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Background: Multifetal gestation could be associated with higher long‐term maternal mortality because it increases the risk of pregnancy complications such as preeclampsia and preterm birth, which are in turn linked to postpartum cardiovascular risk. Objectives: We examined whether spontaneously conceived multifetal versus singleton gestation was associated with long‐term maternal mortality in a racially diverse U.S. cohort. Methods: We ascertained vital status as of 2016 via linkage to the National Death Index and Social Security Death Master File of 44,174 mothers from the Collaborative Perinatal Project (CPP; 1959–1966). Cox proportional hazards models with maternal age as the time scale assessed associations between history of spontaneous multifetal gestation (in the last CPP observed pregnancy or prior pregnancy) and all‐cause and cardiovascular mortality, adjusted for demographics, smoking status, and preexisting medical conditions. We calculated hazard ratios (HR) for all‐cause and cause‐specific mortality over the study period and until age 50, 60, and 70 years (premature mortality). Results: Of eligible participants, 1672 (3.8%) had a history of multifetal gestation. Participants with versus without a history of multifetal gestation were older, more likely to have a preexisting condition, and more likely to smoke. By 2016, 51% of participants with and 38% of participants without a history of multifetal gestation had died (unadjusted all‐cause HR 1.14, 95% confidence interval [CI] 1.07, 1.23). After adjustment for smoking and preexisting conditions, a history of multifetal gestation was not associated with all‐cause (adjusted HR 1.00, 95% CI 0.93, 1.08) or cardiovascular mortality (adjusted HR 0.99, 95% CI 0.87, 1.11) over the study period. However, history of multifetal gestation was associated with an 11% lower risk of premature all‐cause mortality (adjusted HR 0.89, 95% CI 0.82, 0.96). Conclusions: In a cohort with over 50 years of follow‐up, history of multifetal gestation was not associated with all‐cause mortality, but may be associated with a lower risk of premature mortality. [ABSTRACT FROM AUTHOR]

Background: Longitudinal studies show that lower cognitive performance in adolescence and early adulthood is associated with higher risk of suicide death throughout adulthood. However, it is unclear whether this cognitive vulnerability originates earlier in childhood since studies conducted in children are scarce and have inconsistent results. Methods: Vital status of 49,853 individuals born between 1959 and 1966 to participants in the Collaborative Perinatal Project cohort was determined by a probabilistic linkage to the National Death Index, covering all US deaths occurring from 1979 through 2016. Cox proportional hazard models were used to examine associations of general, verbal, and non‐verbal intelligence at ages 4 and 7, and academic skills at age 7 with suicide death coded according to ICD‐9/10 criteria, while accounting for sociodemographic and pregnancy factors previously associated with suicide in this sample. Results: By the end of 2016, 288 cohort members had died by suicide. Cognitive performance at 7 years on tests with verbal components was associated with suicide risk (average vs. high verbal intelligence, HR = 1.97, 95% CI 1.05–3.71; low vs. high spelling skills, HR = 2.02, 95% CI 1.16–3.51; low vs. high reading skills, HR = 2.01, 95% CI 1.27–3.17). Associations were still evident, especially for verbal intelligence and reading skills, but hazard ratios were attenuated after adjusting for prenatal and sociodemographic factors at birth (verbal intelligence, HR = 1.97, 95% CI 1.03–3.78; spelling, HR = 1.61, 95% CI 0.90–2.88; reading, HR = 1.67, 95% CI 1.02–2.72). Conclusions: Childhood neurocognitive performance is associated with vulnerability to suicide mortality through middle‐adulthood, suggesting that there might be a cognitive diathesis for suicide originating in early childhood. Future studies should examine how multiple domains of childhood cognitive performance contribute to vulnerability to suicide risk, including by increasing risk for social and environmental factors that are associated not only with suicide but also with many types of psychiatric disorders. [ABSTRACT FROM AUTHOR]

Understanding the association between mixtures of environmental toxicants and time‐to‐pregnancy (TTP) is an important scientific question as sufficient evidence has emerged about the impact of individual toxicants on reproductive health and that individuals are exposed to a whole host of toxicants rather than an individual toxicant. Assessing mixtures of chemical effects on TTP poses significant statistical challenges, namely (i) TTP being a discrete survival outcome, typically subject to left truncation and right censoring, (ii) chemical exposures being strongly correlated, (iii) appropriate transformation to account for some lipid‐binding chemicals, (iv) non‐linear effects of some chemicals, and (v) high percentage of concentration below the limit of detection (LOD) for some chemicals. We propose a discrete frailty modeling framework (named Discnet) that allows selection of correlated covariates while appropriately addressing the methodological issues mentioned above. Discnet is shown to have better and stable false negative and false positive rates compared to alternative methods in various simulation settings. We did a detailed analysis of the pre‐conception endocrine disrupting chemicals and TTP from the LIFE study and found that older females, female exposure to cotinine (smoking), DDT conferred a delay in getting pregnant, which was consistent across various approaches to account for LOD as well as non‐linear associations. [ABSTRACT FROM AUTHOR]

Background: Feeding problems are common in early childhood, and some evidence suggests that feeding problems may be associated with psychopathology. Few prospective studies have explored whether toddler feeding problems predict later psychopathology. Methods: Mothers of 1,136 children from the Upstate KIDS cohort study provided data when children were 2.5 and 8 years of age. Food refusal (picky eating) and mechanical/distress feeding problems and developmental delays were assessed at 2.5 years. Child eating behaviors (enjoyment of food, food fussiness, and emotional under and overeating) and child psychopathology (attention‐deficit/hyperactivity (ADHD), oppositional‐defiant (OD), conduct disorder (CD), and anxiety/depression) symptoms were assessed at 8 years. Results: Mechanical/distress feeding problems at age 2.5, but not food refusal problems, were associated with ADHD, problematic behavior (OD/CD), and anxiety/depression symptoms at 8 years in models adjusting for eating behaviors at 8 years and child and family covariates. Associations with mechanical/distress feeding problems were larger for ADHD and problematic behavior than anxiety/depression symptoms, though all were modest. Model estimates were similar for boys and girls. Conclusions: Much of the research on feeding problems focuses on picky eating. This study suggests that early mechanical and mealtime distress problems may serve as better predictors of later psychopathology than food refusal. Parents and pediatricians could monitor children with mechanical/distress feeding problems for signs of developing psychopathology. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to determine whether newborn concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and bisphenol A (BPA) are associated with early childhood growth.Methods: A total of 1,954 singletons and 966 twins from the Upstate KIDS Study (born 2008-2010) were included in this study. Newborn dried blood spot concentrations of PFOS, PFOA, and BPA were quantified by liquid chromatography tandem mass spectrometry. Children's weight and height were reported from birth through 3 years of age. Repeated measures were modeled using generalized linear mixed models.Results: PFOS and PFOA were associated with lower BMI (-0.078 kg/m2 [-0.12 to -0.038] and -0.076 kg/m2 [-0.17 to -0.051] per 1 standard deviation increase in log PFOS and PFOA, respectively) and not with early obesity among singletons. Inconsistent associations were observed for twins. BPA levels were higher among neonates with a neonatal intensive care unit stay (P < 0.001), making associations difficult to interpret.Conclusions: Perfluorinated alkyl substances did not exhibit obesogenic associations with early measures of childhood growth. Blood-based BPA measures are limited by the nonpersistent nature of the chemical, and unknown sources from hospital settings may present only transient exposures. [ABSTRACT FROM AUTHOR]

Background: Evidence shows cytokine dysregulation in children with developmental disabilities. The association between immune activity during the perinatal period and child development is less clear.Methods: We examined the relationship between newborn concentrations of immune markers and child development. Within Upstate KIDS, a population-based birth cohort (2008-2010, upstate New York), we assayed immune markers, which are postulated to have neuro-modulatory effects, in newborn dried blood spots (NDBS, n = 3038). Mothers completed the Ages & Stages Questionnaire© (ASQ) for their children repeatedly through age 36 months. At 30 and 36 months, mothers also reported whether their children received any developmental services. We used generalised linear mixed models adjusted for maternal and child characteristics to test associations.Results: Sixteen immune markers were associated with failing ASQ in unadjusted models. After full adjustment (for gestational age, mode of delivery, parity, pregnancy smoking, etc.), we observed that higher levels of 4 markers, including platelet-derived growth factor-AA (PDGF-AA, OR 0.77, 95% CI 0.67, 0.89), plasminogen activator inhibitor-1 (OR 0.80, 95% CI 0.68, 0.94), stromal cell derived factor-1 (OR 0.85, 95% CI 0.73, 0.98), and macrophage inflammatory protein-1beta (OR 0.87, 95% CI 0.77, 0.98) were associated with lower odds of ASQ failure. The associations did not exist if correction for multiple comparisons was performed, except for PDGF-AA. Analyses with developmental service use revealed similar null findings.Conclusions: Immune marker concentrations in NDBS may not be associated with developmental delay in the general population. Newborn concentrations of growth factor PDGF-AA may be protective of developmental delay in childhood. [ABSTRACT FROM AUTHOR]

Objective Equivocal findings have been reported on the association between maternal depression and children's growth, possibly because of the limited attention to its disproportionate impact by child sex. The relationship between the timing of maternal depression and children's growth was assessed in a population-based prospective birth cohort, with particular attention to sex differences. Methods The Upstate KIDS Study comprised 4,394 children followed through 3 years of age from 2008 to 2010. Maternal depression was measured antenatally by linkage with hospital discharge records before delivery and postnatally by depressive symptoms reported from questionnaires. Children's growth was measured by sex- and age-specific weight, height, weight for height, and BMI. Adjusted linear mixed effects models were used to estimate growth outcomes for the full sample and separately by plurality and sex. Results Antenatal depression was associated with lower weight for age (−0.24 z score units; 95% confidence interval [CI]: −0.43, −0.05) and height for age (−0.26 z score units; 95% CI: −0.51, −0.02) among singleton boys. Postnatal depressive symptoms were associated with higher weight for height (0.21 z score units; 95% CI: 0.01, 0.42) among singleton girls. Conclusions The findings of this study suggest that antenatal depression was associated with lower weight and smaller height only for boys, whereas postnatal depressive symptoms were associated with higher weight for height only for girls. The timing of depression and the mechanisms of sex-specific responses require further examination. [ABSTRACT FROM AUTHOR]

Background: Although pregnancy loss affects one-third of pregnancies, the associated signs/symptoms have not been fully described. Given the dynamic nature of maternal physiologic adaptation to early pregnancy, we posited the relationships between signs/symptoms and subsequent loss would vary weekly.Methods: In a preconception cohort with daily follow-up, pregnancies were ascertained by self-administered sensitive home pregnancy tests on day of expected menses. We evaluated the effects of weekly time-varying signs/symptoms (including vaginal bleeding, lower abdominal cramping, and nausea and/or vomiting) on pregnancy loss <20 weeks in Cox proportional hazards models and calculated the week-specific probability of loss by the presence/absence of each sign/symptom.Results: Of 341 pregnancies ascertained by home pregnancy test, 95 (28%) ended in loss. Relationships between signs/symptoms and loss varied across time since first positive pregnancy test. In the first week following pregnancy confirmation, when many losses occurred, bleeding [hazard ratio (HR) 8.7, 95% confidence interval (CI) 4.7, 16.0] and cramping (HR 1.8, 95% CI 1.2, 2.7) were associated with loss even when accompanied by nausea and/or vomiting (HR 5.2, 95% CI 2.6, 10.5). After the second week, new relationships emerged with nausea and/or vomiting inversely associated (HR range 0.6-0.3, all 95% CI upper bounds <1.00) and bleeding no longer associated with loss. Probabilities of loss of ranged from 78% (95% CI 59%, 96%) with bleeding present in week 1 to 8% (95% CI 5%, 12%) with nausea/vomiting present in week 5.Conclusions: Relationships between signs/symptoms and pregnancy loss vary in early pregnancy possibly reflecting maternal physiologic response. [ABSTRACT FROM AUTHOR]

Background: Imperfect follow-up in longitudinal studies commonly leads to missing outcome data that can potentially bias the inference when the missingness is nonignorable; that is, the propensity of missingness depends on missing values in the data. In the Upstate KIDS Study, we seek to determine if the missingness of child development outcomes is nonignorable, and how a simple model assuming ignorable missingness would compare with more complicated models for a nonignorable mechanism.Methods: To correct for nonignorable missingness, the shared random effects model (SREM) jointly models the outcome and the missing mechanism. However, the computational complexity and lack of software packages has limited its practical applications. This paper proposes a novel two-step approach to handle nonignorable missing outcomes in generalized linear mixed models. We first analyse the missing mechanism with a generalized linear mixed model and predict values of the random effects; then, the outcome model is fitted adjusting for the predicted random effects to account for heterogeneity in the missingness propensity.Results: Extensive simulation studies suggest that the proposed method is a reliable approximation to SREM, with a much faster computation. The nonignorability of missing data in the Upstate KIDS Study is estimated to be mild to moderate, and the analyses using the two-step approach or SREM are similar to the model assuming ignorable missingness.Conclusions: The two-step approach is a computationally straightforward method that can be conducted as sensitivity analyses in longitudinal studies to examine violations to the ignorable missingness assumption and the implications relative to health outcomes. [ABSTRACT FROM AUTHOR]

Aim: We examined whether children of mothers with a medical condition diagnosed before or during pregnancy took longer to achieve gross motor milestones up to age 24 months.Method: We obtained information on medical conditions using self-reports, birth certificates, and hospital records in 4909 mothers participating in Upstate KIDS, a population-based birth cohort. Mothers reported on their children's motor milestone achievement at 4, 8, 12, 18, and 24 months of age.Results: After adjustment for covariates (including pre-pregnancy body mass index), children of mothers with gestational diabetes took longer to achieve sitting without support (hazard ratio [HR]=0.84, 95% confidence interval [CI] 0.75-0.93), walking with assistance (HR=0.88, 95% CI 0.77-0.98), and walking alone (HR=0.88, 95% CI 0.77-0.99) than children of females with no gestational diabetes. Similar findings emerged for maternal diabetes. Gestational hypertension was associated with a longer time to achieve walking with assistance. These associations did not change after adjustment for gestational age or birthweight. Severe hypertensive disorders of pregnancy were related to a longer time to achieve milestones, but not after adjustment for perinatal factors.Interpretation: Children exposed to maternal diabetes, gestational or pre-gestational, may take longer to achieve motor milestones than non-exposed children, independent of maternal obesity. [ABSTRACT FROM AUTHOR]

Objective Maternal prepregnancy obesity is associated with several poor infant health outcomes; however, studies that investigated motor development have been inconsistent. Thus, maternal prepregnancy weight status and infants' gross motor development were examined. Methods Participants consisted of 4,901 mother-infant pairs from the Upstate KIDS study, a longitudinal cohort in New York. Mothers indicated dates when infants achieved each of six gross motor milestones when infants were 4, 8, 12, 18, and 24 months old. Failure time modeling under a Weibull distribution was utilized to compare time to achievement across three levels of maternal prepregnancy BMI. Hazard ratios (HR) below one indicate a lower 'risk' of achieving the milestone and translate to later achievement. Results Compared to infants born to thin and normal-weight mothers (BMI < 25), infants born to mothers with obesity (BMI > 30) were slower to sit without support (HR = 0.91, P = 0.03) and crawl on hands and knees (HR = 0.86, P < 0.001), after adjusting for maternal and birth characteristics. Increased gestational age was associated with faster achievement of all milestones, but additional adjustment did not impact results. Conclusions Maternal prepregnancy obesity was associated with a slightly longer time for infant to sit and crawl, potentially due to a compromised intrauterine environment or reduced physically active play. [ABSTRACT FROM AUTHOR]

Current duration data arise in cross-sectional studies from questions on the length of time from an initiating event to the time of interview. For example, in the National Survey on Family Growth, women who were considered at risk for pregnancy were asked (i) 'Are you currently attempting pregnancy?' and (ii) 'If yes, how many months have you been attempting to get pregnant?' The responses to (ii), referred to as the current durations, are length-biased because women with longer durations are more likely to answer yes to question (i) and therefore be included in the sample. Previous methods to analyze such data include continuous time nonparametric and parametric approaches. In this article, we propose a semiparametric Cox model and a piecewise constant baseline model (used to account for digit preference) to analyze grouped current duration data. We discuss and investigate through simulation studies, the robustness properties of the proposed methods when digit preference is present. Lastly, we present an analysis of the current duration data resulting from the 2002 National Survey on Family Growth. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Background Critical data gaps remain regarding infertility treatment and child development. We assessed the utility of a birth certificate registry for developing a population cohort aimed at answering such questions. Methods We utilised the Upstate New York livebirth registry ( n = 201 063) to select births conceived with ( n = 4024) infertility treatment or exposed infants, who were then frequency-matched by residence to a random sample of infants conceived without ( n = 14 455) treatment or unexposed infants, 2008-10. Mothers were recruited at 2-4 months postpartum and queried about their reproductive histories, including infertility treatment for comparison with birth certificate data. Overall, 1297 (32%) mothers of exposed and 3692 of unexposed (26%) infants enrolled. Results Twins represented 22% of each infant group. The percentage of infants conceived with/without infertility treatment was similar whether derived from the birth registry or maternal report: 71% none, 16% drugs or intrauterine insemination, and 14% assisted reproductive technologies ( ART). Concordant reporting between the two data sources was 93% for no treatment, 88% for ART, and 83% for fertility drugs, but differed by plurality. Exposed infants had slightly ( P < 0.01) earlier gestations than unexposed infants (38.3 ± 2.8 and 38.7 ± 2.7 weeks, respectively) based upon birth certificates but not maternal report (38.7 ± 2.7 and 38.7 ± 2.9, respectively). Conversely, mean birthweight was comparable using birth certificates (3157 ± 704 and 3194 ± 679 g, respectively), but differed using maternal report (3167 ± 692 and 3224 ± 661, respectively P < 0.05). Conclusions The birth certificate registry is a suitable sampling framework as measured by concordance with maternally reported infertility treatment. Future efforts should address the impact of factors associated with discordant reporting on research findings. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms that underlie successful human reproduction and development is an ambitious goal, given the many unique methodological challenges surrounding such study. These challenges are well understood by reproductive and perinatal epidemiologists and include its conditional nature, unobservable yet informative outcomes such as conception, multi-scale missing data, correlated or non-independent outcomes, interval censoring and a hierarchical data structure. Novel methodologies for overcoming these challenges and for answering critical data gaps are needed if we are to better understand the inefficiency that currently characterises human reproduction with the goal of improving population health. The exposome is an emerging paradigm that offers promise for understanding the natural history of human reproduction and development, and its many associated impairments that develop later in child- or adulthood. This novel paradigm recognises the need to identify and measure the totality of environmental (non-genetic) exposures from preconception through sensitive windows, and to identify patterns associated with healthy and adverse outcomes. The exposome accommodates research focusing on unique subpopulations, such as couples undergoing assisted reproductive technologies, so that methodological limitations such as unobservable and conditional outcomes can be better addressed. Reproductive and perinatal epidemiology is uniquely suited for proof-of-concept exposome research, given the intricate relations between fecundity, gravid health and later onset disease and the narrow and interrelated sensitive windows that characterise the conditional nature of human reproduction and development. Bold new conceptual frameworks such as the exposome are needed for designing research that may lead to discovery and improve population health. [ABSTRACT FROM AUTHOR]

Summary McLain AC, Sundaram R, Cooney MA, Gollenberg AL, Buck Louis GM. Clustering of fecundability within women. Paediatric and Perinatal Epidemiology 2011; 25: 460-465. Adverse pregnancy outcomes have long been observed to cluster within women resulting in the inclusion of past reproductive history in clinical assessments and perinatal scoring systems. However, limited study has focused on the clustering of fecundability as measured by time to pregnancy (TTP), despite growing evidence suggestive of a possible association with adverse pregnancy outcomes known to cluster within women. We sought to empirically evaluate the clustering of conception delay, and TTP more globally, in one of the few existing prospective pregnancy cohort studies that captured women's successive pregnancies. The study cohort comprised 544 women who contributed 1119 pregnancies in the US Collaborative Perinatal Project. We used a discrete Cox frailty model to estimate the degree and significance of within-woman clustering of TTP. Women with an initial conception delay (TTP > 6 months) were older, less educated and had higher body mass indices than women not experiencing delays (TTP ≤ 6 months). Our analysis indicates that there is significant within-woman clustering of TTP (variance of the frailty = 0.80, [95% confidence interval 0.49, 1.11]) after adjusting for baseline maternal age, body mass index and education level. Similar to many other reproductive and perinatal outcomes, our findings suggest that TTP clusters within women. Identifying exposures or behaviours that affect TTP may offer strategies for reducing conception delay in future pregnancy attempts. [ABSTRACT FROM AUTHOR]

The relationship between the environment and human fecundity and fertility remains virtually unstudied from a couple-based perspective in which longitudinal exposure data and biospecimens are captured across sensitive windows. In response, we completed the LIFE Study with methodology that intended to empirically evaluate a priori purported methodological challenges: implementation of population-based sampling frameworks suitable for recruiting couples planning pregnancy; obtaining environmental data across sensitive windows of reproduction and development; home-based biospecimen collection; and development of a data management system for hierarchical exposome data. We used two sampling frameworks (i.e., fish/wildlife licence registry and a direct marketing database) for 16 targeted counties with presumed environmental exposures to persistent organochlorine chemicals to recruit 501 couples planning pregnancies for prospective longitudinal follow-up while trying to conceive and throughout pregnancy. Enrolment rates varied from <1% of the targeted population (n = 424,423) to 42% of eligible couples who were successfully screened; 84% of the targeted population could not be reached, while 36% refused screening. Among enrolled couples, ∼ 85% completed daily journals while trying; 82% of pregnant women completed daily early pregnancy journals, and 80% completed monthly pregnancy journals. All couples provided baseline blood/urine samples; 94% of men provided one or more semen samples and 98% of women provided one or more saliva samples. Women successfully used urinary fertility monitors for identifying ovulation and home pregnancy test kits. Couples can be recruited for preconception cohorts and will comply with intensive data collection across sensitive windows. However, appropriately sized sampling frameworks are critical, given the small percentage of couples contacted found eligible and reportedly planning pregnancy at any point in time. [ABSTRACT FROM AUTHOR]

MikolajczykPrevious research has described variability in menstrual cycle lengths within and across women, though less attention has focused on characterising patterns of bleeding. While clinical definitions for menstrual bleeding are often given in standard textbooks, the validity of conventional definitions has not been empirically evaluated in epidemiological studies. The definition of menstrual bleeding may affect the analysis of time to pregnancy and pregnancy dating that relies upon the last menstrual period. We used daily records of vaginal bleeding from a prospective cohort study that included 74 women trying to become pregnant who reported 430 bleeding episodes. A longitudinal mixture model (PROC TRAJ) was used to classify patterns of bleeding. Among the first 74 bleeding episodes, 15% comprised only days with spotting or light bleeding (possibly representing non-menstrual bleeding given the length of the cycle defined by these bleeding episodes). When all 430 bleeding episodes were analysed, four distinct bleeding patterns emerged: (1) episodic bleeding comprising 1-3 days of spotting (10%), (2) bleeding lasting 3-6 days (40%), (3) bleeding lasting 6-8 days (33%), and (4) bleeding lasting 8-12 days (17%). These findings suggest that non-menstrual bleeding may be relatively common. Considerable variation in menstrual bleeding patterns is evident, and as such is likely to impact fecundity-related endpoints or gestational age estimates that rely upon menstrual cycle dates. The association between bleeding patterns and female fecundity awaits future research. [ABSTRACT FROM AUTHOR]

In analyzing competing risks data, a quantity of considerable interest is the cumulative incidence function. Often, the effect of covariates on the cumulative incidence function is modeled via the proportional hazards model for the cause-specific hazard function. As the proportionality assumption may be too restrictive in practice, we consider an alternative more flexible semiparametric additive hazards model of ( Biometrika 1994; 81:501-514) for the cause-specific hazard. This model specifies the effect of covariates on the cause-specific hazard to be additive as well as allows the effect of some covariates to be fixed and that of others to be time varying. We present an approach for constructing confidence intervals as well as confidence bands for the cause-specific cumulative incidence function of subjects with given values of the covariates. Furthermore, we also present an approach for constructing confidence intervals and confidence bands for comparing two cumulative incidence functions given values of the covariates. The finite sample property of the proposed estimators is investigated through simulations. We conclude our paper with an analysis of the well-known malignant melanoma data using our method. Published in 2009 by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The Cox model with time-dependent coefficients has been studied by a number of authors recently. In this paper, we develop empirical likelihood (EL) pointwise confidence regions for the time-dependent regression coefficients via local partial likelihood smoothing. The EL simultaneous confidence bands for a linear combination of the coefficients are also derived based on the strong approximation methods. The EL ratio is formulated through the local partial log-likelihood for the regression coefficient functions. Our numerical studies indicate that the EL pointwise/simultaneous confidence regions/bands have satisfactory finite sample performances. Compared with the confidence regions derived directly based on the asymptotic normal distribution of the local constant estimator, the EL confidence regions are overall tighter and can better capture the curvature of the underlying regression coefficient functions. Two data sets, the gastric cancer data and the Mayo Clinic primary biliary cirrhosis data, are analysed using the proposed method. [ABSTRACT FROM AUTHOR]

Objective: Equivocal findings have been reported on the association between maternal depression and children's growth, possibly because of the limited attention to its disproportionate impact by child sex. The relationship between the timing of maternal depression and children's growth was assessed in a population-based prospective birth cohort, with particular attention to sex differences.Methods: The Upstate KIDS Study comprised 4,394 children followed through 3 years of age from 2008 to 2010. Maternal depression was measured antenatally by linkage with hospital discharge records before delivery and postnatally by depressive symptoms reported from questionnaires. Children's growth was measured by sex- and age-specific weight, height, weight for height, and BMI. Adjusted linear mixed effects models were used to estimate growth outcomes for the full sample and separately by plurality and sex.Results: Antenatal depression was associated with lower weight for age (-0.24 z score units; 95% confidence interval [CI]: -0.43, -0.05) and height for age (-0.26 z score units; 95% CI: -0.51, -0.02) among singleton boys. Postnatal depressive symptoms were associated with higher weight for height (0.21 z score units; 95% CI: 0.01, 0.42) among singleton girls.Conclusions: The findings of this study suggest that antenatal depression was associated with lower weight and smaller height only for boys, whereas postnatal depressive symptoms were associated with higher weight for height only for girls. The timing of depression and the mechanisms of sex-specific responses require further examination. [ABSTRACT FROM AUTHOR]