Stillbirth: Genome-wide copy number variation profiling in archived placental umbilical cord samples with pathologic and clinical correlation.

INTRODUCTION: Stillbirth remains a devastating health issue with 26,000 stillbirths occurring annually in the United States. Formalin-fixed, paraffin-embedded (FFPE) umbilical cord samples are available for many stillbirths. Our aim was to validate the use of these samples in identifying genetic variations in stillbirth through microarray analysis. METHODS: This is a retrospective case-control study from a single institution of stillbirths ≥ 23 weeks gestational age and control liveborn infants. Fetal genomic DNA was extracted from FFPE umbilical cord samples of stillborn and control placentas, and genotyping was performed using the Illumina HumanOmniExpresss-12v1 Beadchip. Array results were verified with qPCR. RESULTS: 31 case-specific CNVs (17 deletions and 14 amplifications) with an average size of 294 kb for amplifications and 74 kb for deletions were identified among 94 FFPE samples (86 cases; 8 controls). In total 38 (44%) of the stillbirth samples had a CNV detected. Validation of a subset of microarray findings with qPCR confirmed deletions on 1p (2 cases), 11q (4 cases) and amplifications on 18 (1 case). Placental underperfusion changes were seen in stillborns with deletions on 1p, a region containing complement regulatory genes which have been shown to play a role in preeclampsia. DISCUSSION: This study validated the use of archived FFPE umbilical cord samples for genome-wide copy number profiling in stillbirths, and demonstrates specific CNV deletions and amplifications. Microarray analysis in an expanded cohort of stillbirth FFPE samples has the potential to identify biomarkers involved in stillbirth pathogenesis.

Placental pathologic changes of maternal vascular underperfusion in bronchopulmonary dysplasia and pulmonary hypertension.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy, and BPD-associated pulmonary hypertension (PH) is a serious complication that can negatively impact later childhood health. There is growing evidence that lung injury leading to BPD and PH is due to chronic fetal hypoxia-ischemia. The purpose of this study was to investigate whether placental pathologic changes of maternal vascular underperfusion (MVU) are associated with BPD, and further increased with PH. METHODS: We conducted a 5-year retrospective cohort study of premature infants born ≤28 weeks. BPD was defined as persistent oxygen requirement at 36 weeks corrected gestational age. PH was identified using a standardized algorithm of echocardiogram review. Archived placental slides underwent standardized masked histopathologic review. Logistic regression modeling was performed, taking into account important maternal and infant covariates. RESULTS: Among 283 births, 121 had MVU, of which 67 (55%) developed BPD, and 24 (20%) had PH. Among the common neonatal complications of extreme prematurity, BPD was the only outcome that was increased with MVU (P < 0.001). After adjustment for birth weight, fetal growth restriction, preeclampsia and other factors, infants with MVU were more likely to develop BPD (adjusted odds ratio = 2.6; 95% confidence interval = 1.4, 4.8). Certain MVU sublesions (fibrinoid necrosis/acute atherosis and distal villous hypoplasia/small terminal villi) were increased with PH (P < 0.001). DISCUSSION: Placental MVU may identify BPD infants who were exposed to intrauterine hypoxia-ischemia, which increases their risk for development of PH disease. CONCLUSIONS: Our findings have important implications for providing earlier and more effective therapies for BPD.

Gross patterns of umbilical cord coiling: correlations with placental histology and stillbirth.

INTRODUCTION: The purpose of this study was to define gross patterns of umbilical cord hypercoiling and determine correlations with histological features in the placenta and/or perinatal outcomes such as stillbirth. METHODS: Gross images of placentas with hypercoiled umbilical cords (>3 coils/10 cm) were assigned a major umbilical coiling pattern and the direction (right or left) of the coiling. Definitions of 4 gross coiling patterns were established: undulating, rope, segmented, and linked, each with progressively deeper indentations in cord diameter. Outcome variables obtained from placental pathology reports and maternal medical records included histological abnormalities indicative of significant chronic fetal vascular obstruction, such as fetal vascular thrombi, avascular villi, villous stromal-vascular karyorrhexis, and fetal thrombotic vasculopathy, and stillbirth. RESULTS: 318 placentas/umbilical cords met inclusion criteria. The rope pattern was the most common (52%), followed by the undulating (26%), segmented (19%) and linked (3%) patterns. The segmented and linked gross coiling patterns were significantly correlated with histologic evidence of chronic fetal vascular obstruction and stillbirth, when compared with the ropeand undulating patterns. Cords with right twists were also significantly correlated with histologic evidence of chronic fetal vascular obstruction and stillbirth when compared with cords with left twists. The number of cord coils per 10 cm did not correlate with any of the outcome variables. CONCLUSIONS: Among hypercoiled umbilical cords, specific gross patterns of coiling can be recognized, and patterns with the most significant indentation or pinching of the cord diameter are associated with histological evidence of chronic fetal vascular obstruction and stillbirth.

Changes in the differential treatment of Rajput girls in Khalapur: 1955-1975.

PIP: This article reports on data collected during 2 field trips to Khalapur. The 1st, 1954-55, focused on child rearing. The 2nd, 1974-75, focused on changes in the status of Rajput women. In 1955, neglect of girls, particularly those suffering from longterm illness, resulted in sufficient female mortality to produce a striking preponderance of boys. In 1975, the number of children in the original families sampled had increased from 128 to 250, a rise of 277% in total number of living offspring. In the 1975 sample, 45% were girls. The factors that contributed to this increase in viability of daughters are examined. The overall health of the children had improved from the 50s to the 70s. The improvement in health may be linked to better nutrition and preventive medicine and to the presence of a government sponsored village health center. In 1975, the village had also acquired a semi-skilled midwife. Mothers' reports indicate that there is a 10% difference in the use of this more highly paid midwife to deliver boys. Education emerges as another important factor. In 1975, 75% of Rajput girls between 6-20 were literate or in school, a dramatic 61% increase from the 14% reported in 1955. Moreover, all of the children of educated mothers were in school. The increase in school enrollment figures reflect this improvement in girls' education. Norms for early marriage present strong barriers for college education of women. The greater education of Khalapur women seems to have emerged from the increased education of men. Educated men prefer literate wives. Therefore education becomes an asset in arranging a good marriage for daughters. The government has encouraged education and has facilitated that of girls by not requiring them to pay tuition in elementary school. Despite the obvious improvement in the treatment of girls, some evidence of differential neglect persists. Nonetheless, for the Khalapur Rajput, the overall picture is one of optimism. Finally, it is argued that in view of the extensive literature on the rare practice of female infanticide, it is somewhat surprising that indirect female infanticide from medical and nutritional neglect of girls, has received little attention, since indirect infanticide is probably more widespread and frequent.^ieng

Infanticide as a terminal abortion procedure.

PIP: This study examines the propostion that infanticide is a terminal abortion procedure, practiced when abortion attemps fail, or when the decision to kill an infant is based on characteristics that can be observed only after birth. Infanticide is defined as the deliberate killing of a child by any realistic means including exposure, but excluding accidental or magical means of death. Data on infanticide in 57 societies was collected to determine 1) when infanticide was performed (most often at birth), 2) who performed it (most often the mother), and 3) what kinds of infants were the victims (most often the illegitimate, twins or triplets, and the weak and deformed). There is also data on the time of the birth ceremony, who performed the ceremony, and who received it. It is found that infanticide takes place before the infant's birth ceremony and that the reasons for abortion and infanticide are similar. The victims of infanticide are viewed as fetuses and not newborns. The authors conclude that the majority of societies practicing infanticide do so for reasons that probably benefit women and apparently do not harm them. Appended to the article is a table of categories for coding data on infanticide by each society studied.^ieng