Prevalence of group B Streptococcus colonisation in mother-newborn dyads in low-income and middle-income south Asian and African countries: a prospective, observational study.

BACKGROUND: Rectovaginal group B Streptococcus (GBS) colonisation in pregnant individuals at the time of labour is a major risk factor for invasive GBS disease by age 7 days (early-onset disease). We aimed to investigate the prevalence of rectovaginal GBS colonisation at the time of labour among pregnant women and vertical transmission to their newborns across selected low-income and middle-income African and south Asian countries. METHODS: This prospective, observational study was undertaken at 11 maternity and obstetric care facilities based in Ethiopia, Kenya, Mozambique, Nigeria, Mali, South Africa, Bangladesh, India, and Bhutan. HIV-negative pregnant women aged 18-45 years who were in the early stages of labour and at least 37 weeks' gestation were eligible for inclusion. Lower vaginal and rectal swabs and urine were collected from the women, and swabs of the umbilicus, outer ear, axillary fold, rectum, and throat were obtained from their newborns, for GBS culture. Standardised sampling and culture using direct plating and selective media broth for detection of GBS colonisation was undertaken at the sites. Serotyping of GBS isolates was done in South Africa. The primary outcome was the prevalence of rectovaginal GBS among pregnant women, analysed in participants with available data. This study is registered with the South African National Clinical Trials Register, number DOH-27-0418-4989. FINDINGS: 6922 pregnant women were enrolled from Jan 10, 2016, to Dec 11, 2018, of whom 6514 (94·1%; 759-892 per country) were included in the analysis; data from Bhutan were not included in the study due to issues with specimen collection and processing. Overall, the prevalence of maternal GBS colonisation was 24·1% (95% CI 23·1-25·2; 1572 of 6514); it was highest in Mali (41·1% [37·7-44·6]; 314 of 764) and lowest in Ethiopia (11·6% [9·5-14·1]; 88 of 759). The overall rate of vertical transmission of GBS from women with rectovaginal GBS colonisation was 72·3% (70·0-74·4; 1132 of 1566); it was highest in Mozambique (79·2% [73·3-84·2]; 168 of 212) and lowest in Bangladesh (55·8%, 47·5-63·8; 77 of 138). The five most common GBS colonising serotypes were Ia (37·3% [34·9-39·7]; 586 of 1572), V (28·5% [26·3-30·8]; 448 of 1572), III (25·1% [23·0-27·3]; 394 of 1572), II (9·2% [7·8-10·7]; 144 of 1572), and Ib (6·5% [5·4-7·8]; 102 of 1572). There was geographical variability in serotype proportion distribution; serotype VII was the third most common serotype in India (8·6% [5·3-13·7]; 15 of 174) and serotype VI was mainly identified in Bangladesh (5·8% [3·0-11·0]; eight of 138) and India (5·7% [3·2-10·3]; ten of 174). INTERPRETATION: Our study reported a high prevalence of GBS colonisation in most settings, with some geographical variability even within African countries. Our findings suggest that serotypes not included in current multivalent capsular-polysaccharide GBS vaccines prevail in some regions, so vaccine efficacy and post-licensure effectiveness studies should assess the effect of vaccination on maternal GBS colonisation given the potential for replacement by non-vaccine serotypes. FUNDING: Bill & Melinda Gates Foundation.

Exploring the clinical utility of exome sequencing/Mono, Duo, Trio in prenatal testing: a retrospective study in a tertiary care centre in South India.

OBJECTIVES: With the availability of Next Generation Sequencing (NGS) diagnosis of genetic disorders has improved significantly. Its use is also applicable to ascertain diagnosis and management in a perinatal setting. The study aims to detect the genetic aetiology of various congenital structural and functional defects using NGS technology in the reproductive cohort at a tertiary centre. The secondary objective is to address challenges in the interpretation of variants. METHODS: This was a retrospective study of couples who underwent exome sequencing (Mono-testing proband only or Duo-testing parents only or Trio-testing proband and parents) for suspected single gene disorders between years 2020-2022 at a tertiary care perinatal center in the South India. American College of Medical Genetics (ACMG) guidelines were followed to classify the pathogenicity of the variants identified by exome sequencing. RESULTS: The overall diagnostic yield as defined by pathogenic/likely pathogenic variants obtained was (23/43) 53.4 %. The individual subsets have the following diagnostic yield viz., Mono 5/6 (83 %); Carrier 16/32 (50 %); Trio 2/5 (40 %). Diagnostic yield was significantly higher in consanguineous couples. However, miscarriage history, and organ system involvement did not have a significant effect on the diagnostic yield. Prenatal diagnosis was offered for seven patients based on the exome result. One fetus was confirmed with a compound heterozygous pathogenic variant. CONCLUSIONS: Diagnostic yield of exome sequencing in our cohort was 53 %. The detection of pathogenic variants was maximum in those cases undergoing Mono exome sequencing. In places where there is a high prevalence of consanguinity and endogamy, NGS may be offered as first line test in the context of prenatal diagnosis.

Comparing Obstetric and Perinatal Outcomes Following Elective and Emergency Cervical Cerclage in Singleton and Multiple Pregnancies in a Tertiary Care Perinatal Centre.

Objective: To compare the success, failure rates and perinatal outcomes following emergency and elective cervical cerclage in singleton and twin pregnancies at a tertiary care perinatal centre over half a decade. Methods: All pregnant women, both with singleton and twin pregnancies, who had cervical cerclage between June 2014 and May 2019 were included in the retrospective study. Success rates, failure rates, maternal complications and perinatal outcomes were compared in both groups. Results: There were 129 women enrolled in the study, 48 in the emergency and 81 in the elective group. A significantly greater number of multiparous women were in the elective group (97.5% versus 68.7%; p-value < 0.001). Twins were nearly four times more in the emergency group as compared to  the elective group. The mean cervical length at time of cerclage was 2.05 cm and 1.5 cm; (p-value < 0.001) respectively in the elective and emergency groups. Almost half of the women in the emergency group had bulging membranes. (52.2%). Following cerclage, mean gestational age at delivery was similar in both groups. However, more women in the elective group delivered at or beyond 34 weeks in comparison to the emergency groups (71% versus 53.3%. P-value 0.05). Preterm labour leading to preterm births was almost twice in the emergency group than elective group (49% versus 22%, P-value 0.002). Rates of maternal chorioamnionitis were similar in both groups. The overall live birth rates were comparable (81.3% versus 84.4% P-value 0.85) in both the groups. These results were also seen on doing subgroup analysis of elective versus emergency cerclage in singleton pregnancies only. Failure rates were also similar in both groups (18.7% versus 15.6%, P-value 0.85) Composite neonatal morbidity was more in the emergency group than in the elective group (35.5 versus 14%, P-value 0.01). Conclusion: Live birth rates and failure rates were comparable following elective and emergency cerclage both overall and in singleton pregnancies. Maternal chorioamnionitis and neonatal sepsis  rates were similar in both the groups. However, composite neonatal morbidity was higher in the emergency cerclage group.

Serotype distribution and antimicrobial susceptibility profile of invasive group B streptococcal disease-in South Indian population.

PURPOSE: Invasive group B Streptococcal disease (iGBS) is an important cause of morbidity and mortality in neonates for which the development of an efficacious vaccine remains a global health imperative. The knowledge about the serotype distribution of iGBS is important component for formulation of Capsular polysaccharide (CPS)-based vaccine. However, there were absolute lack of information on serotype distribution in invasive GBS isolates from Indian subcontinent. Methods This study has assessed the serotype distribution and antimicrobial susceptibility profile of invasive group B streptococcal isolates for a period of 13 years from 2009 to 2022 from a tertiary care Center in South India. A total of 155 iGBS isolates were subjected to serotyping by conventional multiplex PCR for identification of all ten GBS serotype. Antimicrobial susceptibility profile and demographic details were extracted from microbiological records. Results Overall, the most common serotype causing invasive GBS were Ia (29%), V (26%), III (15%), II (12%), VI (6%), VII (5%) and Ib (5%). Serotypes IV, VIII and XI were not detected. Among the early-onset iGBS, the common serotype were Ia (36%), V (27%), and III (8%). In late onset iGBS, Serotype III (44%) was predominant. The common serotype in adults were Serotype V (31%) and III (20%). All the invasive GBS isolates were susceptible for penicillin (100%), but the susceptibility for clindamycin and erythromycin were 72% and 80% respectively. Conclusion The serotype distribution of invasive Group B streptococcal isolates from India suggest that hexavalent group B CPS vaccine will cover only 90% of GBS isolates causing invasive disease among the infants in India. Continued surveillance monitoring for serotype distribution and antimicrobial resistance patterns for iGBS are warranted to make public health interventions.

Successful Outcome of Pregnancy in Niemann-Pick Disease Type B: A Case Report and Review of Literature.

Niemann-Pick (NPD) is a rare autosomal recessive disease, caused by deficiency of acid sphingomyelinase enzyme leading to accumulation of lipids mainly in the reticuloendothelial system and lungs. We describe the case of a 29-year-old primigravida, recently diagnosed with NPD type B. At initial evaluation, her platelets were normal, liver enzymes slightly elevated and splenomegaly on scan. Pregnancy care was by a multidisciplinary team which routinely monitored her liver and pulmonary functions along with platelets. Labor was induced at 37 + 1 weeks of gestation because of fetal growth restriction. She underwent an cesarean section for failed induction and delivered a healthy male baby. Conclusion: Successful outcomes in such pregnancies depend upon close monitoring by a multidisciplinary team.

Spectrum of Chromosomal Abnormalities Detected by Conventional Cytogenetic Analysis Following Invasive Prenatal Testing of Fetuses with Abnormal Ultrasound Scans.

Objectives: The frequent association between malformations and chromosomal abnormalities is now well-established. This study looks at the incidence and type of chromosomal abnormalities detected by conventional cytogenetic analysis in women undergoing invasive tests following detection of fetal anomalies on antenatal scans as well as incidence of other genetic abnormalities detected by DNA analysis of fetuses with congenital anomalies that had a normal karyotype. Materials and Methods: A retrospective, observational study of pregnant women undergoing invasive testing following identification of fetal anomalies by ultrasonography was carried out in a tertiary care facility, Vellore, India, between 2011 and 2018. Results: 169 women underwent an invasive diagnostic procedure following detection of fetal anomalies. The most common indication for doing fetal karyotype was the presence of major fetal structural anomalies (142/169, 84%) with over a third (48/142, 34%) having multisystem involvement. Fetal hydrops was the next most common indication, detected in 18/169 (10%) fetuses. Aneuploidy was seen 19 of 25 fetuses (76%) with an abnormal karyotype with autosomal aneuploidy accounting for 13 (68%) and sex chromosome aneuploidy for seven (37%) of the fetuses. One fetus had double aneuploidy. In fetuses with normal karyotype, no additional information was obtained from further genetic testing. Conclusions: The overall detection rate of chromosomal abnormalities in our study using conventional cytogenetic analysis was 14.8%, the majority (72%) being associated with structural malformations, 20% with non-immune hydrops and 4% with soft markers. Abnormal karyotypes were seen in 12.7% of fetuses with structural malformations.

A retrospective study analyzing indications and outcomes of mid-trimester emergency cervical cerclage in a tertiary care perinatal centre over half a decade.

We studied the indications, success rate, perinatal outcomes and maternal complications following mid-trimester emergency cervical cerclage. All women undergoing mid-trimester emergency cerclage at our centre during 2014-2019 were included in this retrospective study.There were 46 women in our cohort. Mean cervical length was 1.5 cm (SD ± 0.7), and 52.1% of them had bulging membranes. The mean gestational age at cerclage was 23.35 weeks (SD ± 3.341). Three were loss to follow up.Out of 43 pregnancies (23 singletons and 20 twins) analyzed, 37/43, 86.4% had livebirths. Success rate in the singletons and twins were 91.3% and 80% respectively. Maternal complications were seen in 56.5% of patients. Composite neonatal morbidity was significantly more in the twin group (p-value 0.04).Overall live birth rate was 86.4% with similar success rates in singleton and multiple pregnancies. Although, evidence for beneficial effect of prophylactic cerclage in multiple gestation is lacking, emergency cerclage may have a role in twin gestation.

Breast milk contains red cell isohaemagglutinins: An observational study of 176 mothers.

BACKGROUND AND OBJECTIVES: Maternal antibodies are transferred to the child, predominantly IgG, via the transplacental route, and mostly IgA through breast milk. Cases reported by us and others have shown the transfer of red cell allo-antibodies through breast milk. This study was conducted to assess the presence of isohaemagglutinins in breast milk, the range of titres, and the correlation between breast milk and maternal plasma titres. MATERIALS AND METHODS: A total of 176 mothers were recruited in this study. Breast milk was collected after sufficient feeding was established and within 2-5 days of delivery in a sterile container without any anticoagulant. Antibody screen, identification and titres were performed on maternal plasma as well as breast milk. RESULTS: Anti-A and anti-B in breast milk corresponding to their respective maternal blood groups were found in all the samples. This study has shown titres in the breast milk of anti-A and anti-B ranging from 2 to 1024 in both saline and Coombs phases. There was no association between plasma and breast milk titres, thus making it impossible to predict which mother may potentially transfer a larger amount of these haemagglutinins. Isotypes of anti-A and anti-B were evaluated in both plasma and breast milk of 11 samples, which showed predominantly IgG in 7 (63.63%) and predominantly IgA in 4 (36.36%) samples. CONCLUSION: Our study demonstrates the presence of a wide range of titres for IgG antibodies of the ABO blood group system in breast milk. The clinical impact of this finding needs to be studied further, as it assumes great relevance in developing countries where anaemia continues to challenge young infants.

Placenta accreta spectrum: Management and outcomes in a tertiary centre in India: An observational cross-sectional study.

Our observational cross-sectional study looked at the risk factors, diagnosis, management and outcomes of placenta accrete spectrum at the Christian Medical College and Hospital, Vellore, India, between January 2013 and December 2018. A total of 21 cases of placenta accrete spectrum are described among whom a preop diagnosis was available in 14 cases. A previous history of Caesarean section and placenta previa was present in 90%. Caesarean hysterectomy was carried out in 80%, but none of those managed conservatively required interval hysterectomy. Urinary tract injury was the most common surgical complication, seen in over 50%. The mean blood loss was 3.5 l and 14 patients required intensive care unit admission, but no maternal mortality ensued. Thus, we conclude that the conservative management in carefully selected cases is feasible.

Peripartum cardiomyopathy: An analysis of clinical profiles and outcomes from a tertiary care centre in southern India.

Peripartum cardiomyopathy is a syndrome of maternal heart failure with decreased left ventricular ejection fraction affecting maternal and fetal well-being. We analysed clinical profiles and outcomes in women with peripartum cardiomyopathy enrolled retrospectively from a tertiary care centre in southern India (1 January 2008-31 December 2014). The incidence of peripartum cardiomyopathy was one case per 1541 live births. Fifty-four women with a mean age of 25.5 years and mean gestational age of 35.4 weeks were recruited; 35 were primigravidae. Maternal and fetal deaths occurred in 9.3% and 24.1% of subjects, respectively. Mild-to-moderate maternal anaemia (80-110 g/L) was associated with fetal mortality (p = 0.02). Reduced left ventricular ejection fraction (<30%, p = 0.04) and cardiogenic shock (p = 0.01) were significantly associated with adverse maternal outcomes. Forty per cent of women were followed up after 24.2 ± 17.7 months, and in these women a significant increase in left ventricular ejection fraction was seen (mean 16.4%, p < 0.01); all were asymptomatic. Peripartum cardiomyopathy with poor left ventricular ejection fraction and shock is associated with adverse maternal outcomes, while non-severe maternal anaemia predisposes to adverse fetal outcomes. Significant left ventricular ejection fraction recovery occurred on follow-up.

An Integrated System for Fetal Scalp Visualization, Blood Collection and Analysis.

KEY MESSAGE: The new NB scope aids in better visualization of the scalp and blood collection and analysis at bed side. OBJECTIVE: Caesarean section rates and inherent complications are on the rise all over the world. One way to avoid a caesarean is to measure fetal scalp blood lactate levels. The methods available to visualize fetal scalp, obtain the blood sample and perform the blood test are separate, cumbersome and expensive, needing a certain level of expertise. We propose a device that incorporates all the steps of obtaining a fetal scalp blood lactate into one sleek, easy to use device. METHODS: The initial design, 3-D print and was tried on mannequin. After ethics committee approval, the prototype was experimented on patients in labour with singleton live fetus in cephalic presentation with no evidence of distress. RESULTS: There were (n = 9) patients recruited. There were (n = 5) primigravida and (n = 4) multigravida all of whom were in active labour. Parity did not seem to influence ease of instrumentation. Of the (n = 9) mothers (n = 2) had meconium-stained liquor and the rest (n = 7) had clear liquor, meconium-stained liquor did not affect visualization. The mean time taken to collect the sample was 184.11(± 33.04) seconds. CONCLUSION: The Neeraj-Bhaskar (NB) scope is an easy to use, affordable device that can be used time and again to decide on cases where emergency caesarean section can be avoided due to fetal distress.

Enzyme-linked immunosorbent assay (ELISA) versus Venereal Disease Research Laboratory test (VDRL) and rapid plasma reagin test (RPR) for screening of syphilis in pregnant women.

OBJECTIVE: To evaluate a treponemal enzyme-linked immunosorbent assay (ELISA) as an alternative screening test for syphilis in pregnant women. METHODS: A cross-sectional study of diagnostic test accuracy was carried out in a large volume laboratory from a tertiary care center. A total of 416 serum samples, including 102 archived syphilis Treponema pallidum hemagglutination (TPHA)-positive samples and 314 samples from pregnant women, were used to determine the sensitivity and specificity of ELISA. All the samples were subjected to Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), ELISA, and TPHA tests. Performance characteristics of VDRL, RPR, and ELISA were calculated with TPHA as a reference standard test. RESULTS: VDRL and RPR exhibited higher false positivity of 10.5% and 9.6%, respectively, compared to 2.5% by ELISA. The sensitivity and specificity of ELISA were 98% and 97.5%, of VDRL were 71.6% and 89.5%, and of RPR were 73.5% and 90.5%, respectively. Moreover, ELISA had an excellent agreement (kappa=0.9) with TPHA compared to VDRL/RPR which had a moderate agreement (kappa=0.6) only. CONCLUSION: ELISA has the potential to replace VDRL/RPR as a screening test for syphilis in centers that can perform ELISA, especially for antenatal screening.

Obstetric and perinatal outcomes in pregnant women with Takayasu's arteritis: single centre experience over five years

Objective: To study obstetric and perinatal outcomes among pregnant women with Takayasu arteritis (TA), attending our hospital for pregnancy and childbirth between January 2011 to December 2016. Material and Methods: Retrospective study was carried out by abstracting clinical charts on all pregnant women with TA who underwent antenatal care and/or delivery in our hospital during this period. American College of Rheumatology criteria was used for diagnosis of TA. Sixteen women with TA were included in the study. Maternal demographic data, stage of disease, complications related to disease, details of treatment taken prior to pregnancy, pregnancy outcomes, and neonatal outcomes were studied. Results: Forty-four percentage (7/16) belonged to type 5 angiographic type, however the same proportion (7/16) had undergone surgical corrections prior to pregnancy and the majority (15/16) were on medical management. Only three women (19%) were diagnosed during pregnancy. Most did not have active disease measured by Kerr's criteria (n=12; 75%), and Indian Takayasu clinical activity scores A. Chronic hypertension was the commonest antenatal complication (56.2%), nearly one-third had growth restricted babies and 25% had preterm labour. There were no cardiovascular events, no maternal deaths, nor fetal or neonatal deaths. Two-thirds of our women were delivered by caesarean section. Conclusion: Preconceptional counselling is of paramount importance in women with TA. Good maternal and fetal outcomes are observed with close antenatal surveillance and multidisciplinary care. Pregnancy should be planned during disease remission, with good antenatal care, close monitoring of clinical symptoms, early diagnosis and treatment of complications.

Decoding stillbirths using the Relevant Condition at Death classification: Study from the developing world

Objective: To determine the stillbirth rate in 2017 at Christian Medical College, a tertiary care perinatal center in South India, and to identify causes for the various stillbirths that occurred using the Relevant Condition at Death (ReCoDe) classification. Material and Methods: Medical records of the women with stillbirths between January 1st, to December 31st, 2017, were retrieved and analyzed using the SPSS software (IBM, version 23). The study was approved by the institutional review board (minute no: 11273, retro dated: 28/3/2018). Results: Of the total 14696 deliveries between January 1st, 2017, to December 31st, 2017, there were 247 stillbirths, a rate of 16.8 per 1000 births. Maternal factors: 156 (64.2%) women were booked and the rest were un-booked. Hypertensive disorders of pregnancy were detected in 27.5% (n=67). A greater number of un-booked women had gestational hypertension as compared with booked women (41% vs 24%, p=0.005). Fetal characteristics: still births secondary to lethal congenital anomalies were seen in 18.2% (n=45). Lethal congenital anomalies were diagnosed 10 times more in the booked patients than un-booked ones (24.7% vs 2.3%, p=0.001). Obstetric factors: one or two previous miscarriages were seen in 29.5% cases. Seventeen women (6.9%) had a prior stillbirth. ReCoDe Classification: we were able to successfully classify 84.2% of the stillbirths, leaving 15.78% unclassified. Fetal growth restriction secondary to uteroplacental insufficiency was found in 25.9% cases. Of the placental causes, abruption accounted for 10.9% of cases. Medical co-morbidities were seen in 46.5% pregnancies. Conclusion: The ReCoDe method of classifying stillbirths is useful in the developing world. It helped to elucidate the cause for stillbirths in 84.2% of cases. The majority of cases in our set were due to fetal growth restriction, hypertensive disorders of pregnancy, and uteroplacental insufficiency. Stillbirths can be prevented by a comprehensive antenatal care system, early recognition, and close monitoring of high-risk pregnancies.

Tumour lysis in newborn: spontaneous or secondary to antenatal steroids?

Malignancies are rare in the early neonatal period. Common congenital tumours include malignant teratoma and neuroblastomas. Tumour lysis syndrome is a serious condition usually seen after commencement of chemotherapy for a malignancy. Rare case reports of spontaneous tumour lysis have been reported though not in the newborn period. We report here an instance of tumour lysis syndrome in a newborn with congenital rhabdoid tumour, where the cause was either spontaneous or related to antenatal steroid exposure.

Prevalence of group B Streptococcal colonization among pregnant women and neonates in a tertiary hospital in India.

OBJECTIVE: To estimate the prevalence of group B Streptococcus (GBS) carriage among pregnant women attending the antenatal clinic, and the colonization rates among newborn born to colonized mothers. MATERIAL AND METHODS: Women attending the antenatal clinic between 35-37 weeks were screened using rectal and lower vaginal swab. Swabs were initially plated on sheep blood agar and LIM broth. The LIM broth was subcultured after 24 hours onto blood agar and CHROMagar StrepB plates with all plates checked for growth at 24 and 48 hours. All babies born to mothers in the study had surface swabs taken to estimate the vertical transmission rate. RESULTS: Between September 2012 and March 2013, 305 consecutive mothers were screened. Of these, eight mothers were GBS positive in 5% blood agar (2.6%) and 23 mothers showed GBS positivity in enriched media (7.6%). Sixteen of 238 babies (6.7%) were colonized. CONCLUSION: Though lower than rates from most countries, 7.6% of mothers attending an antenatal clinic in south India were colonized with GBS. Use of enrichment media markedly increased the detection rate. Approximately two-thirds of newborn born to colonized mothers were also colonized. There were no instances of invasive GBS disease, indirectly proving the efficacy of intrapartum prophylaxis in preventing neonatal GBS disease.