Search

Study Question: Is the death of a child associated with higher subsequent fertility?Summary Answer: Women who had lost a child had higher fertility both shortly after the loss and throughout the entire follow-up, independent of the child's age at the time of death.What Is Known Already: Women who lose a child in the perinatal period often have another child shortly after. However, to our knowledge no previous study has investigated if the death of an older child affects reproductive behavior.Study Design, Size, Duration: The source population for this matched cohort study consisted of all women who gave birth in Denmark from 1978 to 2004 and in Sweden from 1973 to 2002 (N = 1 979 958). Women were followed through to the end of 2008 in Denmark and the end of 2006 in Sweden.Participants/materials, Setting, Methods: Women who had lost a child before the age of 45 years during the study period (exposed group; n = 36 511) were matched with up to five women who were from the same country and of similar age and family characteristics and had not lost a child at the time of matching (unexposed group; n = 182 522).Main Results and the Role Of Chance: During follow-up, 74% of exposed and 46% of unexposed women had another birth (live- or stillbirth) after a gestation of 28 weeks or more. Compared with unexposed women, exposed women had a shorter interpregnancy interval and, consequently, a higher rate of conception leading to a birth (HR = 5.5 [95% CI: 5.4-5.6]). Rates for exposed women were higher from the first month following the child's death, but the largest difference was between 2 and 3 months after the event. This pattern was independent of the age of the deceased child. Exposed women had more subsequent children than unexposed, leading to a comparable number of living children at the end of follow-up.Limitations, Reasons For Caution: The use of population-based registers allows for the inclusion of virtually all eligible women and nearly complete follow-up; the potential for selection bias is thus negligible. However, only pregnancies that led to a live birth or a stillbirth could be identified, thus fetal losses occurring before week 28 of gestation were missing.Wider Implications Of the Findings: Our findings corroborate the previous evidence suggesting that women try to conceive again shortly after a perinatal death, and many succeed. In addition, this is the first study to investigate the reproductive trajectory after losing an older child. The current study indicates that most women who lose a child between the ages of 6 months and 5 years conceive shortly after the loss, and they have a comparable number of living children at the end of the follow-up compared to those who do not lose a child.Study Funding/competing Interest(s): This work was supported by Grant ERC-2010-StG-260242 from the European Research Council, 176673 and 186200 from the Nordic Cancer Union, DFF-6110-00019 from the Danish Council for Independent Research, 904414 and 15199 from TrygFonden, Karen Elise Jensens Fond (2016), and the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation. The authors do not declare any conflicts of interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Objective: Using a simple simulation, we illustrate why associations estimated from studies restricted to preterm births cannot be interpreted causally.Design, Setting and Population: Data simulation involving a hypothetical cohort of fetuses who may be healthy or have one or more of four pathological factors (termed A through D, increasing in severity) with known effects on gestational length and risk of mortality. We focus on babies born at ≤32 weeks of gestation.Methods: We visually represent the simulated population and compare the association between A (which may represent pre-eclampsia) and neonatal death. We then repeat the exercise with D (standing in for chorioamnionitis) as the exposure of interest.Main Outcome Measures: Odds ratios of neonatal death in the simulated data.Results: In most weeks, and for both A and D, the calculated odds ratios are substantially biased and underestimate the true risk of neonatal death associated with each pathology. For example, factor A has a true causal odds ratio of 1.50, yet it appears protective among births ≤32 weeks (estimated crude odds ratio 0.39; gestational age-adjusted odds ratio 0.71).Conclusions: Among very preterm births, virtually all babies are born with pathologies that increase the risk of adverse outcomes. Hence, babies exposed to one factor (e.g. pre-eclampsia) are compared with babies who have a mix of other pathologies. Such selection bias affects studies carried out among very preterm births (e.g. where pre-eclampsia appears to reduce risk of adverse neonatal outcomes).Tweetable Abstract: Selection bias affects studies of preterm births, complicating interpretation. [ABSTRACT FROM AUTHOR]

Study Question: Does maternal age at a daughter's birth predict her subsequent probability of lifelong childlessness?Summary Answer: In this study population, women born to older mothers were more likely to be childless.What Is Known Already: Although maternal age at childbearing is increasing in many countries, there is limited evidence on whether being born to older parents may influence offspring fertility.Study Design Size and Duration: This analysis included 43 135 women from the US-based Sister Study, a cohort study of 50 884 sisters of women with breast cancer recruited between 2003 and 2009.Participants/materials, Setting, Methods: Participants had no breast cancer at baseline. Women were included in the analytic sample if they were born between 1930 and 1964 and were at least 44 years old at enrolment. Median age when reproductive history was last ascertained was 63.8 years. We estimated relative risks (RR) and 95% CI of lifelong childlessness as a function of maternal age at birth, using multivariable log-binomial models, including total number of siblings, birth order, socioeconomic indicators of the family of origin, race and birth cohort. We examined the association in different subgroups and in a sibling-matched analysis including 802 sister pairs discordant for childlessness.Main Results and Role Of Chance: Compared with women born to 20-24-year-old mothers, those born to mothers aged 25-29, 30-34 and ≥35 years were more likely to be childless [RR (95% CI): 1.21 (1.14-1.29), 1.30 (1.22-1.39) and 1.40 (1.31-1.50), respectively]. The association was consistent in strata defined by birth cohort, number of siblings, birth order, and participant's educational level, as well as within sister pairs. Overall, we found weak evidence for an independent contribution of paternal age at birth to the daughter's probability of childlessness.Limitations Reasons For Caution: All participants had at least one sister, and all information was self-reported. We had no knowledge of whether childlessness was intentional and found only a modest association between maternal age at birth and self-reported indicators of infertility. Still, the association with childlessness was highly consistent.Wider Implications Of the Finding: Given the widespread tendency to delay childbearing, evaluating the influence of maternal age at birth on offspring fertility is a public health priority.Study Funding/competing Interests: This research was supported in part by the Intramural Research Programme of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005). The authors report no conflict of interest. [ABSTRACT FROM AUTHOR]

Objective:An individual's growth trajectory is, at least in part, inherited. Mother's early age at menarche has been associated with taller offspring height and greater body mass index (BMI) at age 9 years, suggesting that mother's age at menarche may be an intergenerational marker of growth. We examined the association between mother's age at menarche and childhood size at birth, and at ages 1, 3, 4, 7 and 8 years in the Collaborative Perinatal Project.Subjects:We examined 128 636 measurements obtained from 31 474 Black and White children. We transformed the original measurements into z-scores. Child size was examined in mixed models, adjusted for center, child sex, race, socioeconomic index, child's exact age at measurement (in months), mother's age at recruitment and, depending on which measure was the outcome in the specific model, mother's height, pre-pregnancy weight or BMI.Results:Compared with children whose mother had menarche at age 15 years or later, children whose mothers had age at menarche before age 12 years were taller from 1 year of age and had higher BMI, particularly at ages 7 and 8 years (0.17 and 0.19 z-score units, respectively).Conclusions:Mothers' age at menarche is a modest predictor of their children's growth trajectory. The mechanism is likely to be heritable, although other explanations are possible. [ABSTRACT FROM AUTHOR]

The more men by whom a woman has children, the more diverse will be the foetal antigens of paternal origin introduced into her bloodstream, and we investigated whether this has an impact on subsequent cancer risks. By using population registries we identified 64?704 women who had children with at least two different partners from 1973 to 1996 in Denmark. We compared their cancer incidence with that of women who during the same time period had at least two births with no indication of partner change, adjusting for age, parity, socioeconomic factors and residence. The overall cancer incidence was more than 50% higher in women with two or more partners. Women having children with multiple partners had a higher incidence of cancer of the cervix and corpus uteri, a lower incidence of melanoma but a similar incidence of breast and ovarian cancer. Uncontrolled differences in lifestyle factors may explain the higher cancer risk associated with having multiple partners. The strong protective effect for melanoma was unexpected and deserves further study.British Journal of Cancer (2004) 90, 1374-1377. doi:10.1038/sj.bjc.6601666 www.bjcancer.com Published online 24 February 2004 [ABSTRACT FROM AUTHOR]

To investigate whether parents of children with congenital malformations more often developed cancer after birth of the child, a population-based case-control study in Denmark was undertaken. By linking the Cancer Registry with the Central Population Registry, we identified 8783 cancer patients having their first child born between 1977 and 1995 before the cancer was diagnosed. Parents of 41 206 firstborn children of a 10% random sample of newborns from the Birth Registry between 1980 and 1995 were identified as controls. We obtained malformation diagnoses of children of cases and controls by linking to the Hospital Discharge Registry. We estimated the association between malformation and cancer by using logistic regression, adjusting for maternal age at birth and sex of child. We found no increased risk of cancer in parents having children with malformations in general, but a higher cancer risk in parents of children born with cleft lip/palate, odds ratio (OR) for all cancer=1.8 (95% confidence interval 1.0-3.2), OR for lymphomas=4.2 (1.3-13.5) and OR for leukaemia=8.1 (2.0-33.7). This association was not restricted to cancer cases diagnosed shortly after birth of the child. Our results suggest a common genetic association between these diseases, but further studies are needed. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including chemotherapy, fertility preservation and radiotherapy.

Dichotomising a measure such as birth weight involves loss of information, but it is required when the aim is making decisions about intervention or monitoring of babies. Estimating the expected birth weight for a baby based on the birth weight of its older sibling may offer an interesting alternative approach compared with using gestational age specific birth weight, for identifying high risk babies. Researchers examined whether selected predictors of birth weight influenced the classification of the baby as small or normal according to the two criteria. On a sub-sample of some babies whose mothers responded to an interview about 6 moths after birth, researchers examined how these categories predicted motor development.

An association between pre-eclampsia and febrile convulsions has been reported, but the association may not be causal. We compared the risk of febrile convulsions in 14 974 children who had been exposed to pre-eclampsia in fetal life with that of 39 210 unexposed children. Children exposed to pre-eclampsia had a slightly increased risk of febrile convulsions, but the association was apparently caused by a shorter gestation in pre-eclamptic women. [ABSTRACT FROM AUTHOR]

BACKGROUND: Asthma may have a prenatal origin. We examined whether maternal alcohol consumption during pregnancy increases the risk of hospitalization with asthma in children. METHODS: We conducted a follow-up study on 10,440 singletons born at approximately 36 weeks of gestation or later to mothers attending midwife centers between April 1984 and April 1987 in Denmark. The mothers completed a questionnaire regarding lifestyle and socioeconomic factors, including alcohol consumption. The children were followed up through the Danish Hospital Discharge Registry. We determined the first hospitalization with a discharge diagnosis of asthma as recorded in the Danish Hospital Discharge Registry. RESULTS: Most pregnant women (81.5%) drank at least some alcohol during pregnancy, but only a few (2.1%) consumed 120 g or more per week. In total, 307 children were hospitalized at least once with a discharge diagnosis of asthma during follow-up (the cumulative incidence risk was 3.5% from birth to 12 years of age or the end of follow-up). After adjusting for maternal socioeconomic factors, dietary components, and other lifestyle factors, children whose mothers drank alcohol during pregnancy did not have an increased risk of hospitalization with asthma compared with the children of mothers who reported no alcohol consumption during pregnancy (adjusted incidence rate ratio, 0.95; 95% confidence interval, 0.70-1.29). Further analyses showed no association with the dose and type of alcohol or with binge drinking. CONCLUSIONS: The study provides no support for a causal link between maternal alcohol intake during pregnancy and asthma in childhood. [ABSTRACT FROM AUTHOR]

Study Question: Is maternal stress following the death of a close relative before or during pregnancy associated with the risk of infertility in daughters?Summary Answer: Compared with unexposed women, women whose mothers had experienced bereavement stress during, or in the year before, pregnancy had a similar risk of infertility overall, but those exposed to maternal bereavement during the first trimester had a higher risk of infertility.What Is Known Already: Animal studies have shown that prenatal maternal stress results in reduced offspring fertility. In humans, there is evidence that girls who have been prenatally exposed to stress have a more masculine behaviour and a slight delay in having their first child.Study Design, Size and Duration: This population-based cohort study, included 660 099 females born in Denmark between 1 January 1973 and 31 December 1993 to mothers of Danish origin and with at least one living relative in the exposure window, and followed the women through 31 December 2011.Participants/materials, Setting, Methods: Overall, 13 334 women (2.0%) were considered prenatally exposed to stress because their mother had lost a spouse/partner, a child, a parent, or a sibling during pregnancy or in the year before conception. Infertility was defined as any record of infertility treatment or diagnosis of female infertility. We considered the date of onset as the date of the first appearance of any such record. The association between exposure and outcome was examined using hazard ratios (HR) with 95% confidence intervals (CI).Main Results and the Role Of Chance: Based on our definition, 40 052 (6.5%) women were infertile in the follow-up period (median age at the end of follow-up: 26.7 years, maximum age: 39 years). Overall, prenatal exposure to maternal stress was not associated with risk of infertility (adjusted HR = 1.04 [CI: 0.95-1.14]). However, women prenatally exposed during the first trimester had a higher estimated risk (adjusted HR = 1.40 [CI: 1.05-1.86]). These findings were consistent in subgroups defined by the relationship of the mother to the deceased and in several sensitivity analyses, including a sibling-matched analysis, and in analyses restricted to women who were married or cohabitating with a man, or to women born at term.Limitations, Reasons For Caution: We did not have a direct measure of stress, but bereavement due to death of a close relative is likely to be very stressful. We based the timing of exposure on the date of the death of the family member, although the stress may well have started earlier. Infertility was also defined indirectly, and many women in the cohort were too young at the end of the follow-up to have been diagnosed. However, misclassification of the outcome was most likely non-differential, and the similar results from all sensitivity analyses suggest that it is unlikely that the effect observed in first trimester exposure would be due to chance.Wider Implications Of the Findings: Prenatal exposure to maternal stress in the first trimester may affect the later fecundity of daughters.Study Funding/competing Interests: This study was supported by a grant from the European Research Council (ERC-2010-StG-260242-PROGEURO) to the ProgEuro project (http://progeuro.au.dk). O.P.-R. is partly supported by a fellowship from Aarhus University and a travel grant from Oticon Fonden. The authors report no conflict of interests. [ABSTRACT FROM AUTHOR]

Objective To assess whether maternal plasma antioxidant levels in mid-pregnancy are associated with small-for-gestational-age ( SGA) birth. Design Case-control study nested within a population-based cohort study. Setting Four hospitals in Montreal, Canada. Population Pregnant women recruited before 24 weeks of gestation, whose pregnancies were not complicated by pre-eclampsia or preterm delivery. Methods Blood samples were obtained at 24-26 weeks and assayed for nutritionally derived antioxidant levels in SGA cases ( n = 324) and randomly selected controls with birthweights between the 25th and 75th centiles ( n = 672). We performed logistic regression analyses using the standardised z-score of each antioxidant as the main independent variable, after summing highly correlated antioxidants or combining via principle component analysis. We adjusted for risk factors for SGA that were associated with antioxidant levels. Main outcome measures SGA, birthweight <10th centile for gestational age and sex. Results Retinol was positively associated with risk of SGA (adjusted odds ratio [ OR] 1.41; 95% confidence interval [95% CI] 1.22-1.63, per SD increase). Carotenoids (log of the sum of β-carotene, lutein/zeaxanthin, α- and β-cryptoxanthin) were negatively associated with SGA (adjusted OR 0.64; 95% CI 0.54-0.78, per SD increase). We found no significant associations between SGA and lycopene or any of the forms of vitamin E assessed, including α-tocopherol, corrected α-tocopherol (per nmol/l of low-density lipoprotein articles), or γ-tocopherol. Conclusions Elevated retinol may be associated with an increased risk of SGA, whereas elevated carotenoid levels may reduce the risk. A better understanding of the nature of these associations is required, however, before recommending specific nutritional interventions in an attempt to prevent SGA birth. [ABSTRACT FROM AUTHOR]

Background Before 2012, few studies had addressed pregnancy outcomes following maternal influenza vaccination; however, the number of publications on this topic has increased recently. Objectives To review comparative studies evaluating fetal death or preterm birth associated with influenza vaccination during pregnancy. Search strategy We searched bibliographic databases from inception to April 2014. Selection criteria Experimental or observational studies assessing the relationship between influenza vaccination during pregnancy and fetal death or preterm birth. Data collection and analysis Two reviewers independently abstracted data from studies meeting the inclusion criteria. Main results We included one randomised clinical trial and 26 observational studies. Meta-analyses were not considered appropriate because of high clinical and statistical heterogeneity. Three studies of fetal death at any gestational age reported adjusted effect estimates in the range 0.56-0.79, and four of five studies of fetal death at <20 weeks reported adjusted estimates between 0.89 and 1.23, all with confidence intervals including 1.0. Adjusted effect estimates for four of five studies of fetal death at ≥20 weeks ranged from 0.44 to 0.77 (two with confidence intervals not crossing 1.0), whereas a fifth reported a non-significant effect in the opposite direction. Among 19 studies of preterm birth, there was no strong evidence suggesting any increased risk, and meta-regression did not explain the moderate between-study heterogeneity ( I2 = 57%). Authors' conclusions Most studies reported no association between fetal death or preterm birth and influenza vaccination during pregnancy. Although several reported risk reductions, results may be biased by methodological shortcomings of observational studies of influenza vaccine effectiveness. [ABSTRACT FROM AUTHOR]

The authors evaluated the association between gestational age, birth weight, intrauterine growth, and epilepsy in a population-based cohort of 1.4 million singletons born in Denmark (1979-2002). A total of 14,334 inpatients (1979-2002) and outpatients (1995-2002) with epilepsy were registered in the Danish National Hospital Register. Children who were potentially growth restricted were identified through two methods: 1) sex-, birth-order-, and gestational-age-specific z score of birth weight; and 2) deviation from the expected birth weight estimated based on the birth weight of an older sibling. The incidence rates of epilepsy increased consistently with decreasing gestational age and birth weight. The incidence rate ratios of epilepsy in the first year of life were more than fivefold among children born at 22-32 weeks compared with 39-41 weeks and among children whose birth weight was <2,000 g compared with 3,000-3,999 g. The association was modified by age but remained into early adulthood. Incidence rate ratios of epilepsy were increased among children identified as growth restricted according to either of the two methods. In conclusion, short gestational age, low birth weight, and intrauterine growth restriction are associated with an increased risk of epilepsy. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between infertility, with or without treatment, and fetal growth, as well as perinatal and infant mortality.Methods: From the Danish National Birth Cohort (1997-2003), we identified 51,041 singletons born of fertile couples (time to pregnancy 12 months or less), 5,787 born of infertile couples conceiving naturally (time to pregnancy more than 12 months), and 4,317 born after treatment. We defined small for gestational age (SGA) as the lowest 5% of birth weight by sex and gestational age.Results: Crude estimates suggested an increased risk of perinatal mortality and SGA among infertile couples (treated and untreated), but the odds ratios (ORs) of perinatal mortality among infertile couples were attenuated after adjustment for maternal age and body mass index (1.32, 95% confidence interval [CI] 0.95-1.84 among untreated and 1.26, 95% CI 0.86-1.85 among treated couples). The elevated risk of SGA among infertile couples persisted after adjustment for maternal age, parity, and smoking (OR 1.24, 95% CI 1.10-1.40 among untreated, and OR 1.40, 95% CI 1.23-1.60 among treated). The risk of SGA increased with time to pregnancy, and a longer time to pregnancy was associated with a small reduction in birth weight across the whole distribution.Conclusion: The increased risk of SGA observed among infertile couples with or without infertility treatment suggests that infertility may be a risk factor for intrauterine growth restriction. Treatment per se may have little effect on fetal growth. A small-to-moderate increased risk of perinatal mortality in infertile couples cannot be ruled out due to the small number of cases.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]