Maternal Serum C-Reactive Protein in Women with Preterm Prelabor Rupture of Membranes

Objective

This study evaluated maternal C-reactive protein (CRP) as a predictor of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) in women with preterm prelabor rupture of the membranes (PPROM) before and after 32 weeks of gestation.

Methods

This study was a prospective observational cohort study of 386 women. Maternal serum CRP concentrations were evaluated, and amniotic fluid samples were obtained via transabdominal amniocentesis at the time of admission. Placentas underwent histopathological examination after delivery. MIAC was defined based on a positive PCR for Ureaplasma species, Mycoplasma hominis and Chlamydia trachomatis and/or positive 16S rRNA gene amplification. HCA was defined based on the Salafia classification.

Results

Maternal CRP was significantly higher in women with MIAC and HCA (median 9.0 mg/l) than in women with HCA alone (median 6.9 mg/l), MIAC alone (median 7.4 mg/l) and without MIAC or HCA (median 4.5 mg/l) (p<0.0001). CRP was a weak predictor of the occurrence of MIAC and HCA before and after 32 weeks of gestation. Only the 95^th percentile of CRP and PPROM before 32 weeks exhibited a false-positive rate of 1%, a positive predictive value of 90% and a positive likelihood ratio of 13.2 to predict MIAC and HCA. However, the low sensitivity of 15% limits the clinical utility of this detection.

Conclusion

CRP is a poor predictor of the occurrence of MIAC and HCA, even at early gestational ages.     

Preterm Prelabor Rupture of Membranes and Outcome of Very-Low-Birth-Weight Infants in the German Neonatal Network

Objective

It was the aim of our study to evaluate the independent effect of preterm prelabor rupture of membranes (PPROM) as a cause of preterm delivery on mortality during primary hospital stay and significant morbidities in very-low-birth-weight (VLBW) infants < 32 weeks of gestation.

Design

Observational, epidemiological study design.

Setting

Population-based cohort, German Neonatal Network (GNN).

Population

6102 VLBW infants were enrolled in GNN from 2009-2012, n=4120 fulfilled criteria for primary analysis (< 32 gestational weeks, no pre-eclampsia, HELLP (highly elevated liver enzymes and low platelets syndrome) or placental abruption as cause of preterm birth).

Methods

Multivariable logistic regression analyses included PPROM as potential risk factors for adverse outcomes and well established items such as gestational age in weeks, birth weight, antenatal steroids, center, inborn delivery, multiple birth, gender and being small-for-gestational-age.

Results

PPROM as cause of preterm delivery had no independent effect on the risk of early-onset sepsis, clinical sepsis and blood-culture proven sepsis, while gestational age proved to be the most important contributor to sepsis risk. The diagnosis of PPROM was associated with an increased risk for bronchopulmonary dysplasia (BPD; OR: 1.25, 95% CI: 1.02-1.55, p=0.03) but not with other major outcomes.

Conclusions

The diagnosis of PPROM per se is not associated with adverse outcome in VLBW infants < 32 weeks apart from a moderately increased risk for BPD. Randomized controlled trials with primary neonatal outcomes are needed to determine which subgroup of VLBW infants benefit from expectant or intentional management of PPROM.     

Induction of Labor versus Expectant Management in Women with Preterm Prelabor Rupture of Membranes between 34 and 37 Weeks: A Randomized Controlled Trial

Background

At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term.

Methods and Findings

We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34⁺⁰ and 37⁺⁰ wk of gestation. Participants were randomly allocated in a 1∶1 ratio to induction of labor (IoL) or expectant management (EM) using block randomization. The main outcome was neonatal sepsis. Secondary outcomes included mode of delivery, respiratory distress syndrome (RDS), and chorioamnionitis. Patients and caregivers were not blinded to randomization status. We updated a prior meta-analysis on the effect of both interventions on neonatal sepsis, RDS, and cesarean section rate.From 1 January 2007 to 9 September 2009, 776 patients in 60 hospitals were eligible for the study, of which 536 patients were randomized. Four patients were excluded after randomization. We allocated 266 women (268 neonates) to IoL and 266 women (270 neonates) to EM. Neonatal sepsis occurred in seven (2.6%) newborns of women in the IoL group and in 11 (4.1%) neonates in the EM group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.25 to 1.6). RDS was seen in 21 (7.8%, IoL) versus 17 neonates (6.3%, EM) (RR 1.3; 95% CI 0.67 to 2.3), and a cesarean section was performed in 36 (13%, IoL) versus 37 (14%, EM) women (RR 0.98; 95% CI 0.64 to 1.50). The risk for chorioamnionitis was reduced in the IoL group. No serious adverse events were reported.Updating an existing meta-analysis with our trial results (the only eligible trial for the update) indicated RRs of 1.06 (95% CI 0.64 to 1.76) for neonatal sepsis (eight trials, 1,230 neonates) and 1.27 (95% CI 0.98 to 1.65) for cesarean section (eight trials, 1,222 women) for IoL compared with EM.

Conclusions

In women whose pregnancy is complicated by late PPROM, neither our trial nor the updated meta-analysis indicates that IoL substantially improves pregnancy outcomes compared with EM.

Trial registration

Current Controlled Trials ISRCTN29313500 Please see later in the article for the Editors'' Summary     

Acute Histologic Chorioamnionitis Is a Risk Factor for Adverse Neonatal Outcome in Late Preterm Birth after Preterm Premature Rupture of Membranes

Background

The objective of this study was to determine whether acute histologic chorioamnionitis is associated with adverse neonatal outcomes in late preterm infants who were born after preterm PROM.

Methodology/Principal Findings

The relationship between the presence of acute histologic chorioamnionitis and adverse neonatal outcome was examined in patients with preterm PROM who delivered singleton preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Nonparametric statistics were used for data analysis. The frequency of acute histologic chorioamnionitis was 24% in patients with preterm PROM who delivered preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Newborns born to mothers with histologic chorioamnionitis had significantly higher rates of adverse neonatal outcome (74% vs 51%; p<0.005) than those without histologic chorioamnionitis. This relationship remained significant after adjustment for gestational age at preterm PROM, gestational age at delivery, and exposure to antenatal corticosteroids.

Conclusions/Significance

The presence of acute histologic chorioamnionitis is associated with adverse neonatal outcome in late preterm infants born to mothers with preterm PROM.     

Umbilical Cord Blood IL-6 as Predictor of Early-Onset Neonatal Sepsis in Women with Preterm Prelabour Rupture of Membranes

Objective

To evaluate umbilical cord interleukin (IL)-6 and funisitis as independent predictors of early-onset neonatal sepsis (EONS) in preterm prelabor rupture of membranes (PPROM).

Design

Prospective cohort study.

Setting

Evaluation of umbilical cord IL-6 and funisitis as predictors of early-onset neonatal sepsis in PPROM.

Population

176 women with PPROM between 23+0−36+6 weeks of gestation.

Methods

Umbilical cord IL-6 was assayed by ELISA. Funisitis was defined according to the Salafia classification. Data was adjusted by gestational age at delivery and prenatal administration of corticosteroids and antibiotics.

Main Outcome Measures

Binary logistic regression was performed to assess the independence of umbilical cord IL-6 and funisitis to predict EONS in women complicated with PPROM.

Results

The rate of EONS was 7%. Funisitis was present in 18% of women. Umbilical cord IL-6 was significantly higher in women complicated with EONS than without [median (range) 389.5 pg/mL (13.9–734.8) vs 5.2 (0.1–801–4), p<0.001]. Umbilical cord IL-6 was the only independent predictor of early-onset neonatal sepsis (odds ratio 13.6, p = 0.004).

Conclusion

Umbilical cord IL-6 was the only predictor of early-onset neonatal sepsis in PPROM. Contrary to what is reported, funisitis was not.     

Early Gestational Weight Gain Rate and Adverse Pregnancy Outcomes in Korean Women

During pregnancy, many women gain excessive weight, which is related to adverse maternal and neonatal outcomes. In this study, we evaluated whether rate of gestational weight gain (RGWG) in early, mid, and late pregnancy is strongly associated with adverse pregnancy outcomes. A retrospective chart review of 2,789 pregnant Korean women was performed. Weights were recorded at the first clinic visit, during the screening test for fetal anomaly, and during the 50g oral glucose challenge test and delivery, to represent early, mid, and late pregnancy, respectively. A multivariate logistic regression analysis was performed to examine the relationship between RGWG and adverse pregnancy outcomes. At early pregnancy, the RGWG was significantly associated with high risk of developing gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), large for gestational age (LGA) infants, macrosomia, and primary cesarean section (P-CS). The RGWG of mid pregnancy was not significantly associated with any adverse pregnancy outcomes. The RGWG at late pregnancy was significantly associated with a lower risk of developing GDM, preterm birth and P-CS, but with a higher risk of developing LGA infants and macrosomia. When the subjects were divided into three groups (Underweight, Normal, and Obese), based on pre-pregnancy body mass index (BMI), the relationship between early RGWG and adverse pregnancy outcomes was significantly different across the three BMI groups. At early pregnancy, RGWG was not significantly associated to adverse pregnancy outcomes for subjects in the Underweight group. In the Normal group, however, early RGWG was significantly associated with GDM, PIH, LGA infants, macrosomia, P-CS, and small for gestational weight (SGA) infants, whereas early RGWG was significantly associated with only a high risk of PIH in the Obese group. The results of our study suggest that early RGWG is significantly associated with various adverse pregnancy outcomes and that proper preemptive management of early weight gain, particularly in pregnant women with a normal or obese pre-pregnancy BMI, is necessary to reduce the risk of developing adverse pregnancy outcomes.     

Bacteria Localization and Chorion Thinning among Preterm Premature Rupture of Membranes

Objective

Bacterial colonization of the fetal membranes and its role in pathogenesis of membrane rupture is poorly understood. Prior retrospective work revealed chorion layer thinning in preterm premature rupture of membranes (PPROM) subjects. Our objective was to prospectively examine fetal membrane chorion thinning and to correlate to bacterial presence in PPROM, preterm, and term subjects.

Study Design

Paired membrane samples (membrane rupture and membrane distant) were prospectively collected from: PPROM = 14, preterm labor (PTL = 8), preterm no labor (PTNL = 8), term labor (TL = 10), and term no labor (TNL = 8), subjects. Sections were probed with cytokeratin to identify fetal trophoblast layer of the chorion using immunohistochemistry. Fluorescence in situ hybridization was performed using broad range 16 s ribosomal RNA probe. Images were evaluated, chorion and choriodecidua were measured, and bacterial fluorescence scored. Chorion thinning and bacterial presence were compared among and between groups using Student''s t-test, linear mixed effect model, and Poisson regression model (SAS Cary, NC).

Results

In all groups, the fetal chorion cellular layer was thinner at rupture compared to distant site (147.2 vs. 253.7 µm, p<0.0001). Further, chorion thinning was greatest among PPROM subjects compared to all other groups combined, regardless of site sampled [PPROM(114.9) vs. PTL(246.0) vs. PTNL(200.8) vs. TL(217.9) vs. TNL(246.5)]. Bacteria counts were highest among PPROM subjects compared to all other groups regardless of site sampled or histologic infection [PPROM(31) vs. PTL(9) vs. PTNL(7) vs. TL(7) vs. TNL(6)]. Among all subjects at both sites, bacterial counts were inversely correlated with chorion thinning, even excluding histologic chorioamnionitis (p<0.0001 and p = 0.05).

Conclusions

Fetal chorion was uniformly thinner at rupture site compared to distant sites. In PPROM fetal chorion, we demonstrated pronounced global thinning. Although cause or consequence is uncertain, bacterial presence is greatest and inversely correlated with chorion thinning among PPROM subjects.     

Reported Estimates of Adverse Pregnancy Outcomes among Women with and without Syphilis: A Systematic Review and Meta-Analysis

Background

To estimate probability of adverse pregnancy outcomes (APOs) among women with and without syphilis through a systematic review of published literatures.

Methodology/Principal Findings

Chinese and English literatures were searched for studies assessing pregnancy outcomes in the presence of maternal syphilis through August 2013. The prevalence estimates were summarized and analyzed by meta-analysis. Fifty-four literatures involving 11398 syphilitic women and 43342 non-syphilitic women were included from 4187 records initially found. Among untreated mothers with syphilis, pooled estimates were 76.8% for all APOs, 36.0% for congenital syphilis, 23.2% for preterm, 23.4% for low birth weight, 26.4% for stillbirth or fetal loss, 14.9% for miscarriage and 16.2% for neonatal deaths. Among syphilitic mother receiving treatment only in the late trimester (>28 weeks), pooled estimates were 64.4% for APOs, 40.6% for congenital syphilis, 17.6% for preterm, 12.4% for low birth weight, and 21.3% for stillbirth or fetal loss. Among syphilitic mothers with high titers (≥1∶8), pooled estimates were 42.8% for all APOs, 25.8% for congenital syphilis, 15.1% for preterm, 9.4% for low birth weight, 14.6% for stillbirth or fetal loss and 16.0% for neonatal deaths. Among non-syphilitic mothers, the pooled estimates were 13.7% for all APOs, 7.2% for preterm birth, 4.5% for low birth weight, 3.7% for stillbirth or fetal loss, 2.3% for miscarriage and 2.0% for neonatal death. Begg''s rank correlation test indicated little evidence of publication bias (P>0.10). Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (I ² = 93.9%; P<0.0001) and women without syphilis (I ² = 94.8%; P<0.0001).

Conclusions/Significance

Syphilis continues to be an important cause of substantial perinatal morbidity and mortality, which reminds that policy-makers charged with resource allocation that the elimination of mother-to-child transmission of syphilis is a public health priority.     

Duration of Cord Clamping and Neonatal Outcomes in Very Preterm Infants

Background

Delayed cord clamping (DCC, ≥30s) increases blood volume in newborns and is associated with fewer blood transfusions and short-term neonatal complications. The optimal timing of cord clamping for very preterm infants should maximize placental transfusion without interfering with stabilization and resuscitation.

Aim

We compared the effect of different durations of DCC, 30-45s vs. 60-75s, on delivery room (DR) and neonatal outcomes in preterm infants <32 weeks gestational age (GA).

Methods

This is a single-center prospective observational study. Data were collected prospectively from eligible infants from two groups: 30-45s DCC group (January 2008 to February 2011, n = 187) and 60-75s DCC group (March 2011 to April 2014, n = 166).

Results

The 60-75s DCC group compared to the 30-45s DCC group had higher hematocrits at <2 hours (49.2% vs. 47.4%, p = 0.02). In infants <28 weeks GA, the 12–36 hours hematocrit was higher in the 60-75s DCC group compared to the 30-45s DCC group (47.9% vs. 42.1%, p = 0.002). The 60-75s DCC group had reductions in DR intubation (11% vs. 22%, p = 0.004), hypothermia on admission (1% vs. 5%, p = 0.01), surfactant therapy (13% vs. 28%, p = 0.001), intubation in the first 24 hours (20% vs. 34%, p = 0.004), any intubation (27% vs. 40%, p = 0.007), and any red blood cell transfusion (20% vs. 33%, p = 0.008) during the hospitalization compared to the 30-45s DCC group. These reductions remained significant after adjusting for GA, gender and >48 hours of antenatal steroid exposure. There was no difference between the two groups in neonatal death, intraventricular hemorrhage, chronic lung disease, late onset sepsis, necrotizing enterocolitis and severe retinopathy of prematurity.

Conclusion

In this study cohort increasing DCC duration from 30-45s to 60-75s is associated with decreased hypothermia on admission, neonatal respiratory interventions and red blood cell transfusions without increase in neonatal mortality and morbidities.     

Human Placental-Specific Epipolymorphism and its Association with Adverse Pregnancy Outcomes

Interindividual variation in DNA-methylation level is widespread in the human genome, despite its critical role in regulating gene expression. The nature of this variation, including its tissue-specific nature, and the role it may play in human phenotypic variation and disease is still poorly characterized. The placenta plays a critical role in regulating fetal growth and development in ways that have lifelong effects on health. To identify genes with a high degree of interindividual DNA methylation variation in the human placenta, we surveyed the human genome using the Illumina GoldenGate Methylation Cancer panel targeting 1505 CpG sites of 807 genes. While many sites show a continuous pattern of methylation levels, WNT2, TUSC3 and EPHB4 were identified to have a polymorphic “on-or-off” pattern of DNA methylation variation at their promoter region which was confirmed by pyrosequencing. Methylation of these genes can be found in 7%–25% of over 100 placentas tested. The methylation state at the promoter of these genes is concordant with mRNA allelic expression. In three informative cases TUSC3 was observed to be methylated on the maternal allele, and it is thus possible this represents a polymorphically imprinted gene. Furthermore, TUSC3 promoter methylation showed evidence for association with preeclampsia. A biological significance of these methylation allelic polymorphisms (MAPs) to human placental diversity is further implied by their placental specificity and absence in mouse. An extended study of blood suggests that MAPs may also be found in other tissues, implicating their utility for tissue-specific association with complex disorders. The identification of such “epipolymorphism” in other tissues and their use in association studies, should improve our understanding of interindividual phenotypic variability and complex disease susceptibility.     

Maternal Obesity in Early Pregnancy and Risk of Adverse Outcomes

Objectives

To assess the role of the health consequences of maternal overweight and obesity at the start of pregnancy on gestational pathologies, delivery and newborn characteristics.

Methods

A cohort of pregnant women (n = 6.558) having delivered at the Maternal & Child University Hospital of Gran Canaria (HUMIGC) in 2008 has been studied. Outcomes were compared using multivariate analyses controlling for confounding variables.

Results

Compared to normoweight, overweight and obese women have greater risks of gestational diabetes mellitus (RR = 2.13 (95% CI: 1.52–2.98) and (RR = 2.85 (95% CI: 2.01–4.04), gestational hypertension (RR = 2.01 (95% CI: 1.27–3.19) and (RR = 4.79 (95% CI: 3.13–7.32) and preeclampsia (RR = 3.16 (95% CI: 1.12–8.91) and (RR = 8.80 (95% CI: 3.46–22.40). Obese women have also more frequently oligodramnios (RR = 2.02 (95% CI: 1.25–3.27), polyhydramnios. (RR = 1.76 (95% CI: 1.03–2.99), tearing (RR = 1.24 (95% CI: 1.05–1.46) and a lower risk of induced deliveries (RR = 0.83 (95% CI: 0.72–0.95). Both groups have more frequently caesarean section (RR = 1.36 (95% CI: 1.14–1.63) and (RR = 1.84 (95% CI: 1.53–2.22) and manual placenta extraction (RR = 1.65 (95% CI: 1.28–2.11) and (RR = 1.77 (95% CI: 1.35–2.33). Newborns from overweight and obese women have higher weight (p<0.001) and a greater risk of being macrosomic (RR = 2.00 (95% CI: 1.56–2.56) and (RR = 2.74 (95% CI: 2.12–3.54). Finally, neonates from obese mother have a higher risk of being admitted to special care units (RR = 1.34 (95% CI: 1.01–1.77). Apgar 1 min was significantly higher in newborns from normoweight mothers: 8.65 (95% CI: 8.62–8.69) than from overweight: 8.56 (95% CI: 8.50–8.61) or obese mothers: 8.48 (95% CI: 8.41–8.54).

Conclusion

Obesity and overweight status at the beginning of pregnancy increase the adverse outcomes of the pregnancy. It is important to promote the normalization of bodyweight in those women who intend to get pregnant and to provide appropriate advice to the obese women of the risks of obesity at the start of the pregnancy.     

Inflammatory Bowel Disease and Risk of Adverse Pregnancy Outcomes

Background and Objectives

Existing data on pregnancy complications in inflammatory bowel disease (IBD) are inconsistent. To address these inconsistencies, we investigated potential associations between IBD, IBD-related medication use during pregnancy, and pregnancy loss, pre-eclampsia, preterm delivery, Apgar score, and congenital abnormalities.

Methods

We conducted a cohort study in >85,000 Danish National Birth Cohort women who were pregnant in the period 1996-2002 and had information on IBD, IBD-related medication use (systemic or local corticosteroids, 5-aminosalicylates), pregnancy outcomes and potential confounders. We evaluated associations between IBD and adverse pregnancy/birth outcomes using Cox regression and log-linear binomial regression.

Results

IBD was strongly and significantly associated with severe pre-eclampsia, preterm premature rupture of membranes and medically indicated preterm delivery in women using systemic corticosteroids during pregnancy (hazard ratios [HRs] >7). IBD was also associated with premature preterm rupture of membranes in women using local corticosteroid medications (HR 3.30, 95% confidence interval [CI] 1.33-8.20) and with medically indicated preterm delivery (HR 1.91, 95% CI 0.99-3.68) in non-medicated women. Furthermore, IBD was associated with low 5-minute Apgar score in term infants (risk ratio [RR] 2.19, 95% CI 1.03-4.66). Finally, Crohn’s disease (but not ulcerative colitis) was associated with major congenital abnormalities in the offspring (RR 1.85, 95% CI 1.06-3.21). No child with a congenital abnormality born to a woman with IBD was exposed to systemic corticosteroids in utero.

Conclusion

Women with IBD are at increased risk of severe pre-eclampsia, medically indicated preterm delivery, preterm premature rupture of membranes, and delivering infants with low Apgar score and major congenital malformations. These associations are only partly explained by severe disease as reflected by systemic corticosteroid use.     

Timing of Histologic Progression from Chorio-Deciduitis to Chorio-Deciduo-Amnionitis in the Setting of Preterm Labor and Preterm Premature Rupture of Membranes with Sterile Amniotic Fluid

Background

Histologic chorio-deciduitis and chorio-deciduo-amnionitis (amnionitis) in extra-placental membranes are known to represent the early and advanced stages of ascending intra-uterine infection. However, there are no data in humans about the time required for chorio-deciduitis to develop and for chorio-deciduitis without amnionitis to progress to chorio-deciduitis with amnionitis, and the effect of prolongation of pregnancy on the development of chorio-deciduitis and amnionitis in patients with preterm labor and intact membranes (PTL) and preterm premature rupture of membranes (preterm-PROM). We examined these issues in this study.

Methods

The study population consisted of 289 women who delivered preterm (133 cases with PTL, and 156 cases with preterm-PROM) and who had sterile amniotic fluid (AF) defined as a negative AF culture and the absence of inflammation as evidenced by a matrix metalloproteinase-8 (MMP-8) level <23 ng/ml. We examined the association between amniocentesis-to-delivery interval and inflammatory status in the extra-placental membranes (i.e., inflammation-free extra-placental membranes, choroi-deciduitis only, and chorio-deciduitis with amnionitis) in patients with PTL and preterm-PROM.

Results

Amniocentesis-to-delivery interval was longer in cases of chorio-deciduitis with amnionitis than in cases of chorio-deciduitis only in both PTL (median [interquartile-range (IQR)]; 645.4 [319.5] vs. 113.9 [526.9] hours; P = 0.005) and preterm-PROM (131.3 [135.4] vs. 95.2 [140.5] hours; P<0.05). Amniocentesis-to-delivery interval was an independent predictor of the development of both chorio-deciduitis and amnionitis after correction for confounding variables such as gestational age at delivery in the setting of PTL, but not preterm-PROM.

Conclusions

These data confirm for the first time that, in cases of both PTL and preterm-PROM with sterile AF, more time is required to develop chorio-deciduitis with amnionitis than chorio-deciduitis alone in extra-placental membranes. Moreover, prolongation of pregnancy is an independent predictor of the development of both chorio-deciduitis and amnionitis in cases of PTL with sterile AF.     

Asthma during Pregnancy in a Population-Based Study - Pregnancy Complications and Adverse Perinatal Outcomes

Background

Asthma is one of the most common chronic diseases, and prevalence, severity and medication may have an effect on pregnancy. We examined maternal asthma, asthma severity and control in relation to pregnancy complications, labour characteristics and perinatal outcomes.

Methods

We retrieved data on all singleton births from July 1, 2006 to December 31, 2009, and prescribed drugs and physician-diagnosed asthma on the same women from multiple Swedish registers. The associations were estimated with logistic regression.

Results

In total, 266 045 women gave birth to 284 214 singletons during the study period. Maternal asthma was noted in 26 586 (9.4%) pregnancies. There was an association between maternal asthma and increased risks of pregnancy complications including preeclampsia or eclampsia (adjusted OR 1.15; 95% CI 1.06–1.24) and premature contractions (adj OR 1.52; 95% CI 1.29–1.80). There was also a significant association between maternal asthma and emergency caesarean section (adj OR 1.29; 95% CI 1.23–1.34), low birth weight, and small for gestational age (adj OR 1.23; 95% CI 1.13–1.33). The risk of adverse outcomes such as low birth weight increased with increasing asthma severity. For women with uncontrolled compared to those with controlled asthma the results for adverse outcomes were inconsistent displaying both increased and decreased OR for some outcomes.

Conclusion

Maternal asthma is associated with a number of serious pregnancy complications and adverse perinatal outcomes. Some complications are even more likely with increased asthma severity. With greater awareness and proper management, outcomes would most likely improve.     

Human Cytomegalovirus-Induces Cytokine Changes in the Placenta with Implications for Adverse Pregnancy Outcomes

Human cytomegalovirus (CMV) infection of the developing fetus can result in adverse pregnancy outcomes including death in utero. Fetal injury results from direct viral cytopathic damage to the CMV-infected fetus, although evidence suggests CMV placental infection may indirectly cause injury to the fetus, possibly via immune dysregulation with placental dysfunction. This study investigated the effects of CMV infection on expression of the chemokine MCP-1 (CCL2) and cytokine TNF-α in placentae from naturally infected stillborn babies, and compared these changes with those found in placental villous explant histocultures acutely infected with CMV ex vivo. Tissue cytokine protein levels were assessed using quantitative immunohistochemistry. CMV-infected placentae from stillborn babies had significantly elevated MCP-1 and TNF-α levels compared with uninfected placentae (p = 0.001 and p = 0.007), which was not observed in placentae infected with other microorganisms (p = 0.62 and p = 0.71) (n = 7 per group). Modelling acute clinical infection using ex vivo placental explant histocultures showed infection with CMV laboratory strain AD169 (0.2 pfu/ml) caused significantly elevated expression of MCP-1 and TNF-α compared with uninfected explants (p = 0.0003 and p<0.0001) (n = 25 per group). Explant infection with wild-type Merlin at a tenfold lower multiplicity of infection (0.02 pfu/ml), caused a significant positive correlation between increased explant infection and upregulation of MCP-1 and TNF-α expression (p = 0.0001 and p = 0.017). Cytokine dysregulation has been associated with adverse outcomes of pregnancy, and can negatively affect placental development and function. These novel findings demonstrate CMV infection modulates the placental immune environment in vivo and in a multicellular ex vivo model, suggesting CMV-induced cytokine modulation as a potential initiator and/or exacerbator of placental and fetal injury.     

Risk of Adverse Pregnancy Outcomes among Women Practicing Poor Sanitation in Rural India: A Population-Based Prospective Cohort Study

BackgroundThe importance of maternal sanitation behaviour during pregnancy for birth outcomes remains unclear. Poor sanitation practices can promote infection and induce stress during pregnancy and may contribute to adverse pregnancy outcomes (APOs). We aimed to assess whether poor sanitation practices were associated with increased risk of APOs such as preterm birth and low birth weight in a population-based study in rural India.ConclusionsThis study provides the first evidence, to our knowledge, that poor sanitation is associated with a higher risk of APOs. Additional studies are required to elucidate the socio-behavioural and/or biological basis of this association so that appropriate targeted interventions might be designed to support improved birth outcomes in vulnerable populations. While it is intuitive to expect that caste and poverty are associated with poor sanitation practice driving APOs, and we cannot rule out additional confounders, our results demonstrate that the association of poor sanitation practices (open defecation) with these outcomes is independent of poverty. Our results support the need to assess the mechanisms, both biological and behavioural, by which limited access to improved sanitation leads to APOs.     

Outcome at Two Years of Very Preterm Infants Born after Rupture of Membranes before Viability

PurposeTo compare the respiratory and neurological outcomes at two years of age of preterm children born before 33 weeks of gestation (WG) after early preterm premature rupture of membranes (EPPROM) between 14 and 24 WG with preterm children without EPPROM.ResultsNinety-four cases with EPPROM before 24WG have been included. The 31 children born from 26WG to 32WG were matched with 62 controls. The EPPROM group had poorer clinical evaluation at one year for motor (p = 0.003) and cognitive developmental scores (p = 0.016). Neuromotor rehabilitation was performed more often (p = 0.013). However, there was no difference at 2 years of age. Children born after EPPROM were hospitalized more often for bronchiolitis (p<0.001) during their first 2 years, which correlates with increased incidence of pneumothorax (p = 0.017), pulmonary hypoplasia (p = 0.004) and bronchopulmonary dysplasia (p = 0.005) during neonatal period.ConclusionAt two years, despite an increase in severe bronchiolitis and the need for more neuromotor rehabilitation during the first month of the life after discharge, there was no difference in neurological outcomes in the very preterm children of the EPPROM group compared to those born at a similar GA without EPPROM.     

Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of Women at Risk of Imminent Preterm Birth: A Systematic Review and Meta-Analysis

Background

This study synthesizes available evidence on antenatal corticosteroids (ACS) use among special subgroups of women at risk of imminent preterm birth, including those (1) with pregestational and gestational diabetes mellitus, (2) undergoing elective caesarean section (CS) in late preterm (34 to<37 weeks), (3) with chorioamnionitis, and (4) with growth-restricted fetuses.

Methods

A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Library, POPLINE, and World Health Organization Regional Databases was conducted for all comparative studies. Two reviewers independently determined study eligibility, extracted data, and assessed study quality. Pooled mean differences and odds ratios with 95% confidence intervals were estimated from available data, based on fixed- and random-effects models, as appropriate.

Results

No eligible studies were identified for ACS use in diabetic pregnant women or those undergoing elective CS at late preterm. Nine studies each on ACS use in women with chorioamnionitis and in women with fetal growth restriction met inclusion criteria; eight studies were separately included in the meta-analyses for the two subpopulations. For ACS administration in women with chorioamnionitis, pooled analyses showed reductions in neonatal mortality (OR: 0.49, 95% CI: 0.34–0.73), respiratory distress syndrome (OR: 0.58, 95% CI: 0.44–0.76), intraventricular haemorrhage (OR: 0.41, 95% CI: 0.24–0.69), and severe intraventricular haemorrhage (OR: 0.40, 95% CI: 0.24–0.69). Maternal and long-term newborn outcomes were not reported. Effects of ACS use were inconclusive for cases with fetal growth restriction.

Conclusion

Direct evidence on the effectiveness and safety of ACS is lacking for diabetic pregnant women at risk of preterm birth and those undergoing elective late-preterm CS, though this does not necessarily recommend against their use in diabetic women. While evidence remains inconclusive for women with growth-restricted preterm neonates, ACS appears to benefit preterm neonates delivered by women with chorioamnionitis. High-quality studies on maternal and long-term child outcomes in more diverse settings are needed to establish the balance of potential harms versus benefits in using ACS for these understudied subgroups.     

Pregnancy Outcomes of Anti-Hypertensives for Women with Chronic Hypertension: A Population-Based Study

Background

The impact of anti-hypertensive treatment on fetus was unclear, and hence, remains controversial. We set out in this study to estimate the prevalence of adverse pregnancy outcomes, including low birth weight, preterm delivery and small for gestational age amongst women with chronic hypertension, and to determine whether the use of anti-hypertensive drugs increases the risk of such adverse pregnancy outcomes.

Methodology/Principal Findings

A total of 2,727 hypertension mothers and 8,181 matched controls were identified from the population-based cohort. These hypertension women were divided into seven sub-groups according to different types of prescribed anti-hypertensive drugs. Multivariable logistic regressions were conducted to estimate the risk of low birth weight, preterm birth and small for gestational age. Increased risk of low birth weight (OR = 2.29, 95% CI = 1.95–2.68), preterm birth (OR = 2.18, 95% CI = 1.89–2.52) and small for gestational age (OR = 1.62, 95% CI = 1.45–1.81) were all discernible within the hypertension group after adjusting for potential confounding factors. The increased ORs were found to differ with different types of anti-hypertensive drugs. Women who received vasodilators were associated with the highest risk of low birth weight (OR = 2.96, 95% CI = 2.06–4.26), preterm birth (OR = 2.92 95% CI = 2.06–4.15) and small for gestational age (OR = 2.12, 95% CI = 1.60–2.82).

Conclusions/Significance

This finding is important for practitioners, because it indicates the need for caution while considering the administration of anti-hypertensive drugs to pregnant women. These observations require confirmation in further studies that can better adjust for the severity of the underlying HTN.     

34例胎膜早破孕妇妊娠晚期阴道微生态及免疫因子变化状况分析

目的：胎膜早破是一种常见但发生机制十分复杂的妊娠并发症。在所有的早产儿中,孕妇胎膜早破的比例高达33％。本研究针对胎膜早破产妇妊娠晚期阴道微生态及免疫因子的变化情况,分析阴道内茵群失调或局部免疫反应与胎膜早破的关系,为临床研究提供实验数据。方法：回顾性分析我院于2010年7月-2013年3月收治的34例胎膜早破孕妇的临床资料,同时选取于我院进行健康体检的妇女及产前检查的健康孕妇各34例作为对照。采集所有研究对象的阴道分泌物,对比分析各组样本中病原微生物的分布及免疫因子的浓度。结果：胎膜早破组乳酸杆菌的检出率要明显低于健康妇女组与健康孕妇组（79．4％VS70．6％VS34．1,X2=8．438,P〈0．05）,三组研究对象其他茵属分布的差异比较无统计学意义（P〉0．05）;胎膜早破组阴道分泌物IL-6浓度与TNF．仪浓度要显著高于健康妇女组与健康孕妇组（P〈0．05）。结论：胎膜早破产妇阴道内的菌群分布与健康女性及孕妇有所不同,阴道内茵群失调及局部的免疫反应可能会导致胎膜旱破的发生。