A prospective study on the neonatal compications associated with prolonged premature rupture of membranes at a tertiary care hospital: A comperative analysis

doi:10.21203/rs.3.rs-5063443/v2

Background: Premature rupture of the membranes (PROM) is a common complication during pregnancy, which leads to adverse effects in both mothers and newborns. The management of premature rupture of the amniotic sac is still controversial among physicians, which is associated with a wide range of maternal and neonatal complications. Expectant management might increase the risk of infection in both mothers and neonates. Therefore, in this study we aimed to investigate neonatal outcomes following prolonged PROM(PPROM).

Methods and material: This study is a prospective cross-sectional descriptive study. Based on the inclusion and exclusion criteria, 65 neonates with premature rupture of membranes longer than 18 hours and 65 neo-nates with premature rupture of membranes less than 18 hours were selected through random sam-pling.and included in the study through simple random sampling. After recording the demographic charac-teristics of the mothers and the neonates and the outcomes of the neonates, it was entered into the SPP version 22 software for statistical analysis. A significance level (p.value) less than 0.05 was considered significant

Results: Out of 130 neonates, 57.7% were male and 42.3% were female. 62.3% of the neonates were born by cesarean section and the rest by vaginal delivery. In the studied population, 43% were pre-term neonates and the rest were term. The mean birth weight was 2825.35 ±572.34 grams and The mean Apgar score at fifth minute was 8.8 ± 1.19. The incidence rate of early neonatal infection (EOI) was 26.2% (34 cases) and the in-hospital death rate was 3.8% (5 cases). Based on our findings, the association between the duration PROM with early onset infection and resuscitation was statistically significant (p.value<0.05). The mean Apgar score at 5th minute was significantly higher in neonates with PROM longer than 18 hours than neonates with PROM less than 18 hours. Moreover, no significant association was observed between the duration of PROM and in-hospital mortality of neonates.

Conclusion: Based on the findings of our study, it can be concluded that the increase in the duration of rupture of the amniotic sac until the onset of labor is associated with an increase in the rate of early onset neonatal infection, a low Apgar score in the fifth minute, and the need for higher levels of resuscitation. However, it is not associated with in-hospital mortality of newborns.

Pediatrics

Premature rupture of membranes

Apgar score

Early onset infection

neonatal resuscitation

Premature rupture of the membranes (PROM) is a common complication during pregnancy that occurs in 5–10% of pregnancies(1). This phenomenon is associated with significant neonatal and maternal morbidities. Prolonged rupture of the amniotic sac is one of the main risk factors of premature birth and early onset neonatal sepsis(EOS). (1,2)

As soon as the amniotic sac ruptures, the amniotic fluid around the fetus leaks out and exposes the neonate to intrauterine infection.(2) The time interval between PROM and the induction of labor may last from a few hours to a few days. If the time period between the rupture of amniotic sac and labor lasts more than 18 hours, it is called prolonged PROM, and if it occurs before 37 weeks, it is called preterm PROM. (2,1)

Prolonged PROM significantly increases the risk of early onset infection ( EOI) in Newborns(2,3,4). Neonatal sepsis is the most common complication following prolonged PROM. One of the most important causes of neonatal mortality is early onset neonatal sepsis(EOS). (4) Prematurity, fetal distress, compression of the umbilical cord and impairment of lung development are among the other consequences that may occur after PROM. (2,5)

Studies have shown that PROM may increase the risk of early-onset pneumonia.

In 1952, Dr. Virginia Apgar developed a scoring system that was a rapid way to assess the general clinical condition of a newborn immediately after birth and the need for resuscitation.(6) Studies haves shown that Prolonged PROM is associated with abnormal Apgar score in neonates and considered as a risk factor for neonatal resuscitation.(7)

Thus proper management of premature rupture of membranes aims to balance the aforementioned conditions and prevent adverse complications.

This study was a descriptive cross-sectional -study, which was conducted from 5th May to 21th August 2024 at a tertiary care hospital in Zanjan. The study population is newborns admitted to the NICU department of Ayatollah Mousavi hospital in Zanjan, in 2024.

A number of 65 neonates with a gestational age of 41 − 35 weeks and prolonged PROM and 65 neonates with premature rupture of membranes lasting less than 18 hours were selected through random sampling and included in the study. Immediately after delivery, gender, birth weight, respiratory rate, heart rate, Apgar score are recorded in the fifth minute. In addition, the demographic characteristics of the mother (age, Gravidity, and type of delivery) were retrieved and recorded. Newborns with a gestational age less and more than 37 weeks were considered preterm and term respectively.

Common neonatal morbidities investigated in this study include: early neonatal infection(EOI), low Apgar score at fifth minute, and the need for resuscitation in the delivery room. Moreover, the outcome of the babies was recorded in terms of ((discharge)) or ((death)).

All Newborn in the delivery room first undergo the initial steps of resuscitation, which include tactile stimulation, warming and drying. (7) Newborns with a heart rate above 100 and spontaneous breathing may also undergo CPAP.

If after stimulation, if no respirations are observed and the heart rate remains less than 100 beats per minute, positive pressure ventilation (PPV) should be initiated through an appropriately sized face mask, which is considered as ((basic resuscitation)). If 60 seconds after positive pressure ventilation(PPV) with corrective steps, the newborn’s heart rate remains below 60 beats per minute, the baby should be intubated. If the heart rate remains below 60 beats per minute, chest compressions are started at the same time as ventilation and oxygen saturation is increased to 100%, which is called ((advanced resuscitation)). (7,8)

Within 12 hours after birth, a blood sample was taken from the newborn’s heel and sent for laboratory evaluations such as CBC (complete blood count), CRP (C-reactive protein) and blood sugar. Blood culture is considered the gold gold standard for definite diagnosis of EOS.(1,10)

The clinical manifestations of sepsis are non-specific and include lethargy, respiratory distress, apnea, convulsions, need for mechanical ventilation, abdominal distention, hypotension, meningitis, arthritis, kidney problems, oxygen therapy, jaundice, not feeding well, worsening general condition, and poor feeding. The most important laboratory signs of infection include leukocytosis (white blood cell count above 14,000), leukopenia (white blood cell count below 4,000), thrombocytopenia (blood platelets below 150,000), and C-reactive protein above 6 mg/dL. Neonates who presented with clinical manifestations of EOI in 3–7 days after birth and required continuous resuscitation were considered as ((early neonatal infection)) cases. (9,10,11)

The value of Apgar score Is expressed as an integer number from zero to ten, which was calculated with the help of Apgar scoring system. Apgar score less than 7 is considered abnormal. (6)

Sample size:

Using the information of Yan et al.'s study (12) and using the formula to determine the sample size of quantitative groups and considering the first error of 5% and the study power of 80%, the number of samples required to conduct this study was calculated to be 65 neonates in each group classified by PROM. Considering that various variables measured in this research, the Apgar data of the 5th minute of the mentioned study was used to determine the sample size.

Inclusion criteria:

hospitalized babies born to pregnant mothers with a gestational age of 34–41 weeks and have no congenital anomalies.

Exclusion criteria: Neonates with gestational age of less than 34 weeks, stillbirth, congenital anomalies and hereditary diseases, multiple births, pre-eclampsia, intraventricular hemorrhage, lack of personal consent of the parents.

Variables:

• Gestational age: Discrete variable (independent)

• Birth weight: Continuous variable (background)

• Neonatal resuscitation in the delivery room: Ordinal variable (dependent)

• Apgar score at 5th minute: Discrete variable (dependent)

• Early onset neonatal infection: Nominal quality (dependent)

• Delivery type: Nominal variable (independent)

• Neonatal in-hospital death: Nominal variable (dependent)

• Premature rupture of membranes: Nominal variable (independent)

• Gender of the newborn: nominal variable (background)

• Maternal age: continuous variable (background)

• Gravidity: Discrete variable (background)

Collection of data:

Through random sampling a total number of 130 newborns consisting of 65 newborns with PROM longer than 18 hours and 65 newborns with PROM less than 18 hours was selected and included in the study. The information related to the variables was extracted from the patients’ files and recorded in a checklist.

Analysis of data:

After collecting the relevant information, it was entered into SPSS software (26th version) for comparison and statistical analysis.

Ethical considerations:

Parents’ informed consent was obtained Prior to start of the study. They were also given the necessary explanations about the goals of the study and were assured that the information about their patients will remain anonymous and confidential. Moreover, no cost was imposed on them during the study. All stages of the study were approved by the ethics committee of Zanjan University of Medical Sciences. (IR.ZUMS.REC.1403.043)

As shown in Table No. 1, 57.7% of the neonates were male and 42.3% were female. 62.3 percent of neonates were born through caesarean section and the rest were born through normal vaginal delivery(NVD). In addition, 43% of neonates were pre-term and the rest were term.

Statistical analysis of data showed that the average of maternal age was 29.42 ± 7.27 and The average of gravidity was 2.1 ± 1.2.

The average birth weight of the neonates is 2825.35 ± 572.34 grams. Furthermore, the average gestational age of neonates was 36.88 ± 1.6.

Twenty-three percent of neonates underwent basic resuscitation, five and a half percent underwent advanced resuscitation, and the rest underwent initial steps of resuscitation. A statistically significant association was found between the level of neonatal resuscitation and the type of delivery (p value < 0.05).

Furthermore in neonates born through NVD, no statistically significant association was found between the duration of PROM and the level of resuscitation, while this association was significant in the cesarean group (p value < 0.05). (Table 2)

The incidence rate of early onset neonatal infection(EOI) was 26.2%, In pre-term neonates, no significant was found between the duration of PROM and EOI, however, this association was statistically significant in term neonates (p value < 0.05). Chi-square test results showed a statistically significant association between EOI and gestational age (p-value < 0.05). In addition, the incidence of EOI in the group with PROM over 18 hours was significantly higher (p.value < 0.05).

No significant association was found between the duration of PROM and incidence of EOI in neonates born through NVD, While in neonates born through cesarean section, this association was statistically significant (P.value < 0.05). In addition, the statistical association of EOI rate was significant stratified by the type of delivery (p.value < 0.05). (Table 3)

In our study population, the incidence of EOI in neonates born through NVD (28.5%) was higher than the cesarean group (24.7%). (Table 3)

The rate of neonatal in-hospital mortality was 3.8%. No significant association was observed between the duration of PROM and neonatal in-hospital mortality.( Table 4)

The mean fifth minute Apgar score of the studied sample was 8.8 ± 1.19(Table 5). Apgar score at fifth minute stratified by the type of delivery was measured by independent t-test. The results showed a statistically significant difference in the mean Apgar score of the two groups. (p value < 0.05). The mean fifth minute Apgar score of the neonates born from mothers with PROM less than 18 hours was significantly higher. However, The results showed no significant association between the mean fifth-minute Apgar score in term and pre-term neonates (p value > 0.05). However the difference of the mean fifth-minute Apgar score of the neonates stratified by mode of delivery was statistically significant (p-value < 0.05). (Table 6,7)

Table 1.

This research is conducted regarding the neonatal comlications of PROM at a tertiary care hospital in zanjan, Iran. In this study, we first examined the frequency of the demographic characteristics of the mothers in the study sample. The predominant gender of newborns was male (57.3%).

In our study, 57% of the neonates were term and the rest were preterm. The average geatational age was 36.88 (SD:1.6). In addition, 61% of neonates were born through cesarean section and the rest through NVD.

The average birth weight of the studied infants was 2835 grams (SD:571), which was less than Afjeh's study (2984 grams with a standard deviation of 667).(7)

The findings of our study indicates that the mean maternal age was 29.4 (SD:7.27). In addition, 62.3% of mothers were in the age range of 21–35 years. Moreover in this study, 60% of the mothers were multigravid and the rest were primigravid.

Based on our findings, 34 neonates (26%) had clinical manifestations of early onset neonatal infection (EOI), of which 7 cases (5.4%) had positive blood cultures who were considered definite EOS.

The mean Apgar score at fifth-minute of the nenoates was 8.92(SD:1.19), which is considered within the normal range. However, in the afjeh study, the average five-minute Apgar score was 9.8 (SD:0.8). The statistical analysis of the data demonstrated that the average fifth-minute Apgar score of neonates with PROM over 18 hours was significantly lower, however, there was no significant difference in the fifth-minute Apgar score according to the type of delivery and geatational age.

In the study conducted by Baser, the consequences of prolonged PROM in preterm infants who were managed expectantly were investigated. The results of this study showed that prolonged PROM wasn’t associated with increased neonatal sepsis.(5)

In Afjeh’s study, the association between maternal and neonatal risk factors and neonatal resuscitation was investigated. In that study, the statistical difference between neonatal resuscitation and PROM was significant, which is consistent with the results of our study. However, in our study, there was no significant statistical difference between the levels of neonatal resuscitation and the type of delivery and gestational age, which is contrary to the results of Afjeh’s study. (7)

In Nghitanwa’s study, maternal factors associated with low Apgar scores in infants were investigated. This study showed that the type of delivery is associated with low Apgar score, but there was no statistically significant relationship between low Apgar score and gestational age. In addition, prolonged PROM before the onset of labor was associated with a low Apgar score.(13)

In a case-control study conducted by Afaya, the risk factors associated with neonatal sepsis were investigated. PROM and mode of delivery had a significant relationship with the risk of early neonatal sepsis. In that study, it was mentioned that most of the neonates with early onset sepsis were delivered through cesarean section.(14)

In Chakravarti’s study, 30% of nenoates with PROM over 18 presented with symptoms of early onset sepsis (EOS), which was less than our study (35.3%). It was also shown in that study that there was no significant difference in the incidence of early onet sepsis in the two groups of 18 to 24 hours and 24 to 72 hours. However, the incidence of EOS was significantly higher in preterm newborns and those who were delivered through NVD.(4)

The In-hospital mortality rate among newborns in our study was roughly 3.8% (5 cases). In Muhammad Hanif’s study, the mortality rate in 155 term newborns was approximately 10.3 percent and in Ramesh’s study, it was 5 cases (5%) among 100 newborns. Furthermore, in Shanbhag’s study, the mortality rate was 2.3%, which was less than our study.(1,2,15)

In addition, in our study, there was no statistically significant relationship between in-hospital mortality and duration of PROM which is contrary to the results of Muhammad Hanif and Shanbhag’s studies.(1,15)

Prolonged PROM(PPROM) is associated with low Apgar score at fifth minute, increased rate of early onset neonatal infection(EOI), and need for higher levels of neonatal resuscitation. However, it is not associated with in-hospital mortality of newborns.

PROM

Premature rupture of the membranes

NICU

neonates’ intensive care unit

PPV

Positive pressure ventilation

CPAP

Continuous positive airway pressure

NVD

Normal vaginal delivery

C/S

caesarean section

EOI

early onset infection

SD

Standard deviation

CBC

Complete blood count

CRP

C-reactive protein

PPROM

Prolonged PROM

The concept of the research was proposed by A.M. Methodology of the research was defined by F.KT and S.M. Collection of the data and statistical analysis and preparation of the final report was performed by R.S. All stages of the researche was under the supervision of A.M and F.KT. All authors contributed equally to the research.

Funding Sources. This article was funded by the Research Deputy of Zanjan University of Medical Sciences, Iran, with the approval number (The code " A-11-306-18 ").

Conflict of interests:

No conflict of interest relevant to this article was reported

Availability of data and materials:

The dataset used in the present study is available from the corresponding author upon logical request

Ethical considerations:

All experimental protocols were approved by the Ethics Committee of the Vice Chancellor for Research of Zanjan University of Medical Sciences, Iran with the registration code (IR.ZUMS.REC.1403.043). After informing the study's purposes, written informed consent were obtained from all parents.

They were informed that their information remains confidential and anonymous, and was apprised of their right to withdraw from the research at any time.

Acknowledgment:

Herein We appreciate the Clinical Research Development Unit of Ayatollah Mousavi Hospital in Zanjan University of Medical Sciences for their collaboration, and vice-chancellor of research and technology for their financial support to carry out the study.

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Table 1

illustrates the demographic characteristics of 65 neonates born from mothers with PROM longer than 18 hours and 65 neonates with PROM less than 18 hours who were admitted to the NICU department of Mousavi Zanjan Hospital in 1403.
variable		PROM less than 18 h		PROM more than 18 h		Total
variable		Nember	Percent	Nember	Percent	Nember	Percent
Gender	Male	40	31.5%	35	25.8%	75	57.7%
Gender	female	25	18.5%	30	23.8%	55	42.3%
Gravidity	Primigravid	26	20%	26	20%	52	40%
Gravidity	Multigravid	39	30%	39	30%	78	60%
Gestational age(w)	Preterm	25	19.2%	31	23.8%	56	43%
Gestational age(w)	Term	40	30.8%	34	26.2%	74	57%
Type of delivery	NVD	23	17.7%	26	20%	49	37.7%
Type of delivery	C/S	42	32.3%	39	30%	81	62.3%
Maternal age(year)	< 21	9	6.8%	9	6.8%	18	13.8%
	21–35	35	27%	46	35.3%	81	62.3%
	> 35	21	16.2%	10	7.7%	31	23.8%

Table 2

Frequency of Neonatal resuscitation stratified by Mode of delivery and gestational age
variable			Neonatal resuscitation			p.value
variable			Initial steps (n)	Basic (n)	Advanced (n)	p.value
Type of delivery	NVD	PROM less than 18 h	18	4	1	0.308
	NVD	PROM more than 18 h	15	9	2	0.308
	C/S	PROM less than 18 h	37	5	0	0.007
	C/S	PROM more than 18 h	23	12	4	0.007
Total			93			0.003
Gestational age	Preterm	PROM less than 18 h	25	0	0	0.001
	Preterm	PROM more than 18 h	17	12	2	0.001
	Term	PROM less than 18 h	30	9	1	0.232
	Term	PROM more than 18 h	21	9	4	0.232
Total			93	30	7	0.003

Table 3. Frequency of Early onset neonatal infection stratified by Mode of delivery and Gestational age

variable			Early onset neonatal infection		p.value
variable			Yes	No	p.value
Type of delivery	NVD	PROM less than 18 h	5	18	0.25
	NVD	PROM more than 18 h	9	17	0.25
	C/S	PROM less than 18 h	6	36	0.022
	C/S	PROM more than 18 h	14	25	0.022
Total			34	96	0.014
Gestational age	Preterm	PROM less than 18 h	3	22	0.356
	Preterm	PROM more than 18 h	6	25	0.356
	Term	PROM less than 18 h	8	32	0.007
	Term	PROM more than 18 h	17	17	0.007
Total			34	96	0.014

Table 4

Frequency of Neonatal in-hospital mortality stratified by Mode of delivery and Gestational age
variable			Neonatal in-hospital mortality		P.value
variable			yes	No	P.value
Type of delivery	NVD	PROM less than 18 h	1	22	0.929
	NVD	PROM more than 18 h	1	25	0.929
	C/S	PROM less than 18 h	0	42	0.067
	C/S	PROM more than 18 h	3	36	0.067
Total			5	125	0.17
Gestational age	preterm	PROM less than 18 h	0	25	0.365
	preterm	PROM more than 18 h	1	30	0.365
	Term	PROM less than 18 h	1	39	0.231
	Term	PROM more than 18 h	3	31	0.231
Total			5	125	0.17

Table 5
variable		PROM less than 18 h	PROM more than 18 h	Total	p.value
Apgar score at 5th minute	Mean ± SD	9.14 ± 0.984	8.69 ± 1.34	8.8 ± 1.19	0.032

Table 6
variable		PROM less than 18 h	PROM more than 18 h	p.value
variable		Mean ± SD	Mean ± SD	p.value
Preterm	Apgar score at 5th minute	9.08 ± 0.95	8.81 ± 0.79	0.913
Term	Apgar score at 5th minute	9.18 ± 1.01	8.59 ± 1.69

Table 7
variable		PROM less than 18 h	PROM more than 18 h	p.value
variable		Mean ± SD	Mean ± SD	p.value
NVD	Apgar score at 5th minute	8.7 ± 1.15	8.62 ± 1.13	0.05
C/S	Apgar score at 5th minute	9.38 ± 0.79	8.74 ± 1.46	0.05

The authors declare no competing interests.

A prospective study on the neonatal compications associated with prolonged premature rupture of membranes at a tertiary care hospital: A comperative analysis

Status:

Version 2

Abstract

Background

Method

Sample size:

Inclusion criteria:

Variables:

Collection of data:

Analysis of data:

Ethical considerations:

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Tables

Additional Declarations

Status:

Version 2