Antibody kinetics between birth and three months of life in healthy infants with natural exposure to Group B streptococcus: A UK cohort study.

INTRODUCTION: Capsular polysaccharide (CPS) serotype-specific Immunoglobulin G (IgG) in cord blood has been proposed as a correlate of protection against invasive Group B Streptococcus (iGBS) disease. Although protective levels are required in infants throughout the window of vulnerability up to 3 months of age, little is known regarding the kinetics of GBS-specific IgG over this period. METHODS: We enrolled 33 healthy infants born to mothers colonized with GBS. We collected cord blood and infant blood samples either at one (21-35 days), two (49-63 days), or three months of age (77-91 days). We measured GBS serotype-specific CPS IgG concentrations and calculated the decay rate using a mixed-effects model. We further explored whether the antibody kinetics were affected by common maternal and infant factors and estimated the correlation between IgG concentration at birth and one, two, and three months of age. RESULTS: The half-life estimate of IgG concentration for homologous and non-homologous GBS serotypes in paired samples with detectable IgG levels at both time points was 27.4 (95 % CI: 23.5-32.9) days. The decay rate did not vary by maternal age (p = 0.7), ethnicity (p = 0.1), gravida (p = 0.1), gestation (p = 0.7), and infant sex (p = 0.1). Predicted IgG titres above the assay lower limit of quantification on day 30 strongly correlated with titres at birth (Spearman correlation coefficient 0.71 [95 % CI: 0.60-0.80]). CONCLUSION: Our results provide a basis for future investigations into the use of antibody kinetics in defining a serocorrelate of protection against late-onset iGBS disease.

Optimising the timing of whooping cough immunisation in mums (OpTIMUM) through investigating pertussis vaccination in pregnancy: an open-label, equivalence, randomised controlled trial.

BACKGROUND: Pertussis vaccination in pregnancy is recommended in many countries to provide protection to young infants. The best timing for this vaccination is uncertain. In the UK, vaccination is recommended between 16 weeks and 32 weeks of gestation. In this trial we aimed to investigate the equivalence of three time periods for pertussis vaccination in pregnancy. METHODS: In this open-label, equivalence, randomised controlled trial to investigate equivalence of different time windows for pertussis vaccination in pregnancy, participants were randomly assigned (1:1:1 ratio) to receive a pertussis-containing vaccine (Boostrix-inactivated poliovirus vaccine) in one of three gestational age groups, comprising group 1 (≤23 weeks + 6 days), group 2 (24-27 weeks + 6 days), and group 3 (28-31 weeks + 6 days) using a computer-generated randomisation list. The primary outcome was concentration of pertussis-specific antibodies in the infant born at term at birth. Maternal blood sampling was done before and 2 weeks after vaccination and at delivery, together with a cord sample, and an infant sample was collected at least 4 weeks after primary vaccination. Reactogenicity was assessed for 7 days after vaccination. This trial was registered with ClinicalTrials.gov (NCT03908164). FINDINGS: Between May 7, 2019, and Feb 13, 2020, of 1010 women assessed for eligibility, 364 women were recruited and 351 received the intervention (120 in group 1, 119 in group 2, and 112 in group 3). Equivalence of time periods was demonstrated for anti-pertussis toxin and anti-pertactin IgG concentrations. The cord blood geometric mean concentrations of anti-filamentous haemagglutinin IgG were higher with increasing gestational age at vaccination, such that for infants in group 1 (≤23 weeks + 6 days), equivalence to group 3 (28-31 weeks + 6 days) was not shown. Reported rates of fever were similar between study groups. INTERPRETATION: Pertussis vaccination at three different time intervals in pregnancy resulted in equivalent concentrations of IgG antibodies in infants against two of the three pertussis antigens assessed. Overall, these findings support recommendations to vaccinate any time between 16 weeks and 32 weeks of gestation. FUNDING: The Thrasher Research Fund and the National Immunisation Schedule Evaluation Consortium through the National Institute for Health and Care Research policy research programme.

Developing a serocorrelate of protection against invasive group B streptococcus disease in pregnant women: a feasibility study.

BACKGROUND: Group B streptococcus is the leading cause of infection in infants. Currently, intrapartum antibiotic prophylaxis is the major strategy to prevent invasive group B streptococcus disease. However, intrapartum antibiotic prophylaxis does not prevent maternal sepsis, premature births, stillbirths or late-onset disease. Maternal vaccination may offer an alternative strategy. Multivalent polysaccharide protein conjugate vaccine development is under way and a serocorrelate of protection is needed to expedite vaccine licensure. OBJECTIVES: The ultimate aim of this work is to determine the correlate of protection against the major group B streptococcus disease-causing serotypes in infants in the UK. The aim of this feasibility study is to test key operational aspects of the study design. DESIGN: Prospective cohort study of pregnant women and their infants in a 6-month period (1 July to 31 December 2018). SETTING: Five secondary and tertiary hospitals from London and South England. National iGBS disease surveillance was conducted in all trusts in England and Wales. PARTICIPANTS: Pregnant women aged ≥ 18 years who were delivering at one of the selected hospitals and who provided consent during the study period. There were no exclusion criteria. INTERVENTIONS: No interventions were performed. MAIN OUTCOME MEASURES: (1) To test the feasibility of collecting serum at delivery from a large cohort of pregnant women. (2) To test the key operational aspects for a proposed large serocorrelates study. (3) To test the feasibility of collecting samples from those with invasive group B streptococcus. RESULTS: A total of 1823 women were recruited during the study period. Overall, 85% of serum samples were collected at three sites collecting only cord blood. At the two sites collecting maternal, cord and infant blood samples, the collection rate was 60%. A total of 614 women were screened for group B streptococcus with a colonisation rate of 22% (serotype distribution: 30% III, 25% Ia, 16% II, 14% Ib, 14% V and 1% IV). A blood sample was collected from 34 infants who were born to colonised women. Maternal and infant blood and the bacterial isolates for 15 newborns who developed invasive group B streptococcal disease during the study period were collected (serotype distribution: 29% III, 29% II, 21% Ia, 7% Ib, 7% IV and 7% V). LIMITATIONS: Recruitment and sample collection were dependent on the presence of research midwives rather than the whole clinical team. In addition, individualised consent limited the number of women who could be approached each day, and site set-up for the national surveillance study and the limited time period of this feasibility study limited recruitment of all eligible participants. CONCLUSIONS: We have verified the feasibility of collecting and processing rectovaginal swabs and blood samples in pregnant women, as well as samples from those with invasive group B streptococcal disease. We have made recommendations for the recruitment of cases within the proposed GBS3 study and for controls both within GBS3 and as an extension of this feasibility study. FUTURE WORK: A large case-control study comparing specific immunoglobulin G levels in mothers whose infants develop invasive group B streptococcal disease with those in colonised mothers whose infants do not develop invasive group B streptococcal disease is recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49326091; IRAS project identification number 246149/REC reference number 18/WM/0147. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 67. See the NIHR Journals Library website for further project information.

Group B streptococcus is often carried by healthy women and usually causes no problems. Group B streptococcus may be passed from mother to child, primarily through the birth canal, and, in rare cases, can cause serious disease (i.e. pneumonia, sepsis or meningitis) and even death in babies. It may be possible to prevent group B streptococcus disease in babies by giving a vaccine to pregnant women. The reason for vaccinating the mother is so that she can pass on protection (antibodies) during the pregnancy to her baby. A vaccine is currently being developed against group B streptococcus that aims to boost this protection. To help vaccine development progress faster, we need to find out how much antibody is actually needed to protect babies from group B streptococcus disease. A large study is needed to address this question; therefore, we have performed a feasibility study to assess the practicalities of performing this large study. Specifically, we will assess (1) women's willingness to participate in a swabbing and cord blood study, (2) the ability to collect swabs and cord blood once recruited, (3) the ability to identify group B streptococcus disease in this population and (4) the laboratory processing of samples. We recruited 1823 pregnant women from five maternity units in England in a 6-month period: 22% of all women delivering at all sites and 74% of those women who were approached. In three hospitals, cord blood samples from 85% of 1201 women were collected. In two hospitals, we collected 60% of maternal blood samples, 53% of cord blood samples and 99% of swabs from the vagina and rectum from 622 women. A total of 22% of these women carried group B streptococcus in their vagina or gut and we collected blood samples from 34 healthy babies born to these women. During the study, we collected samples from 15 babies who had developed severe group B streptococcus disease; four babies were born to women participating in the study and the rest were identified through national surveillance. In conclusion, we have verified the feasibility of collecting and processing swabs from the vagina and rectum and blood samples in pregnant women, as well as samples from babies who developed group B streptococcus disease. In addition, we have identified a number of strategies that could be adopted in a future study in order to increase recruitment and sample collection.

Prenatal reflex DNA screening for trisomies 21, 18, and 13.

PURPOSE: The purpose of the study was to determine the screening performance of prenatal reflex DNA screening for trisomies 21 (T21), 18 (T18), and 13 (T13) as part of a routine service at five hospitals. METHODS: Women who accepted screening had a first-trimester combined test (pregnancy-associated plasma protein A, free ß-human chorionic gonadotropin, nuchal translucency interpreted with maternal age). Those with a risk of having an affected pregnancy ≥1 in 800 were reflexed to a DNA sequencing test using stored plasma from the original blood sample, thereby avoiding the need to recall them. RESULTS: Of 22,812 women screened (including 106 with affected pregnancies), 2,480 (10.9%) were reflexed to DNA testing; 101/106 were detected (69/73 T21, 24/25 T18, and 8/8 T13), a 95% detection rate (95% confidence interval 89-98%) with four false positives (0.02%, 95% confidence interval 0.00-0.05%). The odds of being affected given a positive result were 25:1. Of the 105 screen-positive pregnancies, 91 (87%) had an invasive diagnostic test. Reflex DNA screening avoided up to 530 invasive diagnostic tests compared with using the combined test. CONCLUSION: Reflex DNA screening was successfully implemented in routine care, achieving a high detection rate, low false-positive rate, and, consequently, greater safety with fewer invasive diagnostic tests than other methods of screening.

Bilateral neck cysts as an isolated sonographic finding in the antenatal detection of fetal aneuploidy: a case report.

Isolated fetal lateral neck cysts can represent a cystic hygroma or a developmental remnant cyst. In the absence of an increased nuchal translucency or associated malformations the risk of aneuploidy has been considered negligible. Still, dysmorphology in aneuploid fetuses might not be evident except at a later stage. We report on a case of isolated fetal bilateral neck cysts where aneuploidy was suspected and confirmed despite the lack of associated morphologic abnormalities.

Impact on delivery outcome of ultrasonographic fetal head position prior to induction of labor.

OBJECTIVE: To assess clinical and sonographic fetal head position before induction of labor, position at delivery, and whether occiput posterior (OP) position is associated with adverse delivery outcome. METHODS: Abdominal palpation and ultrasonographic fetal head and spine position were determined at 36 weeks or more of gestation in 289 women immediately before induction of labor and the head position at delivery noted. Chi-square, Mann-Whitney U tests, and logistic regression were used to assess whether OP position was associated with cesarean delivery. RESULTS: Ninety-seven (36%) of 270 women with full outcome data had an OP position on ultrasonography before induction of labor. Of these 97 women, eight (8%) were OP at delivery. Sixty-eight percent of the 25 OP positions at delivery occurred due to a mal-rotation from a non-OP position during labor. Logistic regression showed that OP position before induction of labor was not an independent predictor of cesarean delivery (odds ratio 1.75, 95% confidence interval 0.97-3.15, P=.06). CONCLUSION: Two thirds of OP positions at delivery after induction of labor occur due to a mal-rotation in labor from a non-OP position. Ultrasonography is an easy method of assessing fetal head position before induction of labor. In clinical practice, its usefulness is limited by the fact that, contrary to conventional teaching, OP position before induction of labor does not appear to be associated with an increased risk of cesarean delivery. LEVEL OF EVIDENCE: II.

Clinical and ultrasound parameters to predict the risk of cesarean delivery after induction of labor.

OBJECTIVE: To evaluate whether factors in the maternal history and/or ultrasound parameters are useful in predicting the risk of cesarean delivery after induction of labor. METHODS: Maternal age, height, body mass index, parity, gestational age, Bishop score, ultrasonic amniotic fluid volume, fetal head position, estimated fetal weight, and transvaginal cervical length were studied prospectively in 267 women at 36 or more weeks of gestation immediately before induction of labor. Logistic regression analysis was used to determine which factors best predicted the risk of cesarean delivery. Receiver operating characteristic curves and a resampling technique were used to evaluate the model's performance. RESULTS: Eighty (30%) of these 267 women had cesarean delivery. Logistic regression was performed and a final model chosen, which included parity (odds ratio [OR] 20.56, 95% confidence interval [CI] 7.97-53.05, P < .001), body mass index (OR 6.17, 95% CI 2.10-18.13, P < .001), height (OR 0.94, 95% CI 0.89-0.98, P = .005), and ultrasonic transvaginal cervical length (OR 1.07, 95% CI 1.04-1.11, P < .001) as the best predictors of cesarean delivery. A risk score was calculated containing these 4 parameters, which predicted reasonably accurately the risk of cesarean delivery. CONCLUSION: Parity, body mass index, height, and ultrasonic transvaginal cervical length are the most accurate parameters in predicting the risk of cesarean delivery after induction of labor. A predictive model using these would allow more accurate counseling and better informed consent in the decision-making process regarding induction of labor LEVEL OF EVIDENCE: II-2.