Perinatal Risk Factors for Neonatal Early-onset Group B Streptococcal Sepsis after Initiation of Risk-based Maternal Intrapartum Antibiotic Prophylaxis-A Case Control Study.

OBJECTIVES: To identify the perinatal risk factors for early-onset Group B Streptococcus (EOGBS) sepsis in neonates after inception of a risk-based maternal intrapartum antibiotic prophylaxis strategy in 2004. DESIGN: Case control study. METHODS: All newborn with early onset GBS sepsis (born between 2004 and 2013) were deemed to be "cases" and controls were selected in a 1:4 ratio. RESULTS: More than three per vaginal (PV) examinations [odds ratio (OR) 8.57, 95% confidence interval (CI) 3.10-23.6] was a significant risk factors. Peripartum fever (OR 3.54, 95% CI 1.3-9.67), urinary tract infection (OR 2.88, 95% CI 1.08-7.63), meconium-stained amniotic fluid (MSAF) (OR 2.52, 95% CI 1.18-5.37) and caesarean section (OR 1.99, 95% CI 1.16-3.43) were also found to be associated with EOGBS sepsis. CONCLUSION: Multiple vaginal examinations are the strongest risk factors for peripartum Group B Streptococcal (GBS) sepsis. The association of MSAF and caesarean section indicates that foetal distress is an early symptom of perinatal GBS infection.

Ten units intravenous oxytocin over 2-4 h is as effective as 30 units over 8-12 h in preventing postpartum hemorrhage after cesarean section: A randomized controlled trial.

OBJECTIVES: Currently, recommended high-dose oxytocin regimen for the prevention of postpartum hemorrhage (PPH) following cesarean delivery (CD) is associated with maternal side effects frequency of which is greater with a higher cumulative dose and rapid administration of oxytocin. Here, we evaluated the efficacy of single-dose intravenous oxytocin over 2-4 h (total = 10 units) with oxytocin maintenance infusion for 8-12 h (total = 30 units) in postoperative CD women for the prevention of PPH. METHODS: The current double-blinded randomized controlled trial was carried out in a tertiary care institute in Southern India. The primary outcome measures included the following: (a) the need for additional uterotonics to control PPH and (b) significant deterioration of vital signs as assessed by pulse rate and blood pressure in the postoperative period. The secondary outcome measures were as follows: (a) significant difference (≥10% between preoperative and postoperative packed cell volume) and (b) need for blood transfusion. RESULTS AND CONCLUSIONS: Two hundred and seventy-one women were randomized into Group A (oxytocin = 10 units; n = 135) and Group B (oxytocin = 30 units; n = 136). Both the groups were comparable with regard to demographic characteristics. There was no difference in any of primary or secondary outcome measures in the two groups. Thus, low-dose oxytocin regimen is as effective as high-dose oxytocin regimen in the prevention of PPH in postoperative CD women.

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.

A randomized controlled double blind trial comparing the effects of the prophylactic antibiotic, Cefazolin, administered at caesarean delivery at two different timings (before skin incision and after cord clamping) on both the mother and newborn.

BACKGROUND: Caesarean delivery (CD) increases the risk of postpartum infection by 5 to 20 fold. Prevention of surgical site infection (SSI) is the goal of antibiotic prophylaxis. This study was carried out to assess the optimum timing for prophylactic antibiotic administration and to assess the amount of the antibiotic crossing the placental barrier. METHODS: Eligible mothers were recruited, after informed consent, once the decision for CD was made. Each mother received two injections, one prior to skin incision and one after cord clamping, (one being the study drug Cefazolin, and the other, a placebo) based on the randomization code. Demographic, maternal and neonatal monitoring data until discharge from hospital, and at the 6 weeks postpartum visit were collected. Levels of the prophylactic antibiotic were measured from the cord blood in every 8th neonate. The objective of the study was to compare the effects of the prophylactic antibiotic, intravenous Cefazolin 1 g, administered at Caesarean delivery (CD) at two different timings (before skin incision and after cord clamping) on both the mother and newborn. The secondary outcomes that were followed up were the number of maternal and neonatal readmissions. An appropriate test for significance, Fisher's exact test was used to find the association between risk variables and outcome. RESULTS: The total numbers of mothers enrolled were 1106, of whom 553 mothers received antibiotic prior to skin incision (pre-incision) and 543 mothers received antibiotic after cord clamping (post-incision). The pre-incision group had significantly less febrile illness (RR = 0.48, 95% CI: 0.29 - 0.80) and SSI (RR = 0.14, 95% CI: 0.04 - 0.53) when compared with the post- incision group. The post-incision group significantly had >7 days hospital stay when compared to the 4-7 days stay of the pre-incision group (p = 0.005).There were no differences in any of the neonatal outcomes. The quantity of the antibiotic in the cord blood was only 2-3%. CONCLUSIONS: Pre incision prophylactic antibiotic protected the mother from SSI and febrile illness and decreased the hospital stay significantly. TRIAL REGISTRATION: The Clinical Trials Registry India (CTRI) was [ CTRI/2016/03/006710 dated, 04/03/2016].

Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India.

Pregnant women with diabetes may have underlying beta cell dysfunction due to mutations/rare variants in genes associated with Maturity Onset Diabetes of the Young (MODY). MODY gene screening would reveal those women genetically predisposed and previously unrecognized with a monogenic form of diabetes for further clinical management, family screening and genetic counselling. However, there are minimal data available on MODY gene variants in pregnant women with diabetes from India. In this study, utilizing the Next generation sequencing (NGS) based protocol fifty subjects were screened for variants in a panel of thirteen MODY genes. Of these subjects 18% (9/50) were positive for definite or likely pathogenic or uncertain MODY variants. The majority of these variants was identified in subjects with autosomal dominant family history, of whom five were in women with pre-GDM and four with overt-GDM. The identified variants included one patient with HNF1A Ser3Cys, two PDX1 Glu224Lys, His94Gln, two NEUROD1 Glu59Gln, Phe318Ser, one INS Gly44Arg, one GCK, one ABCC8 Arg620Cys and one BLK Val418Met variants. In addition, three of the seven offspring screened were positive for the identified variant. These identified variants were further confirmed by Sanger sequencing. In conclusion, these findings in pregnant women with diabetes, imply that a proportion of GDM patients with autosomal dominant family history may have MODY. Further NGS based comprehensive studies with larger samples are required to confirm these finding.

Masked hypoglycemia in pregnancy.

BACKGROUND: Hypoglycemia is a major hindrance for optimal glycemic control in women with gestational diabetes mellitus (GDM) on insulin. In the present study, masked hypoglycemia (glucose <2.77mmol/L for ≥30 min) was estimated in pregnant women using a continuous glucose monitoring (CGM) system. METHODS: Twenty pregnant women with GDM on insulin (cases) and 10 age-matched euglycemic pregnant women (controls) between 24 and 36 weeks gestation were recruited. Both groups performed self-monitoring of blood glucose (SMBG) and underwent CGM for 72 h to assess masked hypoglycemia. Masked hypoglycemic episodes were further stratified into two groups based on interstitial glucose (2.28-2.77 and ≤2.22 mmol/L). RESULTS: Masked hypoglycemia was recorded in 35% (7/20) of cases and 40% (4/10) of controls using CGM, with an average of 1.28 and 1.25 episodes per subject, respectively. Time spent at glucose levels between 2.28 and 2.77 mmol/L did not differ between the two groups (mean 114 vs 90 min; P = 0.617), but cases spent a longer time with glucose ≤2.2 mmol/L. Babies born to women with GDM were significantly lighter than those born to controls (2860 vs 3290 g; P = 0.012). There was no significant difference in birth weight within the groups among babies born to women with or without hypoglycemia. CONCLUSION: Euglycemic pregnant women and those with GDM on insulin had masked hypoglycemia. Masked hypoglycemia was not associated with adverse maternal or fetal outcomes. Therefore, low glucose levels in the hypoglycemic range may represent a physiologic adaptation in pregnancy. This response is exaggerated in women with GDM on insulin.

Large for Gestational Age Births Among South Indian Women: Temporal Trend and Risk Factors from 1996 to 2010.

BACKGROUND/PURPOSE: Mean birth weight is a good health indicator for any population. In the recent past, there have been many reports in the West indicating that there has been an increase in the proportion of large for gestational age (LGA) babies. The objective is to describe the change in the incidence of LGA babies from 1996 to 2010 in South India and the maternal risk factors. METHODS: A rotational sampling scheme was used, i.e., the 12 months of the year were divided into 4 quarters and a month was from each quarter was selected rotationally. All deliveries for that month were considered. Only deliveries that occurred between 28 and 42 weeks of pregnancy were considered. The association between risk variables was studied using multivariable logistic regression. RESULTS: There were 35,718 deliveries that occurred during these 15-year-study period in the gestational age 28-42 weeks were registered through the outpatient clinics. The incidence of LGA was 9.4 % that has mostly remained at the same level. The incidence of LGA in mothers with gestational diabetes was 6.7, 3 and 17.6 % in overweight, obese and gestational l diabetes mothers. Overweight, obesity in pregnant women and cesarean section were significant risk factors. CONCLUSION: Unlike in Western countries, where the incidence of LGA babies has spiraled upward, has remained nearly at the same level over one and a half decades, in South India. The risk factors for giving birth to LGA babies in South India were similar to other studies.

Birth weight centiles by gestational age for twins born in south India.

BACKGROUND: Birth weight centile curves are commonly used as a screening tool and to assess the position of a newborn on a given reference distribution. Birth weight of twins are known to be less than those of comparable singletons and twin-specific birth weight centile curves are recommended for use. In this study, we aim to construct gestational age specific birth weight centile curves for twins born in south India. METHODS: The study was conducted at the Christian Medical College, Vellore, south India. The birth records of all consecutive pregnancies resulting in twin births between 1991 and 2005 were reviewed. Only live twin births between 24 and 42 weeks of gestation were included. Birth weight centiles for gestational age were obtained using the methodology of generalized additive models for location, scale and shape (GAMLSS). Centiles curves were obtained separately for monochorionic and dichorionic twins. RESULTS: Of 1530 twin pregnancies delivered during the study period (1991-2005), 1304 were included in the analysis. The median gestational age at birth was 36 weeks (1st quartile 34, 3rd quartile 38 weeks). Smoothed percentile curves for birth weight by gestational age increased progressively till 38 weeks and levels off thereafter. Compared with dichorionic twins, monochorionic twins had lower birth weight for gestational age from after 27 weeks. CONCLUSIONS: We provide centile values of birth weight at 24 to 42 completed weeks of gestation for twins born in south India. These charts could be used both in routine clinical assessments and epidemiological studies.

Changing perspectives of infectious causes of maternal mortality.

OBJECTIVE: Infections significantly contribute to maternal mortality. There is a perceived change in the spectrum of such infections. This study aims to estimate the contribution of various types of infections to maternal mortality. MATERIAL AND METHODS: We retrospectively reviewed records of maternal death cases that took place between 2003 and 2012 in the Christian Medical College, Vellore, India. The International Classification of Diseases-Maternal Mortality was used to classify the causes of deaths and World Health Organization near-miss criteria were used to identify organ dysfunction that occurred before death. Infections during pregnancy were divided into three groups, i.e., pregnancy-related infections, pregnancy-unrelated infections, and nosocomial infections. RESULTS: In this study, 32.53% of maternal deaths were because of some type of infection as the primary cause. The contribution of pregnancy-related infections was comparable with that of pregnancy-unrelated infections (16.03% vs. 16.50%). Metritis with pelvic cellulitis, septic abortions, tuberculosis, malaria, scrub typhus, and H1N1 influenza (influenza A virus subtype) were among the most commonly encountered causes of maternal death due to infections. Another 7.07% of cases developed severe systemic infection during the course of illness as nosocomial infection. A significant majority of mothers were below 30 years of age, were primiparae, had advanced gestational age, and had operative delivery. Cardiovascular and respiratory system dysfunctions were the most common organ dysfunctions encountered. CONCLUSION: The contribution of pregnancy-unrelated infections to maternal deaths is significant. Control of these diverse community-acquired infections holds the key to a reduction in maternal mortality along with the promotion of clean birthing practices. Nosocomial infections should not be underestimated as a contributor to maternal mortality.

Small for gestational age births among South Indian women: temporal trend and risk factors from 1996 to 2010.

BACKGROUND: The birth weight and gestational age at birth are two important variables that define neonatal morbidity and mortality. In developed countries, chronic maternal diseases like hypertension, diabetes mellitus, renal disease or collagen vascular disease is the most common cause of intrauterine growth restriction (IUGR). Maternal nutrition, pregnancy induced hypertension, chronic maternal infections, and other infections such as cytomegalovirus, parvovirus, rubella and malaria are the other causes of IUGR. The present study examines the secular trend of Small for Gestational Age (SGA) over 15 years and risk factors for SGA from a referral hospital in India. METHODS: Data from 1996 to 2010 was obtained from the labour room register. A rotational sampling scheme was used i.e. 12 months of the year were divided into 4 quarters. Taking into consideration all deliveries that met the inclusion criteria, babies whose birth weights were less than 10(th) percentile of the cut off values specific for gestational ages, were categorized as SGA. Only deliveries of live births that occurred between 22 and 42 weeks of pregnancy were considered in this study. Besides bivariate analyses, multivariable logistic regression analysis was done. Nagelkerke R(2) statistics and Hosmer and Lemeshow chi-square statistics were used as goodness of fit statistics. RESULTS: Based on the data from 36,674 deliveries, the incidence of SGA was 11.4% in 1996 and 8.4% in 2010. Women who had multiple pregnancies had the higher odds of having SGA babies, 2.8 (2.3-3.3) times. The women with hypertensive disease had 1.8 (1.5-1.9) times higher odds of having SGA. Underweight women had 1.7 (1.3 - 2.1) times and anaemic mothers had 1.29 (1.01 - 1.6) times higher odds. The mothers who had cardiac disease were 1.4 (1.01 - 2.0) times at higher odds for SGA. In teenage pregnancies, the odds of SGA was 1.3 (1.1 - 1.5) times higher than mothers in the age group 20 to 35 years. CONCLUSIONS: There is a significant reduction in the incidence of SGA by 26% over 15 years. The women with the above modifiable risk factors need to be identified early and provided with health education on optimal birth weight.

Maternal mortality and derivations from the WHO near-miss tool: An institutional experience over a decade in Southern India.

OBJECTIVE: Preceding the use of World Health Organization (WHO) near-miss approach in our institute for the surveillance of Severe Maternal Outcome (SMO), we pilot-tested the tool on maternal death cases that took place over the last 10 years in order to establish its feasibility and usefulness at the institutional level. MATERIAL AND METHODS: This was a retrospective review of maternal deaths in Christian Medical College Vellore, India, over a decade. Cases were recorded and analyzed using the WHO near-miss tool. The International Classification of Diseases, 10(th) Revision was used to define and classify maternal mortality. RESULTS: There were 98,139 total births and 212 recorded maternal deaths. Direct causes of mortality constituted 46.96% of total maternal deaths, indirect causes constituted 51.40%, and unknown cases constituted 1.9%. Nonobstetrical cause (48.11%) is the single largest group. Infections (19.8%) other than puerperal sepsis remain an important group, with pulmonary tuberculosis, scrub typhus, and malaria being the leading ones. According to the WHO near-miss criteria, cardiovascular and respiratory dysfunctions are the most frequent organ dysfunctions. Incidence of coagulation dysfunction is seen highest in obstetrical hemorrhage (64%). All women who died had at least one organ dysfunction; 90.54% mothers had two- and 38.52% had four- or more organ involvement. CONCLUSION: The screening questions of the WHO near-miss tool are particularly instrumental in obtaining a comprehensive assessment of the problem beyond the International Classification of Diseases-Maternal Mortality and establish the need for laboratory-based identification of organ dysfunctions and prompt availability of critical care facilities. The process indicators, on the other hand, inquire about the basic interventions that are more or less widely practiced and therefore give no added information at the institutional level.

Preliminary experience with use of recombinant activated factor VII to control postpartum hemorrhage in acute fatty liver of pregnancy and other pregnancy-related liver disorders.

Control of postpartum hemorrhage is difficult in patients with coagulopathy due to acute liver failure. Recombinant activated factor VII (rFVIIa) can help in control of bleed; however, it has short duration of action (2-4 h). The study aimed to report the use of rFVIIa in this setting. We retrospectively analyzed all patients with acute liver failure secondary to pregnancy-related liver disorders who received rFVIIa for control of postpartum hemorrhage (six patients, all six met diagnostic criteria for acute fatty liver of pregnancy). One dose of rFVIIa achieved adequate control of bleeding in five patients, while one patient needed a second dose. rFVIIa administration corrected coagulopathy and significantly reduced requirement of packed red cells and other blood products. No patient had thrombotic complications. In conclusion, rFVIIa was a useful adjunct to standard management in postpartum hemorrhage secondary to acute liver failure of pregnancy-related liver disorders.

New birth weight reference standards customised to birth order and sex of babies from South India.

BACKGROUND: The foetal growth standards for Indian children which are available today suffer due to methodological problems. These are, for example, not adhering to the WHO recommendation to base gestational age on the number of completed weeks and secondly, not excluding mothers with risk factors. This study has addressed both the above issues and in addition provides birthweight reference ranges with regard to sex of the baby and maternal parity. METHODS: Data from the labour room register from 1996 to 2010 was obtained. A rotational sampling scheme was used i.e. the 12 months of the year were divided into 4 quadrants. All deliveries in January were considered to represent the first quadrant. Similarly all deliveries in April, July and October were considered to represent 2nd, 3rd and 4th quadrants. In each successive year different months were included in each quadrant. Only those mothers aged 20-39 years and delivered between 24 to 42 weeks gestational age were considered. Those mothers with obstetric risk factors were excluded. The reference standards were fitted using the Generalized Additive Models for Location Scale and Shape (GAMLSS) method for Box-Cox t distribution with cubic spline smoothing. RESULTS: There were 41,055 deliveries considered. When women with risk factors were excluded 19,501 deliveries could be included in the final analysis. The male babies of term firstborn were found to be 45 g heavier than female babies. The mean birthweights were 2934 g and 2889.5 g respectively. Similarly, among the preterm babies, the first born male babies weighed 152 g more than the female babies. The mean birthweights were 1996 g and 1844 g respectively.In the case of later born babies, the term male babies weighed 116 grams more than the females. The mean birth weights were 3085 grams and 2969 grams respectively. When considering later born preterm babies, the males outweighed the female babies by 111 grams. The mean birthweights were 2089 grams and 1978 grams respectively. There was a substantial agreement range from k=.883, (p<.01) to k=.943, (p<.01) between adjusted and unadjusted percentile classification for the subgroups of male and female babies and first born and later born ones.Birth weight charts were adjusted for maternal height using regression methods. The birth weight charts for the first born and later born babies were regrouped into 4 categories, including male and female sexes of the babies. Reference ranges were acquired both for term and preterm babies.With economic reforms, one expects improvement in birthweights. The mean (sd) birthweights of the year 1996 was 2846 (562) as compared to year 2010 (15 years later) which was 2907 (571). There was only a difference of 61 grams in the mean birthweights over one and a half decade. CONCLUSION: New standards are presented from a large number of deliveries over 15 years, customised to the maternal height, from a south Indian tertiary hospital. Reference ranges are made available separately for first born or later born babies, for male and female sexes and for term and preterm babies.

Amnioinfusion for relief of recurrent severe and moderate variable decelerations in labor.

OBJECTIVE: To determine whether intrapartum amnioinfusion (AI) relieves recurrent moderate and severe variable decelerations in laboring women with clear or grade I meconium-stained amniotic fluid and reduces cesarean section rate for fetal distress. STUDY DESIGN: A randomized controlled trial was conducted in labor unit of Christian Medical College Hospital, Vellore, India, between October 2003 and September 2004. Women were randomized to receive AI (group I) and not to receive it (group II). RESULTS: A total of 150 women (75 in each group) were included in the study. There was significant relief of variable decelerations in group I and no difference in overall cesarean section rate but significant reduction in cesarean section rate for fetal distress in group I, and significant reduction in cesarean section rate for fetal distress in nulliparous women of group I. Neonatal acidemia was also significantly reduced in the nulliparous women receiving AI. The duration of maternal postpartum hospital stay was significantly reduced in group I. There were no adverse maternal or neonatal outcomes. CONCLUSION: AI was a beneficial therapeutic intervention in women patients showing fetal distress in first stage of labor, and it reduced cesarean section for fetal distress and neonatal acidemia.