Prenatal Screening—The Key to Favorable Pregnancy Outcomes

Abstract

Fetal exposure in utero to environmental factors and maternal factors can lead to epigenetic changes that have a lasting impact on metabolic programming in the developing organism. These changes may be either temporary or permanent and can have significant implications for the health of the individual later in life. In this context, prenatal screening is an essential component of prenatal care, providing valuable information about the health status of the developing fetus and allowing healthcare providers to identify potential health risks to both the mother and the baby. Various screening methods are available, including ultrasound scans, non-invasive prenatal testing (NIPT), and biochemical markers. During prenatal care, various conditions are screened for, including preterm birth, preeclampsia, diabetes, fetal growth restriction, chromosomal abnormalities, thrombophilia, infections, and thyroid disease. However, the most crucial screening test during pregnancy is for congenital abnormalities, which affect approximately 2% of newborns. While each screening method has its own advantages and limitations, combining multiple methods may improve the accuracy of detecting fetal abnormalities and provide a more comprehensive picture of fetal health.

Screening for genetic anomalies

There are several screening methods for genetic abnormalities. These include ultrasound screening, serum screening tests, and the non-invasive prenatal test (NIPT).

First-trimester ultrasound has proven to be an effective screening method for aneuploidy, such as trisomy 21 [1]. First-trimester ultrasound screening must include measurement of nuchal translucency [2]. There is a well-known association between the increased dimensions of nuchal translucency and the risk of aneuploidy [3]. Increased nuchal translucency is also associated with other genetic anomalies, as well as with structural defects, the most common being cardiac, gastrointestinal, and musculoskeletal malformations [4,5]. In addition to increased nuchal translucency, the suspicion of trisomy 21 can also be raised based on other ultrasound findings, such as atrial septal defect, atrioventricular canal defects, ventriculomegaly, choroid plexus cyst, duodenal atresia, esophageal atresia, absence of the nasal bone, or hypoplastic nasal bone, and short femur [1].

There are also ultrasound features that have been observed in pregnancies with trisomy 18. These include the heart, central nervous system and neural tube defects, ventriculomegaly, hydrocephalus, omphalocele, diaphragmatic hernia, ureterovesical obstruction, abnormal kidneys, and abnormal bladder [6].

In pregnancies with trisomy 13, several echographic features have also been highlighted, including atrial and ventricular septal defects, multiple anomalies of the atrioventricular canal, single ventricle, tetralogy of Fallot, Dandy-Walker malformation, holoprosencephaly, and ventriculomegaly [7].

The ultrasound assessment can be valuable in identifying anomalies associated with specific genetic syndromes, such as Turner syndrome, 22q11.2 deletion syndrome, Cri du Chat, Beckwith-Widemann, and Noonan syndrome [1].

The first-trimester combined screening, performed between 11-13⁺⁶ weeks, involves reviewing the mother's medical history and age, evaluating nuchal translucency, and measuring free beta-hCG and PAPP-A levels. This screening method can detect more than 90% of trisomy 21 pregnancies and approximately 95% of trisomies 18 and 13 [8]. The addition of other fetal markers, such as nasal bone assessment, Doppler evaluations of the ductus venosus, and blood flow through the tricuspid valve, might further increase the efficiency of the first-trimester combined screening [9,10,11], with a detection rate of 93-96% [8,12]. These supplementary ultrasound parameters can be assessed when performing the combined screen or on a contingent basis [13,14].

Contingent screening implies for patients to be initially divided into 3 categories depending on the traditional combined screen: high risk (≥1:50), intermediate risk (1:51–1:1000), and low risk (≤1:1000). High-risk patients are offered invasive testing, and low-risk patients no longer require additional tests. Intermediate-risk patients will require additional screening tests in the second trimester [5,15].

The second-trimester serum screening includes the triple test that evaluates maternal age in combination with the maternal serum level of alpha-fetoprotein, unconjugated estriol, and hCG. For ultrasound-dated pregnancies, the triple test can detect 71% of pregnancies with Down syndrome with a false-positive rate of 5% [15].

Another screening test is represented by quadruple screening. It involves dosing of hCG, alpha-fetoprotein (AFP), inhibin A, and unconjugated estriol. These parameters in combination with maternal age, race, weight, number of fetuses, presence or absence of diabetes, and gestational age, provide an assessment of the risk of Down syndrome, trisomy 13, trisomy 18, and neural tube defects [16,17]. Quadruple screening has a detection rate of 82% with a false-positive rate of 5% [15]. Another available option is the quintuple screening which uses the same parameters as the quadruple screening, to which another biomarker is added - hyperglycosylated hCG [5].

The integrated screening involves the measurement of nuchal translucency and the dosage of plasma protein A associated with pregnancy in the first trimester and performing the quadruple test in the second trimester, the patient receiving the result only when all the tests have been performed. The detection rate of anomalies using this test is between 85-87% with a rate of false-positive results between 0.8-1.5% [18].

Sequential screening involves the measurement of nuchal translucency, b-hCG, and PAPP-A in the first trimester, followed by the quadruple test in the second trimester. Unlike integrated screening, the patient receives the result after the first series of tests [5]. Patients who are considered high-risk after the tests in the first trimester are offered invasive testing, and low-risk patients are offered additional serum screening tests in the second trimester [15].

Non-invasive prenatal test (NIPT) has become more and more used in recent years because it assures the evaluation of the health status of the fetus, without creating risks for the fetus or the mother [19]. This test is based on the analysis of free circulating fetal DNA and is a screening method that requires confirmation of the result with a diagnostic test, but which also has other applications that do not require subsequent invasive testing: determination of sex, blood group, and Rh [20,21].

Free circulating fetal DNA derives from the trophoblastic cells of the placenta and becomes detectable starting from 4 weeks of gestation. However, levels that allow testing for monogenic disorders are reached at 6-7 weeks of gestation. NIPT is a screening test for aneuploidy and not a diagnostic test [22]. This is due to a risk of discordant results that may occur due to placental mosaicism, fetal mosaicism, maternal neoplasia and vanishing twin syndrome [23,24].

This test has a sensitivity of 99.3% (95% CI 98.9-99.6%) in the detection of Down syndrome, 97.4% (95.8-98.4%) in the detection of Edwards syndrome and 97.4 % (86.1-99.6%) in the detection of Patau syndrome. The specificity is 99.9% (99.9-100%) for all three trisomies [25].

Screening for structural anomalies

Screening for fetal abnormalities has traditionally been done in the second trimester, but many structural abnormalities can be diagnosed between 11 and 14 weeks of gestation. First-trimester ultrasound is a valuable tool in the diagnosis of structural abnormalities in the first trimester [26].

Congenital cardiac anomalies are the most common structural malformations, affecting 8 out of 1000 children. While most of these are minors, 3 out of 1000 fetuses will be affected by a severe form of cardiac pathology [27]. Ultrasound can highlight dextrocardia, mesocardia, ectopic heart, abnormal pulmonary venous return, persistent left superior vena cava, atrial and ventricular septal defects, atrioventricular defects, pulmonary atresia, valvular stenosis, Ebstein's anomaly, tetralogy of Fallot, transposition of large vessels, coarctation of the aorta [28].

Neural tube defects are second in frequency after cardiac anomalies. First-trimester ultrasound was evaluated as a screening modality for these abnormalities. Although some neural tube defects can be identified in the first-trimester ultrasound, the detection rate is much lower than in the second-trimester ultrasound. Spina bifida, anencephaly, are some of the conditions that can be highlighted sonographically [29].

Renal structural anomalies represent 20% of congenital anomalies. The urinary tract can be visualized ultrasonographically from 11 weeks, this allows identification of the mega-bladder between 11-14 weeks of gestation. Second trimester ultrasound allows the detection of most renal anomalies with greater sensitivity. Bilateral renal agenesis can be confirmed ultrasonographically, highlighting the free renal fossas, and the absence of bladder filling accompanied by severe oligoamnios or anhydramnios. Dysplastic kidneys, duplex kidneys, polycystic kidneys, and dilatations of the upper renal tract and posterior urethral valves are other conditions that can be highlighted by ultrasound [30].

Ultrasound can also identify gastrointestinal abnormalities: atresia, stenoses, duplication of the gastrointestinal tract, tumors, cysts, liver, splenic or pancreatic diseases. Limb anomalies, musculofascial, facial and abdominal wall anomalies can also be diagnosed by ultrasound [31].

Screening for gestational diabetes mellitus

Gestational diabetes is the most common metabolic disorder complicating pregnancy. The increasing prevalence correlates with the increase in the prevalence of maternal obesity in recent decades. The etiology of the disease is complex, involving both genetic and environmental factors [32].

Gestational diabetes is defined as diabetes diagnosed in the second or third trimester of pregnancy, which was not present before pregnancy [33]. Considering the large number of pregnant women undiagnosed before pregnancy with diabetes, patients with risk factors for diabetes should be tested at the first prenatal visit using the standard diagnostic criteria [33]. Tests that can be used are blood glucose in patients with symptoms of hyperglycemia, the glucose tolerance test with 75 g of glucose, glycosylated hemoglobin, fasting blood glucose [34]. Patients with positive results should be included in the category of patients with diabetes-complicating pregnancy (most often type 2, less often type 1 or monogenic diabetes) [33].

Screening for gestational diabetes is performed between 24-28 weeks [35]. The used methods are the one-step testing consisting of the oral glucose tolerance test with 75 g of glucose or the two-step testing with the glucose tolerance test with 50 g of glucose, followed by the glucose tolerance test with 100 g of glucose in patients with positive result [36].

Patients with gestational diabetes should be tested 4-12 weeks after birth for prediabetes or diabetes using the glucose tolerance test with 75 g of glucose [37]. Also, patients known with a history of gestational diabetes should be included in the long-term screening for prediabetes and diabetes. The glucose tolerance test can be performed once every 3 years or fasting blood glucose annually or glycosylated hemoglobin annually [38].

There is no international consensus regarding the screening and diagnosis of gestational diabetes. The option of universal screening versus selective screening, the optimal period for screening, the most suitable diagnostic methods, cutoff values, ​​and one-step or two-step testing are discussed [36].

Screening for preeclampsia

Preeclampsia affects 2-3% of pregnancies and is a major global cause of maternal and fetal mortality and morbidity [39]. Preeclampsia was previously defined as the appearance of high blood pressure and significant proteinuria after 20 weeks of gestation. Currently, the universally accepted definition of preeclampsia is that proposed by the ISSHP (International Society for the Study of Hypertension in Pregnancy). Thus, preeclampsia is defined as systolic arterial pressure ≥ 140 mmHg and/or diastolic arterial pressure ≥ 90 mmHg, measured at least twice at intervals of at least 4 hours, values ​​that appear in previously normotensive patients, to which is added one or more of the following criteria, appearing for the first time after 20 weeks of gestation: proteinuria ≥ 300 mg/24 hours, evidence of maternal organ dysfunction including acute renal injury (creatinine ≥ 90 micromol/L, liver damage (transaminases increased >40 IU/L) with or without pain in the right hypochondrium or epigastrium, neurological complications (altered mental status, headache, visual disturbances), hematological complications (thrombocytopenia, disseminated intravascular coagulation, hemolysis) or uteroplacental dysfunction (RCIU, modified Doppler flow on the uterine artery, intrauterine fetal death) [40].

The specialized literature discusses the universal screening of preeclampsia during pregnancy. This should be applied to all patients in the first trimester and involves a combined test that includes maternal risk factors and certain biomarkers [40]. The main risk factors involved in the occurrence of preeclampsia are represented by factors such as nulliparity, personal or family history of preeclampsia, chronic hypertension, diabetes, collagenosis, black race, obesity, and thrombophilia [41]. The most effective combined test is the one that includes maternal risk factors, mean blood pressure, serum level of placental growth factor (PLGF), and uterine artery pulsatility index (UTPI) [40]. This test can predict 90% of cases of preeclampsia with birth <32 weeks and 75% of cases of preeclampsia with birth <37 weeks [42]. When the PLGF and UTPI values are not available, risk can be calculated using maternal risk factors and mean blood pressure, but it should not be calculated using risk factors alone. When the PAPP-A value is measured in the screening for aneuploidy, it can be included in the risk assessment for preeclampsia. Variations from the full combined test lead to reduced screening performance. A patient is considered high risk when the risk is higher than 1:100 [40].

When resources are limited, contingent screening can be applied by using maternal risk factors and mean blood pressure, with the measurement of PLGF and UTPI being reserved for a subgroup of the population [40].

In high-risk patients, calcium and low-dose aspirin are recommended. Daily supplementation with calcium carbonate (1000-2000 mg/day) and aspirin (50-150 mg/day) has been shown to be effective in randomized studies [42]. According to the ASPRE trial, the administration of aspirin resulted in a significant 62% reduction in the incidence of preterm-preeclampsia compared to a placebo. However, there was no significant effect observed on the incidence of term-preeclampsia [43].

Screening for Rhesus incompatibility

Hemolytic disease of the fetus and newborn (HDN) is a condition in which maternal immunoglobulin G (IgG) antibodies destroy the red blood cells (RBCs) of the fetus or newborn, leading to hemolysis. HDN caused by alloimmunization mainly affects the major blood groups including Rh, A, B, AB, and O. However, incompatibilities in minor blood groups such as Kell, Duffy, MNS, P, and Diego systems can also cause significant disease [44].

Incompatibility in the Rh system in pregnancy is represented by the discordance between maternal and fetal erythrocyte antigens belonging to the Rhesus group (most frequently D, E, e, C and c). Maternal alloimmunization to fetal erythrocyte antigens can lead to hemolytic disease in the fetus and the newborn, which can have fatal consequences [45].

Postpartum use of anti-D immunoglobulin in Rh-negative patients resulted in a decrease in alloimmunization from 16% to 2%. The subsequent introduction of antenatal anti-D prophylaxis in the third trimester (around 28 weeks) led to a further decrease in the incidence of hemolytic disease of the fetus and newborn to 0.5% [46].

All pregnant women should be tested for blood group and Rh at the first prenatal visit. Rh negative patients should be screened for anti-D antibodies. Antibody dosing should be repeated before anti-D immunoglobulin administration at 28 weeks of gestation, postpartum, and at any event with risk of alloimmunization in pregnancy [47]. The Romanian Society of Obstetrics and Gynecology recommends screening for Rh alloimmunization by measuring anti-Rh antibody levels at 20, 28, and 36 weeks of pregnancy. Regarding minor blood Groups, ACOG states that monitoring Kell-sensitized patients using antibody titers is not suitable since Kell antibodies do not correspond with the degree of the fetal condition.

Screening for thyroid dysfunctions

Thyroid dysfunctions are in second place in terms of endocrine disorders that affect women of reproductive age [48]. The incidence of hypothyroidism in pregnancy is between 0.3 and 3% and is higher in regions with iodine deficiency [49]. In North America, autoimmune thyroiditis is the main cause of hypothyroidism during pregnancy [48]. Hyperthyroidism affects 0.2% of pregnant women, Graves' disease being the main cause [49].

Maternal hyperthyroidism is associated with a series of adverse effects on the mother and fetus including preeclampsia, premature birth, heart failure, and IUGR [49]. Both overt hypothyroidism and subclinical hypothyroidism are associated with adverse effects such as the risk of abortion, premature birth, growth restriction, gestational hypertension, placental abruption, and impaired neuropsychological development of the newborn [50].

ACOG does not recommend universal screening for thyroid disorders in pregnancy because the identification and treatment of subclinical maternal hypothyroidism did not improve the cognitive function of the newborn [51,52]. Thyroid function testing should be performed in patients with a personal or family history of thyroid disorders, type 1 diabetes or clinical suspicion of thyroid disease. The slight increase in the volume of the thyroid gland is not sufficient criteria for screening, because a 30% increase in the volume of the thyroid gland during pregnancy is physiological. On the other hand, screening is necessary in patients with a significantly enlarged thyroid gland or thyroid nodules [51].

Other organizations, such as the American Association of Clinical Endocrinologists and the American Thyroid Association, have different approaches to screening for hypothyroidism in pregnancy. Since it is estimated that 2-3% of pregnant women have subclinical hypothyroidism, the proper diagnosis cannot be made without systematic screening. Some studies have highlighted the fact that through selective testing of patients considered at high risk, 30-80% of patients with hypothyroidism would remain undiagnosed [48].

A recent meta-analysis demonstrated the association between thyroid disorders during pregnancy and the risk of developing neurological disorders (ADHD, epilepsy), cardiometabolic and respiratory disorders, as well as thyroid dysfunction in childhood. The authors consider that routine testing of thyroid function should be considered in all patients [49].

The screening tests used are TSH and thyroid hormones. The first line screening test is TSH [52]. The presence of thyroid peroxidase antibodies or thyroglobulin antibodies has been shown to be an important risk factor for hypothyroidism during pregnancy or postpartum. Therefore, some authors recommend screening not only by TSH but also by thyroid peroxidase antibodies. The measurement of thyroglobulin antibodies is recommended when TSH has elevated values ​​and anti-thyroid peroxidase antibodies are negative [53].

Screening for preterm birth

Premature birth continues to be one of the main causes of perinatal mortality and morbidity globally. Approximately 11% of children are born prematurely worldwide. Premature babies require prolonged hospitalization and have an increased risk of neurological sequelae, respiratory diseases, blindness, deafness, necrotizing enterocolitis, feeding difficulties and intraventricular hemorrhage [54].

A way of screening for premature birth is represented by the ultrasound measurement of the cervix length. A short cervix in the second trimester is one of the strongest risk factors for premature birth [54]. Transvaginal measurement of the cervix is ​​considered the gold standard, being safe, reliable and reproducible when performed by qualified personnel [54,55]. Between 16-24 weeks a cervix with a length of less than 25 mm is considered short. Even in patients with a normal length of the cervix, the risk of premature birth remains inversely proportional to the cervix length [54].

The ultrasound presence of a dense hyperechoic area at the level of the amniotic fluid near the internal cervical opening was called amniotic sludge. This has been shown to be an independent predictive factor for preterm birth. When combined with cervical length measurement it can improve pregnancy outcomes [56]. A study of 181 patients demonstrated an increased risk of recurrent preterm delivery associated with endocervical canal dilation of 2-4 mm during second-trimester endovaginal ultrasonography, regardless of cervical length [57].In recent years, there has been an increased interest in the development of new techniques to improve the prediction of premature birth. The index of cervical consistency, which is determined by the anteroposterior measurement of the diameter of the cervix with and without cervical pressure, proved to be a comparable predictor to the length of the cervix. However, additional studies are needed [56].

Cervical elastography is proposed as a possible screening method in the future, which can be combined with cervix measurement [58]. Another way of screening is represented by fetal fibronectin, a glycoprotein from the extracellular matrix that is found in amniotic membranes, decidua, and cytotrophoblast. It can be identified in vaginal and cervical secretions in all pregnancies, but values ​​above 50 ng/ml have been associated with an increased risk of premature birth. The use of fetal fibronectin in combination with the measurement of the cervix in patients with acute symptoms of preterm birth could be useful, but the data are limited and the routine implementation requires additional studies [55].

Screening of infectious diseases

Although most infections during pregnancy have a minor impact, some of them can affect the mother, the fetus, or both. The screening must target those infectious diseases that have unfavorable consequences for the mother or the fetus, and moreover, the screening must be cost-effective [59].

Rubella virus infection was the first to be associated with congenital malformations. Before the introduction of the vaccine, the virus caused malformations in approximately 4/1000 births. The rate of vertical transmission is the highest in the first trimester (80-90%) and decreases from 54% between 13-19 weeks to 25% after 20 weeks of gestation. Over 90% of mothers affected by the disease in the first trimester will give birth to children with severe malformations. Screening in pregnancy does not aim to detect the disease but to establish the immune status. Unimmunized mothers are recommended to be vaccinated after birth. Screening for rubella virus immunization is available as a standard screening worldwide. The prevalence of rubella is decreasing, so screening is no longer necessary in certain regions. In regions where vaccine availability is low, such as Africa, Southeast Asia, and Eastern Europe, universal screening must be continued [59].

Group B streptococcus is a gram-positive bacterium that colonizes the upper respiratory tract, gastrointestinal tract, and genitourinary tract in approximately 30% of asymptomatic adults. Group B streptococcus can increase the risk of urinary infections, chorioamnionitis, endometritis, sepsis, premature birth, and intrauterine fetal death. It can also lead to a series of complications in the newborn, such as meningitis, pneumonia, and neonatal sepsis [60].

Regardless of the chosen way of delivery, all pregnant women should be tested for group B streptococcus between 36-38 weeks, unless intrapartum antibiotic prophylaxis is indicated in the context of GBS bacteriuria during pregnancy or a previous newborn infected with GBS [61].

The presence of group B streptococcus requires intravenous antibiotic prophylaxis during labor and in case of ruptured membranes before labor begins. This approach led to a decrease of neonatal streptococcal infection by 80% in the USA [60].

The global prevalence of viral hepatitis is high and increasing. These conditions can significantly affect pregnant women, causing increased mortality and perinatal morbidity. Hepatitis B is the most common form of viral hepatitis, and its screening is routinely done during pregnancy [62].

The identification of pregnant women with chronic hepatitis B virus infection through universal screening had a major impact on reducing the risk of neonatal infection. The recommended screening modality is Hbs antigen testing. Newborns from Hbs antigen-positive mothers should be vaccinated against hepatitis B and receive human immunoglobulin against hepatitis B within the first 12 hours after birth, regardless of whether or not the mother received antiviral treatment during pregnancy [63].

Regarding hepatitis C screening, some organizations, such as ACOG and the Society for Maternal-Fetal Medicine (SMFM), recommend screening for patients at risk of infection. This type of screening has not proven to be effective. Therefore, universal screening is recommended by other organizations (Infectious Disease Society of America and the American Association for the Study of Liver Diseases) [64].

Another condition for which screening is done during pregnancy is HIV infection. This has an increased risk of transmission from mother to fetus if the mother is not treated. Thus, all patients should be offered HIV testing at the first prenatal visit. In the case of HIV-negative patients, but who are part of a category with a high risk for infection, testing should be repeated every trimester [65].

Maternal syphilitic infection is associated with increasing the risk of intrauterine fetal death by 21%, increasing the risk of premature birth by 6%, and increasing the risk of neonatal death by 9%. All pregnant women should be tested for syphilis at the first prenatal visit. Syphilis testing is also recommended as part of the evaluation of intrauterine fetal death. Screening and treatment at the beginning of pregnancy is associated with a decrease in the incidence of congenital syphilis, premature birth, low birth weight, and fetal and neonatal death. Patients with a high risk of acquiring the disease or those from areas with a high prevalence of syphilis should be retested between 28-32 weeks and at birth [66].

Routine screening for patients at low risk of infection with Toxoplasma gondii is not recommended. It is important to consider costs, risk factors, the availability of appropriate tests, the relatively low incidence of acute infection, the low sensitivity of screening (false-positive results), and the effectiveness of treatment during pregnancy. Universal screening is available in many European countries, although the costs and benefits have not been properly evaluated. Therefore, screening is recommended for high-risk patients, such as those who are HIV-positive or immunosuppressed, or if the ultrasound evaluation reveals changes such as intracranial calcifications, microcephaly, hydrocephalus, ascites, hepatomegaly, IUGR [67]. CMV infection is the most common viral infection in pregnancy, as well as the most common cause of sensorineural deafness and neurological damage in newborns infected intrauterine. The serological screening is not proven to have sufficient sensitivity and specificity. In addition, no treatment reduces the risk of vertical transmission or fetal damage. Therefore, universal screening is not recommended. Most countries included in the screening patients with suspicion of infection, seronegative patients who develop symptoms suggestive of CMV or in the case of fetal malformations associated with CMV infection [59].

Screening for intrauterine growth rectiiction (IUGR)

IUGR is a major cause of fetal and neonatal morbidity and is defined by a growth rate that is lower than the growth potential of that fetus [68].

Early fetal growth restriction (before 32 weeks), in absence of congenital anomalies, is defined as the ratio between fetal abdominal circumference and estimated fetal weight (AC/EFW) < 3^rd centile or absent end-diastolic flow in an umbilical artery (UA-AEDF) or AC/EFW < 10 th centile combined with uterine artery pulsatility index (UtA-PI) > 95 th centile and/or umbilical artery pulsatility index (UA-PI) > 95 th centile [69].

Late fetal growth restriction (after 32 weeks), in absence of congenital anomalies is defined as the ratio between fetal abdominal circumference and estimated fetal weight (AC/EFW) < 3^rd centile or at least two out of three of the following: AC/EFW < 10 th centile, AC/EFW crossing centiles >2 quartiles on growth centiles, cerebroplacental ratio (CPR) < 5 th centile or UA-PI > 95 th centile [69].

Currently, routine screening of IUGR using biomarkers is not recommended. However, if biomarkers are available after the genetic screening, they can be used for risk stratification [70].

It was demonstrated that a series of ultrasound markers would have predictive value for IUGR. Among them are the Doppler flow on the uterine arteries, placental morphology and volume. However, considering their modest predictive value, it is not recommended to use them for universal screening [70].

Currently, there is no screening test with sufficiently good predictivity to be used routinely. Research focuses on obtaining predictive models that combine a series of parameters, such as risk factors for IUGR, maternal blood pressure, Doppler flow on the uterine arteries and certain biomarkers. However, these predictive models have not been sufficiently validated, and additional studies must be carried out [70].

Regarding the third trimester morphology for IUGR screening, in countries such as USA, UK and many others, this is only recommended in certain selected cases. Sovio and colleagues demonstrated that universal screening triples the sensitivity of detecting SGA, but for every fetus with low weight for gestational age correctly identified, two false positive results were identified [71].

Screening for thrombophilia

The term thrombophilia is used to describe those conditions associated with an increased risk of venous thromboembolism, conditions that can be inherited or acquired [72].

Screening for thrombophilia is expensive and currently, there is no proven effective treatment for women with recurrent miscarriages and inherited thrombophilia. Some organizations do not recommend screening for inherited thrombophilia, even if the patient has a history of pregnancy complications [72].

ACOG recommends screening for thrombophilia only when the result could influence treatment decisions. Patients who could benefit from screening are those with a history of venous thromboembolism or those who have first-degree relatives with high-risk inherited thrombophilia [73].

Screening for inherited thrombophilia recommended for women with a history of venous thromboembolism should include factor V Leiden mutation, prothrombin gene mutation G20210A, detection of antithrombin deficiency and protein S and C deficiency. Screening for acquired thrombophilia includes antiphospholipid antibody dosing [73].

Conclusion

Prenatal screening is a crucial tool for identifying potential health risks to both mother and fetus during pregnancy. The various tests available provide valuable information that can help obstetricians, materno-fetal specialists, and pediatricians develop a comprehensive plan of care for expectant mothers and help patients in order to make informed decisions about their pregnancy, including options for medical management and care, ensuring the best possible outcome for both mother and baby. However, it is important to note that screening tests are not perfect, and false positive and false negative results can occur. Additionally, it is important to understand the limitations and potential risks associated with invasive diagnostic procedures that may be recommended following a positive screening result. Overall, prenatal screening plays a vital role in ensuring the best possible health outcomes for both mother and baby and should be considered an essential component of prenatal care.