Alfa talasemia e hidrops fetal no inmune a propósito de un caso diagnosticado en la Unidad de Ultrasonografía del Hospital Clínico San Borja Arriarán / Non-immune hydrops fetalis and alfa thalassemia

We report the unique case of a patient of asiatic origin (chinese), who was evaluated, followed and treated at the Sonography Unit of the Maternity Ward, Clinical Hospital San Borja Arriarán (HCSBA), with the collaboration of the Fetal Medicine Unit, Clinical Hospital of the University of Chile. The patient presented a 30 weeks gestation, which at the moment of evaluation showed a fetus with noninmune Hydrops (mother RH(+), Du (-)). Perinatal evaluation discarded cardiopathy, aneuploidiesmarkers and other malformations accounting for this condition. Fetal ultrasonographic evaluation showed severe cardiac insufficiency, middle cerebral artery Doppler (MCA) suggestive of severe anemia and severe oligoamnios with normal kidneys. Dueto these fi ndings and to the asiatic origin of the patient, the ethiological possibilities of viral infection, B19 parvovirus or anemia of genetic origin such as alfa thalassemia were suggested. Cordocentesis shows hematocrite of 39 percent, discordant with the value estimated by MCA Doppler, which reduced the possibility of a viral origin. We sent a fetal blood sample for Hb electrophoresis. Given the critical hemodynamic conditions and having completed the profilaxis of the hyaline membrane, gestation is interrupted by cesarean section, getting a male NB weighing 2.400 gr, in poor condition, who dies at 10 hours from birth. Electrophoresis reported postcesarean section confirms the diagnosis.

Se reporta el caso inédito, de una paciente de origen asiático (China), evaluada, seguida y tratada en la Unidad de Ultrasonografía de la Maternidad del Hospital Clínico San Borja Arriarán (HCSBA), con la colaboración de la Unidad de Medicina Fetal del Hospital Clínico de la Universidad de Chile. La paciente cursaba un embarazo de 30 semanas al momento de ser evaluada en nuestra unidad donde se diagnosticó una gestación única con un feto que presentaba un hidrops no inmune (madre Rh(+), Du (-)). La evaluación perinatal descartó cardiopatía, marcadores de aneuploidía y otras malformaciones que explicaran dicha condición. La evaluación ultrasonográfica fetal mostraba insuficiencia cardiaca severa, Doppler de arteria cerebral media (ACM) sugerente de anemia severa, oligoamnios severo con riñones normales. Debido a estos hallazgos y al origen asiático de la paciente se plantea la posibilidad etiológica de una anemia por infección viral, (parvovirus B19), o una anemia de origen genético, como la alfa talasemia. La cordocentesis muestra un hematocrito de 39 por ciento, discordante con el valor estimado por Doppler de ACM, lo que alejaba la posibilidad de un origen viral y se envía muestra de sangre fetal para electroforesis de hemoglobina(Hb) fetales. Dada las condiciones hemodinámicas críticas y haber completado profilaxis de membrana hialina se interrumpe el embarazo mediante una cesárea obteniéndose un RN de sexo masculino de 2.400 g, hidrópico, en malas condiciones que fallece a las 10 horas de vida. La electroforesis de proteína de sangre fetal, informada post cesárea, confirma el diagnóstico de alfa talasemia.

Antibiotic administration to patients with preterm labor and intact membranes: is there a beneficial effect in patients with endocervical inflammation?

OBJECTIVE: To determine whether broad-spectrum antibiotic administration to patients with preterm labor and intact membranes is associated with an improvement in neonatal and maternal outcomes, particularly in patients with microbial invasion of the amniotic cavity (MIAC) or endocervical inflammation (ECI). METHODS: A prospective clinical trial was conducted in which women in premature labor were alternately allocated to receive either antibiotics or placebo, and information about MIAC and ECI collected. Eighty-four pregnant women between 24 and 34 weeks of gestation with spontaneous preterm labor were enrolled. Exclusion criteria were cervical dilatation greater than 3 cm, clinical chorioamnionitis, abruption, rupture of membranes, vaginal bleeding, and several additional fetal and maternal conditions that may influence perinatal outcome. Amniocentesis was offered to all patients and the cervix and vagina were sampled for microbiological and cytological studies. Eligible patients were allocated to receive either clindamycin-gentamycin or placebo for 7 days. Corticosteroids and tocolysis with beta-adrenergic agents were used according to the standard management of our institution. MIAC was defined as the presence of a positive amniotic fluid culture obtained by trans-abdominal amniocentesis. ECI was diagnosed when a significant increase in the white blood cell count of the endocervical secretions was found. A composite neonatal morbidity/mortality outcome was created, including severe neonatal morbidity (respiratory distress syndrome, asphyxia, sepsis, pneumonia, intraventricular hemorrhage) and mortality. RESULTS: Thirty-nine women received antibiotics and 40 received placebo. The prevalence of ECI and MIAC in both groups was comparable (antibiotic group ECI 61.5% (24/39) and MIAC 20.5% (8/39); placebo group ECI 62.5% (25/40) and MIAC 20% (8/40); p > 0.05). Overall, there were no significant differences in maternal infections and composite neonatal outcomes between antibiotic and placebo groups. Women who received antibiotics had a lower rate of subsequent rupture of membranes compared to patients who received placebo (2.6% (1/39) vs. 25% (10/40), respectively; p = 0.007). A sub-analysis showed that among patients with ECI, antibiotic administration was associated with a lower rate of composite neonatal morbidity/mortality outcome compared to those who received placebo (4.2% (1/24) vs. 28% (7/25), respectively; p < 0.05). This association was also present in patients with ECI without MIAC (0% (0/16) vs. 27.8% (5/18); p < 0.05), but not in patients with ECI and MIAC (antibiotic group 12.5% (1/8) vs. placebo group 28.6% (2/7); p > 0.05). CONCLUSIONS: The combination of antibiotics used in this study did not improve maternal or perinatal outcome in patients with preterm labor and intact membranes. Further studies are required to determine if women with endocervicitis presenting with preterm labor and intact membranes may benefit from antibiotic administration.

Functionally significant SNP MMP8 promoter haplotypes and preterm premature rupture of membranes (PPROM).

Matrix metalloproteinase 8 (MMP8), an enzyme that degrades fibrillar collagens imparting strength to the fetal membranes, is expressed by leukocytes and chorionic cytotrophoblast cells. We identified three single nucleotide polymorphisms (SNPs) at -799C/T, -381A/G and +17C/G from the major transcription start site in the MMP8 gene, and determined the functional significance of these SNPs by analyzing their impact upon MMP8 promoter activity and their association with preterm premature rupture of membranes (PPROM). The minor alleles +17 (G) and -381 (G) were in complete linkage disequilibrium. A promoter fragment containing the three minor alleles had 3-fold greater activity in chorion-like trophoblast cells (BeWo, JEG-3 and HTR-8/SVneo) compared with the major allele promoter construct. Electrophoretic mobility shift assays revealed differences in BeWo nuclear protein binding to oligonucleotides representing the -381 and -799 SNPs, suggesting that the minor alleles have reduced transcription factor binding. A case-control study of African-American neonates using allele-specific primers revealed a statistically significant association between the three minor allele haplotype, which displays the highest MMP8 promoter activity in trophoblast cells, with PPROM with an odds ratio (OR) of 4.63 (P < 0.0001), whereas the major allele promoter appeared to be protective (OR = 0.52, P < 0.0002). None of the minor alleles were individually associated with PPROM. These findings demonstrate the functional significance of SNP haplotypes in the MMP8 gene and associations with obstetrical outcomes.

The CARD15 2936insC mutation and TLR4 896 A>G polymorphism in African Americans and risk of preterm premature rupture of membranes (PPROM).

Infection is believed to be a leading cause of preterm premature rupture of membranes (PPROM). The bacterial cell wall component, lipopolysaccharide (LPS), is thought to initiate tissue responses leading to PPROM in the setting of Gram negative infection. LPS is recognized by the innate immune system, including the proteins encoded by the CARD15 and TLR4 genes. A recently described mutation (2936insC) in CARD15 and a polymorphism in TLR4 896 A>G impair responses to LPS. The objective of this study was to determine if African Americans, who have a higher incidence of PPROM than Caucasians, have different frequencies of the mutant CARD15 allele and the TLR4 hyporesponsive variant, and if risk of PPROM is influenced by fetal carriage of these alleles. The allele frequencies for the CARD15 mutation and the TLR4 896G variant in African Americans were similar to those reported for Caucasians. There was no association between the TLR4 alleles examined and PPROM. However, the CARD15 mutation was only detected in controls and not in PPROM cases. We conclude that the CARD15 mutation and hyporesponsive TLR4 allele do not contribute to ethnic variation in the incidence of PPROM.

A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans.

Fetal membrane rupture is associated with increased expression of matrix metalloproteinase-9 (MMP-9) and matrix degradation. We have determined the functional significance of a variable number tandem repeat and a single nucleotide polymorphism (SNP) in the MMP-9 gene on promoter activity and their association with preterm premature rupture of membranes (PPROM). The 14 CA-repeat allele was a stronger promoter than the 20 CA-repeat allele in amnion epithelial cells and WISH amnion-derived cells, but in THP-1 monocyte/macrophage cells the 14 and 20 CA-repeat alleles had similar activities. An SNP at -1562 did not significantly affect promoter activity. A case-control study of African American neonates revealed that the 14 CA-repeat allele was more common in newborns delivered of mothers who had PPROM than in those delivered at term. There was no association between the -1562 SNP and PPROM. We conclude that there are cell host-dependent differences in MMP-9 promoter activity related to CA-repeat number and that fetal carriage of the 14 CA-repeat allele is associated with PPROM in African Americans.

Microbiología aislada en la rotura prematura de membranas de término y factores de riesgo de infección en la madre y recién nacido / Isolated microbiology in the premature rupture of membranes of term and risk factors of maternal infection and newborn

El manejo óptimo de la rotura prematura de membranas a término, tendiente a reducir la morbilidad infecciosa materna y neonatal, sigue siendo motivo de controversia. Los objetivos de este estudio fueron: conocer la prevalencia y microbiología de la invasión microbiana de la cavidad amniótica e infección cervicovaginal y determinar los factores de riesgo de infección en la madre y recién nacido en la rotura prematura de membranas a término. Entre agosto de 1990 y diciembre de 1993, pacientes con rotura prematura de membranas a término fueron invitadas a participar en este trabajo. Se efectuó amniocentesis transabdominal y se tomó muestra del flujo cervicovaginal, para investigar el estado microbiológico de la cavidad amniótica y del cérvix. Se analizaron factores de riesgo de infección. Ciento cinco mujeres fueron enroladas. La prevalencia de invasión microbiana de la cavidad amniótica fue 41,0 por ciento (43/105) y de infección cervicovaginal 61,0 por ciento (64/105). La tasa de infección materna (infección ovular clínica y/o endometritis) fue 8,6 por ciento (9/105); apareció sólo en mujeres con invasión microbiana de la cavidad amniótica y/o infección cérvicovaginal (14,1 por ciento (9/64 comparada con 0 por ciento (0/41) p<0,01) en pacientes sin infección en ambos compartimentos. Las bacterias más comúnmente aisladas de la cavidad amniótica fueron ureaplasma urealyticum, gardnerella vaginalis y peptostreptococcus sp. Los microorganismos más frecuentes en el cérvix fueron ureaplasma urealyticum, gardnerella vaginalis, mycoplasma hominis y streptococcus agalactiae. No se relacionaron con morbilidad infecciosa materna las variables: intervalo rotura de membranas-parto, duración parto, número de exámenes vaginales, score cervical, manejo activo o expectante, ruta del parto y paridad. La morbilidad infecciosa materna en la rotura prematura de membranas a término se relaciona con la presencia infección cervicovaginal e invasión microbiana de la cavidad amniótica, independdientemente de otros factores de riesgo tradicionales