Determinants of breast-feeding and post-partum amenorrhoea in Orissa

A life table analysis is made of the duration of breast-feeding and post-partum amenorrhoea in Orissa, India, taking one variable at a time using data from a baseline survey of fertility and mortality (BSFM) conducted on the lines of the World Fertility Survey. Then a multivariate (proportional hazard) analysis showed that socioeconomic factors including residence, caste status and education influence the breast-feeding and post-partum amenorrhoea periods. There was no effect of maternal age on the length of breast-feeding, but mean length of post-partum amenorrhoea varied with age. The durations of breast-feeding and post-partum amenorrhoea are strongly related.     

The duration of lactational amenorrhoea in urban Bangladeshi women

The duration of lactational amenorrhoea, and infant feeding patterns and behaviour, were investigated in a sample of 97 mother-infant pairs living in a poor urban area of Dhaka, Bangladesh. A seven-hour time allocation method was used to determine the number of breast-feeding bouts and their duration. The seven-hour observation period was conducted on five occasions: at birth, 1 month, 4 months, 8 months and either 10 or 11 months. The median duration of lactational amenorrhoea was determined to be 24.07 weeks using survival analysis. Mothers who breast-fed their babies for longer and more frequently had, on average, a longer period of lactational amenorrhoea. There was no relationship between sociodemographic characteristics of the mother and duration of lactational amenorrhoea, nor was there any significant relationship between maternal anthropometry and birth weight of the baby and duration of lactational amenorrhoea, but there was a tendency for women with lower body mass index to have longer durations. Using the Cox proportional hazards model, the best predictor of duration of lactational amenorrhoea was the mean of months 0 and 1 durations of breast-feeding, adjusted for the mean frequencies for those months. The introduction of weaning food was also an important predictor.     

Correlation between subsequent lengths of postpartum amenorrhoea in a prospective study of breast-feeding women in rural Bangladesh.

The relationship between subsequent lengths of lactational amenorrhoea for individual women in a prospective study of breast-feeding women in Bangladesh was studied. The data indicate that previous length of amenorrhoea has significant predictive value for the subsequent length of amenorrhoea. Information on previous experience with lactational amenorrhoea should be therefore incorporated into guidelines for the introduction of family planning during lactation.     

Lactational amenorrhoea in well-nourished Toba women of Formosa, Argentina

The proximate causes of the contraceptive effect of lactation are still a matter of productive debate. This study sought to disentangle the relative impact that intense breast-feeding practices and maternal nutrition have on the regulation of ovarian function in nursing women. A mixed-longitudinal, direct-observational, prospective study was conducted of the return to postpartum fecundity in 113 breast-feeding, well-nourished Toba women. A sub-sample of 70 women provided data on nursing behaviour, daily activities, diet quality and urinary levels of oestrone and progesterone metabolites. Well-nourished, intensively breast-feeding Toba women experienced a relatively short period of lactational amenorrhoea (10.2 +/- 4.3 months) and a high lifetime fertility (TFR=6.7 live births/woman). Duration of lactational amenorrhoea was not correlated with any of the nursing parameters under study or with static measures of maternal nutritional status. The results indicated that the pattern of resumption of postpartum fertility could be explained, at least partly, by differences in individual metabolic budgets. Toba women resumed postpartum ovulation after a period of sustained positive energy balance. As the relative metabolic load hypothesis suggests, the variable effect of lactation on postpartum fertility may not depend on the intensity of nursing per se but rather on the energetic stress that lactation represents for the individual mother.     

The effect of initiation of child supplementation on resumption of post-partum menstruation

The effects of initiation of solid and liquid supplementation on resumption of post-partum menstruation are examined, using data from a 2-year prospective study of birth interval dynamics from central Java, Indonesia. The sample analysed consisted of 444 women who experienced resumption of menses while breast-feeding, women who were breast-feeding and amenorrhoeic at the end of the study, or women who resumed menstruation or were censored after infant mortality and weaning which preceded the resumption of menses. Multivariate hazard model analysis was used to assess the significance of supplementation, various breast-feeding covariates, and age and parity of the dependent variable. Because the timing of supplementation varies, the supplementation variables were introduced into the analysis as time-varying covariates. For the mothers in the sample, solid and liquid supplementation was initiated at medians of 2.1 and 8.0 months respectively. The former had a significant effect on resumption of menses, while the latter was only marginally significant. Earlier supplementation meant shorter durations of amenorrhoea for the majority of women. However, the effect was not consistent across all categories of women. For the small group of mothers who were low intensity breast-feeders (less than or equal to 6 minutes per nursing episode) or as low frequency day-time breast-feeders (less than or equal to 6 nursing episodes per day-time), earlier supplementation had no additional effect on their rate of resumption of menses post-partum.     

Extending lactational amenorrhoea in Manila: a successful breast-feeding education programme.

An experimental breast-feeding education programme conducted at the Philippine General Hospital in Manila demonstrated that women could be motivated to improve their breast-feeding practices and lengthen their period of lactational amenorrhoea in comparison to a control group. Mothers who participated in the programme breast-fed their babies more frequently, delayed the introduction of regular supplements, used fewer bottles and pacifiers and maintained night feeding longer than mothers who were not exposed to the positive breast-feeding messages. The programme was successful in lengthening the period of amenorrhoea among women with elementary, high school, or technical school education, but not among college-educated women. Different educational approaches may be necessary for women of different education levels.     

Phylogenetic imputation of plant functional trait databases

Continental‐scale maps of plant functional diversity are a fundamental piece of data of interest to ecosystem modelers and ecologists, yet such maps have been exceedingly hard to generate. The large effort to compile global plant functional trait databases largely for the purpose of mapping and analyzing the spatial distribution of function has resulted in very sparse data matrices thereby limiting progress. Identifying robust methodologies to gap fill or impute trait values in these databases is an important objective. Here I argue that existing statistical tools from phylogenetic comparative methods can be used to rapidly impute values into global plant functional trait databases due to the large amount of phylogenetic signal often in trait data. In particular, statistical models of phylogenetic signal in traits can be generated from existing data and used to predict missing values of closely related species often with a high degree of accuracy thereby facilitating the continental‐scale mapping of plant function. Despite the promise of this approach, I also discuss potential pitfalls and future challenges that will need to be addressed.     

The Design of Intervention Trials Involving Recurrent and Terminal Events

Clinical trials are often designed to assess the effect of therapeutic interventions on the incidence of recurrent events in the presence of a dependent terminal event such as death. Statistical methods based on multistate analysis have considerable appeal in this setting since they can incorporate changes in risk with each event occurrence, a dependence between the recurrent event and the terminal event, and event-dependent censoring. To date, however, there has been limited development of statistical methods for the design of trials involving recurrent and terminal events. Based on the asymptotic distribution of regression coefficients from a multiplicative intensity Markov regression model, we derive sample size formulas to address power requirements for both the recurrent and terminal event processes. We consider the design of trials for which separate marginal hypothesis tests are of interest for the recurrent and terminal event processes and deal with both superiority and non-inferiority tests. Simulation studies confirm that the designs satisfy the nominal power requirements in both settings, and an application to a trial evaluating the effect of a bisphosphonate on skeletal complications is given for illustration.     

The recovery of fertility during breast-feeding in Assiut, Egypt

A longitudinal study of twenty-six breast-feeding and twelve non-breast-feeding postpartum women was conducted in Assiut, Egypt in order to determine the time that ovulation resumed after childbirth, and the effect of breast-feeding frequency on the period of lactational anovulation. Breast-feeding women experienced the onset of follicular development, vaginal bleeding, ovulation and pregnancy significantly later than women who did not breast-feed. Ovulatory and non-ovulatory breast-feeders reported similar frequencies of breast-feeding episodes. The introduction of dietary supplements commonly preceded ovulation. An algorithm using three simple variables observable to the breast-feeding mother was found to predict up to 100% of the first ovulations. All breast-feeding women who did not give supplements and did not have a vaginal bleeding episode by 6 months postpartum were anovular by strict criteria for ovulation. Ovulation did not precede bleeding or supplementation in the women who experienced these events before 6 months, yielding a highly effective formula for preventing unplanned pregnancy by the informed use of breast-feeding.     

Regression analysis of doubly censored failure time data with frailty

In doubly censored failure time data, the survival time of interest is defined as the elapsed time between an initial event and a subsequent event, and the occurrences of both events cannot be observed exactly. Instead, only right- or interval-censored observations on the occurrence times are available. For the analysis of such data, a number of methods have been proposed under the assumption that the survival time of interest is independent of the occurrence time of the initial event. This article investigates a different situation where the independence may not be true with the focus on regression analysis of doubly censored data. Cox frailty models are applied to describe the effects of covariates and an EM algorithm is developed for estimation. Simulation studies are performed to investigate finite sample properties of the proposed method and an illustrative example from an acquired immune deficiency syndrome (AIDS) cohort study is provided.     

Effectiveness of lactational amenorrhoea in prevention of pregnancy in Manila,the Philippines: non-comparative prospective trail.

OBJECTIVE: To determine the contraceptive efficacy of the lactational amenorrhoea method. DESIGN: Non-comparative prospective trial. SETTING: Urban Manila, the Philippines. SUBJECTS: 485 lower income, educated women with extensive experience of breast feeding. INTERVENTION: Women were offered all available contraceptives for use after birth. Those who chose the lactational amenorrhoea method were taught the method, screened for the study, and followed for 12 months to determine the risk of pregnancy when the method was used. MAIN OUTCOME MEASURES: Life table pregnancy rates during correct and incorrect use of the method, censored monthly in the event of sexual abstinence or the use of another contraceptive method. RESULTS: The lactational amenorrhoea method was 99% effective when used correctly (that is, during lactational amenorrhoea and full or nearly full breast feeding for up to six months). At 12 months the effectiveness during amenorrhoea dropped to 97%. CONCLUSIONS: The lactational amenorrhoea method provided as much protection from pregnancy as non-breast feeding women experience with non-medicated intrauterine devices and barrier methods. The contraceptive effect of lactation cannot be attributed to lactational or postpartum abstinence.     

A systematic assessment of normalization approaches for the Infinium 450K methylation platform

The Illumina Infinium HumanMethylation450 BeadChip has emerged as one of the most popular platforms for genome wide profiling of DNA methylation. While the technology is wide-spread, systematic technical biases are believed to be present in the data. For example, this array incorporates two different chemical assays, i.e., Type I and Type II probes, which exhibit different technical characteristics and potentially complicate the computational and statistical analysis. Several normalization methods have been introduced recently to adjust for possible biases. However, there is considerable debate within the field on which normalization procedure should be used and indeed whether normalization is even necessary. Yet despite the importance of the question, there has been little comprehensive comparison of normalization methods. We sought to systematically compare several popular normalization approaches using the Norwegian Mother and Child Cohort Study (MoBa) methylation data set and the technical replicates analyzed with it as a case study. We assessed both the reproducibility between technical replicates following normalization and the effect of normalization on association analysis. Results indicate that the raw data are already highly reproducible, some normalization approaches can slightly improve reproducibility, but other normalization approaches may introduce more variability into the data. Results also suggest that differences in association analysis after applying different normalizations are not large when the signal is strong, but when the signal is more modest, different normalizations can yield very different numbers of findings that meet a weaker statistical significance threshold. Overall, our work provides useful, objective assessment of the effectiveness of key normalization methods.     

A systematic assessment of normalization approaches for the Infinium 450K methylation platform

The Illumina Infinium HumanMethylation450 BeadChip has emerged as one of the most popular platforms for genome wide profiling of DNA methylation. While the technology is wide-spread, systematic technical biases are believed to be present in the data. For example, this array incorporates two different chemical assays, i.e., Type I and Type II probes, which exhibit different technical characteristics and potentially complicate the computational and statistical analysis. Several normalization methods have been introduced recently to adjust for possible biases. However, there is considerable debate within the field on which normalization procedure should be used and indeed whether normalization is even necessary. Yet despite the importance of the question, there has been little comprehensive comparison of normalization methods. We sought to systematically compare several popular normalization approaches using the Norwegian Mother and Child Cohort Study (MoBa) methylation data set and the technical replicates analyzed with it as a case study. We assessed both the reproducibility between technical replicates following normalization and the effect of normalization on association analysis. Results indicate that the raw data are already highly reproducible, some normalization approaches can slightly improve reproducibility, but other normalization approaches may introduce more variability into the data. Results also suggest that differences in association analysis after applying different normalizations are not large when the signal is strong, but when the signal is more modest, different normalizations can yield very different numbers of findings that meet a weaker statistical significance threshold. Overall, our work provides useful, objective assessment of the effectiveness of key normalization methods.     

Postpartum amenorrhoea in Ethiopia: The role of weaning,child death,and socioeconomic factors

Abstract

Using data from the 1990 National Family and Fertility Survey (NFFS) and employing discrete‐time hazards models, we examine the effect of weaning, child death, and socioeconomic factors on postpartum amenorrhoea in Ethiopia. The results show that 91 in every 100 mothers breastfed their child for at least 6 months. The median duration of breastfeeding stands at 18 months, and amenorrhoea lasts for a median duration of 12 months. Significant variations in breastfeeding and amenorrhoea duration are also observed among the different categories of breastfeeding women. The median duration of breastfeeding for lactating women is 24 months, 6 months for those who weaned, and 2 months for those whose child died. The median duration of postpartum amenorrhoea is 14 months for breastfeeding women, 12 months for those who weaned, and 6 months for those whose child died. Discrete‐time hazard models reveal that child death has the strongest effect on the resumption of menses. Net of other factors, the risk of returning to menses increased 3 times for mothers whose child died. The effect of child death, however, decreases over time. Weaning also has a significant positive effect; and, like child death, its effect diminishes as time passes. The study further shows significant differences in the risk of returning to postpartum menses by socioeconomic characteristics of the women, even though they are breastfeeding.     

Adjustments and measures of differential expression for microarray data

MOTIVATION: Existing analyses of microarray data often incorporate an obscure data normalization procedure applied prior to data analysis. For example, ratios of microarray channels intensities are normalized to have common mean over the set of genes. We made an attempt to understand the meaning of such procedures from the modeling point of view, and to formulate the model assumptions that underlie them. Given a considerable diversity of data adjustment procedures, the question of their performance, comparison and ranking for various microarray experiments was of interest. RESULTS: A two-step statistical procedure is proposed: data transformation (adjustment for slide-specific effect) followed by a statistical test applied to transformed data. Various methods of analysis for differential expression are compared using simulations and real data on colon cancer cell lines. We found that robust categorical adjustments outperform the ones based on a precisely defined stochastic model, including some commonly used procedures.     

A new method for choosing sample size for confidence interval-based inferences

Scientists often need to test hypotheses and construct corresponding confidence intervals. In designing a study to test a particular null hypothesis, traditional methods lead to a sample size large enough to provide sufficient statistical power. In contrast, traditional methods based on constructing a confidence interval lead to a sample size likely to control the width of the interval. With either approach, a sample size so large as to waste resources or introduce ethical concerns is undesirable. This work was motivated by the concern that existing sample size methods often make it difficult for scientists to achieve their actual goals. We focus on situations which involve a fixed, unknown scalar parameter representing the true state of nature. The width of the confidence interval is defined as the difference between the (random) upper and lower bounds. An event width is said to occur if the observed confidence interval width is less than a fixed constant chosen a priori. An event validity is said to occur if the parameter of interest is contained between the observed upper and lower confidence interval bounds. An event rejection is said to occur if the confidence interval excludes the null value of the parameter. In our opinion, scientists often implicitly seek to have all three occur: width, validity, and rejection. New results illustrate that neglecting rejection or width (and less so validity) often provides a sample size with a low probability of the simultaneous occurrence of all three events. We recommend considering all three events simultaneously when choosing a criterion for determining a sample size. We provide new theoretical results for any scalar (mean) parameter in a general linear model with Gaussian errors and fixed predictors. Convenient computational forms are included, as well as numerical examples to illustrate our methods.     

Ethnic differentials in early childhood mortality in Nepal

This paper investigates the association of early childhood mortality (between birth and second birthday) with ethnicity in Nepal, based on data from the 1976 Nepal Fertility Survey, which was part of the World Fertility Survey. The approach is through a series of hazard models, which incorporate ethnicity, year of birth, mother's illiteracy, father's illiteracy, rural-urban residence, region, sex, maternal age, survival of previous birth, previous birth interval, and breast-feeding as covariates. Ethnic differentials in early childhood mortality are not explained by the other socioeconomic and demographic covariates, except for a modest effect of illiteracy, but the remaining covariates explain a great deal of variability in early childhood mortality itself. Analysis using an improved specification of breast-feeding as an age-varying covariate indicates, on average, that breast-feeding, relative to not breast-feeding, reduces age-specific mortality risks during the first 2 years of life by 76%, a very large effect.     

Hormonal correlates for the initiation of breast-feeding in Bangladeshi women

Hormonal changes that occur before or during parturition are known to trigger early postpartum maternal behaviors in many mammals. In humans, little evidence has been found for hormonal mediation of early postpartum maternal behavior. In this paper, we investigate associations between fetoplacental hormone concentrations in late pregnancy on the time from parturition to initiation of breast-feeding. A sample of 91 pregnant rural Bangladeshi women, enrolled in a 9-month prospective study, provided twice-weekly urine specimens and structured interviews. The subjects provided self-reports of time from parturition to initiation of breast-feeding. Specimens were assayed for urinary concentrations of human chorionic gonadotropin (hCG), pregnanediol-3alpha-glucuronide (PdG, a metabolite of progesterone), and urinary estrone conjugates (E1C). Parametric hazards analysis was used to investigate the effects of hCG, PdG, and E1C concentrations and other covariates (mother's age, parity, and child's sex) on the duration from parturition to breast-feeding. Mother's age, parity, the child's sex, hCG, and PdG showed no association with the onset of breast-feeding. Urinary E1C was significantly associated with time to initiation of breast-feeding, explaining about 4% of the variation in the behavior. The relationship was positive so that higher prepartum concentrations of EIC were associated with later times to initiation of breast-feeding. The direction of this relationship is opposite that found for many other species of mammals but is consistent with some recent findings in primates.     

Simple methods for the estimation and sensitivity analysis of principal strata effects using marginal structural models: Application to a bone fracture prevention trial

In randomized clinical trials, it is often of interest to estimate the effect of treatment on quality of life (QOL), in addition to those on the event itself. When an event occurs in some patients prior to QOL score assessment, investigators may compare QOL scores between patient subgroups defined by the event after randomization. However, owing to postrandomization selection bias, this analysis can mislead investigators about treatment efficacy and result in paradoxical findings. The recent Japanese Osteoporosis Intervention Trial (JOINT‐02), which compared the benefits of a combination therapy for fracture prevention with those of a monotherapy, exemplifies the case in point; the average QOL score was higher in the combination therapy arm for the unfractured subgroup but was lower for the fractured subgroup. To address this issue, principal strata effects (PSEs), which are treatment effects estimated within subgroups of individuals stratified by potential intermediate variable, have been discussed in the literature. In this paper, we describe a simple procedure for estimating the PSEs using marginal structural models. This procedure utilizes SAS code for the estimation. In addition, we present a simple sensitivity analysis method for examining the resulting estimates. The analyses of JOINT‐02 data using these methods revealed that QOL scores were higher in the combination therapy arm than in the monotherapy arm for both subgroups.