Fetal death: obstetric, placental and fetal necroscopic factors

Universidade do Sul de Santa Catarina, Tubarão, Santa Catarina, Brazil

Corresponding author

Laura Martins Giraldi
0000-0002-8586-1437
e-mail: lauramgiraldi@gmail.com

INTRODUCTION

According to the Brazilian Ministry of Health, fetal death means “death prior to the complete expulsion or extraction from its mother of a product of human conception, irrespective of the duration of pregnancy”⁽¹⁾. This definition therefore includes the definition of abortion, which is the product of conception prior to the 20^th week of gestation – or up to 500 g – when gestational age is uncertain. However, the fetus will receive a death certificate and will be part of the calculation of the stillbirth coefficient only when the death occurs after 20 weeks’ gestation⁽²⁾.

It is estimated that about 2.6 million fetal deaths occur each year, of which 98% are in low- and middle-income countries. It is expected that most fetal deaths are caused by preventable causes⁽³⁾. Among the causes of fetal death, maternal etiologies, both previous (such as obesity, drug use) and related to pregnancy [such as specific pregnancy-induced hypertension (PIH), gestational diabetes mellitus], placental complications, including umbilical cord disorders (such as retroplacental hematoma, cord stenosis), fetal malformations and trauma at birth^(4-8).

There are few studies that investigate the underlying cause of fetal death, and in those found, the percentage of ill-defined causes is high⁽⁹⁾. For appropriate counseling and prevention of future episodes, an accurate assessment of the cause of fetal death based on necropsy findings and clinical data is required⁽⁸⁾, which justifies research in this area.

OBJECTIVES

The objective of this study was to investigate the maternal risk factors and the necropsy findings associated with fetal death from data obtained at the Verification of Death Service [Serviço de Verificação de Óbito (SVO)] in Florianópolis, Santa Catarina, Brazil, between 2010 and 2015. Based on in these data, it was intended: a) to present the maternal sociodemographic and clinical characteristics; b) to analyze the fetal clinical characteristics; and c) to verify the causes of death pointed out from autopsy and anatomical pathology reports.

MATERIAL AND METHOD

It is an observational, cross-sectional study using secondary data. The documents used were autopsy reports obtained at the SVO in Florianópolis, issued by the State Department of Health of Santa Catarina, Brazil, between January 1, 2010 and December 31, 2015. These included the reports of the period with diagnosis of fetal death which were at 20 weeks of gestational age or older, and those with incomplete information were excluded.

In the service concerned, the protocol of fetal referral is performed by the health services, with authorization from the family, in order to elucidate the cause of fetal death, as well as to investigate the presence of malformations. When crime is suspected, the body is referred to the Institute of Forensic Medical. In the Florianópolis SVO, fetuses are classified according to the Brazilian Ministry of Health criteria for autopsy performance (gestational age after 20 weeks or weight above 500 g), and those that do not meet the criteria are considered as a surgical specimen. In the autopsy, gross and microscopical examinations of the fetal organs are performed; placenta is also examined when it is referred. The death certificate presents the fetal and maternal sociodemographic data and the fetal death diagnoses (final and provisional).

Upon receiving stillbirth, ectoscopic analysis and some tests may be performed to diagnose whether or not the death was intrauterine. The most popular test in the expertise services is the Galen hydrostatic test of the lungs or docimasia (lung float test). This safe method is based on lung density compared to that of water. If it floats, it means that the lung has a lower density, which indicates that the newborn had breathed. Otherwise, it is possible to infer that there was intrauterine death. Ideally, this test should be performed within 24 hours after birth, and some confounding factors, such as attempted resuscitation, should be reported to the pathologist so that he can improve the critical eye to look at the test⁽¹⁰⁾.

In this study, maternal age was categorized from the ideal reproductive age group – adult women aged 20 to 34 years – and their extremes: adolescents (10 to 19 years of age) and women at advanced age (≥ 35 years)⁽¹¹⁾. Gestational age was grouped as follows: early preterm (≥ 20 and < 34 weeks); late preterm (≥ 34 and < 37 weeks); full term (≥ 37 and < 42 weeks); and postterm (≥ 42 weeks)⁽¹²⁾. The fetal weight was stratified as: extremely low birth weight (< 1000 g); very low birth weight (≥ 1000 and < 1500 g); low birth weight (≥ 1500 and < 2500 g); normal weight (≥ 2500 g and < 4000 g); and fetal macrosomia (≥ 4000 g)⁽¹³⁾. The placental index was determined by calculating the quotient of the placenta weight in grams in air by the newborn weight in grams⁽¹⁴⁾.

In relation to the classification of cause of death, some disagreements with the literature were found: oligohydramnios, polyhydramnios, placental infection of hematogenous origin and ascending infection (related to chorioamnionitis). In this study, such causes were grouped into maternal etiologies related to pregnancy. Nuchal cord was also considered as a cause of intrauterine death.

Data analysis was performed on the SPSS software v.21 (IBM SPSS Statistics for Windows, Armonk, NY, USA). In the data description, we used measures of central tendency and dispersion for the quantitative variables and percentage for the qualitative variables. The existence of association between the presence of the outcomes of interest (fetal death and obstetric, placental, fetal characteristics) was evaluated by the chi-square test. For the comparison of the mean values of the quantitative variables, Student’s t-test for independent samples (unpaired) was used. The level of significance adopted in the statistical tests was 5% [confidence interval (CI): 95%].

The research protocol is in compliance with The Resolution 466/12 of the National Health Council and was approved by the Research Ethics Committee of the Universidade do Sul de Santa Catarina under protocol no. 2.564.705, dated March 26, 2018, which exempted the use of the term of free and informed consent.

RESULTS

Between 2010 and 2015, the Florianópolis SVO performed autopsy of 210 stillbirths at gestational age older than or equal to 20 weeks, with a mean of 35 cases/year. The annual autopsy distribution is shown in Figure.

Figure − Distribution of autopsies in the period

The sociodemographic and clinical characteristics of the sample are shown in Table 1. The mean maternal age was 27 years [standard deviation (SD): 7], ranging from 14 to 45 years. The fetal weight had a median of 1550 grams, varying between 166 and 4850 grams; and the placental weight, median of 340 grams, varying between 40 and 1010 grams. The calculation of the placental index showed a median of 0.192, which varied between 0.06 and 1.75.

Table 2 shows the causes of death found in the reports in a detailed manner. It should be emphasized that not all individuals had the definition of the cause of death, but some had more than one reason involved in the etiology of the fetal death.

Table 3 shows the comparison of the causes of death grouped according to the variables studied. When we observed the causes involved in the etiology of the fetal death in a grouped form, it was verified that 15.2% (n = 32) presented umbilical cord alterations; 22.4% (n = 47), placental alterations; 49.5% (n = 104), maternal health problem related to pregnancy; and 10% (n = 21), previous maternal disease. Among the fetal characteristics involved, it was observed that 6.7% (n = 14) presented meconium aspiration and 5.2% (n = 11), fetal malformations. In this study, 21.9% (n = 46) did not have their cause defined.

In the analysis between the gestational age and the causes of death, it was verified that the meconial aspiration was associated to the full term pregnancies (p = 0.005); the other gestational ages presented no association (p > 0.05).

When comparing the type of delivery with the causes of death, it was noted that vaginal birth was linked to placental diseases(p = 0.018). There was also a tendency for the association between vaginal birth and meconium aspiration (p = 0.057). The other causes were not related to the type of delivery (p > 0.05).

Maternal age (continuous and categorical variable) showed no association with the causes of death (p > 0.05).

Regarding the place of delivery, the hospital presented a statistically significant association with meconial aspiration (p = 0.04); the other locations were not associated with the causes(p > 0.05).

Regarding fetal weight, it was verified that extreme low weight had a statistically significant association with maternal diseases related to pregnancy (p = 0.028). In addition, normal birth weight was associated with meconium aspiration (p = 0.038).

It was also possible to observe that women with PIH had a mean of 0.191 placental index versus mean of 0.264 in those without the disease (p = 0.02). PIH was not associated with gestational age (p = 0.277), type of delivery (p = 0.212), maternal age (p = 0.863), origin (p = 0.137) and stratified fetal weight(p = 0.134).

Although there was no statistical significance (p > 0.05), all cases of malformation occurred in preterm infants.

DISCUSSION

Maternal and pregnancy-related characteristics

Knowing the profile of pregnant women is essential in prenatal care. In this study, a prevalence of 13.8% of adolescents, 48.6% of adult women and 18.1% of women at advanced age was found. In a similar study conducted in Florianópolis between 2000 and 2009, the prevalence of the age groups was 14.4%, 73% and 12.6%, respectively⁽¹⁵⁾. As it is the same population, there is a slight trend towards increasing maternal age, a fact that has been observed according to national statistics⁽¹⁶⁾. This scenario is due to factors, such as effective birth control, a higher level of maternal education, advances in health care and assisted reproduction technology, and higher rates of divorce followed by new unions⁽¹⁷⁾. As a consequence, there is an increased risk of numerous unfavorable outcomes for the fetus and the mother, such as PIH, abortion and more cesarean indications⁽¹⁸⁾.

Regarding the type of delivery, a higher prevalence of vaginal birth was observed in relation to cesarean section. It is considered that only stillbirths were included in this study and, when the diagnosis is made intrauterine, vaginal birth is the preferred route. Even before disagreements in the literature, it is important to emphasize that cesarean section brings less morbidity to the fetus in relation to vaginal birth, especially in preterms⁽¹⁹⁾; the benefit to the fetus should also be highlighted when choosing the way of delivery. Regarding home birth, it is pointed out that, although studies show greater maternal satisfaction, there is a higher prevalence of unfavorable outcomes for newborns in home deliveries⁽²⁰⁾.

Causes of intrauterine death

Knowing the direction of stillbirth by gestational age is fundamental, since it is a marker of gestational health. In this study, there was a greater tendency (51.9%) of death in early preterm, a finding consistent with a large population-based study conducted in the United States between 2006 and 2012⁽²¹⁾.

Regarding the prenatal follow-up, it was observed that in the study population 12 pregnant women did not perform it, representing 5.7% of the total. Considering the population of live births in the Grande Florianópolis during the period of this study, statistics show that only 1.3% did not present prenatal care⁽¹⁶⁾, which represents a lower prevalence than that which culminated in fetal death.

In addition to clinical data related to previous maternal history and with complications of pregnancy, placental analysis is imperative. The placental membranes can be infected by the accession of microorganisms, causing chorioamnionitis, and by the hematogenous route. The inflammatory reaction caused in these situations is associated with classic anatomopathological findings. In chorioamnionitis, for example, there are polymorphonuclear infiltrates that affect both the amniotic membrane and the villi⁽²²⁾. In this study, among all the outstanding causes of intrauterine death, ascending infection was the most prevalent (20%), corroborating the findings of Man et al. (2016)⁽²³⁾. In cases of placental infection of hematogenous origin, some conditions are considered major, such as syphilis, toxoplasmosis, rubella, cytomegalovirus and infection with herpes simplex virus, known as STORCH. In addition to these, it is important to highlight the participation of listeriosis, related to gestational infection by hematogenous spread, which causes features detectable in the anatomical pathology examination⁽²⁴⁾.

PIH, while pre-eclampsia, affects 3%-5% of pregnancies. Its diagnosis is traditionally made by high blood pressure and the presence of proteinuria. When improperly managed, it can be lethal⁽²⁵⁾. In the present study, PIH was among the main causes of intrauterine death (15.2%). In the pathophysiology of the disease, failure of the second trophoblast invasion acts leading to high-resistance artery of the uteroplacental circulation, which culminates in the occurrence of placental infarction. It is not uncommon in clinical practice to find ultrasound degrees of placenta previa in patients with PIH compared to those without the disease. Such alterations are also observed in the anatomopathological analysis, which shows white and red areas, which indicates old and recent infarctions, respectively. Therefore, a lower placental weight is expected in patients suffering from this condition, as well as a lower placental index. In this study, it was verified that the presence of PIH was associated with a lower placental index (p = 0.02) without a statistically significant change in fetal weight (p = 0.134), when compared with deaths from other causes.

The detailed study of the causes of death brings very important information in the investigation of fetal death, as well as when the causes are grouped together. In the present study, 22.4% of the individuals had changes in the placental bed that culminated in intrauterine death. Stanek et al. (2014)⁽⁶⁾ state that these abnormalities are less common in the second trimester, in addition, they reinforce that chronic hypoxic lesions are more prevalent in the preterm and that signs of intrauterine hypoxia, such as meconium, arise mainly in full term pregnancy⁽²⁶⁾. Corroborating these data, the present study showed a significant relationship between meconial aspiration and full term pregnancies, as well as between hospital origin and normal birth weight. It should be pointed out that such associations were possibly due to the fact that most of the deliveries occurred in a hospital environment, either because the diagnosis of intrauterine death had been made previously, or because many of the pregnant women had diseases that needed continuous monitoring, and the hospital was the appropriate place to act in these high-risk pregnancies.

Investigation of fetal death

In the literature, studies indicate a rate of approximately 60% of fetal deaths without a specific cause^{(9, 27)}. In this study, only 21.9% remained with no justification. It is suggested that this data could be even smaller with the correct completion of the referral and the complete previous information sent to the SVO. According to fetal death investigation flowcharts, autopsy, placental examination, cytogenetic analysis and coagulation tests are essential in the investigation of fetal death. Based on these initial results, other tests may be indicated⁽²⁸⁾.

Limitations of this study

As a limitation of this study, we highlight the non-obligatory referral of stillbirths to the SVO and the poor quality of the information transmitted to the doctor of the service that performs the necroscopic examination. It is emphasized that not only the referral of the fetus, but also that of the placenta, are essential for an appropriate investigation of the cause mortis, and that these data associated with a detailed clinical history make the analysis more complete and reliable.

CONCLUSION

Among all causes of fetal death, ascending infection was the most prevalent. The main cause of death related to the umbilical cord was stenosis, and premature placental abruption was related to the placenta. Regarding the pregnancy, the ascending infection stands out, for previous maternal health problem, systemic arterial hypertension. The fetal causes were the meconial aspiration and the consequences related to trisomy 21 and congenital heart disease. Only 21.9% of the reports did not present the definite cause of death, which is below the average found in the literature.

It was verified that meconial aspiration was associated with full term pregnancy, normal birth weight and hospital origin; vaginal birth was associated with placental diseases. It was noted that extreme low birth weight was associated with maternal diseases; PIH presented a placenta index statistically lower than that in relation to women without this disease. Among all the variables investigated, maternal age showed no association with the causes of death studied.

ACKNOWLEDGMENTS

To the SVO of Florianópolis, for the availability of data, especially to Holdarina A. Menezes M.D. and to Mr. Luiz Carlos Martins.

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