Maternal Glomerular Filtration Rate in Pregnancy and Fetal Size

BackgroundThe relationship of maternal glomerular filtration rate (GFR) in pregnancy to fetal size needs to be better characterized as it impacts an ongoing debate about confounding effect of maternal GFR in investigations of important environmental contaminants. We aimed to characterize the size of the association between maternal GFR and infant birth weight.ResultsMaternal GFR-CG (β: 0.73 g/ml/min, p = 0.04) and GFR-MDRD (β: 0.83 g/ml/min, p = 0.04) were associated with infant birth weight in models adjusted for maternal weight in kilograms, preeclampsia, and gestational age at delivery (days). Partial correlation coefficients for the association between infant birth weight and GFR were 0.07 for both formulas. Although the birth weight-GFR association was stronger among the women with preeclampsia, the difference from women without preeclampsia was not statistically significant.ConclusionThese data support an association between GFR during pregnancy and infant birth weight, and indicate that GFR may confound selected epidemiologic associations.     

Risk Factors for Preterm Birth in Five Maternal and Child Health Hospitals in Beijing

Background

Preterm birth, the birth of an infant prior to 37 completed weeks of gestation, is the leading cause of perinatal morbidity and mortality. Preterm infants are at greater risk of respiratory, gastrointestinal and neurological diseases. Despite significant research in developed countries, little is known about the causes of preterm birth in many developing countries, especially China. This study investigates the association between sciodemographic data, obstetric risk factor, and preterm birth in five Maternal and Child Health hospitals in Beijing, China.

Methods and Findings

A case-control study was conducted on 1391 women with preterm birth (case group) and 1391 women with term delivery (control group), who were interviewed within 48 hours of delivery. Sixteen potential factors were investigated and statistical analysis was performed by univariate analysis and logistic regression analysis. Univariate analysis showed that 14 of the 16 factors were associated with preterm birth. Inter-pregnancy interval and inherited diseases were not risk factors. Logistic regression analysis showed that obesity (odds ratio (OR) = 3.030, 95% confidence interval (CI) 1.166–7.869), stressful life events (OR = 5.535, 95%CI 2.315–13.231), sexual activity (OR = 1.674, 95%CI 1.279–2.191), placenta previa (OR 13.577, 95%CI 2.563–71.912), gestational diabetes mellitus (OR = 3.441, 95%CI1.694–6.991), hypertensive disorder complicating pregnancy (OR = 6.034, 95%CI = 3.401–10.704), history of preterm birth (OR = 20.888, 95%CI 2.519–173.218) and reproductive abnormalities (OR = 3.049, 95%CI 1.010–9.206) were independent risk factors. Women who lived in towns and cities (OR = 0.603, 95%CI 0.430–0.846), had a balanced diet (OR = 0.533, 95%CI 0.421–0.675) and had a record of prenatal care (OR = 0.261, 95%CI 0.134–0.510) were less likely to have preterm birth.

Conclusions

Obesity, stressful life events, sexual activity, placenta previa, gestational diabetes mellitus, hypertensive disorder complicating pregnancy, history of preterm birth and reproductive abnormalities are independent risk factors to preterm birth. Identification of remedial factors may inform local health and education policy.     

Contribution of Risk Factors to Extremely,Very and Moderately Preterm Births – Register-Based Analysis of 1,390,742 Singleton Births

Background

Preterm birth, defined as birth occurring before 37 weeks gestation, is one of the most significant contributors to neonatal mortality and morbidity, with long-term adverse consequences for health, and cognitive outcome.

Objective

The aim of the present study was to identify risk factors of preterm birth (≤36+6 weeks gestation) among singleton births and to quantify the contribution of risk factors to socioeconomic disparities in preterm birth.

Methods

A retrospective population–based case-control study using data derived from the Finnish Medical Birth Register. A total population of singleton births in Finland from 1987−2010 (n = 1,390,742) was reviewed.

Results

Among all singleton births (n = 1,390,742), 4.6% (n = 63,340) were preterm (<37 weeks), of which 0.3% (n = 4,452) were classed as extremely preterm, 0.4% (n = 6,213) very preterm and 3.8% (n = 54,177) moderately preterm. Smoking alone explained up to 33% of the variation in extremely, very and moderately preterm birth incidence between high and the low socioeconomic status (SES) groups. Reproductive risk factors (placental abruption, placenta previa, major congenital anomaly, amniocentesis, chorionic villus biopsy, anemia, stillbirth, small for gestational age (SGA) and fetal sex) altogether explained 7.7−25.0% of the variation in preterm birth between SES groups.

Conclusions

Smoking explained about one third of the variation in preterm birth groups between SES groups whereas the contribution of reproductive risk factors including placental abruption, placenta previa, major congenital anomaly, amniocentesis, chorionic villus biopsy, anemia, stillbirth, SGA and fetal sex was up to one fourth.     

Risk Factors for Severe Cholera among Children under Five in Rural and Urban Bangladesh, 2000–2008: A Hospital-Based Surveillance Study

Background

Children under five bear the largest cholera burden. We therefore sought to identify modifiable risk factors among Bangladeshi children.

Methodology/Principal Findings

We used multivariate Poisson regression to assess risk factors for severe cholera among diarrheal patients presenting at hospitals in Matlab (rural) and Dhaka (urban), Bangladesh. Risk increased with age. Compared to those under one, rural and urban four-year-olds had adjusted risk ratios (aRR) of 4.17 (95% confidence interval (CI) 2.43–7.15) and 6.32 (95% CI: 4.63–8.63), respectively. Breastfeeding halved the risk in both rural (aRR = 0.49, 95% CI: 0.35–0.67) and urban (aRR = 0.51, 95% CI: 0.41–0.62) settings. Rural children’s risk decreased with maternal education (P-trend: <0.001) and increased among those with a family member with diarrhea in the past week (aRR = 1.61, 95% CI: 1.22–2.14) and those with prior vitamin A supplementation (aRR = 1.65, 95% CI: 1.12–2.43). Urban children whose mothers daily (aRR = 0.41, 95% CI: 0.21–0.79) or occasionally (aRR = 0.55, 95% CI: 0.36–0.84) read a newspaper experienced reduced risk. Urban children from households with incomes between 34–84 USD/month had a 30% increased risk compared to those from households with incomes >84 USD/month.

Conclusion/Significance

Increasing age, lower socioeconomic status, and lack of breastfeeding are key correlates of increased risk for cholera hospitalization among those under five in rural and urban Bangladesh. In addition, having a family member with diarrhea in the past week was associated with increased risk among rural children. Continued attention should be directed to the promotion of breastfeeding. Further research is needed to elucidate the relationship between maternal education and cholera risk. Renewed research regarding the use of chemoprophylaxis among family members of cholera cases may be warranted in rural endemic settings.     

The APPLe Study: A Randomized,Community-Based,Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth,with Meta-Analysis

Background

Premature birth is the major cause of perinatal mortality and morbidity in both high- and low-income countries. The causes of preterm labour are multiple but infection is important. We have previously described an unusually high incidence of preterm birth (20%) in an ultrasound-dated, rural, pregnant population in Southern Malawi with high burdens of infective morbidity. We have now studied the impact of routine prophylaxis with azithromycin as directly observed, single-dose therapy at two gestational windows to try to decrease the incidence of preterm birth.

Methods and Findings

We randomized 2,297 pregnant women attending three rural and one peri-urban health centres in Southern Malawi to a placebo-controlled trial of oral azithromycin (1 g) given at 16–24 and 28–32 wk gestation. Gestational age was determined by ultrasound before 24 wk. Women and their infants were followed up until 6 wk post delivery. The primary outcome was incidence of preterm delivery, defined as <37 wk. Secondary outcomes were mean gestational age at delivery, perinatal mortality, birthweight, maternal malaria, and anaemia. Analysis was by intention to treat. There were no significant differences in outcome between the azithromycin group (n = 1,096) and the placebo group (n = 1,087) in respect of preterm birth (16.8% versus 17.4%), odds ratio (OR) 0.96, 95% confidence interval (0.76–1.21); mean gestational age at delivery (38.5 versus 38.4 weeks), mean difference 0.16 (−0.08 to 0.40); mean birthweight (3.03 versus 2.99 kg), mean difference 0.04 (−0.005 to 0.08); perinatal deaths (4.3% versus 5.0%), OR 0.85 (0.53–1.38); or maternal malarial parasitaemia (11.5% versus 10.1%), OR 1.11 (0.84–1.49) and anaemia (44.1% versus 41.3%) at 28–32 weeks, OR 1.07 (0.88–1.30). Meta-analysis of the primary outcome results with seven other studies of routine antibiotic prophylaxis in pregnancy (>6,200 pregnancies) shows no effect on preterm birth (relative risk 1.02, 95% confidence interval 0.86–1.22).

Conclusions

This study provides no support for the use of antibiotics as routine prophylaxis to prevent preterm birth in high risk populations; prevention of preterm birth requires alternative strategies.

Trial registration

Current Controlled Trials ISRCTN84023116 Please see later in the article for the Editors'' Summary     

Perinatal Outcomes by Mode of Assisted Conception and Sub-Fertility in an Australian Data Linkage Cohort

Background

Fertility treatment is associated with increased risk of major birth defects, which varies between in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), and is significantly reduced by embryo freezing. We therefore examined a range of additional perinatal outcomes for these exposures.

Methods

All patients in South Australia receiving assisted conception between Jan 1986–Dec 2002 were linked to the state-wide perinatal collection (all births/stillbirths ≥20 weeks gestation or 400 g birth weight, n = 306 995). We examined stillbirth, mean birth weight, low birth weight (<2500 g, <1500 g), small size for gestational age (<10th percentile, <3rd percentile), large size for gestational age (>90th percentile), preterm birth (32–<37 weeks, <32 weeks gestation), postterm birth (≥41 weeks gestation), Apgar <7 at 5 minutes and neonatal death.

Results

Relative to spontaneous conceptions, singletons from assisted conception were more likely to be stillborn (OR = 1.82, 95% Confidence Interval (CI) 1.34–2.48), while survivors as a group were comprehensively disadvantaged at birth, including lower birth weight (−109 g, CI −129–−89), very low birth weight (OR = 2.74, CI 2.19–3.43), very preterm birth (OR = 2.30, CI 1.82–2.90) and neonatal death (OR = 2.04, CI 1.27–3.26). Outcomes varied by type of assisted conception. Very low and low birth weight, very preterm and preterm birth, and neonatal death were markedly more common in singleton births from IVF and to a lesser degree, in births from ICSI. Using frozen-embryos eliminated all significant adverse outcomes associated with ICSI but not with IVF. However, frozen-embryo cycles were also associated with increased risk of macrosomia for IVF and ICSI singletons (OR = 1.36, CI 1.02–1.82; OR = 1.55, CI 1.05–2.28). Infertility status without treatment was also associated with adverse outcomes.

Conclusions

Births after assisted conception show an extensive range of compromised outcomes that vary by treatment modality, that are substantially reduced after embryo freezing, but which co-occur with an increased risk of macrosomia.     

Maternal Cadmium Levels during Pregnancy Associated with Lower Birth Weight in Infants in a North Carolina Cohort

Cadmium (Cd) is a ubiquitous environmental contaminant, a known carcinogen, and understudied as a developmental toxicant. In the present study, we examined the relationships between Cd levels during pregnancy and infant birth outcomes in a prospective pregnancy cohort in Durham, North Carolina. The study participants (n = 1027) had a mean Cd level of 0.46 µg/L with a range of <0.08 to 2.52 µg/L. Multivariable models were used to establish relationships between blood Cd tertiles and fetal growth parameters, namely birth weight, low birth weight, birth weight percentile by gestational age, small for gestational age, pre-term birth, length, and head circumference. In multivariable models, high maternal blood Cd levels (≥0.50 µg/L) during pregnancy were inversely associated with birth weight percentile by gestational age (p = 0.007) and associated with increased odds of infants being born small for gestational age (p<0.001). These observed effects were independent of cotinine-defined smoking status. The results from this study provide further evidence of health risks associated with early life exposure to Cd among a large pregnancy cohort.     

A Clinical Prediction Rule for Histological Chorioamnionitis in Preterm Newborns

Background

Histological chorioamnionitis (HC) is an intrauterine inflammatory process highly associated with preterm birth and adverse neonatal outcome. HC is often clinically silent and diagnosed postnatally by placental histology. Earlier identification could facilitate treatment individualisation to improve outcome in preterm newborns.

Aim

Develop a clinical prediction rule at birth for HC and HC with fetal involvement (HCF) in preterm newborns.

Methods

Clinical data and placental pathology were obtained from singleton preterm newborns (gestational age ≤32.0 weeks) born at Erasmus UMC Rotterdam from 2001 to 2003 (derivation cohort; n = 216) or Máxima MC Veldhoven from 2009 to 2010 (validation cohort; n = 206). HC and HCF prediction rules were developed with preference for high sensitivity using clinical variables available at birth.

Results

HC and HCF were present in 39% and 24% in the derivation cohort and in 44% and 22% in the validation cohort, respectively. HC was predicted with 87% accuracy, yielding an area under ROC curve of 0.95 (95%CI = 0.92–0.98), a positive predictive value of 80% (95%CI = 74–84%), and a negative predictive value of 93% (95%CI = 88–96%). Corresponding figures for HCF were: accuracy 83%, area under ROC curve 0.92 (95%CI = 0.88–0.96), positive predictive value 59% (95%CI = 52–62%), and negative predictive value 97% (95%CI = 93–99%). External validation expectedly resulted in some loss of test performance, preferentially affecting positive predictive rather than negative predictive values.

Conclusion

Using a clinical prediction rule composed of clinical variables available at birth, HC and HCF could be predicted with good test characteristics in preterm newborns. Further studies should evaluate the clinical value of these rules to guide early treatment individualisation.     

Sparse canonical correlation analysis from a predictive point of view

Canonical correlation analysis (CCA) describes the associations between two sets of variables by maximizing the correlation between linear combinations of the variables in each dataset. However, in high‐dimensional settings where the number of variables exceeds the sample size or when the variables are highly correlated, traditional CCA is no longer appropriate. This paper proposes a method for sparse CCA. Sparse estimation produces linear combinations of only a subset of variables from each dataset, thereby increasing the interpretability of the canonical variates. We consider the CCA problem from a predictive point of view and recast it into a regression framework. By combining an alternating regression approach together with a lasso penalty, we induce sparsity in the canonical vectors. We compare the performance with other sparse CCA techniques in different simulation settings and illustrate its usefulness on a genomic dataset.     

Maternal and Fetal Genetic Associations of PTGER3 and PON1 with Preterm Birth

Objective

The purpose of this study was to identify associations between maternal and fetal genetic variants in candidate genes and spontaneous preterm birth (PTB) in a Norwegian population and to determine the effect size of those associations that corroborate a previous study of PTB.

Methods

DNA from 434 mother-baby dyads (214 cases and 220 controls) collected from the Norwegian Mother and Child Cohort (MoBa) was examined for association between 1,430 single nucleotide polymorphisms in 143 genes and PTB. These results were compared to a previous study on European Americans (EA) from Centennial Women''s Hospital in Nashville, TN, USA. Odds ratios for SNPs that corroborated the Cenntennial study were determined on the combined MoBa and Centennial studies.

Results

In maternal samples the strongest results that corroborated the Centennial study were in the prostaglandin E receptor 3 gene (PTGER3; rs977214) (combined genotype p = 3×10⁻⁴). The best model for rs977214 was the AG/GG genotypes relative to the AA genotype and resulted in an OR of 0.55 (95% CI = 0.37–0.82, p = 0.003), indicating a protective effect. In fetal samples the most significant association in the combined data was rs854552 in the paraoxonase 1 gene (PON1) (combined allele p = 8×10⁻⁴). The best model was the TT genotype relative to the CC/CT genotypes, and resulted in an OR of 1.32 (95% CI = 1.13–1.53, p = 4×10⁻⁴).

Conclusions

These studies identify single locus associations with preterm birth for both maternal and fetal genotypes in two populations of European ancestry.     

Hepatic Hemodynamics and Fetal Growth: A Relationship of Interest for Further Research

Background

It is well known that hepatic hemodynamics is an important physiologic mechanism in the regulation of cardiac output (CO). It has been reported that maternal cardiac output relates to neonatal weight at birth.

Aims

In this study, we assessed the correlation between maternal hepatic vein Doppler flow parameters, cardiac output and neonatal birth weight.

Methods

Healthy women with uncomplicated second or third trimester pregnancy attending the outpatient antenatal clinic of Ziekenhuis Oost-Limburg in Genk (Belgium), had a standardized combined electrocardiogram-Doppler ultrasound with Impedance Cardiography, for measurement of Hepatic Vein Impedance Index (HVI  =  [maximum velocity – minimum velocity]/maximum velocity), venous pulse transit time (VPTT  =  time interval between corresponding ECG and Doppler wave characteristics) and cardiac output (heart rate x stroke volume). After delivery, a population-specific birth weight chart, established from a cohort of 27000 neonates born in the index hospital, was used to define customized birth weight percentiles (BW%). Correlations between HVI, VPTT, CO and BW% were calculated using Spearman''s ρ, linear regression analysis and R² goodness of fit in SPSS 22.0.

Results

A total of 73 women were included. There was a negative correlation between HVI and VPTT (ρ = −0.719, p<0.001). Both HVI and VPTT correlated with CO (ρ = −0.403, p<0.001 and ρ = 0.332, p<0.004 resp.) and with BW% (ρ = −0.341, p<0.003 and ρ = 0.296, p<0.011 resp.)

Conclusion

Our data illustrate that the known contribution of hepatic hemodynamics in the regulation of cardiac output is also true for women with uncomplicated pregnancies. Our study is the first to illustrate a potential link between maternal hepatic hemodynamics and neonatal birth weight. Whether this link is purely associative or whether hepatic vascular physiology has a direct impact on fetal growth is to be evaluated in more extensive clinical and experimental research.     

Differing Prevalence and Diversity of Bacterial Species in Fetal Membranes from Very Preterm and Term Labor

Background

Intrauterine infection may play a role in preterm delivery due to spontaneous preterm labor (PTL) and preterm prolonged rupture of membranes (PPROM). Because bacteria previously associated with preterm delivery are often difficult to culture, a molecular biology approach was used to identify bacterial DNA in placenta and fetal membranes.

Methodology/Principal findings

We used broad-range 16S rDNA PCR and species-specific, real-time assays to amplify bacterial DNA from fetal membranes and placenta. 74 women were recruited to the following groups: PPROM <32 weeks (n = 26; 11 caesarean); PTL with intact membranes <32 weeks (n = 19; all vaginal birth); indicated preterm delivery <32 weeks (n = 8; all caesarean); term (n = 21; 11 caesarean). 50% (5/10) of term vaginal deliveries were positive for bacterial DNA. However, little spread was observed through tissues and species diversity was restricted. Minimal bacteria were detected in term elective section or indicated preterm deliveries. Bacterial prevalence was significantly increased in samples from PTL with intact membranes [89% (17/19) versus 50% (5/10) in term vaginal delivery p = 0.03] and PPROM (CS) [55% (6/11) versus 0% (0/11) in term elective CS, p = 0.01]. In addition, bacterial spread and diversity was greater in the preterm groups with 68% (13/19) PTL group having 3 or more positive samples and over 60% (12/19) showing two or more bacterial species (versus 20% (2/10) in term vaginal deliveries). Blood monocytes from women with PTL with intact membranes and PPROM who were 16S bacterial positive showed greater level of immune paresis (p = 0.03). A positive PCR result was associated with histological chorioamnionitis in preterm deliveries.

Conclusion/Significance

Bacteria are found in both preterm and term fetal membranes. A greater spread and diversity of bacterial species were found in tissues of women who had very preterm births. It is unclear to what extent the greater bacterial prevalence observed in all vaginal delivery groups reflects bacterial contamination or colonization of membranes during labor. Bacteria positive preterm tissues are associated with histological chorioamnionitis and a pronounced maternal immune paresis.     

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.     

Intestinal Microbiota is Different in Women with Preterm Birth: Results from Terminal Restriction Fragment Length Polymorphism Analysis

Preterm birth is a leading cause of perinatal morbidity and mortality. Studies using a cultivation method or molecular identification have shown that bacterial vaginosis is one of the risk factors for preterm birth. However, an association between preterm birth and intestinal microbiota has not been reported using molecular techniques, although the vaginal microbiota changes during pregnancy. Our aim here was to clarify the difference in intestinal and vaginal microbiota between women with preterm birth and women without preterm labor. 16S ribosomal ribonucleic acid genes were amplified from fecal and vaginal DNA by polymerase chain reaction. Using terminal restriction fragment length polymorphism (T-RFLP), we compared the levels of operational taxonomic units of both intestinal and vaginal flora among three groups: pregnant women who delivered term babies without preterm labor (non-PTL group) (n = 20), those who had preterm labor but delivered term babies (PTL group) (n = 11), and those who had preterm birth (PTB group) (n = 10). Significantly low levels of Clostridium subcluster XVIII, Clostridium cluster IV, Clostridium subcluster XIVa, and Bacteroides, and a significantly high level of Lactobacillales were observed in the intestinal microbiota in the PTB group compared with those in the non-PTL group. The levels of Clostridium subcluster XVIII and Clostridium subcluster XIVa in the PTB group were significantly lower than those in the PTL group, and these levels in the PTL group were significantly lower than those in non-PTL group. However, there were no significant differences in vaginal microbiota among the three groups. Intestinal microbiota in the PTB group was found to differ from that in the non-PTL group using the T-RFLP method.     

Characterization of Dietary Patterns in the Danish National Birth Cohort in Relation to Preterm Birth

Background

Dietary patterns better reflect eating habits as opposed to single dietary components. However, the use of dietary pattern analysis in nutritional epidemiology has been hampered by the complexity of interpreting and presenting multidimensional dietary data.

Methods

This study extracts and visualizes dietary patterns from self-reported dietary data collected in mid-pregnancy (25^th week of gestation) from nearly 60,000 mother-child pairs part of a prospective, longitudinal cohort (Danish National Birth Cohort) and further examines their associations with spontaneous and induced preterm birth (gestational age<259 days (<37 weeks)).

Results

A total of seven dietary patterns were extracted by principal component analysis, characterized and visualized by color-coded spider plots, and referred to as: Vegetables/Prudent, Alcohol, Western, Nordic, Seafood, Candy and Rice/Pasta/Poultry. A consistent dose-response association with preterm birth was only observed for Western diet with an odds ratio of 1.30 (95% CI: 1.13, 1.49) comparing the highest to the lowest quintile. This association was primarily driven by induced preterm deliveries (odds ratio = 1.66, 95% CI: 1.30, 2.11, comparing the highest to the lowest quintile) while the corresponding odds ratio for spontaneous preterm deliveries was more modest (odds ratio = 1.18, 95% CI: 0.99, 1.39). All based on adjusted analyses.

Conclusions

In conclusion, this study presented a simple and novel framework for visualizing correlation structures between overall consumption of foods group and their relation to nutrient intake and maternal characteristics. Our results suggest that Western-type diet, high in meat and fats and low in fruits and vegetables, is associated with increased odds of induced preterm birth.     

Raised Trappin2/elafin Protein in Cervico-Vaginal Fluid Is a Potential Predictor of Cervical Shortening and Spontaneous Preterm Birth

Early spontaneous preterm birth is associated with inflammation/infection and shortening of the cervix. We hypothesised that cervico-vaginal production of trappin2/elafin (peptidase inhibitor 3) and cathelicidin antimicrobial peptide (cathelicidin), key components of the innate immune system, are altered in women who have a spontaneous preterm birth. The aim was to determine the relationship between cervico-vaginal fluid (CVF) trappin2/elafin and cathelicidin protein concentrations with cervical length in woman at risk of spontaneous preterm birth. Trappin2/elafin and cathelicidin were measured using ELISA in longitudinal CVF samples (taken between 13 to 30 weeks'' gestation) from 74 asymptomatic high risk women (based on obstetric history) recruited prospectively. Thirty six women developed a short cervix (<25 mm) by 24 weeks'' and 38 women did not. Women who developed a short cervix had 2.71 times higher concentrations of CVF trappin2/elafin from 14 weeks'' versus those who did not (CI 1.94–3.79, p<0.0005). CVF trappin2/elafin before 24 weeks'' was 1.79 times higher in women who had a spontaneous preterm birth <37 weeks'' (CI: 1.05–3.05, p = 0.034). Trappin2/elafin (>200 ng/ml) measured between 14⁺⁰–14⁺⁶ weeks'' of pregnancy predicted women who subsequently developed a short cervix (n = 11, ROC area = 1.00, p = 0.008) within 8 weeks. Cathelicidin was not predictive of spontaneous delivery. Vitamin D status did not correlate with CVF antimicrobial peptide concentrations. Raised CVF trappin2/elafin has potential as an early pregnancy test for prediction of cervical shortening and spontaneous preterm birth. This justifies validation in a larger cohort.