Late-Preterm Antenatal Steroids for Reduction of Neonatal Respiratory Complications: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of antenatal corticosteroids in reducing neonatal respiratory complications when administered to those at risk of preterm delivery between 34 and 36 6/7 weeks of gestation. METHODS: This was a single-center, triple-blind, randomized, placebo-controlled trial in southern India enrolling pregnant participants at risk of preterm delivery between 34 and 36 6/7 weeks of gestation. Computer-generated block randomization was used with participants randomized to either one course of intramuscular betamethasone or placebo. The primary outcome was a composite of treatment for respiratory distress in the neonate, defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life. Neonatal secondary outcomes were transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, hypoglycemia, stillbirth, and early neonatal death; maternal secondary outcomes were chorioamnionitis, postpartum hemorrhage, puerperal fever, and length of hospitalization. All analyses were based on intention to treat. A sample size of 1,200 was planned with 80% power to detect a 30% reduction in rates of respiratory distress. After a planned interim analysis, enrollment was stopped for futility. RESULTS: From March 2020 to August 2022, 847 participants were recruited, with 423 participants randomized to betamethasone and 424 participants randomized to placebo. There were 22 individuals lost to follow-up. There was no statistically significant difference in the primary outcome (betamethasone 4.9% vs placebo 4.8%, relative risk 1.03, 95% CI, 0.57-1.84, number needed to treat 786). There were no statistically significant differences in secondary neonatal or maternal outcomes. CONCLUSION: Betamethasone administered in the late-preterm period to those at risk for preterm delivery did not reduce the need for treatment of neonatal respiratory distress. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry of India, CTRI/2019/09/021321.

The efficacy and safety of 25 µg or 50 µg oral misoprostol versus 25 µg vaginal misoprostol given at 4- or 6-hourly intervals for induction of labour in women at or beyond term with live singleton pregnancies: A systematic review and meta-analysis.

BACKGROUND: Misoprostol is widely used for cervical ripening and labour induction as it is heat-stable and inexpensive. Oral misoprostol 25 µg given 2-hourly is recommended over vaginal misoprostol 25 µg given 6-hourly, but the need for 2-hourly fetal monitoring makes oral misoprostol impractical for routine use in high-volume obstetric units in resource-constrained settings. OBJECTIVES: To compare the efficacy and safety of oral misoprostol initiated at 25 or 50 µg versus 25 µg vaginal misoprostol given at 4- to 6-hourly intervals for labor induction in women at or beyond term (≥ 37 weeks) with a single viable fetus and an unscarred uterus. SEARCH STRATEGY: We identified eligible randomized, parallel-group, labor-induction trials from recent systematic reviews. We additionally searched PubMed, Cochrane CENTRAL, Epistemonikos, and clinical trials registries from February 1, 2020 to December 31, 2022 without language restrictions. Database-specific keywords for cervical priming, labor induction, and misoprostol were used. SELECTION CRITERIA: We excluded labor-induction trials exclusively in women with ruptured membranes, in the third trimester, and those that initiated misoprostol at doses not specified in the review's objectives. The primary outcomes were vaginal birth within 24 h, cesarean section, perinatal mortality, neonatal morbidity, and maternal morbidity. The secondary outcomes were uterine hyperstimulation with fetal heart rate changes, and oxytocin augmentation. DATA COLLECTION AND ANALYSIS: Two or more authors selected studies independently, assessed risk of bias, and extracted data. We derived pooled weighted risk ratios with 95% confidence intervals (CIs) for each outcome, subgrouping trials by the dose and frequency of misoprostol regimens. We used the I2 statistic to quantify heterogeneity and the random-effects model for meta-analysis when appropriate. We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach to assess certainty (confidence) in the effect estimates. MAIN RESULTS: Thirteen trials, from Canada, India, Iran, and the US, randomizing 2941 women at ≥37 weeks of gestation with an unfavorable cervix (Bishop score <6), met the eligibility criteria. Five misoprostol regimens were compared: 25 µg oral versus 25 µg vaginal, 4-hourly (three trials); 50 µg oral versus 25 µg vaginal, 4-hourly (five trials); 50 µg followed by 100 µg oral versus 25 µg vaginal, 4-hourly (two trials); 50 µg oral, 4-hourly versus 25 µg vaginal, 6-hourly (one trial); and 50 µg oral versus 25 µg vaginal, 6-hourly (two trials). The overall certainty in the evidence ranged from moderate to very low, due to high risk of bias in 11/13 trials (affecting all outcomes), unexplained heterogeneity (1/7 outcomes), indirectness (1/7 outcomes), and imprecision (4/7 outcomes). Vaginal misoprostol probably increased vaginal deliveries within 24 h compared with oral misoprostol (risk ratio [RR] 0.82, 95% CI 0.70-0.96; 11 trials, 2721 mothers; moderate-certainty evidence); this was more likely with 4-hourly than with 6-hourly vaginal regimens. The risk of cesarean sections did not appreciably differ (RR 1.00, 95% CI 0.80-1.26; 13 trials, 2941 mothers; very low-certainty evidence), although oral misoprostol 25 µg 4-hourly probably increased this risk compared with 25 µg vaginal misoprostol 4-hourly (RR 1.69, 95% CI 1.21-2.36; three trials, 515 mothers). The risk of perinatal mortality (RR 0.67, 95% CI 0.11-3.90; one trial, 196 participants; very low-certainty evidence), neonatal morbidity (RR 0.84, 95% CI 0.67-1.06; 13 trials, 2941 mothers; low-certainty evidence), and maternal morbidity (RR 0.83, 95% CI 0.48-1.44; 6 trials; 1945 mothers; moderate-certainty evidence) did not differ appreciably. The risk of uterine hyperstimulation with fetal heart rate changes may be lower with oral misoprostol (RR 0.70, 95% CI 0.52-0.95; 10 trials, 2565 mothers; low-certainty evidence). Oxytocin augmentation was probably more frequent with oral compared with vaginal misoprostol (RR 1.29, 95% CI 1.10-1.51; 13 trials, 2941 mothers; moderate-certainty evidence). CONCLUSIONS: Low-dose, 4- to 6-hourly vaginal misoprostol regimens probably result in more vaginal births within 24 h and less frequent oxytocin use compared with low-dose, 4- to 6-hourly, oral misoprostol regimens. Vaginal misoprostol may increase the risk of uterine hyperstimulation with fetal heart changes compared with oral misoprostol, without increasing the risk of perinatal mortality, neonatal morbidity, or maternal morbidity. Indirect evidence indicates that 25 µg vaginal misoprostol 4-hourly may be more effective and as safe as the recommended 6-hourly vaginal regimen. This evidence could inform clinical decisions in high-volume obstetric units in resource-constrained settings.

C- reactive protein levels in women with prelabour rupture of membrane and women with normal labour.

Background: There is a very little information known about CRP in term pregnancies. It is a marker that is easily tested and is inexpensive. Although CRP has been used very effectively in diagnosing infection in the neonate, its clinical use and values have not been studied in term pregnancies. The level of CRP that is truly normal or clinically innocuous is not known. Objectives: This is a cross-sectional study to compare the CRP levels in antenatal women with PROM and women with normal labor and assess its utility to predict sepsis. Methods: This is a prospective study done over a period of one year and approved by the insititutional ethical committee (IRB. Min. No 11102[OBSERVE] dated 10.01.2018). Sample for CRP was collected from 112 antenatal women with prelabor rupture of membranes within 12 hours of admission (Group A) and from 112 antenatal women in spontaneous labor without rupture of membrane (Group B). CRP samples are processed by nephelometry method. Results: The median CRP value in Group A is 9.15 and Group B is 7.26, with no statistical difference. Chorioamnionitis, neonatal sepsis, and endometritis were similar in both the groups. Conclusion: CRP cannot be used as predictor for chorioamnionitis, endometritis, and neonatal sepsis. There was no significant difference in CRP levels between the two groups.

Is new onset hypertension in obese women more likely to be Gestational Hypertension? - A retrospective study.

Introduction: New onset hypertension is more common in antenatal women with increased Body Mass Index (BMI). This may be due to either gestational hypertension (GH) or pre-eclampsia (PE). GH unlike PE is not associated with poor perinatal outcomes and would not require interventions such as increased antenatal visits and induction of labour. Our study assessed the prevalence of GH and PE in women with increased BMI as compared to women with normal BMI. Setting and Design: Historical cohort of a large tertiary centre. Method and Materials: Data from the electronic birth registry of the labour room was used to identify women who had a BMI ≥ 35 kg/m2 at delivery. Women with a normal BMI matched for the mode of delivery was taken as control. 148 women with BMI ≥ 35 kg/m2 were compared with 140 women of normal BMI. Results: New onset hypertension was seen in 41.2% (61/148) and 8.6% (12/140) in the non-obese group RR 4.81 (2.7-8.54) P (<0.001). GH was seen in 24.3% in obese women and 2.9% in normal controls, RR (9.65 (3.54,26.34)), P (<0.001). PE was seen in 16.9% of obese women and 5.7% of women with normal BMI, RR (3.79 (1.78,8.08)) P (<0.001). Proportion of GH in women with new onset hypertension was seen in 59% of obese women with new onset hypertension and 33% of normal controls. Conclusion: This clinically relevant trend towards an increased proportion of GH highlights the importance of identifying pathophysiological mechanism for high BP in obesity when there is new onset hypertension.

Placental chorioangioma with an emphasis on rare giant placental chorioangioma and associated maternal and perinatal outcome: Clinicopathological study in a single centre.

Context: Giant placental chorioangiomas (GPC) are exceedingly rare and harbour potential to cause feto-maternal complications with resultant morbidity. Aims & Materials and Methods: A retrospective study using details from Department of Obstetrics & Gynaecology and Pathology is done to study the various clinical and pathological features of placental chorioangiomas with a special emphasis on the rare GPCs and associated complications. Results: Over a period of 16 years, 20 cases were diagnosed as chorioangioma in our institution. 60% of these occurred in primigravida (n=12) and 71% cases carried a female foetus. Only 25% cases were > 30 years. Maternal and foetal complications occurred in 85% and 50% cases. Pre-term labour was the common maternal complication and foetal death/stillbirth was the most common foetal complication. There were 15 cases of GPC, 73% occurred in primigravida (n=11) and 75% of cases carried a female foetus. There were no cases of maternal death or recurrence. Primigravidity was associated with maternal complication in contrast to multigravidity (P = 0.049). Mean age of mothers with maternal complications and those without maternal complications reached statistical significance (P = 0.001). Though histologically all the cases were similar, calcification and infarction were seen exclusively in GPC cases. Conclusion: GPCs are rare and our data adds evidence to use 4cm as an optimum cut-off in the definition. GPCs were associated with a high percentage of primigravidity, female foetus, and poorer outcome of pregnancy. Routine examination of placenta in unexplained foetal/perinatal demise must be stressed to detect microscopic evidence of chorioangioma.

Study protocol: 'a large cohort study of postnatal events in a not-for-profit referral centre in Vellore, South India'.

INTRODUCTION: In a large developing country, with diverse population characteristics and differential access to healthcare, it is important to identify factors that influence postnatal health. This knowledge will help frame recommendations to enhance universal postnatal care. METHODS AND ANALYSIS: A prospective cohort study will be conducted by recruiting all participants who deliver in a referral centre in South India during a 1-year period after written consent is obtained from them. In addition to clinical information pertaining to their delivery and demographics, details of physical health, mental health socioeconomic status and emotional support will also be collected. Every participant will be followed up physically and/or by telephonic consultation at 3, 9 and 18 months of their postnatal period to reassess their status and that of their babies. As there are several independent and dependent variables requiring multivariate analysis, a sample size of 10 000 is considered adequate. Any unplanned visits to a health facility will be enquired into and documented for analysis.During data analysis, the effect of Caesarean section, high-risk characteristics and gestational age of the baby at delivery on various outcome measures and postnatal status will be evaluated. Interpretation of the large volume of collected data will help frame recommendations to improve postnatal care ETHICS AND DISSEMINATION: The study is approved by the Institutional Review Boards (Research and Ethics Committees) of Christian Medical College, Vellore, Tamil Nadu, India (IRB 12178 date 24 June 2020).Women are provided with a detailed information sheet and written consent is obtained. They are reassured that their care will not be compromised if they do not consent to the study. Data will be available on the clinical trial portal to assist in the dissemination of results after the project is published. TRIAL REGISTRATION NUMBER: CTRI/2022/03/041343.

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.

A randomised double-blind placebo-controlled trial comparing stepwise oral misoprostol with vaginal misoprostol for induction of labour.

A comparison of induction of labour (IOL) using three doses of 25 µg vaginal misoprostol inserted at intervals of 4 h or more with a stepwise oral regime starting with 50 µg followed by two doses of 100 µg was studied in a double-blind placebo-controlled trial in a tertiary centre in South India. Primary outcome was vaginal delivery in 24 h. Significantly more women in the first group required oxytocin augmentation and a third dose of the drug than women in the second group. Uterine tachysystole and other maternal and neonatal complications were similar. Thus it is concluded that women induced with oral, as compared to vaginal misoprostol are more likely to labour without oxytocin.