First live birth before surgical verification of endometriosis-a nationwide register study of 18 324 women.

STUDY QUESTION: Do women with endometriosis have lower first live birth rate before surgical diagnosis than women without verified endometriosis? SUMMARY ANSWER: Compared to reference women, the incidence of first live birth was lower in women prior to surgical verification of endometriosis irrespective of the type of endometriosis. WHAT IS KNOWN ALREADY: Endometriosis is associated with pain and reduced fertility. The mechanism of infertility is partly explained by anatomical, endocrinological, and immunological changes. Over the past decades, the treatment of both endometriosis and infertility has evolved. Knowledge of fertility far before surgical diagnosis of endometriosis in large cohorts and of different types of endometriosis has been lacking. The diagnostic delay of endometriosis is long, 6-7 years. STUDY DESIGN, SIZE, DURATION: Retrospective population-based cohort study focused on the time period before the surgical verification of endometriosis. All women with surgical verification of endometriosis in 1998-2012 were identified from the Finnish Hospital Discharge Register and the reference cohort from the Central Population Register. Data on deliveries, gynecological care, and sociodemographic factors before the surgical diagnosis were gathered from Finnish national registers maintained by the Finnish Institute for Health and Welfare, the Digital and Population Data Services Agency, and Statistics Finland. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women aged 15-49 years at the time of surgical verification of endometriosis (ICD-10: N80.1-N80.9) in Finland during 1998-2012 were identified (n = 21 620). Of them, we excluded women born in 1980-1999 due to the proximity of the surgical diagnosis (n = 3286) and women left without reference (n = 10) for the final endometriosis cohort of 18 324 women. From the final cohort, we selected sub-cohorts of women with isolated diagnosis of ovarian (n = 6384), peritoneal (n = 5789), and deep (n = 1267) endometriosis. Reference women were matched by age and residence and lacked registered clinical or surgical diagnosis of endometriosis (n = 35 793). The follow-up started at the age of 15 years and ended at the first birth, sterilization, bilateral oophorectomy, hysterectomy, or until the surgical diagnosis of endometriosis or corresponding index day-whichever came first. Incidence rate (IR) and the incidence rate ratio (IRR) of first live birth before the surgical verification of endometriosis with corresponding CIs were calculated. In addition, we reported the fertility rate of parous women (the number of all children divided by the number of parous women in the cohort) until the surgical verification of endometriosis. The trends in first births were analysed according to the women's birth cohort, type of endometriosis, and age. MAIN RESULTS AND THE ROLE OF CHANCE: Surgical diagnosis of endometriosis was set at the median age of 35.0 years (IQR 30.0-41.4). Altogether 7363 women (40.2%) with endometriosis and 23 718 (66.3%) women without endometriosis delivered a live born infant before the index day (surgery). The IRs of the first live birth per 100 person-years were 2.64 (95% CI 2.58-2.70) in the endometriosis cohort and 5.21 (95% CI 5.15-5.28) in the reference cohort. Between the endometriosis sub-cohorts, the IRs were similar. The IRR of the first live birth was 0.51 (95% CI 0.49-0.52) between the endometriosis and reference cohorts. Fertility rate per parous woman before the surgical diagnosis was 1.93 (SD 1.00) and 2.16 (SD 1.15) in the endometriosis and reference cohorts (P < 0.01). The median age at the first live birth was 25.5 (IQR 22.3-28.9) and 25.5 (IQR 22.3-28.6) years (P = 0.01), respectively. Between the endometriosis sub-cohorts, women in the ovarian sub-cohort were the oldest at the time of surgical diagnosis with the median age of 37.2 years (IQR 31.4-43.3), (P < 0.001). Altogether 44.1% (2814) of the women with ovarian, 39.4% (2282) with peritoneal, and 40.8% (517) with deep endometriosis delivered a live born infant before the diagnosis. IRRs between the endometriosis sub-cohorts did not differ. Fertility rate per parous woman was lowest, 1.88 (SD 0.95), in the ovarian sub-cohort compared to 1.98 (SD 1.07) in the peritoneal and 2.04 (SD 0.96) in deep endometriosis (P < 0.001). Women with ovarian endometriosis were oldest at first live birth compared to women in other sub-cohorts with a median age of 25.8 years (IQR 22.6-29.1) (P < 0.001). Cumulative distributions of first live birth were presented according to age at first live birth and birth cohorts of the participants. LIMITATIONS, REASONS FOR CAUTION: The increasing age at first live birth, increasing practice of clinical diagnostics, conservative treatment of endometriosis, a possible effect of coexisting adenomyosis, and use of artificial reproductive treatments should be considered when assessing the results. In addition, the study is limited due to possible confounding effects of socioeconomic factors, such as level of education. It should be noted that, in this study, we assessed parity only during the years preceding the surgical verification of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: The need for early diagnosis and relevant treatment of endometriosis appears clear given the impairment of fertility prior to its surgical verification. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Hospital District of Helsinki and Uusimaa and by Finska Läkaresällskapet. The authors report no conflicts of interest. All authors have completed the ICMJE Disclosure form. TRIAL REGISTRATION NUMBER: N/A.

Infections and Acute Lymphoblastic Leukemia: Is the Sum Worth More than the Parts? Evidence from Birth Characteristics.

The etiology of childhood acute lymphoblastic leukemia (ALL) has long been studied piecemeal with investigations leading to a lengthy list of putative risk factors including several with immune modulatory effects. The ubiquity of many of these factors (e.g., daycare attendance, low parity, breastfeeding, normal vaccinations) belies the rarity of ALL as an outcome. In this commentary, Pombo-de-Oliveira and colleagues show that a key feature may be the combination of particular risk factors, as the birth characteristics "cesarean section" and "birth order" when combined interact to impart higher risk of ALL than would be suggested by the additive risk of both factors. This statistical interaction would be predicted by the "delayed infection hypothesis" wherein infant immune isolation promotes developmental vulnerability to ALL upon infection exposure later in childhood. Pombo-de-Oliveira and colleagues show further that lack of breastfeeding, a postnatal factor leading to further immune isolation, induces additional risk. In sum, the data reveal a combination of factors that together could impart a healthy "trained" immune system allowing for moderated responses to later exposures with microbial and viral antigens. Such priming of the immune system avoids maladaptive immunologic consequences of delayed antigenic stimulation leading to ALL and other diseases. Further research utilizing biomarkers of specific exposures (in addition to the proxy measures used here) will be helpful to realize the full potential for immune modification for ALL prevention. See related article by Pombo-de-Oliveira et al., p. 371.

The role of maternal age & birth order on the development of unilateral and bilateral retinoblastoma: a multicentre study.

BACKGROUND/OBJECTIVES: Retinoblastoma is a common childhood intraocular malignancy, the bilateral form of which most commonly results from a de novo germline pathogenic variant in the RB1 gene. Both advanced maternal age and decreasing birth order are known to increase the risk of de novo germline pathogenic variants, while the influence of national wealth is understudied. This cohort study aimed to retrospectively observe whether these factors influence the ratio of bilateral retinoblastoma cases compared to unilateral retinoblastoma, thereby inferring an influence on the development of de novo germline pathogenic variants in RB1. SUBJECTS/METHODS: Data from 688 patients from 11 centres in 10 countries were analysed using a series of statistical methods. RESULTS: No associations were found between advanced maternal age, birth order or GDP per capita and the ratio of bilateral to unilateral retinoblastoma cases (p values = 0.534, 0.201, 0.067, respectively), indicating that these factors do not contribute to the development of a de novo pathogenic variant. CONCLUSIONS: Despite a lack of a definitive control group and genetic testing, this study demonstrates that advanced maternal age, birth order or GDP per capita do not influence the risk of developing a bilateral retinoblastoma.

The Interplay of Cesarean-Section Delivery and First-Birth Order as Risk Factors in Acute Lymphoblastic Leukemia.

BACKGROUND: Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has been associated with early-life exposures, including birth by cesarean section (C-section), and a deficit of social exposure (first child). These exposures as proxies for microbiome acquisition in infancy are essential to prime the immune system and restrain later dysregulated immune responses that can trigger ALL in susceptible individuals. We tested risk factors pertaining to immune stimulation that may impact BCP-ALL development. METHODS: Cases comprised 1,126 children (0-12 years) with ALL (BCP-ALL: 78.5%) from the EMiLI study group in Brazil (2002-2020). Age- and sex-matched controls (n = 2,252) were randomly selected from healthy children whose mothers participated in the National Placental and Umbilical Cord Blood Bank donation. Multiple logistic regression was run fitted and adjusted for selected covariates models. RESULTS: C-section delivery was associated with increased risk for ALL [odds ratio (OR) ALL: 1.10; 95% confidence intervals (CI), 1.04-1.15; ORBCP-ALL: 1.09; 95% CI, 1.03-1.14], as well as being the firstborn child. Interaction analysis showed a significant effect of first birth on the observed C-section associations (P < 0.0001). Indeed, high-risk children, namely, firstborn children delivered via C-section were at increased risk for ALL (OR: 2.33; 95% CI, 2.40-4.84) compared with non-first, vaginally born children. An increased risk was found for firstborn children delivered by C-section and non-breastfed with ALL (ORALL: 2.32; 95% CI, 1.27-4.24; ORBCP-ALL: 2.37; 95% CI, 1.18-4.76). CONCLUSIONS: Our observations are in accord with the prediction that exposures determining microbiome composition and adrenal pathway in infancy contribute to the risk of BCP-ALL. IMPACT: These findings encourage the exploration of potential preventive interventions. See related commentary by Wiemels and Gallant, p. 292.

Birth order and morbidity and mortality to hospital discharge among inborn very low-birthweight, very preterm twin infants admitted to neonatal intensive care: a retrospective cohort study.

OBJECTIVE: To know the association of birth order with the risk of morbidity and mortality in very low-birthweight (VLBW) twin infants less than 32 weeks' gestational age (GA). DESIGN: Retrospective cohort study. SETTING: Infants admitted to the collaborating centres of the Spanish SEN1500 neonatal network. PATIENTS: Liveborn VLBW twin infants, with GA from 23+0 weeks to 31+6 weeks, without congenital anomalies, admitted from 2011 to 2020. Outborn patients were excluded. MAIN OUTCOME MEASURES: Respiratory distress syndrome (RDS), patent ductus arteriosus, bronchopulmonary dysplasia (BPD), necrotising enterocolitis, major brain damage (MBD), late-onset neonatal sepsis, severe retinopathy of prematurity, survival and survival without morbidity. Crude and adjusted incidence rate ratios were calculated. RESULTS: Among 2111 twin pairs included, the second twin had higher risk (adjusted risk ratio (aRR) of RDS (aRR 1.08, 95% CI 1.03 to 1.12) and need for surfactant (aRR1.10, 95% CI 1.05 to 1.16). No other significant differences were found, neither in survival (aRR 1.01, 95% CI 0.99 to 1.03) nor in survival without BPD (aRR 1.02, 95% CI 0.99 to 1.05), survival without MBD (aRR 1.02, 95% CI 0.99 to 1.06) nor in survival without major morbidity (aRR 0.97, 95% CI 0.92 to 1.03). However, second twins born by caesarean section (C-section) after a vaginally delivered first twin had less overall survival and survival without MBD. CONCLUSION: In modern perinatology, second twins are still more unstable immediately after birth and require more resuscitation. After admission to the neonatal intensive care unit, they are at increased risk of RDS, but not other conditions, except for second twins delivered by C-section after a first twin delivered vaginally, who have decreased overall survival and survival without major brain injury.

Association of age at first birth and risk of non-alcoholic fatty liver disease in women: evidence from the NHANES.

BACKGROUND: Numerous studies have suggested that age at first birth (AFB) is inversely associated with metabolic diseases, but positively associated with liver cancer in women. Non-alcoholic fatty liver disease (NAFLD) is a canonical example of metabolic dysfunction and inflammation-based liver disease, while the association between AFB and the risk of NAFLD remains unclear. We aimed to investigate the association between AFB and the odds of NAFLD in women. METHODS: Women older than 20 years at the time of the survey were analyzed using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018 in the US. AFB was obtained with self-administered questionnaires. NAFLD was diagnosed as fatty liver index (FLI) ≥ 60. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression models. RESULTS: Of the 12,188 women included in this study, 5670 (46.5%) had NAFLD. Compared to individuals with AFB of 30-32 years old (reference group), the fully adjusted ORs and 95% CI in women with AFB < 18, 18-20, 21-23, and 24-26 years were 1.52 (95% CI 1.14, 2.03), 1.60 (95% CI 1.21, 2.11), 1.40 (95% CI 1.06, 1.84), and 1.33 (95% CI 1.01-1.76), respectively. Yet there was no significant difference between AFB of 27-29, 33-35, or > 35 years compared to the reference group. CONCLUSIONS: Women with younger AFB have higher odds of NAFLD in later life. Policymakers should consider focusing on those with earlier AFB for screening and prevention of NAFLD.

Age at first birth, age at menopause, and risk of ovarian cyst: a two-sample Mendelian randomization study.

Background: Increasing observational studies have indicated that hormonal reproductive factors were associated with ovarian cyst, a common gynecological disease. A two-sample Mendelian randomization (MR) was carried out by investigating the causality of reproductive factors including age at first birth (AFB), age at natural menopause (ANM), and age at menarche (AAM), and the risk of ovarian cyst (OC). Method: Summary statistics were collected from a large genome-wide association study (GWAS), and we used a two-sample MR study to clarify the causal association between the exposure of AFB (N = 542,901), ANM (N = 69,360), and AAM (N = 29,346) and the outcome of the OC (N case = 20,750, N control = 107,564). We separately selected 51, 35, and 6 single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for assaying the influence of AFB, ANM, and AAM on OC, respectively. Then, the causal relationship was tested through multiple approaches including an inverse-variance weighted method, an MR-Egger regression, and a weighted median method. In addition, the MR-PRESSO method was also used to verify the horizontal pleiotropy. Subsequently, we adjust the confounders for MR design. Results: The MR analysis results showed that AFB was negatively associated with the OC (IVW Beta: -0.09, OR: 0.91, 95% CI: 0.86-0.96, p = 0.00185), and the greater AAM decreased the risk of OC (IVW Beta: -0.10, OR: 0.91, 95% CI: 0.82-0.99, p = 0.0376). However, ANM has a positive correlation with the OC (IVW Beta: 0.05, OR: 1.05, 95% CI: 1.03-1.08, p = 8.38 × 10-6). After adjusting BMI, alcohol intake frequency, and ever smoked, we also obtained a negative relationship between AFB and OC (p < 0.005). Meanwhile, we adjusted weight, alcohol intake frequency, and height, and then found a causal relationship between older AMN and an increased risk of OC (p < 0.005). Conclusion: A causal effect of reproductive factors on the development of OC, affected by AFB, ANM, and AAM, was found convincingly. After adjusting the confounders, we also successfully found the substantial causal effect of younger AFB, younger AAM, and older ANM on an increased risk of OC.

Late age at first birth is a protective factor for oesophageal cancer and gastro-oesophageal reflux: the evidence from the genetic study.

Objective: The primary objective of this research endeavor was to examine the underlying genetic causality between the age at first birth (AFB) and four prevalent esophageal diseases, namely oesophageal obstruction (OO), oesophageal varices (OV), gastro-oesophageal reflux (GOR), and oesophageal cancer (OC). Methods: We conducted a two-sample Mendelian randomization (MR) analysis to examine the causal association between AFB and four prevalent esophageal disorders. We employed eight distinct MR analysis techniques to evaluate causal relationships, encompassing random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed-effects IVW. The random-effects IVW method served as the primary approach for our analysis. Furthermore, we executed several sensitivity analyses to assess the robustness of the genetic causal inferences. Results: The random-effects IVW analysis revealed a significant negative genetic causal association between AFB and both GOR (P < 0.001, Odds Ratio [OR] 95% Confidence Interval [CI] = 0.882 [0.828-0.940]) and OC (P < 0.001, OR 95% CI = 0.998 [0.998-0.999]). Conversely, there was insufficient evidence support to substantiate a genetic causal link between AFB and OO (P = 0.399, OR 95% CI = 0.873 [0.637-1.197]) or OV (P = 0.881, OR 95% CI = 0.978 [0.727-1.314]). The results of sensitivity analyses underscore the robustness and reliability of our MR analysis. Conclusion: The findings of this investigation substantiate the notion that elevated AFB confers a protective effect against GOR and OC. In addition, no causative association was discerned between AFB and OO or OV at the genetic level.

Association between first birth caesarean delivery and adverse maternal-perinatal outcomes in the second pregnancy: a registry-based study in Northern Tanzania.

BACKGROUND: Caesarean delivery (CD) is the commonest obstetric surgery and surgical intervention to save lives of the mother and/or the new-borns. Despite been accepted as safe procedure, caesarean delivery has an increased risk of adverse maternal and fetal outcomes. The rising rate of caesarean delivery has been a major public health concern worldwide and the consequences that come along with it urgently need to be assessed, especially in resource limited settings. We aimed to examine the relationship between first birth caesarean delivery and adverse maternal and perinatal outcomes in the second pregnancy among women who delivered at a tertiary hospital in Northern Tanzania. METHODS: A retrospective cohort study was conducted using maternally-linked data from Kilimanjaro Christian Medical Centre. All women who had singleton second delivery between the years 2011 to 2015 were studied. A total of 5,984 women with singleton second delivery were analysed. Multivariable log-binomial regression was used to determine the association between first caesarean delivery and maternal-perinatal outcomes in the second pregnancy. RESULTS: Caesarean delivery in the first birth was associated with an increased risk of adverse maternal and perinatal outcomes in the second pregnancy. These included repeated CD (ARR 1.19; 95% CI: 1.05-1.34), pre/eclampsia (ARR 1.38; 95% CI: 1.06-1.78), gestational diabetes mellitus (ARR 2.80; 95% CI: 1.07-7.36), uterine rupture (ARR 1.56; CI: 1.05-2.32), peri-partum hysterectomy (ARR 2.28; CI: 1.04-5.02) and preterm birth (ARR 1.21; CI: 1.05-1.38). CONCLUSION: Caesarean delivery in their first pregnancy had an increased risk of repeated caesarean delivery and other adverse maternal-perinatal outcomes in the following pregnancy. Findings from this study highlight the importance of devising regional specific measures to mitigate unnecessary primary caesarean delivery. Additionally, these findings may help both clinicians and women in deciding against or for trial of labor after previous caesarean delivery in an event of absent direct obstetric indication.

Reproductive history, as measured by parity, age at first birth and sex of offspring, and cancer-specific survival after a haematological malignancy.

BACKGROUND: Overall, women have better cancer-specific survival than men following haematological malignancies. The effect of reproductive factors on prognosis in women remains unknown and population-based studies are needed. MATERIAL AND METHODS: A nationwide cohort of 21,237 Swedish women with a recorded haematological malignancy at ages 18-69 years was identified in the Swedish Cancer Register 1970-2018. Pre-diagnosis childbirths for each woman were linked to the Swedish Multigeneration Register. Net survival and excess hazard ratios for parity, age at first birth, time since the latest birth, and sex of offspring were estimated using flexible parametric models adjusted for age, year, and educational level. RESULTS: In unadjusted analyses, parity (p = 0.0012) and high age at first birth (p < 0.0001) were associated with better survival. After co-adjustments for reproductive factors and confounders, the associations were attenuated. The adjusted association with parity was mainly observed among women aged above 40 years at diagnosis (p = 0.0033). The associations with reproductive factors were non-significant across subtypes of haematological malignancy. There was a tendency of higher excess mortality for an increasing number of boys compared to girls, although only significant for women with three or more children (p = 0.0126). CONCLUSION: Reproductive factors were in part associated with survival following diagnosis of a haematological malignancy. However, the effect sizes were small with inconsistent association patterns, and thus reproductive factors may only partly contribute to the survival advantage of women over men.

Determinants of Optimal Breastfeeding Practices in Indonesia: Findings From the 2017 Indonesia Demographic Health Survey.

OBJECTIVES: Understanding the factors influencing mothers' decision to breastfeed their infants is essential to formulate effective breastfeeding interventions. This study explored the determinants of optimal breastfeeding indicators in Indonesia. METHODS: We used the 2017 Indonesia Demographic and Health Survey to analyze factors associated with early initiation of breastfeeding, exclusive breastfeeding (EBF), and continued breastfeeding at 1 year (CBF-1) and 2 years (CBF-2). Multivariate logistic regression models were used to examine bio-demographic, socio-cultural, and behavioral characteristics associated with breastfeeding after considering the survey design effect. RESULTS: The risk of delayed breastfeeding initiation was higher among infants who were born smaller, first-born children, were delivered via cesarean delivery, and did not have immediate skin-to-skin contact (p<0.01). Infant's age, birth pattern, household wealth index, and the mother's occupation and smoking status were predictors of EBF (p<0.05). CBF-1 was less common among first-time mothers and those working in the non-agricultural sector, mothers from wealthier families, and mothers who had cesarean deliveries (p<0.01). Infant's age was negatively associated with CBF-2 (adjusted odds ratio [aOR], 0.85; 95% confidence interval [CI], 0.74 to 0.99). Mothers attending college were less likely to practice CBF-2 than those with no education or primary education (aOR, 0.45; 95% CI, 0.26 to 0.77). The absence of postnatal visits was a risk factor for CBF-1 and CBF-2 (p<0.05). CONCLUSIONS: Breastfeeding interventions in Indonesia should pay particular attention to at-risk groups such as women from wealthier families, working outside the agricultural sector, and with a higher education level. Nutrition-sensitive programs (e.g., postnatal care and smoking cessation) should also be encouraged.

Mode of Delivery, Birth Characteristics, and Early-Onset Non-Hodgkin Lymphoma in a Population-Based Case-Control Study.

BACKGROUND: The etiology of non-Hodgkin lymphoma (NHL) in children and in adolescents and young adults (AYA) is not well understood. METHODS: We evaluated potential associations between mode of delivery, birth characteristics, and NHL risk in a population-based case-control study, which included 3,064 cases of NHL [490 with Burkitt lymphoma, 981 with diffuse large B-cell lymphoma (DLBCL), and 978 with T-cell NHL) diagnosed at the age of 0 to 37 years in California during 1988 to 2015 and 153,200 controls frequency matched on year of birth. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from an unconditional multivariable logistic regression model that included year of birth and birth characteristics. RESULTS: Individuals born via cesarean section had a decreased risk of pediatric Burkitt lymphoma (age 0-14 years; OR = 0.71, 95% CI: 0.51-0.99) and pediatric T-cell NHL (OR = 0.73, 95% CI: 0.55-0.97) compared with those born vaginally. Having a birth order of second (OR = 0.73, 95% CI: 0.57-0.93) or third or higher (OR = 0.76, 95% CI: 0.58-0.99) was associated with a lower risk of pediatric T-cell NHL compared with first-borns. AYA (age 15-37 years) with a heavier birthweight had an elevated risk of DLBCL (OR for each kg = 1.16, 95% CI: 1.00-1.35). Associations between other birth characteristics, including plurality, maternal age, maternal education, and NHL risk, also exhibited variations across subgroups based on age of diagnosis and histologic subtype. CONCLUSIONS: These findings support a role of mode of delivery and birth characteristics in the etiology of early-onset NHL. IMPACT: This study underscores the etiologic heterogeneity of early-onset NHL.

Early life triggers for food allergy that in turn impacts dietary habits in childhood.

INTRODUCTION AND OBJECTIVES: In order to investigate food allergy's prevalence, risk factors and eating behavior of children with relevant anamnesis, a study was performed in Cypriot primary schools. PATIENTS: A specially composed questionnaire for self-reported adverse reactions to food, created in the context of the EuroPrevall study, was distributed in 13 representative primary schools across the country. Participants were sub-grouped into three groups; healthy (H), those with unconfirmed food hypersensitivity reactions (FA-) and children with a confirmed diagnosis by a physician IgE-mediated food allergy (FA+). Food habits, family health history and lifestyle factors were assessed and groups' outcomes were compared with each other. RESULTS: For the study, 202 questionnaires were completed and returned; 31 children (19 FA- and 12 FA+) reported an adverse food reaction. Significant risk factors for developing FA+ were being the first born or having siblings with asthma, attended a day nursery, but also maternal alcohol drinking during pregnancy, parental smoking and parental occupation in food processing or use of latex gloves. The presence of children in the kitchen during cooking showed a protective role. Dietary habits of FA+ children were significantly diminished in terms of variety and frequency of consumption in comparison to the rest, in which had a greater overlap. CONCLUSION: Further research is required for the interesting risk or protective factors revealing from the current investigation. The negative effect of food allergy in the dietary habits of food allergic children documented in the literature, is strongly supported herein.

Number of siblings and survival from childhood leukaemia: a national register-based cohort study from Sweden.

BACKGROUND: Previous studies suggest worse leukaemia survival for children with siblings, but the evidence is sparse, inconsistent and does not consider clinical factors. We explored the associations between number of siblings in the household, birth order and survival from childhood acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML). METHODS: In this nationwide register-based study we included all children aged 1-14, diagnosed with ALL and AML between 1991-mid-2015 in Sweden (n = 1692). Using Cox regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) according to number of siblings and birth order, adjusting for known prognostic and sociodemographic factors. RESULTS: A tendency towards better ALL survival among children with one, or ≥2, siblings was observed, adjHRs (95% CI): 0.73 (0.49-1.10) and 0.63 (0.40-1.00), respectively. However, this was mainly limited to children with low risk profiles. An indication of better AML survival among children with siblings was seen, adjHRs (95% CI) 0.68 (0.36-1.29) and 0.71 (0.34-1.48) but diminished after adjusting for birth order. CONCLUSION: Our results do not support previous findings that a larger number of siblings is associated with poorer survival. Inconsistencies might be explained by underlying mechanisms that differ between settings, but chance cannot be ruled out.

Births: Final Data for 2019.

Objectives-This report presents 2019 data on U.S. births according to a wide variety of characteristics. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. Methods-Descriptive tabulations of data reported on the birth certificates of the 3.75 million births that occurred in 2019 are presented. Data are presented for maternal age, livebirth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates by age are also shown. Trend data for 2010 through 2019 are presented for selected items. Trend data by race and Hispanic origin are shown for 2016-2019. Results-A total of 3,747,540 births were registered in the United States in 2019, down 1% from 2018. The general fertility rate declined from 2018 to 58.3 births per 1,000 women aged 15-44 in 2019. The birth rate for females aged 15-19 fell 4% between 2018 and 2019. Birth rates declined for women aged 20-34 and increased for women aged 35-44 for 2018-2019. The total fertility rate declined to 1,706.0 births per 1,000 women in 2019. Birth rates declined for both married and unmarried women from 2018 to 2019. The percentage of women who began prenatal care in the first trimester of pregnancy rose to 77.6% in 2019; the percentage of all women who smoked during pregnancy declined to 6.0%. The cesarean delivery rate decreased to 31.7% in 2019 (Figure 1). Medicaid was the source of payment for 42.1% of all births in 2019. The preterm birth rate rose for the fifth straight year to 10.23% in 2019; the rate of low birthweight was essentially unchanged from 2018 at 8.31%. Twin and triplet and higher-order multiple birth rates both declined in 2019 compared with 2018.

Birth characteristics and childhood leukemia in Switzerland: a register-based case-control study.

PURPOSE: Initial genetic alterations in the development of childhood leukemia occur in utero or before conception; both genetic and environmental factors are suspected to play a role. We aimed to investigate the associations between childhood leukemia and perinatal characteristics including birth order, birth interval to older siblings, parental age, birth weight, and multiple birth. METHODS: We identified cases diagnosed between 1981 and 2015 and born in Switzerland between 1969 and 2015 from the Swiss Childhood Cancer Registry and randomly sampled five controls per case from national birth records matched on date of birth, sex, and municipality of residence at birth. We used conditional logistic regression to investigate associations between perinatal characteristics and leukemia at ages 0-15 and 0-4 years, and the subtypes acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). RESULTS: The study included 1,403 cases of leukemia. We observed increased risks associated with high birth weight (adjusted OR 1.37, 95% CI 1.12-1.69) and multiple birth (1.89, 1.24-2.86). These associations were similar for ALL and stronger for leukemia at ages 0-4 years. For AML, we observed an increased risk for higher birth order (3.08, 0.43-22.03 for fourth or later born children). We found no associations with other perinatal characteristics. CONCLUSION: This register-based case-control study adds to the existing evidence of a positive association between high birth weight and risk of childhood leukemia. Furthermore, it suggests children from multiple births are at an increased risk of leukemia.

Birth Characteristics and Risk of Pediatric Thyroid Cancer: A Population-Based Record-Linkage Study in California.

Background: Incidence rates of thyroid cancer in children and young adults (age 0-19 years) have nearly doubled over a recent 15-year period in the United States. Children with thyroid cancer may require long-term therapy and surveillance and are at greater risk for second primary malignancies. High-dose exposure to ionizing radiation is the only known nongenetic risk factor; the vast majority of cases have an unknown etiology. Methods: We conducted a population-based nested case-control study to evaluate the relationship between a range of birth characteristics and the risk of pediatric thyroid cancer. Using linked birth records and cancer registry data from California, we included 1012 cases who were diagnosed with first primary thyroid cancer at the age of 0-19 years from 1988 to 2015 and 50,600 birth-year matched controls (1:50 case to control ratio). We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) by using multivariable logistic regression models applied to the full population and stratified by thyroid cancer subtypes (papillary and follicular), race/ethnicity (white and Hispanic), and age at diagnosis (0-14 and 15-19 years). Results: Hispanic ethnicity (OR: 1.20 [CI 1.01-1.42]), higher birth weight (OR: 1.11 [CI 1.04-1.18] per 500g), and higher maternal education (13-15 years OR: 1.35 [CI 1.09-1.68], 16+ years OR: 1.35 [CI 1.07-1.71]) were associated with an increased risk of pediatric thyroid cancer, while male sex (OR: 0.21 [CI 0.18-0.25]) and higher birth order (third or higher OR: 0.81 [CI 0.68-0.98]) were associated with a decreased risk. Some heterogeneity was observed across subtype, most notably an elevated OR with higher birth order for follicular thyroid cancer, in contrast to the reduced risk for this category among papillary thyroid cancer cases (p-value for interaction = 0.01). Hispanic ethnicity was a risk factor for papillary, but not follicular thyroid cancer (p-value for interaction = 0.07). Conclusions: In this population-based study of birth characteristics and pediatric thyroid cancer, we identified several important risk factors for pediatric thyroid cancer, including female sex, Hispanic ethnicity, higher birth weight, higher maternal educational attainment, and lower birth order. Our data provide new areas for replication and investigation of biological mechanisms for this poorly understood malignancy.

Transition to adulthood in Latin America: 1960s-2010s / Transição para a vida adulta na América Latina: 1960-2010 / Transición a la adultez en América Latina 1960-2010

Multidimensional discussion about transition to adulthood is an incipient theme in Latin America. This paper seeks to describe and characterize the process of change in the transition of men and women in the region between the 1960s and 2010's. Using census data from IPUMS-International for 15 Latin American countries, we calculate the mean ages at transition to adulthood, at entering the labor market, at first union, and at first birth. We concluded there was a process of postponing transition to adulthood, although much stronger for males than for females, which we attribute to the events linked to the transition of each group. With these results, we hope to encourage further research into transition to adulthood in Latin America.

A transição para a vida adulta é um tema pouco explorado de forma multidimensional na América Latina. Este artigo busca descrever e caracterizar o processo de mudança na transição de homens e mulheres na região, entre 1960 e 2010. Utilizando dados censitários fornecidos pela plataforma IPUMS para 15 países latino-americanos, foram calculadas as idades médias na transição para a vida adulta, no ingresso no mercado de trabalho, na primeira união e no nascimento do primeiro filho. Conclui-se que houve um processo de postergação da transição para a vida adulta, porém, foi muito mais forte para os homens do que para as mulheres, o que pode ser atribuído aos acontecimentos ligados à transição de cada grupo. Com esses resultados, esperamos encorajar mais investigações sobre a transição para a vida adulta na América Latina.

La transición a la adultez es un tema poco explorado de manera multidimensional en América Latina. Este artículo busca describir y caracterizar el proceso de cambio en la transición de hombres y mujeres en la región entre las décadas de 1960 y 2010. Utilizando datos censales proporcionados por la plataforma IPUMS para 15 países de América Latina, calculamos las edades medias en la transición a la edad adulta, entrada al mercado laboral, primera unión y primer nacimiento. Concluimos que hubo un proceso de postergación de la transición a la adultez que fue mucho más fuerte para los hombres que para las mujeres, lo que atribuimos a los hechos relacionados con la transición de cada grupo. Con estos resultados esperamos impulsar nuevas investigaciones sobre la transición a la vida adulta en América Latina.

Night Shift Among Women: Is It Associated With Difficulty Conceiving a First Birth?

Background: Asynchrony in circadian processes alters many physiological systems, including female reproduction. Thus, there are possible reproductive consequences of night shift work for women including menstrual irregularity, endometriosis, and prolonged time to conception. This study examined whether women who worked night shift were more likely than those who did not to require fertility treatment to conceive a first birth, whether they had specific infertility diagnoses, and if such relationships were age-specific. Methods: In a retrospective data linkage study of 128,852 primiparous women, fertility treatment data were linked to the state perinatal registry for South Australia (1986-2002). Potential exposure to night shift work was assessed using a job-exposure matrix. First, the association between night shift work and fertility treatment was assessed among (1) all women, then (2) women in paid employment, using logistic regression. Interactions between age and shift work status were also examined. Secondly, among women who conceived with fertility treatment, we assessed associations between night shift work and type of infertility diagnosis. Potential confounders were considered in all analyses. Results: Among women ≤35 years, night shift workers were more likely to require fertility treatment (all: OR = 1.40, 95% CI 1.19-1.64; in paid employment: OR = 1.27, 95% CI 1.08-1.50). There were no associations among women >35 years. Ethnicity, socioeconomic status and smoking did not affect these results. Among women who underwent fertility treatment, night shift workers were more likely than day workers to have menstrual irregularity (OR = 1.42, 95% CI 1.05-1.91) or endometriosis (OR = 1.34, 95% CI 1.00-1.80). Conclusions: Night shift work may contribute to increased need for fertility treatment in younger women. This increased risk may reflect young women's vulnerability in terms of poor tolerance of night shift work, and/or lack of control and choice about shift schedule.

Birth Characteristics and Risk of Early-Onset Synovial Sarcoma.

BACKGROUND: Synovial sarcoma is a rare cancer with peak incidence in the young adult period. Despite poor outcomes of this aggressive cancer, there is little epidemiologic research addressing its etiology. METHODS: We collected birth characteristic data on synovial sarcoma cases born during 1978-2015 and diagnosed during 1988-2015 in California (n = 244), and 12,200 controls frequency-matched on year of birth. We also constructed a dataset of cancer cases in siblings of sarcoma subjects to assess familial risk. RESULTS: In multivariable logistic regression analyses, synovial sarcoma was more frequent in Hispanics compared with non-Hispanic whites [OR, 1.48; 95% confidence interval (CI), 1.06-2.08]. Higher birth weight was a risk factor in Hispanics; each 500 g increase in birth weight was associated with a 22% increase in disease risk (OR, 1.22; 95% CI, 1.00-1.48). Also, a strong role for birth order was suggested, with highest risk for the first born (second child compared with first: OR, 0.61; 95% CI, 0.44-0.84; third or later compared with first: OR, 0.53; 95% CI, 0.36-0.77). Siblings of patients with synovial sarcoma did not display elevated cancer incidence, suggesting the low likelihood that strong familial predisposition alleles play a significant role in this disease. CONCLUSIONS: The associations with birth weight and birth order suggest that nutritional, developmental, and environmental factors may play a role in the etiology of synovial sarcoma. IMPACT: Further epidemiologic research on synovial sarcoma should evaluate epigenetic and developmental mechanisms and the formation of the archetypical t(X;18) translocation that defines this disease.