Most Cases of Brain-Damaged Newborns Not Due to Mismanaged Deliveries

January 25, 2016

MAYWOOD, Ill -- January 25, 2016 -- A study published in the Journal of Perinatology is providing new evidence that the vast majority of babies who are born with severe brain damage are not the result of mismanaged deliveries.
Jonathan Muraskas, MD, Loyola University Medical Center and Loyola University, Chicago, Illinois, and colleagues examined the medical records of 32 full-term infants who developed severe cerebral palsy and mental retardation. The records indicated that this brain damage occurred after the babies were born, and despite proper resuscitation.
“All too often in cases of professional liability, the focus is on the last 2 hours of a normal 7,000-hour term pregnancy,” the authors wrote. “This study would support closer scrutiny of the first 2 hours [following birth] as a possible [cause] for non-preventable adverse neurological outcomes in newborns.”
Out of every 1,000 full-term newborns, between 1 and 3 infants experience encephalopathy, marked by impaired level of consciousness, seizures, difficulty breathing, and depressed reflexes. While studies have found that only 8% to 14.5% of such cases are due to inadequate blood supply to the brain during delivery, the syndrome remains a leading cause of allegations of mismanagement by obstetricians.
The cases Dr. Muraskas examined included 18 newborns with chorioamnionitis and 14 newborns with severe anaemia.
Medical records examined in the study showed that the gases in the umbilical cord blood of these newborns were normal, and there was little injury to the brains' deep gray matter. These and other indicators strongly suggest that the babies had not suffered brain damage before birth. However, once the babies were born, they were unable to cope on their own with the devastating effects of their infections or anaemia.
For example, babies infected by chorioamnionitis developed sepsis, an overwhelming immune response to infection that can cause tissue damage and organ failure. Severe cases of chorioamnionitis and anaemia can impede delivery of oxygen to the brain and other vital organs. In such cases, even the best resuscitation efforts are unable to prevent severe brain damage.
Despite appropriate obstetrical and paediatric-neonatal management, the presence of chorioamnionitis or fetal anaemia can result in “devastating outcomes,” the authors wrote.
SOURCE: Loyola University Health System

Anaemic, Underweight Pregnant Women at Greater Risk for Deadly Hepatitis E Virus

January 26, 2016

 

BALTIMORE, Md -- January 26, 2016 -- Researchers have found a link between pre-existing nutritional deficits and immune dysfunction and the risk of hepatitis E infection during pregnancy.
The study, published in the journal American Society of Tropical Medicine and Hygiene, is thought to be the first to identify pre-existing characteristics that lead to an increased risk of hepatitis E infection.
“For decades, we've been asking why pregnant women who get hepatitis E die at an alarming rate,” said Alain Labrique, PhD, Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. “This research suggests that pre-existing differences could be the key we've been seeking. Even though women are exposed to similar environmental risk factors, the differences in pre-existing characteristics seem to put some women at a much higher risk of getting infected, sick and dying.”
“These findings could pave the road for stepped-up nutritional monitoring of pregnant women in this part of the world and lead to recommendations for nutritional supplements,” he added.
The researchers found that anaemia occurred in nearly 3 times the number of women who became infected compared with those who didn’t (27.5% vs 10%). Of the women with hepatitis E, 45% had a body mass index that categorised them as underweight compared with a quarter of the control group.
The researchers also found that women who were deficient in vitamin D in the first trimester were more likely to be infected than the control group of pregnant women at a similar risk level who did not become infected with the virus (95% vs 92.5%).
Women with lower levels of zinc in the third trimester were more likely to be infected than the control group of pregnant women who did not become infected with the virus (17.5% vs 2.5%).
The study, which was conducted at the Bloomberg School’s flagship JiVitA Research Project in Bangladesh, also found that women who became infected had higher levels of both pro- and anti-inflammatory cytokines. This suggests that pre-existing immune dysfunction may also increase the risk of getting hepatitis E or other infectious diseases.
For their study, researchers collected blood samples at 3 different times from 1,100 women living in northern Bangladesh: early in pregnancy, in the third trimester, and 3 months after giving birth. Forty women became infected with the virus over the course of the study. A control group of pregnant women who did not become infected were matched by several factors, including age and residence, to minimise differences in exposure to the virus or other external risk factors.
SOURCE: Johns Hopkins University Bloomberg School of Public Health

Investigation of Adverse Drug Reaction Reveals HIV Infection in Patient

January 27, 2016 MPR

 A recently published case study details the first known incidence of sulfa hypersensitivity in primary HIV. The findings could be significant as they may provide clinical evidence to support the correlation between viral load and adverse drug reactions (ADRs) to trimethoprim-sulfamethoxazole (TMP-SMX) without a severe decrease in CD4 count. The study also sheds new light on how an adverse reaction to sulfa drugs may aid in early diagnosis of HIV.

The study focuses on a 55-year-old African-American male who presented with a diffuse maculopapular rash and difficulty breathing due to an adverse reaction while being treated with TMP-SMX. Three days prior to presenting, he had incision drainage and TMP-SMX therapy for a gluteal fold abscess. The patient denied any IV drug use, sexual relations with men, or high-risk sexual behavior. His initial exam showed mild respiratory distress, severely swollen tongue and lips, and diffuse perioral cracking with fissures; he was negative for lymphadenitis and fever. The patient was administered supplemental oxygen, intramuscular epinephrine, and methylprednisolone for treatment of suspected anaphylaxis.

The rash progressed to his left buccal mucosa and the base of the penile shaft. The patient was subsequently tested for potential infectious etiologies and found to have a positive HIV viral load consistent with an acute HIV infection. This was confirmed two weeks later by a 3^rd generation test. The patient later admitted to having unprotected sex with two women, two weeks prior to initial presentation.

Conclusion

This case suggests how asymptomatic acute HIV infection may be identified by an adverse reaction to TMP-SMX. Also demonstrated is clinical evidence to support the correlation between viral load and ADRs to TMP-SMX without a severely diminished CD4 count. The authors stress that the limitations of one study cannot show causality, and therefore call for further research into whether viral proteins themselves are the root cause of HIV-related sulfa reactions.

FDA Approval of Flibanserin — Treating Hypoactive Sexual Desire Disorder

HSDD  (Hypo-active Sexual Desire Disorder) is characterized by reduced sexual fantasies and desire for sexual activity that causes marked distress or interpersonal difficulty and is not accounted for by coexisting conditions, use of medications, or relationship problems. At a 2014 meeting, the FDA heard from some women about the condition's effects on their sense of identity, emotional well-being, and relationships.1
Although nonpharmacologic approaches to HSDD are important, we recognized that some women could benefit from drug therapy. Such treatments must meet the statutory standard for demonstration of effectiveness (substantial evidence from adequate, well-controlled trials) and have favorable benefit–risk profiles. Assessing flibanserin has proven challenging; the drug has been reviewed three times by the FDA and discussed twice at public advisory committee meetings.

Gene Mutations Linked to Rare Form of Female Infertility

WEDNESDAY, Jan. 20, 2016 (HealthDay News) -- For a small number of women with infertility, mutations in a particular gene may be to blame, a new study finds.
The results, reported in the Jan. 21 issue of the New England Journal of Medicine, apply to a rare form of female infertility. But experts said the findings could potentially allow those women to avoid fertility treatment that will not work for them.
Researchers in China found that mutations in a gene known as TUBB8 were the culprit in seven of 24 families where women could not get pregnant for a specific reason: Their eggs could not mature to the stage where they are ready to be fertilized by sperm.
Exactly how many women have this condition isn't known, said Lei Wang, an associate professor at Fudan University, in Shanghai, who worked on the study.
In China, he said, it's estimated to affect up to 0.1 percent of women who seek treatment for infertility -- based on a study from one medical center.
But while that form of infertility is unusual, the findings are an "important step forward," said Dr. Jurrien Dean, chief of the cellular and developmental biology lab at the U.S. National Institutes of Diabetes and Digestive and Kidney Diseases.
Until now, no one had known that the TUBB8 gene was essential to women's fertility, explained Dean, who wrote an editorial published with the study.
Greater understanding of normal egg maturation could eventually be useful in fertility treatment, Dean said.
But more immediately, he said, fertility clinics could test women for TUBB8 mutations, so they can avoid expensive treatments, like in-vitro fertilization, that would use their own eggs.
"There would be no point in doing those procedures," Dean said. "That's incredibly useful information because it allows patients to move forward and consider other options for having a family -- such as using a surrogate, or adoption."
According to the U.S. Centers for Disease Control and Prevention, about 6 percent of married women younger than 45 are unable to get pregnant after a year of trying. The causes of female infertility can include problems with ovulation or abnormalities in the uterus or fallopian tubes. Sometimes, there is no known explanation.
For the new study, Wang's team looked at 24 families in which women had sought infertility treatment. All were found to have eggs that stopped maturing at a critical point called meiosis I.
According to the experimental data, in seven of the 24 families, affected women carried mutations in the TUBB8 gene, which regulates a protein that appears essential for normal egg development.
Wang said the mutations were inherited from the father in five of the families, and arose spontaneously in the other two. Once they identified the gene, the researchers used experiments with egg cells -- from mice and humans -- to prove that the TUBB8 mutations do halt egg maturation.
"The practical implication of our discovery is that it will now be possible to screen women who seek [infertility] treatment using a simple DNA-based test," Wang said.
If they carry any of the implicated TUBB8 mutations, Wang said, "they can spare themselves the expense and discomfort associated with an [in vitro fertilization] procedure that has little or no chance of success."

Trying to Conceive Soon After a Pregnancy Loss May Increase Chances of Live Birth.

BETHESDA, Md -- January 12, 2016 -- Couples who attempt to conceive within 3 months after losing an early pregnancy, defined as less than 20 weeks gestation, have the same chances, if not greater, of achieving a live birth than those who wait for 3 months or more, according to a study published today in Obstetrics & Gynecology.
The finding questions traditional advice that couples should wait at least 3 months after a loss before attempting a new pregnancy. The World Health Organization (WHO), for example, recommends waiting a minimum of 6 months between a pregnancy loss and a subsequent attempt.
“Couples often seek counselling on how long they should wait until attempting to conceive again,” said senior author Enrique Schisterman, PhD, National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health (NIH), Bethesda, Maryland. “Our data suggest that women who try for a new pregnancy within 3 months can conceive as quickly, if not quicker, than women who wait for 3 months or more.”
Previous studies of pregnancy spacing have focused on when women should become pregnant after experiencing a loss, but few have addressed the question of when couples should start trying to conceive.
For the current study, researchers analysed data from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a multisite block-randomised, double-blinded, placebo-controlled trial that took place from 2007 to 2011. The trial, which evaluated the effect of daily low-dose aspirin on reproductive outcomes in women with a history of pregnancy loss, enrolled 1,228 women aged 18 to 40 years.
The researchers concentrated on 1,083 of these women -- more than 99% of whom had lost a pregnancy at less than 20 weeks gestation. None of the women had an ectopic pregnancy or a molar pregnancy. The participants were followed for up to 6 menstrual cycles and if they became pregnant, they were followed until the outcome of the pregnancy was known.
The researchers found that more than 76% of the women attempted to conceive within 3 months after losing a pregnancy. Compared with those who waited longer, this group was more likely to become pregnant (69% vs 51%) and to have a pregnancy leading to a live birth (53% vs 36%). The investigators did not observe any increase in the risk of pregnancy complications in this group.
“While we found no physiological reason for delaying attempts at conception following a pregnancy loss, couples may need time to heal emotionally before they try again,” said Karen Schliep, PhD, NICHD Epidemiology Branch. “For those who are ready, our findings suggest that conventional recommendations for waiting at least 3 months after a loss may be unwarranted.”
SOURCE: National Institutes of Health

Midazolam Exposure May Impair Hippocampal Growth in Preemies

Higher exposure to midazolam in very preterm babies is linked to impaired hippocampal growth and lower cognitive scores, according to data published in the Annals of Neurology.
“No one wants to see a baby in pain. That said, some very preterm babies require many painful procedures during their neonatal intensive care,” Emma Duerden, PhD, of the Department of Pediatrics at the Hospital for Sick Children in Toronto, Ontario, told Neurology Advisor. “Midazolam is used in some neonatal intensive care units for sedation of very preterm born babies. However, animal experiments suggest that midazolam adversely impacts the developing hippocampus, a brain region important for memory.”
Dr Duerden and colleagues examined preterm neonates (24-32 weeks gestation) with MRI and DTI scans and conducted developmental assessments at approximately 18 months to understand any link between exposure to sedatives or analgesics and hippocampal growth and neurodevelopment.
Of the 138 preterm neonates, 51% were male with a median gestation of 27.7 weeks and 101 invasive procedures. Those with the most invasive procedures were more likely to be born earlier, intubated longer, have more doses of morphine and midazolam, and have more infections and surgical procedures (P<0 .05="" age="" all="" and="" at="" early="" for="" had="" hippocampal="" i="" invasive="" measured="" more="" on="" procedures="" smaller="" term-equivalent="" those="" volumes="" with="">P

<0 .0001="" both="" nbsp="" p=""> After adjustment for surgery and mechanical ventilation and controlling for cerebral volume, midazolam was significantly associated with decreased hippocampal growth (β= -1.96, P<0 .001="" an="" associated="" dose="" i="" increased="" likewise="" md="" midazolam="" the="" total="" value="" was="" with="">P=0.02). “… the reduction in hippocampal volumetric growth coupled with an increase in MD values may indicate that midazolam exposure results in lower cellular density and/or alterations in cellular/synaptic structure, neuronal size, and organization in the hippocampus in preterm born neonates,” the authors wrote.
Most of the participants (85%) returned for neurodevelopmental assessment and were found to have median language and cognitive scores in the normal ranges. The researchers found cognitive scores to be associated with hippocampal volume growth (β=-0.31, P=0.003) with a negative association to total midazolam dose (β=-0.27, P=0.03) in linear regression.
“Slower growth of the hippocampus was associated with poorer cognitive outcome at 18 months of age,” Steven Miller, MD, CM, of the Department of Pediatrics at the Hospital for Sick Children in Toronto, told Neurology Advisor. “Our findings suggest the need for caution in the use of midazolam in the very preterm neonate.”
“It is critical that we identify how to treat pain in preterm neonates in ways that enable optimal brain development and cognitive outcomes,” Dr Miller said.

References:

Duerden EG, Guo T, Dodbiba L, et al. Midazolam dose correlates with abnormal hippocampal growth and neurodevelopmental outcome in preterm infants. Ann Neurol. 2016; doi:10.1002/ana.24601.

Green, Leafy Vegetables Each Day May Help Keep Glaucoma at Bay

THURSDAY, Jan. 14, 2016 (HealthDay News) -- Eating green leafy vegetables daily may decrease the risk of glaucoma -- a serious eye disease -- by 20 percent or more over many years, a new study suggests.
"We found those consuming the most green leafy vegetables had a 20 to 30 percent lower risk of glaucoma," said study leader Jae Kang. Kang is an assistant professor of medicine at Brigham and Women's Hospital and Harvard Medical School in Boston.
Glaucoma is an eye condition that usually develops when fluid increases in the front part of the eye and causes pressure, damaging the optic nerve. It can lead to loss of vision, according to the U.S. National Eye Institute.
Although the study found an association between eating more leafy greens and a lower risk of glaucoma, it didn't prove cause-and-effect.
Kang's team followed nearly 64,000 participants in the Nurses' Health Study from 1984 through 2012, and more than 41,000 participants in the Health Professionals Follow-up Study from 1986 through 2014. The men and women were all 40 or older. None had glaucoma at the start of the study, and they had eye exams every two years.
Over the 25-year follow up, almost 1,500 people developed glaucoma. The researchers looked at the consumption of green leafy vegetables among the participants.
The investigators divided the participants into five groups, from the highest level of leafy green vegetable consumption to the lowest. Those who ate the most averaged about 1.5 servings a day, or about one and a half cups a day, Kang said. Those in the group eating the least leafy greens ate about a serving every three days, according to Kang.
What is it about leafy greens that may help eye health?

"In glaucoma, we think there is an impairment of blood flow to the optic nerve," Kang said. "And an important factor that regulates blood flow to the eye is a substance called nitric oxide." Green leafy vegetables contain nitrates, which are precursors to nitric oxide, the researchers said.
"When you consume the higher amount of green leafy vegetables, you have greater levels of nitric oxide in your body," Kang said.
Findings from the study were published online Jan. 14 in the journal JAMA Ophthalmology.
The findings make sense, said Dr. Rahul Pandit, an ophthalmologist at Houston Methodist Hospital, who reviewed the new research.
This study, he said, is the first study to look at a large population and show that higher consumption of green leafy vegetables appears to decrease glaucoma risk.
"We do have some data that people with glaucoma have impaired nitric oxide production in the eye," added Pandit, who is also an associate professor of ophthalmology at Weill Cornell Medical College in New York City.
The findings suggest that "maybe this is something we can apply clinically," Pandit said.
The advice to eat more green leafy vegetables seems low risk, Pandit said. He suggested people ask their doctor whether eating and increasing green leafy vegetables is a good idea for them.
SOURCES: Jae Kang, Sc.D., assistant professor of medicine, Brigham & Women's Hospital and Harvard Medical School, Boston; Rahul Pandit, M.D., ophthalmologist, Houston Methodist Hospital, and associate professor of ophthalmology, Weill Cornell Medical College; Jan. 14, 2016, JAMA Ophthalmology, online