Materno-Fetal Prognosis and Factors Associated with Neonatal Death after Preterm Premature Rupture of Membranes at More than 28 Weeks Gestation in Yaoundé, Cameroon ()
1. Introduction
Preterm premature rupture of membranes (PROM) is a common occurrence in obstetric practice. It complicates 3% to 10% of pregnancies worldwide. It exposes the mother to a risk of infection and her fetus to premature delivery [1]. These complications are all the more serious when the rupture occurs prematurely.
In Cameroon, according to a study conducted by Pisoh et al. in 2021, PPROM significantly contributes to maternal and perinatal morbidity and mortality. According to this study, 10.53% of women who had preterm premature rupture of membranes (PPROM) had an unfavorable outcome, as did the newborns from these pregnancies (OR = 14.44; 95% CI: 5.42 - 38.48; p < 0.001) [2]. To our knowledge, very few studies clearly present these adverse maternal and fetal outcomes after PPROM in Cameroon. The objectives of this study were to determine the incidence of PPROM, then to assess maternal, fetal and early neonatal outcomes after PPROM, and finally to identify the factors associated with neonatal death in the context of PPROM.
2. Materials and Methods
2.1. Ethical Considerations
The study was conducted in accordance with the fundamental principles of research as set out in the Declaration of Helsinki. We obtained ethical clearance from the Institutional Ethics and Research Committee (CIER) of the Faculty of Medicine and Biomedical Sciences of the University of Yaoundé I and the Gynaecology, Obstetrics and Paediatrics Hospital of Yaoundé, as well as research authorisation from the Central Hospital of Yaoundé. All women were included after giving their informed consent or parental consent for minors.
2.2. Methodology
We conducted a cohort study with prospective data collection. It took place from 1 January to 30 April 2022. We included all pregnant women diagnosed or referred for RPM occurring after 28 weeks of gestation at the Central Hospital and the Gynaecology, Obstetrics and Pediatrics Hospital in Yaoundé. The diagnosis of RPM was clinical; examination with a speculum revealed fluid discharge of endo uterine origin. We did not have colorimetric tests available to confirm that the fluid was amniotic fluid.
Data were collected using a pre-established questionnaire. Maternal variables included maternal sociodemographic characteristics, maternal history, pregnancy history, clinical examination of patients on admission, additional tests performed, treatment and maternal complications observed. Fetal-neonatal variables included the clinical profile of the newborn and fetal and neonatal outcomes. Follow-up was then carried out using medical records until the early neonatal period, and any complications in mothers and their newborns were recorded. The data collected were recorded on a technical data sheet designed for this purpose, then recorded and analyzed.
This data was analyzed using SPSS (Statistical Package for Social Sciences) version 23.0. Microsoft Office Excel 2016 was used to create tables and figures. The incidence of RPM, fetal and neonatal outcomes, and maternal complications were interpreted in terms of frequencies and percentages. Bivariate analysis was performed using the chi-square test, followed by multivariate logistic regression to identify independent predictors. The association between variables and neonatal death was statistically significant if the p-value was <0.05 with a 95% CI after logistic regression.
3. Results
3.1. Maternal Results
During our study, 115 patients were diagnosed with RPM, of whom 3 were discharged from hospital against medical advice, leaving 112 patients.
Table 1. Sociodemographic characteristics of the population.
Variables (n = 112) |
Number (n) |
Percentages (%) |
Age (in years) |
|
|
<20 |
8 |
7.1 |
[20 - 30[ |
70 |
62.5 |
>30 |
34 |
30.4 |
Occupation |
|
|
Housewife |
26 |
23.2 |
Pupil |
15 |
13.4 |
Student |
24 |
21.4 |
Civil servant |
11 |
9.8 |
Shopkeeper |
4 |
3.6 |
Other |
32 |
28.6 |
Marital status |
|
|
Single |
48 |
42.9 |
Married |
20 |
17.9 |
Cohabiting |
44 |
39.3 |
We obtained a PPRM incidence rate of 6.18%. The average age was 27.07 ± 5.82 years. A majority of women (62.5%) were between 20 and 30 years old; this population consisted largely (76.8%) of women who had given birth to few children (Table 1).
Table 2. Background of the population.
Variables (n = 112) |
Number of individuals (n) |
Percentages (%) |
Gynaecological and obstetric background |
|
|
Parity |
|
|
<4 |
86 |
76.8 |
>4 |
26 |
23.2 |
History of abortion |
38 |
33.9 |
RPM ATCD |
11 |
13.6 |
MAP ATCD |
7 |
6.3 |
ATCD cervical-isthmic gap |
4 |
3.6 |
History of cerclage |
2 |
1.8 |
ATCD genital infection |
20 |
17.9 |
Associated pregnancy-related conditions |
|
|
Metrorrhagia |
4 |
3.6 |
Chorioamnionitis |
2 |
1.8 |
Other |
50 |
44.6 |
History of caesarean section |
10 |
8.9 |
Table 3. Physical examination characteristics.
Variables (n = 112) |
Number (n) |
Percentages (%) |
Mode of labour onset |
|
|
Spontaneous |
88 |
78.6 |
Induced |
24 |
21.4 |
Foetal heart rate (bpm) |
111 |
99.1 |
Valsalva |
103 |
92 |
Amniotic fluid colour |
|
|
Clear |
80 |
71.4 |
Tinted |
12 |
10.7 |
Bloody |
1 |
0.9 |
Meconium |
19 |
17.0 |
The most common gynecological and obstetric past history finding was abortion (33.9%), followed by genital infections (17.9%), PPRM (13.6%), cervical incompetence (3.6%) and cerclage (1.8%). Previous caesarean section was the most common surgical history (8.9%) (Table 2). Most of the women in labor went into labor spontaneously (78.6%) and fetal heartbeat was present in almost all women (99.1%). Vaginal fluid discharge (positive Valsalva) was observed in 92% of patients; amniotic fluid was clear in 71.4% of women. Meconium was found in 17% of cases, stained fluid in 10.7% and bloody fluid in 0.9% (see Table 3). The most common biological tests performed were complete blood count and C-reactive protein level (Table 4). No women were tested for Group B streptococcus. The most common abnormality found on ultrasound was oligohydramnios, with a rate of 23.2%.
Table 4. Paraclinical characteristics.
Variables (n = 112) |
Number of subjects (n) |
Percentages (%) |
Infectious assessment |
|
|
ECBU |
17 |
15.2 |
PCV |
10 |
8.9 |
NFS |
85 |
75.9 |
CRP |
30 |
26.8 |
Obstetric ultrasound |
79 |
70.5 |
Normal |
51 |
45.5 |
Oligohydramnios |
26 |
23.2 |
Anamnios |
2 |
1.8 |
Table 5. Treatment provided.
Variables (n = 112) |
Number of individuals (n) |
Percentages (%) |
Medication received |
|
|
Corticosteroid therapy (n = 58) |
37 |
64 |
Antibiotic therapy |
80 |
71.4 |
Tocolytics |
22 |
19.6 |
Outcome of pregnancy |
|
|
IMG |
2 |
1.8 |
Expectant |
110 |
98.2 |
Mode of delivery |
|
|
Vaginal |
84 |
75 |
Caesarean |
28 |
25 |
Among the 58 women with premature rupture of membranes, 64% received corticosteroid therapy and 19.6% received tocolytic therapy for 48 hours. The majority of women, 71.4%, received antibiotic therapy during their hospitalization. The outcome of most pregnancies (98.2%) was expectant, meaning that the pregnancy was monitored clinically and paraclinically, and the most common mode of delivery was vaginal delivery at a rate of 75% compared to a caesarean section rate of 25% (Table 5).
The maternal complications observed showed a premature delivery rate of 50.9%. Caesarean section was chosen as the mode of delivery in 25% of cases. In addition, complications such as Abruptio placenta (3.6%) and intrauterine infections were noted: chorioamnionitis (1.8%) and endometritis (4.5%) (Figure 1).
Figure 1. Maternal complications with percentage scale on y-axis.
3.2. Fetal and Neonatal Outcomes
The most common mode of transfer was in utero (94.6%) from another health facility. The majority of newborns were alive at birth (96.4%) with a birth weight > 2500 g (53.6%) and were males (54.5%). Eighty-two per cent of newborns had complications during the perinatal period and 38% of them had received resuscitation at birth. Neonatal death was observed in 12.5% of newborns, admitted to the neonatal unit in context of PROM (Table 6).
The Apgar score at 5 minutes was 8.35 ± 1.94 on average, with a minimum of 0 and a maximum of 10. The average length of hospitalization was 7.55 ± 7.96 days, with a maximum of 42 days (Table 7).
Fetal outcome after RPM was much more marked by premature births (50.9%). In addition, the death rate was 3.6% at birth (stillbirths) and 9.3% during hospitalization.
Perinatal and neonatal complications were dominated by early neonatal infections (73.14%); prematurity (52.8%); respiratory distress (5.6%); neonatal asphyxia (2.8%); and neonatal jaundice (3.7%) (Table 8).
The factors significantly associated with neonatal death were weight < 2500 g (p-value = 0.001), prematurity (p-value = 0.017), vaginal delivery (p-value = 0.035), an Apgar score at 5 minutes < 7 (p-value = 0.001), and oligohydramnios (p-value = 0.020). After multivariate analysis with logistic regression, only an APGAR score at 5 min < 7 was associated with neonatal death in the context of RPM, with an OR of 8.77 (1.27 - 60.59) and a p-value of 0.028 (Table 9).
Table 6. Clinical profile of newborns.
Variables (n = 112) |
Number (n) |
Percentages (%) |
Mode of transfer |
|
|
In utero |
106 |
94.6 |
Postnatal |
6 |
5.4 |
Status at birth |
|
|
Alive |
108 |
96.4 |
Stillborn |
4 |
3.6 |
Resuscitation at birth |
42 |
37.5 |
Birth weight (g) |
|
|
<2500 |
52 |
46.4 |
>2500 |
60 |
53.6 |
Gender |
|
|
Male |
61 |
54.5 |
Female |
51 |
45.5 |
Neonatal complications |
92 |
82.1 |
Neonatal mortality |
14 |
12.5 |
Pathologies at 7 days of life |
19 |
17 |
Table 7. Different characteristics of the APGAR score and length of hospital stay.
APGAR score |
Min - Max |
Mean ± SD |
1stminute |
0 - 9 |
7.49 ± 1.71 |
5th minute |
0 - 10 |
8.35 ± 1.94 |
10th minute |
0 - 10 |
9.10 ± 2.11 |
Length of stay (days) |
0 - 42 |
7.55 ± 7.96 |
Table 8. Perinatal and neonatal complications.
Complications (n = 108) |
Number (n) |
Percentages (%) |
Early neonatal infections |
79 |
73.1 |
Prematurity |
57 |
52.8 |
Respiratory distress |
6 |
5.6 |
Neonatal jaundice |
4 |
3.7 |
Neonatal asphyxia |
3 |
2.8 |
Table 9. Factors associated with neonatal death.
(a) Bivariate analysis |
Variables (n = 112) |
Deaths, n (%) |
OR (95% CI) |
p-value |
Yes |
No |
Mode of transfer |
|
|
|
|
In utero transfer |
11 (10.4%) |
95 (89.6%) |
0.579 (0.06 - 5.41) |
0.502 |
Postnatal transfer |
1 (16.7%) |
5 (83.3%) |
|
|
Time to rupture |
|
|
|
|
<12 hours |
11 (10.4%) |
95 (89.6%) |
0.579 (0.06 - 5.41) |
0.502 |
>12 hours |
1 (16.7%) |
5 (83.3%) |
|
|
Prematurity |
10 (17.5%) |
47 (82.5%) |
5.638 (1.17 - 27.05) |
0.017 |
Birth weight (g) |
|
|
|
|
<2500 |
11 (21.2%) |
41 (78.8%) |
15.82 (1.96 - 127.40) |
0.001 |
>2500 |
1 (1.7%) |
59 (98.3%) |
|
|
Mode of delivery |
|
|
|
|
Caesarean |
0 (0%) |
28 (100%) |
- |
|
Vaginal delivery |
12 (14.3%) |
72 (85.7%) |
- |
0.035 |
Apgar score at 5 minutes |
|
|
|
|
<7 |
4 (44.4%) |
5 (55.6%) |
9.50 (2.12 - 42.56) |
0.001 |
>7 |
8 (7.8%) |
95 (92.2%) |
|
|
Ultrasound |
|
|
|
|
Oligohydramnios |
6 (23.1%) |
20 (76.9%) |
4 (1.12 - 13.73) |
0.020 |
Anamnios |
(0%) |
2 (100%) |
- |
1 |
Neonatal complications |
12 (13%) |
80 (87%) |
- |
0.120 |
Length of hospital stay |
|
|
|
|
<7 |
9 (13.4%) |
58 (86.6%) |
2.17 (0.55 - 8.51) |
0.256 |
>7 |
3 (6.7%) |
42 (93.3%) |
|
|
Gender |
|
|
|
|
Male |
6 (9.8%) |
55 (90.2%) |
0.82 (0.247 - 2.712) |
0.742 |
Female |
6 (11.8%) |
45 (88.2%) |
|
|
(b) Multivariate analysis |
Variables (n = 112) |
Death, n (%) |
Adjusted OR (95% CI) |
Adjusted p-value |
Yes |
No |
Prematurity |
10 (17.5%) |
47 (82.5%) |
1.12 (0.096 - 12.99) |
0.930 |
Birth weight (g) < 2500 |
11 (21.2%) |
41 (78.8%) |
6.87 (0.42 - 112.63) |
0.177 |
Mode of delivery |
|
|
|
|
Vaginal delivery |
12 (14.3%) |
72 (85.7%) |
- |
0.998 |
Apgar score at 5 min |
|
|
|
|
<7 |
4 (44.4%) |
5 (55.6%) |
8.77 (1.27 - 60.59) |
0.028 |
Ultrasound |
|
|
|
|
Oligoamnios |
6 (23.1%) |
20 (76.9%) |
2.47 (0.58 - 10.49) |
0.220 |
4. Discussion
PPROM is a common condition during both preterm and full-term pregnancies. According to data from African literature, it has a prevalence of 4.63% in Mali and an incidence of 10% in Algeria [3] [4]. In our series, the incidence of PPROM was 6.18%, which is higher than that found in other national studies on PPROM (1.6%, Kasia et al.; 4.91%, Pisoh et al.) [2] [5]. This difference could be explained by the fact that we worked in two recruitment and referral sites for obstetric complications. In 2017 in Cameroon, Belinga et al. found that premature rupture of membranes was statistically significant in patients referred for obstetric complications in Yaoundé [6]. In addition, our population consisted largely of women who had given birth only a few times (77%), in whom PPROM is more common due to the increased fragility of the amniotic membranes, unlike multiparous women, whose membranes have become thicker and more resistant due to repeated pressure during previous pregnancies.
For maternal prognosis after PPROM, a study conducted in India in 2007 by Menon et al. found a prevalence of 40% of premature births in the context of PPROM [7]. This rate was as high as that found in our study, which was 50.9%. Indeed, the literature describes that any woman with premature rupture of membranes will spontaneously go into labor 24 hours after the rupture or even earlier, explaining this high rate of threatened premature delivery in cases of premature rupture of membranes before term. Twenty-five per cent of women had resorted to caesarean section as the mode of delivery. Intrauterine infections were found at rates of 1.8% for chorioamnionitis and 4.5% for endometritis. According to the literature, the genital tract is continuously infected in pregnant women. Thus, certain obstetric situations, such as PPROM, expose these women to ascending infections. In 2002 in Cameroon, Foumane et al. found a clear predominance of Candida albicans (48.45%), Gardnerella vaginalis (22.16%) and Group B β-hemolytic streptococcus (6.70%) during pregnancy [8]. These variations in genital flora during pregnancy may explain the occurrence of intrauterine infections in our series, where patients remained on expectant management for several days without antibiotic coverage (28.6% of women). Furthermore, screening for Group B streptococcus is not systematic in women in our environment.
Neonatal and perinatal outcomes were associated with significant morbidity and mortality. In our study, we recorded complications such as prematurity (52.8%), neonatal infection (73.14%) and neonatal mortality (12.9%). Neonatal infections are justified by our high rate of prematurity, given that we considered RPMs from 28 weeks of gestation (age of extreme prematurity). Premature babies are known to be weak and vulnerable due to their immaturity, which exposes them much more than others to infections and, ultimately, death [9] [10]. Furthermore, this high rate of neonatal infections could also be explained by the fact that, in our context, screening for Group B streptococcus is not systematic during pregnancy, even though this bacterium poses a high risk of neonatal infection given the high frequency of vaginal deliveries (75% in our study). Indeed, Group B streptococcus carriage was found in some women during a study conducted in Cameroon in 2009 by Foumane et al. [8]; the newborn can therefore become infected when passing through the mother’s genital tract. This finding highlights the importance of screening for Group B streptococcus during pregnancy or risk-based prophylaxis such as PROM. The mortality rate found in our series was higher than those reported by Coulibaly in Mali (4.8%) and Chibani in Algeria (7.5%) [3] [4]. This difference may be due to the fact that we considered deaths at birth and deaths in neonatal hospitalization. In addition, neonatal infections worsen the prognosis due to their severity and more pronounced immune immaturity. In 2008 in Cameroon, Chelo et al. found an association between neonatal infection and mortality [10]. Furthermore, as our study was conducted in Africa with limited technical resources, we expected this high neonatal mortality rate. In 2017 in Mali, Coulibaly et al. also reported that limited technical resources were a determining factor in neonatal morbidity after RPM [3].
Approximately 38% of the newborns included in our study required resuscitation at birth due to the high number of cases of neonatal asphyxia (16.7%) and respiratory distress (22.2%). This result could be explained by the pulmonary immaturity of premature newborns and the ineffective pulmonary maturation in many of these newborns; only 64% of women had received corticosteroid therapy, which is due to the fact that these women arrived at the maternity ward already in labor and therefore gave birth quickly. In addition, due to insufficient resources, there was a delay in the availability of medication. In 2008 in Cameroon, Chelo et al. reported that neonatal asphyxia was the leading cause of death among newborns [10]. Our results confirm the link between an Apgar score < 7 at 5 minutes and neonatal death (OR: 9.50; 95% CI: 2.12 - 42.56; p = 0.001).
Some limitations observed:
5. Conclusion
PPROM remains a common occurrence in obstetrics. The maternal prognosis continues to be dominated by significant morbidity. The fetal and perinatal outcome remains unfavorable in our setting, compounded by a considerable rate of neonatal mortality.