Neuromotor development and mental health at 5.5 years of age of singletons born at term after intracytoplasmatic sperm injection ICSI: results of a prospective controlled single-blinded study in Germany

doi:10.1016/j.fertnstert.2007.11.030

Fertility and Sterility

Volume 91, Issue 1, January 2009, Pages 125-132

https://doi.org/10.1016/j.fertnstert.2007.11.030 Get rights and content

Objective

To assess the neurodevelopmental health of children born after intracytoplasmatic sperm injection (ICSI).

Design

Prospective controlled blinded study.

Setting

Tertiary care center.

Patient(s)

A total of 276 term-born singletons conceived by ICSI and 273 matched spontaneously conceived (SC) singletons at the age of 5.5 years.

Main Outcome Measure(s)

Neuromotor development assessed by a detailed neurologic examination, including the standardized motor test MOT 4–6, and emotional/behavioral development and intelligence assessed with the Kaufman-Assessment Battery for Children.

Result(s)

There were no significant differences between ICSI children and control children regarding the neurologic examination, motor skills, emotional/behavioral development, and intelligence.

Conclusion(s)

The ICSI children born at term develop normally, similar to SC children.

Section snippets

Study Design

The aim of the study was to assess a cohort of children conceived by ICSI at the age of 4–6 years (who had been previously assessed at birth). The primary outcome measure was the intelligence measured with the Kaufman Assessment Battery for Children (K-ABC). Other measures were biometric data, health status, acute, chronic, and childhood illnesses, development, and data on family functioning.

The study was designed as a prospective controlled single blinded study with a one-sided equivalence

Participation

We asked 574 eligible ICSI and 2,577 control parents to take part in the study via postal enquiry. A total of 323 ICSI parents (56.3%) and 442 control parents (17.2%) were willing to take part in the study. The examination could be performed in 295 ICSI and 287 control children. A total of 19 ICSI children and 14 controls had to be excluded, because the examination revealed that they did not meet the inclusion criteria. Finally, the data of 276 ICSI and 273 control children were available for

Discussion

We could show that the ICSI singletons born at term showed normal development with good neurologic health and good motor skills at the age of 5.5 years.

Except for a higher incidence of strabismus in the control children, we did not observe any difference in the detailed neurologic examination between the groups. Our neurologic examination included a detailed standardized motor test with 18 different subtests. Most other studies have assessed only fine and gross motor skills, and only a few

Acknowledgments

The authors thank the study's secretary, Ms. Kerstin Greulich, for her technical support and commitment to the study. The pediatricians Björn Becker, Meike Bendiks, Andreas Entenmann, and Anja Karpa and the psychologist Ricarda Gross examined all of the children. The authors thank them for their commitment. They especially thank the participating families for their time and cooperation.

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Cited by (43)

Six-year follow-up of children born from vitrified oocytes
2021, Reproductive BioMedicine Online
Are children born from vitrified-warmed oocytes physically or mentally different from naturally conceived children?
Intracytoplasmic sperm injection (ICSI) of vitrified-warmed oocytes was performed for 282 patients (307 cycles) from August 2000 to March 2020. Long-term follow-up of children born from vitrified-warmed oocytes was performed via a questionnaire that was sent to the parents at regular intervals from 3 to 72 months after the child's birth. Questionnaires were sent 11 times from birth to the age of 6 years. The development of motor function and mental status was evaluated as the primary outcome, based on the reported data. Subsequently, patients were divided into four groups by age at oocyte retrieval (20–29, 30–34, 35–39, and 40 years or older). Clinical outcomes were calculated as a secondary outcome.
For the 282 patients, the birth of 116 babies was reported (110 singletons and three sets of twins), and seven cases are, at the time of writing, unconfirmed. The results of the survey found physical parameters in singletons to be equivalent to the nationally reported average data issued by the Ministry of Health, Labor and Welfare of Japan.
This is the first follow-up report of children born from vitrified-warmed oocytes followed by ICSI. The data suggested that the responses from the study participants on the mental and physical development of children were comparable to the data reported by the government, although more responses from patients should be collected to allow further study.
A comparison of metabolic health parameters in ICSI-conceived and naturally conceived adolescents
2020, Reproductive BioMedicine Online
Citation Excerpt :
This was a prospectively controlled study with 14- to 17-year-old singleton adolescents born using intracytoplasmic sperm injection (ICSI) and their mothers. The adolescents were part of a study cohort that has already been evaluated twice: the first time at birth (Katalinic et al., 2004), the second time at the age of 4–6 years (Ludwig et al., 2009), and now for a third time at the mean age of 16 years. The control group consisted of adolescents born by natural conception and their mothers.
Are there differences in the cardiometabolic health of ICSI-conceived adolescents compared with a control group, taking parental risk factors into account?
ICSI-conceived adolescents (n = 272), their mothers (n = 273) and naturally conceived control adolescents (n = 273) and their mothers (n = 273) provided a blood test and answered a health-related questionnaire. The adolescents also attended a physical examination.
ICSI-conceived males showed significantly higher mean weight (72.6 ± 15.1 versus 67.7 ± 12.6 kg, P = 0.005), body mass index (BMI) (22.2 ± 3.7 versus 21.0 ± 3.2 kg/m², P = 0.007) and waist circumference (79.1 ± 11.6 versus 74.5 ± 8.7 cm, P < 0.001). The mean values for weight and BMI were also significantly higher in the ICSI parents. In the ICSI-conceived females significant differences in high-density lipoprotein cholesterol (1.5 ± 0.3 versus 1.6 ± 0.3 mmol/l, P = 0.033) and triglyceride values (1.1 ± 0.5 versus 1.0 ± 0.4 mmol/l, P = 0.013) were observed. ICSI mothers also had significantly higher triglycerides (P = 0.002), higher glutamate pyruvate transaminase/alanine aminotransferase (P < 0.001) and higher alkaline phosphatase values (P < 0.001).
Increased values for weight were found in the male and differences in lipid parameters in the female ICSI-conceived adolescents, which were reflected in the values of their parents. Adjustment for parental risk factors generally attenuated the differences between the ICSI and the control groups, but did not completely remove them. Whether these observed differences are clinically relevant for the future health of the participants requires further study. To increase knowledge in this area, future studies should also include parental data.
Speech and language development of children born following assisted reproductive technologies
2020, International Journal of Pediatric Otorhinolaryngology
Citation Excerpt :
A variety of studies were performed in different aspects of development in these children [1,12,13]. These aspects include cognitive [14,15], behavioral [16–18], neuromotor [14,19,20], and speech and language characteristics [4,14]. Speech and language capabilities of children born within these techniques were targeted in some studies [4,21,22].
Studies which targeted communication skills of children born following assisted reproductive technologies have reported contradictory results. Concerning the increasing rates of children born in these technologies and the importance of some factors as risk factors like birth weight, gestational age, and the number of children per birth in these procedures, studying speech and language skills is critical. So, the current study aimed to investigate the speech and language capabilities of Persian speaking children born following these procedures.
A descriptive and cross-sectional study was carried out in Babol city in 2016–2017 to investigate the receptive and expressive language and speech of Persian speaking children born in assisted reproductive technologies in the age range of 6–72 months. Parents of 78 children completed the Newsha Developmental Scale to assess language and speech skills. Then, the language and speech performance of the participants were compared in terms of gestational age, birth weight, number of children per birth, and sex in the current research and they are categorized as normal or having delay in language and speech development.
The participants had statistically significant difference for the receptive language in terms of gestational age (χ² (1) = 5.76, p = 0.01) and birth weight (χ² (1) = 8.22, p = 0.004) but in terms of the number of children per birth (χ² (1) = 7.11, p = 0.009) and sex (χ² (1) = 0.037, p = 0.84) did not have statistically significant difference. The children did not show significant difference for the expressive language in terms of gestational age (χ² (1) = 1.09, p = 0.29), birth weight (χ² (1) = 0.34, p = 0.55), the number of children per birth (χ² (1) = 1.58, p = 0.2), and sex (χ2 (1) = 0.037, p = 0.84). The participants of the present study did not have statistically significant difference in speech in terms of gestational age (χ² (1) = 2.82, p = 0.09), the number of children per birth (χ² (1) = 3.57, p = 0.06), and sex (χ2 (1) = 0.06, p = 0.79). They had significant difference in speech only in terms of birth weight (χ² (1) = 4.13, p = 0.04).
Based on the results of the administration of the Newsha Developmental Scale as a screening tool, it seems that some factors like sex and number of children per birth do not affect speech and language performance of children born following ART. Another factor including gestational age and birth weight had effects on some domains. It is essential to design longitudinal studies to follow the speech and language performance of this population.
Third grade academic achievement among children conceived with the use of in vitro fertilization: a population-based study in Texas
2020, Fertility and Sterility
To evaluate if there are differences in standardized testing results at the end of third grade between children conceived with the use of in vitro fertilization (IVF) and those conceived spontaneously.
Retrospective population-based cohort.
Texas public school system.
Singleton and twin children 8–9 years of age who took the third-grade public school standardized testing in Texas from 2012 to 2018.
None.
Standardized testing in reading and mathematics.
After exclusions, there were 6,970 IVF and 12,690 non-IVF children with reading scores and 6,973 IVF and 12,729 non-IVF children with mathematics scores. IVF children scored significantly higher in reading (singletons: 1,543 ± 2 vs. 1,525 ± 1; twins: 1,534 ± 2 vs. 1,504 ± 5 [mean ± SE]), and mathematics (singletons: 1,566 ± 2 vs. 1,550 ± 1; twins: 1,557 ± 2 vs. 1,529 ± 5). Children of mothers ≥30 years of age scored consistently higher than children of mothers 18–29 years of age. The differences were of similar magnitude between IVF and control children for older ages, but not significant for IVF. Within the IVF group, there were no significant differences between children born from fresh versus froze-thawed embryos.
Children of ages 8–9 years who were conceived with the use of IVF performed as well on third-grade reading and math assessments as their counterparts who were conceived spontaneously. We also found consistent racial and ethnic differences, gender differences, and beneficial effects of older maternal age. Because we were not able to adjust adequately for socioeconomic status and other confounding factors, which may explain some of the observed differences, we conclude that there is no negative effect of IVF conception on academic achievement in third grade.
Logro académico de tercer nivel de primaria entre niños concebidos con el uso de fecundación in vitro: un estudio basado en la población en Texas
Evaluar si hay diferencias en resultados de pruebas estandarizadas al final de tercer nivel de primaria entre niños concebidos con el uso de fecundación in vitro (IVF) y aquellos concebidos espontáneamente.
Cohorte retrospectiva basada en la población.
Sistema de escuela pública en Texas.
Niños únicos y gemelares de 8-9 años quienes tomaron la prueba estandarizada de tercer grado en la escuela pública en Texas de 2012 a 2018.
Ninguna.
Pruebas estandarizadas en lectura y matemática.
Luego de las exclusiones, hubo 6,970 niños IVF y 12,690 niños no IVF con puntuaciones de lectura y 6,973 niños IVF y 12,729 niños no IVF con puntuaciones de matemáticas. Los niños IVF puntuaron significativamente más alto en lectura (únicos: 1,543 ± 2 vs. 1,525 ± 1; gemelares 1,534 ± 2 vs. 1,504 ± 5 [media ± SE]), y matemáticas (únicos: 1,566 ± 2 vs. 1,550 ± 1; gemelares 1,557 ± 2 vs. 1,529 ± 5). Niños de madres ≥ 30 años de edad puntuaron considerablemente más alto que niños de madres de 18-29 años de edad. Las diferencias fueron de similar magnitud entre niños IVF y control para edades mayores, pero no significativas para IVF. Dentro del grupo IVF, no hubo diferencias significativas entre niños nacidos de embriones frescos frente a congelados.
Niños de 8-9 años que fueron concebidos con el uso de IVF realizaron tan bien las evaluaciones de lectura y matemáticas como sus contrapartes que fueron concebidos espontáneamente. También encontramos diferencias étnicas y raciales consistentes, diferencias de género, y efectos beneficiosos de mayor edad materna. Porque no somos capaces de ajustar adecuadamente por estatus socioeconómico y otros factores de confusión, que podrían explicar algunas de las diferencias observadas, concluimos que no hay efecto negativo de la concepción por IVF en el logro académico en tercer nivel de educación primaria.
Subfertility factors rather than assisted conception factors affect cognitive and behavioural development of 4-year-old singletons
2016, Reproductive BioMedicine Online
Research on cognitive and behavioural development of children born after assisted conception is inconsistent. This prospective study aimed to explore underlying causal relationships between ovarian stimulation, in-vitro procedures, subfertility components and child cognition and behaviour. Participants were singletons born to subfertile couples after ovarian stimulation IVF (n = 63), modified natural cycle IVF (n = 53), natural conception (n = 79) and singletons born to fertile couples (reference group) (n = 98). At 4 years, cognition (Kaufmann-ABC-II; total IQ) and behaviour (Child Behavior Checklist; total problem T-score) were assessed. Causal inference search algorithms and structural equation modelling was applied to unravel causal mechanisms. Most children had typical cognitive and behavioural scores. No underlying causal effect was found between ovarian stimulation and the in-vitro procedure and outcome. Direct negative causal effects were found between severity of subfertility (time to pregnancy) and cognition and presence of subfertility and behaviour. Maternal age and maternal education acted as confounders. The study concludes that no causal effects were found between ovarian stimulation or in-vitro procedures and cognition and behaviour in childrenaged 4 years born to subfertile couples. Subfertility, especially severe subfertility, however, was associated with worse cognition and behaviour.
Are children born through Intra-Cytoplasmic Sperm Injection (ICSI) having a lower intelligence quotient?
2016, Middle East Fertility Society Journal
Background: There is still concern about delayed mental development for children born through Intra-Cytoplasmic Sperm Injection (ICSI). In the present study, the intelligence quotient (IQ) of ICSI children at the age of 5–6 years was compared with that of the control group of naturally born (NB) children. Outcome measure: Full-scale IQ of the mental development in children born through ICSI in 5–6 years. Design: Cross-sectional study. Setting: Fatemehzahra Infertility and Reproductive Health Research Center of Babol – Iran. Participants: 28 live-birth singleton children 5–6 years of the first generation born after ICSI treatment. Methods: The mental development of 28 born through ICSI children at 5–6 years compared with 32 naturally born children as control using intelligence quotient (IQ) test obtained from the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) (Iranian version). Results: The mean full-scale IQ was 105.9 ± 14 for ICSI and 107.2 ± 12.9 for NB children which showed no significant difference. The only significant possible predictors of slightly lower full-scale IQ in ICSI children were lower parental education level and longer childcare in day center. Conclusion: Our finding provides some reassurance for parents of children born through ICSI regarding the child’s preschool IQ.

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: Funded by the Deutsche Forschungsgemeinschaft (DFG) (LU801/2-1, LU801/2-2).

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In vitro fertilizationNeuromotor development and mental health at 5.5 years of age of singletons born at term after intracytoplasmatic sperm injection ICSI: results of a prospective controlled single-blinded study in Germany

Objective

Design

Setting

Patient(s)

Main Outcome Measure(s)

Result(s)

Conclusion(s)

Section snippets

Study Design

Participation

Discussion

Acknowledgments

Fertil Steril

Reprod Biomed Online

Reprod Biomed Online

Lancet

Lancet

Lancet

J Pediatr

J Pediatr

Lancet

Lancet

Fertil Steril

Fertil Steril

Assisted reproduction—the epigenetic perspective

Hum Reprod Update

Human male infertility: chromosome anomalies, meiotic disorders, abnormal spermatozoa and recurrent abortion

Hum Reprod Update

Hospital care utilization of infants born after IVF

Hum Reprod

Imprinting diseases and IVF: Danish national IVF cohort study

Hum Reprod

In vitro fertilization
Neuromotor development and mental health at 5.5 years of age of singletons born at term after intracytoplasmatic sperm injection ICSI: results of a prospective controlled single-blinded study in Germany