Thursday, July 02, 2009

C-Section Stress Could Alter Baby's Immune Cells

Babies delivered by cesarean section experience changes to the DNA of white blood cells, which might explain why they're at increased risk for immunological diseases such as diabetes and asthma later in life, Swedish researchers say.

"Delivery by C-section has been associated with increased allergy, diabetes and leukemia risks," Dr. Mikael Norman, a pediatric specialist at the Karolinska Institute in Stockholm, said in a news release from Wiley-Blackwell publishers. "Although the underlying cause is unknown, our theory is that altered birth conditions could cause a genetic imprint in the immune cells that could play a role later in life."

Norman and his colleagues analyzed blood samples from 37 infants taken just after delivery and samples taken three to five days after birth. The blood was analyzed to assess the degree of DNA-methylation in the white blood cells, which are a key part of the immune system. In DNA-methylation, DNA is chemically modified to activate or turn off genes in response to changes in the external environment.

The 16 infants born by C-section had higher DNA-methylation rates immediately after delivery than the 21 infants born by vaginal delivery, according to the report, in the July issue of Acta Paediatrica. Three to five days after birth, both groups of infants had similar levels of DNA-methylation.

Further research is needed to determine why infants born by C-section have higher DNA-methylation rates after delivery, the researchers said.

"Animal studies have shown that negative stress around birth affects methylation of the genes, and therefore it is reasonable to believe that the differences in DNA-methylation that we found in human infants are linked to differences in birth stress," the researchers wrote.

"We know that the stress of being born is fundamentally different after planned C-section compared to normal vaginal delivery," they explained. "When babies are delivered by C-section, they are unprepared for the birth and can become more stressed after delivery than before. This is different [from] a normal vaginal delivery, where the stress gradually builds up before the actual birth, helping the baby to start breathing and quickly adapt to the new environment outside the womb."


Wednesday, July 01, 2009

Maternal diet affects infant's long-term bone health

Women who maintain a healthy, well-balanced diet during pregnancy have children with bigger and stronger bones than women with poorer quality diets, according to the results of a study presented Tuesday at the National Osteoporosis Society Conference in Manchester, UK.

"Our data add to evidence that environmental influences during intrauterine life alter the trajectory of skeletal development in the offspring," study presenter Dr. Zoe Cole of the University of Southampton told Reuters Health.

When the researchers assessed the diets of 198 pregnant women, two general patterns began to emerge. The first was a healthy dietary pattern filled with lots of fruits and vegetables, yogurt, whole wheat bread and breakfast cereals. The second diet pattern was less healthy and included large amounts of foods such as chips and roast potatoes, sugar, white bread, processed meat, tinned vegetables and soft drinks.

Bone assessments of the children made up to age 9 years suggested that consuming a healthy maternal diet was associated with greater bone size and density in the offspring.

"Children born to mothers with the healthiest diets, as identified by in the highest quarter of prudent diet score, during late pregnancy had an 11 percent greater whole body bone mineral content and 8 percent great whole body bone area than those born to mothers with the least healthy diet, the lowest quarter of this distribution," Cole said.

Even when mothers were grouped by smoking status, vitamin D status and social class, the differences in diet still had a significant impact on their children's bones, the researchers found. The relationship between a healthy maternal diet and healthier bones in offspring remained even after the child's height, weight, arm circumference and birth weight were considered.

"A healthy diet during pregnancy has long lasting effects on the development of the child's bones," Cole said, and this may lower their future risk of osteoporosis, a potentially disabling bone-thinning disease.


Women with endometriosis need special care during pregnancy

The largest study to date of endometriosis in pregnant women has found that the condition is a major risk factor for premature birth, the 25th annual conference of the European Society of Human Reproduction and Embryology heard today (Wednesday July 1). Dr. Henrik Falconer, of the Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden, said that his team had found that women with endometriosis also had a higher risk of other pregnancy complications, as well as being more likely to give birth through Caesarean section. The research is published on-line in the journal Human Reproduction today*.

The researchers investigated the association between adverse pregnancy outcome, assisted reproduction technology (ART), and a previous diagnosis of endometriosis in 1,442,675 single births to Swedish women. They found 13,090 births among 8922 women diagnosed with endometriosis. Compared with women without endometriosis, they had a 1.33% greater risk of preterm birth. Women with endometriosis were also more likely to have difficulty in conceiving and need to receive ART, which is itself a risk factor for adverse pregnancy outcome.

"Endometriosis appears to be a risk factor for preterm birth, irrespective of ART," said Dr. Falconer. "Our findings indicate that women with endometriosis may be considered a high risk group and have special care during pregnancy."

Endometriosis is a chronic inflammatory disease, affecting up to 15% of all women of reproductive age, in which the endometrial cells that line the uterus are deposited in other areas. Symptoms of endometriosis include severe pelvic pain, heavy menstrual periods, and nausea.

In addition to an increased risk of preterm birth, the researchers also found other differences in the pregnancies of women with endometriosis. "Nearly twice as many women in this group were delivered by Caesarean section," said Dr. Falconer. "We observed that among these women the risk of induced preterm birth was higher than for spontaneous preterm birth. We believe that women with endometriosis are more frequently scheduled for preterm Caesarean section, possibly due to placental complications."

Women with endometriosis were also more likely to suffer from pre-eclampsia, a condition that develops in the second or third trimester of pregnancy and involves the development of high blood pressure and the presence of protein in the urine. Antepartal bleeding was also found to be more common among women with endometriosis, the researchers say.

"Because endometriosis is so strongly associated with infertility," said Dr. Falconer, "we were not surprised to find that women suffering from it were of higher maternal age and had fewer children. However, after adjusting for maternal age and other confounding factors, the strong association between endometriosis and risky pregnancies still remained.

"Our research provides clinicians with important information in the search for the factors associated with premature birth. Given that endometriosis is relatively common in women of childbearing age, we hope that our results will lead to pregnant women with this condition receiving extra attention, thus enabling them to have normal pregnancies and give birth to healthy babies."


Cancer Survivors At Greater Risk Of Birth Complications

Survivors of childhood cancer run particular risks when pregnant and should be closely monitored, the 25th annual conference of the European Society of Human Reproduction and Embryology heard on July 1. Dr. Sharon Lie Fong, of the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands, said that, although such women may have conceived spontaneously and considered themselves to be perfectly healthy, their deliveries should always take place in a hospital.

Dr. Lie Fong and colleagues studied data on the pregnancies of 40 women who had been treated for cancer during their childhood, the majority of them for leukaemia, but also for solid tumours. Six had had radiation treatment directly to the abdomen. The data were compared with those from a control group of more than 9,000 women who had not had cancer treatment. All data were obtained from The Netherlands Perinatal Register, a nationwide database of pregnancy outcomes. Data were matched for age at pregnancy, year and month of delivery, and the number of times the woman had given birth.

"This is the first such study on pregnancy outcome in childhood cancer survivors as compared with normal, healthy women," said Dr. Lie Fong. "Although we found no differences between most of the survivors and the control group, the women treated with abdominal radiotherapy delivered more prematurely. These women also had more postpartum haemorrhages – the loss of more than one litre of blood after delivery."

In addition to the deleterious effects of abdominal radiotherapy on reproductive function, radiotherapy to the head can also cause problems by causing the hypothalamus to reduce the production of follicle stimulating hormone and luteinizing hormone, both important in promoting ovulation. "We believe that it is particularly important for all female children who are treated for cancer, and their parents, to be made aware of this risk. Our research has also shown how important it is that, if they do become pregnant, childhood cancer survivors should be closely monitored throughout their pregnancy and that they are delivered in a clinical setting, rather than at home."


Monday, June 29, 2009

Having a Child to Save a Life

The movie “My Sister’s Keeper” opened this weekend — a tale about a family who conceives a second daughter in order to save the life of their first.

It begins based in fact — the family uses pre-implantation genetic diagnosis, or PGD, to create embryos that are each screened for their suitability as a bone marrow donor. Only those that are perfect matches are transferred back into the womb.

That first part of the story is one I know well. I wrote a magazine piece years ago about the families who seem to form the seed for this movie (and for the book, by Jodi Picoult, on which the movie is based.)

Called “The Race” my article was about two families whose children were both born with a rare blood disease called Fanconi anemia, and who both made the same desperate try for a baby — with very different results. The Nashes succeeded with the new technology — and their daughter, Molly, had a successful marrow transplant with cord blood from the placenta of her baby brother Adam (the baby himself was not touched during the procedure.) The Strongin-Goldbergs, in turn, had nine unsuccessful invitro attempts, and finally had to use marrow from an imperfectly matched unrelated donor to treat their son Henry, who was running out of time. He died of graft vs. host disease at the age of seven. (Allen Goldberg has written about Henry for Motherlode, and you can read his guest post here.)

So I know firsthand the lives that depend on this very real science. And it is why, if the movie follows the book, I worry about the part that comes next — the part that is fictional and false, that might taint how viewers come to feel about PGD.

As Picoult’s tale unfolds, increasingly intrusive sacrifices are asked of the youngest daughter. At first it is just her cord blood at birth, painless and, to my mind, completely justified. Eventually it is her kidney that is needed, and in a completely unbelievable turn of events, the parents go to court to demand this over the young girl’s objections.

One of the reasons that the Strongin-Goldberg family lost Henry was because research on PGD was stalled for a year and a half in the middle of their attempts to use it — stalled by government officials who called it stem cell research, and who feared a slippery slope, and designer babies, and parents who use their children for spare parts. Had this family not lost those 18 months of research time, their real life story might have had a different ending.

My fear is that “My Sister’s Keeper” might leave the impression that the possibility of misuse of this and similar technology is reason to object to its use entirely. There are any number of reasons that lead couples to have a child — to save a marriage, to make the grandparents happy, to perpetuate the family name, because birth control failed.

Saving a life, with a few ounces of cord blood that would otherwise be thrown away, sure sounds like a pretty good reason to me.


Babies Born After Freeze-thawing Embryos Do Just As Well

Analysis of the longest running ICSI programme in the United States has found reassuring evidence that babies born from frozen embryos fertilised via ICSI (intracytoplasmic sperm injection) do just as well as those born from frozen embryos fertilised via standard IVF treatment.

The researchers also compared babies born as a result of cycles in which the women had additional hormone medication with babies born as a result of unmedicated, natural cycles, and, although they found a slightly higher rate of malformations in babies born from medicated cycles, the difference was small – 2.2% versus 0.4%.

Ms Queenie Neri, a research associate at Cornell University (New York, USA) and a member of the team headed by Professor Gianpiero Palermo who pioneered ICSI in 1992, told the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam today (Monday) that she and her colleagues had looked at all births from frozen embryos, conceived via ICSI or IVF, between 1993 and 2007.

Ms Neri identified 720 IVF and 1231 ICSI frozen embryo transfers. The survival rate of the frozen embryos was 74% after IVF and 77.2% after ICSI. The clinical pregnancy rate was 42.8% after IVF and 39.4% after ICSI. These resulted in 84.1% IVF and 89.7% ICSI deliveries. There were 27.8% multiple IVF pregnancies and 21.1% multiple ICSI pregnancies. Outcomes at the time of birth for Apgar scores, gestational ages, birth weights and congenital malformations were similar for both IVF and ICSI singleton babies.

When she grouped the babies according to whether they came from medicated or unmedicated cycles, she found that the clinical pregnancy rate was 42.1% and 39.4% respectively; delivery rates were 86.7% (with 28.7% multiple births) and 87.5% (19.2% multiple births) respectively. Gestational ages and birth weights were similar between the two groups, but the malformation rate was 2.2% from the medicated cycles and 0.4% from the natural cycles.

Ms Neri said: “Freezing embryos as part of fertility treatment has become a fundamental part of assisted reproduction technology. We found no differences in the ability of embryo generated by IVF or ICSI to implant, even after undergoing the stress of cryopreservation. We were unable to confirm a significant benefit of the unmedicated cycle on the neonatal outcome of the cryopreserved embryos; the difference in malformation rates was small.

“The original premise of the study was to identify a difference in neonatal outcome while in the presence or absence of infertility medication, with the assumption that the unmedicated cycles would generate better offspring outcomes. Interestingly, we did not see any clear difference in neonatal outcomes between the medicated and unmedicated groups. From our study, the combination of exposure to cryopreservation and medications or both did not significantly impair offspring outcome.”

The malformations ranged from heart defects to defects caused by hereditary factors and sporadic genetic mutations or interactions. However, Ms Neri said: “They were within the spectrum of malformations observed in newborns in the general population.”

“When you think about it, the reproductive medical field has created a new sub-population. These children are now reaching puberty and their fertility status still remains to be assessed. Therefore, the continuous monitoring of children generated through artificial conception is of paramount importance,” she concluded.


Abortion raises early birth risk

A history of miscarriage and abortions increases a woman's chances of giving birth too early, research has shown.

The same study revealed that premature delivery was also more likely after any complication early in the pregnancy, or in previous pregnancies.

Researchers believe the findings will help doctors identify women who might need greater care and monitoring in the months leading up to child birth.

Scientists from the UK, Denmark and Spain analysed the results of 75 investigations into early pregnancy complications conducted between 1980 and 2008.

They found that a history of one or more miscarriages nearly doubled the risk of pre-term rupture of the membrane that surrounds the baby in the womb, thereby increasing the chances of a premature delivery.

Three or more recurrent miscarriages led to a six-fold increased risk of placenta praevia - a condition caused by the placenta blocking the cervix - and almost doubled the likelihood of congenital malformations in the baby.

If a pregnancy was terminated for any reason, this heightened the risk of premature and very premature delivery in subsequent pregnancies.

The findings were presented at the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam.

The study found that problems encountered in the first three months (trimester) of pregnancy increased the risk of complications later in the same pregnancy.