CLINICAL AND MICROBIOLOGICAL ANALYSIS OF TERM AND PRETERM PREMATURE RUPTURE OF MEMBRANESDR CHINMAI BFIRST YEAR RESIDENT UNDER

CLINICAL AND MICROBIOLOGICAL ANALYSIS OF TERM AND PRETERM PREMATURE RUPTURE OF MEMBRANESDR CHINMAI BFIRST YEAR RESIDENT UNDER

DR PADMAJA Y SAMANT

PROFESSOR

DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY

INVESTIGATORS:

PRINICIPAL INVESTIGATOR: DR PADMAJA Y SAMANT (HEAD OF THE DEPARTMENT, DEPT. OF OBSTETRICS AND GYNAECOLOGY)

CO- INVESTIGATOR: DR CHINMAI B (FIRST YEAR RESIDENT, DEPT. OF OBSTETROCAS AND GYNAECOLOGY)

INTRODUCTION:

Pre-labor rupture of membrane (PROM) is the rupture of fetal membranes after 28 weeks of gestation but before the onset of labor. PROM that occurs before 37 weeks of gestation is referred to as preterm premature rupture of membranes (PPROM), and PROM that occurs after 37 weeks is called term PROM. PROM affects 315% of all pregnancies globally, 3040% of preterm labor, and 810% of term labor. (1) PROM affects 7.7% of primiparous mothers and 10.4% of multiparous mothers in India (2). PPROM affects 220% of all pregnancies and accounts for 1820% of neonatal deaths (3). PROM neonatal mortality ranges from 24% to 720% in singleton and twin pregnancies, respectively (4).

Preterm premature rupture of membranes (PPROM), which is associated with vaginal dysbiosis, is responsible for up to one-third of all preterm births. Consecutive ascending colonization, infection, and inflammation may lead to relevant neonatal morbidity including early-onset neonatal sepsis (EONS)(5)

In the majority of cases, the mechanism of PROM cause is unknown, but it may be related to a structural defect in the membranes caused by collagen deficiency or malformation, which causes the membranes to weaken and be destroyed by the enzymatic process in inflammatory or infectious processes. It is also linked to mechanical factors, such as twin pregnancies caused by uterine volume distention. Based on previous evidence, low family income, maternal age, employment, education level, multiple pregnancies, gestational ages, hypertension, diabetes mellitus, history of abortion, abnormal vaginal discharge, ANC follow-up, urinary tract infection, and history of Chorioamnionitis were risk factors for PROM. (6)

ETIOPATHOGENESIS:

The etiology of PROM is multifactorial. It includes

1. Maternal enzymes like collagenase and trypsin which are found in placenta and amniotic fluid works synergistically to disrupt the collagen matrix resulting in PROM.

2. Maturational changes - Decrease in Type III collagen cause the membrane to lose their elasticity and strength. - Increased mechanical stresses from increasing uterine activity contributes to membrane weakness in 2 distinct ways.

a) Cervical softening and effacement allow for greater downward distention of the chorioamniotic membrane.

b) Increase in hydrophobicity of the amnion and chorion leading to decrease in phosphatidylinositol resulting in loss of membrane phospholipids leading to cellular fracture and PROM.

3.Bacterial involvement - Group B Streptococci - N. Gonorrhoeae - E. Coli - Staphylococci - Pseudomonas aeruginosa - Bacteroids - Chlamydiae, mycoplasma and ureaplasma. These are all the common organisms producing bacterial proteases, collagenases and elastases affecting the amniotic membrane directly.

4. HOST AND FETAL FACTORS Without any host factor influence bacterial infection alone cannot weaken the membrane.

i. Peroxidase in amnion, chorion and placental macrophages produces free radicals along with bacteria.

ii. Smoking affects the nutritional factor and O2 availability.

iii. Cervical integrity

iv. The amnion neutrophil itself produces cytokines like IL-6, IL-8 and also by fetal neutrophils.

v. Phospholipids of fetal membrane are destroyed by bacteria. The end products (PGE2 & PGF2) along with calcium can stimulate uterine contractions predisposing to PROM.

vi. Type V collagen in the basement membrane of amnion can be disturbed by bacterial collagenases. All the above factors play major and interrelated roles in PROM. So, it is clear that products of prostaglandins formation is the major pathway leading to PROM.

RISK FACTORS

Risk factors associated with PROM are:

1. Overdistension of uterus resulting from multiple pregnancy, polyhydramnios 2. Cervical incompetence

3. Chorioamnionitis

4. Coitus especially with presence of chorioamnionitis.

5. Antepartum bleeding in early pregnancy

6. Prior preterm delivery

7. Bacterial vaginosis

8. Maternal diseases like 1 AT deficiency and Ehlers Danlos syndrome

9. Maternal deficiency of trace elements and vitamins especially Zinc and Vit. C.

DIAGNOSIS AND COMPLICATIONS

PROM is likely when there is h/o sudden gush of amniotic fluid from vagina followed by dribbling thereafter. Diagnosis is obvious when there is passage of meconium or vernix. Amniotic fluid must be differentiated from urine and vaginal secretions. There are a variety of tests developed for this purpose.

1. Changes in vaginal pH Nitrazine paper which is orange in colour turns blue and red litmus paper turns to blue colour.

2. Arborization test formation of ferning seen under microscope confirms presence of amniotic fluid.

3. Microscopy test for vernix caseosa and lanugo hair.

4. Cytological methods for detections of fetal cell in the amniotic fluid Nile blue sulphate test.

5. USG study for liquor volume.

COMPLICATIONS :Consequences of PROM depends upon;

1) Duration of PROM

2) Gestational age

3) Associated infection MATERNAL COMPLICATION.

THEY INCLUDE

Preterm labour

Abnormal labour

Increased operative delivery

Uncontrolled infection can lead to septicemia and its complications which warrants delivery of the fetus irrespective of the gestational age.

FETAL / NEONATAL COMPLICATION

PN Mortality- 6.7% in PROM (Singh et al 1990) - Mainly due to sepsis and respiratory distress - 55% is due to infection

PERINATAL Morbidity :1) Infection - Risk of sepsis is inversely related to gestational age - Incidence of infection increases with prematurity and chorioamnionitis - Septicemia - Pneumonitis - Meningitis - Pyoderma

2) Perinatal asphyxia : Incidence of low Apgar and meconium staining occurs more in infection cases. 3) Prematurity : contributes 50% to perinatal mortality. In PPROM poor neonatal outcome is caused by immaturity, neurological injury and infection. Meta analysis reported in 1996 showed incidence of sepsis and intraventricular hemorrhage decreases with antibiotic prophylaxis, but no change is noted in mortality.

4)Pulmonary hypoplasia - Important complication with 70% mortality. - It is related to gestational age at the time of rupture and the presence of oligohydramnios.

5) Developmental delay and cerebral palsy - Increased incidence with prematurity and infection

6) Respiratory distress syndrome more common in PPROM

7) Skeletal deformities Prolonged PROM leads to 47% incidence of pulmonary hypoplasia and skeletal deformities.

RATIONALE:

With regard to the importance of maternal genital tract colonization as an etiologic factor in PROM, appropriate antibiotic therapy has a cardinal role in prevention and treatment of maternal and neonatal complications. With the help of this study, we will be able to the evaluate the bacterial colonization in genital tract of pregnant women with PPROM and PROM and its relationship with maternal and neonatal complications and there by deduce appropriate empirical antibiotic regimen and interventions to reduce maternal and perinatal morbidity and mortality.

REVIEW OF LITERATURE

The earliest known reference to PROM dates back to a long time ago when Ipsissims verha of Soranus Ephesus described this condition which we see today and the period is unknown. He was a Greek anatomist and Physician. Paul and Regina (625 690) outstanding Greek authors in Medicine stated the definition encountered in PROM in their article. Rosessline (1517 1527) wrote many articles in obstetrics. She attributed the definition of PROM in many of her articles. Gould & Pile (1815) reviewed many instances in dry labour related to PROM and the outcome of such a labour. It is only in the recent years that a better picture on the outcome of PROM has been noted and postulated.

A Cohort study was conducted in an academic hospital of Marshad university of medical sciences with an objective of evaluating with an objective of evaluating cervical bacterial colonization in women with PPROM and pregnancy outcomes on 200 pregnant women. The study showed endocervical colonization was associated with higher admission rate but no significant co-relation between endocervical colonization and chorioamnitis, positive blood culture and neonatal mortality rate.(7)

A Case control study involving 73 cases less than 37 weeks gestation and less than 24 hrs duration of rupture of membranes conduction at Central hospital, Benin city, revealed a positive culture of 97.3% which is statistically significant suggestive strong link of genital tract infection with PPROM with most common organism being E.Coli>Proteus>Klebsiella>Bacteroides. The study also revealed ciprofloxacin (but not safe in pregnancy), ceftriaxone, ceftadizime, cefuroxime and erythromycin are antibiotics of significant sensitivity. (8)

A prospective cross sectional study was conducted at Government Medical College and hospital, Chandigarh where 50 pregnant women ( cases) with preterm premature rupture of membranes and 28 pregnant women (controls) without complication were assessed for the type of vaginal flora and its sensitivity to commonly used antibitoics. The study showed among cases E. Coli and Staphylococcus aureus were the commonest isolates and of the 16% positive bacterial cultures in cases, 10% were sensitive to Gentamicin and 6% to Ampicillin. (9)

A cross sectional study conducted including 60 pregnant women with PPROM at KLE Dr.Prabhakar Kore Charitable Hospital, Belagavi, to determine bacteria isolated from PPROM and antibiotic sensitivity of the isolates revealed E. faecalis followed by E. coli growth among others with Gram negative organisms sensitive to Imipenem and Amikacin and Gram negative organisms sensitive to Linezolid and Vancomycin. (10)

A prospective observational study conducted in Government Medical College, Kottayam with an objective of studying high vaginal swab in preterm labour and premature rupture of membranes and its relationship with neonatal sepsis revealed E.Coli as the most common isolate sensitive to 3rd generation cephalosporins. Among the 20 percent positive vaginal swab cultures, 70 percent babies had sepsis. E.coli and MRSA positive cultures had neonatal sepsis in 88% and 100% babies respectively. (11)

OBJECTIVES:

PRIMARY OBJECTIVE:

TO STUDY THE ORGANISMS IN PRETERM PREMATURE RUPTURE OF MEMBRANES AND THOSE IN LABOUR WITH PREMATURE RUPTURE OF MEMBRANES FOR 1 HOUR

CORRELATION OF ORGANISMS WITH NEONATAL BLOOD CULTURE

SECONDARY OBJECTIVE:

ANTIBIOTIC SENSITIVITY AND RESISTANCE OF ORGANISMS ISOLATED IN THE TWO GROUPS

TREATMENT AND INTERVENTION PRACTICES FOR BOTH THE GROUPS

CORRELATION OF MATERNAL AND AGE ADJUSTED NEONATAL SEVERITY IN THE SELECTED CASES

MATERIALS AND METHODOLOGY

This is a prospective study conducted in the department of obstetrics and gynaecology, KEM Hospital including all antenatal women getting admitted with premature rupture of membranes between 28- 36+6 days for PPROM and between 37 42 weeks for PROM. The diagnosis of rupture of membranes will be done on the basis of history, per speculum examination and positive litmus test. High vaginal of swabs of those mothers fulfilling the criteria will be taken and sent for culture and sensitivity in the department of Microbiology, KEM Hospital. The neonates will be followed up for the development of neonatal sepsis and neonatal blood culture.

INCLUSION CRITERIA:

Antenatal women getting admitted with premature rupture of membranes between 28- 36+6 days for PPROM and between 37 42 weeks for PROM

Singleton live fetus in cephalic presentation

EXCLUSION CRITERIA:

Ruptured membranes beyond > 6hrs at the time of admission

Fetal distress and meconium-stained amniotic fluid

Active labour on admission

Medical and surgical diseases complicating pregnancy like oligohydramnios, polyhydramnios, IUD, fetal anomaly, gestational diabetes, abnormal presentation, placenta praevia, gestational hypertension and multifetal gestations.

SAMPLE SIZE:

There are about 8-10 cases of Preterm premature rupture of membranes and 6-8 cases of premature of rupture of membranes satisfying the criteria for inclusion and exclusion.

Considering that, we would be including all the cases satisfying the criteria during the duration of 1 and half years of the study and the corresponding sample size would be 162 pregnant mothers with PPROM and 126 pregnant mothers with PROM.

OUTCOME OF THE STUDY:

Prevalence of genital tract infections in preterm premature rupture of membranes and premature rupture of membranes

Incidence of neonatal sepsis and its relationship with high vaginal swab culture in PPROM and PROM in present study

Identification of common organisms in high vaginal swab culture and its anti microbial sensitivity

STATISTICAL ANALYSIS:

Results of quantitative variables will be expressed in terms of mean, median and mode. The qualitative variables will be expressed in terms of proportion.

REFERENCES:

1.Telayneh AT, Ketema DB, Mengist B, Yismaw L, Bazezew Y, Birhanu MY, et al. Pre-labor rupture of membranes and associated factors among pregnant women admitted to the maternity ward, Northwest Ethiopia [Internet]. Public Library of Science; [cited 2023 May 9]. Available from: https://journals.plos.org/globalpublichealth/article?id=10.1371%2Fjournal.pgph.0001702#references

2. Kaur J, Kaur K: Obstetric complications: Primiparity vs. multiparity.European Journal of Experimental Biology2012, 2(5):14621468

3. Caughey AB, Robinson JN, Norwitz ER: Contemporary diagnosis and management of preterm premature rupture of membranes.Reviews in Obstetrics and Gynecology2008, 1(1):11. pmid:18701929

4.Di Renzo GC, Roura LC, Facchinetti F, Antsaklis A, Breborowicz G, Gratacos E, et al: Guidelines for the management of spontaneous preterm labor: identification of spontaneous preterm labor, diagnosis of preterm premature rupture of membranes, and preventive tools for preterm birth.The Journal of Maternal-Fetal & Neonatal Medicine2011, 24(5):659667. pmid:21366393

5. Dos Anjos Borges LG, Pastuschek J, Heimann Y, Dawczynski K, PEONS study group, Schleuner E, et al. Vaginal and neonatal microbiota in pregnant women with preterm premature rupture of membranes and consecutive early onset neonatal sepsis. BMC medicine [Internet]. 2023 Mar 13 [cited 2023 Apr 16];21(1):92. Available from: https://pubmed.ncbi.nlm.nih.gov/36907851/6.Assefa NE, Berhe H, Girma F, Berhe K, Berhe YZ, Gebreheat G, et al: Risk factors of premature rupture of membranes in public hospitals at Mekele city, Tigray, a case-control study.BMC Pregnancy and Childbirth2018, 18(1):386. pmid:30268103

7.Saghafi, N., Pourali, L., Ghazvini, K., Maleki, A., Ghavidel, M., Sc, M.., Babaki, M. & Sc, M.. (2018). Cervical bacterial colonization in women with preterm premature rupture of membrane and pregnancy outcomes: A cohort study. Int J Reprod Biomed., 16(5), 341348.

8.Jerry D, Uwaifo O. MICROBIOLOGICAL PATTERN IN CASES OF PRETERM PREMATURE RUPTURE OF FETAL MEMBRANES (PPROM) MBBS (BENIN) SUBMITTED TO THE NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA IN PART FULFILLMENT OF THE REQUIREMENTS FOR THE FELLOWSHIP OF THE COLLEGE 2007 [Internet]. [cited 2023 Jul 16]. Available from: https://dissertation.npmcn.edu.ng/index.php/FMCOG/article/download/2090/2047/

9. Rani S, Mehra R, Gupta V, Huria A, Chander J. Vaginal flora in preterm premature rupture of membranes and their sensitivity to commonly used antibiotics. Asian J Med Sci [Internet]. 2014 May 16 [cited 2023 Jul. 16];5(4):58-60. Available from: https://www.nepjol.info/index.php/AJMS/article/view/9889

10. Malla R, Metgud S, Metgud SC. Bacteriological profile of Premature rupture of membranes (PROM) in preterm pregnant women: A cross sectional study in Dr. Prabhakar Kore Charitable Hospital, Belagavi, India. International Journal of Clinical Obstetrics and Gynaecology. 2020 Nov 1;4(6):14750.

11. Amina Beevi P, Girija Kumari AG, Sudhamani C. High vaginal swab study in preterm labour and preterm premature rupture of membranes and its relationship with neonatal sepsis. J. Evid. Based Med. Healthc. 2018; 5(30), 2249-2254. DOI: 10.18410/jebmh/2018/466