Pregnancy and child

Infertility treatments 'not linked' to developmental delays

"There is no heightened risk of developmental delays … in children conceived through IVF or other infertility treatments," the Mail Online reports. A study found that the numbers of children affected with such delays were the same as those conceived naturally.

The study included more than 5,000 mothers, around 1,500 of which had received some form of infertility treatment, and assessed their child’s development at three years of age.

They looked at whether there was a different effect, depending on whether it was a single or twin birth, and the type of infertility treatment given – either assisted reproductive techniques such as IVF, infertility drugs or artificial insemination.

Overall, there was no convincing evidence that infertility treatment had any effect on a child’s development.

Techniques such as IVF have been linked to increased risk of failing a development domain (having a developmental delay), and it is also known to increase the risk of multiple births and low birth weight. Both these factors can impact on a child’s development.

Once these factors were taken into account, no significant links were found.

The study design is unable to prove direct cause and effect, and say for certain whether there is any link between infertility treatment and developmental delays, but the findings will come as a relief to people undertaking treatment.

More research in a larger population, including a wider spread of people who have received the different forms of infertility treatments, is now required to confirm these findings.

Where did the story come from?

The study was carried out by researchers from a number of institutions, including Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the University at Albany School of Public Health. 

It was funded by supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

The study was published in the peer-reviewed medical journal JAMA Pediatrics on an open-access basis, so it is free to read online.

The study has been reported accurately in both the Mail Online and The Sun, with a number of figures from the study. However, they do not explain that this a prospective cohort study, which cannot conclusively prove or disprove direct links, as other factors may be involved.

Also, both headlines focus on IVF, when this is only one of many different infertility treatments that may be used, depending on circumstance. 

What kind of research was this?

This is a prospective cohort study that aimed to assess how the use and type of infertility treatment was associated with children’s development through to age 36 months. This type of study is good for drawing links between an exposure and an outcome over a period of time, but is not able to prove direct cause and effect, as other factors could be involved.

What did the research involve?

Participants in the Upstate KIDS study were infants born in New York State (excluding New York City) from 2008 to 2010. The exposure group was all infants whose birth certificates indicated infertility treatment. The comparison groups were those who were conceived naturally.

Parents were recruited through a mailing of introduction letters and brochures, which explained that the study was interested in pregnancy history, together with the child’s growth and development during the first three years of life.

Screening for eligibility was performed through telephone calls and checked: 

  • mother’s residence at birth and enrolment within the specified catchment area
  • ability to communicate in English or Spanish
  • the index infant or its twin was currently alive

At four months after birth, mothers received a questionnaire asking about all medical services used to become pregnant. Subcategories of infertility treatment were:

  • Assisted Reproductive Technologies (ART), including in vitro fertilisation (IVF – egg incubated with many sperm), intra-cytoplasmic sperm injection (ICSI – egg injected with a single sperm), frozen embryo transfer, donor eggs or embryos
  • ovulation induction using oral or injectable drugs, with or without intrauterine insemination

The child’s development was assessed using the Ages and Stages Questionnaire (ASQ), which is validated for early identification of developmental delays. As part of the questionnaire, parents are encouraged to do activities with their children to be able to accurately respond to questions regarding the five developmental domains:

  • fine motor – such as the ability to manipulate toys with their hands
  • gross motor – such as, in older babies, the ability to sit up unsupported
  • personal-social functioning – such as, in older babies, the ability to feed themselves with a rusk or similar
  • communication
  • problem solving ability

Each item was scored with 10 points (yes), five points (sometimes) and zero points (not yet).

Parents were to complete the ASQ at two-month intervals from four to 12 months, and then at 18, 24 and 36 months (corrected for gestational age).

The researchers examined the link between child development and infertility treatment, separately looking at the effect of single or twin birth, and the type of infertility treatment given. They adjusted their analyses for various confounding factors that could influence results, such as parental age, ethnicity and education, mother’s body mass index (BMI), baby’s weight and gestational age at birth.

What were the basic results?

The researchers included 1,422 mothers (of 1,830 children) exposed to infertility treatment, and a comparison group of 3,402 mothers (of 4,011 children) who hadn't received treatment.

The vast majority of mothers (97%) completed one or more developmental screening instruments. There were some differences between parents who had received the different types of infertility technique – for example, those who had ART were older, had higher educational attainment and lower BMI than those who had just received infertility drugs.

Between 6 and 10% of children failed at least one of the ASQ developmental domains at each screen. Infertility treatment was not associated with risk of a child's failure (Adjusted odds ratio [OR] 1.33, 95% confidence interval [CI] 0.94 to 1.89).

When assessing all births together (singletons and twins) assisted reproductive technologies were associated with an increased risk of failing a developmental domain (Adjusted OR 1.81, 95% CI 1.21 to 2.72). However, when adjusting for birth weight and looking separately at singletons and twins, neither of the subgroups of fertility treatment (ovulation induction/intrauterine insemination or ART) were statistically significantly associated with risk of failing any developmental domain.

How did the researchers interpret the results?

The researchers conclude: "After considering [singletons and twins], children's development through age three years was similar irrespective of infertility treatment or specific type. To our knowledge, these findings are among the first to focus on non-ART treatments in the United States."

Conclusion

This prospective cohort study aimed to assess whether use of and type of infertility treatment was associated with a child's development up to the age of 36 months.

The study found no convincing evidence that infertility treatment had any impact on a child's development, which will come as a relief to parents who have undertaken treatment. However, while this type of observational study is good for looking at links between an exposure and an outcome over a period of time, it is not able to prove direct cause and effect and say for certain whether there is any link between two factors.

For example, various socioeconomic, health and lifestyle factors may be associated both with the chance of a couple experiencing fertility problems, and with the chance of their child experiencing developmental problems. Also, unlike in the UK, infertility treatment is rarely free in the US, which accentuates potential socioeconomic factors – it is less likely that poorer couples could afford treatment.

The researchers have attempted to adjust their analyses for various factors that could be confounding the relationship, but it is not known whether these will have been able to account for the influence of all of them.

Other limitations of the study include potential inaccuracies in completing the questionnaires, and missing data – though the researchers have used statistical modelling to account for gaps in the questionnaires.

The study has many strengths, including that it used a well-validated tool to assess child development and included a large sample size that should be representative of all births in the target region. However, only a population from one US state was used, so these findings may not be applicable elsewhere, particularly as the frequency of use and type of infertility treatments given may vary geographically.

More research in larger and different populations, including a wider spread of people who have received the different forms of infertility support, would be required to confirm these findings.

Still, despite the limitations mentioned above, this was a well-designed study that should hopefully provide some degree of reassurance to people considering or undergoing infertility treatments.   


NHS Attribution