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Pivmecillinam and adverse birth and neonatal outcomes: a population-based cohort study.

A previous study unexpectedly showed an increased, statistically imprecise, risk of low Apgar score in children of women redeeming prescriptions for pivmecillinam in late pregnancy. To improve statistical precision we extended the previous dataset with data for 5 more y, and in addition added more neonatal outcomes. We thus examined the risk of adverse birth and neonatal outcomes among pregnant users of pivmecillinam based on population-based registries in North Jutland County, Denmark. We included 63,659 women with a live birth, or stillbirth after the 28th week of gestation. 2031 had redeemed prescriptions for pivmecillinam any time during pregnancy, 559 in the first trimester and 371 within 28 d before delivery. Adjusted odds ratios were: birth defects 0.83 (95% confidence interval (95% CI) 0.53-1.32) for exposure during first trimester, preterm delivery 0.96 (95% CI 0.79-1.18) and low birth weight 0.79 (95% CI 0.52-1.20) for exposure any time during pregnancy, and stillbirth 1.19 (95% CI 0.30-4.80), low Apgar score 1.17 (95% CI 0.37-3.66), hypoglycaemia 1.03 (95% CI 0.53-2.00), and respiratory distress syndrome 0.79 (95% CI 0.38-1.68) for exposure within 28 d before delivery. Use of pivmecillinam during pregnancy did not appear to increase the risk of adverse birth and neonatal outcomes; however, statistical precision is still low.

Abnormalities, Drug-Induced↗

Effects of home visits by paraprofessionals and by nurses: age 4 follow-up results of a randomized trial.

OBJECTIVE: To examine the effects of prenatal and infancy home visiting by paraprofessionals and by nurses from child age 2 through age 4 years. METHODS: We conducted, in public and private care settings in Denver, Colorado, a randomized, controlled trial with 3 arms, ie, control, paraprofessional visits, and nurse visits. Home visits were provided from pregnancy through child age 2 years. We invited 1178 consecutive, low-income, pregnant women with no previous live births to participate, and we randomized 735; 85% were unmarried, 47% Mexican American, 35% white non-Mexican American, 15% black, and 3% American Indian/Asian. Outcomes consisted of maternal reports of subsequent pregnancies, participation in education and work, use of welfare, marriage, cohabitation, experience of domestic violence, mental health, substance use, and sense of mastery; observations of mother-child interaction and the home environment; tests of children's language and executive functioning; and mothers' reports of children's externalizing behavior problems. RESULTS: Two years after the program ended, women who were visited by paraprofessionals, compared with control subjects, were less likely to be married (32.2% vs 44.0%) and to live with the biological father of the child (32.7% vs 43.1%) but worked more (15.13 months vs 13.38 months) and reported a greater sense of mastery and better mental health (standardized scores [mean = 100, SD = 10] of 101.25 vs 99.31 and 101.21 vs 99.16, respectively). Paraprofessional-visited women had fewer subsequent miscarriages (6.6% vs 12.3%) and low birth weight newborns (2.8% vs 7.7%). Mothers and children who were visited by paraprofessionals, compared with control subjects, displayed greater sensitivity and responsiveness toward one another (standardized score [mean = 100, SD = 10] of 100.92 vs 98.66) and, in cases in which the mothers had low levels of psychologic resources at registration, had home environments that were more supportive of children's early learning (score of 24.63 vs 23.35). Nurse-visited women reported greater intervals between the births of their first and second children (24.51 months vs 20.39 months) and less domestic violence (6.9% vs 13.6%) and enrolled their children less frequently in preschool, Head Start, or licensed day care than did control subjects. Nurse-visited children whose mothers had low levels of psychologic resources at registration, compared with control group counterparts, demonstrated home environments that were more supportive of children's early learning (score of 24.61 vs 23.35), more advanced language (score of 91.39 vs 86.73), superior executive functioning (score of 100.16 vs 95.48), and better behavioral adaptation during testing (score of 100.41 vs 96.66). There were no statistically significant effects of either nurse or paraprofessional visits on the number of subsequent pregnancies, women's educational achievement, use of substances, use of welfare, or children's externalizing behavior problems. CONCLUSIONS: Paraprofessional-visited mothers began to experience benefits from the program 2 years after the program ended at child age 2 years, but their first-born children were not statistically distinguishable from their control group counterparts. Nurse-visited mothers and children continued to benefit from the program 2 years after it ended. The impact of the nurse-delivered program on children was concentrated on children born to mothers with low levels of psychologic resources.

Birth Intervals↗

The effects of breastfeeding and birth spacing on child survival in China.

Using data from the In-depth Fertility Survey, conducted in Shanghai Municipality and Shaanxi Province, People's Republic of China, in April 1985, this study shows that breastfeeding and birth spacing have significant effects on child survival in Shaanxi, but not in Shanghai (controlling for potential confounding factors and reverse causality). The effect of breastfeeding decreases with age. Introducing proper supplemental food is very important for child survival in Shaanxi, where a high proportion of children are breastfed exclusively for much too long, sometimes up to nine months. An increase in the length of the previous birth interval improves child survival in Shaanxi significantly, especially for high-order children, and the first child has the highest survivorship in both Shanghai and Shaanxi. The effects of subsequent birth intervals are statistically significant in Shaanxi, but have a small actual impact on child survival in the first few years of life, since the arrival of a sibling does not affect the index child's risk of dying in the first few months of life, when the mortality rate is extremely high.

Age Factors↗

Differential peripheral expansion and in vivo antigen reactivity of alpha/beta and gamma/delta T cells emigrating from the early fetal lamb thymus.

The concentrations of different lymphocyte subsets in the blood of lambs which had been thymectomized (Tx) in utero between days 67-75 of fetal gestation were measured at birth and at various intervals during the first year of life. Compared to thymus-intact (Ti) controls, Tx lambs were severely depleted of both alpha/beta and gamma/delta T cells at birth (less than 10% of control levels). The majority of the residual alpha/beta T cells present in Tx lambs at birth were CD4+CD8-. As the Tx lambs aged, the concentration of alpha/beta T cells in blood increased steadily to reach levels around 50% of control values. In contrast, the circulating gamma/delta T cells did not expand in Tx animals and remained barely detectable throughout the observation period, although these cells accounted for 30%-60% of the T cells in the blood of Ti lambs. The expansion of alpha/beta but not gamma/delta T cells was also reflected in changes in the cellular composition of solid lymphoid organs in Tx lambs. B cell numbers were similar in both groups at birth but Tx lambs were persistently B lymphopenic from 3 weeks of age onwards. The alpha/beta T cells that had expanded in Tx lambs responded to stimulation with bacterial antigens in a way that was qualitatively similar to the response in Ti lambs. By contrast, the few gamma/delta T cells in Tx lambs responded abnormally. Our results show that although sheep alpha/beta and gamma/delta T cells are equally thymus dependent during ontogeny, the early fetal thymic emigrants which establish the two T cell lineages in the periphery have strikingly different antigen reactivities and capacities for self-renewal and expansion.

Aging↗

Sequential pulmonary function measurements in very low-birth weight infants during the first week of life.

Sequential lung function was measured in 12 very low-birth weight infants (less than or equal to 1,250 g) within 14 hours of birth, and at daily intervals thereafter for the first week of life, using an esophageal balloon and pneumotachograph system. All infants were clinically free of respiratory distress syndrome and radiographically showed no evidence of atelectasis or pulmonary edema. The alveolar-arterial oxygen tension gradient was high at birth and remained elevated over the period during which arterial blood gases were monitored. Increases of lung compliance and tidal volume between the first day and the end of the first week of life were not significant. Day-to-day determinations of lung compliance revealed an individual and group variability without a definite pattern. Lung resistance measurements indicated no clear trend for the group as a whole, but inspiratory resistance was generally lower than expiratory resistance. Possible causes, in addition to technical factors, that may account for the variability in the pulmonary mechanics of these small infants include an instability of lung volume and uneven distribution of pleural pressure due to chest wall distortion, differences in sleep-state, and alteration in the distribution of body fluids, resulting in a change in lung water. Any or all of these mechanisms may result in an unstable lung, even in an apparently clinically stable very low-birth weight infant.

Airway Resistance↗

Reference values of the bioelectrical impedance vector in neonates in the first week after birth.

OBJECTIVE: To determine the reference, bivariate, tolerance intervals of the whole-body impedance vector for healthy white neonates, we performed an observational, cross-sectional study in two university hospitals. METHODS: The impedance vector (standard, tetrapolar analysis at 50-kHz frequency) was measured in 163 consecutive subjects (87 boys and 76 girls) with postnatal ages of 1 to 7 d. Bivariate vector analysis was conducted with the resistance-reactance (RXc) graph method. RESULTS: The age-specific 95% confidence intervals of mean vectors and the 95%, 75%, and 50% tolerance intervals for individual vector measurements were plotted using R and Xc components standardized by the subject's crown-to-heel length (height). Mean vectors from the groups (1, 2, and 3 to 7 d) with overlapping 95% confidence ellipses were considered representative of only one age class of 1 to 7 d. The impedance vector distribution of neonates also was compared with healthy white children (1014 boys and 1030 girls, age 2-15 y) and adult subjects (354 men and 372 women, age 15-85 y) from the same geographic area. There was a definite, progressive, vector shortening from birth, through ages 2 to 15 y, toward the adults' vector position. CONCLUSIONS: We established the reference, bivariate, 95%, 75%, and 50% tolerance intervals of the impedance vector in the first postnatal week for healthy white neonates, with which the vectors from infants with altered body composition can be tested (free software is available from apiccoli@ unipd.it).

Adolescent↗

Enzymes involved in protein transmission by the intestine of the newborn lamb.

The intestine of lambs killed immediately after birth and at intervals after the first feed was studied by electron microscope cytochemistry. Ferritin, incorporated into this feed, was found within 2 h of feeding within vesicles throughout the cytoplasm of enterocytes lining the proximal and mid-intestine. Some of these vesicles had fused with the lateral and basal membranes of the enterocytes. Histochemical reaction products for alkaline phosphatase and a series of lysosomal enzymes were localized within the vesicles; the distribution of acid hydrolases, however, was not uniform within each cell. Biochemical estimations of the activity of these enzymes showed greatest activity in the distal intestine of the newborn lamb. The activity of only one of these enzymes, N-acetyl-beta-glucosaminidase, was maximal in the mid-intestine. These observations indicate that cytoplasmic vesicles, translocating proteins across the enterocyte, probably carry intestinal alkaline phosphatase activity in their limiting membrane. Lysosomal enzymes, particularly glucosaminidase, are introduced into these vesicles as they traverse the enterocytes of the mid-intestine. A less specialized complement of lysosomal enzymes is probably introduced into vesicles in the distal intestine where ingested protein may be digested, rather than transported across the cell.

Acid Phosphatase↗

Maternal pattern of reproduction and risk of breast cancer in daughters: results from the Utah Population Database.

BACKGROUND: Several studies have found that daughters born to older mothers have an elevated risk of breast cancer, and an endocrine hypothesis, among others, has been developed to explain these findings. Three recent studies have failed to find a consistent maternal age effect, indicating a need for further exploration of this issue. PURPOSE: We used Utah breast cancer records linked to genealogical records to investigate maternal and paternal age and other maternal reproductive factors in relationship to the daughter's risk of breast cancer. METHODS: The study group consisted of 2414 breast cancer case patients and 9138 individually matched control subjects. Breast cancer diagnoses were ascertained through the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The case patients and control subjects were born between 1875 and the end of 1947, and the mean age at diagnosis of the case patients was 65.9 years. RESULTS: No consistent effect for maternal or paternal age was found, except possibly among women who were firstborn children (odds ratio [OR] = 1.42 for a 10-year differential in maternal age; 95% confidence interval [CI] = 1.00-2.00). Further examination of the data indicated that mothers of case patients experienced long intervals between marriage and their first birth but not between subsequent births, and they went on to have fewer children. For each year of delay between the mother's marriage and first birth, the odds of breast cancer in the daughter increased 1.05-fold (95% CI = 1.01-1.10). CONCLUSIONS: We found no evidence of a consistent maternal age effect with regard to breast cancer risk in the daughter, but we did find evidence that the mothers of women who go on to get breast cancer have a reproductive pattern that could suggest some form of underlying infertility. IMPLICATIONS: These findings widen the epidemiologic support for the fetal antigen hypothesis, which is an immunogenetic explanation for the relationships between reproductive factors and breast cancer risk. That hypothesis provides strategies for the identification of breast cancer genes and the eventual development of a breast cancer vaccine.

Aged↗

Breast cancer risk in Ashkenazi BRCA1/2 mutation carriers: effects of reproductive history.

BACKGROUND: Younger age at first birth and greater parity generally reduce the risk of developing breast cancer, but whether this reduced risk holds in women with a mutation in the BRCA1 or BRCA2 gene is unknown. METHODS: In a Washington DC community-based study conducted in 1996, we tested 5318 Ashkenazi Jews for three BRCA1/2 founder mutations and identified 120 mutation carriers. Applying an extension of the "kin-cohort" analysis, we compared the effects of reproduction on breast cancer risk in carriers and noncarriers. We also used a case-case analysis among 288 participants who had been diagnosed with breast cancer. RESULTS: In noncarriers, the estimated relative risk (RR) of breast cancer rose 5% with each 5-year increment in age at first birth (RR = 1.05; 95% confidence interval [CI] = 0.97-1.15). By contrast, the estimated risk in mutation carriers fell with each 5-year increment in age (RR = 0.65; 95% CI = 0.37-1.16). Among the 288 participants who were breast cancer survivors themselves, the comparison of carriers with noncarriers also showed no protection associated with early birth in the presence of a mutation in BRCA1 or BRCA2. CONCLUSIONS: It is not yet clear whether the recognized breast cancer risk factors operate in the same way in women who carry a mutation in the BRCA1 or BRCA2 genes.

Adult↗

Signal content of red facial coloration in female mandrills (Mandrillus sphinx).

Studies of secondary sexual ornamentation and its maintenance by sexual selection tend to focus on males; however, females may also possess showy ornaments. For example, female mandrills possess facial coloration that ranges from black to bright pink. We used fortnightly photographs of 52 semi-free-ranging females aged above 3years over 19 months to evaluate whether colour conveys information concerning female competitive ability, reproductive quality, age or reproductive status. Colour was not related to female rank or quality (body mass index, age at first birth or mean inter-birth interval); however, colour did increase significantly with age and primiparous females were darker than multiparous females. Colour may therefore signal reproductive quality, as younger females are less fertile and produce smaller offspring. Colour was brighter during the follicular phase than during the luteal phase, suggesting that it may signal fertility. Colour also varied across gestation and peaked at four and eight weeks post-parturition, suggesting that it may signal approaching parturition and lactation. Future studies should examine the relationship between colour and the menstrual cycle in more detail, the hormonal basis of female colour, and determine experimentally whether mandrills of both sexes attend to differences in colour between and within females.

Aging↗

The impact of family planning on women's health.

Approximately half a million women in developing countries die each year as a result of complications during pregnancy. Sadly, illegal abortion is one of the five major causes of these deaths. International data suggest that maternal mortality is decreasing in regions where the use of family planning is increasing because of the consequent avoidance of unwanted pregnancies, although accurate data on maternal mortality are difficult to obtain in most developing countries. Use of family planning to delay first births and to increase interpregnancy intervals has the potential to decrease infant mortality by at least 20%. Data from developing countries show that some of this potential has already been realized during the past 20 years, but additional improvement is possible. In countries where maternal mortality is low, women may avoid using contraceptives because of the perceived dangers of the most effective methods. Recent analyses show that cardiovascular risks associated with oral contraceptives are low, and that the net effect of oral contraceptives on cancer of the ovary and endometrium is one of protection. While there remain unanswered questions regarding cervical and breast cancer, the net effect is small at worst.

Abortion, Illegal↗

Intraocular pressure in premature babies in the first month of life.

PURPOSE: The purpose of this work was to study the values of intraocular pressure (IOP) in premature babies during the first month of life. METHODS: Using a hand-held applanation tonometer, IOP was measured in 40 eyes of 20 preterm infants (gestational age ranging from 26 to 32 weeks) shortly after birth and at weekly intervals for the first month of life. RESULTS: IOP values in preterm infants ranged from 7.6 to 18.3 mm Hg. The mean IOP decreased during the study period from 13.25+/-2.86 mm Hg to 10.96+/-2.01 mm Hg (P< .001). CONCLUSIONS: Although the values of IOP found in this study are by no means within the range that is considered to be pathologic for newborns, the possible lack of the decreasing tendency of IOP observed during the first month of life could have, in a given case, some clinical implications. Because systemic blood pressure in preterm infants is already quite low, even a moderately elevated IOP during the first weeks of life might in some cases result in a significant reduction of the ocular perfusion pressure. The latter might play a contributory role in the development of retinopathy of prematurity by decreasing the blood supply to the peripheral retinal tissues.

Circadian Rhythm↗

Shared HLA antigens and reproductive performance among Hutterites.

Shared histocompatibility antigens between spouses may affect reproductive outcome adversely as a result of prenatal selection against compatible fetuses. Evidence from both animal and human studies suggest that histocompatible fetuses may not initiate a maternal immunologic response that prevents rejection of the embryo. Therefore, parents sharing HLA antigens may produce compatible fetuses and consequently experience a greater frequency of early fetal losses and show poorer reproductive outcome than couples not sharing antigens. In the Hutterites, an inbred human isolate that proscribes contraception, we tested the hypothesis that couples sharing HLA antigens have poorer reproductive outcomes than couples who do not. The Hutterites are characterized by high fertility and large family sizes. Couples that share zero (no. = 21), one (no. = 15), and more than one (no. = 10) HLA-A or HLA-B antigens were compared for reproductive performance. Median intervals between births were larger among couples that share more than one antigen in eight of 11 intervals examined. In addition, the median intervals from marriage to first, fifth, and tenth birth were consistently larger among couples that share more than one antigen. Differences among the groups appear to become larger with increasing parity, suggesting that the effect of histocompatibility on reproductive performance becomes more evident in later pregnancies. These differences in reproductive performance between couples that share zero, one, or more than one HLA-A or HLA-B antigens may have significant evolutionary consequences. However, our results demonstrate that sharing HLA antigens does not preclude normal pregnancy and caution should be exercised before concluding that shared HLA antigens are solely responsible for repeated fetal losses.

Birth Intervals↗

Effects on pregnancy outcome of changing partner between first two births: prospective population study.

OBJECTIVE: To compare the effects on pregnancy outcomes of changing partner between the first two births with having the same partner for both births. DESIGN: Prospective population study. SETTING: Norway. PARTICIPANTS: 31 683 women who changed partner between their first two births and 456 458 women with the same partner for both births. RESULTS: After adjustment for maternal age and education, interval between births, and decade of birth, the risk of adverse pregnancy outcomes for the second birth was higher for women who changed partner between the first two births compared with those who had the same partner for both births: preterm birth (< 37 weeks; relative risk 2.0, 95% confidence interval 1.9 to 2.1), low birth weight (< 2500 g; 2.5, 2.3 to 2.6), and infant mortality (1.8, 1.6 to 2.1). For the first birth, the risk of these adverse pregnancy outcomes was only slightly higher for mothers who subsequently had a second birth with another partner. CONCLUSION: Women who change partner between their first two births are at an increased risk of delivering a preterm, low birthweight baby with an increased risk of infant mortality compared with women who have the same partner for both births.

Birth Order↗

Neonatal intraventricular hemorrhage: a serial computed tomography study.

Thirty infants weighing less than 1,500 g at birth and requiring assisted ventilation were studied by computed tomography (CT) as soon as possible after birth and at intervals thereafter. Hemorrhage were frequently detected within the first 48 hr of birth. Two infants had normal scans initially but developed intraventricular hemorrhage later. One infant had subependymal hemorrhage that later ruptured into the ventricles. Six deaths were due directly to intracranial hemorrhages. Hydrocephalus developed in seven and atrophy in two survivors. There was poor correlation between CT scan and clinical evidence of intracranial hemorrhage.

Brain Diseases↗

Effects of twinning on postpartum reproductive performance in cattle selected for twin births.

The effects of twinning, dystocia, retained placenta, and body weight on postpartum reproduction were evaluated for 3,370 single and 1,014 twin births. Females were bred by AI for 40 d followed by 20 or 30 d of natural service with equal numbers bred and calved in spring and fall. Percentage of dams cyclic by the end of the AI period was lower (P<.05) for dams birthing and nursing a single calf (92.4%) than for dams birthing twins and nursing zero (98.7%) or two (94.7%) calves. Whereas the interval from parturition to first estrus was shorter (P<.01) for dams birthing and nursing a single (56.9 d) than for dams birthing twins and nursing one (68.5 d) or two (69.6 d) calves, length of the interval was further reduced by dystocia in nonlactating dams of either twins or singles (type of birth x dystocia, P<.05). Ensuing pregnancy rates were also affected by type of birth and dystocia. Without dystocia, dams birthing and nursing a single calf had a higher pregnancy rate (79.2%) than dams birthing twins and nursing one (61.7%) or two (66.3%) calves, whereas the lower ensuing pregnancy rates associated with dystocia in dams of singles (71.9%) resulted in similar rates among dams of singles and twins with dystocia (type of birth x dystocia; P<.01). Having a retained placenta resulted in a lower incidence of (93.5 vs. 96.4%, with vs. without; P<.05) and a longer interval to (64.7 vs. 59.2 d; P<.01) estrus while reducing subsequent pregnancy rates (X = 9.6%) in 3 of the 7 yr evaluated (retained placenta x year, P<.01). Because all parous females were bred during the same calendrical period, the shorter gestation length for twin calves (275.6 vs. 281.3 d) resulted in a longer interval from parturition to conception for twin births, whereas means for conception date differed by only 2 d between dams of twins and singles. Furthermore, a reduction (P<.01) in the interval to conception occurred with dystocia in dams of singles (89.3 vs. 85.0 d, without vs. with dystocia) and of twins nursed by zero (116.9 vs. 83.5 d), one (100.2 vs. 92.8 d), or two (96.1 vs. 97.2 d) calves. Another detriment to fertility was the higher incidence of fetal mortality or abortions associated with twin vs. single pregnancies (12.4 vs. 3.5%; P<.01). However, despite the lower conception rates for dams of twins, the increased prolificacy provides an opportunity to increase total beef production with a twinning technology.

Animals↗

[Birth order, behavioural problems, and the mother-child relationship in siblings aged 4 to 11 years from a 2-child family].

UNLABELLED: Birth Order, Behavioural Problems, and the Mother-Child Relationship in Siblings Aged 4 to 11 Years From a 2-Child Family OBJECTIVE: This study was designed to define the relation between some sibling characteristics (birth order, sex, and interval between successive births) and some behavioral problems in children, on the one hand, and certain dimensions of the mother-child relationship, on the other hand. METHOD: The sample, from National Longitudinal Survey of Children and Youth, included 1,196 families with 2 biological children aged 4 to 11 years. Behavioural problems and dimensions of the mother-child relationship were assessed by mothers. Repeated-measures multivariate analyses of variance were conducted. RESULTS: Analyses showed that first-born children have more internalized symptoms than second-born children. Second-born children also have more positive interactions with their mothers than first-born children. The interval between successive births does not affect these results. CONCLUSION: Several differences emerged between siblings. Health professionals should take these findings into account in their clinical assessments.

Birth Order↗