Biochemical surveillance versus clinical observation of term infants born after prolonged rupture of membranes - A quality assurance initiative.

AIM: To examine whether biochemical surveillance vs clinical observation of term infants with prolonged rupture of membranes as a risk factor for early-onset sepsis is associated with differences in patient trajectories in maternity and neonatal intensive care units. METHODS: A retrospective study of live-born infants with gestational age ≥ 37 + 0 weeks born after prolonged rupture of membranes (≥24 h) in four Norwegian hospitals 2017-2019. Two hospitals used biochemical surveillance, and two used predominantly clinical observation to identify early-onset sepsis cases. RESULTS: The biochemical surveillance hospitals had more C-reactive protein measurements (p < 0.001), neonatal intensive care unit admissions (p < 0.001) and antibiotic treatment (p < 0.001). Hospitals using predominantly clinical observation initiated antibiotic treatment earlier in infants with suspected early-onset sepsis (p = 0.04) but not in infants fulfilling early-onset sepsis diagnostic criteria (p = 0.09). There was no difference in antibiotic treatment duration (p = 0.59), fraction of infants fulfilling early-onset sepsis diagnostic criteria (p = 0.49) or length of hospitalisation (p = 0.30), and no early-onset sepsis-related adverse outcomes. CONCLUSION: The biochemical surveillance hospitals had more C-reactive protein measurements, but there was no difference in antibiotic treatment duration, early-onset sepsis cases, length of hospitalisation or adverse outcomes. Personnel resources needed for clinical surveillance should be weighed against the limitation of potentially painful procedures.

Antenatal corticosteroids for pregnant women with COVID-19 infection and preterm prelabor rupture of membranes: a decision analysis.

BACKGROUND: While antenatal corticosteroids are routinely used to decrease adverse neonatal outcomes following preterm delivery, corticosteroids are also associated with worse outcomes in patients with viral respiratory infections. Currently in the setting of the COVID-19 pandemic, it is unclear whether antenatal corticosteroids for infant benefit outweigh the potential harm to a pregnant woman with a COVID-19 infection. OBJECTIVE: To determine at which gestational ages administering antenatal corticosteroids is the optimal management strategy for hospitalized women with preterm prelabor rupture of membranes (PPROM) who have a COVID-19 infection. METHODS: We designed a decision-analytic model to assess the maternal and infant outcomes associated with antenatal corticosteroid administration for risk of preterm delivery following rupture of membranes in the setting of a COVID-19 infection. We used a theoretical cohort of 10,000 women at each gestational age between 24 and 32 weeks who were hospitalized with PPROM and found to be COVID-19 positive. Maternal outcomes included intensive care unit admission and death related to COVID-19 infection. The infant outcomes of interest included respiratory distress syndrome, intraventricular hemorrhage, neurodevelopmental delay, and death, and were assessed along with maternal and infant quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were used to evaluate model assumptions. RESULTS: In our theoretical cohort of 10,000 women with COVID-19 infection and preterm prelabor rupture of membrane between 24 and 32 weeks, corticosteroid administration resulted in 2,200 women admitted to the ICU and 110 maternal deaths at each gestational age. No antenatal corticosteroid use resulted in 1,500 ICU admissions and 75 maternal deaths at each gestational age. Antenatal corticosteroid administration also resulted in fewer cases of respiratory distress syndrome, intraventricular hemorrhage, and infant death. Overall, we found that between 24 and 30 weeks of gestation, administering antenatal corticosteroids was the optimal management strategy as it resulted in higher combined QALYs than no corticosteroid use. For 31 and 32 weeks of gestation, antenatal corticosteroid administration resulted in lower combined QALYs. On sensitivity analyses, we found that with increasing gestational age, the probability which antenatal corticosteroids was the optimal management strategy decreased. CONCLUSION: Administration of antenatal corticosteroids was an effective management strategy compared to no corticosteroid administration at gestational ages less than 31 weeks. These results provide data for clinicians to utilize when counseling pregnant patients hospitalized with PPROM and have a COVID-19 infection.

Granulocyte-macrophage colony-stimulating factor initiates amniotic membrane rupture and preterm birth in a mouse model.

OBJECTIVE: Preterm premature rupture of membranes is associated with 30% of all preterm births. The weakening of amniotic membranes is associated with an increase in matrix metallopeptidases (MMPs) along with a decrease in their inhibitors, tissue inhibitor metallopeptidases (TIMPs). Additionally, granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to weaken fetal membranes in-vitro. We hypothesize pregnant mice treated with GM-CSF lead to increased MMPs:TIMPs resulting in membrane rupture and preterm birth. STUDY DESIGN: Pregnant CD-1 mice on gestational day 17 received either an intrauterine injection of GM-CSF or vehicle control. A second series of mice were administered an intrauterine injection of Lipopolysaccharide along with either anti-mouse GM-CSF or control antibody. Mice were evaluated for rupture of membranes and/or preterm birth and the uterus, amniotic fluid, and serum were collected for analysis. RESULTS: 87.5% of GM-CSF mice exhibited evidence of membrane rupture or preterm birth, compared with 0% in control mice (p < .001). Treatment with GM-CSF decreased the expression of TNFα (p < .05) while increasing the ratio of MMP2:TIMP1 (p < .05), MMP2:TIMP2 (p < .05), MMP2:TIMP3 (p < .001), MMP9:TIMP1 (p < .01), MMP9:TIMP2 (p < .05), MMP9:TIMP3 (p < .001), and MMP10:TIMP1 (p < .05). Mice treated with LPS and the GM-CSF antibody resulted in a decrease in the ratio of MMP2:TIMP1 (p < .0001) compared with controls. CONCLUSION: These studies demonstrate GM-CSF will result in membrane rupture and preterm birth by increasing the ratio MMPs:TIMPs in our animal model. By increasing our understanding of the molecular pathways associated with GM-CSF, we may be able to develop future therapies to prevent preterm birth and reduce neonatal morbidity.

Maternal proximity to petrochemical industrial parks and risk of premature rupture of membranes.

BACKGROUND: Living near petrochemical industries has been reported to increase the risks of adverse birth outcomes, such as low birth weight and preterm delivery. However, evidence regarding the role of petrochemical exposure in pregnancy complications remains limited. This study evaluated the association between maternal proximity to petrochemical industrial parks (PIPs) during pregnancy and the occurrence of premature rupture of membranes (PROM). METHODS: We performed a population-based 1:3 case-control study by using the 2004-2014 Taiwanese Birth Certificate Database. Birth records reported as stillbirth or bearing congenital anomalies were excluded. Cases were newborns reported to have PROM, whereas controls were randomly sampled from those without any pregnancy complications by matching birth year and urbanization index of the residential township. The proximity to PIPs was evaluated by calculating the distance to the nearest PIP of the maternal residential township during pregnancy. Furthermore, petrochemical exposure opportunity, accounting for monthly prevailing wind direction, was quantified during the entire gestational period. We applied conditional logistic regression models to evaluate the associations. RESULTS: In total, 29371 PROM cases were reported during the study period, with a corresponding 88113 healthy controls sampled. The results revealed that living within a 3-km radius of PIPs during pregnancy would increase the risk of PROM (odds ratio [OR] = 1.76, 95% CI: 1.66-1.87). Furthermore, compared with the lowest exposed group, those with high petrochemical exposure opportunity had a significantly increased risk of PROM occurrence (OR = 1.69-1.75). The adverse effects remained robust in the subgroup analysis for both term- and preterm-PROM. CONCLUSIONS: The results of the present work provide evidence that living near PIPs during pregnancy would increase the risk of PROM, and additional studies are warranted to confirm our findings.

Association between prenatal rare earth elements exposure and premature rupture of membranes: Results from a birth cohort study.

BACKGROUND: The widespread exploitation and application of rare earth elements (REE) have led to the risk of human exposure and might result in the adverse health effect on pregnant women. However, no epidemiological studies have explored the associations between prenatal REE exposure and premature rupture of membranes (PROM). OBJECTIVE: We aimed to investigate the associations of maternal urinary REE levels with the risk of PROM. METHODS: A total of 4897 mother-newborn pairs were recruited from a birth cohort study in Wuhan, China. Urinary concentrations of REE were measured by inductively coupled plasma mass spectrometry (ICP-MS). The associations of prenatal REE exposure with PROM were evaluated using logistic regression models. False discovery rate (FDR) was applied to adjust for multiple testing. Weighted quantile sum (WQS) regression was used to estimate the association of urinary REE mixture with PROM. RESULTS: With one unit increase (µg/g creatinine) in natural log-transformed urinary REE levels (Ce, Yb, La, Pr, Nd, Eu, Gd, Dy, Ho, Er, Tm), the adjusted ORs (95% CIs) for the PROM were from 1.143 (1.078, 1.211) to 1.317 (1.223, 1.419), and the associations were still observed after FDR adjustment (all PFDRs < 0.05). The associations were stronger among male infants than female infants. Furthermore, the urinary REE mixture was also associated with the risk of PROM, a quartile increase in the WQS index of REE resulted in ORs (95% CI) for the PROM of 1.494 (1.356, 1.645) in the adjusted model. CONCLUSIONS: Our findings suggested that prenatal exposure to REE (Ce, Yb, La, Pr, Nd, Eu, Gd, Dy, Ho, Er, and Tm) and REE mixture were associated with the increased risk of PROM. Further studies from different populations are needed to confirm the associations and to explore the mechanisms.

Maternal exposure to ambient fine particulate matter and risk of premature rupture of membranes in Wuhan, Central China: a cohort study.

BACKGROUND: The associations between maternal exposure to ambient PM2.5 during pregnancy and the risk of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) are controversial. And no relevant study has been conducted in Asia. This study aimed to determine the association between maternal exposure to ambient PM2.5 during pregnancy and the risk of (P)PROM. METHODS: A cohort study including all singleton births in a hospital located in Central China from January 2015 through December 2017 was conducted. Multivariable logistic regression models, stratified analysis, generalized additive model, and two-piece-wise linear regression were conducted to evaluate how exposure to ambient PM2.5 during pregnancy is associated with the risks of PROM and PPROM. RESULTS: A total of 4364 participants were included in the final analysis, where 11.71 and 2.34% of births were complicated by PROM and PPROM, respectively. The level of PM2.5 exhibited a degree of seasonal variation, and its median concentrations were 63.7, 59.3, 55.8, and 61.8 µg/m3 for the first trimester, second trimester, third trimester, and the whole duration of pregnancy, respectively. After adjustment for potential confounders, PROM was positively associated with PM2.5 exposure (per 10 µg/m3) [Odds Ratio (OR) = 1.14, 95% Confidence Interval (CI), 1.02-1.26 for the first trimester; OR = 1.09, 95% CI, 1.00-1.18 for the second trimester; OR = 1.13, 95% CI, 1.03-1.24 for the third trimester; OR = 1.35, 95% CI, 1.12-1.63 for the whole pregnancy]. PPROM had positive relationship with PM2.5 exposure (per 10 µg/m3) (OR = 1.17, 95% CI, 0.94-1.45 for first trimester; OR = 1.11, 95% CI, 0.92-1.33 for second trimester; OR = 1.19, 95% CI, 0.99-1.44 for third trimester; OR = 1.53, 95% CI, 1.03-2.27 for the whole pregnancy) Positive trends between the acute exposure window (mean concentration of PM2.5 in the last week and day of pregnancy) and risks of PROM and PPROM were also observed. CONCLUSIONS: Exposure to ambient PM2.5 during pregnancy was associated with the risk of PROM and PPROM.

Estimating the acute effects of ambient ozone pollution on the premature rupture of membranes in Xinxiang, China.

While increasing evidence suggests that ozone (O3) exposure is associated with adverse birth outcomes, only one study has focused on its impact on the premature rupture of membranes (PROM). Therefore, we thus examined the effect of O3 on PROM in Xinxiang, China, using an over-dispersed Poisson generalized additive model. Several confounding factors, including meteorological factors, temporal trends, the day of the week, and public holidays, were considered in the model. We identified a total of 3255 instances of PROM from January 1, 2015 to December 31, 2017, and there was a significant association between the daily maximum 8-h mean concentrations (O3-8h) and PROM. Each 10 µg/m3 increase in the 3-day average concentration (lag02) of O3-8h corresponded to an increment in PROM of 5.42% (95% CI: 1.45-9.39%). Although the results of the stratified analyses were insignificant, a few trending results were observed: stronger associations between O3 and PROM would occur in women with advanced age (≥35) or during the warm season than those in younger women (<35) or during the cool season. Our study indicates that O3 exposure is an important risk factor of PROM and should be considered in its prevention and control in the study area.

Drastic induction of MMP-7 by cortisol in the human amnion: implications for membrane rupture at parturition.

Preterm premature rupture of fetal membranes precedes 30-40% of preterm births. Activation of matrix metalloproteases (MMPs) is the one of the major causes of extracellular matrix (ECM) degradation in membrane rupture. Increased cortisol, regenerated by 11ß-hydroxysteroid dehydrogenase 1 in the amnion at parturition, is known to participate in a number of parturition-pertinent events. However, whether cortisol has a role in the regulation of MMPs in the membranes is not known. Here, we addressed this issue using human amnion tissue, the most tensile layer of the membranes. RNA-sequencing revealed that cortisol induced MMP7 expression dramatically in amnion fibroblasts, which was confirmed by real-time quantitative RT-PCR and Western blotting analysis in cortisol-treated amnion explants and fibroblasts. Measurement of collagen IV α5 chain (COL4A5), a substrate for MMP-7, showed that cortisol reduced its extracellular abundance, which was blocked by an antibody against MMP-7. Moreover, increased MMP-7 but decreased COL4A5 abundance was observed in the amnion tissue following labor-initiated spontaneous rupture of membranes. Mechanistic studies showed that cortisol increased the phosphorylation of c-Jun and the expression of c-Fos, the 2 major components of activated protein 1 (AP-1), respectively. The knocking down of c-Fos or c-Jun significantly attenuated the induction of MMP7 expression by cortisol. Chromatin immunoprecipitation assays showed that cortisol stimulated the enrichment of c-Fos and c-Jun at the AP-1 binding site in the MMP7 promoter. The data suggest that induction of MMP7 by cortisol via AP-1 may be a contributing factor to ECM degradation in membrane rupture at parturition.-Wang, L.-Y., Wang, W.-S., Wang, Y.-W., Lu, J.-W., Lu, Y., Zhang, C.-Y., Li, W.-J., Sun, K., Ying, H. Drastic induction of MMP-7 by cortisol in the human amnion: implications for membrane rupture at parturition.

Maternal lead exposure and premature rupture of membranes: a birth cohort study in China.

OBJECTIVES: Maternal exposure to lead (Pb) has been suggested to correlate with adverse birth outcomes, but evidence supporting an association between Pb exposure and premature rupture of membranes (PROM) is limited. The aim of our study was to investigate whether maternal Pb exposure was associated with PROM and preterm PROM. DESIGN: Cross-sectional cohort study. STUDY POPULATION: The present study involved 7290 pregnant women from the Healthy Baby Cohort in Wuhan, China, during 2012-2014. MAIN OUTCOME MEASURES: PROM was defined as spontaneous rupture of amniotic membranes before the onset of labour and was determined with a pH ≥6.5 for vaginal fluid. Maternal urinary Pb level was adjusted by creatinine concentration, and its relationship with PROM was analysed by logistic regression. RESULTS: The IQR of maternal urinary Pb concentrations of the study population was 2.30-5.64 µg/g creatinine with a median of 3.44 µg/g creatinine. Increased risk of PROM was significantly associated with elevated levels of Pb in maternal urine (adjusted OR 1.23, 95% CI 1.0 to 1.47 for the medium tertile; adjusted OR 1.51, 95% CI 1.27 to 1.80 for the highest tertile). The risk of preterm PROM associated with Pb levels was significantly higher when compared with the lowest tertile (adjusted OR 1.24, 95% CI 0.80 to 1.92 for the medium tertile; adjusted OR 1.73, 95% CI 1.15 to 2.60 for the highest tertile). In addition, the relationship between Pb and PROM was more pronounced among primiparous women than multiparous women (p for interaction <0.01). CONCLUSIONS: Our study found that higher levels of maternal Pb exposure was associated with increased risk of PROM, indicating that exposure to Pb during pregnancy may be an important risk factor for PROM.

Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: a 20-year international cohort study of 1170 patients.

BACKGROUND: Awareness is growing that cancer can be treated during pregnancy, but the effect of this change on maternal and neonatal outcomes is unknown. The International Network on Cancer, Infertility and Pregnancy (INCIP) registers the incidence and maternal, obstetric, oncological, and neonatal outcomes of cancer occurring during pregnancy. We aimed to describe the oncological management and obstetric and neonatal outcomes of patients registered in INCIP and treated in the past 20 years, and assess associations between cancer type or treatment modality and obstetric and neonatal outcomes. METHODS: This descriptive cohort study included pregnant patients with cancer registered from all 37 centres (from 16 countries) participating in the INCIP registry. Oncological, obstetric, and neonatal outcome data of consecutive patients diagnosed with primary invasive cancer during pregnancy between Jan 1, 1996, and Nov 1, 2016, were retrospectively and prospectively collected. We analysed changes over time in categorical patient characteristics, outcomes, and treatment methods with log-binomial regression. We used multiple logistic regression to analyse preterm, prelabour rupture of membranes (PPROM) or preterm contractions, small for gestational age, and admission to the neonatal intensive care unit (NICU). The INCIP registry study is registered with ClinicalTrials.gov, number NCT00330447, and is ongoing. FINDINGS: 1170 patients were included in the analysis and 779 (67%) received treatment during pregnancy. Breast cancer was the most common malignant disease (462 [39%]). Every 5 years, the likelihood of receiving treatment during pregnancy increased (relative risk [RR] 1·10, 95% CI 1·05-1·15), mainly related to an increase of chemotherapeutic treatment (1·31, 1·20-1·43). Overall, 955 (88%) of 1089 singleton pregnancies ended in a livebirth, of which 430 (48%) of 887 pregnancies ended preterm. Each 5 years, we observed more livebirths (RR 1·04, 95% CI 1·01-1·06) and fewer iatrogenic preterm deliveries (0·91, 0·84-0·98). Our data suggest a relationship between platinum-based chemotherapy and small for gestational age (odds ratio [OR] 3·12, 95% CI 1·45-6·70), and between taxane chemotherapy and NICU admission (OR 2·37, 95% CI 1·31-4·28). NICU admission seemed to depend on cancer type, with gastrointestinal cancers having highest risk (OR 7·13, 95% CI 2·86-17·7) and thyroid cancers having lowest risk (0·14, 0·02-0·90) when compared with breast cancer. Unexpectedly, the data suggested that abdominal or cervical surgery was associated with a reduced likelihood of NICU admission (OR 0·30, 95% CI 0·17-0·55). Other associations between treatment or cancer type and outcomes were less clear. INTERPRETATION: Over the years, the proportion of patients with cancer during pregnancy who received antenatal treatment increased, especially treatment with chemotherapy. Our data indicate that babies exposed to antenatal chemotherapy might be more likely to develop complications, specifically small for gestational age and NICU admission, than babies not exposed. We therefore recommend involving hospitals with obstetric high-care units in the management of these patients. FUNDING: Research Foundation-Flanders, European Research Council, Charles University, Ministry of Health of the Czech Republic.

Exposure to Ambient Air Pollution and Premature Rupture of Membranes.

Premature rupture of membranes (PROM) is a major factor that predisposes women to preterm delivery. Results from previous studies have suggested that there are associations between exposure to air pollution and preterm birth, but evidence of a relationship with PROM is sparse. Modified Community Multiscale Air Quality models were used to estimate mean exposures to particulate matter less than 10 µm or less than 2.5 µm in aerodynamic diameter, nitrogen oxides, carbon monoxide, sulfur dioxide, and ozone among 223,375 singleton deliveries in the Air Quality and Reproductive Health Study (2002-2008). We used log-linear models with generalized estimating equations to estimate adjusted relative risks and 95% confidence intervals for PROM per each interquartile-range increase in pollutants across the whole pregnancy, on the day of delivery, and 5 hours before delivery. Whole-pregnancy exposures to carbon monoxide and sulfur dioxide were associated with an increased risk of PROM (for carbon monoxide, relative risk (RR) = 1.09, 95% confidence interval (CI): 1.04, 1.14; for sulfur dioxide, RR = 1.15, 95% CI: 1.06, 1.25) but not preterm PROM. Ozone exposure increased the risk of PROM on the day of delivery (RR = 1.06, 95% CI: 1.02, 1.09) and 1 day prior (RR = 1.04, 95% CI: 1.01, 1.07). In the 5 hours preceding delivery, there were 3%-7% increases in risk associated with exposure to ozone and particulate matter less than 2.5 µm in aerodynamic diameter and inverse associations with exposure to carbon monoxide and nitrogen oxides. Acute and long-term air pollutant exposures merit further study in relation to PROM.

High bisphenol A (BPA) concentration in the maternal, but not fetal, compartment increases the risk of spontaneous preterm delivery.

OBJECTIVE: The objective of this study is to determine if BPA exposure, as measured by maternal plasma (MP) and amniotic fluid (AF) BPA concentrations is associated with an increased risk of spontaneous preterm birth (PTB) and preterm premature rupture of membranes (pPROM). METHODS: In this nested case-control study, MP samples from women in term labor (n = 30), preterm labor that ended with preterm delivery (n = 25), or who had pPROM (n = 30) and amniotic fluid samples from term labor (n= 45), preterm labor (n = 60), and pPROM (n = 35) were assayed for BPA by enzyme immunoassay. RESULTS: BPA was detectible in 100% of MP and AF samples. Women with MP BPA concentrations in the fourth quartile were at increased risk of PTB (cOR = 4.12, 95% CI = 1.32-12.87; aOR = 4.78, 95% CI = 1.14-20) but not pPROM. High (fourth quartile) AF BPA values also tended to increase the risk of pPROM (cOR = 2.47, 95% CI = 0.96-6.37) but results were not statistically significant. CONCLUSIONS: Increased BPA concentration is associated with an increased risk for PTB or pPROM depending on the maternal-fetal compartment(s) affected. High MP plasma BPA concentrations are associated with PTB with intact membranes but high AF BPA concentrations may weakly be associated with pPROM.

Chemotactic activity of gestational tissues through late pregnancy, term labor, and RU486-induced preterm labor in Guinea pigs.

PROBLEM: Is increased leukocyte chemotactic activity (CA) from gestational tissues necessary for term or preterm labor in guinea pigs? METHOD OF STUDY: Tissue extracts were prepared from pregnant guinea pig decidua-myometrium, cervix, fetal membranes (amniochorion), and placenta during early third trimester (n = 8), term not in labor (TNL, n = 5), and term spontaneous labor (TL, n = 6), RU486-induced preterm labor (PTL, n = 6), or controls (cPTL, n = 5). Leukocyte CA was assessed using a modified Boyden chamber assay. Extract chemokine and maternal progesterone concentrations were quantified by enzyme immunoassay. RESULTS: Only the extracts from amniochorion demonstrated increased CA through late gestation and labor. In contrast, CA was decreased in extracts from amniochorion and cervix from animals after RU486-induced PTL. Maternal progesterone concentrations remained high in all groups. CONCLUSION: Leukocyte CA of intrauterine tissues is increased in term spontaneous labor. However, RU486-induced preterm labor occurs in the absence of increased CA.

Air pollution and preterm premature rupture of membranes: a spatiotemporal analysis.

Preterm premature rupture of membranes (PROM) is the leading identifiable predisposing factor for preterm birth. Although maternal exposure to air pollution can potentially have an impact on preterm PROM, there is no available evidence on such an impact. In this study, based on 5,555 singleton births occurring in Barcelona, Spain (2002-2005), we investigated the associations of maternal exposure to nitrogen dioxide, nitrogen oxides, and particulate matter with aerodynamic diameters of ≤2.5 µm (PM2.5), 2.5 µm-10 µm, and ≤10 µm and PM2.5 light absorption with preterm PROM and gestational age at the rupture of membranes (ROM). We utilized temporally adjusted land-use regression models to predict pollutant levels at each subject's home address during each week of her pregnancy. We conducted matched (according to the length of exposure) case-control analyses to estimate the preterm PROM risk associated with 1 interquartile-range increase in exposure levels during the entire pregnancy and during the last 3 months prior to ROM. We found an increase in preterm PROM risk of up to 50% (95% confidence interval: 4, 116) and a 1.3-day (95% confidence interval: -1.9, -0.6) reduction in gestational age at ROM associated with PM2.5 absorbance, nitrogen dioxide exposure, and nitrogen oxide exposure during the entire pregnancy and the last 3 months prior to ROM.

Obstetrical and neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitors: the relevance of dose.

OBJECTIVE: The purpose of this study was to evaluate the effects of prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) on obstetrical and neonatal outcomes. METHOD: A case-control study was conducted to compare perinatal outcomes among pregnant women with affective disorder (DSM-IV criteria) and who received SSRIs during pregnancy with those of women without an active psychiatric disorder during pregnancy who were non-exposed to antidepressants during pregnancy. Each case was matched to two controls for maternal age (± 2 years) and parity. RESULTS: A total of 252 women were enrolled in the study, 84 exposed and 168 non-exposed. Demographic and clinical characteristics did not differ significantly between the groups. The rates of prelabor rupture of membranes, induction of labor and cesarean delivery were slightly higher but not statistically significant in the exposed group. The mean gestational age at birth was 38.8 (± 1.86) weeks for the exposed group and 39.4 (± 1.52) weeks for the non-exposed group (p=.005). Rates for preterm birth were higher in the exposed group (OR=3.44, 95% CI=1.30-9.11). After stratification for dose, it was found that exposure to a high-dose was associated with lower gestational age (p=.009) and higher rates of prematurity (OR=5.07, 95% CI=1.34-19.23). The differences remained significant after controlling for maternal status and the length of exposure. CONCLUSION: Women treated with SSRIs during pregnancy, mainly at high-dose, had an increased risk of preterm birth compared to healthy women of similar age and parity who were not exposed to SSRI during pregnancy.

Cigarette smoke induces oxidative stress and apoptosis in normal term fetal membranes.

Cigarette smoking and bacterial infections are two major risk factors associated with preterm prelabor rupture of membranes (pPROM). We hypothesized that exposure of fetal membranes to cigarette smoke extracts might induce oxidative stress (OS) and fetal membrane apoptosis, culminating in an alternate pathway to that commonly activated by infection. To test this, we characterized the production of prostanoids and biomarkers of apoptosis in normal term human fetal membrane explant cultures. Fetal membrane explants collected at term (from cesarean deliveries, not in labor) were stimulated with cigarette smoke extract (CSE) for 24 h. Two classes of prostanoids, F2-Isoprostane (F2-IsoP), a marker of OS and PGF2α, a classical uterotonin, were measured by gas chromatography/mass spectrometry. Western blot analyses of tissue lysates were performed to quantify the anti-apoptotic protein Bcl2 and actin (as a control). Fetal membrane apoptosis was detected by immunohistochemistry for active caspase 3 and confirmed by TUNEL staining for nuclear fragmentation. CSE exposure resulted in significantly more F2-IsoP production from fetal membranes (242.8 ± 79.3 pg/ml/mg of total membrane protein) compared to unstimulated controls (131.5 ± 53.1 pg/ml/mg; p < 0.0001). By contrast, PGF2α was not different in CSE vs. controls (1083 ± 527 vs. 1136 ± 835 pg/ml/mg of protein; p = 0.80). CSE-exposed tissues demonstrated a dose-dependent decrease in Bcl2 expression and increases in active caspase 3 and nuclear fragmentation in both amnion and chorion cells compared to controls. In summary, fetal membranes exposed to CSE manifest evidence of OS and apoptosis. The differential pattern of prostanoid production observed in this study supports the hypothesis that an alternate non-inflammatory pathway mediated by OS and apoptosis in pPROM may promote proteolysis resulting in membrane weakening and rupture.

Early pregnancy blood lead levels and the risk of premature rupture of the membranes.

To clarify the effects of lead on fetal premature rupture of the membranes (PROM), blood lead concentrations were measured using inductively coupled plasma-mass spectrometry in 332 women, aged 16-35 years, during their early pregnancy period (8-12 weeks). Blood lead concentrations were significantly higher in the 36 PROM deliveries than in the 296 non-PROM deliveries (mean ± SD, 4.61 ± 2.37 and 3.69 ± 1.85 µg/dl, respectively; p<0.05). The logistic regression analysis revealed that a 1-unit increase in the logarithm of the blood lead level led to a several-fold increase in the risk of PROM (unit risk=17.98, 95% CI 1.6-198.6). Thus, it is suggested that lead can increase the risk of PROM in pregnant women with mean blood lead less than 5 µg/dl.

Effect of low lead exposure on gestational age, birth weight and premature rupture of the membrane.

OBJECTIVE: To find out the effect of prenatal exposure to low lead from cosmetics on gestational age, premature rupture of the membrane and birth weight. METHODS: The study was carried out in the mountainous Aseer region, Southwest of Saudi Arabia where the air is thought to be clean and free of lead pollution due to the absence of petroleum smelting and other heavy industries. The region is famous as a holiday resort for tourists from Arabia and the gulf countries. All 176 pregnant women included in the study were of singleton pregnancies of gestational age 27 weeks or more who attended the antenatal outpatient clinic of the main maternity hospital. On the day of delivery 4 milliliters of venous blood from each singleton parturient was placed in a heparinized non-silica containing tube and stored at -20 degrees C prior to analysis. RESULTS: Ninety-four (70.1%) women out of 134 had maternal blood lead concentration < 200 microg/L and only 40 women had > 200 microg/L. The mean difference in gestational age was 10.5 days, showing a non significant difference (P=0.152). Ninety-three women (72.7%) out of a total of 128 who had blood lead concentration <200 microg/L gave birth to infants weighing an average of 2.87 kg while 35 women who had blood lead level > 200 microg/L gave birth to infants weighing an average of 2.99 kg. The mean difference was 0.12 kg which is non-significant (P=0.261). Regarding premature.rupture of the membrane a total of 127 women with maternal blood lead levels above 200 microg/L showed no significant differences (P=0.64). The Chi-square test of the relationship between the birth weight (kg) and the levels of blood lead below 150 microg/L was not significant while the relationship between the birth weight (kg) and the levels of blood lead above 200 microg/L resulted in very slight differences in the values of infants' birth weight. CONCLUSION: The detected low lead exposures from cosmetics does not produce statistically significant effects on the three pregnancy outcomes; gestational age, premature rupture of the membrane or birth weight. However, the importance of low lead exposure from the 100% lead sulfide eye cosmetic "kohl" is emphasized".

Water disinfection by-products and pre-labor rupture of membranes.

The causes of term pre labor rupture of membranes (term PROM) remain poorly defined. The authors conducted a record-based prevalence study to explore a possible relation between disinfection by-products in drinking water and term PROM in an Australian community with spatially variable trihalomethane and nitrate levels. A multilevel statistical model was used to examine the relation between factors operating at the levels of the individual, district, and water distribution zone and the prevalence of PROM at term among 16,229 women in Perth, Western Australia (2002-2004). Adjusted odds ratios for term PROM increased with increasing tertiles of nitrate exposure (moderate exposure: odds ratio = 1.23, 95% confidence interval: 1.03, 1.52; high exposure: odds ratio = 1.47, 95% confidence interval: 1.20, 1.79), but there was no significant relation with exposure to trihalomethanes. This study raises the possibility that water contaminants may promote the development of PROM at term.