Innate immune system gene polymorphisms in maternal and child genotype and risk of preterm delivery.

OBJECTIVE: There is little information about the combination of genetic variability in pregnant women and their children in relation to the risk of preterm delivery (PTD). In a sub-cohort of 487 non-Hispanic white and 288 African-American mother/child pairs, the Pregnancy Outcomes and Community Health Study assessed 10 functional polymorphisms in 9 genes involved in innate immune function. METHODS: Race-stratified weighted logistic regression models were used to calculate odds ratios for genotype and PTD/PTD subtypes. Polymorphisms significantly associated with PTD/PTD subtypes were tested for mother/child genotype interactions. RESULTS: Three maternal polymorphisms (IL-1 receptor antagonist intron two repeat (IL-1RN), matrix metalloproteinase- -C1562T, and TNF receptor two M196R (TNFR2)) and three child polymorphisms (IL1-RN, tumor necrosis factor-alpha -G308A, and TNFR2) were associated with PTD, but associations varied by PTD subtype and race. Two interactions were detected for maternal and child genotype. Among non-Hispanic white women, the odds of PTD was higher when both mother and child carried the IL-1RN allele two (additive interaction p < 0.05). Among African-American women, the odds of PTD were higher when both mother and child carried the TNFR2 R allele (multiplicative interaction p < 0.05). CONCLUSION: These results highlight the importance of assessing both maternal and child genotype in relation to PTD risk.

Relation of body fat distribution to femoral neck bone density and endometrial thickness in postmenopausal women.

OBJECTIVE: Menopause is associated with accelerated bone loss, a decrease in lean mass, an increase and redistribution of fat mass in the trunk region. Trunk obesity has been considered as a risk factor for endometrial cancer. We aimed to determine if body composition and fat distribution are determinants of femoral neck bone mineral density (BMD) and endometrial thickness in healthy postmenopausal women. STUDY DESIGN: Subjects were 40 healthy postmenopausal women with biopsy proven atrophic endometrium. Anthropometrical variables (total fat mass, trunk and leg fat masses, lean body mass and femoral neck BMD) were measured by dual energy X-ray absorptiometry. RESULTS: Femoral neck BMD was positively correlated with body mass index, total fat mass, trunk fat mass, leg fat mass and endometrial thickness, and negatively correlated with age, years since menopause and FSH levels. Trunk fat and age remained significant determinants of femoral neck BMD (R(2) = 32.9 %, p < 0.001) and endometrial thickness was significantly associated with femoral neck BMD and oestradiol levels (R(2) = 46.5%, p < 0.0001) on regression analysis. CONCLUSION: Truncal adiposity rather than overall adiposity or lean mass are more closely associated with femoral neck BMD and there is no relationship between subcutaneous fat mass and endometrial thickness in postmenopausal women.

Hyaluronan modulates pro-inflammatory immune activity in the mid-trimester amniotic cavity.

Hyaluronan (HA), which comprises repeating disaccharides of D-glucuronic acid and N-acetyl-glucosamine, is a component of the extracellular matrix. In response to infection or tissue injury HA is released into the extracellular milieu where it modulates immune activity. We hypothesized that HA is present in mid-trimester amniotic fluid and contributes to immune regulation at that site. Amniotic fluid from 392 women undergoing a mid-trimester amniocentesis were tested for HA by ELISA. Amniotic fluids from 41 women were also cultured ex vivo in the presence or absence of lipopolysaccharide (LPS). Supernatants were collected after 24h and tested for tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-10 by ELISA. Clinical parameters were obtained after completion of laboratory testing. All amniotic fluids were positive for HA. The median (range) concentration was 3.2 (0.6-91.7) microg/mg amniotic fluid protein. Women with at least 2 prior pregnancies and a history of > or =2 spontaneous abortions had a higher median HA concentration than did previously pregnant women with 0-1 prior abortions. Women who conceived following in vitro fertilization also had an elevated median amniotic fluid HA compared to women with spontaneous conceptions. Both endogenous and LPS-induced TNFalpha production by ex vivo cultured amniotic fluid cells, but not IL-10 production, was inversely proportional to the amniotic fluid HA concentration. In conclusion, intraamniotic HA levels are elevated in pregnancies at risk for adverse outcome and HA may be a component of the fetal response to immune alterations that threaten gestation.

Endogenous adenosine down-modulates mid-trimester intraamniotic tumor necrosis factor-alpha production.

PROBLEM: To determine whether adenosine in amniotic fluid down-regulates pro-inflammatory cytokine production. METHOD OF STUDY: Mid-trimester amniotic fluid from 21 women was incubated ex vivo in the presence or absence of human adenosine deaminase, the enzyme that irreversibly degrades adenosine. After 24 hr, supernatants were assayed by ELISA for tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-10. Clinical parameters were obtained after completion of laboratory testing. RESULTS: Inclusion of adenosine deaminase resulted in a median increase in TNF-alpha production from 0.9 to 7.3 pg/mL (P = 0.0014). IL-6 production exhibited a non-significant median increase from <2.0 to 53.0 pg/mL (P = 0.0780). Median IL-10 production increased slightly from a median of <0.2 to 1.3 pg/mL. Adenosine deaminase-stimulated TNF-alpha production was proportional to parity and unrelated to gestational age, time of delivery, maternal age or indication for amniocentesis. CONCLUSION: Adenosine deaminase treatment increases TNF-alpha production by ex vivo-cultured amniotic fluid. Adenosine contributes to immune modulation in the amniotic cavity.

Gelsolin down-regulates lipopolysaccharide-induced intraamniotic tumor necrosis factor-alpha production in the midtrimester of pregnancy.

OBJECTIVE: The purpose of this study was to identify gelsolin in midtrimester amniotic fluid and evaluate its interaction with lipopolysaccharide (LPS). STUDY DESIGN: Supernatants from 40 midtrimester amniotic fluid samples were incubated with Escherichia coli LPS, and gelsolin binding was measured by enzyme-linked immunosorbent assay. Unfractionated aliquots of 25 of the fluids were cultured ex vivo for 24 hours in the presence of LPS and supernatants tested for tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 production, and the influence of antigelsolin antibody was evaluated. RESULTS: Each amniotic fluid was positive for gelsolin that bound to LPS. LPS-induced TNF-alpha production was inversely proportional to the amniotic fluid concentrations of LPS-bound gelsolin (r = -0.5047; P = .006). Preincubation with monoclonal antibody to gelsolin led to an increase in LPS-induced TNF-alpha production (P = .01). There was no relationship between gelsolin and IL-10 production. CONCLUSION: Gelsolin is present in midtrimester amniotic fluid, binds to LPS, and inhibits the induction of TNF-alpha.

Ex vivo cytokine production by whole mid-trimester amniotic fluid.

We hypothesized that ex vivo measurement of intraamniotic production of immune mediators differed from analysis of these mediators within unincubated amniotic fluid. Mid-trimester amniotic fluid from 72 women were incubated ex vivo with or without 50 ng/ml lipopolysaccharide (LPS). Supernatants and the corresponding unincubated amniotic fluids were tested for interleukin (IL)-6, IL-1 receptor antagonist (IL-1ra), IL-10 and nitric oxide. Ex vivo culture resulted in increased release of IL-6, IL-10 and nitric oxide; IL-1ra levels were decreased following the incubation. A spontaneous preterm birth (SPTB) occurred in 12 (16.7%) of the subjects. Women with a subsequent SPTB had decreased IL-6 and increased IL-10 production following ex vivo culture compared to women with a term delivery. This association was not evident with unincubated amniotic fluids. Conversely, IL-1ra concentrations were elevated in women with subsequent SPTB only in unincubated amniotic fluids. Immune mediator production by ex vivo amniotic fluid culture differs from that present in amniotic fluid supernatants and may provide a more accurate indication of the immune potential of the intraamniotic environment.

Thoraco-omphalopagus conjoined twins detected at as early as 9 weeks of gestation: transvaginal two-dimensional ultrasound, color Doppler and fetoplacental Doppler velocity waveform findings.

Here we report a case of conjoined twins that were diagnosed antenatally by routine two-dimensional transvaginal ultrasound examination at as early as the 9th week of gestational age. The fetuses were of the thoraco-omphalopagus type and were sharing the liver, as confirmed by color Doppler. There was a reversed flow in the single ductus venosus of the twins. Umbilical arterial and venous blood flow waveform did not show any abnormality for this gestational age. This case demonstrated the possibility of making an accurate diagnosis of conjoined twins in the first trimester by transvaginal two-dimensional ultrasound and color Doppler examination. Although conjoined twins were described at first trimester before, fetoplacental Doppler waveform findings at this gestational age have been described very rarely. This case demonstrated the possibility of making an accurate diagnosis of conjoined twins and delineating the extent of organ sharing in the first trimester, and early diagnosis can help the parents with the option for pregnancy termination. The importance of expert early vaginal sonography and color Doppler findings is emphasized.

Ongoing pregnancy in a woman who inadvertently underwent office hysteroscopy during early pregnancy.

OBJECTIVE: To report a case of ongoing pregnancy in a woman who underwent hysteroscopy during the implantation phase. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 34-year-old woman with unexplained infertility who was scheduled for IVF. INTERVENTION(S): Office hysteroscopy. MAIN OUTCOME MEASURE(S): Hysteroscopy during early pregnancy. RESULT(S): An ongoing pregnancy after hysteroscopy during the implantation phase. CONCLUSION(S): The risk of a properly performed hysteroscopy in the implantation phase of an unrecognized pregnancy may be less than expected.

Maternal serum, amniotic fluid and cord leptin levels at term: their correlations with fetal weight.

AIMS: To investigate the relationship between fetal weight and leptin levels in maternal serum, amniotic fluid and umbilical cord. METHODS: Forty pregnant women presenting for antenatal care at early weeks of gestation were enrolled for the study. Maternal and cord blood samples for leptin measurement were obtained at birth. Amniotic fluid samples were recovered by amniotomy performed during labor. Maternal body mass index and placental weight were also recorded. Leptin measurement was carried out using the ELISA method. Spearman's correlation test was used for comparison of non-parametric data. RESULTS: Leptin concentration in venous cord blood correlated significantly with birth weight and placental weight whereas maternal serum and amniotic fluid leptin levels did not show correlation with birth weight. There were no significant correlations between leptin levels in maternal serum, cord blood and amniotic fluid. CONCLUSION: We conclude that lack of correlation between leptin levels in mother, cord and amniotic fluid suggest that these compartments may be non-communicating separate units or have different mechanisms regulating leptin synthesis or degradation, and that leptin in maternal blood and amniotic fluid may not have a direct effect on fetal growth but rather a different role in pregnancy.