Although the stillbirth rate has declined in recent years, it is still an important obstetric health problem due to its association with increased perinatal mortality. Stillbirth rates remain high, especially in low and middle-income countries, where rates are 25 per 1000, ten times higher than in high-income countries.
In our study, the rate of fetal deaths was 7/1000, which is lower than the mean for Latin American countries (in 2015 rate was 8.1 per 1000 births, range 3.1-24.9) but is close to Mexico’s average rate of 7.9/1000 . However, problems in the notification of stillbirth and the study’s duration could influence our incidence. A long-term evaluation should be performed for more accurate data. Nevertheless, it represents a public health issue for which identifying risk factors is important to propose prevention strategies.
From the major causes of stillbirths, we can point out the following: childbirth complications, multiple pregnancies, post-term pregnancy, maternal infections (malaria, syphilis, and HIV), maternal disorders (especially hypertension, obesity, and diabetes), fetal growth restriction, and congenital abnormalities. Several algorithms have been proposed for the study of stillbirth to identify possible causes of this fatal outcome of pregnancy.
In this multidisciplinary workup, we used different tools. The maternal medical history, physical examination, photographs, medical record, prenatal ultrasound, x-ray, or autopsy were obtained. MLPA was performed in all cases.
The correlation between maternal medical history and the description of birth defects in the fetus gave us information for possible risk factors in 16 cases, representing a usefulness of 76%, higher than 26% reported by Pauli et al.  and Wojcik .
External physical examination is important for the detection of birth defects. This procedure must be performed by a medical professional who has been trained in dysmorphology. Nevertheless, the maceration grade should be between 0 and III to facilitate the examination . This approach let us identify malformations in 8 cases. Macroscopic evaluation should complement an autopsy which is considered the most useful study for stillbirth since it allows identifying characteristics not observable by physical examination. A complete autopsy should include an analysis of the placenta and umbilical cord [8,9,11]. It can identify stillbirth etiology in about 90% of cases . However, to maximize the autopsy’s efficacy, it is important to consider the time from fetal death to the autopsy. The longer it takes to perform the autopsy, the less efficient it will be [9,14]. In our workup, only three autopsies were accomplished. The rest could not be achieved due to delayed notification, and in two cases, the mothers did not consent to the autopsy. It was difficult to assess the efficiency of the autopsy in our study with the data obtained, but the shortage of information obtained in those three cases may relate to a prolonged time from fetal death to evaluation.
Approximately 3% of prenatal ultrasounds detect an abnormality. This can range from minor to multiple defects, which can put the development of the fetus at risk . The detection of anomalies in prenatal ultrasound can affect the pregnancy outcome, so it should be considered a part of the prenatal care of all women . In the present study, 17 (53 %) women had a prenatal ultrasound, of which 9 (53%) showed either fetal or placental findings of relevance for diagnosis, such as holoprosencephaly, anencephaly, hydrops fetalis, and placenta previa. The efficiency of prenatal ultrasound for detecting birth defects has been reported as 3% , with our rate of detection being higher.
A plain X-ray is also considered an adequate study when an autopsy cannot be performed . It can identify stillbirth etiology in about 16% . However, a plain X-ray might be more efficient when skeletal pathology is suspected. We only detected suggestive findings in one patient (4.8%) with congenital syphilis.
Genetic etiology of stillbirth can be found in 25-35% [2,9], and 6 to 12% are chromosomal alterations . Conventional genetics was once considered the gold standard for stillbirth evaluation [3,11,15,16,17]. We decided to perform MLPA containing probes for chromosomes X, Y,13,18 and 21, to evaluate the most common chromosomal causes of stillbirth, which were not the case in our study; therefore, we cannot discard other chromosomal or genetic etiology. Chromosomal microarrays (CMA) are now considered the first line of study [16,17].
Maternal obesity (BMI > 30 Kg/m2), has been positively associated with stillbirth ; however, no BMI score has been reported as secure or protective for stillbirth. In a meta-analysis by Aune et al., 18 cohorts were included to analyze BMI and stillbirth risk, finding that this association is positive for obesity and an important higher risk with a BMI of 40 . In our study, 43% of the mothers had a BMI >30, which can account for the outcome of their pregnancies.
Pre-gestational diabetes mellitus (DM) (either type 1 or 2) is associated with an increased risk of fetal macrosomia, birth defects, and stillbirth at 36 to 42 weeks of gestation. Similar results have been reported in gestational diabetes [20,21,22]. Fifty-seven percent of the mothers in this study had poorly controlled pre-gestational DM, which is a high proportion compared to the 5.2% reported in another study (20). The physiopathology that explains how hyperglycemia might contribute to the events that lead to fetal death has not been fully determined. Elevation of plasma lactate was reported, predominantly in the third trimester, as a possible cause . This result suggests that a lactic acid elevation leads to anaerobic metabolism, causing hypoxia, acidosis, and subsequent fetal death . Obesity and diabetes are serious health problems in our country, mostly in northern Mexico, and occur in 5.2% of pregnancies .
It is important to establish that even if diabetes or obesity is identified as an important risk factor in a woman, a complete study of stillbirth should be done because that does not eliminate the probability of other causes.
Amongst maternal factors, infections account for 20% of stillbirths in developed countries . Infections like cytomegalovirus and syphilis are frequently reported in these patients; usually, infectious etiology is not directly looked for; suspicion based on prenatal ultrasound or physical examination leads to its evaluation [8,25]. We identified infection risk factors by medical record data and plain X-ray.
Other maternal diseases have been implicated in stillbirth like thyroid pathologies, cardiovascular, renal, rheumatic diseases, and cancer. These conditions can be associated with stillbirth in either acute or chronic states; however, most women with these conditions can achieve live births, so they are considered important for stillbirth assessment, but causality should be evaluated in every case .
In Mexico, one of every 90 pregnancies are twin pregnancies. These convey a higher risk of birth defects (10 times more than singleton pregnancies) , as well as an increased stillbirth risk, 13 times higher in monochorionic pregnancies, and 5 times higher in dichorionic pregnancies .
The global strategy to end stillbirth classifies twin pregnancies as an important risk factor, recommending early delivery between 34 and 37 weeks of gestation in monochorionic pregnancies and 37 to 29 in dichorionic pregnancies [27,28,29]. Prenatal care in this scenario should be stricter.
Placental causes are attributed in 64.9% of stillbirths. Identification of placental pathology requires a microscopical and macroscopical evaluation after birth, prenatal markers are not considered useful for evaluation 
Placental causes may be associated with growth restriction, but not all patients present growth restriction, and the ones that do, do not all result in stillbirth . We did not perform studies on the placenta, so we cannot confirm or exclude placental etiology.
Another risk factor identified in our study was tobacco consumption. Exposure to tobacco, either active or passive, has been positively identified as a stillbirth risk factor. However, when exposure is implicated, fetal growth restriction is reported, when that significant data is lacking, the risk of stillbirth has been proposed to be like women without tobacco consumption [18, 31]