José A. Poblete

Gestational diabetes and pre‐pregnancy overweight: Possible factors involved in newborn macrosomia

Aim:  Good glycemic control in gestational diabetes mellitus (GDM) seems not to be enough to prevent macrosomia (large‐for‐gestational‐age newborns). In GDM pregnancies we studied the effects of glycemic control (as glycosylated hemoglobin [HbA1c]), pre‐pregnancy body mass index (PP‐BMI) and gestational weight gain per week (GWG‐W) on the frequency of macrosomia.

Maternal hypertriglyceridemia: A link between maternal overweight-obesity and macrosomia in gestational diabetes

Infants born from overweight and obese mothers with glucose‐controlled gestational diabetes (GDM) tend to be large‐for‐gestational age (LGA). It is hypothesized that this is due to an excessive rise in maternal triglyceride levels.

Successful liver transplantation and delivery in a woman with fulminant hepatic failure occurring during the second trimester of pregnancy

Abstract: Background: Severe liver dysfunction occurring during pregnancy is an unusual but dramatic event that poses special technical and ethical issues because it involves two lives.

Brain Natriuretic Peptide (BNP) Produced by the Human Chorioamnion May Mediate Pregnancy Myometrial Quiescence

We aim to demonstrate that Brain Natriuretic Peptide (BNP) is synthesized and released from the fetal membranes and mediates pregnancy myometrial quiescence. Myometrium and fetal membranes (FM) were obtained from term and preterm pregnancies at the time of cesarean section, either in labor or not in labor. BNP was measured in term and preterm FM, in culture cells, and conditioned media. We found BNP (but not ANP or CNP) inhibited contractions of preterm, but not term, human myometrium. BNP (both protein and mRNA) was detected in all tissues, conditioned media and cultured cells. BNP was higher in samples from preterm women not in labor compared to those at term not in labor. BNP concentrations were significantly reduced in women in spontaneous preterm labor. We conclude that locally produced BNP may be involved in generating myometrial quiescence during pregnancy. Further, a premature decrease of BNP production may cause preterm labor.

Mechanisms of Paracrine Regulation by Fetal Membranes of Human Uterine Quiescence

Objective: To test the hypothesis that fetal membranes (chorion or amnion) release one or more factors responsible for myometrial quiescence. Methods: Myometrial samples were excised from women at elective term cesarean delivery prior to the onset of labor. Fetal membranes were obtained after cesarean delivery either before or during labor, and either term (greater than 37 weeks) or preterm (less than or equal to 36 weeks). Myometrial strips were placed in organ baths and contractions stimulated by oxytocin (10-8 M). Contractility was measured under isometric conditions before and after exposure to fetal memranes or conditioned medium. The impact of either memrane or conditioned media on contractility was determined before and after myometrial K+ channel blockade. Results: Both chorion and amnion and their respective conbditioned mediums decrease oxytocin-stimulated myometrial contraction. The inhibitory effect was greatest with membranes from preterm pregnancies (mean gestation 32 weeks, P <.05). The inhibitory effect was detectable in the presence of term labor, but was absent when the fetal membranes were obtained after prterm labor. Iberiotoxin, an inhibitor of large conductance Ca2+-activated K+ channels (BKCa) reduced the effect of fetal membranes by 50% (P <.05). Conclusion: We conclude that human fetal membranes release one or more factors that inhibit oxytocin-induced myometrial contractility. We suggest this factor (or factors) acts mainly by opening myometrial BKCa. The findinigs further support our hypothesis that the fetal membranes release a factor (or factors) that is central to myometrial quiescence and its premature loss leads to preterm delivery.

La edad de la mujer como factor de riesgo de mortalidad materna, fetal, neonatal e infantil

Background: Adolescent pregnancy and advanced maternal age are associated with increased risk for maternal, perinatal and infant death. However, the maternal age with the lowest reproductive risk has not been established. Aim: To determine the range of maternal age with the lowest reproductive risk. Material and methods: A population-based study (2005-2010) was performed analyzing raw data from vital statistics yearbooks of the National Institute of Statistics of Chile. The association of maternal, fetal, neonatal and infant mortality with maternal age was analyzed. The latter was stratified in quinquenniums, between ages 10 and 54 years. Maternal, fetal, neonatal and infant mortality rates were calculated for each quinquennium. The lowest rate was selected as a control group for risk analysis, which was estimated according to Odds Ratio with 95% confidence intervals. Results: Women of 20-29, 25-34 and under 30 years, had the lowest rate of fetal, neonatal/infant and maternal death, respectively. Women aged 45-49 years had the higher rate of maternal, fetal, neonatal and infant mortality. The risk of fetal, neonatal and infant mortality doubled from 40-44 years onwards, and maternal mortality from the age of 30-34 years. Conclusions: Our results suggest that the maternal age range with the lesser general reproductive risk is between 20-29 years. This finding should be considered in future studies of reproductive risk and for an appropriate counseling about conception.

Isoform Alpha of PKC May Contribute to the Maintenance of Pregnancy Myometrial Quiescence in Humans

We postulate that protein kinase C α (PKCα) may contribute to the maintenance of pregnancy myometrial quiescence in humans. We studied the changes in myometrial PKCα gene products (messenger RNA [mRNA] and protein) in 4 groups of women: preterm not in labor (PT-NL), preterm in labor (PT-L), term not in labor (T-NL), and term in labor (T-L). The degree of PKCα activation was studied by comparing the levels of particulate (active) PKCα with the total PKCα protein levels and by measuring PKCα activity in the cytosolic and particulate fractions. Protein kinase Cα abundance (mRNA and protein) did not increase during myometrial quiescence (PT-NL), whereas the level of PKCα activity significantly increased during quiescence. The activity of PKCα significantly decreased in the T-NL, T-L, and PT-L groups. These findings suggest that PKCα plays a significant role in the maintenance of myometrial quiescence and that PKCα activity must decrease at the end of pregnancy allowing myometrial activation. Additionally, our data demonstrate an association between reduced PKCα activity and preterm labor, which merits further investigation.

Mechanical Stretch Increases Brain Natriuretic Peptide Production and Secretion in the Human Fetal Membranes

Brain natriuretic peptide (BNP) is synthesized by human fetal membranes, both the amnion and chorion. This locally produced BNP inhibits the contraction of the human myometrium, contributing to the maintenance of myometrial quiescence during pregnancy. We tested the hypothesis that BNP production is increased by fetal membrane stretching, which is predicted to occur in the expanding uterus, and inhibited by epidermal growth factor (EGF), whose production in the fetal membranes increases in late pregnancy. Term fetal membranes were obtained during elective cesarean delivery before labor. Sections of membranes were placed in an isolated chamber containing DMEM: F12 medium (37°C) and stretched with a 35 g weight. Medium and tissue samples were collected at 0, 3, 6, 18, and 24 hours for measurement of messenger RNA (mRNA) and BNP levels in the presence/absence of EGF (2 × 10−9 mol/L). Inducible nitric oxide synthase (iNOS) and β-actin were also evaluated to discard a nonspecific effect of mechanical stretch on protein expression. We found that amnion and chorion stretching increased the BNP mRNA (reverse transcription–polymerase chain reaction [RT-PCR]) and protein (radioimmunosorbent assay [RIA]) levels from 18 hours onward. The effect of stretching was inhibited by EGF (2 × 10−9 mol/L). Stretch did not increase iNOS or β-actin protein levels. We concluded that chorion and amnion stretching may increase BNP expression in the fetal membranes during pregnancy, while increasing biological activity of EGF may decrease BNP production in the chorion and amnion late in pregnancy. We postulate BNP is an important regulator of myometrial contractility during pregnancy, and its production is modulated by both stretch and progressive increase in EGF levels during pregnancy.

La suplementación materna con ácido docosahexaenoico (DHA) carece de beneficio clínicamente significativo

Objetivo: Evaluar los beneficios maternos y fetales de la suplementacion prenatal con acido docosahexae-noico (DHA). Metodo: Revision sistematica de investigaciones clinicas controladas aleatorizadas. Resultados: La suplementacion prenatal con DHA incremento los niveles de DHA en sangre materna, en la leche materna o celulas neonatales. La suplementacion con DHA no redujo los sintomas depresivos maternos ni mejoro el desempeno neurologico y visual de los ninos. Aunque se aprecio un menor riesgo de retraso cognitivo entre los hijos de mujeres suplementadas con DHA (RR 0,4; IC 95% 0,22-0,78) y un mejor desempeno en el procesamiento mental a los 4 anos, el seguimiento a 7 anos mostro ausencia de diferencias significativas en el nivel intelectual. El analisis secundario de dos estudios mostro que la suplementacion con DHA redujo el riesgo de parto prematuro < 34 semanas (RR 0,49; IC95% 0,25-0,94; p=0,03), ingreso a UCI neonatal (RR 0,57; IC95% 0,34-0,97; p=0,04), peso < 2500 g (RR 0,65; IC95% 0,44-0,96; p=0,03) y restriccion de crecimiento intrauterino en pacientes primigestas (RR 0,5; IC 95% 0,3-1,0; p=0,03). Sin embargo, la prevencion de parto prematuro no fue reproducida en estudio disenado especificamente para ello. Conclusiones: Los estudios reportan un mayor contenido de DHA materno y neonatal en respuesta a la su-plementacion prenatal con este acido graso. Sin embargo, la ausencia actual de efectos clinicos relevantes no permite apoyar ni descartar completamente esta intervencion durante el embarazo.