A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants.

BACKGROUND: The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. RESULTS: As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. CONCLUSIONS: This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. TRIAL REGISTRATION: The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011.

Incidence and Persistence of High-risk Anogenital Human Papillomavirus Infection Among Female Youth With and Without Perinatally Acquired Human Immunodefiency Virus Infection: A 3-year Observational Cohort Study.

BACKGROUND: Female youth with perinatally acquired human immunodeficiency virus (PHIV) may be at higher risk than uninfected youth for persistent anogenital human papillomavirus (HPV) infection, due to prolonged immunodeficiency. METHODS: A 3-year cohort study was conducted between 2013 and 2017 among Thai and Vietnamese PHIV and HIV-uninfected females 12-24 years, matched by age group and number of lifetime sexual partners. For HPV genotyping, cervical and anal samples were obtained at baseline and annually. Vaginal samples were collected at baseline and every 6 months. Factors associated with high-risk HPV (HR-HPV) persistence and incidence were assessed. RESULTS: We enrolled 93 PHIV and 99 HIV-uninfected females. Median age was 19 (interquartile range [IQR] 18-20) years. For the 7 HR-HPV types (16, 18, 31, 33, 45, 52, 58) in the nonavalent HPV vaccine, PHIV had significantly higher incidence (P = .03) and persistence (P = .01) than HIV-uninfected youth over a 3-year period. Having HIV (adjusted hazard ratio [aHR] 2.1, 95% confidence interval [CI] 1.1-3.9) and ever using illegal substances (aHR 4.8, 95% CI 1.8-13.0) were associated with incident 7 HR-HPV infections. HIV-positive status (adjusted prevalence ratio [aPR] 2.2, 95% CI 1.5-3.2), recent alcohol use (aPR 1.75, 95% CI 1.2-2.5), and higher number of lifetime partners (aPR 2.0, 95% CI 1.4-3.1, for 3-5 partners; aPR 1.93, 95% CI 1.2-3.2, for ≥6 partners) were significantly associated with persistent 7 HR-HPV infections. CONCLUSIONS: Female PHIV were at higher risk of having anogenital HR-HPV acquisition and persistence. Primary and secondary prevention programs for HPV infection and HPV-related diseases should be prioritized for PHIV children and youth.

Gaps in the elimination of congenital syphilis in a tertiary care center in Thailand.

BACKGROUND: The World Health Organization has set a goal to eliminate mother-to-child transmission of syphilis to a target of <50 cases per 100 000 live births. This study aimed to determine the rate of congenital syphilis and identify gaps in prevention. METHODS: A retrospective chart review was conducted in a tertiary care center in Bangkok, Thailand. The study included all pregnant women with positive syphilis serology and their infants. All congenital syphilis cases were categorized according to Centers for Disease Control criteria. RESULTS: From 2013 to 2017, 69 syphilis-infected pregnant women were included, with 30 congenital syphilis cases. The rate of congenital syphilis was 115 cases (95% CI 78-164) per 100 000 live births. The median (interquartile range) maternal age was 21 (18-32) years and 12 (17%) women had human immunodeficiency virus co-infection. Regarding maternal treatment, 28 (41%) women had inadequate treatment due to 13 cases (19%) of late or no antenatal care, six cases (8%) of recent infection near delivery, five cases (7%) of failure of treatment provision, and four (6%) others. There were three syphilitic stillbirths who were prematurely born to untreated pregnant women and 67 live births (one set of twins) of which 27 met definitions of probable congenital syphilis. They received complete treatment with penicillin and had non-reactive rapid plasma reagin within the first 6 months of life, with the exception of one who had non-reactive rapid plasma reagin at the age of 7 months. CONCLUSIONS: Congenital syphilis remains a problem in our setting. Nearly half of pregnant women who had syphilis had inadequate treatment. There is an urgent need to strengthen diagnosis and the treatment cascade of syphilis during antenatal care.

Risk Factors for Human Papillomavirus Infection and Abnormal Cervical Cytology Among Perinatally Human Immunodeficiency Virus-Infected and Uninfected Asian Youth.

Background: Infection with high-risk human papillomavirus (HR-HPV) may be higher in perinatally human immunodeficiency virus (HIV)-infected (PHIV) than HIV-uninfected (HU) adolescents because of long-standing immune deficiency. Methods: PHIV and HU females aged 12-24 years in Thailand and Vietnam were matched by age group and lifetime sexual partners. At enrollment, blood, cervical, vaginal, anal, and oral samples were obtained for HPV-related testing. The Wilcoxon and Fisher exact tests were used for univariate and logistic regression for multivariate analyses. Results: Ninety-three PHIV and 99 HU adolescents (median age 19 [18-20] years) were enrolled (June 2013-July 2015). Among PHIV, 94% were currently receiving antiretroviral therapy, median CD4 count was 593 (392-808) cells/mm3, and 62% had a viral load <40 copies/mL. Across anogenital compartments, PHIV had higher rates of any HPV detected (80% vs 60%; P = .003) and any HR-HPV (60% vs 43%, P = .02). Higher proportions of PHIV had abnormal Pap smears (eg, atypical squamous cells of unknown significance [ASC-US], 12% vs 14%; low-grade squamous intraepithelial neoplastic lesions, 19% vs 1%). After adjusting for ever being pregnant and asymptomatic sexually transmitted infections (STI) at enrollment, PHIV were more likely to have HR-HPV than HU (odds ratio, 2.02; 95% confidence interval, 1.09-3.77; P = .03). Conclusions: Perinatal HIV infection was associated with a higher risk of HR-HPV and abnormal cervical cytology. Our results underscore the need for HPV vaccination for PHIV adolescents and for prevention and screening programs for HPV and other STIs.

Use of copper intrauterine device is not associated with higher bacterial vaginosis prevalence in Thai HIV-positive women.

The study assessed and compared bacterial vaginosis (BV) prevalence in Thai women in reproductive age in four study groups - group 1, HIV-positive with copper intrauterine device (Cu-IUD); group 2, HIV-positive without Cu-IUD; group 3, HIV-negative with Cu-IUD; and group 4, HIV-negative without Cu-IUD. We conducted a cross-sectional study. BV prevalence was assessed by Nugent score and Amsel criteria. Descriptive statistics was used to present baseline characteristics; kwallis rank test - to compare variables between the four groups; logistic regression - to assess factors, related to BV prevalence. The analysis included 137 women in the four study groups with a median age of 39 years. Median BV prevalence by Nugent score was 45%, intermediate vaginal flora - 7% and normal vaginal flora - 48%. There was no statistically significant difference in the BV prevalence between the four study groups, p = 0.711. Threefold lower BV prevalence was found, assessed by Amsel criteria compared to Nugent score. Women with body mass index (BMI) < 20 had higher probability to have BV or intermediate vaginal flora, OR = 3.11, 95% CI (1.2-8.6), p = 0.025. The study found a high BV prevalence in the four study groups, related neither to HIV status, nor to Cu-IUD use. BV prevalence was associated only with low BMI. Thus, Cu-IUD could be a good contraceptive choice for HIV-positive women. Research in defining normal vaginal microbiota and improve diagnostic methods for BV should continue.

Effect of Synbiotic on the Gut Microbiota of Cesarean Delivered Infants: A Randomized, Double-blind, Multicenter Study.

We determined the effect of short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V on the gut microbiota of cesarean-born infants. Infants were randomized to receive a standard formula (control), the same with scGOS/lcFOS and B. breve M-16V (synbiotic), or with scGOS/lcFOS (prebiotic) from birth until week 16, 30 subjects born vaginally were included as a reference group. Synbiotic supplementation resulted in a higher bifidobacteria proportion from day 3/5 (P < 0.0001) until week 8 (P = 0.041), a reduction of Enterobacteriaceae from day 3/5 (P = 0.002) till week 12 (P = 0.016) compared to controls. This was accompanied with a lower fecal pH and higher acetate. In the synbiotic group, B. breve M-16V was detected 6 weeks postintervention in 38.7% of the infants. This synbiotic concept supported the early modulation of Bifidobacterium in C-section born infants that was associated with the emulation of the gut physiological environment observed in vaginally delivered infants.

Performance of Chemiluminescent Microparticle Immunoassay in Screening for Syphilis in Pregnant Women from Low-Prevalence, Resource-Limited Setting.

OBJECTIVE: This study evaluated the diagnostic performance of chemiluminescent microparticle immunoassay (CMIA) in screening for syphilis in Asian pregnant women. MATERIAL AND METHOD: This study retrospectively reviewed the CMA results of pregnant women attending the antenatal care clinic, King Chulalongkorn Memorial Hospital. Women with reactive CMA results were extracted from the laboratory database and further analyzed. A reactive/positive result for Treponema pallidum was defined as having a sample/cut-off absorbance ratio of ≥ 1.0. Samples were also tested by rapid plasma reagin (RPR) and Treponema pallidum particle agglutination assay (TPPA). RESULTS: From February 2011 to January 2013, a total of 11,640 pregnant women were tested and 65 women (0.56%) had reactive CMIA results. Among these cases, 58 women (89.2%) had non-reactive RPR results. TPPA were non-reactive in 35 women (60.3%) who had non-reactive RPR results. A total of 23 women (39.7%) with RPR non-reactive and TPPA reactive results; therefore, the prevalence rate of syphilis in this population was estimated as 1.98 per 1,000 pregnant women. Among this, 7 cases had a history of past, partial treatment for syphilis and 16 cases were considered as untreated, late, latent syphilis. If RPR tests were used as the screening test, 16/23 cases (69.6%) cases with untreated syphilis would be missed. CONCLUSION: Even though CMIA has high false positive results, however it is still recommended that this reverse sequence screening be used instead of the traditional algorithm. The rate of false positive results can be decreased by adjusting the sample/cut-off absorbance ratio of CMIA.

Low uptake of HIV testing and no HIV positivity in stable serodiscordant heterosexual partners of long-term treated HIV-infected Thais.

The objective of this study was to characterize HIV-serodiscordant heterosexual couples and to evaluate acceptance for HIV testing and HIV prevalence in nonindex partners. We conducted a cross-sectional study with quantitative and qualitative components. Two cohorts of 1767 HIV-positive people were screened to identify heterosexual HIV-serodiscordant couples. HIV-positive partners (index) were administered a questionnaire; CD4, viral load (VL), and antiretroviral therapy (ART) history were gathered from clinical records. HIV-negative/unknown status partners (nonindex) were invited for a similar questionnaire and HIV testing. In-depth interviews with three HIV-serodiscordant couples were conducted. Two hundred and ninety-seven index partners agreed to enroll in this study. The median duration of the relationship was 10 years, and 81% were sexually active. All but two index partners were on ART, and 98% had VL < 1000 copies/mL. Only 111 (37%) nonindex partners came for HIV testing, and all of them tested HIV-negative. In addition, only 41% of nonindex partners had HIV testing in the last one year. The main reasons for the nonindex partners not to come for HIV testing were "no interest" (n = 117, 63%) and "nondisclosure of HIV status" (n = 46, 25%). The latter was substantiated and explained by the qualitative outcome of this study, suggesting relation to stigma against HIV-positive people. Our results support the WHO recommendation for starting ART for treatment and prevention in HIV-serodiscordant couples at any CD4 count. Furthermore, we recommend the dissemination of data showing that no HIV transmission in heterosexual couples through sex practice has been observed provided VL is suppressed. This could be a powerful tool for effective fight against stigma and self-stigma in people living with HIV.

Prophylactic oral betamimetics for reducing preterm birth in women with a twin pregnancy.

BACKGROUND: Twin pregnancies are associated with a high risk of neonatal mortality and morbidity due to an increased rate of preterm birth. Betamimetics can decrease contraction frequency or delay preterm birth in singleton pregnancies by 24 to 48 hours. The efficacy of oral betamimetics in women with a twin pregnancy is unproven. OBJECTIVES: To assess the effectiveness of prophylactic oral betamimetics for the prevention of preterm labour and birth for women with twin pregnancies. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (21 September 2015), MEDLINE (January 1966 to 31 July 2015), EMBASE (January 1985 to 31 July 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials in twin pregnancies comparing oral betamimetics with placebo or any intervention with the specific aim of preventing preterm birth. Quasi-randomised controlled trials, cluster-randomised trials and cross-over trials were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two authors assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: Overall, the quality of evidence is low for the primary outcomes. All of the included trials had small numbers of participants and few events. Preterm birth, the most important primary outcome, had wide confidence intervals crossing the line of no effect.Six trials (374 twin pregnancies) were included, but only five trials (344 twin pregnancies) contributed data. All trials compared oral betamimetics with placebo.Betamimetics reduced the incidence of preterm labour (two trials, 194 twin pregnancies, risk ratio (RR) 0.37; 95% confidence interval (CI) 0.17 to 0.78; low quality evidence). However, betamimetics did not reduce prelabour rupture of membranes (one trial, 144 twin pregnancies, RR 1.42; 95% CI 0.42 to 4.82; low quality evidence), preterm birth less than 37 weeks' gestation (four trials, 276 twin pregnancies, RR 0.85; 95% CI 0.65 to 1.10; low quality evidence), or less than 34 weeks' gestation (one trial, 144 twin pregnancies, RR 0.47; 95% CI 0.15 to 1.50; low quality evidence). Mean neonatal birthweight in the betamimetic group was significantly higher than in the placebo group (three trials, 478 neonates, mean difference 111.22 g; 95% CI 22.21 to 200.24). Nevertheless, there was no evidence of an effect of betamimetics in reduction of low birthweight (two trials, 366 neonates, average RR 1.19; 95% CI 0.77 to 1.85, random-effects), or small-for-gestational age neonates (two trials, 178 neonates, average RR 0.90; 95% CI 0.41 to 1.99, random-effects). Two trials showed that betamimetics significantly reduced the incidence of respiratory distress syndrome (388 neonates, RR 0.30; 95% CI 0.12 to 0.77), but the difference was not significant when the analysis was adjusted to account for the non-independence of twins (194 twins, RR 0.35; 95% CI 0.11 to 1.16). Three trials showed no evidence of an effect of betamimetics in reducing neonatal mortality, either with the unadjusted analysis, assuming twins are completely independent of each other (452 neonates, average RR 0.90; 95% CI 0.15 to 5.37, random-effects), or in the adjusted analysis, assuming non-independence of twins (226 twins, average RR 0.74; 95% CI 0.23 to 2.38, random-effects). A maternal death was reported in one trial without a significant difference between the groups (144 women, RR 2.84; 95% CI 0.12 to 68.57). AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the use of prophylactic oral betamimetics for preventing preterm birth in women with a twin pregnancy.

Pneumococcal vaccination during pregnancy for preventing infant infection.

BACKGROUND: Approximately 450,000 children worldwide die of pneumococcal infections each year. The development of bacterial resistance to antimicrobials adds to the difficulty of treatment of diseases and emphasizes the need for a preventive approach. Newborn vaccination schedules could substantially reduce the impact of pneumococcal disease in immunized children, but do not have an effect on the morbidity and mortality of infants less than three months of age. Pneumococcal vaccination during pregnancy may be a way of preventing pneumococcal disease during the first months of life before the pneumococcal vaccine administered to the infant starts to produce protection. OBJECTIVES: To assess the effect of pneumococcal vaccination during pregnancy for preventing infant infection. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014) and reference lists of retrieved studies. SELECTION CRITERIA: Randomized controlled trials in pregnant women comparing pneumococcal vaccine with placebo or doing nothing, or with another vaccine to prevent infant infections. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We contacted study authors for additional information. MAIN RESULTS: Seven trials were included, but only six trials (919 participants) contributed data. There was no evidence that pneumococcal vaccination during pregnancy reduces the risk of neonatal infection (risk ratio (RR) 0.66; 95% confidence interval (CI) 0.30 to 1.46; two trials, 241 pregnancies, low quality evidence). Although the data suggest an effect in reducing pneumococcal colonization in infants by 16 months of age (average RR 0.33; 95% CI 0.11 to 0.98; one trial, 56 pregnancies), there was no evidence of this effect in infants at two to three months of age (average RR 1.13; 95% CI 0.46 to 2.78; two trials, 146 pregnancies, low quality evidence) or by six to seven months of age (average RR 0.67, 95% CI 0.22 to 2.08; two trials, 148 pregnancies, low quality evidence). None of the trials included in this review reported neonatal death as a result of pneumococcal infection.Neonatal antibody levels were reported as geometric mean and 95% CI. There were inconsistent results between studies. Two studies showed significantly higher immunoglobulin G (IgG) levels in cord blood in the pneumococcal vaccine group when compared with the control group for all serotypes. In contrast, another trial showed no difference in neonatal antibody levels between the pneumococcal vaccine group and the control group.Maternal antibody levels were also reported as geometric mean and 95% CI. One study showed significantly higher IgG levels in maternal serum in women immunized with pneumococcal vaccine when compared with control vaccine regardless of any serotypes. Another study showed significantly higher maternal antibody levels only for serotype 14, but no evidence of an effect for other serotypes.The percentage of women with seroprotection was measured in one trial at delivery and at 12 months post-delivery. At delivery, results favored the intervention group for serotype 6 (RR 1.49, 95% CI 1.31 to 1.69), serotype 14 (RR 1.40, 95% CI 1.25 to 1.56) and serotype 19 (RR 2.29, 95% CI 1.89 to 2.76). There were no group differences seen at 12 months post-delivery for serotypes 6 or 14 (RR 1.06, 95% CI 1.00 to 1.12 and RR 1.06, 95% CI 0.98 to 1.15, respectively), but results favored the intervention group for serotype 19 (RR 1.59, 95% CI 1.37 to 1.85).No significant difference for tenderness at the injection site between women who received pneumococcal vaccine and those who received control vaccine (average RR 3.20; 95% CI 0.32 to 31.54; two trials, 130 women).The overall quality of evidence is low for primary outcomes. Most outcomes had wide confidence intervals crossing the line of no effect, and most of the included trials had small numbers of participants and few events which led to downgrading evidence for imprecision of findings. AUTHORS' CONCLUSIONS: There is insufficient evidence to assess whether pneumococcal vaccination during pregnancy could reduce infant infections.

Conceptive options for people living with HIV.

Seroconcordant and serodiscordant couples living with HIV should be counseled and informed regarding reproductive health issues, including conceptive options. Assisted conception, sperm washing, timed intercourse, and vaginal self-insemination are options to be considered by HIV-affected couples who wish to conceive with a lowered risk of viral transmission. Pre-exposure prophylaxis may be an adjunctive method to reduce the risk, particularly among serodiscordant couples.

Associated factors of prenatal depression among teenage pregnant women at King Chulalongkorn Memorial Hospital.

OBJECTIVE: Depression during pregnancy is associated with deteriorating maternal health and increasing risk of preterm birth, fetal growth restriction, and suicidal attempt. The problems may be worse in adolescents who are more vulnerable. This study was conducted to determine the percentage of depression among teenage mothers and its associated factors. MATERIAL AND METHOD: Two hundred teenage pregnant women aged between 13 and 19 years who visited King Chulalongkorn Memorial Hospital (KCMH) participated in the present study. They were asked to complete the validated Thai Edinburgh Postnatal Depression Scale (EPDS) questionnaire for depression screening. The cut-offscore of 11 was used for the diagnosis of prenatal depression. RESULTS: Ninety-two (46%) teenage pregnant women were found to have prenatal depression using the EPDS cut-off score of 11. The mean age of participants was 17.5 years with the mean gestational ages of 23 weeks. Most of the participants (67%) resignedfrom school and 16% had history of attempted abortion during current pregnancy. There was no significant association between prenatal depression and unplanned pregnancy, unemployment, leaving school, or trimester at screening. Logistic regression analyses showed that history of attempted abortion and inadequate income were significantly associated with prenatal depression (odd ratio = 8.03, 95% CI 1.59 to 40.37 and 4.16, 95% CI 1.35 to 12.83, respectively). CONCLUSION: Prenatal depression was common among teenage pregnant women who visited KCMH. Attempted abortion and inadequate income were found to be significantly associated with prenatal depression.

Comparable detection of HPV using real-time PCR in paired cervical samples and concentrated first-stream urine collected with Colli-Pee device.

We compared high-risk human papillomavirus (HPV) detection on first-stream urine from self-sampled collection device (Colli-Pee) and same-day clinician-collected cervical swab in 240 women. Testing with automated cobas 4800 system showed 96.7 % concordance (198 concordant-negative, 34 concordant-positive, Cohen's kappa=0.87). HPV testing on Colli-Pee urine offers advantages for acceptable non-invasive HPV screening.

Transplacental transfer of maternal antibodies following immunization with recombinant pertussis vaccines during pregnancy: Real-world evidence.

AIM/OBJECTIVE: This study investigates placental antibody transfer following recombinant pertussis vaccination in pregnancy in a real-world setting. METHODS: This postmarketing observational study recruited pregnant women vaccinated with monovalent recombinant acellular pertussis (aP) vaccine (aPgen; n = 199) or combined to tetanus-diphtheria (TdaPgen; n = 200), or Td-vaccine only (n = 54). Pregnancy, delivery, and neonatal outcomes were assessed. Cord blood was collected postdelivery and pertussis toxin (PT)-IgG, filamentous hemagglutinin (FHA)-IgG, and PT-neutralizing antibodies (PT-Nab) were assessed. RESULTS: No adverse pregnancy, delivery, or neonatal outcomes attributed to aPgen, TdaPgen, or Td vaccination were reported. High anti-PT antibody levels were detected in cord samples from women vaccinated with aPgen (geometric mean concentration [GMC] PT-IgG 206.1 IU/ml, 95% confidence intervals [CI]: 164.3-258.6; geometric mean titer [GMT] PT-Nab 105.3 IU/ml, 95% CI: 81.7-135.8) or TdaPgen (GMC PT-IgG 153.1 IU/ml, 95% CI: 129.1-181.5; GMT PT-Nab 81.5 IU/ml, 95% CI: 66.4-100.0). In the Td-only group, anti-PT antibodies were low (GMC PT-IgG 6.5 IU/ml, 95% CI: 4.9-8.8; GMT PT-Nab 3.8 IU/ml, 95% CI: 2.8-5.1). The same was found for FHA-IgG. Recombinant pertussis vaccination at <27 or 27-36 weeks gestation induced similar cord pertussis antibody levels. CONCLUSION: This first real-world study confirms that recombinant pertussis vaccination in the second or third trimester of pregnancy results in high levels of passive immunity in infants. Thai Clinical Trial Registry: TCTR20200528006.

Effective and safe transfer of maternal antibodies persisting two months postpartum following maternal immunization with different doses of recombinant pertussis-containing vaccines.

INTRODUCTION: Recombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PTgen) and filamentous hemagglutinin (FHA) with or without tetanus (TT) and diphtheria (DT) vaccines (Td) were found safe and immunogenic in non-pregnant and pregnant women. We report here maternal antibody transfer and safety data in mothers and neonates. METHODS: This is the follow up of a phase 2 trial in 2019 among 400 pregnant women who randomly received one dose of recombinant pertussis-only vaccine containing 1 µg PTgen and 1 µg FHA (ap1gen), or Td combined with ap1gen (Tdap1gen), or with 2 µg PTgen and 5 µg FHA (Tdap2gen), or with 5 µg PTgen and 5 µg FHA (TdaP5gen, Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8chem, Boostrix™, GSK, Belgium), either in the second or third trimester of gestation. IgG against PT, FHA, TT and DT were assessed by ELISA, PT-neutralizing antibodies (PTNA) by Chinese Hamster Ovary cell assay and safety outcomes at delivery in mothers and at birth. RESULTS: Anti-PT and anti-FHA geometric mean concentration (GMC) ratio between infants at birth and mothers at delivery was above 1 in all groups. PT GMC in infants at birth were ≥30 IU/mL in all groups with the highest titers in infants found in TdaP5gen group at birth (118.8 [95% CI 93.9-150.4]). At 2 months, PT GMC ratio to Tdap8chem (98.75% CI) was significantly higher for TdaP5gen (2.6 [1.7-4.0]) and comparable for other recombinant vaccines. No difference in PTNA titers at birth was observed between all groups nor between time of vaccination. Adverse events were comparable in all vaccine groups. CONCLUSIONS: BioNet licensed (TdaP5gen and Tdap2gen) and candidate vaccines (Tdap1gen and ap1gen) when given to pregnant women in the second or third trimester of gestation are safe and have induced passive pertussis immunity to infants.

Uptake and continuous use of copper intrauterine device in a cohort of HIV-positive women.

Copper intrauterine device (IUD) is not commonly used in many countries, though it provides effective reversible contraception with no or minimal primary systemic side effects. We assessed its uptake and continuation of use among HIV-positive Thai women. Sixty-six of 322 women of reproductive age, whom we approached for the study, met the eligibility criteria. Sterilization (62%) was the main reason for failure to enroll. Twenty-nine of them (44%) underwent IUD insertion. Considering condom use sufficient for pregnancy prevention (12%) was the main reason among eligible women for the refusal to participate in the study. At six months, 54% of enrolled participants reported one or more side effects such as increased menstrual flow (43%), spotting (21%) and dysmenorrhea (11%). The continuation rate of IUD use was high (93%), in spite of the persistent non-systemic side effects. The study showed that copper IUD could be an acceptable contraceptive choice for Thai HIV-positive women. Easy access to the method in a setting linked with the HIV service, and education on IUD risks and benefits is needed to promote the use of IUD in addition to condoms as an effective contraceptive option in HIV-infected women.

A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in pregnant women.

INTRODUCTION: Despite a decrease in infections caused by Bordetella pertussis due to COVID-19 pandemic, booster vaccination of pregnant women is still recommended to protect newborns. Highly immunogenic vaccines containing genetically inactivated pertussis toxin (PTgen) and filamentous hemagglutinin (FHA) may generate comparable anti-PT antibody concentrations, even at lower doses, to chemically inactivated acellular pertussis vaccines (Tdapchem) shown effective for maternal immunization. METHODS: This phase 2 randomized, observer-blind, active-controlled non-inferiority trial was conducted in healthy Thai pregnant women randomly assigned to receive one dose of low-dose recombinant pertussis-only vaccine containing 1 µg PTgen and 1 µg FHA (ap1gen), or tetanus, reduced-dose diphtheria combined with ap1gen (Tdap1gen), or combined with 2 µg PTgen and 5 µg FHA (Tdap2gen), or with 5 µg PTgen and 5 µg FHA (TdaP5gen, Boostagen®) or comparator containing 8 µg of chemically inactivated pertussis toxoid, 8 µg FHA, and 2.5 µg pertactin (Boostrix™, Tdap8chem). Blood was collected at Day 0 and Day 28 post-vaccination. The non-inferiority of the study vaccines was assessed based on anti-PT IgG antibody levels on Day 28 pooled with results from a similarly structured previous trial in non-pregnant women. RESULTS: 400 healthy pregnant women received one dose of vaccine. Combined with data from 250 non-pregnant women, all study vaccines containing PTgen were non-inferior to comparator vaccine (Tdap8chem). Both ap1gen and TdaP5gen vaccines could be considered to have superior immunogenicity to Tdap8chem. Local and systemic solicited reactions were similar among all vaccine groups. CONCLUSIONS: Vaccine formulations containing PTgen were safe and immunogenic in pregnant women. The ap1gen vaccine, with the lowest cost and reactogenicity, may be suitable for use in pregnant women when diphtheria and tetanus toxoids are not needed. This study is registered in the Thai Clinical Trial Registry (www. CLINICALTRIALS: in.th), number TCTR20180725004.

Sexual life, options for contraception and intention for conception in HIV-positive people on successful antiretroviral therapy in Thailand.

This article reports on the sexual life of HIV-positive heterosexual men and women in a stable relationship and on successful antiretroviral therapy in Thailand. We focused on one side on their sexual practices and options for contraception, and on the other on their intention for conception and factors influencing it, in the time of highly active antiretroviral therapy. In a cross-sectional study, 200 participants completed a questionnaire. Eleven female participants took part in focus group discussions (FGD), based on their intention for conception. We used descriptive statistics, logistic regression, and Chi-square exact test to present the results from the questionnaire, and a narrative approach for the FGD results. The median age of the participants was 37 years. Almost all were sexually active (88%) and rarely engaged in risky sexual behavior. The most common method of contraception for women was the male condom (95%), followed by female sterilization (40%). Almost all men reported consistent condom use. One-third of the main sexual partners were HIV-negative. The intention for conception was significantly less after being diagnosed with HIV (29% intended pregnancies after HIV diagnosis vs. 72% before HIV diagnosis). Nevertheless, 25% of the participants expressed a desire to have a child. We found a significant positive association between the intention for conception and less years of being married, the lower number of children and the higher levels of education. Therefore, we conclude that HIV-positive men and women are sexually active and in need of comprehensive reproductive health care services including counseling on safe ways to conceive and offering a diverse choice of contraceptive methods to those who do not wish to have children.

Prophylactic oral betamimetics for reducing preterm birth in women with a twin pregnancy.

BACKGROUND: Twin pregnancies are associated with a high risk of neonatal mortality and morbidity due to an increased rate of preterm birth. Betamimetics can decrease contraction frequency or delay preterm birth in singleton pregnancies by 24 to 48 hours. The efficacy of oral betamimetics in women with a twin pregnancy is unproven. OBJECTIVES: To assess the effectiveness of prophylactic oral betamimetics for the prevention of preterm labour and birth for women with twin pregnancies. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (31 January 2012), the Central Register of Controlled Trials (The Cochrane Library 2012, Issue 2), MEDLINE (January 1966 to 1 February 2012) and EMBASE (January 1985 to 1 February 2012). SELECTION CRITERIA: Randomised controlled trials in twin pregnancies comparing oral betamimetics with placebo or any intervention with the specific aim of preventing preterm birth. Quasi-randomised controlled trials, cluster-randomised trials and cross-over trials were not included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and trial quality. Two review authors extracted data. Data were checked for accuracy. MAIN RESULTS: Six trials (374 twin pregnancies) were included, but only five trials (344 twin pregnancies) contributed data. All trials compared oral betamimetics with placebo.Betamimetics reduced the incidence of preterm labour (one trial, 50 twin pregnancies, risk ratio (RR) 0.40; 95% confidence interval (CI) 0.19 to 0.86). However, betamimetics did not reduce preterm birth less than 37 weeks' gestation (four trials, 276 twin pregnancies, RR 0.85; 95% CI 0.65 to 1.10) or less than 34 weeks' gestation (one trial, 144 twin pregnancies, RR 0.47; 95% CI 0.15 to 1.50). Mean neonatal birthweight in the betamimetic group was significantly higher than in the placebo group (three trials, 478 neonates, mean difference 111.22 g; 95% CI 22.2 to 200.2). Nevertheless, there was no evidence of an effect of betamimetics in reduction of low birthweight (two trials, 366 neonates, average RR 1.19; 95% CI 0.77 to 1.85, random-effects) or small-for-gestational age neonates (two trials, 178 neonates, RR 0.92; 95% CI 0.52 to 1.65). Two trials (388 neonates) showed that betamimetics significantly reduced the incidence of respiratory distress syndrome but the difference was not significant when the analysis was adjusted for correlation of babies from twins. Three trials (452 neonates) showed no evidence of an effect of betamimetics in reducing neonatal mortality (RR 0.80; 95% CI 0.35 to 1.82). AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the use of prophylactic oral betamimetics for preventing preterm birth in women with a twin pregnancy.

Pneumococcal vaccination during pregnancy for preventing infant infection.

BACKGROUND: Each year at least one million children worldwide die of pneumococcal infections. The development of bacterial resistance to antimicrobials adds to the difficulty of treatment of diseases and emphasizes the need for a preventive approach. Newborn vaccination schedules could substantially reduce the impact of pneumococcal disease in immunized children, but does not have an effect on the morbidity and mortality of infants less than three months of age. Pneumococcal vaccination during pregnancy may be a way of preventing pneumococcal disease during the first months of life before the pneumococcal vaccine administered to the infant starts to produce protection. OBJECTIVES: To assess the effect of pneumococcal vaccination during pregnancy for preventing infant infection. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2011) and reference lists of retrieved studies. SELECTION CRITERIA: Randomized controlled trials in pregnant women comparing pneumococcal vaccine with placebo or doing nothing or with another vaccine to prevent infant infections. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, methodological quality and extracted data using a data collection form. Data were checked for accuracy. We contacted study authors for additional information. MAIN RESULTS: Seven trials were included, but only five trials (579 participants) contributed data. There was no evidence that pneumococcal vaccination during pregnancy reduces the risk of neonatal infection (risk ratio (RR) 0.66; 95% confidence interval (CI) 0.30 to 1.46; two trials, 241 pregnancies). Although the data suggest an effect in reducing pneumococcal colonization in infants by 16 months of age (RR 0.33; 95% CI 0.11 to 0.98; one trial, 56 pregnancies), there was no evidence of this effect in infants at two to three months of age (RR 1.13; 95% CI 0.46 to 2.78; two trials, 146 pregnancies) or by six to seven months of age (RR 0.66; 95% CI 0.20 to 2.17; two trials, 144 pregnancies). No significant difference for tenderness at the injection site between women who received pneumococcal vaccine and those who received control vaccine (RR 3.20; 95% CI 0.32 to 31.54; two trials, 130 women). AUTHORS' CONCLUSIONS: There is insufficient evidence to assess whether pneumococcal vaccination during pregnancy could reduce infant infections.