Articles

N Engl J Med 2012; 366:1803-1813 May 10, 2012

COMMENTARY
Although reproductive technologies like in vitro fertilization and intracytoplasmic sperm injection are considered safe and effective, there is a considerable body of evidence linking these technologies to increased rates of birth defects. It is not clear, however, whether these technologies are these excess birth defects can be attributed to the procedures or to other factors which are actually linked to those who are more likely to need these procedures. This study sought to use a registry in South Australia to compare the risk of birth defects in women who used reproductive technology, women who achieved a spontaneous pregnancy but had used reproductive technology previously, women who had a history of infertility but had achieved pregnancy without reproductive technology, and pregnancies in women with no history of infertility. More than 300,000 births were included in the analysis, and 6163 of them involved reproductive technology. Before adjusting for other factors, the birth defect rate for those using reproductive technology was 8.3%, versus 5.8% in those not using reproductive technology. After adjusting for other factors, however, in vitro fertilization was no longer significantly associated with an increased risk of birth defects. Intracytoplasmic sperm injection, however, was still significantly associated with an increased risk of birth defects (adjusted odds ratio 1.57) even after adjusting for other factors. This study adds to our knowledge in this area by showing that although reproductive technology are associated with increased risks of birth defects, it does not appear that IVF adds risk above that already inherent in those who might use the technology. Intracytoplasmic sperm injection still appears to do so, although it may still be that currently unaccounted for factors are the real risk, and not the procedure.

N Engl J Med 2012; 366:1803-1813 May 10, 2012

COMMENTARY
Although reproductive technologies like in vitro fertilization and intracytoplasmic sperm injection are considered safe and effective, there is a considerable body of evidence linking these technologies to increased rates of birth defects. It is not clear, however, whether these technologies are these excess birth defects can be attributed to the procedures or to other factors which are actually linked to those who are more likely to need these procedures. This study sought to use a registry in South Australia to compare the risk of birth defects in women who used reproductive technology, women who achieved a spontaneous pregnancy but had used reproductive technology previously, women who had a history of infertility but had achieved pregnancy without reproductive technology, and pregnancies in women with no history of infertility. More than 300,000 births were included in the analysis, and 6163 of them involved reproductive technology. Before adjusting for other factors, the birth defect rate for those using reproductive technology was 8.3%, versus 5.8% in those not using reproductive technology. After adjusting for other factors, however, in vitro fertilization was no longer significantly associated with an increased risk of birth defects. Intracytoplasmic sperm injection, however, was still significantly associated with an increased risk of birth defects (adjusted odds ratio 1.57) even after adjusting for other factors. This study adds to our knowledge in this area by showing that although reproductive technology are associated with increased risks of birth defects, it does not appear that IVF adds risk above that already inherent in those who might use the technology. Intracytoplasmic sperm injection still appears to do so, although it may still be that currently unaccounted for factors are the real risk, and not the procedure.

PEDIATRICS Vol. 129 No. 5 May 1, 2012, pp. e1155 -e1164 (doi: 10.1542/peds.2011-1379)

COMMENTARY
Acute diarrhea and acute respiratory tract infections are all too common in low-socioeconomic communities like Jakarta, Indonesia. Some have theorized that diets of probiotics or calcium might help to reduce the risk of these illnesses in children. This study was a randomized controlled trial of healthy children between one and six years of age who consumed one of the study diets over a six month period. These diets included (1) low-lactose milk with low calcium, (2) low-lactose milk with regular calcium, (3) low-lactose milk with regular calcium plus 5.1⁸ colony-forming units per day of Lactobacillus casei, and (4) low-lactose milk with regular calcium plus 5.1⁸ colony-forming units per day of Lactobacillus reuteri. The primary outcome of interest was the number of episodes of diarrhea and acute respiratory infections; the secondary outcome was the duration of these episodes. When diarrhea was defined as at least three liquid/loose stools in a day, no differences were seen in any of the diets among all children in the study. If the definition was lowered to at least 2 liquid/loose stools per day, than the Lactobacillus reuteri diet resulted in significantly fewer cases than the low-lactose milk with regular calcium diet. A subgroup analysis of children with low nutritional status showed that the Lactobacillus reuteri performed especially well in preventing diarrhea in that sub-population of children. The diets had no effect at all on the incidence of acute respiratory infections. The take home message from this is that regular calcium milk, with or without Lactobacillus casei, has no effect on diarrhea or acute respiratory infections in children in Indonesia. Lactobacillus reuteri may prevent some diarrhea, particularly in children with low nutritional status.

Arch Pediatr Adolesc Med. 2012;166(5):431-436. doi:10.1001/archpediatrics.2011.1665

COMMENTARY
With the rate of obesity and overweight ever increasing, many are trying to turn to prevention as a better means of confronting the epidemic than treatment. And, as more and more children are becoming overweight and obese at younger and younger ages, preventing its occurrence must also occur at younger and younger ages. Some studies have shown that breastfeeding may be protective against rapid weight gain in infancy, and may be linked to lower rates of obesity and overweight later in childhood. This study took things a step further. It sought to tease out the relative contributions of the mechanism of feeding as opposed to the type of milk being fed. The study followed infants through their first year and recorded not only the type of milk they were being fed, but also whether they got it by bottle or from the breast. Infants who were fed nonhuman milk by bottle gained, on average, 71g more per month above those who were exclusively breastfed. But even infants who were fed human breast milk only by bottle gained 89g more per month than infants who were exclusively breastfed. In other words, it appears that the feeding by bottle is more likely associated with increased weight gain as opposed to the type of milk given. For those infants who received only breast milk by a variety of sources, those with more bottle feedings gained more weight. This may be because infants are less able to self-regulate with the bottle, or because those fed at the breast receive less milk in general. Regardless, there is something different about bottle feeding as opposed to breastfeeding when it come s to weight gain, and we should be cognizant of this when advising mothers against allowing their children to become too heavy.

PEDIATRICS Vol. 129 No. 5 May 1, 2012, pp. 809 -814 (doi: 10.1542/peds.2011-3198)

COMMENTARY
As with the preceding study, monitoring for rare sequela after vaccine administration requires surveillance studies conducted after vaccines have been approved and started to be given in large numbers. In the US, children receive two doses each of the MMR and varicella vaccines, one between 1-2 years and another between 4-6 years. Parents can opt for their children to receive two separate shots, or a formulation that combines both of these vaccines into one shot. Previous studies, however, have shown that the risk of a febrile seizure 7 to 10 days after receiving both these vaccines in one shot that of receiving them separately. This study sought to confirm if this same finding occurred in children 4-6 years old who received the vaccine. The study used the Vaccine Safety Datalink to identify seizures in emergency departments and hospitals occurring up to 6 weeks after receiving the vaccines, whether together or separate. Over a two year study period, data were available for over 86,000 children who received the two vaccines in one shot, and these were compared to more than 67,000 children who received the shots separately over an 8 year period. Seizures were rare in this age group for the entire study period, and they did not peak 7 to 10 days after vaccine administration. Overall, there was one febrile seizure 7 to 10 days in the 86,750 kids who received the combined formulation. There were no children who had a febrile seizure 7 to 10 days after the administration of the shots separately. Because of the low numbers, a relative risk could not be calculated, but there seems to be no increased risk of the combined formulation leading to more febrile seizures in 4-6 year olds as it does in 1-2 year olds. The CDC continues to recommend that parents of 1-2 year olds receiving their first doses of these vaccines who don’t have a strong preference for the combined formulation should have their children receive separate shots. It seems unlikely they will make the same recommendation for 4-6 year olds.

Arch Dis Child 2012;97:487-490 doi:10.1136/archdischild-2011-301163

COMMENTARY
When doing prospective studies of vaccines, and all drugs for that matter, it is difficult to estimate how often they might lead to rare adverse events. Properly done surveillance after vaccine approval, however, can allow researchers to monitor large numbers of people receiving drugs or vaccines to see if adverse events are occurring at rates that might be significant. One sequela that might arise from vaccines is anaphylaxis. This study monitored all in the UK and Ireland who received vaccines for just over a one year period from 2008-2009. Any child who had anaphylaxis after receiving a vaccine was reported to the British Paediatric Surveillance Unit. Thankfully, anaphylaxis was very rare. Even though 15 children were reported as part of the study, fewer than half of them had true anaphylaxis. All of the children made a full recovery. So many vaccines are given, that the rates of these events were quite small overall. For the single component measles vaccine, the rate of anaphylaxis post-administration was 12 per 100,000 doses. For the HPV vaccine, it was 1.4 cases per 1,000,000 doses. Although there are no solid numbers on how many vaccines were given over this period, it is estimated that the number was more than 5,500,000. And, for all of those, only 7 children had true anaphylaxis following immunization. Of course, if a child has a history, they should always be monitored carefully after getting any medication or vaccination. They should also be monitored for more than 30 minutes, as many of the cases of anaphylaxis occurred after this amount of time. But we should rest assured that vaccines are safe, and that anaphylaxis after vaccine administration is very rare.