Information

Could a fetus properly develop in micro/zero-gravity?


I suppose another way of looking at the question is: how important is gravity for the development of mammal fetuses?

And if things would go wrong, what sort of things would they be, and what would be the result?


There is some evidence that fetal development under zero gravity conditions might be problematic.

Wakayama S, Kawahara Y, Li C, Yamagata K, Yuge L, et al. (2009) Detrimental Effects of Microgravity on Mouse Preimplantation Development In Vitro. PLoS ONE 4(8): e6753. doi:10.1371/journal.pone.0006753

The paper is here.

These authors studied aspects of reproduction of mice in a clinostat under 10-3G. They found that fertilisation was unaffected, but that preimplantation development of the embryo was affected by the mG environment.

The introduction to the paper gives a good brief review of this area of research. Perhaps of particular relevance is this section:

In the STS-80 space shuttle mission, mouse 2-cell embryos were collected on the ground, launched into space and cultured for four days in µG. The control embryos on Earth developed to normal blastocysts, but in the space flight group, none of the embryos showed any sign of development, and all degenerated (Schenker & Forkheim, 1998) . A more reliable experiment was done on the Cosmos 1129 mission in 1979, when mature male and female rats were sent into orbit and then allowed to intermingle in a common breeding chamber (Serova & Denisova, 1982). However, none of the females gave birth, although postflight examinations revealed that ovulation had occurred. Two of the females were reported to have achieved pregnancy, but the embryos appear to have been resorbed.

Schenker E, Forkheim K (1998) Mammalian mice embryo early development in weightlessness environment on STS 80 space flight. Israel Aerospace Medicine Institute Report.

Serova LV, Denisova LA (1982) The effect of weightlessness on the reproductive function of mammals. Physiologist 25: S9-12.


Scientists can predict which women will have serious pregnancy complications

Credit: CC0 Public Domain

Women who will develop potentially life-threatening disorders during pregnancy can be identified early when hormone levels in the placenta are tested, a new study has shown.

Pregnancy disorders affect around one in ten pregnant women. Nearly all of the organ systems of the mother's body need to alter their function during pregnancy so that the baby can grow. If the mother's body cannot properly adapt to the growing baby this leads to major and common issues including fetal growth restriction, fetal over-growth, gestational diabetes, and preeclampsia—a life-threatening high blood pressure in the mother.

Many of these complications lead to difficult labors for women with more medical intervention and lifelong issues for the baby including diabetes, heart issues and obesity.

Pregnancy disorders are usually diagnosed during the second or third trimester of gestation when they have often already had a serious impact on the health of the mother and baby. The current methods to diagnose pregnancy disorders are not sensitive or reliable enough to identify all at risk pregnancies.

Now scientists have found a way to test hormone levels in the placenta to predict which women will have serious pregnancy complications.

Dr. Amanda N. Sferruzzi-Perri, a Fellow of St John's College, University of Cambridge, runs a lab in the Department of Physiology, Development and Neuroscience and is the lead author of a new paper published today in Nature Communications Biology.

Dr. Sferruzzi-Perri said: "The female body is remarkable and from the moment of conception, a pregnant woman's body needs to change nearly every single organ system so the fetus can develop. The fetus also needs nutrients and oxygen to grow so the mother has to change her metabolism and vascular system so she can provide them.

"We know that the placenta drives many of the changes in a women's body during pregnancy and our study found hormonal biomarkers from the placenta could indicate which women would have pregnancy complications. We found that these biomarkers are present from the first trimester of pregnancy, normally women are only diagnosed with complications during the second or third trimester when disorders may already have had serious consequences for the health of the mother and her developing baby.

"This is a highly important finding given that pregnancy disorders affect around one in ten pregnant women and are often diagnosed too late when the complications are already wreaking havoc on the mother's body and the fetal development."

The placenta is a complex biological organ. It forms and grows from the fertilized egg, and attaches to the wall of the uterus. It allows nutrients and oxygen to flow from mother to baby, and removes fetal waste products. Despite its importance, the placenta is a very understood organ and is notoriously difficult to study in pregnant women. But its ability to function properly is vital as it impacts on pregnancy outcomes and the lifelong health of mother and child.

The placenta develops during pregnancy and connects the developing baby to the mother. It serves as the lungs, kidneys, gut and liver for growing babies and carries oxygen and nutrients to the fetus whilst secreting hormones and discarding waste.

Using mouse models, researchers looked at the proteins made by the placenta and compared them to blood samples from women who had uneventful pregnancies and those who developed gestational diabetes. The team developed new methods to isolate and study the endocrine cells in the mouse placenta because these cells are responsible for secreting hormones during pregnancy. They profiled the placenta to identify the hormones that are secreted to create a comprehensive map of proteins in the mysterious organ.

The mouse model map of hormonal proteins from the placenta was then compared with datasets from studies of the human placenta and pregnancy outcomes and researchers discovered a lot of biological overlap.

Dr. Sferruzzi-Perri said: "We found that around a third of the proteins we identified changed in women during pregnancies with disorders. Using a small study to test if these placental proteins will have some clinical value, we also discovered that abnormal levels of hormones were present in the mother's blood as early as the first trimester—week 12 of gestation—in women who developed gestational diabetes, a pregnancy complication usually diagnosed at 24-28 weeks.

"We also identified several specific transcription factors—proteins within the cell that turn on or off genes—that are likely to govern the production of placental hormones which have important implications for understanding how we may improve pregnancy outcomes."

The scientists explored whether these genetic biomarkers were detectable during pregnancy and used a study that tracked pregnancy outcomes in women at Addenbrooke's Hospital in Cambridge. They found that blood samples showed these biomarkers in early pregnancy which could lead to earlier diagnosis of complications allowing treatment to begin more quickly.

Dr. Claire Meek, a diabetes in pregnancy physician and researcher at Addenbrooke's, said: "This pregnancy-induced form of diabetes causes accelerated growth of the baby and complications at the time of delivery. Unfortunately, some women already have signs of a big baby at the time of diagnosis at 28 weeks. This new test might be able to identify gestational diabetes earlier in pregnancy, providing opportunities to prevent the disease, or to protect mums and babies from the most harmful complications."

Dr. Sferruzzi-Perri said: "This work provides new hope that a better understanding of the placenta will result in safer, healthier pregnancies for mothers and babies. Our team is now working to assess if these discoveries could improve clinical care in future, either through earlier diagnosis or to provide new opportunities to treat these pregnancy complications by targeting the placenta."


Contents

There are three purposes of prenatal diagnosis: (1) to enable timely medical or surgical treatment of a condition before or after birth, (2) to give the parents the chance to abort a fetus with the diagnosed condition, and (3) to give parents the chance to prepare psychologically, socially, financially, and medically for a baby with a health problem or disability, or for the likelihood of a stillbirth. Prior information about problems in pregnancy means that healthcare staff as well as parents can better prepare themselves for the delivery of a child with a health problem. For example, Down Syndrome is associated with cardiac defects that may need intervention immediately upon birth. [2]

Qualifying risk factors Edit

The American College of Obstetricians and Gynecologists (ACOG) guidelines currently recommend that all pregnant women, regardless of age, be offered invasive testing to obtain a definitive diagnosis of certain birth defects. Therefore, most physicians offer diagnostic testing to all their patients, with or without prior screening and let the patient decide. Also, the ACOG recommends genetic screening before pregnancy to all women planning to have a family. [3]

The following are some reasons why a patient might consider her risk of birth defects already to be high enough to warrant skipping screening and going straight for invasive testing.

  • Women over the age of 35
  • Women who have previously had premature babies or babies with a birth defect, especially heart or genetic problems
  • Women who have high blood pressure, lupus, diabetes, asthma, or epilepsy
  • Women who have family histories or ethnic backgrounds prone to genetic disorders, or whose partners have these
  • Women who are pregnant with multiples (twins or more)
  • Women who have previously had miscarriages

Diagnostic prenatal testing can be performed by invasive or non-invasive methods. An invasive method involves probes or needles being inserted into the uterus, e.g. amniocentesis, which can be done from about 14 weeks gestation, and usually up to about 20 weeks, and chorionic villus sampling, which can be done earlier (between 9.5 and 12.5 weeks gestation) but which may be slightly more risky to the fetus. One study comparing transabdominal chorionic villus sampling with second trimester amniocentesis found no significant difference in the total pregnancy loss between the two procedures. [4] However, transcervical chorionic villus sampling carries a significantly higher risk, compared with a second trimester amniocentesis, of total pregnancy loss (relative risk 1.40 95% confidence interval 1.09 to 1.81) and spontaneous miscarriage (9.4% risk relative risk 1.50 95% confidence interval 1.07 to 2.11). [4]

Non-invasive techniques include examinations of the woman's womb through ultrasonography and maternal serum screens (i.e. Alpha-fetoprotein). Blood tests for select trisomies (Down syndrome in the United States, Down and Edwards syndromes in China) based on detecting cell-free placental DNA present in maternal blood, also known as non-invasive prenatal testing (NIPT), have become available. [5] If an elevated risk of chromosomal or genetic abnormality is indicated by a non-invasive screening test, a more invasive technique may be employed to gather more information. [6] In the case of neural tube defects, a detailed ultrasound can non-invasively provide a definitive diagnosis.

Cell-free fetal DNA also allows whole genome sequencing of the fetus, thus determining the complete DNA sequence of every gene. [11]

Pre-conception Edit

Prior to conception, couples may elect to have genetic testing done to determine the odds of conceiving a child with a known genetic anomaly. The most common in the caucasian population are:

Hundreds of additional conditions are known and more discovered on a regular basis. However the economic justification for population-wide testing of all known conditions is not well supported, particularly once the cost of possible false positive results and concomitant follow-up testing are taken into account. [17] There are also ethical concerns related to this or any type of genetic testing.

One or both partners may be aware of other family members with these diseases. Testing prior to conception may alleviate concern, prepare the couple for the potential short- or long-term consequences of having a child with the disease, direct the couple toward adoption or foster parenting, or prompt for preimplantation genetic testing during in vitro fertilization. If a genetic disorder is found, professional genetic counseling is usually recommended owing to the host of ethical considerations related to subsequent decisions for the partners and potential impact on their extended families. Most, but not all, of these diseases follow Mendelian inheritance patterns. Fragile X syndrome is related to expansion of certain repeated DNA segments and may change generation-to-generation.

First trimester Edit

At early presentation of pregnancy at around 6 weeks, early dating ultrasound scan may be offered to help confirm the gestational age of the embryo and check for a single or twin pregnancy, but such a scan is unable to detect common abnormalities. Details of prenatal screening and testing options may be provided.

Around weeks 11–13, nuchal translucency scan (NT) may be offered which can be combined with blood tests for PAPP-A and beta-hCG, two serum markers that correlate with chromosomal abnormalities, in what is called the First Trimester Combined Test. The results of the blood test are then combined with the NT ultrasound measurements, maternal age, and gestational age of the fetus to yield a risk score for Down Syndrome, Trisomy 18, and Trisomy 13. First Trimester Combined Test has a sensitivity (i.e. detection rate for abnormalities) of 82–87% and a false-positive rate of around 5%. [18]

Second trimester Edit

The anomaly scan is performed between 18–22 weeks of gestational age. The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) recommends that this ultrasound is performed as a matter of routine prenatal care, to measure the fetus so that growth abnormalities can be recognized quickly later in pregnancy, and to assess for congenital malformations and multiple pregnancies (i.e. twins). [19] The scan can detect anencephaly, open spina bifida, cleft lip, diaphragmatic hernia, gastroschisis, omphalocele, congenital heart defect, bilateral renal agenesis, osteochondrodysplasia, Edwards syndrome, and Patau syndrome. [20]

A second trimester Quad blood test may be taken (the Triple test is widely considered obsolete but in some states, such as Missouri, where Medicaid only covers the Triple test, that's what the patient typically gets). With integrated screening, both a First Trimester Combined Test and a Triple/Quad test is performed, and a report is only produced after both tests have been analyzed. However patients may not wish to wait between these two sets of test. With sequential screening, a first report is produced after the first trimester sample has been submitted, and a final report after the second sample. With contingent screening, patients at very high or very low risks will get reports after the first trimester sample has been submitted. Only patients with moderate risk (risk score between 1:50 and 1:2000) will be asked to submit a second trimester sample, after which they will receive a report combining information from both serum samples and the NT measurement. The First Trimester Combined Test and the Triple/Quad test together have a sensitivity of 88–95% with a 5% false-positive rate for Down Syndrome, though they can also be analyzed in such a way as to offer a 90% sensitivity with a 2% false-positive rate. Finally for patients who do not receive an NT ultrasound in the 1st trimester may still receive a Serum Integrated test involving measuring PAPP-A serum levels in the 1st trimester and then doing a Quad test in the 2nd trimester. This offers an 85–88% sensitivity and 5% false-positive rate for Down Syndrome. Also, patient may skip the 1st trimester screening entirely and receive only a 2nd trimester Quad test, with an 81% sensitivity for Down Syndrome and 5% false-positive rate. [18]

Third trimester Edit

In the third trimester, a test for Group B streptococcal infection (also called Group B strep) may be offered. Group B strep is an infection that may be passed to an infant during birth.

First trimester maternal serum screening can check levels of free β-hCG, PAPP-A, intact or beta hCG, or h-hCG in the woman's serum, and combine these with the measurement of nuchal translucency (NT). Some institutions also look for the presence of a fetal nasalbone on the ultrasound.

Second trimester maternal serum screening (AFP screening, triple screen, quad screen, or penta screen) can check levels of alpha fetoprotein, β-hCG, inhibin-A, estriol, and h-hCG (hyperglycosolated hCG) in the woman's serum.

The triple test measures serum levels of AFP, estriol, and beta-hCG, with a 70% sensitivity and 5% false-positive rate. It is complemented in some regions of the United States, as the Quad test (adding inhibin A to the panel, resulting in an 81% sensitivity and 5% false-positive rate for detecting Down syndrome when taken at 15–18 weeks of gestational age). [21]

The biomarkers PAPP-A and β-hCG seem to be altered for pregnancies resulting from ICSI, causing a higher false-positive rate. Correction factors have been developed and should be used when screening for Down's syndrome in singleton pregnancies after ICSI, [22] but in twin pregnancies such correction factors have not been fully elucidated. [22] In vanishing twin pregnancies with a second gestational sac with a dead fetus, first trimester screening should be based solely on the maternal age and the nuchal translucency scan as biomarkers are altered in these cases. [22]

Measurement of fetal proteins in maternal serum is a part of standard prenatal screening for fetal aneuploidy and neural tube defects. [23] [24] Computational predictive model shows that extensive and diverse feto-maternal protein trafficking occurs during pregnancy and can be readily detected non-invasively in maternal whole blood. [25] This computational approach circumvented a major limitation, the abundance of maternal proteins interfering with the detection of fetal proteins, to fetal proteomic analysis of maternal blood. Entering fetal gene transcripts previously identified in maternal whole blood into a computational predictive model helped develop a comprehensive proteomic network of the term neonate. It also shows that the fetal proteins detected in pregnant woman's blood originate from a diverse group of tissues and organs from the developing fetus. Development proteomic networks dominate the functional characterization of the predicted proteins, illustrating the potential clinical application of this technology as a way to monitor normal and abnormal fetal development.

The difference in methylation of specific DNA sequences between mother and fetus can be used to identify fetal-specific DNA in the blood circulation of the mother. In a study published in the March 6, 2011 online issue of Nature, using this non-invasive technique a group of investigators from Greece and UK achieved correct diagnosis of 14 trisomy 21 (Down Syndrome) and 26 normal cases. [26] [27] Using massive parallel sequencing, a study testing for trisomy 21 only, successfully detected 209 of 212 cases (98.6%) with 3 false-positives in 1,471 pregnancies (0.2%). [5] With commercially available non-invasive (blood) testing for Down syndrome having become available to patients in the United States and already available in China, in October 2011, the International Society for Prenatal Diagnosis created some guidance. Based on its sensitivity and specificity, it constitutes an advanced screening test and that positive results require confirmation by an invasive test, and that while effective in the diagnosis of Down syndrome, it cannot assess half the abnormalities detected by invasive testing. The test is not recommended for general use until results from broader studies have been reported, but may be useful in high-risk patients in conjunction with genetic counseling. [6]

A study in 2012 found that the maternal plasma cell-free DNA test was also able to detect Trisomy 18 (Edwards syndrome) in 100% of the cases (59/59) at a false-positive rate of 0.28%, and Trisomy 13 (Patau syndrome) in 91.7% of the cases (11/12) at a false-positive rate of 0.97%. The test interpreted 99.1% of samples (1,971/1,988) among the 17 samples without an interpretation, three were Trisomy 18. The study stated that if z-score cutoffs for Trisomy 18 and 13 were raised slightly, the overall false-positive rates for the three aneuploidies could be as low as 0.1% (2/1,688) at an overall detection rate of 98.9% (280/283) for common aneuploidies (this includes all three trisomies- Down, Edwards and Patau). [28]

Ultrasound Edit

Use of ultrasound for nuchal translucency will screen for aneuploidy such as Down Syndrome (Trisomy 21), Edwards Syndrome (Trisomy 18), and Patau Syndrome (Trisomy 13), whilst screens that only use serum markers will screen for Down Syndrome and Trisomy 18, but not Trisomy 13. Considering that Trisomy 13 is extremely rare, maybe 1:5000 pregnancies and 1:16000 births, this difference is probably not significant. The AFP marker, whether alone or as part of the Quad test, can identify 80% of spina bifida, 85% of abdominal wall defects, and 97% of anencephaly. Frequently women will receive a detailed 2nd trimester ultrasound in Weeks 18–20 (Morphology scan) regardless of her AFP level, which makes the AFP score unnecessary. Morphology ultrasound scans being undertaken on larger sized fetuses than in earlier scans, detect other structural abnormalities such as cardiac and renal tract abnormalities. [ citation needed ]

Interphase-fluorescence in situ hybridization (FISH), quantitative PCR and direct preparation of chromosomes from chorionic villi are all current methods being used that are the most effective for detecting fetal aneuploidy. [29]

Genetic tests Edit

Due to the detection of fetal cells and fetal DNA circulating in maternal blood, noninvasive diagnosis of fetal aneuploidy is becoming more promising. [29] [30] The development of a variety of screening methods for fetal aneuploidy and other chromosomal aberrations is now a prominent research area because of the discovery of circulating fetal nucleic acid in maternal blood plasma. A meta-analysis that investigated the success rate of using fetal cell-free DNA from maternal blood to screen for aneuploidies found that this technique detected trisomy 13 in 99% of the cases, trisomy 18 in 98% of the cases and trisomy 21 in 99% of the cases. [30] [31] Failed tests using fetal cell-free DNA are more likely to occur in fetuses with trisomy 13 and trisomy 18 but not with trisomy 21. [32] Previous studies found elevated levels of cell-free fetal DNA for trisomy 13 and 21 from maternal serum when compared to women with euploid pregnancies. [33] [34] [35] [36] However, an elevation of cell-free DNA for trisomy 18 was not observed. [33] The key problem with the use of cell-free DNA is that circulating fetal nucleated cells comprise only three to six percent of maternal blood plasma DNA. [36] Therefore, two effective approaches have been developed that can be used for the detection of fetal aneuploidy. The first involves the measuring of the allelic ratio of single nucleotide polymorphisms (SNPs) in the mRNA coding region in the placenta. The next approach is analyzing both maternal and fetal DNA and looking for differences in the DNA methylation patterns. [36]

Digital PCR Edit

Recently, it has been proposed that digital PCR can be used for detection of fetal aneuploidy using fetal DNA and RNA found in maternal blood plasma. Research has shown that digital PCR can be used to differentiate between normal and aneuploid DNA using fetal DNA in the maternal blood plasma. [37]

A variation of the PCR technique called multiplex ligation-dependent probe amplification (MLPA), targeting DNA, has been successively applied for diagnosing fetal aneuploidy as a chromosome- or gene-specific assay. [38]

Shotgun sequencing Edit

Fetal cell DNA has been directly sequenced using shotgun sequencing technology. This DNA was obtained from the blood plasma of eighteen pregnant women. This was followed by mapping the chromosome using the quantification of fragments. This was done using advanced methods in DNA sequencing resulting in the parallel sequencing of the fetal DNA. The amount of sequence tags mapped to each chromosome was counted. If there was a surplus or deficiency in any of the chromosomes, this meant that there was a fetal aneuploid. Using this method of shotgun sequencing, the successful identification of trisomy 21 (Down syndrome), trisomy 18 (Edward syndrome), and trisomy 13 (Patau syndrome) was possible. This method of noninvasive diagnosis is now starting to be heavily used and researched further. [10]

Other techniques Edit

Fetal components in samples from maternal blood plasma can be analyzed by genome-wide techniques not only by total DNA, but also by methylated DNA immunoprecipitation (with tiling array), microRNA (such as with Megaplex) and total RNA (RNA-sequencing). [38]

Patient acceptance Edit

Research was conducted to determine how women felt about noninvasive diagnosis of fetal aneuploid using maternal blood. This study was conducted using surveys. It was reported that eighty-two percent of pregnant women and seventy-nine percent of female medical students view this type of diagnosis in a positive light, agreeing that it is important for prenatal care. Overall, women responded optimistically that this form of diagnosis will be available in the future. [39]

Non-genetic prenatal testing Edit

Parents need to make informed decisions about screening, diagnosis, and any actions to be taken as a result. Many screening tests are inaccurate, so one worrisome test result frequently leads to additional, more invasive tests. If prenatal testing confirms a serious disability, many parents are forced to decide whether to continue the pregnancy or seek an abortion. The "option" of screening becomes an unexpected requirement to decide. See wrongful abortion.

In some genetic conditions, for instance cystic fibrosis, an abnormality can only be detected if DNA is obtained from the fetus. Usually an invasive method is needed to do this. [ citation needed ]

Ultrasound of a fetus, which is considered a screening test, can sometimes miss subtle abnormalities. For example, studies show that a detailed 2nd trimester ultrasound, also called a level 2 ultrasound, can detect about 97% of neural tube defects such as spina bifida [ citation needed ] . Ultrasound results may also show "soft signs," such as an Echogenic intracardiac focus or a Choroid plexus cyst, which are usually normal, but can be associated with an increased risk for chromosome abnormalities.

Other screening tests, such as the Quad test, can also have false positives and false negatives. Even when the Quad results are positive (or, to be more precise, when the Quad test yields a score that shows at least a 1 in 270 risk of abnormality), usually the pregnancy is normal, but additional diagnostic tests are offered. In fact, consider that Down Syndrome affects about 1:400 pregnancies if you screened 4000 pregnancies with a Quad test, there would probably be 10 Down Syndrome pregnancies of which the Quad test, with its 80% sensitivity, would call 8 of them high-risk. The quad test would also tell 5% (

200) of the 3990 normal women that they are high-risk. Therefore, about 208 women would be told they are high-risk, but when they undergo an invasive test, only 8 (or 4% of the high risk pool) will be confirmed as positive and 200 (96%) will be told that their pregnancies are normal. Since amniocentesis has approximately a 0.5% chance of miscarriage, one of those 200 normal pregnancies might result in a miscarriage because of the invasive procedure. Meanwhile, of the 3792 women told they are low-risk by the Quad test, 2 of them will go on to deliver a baby with Down Syndrome. The Quad test is therefore said to have a 4% positive predictive value (PPV) because only 4% of women who are told they are "high-risk" by the screening test actually have an affected fetus. The other 96% of the women who are told they are "high-risk" find out that their pregnancy is normal. [ citation needed ]

By comparison, in the same 4000 women, a screening test that has a 99% sensitivity and a 0.5% false positive rate would detect all 10 positives while telling 20 normal women that they are positive. Therefore, 30 women would undergo a confirmatory invasive procedure and 10 of them (33%) would be confirmed as positive and 20 would be told that they have a normal pregnancy. Of the 3970 women told by the screen that they are negative, none of the women would have an affected pregnancy. Therefore, such a screen would have a 33% positive predictive value.

The real-world false-positive rate for the Quad test (as well as 1st Trimester Combined, Integrated, etc.) is greater than 5%. 5% was the rate quoted in the large clinical studies that were done by the best researchers and physicians, where all the ultrasounds were done by well-trained sonographers and the gestational age of the fetus was calculated as closely as possible. In the real world, where calculating gestational age may be a less precise art, the formulas that generate a patient's risk score are not as accurate and the false-positive rate can be higher, even 10%.

Because of the low accuracy of conventional screening tests, 5–10% of women, often those who are older, will opt for an invasive test even if they received a low-risk score from the screening. A patient who received a 1:330 risk score, while technically low-risk (since the cutoff for high-risk is commonly quoted as 1:270), might be more likely to still opt for a confirmatory invasive test. On the other hand, a patient who receives a 1:1000 risk score is more likely to feel assuaged that her pregnancy is normal.

Both false positives and false negatives will have a large impact on a couple when they are told the result, or when the child is born. Diagnostic tests, such as amniocentesis, are considered to be very accurate for the defects they check for, though even these tests are not perfect, with a reported 0.2% error rate (often due to rare abnormalities such as mosaic Down Syndrome where only some of the fetal/placental cells carry the genetic abnormality).

A higher maternal serum AFP level indicates a greater risk for anencephaly and open spina bifida. This screening is 80% and 90% sensitive for spina bifida and anencephaly, respectively. [ citation needed ]

Amniotic fluid acetylcholinesterase and AFP level are more sensitive and specific than AFP in predicting neural tube defects.

Many maternal-fetal specialists do not bother to even do an AFP test on their patients because they do a detail ultrasound on all of them in the 2nd trimester, which has a 97% detection rate for neural tube defects such as anencephaly and open spina bifida. Performing tests to determine possible birth defects is mandatory in all U.S. states. Failure to detect issues early can have dangerous consequences on both the mother and the baby. OBGYNs may be held culpable. In one case a man who was born with spina fibia was awarded $2 million in settlement, apart from medical expenses, due to the OBGYN's negligence in conducting AFP tests. [40]

No prenatal test can detect all forms of birth defects and abnormalities.

Prenatal genetic testing Edit

Another important issue is the uncertainty of prenatal genetic testing. Uncertainty on genetic testing results from several reasons: the genetic test is associated with a disease but the prognosis and/or probability is unknown, the genetic test provides information different than the familiar disease they tested for, found genetic variants have unknown significance, and finally, results may not be associated with found fetal abnormalities. [41] Richardson and Ormond thoroughly addressed the issue of uncertainty of genetic testing and explained its implication for bioethics. First, the principle of beneficence is assumed in prenatal testing by decreasing the risk of miscarriage, however, uncertain information derived from genetic testing may harm the parents by provoking anxiety and leading to the termination of a fetus that is probably healthy. Second, the principle of autonomy is undermined given a lack of comprehension resulting from new technologies and changing knowledge in the field of genetics. And third, the principle of justice raised issues regarding equal access to emerging prenatal tests.

Availability of treatments Edit

If a genetic disease is detected, there is often no treatment that can help the fetus until it is born. However, in the US, there are prenatal surgeries for spina bifida fetus. [ citation needed ] Early diagnosis gives the parents time to research and discuss post-natal treatment and care, or in some cases, abortion. Genetic counselors are usually called upon to help families make informed decisions regarding results of prenatal diagnosis.

Patient education Edit

Researchers have studied how disclosing amniocentesis or chorionic villous sampling (CVS) results on a fixed date versus a variable date (i.e. "when available") affects maternal anxiety. Systematic review of the relevant articles found no conclusive evidence to support issuing amniocentesis results as soon as they become available (in comparison to issuing results on a pre-defined fixed date). The researchers concluded that further studies evaluating the effect of different strategies for disclosing CVS results on maternal anxiety are needed. [42]

Concerns from disability rights activists and scholars Edit

Disability rights activists and scholars have suggested a more critical view of prenatal testing and its implications for people with disabilities. They argue that there is pressure to abort fetuses that might be born with disabilities, and that these pressures rely on eugenics interests and ableist stereotypes. [43] This selective abortion relies on the ideas that people with disabilities cannot live desirable lives, that they are "defective," and that they are burdens, ignoring the fact that disability scholars argue that "oppression is what's most disabling about disability." Marsha Saxton suggests that women should question whether or not they are relying on real, factual information about people with disabilities or on stereotypes if they decide to abort a fetus with a disability. [44]

Societal pressures Edit

Amniocentesis has become the standard of care for prenatal care visits for women who are "at risk" or over a certain age. The wide use of amniocentesis has been defined as consumeristic. [45] and some argue that this can be in conflict with the right to privacy, [46] Most obstetricians (depending on the country) offer patients the AFP triple test, HIV test, and ultrasounds routinely. However, almost all women meet with a genetic counselor before deciding whether to have prenatal diagnosis. It is the role of the genetic counselor to accurately inform women of the risks and benefits of prenatal diagnosis. Genetic counselors are trained to be non-directive and to support the patient's decision. Some doctors do advise women to have certain prenatal tests and the patient's partner may also influence the woman's decision.


How Young Can a Human Be and Still Survive Premature Birth?

Recall from Part One that pregnancy is normally measured from the first day of the last menstrual period (gestational age). The gestational age at which a newborn has a 50 percent chance of surviving is called the “age of viability.” In 2015 this age was estimated to be 23 to 24 weeks in developed countries where good intensive care nurseries are available. (In less developed countries the age of viability was up to 34 weeks.) Thanks to technological improvements, in 2018 the age of viability was lowered to 22 to 23 weeks (gestational age). In other words, a fetus has a 50 percent chance of surviving by 20 weeks (fetal age).

I have seen no evidence that passage through the birth canal jumpstarts a human’s ability to perceive pain. So the available evidence clearly shows that a 20-week-old fetus can feel pain. Indeed, pain might be felt even earlier: Anesthesiologists who participate in fetal surgeries report that “a physiological fetal reaction to painful stimuli” occurs from 16 weeks (gestational age) on. But this is indirect evidence. By observing premature babies directly we know — as well as we know anything in science — that a fetus can feel pain by the time it is 20 weeks old (fetal age).


A (New) Argument for Abortion

There’s an argument making the rounds in the pro-abortion movement that’s important, both for the inanity of its logic and its implications for the state of the debate about human exceptionalism and the protection of innocent life.

Dr. Willie Parker is an abortionist in Alabama, and in his new book, Life’s Work: A Moral Argument for Choice, he defends abortion from his Christian perspective (he’s an Evangelical). Parker’s argument is this: there is no question that a baby in the womb is alive (he calls it “the pregnancy”) but it is not life that warrants protection, but persons. And the mother is a person, whereas, according to Parker, the baby is not. So the mother’s suffering with an unwanted pregnancy takes precedence over the life of “the pregnancy” (the baby), because the baby is not a person, has no rights, and cannot suffer.

From an interview with Parker, with my commentary:

Here’s the thing: Life is a process, not an event. If I thought I was killing a person, I wouldn’t do abortions. A fetus is not a person it’s a human entity. In the moral scheme of things, I don’t hold fetal life and the life of a woman equally. I value them both, but in the precedence of things, when a woman comes to me, I find myself unable to demote her aspirations because of the aspirations that someone else has for the fetus that she’s carrying.

Life is not a “process,” in Parker’s sense of the word. Parker means that, in his view, human life has no sharp beginning, but gradually develops from gametes to being a human being. He is mistaken about the science.

Life is an activity, a state, of an individual organism. It entails processes, of course (growth, metabolism, sensation, perception, etc.), but there is not a seamless continuum between inanimate matter, parts of human beings, and a human being.

A human life begins at fertilization of the egg by the sperm. I am alive. A fetus in the womb is alive, as is an embryo, as is a zygote. A cell in my body is alive in the sense that it is part of me, but a somatic cell is not a human life itself. A sperm cell is not a human life. Nor is an egg cell.

A zygote is a human life, because it is, from a biological perspective, a human being. Human life begins at fertilization: the new human being at this stage has its genetic complement and will, if nourished and unimpeded, mature to an embryo, a fetus, a baby, a child, and an adult.

Human life begins at fertilization, and ends at death. Individual parts of human beings — cells and tissues and organs — are not lives in themselves, but are parts of a human being.

There is no scientific debate about the fact that human life begins at fertilization and ends at death. This is a simple biological fact, known since the 19th century when the science of human reproduction was established.

Whether a human being at the stage of an embryo or a fetus is a “person” is another matter. A person is (in this context) a human being who is worthy of moral respect and legal protection. It is on the question of personhood of the child in the womb that the abortion debate hinges, not on the question of whether the child, from zygote to embryo to fetus, is a human being.

A fetus isn’t a “human entity.” He or she is a human being. Human life begins at fertilization. That is a fact of biology, and has been settled by science for two centuries, and it’s regrettable that Dr. Parker, an abortionist, misrepresents the science to defend his trade.

The real question in the abortion debate is this: Are all human beings persons, or does personhood depend on certain characteristics of human beings? One hopes that African-Americans especially will reject Dr. Parker’s argument that a certain class of human beings, because of their condition of vulnerability, aren’t persons and aren’t entitled to respect and legal protection.


Which fertilized eggs will become healthy human fetuses? Researchers predict with 93% accuracy

Two-thirds of all human embryos fail to develop successfully. Now, in a new study, researchers at the Stanford University School of Medicine have shown that they can predict with 93 percent certainty which fertilized eggs will make it to a critical developmental milestone and which will stall and die. The findings are important to the understanding of the fundamentals of human development at the earliest stages, which have largely remained a mystery despite the attention given to human embryonic stem cell research.

Because the parameters measured by the researchers in this study occur before any embryonic genes are expressed, the results indicate that embryos are likely predestined for survival or death before even the first cell division. Assessing these parameters in the clinic could make it easier for in vitro fertilization specialists to select embryos for transfer for a successful pregnancy.

"Until recently, we've had so little knowledge about the basic science of our development," said the study's senior author Renee Reijo Pera, PhD. "In addition to beginning to understand more about our development, we're hopeful that our research will help improve pregnancy rates arising from in vitro fertilization, while also reducing the frequency of miscarriage and the need for the selective reduction of multiple embryos."

Reijo Pera is a professor of obstetrics and gynecology at the medical school and the director of the Center for Human Embryonic Stem Cell Research and Education at Stanford's Institute for Stem Cell Biology and Regenerative Medicine. The study will be published online Oct. 3 in Nature Biotechnology. Postdoctoral scholar Connie Wong, PhD, and former postdoctoral scholar Kevin Loewke, PhD, are the co-first authors of the research. Loewke is currently the lead engineer at the Menlo Park, Calif., biotechnology company Auxogyn Inc.

The researchers conducted their studies on a unique set of 242 frozen, one-cell human embryos from the Reproductive Medicine Center at the University of Minnesota. The embryos were created at the in vitro fertilization program at Lutheran General Hospital in Illinois over a period of several years prior to 2002, and when the clinic was closed, the patients gave their consent for their embryos to be used in research.

Nowadays it's unusual to freeze embryos so soon after fertilization (about 12 to 18 hours). Instead, clinicians monitor embryonic development for three to five days in an attempt to identify those that are more likely to result in healthy pregnancies after transfer. Despite their best efforts, though, they have only about a 35 percent success rate. As a result, most women elect to transfer two or more embryos to increase the chance of a live birth. However, if multiple embryos implant and develop successfully, a woman and her physician may choose to selectively abort one or more to better the odds for the remaining embryos.

Reijo Pera and her colleagues received a large grant from an anonymous donor to investigate ways to better predict embryonic developmental success within one or two days of fertilization. Not only would such an advance decrease the likelihood of miscarriage or the possible need for a selective reduction, it would also reduce the amount of time the embryo would be have to be cultured in the laboratory before transfer. (Although it's not been conclusively shown, some researchers are concerned that genetic changes may accumulate in a cultured embryo and cause subtle, long-lasting effects in the fetus.)

The researchers thawed the embryos, split them into four groups and tracked their development during the first few days using time-lapse video microscopy and computer software specially designed by Loewke, a former Stanford mechanical engineering graduate student, for this study. They followed the cells through the development of a hollow ball called a blastocyst, which typically occurs within five to six days after fertilization. A blastocyst is usually an indication of a healthy embryo.

They found that of the 242 embryos, 100 were able within five or six days to form normal-looking blastocysts -- about the same proportion that would be expected to be successful in normal pregnancies. Because they had tracked the embryos' development so closely, they were then able to go back and identify three specific parameters collectively associated with successful blastocyst formation: the duration of first cytokinesis (the last step of a period in the cell cycle called mitosis in which the cell physically divides), the time between first and second mitoses, and the synchronicity of the second and third mitoses. All of these events occur as the embryo progresses from one cell to four cells within the first two days after fertilization.

"It completely surprised me that we could predict embryonic fate so well and so early," said Reijo Pera. If an embryo's values fell within certain windows of time for the three predictive parameters, that embryo was more than 90 percent likely to go on to develop successfully into a blastocyst.

When the researchers looked at the gene expression profiles of individual cells from the embryos, they found that, as had been previously shown, the embryos at first express only genes from the maternally derived egg. By roughly the third day (the eight-cell stage) they begin to express genes specific to embryonic development, and the relative proportion of embryonic to egg genes increases steadily during the next few cell divisions.

Surprisingly, however, they found that not all cells in an embryo are behaving identically: While some cells may be expressing mostly maternal genes, others in the same embryo are churning out mostly embryonic genes.

Similarly, not all cells in an embryo are dividing in synchrony: The researchers found embryos in which some cells were dividing on schedule while others were seemingly stuck, or paused.

"We've always thought of embryos as living or dying, but in reality we find that each cell in the embryo is making decisions autonomously," said Reijo Pera. "No one has ever looked at this before." She and her colleagues found that embryos in which individual cells varied significantly in their cell-division schedules or gene-expression profiles were less likely to become successful blastocysts.

Together the research indicates that the maternal RNA transcripts -- that is, the molecules that carry instructions from the mother's DNA to the embryo's protein-making factories -- must be actively degraded in each cell of the embryo, and that this degradation is necessary for the cells to begin to express embryonic genes. Cells that fail to execute some part of this delicate process get out of sync with their neighbors and jeopardize the life of the embryo. The whole endeavor is complicated, and may explain why human embryonic development is so precarious and unique.

The research also highlights the importance of studying human embryos, which currently cannot be supported by federal funds. (Every year since 1996, Congress has approved a provision known as the Dicky-Wicker amendment that prohibits the use of federal funds for research in which a human embryo is destroyed -- even ones that would otherwise be discarded.)

"In mice, about 80 to 90 percent of embryos develop to the blastocyst stage. In humans, it's about 30 percent," said Reijo Pera. "In addition, about one in 100 mouse embryos are chromosomally abnormal, versus about seven out of 10 human embryos. That's why human studies like these are so important. Women, their families and their physicians want to increase the chances of having one healthy baby and avoid high-risk pregnancies, miscarriages or other adverse maternal and fetal outcomes. It's truly a women's health issue that affects the broader family."

The research was funded by an anonymous donor, the March of Dimes and the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

The researchers have developed an automated algorithm for clinical use that could assess these time-lapse microscopy videos and determine with high accuracy which of these very early embryos would be successful by the four-cell stage. That technology has been licensed exclusively to Auxogyn Inc. by Stanford. Reijo Pera and the other coauthors of the manuscript own or have the right to purchase stock in the company.

Story Source:

Materials provided by Stanford University Medical Center. Note: Content may be edited for style and length.


Outside the womb:

M anish Arora’s desk at the Icahn School of Medicine at Mount Sinai in New York City is a chaotic jumble of half-empty coffee mugs, philosophy books and baby teeth. The tiny teeth were donated for a study unrelated to autism, but they may uncover secrets about the condition nonetheless, he says.

Arora is many things: a dentist, a scientist and a father to 6-year-old triplets. He is soft-spoken and often speaks in metaphors. In his professional life, he strives to understand how chemical exposures early in life affect brain development, a passion shaped by his childhood growing up on the border of Zambia and what is now Zimbabwe. He remembers trucks spraying pesticides such as DDT on the ground — and sometimes also on children playing outside — to control malaria, a practice that he continued to think about as he got older because of its potential harm.

As Arora knows from his dentistry work, baby teeth provide a record of a body’s chemical exposures. Teeth, he explains, are like trees: As they grow, they create rings — about one-tenth the diameter of a human hair — that record the chemicals and metals they encounter. These growth rings begin to form at the end of the first trimester of gestation and continue throughout life. “Today, you and me are forming a growth ring and it’s capturing everything that we’re exposed to,” he says. By studying the growth rings of discarded baby teeth, he and his colleagues can analyze what fetuses were exposed to in utero. The stress of birth creates a dark mark that can be used as a reference point.

In May, Arora and his colleagues reported an analysis of baby teeth collected from 193 children, including 32 sets of twins in which one twin is autistic and the other is not. The team analyzed the children’s tooth growth rings using a highly sensitive form of mass spectrometry. The levels of metals such as zinc and copper typically cycle together in a pattern — both metals help to regulate neuronal firing — but in autistic children, the cycles are shorter, less regular and less complex than in controls. Arora’s team created an algorithm based on these group differences that can predict a child’s autism with more than 90 percent accuracy.

Arora’s work is part of a growing field that is attempting to decipher what kinds of environmental exposures increase the odds of autism and how they interact with human biology and genetics. These are tough questions to answer. Researchers cannot easily collect blood or saliva samples from fetuses to see what’s circulating through them. Instead, they try to discern fetal exposures by using the mother’s environment as a proxy. If a pregnant woman takes a particular medication, for instance, researchers can extrapolate that the fetus, too, was exposed.

So far, though, results have been mixed. Studies suggest that autism is associated with thalidomide, a drug prescribed for morning sickness in the 1950s and 1960s and later found to cause serious birth defects. Valproate, a drug used to treat epilepsy, bipolar disorder and migraines, is also linked to autism when taken during pregnancy. But for other common drugs, such as antidepressants, an association with autism is harder to discern.

Chemical record: Growth rings in baby teeth reveal exposures before and after birth.

Part of the problem is that women take antidepressants for underlying mental-health conditions — so if an association is found, it is often unclear whether the root cause is her medication or her genetics. “It’s very difficult to disentangle,” says Hilary Brown, an epidemiologist at the University of Toronto Scarborough in Canada. Last year, through a clever study design, she and her colleagues inched a bit closer to the truth. They studied sibling pairs in which one sibling had been exposed to antidepressants in utero and the other had not, allowing them to control for the severity of the mother’s depression, among other factors. They reported that the siblings exposed to antidepressants were no more likely to have autism than their unexposed siblings. The results suggest that the medications themselves do not increase autism risk.

Some research has also linked the use of acetaminophen (commonly marketed as Tylenol) during pregnancy to autism. But again, it is unclear whether it is acetaminophen that is the problem, or the underlying reason for its use — pain or an infection, leading back to the maternal immune activation hypothesis.

Air pollution might also be linked to autism risk, but the details are hazy. At least 14 studies have suggested an association with autism, and air pollution is known to trigger inflammation, but analyses of individual airborne chemicals have been inconsistent. Researchers are also confused by the fact that cigarette smoking, which contains many of the same chemicals as air pollution, is not associated with the condition.

Certain pesticides, such as chlorpyrifos, can disrupt sex-hormone pathways implicated in animal models of autism. But again, studies linking pesticides to autism have been mixed, and questions about causation are unresolved. More answers may emerge, however, as researchers uncover new ways to study interactions between fetuses and the outside world. In addition to Arora’s work on baby teeth, researchers are investigating what kinds of chemical stories meconium, a newborn’s first feces, can tell.


Developmental consequences of fetal exposure to drugs: what we know and what we still must learn

Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.

Figures

Major neurodevelopmental events across species.…

Major neurodevelopmental events across species. Schematic diagram that aligns human brain development with…

Biological targets of fetal drug…

Biological targets of fetal drug exposures. Drugs of abuse not only target the…

Schematic summary of effects of…

Schematic summary of effects of distinct drug classes on offspring development. A wide…


Heart

The heart begins developing around the middle of the third week of pregnancy. It forms from 2 side-by-side, primitive tubes. These tubes fuse into a single tube, the heart tube. Other tissues are added to this tube as it thickens, grows and begins to bend and fold as it enlarges. By the fourth week of pregnancy, blood flows through the primitive heart, which begins contracting to send blood through early blood vessels to the entire fetus. As heart development continues, the walls of the folded tube thicken and certain parts of the folding tube fuse with each other. Several walls, each called a septum, also develop to divide the heart chambers from each other. By the end of the fifth week, the heart is made up of its final four chambers, and valves have developed to manage blood flow. By 20 weeks, nerves and other special tissues that control heart function develop fully, and the heart, now completely formed, continues to enlarge until birth.


Avoid exposure to toxic substances.

During pregnancy, exposure to radiation, pesticides, some metals, and certain chemicals can cause birth defects, premature birth, and miscarriage. 14 If you're not sure if something might be harmful to you or your fetus, avoid contact with it until you check with your health care provider.

If you work in a job on a farm, a dry cleaner, a factory, a nail or hair salon, you might be around or come into contact with potentially harmful substances. Talk to your health care provider and your employer about how you can protect yourself before and during pregnancy. You may need extra protection at work or a change in your job duties to stay safe. 14

A few examples of exposures that are known to be toxic to the developing fetus are:

Lead: Lead is a metal that may be present in house paint, dust, and garden soil. Any home built before 1978 may have lead paint. Exposure can occur when removing paint in old buildings (or if the paint is peeling) and working in some jobs (for example, manufacturing automotive batteries). Lead is also present in some well water and in water that travels through lead pipes. High levels of lead during pregnancy can cause miscarriage, stillbirth, low birth weight, and premature delivery, as well as learning and behavior problems for the child. 15 Women who had exposure to lead in the past should have1 their blood levels checked before and during pregnancy. 15 Call the National Lead Information Center for information about how to prevent exposure to lead at: 800-424-LEAD.

Radiation: Radiation is energy that travels through space. It can be in the form of X-rays, radio waves, heat, or light, or it can come from "radioactive" materials like dust, metals, or liquids that give off energy called radioactivity. Low exposures to radiation from natural sources (such as from the sun) or from microwave ovens or routine medical X-rays are generally not harmful. Because the fetus is inside the mother, it is partially protected from radiation's effects. 14,16 Pregnant women or women who might be pregnant should make sure their dentists and doctors are aware of this so appropriate precautions can be taken with medical scans (X-rays or CT scans) or treatments that involve radiation. 14 Pregnant women who may be exposed to radiation in the workplace should speak with their employer and health care provider to make sure the environment is safe during their pregnancy. Nuclear or radiation accidents, while rare, can cause high radiation exposures that are extremely dangerous, especially to the developing fetus.

Solvents: Solvents are chemicals that dissolve other substances. Solvents include alcohols, degreasers, and paint thinners. Some solvents give off fumes or can be absorbed through the skin and can cause severe health problems. During pregnancy, being in contact with solvents, especially if you work with them, can be harmful. Solvents may lead to miscarriage, slow the growth of the fetus, or cause preterm birth and birth defects. 14 Pregnant women who may be exposed to solvents in the workplace should speak with their employer and health care provider to make sure the environment is safe during their pregnancy. 17 Whenever you use solvents, be sure to do so in a well-ventilated area, wear safety clothes (such as gloves and a face mask), and avoid eating and drinking in the work area. 14

Many chemicals are commonly found in the blood and body fluids of pregnant women and their infants. However, much remains unknown about the effects of fetal exposure to chemicals. 18 It's best to be cautious about chemical exposure when you are planning to get pregnant or if you are pregnant. Talk to your health care provider if you live or work in or near a toxic environment. 17


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