The human chorion contains definitive hematopoietic stem cells from the fifteenth week of gestation.

We examined the contribution of the fetal membranes, amnion and chorion, to human embryonic and fetal hematopoiesis. A population of cells displaying a hematopoietic progenitor phenotype (CD34++ CD45low) of fetal origin was present in the chorion at all gestational ages, associated with stromal cells or near blood vessels, but was absent in the amnion. Prior to 15 weeks of gestation, these cells lacked hematopoietic in vivo engraftment potential. Differences in the chemokine receptor and ß1 integrin expression profiles of progenitors between the first and second trimesters suggest that these cells had gestationally regulated responses to homing signals and/or adhesion mechanisms that influenced their ability to colonize the stem cell niche. Definitive hematopoietic stem cells, capable of multilineage and long-term reconstitution when transplanted in immunodeficient mice, were present in the chorion from 15-24 weeks gestation, but were absent at term. The second trimester cells also engrafted secondary recipients in serial transplantation experiments. Thus, the human chorion contains functionally mature hematopoietic stem cells at mid-gestation.

Maternal depression and anxiety are associated with altered gene expression in the human placenta without modification by antidepressant use: implications for fetal programming.

We sought to determine if maternal depression, anxiety, and/or treatment with selective serotonin reuptake inhibitors (SSRIs) affect placental human serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2), and 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) gene expression. Relative mRNA expression was compared among placental samples (n = 164) from healthy women, women with untreated depression and/or anxiety symptoms during pregnancy, and women who used SSRIs. SLC6A4 expression was significantly increased in placentas from women with untreated mood disorders and from women treated with SSRIs, compared to controls. SLC6A2 and 11ß-HSD2 expression was increased in noncontrol groups, though the differences were not significant. SLC6A4, SLC6A2, and 11ß-HSD2 expression levels were positively correlated. The finding that maternal depression/anxiety affects gene expression of placental SLC6A4 suggests a possible mechanism for the effect(s) of maternal mood on fetal neurodevelopmental programming. SSRI treatment does not further alter the elevated SLC6A4 expression levels observed with exposure to maternal depression or anxiety.

Project Console: a quality improvement initiative for neonatal abstinence syndrome in a children's hospital level IV neonatal intensive care unit.

OBJECTIVE: To improve care for infants with neonatal abstinence syndrome. DESIGN: Infants with a gestational age of ≥35 weeks with prenatal opioid exposure were eligible for our quality improvement initiative. Interventions in our Plan-Do-Study-Act cycles included physician consensus, re-emphasis on non-pharmacological treatment, the Eat Sleep Console method to measure functional impairment, morphine as needed, clonidine and alternative soothing methods for parental unavailability (volunteer cuddlers and automated sleeper beds). Pre-intervention and post-intervention outcomes were compared. RESULTS: Length of stay decreased from 31.8 to 10.5 days (p<0.0001) without an increase in readmissions. Composite pharmacotherapy exposure days decreased from 28.7 to 5.5 (p<0.0001). This included reductions in both morphine exposure days (p<0.0001) and clonidine exposure days (p=0.01). Fewer infants required pharmacotherapy (p=0.02). CONCLUSIONS: Our study demonstrates how a comprehensive initiative can improve care for infants with neonatal abstinence syndrome in an open-bay or a high-acuity neonatal intensive care unit when rooming-in is not available or other comorbidities are present.

Uterine Rupture on MRI Presenting as Nonspecific Abdominal Pain in a Primigravid Patient with 28-Week Twins Resulting in Normal Neurodevelopmental Outcomes at Age Two.

BACKGROUND: Uterine rupture is a rare occurrence that requires a high index of suspicion, particularly in a primigravid patient who presents prior to the onset of labor. Mortality rates are particularly high in primigravid patients. CASE: A 36-year-old gravida 1, para 0 patient with dichorionic diamniotic twins presented at 28-weeks of gestation with abdominal pain. The pain was initially intermittent and felt to be musculoskeletal in origin. Ultrasound imaging after 3 days of worsening abdominal pain revealed extrauterine fluid, prompting an urgent MRI. MRI diagnosed the uterine rupture with hemoperitoneum and herniation of both amniotic sacs outside of the uterus, including one twin's torso and extremities, prompting emergency cesarean section. The premature twins required 2-month hospitalizations and had no neurodevelopmental impairments at 2-year follow-up. CONCLUSION: We present a unique case of rupture of an unscarred uterus in a primigravid patient prior to the onset of labor. Multiple gestation is a risk factor. This report adds to a handful of cases in which a history of endometriosis or extrauterine pelvic surgery was also present. The use of ultrasound and MRI to evaluate nonspecific abdominal pain led to the diagnosis and survival of both the mother and her premature twins.

Preeclampsia and Inflammatory Preterm Labor Alter the Human Placental Hematopoietic Niche.

BACKGROUND: The human placenta is a source of hematopoietic stem and progenitor cells (HSPCs). The RUNX1 transcription factor is required for the formation of functional HSPCs. The impact of preeclampsia (PE) and preterm labor (PTL, spontaneous preterm labor [sPTL] and inflammatory preterm labor [iPTL]) on HSPC localization and RUNX1 expression in the human placenta is unknown. METHODS: We compared the frequency and density of HSPC in control samples from sPTL (n = 6) versus PE (n = 6) and iPTL (n = 6). We examined RUNX1 protein and RNA expression in placentas from normal pregnancies (5-22 weeks, n = 8 total) and in placentas from the aforementioned pregnancy complications (n = 5/group). RESULTS: Hematopoietic stem and progenitor cells were rare cell types, associated predominantly with the vasculature of placental villi. The HSPC density was greater in the chorionic plate (CP) compared to the villi (P < .001) and greater in PE and iPTL samples as compared to controls within the CP (not significant) and overall (P < .05). During the fetal period, RUNX1 was expressed in the mesenchyme of the CP and villi. Inflammatory PTL samples were more likely to exhibit intraluminal RUNX1(+) cell populations (P < .001) and RUNX1(+) cell clusters attached to arterial endothelial cells. CONCLUSION: Placental HSPCs likely arise from hematopoietic niches comprised RUNX1(+) mesenchyme and vascular endothelium. Pregnancy complications that result in preterm birth differentially affect placental HSPC localization and RUNX1 expression. Our results support previous findings that inflammation positively regulates hematopoiesis. We present new evidence that hemogenic endothelium may be active at later stages of human fetal development in the context of inflammation.

Damage control: unintended pregnancy in the United States military.

Women's access to reproductive health care is an ongoing source of conflict in U.S. politics; however, women in the military are often overlooked in these debates. Reproductive health care, including family planning, is a fundamental component of health care for women. Unintended pregnancy carries substantial health risks and financial costs, particularly for servicewomen. Compared with their civilian counterparts, women in the military experience greater challenges in preventing unwanted pregnancy and have less access to contraceptive services and abortion. Current military policies, federal laws, and health care practices are not always consistent with evidence-based research and patient-centered care. A multidisciplinary effort on the part of military personnel, lawmakers, and health care providers is needed to eliminate these disparities. We discuss recommendations in the following categories: improving contraceptive education and adherence, expanding research, broadening access to the full range of contraceptive options including emergency contraception, and ensuring access to safe abortion.

Delayed diagnoses: nonspecific findings and diagnostic challenges in eating disorders.

Objective. Eating disorders commonly present with nonspecific findings, masquerading as other, more common etiologies of malnutrition and wasting. In low-prevalence populations, these ambiguities can complicate clinicians' diagnostic reasoning, resulting in delayed or missed diagnoses. Method. We report the atypical case of a 51-year-old male with a five-year history of unexplained weight loss despite extensive past medical evaluation. Previous documentation of profound lymphopenia and bone marrow atrophy had not been linked to a known association with eating disorders. Results. Evaluation for medical etiologies of wasting was negative. Following psychiatric evaluation, the patient was diagnosed with an eating disorder, not otherwise specified, and admitted to a specialized nutritional rehabilitation program. Conclusion. The nonspecific clinical history, physical exam, and laboratory abnormalities of eating disorders can make these diagnoses challenging and delay appropriate treatment. Clinicians should consider eating disorders in patients with malnutrition, severe lymphopenias, and gelatinous marrow transformation early in their workup, so as to avoid potentially negative outcomes.

Fetal effects of psychoactive drugs.

Psychoactive drug use by pregnant women has the potential to effect fetal development; the effects are often thought to be drug-specific and gestational age dependent. This article describes the effects of three drugs with similar molecular targets that involve monoaminergic transmitter systems: cocaine, methamphetamine, and selective serotonin re-uptake inhibitors (SSRIs) used to treat maternal depression during pregnancy. We propose a possible common epigenetic mechanism for their potential effects on the developing child. We suggest that exposure to these substances acts as a stressor that affects fetal programming, disrupts fetal placental monoamine transporter expression and alters neuroendocrine and neurotransmitter system development. We also discuss neurobehavioral techniques that may be useful in the early detection of the effects of in utero drug exposure.