-Wallis and Chi-Square tests, followed by age-adjusted linear and logistic regression models. We compared results from this parous cohort to those from a separate cohort of nulliparous MCBDR participants with BC diagnosed at age <55 years.ResultsIn 436 parous respondents with subtype data abstracted, we identified a higher frequency of BRCA1 mutation, earlier age at diagnosis, and lower BI in patients with triple negative BC. Comparing parous to nulliparous young women with breast cancer, the proportion with TNBC was larger in the latter (12.2% vs. 15.1%, p = 0.03).ConclusionsEarly age at diagnosis and deleterious BRCA1 mutation were more frequent among TNBC patients. In addition, parous young women with TNBC had a lower BI than those with other BC subtypes, a hypothesis-generating finding that supports the need for additional research on the cycle of pregnancy-lactation-postpartum involution and BC etiology.     

Intracellular preoptic and striatal monoamines in pregnant and lactating rats: possible role in maternal behavior

In many mammals, hormonal fluctuations during pregnancy and parturition produce neurochemical events that are necessary for the transition from a non-maternal state to a maternal state that occurs when infants are born. However, the nature of these events is mostly unknown. We investigated whether changes in dopamine (DA) and serotonin (5-HT) activity within the preoptic area (POA) and striatum, neural sites important for some maternal behaviors, could be part of this process. Female rats were sacrificed as either diestrus virgins, on pregnancy day 10 or 20, on the day of parturition, or on day 7 or 17 of lactation. Bilateral tissue punches from the POA, dorsolateral striatum (ST_dl), and nucleus accumbens (NA) were obtained and levels of intracellular DA and 5-HT analyzed with high-performance liquid chromatography with electrochemical detection (HPLC–EC). In the POA, DA was high in virgins and during early pregnancy, lowest on the day of parturition, and very high during lactation. Although there were no changes in the DOPAC to DA ratio (i.e., turnover), DOPAC levels also followed this pattern. 5-HT turnover in the POA was lower in virgins compared to other groups. In the ST_dl, DA turnover was highest during late pregnancy and on the day of parturition, while no changes in 5-HT measures were found. No significant effects were found in the NA. Therefore, decreased DAergic activity in the POA and increased DAergic activity in the ST_dl occurs around parturition, the time when maternal behavior emerges, and may influence its onset.     

Dorsolateral columns of the spinal cord are necessary for both suckling-induced neuroendocrine reflexes and the kyphotic nursing posture in lactating rats

Maternal behavior in rats consists of active behaviors, such as retrieval and licking of pups, and quiescent nursing, including the suckling-induced kyphotic (upright, dorsally-arched) posture. Because lesions of the dorsolateral, but not of the dorsal, columns are known to prevent the suckling-induced milk-ejection reflex, we asked whether the same is true for kyphosis as well. Bilateral lesions of the dorsolateral funiculus (DLF) or dorsal columns (DC) at spinal segments C(4-6) were made on day 5-8 postpartum; controls (CON) were subjected to a sham procedure. All aspects of maternal behavior and lactation were present in CON and DC dams soon after treatment. Among DLF dams, two had poor postural, ambulatory, and ingestive recovery that was associated with large lesions extending to the ventrolateral columns, while one with very small lesions continued to lactate. Of the remaining eight DLF dams, milk ejection was lost while recovery of retrieval and licking of pups occurred in all (between 1 and 4 days after surgery). All eight were quiescent for long periods in response to suckling but they did not display sustained kyphosis; rather, they nursed while prone or hunched over the pups, with little or no leg support, or while supine. Ventral trunk cutaneous sensitivity was present in all subjects. These data suggest that the dorsolateral funiculus relays both suckling-induced neuroendocrine and postural nursing reflexes that are mediated by separate supraspinal regions, hypothalamus and the ventrolateral sectors of the caudal periaqueductal gray, respectively.     

Relationship between serum prolactin, lactation and changes in maternal blood B-cell (CD19+) percents during the first 8 months post-partum

Lactation is an immunologically unique state when immune factors are produced by the mother for the protection of the infant rather than the mother. While several studies have focused on the immunological composition of human milk, much less information is available on maternal immune status during lactation. Sixty-four lactating and 43 bottlefeeding women at 1–2 weeks, 1, 2, 4 or 8 months post-partum were studied in a cross-sectional design, with 14 nulliparous women as controls. Flow cytometry analysis of peripheral blood lymphocytes showed dynamic, post-partum changes in the B-cell subpopulation. Among lactating women, the relative percents of CD19+ B-cells were significantly lower (P < 0.05) than control levels at 1–2 weeks and 1 month post-partum, but showed a significant, polynomial-linear rise (P < 0.05) over time, reaching control values by 2–4 months post-partum. Bottle-feeding women had an earlier rise in the percentage of CD 19 + cells, with relative percents always significantly higher than their lactating counterparts. The differing patterns may be due to changes in serum prolactin concentrations because, among the post-partum women, relative percents of CD19+ cells were negatively correlated with baseline serum prolactin concentrations. These results have implications for maternal immunization programs designed to enhance maternal and/or infant well-being as well as other maternal health effects related to breastfeeding.     

Management strategies for patients with nipple discharge

BACKGROUND AND AIMS: The aim of this study was to assess management strategies for patients with nipple discharge (ND). PATIENTS AND METHODS: The records of 13,443 women with breast-related complaints who were examined by the same surgeon between 1 January 1960 and 31 December 2000 were retrospectively assessed. Patients with ND were grouped according to whether they had had a spontaneous or provoked discharge. The parameters investigated in each group were age, physical findings, number of pregnancies, duration of lactation, duration of discharge, colour of discharge, and histopathological features. Chi-square and Mann-Whitney U-tests were used for statistical analysis. RESULTS: ND was the presenting symptom in 603 (4.5%) of the cases. Two hundred and eighty-seven (48%) of the 603 patients showed spontaneous nipple discharge (SND group) and the other 316 (52%) showed provoked nipple discharge (PND group). In the SND group, 124 (43%) tissue specimens were obtained by either biopsy or sub-areolar exploration. Histopathological examination revealed that the most frequent causes of ND in these cases were intraductal papilloma (49 patients; 40%), intraductal carcinoma (35 patients; 28%), and cystic disease (15 patients; 12%). Twenty tissue specimens were obtained from the group with PND. In these cases, the most frequently identified causes of ND were cystic disease (seven patients; 35%), intraductal papilloma (six patients; 30%), ductal ectasia (two patients; 10%), and carcinoma (one patient; 5%). The SND and PND groups differed significantly with respect to age (P = 0.001) and duration of ND (P = 0.008). The incidence of cancer was higher in the SND specimens than in the PND specimens (28% vs 5%, respectively; P = 0.01). The number of pregnancies was significantly higher and the duration of lactation was significantly longer in the SND group (P = 0.03 and P = 0.02, respectively). CONCLUSION: The study confirms previous reports that patients with SND have a higher incidence of carcinoma than those with PND. The results suggest that older age, higher number of pregnancies, and longer duration of lactation may predispose to cancer development in patients with SND. The possibility of breast cancer should also be kept in mind when one is assessing patients with PND. Careful physical examination and close follow-up is the optimal management strategy for patients with any type of ND.     

Ethosuximide Pharmacokinetics in a Pregnant Patient and Her Newborn

Ethosuximide concentration in serum was monitored during the last trimester of pregnancy in a patient. After delivery, the decline in serum concentration of ethosuximide was observed in the nonnursing neonate. The half-life of elimination of transplacentally acquired ethosuximide in this neonate was 41.3 hr. The ratio of breast milk to maternal serum concentration of ethosuximide was approximately 1. A total daily exposure to ethosuximide of 12.8 to 38.4 mg (3.6 to 11.0 mg/kg) as a result of nursing was predicted.     

Levetiracetam concentrations in serum and in breast milk at birth and during lactation

PURPOSE: To study the pharmacokinetics of levetiracetam (LEV) at birth, during lactation, and in the nursed infant. METHODS: Eight consecutive breast-feeding women with epilepsy treated with LEV twice daily and their infants were studied. RESULTS: The mean umbilical cord serum/maternal serum ratio was 1.14 (range, 0.97-1.45) (n = 4). The mean milk/maternal serum concentration ratio was 1.00 (range, 0.76-1.33) at 3 to 5 days after delivery (n = 7). At sampling 2 weeks to 10 months after delivery (n = 5), it was similar (range, 0.85-1.38). At 3 to 5 days after delivery, the infants had very low LEV serum concentrations (<10-15 microM), a finding that persisted during continued breast-feeding. No malformations were detected, and in none of the infants did signs of adverse effects develop. CONCLUSIONS: Our data indicate an extensive transfer of LEV from mother to fetus and into breast milk. However, breast-fed infants had very low LEV serum concentrations, suggesting a rapid elimination of LEV.     

Mothers' decisions to change from formula to mothers' milk for very-low-birth-weight infants

OBJECTIVE: The purpose of this study was to examine maternal decisions about providing milk for a very-low-birth-weight (VLBW) infant, when the initial maternal intent was to formula-feed. DESIGN: Using prospective, purposive sampling, semistructured interviews were conducted with 21 of 23 eligible mothers over a 9-month period. Audio-recorded data were transcribed verbatim, coded, categorized, and subjected to dimensional analysis. SETTING: The study took place in a 52-bed, tertiary urban neonatal intensive-care unit. PATIENTS/PARTICIPANTS: Mean maternal age was 26.5 years (range = 18-38), and mean infant birth weight and gestational age were 705.4 g (range = 504-1,310), and 25.8 weeks (range = 23-33), respectively. Of the 21 mothers, 76% were African American or Latina; 62% were low income. MAIN OUTCOME MEASURES: We evaluated mothers' initial reasons for selecting formula and changing the decision to provide their milk, whether they were made to feel guilty or coerced, the processes of establishing and maintaining lactation, and breastfeeding outcomes at 1-month postbirth. RESULTS: Mothers initially chose formula because they had no breastfeeding role models and were fearful of pain and lifestyle modifications. They changed this decision after the nurse or physician talked with them about the health benefits for their infant. Of the 21 women, all denied feeling pressured, coerced, or guilty about the decision change, and all identified rewards to themselves and their infants. All mothers provided milk for greater than or equal to 30 days, 19 went on to feed at breast, and 2 became certified breastfeeding peer counselors for the Rush Mothers' Milk Club. CONCLUSION: These findings underscore the role of nurses and physicians in providing evidence-based information about mothers' milk and indicate that sharing this knowledge does not make mothers of VLBW infants feel pressured, coerced, or guilty.     

Anatomy and development of the koala, Phascolarctos cinereus: an evolutionary perspective on the superfamily Vombatoidea

Fifteen koalas (Phascolarctos cinereus) – 5 pouched young from 4 to 6.5 months and 10 adults from 5 to 16.5 years – were analyzed for functional parameters (body composition, limb segment and muscle mass, post-cranial skeletal characters) and developmental expressions (growth of body, brain, musculature). These data were compared with a convergent eutherian, the three-toed sloth, Bradypus infuscatus, and with the koala’s distant (Macropodid; wallabies) and proximate (Vombatid; wombats) marsupial relatives. Musculoskeletal structures correlated with sitting and climbing; the growth of the young and the physiological demands of adulthood correlated with the low-quality diet of Eucalyptus foliage. The gestalt of the ancestral Vombatoids (pronograde quadrupeds, generalist browsers and social conservatives with low basal metabolism and attenuated development) provided the baseline essential for their locomotor and nutritional divergence into arboreal browsers, the koalas, and fossorial grazers, the wombats. Accepted: 25 October 2000