Hum. Reprod. Advance Access originally published online on May 16, 2008
Human Reproduction 2008 23(8):1849-1857; doi:10.1093/humrep/den179
Socio-emotional and language development of 2-year-old children born after PGD/PGS, and parental well-being
1 Department of Developmental and Lifespan Psychology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium 2 Centre for Medical Genetics, UZ Brussel (University Hospital of Brussels), Brussels, Belgium
3 Correspondence address. E-mail: julie.nekkebroeck{at}vub.ac.be
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
BACKGROUND: The objective of this study was to assess socio-emotional and language development in 2-year-old children born after preimplantation genetic diagnosis (PGD) and genetic aneuploidy screening (PGS), intracytoplasmic sperm injection (ICSI) and natural conception (NC) and to assess parental well-being.
METHODS: Parents of 2-year-old PGD/PGS (n = 41), ICSI (n = 35) and NC (n = 53) singleton children were recruited. The socio-emotional development of the children was assessed using the Child Behavioural Checklist (CBCL) and the Short Temperament Scale for Toddlers. Parental stress and health status was measured with the Parent Stress Index and the General Health Questionnaire. Language development was assessed with the McArthur Communicative Development Inventories.
RESULTS: No differences were found for temperament, language development, parental stress or health status. The mothers in the PGD/PGS and ICSI group reported significantly fewer CBCL Total problems than their NC counterparts, whereas for the CBCL Externalizing problems, only the ICSI mothers reported fewer problems than their PGD/PGS and NC counterparts. Fathers in the ICSI group also rated their children as having fewer Externalizing and Total behavioural problems.
CONCLUSIONS: PGD/PGS conception does not adversely affect children's socio-emotional and language development at age 2, nor did parents differ from ICSI and NC parents for parental stress and health status.
Key words: embryo biopsy/child development/parental well-being/PGD/PGS
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
Preimplantation genetic diagnosis (PGD) is a procedure that was developed in the early nineties in which embryos obtained through intracytoplasmic sperm injection (ICSI) are analysed for a genetic disorder before the ‘unaffected’ embryos are implanted in the woman's uterus. As such, PGD is a very early form of prenatal diagnosis (Braude et al., 2002
). PGD is used for two broad indication groups (Sermon, 2006). The first group consists of couples at risk of having children with a genetic disease or chromosomal aberrations. The second group of patients consists of IVF patients with a low genetic risk but whose embryos are screened for chromosome aneuploidies to increase their chance of a successful pregnancy (Sermon, 2006). PGD for aneuploidy screening (PGS) is applied to improve the effectiveness of IVF in low prognosis patients, such as those with an advanced maternal age (Sermon, 2006). With every new procedure in artificial reproductive technology (ART), questions arise on the well-being of the children who are conceived in this way. The focus of most studies is on the physical health of these children (e.g. neonatal assessment, incidence of congenital anomalies) before neurodevelopmental outcomes expressed by cognitive and psychomotor development are addressed. Finally, but not less importantly, the psycho-social development of the child and parental well-being are investigated.
Every year, the European Society for Human Reproduction and Embryology (ESHRE) Consortium reports a steady rise in the number of centres practicing PGD and PGS and in the number of cycles, pregnancies and babies born (ESHRE PGD Consortium Committee, 2007). This growing popularity of PGD has highlighted the fact that there are no comprehensive data available on the use of PGD or on the health outcomes of babies born after this treatment (Baruch et al., 2006). In spite of the fact that PGD and PGS procedures include an ICSI treatment to obtain embryos in vitro and the apparent comparability between PGD/PGS and ICSI babies with regard to biometric characteristics (birth weight, length and head circumference) (Sermon, 2006), the developmental outcomes of ICSI children and parental well-being after ICSI conception cannot be generalized for children and families created after PGD/PGS because of the more invasive nature of the latter. In contrast to the child follow-up after PGD/PGS conception, the development of ICSI children and parental well-being have been investigated at different developmental stages by different centres around the world (Ponjaert-Kristoffersen et al., 2004; Barnes et al., 2004). From a theoretical point of view, it is argued that in ART families the transition to parenthood has been complicated by a fertility problem often resulting in delayed and stressful fulfillment of their desire for a child, which may induce problems in both the individual and relational well-being of parents and children. It has been suggested that parents who conceived after ART might suffer from more parenting stress, more marital conflict and may tend to overprotect their child or have unrealistic expectations towards their child, as the child is regarded as a very ‘precious’ (van Balen, 1998). However, these theoretical assumptions have not found empirical support. The health of the parent–ICSI child relationship and the couple relationship of those who conceived after ICSI has been investigated, and the results are reassuring. Some authors have found ICSI mothers to be more committed to being a parent, to be less hostile or aggressive towards their child (Barnes et al., 2004) and to experience less parenting stress than those who conceived naturally (Ponjaert-Kristoffersen et al., 2004), whereas ICSI fathers experience more warmth and affection and fewer feelings of neglect or indifference towards their child than their natural conception (NC) counterparts (Leunens et al., 2007). Overall, these parents were no more likely to have marital difficulties, mental health problems or parenting stress than parents who conceived naturally (Place and Englert, 2002; Barnes et al., 2004; Leunens et al., 2007).
The individual psycho-social well-being of ICSI children has also been investigated from an early age. Most studies failed to find any differences in temperament between ICSI and NC children (Barnes et al., 2004) or increased levels of behavioural problems in ICSI children (Gibson et al., 2002; Place and Englert, 2002; Wennerholm et al., 2003; Barnes et al., 2004). Some studies even report that ICSI children display fewer behavioural problems (Sutcliffe et al., 2004; Ponjaert-Kristoffersen et al., 2005; Leunens et al., 2007). Place and Englert (2003) administered the Brunet-Lézine scale and found that ICSI children at the age of 9 months and 18 months obtained comparable developmental quotients constituted on the basis of four developmental areas: posture and coordination (motricity), language and sociability. Agarwal et al. (2005) found no statistical differences after adjustment for socio-demographic factors between 2-year-old ICSI and NC children on the Vineland Adaptive Behaviour Scale, which assesses general adaptive behaviour, communication, socialization and motor skills. In a study by Sutcliffe et al. (2001, 2003), children of around 15 months were assessed with the Griffiths mental development scales (Griffiths, 1996), yielding several subquotients including subquotients for locomotor, personal-social and hearing-speech skills. ICSI children were around the midpoint for the Griffiths scales and did not differ significantly for Griffiths' quotients and subquotients. Squires et al. (2003) studied 4- to 48-month-old ICSI children with the Ages and Stages Questionnaires. ICSI children were not more at risk of developmental delay in gross and fine motor skills, communication and problem-solving or in the personal-social domain compared with a normative sample.
Different authors have therefore concluded that the children's socio-emotional development (Place and Englert, 2003; Barnes et al., 2004; Ponjaert-Kristoffersen et al., 2004, 2005; Leunens et al., 2007) and language development (Place and Englert, 2003; Squires et al., 2003; Sutcliffe et al., 2001, 2003; Agarwal et al., 2005) as well as parental well-being, family functioning, and parent-child relationships in families who conceived after ICSI appear to be very similar to those conceived naturally (Barnes et al., 2004).
For patients who conceived after PGD/PGS, as well as practitioners and policy-makers, it is of great importance that the safety of the biopsy procedures be fully guaranteed. From this perspective, it is essential to ensure prenatal and neonatal follow-up, but formal child assessment and the assessment of parental well-being are equally important. To date, only one study has investigated the development of PGD/PGS children focusing on the mental and motor development (Nekkebroeck et al., 2008). However, research into the specific psychosocial developmental outcomes of PGD/PGS children and parental well-being is still non-existent. This study is part of a larger overall study in which mental and motor development of a cohort of 2-year-old children born after PGD/PGS was also assessed and reassuring results for these developmental areas were found (Nekkebroeck et al., 2008). The objective here is to compare the socio-emotional and language developmental outcomes of children born after PGD/PGS, ICSI and NC, and to evaluate parental well-being in all three conception groups. The three most common psychological problems in childhood are communication disorders, mild mental impairment and behaviour problems (Sutcliffe and Derom, 2006). According to Piaget, toddlers are entering a new phase of cognitive development called the ‘preoperational phase’ that is characterized by thought in symbolic form or the child's ability to use a symbol, an object or a word to stand for something. Around 18 months, children experience a language spurt, which is an important predictor not only of cognitive development, but also of social development because the child's ability to be a successful communicator can affect social relationships with parents, peers and others (Bukatko and Daehler, 1995). Thus, in this study in conjunction with the study on mental and psychomotor development (Nekkebroeck et al., 2008), all of the important areas of psychological development of 2-year-olds are covered.
A control group of children born after ICSI and their parents was included to identify any differences in child or parental outcomes attributable to the embryo biopsy or to the ICSI method. Given that this is the first follow-up study on PGD/PGS children's socio-emotional and language development and on parental well-being, the main research question was rather explorative: ‘Does PGD/PGS have any impact on the child's socio-emotional and language development and the well-being of parents, after controlling for socio-demographic variables?’
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
Study participants
Parents of PGD, PGS and ICSI children were recruited from the register of the Centre for Medical Genetics of the UZ Brussels. Parents of NC children were recruited from the university day-care centres and from a paediatrician's practice. Parents of twins were excluded because of the possible confounders (e.g. extreme prematurity and low birth weight) that may have interfered with developmental outcome (Miceli et al., 2000
; Sutcliffe and Derom, 2006). Parents of children born between December 2002 and February 2005 were recruited and invited to complete a number of questionnaires. Within this period 138 PGD/PGS singleton children were born of which 74 PGD/PGS children were eligible because they were singleton, Caucasian, living in Belgium and their mother tongue was Dutch, French or English.
Because this is the first study on the socio-emotional and language development of these children and the well-being of their parents, we wanted to reach and include as many children as possible. Therefore a small number of children (n = 10) born at <37 weeks of gestation equally distributed over the different conception types were not excluded from the study. In combination with the gestational age, birth weight (low or very low) is also an important factor that determines the health of the newborn. Especially newborns that are small for gestational age are at risk (Clausson et al., 1998). These children (n = 10) were only ‘moderately’ premature (33–36 weeks of gestation) and most had a normal birth weight (
2500 g). Four children had a low birth weight (>1500 g). None of the children had a very low birth weight or obtained an Apgar score of less than 9 after 10 min.
Of the initial cohort, 70 PGD/PGS children were actually assessed for mental and motor developments. ICSI (n = 70) and NC (n = 70) controls were selected to match the initial cohort of 70 PGD/PGS cases as closely as possible for gender, maternal educational level (high:higher education qualification or a degree; medium:fully passed school matriculation; low:partially passed school matriculation or no qualification at all), mother tongue and birth order (having an older sibling or otherwise) and, they were also assessed for mental and motor development. The results are reported elsewhere (Nekkebroeck et al., 2008). From this cohort, only those parents understanding enough Dutch in order to complete some questionnaires were invited to participate in the study. Since not every parent in each of the conception groups responded to the questionnaires, the matching in the context of the investigation of the mental and motor development was not useful when comparing data obtained from the questionnaires filled out by the parents. Of the PGD/PGS parents, 52 out of 138 children met the inclusion criteria, i.e. having a Caucasian singleton child, living in Belgium and having a Dutch mother tongue. Most of the other parents (n = 61) lived abroad, 7 parents who met the inclusion criteria refused to participate, and 18 parents did not speak or understand enough Dutch to complete the questionnaires. Of the eligible PGD/PGS parents (n = 52), 41 (78.8%) participated in the study. The participation rate of the parents who conceived after ICSI (n = 54) was 64.8% (n = 35). Of the parents who conceived naturally (n = 69), 53 (76.8%) participated in the study. Because of a limited time frame and funding, it was not possible to recruit additional ICSI children and invite their parents to fill out questionnaires. The reason for the higher number of parents participating in the NC group was because we recruited these parents in Dutch speaking day-care centres. So, there were more parents in this group understanding enough Dutch in order to complete some questionnaires and hence could be invited to participate in the study.
In the case of parents who had received PGD or PGS treatment, the biopsy technique used (aspiration of blastomeres) on 8-cell embryos was the same. Embryos were decompacted prior to biopsy by short incubation (5–10 min) in a Ca2+- and Mg2+-free medium (EB-10, Vitrolife). Laser technology was used to create an opening in the zona pellucida (Fertilase, MTM Medical Technologies, Montreux, Switzerland, or Octax Laser Shot, Octax Microscience GmbH, Germany, using Octax Eye Ware software). One or two nucleated blastomeres were then gently aspirated through the hole by means of an aspiration pipette (inner diameter 35–40 µm). After biopsy, the embryo was transferred to the sequential medium for blastocyst culture, leaving the blastomeres in the biopsy dish (De Vos, personal communication). One nucleated blastomere was removed in 4 of the PGD/PGS cases (n = 41) and two blastomeres were removed in 36 of the PGD/PGS cases (n = 41). For one case, it was not possible to recover the number of blastomeres removed. Because of the small number of children in each conception group and the similar nature of the embryo biopsy (aspiration of blastomeres) in case of PGD and PGS treatment, we considered the PGD (n = 19) and PGS (n = 22) children to be part of one and the same conception group.
Procedure
In order to assess the child's socio-emotional and language development and parental well-being, parents were asked to complete five questionnaires and return them in a postage-paid envelope. The protocol was approved by the ethics committee of the UZ Brussel in accordance with national regulations. In parallel to the questionnaire survey, the 2-year-old children received an assessment of their mental and psychomotor development using the Bayley Scales of Infant Development-II-NL (Dutch version) (BSID-II-NL) (van der Meulen et al., 2002; Nekkebroeck et al., 2008). This assessment was followed by a medical examination of the child by a paediatrician who also questioned the mothers about socio-demographic aspects, pregnancy, delivery, and the neonatal outcomes of their child (Desmyttere et al., submitted).
Outcome measures
In order to gather information about the child's socio-emotional development, parents were asked to complete the short version of the Short Temperament Scale for Toddlers (STST) by Prior et al. (2000) and the Child Behavioural Checklist (CBCL) by Achenbach and Rescorla (2000). The STST (Prior et al., 2000) is based on factor analyses of the 94-item Toddler Temperament Scale by Fullard et al. (1984), generating a 30-item, parent-completed questionnaire eliciting information on their toddler's temperament. Each item is rated on a 6-point scale ranging from 1 (‘almost never’) to 6 (‘almost always’), reflecting how much the parent considers each of the behaviours to be characteristic of their child (e.g. the child gets sleepy at around the same time every evening). The 30 items are then averaged, generating six dimensions of temperament (approach, cooperation/manageability, persistence, rhythmicity, distractibility and reactivity). On the basis of the averaged score of three dimensions (approach, cooperation/manageability, reactivity), children were placed in one of the three temperament categories, i.e. easy, average or difficult, with a higher score indicating a more ‘difficult’ temperament.
The CBCL (Achenbach and Rescorla, 2000) gives information about the child's emotional and behavioural problems. Descriptions of 113 problems are presented, and the parent indicates whether they are ‘not true’, ‘somewhat or sometimes true’ or ‘very true or often true’ of their child, with item scores of 0, 1 or 2. The Total score (adding all items) is converted into a T-score to normalize the distribution and to take into account child age (range 23–100), with different conversion tables for boys and girls. The symptoms are further subdivided into externalizing problems (e.g. fights, temper tantrums) and internalizing problems (e.g. worries), which are also converted to normalized T-scores with a score of 50 representing the 50th percentile. A T-score of 60 is at the bottom of the clinical range, with T-scores of 64 or more representing marked problems.
Language comprehension and production were rated according to the Dutch version of the McArthur Communicative Developmental Inventories (N-CDI) (Zink and Lejaegere, 2003). The N-CDI is used for prevention and early detection of communication problems in 8- to 30-month-old children with Dutch mother tongue. Parents are presented with a list of words and have to check whether the child understands and/or produces the word. The number of words understood and produced is summated and translated in a percentile score and a corresponding ‘language age’.
As an indication of current parental health, parents completed the 28-item version of the General Health Questionnaire (GHQ) (Goldberg and Hillier, 1979), which describes four dimensions: somatic symptoms, anxiety, social dysfunction and severe depression, each with seven items (scored 0, 1, 2 or 3), with scores ranging from 0 to 21 and a total symptom score (range 0–84). Current stress regarding parenting was examined using the Nijmeegse Ouderlijke Stress Index-Korte vorm (NOSIK) (de Brock et al., 1992). This is the Dutch Short version of the Parent Stress Index (Abidin, 1990). The NOSIK consists of 25 items to be rated on a 6-point scale ranging from 1 (‘totally disagree’) to 6 (‘totally agree’). The total parenting stress score is the summation of all 25 item scores. By comparing the raw score with the norm, the score is translated into a stress level category (very low, low, below average, average, above average, high or very high stress level). There are different conversion tables for mothers and fathers and for clinical and non-clinical populations.
Statistics
Univariate analyses of continuous variables were conducted using SPSS 15.0 for Windows to determine differences in mean scores between children conceived after PGD/PGS, ICSI and NC controls. If a group effect was identified post hoc, Tukey's test was conducted to determine which conception groups differed significantly from each other. Categorical variables were analysed using 
2. Because this was the first study that investigated PGD/PGS children's development, the analyses were not designed to test a preconceived model of factors influencing socio-emotional, language development or parental well-being, but instead to control for socio-demographic variables that might interfere with the child and parental outcomes. Hierarchical regression analyses were conducted in SPSS 15.0 to control for socio-demographic differences between the conception groups. In addition to conception mode, demographic factors were regressed as independent variables on the outcome measures for socio-emotional and language development and parental well-being. A significance level of P < 0.05 was accepted throughout.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
Demographics
The parents of 129 children, of whom 41 were conceived after PGD/PGS, 35 after ICSI and 53 naturally, completed a number of questionnaires in Dutch. Most questionnaires were filled out by both parents (72.1%, n = 93). In 25.6% of cases, only the mother filled out the questionnaire (n = 33), and in 2.3% of the cases, only the father filled out the questionnaire (n = 3) [
2 (6) = 6.06, P = 0.416]. The response rate per respondent (mother and/or father) and per questionnaire are shown in Table I.
|
Gender, maternal and paternal educational level, paternal employment rate, birth order, mother tongue and type of childcare were not associated with the mode of conception (Table II). Moreover, birth weight, gestational age and the number of children born after <37 weeks of gestation were the same in the three conception groups (Table II). The included ‘preterm’ children in the PGD/PGS group (n = 3) were born between 35–36 weeks of gestation. In the ICSI group (n = 4), these children were born between 32–36 weeks of gestation and in the NC group (n = 3), these children were born between 34–36 weeks of gestation.
|
Although not clinically relevant, there was a difference in the average age of the children at the time of assessment between the conception groups, with the PGD/PGS children being slightly yet significantly younger than the ICSI children (post hoc Tukey: PGD/PGS<ICSI P = 0.042) (Table II). Moreover, the NC mothers were significantly younger at the time of delivery than the mothers in the PGD/PGS and ICSI groups (post hoc Tukey: NC<PGD/PGS P = 0.000 and NC<ICSI P = 0.000) (Table II). The mean age of the NC fathers tends to be younger than that of the fathers in the ICSI conception group (post hoc Tukey: NC<ICSI P = 0.062). On average, the mothers who conceived after PGD/PGS more often worked part-time (working 65% of the time) more often than the NC mothers (working 89% of the time) (post hoc Tukey: PGD/PGS<NC P = 0.001) (Table II). Most of the children in all three conception groups lived in a two-parent family consisting of both biological parents, although more NC children had parents who were divorced in comparison to the PGD/PGS children (
2(3) = 7.53, P = 0.057) and ICSI children [2(3) = 5.86, P = 0.053] (Table II). Additional analyses, comparing respondents with parents who did not return the questionnaires for the socio-demographic characteristics listed in Table II, revealed no significant differences between these two groups.
Controlling for socio-demographic factors
Hierarchical regression analyses were performed following the analytical procedure of Pedhazur (1982) in order to remove all the variance in socio-emotional and language developmental outcomes and outcomes on parental well-being that is associated with the socio-demographic variables. All the steps in the hierarchical regression analysis were performed for all outcome scores separately. The dependent variables in the regression were: the CBCL Total, externalizing and internalizing scores, the STST Total scores, the GHQ Total scores and the NOSIK Total scores of both mothers and fathers and the N-CDI comprehension and production scores. The socio-demographic variables included in the regressions are: gender, birth order, mother tongue, age at assessment, gestational age in weeks, Apgar score at 5 min, birth weight, maternal age at child birth, paternal age at assessment, educational levels of mothers and fathers, family composition, mean percentages of maternal and paternal employment and type of childcare (Table II). According to Tabachnik and Fidell (2001) the number of socio-demographic variables controlled for in the analyses is still in balance with the number of cases included in the analyses. In order to remove the variance due to the non-linear relationships, the first step in the hierarchical regression analysis was to test for a quadratic trend in the relationship between the outcomes for socio-emotional development, language development, and parental well-being and the socio-demographic variables by comparing the two R2 values. The first R2 includes all non-quadratic terms, whereas the second R2 additionally includes the quadratic terms. The difference between the two R2 indicates the increment in the proportion of variance accounted for by the quadratic terms. All the increments for the dependent variables were non-significant, hence in the subsequent steps of the analysis a linear model (linear regression curves) was used. Next, we investigated whether the linear regression curves for the dependent variables were parallel for all three conception groups. To test this interaction between the conception groups and the socio-demographic variables for all dependent variables, all singular terms were compared with the same terms including the interaction terms. The increments in explained variance due to the group interaction for scores reported by the mothers and fathers on the CBCL Total problem scale, internalizing problem scale and externalizing problem scale, the GHQ, the NOSIK, the STST, and the N-CDI word comprehension and production scale were all non-significant. These non-significant interaction effects indicate that the socio-demographic variables are related in the same way (parallel regression curves) to the scores on these scales for the three conception groups. Finally, and most importantly, the overall effects indicate whether after controlling for socio-demographic variables, the inclusion of the predictor variable ‘conception group’ significantly contributes towards explaining the variance in the CBCL Total, the externalizing and internalizing scores, the STST Total scores, the GHQ Total scores and the NOSIK scores as reported by both mothers and fathers and the N-CDI word comprehension and production scores.
Socio-emotional development
There were no differences in the proportion of children above the clinical threshold points of the CBCL according to both mothers and fathers [CBCL Total score: mothers: 2 (2) = 1.71, P = 0.43, Fathers: 2 (2) = 1.04, P = 0.59; Internalizing score: mothers: 2 (2) = 2.54, P = 0.28, Fathers: 2 (2) = 1.28, P = 0.53; Externalizing score: mothers: 2 (2) = 2.66, P = 0.27, Fathers: 2 (2) = 2.14, P = 0.34]. Even after all the confounding variables have been controlled for, the three groups are indistinguishable for CBCL internalizing scores as reported by both mothers and fathers (Table III). Furthermore, no significant conception group differences were found for externalizing and Total problem behaviour (Table III). However, for the CBCL externalizing scores and the CBCL Total scores according to both parents, the predictor variable ‘conception group’ does significantly contribute towards explaining the variance after controlling for socio-demographic variables (Table V). More precisely, after controlling for socio-demographic variables, the mothers in the PGD/PGS group as well as those in the ICSI group report significantly fewer Total problems than their NC counterparts (CBCL Total PGD/PGS Mothers: standardized β = –0.25, P = 0.031; CBCL Total ICSI Mothers: standardized β = –0.31, P = 0.007), while for the CBCL Externalizing problems, only the ICSI mothers report fewer problems than their NC counterparts (CBCL EXT ICSI Mothers: standardized β = –0.31, P = 0.010) and a trend was observed for the PGD/PGS mothers indicating that they also report fewer externalizing problems (CBCL EXT PGD/PGS Mothers: standardized β = –0.21, P = 0.074). As for the CBCL Total and Externalizing scores as reported by the fathers, again only the ICSI fathers gave lower ratings on these scales than their PGD/PGS and NC counterparts (Table V) (CBCL EXT ICSI Fathers: standardized β = –0.41, P = 0.008; CBCL Total ICSI Fathers: standardized β = –0.44, P = 0.005).
|
|
A similar proportion of mothers and fathers from all three conception groups experienced their child's temperament as easy, average or difficult [Mothers:
2 (4) = 5.90, P = 0.21, Fathers: 2 (4) = 5.10, P = 0.28]. There were no differences in temperament subscale scores between the children from all three conception groups according to mothers or fathers, nor were there any differences in total temperament scores of children according to mothers or fathers, after controlling for socio-demographic variables (Table III).
Language development
Even after controlling for socio-demographic confounders, the mean Language Comprehension score and Language Production score did not significantly differentiate between the three conception groups, nor did the corresponding age for language comprehension and production differ between the PGD/PGS, ICSI and NC groups (Table III).
Parental well-being
No differences were found between the three conception groups for mothers and fathers when parenting stress levels were compared with the NOSIK (Table IV). However, when socio-demographic confounders were taken into account, a trend was observed for the scores of mothers and fathers on the NOSIK when the predictor variable ‘conception groups’ was included in the analyses (see Table V). The ICSI mothers and fathers reported less stress from parenting (NOSIK Mothers: standardized β = –0.279, P = 0.020; NOSIK Fathers: standardized β = –0.275, P = 0.048). On the other hand, an equal proportion of women and men from all three conception groups experienced low, moderate or high levels of parenting stress (Table IV). Total scores on the GHQ were not significantly different between women and men from all three conception groups, even after controlling for socio-demographic confounders. Parents from all three conception groups obtained similar scores on the subscales: somatic symptoms, anxiety, social dysfunction and severe depression (Table IV).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
The aim of this study was to explore the socio-emotional and language development of 2-year-old singleton PGD/PGS children compared with ICSI and NC controls and to assess parental well-being in all three conception groups. This study is part of a larger overall study in which mental and motor development of a cohort of 2-year-old children born after PGD/PGS was also assessed, and reassuring results for these developmental areas were found (Nekkebroeck et al., 2008
). Because this is the first study on the socio-emotional and language development of these children and of parental well-being, we wanted to reach and include as many children as possible. Therefore a small number of children (n = 10) born at <37 weeks of gestation and equally distributed over the different conception types participated in the study. Most of these few children were born ‘moderately’ premature (33–36 weeks of gestation) but had a normal birth weight (2500 g). Four children had a low birth weight (>1500 g) and none of the children had a very low birth weight. Furthermore we controlled for gestational age in the analyses. So, there was no reason to exclude these children from the analyses neither from a medical, nor from a methodological, point of view. As this was the first study focusing on developmental areas, other than mental and motor development, of children conceived after PGD and PGS, the research question was kept rather explorative and the findings cannot be compared with the outcomes of similar studies. In reply to our main research question, we can conclude that conception after embryo biopsy in the case of PGD and PGS has no adverse impact on the socio-emotional and language development of 2-year-old children compared with ICSI and NC children. Moreover, the well-being of parents who conceived after PGD/PGS was comparable to the well-being of the ICSI and NC parents.
Even after controlling for socio-demographic variables, the mode of conception had no impact on most of the child and parental outcomes. However, even after controlling for the socio-demographic variables, the PGD/PGS mothers deviated from the mothers who conceived naturally in that they reported fewer overall behavioural problems with their child according to the CBCL. The same was true for both ICSI parents, who, additionally, also reported fewer externalizing behavioural problems according to the CBCL than the parents who conceived naturally. These findings cannot be explained by the somewhat lower response rate to the questionnaires in the ICSI group, since there were no differences in socio-demographic features between the participating parents and those who did not participate in the study. On the other hand, these findings are not very surprising, because they are in line with previous studies of ICSI children in which the authors found that ICSI parents tend to report fewer behavioural problems (Sutcliffe et al., 2004; Ponjaert-Kristoffersen et al., 2005; Leunens et al., 2007).
It has been assumed that ICSI parents might be more tolerant towards their child's behaviour because they have made greater efforts to have their child than parents who conceived naturally. A more complicated transition to parenthood might generate more awareness and sensitiveness towards their ICSI child, resulting in greater efforts to manage and support their children (Sutcliffe et al., 2004). On the other hand, it could also be that it is especially parents who conceived after ICSI who tend to under-report child behavioural problems because of their need to demonstrate their suitability as a parent and their need to move on from the issue of infertility and the associated treatment in order to complete the transition to ‘normal parenthood’ (Greenfeld et al., 1996). However, the results need to be put in perspective, since none of the average scores reported by parents in all three conception groups fell within a clinical range, which suggests that most children in all three conception groups display normal behaviour. However, it is not clear why only the mothers, and not the fathers, in the PGD/PGS group reported fewer overall behavioural problems. In this study, the PGD and PGS children were considered as one and the same conception group, since in both treatment groups an embryo biopsy is performed by aspiration of blastomeres. However, the indication to perform PGD or PGS differs, with PGD being a more suitable choice in the case of genetic problems and PGS in the case of advanced maternal age and/or fertility problems. The PGD and PGS populations therefore have different medical histories and family backgrounds, a fact that might indirectly influence the socio-emotional and language outcomes. Because of the sampling limitations (only parents of children born within a specific period who met the inclusion criteria were eligible) it was not possible to recruit enough parents to compare the four conception groups (PGD, PGS, ICSI and NC controls) and to investigate whether the PGS children and their families more resemble their ICSI or PGD counterparts.
The strengths of this study are manifold. Participation rates were high, which means that participation bias was reduced to a minimum. Very similar control groups were recruited and the possible confounding effect of the socio-demographic variables was eliminated in the statistical analyses. Given that twins were excluded from this study because of the possible interference of prematurity and low birth weight with developmental outcome, which are known to be more common in twins and triplets, and the more complicated parenting situation, the generalizability of our findings is limited. Moreover, the results obtained are based exclusively on parental reports. A multiple informant approach would have made the results more valid, e.g. by including reports of a secondary caregiver (e.g. child-minder). In sum, the weaknesses of this study are that data were collected from a small sample exclusively by relying on parental reports, multiples were excluded and there was no distinction between children born after PGD or PGS.
In conclusion, the results of this study suggest that according to parental judgement, PGD and PGS singleton children are not at greater risk of developing behaviour or language problems at the early age of 2 than are ICSI and NC controls. Since this was a single-centre study, confirmatory investigations from other centres with larger cohorts are needed. Further research could benefit from considering PGD and PGS as different conception groups and might also include PGD and PGS twins and preferably compare them with NC twins. Furthermore, it is evident that continuing assessment of PGD/PGS children and their parents at later ages with a multiple-method, multiple-informant approach is necessary in order to make these reassuring results more solid.
|
Funding |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
The Willy Gepts Fund financed the original project, which was entitled: Follow-up study of 2-year-old children born after PGD and aneuploidy screening on 8-cell embryos. The funding source had no responsibility for the design of the study or for the interpretation of data.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
The authors wish to thank the parents and children who participated in the study. A special word of thanks goes to Sarah Maes, research nurse, and Christine Merckx for their assistance in the recruitment of families and children and logistic support.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
Abidin R. Parenting Stress Index Test Manual. (1990) Charlotsville, VA: Pediatric Psychology Press.
Achenbach TM, Rescorla LA. Manual for ASEBA Preschool Forms & Profiles (2000) Burlington, VT: University of Vermont, Research Center for Children, Youth, & Families.
Agarwal P, Loh SKE, Lim SB, Sriram B, Daniel ML, Yeo SH, Heng Derrick. Two-year neurodevelopmental outcome in children conceived by intracytoplasmic sperm injection: prospective cohort study. BJOG (2005) 112:1376–1383.[Medline]
Barnes J, Sutcliffe AG, Kristoffersen I, Loft A, Wennerholm U-B, Tarlatzis BC, Kantaris X, Nekkebroeck J, Hagberg BS, Madsen SV, et al. The influence of assisted reproduction on family functioning and children's socio-emotional development: results from a European study. Hum Reprod (2004) 19:1480–1487.
Baruch S, Adamson GD, Cohen J, Gibbons WE, Hughes MR, Kuliev A, Munné S, Rebar RW, Simpson JL, Verlinsky Y, et al. Genetic testing of embryos: a critical need for data. Reprod Biomed online (2006) 12:389. author reply 390.[Medline]
Braude P, Pickering S, Flinter F, Ogilvie CM. Preimplantation genetic diagnosis. Nat Rev Genet (2002) 3:941–953.[CrossRef][Web of Science][Medline]
Bukatko D, Daehler W. Child Development: A Thematic Approach (1995) 2nd edn. Boston: Houghton Mifflin Company.
Clausson B, Cnattingius S, Axelsson O. Preterm and term births of small for gestational age infants: a population-based study of risk factors among nulliparous women. Br J Obstet Gynaecol (1998) 105:1011–1017.[Web of Science][Medline]
de Brock AJLL, Vermulst AA, Gerris JRM, Abidin RR. NOSI: Nijmeegse Ouderlijke Stress Index. Swets Test services. (1992).
Desmyttere S, De Schepper J, Nekkebroeck J, De Vos A, De Rijcke M, Staessen S, Liebaers I, Bonduelle M. Two year auxological and medical outcome of singletons born after embryo biopsy applied in preimplantation genetic diagnosis or preimplantation genetic screening. Hum Reprod. (submitted).
ESHRE PGD Consortium Committee. ESHRE Preimplantation genetic diagnosis consortium: data collection VI. Hum Reprod (2007) 22:323–336.
Fullard W, McDevitt SC, Carey WB. Toddler Temperament Scale. J Pediatr Psychol (1984) 9:205–217.
Gibson FL, McMahon C, Cohen J, Leslie G, Saunders D. Children conceived through ICSI and IVF at 5 years of age: Behavioral adjustment, parenting stress and attitudes: A comparative study. Fertil Steril (2002) 78(Suppl 1):3.
Goldberg DP, Hillier VF. A scaled version of the General Health Questionnaire. Psychol Med (1979) 9:139–145.[Web of Science][Medline]
Greenfeld DA, Ort SI, Greenfeld DG, Jones EE, Olive DL. Attitudes of IVF parents regarding the IVF experience and their children. J Assist Reprod Genet (1996) 13:266–274.[CrossRef][Web of Science][Medline]
Griffiths R. The Griffiths Mental Development Scales. (1996) Henley: Association for Research in Infant and Child Development. Test Agency.
Leunens L, Célestin-Westreich S, Bonduelle M, Liebaers I, Ponjaert-Kristoffersen I. The influence of intracytoplasmic sperm injection (ICSI) on children's Cognitive, Psychomotor, Socio-emotional Development and Family Functioning. (2007) Brussels, Belgium: Vrije Universiteit Brussel. Doctoral dissertation.
Miceli PJ, Goeke-Morey MC, Whitman TL, Kolberg KS, Miller-Loncar C, White RD. Brief report: birth status, medical complications and social environment: individual differences in development of preterm, low birth weight infants. J Pediatr Psychol (2000) 25:353–358.
Nekkebroeck J, Bonduelle M, Desmyttere S, Van den Broeck W, Ponjaert-Kristoffersen I. Mental and Psychomotor development of 2-year-old children born after PGD/PGS. Hum Reprod (2008) Epub February 19, 2008.
Pedhazur EJ. Multiple Regression in Behavioral Research: Explanation and Prediction. (1982) Holt: Rinehart and Winston.
Place I, Englert Y. The emotional and behavioral development of ICSI children. How are the ICSI families coping in comparison with the IVF and run-of-the-mill families? Abstracts of the 18th Annual Meeting of the ESHRE, Vienna, Austria (2002).
Place I, Englert Y. A prospective longitudinal study of the physical, psychomotor and intellectual development of singleton children up to 5 years who were conceived by intracytoplasmic sperm injection compared with children conceived spontaneously and by in vitro fertilization. Fertil Steril (2003) 80:1388–1397.[CrossRef][Web of Science][Medline]
Ponjaert-Kristoffersen I, Tjus T, Nekkebroeck J, Squires J, Verté D, Heirman M, Bonduelle M, Palermo G, Wennerholm U-B, on behalf of the Collaborative study of Brussels, Göteborg, New York. Psychological follow-up of 5-year-old ICSI children. Hum Reprod (2004) 19:2791–2797.
Ponjaert-Kristoffersen I, Bonduelle M, Barnes J, Nekkebroeck J, Loft A, Wennerholm U-B, Tarlatzis BC, Peters C, Hagberg BS, Berner A, et al. International collaborative study of intracytoplasmic sperm injection-conceived, in vitro fertilization- conceived and naturally-conceived 5-year-old child outcomes: cognitive and motor assessments. Pediatrics (2005) 115:e283–e289.
Prior M, Sanson AV, Smart DF, Oberklaid F. Pathways from infancy to adolescence: Australian Temperament project 1983–2000. In: Australian Institute of Family Studies (2000) Melbourne. Australia.
Sermon KD. Preimplantation genetic diagnosis. Verh K Acad Geneeskd Belg (2006) 68:5–32.[Medline]
Squires J, Carter A, Kaplan P. Developmental monitoring of children conceived by intracytoplasmic sperm injection and in vitro fertilization. Fertil Steril (2003) 79:453–454.[CrossRef][Web of Science][Medline]
Sutcliffe AG, Derom C. Follow-up of twins: Health, behaviour, speech, language outcomes and implications for parents. Early Hum Dev (2006) 82:379–386.[CrossRef][Web of Science][Medline]
Sutcliffe AG, Taylor B, Saunders K, Thornton S, Leiberman BA, Grudzinkas JG. Outcome in the second year of life after in-vitro fertilisation by intracytoplasmic sperm injection: a UK case control study. Lancet (2001) 357:2080–2084.[CrossRef][Web of Science][Medline]
Sutcliffe AG, Saunders K, McLachlan R, Taylor B, Edwards Ph, Grudzinkas G, Leiberman B, Thornton S. A retrospective case-control study of developmental and other outcomes in a cohort of Australian children conceived by intracytoplasmic sperm injection compared with a similar group in the United Kingdom. Fertil Steril (2003) 79:512–516.[CrossRef][Web of Science][Medline]
Sutcliffe AG, Edwards PR, Beeson C, Barnes J. Comparing parent's perceptions of IVF conceived children's behaviour with naturally conceived children. Inf Ment Health J (2004) 25:163–170.[CrossRef]
Tabachnik BG, Fidell LS. Using Multivariate Statistics (2001) 4th edn. Boston: Allyn and Bacon.
van Balen F. Development of IVF children. Dev Rev (1998) 18:30–46.[CrossRef][Web of Science][Medline]
van der Meulen BF, Ruiter SAJ, Lutje Spelberg HC, Smrkovsky M. Bayley Scales of Infant Development (2002) 2nd edn. Swets & Zeitlinger. Dutch version (BSID-II-NL).
Wennerholm UB, Bergh C, Niklasson A, Borres M, Amark K, Heiman M, Tjus T, Hök Wikstrand M. Health and development in children born after ICSI. Abstracts of the 19th Annual Meeting of the ESHRE, Madrid, Spain (2003).
Zink I, Lejaegere M. N-CDI's Lijsten voor Communicatieve ontwikkeling: korte vormen. (2003) Aanpassing en hernormering van de Mac Arthur Short Form Vocabulary Checklists van Fenson et al. Acco: Leuven/Leusden.
Submitted on February 6, 2008; resubmitted on March 25, 2008; accepted on April 8, 2008.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||