Cross-Generational Contributors to Preterm Birth in California: Singletons Based on Race/Ethnicity.

OBJECTIVE: Multiple studies have examined cross-generational patterns of preterm birth (PTB), yet results have been inconsistent and generally focused on primarily white populations. We examine the cross-generational PTB risk across racial/ethnic groups. STUDY DESIGN: Retrospective study of 388,474 grandmother-mother-infant triads with infants drawn from birth registry of singleton live births between 2005 and 2011 in California. Using logistic regression (odds ratios [ORs] and confidence intervals [CIs]), we examined the risk of preterm delivery by gestational age, sociodemographic, socioeconomic, and obstetric clinical characteristics stratified by maternal race/ethnicity. RESULTS: The risk of having a preterm infant <32 weeks was greater for women born at <32 weeks (OR: 2.09, 95% CI: 1.62-2.70) and 32 to 36 weeks (OR: 1.51, 95% CI: 1.35-1.70). This increased risk of preterm delivery was present among women in all race/ethnicity groups (white [AOR: 2.00, 95% CI: 1.52-2.63), black [AOR: 1.79, 95% CI: 1.37-2.34], Hispanic [AOR: 2.39, 95% CI: 2.05-2.79], and Asian [AOR: 2.12, 95% CI: 1.20-3.91]), with hypertension as the only consistent risk factor associated with increased risk of preterm delivery. CONCLUSION: Our findings suggest a cross-generational risk of PTB that is consistent across race/ethnicity with hypertension as the only consistent risk factor.

Down-regulation of the placental BCRP/ABCG2 transporter in response to hypoxia signaling.

INTRODUCTION: The BCRP/ABCG2 efflux transporter protects the developing fetus by limiting the transplacental transfer of drugs and chemicals and prevents the apoptosis of trophoblasts. The purpose of this study was to determine whether hypoxia-related signaling alters placental BCRP expression and function in vitro and in human pregnancies. METHODS: Human BeWo choriocarcinoma cells were treated with the hypoxia mimetic, cobalt chloride (CoCl2), or 3% oxygen for 24-48 h. Activation of HIF-1α signaling and regulation of BCRP was assessed using qPCR, ELISA, western blotting and a fluorescent substrate transport assay. In addition, healthy term placentas from high altitude pregnancies with chronic hypoxia were assessed for BCRP expression. RESULTS: CoCl2 and 3% oxygen increased HIF-1α protein signaling and decreased the mRNA and protein expression of BCRP by 30-75% in BeWo cells. Reduced BCRP expression corresponded with impaired efflux activity during hypoxia as evidenced by accumulation of the substrate Hoechst 33342. A number of transcription factors known to regulate BCRP, including AHR, NRF2 and PPARγ, were also coordinately down-regulated by 3% oxygen in BeWo cells. Moreover, women who gave birth at a high altitude (3100 m) exhibited signs of chronic placental hypoxia, including enhanced protein expression of the HIF-1α target GLUT1, and had reduced BCRP levels in microvillous membranes compared to women at a moderate altitude (1600 m). DISCUSSION: This study provides novel insight into the regulation of the placental BCRP transporter by hypoxia, which may be important for exposure of the fetus to chemicals during early development and in hypoxia-related pregnancy disorders.

7q21.11 Microdeletion in a Neonate With Goldenhar Syndrome: Case Report and a Literature Review.

The oculoauriculovertebral spectrum or Goldenhar syndrome is characterized by varying degrees of prevalently unilateral underdevelopment of the craniofacial structures (orbit, ear, and mandible) in association with vertebral, cardiac, renal, and central nervous system defects. We report on a term neonate with a partial monosomy 7q21.11 with marked hemifacial microsomia, facial clefting, and spinal anomaly. The estimated size of the monosomic region of 7q21.11 was approximately 55 kilobases. This is the first report of a patient with partial monosomy 7q21.11 associated with oculoauriculovertebral spectrum.

Clival encephalocele and 5q15 deletion: a case report.

A preterm neonate presenting with respiratory distress after birth was found to have a clival encephalocele, which is a variant of a basal encephalocele, and hypoplasia of the cerebellum. Genetic studies revealed a small deletion of the long arm of chromosome 5: 5q15 deletion. We report a rare variant of a basal encephalocele with a cerebellar malformation and 5q15 deletion.

Counseling a patient with the antenatal diagnosis of a cerebellar abnormality and a pharyngeal cyst.

Introduction Prenatal counseling with regards to the prognosis of a cerebellar abnormality is hindered not only by the diverse clinical presentations but also by the presence of subtle findings. We present a case of a distinct combination of asymmetric cerebellar hypoplasia secondary to an anterior meningoencephalocele through a clival defect that caused a severe airway obstruction in the newborn. Case Description A 21-year-old gravida 4 para 0 mother with a dichorionic-diamniotic twin pregnancy was referred for a second trimester sonographic survey. An asymmetric cerebellar hypoplasia, mega cisterna magna, and a pharyngeal cystic mass were noted on twin A. Magnetic resonance imaging report confirmed posterior fossa abnormalities and shed no light on the differential diagnosis of the cystic mass. The pregnancy ended by Cesarean delivery at 32 weeks' gestation after a preterm premature rupture of the membranes. Twin A had a severe airway obstruction. Postnatal evaluation confirmed a midline anterior meningoencephalocele through a defect in the clivus. The microarray chromosomal analysis demonstrated a 5q15 variant with uncertain clinical significance. Conclusion Antenatal recognition of the unique combination of a cerebellar hypoplasia with a pharyngeal cyst can impact the prenatal counseling as well as neonatal management.

Screening for Down syndrome in dichorionic twin pregnancies conceived by in vitro fertilization (IVF): a clinical pilot study to confirm the laboratory methods.

PURPOSE: The corrections necessary to estimate the risk for Down syndrome in twin pregnancies have been pointed out. We performed a nested controlled study to evaluate the validity of these corrections in dichorionic twins conceived by IVF. METHODS: Detailed clinical data was collected from the medical records. Twins were matched with a contemporaneous cohort of spontaneously conceived singleton pregnancies that serve as reference in a 1 to 4 ratio. All patients had their entire obstetrical care at our Hospital. The Student t-test was used for group comparisons and a p-value <0.05 was considered significant. RESULTS: Nineteen sets of normal twins concordant in size and with appropriate weight for gestational age were matched with 80 normal and mature newborns. Significant differences between groups were found for maternal age, gestational age at delivery and newborn weight (all p < 0.01). No statistical differences were noted for the levels of the biochemical markers expressed as multiples of the median. However, a 15 % closer approximation to the laboratory median for PAPP-A and a 10 % closer approximation to the laboratory median for free ß-hCG was evident in twins when compared to the reference group. CONCLUSIONS: These findings support the methods used to estimate the risk for Down syndrome in dichorionic twin pregnancies conceived after IVF. A future study with a larger sample size could confirm if the laboratory corrections done on the combined screening test improve the predictability of Down syndrome in dichorionic twin pregnancy conceived by IVF when compared to singleton pregnancies.

Baseline TNFα operational capacity in fetal and maternal circulation prior to the onset of labor: "tuned for different purposes".

OBJECTIVE: In this study, we sought to characterize the tumor necrosis factor α (TNFα) baseline operational capacity in mature fetuses and their mothers prior to the onset of labor. MATERIALS AND METHODS: We used an experimental pregnant nonhuman primate model to measure the plasma concentration of TNFα, TNF transmembrane receptor I (TNFRI), and TNFRII with validated enzyme-linked immunosorbent assays. Coefficients of correlations between the maternal and the fetal values and the soluble TNFα, TNFRI, or TNFRII concentrations and ratios were calculated. RESULTS: The TNFα/TNFRI ratio was 3 times lower in fetal circulation than in maternal circulation. No correlations were noted between the maternal and the fetal TNFα, TNFRI, or TNFRII plasma concentrations. CONCLUSIONS: These findings suggest that the fetal and maternal baseline circulatory operational capacities of TNFα are independent of each other and tuned differently. This differential regulation of TNFα in fetal and maternal circulation at the end of pregnancy may be guided to protect the fetus from the systemic inflammatory response that is essential for the mechanisms of labor to proceed in the mother.