Maternal urinary tract infection: is it independently associated with adverse pregnancy outcome?

Objective. This population-based study was aimed to determine whether there is an association between urinary tract infections (UTI) during pregnancy, among patients in whom antibiotic treatment was recommended, and maternal and perinatal outcome.

Methods. A retrospective population-based study comparing all singleton pregnancies of patients with and without UTI was performed. Multiple logistic regression models were performed to control for confounders.

Results. Out of 199,093 deliveries, 2.3% (n = 4742) had UTI during pregnancy and delivery. Patients with UTI had significantly higher rates of intra-uterine growth restriction (IUGR), pre-eclampsia, caesarean deliveries (CD) and pre-term deliveries (either before 34 weeks or 37 weeks of gestation). Although controlling for possible confounders such as maternal age and parity, using multivariable analyses, the significant association between UTI and IUGR, pre-eclampsia, CD and pre-term deliveries persisted. In contrast, no significant differences in 5-min Apgar scores less than 7 or perinatal mortality were noted between the groups (0.6%vs. 0.6%; p = 0.782, and 1.5%vs. 1.4%; p = 0.704, respectively).

Conclusion. Maternal UTI is independently associated with pre-term delivery, pre-eclampsia, IUGR and CD. Nevertheless, it is not associated with increased rates of perinatal mortality compared with women without UTI.     

Perinatal outcomes and complications of pregnancy in women with immune thrombocytopenic purpura

Objective.?To investigate pregnancy and perinatal outcomes in women with immune thrombocytopenic purpura (ITP).

Methods. A retrospective study comparing all singleton pregnancies of women with and without ITP was conducted. Deliveries occurred between the years 1988 and 2007. Multiple logistic regression models were performed to control for confounders.

Results.?During the study period, 186,602 deliveries were recorded, out of which 104 (0.06%) occurred in patients with ITP. In a multivariable analysis, we found the following conditions to be significantly and independently associated with ITP: hypertensive disorders, diabetes mellitus, and preterm delivery (<34 weeks gestation). Patients with ITP had significantly higher rates of preterm delivery (<34 weeks gestation; 6.7%vs. 2.2%; p < 0.001) and perinatal mortality (4.8%vs. 1.3%; p = 0.011) when compared with patients without ITP. Two multivariable logistic regression models were constructed with perinatal mortality and preterm delivery (<34 weeks gestation) as the outcome variables to control for possible confounders such as congenital malformations, hypertension, diabetes mellitus, and maternal age. In these models, ITP was found to be an independent risk factor for perinatal mortality (OR = 3.77; 95% CI 1.32–10.78, p = 0.013), as well as for preterm delivery before 34 weeks gestation (OR = 3.01; 95% CI 1.39–6.52, p = 0.005).

Conclusion.?ITP is significantly and independently associated with preterm delivery before 34 weeks gestation and with perinatal mortality.     

Pentraxin 3 in maternal circulation: An association with preterm labor and preterm PROM,but not with intra-amniotic infection/inflammation

Objective.?Pentraxin 3 (PTX3) is an acute-phase protein that has an important role in the regulation of the innate immune response. The aim of this study was to determine if maternal plasma PTX3 concentration changes in the presence of intra-amniotic infection and/or inflammation (IAI) in women with preterm labor (PTL) and intact membranes, as well as those with preterm prelabor rupture of membranes (preterm PROM).

Study design.?This cross-sectional study included women in the following groups: (1) nonpregnant (n?=?40); (2) uncomplicated pregnancies in the first (n?=?22), second (n?=?22) or third trimester (n?=?71, including 50 women at term not in labor); (3) uncomplicated pregnancies at term with spontaneous labor (n?=?49); (4) PTL and intact membranes who delivered at term (n?=?49); (5) PTL without IAI who delivered preterm (n?=?26); (6) PTL with IAI (n?=?65); (7) preterm PROM without IAI (n?=?25); and (8) preterm PROM with IAI (n?=?77). Maternal plasma PTX3 concentrations were determined by ELISA.

Results.?(1) Maternal plasma PTX3 concentrations increased with advancing gestational age (r?=?0.62, p?<?0.001); (2) women at term with spontaneous labor had a higher median plasma PTX3 concentration than those at term not in labor (8.29?ng/ml vs. 5.98?ng/ml, p?=?0.013); (3) patients with an episode of PTL, regardless of the presence or absence of IAI and whether these patients delivered preterm or at term had a higher median plasma PTX3 concentration than normal pregnant women (p?<?0.001 for all comparisons); (4) similarly, patients with preterm PROM, with or without IAI had a higher median plasma PTX3 concentration than normal pregnant women (p?<?0.001 for both comparisons); and (5) among patients with PTL and those with preterm PROM, IAI was not associated with significant changes in the median maternal plasma PTX3 concentrations.

Conclusions.?The maternal plasma PTX3 concentration increases with advancing gestational age and is significantly elevated during labor at term and in the presence of spontaneous preterm labor or preterm PROM. These findings could not be explained by the presence of IAI, suggesting that the increased PTX3 concentration is part of the physiologic or pathologic activation of the pro-inflammatory response in the maternal circulation during the process of labor at term or preterm.     

Activation of coagulation system in preterm labor and preterm premature rupture of membranes

Objective: Thrombin, originally discovered as a coagulation factor, is a multifunctional protease capable of inducing myometrial contractions in vitro and in vivo. This enzyme has been implicated in the mechanisms of premature labor. Plasma concentrations of thrombin-antithrombin (TAT) complexes are an index of in vivo thrombin generation. The purpose of this study was to determine whether patients with premature labor and preterm premature rupture of membranes (PROM) have evidence of increased thrombin generation in maternal blood, as determined by the TAT complex concentrations. Methods: A cross-sectional study was designed to determine plasma concentrations of TAT complexes in 110 women in the following groups: non-pregnant women (n = 20); normal pregnant women (n = 30); women in preterm labor with intact membranes (n = 30); and women with preterm PROM (n = 30). TAT complex concentrations were determined with a sensitive and specific immunoassay. Statistical analysis was conducted with non-parametric statistics. Results: Patients with preterm labor and intact membranes had a significantly higher median plasma TAT complex concentration than normal pregnant women (women in preterm labor, median 19.1 μg/l; range 7.4-406 vs. normal pregnant women, median 15 μg/l; range 6.8-32.5; p = 0.03). Patients with preterm PROM had a higher median TAT complex concentration than normal pregnant women (preterm PROM, median 19.1 μg/l; range 4.7-738.6 vs. normal pregnant women, median 15 μg/l; range 6.8-32.5; p = 0.03). Normal pregnancy was associated with a higher median plasma TAT complex concentration than the non-pregnant state (normal pregnant women, median 15 μg/l; range 6.8-32.5 vs. non-pregnant women, median 2.7 μg/l; range 0.9-14.2; p < 0.001). Conclusion: Preterm labor and preterm PROM are associated with an excess generation of thrombin.     

Sonographic Maturation of the Placenta at 30 to 34 Weeks Is Not Associated With Second Trimester Markers of Placental Insufficiency in Low-risk Pregnancies

ObjectiveAdvanced placental maturation (Grannum [G] grade 3) before term is associated with adverse perinatal outcomes associated with placental insufficiency. The nature and timing of the underlying pathology of this process is presently unclear. We hypothesized that advanced placental maturation at 30 to 34 weeks’ gestation is not associated with established second trimester markers of severe placental dysfunction.MethodsIn a cohort study of 1238 low-risk Caucasian women with singleton pregnancies who had sonographic assessment of placental maturation and fetal growth at 34 weeks, the results of maternal serum screening (MSS) and uterine artery Doppler (UtAD) flow studies at 16 weeks were related to adverse perinatal outcomes associated with placental insufficiency: antepartum hemorrhage, preeclampsia, preterm birth < 37 weeks, small for gestational age (< 10th percentile), or postnatal evidence of intrauterine growth restriction (IUGR; ponderal index < 5th percentile).ResultsG1 was found in 127 women (10.3%), G2 was found in 18 women (1.5%), and no cases of G3 were observed. Advanced Grannum grading was significantly associated with IUGR (48 [4.4%] in G0, 9 [7.1%] in G1, 5 [27.8%] in G2; P < 0.001), but was dependent on smoking status. IUGR was not predicted by abnormal MSS or abnormal UtAD findings at either the second or third trimester ultrasounds.ConclusionG2 maturation at 30 to 34 weeks’ gestation is associated with mild IUGR at delivery in low-risk women and with smoking. IUGR was not predicted by either second or third trimester markers of severe placental dysfunction. Future studies directly observing the placenta in the late third trimester may aid the elusive diagnosis of “late-onset” mild IUGR.     

Waiting for postterm in healthy women,is it an accident waiting to happen?

Abstract

Objective: To establish whether postterm pregnancies are associated with adverse perinatal outcomes in a linear fashion.

Study design: A retrospective cohort study investigating perinatal outcomes in singleton term (≥37 weeks gestation) and postterm pregnancies was conducted. Deliveries occurred between the years 1988 and 2010. Parturients were classified into three groups according to their gestational age: 37–39?+?6, 40–41?+?6 and over 42 weeks’ gestation (postterm). Statistical analysis included multiple logistic regression model to control for possible confounders.

Results: Out of 202?462 deliveries, meeting the inclusion criteria, during the study period, 47.7% occurred at 37–39?+?6 weeks, 47.4% occurred at 40–41?+?6 weeks and 4.9% were postterm. Fertility treatments, diabetes mellitus, hypertensive disorders, intrauterine growth restriction (IUGR) and premature rupture of membranes (PROM) were less likely to be associated with postterm pregnancies. However, postterm was found as a significant risk factor for labor complications and adverse perinatal outcome including perinatal mortality. Using a multivariable logistic regression model, controlling for confounders such as maternal age and macrosomia, postterm was found to be an independent risk factor for perinatal mortality (adjusted OR?=?1.5; 95% CI?=?1.20–2.0; p?<?0.001).

Conclusion: Although postterm pregnancies were less likely to be associated with obstetrical risk factors and complications such as fertility treatments, diabetes mellitus, hypertensive disorders, IUGR and PROM, postterm is an independent risk factor for perinatal mortality.     

Poor pregnancy outcome in women with type 1 diabetes is predicted by elevated HbA1c and spikes of high glucose values in the third trimester

Abstract

Objective: To analyse data from a randomised, controlled study of prandial insulin aspart versus human insulin, both with NPH insulin, in pregnant women with type 1 diabetes for potential factors predicting poor pregnancy outcomes.

Research design/method: Post hoc analysis including 91 subjects randomised prior to pregnancy with known outcome in early pregnancy and 259 subjects randomised prior to pregnancy/during pregnancy of <10 weeks’ gestation with known late-pregnancy outcomes. Poor early-pregnancy outcomes included fetal loss <22 gestational weeks and/or congenital malformation (n?=?18). Poor late-pregnancy outcomes included: composite endpoint including pre-eclampsia, preterm delivery and perinatal death (n?=?78); preterm delivery (n?=?63); and excessive fetal growth (n?=?88).

Results: 18 patients experienced a malformed/lost fetus in early pregnancy – none preceded by severe hypoglycaemia. Albuminuria in early pregnancy was a significant predictor of poor late-pregnancy outcome (composite endpoint; p?=?0.012). In the third trimester, elevated HbA_1c,?≥?1 plasma glucose (PG) measurement >11?mmol/L (198?mg/dL) and %PG values outside 3.9–7.0?mmol/L (70–126?mg/dL) were significant predictors of poor late-pregnancy outcomes (all p?<?0.05).

Conclusions: Elevated HbA_1c, high glucose spikes and out-of-range %PG in the third trimester, and albuminuria in early pregnancy, are associated with poor late-pregnancy outcomes.     

Lower Rate of Preeclampsia After Antioxidant Supplementation in Pregnant Women with Low Antioxidant Status

Objective: To investigate maternal and neonatal outcomes after antioxidant supplementation relatively early in pregnancy (8 to 12 weeks) for pregnant women with low antioxidant status. Methods: A randomized, double-blind, placebo-controlled trial of daily antioxidant supplementation was performed on pregnant women screening positive for low antioxidant status at 8 to 12 weeks of gestation. Low antioxidant status was defined as a superoxidedismutase (SOD) level below 1102 U/g Hb or 164 U/mL. The supplementation group received the following antioxidants daily: vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 μg), C (200 mg), and E (400 IU), folic acid (400 μg), N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg), Fe (30 mg), calcium (800 mg), and selenium (100 μg). The control group received Fe (30 mg) and folic acid (400 μg). Maternal (preeclampsia, abortion, and hypertension) and perinatal outcomes were assessed. Results: In the supplementation group (29 subjects), we observed 2 cases of preeclampsia (6.8%, 1 mild and 1 severe), 1 of IUGR (birth weight 2300 g at 38 weeks), and 1 preterm delivery. In the control group (31 subjects), there were 8 abortions, 9 cases of preeclampsia (29%, 6 mild and 3 severe) with perinatal outcome: 3 preterm delivery cases and 1 IUGR (birth weight 2030 g at 39 weeks). Preeclampsia was significantly less frequent in the supplementation group when compared to the control group (2 vs. 9 cases, p = 0.043, OR = 0.18 [95% CI: 0.03, 0.92]). Finally we focused on the prediction of preeclampsia at 8 to 12 weeks. Combined sensitivity of markers of antioxidant status (SOD slutathione peroxidase, [GPx], and total anti-oxidant status [TAS]) was 33% (false-positive rate of 4.5%). Conclusion: Antioxidant supplementation was associated with better maternal and perinatal outcome in pregnant women with low antioxidant status than control supplementation with iron and folate alone. In a selected population already screened positive for low SOD, preeclampsia can be detected in 33% of asymptomatic cases in the first trimester using SOD, GPx, and TAS. It seems feasible that panels of both biochemical and molecular markers may be clinically useful in the prediction of this disease.     

Maternal serum soluble HLA-G in complicated pregnancies

Abstract

Preeclampsia, intrauterine growth retardation (IUGR), oligohydramnios, abortus, preterm birth and premature rupture of the membranes (PROM) are significant complications of pregnancy. Insufficient trophoblastic invasion plays an important role in the pathophysiology of pregnancy complications. Soluble human leukocyte antigen-gestation (HLA-G)1/G5 is a molecule associated with trophoblast invasion. When pregnancy complications are predicted early, strategies to prevent these complications can be implemented. The aim of this study was to investigate the relationship between first trimester maternal serum soluble HLA-G1/G5 levels and high-risk pregnancies. A total of 232 pregnant women were followed prospectively. Maternal blood samples were collected for determination of soluble HLA-G1/G5 levels at 11–14 weeks, during which routine serum free beta human chorionic gonadotropin (βhCG) and pregnancy associated plasma protein-A (PAPP-A) level determinations in addition to nuchal translucency (NT) measurements for Down’s syndrome screening were done during 20–22 weeks gestation. The subjects were classified into normal pregnancy, preeclampsia, oligohydramnios, IUGR, preterm birth and PROM groups. First trimester maternal serum soluble HLA-G1/G5 levels were not significantly different between the groups. First trimester soluble HLA-G1/G5 did not predict high-risk pregnancies. Studies with larger number of cases are need to confirm our findings.     

Correlation between spontaneous preterm birth and mid-trimester maternal serum estriol

Abstract

Objective: Elevated third trimester salivary estriol levels have been associated with preterm birth. We evaluated whether maternal estriol concentrations from second trimester serum correlated with preterm delivery.

Methods: A retrospective cohort study of 7767 patients evaluated with second trimester aneuploidy screening. Unconjugated serum estriol was measured by immunoassay, expressed as multiples of the median (MoM) for gestational age and evaluated for association with preterm (<37 week) birth.

Results: Elevated maternal serum estriol was significantly associated with preterm birth (1.15 MoM versus 1.03 MoM for delivery at term, OR 1.69 CI 1.41 to 2.02). 9.95% of spontaneously laboring patients <34 weeks had estriol MoM?>?2, as opposed to 6.23% of >34 week deliveries (p?=?0.031). There was a direct correlation between level of estriol concentrations and gestational age at time of delivery.

Conclusions: Elevated second trimester maternal serum unconjugated estriol is independently associated with a higher rate of spontaneous preterm birth.     

A new anti-microbial combination prolongs the latency period,reduces acute histologic chorioamnionitis as well as funisitis,and improves neonatal outcomes in preterm PROM

Objective: Antibiotic administration is a standard practice in preterm premature rupture of membranes (PROM). Specific anti-microbial agents often include ampicillin and/or erythromycin. Anaerobes and genital mycoplasmas are frequently involved in preterm PROM, but are not adequately covered by antibiotics routinely used in clinical practice. Our objective was to compare outcomes of PROM treated with standard antibiotic administration versus a new combination more effective against these bacteria.

Study design: A retrospective study compared perinatal outcomes in 314 patients with PROM <34 weeks receiving anti-microbial regimen 1 (ampicillin and/or cephalosporins; n?=?195, 1993–2003) versus regimen 2 (ceftriaxone, clarithromycin and metronidazole; n?=?119, 2003–2012). Intra-amniotic infection/inflammation was assessed by positive amniotic fluid culture and/or an elevated amniotic fluid MMP-8 concentration (>23?ng/mL).

Results: (1) Patients treated with regimen 2 had a longer median antibiotic-to-delivery interval than those with regimen 1 [median (interquartile range) 23?d (10–51?d) versus 12?d (5–52?d), p?<?0.01]; (2) patients who received regimen 2 had lower rates of acute histologic chorioamnionitis (50.5% versus 66.7%, p?<?0.05) and funisitis (13.9% versus 42.9%, p?<?0.001) than those who had received regimen 1; (3) the rates of intra-ventricular hemorrhage (IVH) and cerebral palsy (CP) were significantly lower in patients allocated to regimen 2 than regimen 1 (IVH: 2.1% versus 19.0%, p?<?0.001 and CP: 0% versus 5.7%, p?<?0.05); and (4) subgroup analysis showed that regimen 2 improved perinatal outcomes in pregnancies with intra-amniotic infection/inflammation, but not in those without intra-amniotic infection/inflammation (after adjusting for gestational age and antenatal corticosteroid administration).

Conclusion: A new antibiotic combination consisting of ceftriaxone, clarithromycin, and metronidazole prolonged the latency period, reduced acute histologic chorioamnionitis/funisitis, and improved neonatal outcomes in patients with preterm PROM. These findings suggest that the combination of anti-microbial agents (ceftriaxone, clarithromycin, and metronidazole) may improve perinatal outcome in preterm PROM.     

Was the military operation “cast lead” a risk factor for preterm deliveries?

Objective: To investigate the influence of operation “Cast Lead” on rates of preterm delivery (PTD) and other adverse pregnancy outcomes at the main region under missile attack during the operation. Methods: A retrospective cohort study comparing pregnancy and delivery outcomes of women who gave birth at the time of the military operation “Cast Lead” with women who gave birth at the same time period 1 and 2 years before and after the war. Results: Out of 1272 women exposed to stress during the war, there were 126 preterm deliveries (9.9%) as compared with 381 preterm deliveries (9.6%) among the 3984 women of the control group (p = 0.719). The group exposed to stress of the military campaign had significantly more preterm deliveries at gestational age 32–34 weeks (1.6% vs. 0.8%; RR = 2.04, p = 0.011). Conclusion: Military operation period was adversely associated with an increase in the rate of early PTD (<34 weeks gestation). From a public health perspective, pregnant women should be considered a special population and should be taken into account in a preparedness program for an emergency crisis and must be an important part of the public agenda and the state’s infrastructure.     

Fragment Bb in amniotic fluid: evidence for complement activation by the alternative pathway in women with intra-amniotic infection/inflammation

Objective.?Fragment Bb is an activator of the alternative pathway of the complement system. Recently, increased first trimester maternal plasma concentrations of this fragment were reported in patients destined to have a spontaneous preterm delivery before 34 weeks of gestation. The aim of this study was to determine whether the amniotic fluid (AF) concentrations of fragment Bb change with gestational age, spontaneous labor (term and preterm) and in the presence of intra-amniotic infection/inflammation (IAI).

Study design.?This cross-sectional study included patients in the following groups: (1) mid-trimester (n = 64); (2) term in spontaneous labor (n = 70); (3) term not in labor (n = 43); (4) spontaneous preterm labor (PTL) who delivered at term (n = 76); (5) PTL without IAI who delivered preterm (n = 73); (6) PTL with IAI (n = 76); (7) preterm prelabor rupture of membranes (PROM) without IAI (n = 71); and (8) preterm PROM with IAI (n = 71). Fragment Bb concentration in AF was determined by an enzyme-linked immunoassay. Non-parametric statistics were used for analyses.

Results.?(1) Fragment Bb was detected in all AF samples (n = 544); (2) The median AF concentration of fragment Bb in patients at term not in labor was significantly higher than that of those in the mid-trimester [2.42 μg/ml, interquartile range (IQR) 1.78–3.22 vs. 1.64 μg/ml, IQR 1.06–3.49; p < 0.001]; (3) Among patients with PTL, those with IAI had a higher median AF fragment Bb concentration than that of woman without IAI, who delivered preterm (4.82 μg/ml, IQR 3.32–6.08 vs. 3.67 μg/ml, IQR 2.35–4.57; p < 0.001) and than that of women with an episode of PTL, who delivered at term (3.21 μg/ml, IQR 2.39–4.16; p < 0.001); (4) Similarly, among patients with preterm PROM, the median AF fragment Bb concentration was higher in individuals with IAI than in those without IAI (4.24 μg/ml, IQR 2.58–5.79 vs. 2.79 μg/ml, IQR 2.09–3.89; p < 0.001). (5) Among patients at term, the median AF fragment Bb concentration did not differ between women with spontaneous labor and those without labor (term in labor: 2.47 μg/ml, IQR 1.86–3.22; p = 0.97).

Conclusions.?(1) Fragment Bb, an activator of the alternative complement pathway, is a physiologic constituent of the AF, and its concentration increases with advancing gestational age; (2) AF concentrations of fragment Bb are higher in pregnancies complicated with IAI; and (3) labor at term is not associated with changes in the AF concentrations of fragment Bb. These findings suggest a role for fragment Bb in the host immune response against IAI.     

Effects of zinc supplementation during pregnancy on pregnancy outcome in women with history of preterm delivery: A double-blind randomized,placebo-controlled trial

Objectives.?The aim of this study was to assess the effect of high dose zinc (Zn) supplement during pregnancy in pregnancy outcome in healthy pregnant women with a previous preterm delivery in Isfahan, Iran.

Methods.?A double-blind placebo-controlled randomized clinical trial was conducted between January 2007 and June 2008. Eighty-four pregnant women with a previous preterm delivery age 19 to 35 years were randomly allocated to receive either 50?mg/day Zn as Zn sulfate or placebo from 12 to 16 weeks of gestation till delivery. Pregnancy outcome was assessed in term of incidence of intrauterine growth retardation (IUGR), birth weight, crown-heel length, head circumference, Apgar score, and gestational age at delivery.

Results.?The mean birth head circumference was higher in Zn supplemented group than in the placebo group (35.0?cm vs. 33.7?cm, P?<?0.05). Although gestational age at delivery (37.1 week vs. 36.7 week) and birth weight (2960.6?g vs. 2819.0?g) of babies born in Zn supplemented group was slightly higher than placebo group, it was not statistically significant. No significant differences were seen for infant length, Apgar score, and IUGR.

Conclusions.?Adding Zn supplementation during pregnancy to routine care of women with a previous preterm delivery had no significant effect on the gestational age at delivery and birth weight but increased the birth head circumference.     

Perinatal outcomes in oocyte donor pregnancies

Abstract

Objective: To assess the obstetric outcomes of pregnancy following intracytoplasmic sperm injection (ICSI) using donor oocytes.

Methods: Twenty-six deliveries from oocyte donor ICSI (d-ICSI) were compared to the next two consecutive deliveries from homologous ICSI (h-ICSI group) (n?=?52) and with the two consecutive deliveries from women older than 40 years (Advanced Maternal Age: AMA) (n?=?52). We evaluated the occurrence of gestational hypertension (GH), preeclampsia (PE), fetal growth restriction (IUGR), gestational diabetes mellitus (GDM), preterm premature rupture of membranes (pPROM), preterm birth, placental anomalies, mode of delivery, hemorrhage, gestational age at birth and birth weight.

Results: d-ICSI had significantly more PE (d-ICSI 19.2%, h-ICSI 0%, AMA 0%, p?<?0.001); higher rates of IUGR than AMA pregnancies (d-ICSI 19.2%, AMA 3.8%, p?<?0.025). Placental accretism was found only in the d-ICSI group (15.4%, p?<?0.043). No postpartum bleeding was observed.

Conclusions: This is the first study that compares the obstetric outcomes of donor pregnancies to the outcomes of h-ICSI and AMA. Obstetricians who deal with pregnancies from oocyte donation need to be aware of the more severe obstetric outcomes, especially placenta accreta and preeclampsia. All women who conceive through oocyte donation should be counseled as early as the pre-conception period and referred to specific centers for high-risk pregnancies.     

Gestational age at glucocorticoids administration after premature rupture of membranes and cerebral white matter damage

Objective.?We investigated whether gestational age at glucocorticoids administration in very preterm premature rupture of membranes (PROM) affects the occurrence of neonatal cerebral white matter damage (WMD).

Methods.?In a cohort of singleton neonates born at 24.0–33.6 weeks after PROM who underwent at least one full course of glucocorticoids (n?=?130), we compared the gestational age at first and last course of glucocorticoids between those who developed WMD (n?=?8) and those who did not (n?=?122) after adjusting for gestational age at PROM using logistic regression with P?<?0.05 considered significant.

Results.?Gestational age at first course of glucocorticoids (P?=?0.2), at last course of glucocorticoids (P?=?0.2) and at delivery (P?=?0.2), were not significantly different between those who developed WMD and those who did not. Although latency between PROM and first course of glucocorticoids was protective against WMD (P?=?0.02), the significance was lost after controlling for gestational age at PROM, which was significantly lower in cases that developed WMD (P?<?0.01).

Conclusions.?In very preterm PROM, the beneficial effect of glucocorticoids on occurrence of WMD is not related to gestational age at steroid administration.     

Unexplained fetal death: Another anti-angiogenic state

Background.?Pregnancy creates a unique situation in which both vasculogenesis and extensive angiogenesis are required for successful fetal and placental development. Recently, the soluble form of vascular endothelial growth factor (VEGF) receptor-1 (sVEGFR-1), an antagonist to VEGF and placental growth factor (PlGF) (two important angiogenic factors), has been implicated in the pathophysiology of preeclampsia and small for gestational age (SGA) without preeclampsia. There is, however, a paucity of information concerning plasma sVEGFR-1 concentrations in other obstetrical disorders. The purpose of this study was to determine plasma sVEGFR-1 concentrations in normal pregnancy, term gestation in labor, and in patients with pregnancy complications including spontaneous preterm labor, preterm premature rupture of the membranes (PROM), fetal death, and acute pyelonephritis.

Methods.?A cross-sectional study was conducted to determine the concentrations of sVEGFR-1 in plasma obtained from 499 women in the following groups: (1) non-pregnant women (n = 40); (2) pregnant women (n = 135); (3) normal pregnant women at term in labor (n = 60); (4) fetal death (n = 60); (5) spontaneous preterm labor with intact membranes (n = 102); (6) preterm PROM (n = 64); and (7) pregnancy with acute pyelonephritis (n = 38). Since plasma sVEGFR-1 concentration changes with gestational age, the difference between the actual and the expected plasma sVEGFR-1 concentration (derived from regression equation of normal pregnancy) for each patient (delta value) was calculated and used to examine the differences of plasma sVEGFR-1 concentrations among various groups. Plasma concentrations of sVEGFR-1 were determined by enzyme-linked immunoassay. Regression analysis and non-parametric statistics were used for analysis.

Results.?(1) Normal pregnant women before term had a median plasma sVEGFR-1 concentration significantly higher than non-pregnant women (p < 0.001); (2) plasma sVEGFR-1 concentration increased with advancing gestational age in normal pregnancy (r = 0.5; p < 0.001); (3) there was no significant difference in the median delta plasma concentration of sVEGFR-1 between normal pregnant women at term with and without labor (p = 0.09); (4) patients with fetal death had a median delta plasma concentration of sVEGFR-1 significantly higher than normal pregnant women (p = 0.001). Among patients with fetal death, those with unexplained causes (p = 0.04) and those with preeclampsia (p < 0.001) had a significantly higher delta plasma sVEGFR-1 concentration than normal pregnant women; and (5) there was no significant difference in the median delta plasma sVEGFR-1 concentration between normal pregnancy and preterm labor with intact membranes, preterm PROM (regardless of the presence or absence of microbial invasion of the amniotic cavity), or acute pyelonephritis (all p > 0.05).

Conclusions.?Plasma sVEGFR-1 concentration is increased in a subset of patients with fetal death, but does not change in term and preterm parturition, rupture of fetal membranes, or acute pyelonephritis.     

Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis,term and preterm parturition

Objective. Heat shock protein (HSP) 70, a conserved member of the stress protein family, is produced in almost all cell types in response to a wide range of stressful stimuli, and its production has a survival value. Evidence suggests that extracellular HSP70 is involved in the activation of the innate and adaptive immune response. Furthermore, increased mRNA expression of HSP70 has been observed in human fetal membranes following endotoxin stimulation. This study was conducted to determine the changes in amniotic fluid HSP70 concentrations during pregnancy, term and preterm parturition, intra-amniotic infection (IAI), and histologic chorioamnionitis.

Study design. A cross-sectional study was conducted in 376 pregnant women in the following groups: (1) women with a normal pregnancy who were classified into the following categories: (a) women in the mid-trimester (14–18 weeks) who underwent amniocentesis for genetic indications and delivered normal infants at term (n=72); (b) women at term not in labor (n = 23); and (c) those at term in labor (n = 48). (2) Women with spontaneous preterm labor and intact membranes who were subdivided into the following categories: (a) preterm labor who delivered at term without IAI (n = 42); (b) preterm labor who delivered preterm without IAI (n = 57); and (c) preterm labor and delivery with IAI (n = 30). (3) Women with preterm prelabor rupture of membranes (PROM) with (n = 50) and without (n = 54) IAI. Among patients with preterm labor with intact membranes and preterm PROM who delivered within 72 hours of amniocentesis, placenta, umbilical cord, and chorioamniotic membranes were collected and assessed for the presence or absence of acute inflammatory lesions in the extraplacental membranes (histologic chorioamnionitis) and/or umbilical cords (funisitis). HSP70 concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. Non-parametric statistics were used for analysis. A p value of <0.05 was considered statistically significant.

Results. Immunoreactive HSP70 was detected in 88% (332/376) of amniotic fluid samples. The median amniotic fluid HSP70 concentration was significantly higher in women at term without labor than in those in the mid-trimester (term no labor: median 34.9 ng/mL, range 0–78.1 ng/mL vs. mid-trimester; median 6.6 ng/mL, range 0–20.8 ng/mL; p<0.001). Among patients with spontaneous preterm labor and preterm PROM, those with IAI had a significantly higher median amniotic fluid HSP70 concentration than those without IAI (preterm labor with IAI: median 82.9 ng/mL, range 0–500 ng/mL vs. preterm labor without IAI: median 41.7 ng/mL, range 0–244 ng/mL; p = 0.001; preterm PROM with IAI: median 86.5 ng/mL, range 0–428 ng/mL vs. preterm PROM without IAI: median 55.9 ng/mL, range 14.9–299.9 ng/mL; p = 0.007). There was no significant difference in the median amniotic fluid HSP70 concentration between patients with preterm labor who delivered preterm without IAI and those who delivered at term (p = 0.6). However, among patients with preterm labor without IAI, there was an inverse relationship between amniotic fluid concentration of HSP70 and the amniocentesis-to-spontaneous delivery interval (Spearman's Rho = ?0.26; p = 0.02). Patients with histologic chorioamnionitis/funisitis had a significantly higher median amniotic fluid HSP70 concentration than those without inflammation (inflammation: median 108.7 ng/mL, range 0–500 ng/mL vs. without inflammation: median 67.9 ng/mL, range 7.1–299.9 ng/mL; p = 0.02). Women at term in labor had a median amniotic fluid concentration of HSP70 significantly higher than those not in labor (term in labor: median 60.7 ng/mL, range 0–359.9 ng/mL vs. term not in labor: median 34.9 ng/mL, range 0–78.1 ng/mL; p = 0.02).

Conclusions. Intra-amniotic infection, histologic chorioamnionitis, and term parturition are associated with elevated amniotic fluid HSP70 concentrations. HSP70 plays a role in the host defense mechanism by activating the innate arm of the immune response in women with intrauterine infection. The mechanisms of preterm and term parturition in humans may involve extracellular HSP70.     

Pregnancy complications with abnormal results of biochemical screening for Down syndrome in second trimester and normal fetal karyotype

Pregnancy complications were studied in the following groups of pregnancies with structurally and chromosomally normal fetuses: 1) 216--with elevated free beta-hCG above 2 MoM and 134--above 2.5 MoM; 2) 37--with elevated alpha-fetoprotein [AFP] above 2 MoM; 3) 67 screen-positive patients below the age of 35. The following complications were compared in the studied and the control groups: preterm delivery and premature rupture of membranes [PROM], preeclampsia (in general and severe one), IUGR without preeclampsia, delivery of small for gestational age [SGA] and low birth weight [LBW] infants and perinatal fetal loss. Pregnancy outcome in cases with free beta-hCG above 2 MoM was not different from that in the control group. With 2.5 cut-off level the incidence of preeclampsia and of LBW infants was higher in the studied than in the control group. Elevated AFP above 2 MoM alone was associated with more frequent preeclampsia including severe one (in all the latter cases--IUGR present). In the screen-positive group the incidence of preeclampsia (in general and severe one with IUGR), SGA and LBW infants and perinatal mortality rate were significantly higher than in the control group. No difference was found between the studied and the control groups regarding subsequent development of IUGR without preeclampsia, preterm delivery and PROM. Abnormal second trimester serum screening test results (elevated free beta-hCG or AFP alone above 2.5 and 2 MoM respectively) in pregnancies with normal fetal karyotype indicate higher risk for subsequent development of preeclampsia. Screen-positive patients, being a heterogeneous group (including ones with elevated free bb-hCG alone and ones with elevated both free beta-hCG and AFP), are at increased risk for other pregnancy complications too.