Outcome of neonates born to mothers with premature rupture of membranes

Introduction: Premature rupture of membranes (PROM) refers to rupture of fetal membranes prior to the onset of labour regardless of the gestation. Objectives: To assess the outcome (morbidity/ mortality) of neonates born to mothers with PROM and to assess the prevalence of PROM in the Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi (Meghe), Wardha, Maharashtra, India. Method: This is a prospective observational study, conducted in the Department of Paediatrics, AVBRH, over a 2 year period with a sample size of 125 neonates born to mothers with history of PROM (≥ 8 hours). Results: The male to female ratio was 0.8 and the ratio of normal vaginal delivery (NVD) to lower segment caesarean section (LSCS) was 1.85. Common associated morbidities were respiratory distress (30.4%), clinical sepsis (28.8%), culture positive sepsis (9.6%), birth asphyxia (5.6%), pneumonia (2.4%) and meningitis (2.4%). Neonates with blood cultures positive for coagulase negative staphylococcus and pseudomonas had 100% mortality. Mortality rate in neonates born to mothers with a history of PROM was 2.4%, sepsis and birth asphyxia being the leading causes of mortality. Conclusions: The prevalence of PROM ≥8 hours’ duration in mothers of in AVBRH was 2.93%. The mortality rate was 2.4%, sepsis and birth asphyxia being the leading causes of mortality. http://dx.doi.org/10.4038/sljch.v49i3.9144 _________________________________________ Junior Resident, Professor, Department of Paediatrics, Jawaharlal Nehru Medical College, Sawangi (M), Wardha, India *Correspondence: anjalimkher@gmail.com orcid.org/ 0000-0003-0214-6954 (Received on 23 October 2019: Accepted after revision on 20 December 2019) The authors declare that there are no conflicts of interest Personal funding was used for the project. Open Access Article published under the Creative Commons Attribution CC-BY License (


Introduction
Premature rupture of membranes (PROM) refers to rupture of fetal membranes prior to the onset of labour regardless of gestation. It is subdivided into preterm premature rupture of membranes (PPROM) which is rupture prior to 37 weeks of gestation and term premature rupture of membranes (TPROM), which is rupture after 37 weeks of gestation. Prolonged rupture of membranes is any rupture of membranes that persists for more than 24 hours and prior to the onset of labour 1 . PROM is one of the most common problems in obstetrics, complicating 8% to 10% of term pregnancies and approximately 1% of all preterm pregnancies 1 .
Current neonatal mortality rate globally is 18 per 1000 live births 2 . In India the neonatal mortality rate was 24 per 1000 live births 2 according to UNICEF data 2015. Neonatal sepsis contributing to neonatal mortality rate is 13.6% 3 . The fetal and neonatal morbidity and mortality risks are significantly affected by duration of latent period and gestation in PROM. The latent period is defined as the time from membrane rupture to onset of contractions 1 .The primary complication due to PROM for the mother is risk of infection and this risk increases with the duration of membrane rupture. Complications due to PROM for the newborn consists of prematurity, sepsis, fetal distress, deformation and altered pulmonary development 4 .
For patients with PPROM, the most likely outcome is preterm delivery within one week, with its associated morbidity and mortality risks such as respiratory distress, necrotizing enterocolitis (NEC), intra-ventricular haemorrhage and sepsis 5 . The association between neonatal sepsis and the duration of membrane rupture was first reported in 1963 in a study which showed a higher rate of clinical or proved sepsis in neonates born to mothers with ruptured membranes of more than 6 hours 6 . In the absence of early specific and sensitive diagnostic tools for neonatal sepsis, management of infants born to mothers with PROM proves to be a dilemma, especially for asymptomatic neonates at birth 7 .
The predictability of laboratory investigations such as complete blood count (CBC) and C-reactive protein (CRP) is low, especially at the onset of illness, or initially in asymptomatic newborns. Their use to rule out sepsis should depend on serial measurements 8 . This diagnostic challenge might justify the practice of admitting all neonates born to mothers with PROM and administering empirical broad-spectrum antibiotics to these asymptomatic neonates without sepsis for prolonged period. This practice drastically increases the load on neonatal units, and exposes the newborn infants to hospitalacquired infections and medication side effects 9 .

Objectives
This study was undertaken to assess the outcome (morbidity/mortality) of neonates born to mothers with PROM and to assess the prevalence of PROM in the Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi (Meghe), Wardha, Maharashtra, India.

Method
This was a prospective observational study, conducted in the Department of Paediatrics, AVBRH, Sawangi (Meghe), Wardha, Maharashtra, India, with a sample size of 125 neonates born to the mothers with history of PROM (≥ 8 hours). Inclusion criteria: All neonates born to mothers with premature rupture of membranes (PROM> =8 hrs) more than or equal to eight hours and delivered in AVBRH hospital Sawangi (Meghe). Exclusion criteria: Those who did not give consent. The data was collected in a pre-validated proforma which included age, parity, socio-economic status, maternal and obstetric history of the mother, and birth history of neonate. A thorough general examination of the neonates was done and all essential investigations were carried out. All data were entered in the Microsoft Excel spreadsheets and Stata software (Stata 10, Stata corporation Texas, USA) was used for data analysis. Differences between means were compared by unpaired Student t-test where data was normally distributed and Mann Whitney U test for nonnormally distributed data. p value less than 0.05 is considered as level of significance. Distribution of data was studied by Kolmogorov Smirnov test. Quantitative data was analysed using mean, median and standard deviation. Qualitative data was summarized using percentage and proportions differences in proportion were compared by chi square test and Fischer's exact text. Differences between means were compared by unpaired Student t-test where data was normally distributed and Mann Whitney U test for non-normally distributed data. To know the true positive cases, true negative cases, probability that the cases with positive CRP truly have Septicaemia, probability that the cases with negative CRP truly don't have Septicaemia and to know the potential utility of CRP respectively, for which 2x2 contingency tables were formed. Also, to know the accuracy of the CRP for septicaemia we calculated the Sensitivity, Specificity, positive predictive value, negative predictive value, Positive Likelihood ratio, and Negative Likelihood ratio for each physical sign. p value less than 0.05 is considered as level of significance.

Results
The mean age of mothers with a history of PROM was 25 years, with a standard deviation of 2.15 years. Mean gestational age of neonates was 36.8 weeks, with a standard deviation of 2.3 weeks. Mean birth weight of neonates was 2.38kg, with a standard deviation of 0.54kg. Mean duration of PROM was 28.7 hours, with a standard deviation of 29.2 hours. In our hospital, total number of deliveries conducted during the study period was 4,261. The prevalence of PROM in mothers of >8 hours duration in our hospital was 2.93%. The prevalence of PROM in mothers of >18 hours duration in our hospital was 1.17%. The incidence of culture positive early onset sepsis (EOS) attributable to PROM in this institute was 9.6%. The baseline characteristics of the neonates included in the study are shown in Table 1. Male to female ratio of the neonates was 0.87 and ratio of normal vaginal delivery (NVD) to lower segment caesarean section (LSCS) was 1.85. Most mothers belonged to the lower socio-economic class according to modified Kuppuswamy classification and there was no correlation between socioeconomic status and duration of PROM. More number of cases were low birth weight (<2.5kg) neonates. It was observed that infection to mother was a major risk factor for PROM >18 hrs duration and previous h/o PROM was the second most common risk factor Distribution of cases based on neonatal morbidities and duration of PROM is shown in Table 2.  Table 2).
Distribution of cases based on birth weight and neonatal morbidities is shown in Table 3. . It was seen that extremely low birth weight babies were more prone to respiratory distress, clinical sepsis and culture positive sepsis. There is statistical significance between neonates with low birth weight and neonatal morbidities like respiratory distress, clinical sepsis and culture proven sepsis ("p" value <0.05 and based on percentages) ( Table 3).
Distribution of cases based on gestational age and neonatal morbidities is shown in Table 4.  Table 4).
Distribution of cases based on prophylactic prenatal antibiotics received by mothers with a history of PROM to neonates with clinical and culture proven sepsis is shown in Table 5. between prenatal prophylactic antibiotics and culture positive sepsis ( Table 5).
Distribution of cases based on outcome in relation to clinical sepsis, culture positive sepsis and birth asphyxia is shown in Table 6. Blood culture positive sepsis was seen in 12 neonates. Out of them coagulase negative staphylococcus and pseudomonas attributed to mortality whereas most common organism grown was methicillin resistant staphylococcus aureus (MRSA). The mortality rate was 2.4%, with sepsis and birth asphyxia being the leading causes of mortality ( Table 6)

Discussion
The incidence of PROM >8 hours duration in AVBRH was 2.93%. Most studies have included neonates born to mothers with PROM >18 hours duration, but we have included neonates with PROM >8 hours duration because we wanted to find out the incidence of early onset sepsis in these neonates also. The incidence of PROM >18 hrs duration in mothers in our hospital was 1.17%. This was similar to the incidence rate of 1.3% in a study by Idrisia et al 11 , but lower than the 2.7% incidence rate in the study by Alam et al 17 , and the 4.2% incidence rate in the study by Sharma et al 13 .
In this study, 70% cases were in the lower socioeconomic class and 30% were in the lower middle socio-economic class. This is consistent with the study by Amulya N et al 10 in which 80% of cases belonged to low socioeconomic status, 13.3% belonged to middle socioeconomic status and 6.7% belonged to higher socioeconomic status. Similar results were seen in a study by Idrisia et al 11  In this study, 28.8% had clinical sepsis and 9.6% had culture-positive sepsis, similar results were found in a study conducted by Thayi S et al 18 where clinical sepsis was observed in 30% of cases and culturepositive sepsis was observed in 11% of neonates. In a study by Nili et al 4 clinical sepsis was observed in 20.2% of cases and culture-positive sepsis was observed in 5.5% of cases. These lower numbers could be attributed to selection criteria of cases, they have included duration of PROM from 1 hour.
In this study total mortality was 2.4%, and the most common causes leading to death were sepsis and birth asphyxia. A study by Lokhande et al 19 16 which could be attributed to the inclusion criteria as they have included neonates whose mother had a history of PROM for more than 18 hours. In the study by Poovathi et al 22 the mortality was 10% and this could be due to the inclusion of only preterm neonates in their study.

Conclusions
The prevalence of PROM ≥8 hours' duration in mothers delivered in AVBRH was 2.93% and in >18 hours duration of PROM it was 1.17%. Neonatal morbidities like clinical sepsis, respiratory distress, culture-positive sepsis, meningitis, pneumonia, and birth asphyxia increased as the duration of PROM increased. The mortality rate was 2.4%, sepsis and birth asphyxia being the leading causes of mortality.