What is the most common cause of spontaneous abortion in the first week of development?

Fetal Infection (Hydrops Fetalis and Miscarriage)

B19V causes 10% to 15% of all cases of nonimmune hydrops fetalis.106 Nonimmune hydrops fetalis is rare (1 per 3000 births), and in approximately 15% of cases the etiology is unknown. In a study of 63 cases, 8 were due to B19V infection. When pathologic studies have been undertaken, B19-infected fetuses showed evidence of leukoerythroblastic reaction in the liver and large pale cells with eosinophilic inclusion bodies and peripheral condensation or margination of the nuclear chromatin. B19V DNA can be detected by PCR and in situ hybridization, and viral particles by electron microscopy.

Even in the absence of treatment, an adverse fetal outcome is not typical after maternal B19V infection. In a prospective British study of more than 400 women with serologically confirmed B19V during pregnancy, the excess rate of fetal loss was confined to the first 20 weeks of pregnancy and averaged only 9%.107 No abnormalities were found at birth in the surviving infants, even when there was evidence of intrauterine infection by the presence of B19V IgM in the umbilical cord blood, and there were no long-term sequelae in the 129 children observed for more than 7 years. Similar findings have been found in studies in other countries.108,109

No systematic studies have shown evidence for congenital abnormalities after B19V infection,107,110 although there are case reports of congenital ocular and neurologic abnormalities after maternal B19V infection. Rare cases of congenital anemia after a history of maternal B19V exposure have been reported.111,112 In these cases the virus load is generally low, and the anemia does not respond to immunoglobulin therapy. The B19V infection may mimic Diamond-Blackfan anemia,113 and investigation of erythrocyte enzyme activity and ribosomal protein genes may be needed to distinguish the two.114

Conclusion

Miscarriage is a very frequent pregnancy complication and should be managed following recommendations for diagnosis. It will avoid numerous sonographic controls before diagnosis. For management, surgery and medical treatment are equivalent for asymptomatic women but expectant management should be avoid whereas, all of these treatments can be performed in women with bleeding.

When there are three or more miscarriages, the diagnosis of repeat miscarriages can be done and required a restricted medical check to diagnose abnormalities that can be corrected to avoid a subsequent miscarriage. When the medical check is normal, folic acid and progesterone supplementation should be given until 14 weeks of gestation.

In all cases, women with a previous miscarriage need to be reassure and repeated early sonographies for the next pregnancy might be necessary all the more in case of repeat miscarriage.

Impact of Spontaneous Miscarriages on First-Trimester Screening

A potential disadvantage of earlier screening is that chromosomally abnormal pregnancies that are destined to miscarry will be identified. Of trisomy 21 fetuses living in the first trimester, 69% will be born alive, and 76% of trisomy 21 fetuses alive in the second trimester will be born alive. Using this information, Dunstan and Nix calculated that a detection rate of 80% in the first trimester is approximately equivalent to a second-trimester sensitivity of 75%, suggesting that even when early spontaneous losses of trisomy 21 pregnancies are considered, first-trimester screening is superior to screening presently available in the second trimester.31a

First-trimester screening would be less desirable if screen-positive pregnancies or pregnancies with enlarged NTs were preferentially lost. In a study of 108 fetuses with trisomy 21 diagnosed in the first trimester because of increased NT, Hyett and colleagues found that six patients elected to continue the pregnancy. In five of the six fetuses, the translucency resolved, and at the second-trimester scan the nuchal fold thickness was normal. All six of these trisomy 21 fetuses were born alive.32 Wapner and colleagues16 calculated that greater than 80% of screen-positive trisomy 21 pregnancies would be born alive.

Miscarriage

Miscarriage or spontaneous abortion involves the loss of a pregnancy, usually within the first 3 months of conception. The estimated frequency of spontaneous abortion is between 12% and 24% of all clinically identified pregnancies. The risk factors for miscarriage include extremes of age, smoking history, obesity, previous miscarriage, hypertension, and diabetes. All of these are also overlapping risk factors for SDB. Data linking SDB and miscarriage are limited, and any discussions are mostly theoretical in nature. In a retrospective review of sequential clinic charts of 147 premenopausal women who had been referred to a sleep disorders clinic for an evaluation of sleep complaints, an association between SDB and number of miscarriages was demonstrated. In that review, overweight or obese women with SDB, especially those with moderate to severe SDB, were more likely to have had a miscarriage than women without SDB.87

Maternal Causes:

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Uterine anomalies: Müllerian abnormalities such as unicornuate, bicornuate, or septated uterus are associated with increased miscarriage risk, although rates vary in different studies. A septated uterus is most highly associated with recurrent loss and can be surgically corrected and thus is important to diagnose. Other intrauterine pathologies such as synechiae, leiomyomas, or prior DES exposure are important to rule out also.

Incompetent cervix (iatrogenic or congenital, associated with 20% of midtrimester losses).

Antiphospholipid antibody syndrome.

Uncontrolled diabetes mellitus.

Rare or controversial causes include HLA associations between mother and father; infections such as tuberculosis,Chlamydia, andUreaplasma; smoking and alcohol use; irradiation; progesterone deficiency; and environmental toxins. Most of the literature is observational in nature, which may skew risk factor data.

With two or more spontaneous miscarriages, a karyotype can be performed on the products of conception to evaluate for aneuploidy, which may be associated with a balanced translocation in one of the parents, and which has a substantially increased risk for abortion (depending on the actual type of translocation); if the pregnancy is carried to term, it has a 3% to 5% risk for an unbalanced karyotype. In patients with habitual abortion, evaluation for anatomic defects such as uterine septum and for antiphospholipid syndrome (lupus anticoagulant, beta 2 glycoprotein IgG/IgM, and anticardiolipin antibody IgG/IgM) should also be obtained.

Recurrent Miscarriage

Miscarriage is a common pregnancy complication with a risk of 12%–15% in each pregnancy and is defined as the premature loss of a fetus up to 20 weeks of gestation in most countries. Recurrent miscarriage has been defined as three or more consecutive miscarriages, but this is increasingly being revised to two or more miscarriages. The incidence of recurrent miscarriage is 1%–3%. Women with a history of miscarriage are shown to be at a higher risk of CHD compared to women who have not experienced miscarriage. Women with a history of miscarriage are shown to be at 45% risk of CHD, while those with a history of recurrent miscarriage have a 2-fold increased risk of CHD (Oliver-Williams et al., 2013). Although a link between recurrent miscarriage and CHD has been reported, most studies on miscarriage have not classified miscarriage phenotypically, and a recent systematic review and metaanalysis failed to show an association between recurrent miscarriage and CHD (Heida et al., 2016). Since a large proportion of early miscarriage may be due to anembryonic losses, it is difficult to draw conclusions from the above findings. Furthermore, whether miscarriage occurs in first trimester or second trimester may be influential.

Miscarriage

Miscarriage is the most frequent complication in pregnancy. It has been reported that 12% to 24% of women who have missed a menstrual period and had a positive pregnancy test result experience the loss of a pregnancy.1 The rate of miscarriage reduces as the gestational age increases. Three percent of women having a routine first trimester ultrasound between 10 and 13 weeks are diagnosed with a delayed miscarriage, and the incidence of a second trimester miscarriage has been reported as between 1% to 4%.2,3 Approximately 25% to 50% of women experience at least one miscarriage during their reproductive years.4 An estimated 125,000 miscarriages occur every year in the United Kingdom, and these account for more than 50,000 admissions.5,6

The majority of first trimester miscarriages resolve spontaneously without causing any maternal morbidity or requiring treatment. However, because of their high incidence, miscarriages and the associated costs of investigation, hospital admission, treatment and follow-up are a significant burden. Miscarriage has a negative impact on the quality of life of women. It signifies a loss of a baby, even in early gestations, and is a stressful and sad time for the women and their partners.

The maternal mortality rates after miscarriage in the United Kingdom ranged from 0.05 to 0.22 per 100,000 pregnancies between 1985 and 2008. Haemorrhage and sepsis, which mainly occurred after second trimester losses, were the most common causes of death.7

Introduction

Spontaneous abortion also called spontaneous miscarriage is defined as the loss of pregnancy prior to 20 weeks of gestation (Katz, 2012) and can be divided in to chemical pregnancy and clinical pregnancy. Pregnancy termination and miscarriage include chemical and clinical pregnancies, respectively (Bennett et al., 1998). Chemical pregnancy is defined as the early period of pregnancy, which is just prior to, and a few days after, implantation of the embryo. Early pregnancy is detected by the presence of increasing levels of circulating human chorionic gonadotropin (hCG), produced by placental trophoblast cells of the conceptus. Clinical pregnancy is defined as the presence of an embryonic unit documented by ultrasound several days to weeks after implantation of the embryo. During clinical pregnancy, hCG levels are increasing. Spontaneous termination of a clinical pregnancy is referred to as miscarriage or spontaneous abortion (Bennett et al., 1998).

Miscarriage

Miscarriage is variously defined but usually refers to a pregnancy loss, or spontaneous abortion, before 20 weeks' gestation. The definition of a spontaneous abortion is “the spontaneous termination of a pregnancy occurring before 20 completed weeks of gestation by expulsion complete or incomplete of the products of conception from the uterus, by failure of the embryo to develop or by death of the fetus in utero.”6 In a large population study examining more than 1 million pregnancy outcomes, 11% of pregnancies that were intended to be carried to term ended in spontaneous abortion.7 In a study that used a sensitive assay to detect pregnancy, 12% of clinically recognized pregnancies ended in spontaneous abortion, but another 22% ended in spontaneous abortion before being recognized.8 Miscarriage is relatively common and is diagnosed even more frequently when pregnancy is detected earlier with sensitive home-based pregnancy tests.

In a study of bleeding as a risk factor for miscarriage, 4510 women were enrolled prospectively before pregnancy; 1204 (27%) experienced bleeding in the first trimester of pregnancy. Not all women who bled went on to miscarry, but 517 (43%) of those who experienced bleeding ultimately did miscarry. Heavy bleeding (similar to or greater than that of a menstrual period) was strongly predictive of miscarriage, with 3 times the risk compared with no bleeding (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.9 to 4.6), whereas spotting or light bleeding did not increase the risk of miscarriage.9

Bleeding that accompanies miscarriage increases with gestational age, as does the case fatality rate from miscarriage. The risk of maternal death in association with spontaneous abortion was eightfold higher with a fetal gestational age of 12 weeks or longer than with a gestational age of less than 12 weeks, which suggests that bleeding complications are much greater with increasing gestation. Spontaneous abortion accounts for 3% of all pregnancy-related deaths in the United States.10 In a national study in the United States the leading cause of maternal death associated with spontaneous abortion was infection (59%), followed by hemorrhage (18%), embolism (13%), anesthesia complications (5%), and other causes (5%); disseminated intravascular coagulation (DIC) was an associated condition in half of the cases of spontaneous abortion–related maternal death.6

After a determination has been made that the pregnancy has ended, either because no embryo or fetus has developed, because the embryo or fetus has died, or because the miscarriage is actually in progress, the obstetrician-gynecologist will surgically evacuate the uterus or await spontaneous expulsion of the products of conception. Historically, obstetrician-gynecologists believed that all miscarriages should be surgically evacuated, but in the past 25 years, the necessity of surgical evacuation in all cases has been questioned, and there have been a number of randomized trials examining surgical evacuation versus expectant management. In a Cochrane review of five trials with 689 participants, the patients managed expectantly were less likely to have infection (relative risk [RR], 0.29; 95% CI, 0.09 to 0.87) but more likely to have an incomplete miscarriage necessitating unplanned surgical treatment. The expectantly managed patients experienced a significantly greater number of days of bleeding (weighted mean difference, 1.59; 95% CI, 0.74 to 2.45) and a significantly greater amount of bleeding according to a scale (weighted mean difference, 1.00; 95% CI, 0.60 to 1.40).11 Therefore surgical management of spontaneous abortion is preferred in the patient at risk of bleeding due to a preexisting hemostatic abnormality.

Prevalence and Epidemiology

Spontaneous abortion is the most common complication of pregnancy, occurring in at least 15% of clinically recognized pregnancies. In more than half of patients who present with symptoms of spontaneous abortion, retained POCs will be present in the uterus. These retained POCs will be due to an incomplete miscarriage in half (49%) of patients, with missed miscarriage (31%) and anembryonic pregnancy (20%) accounting for the remainder of cases.1 After first trimester pregnancy termination, retained POCs are uncommon, reported in 3.7% of cases.2

Retained POCs are less common in the postpartum period, complicating approximately 1% of term vaginal deliveries. They represent, however, one of the most common reasons for hospital referral and readmission in the postpartum period. Retained POCs are more commonly seen with preterm delivery and with manual extraction of the placenta at delivery.