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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
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Mother's blood test may predict birth complications

DLK1 protein found in the blood of pregnant women could be developed to test the health of babies and aid in decisions on early elective deliveries, according to a study led by Queen Mary University of London.

Tests in pregnant mice and again in a small sample of women, found that low levels of the blood marker known as DLK1 was a good predictor of poor fetal growth and other complications of pregnancy. Such a test could potentially be used as a non-invasive prenatal procedure for diagnosing the health of a fetus.

At Queen Mary University of London (QMUL), lead researcher Dr Marika Charalambous explains: "At the moment, there are very few ways of predicting which pregnancies will go wrong, and which small babies are small because they are not getting enough nutrition, and which are small simply because of their genes."

"It's incredibly important to start developing tests that can give an obstetrician much more information on the pregnancy before delivery, so that they can intervene before complications come to a crisis point.

"Measuring DLK1 levels in the mother's blood could be a reliable and non-invasive way of predicting whether there are likely to be complications, especially those that cause reduced nutrient supply to the baby. In those instances, you really need to get the baby out quickly, so women could opt to have an early elective delivery."

DLK1 is a protein found in high levels in a mother's blood during pregnancy, both in humans and rodents.

However, little is known about its source, what it does, and whether it can indicate anything about the health of a fetus. Funded by the Medical Research Council and published in Nature Genetics, experiments involved knocking out mouse genes in either fetus or mother, then measuring the DLK1 level in either to determine its source.

Researchers found that DLK1 originates from the embryo. This means its levels in maternal blood could provide a direct readout of the embryo's health.

The team then looked at how DLK1 affects a pregnant mouse's metabolism. Humans start a process known as ketosis after fasting for 24 hours. A process the Atkins diet counts on — burning of energy from stored fats keeps our body functioning.

When DLK1 was inactivated in pregnant mice, their fasting response was impaired as they do not enter ketosis. This indicates the importance of DLK1 to provide energy for their fetal pups to grow. And, DLK1 levels in the mouse moms were found to be a good predictor of the mass weight of their pups.

Finally, with help from the Pregnancy Outcome Prediction Study or POPs study at the University of Cambridge, researchers were able to study 129 first time mothers by taking measurements of DLK1 levels in their blood and recording outcomes of their pregnancies.

Low human DLK1 levels were associated with reduced growth of the fetus — resulting in poor blood flow through the umbilical cord and pregnancy complications.

Researchers warn that further clinical studies in humans will be required to fully determine DLK1's potential as a prenatal diagnostic.

Pregnancy is a state of high metabolic demand. Fasting diverts metabolism to fatty acid oxidation, and the fasted response occurs much more rapidly in pregnant women than in non-pregnant women. The product of the imprinted DLK1 gene (delta-like homolog 1) is an endocrine signaling molecule that reaches a high concentration in the maternal circulation during late pregnancy. By using mouse models with deleted Dlk1, we show that the fetus is the source of maternal circulating DLK1. In the absence of fetally derived DLK1, the maternal fasting response is impaired. Furthermore, we found that maternal circulating DLK1 levels predict embryonic mass in mice and can differentiate healthy small-for-gestational-age (SGA) infants from pathologically small infants in a human cohort. Therefore, measurement of DLK1 concentration in maternal blood may be a valuable method for diagnosing human disorders associated with impaired DLK1 expression and to predict poor intrauterine growth and complications of pregnancy.

Research paper: 'Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction'. Mary A M Cleaton, Claire L Dent, Mark Howard, Jennifer A Corish, Isabelle Gutteridge, Ulla Sovio, Francesca Gaccioli, Nozomi Takahashi, Steven R Bauer, D Steven Charnock-Jones, Theresa L Powell, Gordon C S Smith, Anne C Ferguson-Smith & Marika Charalambous. Nature Genetics 2016 doi:10.1038/ng.3699. http://dx.doi.org/10.1038/ng.3699

The study was also funded by the Centre for Trophoblast Research at the University of Cambridge.

About Queen Mary University of London
Queen Mary University of London (QMUL) is one of the UK's leading universities, and one of the largest institutions in the University of London, with 21,187 students from more than 155 countries. A member of the Russell Group, we work across the humanities and social sciences, medicine and dentistry, and science and engineering, with inspirational teaching directly informed by our research. In the most recent national assessment of the quality of research, we were placed ninth in the UK (REF 2014).

As well as our main site at Mile End - which is home to one of the largest self-contained residential campuses in London - we have campuses at Whitechapel, Charterhouse Square, and West Smithfield dedicated to the study of medicine, and a base for legal studies at Lincoln's Inn Fields. We have a rich history in London with roots in Europe's first public hospital, St Barts; England's first medical school, The London; one of the first colleges to provide higher education to women, Westfield College; and the Victorian philanthropic project, the People's Palace at Mile End. Today, as well as retaining these close connections to our local community, we are known for our international collaborations in both teaching and research. QMUL has an annual turnover of £350m, a research income worth £125m (2014/15), and generates employment and output worth £700m to the UK economy each year.

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Nov 7, 2016   Fetal Timeline   Maternal Timeline   News   News Archive   

Tests in pregnant mice and women found low levels of DLK1
predict poor fetal growth and complications in pregnancy.
Therefore, it could be used as a non-invasive prenatal diagnostic.

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public domain


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