Maternal antenatal mood and child development: an exploratory study of treatment effects on child outcomes up to 5 years.

Effective treatment of maternal antenatal depression may ameliorate adverse neurodevelopmental outcomes in offspring. We performed two follow-up rounds of children at age 2 and age 5 whose mothers had received either specialized cognitive-behavioural therapy or routine care for depression while pregnant. Of the original cohort of 54 women, renewed consent was given by 28 women for 2-year follow-up and by 24 women for 5-year follow-up. Child assessments at the 2-year follow-up included the Parenting Stress Index (PSI), Bayley Scales of Infant Development (BSID-III) and the Child Behaviour Checklist (CBCL). The 5-year follow-up included the Wechsler Preschool and Primary Scales of Intelligence (WPPSI-III) and again the CBCL. Treatment during pregnancy showed significant benefits for children's development at age 2, but not at age 5. At 2 years, intervention effects were found with lower scores on the PSI Total score, Parent Domain and Child domain (d=1.44, 1.47, 0.96 respectively). A non-significant trend favoured the intervention group on most subscales of the CBCL and the BSID-III (most notably motor development: d =0.52). In contrast, at 5-year follow-up, no intervention effects were found. Also, irrespective of treatment allocation, higher depression or anxiety during pregnancy was associated with higher CBCL and lower WPPSI-III scores at 5 years. This is one of the first controlled studies to evaluate the long-term effect of antenatal depression treatment on infant neurodevelopmental outcomes, showing some benefit. Nevertheless, caution should be taken interpreting the results because of a small sample size, and larger studies are warranted.

Reduced fecundity in HIV-positive women.

STUDY QUESTION: Is HIV associated with increased time to pregnancy (TTP)? SUMMARY ANSWER: HIV-positive women who discontinue a contraceptive method to become pregnant have increased TTP, particularly among those who likely do not know their status. WHAT IS KNOWN ALREADY: HIV-positive women have fewer children on average than their HIV-negative counterparts due to both behavioral and biological factors. There is a need to better describe and quantify fecundity patterns associated with HIV in the general population. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was based on data from 12 Demographic and Health Surveys (DHSs) conducted between 2003 and 2013 in 11 African countries. All studies collected dried blood spot samples for HIV testing and included a retrospective calendar module that recorded women's monthly reproductive status in the 5 years preceding the survey. TTP was measured among 3181 women discontinuing a contraceptive method within 2 years of the survey in order to become pregnant. PARTICIPANTS/MATERIALS, SETTING, METHODS: We use Cox proportional hazard models for discrete survival data to model TTP and estimate fecundability odds ratios (FOR) and 95% CIs for the 12-month period following contraceptive discontinuation. In addition to employing a binary measure of HIV status, we also develop an additional explanatory measure that combines HIV status with information on whether respondents had ever been tested for HIV and received their results (which proxies for knowledge of HIV status) to reduce the threat of confounding from behavioral changes following an HIV diagnosis. MAIN RESULTS AND THE ROLE OF CHANCE: In our sample, 10.3% of women were HIV-positive, and a little more than half (51.8%) of women received test results and likely knew their status. Over a 12-month observation period, HIV-positive women had a 25% average reduction in fecundity compared to HIV-negative women [adjusted FOR (aFOR) = 0.75 (0.62-0.92)] after adjusting for confounders. The 12-month fecundity patterns differed by women's likely knowledge of their status such that results were primarily driven by HIV-positive women who likely did not know their status. Moreover, reductions in fecundity attributable to HIV were not uniform over time. Among women who were still trying for pregnancy after 3 unsuccessful months, HIV-positive women had half the odds of becoming pregnant compared to HIV-negative women [aFOR = 0.50 (0.35-0.71)]. Conversely, there were no significant differences in FORs between HIV-negative and HIV-positive women in the first 3 months. LIMITATIONS REASONS FOR CAUTION: Because dried blood spot samples for HIV testing were collected at the time of the survey but reproductive calendar data were collected retrospectively, it is possible that we introduced misclassification bias, as we have no knowledge if the acquisition of HIV occurred before or after pregnancy attempt. WIDER IMPLICATIONS OF THE FINDINGS: As life expectancy and quality health status improve due to earlier initiation of antiretroviral (ARV) treatment in HIV-positive women, there has been growing awareness that services should also address the fertility desires of HIV-positive women who want children. These findings indicate that if a pregnancy does not occur after 3 months of attempting pregnancy, HIV-positive women and HIV-discordant couples should request access to HIV and reproductive pre-pregnancy counseling and health assessments. STUDY FUNDING/COMPETING INTEREST(S): A.G. was supported by the National Institutes of Health (contract T32-HD007275) during the study. During the conceptualization, data collection and analysis time frame, S.vdP. was supported by WHO/RHR/HRP Special Program in Reproductive Health and Research, Geneva, Switzerland, and HRP (the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction). The authors have no conflicts of interest to declare.

Reproductive suppression follows threats to child survival.

Natural selection presumably conserved mechanisms that allow females to block or terminate gestation when environmental circumstances threaten the survival of offspring. One example of this adaptive reproductive suppression, the Bruce effect, has been identified in several species, both in the laboratory and in the wild. Although descriptive epidemiology reports low fertility among women experiencing stressful circumstances, attempts to detect a Bruce effect in humans have been rare and limited. We contribute to this limited work by examining the relationship between the odds of child death and the sex ratio at birth in Sweden for the years 1751-1840. We find evidence of a generalized Bruce effect in humans in that unexpected changes in child mortality predict opposite unexpected changes in the secondary sex ratio in the following year, even after adjusting for period life expectancy. Our analysis broadens the scope of the Bruce effect literature to include humans, suggesting that women, through noncognitive decisional biology, adjust reproductive strategies and investments in response to changing environmental conditions.

Adolescent experience predicts longevity: evidence from historical epidemiology.

Human development reportedly includes critical and sensitive periods during which environmental stressors can affect traits that persist throughout life. Controversy remains over which of these periods provides an opportunity for such stressors to affect health and longevity. The elaboration of reproductive biology and its behavioral sequelae during adolescence suggests such a sensitive period, particularly among males. We test the hypothesis that life expectancy at age 20 among males exposed to life-threatening stressors during early adolescence will fall below that among other males. We apply time-series methods to cohort mortality data in France between 1816 and 1919, England and Wales between 1841 and 1919, and Sweden between 1861 and 1919. Our results indicate an inverse association between cohort death rates at ages 10-14 and cohort life expectancy at age 20. Our findings imply that better-informed and more strategic management of the stressors encountered by early adolescents may improve population health.

Host immune status affects maturation time in two nematode species--but not as predicted by a simple life-history model.

In theory, the age at which maturation occurs in parasitic nematodes is inversely related to pre-maturational mortality rate, and cross-species data on mammalian nematodes are consistent with this prediction. Immunity is a major source of parasite mortality and parasites stand to gain sizeable fitness benefits through short-term adjustments of maturation time in response to variation in immune-mediated mortality. The effects of thymus-dependent immune responses on maturation in the nematode parasites Strongyloides ratti and Nippostrongylus brasiliensis were investigated using congenitally thymus-deficient (nude) rats. As compared with worms in normal rats, reproductive maturity of parasites (presence of eggs in utero) in nude rats occurred later in S. ratti but earlier in N. brasiliensis. Immune-mediated differences in maturation time were not associated with differences in worm length. Thymus-dependent immunity had no effect on prematurational mortality. Results are discussed in relation to theoretical expectations and possible explanations for the observed patterns in parasite maturation.

The evolutionary ecology of host-specificity: experimental studies with Strongyloides ratti.

Factors constraining the evolution of host-specificity were investigated using a gastrointestinal parasitic nematode, Strongyloides ratti. S. ratti is a natural parasite of rats which can also reproduce, with decreased success, in laboratory mice. Observed host-specificity arose from lower establishment, reduced per capita fecundity and more rapid expulsion of parasites from mice relative to rats. Variation in the efficacy of thymus-dependent immunity between host species (rats and mice) was insufficient to explain the majority of the observed differences in parasite establishment and reproductive success. The role of natural selection in determining host-specificity was addressed using experimental selection followed by reciprocal fitness assays in both host species. Experimental selection failed to modify the host-specificity of S. ratti to any measurable degree, suggesting either a lack of genetic variation for this trait or the involvement of as yet unidentified factors underlying the differences in S. ratti fitness in rats and mice respectively. These results are discussed in relation to competing theoretical models of ecological specialization, host immunology and previous attempts to experimentally alter the host-specificity of parasitic nematodes.

The control of morph development in the parasitic nematode Strongyloides ratti.

The parasitic nematode Strongyloides ratti has a complex life cycle. The progeny of the parasitic females can develop into three distinct morphs, namely directly developing infective third-stage larvae (iL3s), free-living adult males and free-living adult females. We have analysed of the effect of host immune status (an intra-host factor), environmental temperature (an extra-host factor) and their interaction on the proportion of larvae that develop into these three morphs. The results are consistent with the developmental decision of larvae being controlled by at least two discrete developmental switches. One is a sex-determination event that is affected by host immune status and the other is a switch between alternative female morphs that is affected by both host immune status and environmental temperature. These findings clarify the basis of the life cycle of S. ratti and demonstrate how such complex life cycles can result from a combination of simple developmental switches.

Influence of rat strain on larval production by the parasitic nematode Strongyloides ratti.

The course of infection with Strongyloides ratti in a range of rat strains was assessed by monitoring the production of larvae. To our knowledge, this is the first such study of S. ratti using its natural host Rattus norvegicus. Host strain influenced the pattern of larval production. The results were qualitatively the same for 2 S. ratti lines of North American and Japanese origin.