Maternal Genitourinary Infections Research Articles

Association between maternal genitourinary infections and the risk of attention deficit hyperactivity disorder and autism spectrum disorder in children according to a systematic review

Introduction. Autism spectrum disorders and attention deficit hyperactivity disorder are among the most significant and widespread mental disorders that manifest in childhood and adolescence. Their etiology and pathogenesis have not been studied enough and most likely a complex of factors leads to their formation. Among other things, data are accumulating on the role of various hazards and diseases of the mother, which increase the risk of neuropsychiatric disorders in offspring. These include genitourinary infections, whose contribution to the development of autism spectrum disorders and attention deficit hyperactivity disorder has not yet been systematically studied.Aim. To establish the contribution of maternal genitourinary infections to the formation of autism spectrum disorders and attention deficit hyperactivity disorder in children.Materials and methods. An electronic search was conducted in the Scopus and Pubmed databases to obtain relevant literature by August 2022. The search strategy included a combination of keywords and MESH terms: urogenital infections, and autism, and autism spectrum disorders, and attention deficit hyperactivity disorder, and maternal infections.Results. On this topic 10 papers have been identified in the available literature – 6 on autism spectrum disorders and 4 on attention deficit hyperactivity disorder. In all the papers on attention deficit hyperactivity disorder included in the analysis, an association between genitourinary infections and neuropsychiatric disorders was revealed. In the case of autism spectrum disorders, the data obtained were more contradictory. The heterogeneity of the available data (different designs, different deficits and approaches to the diagnosis of genitourinary infections) did not allow for a meta-analysis.Conclusions. Genitourinary infections play a pathogenetic role in the formation of attention deficit hyperactivity disorder, while the effect of genitourinary infections on the development of autism spectrum disorders seems less unambiguous. It is necessary to continue work in this area with a more unified design to form practical recommendations for the prevention of neuropsychiatric disorders.

Maternal Prenatal Infections and Biliary Atresia in Offspring

Investigations into the association of antepartum maternal infections with the pathogenesis of biliary atresia (BA) in human offspring are insufficient. To examine the association between prenatal infections in mothers and the development of BA in their offspring. This population-based case-control study obtained administrative data from the Taiwan National Health Insurance Research Database with linkage to the Taiwan Maternal and Child Health Database, capturing demographic and medical information on nearly all 23 million of the Taiwan population. The cohort comprised 2 905 978 singleton live births among mother-infant dyads between January 1, 2004, and December 31, 2020, in Taiwan. The case group of infants with BA was identified from use of International Classification of Diseases diagnostic codes for BA and subsequent Kasai procedure or liver transplant. The control group was randomly selected from infants without BA, representing approximately 1 in 1000 study population. Data analyses were performed from May 1 to October 31, 2023. Prenatal maternal infections, including intestinal infection, influenza, upper airway infection, pneumonia, soft-tissue infection, and genitourinary tract infection. The main outcome was exposure to prenatal maternal infections. Inverse probability weighting analysis was performed by building a logistic regression model to estimate the probability of the exposure observed for a particular infant and using the estimated probability as a weight in subsequent analyses. The weighted odds ratio (OR) estimated by logistic regressions was then used to assess the risk of BA in offspring after prenatal maternal infections. Among the mother-infant dyads included, 447 infants with BA were cases (232 females [51.9%]) and 2912 infants without BA were controls (1514 males [52.0%]). The mean (SD) maternal age at childbirth was 30.7 (4.9) years. Offspring exposed to prenatal intestinal infection (weighted OR, 1.46; 95% CI, 1.17-1.82) and genitourinary tract infection (weighted OR, 1.22; 95% CI, 1.05-1.41) in mothers exhibited a significantly higher risk of BA. Furthermore, maternal intestinal infection (weighted OR, 6.05; 95% CI, 3.80-9.63) and genitourinary tract infection (weighted OR, 1.55; 95% CI, 1.13-2.11) that occurred during the third trimester were associated with an increased risk of BA in offspring. Results of this case-control study indicate an association between prenatal intestinal infection and genitourinary tract infection in mothers and BA occurrence in their offspring. Further studies are warranted to explore the underlying mechanisms of this association.

Neonatal Sepsis: Insight into Incidence, Classification, Risk Factors, Causative Organisms, Pathophysiology, Prognosis, Clinical Manifestations, Complications, Systemic Examination, and Treatment

Background: Neonatal sepsis is a clinical syndrome of bacteremia with systemic signs and is the most important cause of neonatal death in developing country. Mortality increase with delay in diagnosis and initiation of antibiotics. So, improvements in diagnosis and management of sepsis can significantly decrease the sepsis complications and improve its outcome. Objectives: The current review aims to high light on the incidence of neonatal sepsis, classification, risk factors, causative organisms, pathophysiology, prognosis, clinical manifestations, complications, systemic examination, and treatment. The incidence of neonatal sepsis varies among the different geographic areas, the highest being registered in Africa and Asia and the lowest in the U.S.A and Australia. The sepsis has been classified as early-onset sepsis (EOS) and the late-onset sepsis. Late-onset infections onset after 1 month of life, which occurs particularly in VLBW preterm infants or term infants requiring prolonged neonatal intensive care for other chronic problems. Neonatal sepsis includes maternal risk factors and neonatal risk factors. Septic or traumatic risk factors delivery, maternal poverty, pre-eclampsia, cardiac disease and diabetes mellitus are significant risk factors. Prolonged rupture of fetal membranes before the onset of labour, chorio-amnionitis, and maternal genitourinary tract infections have been significantly associated with a wide range of adverse perinatal and maternal outcomes, including miscarriage, stillbirth, preterm birth, fetal growth restriction, neonatal and puerperal sepsis, neonatal encephalopathy and neonatal and maternal mortality. Improvement in the socio-economic status of the population and availability of affordable antenatal care would reduce the incidence of neonatal septicemia. Amniocentesis, cervical cerclage, transcervical chorionic villus sampling, or percutaneous blood sampling, can permit entry of skin or vaginal organisms, causing amnionitis and secondary fetal infection. Infection of skin abrasions after use of obstetric forceps increases the risk of infection in neonates. Infant birth weight is inversely related to risk of early- onset sepsis. Prematurity and low birth weights are the most important neonatal factors predisposing to infection. Endotracheal intubation, insertion of an umbilical vessel catheter, or both, is associated with an increased risk of bacterial infection. Prolonged intravascular access and mechanical ventilation, the use of intravenous intralipids, and the duration of total parenteral nutrition are among the proposed risk factors associated with NICU-acquired coagulase- negative staphylococcus infections. Males have an approximately two-fold higher incidence of sepsis than females. Systemic antibiotics potentiate the overgrowth of certain organisms as Staphylococcus epidermidis. Corticosteroid treatment increases the risk of invasive candidiasis among premature infants. Hospital Acquired Infections are one of the leading causes of mortality and morbidity in (NICU). Group B Streptococcus (GBS) and E. coli as the dominant early onset sepsis (EOS) pathogens and coagulase- negative staphylococci (CONS) as the dominant late onset sepsis (LOS) pathogen followed by GBS and Staph aureus. In developing countries, Gram negative organisms are more common and are mainly represented by Klebsiella, E.coli and Pseudomonas of the Gram positive organisms, Staph aureus, CONS, Streptococcus pneumoniae, and Streptococcus pyogenes are most commonly isolated. Agents that commonly cause nosocomial infection are coagulase-negative staphylococci, gram-negative bacilli, Enterococci, and S. aureus. Causative organisms are bacterial, fungal, viral, and protozoal organism's infections. Mode of infection is prenatal, natal, and postnatal infections. Soon after birth, the newborns are exposed to the "hostile world" of bacteria, viruses, fungi and parasites, so they must immediately defend themselves. Necotizing enterocolitis, Neonatal thrombocytopenia, endophthalmitis, abdominal aortic-iliac thrombosis, fatal complete atrioventricular block, and wide range of signs and symptoms that may be observed in neonates with septicemia frequently suggest a number of alternative diagnoses. Identification of infection may be made by isolating the etiologic agent from a sterile body fluid (blood, CSF, and urine), or by demonstrating endotoxin or bacterial antigen in a body fluid. Investigations are including isolation of the microorganism, blood culture, urine culture, tracheal aspirate culture, isolation of organisms from CSF, complete blood cell count, cerebrospinal fluid analysis, C-Reactive protein, and tissue release of procalcitonin. Purpose of supportive care is to normalize the temperature, stabilize the cardiopulmonary status, correct hypoglycemia, and prevent bleeding tendency. Treatment of sepsis includes antibiotics, antiviral, antifungal, intravenous immunoglobulin, granulocyte transfusion, .......

Evaluation of Maternal Infection During Pregnancy and Childhood Leukemia Among Offspring in Denmark

Maternal infection is common during pregnancy and is an important potential cause of fetal genetic and immunological abnormalities. Maternal infection has been reported to be associated with childhood leukemia in previous case-control or small cohort studies. To evaluate the association of maternal infection during pregnancy with childhood leukemia among offspring in a large study. This population-based cohort study used data from 7 Danish national registries (including the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Cancer Registry, and others) for all live births in Denmark between 1978 and 2015. Swedish registry data for all live births between 1988 and 2014 were used to validate the findings for the Danish cohort. Data were analyzed from December 2019 to December 2021. Maternal infection during pregnancy categorized by anatomic locations identified from the Danish National Patient Registry. The primary outcome was any leukemia; secondary outcomes were acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Offspring childhood leukemia was identified in the Danish National Cancer Registry. Associations were first assessed in the whole cohort using Cox proportional hazards regression models, adjusted for potential confounders. A sibling analysis was performed to account for unmeasured familial confounding. This study included 2 222 797 children, 51.3% of whom were boys. During the approximately 27 million person-years of follow-up (mean [SD], 12.0 [4.6] years per person), 1307 children were diagnosed with leukemia (ALL, 1050; AML, 165; or other, 92). Children born to mothers with infection during pregnancy had a 35% increased risk of leukemia (adjusted hazard ratio [HR], 1.35 [95% CI, 1.04-1.77]) compared with offspring of mothers without infection. Maternal genital and urinary tract infections were associated with a 142% and 65% increased risk of childhood leukemia, with HRs of 2.42 (95% CI, 1.50-3.92) and 1.65 (95% CI, 1.15-2.36), respectively. No association was observed for respiratory tract, digestive, or other infections. The sibling analysis showed comparable estimates to the whole-cohort analysis. The association patterns for ALL and AML were similar to that for any leukemia. No association was observed for maternal infection and brain tumors, lymphoma, or other childhood cancers. In this cohort study of approximately 2.2 million children, maternal genitourinary tract infection during pregnancy was associated with childhood leukemia among offspring. If confirmed in future studies, our findings may have implications for understanding the etiology and developing preventive measures for childhood leukemia.

Reducing Birth Defects by Decreasing the Prevalence of Maternal Chronic Diseases-Evaluated by Linked National Registration Dataset.

Birth defects (BDs) are an important cause of abortion, stillbirth, and infant mortality that may cause lifelong disability. The defects can be caused by genetics, environmental exposure, or maternal chronic diseases. We conducted a study to analyze the association between maternal chronic diseases and BDs and to evaluate the effect of decreasing the prevalence of maternal chronic diseases on reducing BDs. The data of newborns and their mothers were concatenated and analyzed from three national population databases: the National Health Insurance Research Database, the Birth Certificate Application, and the Birth Registration Database in Taiwan during the period of 2005 to 2014. Codes 740-759 of the International Classification of Diseases 9th Revision-Clinical Modification (ICD-9-CM) were used as the diagnosis of BDs. The prevalence of BDs was 2.72%. Mothers with cardiovascular diseases, hypertension, anemia, genitourinary tract infections, renal diseases, neurotic or psychotic disorders, gestational diabetes mellitus (DM), and pregestational type 1 or type 2 DM had a significantly higher prevalence of BDs. The population attributable risk percent (PAR%) of BDs was 1.63%, 0.55%, 0.18%, 1.06%, 0.45%, 0.22%, 0.48%, and 0.24% for maternal hypertension, cardiovascular disease, renal disease, genitourinary infection, anemia, neurotic and psychotic disorders, gestational DM, and pregestational type 1 or type 2 DM, respectively. The percentage change (-1%, -5%, and -10% of prevalence in 2034 compared with the prevalence in 2005-2014) of maternal disease and the predicted number of live births was used to estimate the decrease in the number of newly diagnosed BDs in 2034. By using the middle-estimated number of live births in 2034, we predicted that the number of BDs would decrease by 302, 102, 33, 196, 83, 41, 89, and 44 with a -5% prevalence of maternal hypertension, cardiovascular disease, renal disease, genitourinary infection, anemia, neurotic and psychotic disorders, gestational DM, and pregestational type 1 or type 2 DM, respectively. We conclude that mothers with chronic diseases, including cardiovascular diseases, hypertension, anemia, genitourinary tract infections, renal diseases, neurotic or psychotic disorders, gestational DM, and pregestational type 1 or type 2 DM, have a significantly higher (p < 0.01) prevalence of having offspring with BDs. Mothers with chronic diseases are associated with BDs. It is very important to set up a policy to decrease the prevalence of these maternal chronic diseases; then, we can reduce the incidence of BDs.

Maternal urogenital infection and fetal heart functional assessment - what is the missing link?

Maternal urogenital infections during pregnancy are worldwide frequent problem. The aim was to analyze influence of maternal genitourinary infection on fetal cardiac function, pregnancy development and obstetrical outcomes. This was a single-center cohort study on fetuses (average at 28th week) in two groups: with maternal urogenital infections (study group n=49) and control group with no infections (n=59). Parvovirus B19, toxoplasmosis, cytomegalovirus, herpes simplex infections, congenital malformations, fetal growth restriction, chronic maternal diseases, as well as patients with body mass index (BMI) >25kg/m2 were excluded. We analyzed: maternal age, time of delivery, neonatal birth weight, Apgar scores, average time of hospitalization of newborns after birth and several fetal echocardiographic parameters. The only statistical differences was found for shorter isovolumetric relaxation time (IRT) (40±10 vs. 45±9; p=0.03) and longer ejection time (ET) [ms] for right ventricle (RV) (176±24 vs. 164±18; p=0.01). Thick placenta was observed more frequent in study group than in controls (36.7 vs. 16.9%; p= 0.02). The missing link for explanation of these findings was coincidence with thick placenta. This is probably the first observation suggesting that thick placenta (>5cm) may affect fetal RV function in normal heart anatomy: prolongation of right ventricular ET and shortening of fetal right ventricular IVRT.

Maternal infection during pregnancy and the risk of attention-deficit/hyperactivity disorder in the offspring: A systematic review and meta-analysis.

The effects of maternal infection during pregnancy on the risk of attention-deficit/hyperactivity disorder (ADHD) in the offspring are unclear, and no overview is available. We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. We found that that maternal infection during pregnancy was associated with a small increase in the risk of ADHD (OR 1.25, 95% CI 1.09, 1.44, P<0.0001; I2 = 92.9%, p<0.0001) in the offspring. In subgroup analyses, the association remained for maternal genitourinary (GU) infection (OR, 1.19, 1.12, 1.27, P<0.001; I2 = 0%; p=0.517). However, there was no significant association when we pooled data from siblings from other pregnancies (OR = 1.06, 95% CI, 0.99-1.13, P=0.084; I2 = 0%; p=0.859), implying that the association was due to confounding. The statistically significant association between maternal infection during pregnancy and ADHD in the offspring can be partially explained by unmeasured confounding.

Risk Factors for Neonatal Sepsis in Lubumbashi, Democratic Republic of Congo: A Retrospective Case-Control Study

Background: Neonatal Sepsis (NS) is a major cause of neonatal morbidity and mortality, particularly in developing countries. Delays in the identification and treatment of NS are the main contributors to the high mortality. This study aims to identify risk factors for NS in newborns in the two university hospitals in Lubumbashi, in the Democratic Republic of Congo. Methods: This hospital-based case-control study was carried out on 486 mother-newborn pairs using the systematic sampling method during November 2019 to October 2020. Data were analyzed using STATA software (version 15). Binary and multivariable logistic regression analyses were computed to identify the associated factors at 95% CI. Results: A total of 162 cases and 324 controls were included in this study. Multiple logistic regression analysis showed that the possible risk factors for NS in this study were low level of education (AOR=9.16 [2.23-37.67]), maternal genitourinary tract infections (AOR=42.59 [17.90-101.37]), premature rupture of membranes (AOR=19.95 [7.27-54.76]), peripartum fever (AOR=26.25 [2.31-297.83]), prolonged labor (AOR=14.16 [3.88-51.71]), cesarean section (AOR=3.57 [1.48-8.61]), obstructed vaginal delivery (AOR=13.40 [1.32- 136.19]), birth weight &lt;1500 grams (AOR=70.38 [8.64-572.95]), and between 1500-2500 grams (AOR=7.90 [3.04-20.52]). Conclusion: The study found that maternal and neonatal factors were strongly associated with the risk of developing NS. The present study suggests the possibility of routine assessment of sepsis in newborns born with the above characteristics.

Mycoplasma hominis meningitis in an extremely preterm newborn: a case report

BackgroundMycoplasma Hominis is a micro-organism which is a part of the human genitourinary tract flora. Neonates are susceptible to acquire this pathogen either in utero or through vertical transmission. In rare cases, it may cause central nervous system infections with severe morbidity and mortality in preterm and term neonates.Case presentationWe present a case of Mycoplasma Hominis meningitis in an extremely preterm neonate who presented with lethargy, tachycardia and seizures on day 7 of life. There was no history of maternal systemic or genitourinary infection during pregnancy and at the time of delivery. Empirical antibiotic therapy for neonatal meningitis was commenced after sending blood and cerebrospinal fluid cultures. Cerebrospinal fluid analysis showed pleocytosis with neutrophilic predominance, but no bacteria was identified on gram staining. Blood culture yielded no growth of any bacterial pathogen. However, growth of Mycoplasma Hominis was suspected in cerebrospinal fluid culture which was confirmed by 16S ribosomal ribonucleic acid (RNA) polymerase chain reaction analysis. Subsequently, antibiotics were changed to Moxifloxacin and Doxycycline which were given for a total duration of 6 weeks. Multiple cerebrospinal fluid cultures were performed during this treatment. No growth of any pathogen was identified on any of these cerebrospinal fluid cultures.ConclusionsWe report a rare case of Mycoplasma Hominis meningitis in an extremely preterm neonate which was successfully treated with a combination therapy of Moxifloxacin and Doxycycline.It is important to consider the possibility of Mycoplasma Hominis meningitis in neonates who present with clinical signs and pleocytosis in cerebrospinal fluid but negative gram staining and no growth on conventional culture media.

Эффективность и безопасность использования препарата на основе рекомбинантного интерферона α-2b в комплексе с антиоксидантами (витаминами Е и С) у новорожденных, в том числе недоношенных детей, для лечения и профилактики инфекций вирусной и бактериальной этиологии (результаты мета-анализа)

The article presents the results of a systematic review and meta-analysis of studies assessing the efficacy and safety of the drug based on recombinant interferon α-2b in combination with antioxidants (vitamins C and E) in newborns, including premature infants, for the treatment and prevention of infections of viral and bacterial etiology. A positive effect of the drug on clinical manifestations and disease outcomes was shown, which was demonstrated by symptoms relief; reduced length of stay; reduced duration of intensive and antibacterial therapy, parenteral nutrition, artificial lung ventilation, hemo- and plasma transfusions, length of stay in the intensive care unit and neonatal pathology; elimination of pathogens; prevention of contamination by other pathogens; reduced risk of the mother-to-child pathogen transmission; decreased mortality rate (by 3 times); improvement of hemo- and immunogram: activation of a Th1-type immune response and phagocytosis system, normalization of serum immunoglobulin levels, pro/anti-inflammatory cytokines and endogenous interferon system, as well as non-infectious pathology (fetal growth restriction, birth asphyxia, fetal hypoxia, morphofunctional immaturity). The prophylactic effect of the drug was noted, which significantly reduced the incidence of intrauterine fetal infection caused by maternal genitourinary infections, preventing the development of congenital pneumonia and severe forms of the disease. No adverse effects or reactions were observed in all studies. Key words: pregnancy, viral and bacterial infections in newborns, congenital pneumonia, interferon α-2b, antioxidants, perinatal pathology, genitourinary infections, intrauterine infection

Risk factors for neonatal sepsis in Lubumbashi, Democratic Republic of Congo: A retrospective case-control study

Purpose: Neonatal sepsis (NS) is a major cause of neonatal morbidity and mortality, particularly in developing countries. Delays in the identification and treatment of NS are the main contributors to the high mortality. This study aims to identify risk factors for NS in newborns in the two university hospitals in Lubumbashi, in the Democratic Republic of Congo. Methods: This hospital-based case-control study was carried out on 486 mother-newborn pairs using the systematic sampling method during November 2019 to October 2020. Data were analyzed using STATA software (version 15). Binary and multivariable logistic regression analyses were computed to identify the associated factors at 95% CI. Results: A total of 162 cases and 324 controls were included in this study. Multiple logistic regression analysis showed that the possible risk factors for NS in this study were low level of education (AOR = 9.16 [2.23-37.67]), maternal genitourinary tract infections (AOR = 42.59 [17.90-101.37]), premature rupture of membranes (AOR = 19.95 [7.27-54.76]), peripartum fever (AOR = 26.25 [2.31-297.83]), prolonged labor (AOR = 14.16 [3.88-51.71]), cesarean section (AOR = 3.57 [1.48-8.61]), obstructed vaginal delivery (AOR = 13.40 [1.32-136.19]), birth weight &lt;1500 grams (AOR = 70.38 [8.64-572.95]), and between 1500-2500 grams (AOR = 7.90 [3.04-20.52]). Conclusion: The study found that maternal and neonatal factors were strongly associated with the risk of developing NS. The present study suggests the possibility of routine assessment of sepsis in newborns born with the above characteristics.

Maternal genitourinary infections and poor nutritional status increase risk of preterm birth in Gasabo District, Rwanda: a prospective, longitudinal, cohort study

BackgroundPreterm birth (PTB) is a leading cause of early childhood mortality and morbidity, including long-term physical and mental impairment. The risk factors for PTB are complex and include maternal nutritional status and infections. This study aimed to identify potentially modifiable risk factors for targeted interventions to reduce the occurrence of PTB in Rwanda.MethodsWe conducted a prospective, longitudinal cohort study of healthy pregnant women aged 18 to 49 years. Women at 9–15 gestational weeks were recruited from 10 health centers in Gasabo District, Kigali Province between September and October 2017. Pregnancy age was estimated using ultrasonography and date of last menstruation. Anthropometric and laboratory measurements were performed using standard procedures for both mothers and newborns. Surveys were administered to assess demographic and health histories. Categorical and continuous variables were depicted as proportions and means, respectively. Variables with p < 0.25 in bivariate analyses were included in multivariable logistic regression models to determine independent predictors of PTB. The results were reported as odds ratios (ORs) and 95% confidence intervals (CI), with statistical significance set at p < 0.05.ResultsAmong 367 participants who delivered at a mean of 38.0 ± 2.2 gestational weeks, the overall PTB rate was 10.1%. After adjusting for potential confounders, we identified the following independent risk factors for PTB: anemia (hemoglobin < 11 g/dl) (OR: 4.27; 95%CI: 1.85–9.85), urinary tract infection (UTI) (OR:9.82; 95%CI: 3.88–24.83), chlamydia infection (OR: 2.79; 95%CI: 1.17–6.63), inadequate minimum dietary diversity for women (MDD-W) score (OR:3.94; CI: 1.57–9.91) and low mid-upper arm circumference (MUAC) < 23 cm (OR: 3.12, 95%CI; 1.31–7.43). indicators of nutritional inadequacy (low MDD-W and MUAC) predicted risk for low birth weight (LBW) but only UTI was associated with LBW in contrast with PTB.ConclusionTargeted interventions are needed to improve the nutritional status of pregnant women, such as maternal education on dietary diversity and prevention of anemia pre-pregnancy. Additionally, prevention and treatment of maternal infections, especially sexually transmitted infections and UTIs should be reinforced during standard antenatal care screening which currently only includes HIV and syphilis testing.

245: Maternal genitourinary and wound infections: Early postpartum readmissions and emergency department visits

245: Maternal genitourinary and wound infections: Early postpartum readmissions and emergency department visits

Risk of gastroschisis with maternal genitourinary infections: the US National birth defects prevention study 1997–2011

ObjectiveTo assess the association between occurrence and timing of maternal self-reported genitourinary tract infection (urinary tract infections [UTIs] and/or sexually transmitted infection [STI]) and risk for gastroschisis in the offspring.DesignPopulation-based...

Effect of population-based antenatal screening and treatment of genitourinary tract infections on birth outcomes in Sylhet, Bangladesh (MIST): a cluster-randomised clinical trial.

SummaryBackgroundOne-third of preterm births are attributed to pregnancy infections. We implemented a community-based intervention to screen and treat maternal genitourinary tract infections, with the aim of reducing the incidence of preterm birth.MethodsWe did an unblinded cluster-randomised controlled trial in two subdistricts of Sylhet, Bangladesh. Clusters were defined as the contiguous area served by a single community health worker, and each cluster comprised several contiguous villages, contained roughly 4000 people, and had about 120 births per year. Eligible participants within clusters were all ever-married women and girls of reproductive age (ie, aged 15–49 years) who became pregnant during the study period. Clusters were randomly assigned (1:1) to the intervention or control groups via a restricted randomisation procedure. In both groups, community health workers made home visits to identify pregnant women and girls and provide antenatal and postnatal care. Between 13 and 19 weeks' gestation, participants in the intervention group received home-based screening for abnormal vaginal flora and urinary tract infections. A random 10% of the control group also received the intervention to examine the similarity of infection prevalence between groups. If present, abnormal vaginal flora (ie, Nugent score ≥4 was treated with oral clindamycin (300 mg twice daily for 5 days) and urinary tract infections with cefixime (400 mg once daily for 3 days) or oral nitrofurantoin (100 mg twice daily for 7 days). Both infections were retreated if persistent. The primary outcome was the incidence of preterm livebirths before 37 weeks' gestation among all livebirths. This trial is registered with ClinicalTrials.gov, number NCT01572532. The trial is closed to new participants, with follow-up completed.FindingsBetween Jan 2, 2012, and July 28, 2015, 9712 pregnancies were enrolled (4840 in the intervention group, 4391 in the control group, and 481 in the control subsample). 3818 livebirths in the intervention group and 3557 livebirths in the control group were included in the primary analysis. In the intervention group, the prevalence of abnormal vaginal flora was 16·3% (95% CI 15·1–17·6) and that of urinary tract infection was 8·6% (7·7–9·5). The effective coverage of successful treatment in the intervention group was 58% in participants with abnormal vaginal flora (ie, abnormal vaginal flora resolved in 361 [58%] of the 622 participants who initially tested positive), and 71% in those with urinary tract infections (ie, resolution in 224 [71%] of the 317 participants who initially tested positive). Overall, the incidence of preterm livebirths before 37 weeks' gestation did not differ significantly between the intervention and control groups (21·8% vs 20·6%; relative risk 1·07 [95% CI 0·91–1·24]).InterpretationA population-based antenatal screening and treatment programme for genitourinary tract infections did not reduce the incidence of preterm birth in Bangladesh.FundingEunice Kennedy Shriver National Institute of Child Health and Human Development and Saving Lives at Birth Grand Challenges.

Maternal genitourinary infections and risk of birth defects in the National Birth Defects Prevention Study.

Genitourinary infections (GUIs) are common among sexually active women. Yet, little is known about the risk of birth defects associated with GUIs. Using data from the National Birth Defects Prevention Study, a multisite, population-based, case-control study, we assessed self-reported maternal GUIs in the month before through the third month of pregnancy (periconception) from 29,316 birth defect cases and 11,545 unaffected controls. We calculated odds ratios (ORs) and 95% confidence intervals to estimate the risk of 52 major structural birth defects associated with GUIs. We also calculated risk of birth defects associated with each type of GUI: urinary tract infection (UTI) and sexually transmitted infection (STI). In our analysis, 10% (n = 2,972) of case and 9% (n = 1,014) of control mothers reported a periconceptional GUI. A GUI was significantly associated with 11 of the 52 birth defects examined (ORs ranging from 1.19 to 2.26): encephalocele, cataracts, cleft lip, esophageal atresia, duodenal atresia/stenosis, small intestinal atresia/stenosis, colonic atresia/stenosis, transverse limb deficiency, conoventricular septal defect, atrioventricular septal defect, and secundum atrial septal defect. A periconceptional UTI was significantly associated with nine birth defects (ORs from 1.21 to 2.48), and periconceptional STI was significantly associated with four birth defects (ORs ranging from 1.63 to 3.72). While misclassification of GUIs in our analysis is likely, our findings suggest GUIs during the periconceptional period may increase the risk for specific birth defects.

Fever and infections during pregnancy and psychosis-like experiences in the offspring at age 11. A prospective study within the Danish National Birth Cohort.

Maternal exposures to fever and infections in pregnancy have been linked to subsequent psychiatric morbidity in the child. This study examined whether fever and common infections in pregnancy were associated with psychosis-like experiences (PLEs) in the child. A longitudinal study of 46 184 children who participated in the 11-year follow-up of the Danish National Birth Cohort was conducted. Pregnant women were enrolled between 1996 and 2002 and information on fever, genitourinary infections, respiratory tract infection, and influenza-like illness during pregnancy was prospectively collected in two interviews during pregnancy. PLEs were assessed using the seven-item Adolescent Psychotic-Like Symptom Screener in a web-based questionnaire completed by the children themselves at age 11. PLEs were reported among 11% of the children. Multinomial logistic regression models with probability weights to adjust for potential selection bias due to attrition suggested that maternal fever, genitourinary infections and influenza-like illness were associated with a weak to moderate increased risk of subclinical psychosis-like symptoms in the offspring, whereas respiratory tract infections were not. No clear pattern was observed between the strengths of the associations and the timing of exposure, or the type of psychosis-like symptom. In this study, maternal exposures to fevers and common infections in pregnancy were generally associated with a subtle excess risk of PLEs in the child. A more pronounced association was found for influenza-like illness under an a priori definition, leaving open the possibility that certain kinds of infections may constitute important risk factors.

Risk Factors for Preterm Birth and Low Birth Weight Among Pregnant Indian Women: A Hospital-based Prospective Study

Objectives:The present study was undertaken to study the maternal risk factors for preterm birth (PTB) and low birth weight (LBW) with a special emphasis on assessing the proportions of maternal genitourinary and periodontal infections among Indian women and their association with adverse pregnancy outcomes.Methods:A hospital-based prospective study comprising 790 pregnant women visiting the obstetrics clinic for a routine antenatal check-up was undertaken. Once recruited, all study participants underwent clinical and microbiological investigations for genitourinary infections followed by a dental check-up for the presence of periodontitis. The study participants were followed up until their delivery to record the pregnancy outcomes. Infectious and non-infectious risk factors for PTB and LBW were assessed using univariate and multivariate Cox regression analysis. Independent risk factors for PTB and LBW were reported in terms of adjusted relative risk (ARR) with the 95% confidence interval (CI).Results:Rates of PTB and LBW in the study population were 7.6% and 11.4%, respectively. Previous preterm delivery (ARR, 5.37; 95% CI, 1.5 to 19.1), periodontitis (ARR, 2.39; 95% CI, 1.1 to 4.9), Oligohydramnios (ARR, 5.23; 95% CI, 2.4 to 11.5), presence of Nugent’s intermediate vaginal flora (ARR, 2.75; 95% CI, 1.4 to 5.1), gestational diabetes mellitus (ARR, 2.91; 95% CI, 1.0 to 8.3), and maternal height <1.50 m (ARR, 2.21; 95% CI, 1.1 to 4.1) were risk factors for PTB, while periodontitis (ARR, 3.38; 95% CI, 1.6 to 6.9), gestational hypertension (ARR, 3.70; 95% CI, 1.3 to 10.8), maternal height <1.50 m (ARR, 2.66; 95% CI, 1.3 to 5.1) and genital infection during later stages of pregnancy (ARR, 2.79; 95% CI, 1.2 to 6.1) were independent risk factors for LBW.Conclusions:Our study findings underscore the need to consider screening for potential genitourinary and periodontal infections during routine antenatal care in developing countries.

Screening and treatment of maternal genitourinary tract infections in early pregnancy to prevent preterm birth in rural Sylhet, Bangladesh: a cluster randomized trial.

BackgroundApproximately half of preterm births are attributable to maternal infections, which are commonly undetected and untreated in low-income settings. Our primary aim is to determine the impact of early pregnancy screening and treatment of maternal genitourinary tract infections on the incidence of preterm live birth in Sylhet, Bangladesh. We will also assess the effect on other adverse pregnancy outcomes, including preterm birth (stillbirth and live birth), late miscarriage, maternal morbidity, and early onset neonatal sepsis.Methods/DesignWe are conducting a cluster randomized controlled trial that will enroll 10,000 pregnant women in Sylhet district in rural northeastern Bangladesh. Twenty-four clusters, each with ~4000 population (120 pregnant women/year) and served by a community health worker (CHW), are randomized to: 1) the control arm, which provides routine antenatal and postnatal home-based care, or 2) the intervention arm, which includes routine antenatal and postnatal home-based care plus screening and treatment of pregnant women between 13 and 19 weeks of gestation for abnormal vaginal flora (AVF) and urinary tract infection (UTI). CHWs conduct monthly pregnancy surveillance, make 2 antenatal and 4 postnatal home visits for all enrolled pregnant women and newborns, and refer mothers or newborns with symptoms of serious illness to the government sub-district hospital. In the intervention clusters, CHWs perform home-based screening of AVF and UTI. Self-collected vaginal swabs are plated on slides, which are Gram stained and Nugent scored. Women with AVF (Nugent score ≥4) are treated with oral clindamycin, rescreened and retreated, if needed, after 3 weeks. Urine culture is performed and UTI treated with nitrofurantoin. Repeat urine culture is performed after 1 week for test of cure. Gestational age is determined by maternal report of last menstrual period at study enrollment using prospectively completed study calendars, and in a subset by early (<20 week) ultrasound. CHWs prospectively collect data on all pregnancy outcomes, maternal and neonatal morbidity and mortality.Implications/DiscussionFindings will enhance our understanding of the burden of AVF and UTI in rural Bangladesh, the impact of a maternal screening-treatment program for genitourinary tract infections on perinatal health, and help formulate public health recommendations for infection screening in pregnancy in low-resource settings.Trial registrationThe study was registered on ClinicalTrials.gov:NCT01572532 on December 15, 2011. The study was funded by NICHD: R01HD066156.

BQ-123 prevents LPS-induced preterm birth in mice via the induction of uterine and placental IL-10

Preterm birth (PTB), defined as any delivery occurring prior to the completion of 37weeks' gestation, currently accounts for 11–12% of all births in the United States. Maternal genito-urinary infections account for up to 40% of all PTBS and induce a pro-inflammatory state in the host. The potent vasoconstrictor Endothelin-1 (ET-1) is known to be upregulated in the setting of infection, and elicits its effect by binding to the ETA receptor. We have previously shown that antagonism of the ETA receptor with BQ-123 is capable of preventing LPS-induced PTB in mice. We hypothesize that the administration of BQ-123 post LPS exposure will dismantle a positive feedback loop observed with pro-inflammatory cytokines upstream of ET-1. On GD 15.5, pregnant C57BL/6 mice were injected with PBS, LPS, BQ-123, or LPS+BQ-123. Changes at both the level of transcription and translation were observed in uterus and placenta in the ET-1 axis and in pro- and anti-inflammatory cytokines over the course of 12h. We discovered that BQ-123, when administered 10h post LPS, is capable of increasing production of uterine and placental Interleukin-10, causing a shift away from the pro-inflammatory state. We also observed that antagonism of the ETA receptor decreased IL-1β and TNFα in the placenta while also decreasing transcription of ET-1 in the uterus. Our results reinforce the role of ET-1 at the maternal fetal interface and highlight the potential benefit of ETA receptor blockade via the suppression of ET-1, and induction of a Th2 cytokine dominant state.