In this paper, a new type of electric field sensor is proposed for the health and safety protection of inspection staff in high-voltage environments. Compared with the traditional power frequency electric field measurement instruments, the portable instrument has some special performance requirements and, thus, a new kind of double spherical shell sensor is presented. First, the mathematical relationships between the induced voltage of the sensor, the output voltage of the measurement circuit, and the original electric field in free space are deduced theoretically. These equations show the principle of the proposed sensor to measure the electric field and the effect factors of the measurement. Next, the characteristics of the sensor are analyzed through simulation. The simulation results are in good agreement with the theoretical analysis. The influencing rules of the size and material of the sensor on the measurement results are summarized. Then, the proposed sensor and the matching measurement system are used in a physical experiment. After calibration, the error of the measurement system is discussed. Lastly, the directional characteristic of the proposed sensor is experimentally tested. High-voltage equipment is always surrounded by a strong electric field, and studies have shown that power frequency electric fields have potential harmful effects on human health and safety ,2,3. An Power frequency electric field measurement is mainly governed by two principles: electromagnetic induction and optical effect. The electric field measurement instruments based on the Pockels optical effect include a laser generator, optical detector, photoelectric conversion, optical fiber, and other parts. There are more factors affecting measurement due to such a complex structure, leading to higher design complexity. Further, the movement of the human body will affect the incident angle of the laser, the internal stress of the optical fiber, and so on, which will change the phase delay of the laser, causing large measurement error. Thus, instruments based on optical effect are not suitable for portable measurement. The electric field measurement instruments based on capacitive sensing—a type of electromagnetic induction—are more widely used in power system environmental measurement because of their convenient manufacture, high accuracy, and strong overload capacity ,12,13. TThere are some commercialized electric field measurement instruments, such as the series of Narda, PMM, CA, etc., and a number of studies have continued to develop new electric field measurement instruments for special purposes ,15,16,17A portable electric field sensor must meet the following performance requirements, which make it different from existing sensors: Requirement (1) is that the sensor should be small and light enough to wear on a person’s arm or waist. Requirement (2) is that the output of the sensor must be steady and accurate at a given measuring point even if the sensor is rotated. Requirement (3) is that the sensor must be suited to measure the complex power frequency electric field produced by varied electrical equipment in a power system.(1)The charges gather on the edge of electrodes, which causes electric field distortion in the adjacent space of the edges. The distortion is difficult to evaluate quantitatively, so it increases the uncertainty and instability of measurement.(2)The sensors are too large and heavy for portable measurement. The size of the sensors is unlikely to be much reduced because the smaller the sensor size, the more serious the distortion caused by the edge effect.(3)Because of their multi-electrode configuration, when the sensors are used for portable measurements, the mutual capacitances between the human body and these electrodes are extremely complicated , which wThere are cubical and spherical sensors ,19,20,21After comparative studies on the existing sensor structures and measurement results, a new type of electric field sensor with double spherical shells is proposed to meet the requirements of portable measurement.The double spherical shell sensor is shown in r1, the slot between which will be sealed up with conductive paint. Part C is a metal hollow shell with radius r2. Part D is a fill medium. The output signal of the sensor is the induced differential voltage UAC, which is extracted by shielded wire and connected to a differential amplifier. Besides this, the shielding layer of the shielded wire is connected to the reference ground of the signal processing circuit, which can eliminate the common-mode interference from the shielded cable in the electric field.The double spherical shell sensor is composed of the inner shell, the outer shell, and the fill medium. Parts A and B are two metal hemispherical shells with radius The inner and outer shells represent the two electrodes of the sensor. Each electrode is an entire spherical shell, enabling the sensor to increase in induction area and decrease in size. The inner electrode is hollow, which is conducive to reducing the weight. The measurement remains stable and the output value is fixed when the sensor is rotated because of the nearly symmetrical structure. Therefore, the requirements of portable measurement are all met.The induced charge will be generated and distributed on the surface of the outer shell when the sensor is placed in an electric field.r1 is ungrounded and it is actually far away from the point charge.To explain the measurement theory as a mathematical expression, we analyze the case that the electric field is generated by a point charge. The sketch of the calculation is shown in Q′ and Q″ are set on the line linked by the center point O and point charge Q according to the uniqueness theorem and the image method. The position and value of the image charges are expressed as [Considering that the spherical shell is equipotential, the image charges essed as (1)Q′=−rP in the space out of the outer shell is given byThe potential at any point Then the three components of electric field in the spherical coordinates are calculated byr = r1 as r1 << H, the electric field on the outer surface of shell can be calculated by bringing Equation (2) into Equations (5)–(7):Setting x, and it reaches the maximum when x = H − r1, while it is equal to zero when x = H.The electric field on the outer surface of the shell is perpendicular to the surface. The field intensity changes with If there is no spherical shell in the space, the original electric field generated by the same point charge along the virtual circle shown in Er2 between the outer and inner shells. Because of the spherically symmetric structure of the sensor, Er2 is a spherically symmetric distribution between the two shells. The radial component Er2 can be expressed asIf the material of the shells is not a perfect conductor and the electric field is an alternating field, the electric field cannot be shielded completely by the outer shell; this results in the existence of an electric field UAC is calculated by the integral of the electric fieldThe induced voltage E2 is spherically symmetric, no matter what the field distribution on the surface of the outer shell is, Since K1 is related to the radius, thickness, and conductivity of the outer shell, the conductivity of the fill medium, and the frequency of the original electric field.The coefficient UAC and the original electric field E0 are in the following relationship:Substituting Equation (14) into Equation (13), the induced voltage K2 is obtained by simulation in The value of the coefficient UAC.The potential of the shells is a floating potential, and the output signal of the sensor is the differential potential of the two shells. A differential amplifier is needed in the signal extraction module, as shown in UAC with angular frequency ω. SC is the inherent capacitance of the shells, and can be calculated byIn R11 and R21 are the current-limiting resistors. R22 and R12 are the DC bias resistors. The AD620 requires only one external resistor GR to set the gain G from 1 to 10,000.SC, R11, R12, R22, and R21 form a loop, and the output voltage OU can be obtained as follows.Considering that the ports “+” and “−” are connected to operational amplifiers in the chip AD620, the current flow into the two ports is zero. Thus, the components OU can be expressed as follows.Further, the RMS value of E0_rms can be expressed asCombining Equation (15) with Equation (19), the RMS value E0_rms in the free space can be determined by the measurement voltage OU_rms, and the coefficient allK is obtained and verified by experiment in Therefore, the electric field r1 = 12.5 mm and r2 = 8 mm, respectively. The material of the shells was stainless steel, and the fill medium was epoxy resin. The sensor was placed in a homogeneous electric field, which was generated by a wide parallel plate capacitor.A 3-D simulation model was built based on the software Ansoft/Maxwell . The radA sinusoidal voltage with power frequency of 50 Hz and adjustable amplitude was set on the parallel plates. When the original electric field between the plates was set as 3 kV/m, the distribution of electric field in the outer and inner parts of the sensor were as shown in uA, the inner shell potential uC, and the potential difference, i.e., the induced voltage uAC, are shown in The time domain waveforms of the outer shell potential uAC is a sine wave with frequency 50 Hz and the effective value is approximately 4.28 mV.According to E0_rms is changed, and the corresponding induced voltages UAC_rms are shown in The intensity of the original electric field E0_rms and UAC_rms is close to 1.00, which means that UAC_rms has a significant positive relationship with E0_rms. Therefore, the induced voltage can be regarded as being proportional to the original electric field. The proportionality coefficient between E0_rms and UAC_rms is defined as K2 in Equation (15), and K2 ≈ 1.42 × 10−6 m.Analyzing the data above, the linearly dependent coefficient between r1 and inner shell r2 were changed, and the corresponding induced voltages UAC_rms are shown in The original electric field was fixed at 3 kV/m. The materials of shells and fill medium were stainless steel and epoxy resin, respectively. The radii of the outer shell Based on r1 = 12.5 mm and r2 = 8 mm.The size of the sensor affects the magnitude of induced voltage and the fabrication complexity of the sensor. The requirements of small size and light weight should also be considered. Thus, the size of sensor in this paper was chosen as UAC_rms are shown in Only metal material was taken into account because the shells must have equipotential character. In the simulation, the original electric field was fixed at 3 kV/m, and the material of the shells ranged over stainless steel, iron, aluminum, copper, and perfect conductor. The spacer material was epoxy resin, and the thickness of the two shells was set as 0.5 mm. The corresponding induced voltages It can be seen from UAC_rms are shown in The filling material between the two shells ranged over vacuum, epoxy resin, glass, and mica. The corresponding induced voltages −15~10−13) S/m, and the dielectric loss tangent (tgδ) is less than 0.004.It can be seen from The designed portable electric field sensor and measurement system are shown in RG of AD620 was set as 100 Ω, so the gain G can be calculated as 495 according to Equation (17). In R11 and R21 are set as 1 kΩ, and R22 and R12 are set as 50 MΩ, so the coefficients K3 and allK can be calculated as 133 and 5285 m−1, according to Equations (19) and (20), respectively. The value of allK will be verified by experiment.The radii of the outer and inner shell were 12.5 mm and 8 mm, respectively, so the inherent capacitance of the shells can be calculated as 8.897 pF according to Equation (16). The external resistor In order to study the characteristic of the instrument in an inhomogeneous electric field, an experimental platform was built as shown in allK as shown in Equation (20) by experiment, a series of experiments were carried out.To calculate the proportionality coefficient E0_rms and OU_rms are shown in Firstly, the measurement position was fixed, and electric fields in space with different intensity were generated by setting different excitation voltages on the conductor. The measurement data of OU_rms is proportional to E0_rms. According to the fitting curve, the proportionality coefficient is calculated as Kall = 5950 m−1, which is closed to the theoretical value (5285 m−1).It is clear that l) between the conductor and the sensor, and accordingly performed three sets of experiments to obtain OU_rms under a series of electric fields E0_rms. Then, OU_rms multiplied by 5950 m−1 gives E*0_rms which represents the measuring electric field obtained by the designed instrument. The correlation between E*0_rms and E0_rms is shown in To confirm that the coefficient is valid when the measurement position is changed, we set three kinds of vertical distance (E*0_rms = E0_rms. It is clear that most of the points fall on the reference line or are very close to the line no matter what kind of measurement distance or original electric field intensity was set. The absolute error is less than ±50 V/m with standard deviation 25 V/m, no matter the original electric field strength. The maximum relative error is 11%, which appears when the electric field is about 247 V/m, and it was found by further analysis that the relative error would be less than 5% when the original electric field is stronger than 1 kV/m. The reason for this is that the stronger the original electric field, the greater the signal-to-noise ratio. Considering the fact that the proposed electric field sensor and measurement system are designed for use in strong electric field environments, and a weak electric field will not trigger the alarm of the instrument, this error in measurement is acceptable.In Theoretically speaking, the output voltage will not change when the designed sensor is rotated in the same electric field because of the symmetrical structure. This section presents the directional performance test of the instrument.The center position of the instrument was fixed, and the measuring system was rotated along the vertical axes, as shown in The measurement results are shown in Portable electric field measurement is a new kind of demand, at the core of which is the need to design a new sensor that meets specific performance requirements. This paper presented a new type of sensor with a double spherical shell. The mathematical relationships between output voltage of the sensor, measuring voltage of the measurement circuit, and original electric field were derived in theory. The analysis demonstrated the feasibility of the sensor and the factors that affect the measurement.The characteristic of the electric field sensor was simulated in a homogeneous field. The output voltage of the sensor is mainly affected by the radii of outer and inner shells as well as the material used for the shells and fill medium. Considering the requirements of small size, light weight, and convenient processing, the radii of the outer and inner shells were set at 12.5 and 8 mm, respectively, and stainless steel and epoxy resin were chosen as the material of the shells and fill medium, respectively.The experiment was conducted in an inhomogeneous field generated by a conductor. The results demonstrate the high accuracy of the sensor, with absolute error less than 50 V/m, and relative error less than 5% when the original electric field is stronger than 1 kV/m. Furthermore, when the double spherical shell sensor is rotated along the axes but the center position remains fixed, the output voltage remains almost unchanged, which is what is required for portable measurement.


A case of intraprostatic cyst is reported. The patient presented with a completely evacuated hydatid cyst of the prostate. The intraprostatic cystic cavity that was communicating with the urethra developed urinary stones. The patient had transurethral resection of the prostate, the stones in the cyst were pushed into the bladder and fragmented using a ballistic lithotripter. Pathological examination concluded to a prostatic hydatid cyst that had evacuated through the urethra and was complicated by stone formation within the residual cavity. Postoperative course was uneventful and follow-up did not show evidence of recurrence. This is the first case of hydatid cyst of the prostate to present as an intraprostatic stone pouch.


Porphyromonas gingivalis is a Gram-negative, anaerobic bacterium considered to be an important pathogen of periodontal disease that is also implicated in adverse pregnancy outcome (APO). Until recently, our understanding of the role of P. gingivalis in APO has been limited and sometimes contradictory. The purpose of this review is to provide an overview of past and current research on P. gingivalis that addresses some of the controversies concerning the role of this organism in the pathogenesis of APO. Porphyromonas gingivalis is a Gram-negative, anaerobic bacterium considered to be an important pathogen of periodontal disease [P. gingivalis may indirectly contribute to adverse pregnancy outcomes (APO) by facilitating the release of bacterial products or inflammatory mediators into the maternal circulation that reach the maternal-fetal interface [P. gingivalis could also directly promote APO via invasion and injury to utero-placental tissues; this is supported by several studies that have detected P. gingivalis DNA/antigen in the placenta, amniotic fluid, umbilical cord, and neonatal nasogastric aspirates from complicated pregnancies [P. gingivalis as a causative agent of APO is sometimes viewed with skepticism due to several confounding factors. For instance, periodontal disease in of itself is a poor predictor of preterm birth, preeclampsia, fetal growth restriction, or perinatal death [P. gingivalis DNA or antigen has also been detected in placentas from healthy pregnancies, albeit at a lower microbial load and lower frequency than women with preeclampsia or preterm birth [P. gingivalis to APO when its detection in utero-placental tissues is usually in association with other oral bacterial species [ disease . As a penterface . P. ginggnancies –11. Howeal death ,12. Morerm birth –7. It is species –5, or wh species .P. gingivalis produces a diverse array of APO, including utero-placental pathology, enhanced expression of pro-T helper (TH)1 type cytokines , fetal growth restriction (FGR), and spontaneous preterm delivery [Experimental infection in various animal models confirms that invasion of the uterine compartment by delivery . Since tdelivery . Inflammdelivery . On the delivery ,16. In tP. gingivalis provide new insights into the role of this organism in periodontal disease and/or APO. The purpose of this review is to provide an overview of past and current research on P. gingivalis that addresses some of the controversies concerning the role of this organism in the pathogenesis of APO. In addition to presenting new data generated by our research group, we searched PubMed for publications relevant to the topic of this review. Search terms for this review included: Porphyromonas gingivalis, periodontal disease, periodontitis, gingivitis, hormones and pregnancy, preeclampsia, preterm delivery, fetal growth restriction, defective deep placentation, uterine NK cells, and decidual macrophages.Recent studies regarding the pathogenic mechanisms of The phenomenon of pregnancy-induced gingivitis is widely reported ,18, and Prevotella intermedia and P. gingivalis are able to reduce testosterone to 5-alpha dihydrotestosterone (DHT) and induce DHT synthesis by fibroblasts [P. gingivalis that are capable of interfering with androgen signaling may adversely impact placental development through this mechanism.In general, sex hormones are reported to increase vascular permeability and proliferation while inhibiting oral mucosal tissue repair, suggesting that sex hormone associated gingivitis  alters the effectiveness of the epithelial barrier to the oral microbiota ,18,21. Oroblasts . More reroblasts . These aroblasts ,25. In sP. intermedia growth [P. intermedia and P. gingivalis in response to hormonal changes during pregnancy [Female sex hormones may directly promote microbial growth, as they stimulate a growth ,27 and aregnancy ,19 has bregnancy . Thus, iP. gingivalis ligand-induced inflammatory process [P. gingivalis favors T helper cell polarization to a TH17 profile with generation of TH17-related cytokines [P. gingivalis induced T cell differentiation shift is highly specific towards a TH17 cell phenotype in an IL-6 dependent manner [P. gingivalis-induced periodontitis exacerbates arthritis in an IL-17RA (receptor A) dependent manner in an antigen-induced arthritis murine model [P. gingivalis placental colonization would increase the risk of APO in part by inducing a TH17/Treg cell imbalance.TH17 cells and IL-17 are reported to increase in periodontal lesions and exacerbate the  process . More reytokines  and thatt manner . Moreovet manner . This hyne model . The balne model . Pregnanne model . TherefoFusobacterium species in placentas from preterm and low-birth-weight pregnancies [Porphyromonas, Prevotella, Variovorax, and Dialister in placentas from preeclamptic women [P. gingivalis promotes oral dysbiosis [P. gingivalis contributes to adverse pregnancy outcomes. In a pilot study conducted by our research group, we examined the composition of the oral microbiome of Sprague-Dawley (SD) rats that received repeated oral inoculations of sterile vehicle or 109 CFU of P. gingivalis strain A7A1-28  structures that either activate or antagonize TLR4, such as lipid A1 and 4′ phosphatases [P. gingivalis lipid A is required for successful colonization and overgrowth of plaque bacteria [in vivo with a ligature model of periodontitis in rabbits that were inoculated with P. gingivalis strain A7436 or lipid phosphatase mutants that were ‘locked’ into producing a TLR4 agonist or antagonist [Fusobacterium nucleatum, which is implicated in preterm delivery [P. gingivalis in placenta, amniotic fluid, and nasogastric aspirates from preterm infants [in vitro, hemin-rich medium promotes the growth of TLR4 antagonist forms of P. gingivalis [Campylobacter rectus and P. gingivalis strain A7436 coinfection in a rodent model of APO [C. rectus-induced expression of TLR4 in the placenta, but produced FGR that did not occur in animals singly infected with C. rectus [P. gingivalis-induced FGR is indeed associated with an increased placental expression of TH1-type cytokines: IFN-γ, IL-2, and IL-12 with a concurrent reduction in TH2 type IL-10 and TGF-β2 [The microbial community-wide dysbiotic effect of engallis . Althougysbiosis , the abiphatases , is partphatases ,52. In tbacteria . This watagonist . In thisdelivery ,54 and i infants . Furtherngivalis , and thul of APO . Specifi. rectus . P. gingd TGF-β2 . It shoud TGF-β2 ,58. UndeP. gingivalis has on this system. Successful pregnancy depends on adequate remodeling of uterine spiral arteries from narrow lumen/high resistance vessels to dilated/low resistance vessels that lack their musculoelastic wall. Optimal transformation of the uterine arteries allows the placenta to receive an adequate blood supply without pulsatile turbulent flow that could damage the placenta. The actual process of spiral artery remodeling involves endothelial cell swelling, separation and dedifferentiation of vascular smooth muscle cells (VSMC), degradation of the extracellular matrix with deposition of fibrinoid material, and infiltration of the vessel wall with invading trophoblasts [Although a thorough understanding of uterine changes during pregnancy is beyond the scope of this review, it is important to summarize some key features of this process in order to appreciate the impact hoblasts . Effectihoblasts . Changeshoblasts .bright/CD16− and express a repertoire of activating and inhibitory receptors (NKRs) that can fluctuate in response to EVT and invading pathogens [in vitro, possibly making the arteries more penetrable to EVT cells [During early pregnancy, uNK cells make up ~70% of leukocytes within the placental bed ,62. uNK athogens . Althougathogens . Human uVT cells . Their rMacrophages comprise ~20% of the decidual leukocyte population . Unlike EVTs facilitate spiral artery remodeling by promoting apoptosis of arterial endothelium and VSMC . AnotherIt is important to note that EVTs are functionally distinct from villous trophoblasts. First, EVT are highly motile and capable of invading the uterus, whereas villous trophoblasts are not . Second,Inadequate remodeling of the myometrial segments of the uterine spiral arteries is referred to as defective deep placentation (DDP) ,75. StudP. gingivalis colonizes the deep uterine vasculature or if this is linked to APO. However, there are some implications that support this notion. The inner third of the placental bed, the decidua, ‘peels off’ with the placenta when it is removed, so it is readily available for analysis. Studies that have sampled the decidua for the presence of P. gingivalis DNA reported that 70–92% of specimens from women with preeclampsia were positive [P. gingivalis within the placenta significantly linked to shorter gestation lengths , regardless of the diagnosis of APO [P. gingivalis could contribute to APO.Given the difficulty in obtaining human placental bed specimens, it is not surprising that there is no information to identify whether positive ,5. Anoths of APO . Thus, Din vivo and in vitro infection models indicate that P. gingivalis can interfere with remodeling of the uterine spiral arteries. In a pregnant rat model of infection, Belanger et al. were the first to provide evidence that P. gingivalis induces metrial arteritis [P. gingivalis strain A7436. Subsequent studies by our research group have demonstrated that infection with fimbriae-expressing P. gingivalis strain A7436 or A7A1-28 does indeed interfere with the physiologic remodeling of the uterine spiral artery in rats . Decidual cells were isolated as previously described [bright dNK cells during P. gingivalis infection, with a concomitant increase in CD16+ NK cells. Both of these subsets had increased expression of cytotoxicity receptor NKp46 and activation marker NKG2D with infection; however, we did not observe significant differences in the expression of activation marker CD69, proliferation marker Ki-67, or inhibitory marker PD-1 in dNKs from our infected versus control cohorts.A preliminary study conducted by our group in nonhuman primates suggests that infection with escribed  and evalescribed  to generescribed  populati+ NK cells are the predominant NK cell type in peripheral blood, they have high cytotoxicity and are present at much lower levels in the decidua. In a healthy pregnancy, most dNKs are CD56bright cells that possess granules such as perforin and granzyme B but have low potential for degranulation and are mainly pro-angiogenic, cytokine secreting and immunomodulatory. Double-negative or CD56dim populations have been described as secreting low levels of IFN-γ and TNF-α and having a detrimental impact on pregnancy [+ to CD56+ cells appears to be important for pregnancy success, likely due to the pro-inflammatory nature of CD16+ cells.While CD16regnancy . A numberegnancy –84. In pregnancy  found thP. gingivalis induces loss of CD56+ dNK cells and an increase in CD16+ dNK cells in the first trimester. The ratio of CD16+ cells to CD56+ cells increases to 0.63 with infection versus 0.32 in control animals, and to a lesser extent so does the ratio of NKp46+ cells to CD56+ cells with infection (0.24) versus control (0.20), indicating a shift towards an activated phenotype [bright cells have a crucial role in implantation, trophoblast migration, and spiral artery remodeling [Our preliminary data suggest that infection with henotype ,86. Thermodeling , and thamodeling ,88.+ T cells in infected animals (data not shown). Within this subset, P. gingivalis infection also correlated with higher expression of PD-1 (46.8 ± 7% vs 4.35% control) and lower expression of IFN-γ (3.3 ± 1.5% vs 41% control), which may contribute to chronic infection by suppressing adaptive T cell responses.Although our flow cytometric analysis of macaque decidual cells was not designed to comprehensively investigate T cell lineage and function , we did P. gingivalis infection alters the phenotype or function of these cells. As already mentioned, dMΦ also appear to have a role in spiral artery remodeling and trophoblast migration, typically bear markers associated with tissue remodeling and phagocytosis of debris, and have recently been divided into two subsets: one more regulatory, and the other more pro-inflammatory [P. gingivalis infection resulted in a notable decrease in CD206+ dMΦs  or proliferation marker Ki-67 expression between infected and control dMΦs. Although we cannot rule out the possibility that some of these differences are due to the variation inherent to a genetically diverse nonhuman primate model rather than a disease state, these results provide a possible mechanism for P. gingivalis-mediated effects on spiral artery remodeling. Further characterization will be necessary to determine the biological significance of our findings.In addition to lymphocytes, we examined markers of macrophages in the decidua to assess whether ammatory . P. ging06+ dMΦs . CD206 iP. gingivalis-mediated DDP. HTR8/SvNeo cells are human EVTs [P. gingivalis effects on trophoblasts in vitro. P. gingivalis can invade HTR8/SvNeo cells and inhibit their proliferation through induction of G1 arrest and apoptosis [P. gingivalis induces IFN-γ expression [P. gingivalis inhibit migration of HTR8/SvNeo through Matrigel [in vitro or in vivo.EVTs may also be a target for man EVTs ,91 that man EVTs . HTR8/Svman EVTs  and havepoptosis ,94. Furtpression . While EMatrigel . FactorsMatrigel . This isP. gingivalis strains exhibit different degrees of pathogenicity based on their ability to invade host cells, disseminate to various organ/tissue sites, and induce disease [P. gingivalis strains that have been used extensively in pregnancy outcome studies are W83 and A7436. Although in silico comparison of the whole genome of these strains shows that they are closely related [It is already well established that  disease ,98–100.  disease . To date related , W83 andP. gingivalis strain A7436 has been examined in various species including hamsters, mice, rats, and rabbits [9 CFU) of A7436 given intravenously to pregnant rats induces moderate decidual necrosis without any evidence of inflammation in the labyrinth, chorioamnion, or amniotic cavity [ rabbits ,101–103. rabbits ,101,102. rabbits  (Figure  rabbits . Interesc cavity . Taken tc cavity . Insteadc cavity ,104,105.P. gingivalis strains.Unlike A7436, W83 is more likely to induce spontaneous preterm delivery, at least in mice ,107. In P. gingivalis strain diversity on APO, determining simply whether or not an individual is colonized is insufficient for establishing who is at risk of having a complicated pregnancy. Furthermore, studies that specifically address the role of P. gingivalis virulence mechanisms at the maternal-fetal interface are needed in order to define how this microbe contributes to a wide array of APOs. Regardless of microbial strain diversity, the ability of P. gingivalis to disrupt first trimester processes, namely the physiologic remodeling of the uterine spiral arteries, suggests that timing of oral therapies during pregnancy is important and should begin as early as possible including pregnancy or, if possible, prior to conception. Although it has been established that P. gingivalis can induce dysbiosis of the oral mucosal microbiota, the impact of this effect on systemic illness, particularly APOs, requires further investigation. The notion that P. gingivalis invasion of the maternal-fetal interface could also promote placental dysbiosis linked to APOs is intriguing, but is yet to be tested. Additional studies are warranted to test this hypothesis and to elucidate the microbial mechanisms through which placental dysbiosis occurs.Given the effect of


Synechocystis sp. PCC 6803 in solution or immobilized on FTO conducting glass was compared using time-resolved fluorescence. Deposition of PSI on glass preserves bi-exponential excitation decay of ~4–7 and ~21–25 ps lifetimes characteristic of PSI in solution. The faster phase was assigned in part to photochemical quenching (charge separation) of excited bulk chlorophylls and in part to energy transfer from bulk to low-energy (red) chlorophylls. The slower phase was assigned to photochemical quenching of the excitation equilibrated over bulk and red chlorophylls. The main differences between dissolved and immobilized PSI (iPSI) are: (1) the average excitation decay in iPSI is about 11 ps, which is faster by a few ps than for PSI in solution due to significantly faster excitation quenching of bulk chlorophylls by charge separation (~10 ps instead of ~15 ps) accompanied by slightly weaker coupling of bulk and red chlorophylls; (2) the number of red chlorophylls in monomeric PSI increases twice—from 3 in solution to 6 after immobilization—as a result of interaction with neighboring monomers and conducting glass; despite the increased number of red chlorophylls, the excitation decay accelerates in iPSI; (3) the number of red chlorophylls in trimeric PSI is 4 (per monomer) and remains unchanged after immobilization; (4) in all the samples under study, the free energy gap between mean red (emission at ~710 nm) and mean bulk (emission at ~686 nm) emitting states of chlorophylls was estimated at a similar level of 17–27 meV. All these observations indicate that despite slight modifications, dried PSI complexes adsorbed on the FTO surface remain fully functional in terms of excitation energy transfer and primary charge separation that is particularly important in the view of photovoltaic applications of this photosystem.Excitation energy transfer in monomeric and trimeric forms of photosystem I (PSI) from the cyanobacterium  Two large subunits  form a heterodimer; they bind most of the Chls and Cars molecules and coordinate the functionally most important part of PSI reaction center (RC), where charge separation occurs. The RC is composed of 6 Chls , two phylloquinones and three iron-sulfur cofactors. The remaining Chls and Cars form the core antenna whose role is to harvest photons and transfer excitation energy to the RC. The primary donor of PSI (P700) absorbs at around 700 nm, whereas the vast majority of Chls (“bulk” Chls) absorbs at around 680 nm. However, in almost all PSI complexes, a pool of Chls that absorbs at an energy lower than the primary donor can be distinguished. These forms are the so-called red or long-wavelength Chls (“red” Chls) due to their redshifted absorption. While all red Chls are present in cyanobacterial PSI core complexes, in green algae and plants most of the red Chls are located in LHCI , 10 mM NaCl, 5 mM NaH2PO4 and 5 mM K2HPO4 (buffer A). Cultures from ~8 l of such cultivation were concentrated in buffer A at a chlorophyll a concentration of ~1 mg/ml. The chlorophyll concentration was determined according to Porra et al. ] was added to the sample and centrifuged at 235,000×g for 30 min at 4 °C in a Sorvall S100-AT6 rotor. The supernatant was discarded, and the procedure was repeated twice with buffer B with 0.03 % β-DM. Thylakoids were resuspended in buffer C  at a chlorophyll a concentration of ~1 mg/ml, and 10 % β-DM was added (v/v) to a final concentration of 1 % with 1 mg/ml of chlorophyll a. The sample was incubated at 4 °C for 20 min in the dark, and subsequently ultra-centrifugation was performed . The final stage of isolation is based on Ramesh et al.  in buffer C was applied. The concentration of MgSO4 needed for elution was about 15 mM for monomeric PSI and above 50 mM for trimeric PSI. Those values, however, depend strongly on the concentration of the other salts and pH of the buffer. Fractions with a Qy maximum absorption band above 678 nm were pooled and concentrated using Amicon 100 kDa ultra-filters. In order to remove excess of MgSO4, samples were dialyzed in buffer D (buffer C without taurine), using the aforementioned filters and kept frozen at −20 °C until further use.Phycobilisomes were removed as follows. One volume of buffer B [20 mM Bis Tris, pH 6.5, 5 mM NaHh et al.  with sevg for 30 min at 4 °C in a Sorvall S100-AT6 rotor). The initial detergent dilution was sufficient for partial precipitation of the PSI complexes. About 80 % of the supernatant was discarded. Then, the same volume of buffer without detergent was added. Aliquots of 1 ml of PSI sample were then dialyzed in distilled water (of volume exceeding the volume of the PSI solution 600 times) with addition of 10 mM Bis Tris pH 7.0.Deposition of the PSI complexes onto PSI glass was performed as follows. Pre-diluted PSI samples  were washed by ultracentrifugation  or a different ionic strength of the used buffer. The estimated number of PSI layers deposited onto FTO was about 14 assuming the cross-sectional size of a PSI monomer of the order of 100 nm2. OD679 nm of the PSI complexes immobilized on FTO was about 0.04.Samples with a reduced amount of salts and detergent were deposited onto FTO glass, with the help of an externally applied electrical field. A drop of PSI solution was placed between two FTO electrodes, separated by a ~2 mm spacer. Next, the electrodes were connected to a stable voltage source (NDN DF-1730). Different voltage values, electrodes polarization and time of electrically assisted deposition were tested—the most homogeneous and durable layers were formed with 2.5 V applied for 5 min. Another group also found similar conditions as optimal  is a radius of a hypothetical hard sphere, which diffuse in a particular solution at the same rate as the molecule under observation. Any solvent or detergent molecules permanently attached to the surface of the molecule under study contribute to the measured hydrodynamic radius.679nm,1cm ~ 1 in buffer D, then diluted again 50 times with distilled water. Measurements aiming to compare the diffusion time of monomeric and trimeric PSI complexes were repeated 8 times under identical conditions, each time using a fresh sample and then averaged. To improve the signal/noise ratio of the autocorrelation function, each measurement series was based on 40 scans of the diffusion time, with a duration of 15 s each. More details about the used setup can be found in Banachowicz et al.  equipped with a water-immersion objective Zeiss C Apochromat 40×/1.2 W. The light source was a standard Helium–Neon 633 nm 5 mW laser with an output power set to 3 %. The detection line contained a 650 nm low pass filter. The SP value (parameter specifying dimensions of the focus) was set upon measurement of the Atto633 dye in water to a value of 6.3. The samples of PSI were diluted to ODz et al. . The resz et al. . The simz et al. .679nm,1cm ~ 1. Both the monomeric and trimeric forms of PSI were measured in two cases: a) P700 in the neutral state (open RC)—addition of 20 µM phenazine methasulfate (PMS) supplemented with 20 mM ascorbic acid; b) P700 in the oxidized state (closed RC)—addition of 3 mM potassium ferricyanide. Examples of using those agents to modulate the RC state can be found in the literature  at room temperature. All measurements were performed using 400-nm, 100-fs laser pulses, repetition rate 125 kHz for excitation. Those pulses were generated in an 800 nm titanium:sapphire laser (Coherent Vitesse) amplified by a regenerative amplifier (Coherent RegA 9000) and fed into an optical parametric amplifier (Coherent OPA 9400) where the second harmonic was generated.In order to avoid excessive irradiation, solutions of PSI were placed in a rotating cuvette and FTO glasses with adsorbed iPSI and were moved by a mechanical motion controller. The energy of a single pulse was below 1 nJ at the spot size of approximately 150 µm. At this excitation level, effects due to singlet–singlet annihilation could not be observed.The fluorescence was collected at a right angle with respect to the excitation beam. Spectral and time resolution was achieved by the spectrograph (Chromex 250IS) and the streak camera (Hamamatsu C5680), respectively. The streak images were recorded by Hamamatsu C4880 CCD device, in three different time domains : TR1 ~140 ps, TR2 ~400 ps and TR3 ~1400 ps. Time resolution in those modes was ~3.5, ~6 and ~15 ps, respectively. The wavelength scale of the spectrograph was calibrated using an argon lamp.The exposure time per image was chosen so as to obtain a similar signal for each time range and each sample (about 4000 counts at maximum). In order to improve the signal/noise ratio, four images of each sample were collected and averaged. Each experiment was corrected by background subtraction and then analyzed with Glotaran software . In order to further confirm the homogeneity of the two fractions, fluorescence correlation spectroscopy was applied. This technique allows the estimation of diffusion coefficients of dissolved emitting molecules and their effective (hydrodynamic) radii . As shown in the inset to Fig. Qy absorption bands in monomeric and trimeric PSI. Trimeric complexes show larger absorption at 705 ± 10 nm than monomeric complexes thus demonstrating the existence of extra red Chls in the former preparation. This effect was reported previously, and the extra red Chls were proposed to be formed at the interface of interacting PSI monomers forming a trimer . The same effects were observed for trimeric PSI . However, the exact value of this initial distribution was not critical for the obtained results of the target analysis, meaning that for different initial distributions the fitting always converged to the same final values of molecular rate constants and the same shapes of SAS. The maximum of the bulk Chls SAS amplitude is somewhat higher than that of the red Chls SAS, but the width of the latter spectrum is larger than that of the former one . However, this difference does not strongly influence the overall fluorescence kinetics. The reason for the accelerated bulk to red Chls energy transfer is most likely the presence of extra red Chls in trimeric PSI discussed above. One needs to remember that the “Red” compartment in our model reflects a “mean” red Chls pool, most likely composed of a few individual red Chl-states, each of them having a potentially different spectrum and coupling to bulk Chls.Molecular lifetimes and SASes obtained from the target analysis for open PSI trimers shown in Fig. τ1 from 12.1 to 15.4 ps, very similar to that observed for monomeric PSI.Closing trimeric PSI leads to only one significant change: ~25 % increase of The redox state of the primary donor in dried PSI monomers and trimers immobilized on FTO (iPSI) is uncertain. However, regarding that no chemicals intended to keep RCs open or closed were added to the PSI solution used for their adsorption on FTO and that under such conditions PSI complexes in solution stay preferentially in the closed state (data not shown), we assume that our iPSI is mostly in the closed state. Decay-associated spectra for iPSI monomers and trimers Fig. c, f are The third, slowest component is of very small amplitude, as in the case of PSI in solution, but its lifetime is much shorter  and its values are highly uncertain due to small amplitudes. Additionally, the respective DASes of this component display very broad spectra slightly peaking at 730 nm  ps and τ3 = (7.6–8.4) ps Fig. Analysis of molecular lifetimes estimated from the target analysis reveals that immobilization of both monomeric and trimeric PSI on FTO Fig. a, d leadIn this chapter, we apply the basic thermodynamic equations in order to estimate the “effective” numbers of bulk and red Chls present in PSI monomeric and trimeric complexes in solution and immobilized on FTO. The primary goal of these considerations is not to determine the thermodynamic functions of PSI antenna in the rigorously correct way but only to demonstrate in a quantitative way how the immobilization of PSI complexes influences the “effective” number of the red states. The “effective” numbers are the hypothetical numbers of isoenergetic bulk states and isoenergetic red states which would give the ratio of energy transfer rates from bulk to red and from red to bulk states, that is observed in the experiment . Thus, our main simplifying assumption is isoenergeticity of all bulk Chls and all red Chls. Similar simplification  free energy difference between bulk and red states  and backward (bulk → red) transitions, kr→b and kb→r, in the following way:kr→b and kb→r is equivalent to transition times τ3 and τ2 (respectively) found in the target analysis. Thus, combining Eqs.  between bulk and red states  free energy (S0) is nonzero because each of the states can be realized in a different number of ways  determined by the number of Chls assigned to each of the two pools. In fact, the number of microstates (N) may be somewhat different from the exact numbers of the bulk and red Chls, because the redshift of the red Chls is assumed to be an effect of excitonic coupling within dimers or trimers of Chls mixed with charge transfer states and these two phenomena exert an unknown effect on the oscillator strength of the red Chls emitting states. Therefore, in further discussion we will relate number of microstates to the effective numbers of bulk and red Chls, Nbeff and Nreff, with the normalization condition:S0):H0 and ΔG0 based on the experimental data  that is significantly exceeding the number of red Chls (Nreff). For a better understanding of the problem, the working energetic model for bulk and red states is presented in Fig. Target analysis showed that H0, the wavelengths of the fluorescence maxima of the respective SASes  and particularly blueshifted red Chls (maximum at 708.5 nm), the latter being likely related to the set of specific red Chls in these samples (see below). Obviously, the enthalpy of the bulk Chls is always higher than the enthalpy of the red Chls.In order to calculate the enthalpy difference between bulk and red Chls, Δes Figs. , 5 were Nreff, were calculated from Eqs. Effective numbers of red Chls, τ1) was estimated by Gobets et al. at 18 ps for both complexes which is significantly larger value than our estimates (12.1–12.8 ps). The difference may originate from partially closed RCs in the cited paper and/or somewhat different preparation. Also the energy transfer from bulk to red Chls (τ2) in monomers with open RCs was found by Gobets et al. to be significantly slower than in the case of our modeling (31 vs. 22.4 ps). Obviously, this results in larger free energy gap between bulk and red Chls reported by Gobets for monomers (open RC) compared to our case , which in the case of van Stokkum et al.   increasing from 8.9 ps in open state to 11.4 ps in the closed state  or an uncertain state, maybe ground state recovered after charge recombination depicted by the molecular lifetime τirr (in the case of closed RC). Since the excitation energy transfer from bulk to red Chls is evident in the case of cyanobacterial PSI and model (10) ignores such a reaction, we could not have applied this model to cyanobacterial PSI. Instead, we connected the model (10) with the one shown in Figs. τ1), was used for our results:τ1). Obviously, we can expect that this lifetime modeled in target analysis would be almost the same as an average fluorescence lifetime calculated based on global analysis. Therefore, molecular lifetimes (τ1) obtained here for cyanobacterial PSI monomers  the primary charge separation likely leads to formation of the state A+A0− *, was blocked, then the overall fluorescence decay in this system would be described directly by the forward reaction rate equal to ~11 ps. Therefore, we can hypothesize here that the observed acceleration of photochemical quenching in the iPSI is the effect of blocking the reverse reaction in the primary charge separation . This blockage of the reverse reaction could be the result of very fast re-reduction of A+ by electron from FTO or injection of electron from A0− to FTO. Similar effects are well documented for dyes on conducting surfaces , but also the interaction between bulk and red Chls: both forward and backward energy transfer rates between these two pools decrease after immobilization (both for monomeric and trimeric PSI) although the free energy gap between them is strongly affected only for monomeric iPSI (−17 meV for iPSI instead of −27 meV for PSI in solution; Table Based on our approach, it is difficult to conclude on the nature and exact localization of the red Chls. However, our results are consistent with the idea that the additional, fourth red Chl in each monomer forming the trimeric PSI is at the very periphery of a monomer, in its contact region with another monomer. In our modeling Figs. , 5, we aIn conclusion, we state that first steps of energy and electron transfer in monomeric and trimeric cyanobacterial PSI are well preserved and even slightly accelerated after removal of water solvent and after dense protein packing on the flat surface of FTO conducting glass. The trimeric PSI is less susceptible to modifications of Chl–Chl interaction after immobilization. These observations further confirm the usefulness of cyanobacterial PSI in biophotovoltaic applications.


Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history.We conducted a population-based case–control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967–2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders.We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites . As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found.In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women. Colorectal cancer is the second most common cancer in women worldwide (GLOBOCAN 2012), and ∼55% of the cases occur in more developed regions. In the Nordic countries during 2010–2014, the cumulative risk of disease before age 75 was 4.1% in males and 3.2% in females (NORDCAN) -beta, the predominant ER subtype in the human colon  use and risk of colorectal cancer , being a surrogate measure of her lifetime exposure to endogenous sex steroids or other biomarkers related to reproductive events.This study was based on data collected from nationwide population-based registries in the four Nordic countries. Nordic birth registries contain information on all births in Denmark, Finland, Norway, and Sweden since 1973, 1987, 1967, and 1973, respectively (n=4680), Finland , Norway , and Sweden  among women registered with a prior pregnancy (lasting longer than 22 weeks) in the birth registries. The rationale for including only parous women was to create a study group as homogenous as possible with respect to fertility. We included only the first cancer (any cancer) for each case. Up to 10 controls per case were sampled among women in the birth registries with a prior pregnancy lasting longer than 22 weeks, and they had to be alive and free of any cancer at the time of diagnosis of the corresponding case. Controls were matched to cases on country and birth year of the case. In total 22 185 cases and 220 246 controls were included in the study.The data were analysed within a case–control design, including all colorectal adenocarcinoma cases diagnosed in Denmark , C18.0–C18.5; and ICD-7 (Sweden), 153.0–153.1 and 153.4); distal colon ; other colon ; and rectum .Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We examined the following reproductive variables: parity – number of births at the time of matching ; age at first birth ; age at last birth ; time since first birth ; and time since last birth . Stratified analyses were performed for ages <50, 50–59, and ⩾60 years, which served as proxies for pre-, peri-, and postmenopausal status, respectively. We had limited information available on potential confounders.We tested for differences between the countries by fitting logistic regression models with and without interaction terms between country of birth and the reproductive variables. The data were analysed using IBM SPSS Statistics 22  and Stata/IC 14.0 .This study was approved by the ethical committees in Norway and Sweden. In Denmark, the study was approved by the Data Protection Agency. In Finland, we obtained permission to use health registry data from the National Institute for Health and Welfare after approval by the data protection authority.Characteristics of the study population are presented in When we tested for potential differences between countries, no significantly improved fit emerged of models including interaction terms (data not shown).In this large population-based Nordic study, no evidence for associations was observed between women's reproductive history and colorectal adenocarcinoma in parous women.Studies to date regarding reproductive factors and colorectal cancer have been inconclusive. Our results showing no evidence for associations between reproductive history and colorectal adenocarcinoma, accord with some studies , with information on subsite, among women with at least one registered pregnancy in the four Nordic countries, and linkage of comprehensive databases with valid information and mandatory reporting . The stuA study weakness was lack of information on possible confounders, such as use of exogenous hormones (OCs and HT), age at menarche and menopause, obesity, smoking, physical activity, and aspirin/NSAID use. It is possible that these factors act in opposite directions, and thus contribute to an overall null effect. However, in the Swedish study on reproductive history and colorectal adenocarcinoma, adjustment for diabetes, obesity, diagnoses associated with tobacco smoking and alcohol overconsumption, as well as bilateral oophorectomy (representing HT) did not change risk estimates materially  and colorectal adenocarcinoma in parous women.


Adequate maternal nutrition is a key factor for achieving good pregnancy outcomes. Moreover, inadequate dietary intake during pregnancy is considered an important contributor to maternal malnutrition in developing countries. Although some studies have examined the effect of the entire diet on birth outcome, most studies have been very narrow because they considered the effect of single nutrient. The single nutrient approach is a major setback because usually several nutrient deficiencies are more likely to occur than single deficiencies especially in low-income settings.The main aim of this study was to investigate the association between maternal dietary patterns, and practices and birth weight in Northern Ghana.A facility-based cross-sectional survey was performed in two districts in the Northern Region of Ghana. The selected districts were the Tamale Metropolis and Savelugu-Nanton District. These districts were purposively sampled to represent a mix of urban, peri-urban and rural populations, therefore ensuring that the distribution in social groups of the study population was similar to the entire population of the region. In all, 578 mothers who were drawing antenatal and postnatal care services were interviewed using a questionnaire, which asked the mothers about their frequency of consumption of individual foods per week since they became pregnant or when they were pregnant.We determined dietary patterns by applying a factor analysis with a varimax rotation using STATA. Multivariate analysis was used to establish association between maternal factors and dietary patterns. Logistic regression was used to assess the association between dietary practices and patterns and birth weight.Women who ate outside the home twice a week  and those who practiced ‘pica’  had increased odds for low birth. Two dietary patterns were identified—namely ‘health conscious’ and ‘non-health conscious’. Health conscious diet  and dietary diversity score  showed a protective effect for low birth weight respectively after adjusting for gestational age.Mothers who practiced good nutrition such as consuming foods across and within the various food groups were less likely to have low birth weight babies. Our findings buttress the importance of optimal nutrition during pregnancy. Pregnancy is a critical period during which good maternal nutrition is key in ensuring successful pregnancy outcome. Nutritional needs are higher when pregnant and meeting these needs helps protect the long-term health of both fetus and mother. Pregnancy is a period of increased metabolic demands, with modifications in the woman's physiology and the requirements of a growing fetus . There iDietary intake during pregnancy has the potential to influence birth outcomes , 13. WomAlthough some studies have examined the effect of the entire diet on birth outcome, most studies have been very narrow because they considered the effect of single nutrient . The sinVarious dietary patterns have been identified by several studies, which could influence pregnancy outcome. For example, Thompson & co.  have desMoreover, it is suggested that dietary diversity scores could also be used as a proxy measure of micronutrient and diet adequacy of women , 22. IncReports suggest that pregnant women using district and community health facilities may not necessarily have access to expert knowledge on maternal nutrition in Ghana. Therefore it is advocated by local experts that the development of more effective nutrition intervention is needed , 29 in oSince dietary habits are often induced by culture and by the kind of food available, for consumption, investigating the characteristic of diet and practices therein within a study population may provide basis for future interventions to improve maternal and infant nutrition. Therefore the main aim of this study was to investigate maternal dietary patterns and practices in relation to birth weight in Northern Ghana. Specifically the study investigated; (1) The association between dietary practices and low birth weight; (2) Dietary patterns and associated factors during pregnancy; (3) The association between dietary patterns and low birth weight.The study design including the methods used to generate data on demographic and socio-economic factors as well as antenatal records used in the present study have been described previously and published . The stuA longitudinal component was conducted at the Tamale Teaching Hospital. The target group was pregnant women who were in the second trimester of their pregnancy and attending antenatal clinic (ANC) at the Tamale Teaching Hospital. Only singleton pregnancy was considered. Two hundred and sixteen (216) pregnant women were selected using consecutive sampling technique and those who agreed to participate in the study were asked to sign a consent form. They were followed until delivery for data that is not relevant to the present analysis.The 2016 was arrived at using the following expression;1-α = Z0.95 = 1.96 Where ZThe prevalence of low birth weight (P) at the Tamale Teaching Hospital was 16% = 0.16And the degree of precision for this study was estimated at 5% implying that the prevalence of abnormal birth weight babies at the Hospital will be between 11–21%.2) (0.16 (1–0.16)/0.052) = 206. We assumed 5% lost to follow up, hence the actual number of women required to estimate the prevalence of low birth weight between 11–21% was 206/0.95 = 216.This implies that N =  was 216.The 216 pregnant women were selected based on the following; the pregnancy was in the second trimester; the pregnant woman was not severely ill and regular ANC attendance. Consecutive sampling procedure was used to select the pregnant women. This implied that all pregnant women who met the criteria enumerated above were selected per every visit we made to the Hospital until all the 216 women were selected.The study also targeted mothers receiving postnatal and child welfare clinic services and have babies who were ≤ 40 days old. This was because we needed to take pregnancy records from the antenatal booklet, which is only available during the postnatal visit after which child welfare book is used.Three hundred and eighty four (384) mothers were approached and those who agreed to participate in the study were asked to sign a consent form. The sample size was determined using an estimated low birth weight prevalence of 50% for the entire Northern Region since the prevalence of Low birth weight in the entire region was not known. Therefore, the prevalence of low birth weight in the four hospitals/in the Northern Region was estimated to be between 45–55% since the precision and the confidence interval remained 5% and 95% respectively.Hence the sample size for the cross sectional component of this study was determined as below;2) (0.5 (1–0.5)/0.052) = 384Using This means that a total of 384 mothers were sampled.In all 96 women were selected from each of the four hospitals, which included Tamale Teaching Hospital , Tamale Central, Tamale West and Savelugu District Hospital using consecutive sampling technique.Therefore, in all 600 subjects were approached and recruited for the entire study but 216 of them were pregnant mothers attending antenatal clinics at the TTH while the remaining 384 were mothers with babies between 0 and 1 months old.Structured questionnaires were administered to the mothers by a team of interviewers. The questionnaires collected information on demographic and socio-economic characteristics of mothers. Information on health status, weight at first antenatal and weight per antenatal Care (ANC) visit, height of mother and birth weight were retrospectively recorded from the ANC booklet for the nursing mothers where as the remaining information  of the pregnant women were recorded as and when they came for ANC visit until delivery.Food frequency questionnaire were administered to the mothers within the first month after delivery while the pregnant women completed the questionnaire in the second trimester. The food frequency questionnaire used was identical to and derived from Nti  and GDHSThe data was entered using Epi Info  and later imported to STATA  for analysis. Consistency and plausibility checks were done after the data entry to ensure that errors were reduced.Descriptive statistics including percentages and frequencies were computed for dietary practices such as ‘out of home eating’, ‘pica’ practices (consumption of rocks and clay during pregnancy), skipping of meals and pregnancy related conditions such as nausea and vomiting.The analysis to determine characteristics of dietary patterns was carried out using all the 36 food items from the questionnaire. Dietary patterns can be derived a priori, where foods are classified into patterns based on their known functions and effects on health, or a posteriori, where statistical methods such as factor analysis or principal component analysis are used to categorize foods that are usually eaten together into groups . Both meIn this analysis we determined dietary patterns using factor analysis with a varimax rotation. Variance was based on rotated sums of squared loading and the varimax with Keiser Normalization was used as the orthogonal rotation method, as it maximizes the loading of each variable on one of the extracted factors whilst minimizing the loading on all other factors.Using a varimax rotation ensured that the distributions of the scores were centered around 0, with a standard deviation of 1. This allows easy interpretation of the results, as the point estimates from the regression analyses will be equivalent to a change of the magnitude of the corresponding number of standard deviations . The facPrior to the analysis the Kaiser-Meyer-Olkin measure of sample adequacy, which is prerequisite for PCA or factor analysis, was performed and found to be in an acceptable range (0.756). Besides this, Bartlett’s test of sphericity performed showed no evidence of identity of correlation matrix in the data and for that matter the data set was considered appropriate for factor analysis (Prob>chi2 = 0.0000).Dietary quality of the women was determined using women dietary diversity score (WDDS) . The potClassification of weight gain during pregnancy was based on pre-pregnancy BMI and according to IOM recommendations , 40. DetThe socio-economic status of the household was determined using the household wealth index as a proxy, which was derived from household assets such as availability of potable water, electricity, television, refrigerator, motorcycle, car/tractor/truck, washing machine, gas cooker and livestock. The calculation of wealth index has also been described and published previously .According to the world health Organization , a low bt-test. One-way ANOVA was used to compare means where more than two categories were formed. Multiple testing was controlled for by the use of Bonferroni corrections. The associations between dietary patterns and socio-demographic and life style factors of mothers were determined using multivariate regression.Associations between maternal and infant characteristics and mean women dietary diversity score were determined by independent To determine the factors influencing the mother’s choice of a particular dietary pattern a multivariate analysis was done. The mother’s factor score for each dietary pattern  were used as dependent variables. A Logistic regression was used to establish association between dietary practices, and patterns and birth weight. A p-value<0.05 at 95% confident level was considered statistically significant.The mothers were asked to sign a written consent form. For those who could not read and write, this was done through an interpreter. The guardians or parents were asked to sign a written parental or guardian form on behalf of the minors while the minors were asked to sign an assent form. The Ethics committees of Navarongo Health Research Center (Ref. No: App/MatNut/01/2014) and the University of Heidelberg institutional review board approved this study.The study took place between February and August 2014. In all, 578 out of 600 women completed the study questionnaire representing a response rate of 96.0%. The study participants were mostly married women and predominantly Dagombas (the largest ethnic group in Northern Region). They were predominantly Muslims (94.29%). About 60% of the women had some formal education while 40% had no formal education. Also, about 77% of the respondents worked in the formal/informal sector but 23% of them were either house wives/students. Moreover, about 78% of the women we interviewed were urban dwellers where as 22% were rural dwellers. More to the point, 60% of the mothers had 1–2 babies while the rest had 3 or more babies.The socio-economic status of the household was divided in to three categories. About 33% of the respondents were in the lower socio economic class, 34% in the middle class while about 32% were in the upper socio-economic class .The data analysis revealed that two distinct dietary patterns best explained the dietary habits of women in this study. For descriptive purposes, they are labeled as ‘Health conscious’ and ‘non-health conscious’. The list of foods and the loading factors are shown in Among the respondents the mean dietary diversity score was 4.3±1.6. Higher mean dietary diversity score that was significantly different was observed in mothers who live in urban areas (0.6) as compared to those who live in rural areas. Although, there were slight differences in absolute terms within the other variables they were statistical not insignificant .In addition to this, higher dietary diversity score that were statistically significant were observed among mothers who had normal hemoglobin level (≥10.5 g/dL) (0.5), gained excessive weight during pregnancy (0.1), were overweight (0.6), were obese (0.8) and mothers who had macrosomic births (Birth weight ≥ 4.0kg). On the other hand, lower dietary diversification was observed in mothers who had low gestational weight gain (-1.0), were underweight before pregnancy (-1.3) and those who had low birth weight infants (2.8) .Factors that could potentially influence the mother’s choice of a particular dietary pattern were also analyzed. ‘Pica’ practice  and upper socio-economic class status  had higher loading respectively for non-health conscious diet. However, mothers who had no any formal education , avoid both fish and meat , P; 0.043) during pregnancy had significantly lower loading respectively for non-health conscious diet .On the other hand, mothers who avoid meat but eat fish  and women who were overweight  had significantly higher loading respectively for health conscious diet where as those who practice out of home eating , P; 0.003) during pregnancy period, skip breakfast  and were underweight , P; 0.036) had significantly lower loading respectively for health conscious diet .It was observed that 29.6% of the mothers practice ‘out of home eating’ (eating >2x/week from food venders and fast food restaurants). A majority (51.9%) reported eating less than usual during pregnancy while 45% ate normal and the remaining 3.1% reported eating more than usual. Moreover, the prevalence of ‘pica’ (craving for clay and rocks) practice was 22.8%. Also 87.8% of the respondents reported skipping breakfast while the remaining (12.1%) had breakfast on the regular basis during pregnancy period .In addition to this, women who ate outside the home during pregnancy were 1.6 times more likely to give birth to low birth weight infant than those who ate regularly at home during pregnancy . In the same vein, those who practice ‘pica’ during pregnancy were 1.7 times more likely to give birth to a low birth weight baby as compare to those who did not practice pica . Mothers who consumed more food (increased food intake compare to pre-conception period) during pregnancy period were 88% less likely to give birth to a low birth weight infants than those who ate the same as before pregnancy  and dietary diversity score  showed a protective effect for low birth weight respectively. The same trend was observed in the multiple logistic regressions adjusted by gestational age. The health conscious diet showed a reduced risk of LWB  per standard deviation change in scores) as well as dietary diversity scores  .We have defined two dietary patterns and also demonstrated the relationship between pattern of diet that a mother is consuming and how it is associated with birth weight. Health conscious diet and dietary diversity were associated with decreased odds for low birth weight. Also, women who gave birth to low birth weight infant had significantly low mean dietary diversity scores.We found that mothers who ate out of home and those who practice ‘pica’ during pregnancy have increased odds for low birth weight while those who reported that they consumed more food during pregnancy than before conception have decreased odds for low birth weight.Beside this, factors that influence dietary patterns were also identified. For instance skipping breakfast, out of home eating and underweight were associated with low factor loading for health conscious diet while eating fish but not meat and overweight were associated with high factor loading for health conscious diet. On the other hand, pica practice and upper socio economic class were also associated with high factor loading for non-health conscious diet while low socio economic class, no any formal education and avoiding eating both meat and fish during pregnancy were associated with low factor loading for non-health conscious diet.Many studies have shown that there exist a link between pica and maternal anemia but in contrast to this study they found no association between pica and mean birth weight , 43. OthIt has been observed that until recently, there have been few studies on dietary patterns of mothers during pregnancy  especialMost of the studies conducted on maternal dietary patterns demonstrated the relationship between the patterns identified and birth weight, which is consistent with this study. For instance, the study conducted among Mexican-American women showed that nutrient dense and protein rich foods were associated with an increased infant birth weight whereas a diet term traditional contained fats and oil, high-fat meats and sugar was associated with a decreased in birth weight . In DenmBeside this, quality of diet among women in developing countries has always been a challenge especially during pregnancy. Researchers have attributed this to imbalance macronutrients consumption, inadequate micronutrient intake and predominantly plant-based diet , 47. SimIt is important to state that apart from maternal nutrition, there are several other factors that could influence infant weight at birth. The most important ones include smoking, alcohol consumption, malaria and HIV infections. None of the study participants in the present study smoked, consumed alcohol or was HIV positive. Besides this, prophylactic drugs such as Sulfadoxine-pyrimethamine are administered to all pregnant women attending antenatal care clinics in Ghana and so malaria prevalence among the women in the present study was not evident.19. However, to date the results generated from this kind of analysis according to researchers have shown logical relationships of dietary patterns to socio-economic factors and to outcomes such as birth weight as observed in this study. This reinforces the suitability of using this type of analysis to analyze data on diet.It is observed that there are weaknesses to using the posteriori method to determine dietary patterns since dietary patterns are not chosen in advance but are determined by the data. As a result of this two studies cannot identify identical diets thus making direct comparison between different studies impossible . Beside Also fasting during pregnancy could affect dietary intake as well as fetal growth as some of the women might have fasted in the month of Ramadan. However, there were not questions on whether the mothers fasted or not during the month of Ramadan which, is a set back to the current study because the effect of fasting in the month of Ramadan was not ascertained and for that matter the result presented here should be interpreted with caution.Another limitation was that information on pregnancy dietary intakes was taken retrospectively. As a result, recall bias could be inevitable, especially for mothers who just delivered but we did, however, probe or give cues to the mother about the period in question, to help recall.Besides this, the researchers tried to make the food list as comprehensive as possible but this not withstanding, some other lesser-consumed foods might have been left out. For example some wild fruits and vegetables, which are seasonal could have been left out but this was unlikely to alter the patterns identified in the current study since they are less frequently consumed.Poor dietary practices during pregnancy such as ‘pica’ and ‘out of home eating’ were found to be associated with increase odds for low birth weight. We also identified two dietary patterns among pregnant women in Northern Ghana. These are Health conscious diet and non-health conscious diet. Women dietary diversity score and dietary patterns were found to be protective against low birth weight. Our findings buttress the importance of optimal nutrition during pregnancy. Therefore, it is important that emphasis should be placed on counseling and assisting pregnant women and prospective mothers to practice optimal nutrition through the consumption of foods across the various food groups that are good sources of both macro and micronutrients during nutrition counseling in antenatal clinics more so in Ghana.S1 Dataset(DTA)Click here for additional data file.


The clinical consequences of hypothyroidism and hypothyroxinemia during pregnancy such as preterm birth are not still clear.  The aim of this meta-analysis was to estimate the relation of clinical and subclinical hypothyroidism and hypothyroxinemia during pregnancy and preterm birth.2 index. Both random and fixed-effects models were used for combining the relative risk and 95% confidence intervals. Data were analyzed using Comprehensive Meta-Analysis software version 2. In this meta-analysis, Preferred Reporting Items for Systematic review and Meta-Analysis were utilized. Searching the cohort studies were done by two researchers independently without any restrictions on Scopus, PubMed, Science Direct, Embase, Web of Science, CINAHL, Cochrane, EBSCO and Google Scholar databases up to 2017. The heterogeneity of the studies was checked by the Cochran's Q test and ITwenty-three studies were included in the meta-analysis. The relative risks of the clinical hypothyroidism, subclinical hypothyroidism and hypothyroxinemia during pregnancy on preterm birth was estimated 1.30 , 1.36  and 1.31 , respectively. The incidence of preterm birth was higher among mothers with clinical and subclinical hypothyroidism or hypothyroxinemia during pregnancy compared to euthyroid mothers, and these relations were significant. Therefore, gynecologists and endocrinologists should manage these patients to control the incidence of adverse pregnancy outcomes such as preterm birth. Thyroid hormones are needed for normal metabolism, regulation of body temperature, energy production, and fetal development . ChangesIn order to achieve the favorable result of pregnancy, which is a full-term and alive baby, all the conditions should be optimized in early pregnancy. Proper thyroid function of the mother, especially in the first trimester for fetus brain development and also when the fetus is not capable of producing thyroid hormones, is critical . The cliGiven the importance of these disorders, especially hypothyroidism during pregnancy and also the inconsistent results of different studies in this field, this systematic review and meta-analysis study was conducted with the purpose of assessing the adverse effects of clinical hypothyroidism, subclinical hypothyroidism, and hypothyroxinemia during pregnancy on preterm birth. The results obtained in this study could provide valuable information from the findings of multiple studies. It also can be a basis for creating new plans and programs to properly manage these disorders during pregnancy for prevention of preterm birth.Study protocolThis meta-analysis was done in several detailed stages, including search strategy, determining the inclusion and exclusion criteria, quality evaluation of studies, data extraction, analysis and interpretation of findings by using the preferred reporting items for systematic reviews and meta-analyses protocol (PRISMA-P) . In ordeSearch strategyLiterature searching was done by two researchers independently who were familiar with search methods and information sources without any restrictions on Scopus, PubMed, Science Direct, Embase, Web of Science, CINAHL, Cochrane, EBSCO as well as Google scholar databases up to 2017 using keywords including thyroid disease, thyroid, hypothyroidism, subclinical hypothyroidism, clinical hypothyroidism, hypothyroxinemia, preterm delivery, premature delivery, preterm labor, premature labor, preterm birth and premature birth which being searched in combination using AND & OR operators. Combined search in PubMed is shown in Appendix 1. In order to achieve more studies, review articles and all relevant references were evaluated as well. Also, any encounters discussed by third expert researcher.Inclusion and exclusion criteriaThe study was considered to be eligible if the following criteria were met: 1) A prospective cohort study; 2) The mother suffered from clinical or subclinical hypothyroidism or hypothyroxinemia during pregnancy for case group; 3) Preterm birth was investigated in the outcome 4) The mother was not thyroid autoimmunity disease; 5) The mother was not receiving treatment for thyroid hypofunction and 6) Information about the number of preterm births in each generation was reported. In this investigation, data from review articles, case-controls, case reports, and letters to the editor were not reviewed.DefinitionsPreterm birth defined as a premature birth in less than 37 gestational weeks. A high thyroid-stimulating hormone (TSH) level with a low free thyroxine (FT4) level; a high TSH level with a normal FT4 level; and a low FT4 level with a normal TSH level was defined as clinical hypothyroidism, subclinical hypothyroidism, and hypothyroxinemia, respectively.Quality evaluationAfter determining the relevant investigations, selected papers were evaluated according to the STROBE checklist . The cheData extractionThe researchers used a checklist containing the required information for studying the articles, including the author's name, article title, year of study, place of study, sample size, age, gestational age, any information on the incident of maternal thyroid disease, and preterm birth compared to a reference group.Statistical analysis2 index. There are three categories for heterogeneity  (Relative risk (RR) was used in order to determine the effect size of maternal hypothyroidism and hypothyroxinemia during pregnancy on preterm birth. RR with 95% confidence intervals (CIs) from selected studies was pooled. Heterogeneity among the investigated studies was determined using Cochran's Q test and Igeneity) .Therefore, in this study fixed-effects and random-effects were performed for low and high heterogeneity, respectively . BecuaseSearch resultsIn this systematic search, 364 possible relevant studies were identified After further investigation, 342 studies were removed due to the lack of following criteria: duplication (182); irrelevant (92); not being based on a prospective cohort study (3); the participated mothers did not suffer from clinical or subclinical hypothyroidism or hypothyroxinemia during pregnancy (n=32); preterm birth has not been investigated as an outcome (n=24); review studies, case reports and letters to the editor (n=8) . FinallyClinical hypothyroidismet al and Wikner et al the total p-value for this relationship increased to 0.105 and 0.054, respectively, indicating the low sensitivity of this meta-analysis (In 10 studies (20079 cases and 2452817 control pregnant women), the combined RR of maternal clinical hypothyroidism during pregnancy on preterm birth was estimated 1.30  . In a seanalysis . The cumanalysis . The comanalysis , and RR Subclinical hypothyroidismIn 17 studies (3580 cases and 64885 control pregnant women), the combined RR of maternal subclinical hypothyroidism during pregnancy on preterm birth was estimated 1.36  . The resIsolated hypothyroxinemiaIn 7 studies (1078 cases and 44377 control pregnant women), the combined RR of maternal hypothyroxinemia during pregnancy on preterm birth was estimated was estimated 1.31 , and the association was statistically significant . Also, aPublication biasThe Result for Egger test in clinical hypothyroidism (0.57), subclinical hypothyroidism (0.37) and hypothyroxinemia (0.22) was estimated. The Result for Begg’s test in clinical hypothyroidism (0.21), subclinical hypothyroidism (0.23) and hypothyroxinemia (0.76) was estimated. Publication bias in the obtained results is shown in In the present meta-analysis, the combined 17, 10 and 7 studies for subclinical hypothyroidism, clinical hypothyroidism and hypothyroxinemia during pregnancy showed that are related to preterm birth, with p-values of, 0.013, 0.005, and 0.020, respectively. The mechanism that hypothyroidism can increase the risk of premature birth may be affected by different paths. One possible explanation is that inflammatory process with a change in the regulation of cytokine networks in the uterus and omission of the pair-control inflammatory processes can be linked with premature birth -42. Anotet al. in a systematic review study suggested that further studies on neonatal outcomes of maternal subclinical hypothyroidism are essential (The findings of one meta-analysis study on maternal thyroid dysfunction and its impact on pregnancy with combining only two studies concluded that there is no relationship between maternal thyroid disorder and unpleasant pregnancy outcomes . Accordissential . For hypssential . Hypothyssential . However, one important limitation of their studies compared to the present study was the lack of studies and less sample size, which can affect the results of the analysis. The results of the meta-analysis are reliable when all the investigations get through the quantitative analysis process which leads to lower variations and possibilities -17.The incidence of preterm birth was higher among mothers with clinical hypothyroidism or subclinical hypothyroidism or hypothyroxinemia during pregnancy compared to euthyroid mothers, and these relations were significant. Therefore, gynecologists and endocrinologists should manage these patients to control the incidence of adverse pregnancy outcomes such as preterm birth. In future studies, clinical trial studies in the field of subclinical and clinical hypothyroidism, as well as the role of various treatments to prevent premature birth, is recommended.


To assess whether women with a history of preterm birth, independent on the presence of prelabour rupture of the membranes (PROM) and growth deviation of the newborn, are more likely to develop preeclampsia with preterm or preterm birth in a subsequent pregnancy.We conducted a population-based cohort study, based on Medical Birth Registry of Norway between 1967 and 2012, including 742,980 women with singleton pregnancies who were followed up from their 1st to 2nd pregnancy. In the analyses we included 712,511 women after excluding 30,469 women with preeclampsia in the first pregnancy.After preterm birth without preeclampsia in the first pregnancy, the risk of preterm preeclampsia in the second pregnancy was 4–7 fold higher than after term birth  3.0–4.0 to 6.5; 95% CI 5.1–8.2). The risk of term preeclampsia in the pregnancy following a preterm birth was 2–3 times higher than after term birth . After spontaneous non-PROM preterm birth and preterm PROM, the risk of preterm preeclampsia was 3.3–3.6 fold higher than after spontaneous term birth. Corresponding risks of term preeclampsia was 1.6–1.8 fold higher. No significant time trends were found in the effect of spontaneous preterm birth in the first pregnancy on preterm or term preeclampsia in the second pregnancy.The results suggest that preterm birth, regardless of the presence of PROM, and preeclampsia share pathophysiologic mechanisms. These mechanisms may cause preterm birth in one pregnancy and preeclampsia in a subsequent pregnancy in the same woman. The association was particularly evident with preterm preeclampsia. Growing evidence suggests that some cases of preterm birth, preterm prelabour rupture of the membranes (PROM), foetal growth restriction, preeclampsia and placental abruption share a pathophysiological mechanism involving placental dysfunction –4.Another cause of preterm birth is inflammation of the placenta or membranes . In the analyses we included 712,511 women, excluding 30,469 women with preeclampsia in the first pregnancy.From 1967 to 2012 a total of 2,707,724 births were recorded in the national Medical Birth Registry of Norway. Using the mothers’ national identification number, the first and second births were linked. In the present study we included women with at least two singleton births with gestational age between 16 and 44 weeks  and preterm (<37 weeks) preeclampsia. In Norway, the diagnosis of preeclampsia is in accordance with the recommendations of the American College of Obstetricians and Gynecologists  which dePossible predictors in the first pregnancy were gestational age at birth  and preterm PROM. This extensive gestational age range allowed study of effects of second trimester miscarriage as well as extreme preterm delivery (<28 weeks), very preterm delivery (28–32 weeks) and near term preterm delivery (33–36) on later preeclampsia. Gestational age was estimated from the last menstrual period. From December 1998, gestational age based on ultrasound dating was available and was used when data on the last menstrual period were lacking. Until 1998 PROM was notified by plain text as rupture of the membranes more than 24 hours before birth, and from 1998 by a check box. Premature rupture of membranes occurring before 37 weeks of gestation was referred to as preterm PROM.The associations between gestational age in the first pregnancy and preeclampsia in the second were assessed by odds ratios (ORs) obtained by forward stepwise logistic regression analyses. The following possible confounders in the second pregnancy were entered in the regression models: Birthweight <10th and >90th centiles , maternal age , marital status , inter-birth interval , asthma, chronic hypertension, chronic renal disease, rheumatoid arthritis, maternal cardiac disease, gestational diabetes- or pre-gestational diabetes and year of birth .n = 109, 958). Maternal pre pregnant BMI was categorized according to the definitions of the World Health Organization into <18.5 kg/m2 (underweight), 18.5–24.9 , 25.0–29.9 (overweight) and ≥30.0 (obese).From 1998 smoking was recorded. We included smoking at the beginning of the second pregnancy in the analyses, categorized as no, occasionally, daily and not specified. From 2007 data on maternal body mass index (BMI) were registered in 38% of the second births .The study was approved by the Regional Ethics Committee for Medical and Health Research Ethics (REK nord case no. 2013/1200).In the first and second pregnancies, the occurrence of preeclampsia was 30,469/742, 980 (4.1%) and 14,645/742,980 (2.0%), respectively. Women with preeclampsia in the second pregnancy tended to be older, had higher BMI and had more often chronic disease and gestational diabetes mellitus . This paIn women without preeclampsia in the first pregnancy the occurrence of preeclampsia in the second pregnancy generally increased with decreasing gestational age at birth in the first pregnancy .th birth weight centile.After preterm birth in the first pregnancy, preterm and term preeclampsia were 4–7 and 2–3 times more likely to occur in the second pregnancy compared with after term birth, respectively . These aRestricting the analysis to spontaneous births in the first pregnancy, the associations persisted, but were less pronounced ; after pn = 42,089) had negligible effect; for preterm and term delivery in the first pregnancy proportions of preeclampsia in the second were 0.8% (19/2299) and 0.3% (105/39790), respectively, with unadjusted and adjusted ORs of 3.2; 95% CI 1.9–5.1 and 3.1; 1.9–5.1.Restricting the analysis to 153,009 women with spontaneous first births after 1998 when the new notification form was introduced, and PROM was more completely recorded as indicated by higher frequencies of PROM, we assessed the possible associations of spontaneous preterm birth without and with PROM in the first pregnancy with preterm and term preeclampsia in the second. The effects of spontaneous preterm birth with and without PROM were similar . After sNo significant time trends were found in the effect of spontaneous preterm birth in the first pregnancy on preterm or term preeclampsia in the second pregnancy.This population based study indicates that a history of preterm birth irrespective of PROM, and regardless growth deviation of the first born, is associated with preeclampsia and particularly preterm preeclampsia in a following pregnancy.Strengths of the study include the prospective collection of data and its population-based design. Furthermore, our database holds data on several possible confounders. Preeclampsia is associated with a number of risk factors such as maternal age, previous preeclampsia, chronic hypertension, pre-gestational diabetes, asthma, renal disease, thyroid disease, rheumatoid arthritis and maternal obesity. It is negatively associated with smoking. However, adjusting for these variables and year of birth in the subsequent pregnancy had small effects. Another strength is high validity of the outcome  and otheThat data on maternal BMI were available only in a subset of women represented a limitation. However, we have shown that this subset is representative of the whole Norwegian birth population . Data onOur observation that preterm birth is associated with subsequent preeclampsia is consistent with another population based study . A new fThe finding that spontaneous preterm birth with and without PROM was predictive of later preeclampsia, supports a hypothesis that a common pathophysiologic mechanism may cause preterm birth in one pregnancy and preterm as well as term preeclampsia in the next. A significant proportion of preterm births is caused by improper remodelling of the uterine spiral arteries in early pregnancy . These dAnother possible shared mechanism which may cause both preterm labour and preeclampsia is generalized systemic inflammation with chorioamnionitis , which also may be associated with endothelial dysfunction , 8. ConsAlso local microorganisms in the placenta may cause preterm birth and preeclampsia. In preterm birth bacterial infection in the placenta, membranes and amniotic cavity have been observed . Recent Our study suggests that preterm birth, regardless of the presence of PROM, and preeclampsia share pathophysiologic mechanisms. These mechanisms may cause preterm birth in one pregnancy and preeclampsia in a subsequent pregnancy in the same woman. The association was particularly evident with preterm preeclampsia. Future longitudinal studies should elucidate the relative importance of recurrent decidual vasculopathy and infection or inflammation in the development of preeclampsia in women with a history of preterm birth. Genetic or large-scale family studies are needed to assess possible paternal genetic influence on the association between preterm birth and subsequent preeclampsia, e.g. assessing whether men who had fathered a pregnancy with preterm birth are more likely to father a pregnancy with PE in another woman. Whether a history of preeclampsia involves an excess risk of preterm birth in a subsequent pregnancy also warrants study.