Rhipicephalus (Boophilus) annulatus and Rhipicephalus (Boophilus) microplus , collectively known as cattle-fever ticks (CFTs), are vectors of protozoal parasites (Babesia bigemina and Babesia bovis) that cause bovine babesiosis . One traditional strategy for CFT eradication involves the implementation of a “pasture vacation,” which involves removing cattle (Bos taurus) from an infested pasture for an extended period of time. However, vacated pastures are often inhabited by wildlife hosts, such as white-tailed deer , which can serve as alternate hosts for questing CFTs. We hypothesized that the distribution of host-seeking larvae among habitat types post-pasture vacation would reflect habitat use patterns of WTD, and in turn, affect the subsequent rate of pasture infestation by CFT.We adapted a spatially explicit, individual-based model to simulate interactions among SCFT, cattle, and WTD as a tool to investigate the potential effects of WTD habitat use preferences on the efficacy of a pasture vacation. We parameterized the model to represent conditions typical of rangelands in south Texas, USA, simulated a 1-year pasture vacation under different assumptions regarding WTD habitat use preferences, and summarized effects on efficacy through (1) time post-vacation to reach 100% of pre-vacation densities of host-seeking larvae, and (2) the ecological conditions that resulted in the lowest host-seeking larval densities following pasture vacation.Larval densities at the landscape scale varied seasonally in a similar manner over the entire simulation period, regardless of WTD habitat use preferences. Following the removal of cattle, larval densities declined sharply to < 100 larvae/ha. Following the return of cattle, larval densities increased to > 60% of pre-vacation densities ≈ 21 weeks post-vacation, and reached pre-vacation levels in less than a year. Trends in larval densities in different habitat types paralleled those at the landscape scale over the entire simulation period, but differed quantitatively from one another during the pasture vacation. Relative larval densities (highest to lowest) shifted from (1) wood/shrub, (2) grass, (3) mixed-brush during the pre-vacation period to (1) mixed-brush, (2) wood/shrub, (3) grass or (1) wood/shrub, (2) mixed-brush, (3) grass during the post-vacation period, depending on WTD habitat use preferences.By monitoring WTD-driven shifts in distributions of SCFT host-seeking larvae among habitat types during simulated pasture vacation experiments, we were able to identify potential SCFT refugia from which recrudescence of infestations could originate. Such information could inform timely applications of acaricides to specific refugia habitats immediately prior to the termination of pasture vacations. Rhipicephalus (Boophilus) annulatus and Rhipicephalus (Boophilus) microplus , collectively known as cattle-fever ticks (CFTs), are vectors of protozoal parasites (Babesia bigemina and Babesia bovis) that cause bovine babesiosis (cattle fever), which is considered the most economically important livestock disease worldwide  for each habitat type, size of activity range (ha), relative number of larvae they can carry at any given time , and numbers of larval, nymphal, and adult SCFTs in each age-class that hosts currently carry. Spatial scales are defined in terms of the 900, square, 1-ha habitat cells. The temporal scales explored are a weekly time step for a total of 3 years for calculation of SCFT development and survival. However, hosts move about the landscape 30 times per week, acquiring and depositing SCFTs among the habitat cells they visit.processes represented in the model include (1) temperature-dependent and habitat-specific development and survival of off-host SCFTs, (2) host-specific survival of on-host SCFTs and host-specific fecundity of deposited (fed) SCFTs, (3) the movement of hosts based on habitat preferences, and (4) host-specific and habitat-specific acquisition and deposition of SCFTs. Tick development, survival, and reproduction occur at the beginning of each weekly time step. Host movement, tick acquisition, and tick deposition occur 30 times within each weekly time step. .The most important design concept is that the SCFT life cycle is influenced by climatic conditions, landscape structure, and the composition of the host community. Survival and development of off-host stages are dependent on the temperature and relative humidity in habitat types to which they are exposed as a consequence of host-driven dispersal of gravid females. Completion of the SCFT life cycle depends on larvae encountering an appropriate host, which is influenced by species abundance, composition of the host community, and habitat preferences of potential host species. Spatial and temporal patterns of abundance of off-host SCFT larvae emerge as system-level properties as a result of equations describing rates of off-host tick development and survival, and rules governing the movements of hosts within the landscape , which We simulated a 1-year pasture vacation experiment under different assumptions regarding WTD habitat use preferences. We used a 3-year simulation period  in which cattle were removed from the system at the beginning (1st week in January) of the vacation year, and were restocked at the beginning of the 1st year post-vacation. The experimental design consisted of 5 Monte Carlo simulations for each of 11 WTD habitat use preferences for good SCFT habitat . As in Wang et al. , simulatMean weekly host-seeking larval densities at the landscape scale varied seasonally in a similar manner regardless of WTD habitat use preferences Fig. a. LarvalTrends in larval densities in different habitat types paralleled those at the landscape scale during all scenarios Fig. b–d. Not Distribution of larval densities among habitat types at their lowest point, 10 weeks post-vacation, was higher in mixed-brush when WTD habitat use preferences for wood/shrub were ≤ 0.3 and was higher in wood/shrub when preferences were ≥ 0.4; larval densities always were lowest in grass Fig. . Thus, rSpatial distributions of host-seeking larvae immediately pre-vacation and 1-year post-vacation were similar, regardless of WTD habitat use preferences; however, distributions immediately following the vacation period differed depending on preferences Fig. . The ratThe simulated effects of WTD habitat use preferences on the efficacy of pasture vacation can be summarized by shifts in the distribution of host-seeking larvae among habitat types during the pasture vacation. These shifts in larval distributions did not have the hypothesized effect on subsequent rates of pasture infestation. Rather, they provided potential SCFT refugia from which recrudescence of infestations could originate. Pre-vacation distributions of host-seeking larvae primarily reflected habitat use preferences of cattle, superimposed on habitat-specific differences in larval survival, thus masking the role of WTD in the maintenance of larvae. Larval densities were highest in wood/shrub, which was used relatively frequently (≈ 30% of the time) by cattle and in which larval survival was highest, followed by grass, which was used most frequently (≈ 60%) by cattle but in which larval survival was lowest. Larval densities were lowest in mixed-brush, where survival was intermediate and cattle use was lowest ≈ 10%). Post-vacation, before tick population recovery began, relative larval densities primarily reflected habitat use preferences of WTD, again superimposed on habitat-specific differences in larval survival. When WTD preferences were close to those assumed by Wang et al. [%. Post-vThe potential for the existence of tick refugia is inherent in the heterogeneous distribution of favorable tick habitats and varied patterns of landscape use by cattle and WTD . LandscaBoselaphus tragocamelus) have been implicated in potential CFT reinfestations [By monitoring the WTD-driven shifts in distributions of host-seeking larvae among habitat types during our simulated pasture vacation experiments, we were able to identify potential SCFT refugia from which recrudescence of infestations could originate following reintroduction of cattle. The importance of feedback mechanisms at the habitat–wildlife–livestock interface in the control of infectious diseases is recognized globally –47. PéreAlthough cattle are the main hosts of CFT, WTD are also confirmed hosts in and around the permanent CFT quarantine zone along the US-Mexico border. Recent CFT infestations outside the quarantine zone pose a serious threat to the US cattle industry. The effects of interactions among host species composition, habitat heterogeneity, and climatic variability on the efficacy of CFT eradication strategies are virtually impossible to investigate in the field. The effects of habitat use preferences of WTD, as well as other potential wildlife hosts, are poorly understood within the context of CFT management. Spatially explicit, individual-based models such as the present one are useful tools for identifying CFT distribution patterns that emerge from a wide variety of tick-host-habitat-climate interactions. Such models allow preliminary a priori evaluation of alternative eradication strategies, including novel strategies involving new technologies, which might require significant investment before a field trial would be possible.Additional file 1. Summary of model parameters and equations.


To explore the therapeutic effect of percutaneous nephroscopy combined with Green Light laser on simple renal cyst.A retrospective analysis was conducted to review the clinical data, surgical procedures, intraoperative bleeding, postoperative adverse reactions, and length of stay of 32 patients who had been admitted to Affiliated Hospital of Hebei University from January 2018 to February 2019. All patients had been diagnosed with simple renal cyst by imaging examination and met the surgical indications for single-port percutaneous nephroscopy combined with GreenLight laser for unroofing and decompression of the renal cyst. Among the 32 patients, there were 18 males and 14 females, with 15 cases on the left and 17 on the right. The patients aged 38 to 62 years old, with an average of 45 years old. Thirteen cases were hospitalized mainly due to complaint of lumbar pain, and 19 cases were admitted after a renal cyst was found by physical examination. The diameter of the cyst ranged from 4.2 to 9.1 cm, with an average of 6.1 cm. A percutaneous nephroscopic channel was established during the surgery. Once a nephroscope was placed into the cyst, GreenLight laser (energy of 80W) was used to remove the free cyst wall 0.3cm from the renal parenchymal margin under direct vision. After the incision margin was observed with no obvious exudation under microscope, the cyst wall was removed through the channel and sent for pathological examination. A drainage catheter was placed near the cyst cavity.All the 32 patients were successfully operated, without transition to laparoscopic and open surgery. The operations took 30 to 62 minutes, with an average of 45 minutes. The intraoperative bleeding ranged from three to 14 ml, with an average of 10 ml. No adverse events such as postoperative infection, fever, or active bleeding occurred. The drainage catheters were removed one to three days after operation, with an average of 1.5 days after operation. The drainage volume was 20 to 55 ml, with an average of 35 ml. No obvious liquid extravasation was seen in all cases. The length of stay after operation ranged from three to five days, with an average of 3.5 days. Postoperative pathological reports all suggested renal cyst wall. The patients were followed up for six months, and no cyst recurred.Single-port percutaneous nephroscopy combined with Green Light laser could provide significant clinical effect in treating simple renal cyst with minimal trauma. Simple renal cyst is the most common benign kidney disease. Studies have shown that the condition can be developed from the tubular diverticulum, with the highest incidence among kidney cystic diseases. It is commonly found in adults over 50 years old, with an incidence rate of approximately 33% in those over 60 years old, but it is rare in children. The incidence rate increases with age.This is a retrospective study. A total of 32 patients with simple renal cyst who had been admitted to Affiliated Hospital of Hebei University from January 2018 to February 2019 were enrolled in this study. All patients underwent single-port percutaneous nephroscopy combined with GreenLight laser for unroofing and decompression. Among the 32 patients, 13 cases were hospitalized mainly due to complaint of lumbar pain, and 19 cases were admitted after a renal cyst was found by physical examination. There were 18 males and 14 females, aged 38 to 62 years old, with an average of (48.5±10.8) years old. All cases were diagnosed as simple renal cyst  upon admission, which ranged from 4.2 to 9.1 cm in diameter, with an average of 6.1cm. Among them, 15 cases were found on the left and 17 on the right. Twelve patients had complications with hypertension, which was adjusted with antihypertensive medication before operation, and the blood pressure was lowered and controlled. Eight patients had complications with diabetes, hence insulin should be administered throughout the perioperative periods to stabilize the blood glucose level. One patient was found with urinary tract infection through routine urine test, the urine culture and drug sensitivity should be confirmed, the use of sensitive antibiotics should be guided before operation, and then the operation could be scheduled after review of urine routine became normal.The study was approved by the Institutional Ethics Committee of Affiliated Hospital of Hebei University at January 30, 2020, and written informed consent was obtained from all participants.a.) Cystic space-occupying lesion located on the dorsal side suggested by urinary Color Doppler ultrasound, b.) A cyst of more than >4 cm in diameter confirmed by CT plain scan, with cystic renal tumor excluded by enhanced scan. Figs. a.) Polycystic kidney or cystic renal tumor, b.) Complication with other serious organic lesions such as bleeding diseases, cerebral infarction, and myocardial infarction, c.) Any surgical contraindication found by preoperative examination.All patients followed the surgical requirements: General anesthesia was administered. After successful anesthesia, the patient was placed in a side-lying position (on either side), and the lumbar portion should be heightened with the pillow. Then the patient was routinely disinfected and covered with sterile drapes, and the light source and flushing system were powered on: 1) A percutaneous nephroscopy channel was established. Once a suitable puncture point was selected under ultrasound guidance, a puncture trocar was inserted into the cyst, and then the needle core was withdrawn. A guide wire was placed after the cystic fluid flowed out. After the needle passage was dilated with a fascial dilator along the guide wire, a balloon catheter was inserted along the wire. Then the catheter was connected to a pneumatic pump, and the pressure was increased by water injection to 25 KPa for three minutes. After the sheath was inserted, the balloon dilator (F30) was withdrawn and the nephroscope was placed. 2) After the nephroscope was placed into the cyst, the cyst wall could be observed to be smooth under microscope, so that diseases such as cystic kidney cancer could be excluded. GreenLight laser (energy of 80W) was used to remove the free cyst wall 0.3cm from the renal parenchymal margin under direct vision. 3) After the incision margin was observed with no obvious exudation under microscope, the cyst wall was removed through the channel and sent for pathological examination. A drainage catheter was placed near the cyst cavity.Surgical procedures, intraoperative bleeding, postoperative adverse reactions, length of stay, drainage catheter removal time and drainage volume, liquid extravasation, and relapse were noted during follow-up.All the 32 patients were Successfully operated, without transition to laparoscopic and open surgery. The operations took 30 to 62 minutes, with an average of 45 minutes. The intraoperative bleeding ranged from three to 14 ml, with an average of 10 ml. No adverse events such as postoperative infection, fever, or active bleeding occurred. The drainage catheters were removed one to three days after operation, with an average of 1.5 days after operation. The drainage volume was 20 to 55 ml, with an average of 35 ml. No obvious liquid extravasation was seen in all cases. The length of stay after operation ranged from three to five days, with an average of 3.5 days. Postoperative pathological reports all suggested renal cyst wall. As annual physical examinations become widely adopted, the diagnosis rate of simple renal cyst has gradually increased. However, since simple renal cyst progresses slowly and often has no significant effect on renal function, the condition is usually treated conservatively. Clinically, a cyst of less than four cm in diameter can be regularly followed up, to observe the changes in its size, morphology, and internal texture.The single-port percutaneous nephroscopy features advantages in the following aspects:It requires only one operation channel, and the use of ultrasound guidance during the operation will be beneficial to the locating of the cyst, and the puncture can be made easier,The multi-port laparoscopic approach requires a supine position during surgery, but some patients cannot lie supine due to spinal deformity or medical conditions.It is not technically difficult, as there is no need to manually establish a retroperitoneal space, thereby reducing the occurrence of subcutaneous emphysema and acidosis. It is performed under the direct view via the nephroscope, reducing the chance of vascular injury and providing a clear observation of the boundary between the renal cyst wall and the renal parenchyma. Therefore, it would be safer to operate.It omits the dissection of the perirenal space and fat during surgery, allows less postoperative exudation, and enables a shorter removal time of the drainage catheter after surgery. Proficiency in surgical techniques is key to improving the success rate of surgery and reducing perioperative complications.Green-Light laser has obvious advantages in vaporization. Its penetration depth into the tissue is 800 nm, and extremely high laser energy can be concentrated on the superficial tissue level. As a result, a higher power per unit volume of the local tissue, which allows the tissue to evaporate more efficiently. The GreenLight laser is used to completely destroy the integrity of the cyst wall during the operation, completely remove the cyst wall protruding from the renal parenchyma, and completely evaporate the cyst wall that cannot be removed and borders with the renal parenchyma. By destroying its function, the residual cyst wall will cause a lower chance of recurrence.The effect of F30 is better than that of F24. During the operation, a larger operating channel can significantly increase the gap between the nephroscope and the sheath, so as to increase the water output speed and make the surgical field clearer, which will facilitate the return of water. By doing so, the postoperative infections can be avoided, and there will be no or significantly less postoperative extravasation than using F24. Meanwhile, a larger gap makes the scope’s movement and angle less restricted. This shortens the operation time to a certain extent and thus reduces the risk of surgery.Although single-port percutaneous nephroscopy has the above advantages in treating renal cyst, this technique is not suitable for all types of renal cyst patients. The minimal trauma is achieved by reduced number of operating channel, and only one operation tool can be used. For complex renal cyst, laparoscopy and percutaneous nephroscopy should be selected carefully to ensure smooth surgery and patient safety.This study is a retrospective study. In order to compare laparoscopic renal cyst unroofing with other laser treatments, prospective randomized controlled trials should be further improved.Single-port percutaneous nephroscopy combined with Green Light laser for unroofing and decompression has good clinical effects and high safety, and this technique should be widely applied. However, this study has limitation of an insufficient sample size, hence further studies should be conducted in depth with larger sample size, with interference factors removed, in order to obtain more reliable and objective results.WZY and ZYC designed this study and prepared this manuscript.ZYC is responsible and accountable for the accuracy or integrity of the work.TM collected and analyzed clinical data.YFS significantly revised this manuscript.


Congenital hypothyroidism (CH) is one of the most common neonatal endocrine diseases. This retrospective cohort study aimed to identify the potential perinatal risk factors for CH and to differentiate between transient and permanent CH  as well as determine their prevalence in a southeastern Chinese population.This study was based on an 18-year surveillance of a neonatal CH screening program in a large tertiary hospital. A retrospective review of the maternal and neonatal perinatal exposures was conducted.P = .001, .000, and .001, respectively). Significant associations were found with regard to parity and the risk of CH in the offspring (P = .000). In the neonatal characteristics model, infants with female sex, preterm birth, post-term birth, low birth weight, other birth defects, and those born as part of multiple births  had increased risk of CH. The rate of newborns with other birth defects was higher in the PCH group than that in the TCH group (P = .008), whereas the rate of maternal thyroid disease, newborns with low birth weight, and newborns with preterm birth was higher in the TCH group than that in the PCH group . The levothyroxine dose (μg/kg/day) at 1 year, 2 years, and 3 years old was significantly lower in the TCH group than that in the PCH group .Of the 205,834 newborns screened between 2000 and 2018, 189 were diagnosed with CH (1/1089). Among the 131 CH patients who again underwent thyroid function testing (TFT) after discontinuation of levothyroxine at the age of 3 years, 61 (46.6%) were diagnosed with PCH and 70 (53.4%) were diagnosed with TCH. In the maternal characteristics model, women aged 35 years or older and those who had thyroid disease and/or diabetes mellitus during pregnancy had increased risk of having an offspring with CH (Perinatal factors should be considered during the diagnosis and treatment of CH. Approximately 85% of CH cases are caused by thyroid dysgenesis, and the remaining 15% results from dyshormonogenesis. Most infants with CH at birth often have a normal appearance and nonspecific clinical symptoms and signs. If undiagnosed and untreated after birth, it can lead to growth failure and intellectual impairment, which are caused by the insufficient production of thyroid hormone. Screening programs for CH, which have been extensively carried out in many countries worldwide, provide the opportunity to investigate the epidemiology and etiology of CH. The incidence of CH in China is approximately 1 in 2000 live births.Congenital hypothyroidism (CH) is one of the most common neonatal endocrine diseases, and with the increasing availability of neonatal screening programs, improved thyroid-stimulating hormone (TSH) assay sensitivity, and increased survival rate of preterm infants, the incidence of CH has increased worldwide.,5 the occurrence of CH with genetic origin has been observed only in a relatively small proportion of patients. As CH mainly occurs in utero, maternal pregnancy complications, and abnormal fetal growth and development may be closely related to the condition. Some studies have recently shown that modifiable environmental risk factors contribute to the etiology of the disease,,7 which hints at the possibility of preventing CH; hence, investigating those modifiable perinatal risk factors of CH is important.Although a variety of gene mutations have been involved in the mechanisms of CH, Thus, diagnosis and identification of and TCH are important to avoid unnecessary overtreatment as well as its possible side effects. However, the risk factors for TCH are not yet well established.Many CH cases are transient; they result from temporary abnormalities of thyroid hormone concentrations rather than permanent dysfunction. Current guidelines recommend that all infants with CH undergo levothyroxine treatment for up to 3 years old and have a repeat thyroid function test (TFT) to determine of the condition is permanent (PCH) or transient (TCH). A previous study has highlighted that overtreatment with thyroid hormone may have negative impact on developmental outcomes of infants.–11 the rate of TCH in Fujian Province, Southeast China, is unknown; therefore, we also aimed to differentiate between TCH and PCH and determine their prevalence.The current information about the relationship between perinatal factors and the incidence of CH is mainly based on case-control studies, but clinical information from large-sample-size studies has been rarely reported. To identify the potential perinatal risk factors for CH, we conducted a retrospective cohort study to search for maternal and neonatal exposure in Fujian Province, Southeast China. Furthermore, although previous Chinese studies have reported the proportion of TCH cases (from 19.9% to 55.5%),22.1This was a retrospective cohort study of maternal and neonatal perinatal exposure based on an 18-year surveillance of a neonatal CH screening program in a large tertiary hospital with 1500 beds in Fujian Province Maternity and Child Care Hospital, China. A total of 205,834 newborns under neonatal screening from January 1, 2000 to December 31, 2018, were included, and the subjects without neonatal screening were excluded. Neonatal screening tests (NSTs) were performed 3 to 7 days after birth. A dried heel prick blood sample was saved on filter paper, which was then processed at the laboratory of Fujian Province Maternity and Child Care Hospital. The level of TSH was determined using time-resolved immunofluorescence assay. Screen-positive cases of CH were divided into 2 thresholds based on TSH level: > 9 and > 18 μIU/ml. Patients with TSH above the thresholds were recalled, and the serum-free thyroxine (FT4) and TSH were measured from peripheral venous blood using electrochemiluninescence immunoassay . CH was diagnosed if the FT4 level was <0.9 ng/dl or if the TSH level was above the cutoff value (>20 μIU/ml at any time or > 10.0 μIU/ml after 4 weeks old).Using a medical record system, we collected data on 11 types of information with the participants based on 2 categories: 1 was maternal reproductive and medical history, including demographic characteristics, gravidity, parity, gestational diabetes mellitus (GDM), thyroid disorder, and hypertensive disorder complicating pregnancy (HDCP); the other was neonatal characteristic, including sex, birth weight, gestational age, presence of other birth defects, multiple births, and fetal distress. If a newborn was diagnosed with CH, the TFT results and levothyroxine dosage information were also collected.Levothyroxine treatment was performed after diagnosis of hypothyroidism. The initial levothyroxine dosage was 10 to 15 μg/kg/day, and it was adjusted according to follow-up TFT results. During the ages of 2.5 to 3 years, trial drug discontinuation was performed, and follow-up TFT were performed at 1, 6, and 12 months after levothyroxine discontinuation. Patients with normal TFT results for up to 12 months after discontinuation of levothyroxine were diagnosed with TCH. If the TFT showed FT4 level <0.9 ng/dl or TSH level >10.0 μU/ml, PCH was diagnosed, and levothyroxine was restarted.2.2t test or Mann–Whitney test, and categorical data were compared with χ2 test or Fisher exact test. All statistical analyses were conducted with SPSS version 17.0 , and P < .05 was considered statistically significant.Measurement data were described as mean ± standard deviation (SD) or median and percentiles for quantitative variables and as proportions for all categorical data. Differences in means or median were tested for statistical significance with independent-samples 33.1From January 2000 to December 2018, 205,834 newborns were screened, and 2237 newborns had high TSH levels in the first dry sample. A total of 189 cases of CH were finally identified through confirmatory test, suggesting an overall incidence rate of 1 per 1089 screened newborns. Of the 189 subjects, 101 (53.4%) were female. The clinical and laboratory characteristics of CH are shown in Table 3.2P = .001; OR = 3.558, 95% CI = 1.751–7.232, P = .000; OR = 2.167, 95% CI = 1.348–3.483, P = .001, respectively. Significant associations were observed between parity and the risk of CH in the offspring . However, no significant associations were observed between gravidity or HDCP and the risk of CH in the offspring , preterm birth , post-term birth , low birth weight , other birth defects , and those born as part of multiple births  had increased risk of CH. However, no significant association was observed between fetal distress and the risk of CH  (Table P = .020 and .013) (Table P = .041 and .008), but the confirmatory FT4 level exhibited no differences between the 2 groups (P = .196) . However, the subjects age at the time of treatment initiation and the initial levothyroxine dose showed no significant differences between the TCH and PCH groups  underwent trial discontinuation. Discontinuation of replacement treatment failed in 61 infants 46.6%), and they were diagnosed with PCH (PCH group), whereas the rest  who successfully discontinued replacement treatment were diagnosed with TCH (TCH group). The rate of maternal thyroid disease and newborns with other birth defects showed significant differences between the TCH and PCH groups  are more susceptible to developing CH. In the current study, we found that gestational age and birth weight were not significantly different between the TCH and PCH groups. However, the rates of low birth weight and preterm birth were higher in the TCH group, and further research is needed to confirm the relationships. Twins had increased risk for either PCH or TCH. Twins are frequently born preterm and/or have low birth weight, which can impair the function of the hypothalamic-pituitary-thyroid axis. A recent study on twins with CH showed that 64% common environmental  and genetic factors and 34% unshared environmental factors (36%) are responsible in PCH, whereas 95% genetic factors and 5% unshared environmental factors are responsible for TCH. As expected,,28 in our study, infants with other birth defects had increased risk of CH, and the PCH group had a higher frequency of malformations than the TCH group. It was reported that a group of cases with CH associated with other birth defects had higher prevalence of thyroid agenesis than the group with no other birth defects. Hence, it is important to investigate the molecular mechanisms underlying the events of the abnormal formation of the thyroid and other organs. The paired box gene 8 (PAX8), which encodes 1 family of 9 transcription factors in humans, plays a crucial role in embryogenesis, especially in the thyroid gland. Interestingly, a previous study showed heterozygous PAX8 mutation was associated with urogenital malformations in CH patients. Homozygous mutations in thyroid transcription factor 2 were confirmed in patients with a syndromic form of CH.NKX2–5 gene plays an important role in heart development, and mutations in the NKX2–5 gene have been found in CH cases with ectopy or athyreosis. Despite recent progress, the relationship between malformations and CH remains to be elucidated.Our study confirmed a significantly higher prevalence of CH in female than in male offspring. However, underlying causes of the difference are unclear. Thyroid dysgenesis is the leading cause of PCH, and the high female-to-male ratio among cases of CH is mostly associated with dysgenesis of the thyroid gland.,10 To maintain normal thyroid function, the dose of levothyroxine required in the PCH group was higher than that in the TCH group.,36 Several studies suggested that different doses of levothyroxine required during treatment or at discontinuation might be used to predict PCH.,37,38 In the current study, the levothyroxine doses at 1 year, 2 years, and 3 years old were significantly higher in the PCH group than those in the TCH group, which was similar to the findings of previous studies.,38 Whether laboratory findings can predict TCH is controversial. A significant reduction in confirmatory TSH levels in infants with TCH compared to infants with PCH was reported. However, other studies have shown no difference in the confirmatory FT4 and TSH levels between cases with TCH and PCH.,37 In the current study, the initial NST and confirmatory TSH levels in the TCH group were significantly lower than those in the PCH group, but there was no difference in the FT4 between the 2 groups.In our study, 53.4% of the cases with CH were diagnosed with TCH, which was similar to the results of previous Chinese studies.The limitations of our study were its retrospective design and the lack of analysis of other potential risk factors such as genetic susceptibility and environmental exposure. It is also important to investigate the cognitive function and growth outcomes of patients with CH. Nevertheless, our study had some advantages. It has a relatively large number of infants. Furthermore, this was a single-center study, which is conducive to relatively consistent quality control of disease diagnosis and treatment.In conclusion, the results of the current study have shown that maternal and neonatal perinatal factors contribute to the etiology of CH. Low birth weight and preterm birth are risk factors for TCH, whereas the presence of other birth defects is closely related to PCH. These results provide insights into the role of perinatal factors in the pathogenesis of CH and in the treatment of CH. Notably, maternal and neonatal perinatal factors should be considered during the diagnosis and treatment of CH. In future studies, we will explore and investigate other potential causes of CH, such as susceptible genes, environmental factors, and epigenetic characteristics.JZ, JL, WZ and GL conceived and designed the study; JZ, JuL, YZ and XQ carried out this study; JZ, JL, JuL, YZ and XQ analyzed the data of this study; JZ and JL wrote the paper; JZ, WZ and GL reviewed and edited the manuscript. All authors read and approved the manuscript.


Paramesonephric duct or Mullerian ducts forms female genital organs whereas mesonephric duct forms male genital organs. The remnant of the mesonephric duct or Wolffian duct in females sometimes forms a mesonephric cyst or Gartner's duct cyst. They are usually asymptomatic and <2 cm but sometimes can be bigger. It is diagnosed with pelvic examination. It is treated with surgical excision of the cyst. This is a unique case in urogynecology as it confuses with pelvic organ prolapse and the mode of treatment is completely different. We report a case of 32-years old lady who presented in urogynecology outpatient department with complain of pelvic organ prolapse. After examination she was diagnosed as vaginal cyst and excision was done and confirmed as Gartners cyst in histopathological examination. Other common vaginal cysts include epidermal inclusion cyst, Bartholin duct cyst, and Muellerian cyst. Gartner duct cyst is frequently associated with other renal congenital abnormalities.2Wolffian duct forms the male genital tract. In females, they regress. Occasionally they remain and the caudal portion forms the vaginal inclusion cyst known as Gartner duct cyst.3 We report a Gartner duct cyst which was approximately 6 cm and presented with mass coming out per vaginum.They are usually less than <2 cm but can present with bigger mass as well.She was non-diabetic, non-hypertensive, non-smoker, and no such history in her family members. She showed in the local hospital and was diagnosed as pelvic organ prolapse (cystocele) and referred to our centre. She has no other complaint of discharge per vaginum, urinary retention, urinary incontinence, bowel problems, and bleeding per vaginum.On per speculum examination, there was a cystic, nontender, mobile mass of 6 × 6 cm mass in the suburethral region, protruding from the left posterolateral vaginal wall .A 32-year para 2, living 2, last childbirth 7 months back, presented with complaints of mass coming out per vaginum for 4 months which was progressive. She first noticed it 4 months back when it was small in size. She delivered both babies vaginally and there was no history of difficult, prolonged, or instrumental delivery.Cervix was normal. The uterus was normal size and adnexa was free and non-tender bilaterally. We ruled out other diagnoses of Bartholin's duct cyst, cystocele with the examination. The endometriotic cyst was ruled out with no other significant symptoms, the free pouch of Douglas and normal uterus, and ovaries. We did a transvaginal ultrasound to rule out urethral diverticulum. It showed a single cyst of 6 × 6 cm, with no connection to the urethra. We also did cystourethroscopy to rule out urethral diverticulum with zero degrees cystoscope and 30-degree cystoscope to rule out bladder diverticulum.The provisional diagnosis of the Gartner duct cyst was made. Her routine blood investigations and urinalysis was normal. Transabdominal ultrasound was done to rule out any abdominal and genitourinary abnormalities. Magnetic resonance imaging (MRI) could have been done but it was not done as it was expensive and don't add much in our diagnosis and further management.The patient was posted for surgical excision and cystectomy was done in a lithotomy position under spinal anesthesia. The cyst was sent for histopathology. It came as non-mucin secreting low columnar and cuboidal epithelium, consistent with the Gartner duct cyst. The patient was followed up after 2 weeks and 3 months. She did not have any complaints then.4Gartner's duct cyst may present with mass coming out per vaginum. General vaginal examination and transvaginal ultrasound are sufficient for diagnosis. Surgical excision is the mainstay of treatment if they are symptomatic and large. MRI is more diagnostic but not needed in most of the cases.4 This forms the Gartner duct cyst and is typically located in the anterolateral vaginal wall following the course of the duct.5 They are usually asymptomatic but may cause dyspareunia, mass coming out per vaginum and urinary symptoms.4 MRI is more diagnostic but are not recommended as it is the expensive and general pelvic examination and transvaginal ultrasound are sufficient for management.3 Malignant transformation of cyst is very rare.6 Though surgical excision is the mainstay of treatment, it can be managed expectantly if it is asymptomatic and small.7 In our case the cyst was large so we did surgical excision. Diagnosis is confirmed with histopathology which shows cyst lined with a non-mucinous cuboidal or low columnar epithelium. Smooth muscles may be seen around the Gartner duct cyst in pathological examination.8In female Mullerian ducts form the female genital system whereas Wolffian duct regress and form a vestigial system.JNMA Case Report Consent Form was signedby the patient and the original article is attached withthe patient's chart.None.


Premature delivery is among the leading causes of perinatal mortality and morbidity in developed societies, which is an important obstetrics problem. Maternal periodontitis is a prevalent condition that has been suspected to be associated with adverse pregnancy outcomes such as premature birth. However, there are still conflicting results about this possible relationship, therefore this study was designed to test the association between maternal periodontitis and premature birth. This study also provides information about a new screening tool recommended for use by nurses and midwives to screen for periodontal diseases during antenatal consultations in order to improve the health of mothers and children.A retrospective case-control study was conducted at 12 health facilities in the Southern Province of Rwanda from February to August, 2018. A total of 555 women in the postpartum period were enrolled in the study. Cases and controls were enrolled in a ratio of 1:2; each enrolled case of preterm birth was followed by 2 unmatched control subjects that were next on the register and who delivered at term gestation. A total of 185 cases of preterm deliveries and 370 controls of term delivery were enrolled in the study. Multivariate regression analysis was used and the independent variables were hierarchically entered in three groups: The first group involved demographic variables that were put in the regression model as Step 1. The second group was made up of other potential risk factors that were placed in the regression model as the second step. Periodontitis was entered in the final regression step, as it was hypothesized as the main predictor variable.A statistically significant association was found between periodontitis and premature birth. Women who had periodontitis had 6 times the odds of giving birth to premature birth infants compared to women who had no periodontitis .The study results indicate that periodontitis is strongly associated with premature birth. Preventive solutions including the use of a periodontitis screening tool for nurses and midwives during antenatal care consultations, are highly recommended. Premature births are among the leading causes of perinatal mortality and morbidity globally . In the Neonatal delivery before 37 weeks of gestation is the leading cause of low birth weight . PrematuStudies have identified numerous risk factors related to premature birth and they can be categorized in three ways: a) non-gynecological causes: low socio-economic status, malnutrition, early maternal age, short maternal stature, low maternal weight, low maternal heart volume, smoking, alcohol consumption, inadequate prenatal care, stress, genitourinary tract infections and malaria, b) gynecological causes: uterine malformations, uterine adhesions and pregnancy with intrauterine infection, c) obstetric causes: primiparity in both young and old mothers, short inter-conception interval, grand multiparity, previous premature births, previous stillbirth, multiple pregnancies, low insertion of the placenta and chorioamnionitis .. Studies suggest that inflammation in periodontal tissues due to periodontitis increases secretion of different inflammatory cytokines, notably interleukin B (IL-1β), interleukin IL-6, interleukin 8 (IL-8), interleukin 17 (IL-17), and tumor necrosis factors alpha (TNF-α) [Although several risk factors are known, 25% of premature births are believed to be of unknown etiology . The rec (TNF-α) , 14–17.In Africa, studies have associated poor periodontal status with premature birth and low birth weight deliveries. For example, a study done in Nigeria by Umoh and colleagues concluded that periodontal disease management reduced the prevalence of low birth weight deliveries . The recA retrospective unmatched case-control study was conducted to test the association link between periodontitis and premature birth. The study is considered retrospective because both the exposure and the outcome happened prior to subject enrolment. In this study the outcome was preterm delivery and the hypothesized exposure was presence of maternal periodontitis. Participants were selected through hospital registers whereby the research team would verify cases of preterm deliveries and the controls would be selected from the next 2 full-term births on the register. An a priori estimate of the required sample size was calculated using G*Power 3.1.9.6. by Faul , Kiel, GA structured clinical exam and standardized questionnaire were used to collect information regarding the presence of periodontal infection among pregnant women attending antenatal care clinics in the Southern Province of Rwanda. The study adapted the questionnaire from the WHO Oral Health Assessment Tool for Adults of 2013 [Prior to use in the study in southern Rwnda, the questionnaire was piloted in Nyamata District Hospital in the Eastern Province to ensure that it captured all the required information and that the questions were clear to respondents. After the pilot study, the feedback from the participants was considered and any questions that were not clear were corrected accordingly. The questionnaire was translated in Kinyarwanda using forward and backward translation whereby this questionnaire was first translated in Kinyarwanda from English and then it was again translated back to English by another translator to determine whether the content remained consistent.The questionnaire collected information on the following variables: age of the respondent, education level, health and lifestyle behaviors (e.g. tobacco use), socio-economic status, mother’s weight, number of previous pregnancies, previous preterm delivery, weight gain during pregnancy, illnesses during pregnancy and stress during pregnancy. The main outcome variable of interest was premature birth.The inclusion criteria were postpartum mothers aged 18–35 who delivered singleton infants in all selected health facilities within 1 to 5 days before recruitment. Those women who delivered premature were recuited as cases and those who delivered at term were recruited as controls. Maternal registers were checked in order to determine who could be recruited as case or controls based on the above criteria. Cases and controls were enrolled in a ratio of 1:2 and each enrolled case of premature birth was followed by 2 control subjects who delivered at term gestation that were next on the register. A case was defined as any delivery below 37 weeks and a control was defined as any delivery of 37 weeks and above. We used ratio of 1:2 in order to increase the study power and reduce data collection time as there were limited cases of premature birth. Mothers with twin infants, those with systemic conditions like uncontrolled diabetes, HIV infection and those without teeth in one or more sextants were excluded from the study. Women established risk factors for prematurity, like abnormal placentation, eclampsia, uterine abnormalities, and other pregnancy complications that may easily lead to prematurity were also excluded from the study so that they would not bias the results. Other variables that were likely to cause prematurity were documented via the study questionnaire and were controlled during the multivariate analysis.A periodontal examination was performed on all women enrolled in the study. The study examiners used a Williams graduated periodontal probe to perform the periodontal clinical examination . Six datThe current study defined periodontitis as presence of pocket depth greater than 3 mm on either maxilla or mandible or both and presence of interdental clinical attachment loss (CAL) on ether maxilla, mandible or both of 2 mm or above and buccal or oral CAL of 3 mm or above .Based on Jati et al , gingivaClinical attachment loss was measured as follows: when the gingival margin was at the cemento-enamel junction and there was no recession, then the CAL was equal to the pocket depth; when the gingival margin was apical to the cemento-enamel junction, CAL was equal to pocket depth plus gingival recession; when the gingival margin was on the anatomical crown in case of gingival overgrowth, CAL was equal to pocket depth minus gingival recession. CAL was not considered in some of the specific cases that were of non-periodontal cause. For example, when the gingival recession was of traumatic origin, dental caries extending in the cervical area of the tooth and in the cases of recession by malposition of the tooth .The current study defined some of the questionnaire variables as follows; i) physical trauma as a wound on the body that was caused by a sudden physical injury, for example, an accident; ii) violence as any behavior or action that intends to hurt someone, physical or verbal and iii) stress during pregnancy as anything that causes emotional strain or tension to the pregnant women..IBM SPSS for windows version 21.0  was used for all data analyses . Descripp < 0.05. The fit of the logistic regression models was assessed using regression diagnostic information, such as the − 2 log likelihood and Hosmer-Lemshow chi square values.The odds ratio was obtained with 95% confidence intervals, thus statistical significance was defined as n = 338, 60.9%) were in the age range of 26–35 years, 47.6% had primary education, 38.7%, had secondary education, 7% had tertiary education and 6.7% had no formal education. The majority of the study participants  are from a rural setting, 63.2% are farmers and 55.5% are in category 3 (low) or the “Ubudehe”/ socio-economic status as categorized using the Rwanda national socio-economic status categories. When these demographic variables were associated with premature birth, only employment status was statistically associated with premature birth (p = 0.054)  ranging from 18 to 35 years. Most participants  and therefore eligible for the multivariate logistic regression analysis.To assess if there was a relationship between premature birth and the study vaiables, characteristics were compared initially in a univariate fashion between the cases and controls Table . ResultsMultivariate regression analysis was then performed and the variables were hierarchically grouped into three groups: whereby demographic variable of employment status was put first in the regression model as step 1 and followed by other potential factors of ever used tobacco, mother’s weight, last pregnancy, previous premature delivery, history of stress, presence of malaria or urinary tract infection during pregnancy, physical trauma during pregnancy and domestic violence during pregnancy. In the third step of the regression model, periodontitis was added on its own as it was hypothesized as the study’s main exposure variable.After adjusting for the other variables in the model, the mutiple logistic regression analysis revealed a strong independent association between periodontitis and premature birth, where periodontitis could lead to a six-fold higher risk of delivering premature infants compared to women who had no periodontitis . It is worth noting that only previous pre-term birth (OR = 10.6) had a higher risk estimate than periodontitis status. Other significant results from Table Premature birth is a major healthcare challenge and is associated with many potential consequences such as lifelong disabilities and high healthcare costs . PrematuP < 0.005) [Many studies have reported the association between maternal age and premature birth; both extreme ages either under 18 years or above 40 years are considered to be risk factors for premature birth –29. Thou< 0.005) . This wa< 0.005) .On the other hand, Mumghamba in Tanzania compared mothers who had PTB infants and those with normal weight infants and reported that PLBW had a lower mean age . Our stuMaternal weight has also been reported to be associated with premature birth, whereby in our study the logistic regression revealed that mothers with low weight had higher chances of premature deliveries as opposed to mother with normal weight whereas the odds of having a premature birth baby was 3.2 times for underweight compared to those with normal weight mothers . Our study findings were echoed by Zhen and colleagues, who revealed that neonates born to underweight mothers had higher chances of preterm delivery  . Also inIn this study, the presence or absence of periodontitis disease was a major predictor of preterm delivery. After controlling for other variables, the logistic regression analysis revealed a strong association between periodontitis and premature birth, where periodontitis could lead to a six-fold higher risk of giving birth to premature birth infants compared to women who had no periodontitis . It is note worthy that our study results are different in comparison to other studies, for instance, the study done in Germany by Noack and colleagues who did not find any association between periodontitis and premature birth . Similarp = 0.0004; RR = 3.5) [However, our study findngs are in agreement with several other studies that have supported the association between periodontitis and premature birth. Offenbacher et al.,  reportedR = 3.5) . SeveralR = 3.5) , 37–40. R = 3.5) .Also, in Africa, other studies have examined the link between premature birth and low birth weight deliveries and these were significantly associated with poor periodontal status; for example, a study done in Nigeria by Umoh and colleagues revealed that periodontal treatment was effective in preventing low birth weight deliveries . In UganThe study results suggest there is a strong association between maternal periodontitis and the risk of preterm birth. There is a need to improve awareness of non-dental professionals working in antenatal care clinics especially nurses and midwives about the possible obstetric implications of periodontal diseases and to include periodontal screening in the antenatal care package for early detection. The study results indicate there is a need to proactively promote periodontal health during pregnancy.The limitations of this study include those relevant to most case control studies, including possiblerecall bias. For example, the reported occurrence of some illnesses, like UTI and other medical conditions during pregnancy was based on mothers’ self-report of symptoms and not on laboratory confirmation and therefore over-reporting was possible. Also only mothers who had live births were interviewed and their babies assessed for gestational age. The study did not address factors associated with preterm stillbirth. Lastly, the training and calibration of the data collection examiners was not formalized and no formal agreement analysis was done therefore it is possible that there was still some imprecision of periodontal examination results between examiners.The study results suggest that periodontitis is associated with a six-fold increase in the risk of premature birth. Thus, preventive solutions such as having the development of a periodontitis screening tool for nurses and midwives during antenatal care consultations is highly recommended.


The maternal effect from environmental origin (c2 = 0.23 ± 0.08) far exceeded the results previously calculated in cattle. There was no difference in reliability between BLUP1 and BLUP2 models, and both of them were more accurate than the ANOVA model. Based on the results of this study, we conclude that the birth weight of dromedary calves was more influenced by the dam’s intrauterine rearing capacity and by the environment, management, and feeding of the pregnant female camels than the hereditary growth potential. Considerable differences were found among male dromedaries in their breeding values for the birth weight trait.Birth weight data of dromedary calves from the database of one of the world’s largest dairy herds  were analyzed for the period from 2007 to 2018. The assessment included the data of 4124 camel calves that were classified into six ecotypes . The aim of the study was to describe the heritability of birth weight of calves and the breeding value of sires. Genetic parameters of birth weight were estimated by ANOVA model and two BLUP animal models as well. The mean value of the camel calves’ birth weight was 34.75 ± 5.67 kg. The direct heritability of birth weight ( Camelus dromedarius) belongs, within the class of mammals , to the biungulate (Artiodactyla) order, the “calloused foot” animals (Tylopoda) suborder, and to the camel (Camelidae) family. The species was domesticated approximately 3000–4000 years ago on the East Coast of the Arabian Peninsula  were born with lighter weight. The birth weight of calves born in Sudan was 26.2 kg Bulliet . AccordiSome significant effect of various genetic  and environmental  factors on the birth weight of camel calves has been described earlier . In addition, we found no reference on the breeding value estimation of male dromedaries in the relevant literature.There are only limited and decades old data in the literature on the heritability estimates of birth weight of dromedary calves. These data are exclusively from India and show a big variation in the heritability value among studies. Ram et al.  publishehowdhary , Tandon howdhary , and Khahowdhary  reportedh2d) of birth weight of cattle calves was high (0.4–0.5), while the maternal heritability (h2m) was quite low  of the birth weight was ranging from 0.2 to 0.4  to determine some genetic parameters especially heritability of birth weight of dromedary camel calves and (2) to estimate the breeding value of dromedary bulls for this trait (3) using and testing different ANOVA and BLUP models on the world’s largest available dromedary camel dataset. Based on our previous results (Nagy and Juhász The study was conducted over 11 breeding seasons from 2007 through 2018 at the premises of Emirates Industry for Camel Milk and Products (EICMP), the world’s first large-scale camel dairy farm that is located in Dubai, United Arab Emirates . During this period, a total of 58 male (bull) and 2087 female (dam) dromedaries were included into the breeding program and 4124 progeny  delivered on the farm (Table Chloris gayana) with or without wheat bran and formulated feed in different quantities depending on age, production, reproductive status, and body condition of the animals. Water and mineral licking stones were available ad libitum. The breeding season extended from September until June with a peak from December to January. Further details on farm management have been described previously  based on geographical origin, color, appearance, and body conformation , date and time of birth, type of delivery, gender and weight of the calf, status of the calf , and time to sitting position and to standing of the calf. In this work, we only considered gestations with normal parturition and viable newborns.best linear unbiased prediction; Henderson Birth weight was considered as character of the calf. To estimate the genetic parameters of birth weight trait, three different models ; b = vector of fixed effects ; u = vector of random effect ; m = vector of maternal genetic effect; pe = vector of maternal permanent environmental effect; e = vector of random residual effect; X = matrix of fixed effects; Z = matrix of random effects; W = matrix of maternal genetic effect; and S = matrix of maternal permanent environmental effect.ANOVA model did not contain information on the dam; BLUP1 model contained total maternal effect ; BLUP2 model contained genetic and environmental maternal effects separately. It was supposed that BLUP1 model would support the previous results of Nagy and Juhász  on matere2 values and log-likelihood values (− 2 log L) for the three different models were compared  factors were as follows: ecotype of dam , parities of dam , breeding season (11 classes), month of mating , and the sex of the calf   with at least 100 progeny.Breeding value (BV) of the dromedary sires for birth weight trait was estimated with all three models . BV was considered as a double of the realized progeny difference (RPD), namely, BV = 2 RPD. The RPD was defined as the difference of the mean value of the birth weight data of close relatives  of a particular dromedary sire and the mean value of the birth weight data of the contemporary calf group. Breeding values were estimated only for sires  was found between the birth weight and gestation length of dromedary camels. This is the reason why gestation length was not considered as a covariant in the various models.The weight of healthy, newborn calves was recorded for 4124 parturitions. The descriptive statistical parameters of birth weight trait are shown in Table h2d = 0.09 ± 0.04–0.11 ± 0.03) with all three models. Hence, the contribution of the direct genetic variance to the phenotypic variance was much lower than that of the environmental variance. There was difference in magnitude of the maternal heritability between the two BLUP models. When permanent maternal environmental effects were not included in the model (BLUP1), the maternal heritability value was quite high (h2m = 0.50 ± 0.06). However, when this effect was included in the model (BLUP2), the maternal heritability value was much lower (h2m = 0.23 ± 0.10), but still exceeded direct heritability (h2d) more than twice. The correlation estimated between direct and maternal genetic effects seemed to be negative and quite weak (rdm = − 0.33 ± 0.23 and − 0.23 ± 0.31). In addition, because the SE values were too high, the rdm values were not reliable and informative. The maternal environmental effect estimated by the BLUP2 model is fairly high (c2 = 0.23 ± 0.08) that indicates poor genetic but strong environmental  effects of the gestation period on the birth weight of dromedary calves.Genetic parameters estimated with the three models  are summarized in Table Breeding values of dromedary sires for birth weight estimated by ANOVA and BLUP models are summarized in Table Concerning the breeding values for maternal genetic effects, results obtained by two BLUP models were different. Breeding value data obtained with the BLUP1 model were higher than that obtained with BLUP2. Also, there were differences between the breeding values for direct genetic and maternal genetic effects of the same sire. In general, the breeding values obtained for maternal genetic effect were higher than that obtained for direct genetic effects. Also, the range of breeding values was different between the two models. Namely, the difference between the first and last sire in the rank was 6.38 kg and 4.35 kg when estimation was done with the BLUP1 model and with the BLUP2 model, respectively.Published data on the heritability of the birth weight of different ecotypes or breeds of dromedary camels are rather limited and heterogeneous. Results of our study using the world’s largest dromedary camel dataset provide new information that can help breeding programs and sire selection in this species. This research extended the results of a recent multi-trait study  that had been reported in the literature  shows similar tendency as it was published for beef cattle  on the birth weight of dromedary calves was higher than that published for cattle. Namely, Phocas and Laloë  in Angus, Hereford, Simmental, and Piedmontese breeds  and by the environment, management, and feeding of pregnant female camels  than the hereditary growth potential (additive direct genetic effect) of the calf. Most likely, this is the result of the fact that until recently no proper selection and specific breeding programs were applied in this species to improve its production potential Hermas . In agreTo our best knowledge, breeding value estimates for birth weight or for any other trait have not been published for the dromedary camel until now. Therefore, from the population genetics point of view, the results of this study on breeding values of individual male animals can be considered as pioneer information. As a result, dromedary bulls were ranked according to their direct and maternal genetic effects that are of great significance for the development of dromedary breeding. These results also highlight the importance of maintaining genetic diversity within the dromedary camel population. However, we also have to note that breeding values might have some limitations in this species. Our data were obtained in one well-managed dromedary camel population. But, due to the interaction of genotype by environment, the ranking of these dromedary males could have been different under different management conditions. We assume that genetic evaluation of dromedary sires in one particular environment may not be an accurate predictor of progeny performance in another environment.In this study, we provided new data on genetic parameters of birth weight trait using the world’s largest dromedary camel dataset. Heritability values for the evaluated trait advanced our understanding of the interaction between genetic and environmental effects. Breeding value data allowed the ranking of dromedary bulls and also draw the attention to the genetic diversity of the dromedary population. The reasonable genetic and, to some extent, more environmental variance and breeding value data indicate the heterogeneity and selection possibility of the dromedary camel population offering a good opportunity both for genetic and environmental improvement. Future studies should be directed towards defining similar genetic parameters and heritability estimates for many other traits in this species. The present experience using various methods for genetic analysis for birth weight, as a model trait, will be beneficial for future studies.


Perfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are used in consumer products for their water repellent and flame retardant properties, respectively. However, there is widespread prenatal exposure and concern about their potential harm to the developing fetus. Here, we utilized data from a demographically diverse cohort of women in San Francisco, CA to examine associations between prenatal exposure to PFAS and PBDEs with gestational age and birth weight for gestational age z-scores.N = 506). PFAS and PBDEs were measured in serum obtained during the second trimester of pregnancy. Linear regression models were used to calculate crude and adjusted β coefficients for the association between PFAS and PBDE concentrations in tertiles and gestational age and birth weight z-scores. Individual PFAS and PBDE concentrations, as well as their sums, were examined in separate models.Women included in this analysis were enrolled in the Chemicals in our Bodies (CIOB) cohort study . Additionally, exposure to BDE-47 and BDE-99 in the middle tertile was also associated with a reduction in birth weight z-scores  compared to those in the lowest tertile of exposure. No consistent associations were observed between increasing PFAS concentrations and gestational age or birth weight z-scores.Among a diverse group of pregnant women in the San Francisco Bay Area, we found non-linear associations between prenatal exposure to PBDEs during the second trimester of pregnancy and birth weight z-scores. However, most PFAS congeners were not associated with adverse birth outcomes. PFAS and PBDE concentrations were lower in our cohort relative to other studies. Future research should assess the effects of emerging and persistent PFAS and PBDEs on birth outcomes, as some congeners are being phased out and replaced by chemically similar structures. Perfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are persistent in the environment and ubiquitous due to their use in many consumer and industrial products. PFAS are in a wide range of products such as cookware, food containers, clothing, and fire-fighting foam due to their oil and water-repellent properties . PBDE flIn humans, studies have shown that PFAS and PBDEs travel through the placenta to the fetus –10. PFASStudies on the effects of PBDEs on birth outcomes are also mixed. In a recent meta-analysis, a one log unit increase in exposure to multiple PBDEs  was associated with a − 50.6 g decrease in birth weight  . HoweverIn response to health concerns, the US EPA worked with industry for a voluntary phase out of new production and import of PFOA in 2006 , PFOS byTo date, most studies have focused on specific PFAS and PBDE congeners, such as PFOA, PFOS, BDE-47, and BDE-99. However, there are continued widespread exposures to these persistent chemicals and newer chemicals are constantly being introduced to the market. Thus, there is uncertainty about the relationship between prenatal exposure to certain PFAS and PBDEs and adverse pregnancy outcomes. Therefore, the goal of this study was to characterize the association between prenatal exposure to PFAS and PBDEs and adverse birth outcomes. We included a number of PFAS and PBDE congeners not previously explored in this context, and hypothesized that higher maternal exposure to PFAS and PBDEs during pregnancy would be associated with a reduction in gestational age and birth weight z-scores.Women included in the analysis were enrolled in the Chemicals in our Bodies (CIOB) study, a prospective birth cohort examining the effects of chemical and chronic psychosocial stress during pregnancy. All participants were recruited between 2014 and 2018 from prenatal clinics at the Zuckerberg San Francisco General Hospital (ZSFG) or Mission Bay (MB)/Moffitt Long (ML) hospitals during their 2nd trimester of pregnancy (between 12 and 28 weeks of gestation). Participants recruited from ZSFG were predominantly lower income women of color without private health insurance, whereas participants recruited from MB/ML were economically and racially/ethnically diverse and included women of higher socioeconomic status.Women were eligible for inclusion in CIOB if they were older than 18 years of age, did not have a diagnosed pregnancy complication, were English or Spanish speaking, expecting a singleton birth, and planned to deliver at ZSFG or MB/ML. CIOB study protocols were approved by the Institutional Review Boards of the University of California, San Francisco (10–00861) and Berkeley (2010-05-04). All women provided written, informed consent prior to participating in the study. Further information describing recruitment methods for CIOB is available elsewhere .2, 18.5–24.9 kg/m2, 25–29.9 kg/m2, ≥ 30 kg/m2), maternal education , parity , smoking status , and country of birth .Demographic information was collected via standardized questionnaire following informed consent and included: maternal age, maternal race/ethnicity , pre-pregnancy body mass index . Analyses were performed by the Environmental Chemical Laboratory at the California Department of Toxic Substances Control (DTSC). Method detection limits (MDL) were calculated as 3 times the standard deviation of the blank concentrations for all PFAS and PBDEs . QualitySerum preparation and extraction procedures were completed in the laboratory of DTSC. Briefly, serum was thawed, spiked with surrogate standards, denatured, and ran on an automated Biotage rapid trace SPE Work Station. Extractions were concentrated, cleaned up with acidic silica gel, reconcentrated, combined with internal standards, and analyzed for PBDEs by gas chromatography/high resolution mass spectrometry  using isotope dilution . PFAS weAll wet-weight PBDE congeners were adjusted with lipid serum concentrations. For consistency with previous research, we included PFAS and PBDE congeners with ≥ 80% of samples above the MDL in our statistical analysis . Based oN = 6). Birth weight for gestational age z-scores were calculated using a U.S. population reference [Participants’ medicals records were abstracted by trained study staff for the following measures: final gestational age at delivery in weeks, birth weight in grams, infant length, and infant head circumference. Gestational age on the medical record was calculated based on best-estimated date of delivery. If gestational age was missing on the medical record, it was imputed by subtracting date of last menstrual period from date of birth when this information was available  as exposures in separate models. All demographic characteristics were explored as potential covariates in adjusted analyses. Covariates retained in final adjusted models were associated with birth weight or gestational age in bivariate analyses at We conducted a number of sensitivity analyses to examine the robustness of our findings, and present the results in the supplemental information. First, we used linear regression to examine associations between tertiles of PFAS and PBDE concentrations with continuous birth weight restricted to term births only. We restricted our analysis to term births as birth weight is often confounded by gestational age. Second, we explored infant sex differences by examining the association between tertiles of individual PFAS and PBDE congeners and gestational age and birth weight z-scores stratified by infant sex, as prior research has shown sex-specific effects of endocrine disrupting chemicals. Lastly, we examined wet-weight PBDE concentrations with lipids as a covariate in relation to gestational age and birth weight z-scores.All analyses were conducted in R Version 3.6.0. In all regression models, missing data for birth outcomes, covariates, and tertiles of PFAS and PBDE concentrations was handled using Multiple Imputation via Chained Equations (mice). Measurements that were below the MDL and did not have a machine read value (< 1% of measurements) were treated as missing. Using the mice approach, the variables with complete data are used to predict the missing values. We used the ‘mice’ package  to produThere were 510 pregnant women enrolled in the CIOB study. Of this group, 4 participants withdrew prior to delivery, leaving a sample size of 506 for our analysis. The majority of women self-identified as Non-Hispanic (NH) White (38.6%) or Hispanic (34%), and over half of our analytic sample was between 25 and 34 years of age . PFAS concentrations were also moderately correlated with one another  but not with PBDEs . Among the PFAS, PFOS had the highest median 1.93 ng/mL) followed by PFOA (0.76 ng/mL) Table . BDE-99  ng/mL foIn adjusted models, the highest compared to the lowest tertiles of PFOA, PFOS, PFNA, and total PFAS concentrations were moderately associated with a reduction in gestational age, although the confidence intervals included the null value Table . The uppMe-PFOSA-AcOH was associated with a reduction in birth weight z-scores . No associations were observed between other PFAS congeners  and birth weight z-scores Table .Logistic regression models indicated that increasing tertiles of PFAS and PBDE concentrations were associated with a moderate, non-significant, increase in odds of PTB across all congeners examined Table . The higResults from models using wet-weight measurements of PBDEs, controlling for lipid levels, in relation to gestational age and birth weight z-scores were similar to models using lipid-adjusted PBDE measures Table S-S6. WhenIn a demographically diverse cohort of pregnant women in San Francisco, California, we observed that women with elevated levels of BDE-47 and BDE-99 had shortened gestational age and a reduction in birth weight z-scores. We did not observe consistent associations between PFAS concentrations and gestational age or birth weight for gestational age z-scores. In our cohort, PFAS and PBDE concentrations were lower relative to other studies , 34, 44.The inverse association between gestational age and prenatal exposure to BDE-47 in the highest compared to lowest tertile is consistent with prior research. For example, a study in Texas found that women in the upper two quartiles of BDE-47 had increased odds of PTB . In contWe observed no clear associations between PFAS, gestational age, and birth weight z-scores. Other studies have also observed inconsistent associations between exposure to certain PFAS congeners and continuous measures of gestational age or birth weight , 17, 45.Discrepancies across studies may be due to differences in the timing during pregnancy when PFAS is measured, as studies assessing temporal trends in PFAS levels during pregnancy have shown that levels tend to decrease with increasing gestational age . InconsiPFAS and PBDEs may be affecting fetal growth through several mechanisms. One hypothesis is that PFAS disrupt estrogen and thyroid hormones. Both estrogen and thyroid hormones are important for normal fetal growth and development, and maternal hypothyroidism has been associated with lower birth weight , 52. HumOur study has several important strengths. We measured several PFAS, including PFHxS, PFNA, Me-PFOSA-AcOH, that have not been as extensively studied as PFOA and PFOS. Our study population also included a racially/ethnically and socioeconomically diverse group of pregnant women. There is a need for more research among understudied minority populations that investigate how these groups may be disproportionately affected by environmental chemical exposures. Additionally, our study is larger than many previous studies examining the association between PBDEs and PFAS and birth outcomes. We also acknowledge several limitations of our study. Levels of some PBDEs and PFAS have been decreasing in the U.S. population over time and it is possible that the levels we measured in our study were at lower concentrations than the levels that would negatively impact birth outcomes. Our study may also have lacked adequate power to detect statistically significant effects. Furthermore, multiple tests were conducted and we cannot rule out the possibility of chance findings. Lastly, while we did adjust for many key covariates, residual confounding may still be a concern.Among a diverse group of pregnant women in the San Francisco Bay Area, we found non-linear associations between prenatal exposure to PBDEs during the second trimester of pregnancy, birth weight z-scores, and gestational age. With the exception of Me-PFOSA-AcOH, we did not observe an association between increasing PFAS exposure and gestational age or birth weight z-scores, although our results suggested that certain PFAS were slightly associated with PTB. Future studies should focus on emerging PFAS and PBDE congeners and substitutes, which are replacing those chemicals that are declining.Additional file 1: Table S1. Demographic characteristics of Chemicals in Our Body (CIOB) study population stratified by delivery hospital. Table S2. Crude linear regression coefficients and 95% confidence intervals for the associations between tertiles of PFAS (ng/mL) and PBDE (ng/g lipid) concentrations in maternal serum and gestational age in weeks (N = 506). Table S3. Crude linear regression coefficients and 95% confidence intervals for the associations between tertiles of PFAS (ng/mL) and PBDE (ng/g lipid) concentrations in maternal serum and birth weight z-scores (N = 506). Table S4. Crude odds ratios and 95% confidence intervals for the associations between tertiles of PFAS (ng/mL) and PBDE (ng/g lipid) concentrations in maternal serum and preterm birth (N = 506). Table S5. Linear regression coefficients and 95% confidence intervals for the associations tertiles of wet weight PBDE (ng/mL) concentrations in maternal serum and gestational age in weeks (N = 506). Table S6. Linear regression coefficients and 95% confidence intervals for the associations tertiles of wet weight PBDE (ng/mL) concentrations in maternal serum and birth weight z-scores (N = 506). Table S7. Linear regression coefficients and 95% confidence intervals for the associations between tertiles of PFAS (ng/mL) and PBDE (ng/g lipid) concentrations in maternal serum and birth weight (grams) among full term births (N = 461). Table S8. Linear regression coefficients and 95% confidence intervals for the associations between tertiles of PFAS (ng/mL) and PBDE (ng/g lipid) concentrations in maternal serum and birth weight z-scores stratified by infant sex (N = 506). Table S9. Linear regression coefficients and 95% confidence intervals for the associations between tertiles of PFAS (ng/mL) and PBDE (ng/g lipid) concentrations in maternal serum and gestational age stratified by infant sex (N = 506).


Women with polycystic ovary syndrome (PCOS) have increased risk of pregnancy complications, including preterm birth before 37 weeks. However, if this increased risk also includes extremely preterm births (<28 weeks) is unknown. Such information is important to identify women at risk and tailor antenatal care, since child morbidity and mortality become more prevalent with increasing prematurity.To investigate the association between PCOS and extremely preterm birth, and whether onset of PCOS-related preterm birth is predominantly spontaneous or medically indicated.This was a nationwide register-based cohort study in Sweden. The study population was all live singleton births registered in the Swedish Medical Birth Register 2005–2014 (n = 1 046 448). Women with and without PCOS were compared by severity of preterm birth  and delivery onset mode . Multinomial logistic regression was performed to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI). Adjustments were made for maternal age, parity, body mass index, smoking, country of birth and year of delivery.During the study period, 1.3% of the women giving birth had PCOS diagnosis. They had an overall higher preterm birth rate than women without PCOS . Women with PCOS had increased odds of preterm birth of all severities, with the highest odds for extremely preterm birth , particularly of spontaneous onset .Women with PCOS had more than a two-fold increased risk of extremely preterm birth with spontaneous onset than women without such diagnosis. This can be important in antenatal risk assessment of preterm birth in women with PCOS. Future research is warranted to investigate the biological mechanisms behind preterm birth in women with PCOS. Polycystic ovary syndrome (PCOS) is an endocrine condition affecting 6–10% of women of reproductive age . Women wPreterm birth affects approximately 5–15% of all infants globally and is associated with substantial morbidity and mortality . With dePrevious studies have reported that women with PCOS are at increased risk of preterm birth –12, but The primary aim of this study was to investigate the association between PCOS and preterm birth by severity of prematurity, particularly extremely preterm birth, in a large population-based cohort including more than one million live births. A secondary aim was to study the association between PCOS and preterm birth according to onset of delivery.The ethics committee did not waive the requirement for informed consent since the study is register-based and includes neither any deviation from clinical routine nor a direct contact with the study participants.Prenatal care in Sweden is standardized and free of charge, and attendance is close to 100% . During The Swedish Medical Birth Register prospectively collects information on pregnant women as well as on pregnancy, delivery and the neonatal period, starting at the first prenatal visit. The register includes information on about 98% of all births in Sweden since 1973  and infoAll women with live born singleton pregnancies giving birth, to an infant at 22+0 gestational weeks or later, between 2005 and 2014 (n = 1 061 739) in Sweden were included in the study. The cohort was obtained from the Swedish Medical Birth Register. Pregnancies with unknown gestational age at birth (n = 484) or without personal identification number (n = 14 115) were excluded. According to clinical routines in Sweden during the study period, pregnancies should be induced before 43 weeks and 0 days. Based on this, women with gestational age more than 43 weeks and 6 days (n = 692) were excluded, assuming that the gestational age had been incorrectly registered. Thus, a total of 1 046 448 women were included in the final study cohort .The exposure was diagnosis of PCOS identified in the Swedish Patient Register, until the date of discharge after the index delivery. PCOS diagnosis was identified according to the corresponding ICD codes . In 1990The primary outcome, preterm birth, was defined as gestational age <37 weeks at birth and was categorized, in accordance with the World Health Organization´s categorization, as extremely preterm birth (22+0 to 27+6 weeks), very preterm birth (28+0 to 31+6 weeks) or moderately preterm birth (32+0 and 36+6 weeks). The secondary outcome was preterm birth according to onset of delivery, categorized as spontaneous or medically indicated preterm birth. The categorization of onset of delivery was regardless of whether the child was subsequently delivered vaginally or with cesarean section. Information on onset of delivery is routinely recorded in a standardized manner (checkbox) by the delivery ward midwife and is categorized as spontaneous, induced vaginal or cesarean section before onset of labor. According to national guidelines , the defIn Sweden, all pregnant women are offered a first- or early second-trimester ultrasound scan free of charge to accurately date the pregnancy and to scan for congenital anomalies. In this cohort, gestational age was determined according to the following hierarchy: first-trimester or early second-trimester scan (950 571 [90.8%]), date of last menstrual period reported at the first prenatal visit (46 365 [4.4%]) and postnatal assessment (49 512 [4.7%]).weight (kg)/height (m)2. Covariates were categorized according to Covariates were maternal age, parity, infertility treatment in index pregnancy, height, weight in early pregnancy, daily smoking in early pregnancy, cohabitation, reproductive history, presence of hypertensive or diabetic disease, country of birth, educational length and year of delivery. Early pregnancy maternal body mass index (BMI) was calculated, using the equation http://www.dagitty.net/) [Logistic regression analysis was used to estimate the association between maternal PCOS and risk of preterm birth. In all analyses, crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the generalized estimation equation method, as observations are not independent in women who gave birth more than once during the study period. In order to obtain systematic representation of causal relationships between PCOS diagnosis and preterm birth, as well as to decide which covariates should be included, we drew a directed acyclic graph   S1 Fig)http://wwAs a sensitivity analysis, we calculated the risk of preterm birth in PCOS women, where we even adjusted for infertility treatment (ovulation stimulation and other assisted reproduction treatment) in the adjusted model 2.We also wanted to investigate whether the preterm birth risk in PCOS women was mainly explained by PCOS-related disorders such as hypertension and diabetes. We therefore calculated the risk of preterm birth in PCOS women after excluding women with hypertensive and diabetic diseases .Finally, we restricted our population to primiparous women and estimated the association between PCOS and risk for preterm birth by severity.When analyzing the risk of very preterm birth, women who had given birth extremely preterm were excluded since they were no longer at risk of giving birth. Similarly, when analyzing the risk of moderately preterm birth, women who had given birth before 32 weeks of gestation were excluded.Data were analyzed using IBM SPSS 25 and SAS software version 9.4. P-values were two-sided and p-values <0.05 were considered statistically significant.The study was approved by the Regional Ethics Committee at the Karolinska Institute, Stockholm, Sweden (2008/1182-31/4 and 2011/1856-32). All data were fully pseudonymized before our access to them.Among all women giving birth to singletons in Sweden during 2005–2014, 13 559 (1.3%) had a PCOS diagnosis. PCOS diagnosis became more frequent as the years passed; 0.8% of the women giving birth in Sweden during 2005–2008 had a PCOS diagnosis, while the corresponding proportion was 1.9% during 2012–2014. Maternal characteristics in women with and without PCOS diagnosis are shown in In the final cohort of 1 046 448 women, 4.8% delivered preterm (<37 weeks); 4.1% moderately preterm (32w0d to 36w6d), 0.4% very preterm (28w0d to 31w6d) and 0.2% extremely preterm (22w0d to 27w6d). Preterm birth was more common in women with PCOS  than in women without PCOS . Of 13 559 births in women with PCOS, 81 (0.6%) were extremely preterm, 93 (0.7%) very preterm and 731 (5.4%) moderately preterm. The corresponding proportions were 0.2%, 0.4% and 4.1%, respectively, in women without PCOS.Comparisons of maternal characteristics according to preterm severity are shown in Maternal characteristics in women with PCOS giving birth preterm compared to term are shown in Maternal PCOS was associated with a 43% higher risk of preterm birth . The association remained at the same level when we adjusted for maternal age, parity, smoking habits, country of birth and year of delivery  and marginally decreased when we added BMI into the model .In a sensitivity analysis, with adjustment for even infertility treatment (ovulation stimulation and other assisted reproduction treatment) in model 2, the association was slightly weaker .When the population was restricted to primiparous women, we found a similar association between PCOS and extremely preterm birth  as in the whole population . PresentAmong the 13 495 women with PCOS and information on onset of delivery, 623 (4.6%) had spontaneous preterm birth and 274 (2.0%) had medically indicated preterm birth. The corresponding numbers in women without PCOS (n = 1 028 547) were 34 649 (3.4%) for spontaneous preterm birth and 13 896 (1.4%) for medically indicated preterm birth. Of all the preterm deliveries (<37 weeks) with spontaneous onset (n = 35 272), 14 590 (41.4%) started with spontaneous rupture of membranes (PPROM).Maternal PCOS was associated with increased risk of both spontaneous and medically indicated preterm birth .For all analyses, excluding women with diabetic or hypertensive disease failed to affect any of the observed associations , particularly with spontaneous onset. This finding is of clinical importance, since the risks of infant morbidity and mortality increase with decreasing gestational age ,5.The main strength of the study was the large cohort, in which all singleton pregnancies in Sweden during the study period were included and enabled further stratification of the cohort. Another strength is the prospective collection of data. Earlier studies on the risk of preterm birth in women with PCOS are heterogeneous in their design when it comes to both study populations and confounders. Some studies include only women with PCOS undergoing assisted reproductive treatment ,24, thusAn important limitation is the low registered prevalence of PCOS. This is related to the incomplete reporting of women with PCOS to the Patient Register. In order for women to obtain a PCOS diagnosis, they had to have sought specialized medical care for their symptoms or infertility and women with no or low degree of symptoms will not seek care. This results in a proportion of the non-PCOS group represents women with PCOS but not diagnosed. This entails that our findings might be more relevant for women with severe form of PCOS. We expect however that the misclassified group is small compared to the whole non-PCOS group, and that the effect therefore will be marginal. Another reason to the low prevalence of PCOS in our population might be a selection bias, with inclusion only of women who are fertile and have given birth. Since PCOS is associated with infertility, the prevalence will be underestimated. A further limitation is that no information on PCOS phenotype was available, as it is not captured by ICD coding.A recent systematic review and meta-analysis , and a cEarlier studies on the risk of preterm birth in women with PCOS are heterogeneous in their design when it comes to both study populations and confounders. Some studies include only women undergoing assisted reproductive treatment ,24, thusWe found a positive association between PCOS and the more severe degrees of spontaneous preterm birth. Still, the mechanism causing preterm birth in women with PCOS is unknown. PCOS is associated with low-grade adipose-tissue-related systematic inflammation ,27, and Overweight and obesity are known risk factors for preterm birth , and womWhen we restricted our population from women with hypertensive and diabetic diseases, the association between PCOS and preterm birth was slightly weakened but remained significant. We can thus confirm that increased risk of medically indicated preterm birth is probably not caused by hypertensive and diabetic disease in women with PCOS. Further, when adjusting for even infertility treatment in the regression model, the estimate changed only marginally suggesting the association of PCOS and preterm birth is not fully explained by these factors either.Hyperandrogenism might also be an important predictor of preterm birth in women with PCOS . It has Women with PCOS are at more than a twofold increased risk of extremely preterm birth, compared to women without PCOS. The association was particularly strong for spontaneous onset of extremely preterm delivery, for which the risk was increased threefold. This can be important in antenatal risk assessment of preterm birth in women with PCOS. Future research is warranted to investigate the pathogenic mechanisms between PCOS and preterm birth.S1 Fig(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 TableRisk for severity of preterm birth in primiparous women giving birth in Sweden during 2005–2014 by PCOS diagnosis.(DOCX)Click here for additional data file.