Is Time of Ruptured Membranes A Risk Factor for Low Apgar? A Case-Control Study of Apgar Score Less Than Seven At Five Minutes in Term Pregnancy Accessing Many Variables

doi:10.21203/rs.3.rs-1350886/v1

Download PDF

Research Article

Is Time of Ruptured Membranes A Risk Factor for Low Apgar? A Case-Control Study of Apgar Score Less Than Seven At Five Minutes in Term Pregnancy Accessing Many Variables

https://doi.org/10.21203/rs.3.rs-1350886/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

PURPOSE To search for maternal, labor related and fetal variables associated with low Apgar in the fifth minute in term pregnancy.

METHODS Retrospective case-control study with term births in a public teaching hospital from 2013 to 2020. Cases were term births with Apgar score less than seven in the fifth minute, and controls, the next one or two births following a case, with Apgar of seven or more. Were excluded non cephalic presentations, multiples and malformations. We accessed 100 cases and 190 controls. We considered significant values of p < 0.05.

RESULTS Were accessed 27 variables which could be risk factors, from which 12 were associated with the outcome. We found a protective effect of prelabor cesarean for the outcome, odds ratio (OR) 0.37, p=0.011. Consequently, we conducted two sets of analyses: in the whole group and in the group of laboring women. The values OR were in general greater in the group of laboring women, compared with the whole group. We conducted multivariate analysis within the group of women in labor. The variables which fitted best in the model were nulliparity, male sex of the fetus, less than six prenatal visits and abnormal cardiotocography; all remained significant. It was found an association of rupture of membranes more than 360 minutes with the outcome, even after controlling for duration of labor; adjusted OR 2.45, p=0.023.

CONCLUSION Twelve variables were associated with the outcome. Prelabor cesarean had a protective effect. Time of ruptured membranes was associated with low Apgar.

The Apgar score was created by the anesthesiologist Virgínia Apgar in 1953, with the purpose to evaluate the need of neonatal ressucitation [1]. Since then, however, its utilization has been widened, and nowadays the Apgar score is the standard method for evaluation of the condition of the neonate in most of the settings that offer care for birth throughout the world [2- 3]. The score has a scale of ten points sharp (0 to 10, where the lower score represents the worst neonate’s prognosis), and is usually applied in the first and fifth minute after birth. Scores of six or less are considered low Apgar score [3]. The score measured in the fifth minute is more strongly associated with short and long-term morbidity compared with the score in the first minute [4]. Most of the cases of low Apgar are secondary to hypoxia/asphyxia of the neonate, but a few cases can have other causes such as depression by drugs, infections, extreme prematurity and other [5]. This lack of absolute correspondence between Apgar score and hypoxia/asphyxia motivated some authorities to publish articles recommending to not consider low Apgar and hypoxia/asphyxia as being the same condition [6-7]. Within this context, and with the purpose to have a precise diagnosis of hypoxia/asphyxia, many institutions adopted the practice of collecting a sample of blood from umbilical cord soon after birth to measure pH, blood gases and concentration of bases. The documentation of acidosis, especially metabolic acidosis, would then be a more objective diagnosis of hypoxia/asphyxia. Some institutions utilize this tool selectively in cases of low Apgar score, or after interventions indicated for suspected fetal distress. The objective is to obtain a more precise evaluation to better program the neonatal care, but it can also be utilized for medico-legal purposes [8-9]. However, some authors propose to utilize this tool in every birth [10].

When compared to Apgar score, however, the postpartum cord blood analysis has been shown to be worse to predict adverse neonatal outcomes. The Apgar score is a better predictor of neonatal death either in term as well in as in preterm neonates [11]. It is also a better predictor of neonatal morbidity [12]. With an Apgar score of seven or more in the fifth minute and abnormal values of cord blood analysis, only a small residual proportion of neonates had an abnormal evolution [13-14].

In what refers to long term morbidity, Leinonen et al. [15], carried out a population based study, where it was reported that Apgar score below four was a better predictor of neurologic morbidity compared with the lower cut off values of cord blood analysis. Kayani et al. [16] compared children at the age of two years old which had pH of umbilical vein below 7.00 and normal Apgar, with controls with both normal pH and Apgar. They did not find differences in the fields of cognition and motricity. Many other studies reported association of low Apgar score, especially the fifth minute score, with many short-term as well as long-term neonatal adverse outcomes [17-28]. Razzaz et al. [29], in a population-based study, reported a significant difference in neonatal mortality and morbidity even within what is considered the normal range of Apgar scores, from eight to ten. Chong et al. [30] argue that a cut off value of 8 or less for Apgar in the fifth minute would be a better predictor of mortality in the first year of life than the traditional value of 6 or less. We can probably state that, if we have to adopt a single tool to evaluate the condition and risk of adverse outcomes of the neonate, the Apgar score is the most comprehensive.

Most of the cases of low Apgar score are secondary to intrapartum events [31]. Cardiotocography (CTG) is probably the most utilized method to detect fetal distress during labor, but it has a great number of false positive results [32], and a not negligible proportion of false negative results [33-35]. A recent study showed that the analysis of blood of fetal scalp during labor is not an adequate tool to distinguish false positive from false negative tracings of CTG, due to its low sensitivity [36]. We can probably assume that, despite being an uncommon condition, especially in the fifth minute, a low Apgar score is a relevant adverse outcome and, with the resources available presently, we cannot avoid completely its occurrence. Hence the interest in finding variables associated with this outcome, with the aim of identifying potential preventive measures.

Many research works accessed antenatal and intrapartum variables associated with low Apgar score. Many of them studied a single specific variable [21, 37-44], while others studied more than one [28, 45-50]. Some of these latter works, however, accessed a relatively small number of variables. It is the opinion of the authors of the present study that this issue has received less attention than it deserves, and that a research studying a great number of variables would be welcome.

OBJECTIVES

To look for antenatal and intrapartum variables associated with Apgar score of 6 or less in the fifth minute in term pregnancy.

We conducted a retrospective case control study. The cases were births of term singleton pregnancies assisted in a single institution, and had Apgar score below seven in the fifth minute. The controls were the two births following a case, which fulfilled the same criteria of the controls, but had Apgar scores at five minutes of seven or more. Intrapartum scalp blood analysis and postpartum cord blood analysis are not available in the institution. Were excluded: multiples, non-cephalic presentations, stillbirths, malformations or congenital diseases detected during prenatal care or in the first neonatal evaluation, and births with missing data about gestational age or Apgar score in the fifth minute.

The institution is Hospital Municipal Universitário de São Bernardo do Campo, a public teaching hospital dedicated to women’s health. It is located in São Bernardo do Campo, an industrial city of about 840,000 inhabitants, in the metropolitan area of São Paulo, Brazil. The hospital attends an average of 4000 births per year, and has 24 hour dedicated teams of gynecologists/obstetricians, neonatologists and anesthesiologists. It is also field for training of medical students, and has medical residents in these three specialties. It is the only public institution that offers care for birth in this city, and consequently attends a mixed high risk and low risk pregnancy population.

The search for the cases was done through the book of births, filled by nurses in the obstetric ward, which has data about Apgar score, gestational age and presentation of the fetus (besides other) of all births assisted. We then accessed the medical records of all potential cases and controls for review. The data were extracted by the authors (LCMJ, CNP, CSG, ECGP). In order to obtain more homogeneity during this process, it was created a tool (pre-specified chart) where the data were included according to previous training.

The variables assessed were those cited in previous works as associated with low Apgar [21, 28, 37-45, 47, 49-50]. These were: maternal age, less than six prenatal visits, smoking habit, regular use of illicit drugs, gestational age as continuous variable, by the best criterion, at the discretion of the researcher (most of the women had first trimester ultrasound), parity, one previous cesarean; maternal diseases: hypertensive diseases as a single variable including chronic hypertension, gestational hypertension and preeclampsia, diabetes (gestational and overt as a single variable), “other maternal diseases”; placenta previa, and birth conditions/risk factors related to birth: mode of delivery: prelabor cesarean or women in labor, labor induction with oxytocin or prostaglandins (mostly misoprostol), labor augmentation with oxytocin, duration of labor from the beginning of active phase of first stage until delivery (as continuous variable), time from rupture of membranes until delivery both as continuous and dichotomic variable (excluding rupture at the moment of delivery, that is, zero minutes), tachisystole (six or more contractions in ten minutes) less than three hours before birth, intrapartum fever (37.8º Celsius or more), meconium stained amniotic fluid, malodorous amniotic fluid, abnormalities in clinical auscultation of fetal heart rate (sustained bradicardia or profound decelerations), abnormal CTG [51], wrong interpretation of CTG, fetal sex and birthweight, and labor accidents: placental abruption, cord prolapse, shoulder dystocia and uterine rupture. We created the composite outcome “obstetric catastrophes”, which included placental abruption, uterine rupture, cord prolapse, shoulder dystocia and eclampsia, and conducted the analysis with these latter outcomes only as composite outcome. Some known risk factors were not included, since we anticipated some difficulties to collect data with good accuracy: fetal growth restriction, because of a low antepartum diagnostic rate; oligohydramnios, because most of the women did not have an ultrasound examination shortly before birth; duration of the second stage, because the strategy of documentation (partograph) in the charts tended to underestimate the true duration of this period, and epidural analgesia, because most of the women did not receive conduction analgesia, and those who received were mostly combined spinal-epidural analgesia. We considered beginning of active phase the point from which cervical dilatation began to progress at an average rate of at least 1 cm/hour, usually beginning with 4 to 5 cm dilatation. Since we anticipated some lack of accuracy in the information given by the woman about the exact time of rupture of membranes, because of frequent confusion with cervical secretion, urine, and aqueous fluid with candidiasis, we considered time zero of rupture, for both cases and controls, the moment at which a member of the attending team detected ruptured membranes. Although this strategy tends to underestimate the average time elapsed from rupture to delivery, especially for those women who had rupture before admission, since the main purpose is to compare the duration in cases vs. in controls, this underestimation is of less importance. Also, we believe there would be no reason to suppose that the size or the direction of this underestimation would be different in cases vs. in controls. In our hospital, most of women are submitted to intrapartum CTG. However, it is very uncommon to perform strictly continuous CTG, in the sense that the tracing covers the whole process of labor, even in high risk pregnancies. What is usual is performing tracings with 20 minutes in intervals of about two hours, changing to smaller intervals in the second stage of labor or after the finding of abnormal tracings (usually class II). This routine is utilized indistinctly in high risk as well as in low risk pregnancies. In the intervals between CTG tracings, the fetal heart rate is accessed through clinical auscultation at 30-minute intervals, before, during and after a contraction, and at 15 minutes intervals in the second stage. Most of the times, abnormalities in clinical auscultation are confirmed through CTG. In our study, all CTG tracings were reviewed by the leading author (LCMJ). For the study, the definition of wrong interpretation of CTG was made by LCMJ with at least one more author, and disagreement was resolved through consensus. Wrong interpretation was considered only if it was for “less”, that is, abnormal tracings that were wrongly considered normal ones, what could lead to postponing or not deciding for a necessary intervention. We considered that an inadequate interpretation for “more”, that is, considering a normal tracing wrongly as abnormal, could lead to an unnecessary intervention, but not to a low Apgar score. Since abnormal CTG before prelabor cesareans was an uncommon occurrence, we decided to make analyses with CTG only in the group of laboring women (see below).

Taking into account the previous reports of a protective effect of prelabor cesarean for severe neonatal complications in term pregnancy [52-54], we also anticipated that most of the risk factors for low Apgar would express their effect in a stronger manner in laboring women as compared with women submitted to prelabor cesareans. Then, we planned to conduct analyses a) with the whole sample and b) with laboring women (regardless of the final mode of delivery) excluding placental abruption. The reason to exclude this latter condition is that, besides being a serious accident, it is usually difficult to decide if a case of abruption can actually be defined as labor.

We deliberately decided to access the greatest possible number of variables. As stated in Introduction, it is the opinion of the authors that low Apgar and other adverse neonatal outcomes in term pregnancy has received less attention in research than it deserves. Consequently, we gave an “exploratory” character to our research, not focusing only on some specific potential associated factors.

The calculation of the size of the sample was not feasible, because of the great number of variables assessed which could be associated with the outcome. Besides this, we were limited by the fact that the book of births covered the period of April 2013 until the present day, so we decided to study the births from this date until July 31th, 2020, when we began to conduct the analyses. We did not study the neonatal outcomes consequent to low Apgar score, like neonatal death, admission to neonatal intensive care unit, and other, but rather, as stated above, we focused on antenatal and intrapartum conditions that could be determinants of low Apgar. The reason why we excluded preterm births is that prematurity, especially extreme prematurity, by itself can be the cause of the low Apgar. Consequently, studying a sample with preterm birth would make prematurity to become an important confounding factor for other variables accessed.

Since we collected data of births assisted until the end of July 2020, maternal infection with Covid 19 virus could be a new risk factor for low Apgar score. However, none of the pregnant women included in the study had a clinical picture or laboratory findings suggestive of this condition.

We did not make imputation for missing data. The association between potential risk factors and the outcome was accessed through qui square test or Fischer’s exact test for categorical variables and t Student or Mann-Whitney test for continuous variables. Values of Odds Ratios (OR) and 95% Confidence Intervals (CI 95%) were calculated for each analysis. Multivariate analyses were conducted through logistic regression. Significant association was considered for values of p<0.05. Data was first entered in Epi Data program. The Stata 13 program was utilized for the analyses.

All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the Faculty of Medicine of ABC under number 1.9893.818 (Ethical process n. CAEE 3481414.0.0000.0082). We were dispensed by the Committee to obtain informed consent, since we accessed only medical records and the data were anonymously analyzed and presented.

From April 1st 2013 to July 31th 2020, were found 100 cases of low Apgar which fulfilled the inclusion criterion. For these cases, we included 190 controls, totalizing 290 observations. During this period, were assisted 28,453 term births, with 132 term births (exclusions not made) with fifth minute Apgar less than seven, a rate of 0.46%, or 4.6 cases per 1,000 births. In this period, the monthly rate of cesarean sections for all births varied from 34 to 40%, with no clear tendency of growth or decline, with an average of about 36% for the whole period.

Table 1 shows the associations of variables with the outcome in the whole sample studied, and table 2 shows the associations in the group of women in labor. Some variables in table 2, like tachisystole and abnormal CTG, were not presented in table 1, because they apply only to women in labor. From the 27 variables studied at all, 12 were significantly associated with the outcome. Were included in the tables only the associated variables, with the exception of sex of the fetus, to show that this variable turned significant in the analysis of laboring women, and hypertensive disease, to give emphasis that this variable was not significantly associated with the outcome. As expected, there was a great association with the composite outcome “obstetric catastrophes”: OR 11.00; CI 95% 3.10–39.00; p<0.001. However, these catastrophes accounted for only 15% of the cases of low Apgar. As we anticipated, it was found a protective effect of prelabor cesarean for the outcome, OR 0.37; CI 95% 0.17–0.81; p=0.011. It is interesting to compare tables 1 and 2. For all variables that are presented in both tables, that is, variables that apply to both groups of women (women in labor and whole group), the values of OR are greater in the group of laboring women, despite a smaller sample, with exception of malodorous amniotic fluid (same number of events) and ruptured membranes more than 360 minutes (see commentary in Discussion). These findings reinforce the adequacy of our strategy to conduct a separate analysis for laboring women.

We then conducted a multivariate analysis. To be coherent with our arguments, we included in the latter only the analyses conducted in laboring women. Since we had a great number of variables associated with the outcome, we had to make a choice about which variables to include in the multivariate model. We gave priority to variables that were more frequently found in clinical practice, and also had greater values of OR. The model which fitted best included nulliparity, fetal sex, less than six prenatal visits and abnormal CTG (table 3).

An interesting finding was the association of low Apgar with time of ruptured membranes. This association was found in the analysis taking time of ruptured membranes as a dichotomic variable (tables 1, 2 and 4), as well as continuous variable (mean of 458 min in cases vs. 235 min in controls, p=0.002; not shown in tables). From the clinical point of view, a very likely confounding variable for time of ruptured membranes in the association with low Apgar would be the duration of labor from the beginning of the active phase, since long labors tend to have longer time of ruptured membranes. Although duration of labor was not associated with the outcome in the univariate analysis (median of 256 min in cases vs. 227 min in controls, p=0.207; not shown in tables), we decided to conduct a distinct multivariate analysis including only duration of active phase of labor as a continuous variable and time of ruptured membranes as a dichotomic variable, to be sure that duration of active phase did not confound the association. There remained an association of time of ruptured membranes and low Apgar with two distinct cut-off values, 260 and 360 minutes, and lack of association of duration of labor (table 4).

The present study found a great number of variables associated with Apgar score below seven in the fifth minute in term pregnancy. Also, it was found a protective effect of pre-labor cesarean for this outcome; consequently, we conducted separate analyses with laboring women, which showed a greater influence of the risk factors over low Apgar in this group. A non-expected finding was a strong positive association with time of ruptured membranes, even after controlling for duration of labor. The frequency of Apgar less than seven in the fifth minute in term birth for the whole population of the study period in the institution (without the exclusions made for the study), of 0.46%, compares well with recent reports of large series of developed countries, like 0.9% of Lai et al. [47] (LAI 2017) and 1,4% of Thavarajah et al. [21], both from Australia, which are results after the exclusion of multiples, malformed and non cephalic; it is also lower than the report of Leinonen et al. [20], of 1.3%, from the general population of term birth in Finland. But it is a little higher than the report of Gutbir et al. [17], of 0.3% from Israel. We do not have a clear explanation for these differences. In the same line, in a period very similar to the one of the study, from January 2014 to March 2021, with 28,080 term births, the neonatal death rate during the admission for birth in term pregnancy was 0.81/1000, falling to 0.28/1000 after exclusion of serious malformations, what can be considered a low rate.

Some variables which were associated with low Apgar in other studies were not associated in the present one. But some of these variables were more frequent in the cases than in controls, although not significantly, like, besides others, “other maternal diseases”, 12.5 vs. 8.1% p=0.271; “one previous cesarean, 15.9 vs. 12.2% p=0.416; intrapartum fever, 2.3% vs. 0, p=0.065. It is likely that a significant association with these variables would be found with a larger sample.

The question of neonatal outcomes associated with mode of delivery in term pregnancy has been an issue of great debate. A first and very important aspect is that vaginal and abdominal are not two independent routes; that is, very often cesareans are performed to solve problems of trial of vaginal birth, like, for example, fetal distress in labor or cephalopelvic disproportion. Many studies reported a higher frequency of respiratory morbidity in prelabor cesareans as compared with vaginal births or with trial of labor in term pregnancy [55-58]. However, it is necessary to consider the whole picture of neonatal outcomes. Respiratory morbidity in term pregnancy, although not uncommon, seldom cause death or long-term morbidity, different from severe hypoxic/ischemic encephalopathy, meconium aspiration syndrome, serious trauma and other, which are more frequent in trial of labor or laboring women, when compared with prelabor cesareans, The same can be told about low Apgar scores, and the present study showed a significant lower frequency of this outcome in prelabor cesareans. A recommendation of National Institutes of Health from United States (NIH) in 2006 stated that comparisons of outcomes related to mode of delivery should be made between prelabor cesareans and other forms of birth [59]. When conducted in this manner, some studies reported a protective effect of prelabor cesarean for serious neonatal morbidities [52-54] or neonatal death [53] in term pregnancy, as stated in Methods. Some studies showed association of emergency cesarean with low Apgar [21, 45, 47-48], but did not discuss in depth the aspects above. In the works of Thavarajah et al. [21] and Lai et al. [47], both conducted in the same institution and in similar periods, the authors report a significant lower frequency of low Apgar in prelabor cesareans, and a significant higher frequency in emergency cesarean and operative vaginal delivery. In the discussion, in both studies, the authors state that emergency cesarean and operative vaginal delivery are important risk factors for low Apgar. This gives the wrong idea of cause-effect relationship. We had similar results in the present study: a protective effect of prelabor/elective cesarean (table 1) and a greater significant frequency of emergency cesarean in the cases, 24.4% vs 12.2% in the controls, p=0.019 (not shown in tables). Very likely, the correct interpretation is that the causes of low Apgar in emergency cesarean and operative vaginal are mostly the conditions which indicated the procedure (reverse causality), and not the procedure itself.

Another relevant finding, as stated in Results, is that we did not find associations of the outcome with maternal diseases. In the analyses conducted within the group of laboring women, hypertensive disease almost reached significance, with an OR of 1.81 and a p value of 0.089 (table 2). As stated above, it is likely that that with a larger sample, a significant result would be reached. Also, the variable “other maternal diseases”, although more common in the group of cases, did not reach significant association, as stated above. It is possible that this weak expression of maternal diseases is secondary to its low frequency in the population compared with other risk factors like nulliparity or male sex. Besides this, many pregnant women with serious diseases, like severe preeclampsia, have medically indicated deliveries in the preterm period for maternal or fetal indications. But it is probably also true that other conditions, like nulliparity, fetal sex, maternal age, and conditions related to the course of labor have greater influence in the outcome than it is usually considered. This raises the question: is the concept of high-risk pregnancy interchangeable with the concept of high-risk birth? The belief that the conditions which are good predictors of adverse neonatal outcomes at term are mainly those who classify the pregnancy as high risk has been challenged by some research work [50, 53, 60-61]. Similar comments could be made about the outcome “obstetric catastrophes”. In this composite outcome, we included conditions that are acute, usually associated with serious morbidity, and almost unpredictable. Despite strongly associated with the outcome, only 15% of the cases of low Apgar in our study were related to these conditions; the remaining 85% of cases were in somehow “normal” birth contexts.

Some studies have reported the utility of Doppler assessment of umbilical and fetal vessels in the end of pregnancy in the prediction of low Apgar and other adverse perinatal outcomes [62-63]. Although we have this resource in the institution, we are not able, by now, to submit all women admitted for spontaneous labor or labor induction to this exam.

Much controversy exists about the benefit of intrapartum CTG in preventing adverse outcomes for the neonate [33, 64-65]. In the present study, more than the association of abnormal CTG with low Apgar, the strong association of wrong interpretation of this exam with the outcome (OR 2.99; p=0.006; table 2) is an argument to affirm that, at least in our context, intrapartum CTG has very likely some benefit in preventing low Apgar.

A third interesting finding was the association of the outcome with time of ruptured membranes. It is probably the most original finding of our work. We authors did not expect to find this association. We included this variable because of the report of Martinez-Biarge et al. [66], who found association of time of ruptured membranes with hypoxic-ischemic encephalopathy, what could be a proxy for low Apgar; however, they did not conduct analyses with low Apgar as an outcome. To our knowledge, few studies reported this association. Omokhodion et al. [67], in Nigeria, found association of Apgar less than 7 at one minute, but not at five minutes, with rupture of membranes for more than 24 hours before labor. Kaye [68] reported association of Apgar of 4 or less in five minutes with rupture of membranes more than 24 hours before labor in term pregnancy in Uganda. However, these both studies included only referred women; the authors inform that in the regions they were conducted, most of uncomplicated labors occur at primary level (not in hospitals). Hence, in both works the frequency of low Apgar in the fifth minute was very high: 4% in the work of Omokhodion et al. [67], and 13.1% in the one of Kaye [68]. Also, they did not control for duration of labor. Salustiano et al. [49], in Brazil, found greater duration of ruptured membranes in term pregnancy in cases (Apgar < 7 in five minutes), 10 hours, than in controls, 8 hours, but the difference was not significant (p=0.11).

Although we did not include this variable in the multivariate analysis, we controlled for duration of labor, which could be an important confounding variable, and the association persisted, The data of the present work do not allow us to find a clear motif for this association, but we can try to give some theoretical explanations. Most would evoke fetal infection as the probable cause, but only few neonates had a clear, definite clinical picture of infection. Besides this, low Apgar in the fifth minute is not so strongly related to infection. Jessop et al. [39] studied the association of histological findings related to inflammation in placental tissues in term singletons with adverse outcomes, including Apgar <7 in the first minute. They found association of these findings, especially funisitis, with low Apgar and the other outcomes. They suggest that fetal inflammatory response syndrome, and not necessarily clinically evident infection, could lead to adverse outcomes. Mynarek et al. [69] studied the association of ruptured membranes and risk of cerebral palsy in term pregnancy. They found association of rupture of more than 24 hours before labor and the outcome. They also found that the pattern of cerebral MRI suggestive of hypoxic-ischemic injuries increased with increased intervals from rupture to delivery. They speculate that rupture of membranes could somehow increase the vulnerability of fetal brain to hypoxic-ischemic injury. Another possible explanation could be more frequent cord compression secondary to oligohydramnios after rupture. Although a more frequent cord compression could contribute to low Apgar, some reports challenge the concept of this mechanism as the only to explain this outcome. Ghosh et al. [70] studied two groups of low risk term pregnancies, one with intact and other with ruptured membranes. Both groups were submitted to evaluation of amniotic fluid index (AFI) at admission for labor. They then compared within each group the frequency of adverse outcomes between oligohydramnios (AFI 50 mm or less) and normal amniotic fluid. They found a greater significant difference in operative delivery for fetal distress in the group with oligohydramnios with ruptured membranes, but not in the group with oligohydramnios and intact membranes. Interestingly, in principle, we would expect to have a greater frequency of interventions in the group with intact membranes, since within this group, at least some cases of oligohydramnios would be secondary to placental malfunction. Besides this, the studies of Omokhodion et al. [67], Kaye [68] and Minarek et al. [69], discussed above, showed association of low Apgar or markers of hypoxia/asphyxia with time of ruptured membranes before established labor, when the frequency and intensity of contractions are low. Also in the present study, for the variable rupture of membranes for more than 360 minutes, we found a higher value of OR in the general group, which included also non laboring women (OR=2.30; p=0.003; table 1), than in the group of laboring women (OR= 2.03; p= 0.031; tables 1 and 2). If more frequent cord compression was the only mechanism, the contrary would be expected. However, if we consider the condition of prelabor rupture of membranes in the context of the preterm population, the findings above are not in accordance with the ones of PPROMEXIL trial [71], who found no significant difference in neonatal outcomes with labor induction at 34 weeks compared with expectant management until 37 weeks, and also with PPROMT trial [72], who found better neonatal outcomes with expectant management in the same comparison. It is possible that other mechanisms play a role in this specific population. Our findings are not enough to change management protocols about ruptured membranes, but they raise the question of the likely association of time of rupture of membranes and low Apgar in term pregnancy, and the need to study this issue in a more comprehensive manner.

The weak points of our work are those inherent to retrospective studies, with risk of information bias. Besides this, we could not assess some important variables, such as duration of second stage of labor and fetal growth restriction, due to non-reliable information. The strong aspects are the case-control design, which enabled us to find a great number of associations with a relatively small sample, the analyses conducted in a correct manner in what refers to mode of delivery, the confirmation of association of variables not related to maternal diseases with the outcome, as reported in recent studies, and the finding of association with time of ruptured membranes, even after controlling for duration of labor, which is an original finding.

The authors of the present study intend to utilize the same sample to build a risk score for low Apgar in term pregnancy, with variables that are accessible at the moment of admission for labor, to be reported in another article.

[1] Apgar V (1953) A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg. 32(4):260-7.

[2] Skolnick AA (1996) Apgar quartet plays perinatologist’s instruments. JAMA 276:1939-40. [Erratum, JAMA 1997;277:1762. https://doi.org/10.1001/jama.1996.03540240017009

[3] Cunningham FG, Leveno KJ, Bloom SL et al. (2018). Transtornos hipertensivos. Cap. 40, Sec 11. In Cunningham FG, Leveno KJ, Bloom SL et al. (2018) Williams Obstetrics, 25. ed., São Paulo: Ed. McGraw Hill. pp. 710-55 (710-11).

[4] Watterberg KL, Aucott S, Benitz WD et al (2015) The Apgar Score. Pediatrics 136(4): 819-22. https://doi.org/10.1542/peds.2015-2651

[5] Hogan L, Ingemarsson I, Thorngren-Jerneck K, Herbst A (2007) How often is a low 5-min Apgar score in term newborns due to asphyxia? Eur J Obstet Gynecol Reprod Biol 130(2):169-75. https://doi.org/10.1016/j.ejogrb.2006.03.002

[6] American Academy of Pediatrics (1996) Use and abuse of the Apgar score. Pediatrics 98:141-2. https://doi.org/10.1542/peds.98.1.141

[7] ACOG Committee on Obstetric Practice, American Academy of Pediatrics Committee on Fetus and Newborn (1996) Use and abuse of the Apgar score. Number 174 — July 1996 (Replaces No. 49, November 1986) Committee on Obstetric Practice and American Academy of Pediatrics: Committee on Fetus and Newborn. Int J Gyncol Obstet 54(3):303-5. https://doi.org/10.1016/S0020-7292(96)90089-2

[8] Harris M, Beckley SL, Garibaldi JM, Keith RD, Greene KR (1996) Umbilical cord blood gas analysis at the time of delivery. Midwifery 12(3):146- 50. https://doi.org/10.1016/S0266-6138(96)90059-5

[9] Thorp JA, Rushing RS (1999) Umbilical cord blood gas analysis. Obstet Gynecol Clin North Am 26(4):695-709. https://doi.org/10.1016/s0889-8545(05)70107-8

[10] White CRH, Doherty DA, Cannon JW, Kohan R, Newnham JP, Pennell CE (2016) Cost effectiveness of universal umbilical cord blood gas and lactate analysis in a tertiary level maternity unit. J Perinat Med 44(5):573-84.

[11] Casey BM, McIntire DD, Leveno KJ (2001) The continuing value of the Apgar score for the assessment of newborn infants. N Engl J Med 344(7):467-71. https://doi.org/10.1056/NEJM200102153440701

[12] Yeh P, Emary K, Impey L (2012) The relationship between umbilical cord arterial pH and serious adverse neonatal outcome: analysis of 51,519 consecutive validated samples. BJOG 119(7):824-31. https://doi.org/10.1111/j.1471-0528.2012.03335.x

[13] Anayegbunam A, Fleischer A, Whitty J, Brustman G, Langer O (1991) Association between umbilical artery cord pH, five-minute Apgar scores and neonatal outcome. Gynecol Obstet Invest. 32(4):220-3. https://doi.org/10.1159/000293036

[14] Sabol AB, Caughei AB (2016) Acidemia in neonates with a 5-minute Apgar score of 7 or greater - What are the outcomes? Am J Obstet Gynecol 215(4):486.e1-6. https://doi.org/10.1016/j.ajog.2016.05.035

[15] Leinonen E, Gissler M, Haataja L et al (2019) Umbilical artery pH and base excess at birth are poor predictors of neurodevelopmental morbidity in early childhood. Acta Paediatr 108(10):1801-10. https://doi.org/10.1111/apa.14812

[16] Kayani SI, Tan MJ, Shaw NJ et al (2014) Two-year outcomes for infants with low cord pH at birth. J Matern Fetal Neonatal Med 27(10):1010-4. https://doi.org/10.3109/14767058.2013.847915

[17] Gutbir Y, Wainstock T, Sheiner E et al (2020) Low Apgar score in term newborns and long-term infectious morbidity: a population-based cohort study with up to 18 years of follow-up. Eur J Pediatr 179(6):959-71. https://doi.org/10.1007/s00431-020-03593-9

[18] Leybovitz-Haleluya N, Wainstock T, Sheiner E, Segal I, Landau D, Walfisch A (2019) Low Apgar scores in term newborns and long-term gastro-intestinal morbidity: a population-based cohort study with up to 18 years of follow-up. J Matern Fetal Neonatal Med 32(10):1609-14. https://doi.org/10.1080/14767058.2017.1411475

[19] Ernest E, Wainstock T, Sheiner E, Segal I, Landau D, Walfisch A (2019) Apgar score and long-term respiratory morbidity of the offspring: a population-based cohort study with up to 18 years of follow-up. Eur J Pediatr 178(3):403-11. https://doi.org/10.1007/s00431-018-03311-6

[20] Leinonen E, Gissler M, Haataja L et al (2018) Low Apgar scores at both one and five minutes are associated with long-term neurological morbidity. Acta Paediatr 107(6):942-51. https://doi.org/10.1111/apa.14234

[21] Thavarajah H, Flatley C, Kumar S (2018) The relationship between the five minute Apgar score, mode of birth and neonatal outcomes. J Matern Fetal Neonatal Med 31(10):1335-41. https://doi.org/10.1080/14767058.2017.1315666

[22] Persson M, Razaz N, Tedroff K, Joseph KS, Cnattingius S (2018) Five and 10 minute Apgar Scores and risk of cerebral palsy and epilepsy: population based cohort study in Sweden. BMJ 360: k207. https://doi.org/10.1136/bmj.k207

[23] Eun S, Lee JM, Yi DY et al (2016) Assessment of the association between Apgar scores and seizures in infants less than 1 year old. Seizure 37:48-54. https://doi.org/10.1016/j.seizure.2016.03.001

[24] Tweed EJ, Mackay DF, Nelson SM, Cooper SA, Pell JP (2016) Five-minute Apgar score and educational outcomes: retrospective cohort study of 751,369 children. Arch Dis Child Fetal Neonatal Ed. 101(2):F121-6. https://doi.org/10.1136/archdischild-2015-308483

[25] Iliodromiti S, Mackay DF, Smith GCS, Pell JP, Nelson SM (2014) Apgar score and the risk of cause-specific infant mortality: a population-based cohort study. Lancet 384(9956):1749-55. https://doi.org/10.1016/s0140-6736(14)61135-1

[26] Li F, Wu T, Lei X, Zhang H, Mao M, Zhang J (2013) The Apgar score and infant mortality. PLoS One 8(7):e69072. https://doi.org/10.1371/journal.pone.0069072

[27] Sun Y, Vestergaard M, Pedersen CB, Christensen J, Olsen J (2006) Apgar scores and long-term risk of epilepsy .Epidemiology 17(3):296-301. https://doi.org/10.1097/01.ede.0000208478.47401.b6

[28] Thorngren-Jerneck K, Herbst A (2001) Low 5-minute Apgar score: a population-based register study of 1 million term births. Obstet Gynecol 98(1):65-70. https://doi.org/10.1016/S0029-7844(01)01370-9

[29] Razzaz N, Cnattingius S, Joseph KS (2019) Association between Apgar scores of 7 to 9 and neonatal mortality and morbidity: population based cohort study of term infants in Sweden. BMJ 7;365:l1656. https://doi.org/10.1136/bmj.l1656

[30] Chong DSY, Karlberg J (2004) Refining the Apgar score cut-off point for newborns at risk. Acta Paediatr 93(1): 53-9. PMID: 14989440

[31] Hayes B, McGarvey C, Mulvany S et al (2013) A case-control study of hypoxic-ichemic encephalopathy in newborn infants at > 36 weeks gestation. Am J Obstet Gynecol 209(1):29.e1-29.e19. https://doi.org/10.1016/j.ajog.2013.03.023

[32] Pinas A, Chandraharan E (2016) Continuous cardiotocography during labour: Analysis, classification and management. Best Pract Res Clin Obstet Gynaecol 30:33-47. https://doi.org/10.1016/j.bpobgyn.2015.03.022

[33] Farquhar, CM, Armstrong S, Masson V, Thompson JMD, Sadler L (2020) Clinician Identification of Birth Asphyxia Using Intrapartum Cardiotocography Among Neonates With and Without Encephalopathy in New Zealand. JAMA Netw Open 3(2):e1921363. https://doi.org/10.1001/jamanetworkopen.2019.21363

[34] Schifrin BS, Soliman M, Koos B (2016) Litigation related to intrapartum fetal surveillance. Best Pract Res Clin Obstet Gynaecol 30: 87-97. https://doi.org/10.1016/j.bpobgyn.2015.06.007

[35] Bogdanovic G, Babovic A, Rizvanovic M, Ljuca D, Grgic G, Djuranovic-Milcic J (2014) Cardiotocography in the prognosis of perinatal outcome. Med Arh 68(2):102-5. https://doi.org/10.5455/medarh.2014.68.102-105

[36] Al Wattar BH, Lakhiani A, Sacco A et al (2019) Evaluating the value of intrapartum fetal scalp blood sampling to predict adverse neonatal outcomes: A UK multicentre observational study Eur J Obstet Gynecol Reprod Biol 240: 62-7. https://doi.org/10.1016/j.ejogrb.2019.06.012

[37] Blankenship SA, Raghuraman N, Delhi A et al (2020) Association of abnormal first stage of labor duration and maternal and neonatal morbidity. Am J Obstet Gynecol 223:445.e1-15. https://doi.org/10.1016/j.ajog.2020.06.053

[38] Dior UP, Kogan L, Eventof-Friedman S et al (2016) Very High Intrapartum Fever in Term Pregnancies and Adverse Obstetric and Neonatal Outcomes. Neonatology 109(1):62-8. https://doi.org/10.1159/000440938

[39] Jessop FA, Lees CC, Pathak S, Hook CE, Sebire NJ (2016) Funisitis is associated with adverse neonatal outcome in low-risk unselected deliveries at or near term. Virchows Arch 468(4):503-7. https://doi.org/10.1007/s00428-015-1899-0

[40] Almeida NK, Almeida RM, Pedreira CE (2015) Adverse perinatal outcomes for advanced maternal age: a cross-sectional study of Brazilian births. J Pediatr (Rio J) 91:493-8. https://doi.org/10.1016/j.jped.2014.12.002

[41] Aviram A, Raban O, Melamed N, Hadar E, Wiznitzer A, Yogev Y (2013) The association between young maternal age and pregnancy outcome. J Matern Fetal Neonatal Med 26(15):1554-8. https://doi.org/10.3109/14767058.2013.794212

[42] Wallin MC, Ekström P, Marsál K, Källén K (2010) Apgar score and perinatal death after one previous caesarean delivery. BJOG 117(9):1088-97. https://doi.org/10.1111/j.1471-0528.2010.02614.x

[43] Chen XK, Wu SW, Fleming N et al (2007) Teenage pregnancy and adverse birth outcomes: a large population based retrospective cohort study. Int J Epidemiol 36(2):368-73. https://doi.org/10.1093/ije/dyl284

[44] Källén K (2001) The impact of maternal smoking during pregnancy on delivery outcome. Eur J Public Health 11(3):329-33. https://doi.org/10.1093/eurpub/11.3.329

[45] Wen PY, Broom E, Flatley C, Kumar S (2020) Maternal demographic and intrapartum antecedents of severe neonatal outcomes at term. J Matern Fetal Neonatal Med 33(12):2103-8. https://doi.org/10.1080/14767058.2018.1540581

[46] Crovetto F, Fumagalli M, De Carli A et al (2018) Obstetric risk factors for poor neonatal adaptation at birth. J Matern Fetal Neonatal Med 31(18):2429-35. https://doi.org/10.1080/14767058.2017.1344635

[47] Lai S, Flatley C, Kumar S (2017) Perinatal risk factors for low and moderate five-minute Apgar scores at term. Eur J Obstet Gynecol Reprod Biol 210:251-6. https://doi.org/10.1016/j.ejogrb.2017.01.008

[48] De Zorzi PM, Madi JM, Rombaldi RL et al (2012) Perinatal factors associated with pH <7.1 in umbilical artery and Apgar 5 min <7.0 in term newborn. Rev Bras Ginecol Obstet 34(8):381-5. https://doi.org/10.1590/S0100-72032012000800007

[49] Salustiano EMA, Campos JADB, Ibidi SM et al (2012) Low Apgar scores at 5 minutes in a low risk population: maternal and obstetrical factors and postnatal outcome. Rev Assoc Med Bras 58(5):587-93. https://doi.org/10.1590/S0104-42302012000500017

[50] Palsodottir K, Dagbjartsson A, Thorkelsson T, Hardartottir H (2007) Birth asphyxia and hypoxic ischemic encephalopathy, incidence and obstetric risk factors. Laeknabladid 93(9):595-601. PMID: 17823499

[51] Macones GA, Hankins GD, Spong CY et al (2008) The 2008 NICHHD workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. J Obstet Gynecol Neonatal Nurs 37(5):510-5. https://doi.org/10.1111/j.1552-6909.2008.00284.x

[52] Dahlgren LS, von Dadelszen P, Christilaw J et al (2009) Caesarean section on maternal request: Risks and benefits in healthy nulliparous women and their infants. J Obstet Gynaecol Can 31(9):808-17. https://doi.org/10.1016/S1701-2163(16)34299-2

[53] Machado Junior LC, Sevrin CE, Oliveira E et al (2014) Association between mode of delivery and neonatal deaths and complications in term pregnancy: a cohort study in Brazil. Minerva Pediatr 66(2):111-22.

[54] Liu X, Landon MB, Cheng W, Chen Y (2015) Cesarean delivery on maternal request in China: what are the risks and benefits? Am J Obstet Gynecol 212:817.e1-9. https://doi.org/10.1016/j.ajog.2015.01.043

[55] Farchi S, Di Lallo D, Franco F et al (2009) Neonatal respiratory morbidity and mode of delivery in a population-based study of low-risk pregnancies. Acta Obstet Gynecol Scand 88(6):729-32. https://doi.org/10.1080/00016340902818154

[56] Quiroz LH, Chang H, Blomquist J, Okoh YK, Handa VL (2009) Scheduled cesarean delivery: maternal and neonatal risks in primiparous women in a community hospital setting. Am J Perinatol 26(4):271-7. https://doi.org/10.1055/s-0028-1103155

[57] Hansen AK, Wisborg K, Uldbjerg N, Henriksen TB (2008) Risk of respiratory morbidity in term infants delivered by elective caesarean section: cohort study. BMJ 336(7635):85-7. https://doi.org/10.1136/bmj.39405.539282.be

[58] Richardson BS, Czikk MJ, daSilva O, Natale R (2005) The impact of labor at term on measures of neonatal outcome. Am J Obstet Gynecol 192(1):219-26. https://doi.org/10.1016/j.ajog.2004.06.034

[59] National Institute of Health (2006) State-of-the-Science conference Statement on Cesarean Delivery on Maternal Request. NIH consensus Science Statements 23(1):1-29. PMID: 17308552.

[60] Joyce NM, Tully E, Kirkham C, Dicker P, Breathnach FM (2018) Perinatal mortality or severe neonatal encephalopathy among normally formed singleton pregnancies according to obstetric risk status:" is low risk the new high risk?" A population-based cohort study. Eur J Obstet Gynecol Reprod Biol 228:71-75. https://doi.org/10.1016/j.ejogrb.2018.06.010

[61] Westergate JA, Gunn AJ, Gunn JA (1999) Antecedents of neonatal encephalopathy with fetal acidaemia at term. Br J Obstet Gynaecol 1106(8):774-82. https://doi.org/10.1111/j.1471-0528.1999.tb08397.x

[62] Bligh LN, Alsolai A, Greer RM, Kumar S (2018) Screening for adverse perinatal outcomes: uterine artery Doppler, cerebroplacental ratio and estimated fetal weight in low-risk women at term. J Matern Fetal Neonatal Med 31(24):3301-3307. https://doi.org/10.1080/14767058.2017.1369518

[63] Dunn L, Sherrel H, Kumar S (2017) Review: Systematic review of the utility of the fetal cerebroplacental ratio measured at term for the prediction of adverse perinatal outcome. Placenta 54:68-75. https://doi.org/10.1016/j.placenta.2017.02.006

[64] Alfirevic Z, Devane D, Gyte GM, Cuthbert A (2017) Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour. Cochrane Database Syst Rev 2(2):CD006066. https://dx.doi.org/10.1002%2F14651858.CD006066.pub3

[65] Philopoulos D (2015) Electronic fetal monitoring and its relationship to neonatal and infant mortality in a national database: a sensivity analysis. J Gynecol Obstet Biol Reprod (Paris) 44(5):451-62. https://doi.org/10.1016/j.jgyn.2014.07.003

[66] Martinez-Biarge M, Diez-Sebastian J, Wusthoff CJ et al (2013) Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy. Pediatrics 132(4): e952-e959. https://doi.org/10.1542/peds.2013-0511

[67] Omokhodion FO, Roberts OA, Onadeko MO, Beach JR, Cherry N, Burstyn I (2018) Social, obstetric and environmental determinants of low Apgar score among infants born in four selected hospitals in Ibadan, Nigeria. J Obstet Gynaecol 38(4):454-460. https://doi.org/10.1080/01443615.2017.1367764

[68] Kaye D (2003) Antenatal and intrapartum risk factors for birth asphyxia among emergency obstetric referrals in Mulago Hospital, Kampala, Uganda. East Afr Med J 80(3):140-3. https://doi.org/10.4314/eamj.v80i3.8683

[69] Mynarek M, Bjellmo S, Lyndersen S et al (2020) Prelabor rupture of membranes and the association with cerebral palsy in term born children: a national registry-based cohort study. BMC Pregnancy Childbirth 31;20(1):67. https://doi.org/10.1186/s12884-020-2751-3

[70] Ghosh G, Marsál K, Gudmundsson G (2002) Amniotic fluid index in low-risk pregnancy as an admission test to the labor ward. Acta Obstet Gynecol Scand 81(9):852-5. https://doi.org/10.1034/j.1600-0412.2002.810909.x

[71] van der Ham DP, Vijgen SMC, Nijhuis JG et al (2012) Induction of labor versus expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks: a randomized controlled trial. PLoS Med 9(4):e1001208. https://doi.org/10.1371/journal.pmed.1001208

[72] Morris JM, Roberts CL, Bowen JR et al (2016) Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial. Lancet 387(10017):444-52. https://doi.org/10.1016/s0140-6736(15)00724-2

Table 1: Association of maternal, fetal and intrapartum variables with Apgar Score less than seven in the fifth minute.

Variable	Apgar ≤6		Apgar ≥7		OR	95% CI	Value of P
Variable	n	(%)	n	(%)	OR	95% CI	Value of P
Nullipara	58	(58)	74	(41.1)	1.98	1.21 - 3.24	0.006
Maternal age less than 19	21	(21)	23	(12.1)	1.93	1.00 - 3.69	0.047
Less than six prenatal visits	24	(24)	25	(13.4)	2.04	1.09 - 3.81	0.024
Male sex of the fetus	57	(62)	91	(49.5)	1.66	0.99 - 2.77	0.051
Ruptured mmbranes ≥ 360 minutes	35	(35)	36	(19)	2.30	1.33 - 3.98	0.003
Meconium stained amniotic fluid	31	(32)	27	(14.3)	2.81	1.56 - 5.08	0.001
Malodorous amniotic fluid	5	(5)	0	-	-	-	0.002
Prelabor cesarean	9	(9.3)	40	(21.3)	0.37	0.18 - 0.82	0.011
Obstetric catastrophes	15	(15)	3	(1.6)	11.00	3.10 - 39.00	<0.001
Hipertensive disease	22	(22.2)	34	(17.9)	1.31	0.72 - 2.39	0.39

OR: Odds Ratio CI: Confidence Interval
Obstetric catastrophes: composite outcome including placental abruption, uterine rupture, cord prolapse, shoulder dystocia and eclampsia.

Table 2: Association of maternal, fetal and intrapartum variables with Apgar Score less than seven in the fifth minute in the group of women in labor.

Variable	Apgar ≤ 6		Apgar ≥ 7		OR	95% IC
Variable	n	(%)	n	(%)	OR	95% IC
Nullipara	56	(63.4)	65	(43.9)	2.33	1.29 - 3.84
Maternal age less than 19	21	(23.9)	18	(12.2)	2.26	1.12 - 4.53
Less than six prenatal visits	23	(26.1)	21	(14.4)	2.10	1.08 - 4.08
Male sex of the fetus	54	(67.5)	77	(51.1)	1.99	1.12 - 3.52
Ruptured mmbranes >= 360 minutes	24	(27.3)	23	(15.6)	2.03	1.07 - 3.89
Abnormal cardiotocography	34	(40.5)	19	(13.0	2.82	1.67 - 4.76
Wrong Interpretation of cardiotocography	18	(21.7)	4	(2.8)	2.99	1.36 - 6.58
Abnormal clinical auscultation of FHR	10	(11.4)	4	(2.7)	4.61	1.40 - 15.19
Meconium stained amniotic fluid	27	(31.4)	20	(13.6)	2.90	1.50 - 5.59
Tachysystole less than three hours before birth	19	(19.3)	5	(3.4)	6.8	2.41 - 19.18
Malodorous amniotic fluid	5	(5.7)	0	-	-	-
Hypertensive disease	20	(23)	21	(14.2)	1.81	0.91 - 3.56

OR: Odds Ratio CI: Confidence Interval FHR: Fetal Heart Rate

Table 3: Multivariate analysis for associations with low Apgar in the fifth minute in the group of women in labor.

Variable	OR	95% IC	Value of P
Nullipara	2.12	1.09 - 4.10	0.026
Less than six prenatal visits	2.85	1.24 - 6.54	0.014
Male fetal sex	2.00	1.03 - 3.90	0.041
Abnormal cartiotocography	4.46	2.17 - 9.16	<0.001

OR: Odds Ratio CI: Confidence Interval

Table 4: Multivariate analyses for association with low Apgar in the fifth minute including time of ruptured membranes and duration of labor*

Variable	OR	95% CI	Value of P
Ruptured membranes ≥ 360 minutes	2.45	1.13 - 5.33	0.023
Duration of active phase of labor	1.00	0.99 - 1.01	0.614
Ruptured membranes ≥ 260 minutes	2.54	1.21 - 5.34	0.014
Duration of active phase of labor	1.00	0.99 - 1.01	0.722

OR: Odds Ratio CI: Confidence Interval
a) analysis with a cut-off value of 360 minutes

b) analyses with a cut-off value of 260 minutes

* Duration of labor taken as continuous variable.

Download PDF

Reviewers agreed at journal
02 Jun, 2022
Reviews received at journal
01 May, 2022
Reviewers invited by journal
09 Mar, 2022
Editor invited by journal
15 Feb, 2022
Editor assigned by journal
14 Feb, 2022
First submitted to journal
11 Feb, 2022

You are reading this latest preprint version

Is Time of Ruptured Membranes A Risk Factor for Low Apgar? A Case-Control Study of Apgar Score Less Than Seven At Five Minutes in Term Pregnancy Accessing Many Variables

Status:

Version 1

Abstract

Introduction

Methods

Results

Discussion

References

Tables

Status:

Version 1