The Effects of Conflict on Fertility Desires and Behavior in Rwanda

Rwanda experienced genocide from April to July 1994 during which over 800,000 people were murdered. Among the far-reaching changes that followed this event among individuals and in society overall, the Rwandan Demographic and Health Surveys (DHS) showed that contraceptive prevalence declined from 13% in 1992 to 4% in 2000 among married women of reproductive age. This dissertation has two hypotheses concerning Rwandan women's fertility preferences and behavior following the genocide. It is hypothesized that, first, high levels of conflict reduced women's desire for a child or for additional children and second, that women who experienced relatively high levels of conflict were more likely to act on their wish to not have a child or another child by using modern contraceptives than were women who experienced relatively low levels of conflict. The study's logistic regression dependent (outcome) variables were desire for a or another child and the use of modern contraceptives; the source for these data was the 2000 DHS. Three groups of independent variables were included: socio-demographic variables, also from the 2000 DHS, included age, number of living children, education level, urban/rural residence and socio-economic status; availability of family planning services, assessed using women's perception of distance as a barrier to obtaining health care for themselves, from the 2000 DHS, and quality of health services, assessed with data from the 2001 Service Provision Assessment; and experience of conflict, measured as the percentage of the 1994 commune populations that resided in refugee camps in 1995. Communes were considered `high migration' if 10 percent or more of their populations migrated to camps and `low migration' if less than 10 percent of their populations migrated to camps. Women who lived in high migration communes were considered to have relatively high experience of conflict and those who lived in low migration communes were consider dot have relatively low experience of conflict. Analysis showed that residents of high migration communes were significantly less likely to want a or another child as compared to residents of low migration communes (OR = .74); it appeared that the social environment of high migration had a dampening effect on desire for children. The analysis also showed that residents of high migration communes were significantly less likely to use a modern contraceptive method than were those of low migration communes (OR = .57), even though they were less likely to want a or another child and even when family planning services were reasonably available. The reasons for these results are unclear, and many factors may contribute. The generalized trauma experienced by the population may have had a numbing effect, in which taking action in any domain was difficult. Women may have felt pressured by society to have children as the society emerged from war, despite their own preferences. The population may also have distrusted government health facilities - the only source of services for most - in light of the interactions with officials during and after the genocide. However, another set of reasons specific to women and women's health may also have influenced the findings. There is a pervasive social stigma around reproductive health; these services have generally lagged behind other primary health care components. Moreover, rape was used as a weapon of war in the genocide; these experiences may have reduced women's willingness to seek reproductive health services specifically. Finally, the Rwandan genocide and its preparation were decidedly misogynistic; this pervasive dehumanization may have made it particularly difficult for women to seek care for their sexual and reproductive health needs and desires. This complex personal, social, physical and political context may explain why Rwandan women who may not have wanted a child or additional children nonetheless did not consistently act on their desires in the years following the 1994 genocide. The dissertation includes a series of essays providing the author's personal perspective on working in Rwanda in the 1980s and 1990s and being present in the country at the start of the genocide in April 1994

Why don’t humanitarian organizations provide safe abortion services?

Background Although sexual and reproductive health services have become more available in humanitarian settings over the last decade, safe abortion services are still rarely provided. The authors’ observations suggest that four reasons are typically given for this gap: ‘There’s no need’; ‘Abortion is too complicated to provide in crises’; ‘Donors don’t fund abortion services’; and ‘Abortion is illegal’. Discussion However, each of these reasons is based on false premises. Unsafe abortion is a major cause of maternal mortality globally, and the collapse of health systems in crises suggests it likely increases in humanitarian settings. Abortion procedures can be safely performed in health centers by mid-level providers without sophisticated equipment or supplies. Although US government aid does not fund abortion-related activities, other donors, including many European governments, do fund abortion services. In most countries, covering 99 % of the world’s population, abortion is permitted under some circumstances; it is illegal without exception in only six countries. International law supports improved access to safe abortion. Summary As none of the reasons often cited for not providing these services is valid, it is the responsibility of humanitarian NGOs to decide where they stand regarding their commitment to humanitarian standards and women’s right to high quality and non-discriminatory health services. Providing safe abortion to women who become pregnant as a result of rape in war may be a more comfortable place for organizations to begin the discussion. Making safe abortion available will improve women’s health and human rights and save lives

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Family planning in conflict: results of cross-sectional baseline surveys in three African countries

Background: Despite the serious consequences of conflict for reproductive health, populations affected by conflict and its aftermath face tremendous barriers to accessing reproductive health services, due to insecurity, inadequate numbers of trained personnel and lack of supplies. Family planning is often particularly neglected. Methods: In six conflict-affected areas in Sudan, northern Uganda and the Democratic Republic of Congo, household surveys of married or in-union women of reproductive age were conducted to determine baseline measures of family planning knowledge, attitudes and behaviors regarding contraception. Health facility assessments were carried out to assess baseline measures of family planning services availability. Data were double-entered into CSPro 3.2 and exported to SAS 9.2, which was used to calculate descriptive statistics. The studies' purposes were to guide program activities and to serve as a baseline against which program accomplishments could be measured. Results: Knowledge of modern contraceptive methods was low relative to other sub-Saharan African countries, and use of modern methods was under 4% in four sites; in two sites with prior family planning services it was 12% and 16.2%. From 30% to 40% of women reported they did not want a child within two years, however, and an additional 12% to 35% wanted no additional children, suggesting a clear need for family planning services. The health facilities assessment showed that at most only one-third of the facilities mandated to provide family planning had the necessary staff, equipment and supplies to do so adequately; in some areas, none of the facilities were prepared to offer such services. Conclusions: Family planning services are desired by women living in crisis situations when offered in a manner appropriate to their needs, yet services are rarely adequate to meet these needs. Refugee and internally displaced women must be included in national and donors' plans to improve family planning in Africa

Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6–1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin

Complete sequence of the 22q11.2 allele in 1,053 subjects with 22q11.2 deletion syndrome reveals modifiers of conotruncal heart defects

The 22q11.2 deletion syndrome (22q11.2DS) results from non-allelic homologous recombination between low-copy repeats termed LCR22. About 60%-70% of individuals with the typical 3 megabase (Mb) deletion from LCR22A-D have congenital heart disease, mostly of the conotruncal type (CTD), whereas others have normal cardiac anatomy. In this study, we tested whether variants in the hemizygous LCR22A-D region are associated with risk for CTDs on the basis of the sequence of the 22q11.2 region from 1,053 22q11.2DS individuals. We found a significant association (FDR p < 0.05) of the CTD subset with 62 common variants in a single linkage disequilibrium (LD) block in a 350 kb interval harboring CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64-4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21 × 10-5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression

Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6–1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin

A normative chart for cognitive development in a genetically selected population

Certain pathogenic genetic variants impact neurodevelopment and cause deviations from typical cognitive trajectories. Understanding variant-specific cognitive trajectories is clinically important for informed monitoring and identifying patients at risk for comorbid conditions. Here, we demonstrate a variant-specific normative chart for cognitive development for individuals with 22q11.2 deletion syndrome (22q11DS). We used IQ data from 1365 individuals with 22q11DS to construct variant-specific normative charts for cognitive development (Full Scale, Verbal, and Performance IQ). This allowed us to calculate Z-scores for each IQ datapoint. Then, we calculated the change between first and last available IQ assessments (delta Z-IQ-scores) for each individual with longitudinal IQ data (n = 708). We subsequently investigated whether using the variant-specific IQ-Z-scores would decrease required sample size to detect an effect with schizophrenia risk, as compared to standard IQ-scores. The mean Z-IQ-scores for FSIQ, VIQ, and PIQ were close to 0, indicating that participants had IQ-scores as predicted by the normative chart. The mean delta-Z-IQ-scores were equally close to 0, demonstrating a good fit of the normative chart and indicating that, as a group, individuals with 22q11DS show a decline in IQ-scores as they grow into adulthood. Using variant-specific IQ-Z-scores resulted in 30% decrease of required sample size, as compared to the standard IQ-based approach, to detect the association between IQ-decline and schizophrenia (p < 0.01). Our findings suggest that using variant-specific normative IQ data significantly reduces required sample size in a research context, and may facilitate a more clinically informative interpretation of IQ data. This approach allows identification of individuals that deviate from their expected, variant-specific, trajectory. This group may be at increased risk for comorbid conditions, such as schizophrenia in the case of 22q11DS