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Risk of breast cancer after miscarriage or induced abortion: a Scottish record linkage case-control study.

STUDY OBJECTIVE: To assess the risk of breast cancer in patients with a previous history of miscarriage or induced abortion. DESIGN: Case-control study relating "exposure" to outcome by linkage of national hospital discharge and maternity records, the national cancer registry, and death records. SETTING: Scotland. PARTICIPANTS: Miscarriage analysis-2828 women with breast cancer and 9781 matched controls; induced abortion analysis-2833 women with breast cancer and 9888 matched controls. MAIN RESULTS: After stratification for age at diagnosis, parity, and age at first birth, the odds ratio (95% confidence intervals) of breast cancer was 1.02 (0.88 to 1.18) in women with a previous miscarriage, and 0.80 (0.72 to 0.89) in women with a previous induced abortion. Further adjustments for age at bilateral oophorectomy, socioeconomic status (based on small area of residence), and health board area of residence had only minor effects on these odds ratios. CONCLUSION: These data do not support the hypothesis that miscarriage or induced abortion represent substantive risk factors for the future development of breast cancer.

Abortion, Induced↗

Early development of the thyroid axis in the Brattleboro rat.

Plasma concentrations of thyrotrophin (TSH), thyroxine (T4), and triiodothyronine (T3), and pituitary TSH concentrations were determined at weekly intervals during the first 42 days following birth in Brattleboro homozygous (DI), Brattleboro heterozygous (HZ), and Long-Evans (LE) rats. Offspring from matings of Brattleboro rats were divided into DI and HZ animal subgroups on the basis of hypothalamic vasopressin content. In control LE rats, circulating levels of TSH, T4, and T3, and pituitary TSH concentrations increased during the early postnatal period to reach relatively stable levels between 28 and 42 days of age. In DI and HZ rats, the thyroid axis developed in parallel to that of LE rats during initial postnatal weeks. However, by 42 days of age, pituitary TSH concentrations were clearly elevated in Brattleboro rats relative to levels in age-matched LE animals. These data indicate that differences in thyroid axis function between Brattleboro and LE rats occur only after the attainment of a degree of maturity.

Animals↗

Development of the hypothalamic-pituitary-thyroid axis in the neonatal rat.

The hypothalmic content of thyrotropin-releasing hormone (TRH), the pituitary concentration of thyroid-stimulating hormone (TSH), and the serum concentrations of TSH, thyroxine (T4), and triiodothyronine (T3) have been determined at different intervals during the first 50 days following birth in the rat. From a minimum concentration of 1 pg/mug protein at birth, the hypothalamic concentration of TRH increased to a maximum of 5 to 6 pg between 16 and 28 days of age. Serum and pituitary TSH concentrations increased to maximum levels by the end of the first post-natal week; the elevated hormone levels were then maintained to the end of the third post-natal week. Circulating thyroid hormone concentrations were very low at birth. T4 increased rapidly between days 4 and 16 to reach a peak concentration of 6 mug/100 ml, while T3 followed a parallel pattern with a peak concentration of 108 ng/100 ml obtained only at day 28. These data indicate that, in the rat, components of the hypothalamic-pituitary-thyroid axis develop simultaneously during the post-natal period.

Aging↗

Transcutaneous bilirubin levels in the first 96 hours in a normal newborn population of > or = 35 weeks' gestation.

OBJECTIVE: To obtain transcutaneous bilirubin (TcB) measurements, at 6-hour intervals, in the first 96 hours after birth in a normal newborn population (gestational age: > or =35 weeks). METHODS: We performed 9397 TcB measurements on 3984 healthy newborn infants (gestational age: > or =35 weeks) from 6 to 96 hours of age. All measurements were performed in the well-infant nursery with a Draeger Air-Shields transcutaneous jaundice meter (model JM-103), within 2 hours of the designated time. RESULTS: There was a distinct pattern to the velocity of the increase in TcB levels over different time periods. TcB levels increased in a linear manner most rapidly in the first 6 to 18 hours and then less rapidly from 18 to 42 hours, followed by a much slower increase until peak levels occurred. Decreasing gestational age was associated significantly with higher TcB levels. CONCLUSIONS: We provide data on neonatal bilirubinemia, based on TcB levels determined in a large, predominately white and breastfed, North American population. Infants who require closer evaluation and observation initially are those whose bilirubin levels are > or =95th percentile, ie, increasing more rapidly than 0.22 mg/dL per hour in the first 24 hours, 0.15 mg/dL per hour between 24 and 48 hours, and 0.06 mg/dL per hour after 48 hours. These data should be useful for detecting aberrant trends, identifying infants who need additional evaluation, and planning appropriate follow-up for jaundiced newborns.

Bilirubin↗

Central opioids: a possible role in parturition?

Pregnant rats were implanted with subcutaneous minipumps to deliver either naloxone or saline. The time-course of subsequent parturition was different between the two groups: the interval between successive births was significantly shorter for the naloxone-treated rats. This supports the hypothesis that the opioid innervation of the neurohypophysis, which is known to influence oxytocin release profoundly, has a physiological role in parturition. To test the further hypothesis that this role is particularly important in a stressful environment, pregnant rats, again implanted with minipumps, were regularly transferred, at 15-min intervals beginning with the birth of the first pup, between their normal cage and the unfamiliar environment of a glass observation chamber. No difference was noted between the time-courses of parturition for the naloxone- and saline-treated groups, although the time-courses were markedly altered from those observed in rats not subjected to an unfamiliar environment. We conclude that opioid modulation of oxytocin release may play a role in 'spacing' the delivery of successive births during normal parturition.

Animals↗

Long-term impact of reproductive factors on the risk of cervical, endometrial, ovarian and breast cancer.

The influence of maternal age, parity, low or high birthweight, multiple births, and pre-eclampsia on the risk of cervical, endometrial, ovarian and breast cancers was studied. Data on 40951 women and the outcomes of their deliveries between 1955 and 1995 were obtained from birth registers. For the mothers, data from the Swedish Cancer Registry and the Cause of Death Register were added. The sample was evaluated using Cox's regression in univariate and bivariate analyses where the relative risk and its 95% confidence interval were calculated. Increasing maternal age at first birth was associated with an increasing relative risk of endometrial, ovarian, and breast cancers, and with a decreased risk of cervical cancer. Multiparity was a protective factor for all gynaecological cancers, including cervical and breast cancers. Multiple births were associated with an increased risk of endometrial cancer.

Adolescent↗

Educational expansion and changes in entry into marriage and motherhood. The experience of Italian women.

"The purpose of this paper has been to assess empirically the question of whether women's growing economic independence, resulting from better education, is one of the major factors in determining the timing of marriage and motherhood in Italy.... We have analysed the life histories of a sample of Italian women from different cohorts, collected on the occasion of the National Survey on Family Structures and Behaviours carried on by the National Institute of Statistics.... The effect of level of education is negative. That is, it increases the age of entry into marriage. However, the size of the effect is small and seems limited to the passage from youth to adulthood, because the longer time the woman spends in the educational system increases the age at which she feels herself ready to marry. As far as the timing of the first child, it is almost independent of educational attainment, once marital status is taken into account." (SUMMARY IN FRE AND ITA)

Birth Intervals↗

[Change of partner between births and adverse pregnancy outcomes].

BACKGROUND: Childbearing with different fathers has increased in western societies because of the higher frequency of divorce and remarriage. Pregnancy outcomes may differ between mothers who have changed partner between first and second birth and mothers who have the same father for both births. Women who change partner may have individual characteristics that increase risk of adverse outcomes, but change of partner could also be associated with unfavourable changes in behaviour. MATERIAL AND METHODS: The Medical Birth Registry of Norway was established in 1967 and includes information on approximately 1.8 million births until 1998. Both parents are recorded. We have compared pregnancy outcomes for 30 176 mothers who changed partner between first and second birth and 461 154 mothers who had the same partner for both births. RESULTS: In relation to the first birth, the risk of adverse pregnancy outcomes was not clearly different between mothers who later had a second birth with another partner and mothers who had the same partner for both births. Offsprings of mothers who changed partner between first and second birth were at higher risk of infant mortality (relative risk 1.5, 95 % confidence interval, 1.3-1.7), preterm birth (< 37 weeks; relative risk 1.3, 95 % confidence interval, 1.2-1.4), and low birth weight (< 2500 gram; relative risk 1.5, 95 % confidence interval, 1.4-1.6), after adjustment for maternal age and level of education, interval between births, and time period. INTERPRETATION: Mothers who change partner between first and second birth are at increased risk of having a preterm, low birth weight baby with increased risk of infant death for the second child compared to mothers who have the same partner for both births.

Birth Order↗

Breast cancer risk by age at birth, time since birth and time intervals between births: exploring interaction effects.

In a Norwegian, prospective study we investigated breast cancer risk in relation to age at, and time since, childbirth, and whether the timing of births modified the risk pattern after delivery. A total of 23,890 women of parity 5 or less were diagnosed with breast cancer during follow-up of 1.7 million women at ages 20-74 years. Results, based on Poisson regression analyses of person-years at risk, showed long-term protective effects of the first, as well as subsequent, pregnancies and that these were preceded by a short-term increase in risk. The magnitude and timing of this adverse effect differed somewhat by birth order, maternal age at delivery and birth spacing. No transient increase in risk was seen shortly after a first birth below age 25 years, but an early first birth did not prevent a transient increase in risk after subsequent births. In general, the magnitude of the adverse effect was strongest after pregnancies at age 30 years or older. A wide birth interval was also related to a more pronounced adverse effect. Increasing maternal age at the first and second childbirth was associated with an increase in risk in the long run, whereas no such long-term effect was seen with age at higher order births.

Adult↗

[Effect of birth interval on the rate of cesarean section for the second twin after vaginal delivery of the first twin].

Cesarean section for delivery of the second twin after successful vaginal delivery of the first twin is an infrequent and unusual occurrence. But this management of twin delivery has increased during the last years. A series of 371 pairs of twins born between 1978 and 1991 were reviewed. 12 second twins (3.2%) were delivered by cesarean section after vaginal delivery of the first twin. The initial 20 minutes the main indications were fetal distress and prolapsed umbilical cord. Beyond the first 20 minutes malpresentations were more frequent. In this group we have seen a better fetal outcome. An influence of the interdelivery time on the cesarean section rate of the second twin was not noted. No significant differences were seen for neonatal morbidity for all 197 vaginal delivered second twins with increasing interval.

Acid-Base Equilibrium↗

Consanguineous marriage in Turkey and its impact on fertility and mortality.

Turkey has a high rate of consanguineous marriage (21.1%), indicating strong preference for this traditional form of marital union. Social and cultural factors are especially important in marriages between first and second cousins. Fertility is high, the closed birth interval is long, and the sterility rate is low among these couples. Post-neonatal, infant and under-5 mortalities are high in first cousin unions by comparison with non-consanguineous marriages. According to the results of the study, first cousin marriage is a significant determinant underlying the high total fertility and infant mortality rates in Turkey.

Adolescent↗

Progress of farrowing and early postnatal pig behavior in relation to genetic merit for pig survival.

The objective of this study was to investigate whether pigs with different genetic merit for survival differed in birth weight, progress of farrowing, early postnatal behavior, or rectal temperature within 24 h after birth. On a nucleus farm in Rio Verde, Brazil, information was collected on 280 pigs, originating from 25 litters with known estimated breeding values for pig survival (EBVps). Litters were selected in such a way that a continuous range of EBVps with a maximum genetic contrast was achieved. Birth weight was recorded for all pigs. Indicators for progress of farrowing were birth intervals and duration of farrowing. Behavioral indicators of pig vitality were time until first upright standing (FUS), time until first udder contact (FUC), time until first teat in mouth (FTM), and time until first colostrum uptake (FCU). Rectal temperature was measured within 24 h after birth. Farrowing survival and early postnatal survival (within 3 d after farrowing) were registered. Farrowing survival and early postnatal survival both increased with increasing EBVps (farrowing survival: P = 0.007; early postnatal survival: P = 0.027). Birth weight decreased with increasing EBVps (P = 0.01). Birth intervals tended to increase with increasing EBVps (P = 0.10) and duration of farrowing was not related to EBVps. Time until first teat in mouth increased with increasing EBVps (P = 0.05), but the other behavioral indicators of pig vitality were not related to EBVps. Rectal temperature within 24 h after birth was not related to EBVps. Pigs with a higher genetic merit for survival have a lower birth weight but nevertheless have an increased farrowing survival and early postnatal survival. Their increased survival cannot be explained by differences in progress of farrowing, early postnatal behavior, or rectal temperature within 24 h after birth.

Animals↗

Changing paternity and the risk of preeclampsia/eclampsia in the subsequent pregnancy.

To determine whether changing paternity affects the risk of preeclampsia or eclampsia in the subsequent pregnancy and whether the effect depends on a woman's history of preeclampsia/eclampsia with her previous partner, a cohort study was conducted based on 140,147 women with two consecutive births during 1989-1991 identified through linking of annual California birth certificate data. Among women without preeclampsia/eclampsia in the first birth, changing partners resulted in a 30% increase in the risk of preeclampsia/eclampsia in the subsequent pregnancy compared with those who did not change partners (95% confidence interval: 1.1, 1.6). On the other hand, among women with preeclampsia/eclampsia in the first birth, changing partners resulted in a 30% reduction in the risk of preeclampsia/eclampsia in the subsequent pregnancy (95% confidence interval: 0.4, 1.2). The difference of the effect of changing paternity on the risk of preeclampsia/eclampsia between women with and those without a history of this condition was significant (p < 0.05 for the interaction term). The above estimates were adjusted for potential confounders. These findings suggest that the effect of changing paternity depends on the history of preeclampsia/eclampsia with the previous partner and support the hypothesis that parental human leukocyte antigen sharing may play a role in the etiology of preeclampsia/eclampsia.

Adult↗

Effects of infant feeding practices and birth spacing on infant and child survival: a reassessment from retrospective and prospective data.

Retrospective and prospective data collected in Cameroon were used to reassess hypotheses about how infant and early childhood mortality is affected by birth spacing and breast-feeding. These data show that: (a) a short preceding birth interval is detrimental for child survival in the first 4 months of life; (b) full and partial breast-feeding have direct protective effects on child survival in the first 4-6 months of life, with the effects of the former stronger than those of the latter; (c) early subsequent conception significantly increases mortality risks in the first 16 months of life of the index child. These findings are robust to various controls, e.g. study design, data defects, child's health conditions at/around birth, postnatal maternal and child recurrent illnesses, patterns of utilisation of health care services, and immunisation status of the child.

Birth Intervals↗

A prospective study of reproductive factors and risk of epithelial ovarian cancer.

BACKGROUND: Parity and long term use of oral contraceptives have been associated consistently with a decreased risk of ovarian cancer. However, previous reports of the relationship of other reproductive factors (time since first use or last use of oral contraceptives, age at menarche or menopause, age at first birth) with ovarian cancer have been inconsistent. METHODS: The authors studied these relationships in the Nurses' Health Study, a prospective cohort study of 121,700 female registered nurses aged 30-55 years in 1976 when the study began. From 1976 to 1988, 260 cases of confirmed epithelial ovarian cancer occurred among 1.2 million person-years of follow-up. RESULTS: A statistically significant inverse association was observed between parity and ovarian cancer risk (relative risk [RR] = 0.84; 95% confidence interval [CI] = 0.77-0.91 per pregnancy); age at first birth was not associated independently with risk. In age-adjusted analyses, a significant inverse association was noted between long term use of oral contraceptives and ovarian cancer, which was no longer significant after controlling for other ovarian cancer risk factors (RR with > or = 5 years' use: 0.65; 95% CI = 0.40-1.05). After control for duration of use, a weak nonsignificant inverse association was observed with time since first oral contraceptive use and no independent effect of time since last use. Neither age at menarche nor age at menopause was associated significantly with ovarian cancer risk. CONCLUSIONS: In this large prospective study, parity was the only reproductive factor that had a substantial independent association with ovarian cancer. Long term oral contraceptive use also appeared to have an inverse relationship with ovarian cancer, although this association was of borderline significance (P = 0.11) after adjustment for other risk factors.

Age Factors↗

Previous cesarean delivery and risks of placenta previa and placental abruption.

OBJECTIVE: To examine the association between cesarean delivery and previa and abruption in subsequent pregnancies. METHODS: A retrospective cohort study of first 2 (n = 156,475) and first 3 (n = 31,102) consecutive singleton pregnancies using the 1989-1997 Missouri longitudinally linked data were performed. Relative risk (RR) was used to quantify the associations between cesarean delivery and risks of previa and abruption in subsequent pregnancies, after adjusting for several confounders. RESULTS: Rates of previa and abruption were 4.4 (n = 694) and 7.9 (n = 1,243) per 1,000 births, respectively. The pregnancy after a cesarean delivery was associated with increased risk of previa (0.63%) compared with a vaginal delivery (0.38%, RR 1.5, 95% confidence interval [CI] 1.3-1.8). Cesarean delivery in the first and second births conferred a two-fold increased risk of previa in the third pregnancy (RR 2.0, 95% CI 1.3-3.0) compared with first two vaginal deliveries. Women with a cesarean first birth were more likely to have an abruption in the second pregnancy (0.95%) compared with women who had a vaginal first birth (0.74%, RR 1.3, 95% CI 1.2-1.5). Two consecutive cesarean deliveries were associated with a 30% increased risk of abruption in the third pregnancy (RR 1.3, 95% CI 1.0-1.8). A second pregnancy within a year after a cesarean delivery was associated with increased risks of previa (RR 1.7, 95% CI 0.9-3.1) and abruption (RR 1.5, 95% CI 1.1-2.3). CONCLUSION: A cesarean first birth is associated with increased risks of previa and abruption in the second pregnancy. There is a dose-response pattern in the risk of previa, with increasing number of prior cesarean deliveries. A short interpregnancy interval is associated with increased risks of previa and abruption. LEVEL OF EVIDENCE: II-2.

Abruptio Placentae↗

Reproduction in high altitude Aymara: physiological stress and fertility planning?

Reproductive characteristics at high altitude are described based on the reproductive histories of 720 Aymara women, collected in 1998 and 1999 in a group of twelve peasant communities at a mean altitude of 4000 m in the Bolivian Altiplano. The reproductive pattern is shaped by a late onset of childbearing, associated with a rather short reproductive span and large birth intervals. Environmental conditions could explain the particularly late age at menarche of rural girls compared with their urban counterparts, whereas the age at first birth is likely to be under cultural control. The short reproductive span appears to result from a large mean interval between last birth and menopause, which is essentially determined by cultural decisions. The birth intervals, which are longer than in many traditional societies, could be the result of a slower restoration of postpartum fecundability induced by the hard way of life inherent in the Altiplano (including poor sanitary and nutritional conditions and high workload), perhaps aggravated by hypoxia. However, a secular trend in fertility is perceptible, towards earlier menarche, earlier age at first birth, increasing reproductive span and a slight increase in live births and surviving offspring, which is probably the result of a slow improvement in living conditions. The existence of birth control on the one hand, and a total fertility rate averaging six live births among the couples who do not practise contraception on the other, are other arguments against the hypothesis of a low natural fecundity in these Aymara groups.

Adolescent↗

Fertility patterns after appendicectomy: historical cohort study.

OBJECTIVE: To examine fertility patterns in women who had their appendix removed in childhood. DESIGN: Historical cohort study with computerised data and fertility data for this cohort and for an age matched cohort of women from the Swedish general population. The cohorts were followed to 1994. SETTING: General population. PARTICIPANTS: 9840 women who were under 15 years when they underwent appendicectomy between 1964 and 1983; 47 590 control women. MAIN OUTCOME MEASURES: Diagnoses at discharge. Distributions of age at birth of first child among women with perforated and non-perforated appendix and women who underwent appendicectomy but were found to have a normal appendix compared with control women by using survival analysis methods. Parity distributions at the latest update of the registry were also examined. RESULTS: Women with a history of perforated appendix had a similar rate of first birth as the control women (adjusted hazard ratio 0.95; 95% confidence interval 0.88 to 1. 04) and had a similar distribution of parity at the end of follow up. Women who had had a normal appendix removed had an increased rate of first births (1.48; 1.42 to 1.54) and on average had their first child at an earlier age and reached a higher parity than control women. CONCLUSION: A history of perforated appendix in childhood does not seem to have long term negative consequences on female fertility. This may have important implications for the management of young women with suspected appendicitis as the liberal attitude to surgical explorations with a subsequently high rate of removal of a normal appendix is often justified by a perceived increased risk of infertility after perforation. Women whose appendix was found to be normal at appendicectomy in childhood seem to belong to a subgroup with a higher fertility than the general population.

Adolescent↗