Porphyrin a as a precursor of heme a in Candida utilis

Background: An increased risk of major congenital abnormalities after IVF and ICSI has been described, but underlying mechanisms are unclear. This study evaluates the effects of ovarian hyperstimulation, the in vitro procedure and time to pregnancy (TTP) - as proxy for the severity of subfertility - on the prevalence of dysmorphic features. Design/methods: Participants were singletons born following controlled ovarian hyperstimulation-IVF/ICSI (COH-IVF/ICSI; n = 66), or modified natural cycle-IVF/ICSI (MNC-IVF/ICSI; n = 56), or to subfertile couples who conceived naturally (Sub-NC; n = 86). Dysmorphic features were assessed according to the method of Merks et al., and are classified into 'minor variants' (minor anomalies or common variants) and 'abnormalities' (clinically relevant or irrelevant abnormalities). We focussed on minor anomalies as they indicate altered embryonic development and because they have the advantage of a higher prevalence. Results: The prevalences of any of the outcome measures were similar in the three groups. One or more minor anomalies, our primary outcome measure, occurred in 50% of COH-IVFACSI, 54% of MNC-IVF/ICSI and 53% of Sub-NC children. TTP in years was significantly associated with abnormalities (adjusted0R= 120; 95%CI = 1.02-1.40). especially with clinically relevant abnormalities (adjustedOR = 1.22; 95%CI = 1.01-1.48). Conclusions: The study indicates that ovarian hyperstimulation and the in vitro procedure are not associated with an increase in dysmorphic features. The positive association between TTP and clinically relevant abnormalities suggests a role of the underlying subfertility and its determinants in the genesis of dysmorphic features. (C) 2012 Published by Elsevier Ireland Lt

Maternal anxiety is related to infant neurological condition, paternal anxiety is not

Background: Parental anxiety and stress may have consequences for infant neurological development. Aims: To study relationships between parental anxiety or well-being and infant neurological development approximately one year after birth. Study design: Longitudinal study of a birth cohort of infants born to subfertile couples. Subjects: 206 parent-child dyads. Outcome measures: Infant neurology was assessed with the Touwen Infant Neurological Examination (TINE) at 10 months and a developmental questionnaire at 12 months. Parental measures included trait anxiety measured by the State-Trait Anxiety Inventory (STAI) and well-being measured by the General Health Questionnaire (GHQ). Results: Maternal trait anxiety was associated with a less optimal neurological condition (r(s) = -0.19, p <0.01) of the infant. This association persisted after adjusting for confounders and results were confirmed by the outcome of the developmental questionnaire. Paternal trait anxiety and parental well-being were not related to the infant's neurodevelopmental outcome. Conclusions: Infants of mothers with high trait anxiety have an increased vulnerability to develop a non-optimal nervous system. The association may be mediated in part by early programming of monoaminergic systems. Future research should include an exploration of specific windows of vulnerability to maternal anxiety. (c) 2010 Elsevier Ireland Ltd. All rights reserved

The assessment of minor neurological dysfunction in infancy using the Touwen Infant Neurological Examination:strengths and limitations

Aim Little is known of minor neurological dysfunction (MND) in infancy. This study aimed to evaluate the inter-assessor reliability of the assessment of MND with the Touwen Infant Neurological Examination (TINE) and the construct and predictive validity of MND in infancy. Method Inter-assessor agreement was determined in a sample of 40 infants (24 males, 16 females) aged 3 to 12 months (25 born at term: gestational age 37-41wks, median 39; and 15 born preterm, gestational age 24-35wks, median 32). Thirty typically developing term infants (18 males, 12 females; gestational age 37-42wks, median 40) and 59 preterm infants (34 males, 25 females) born at <35 weeks' gestation (gestational age 25-34wks, median 29) participated in the validity study. They were neurologically assessed with the TINE at the corrected ages of 4, 6, 10, and 12 months and with the Hempel assessment at 18 months. Results The findings indicated that MND can be assessed reliably (inter-assessor agreement: kappa=0.83). MND during infancy was related to prenatal, perinatal, and social factors, and in particular to preterm birth. Neurological condition during infancy was prone to change, but was related to neurological condition at 18 months at all ages tested. Interpretation We conclude that MND can be determined reliably in infancy. Important considerations in the construct of MND in infancy are its relation to prenatal and perinatal factors, its limited stability, and its moderate predictive value

The Groningen assisted reproductive technologies cohort study:developmental status and behavior at 2 years

To evaluate whether children's cognitive and psychomotor development and behavior at 2 years are affected by ovarian hyperstimulation and the IVF laboratory procedures or subfertility. Prospective longitudinal cohort study. University Medical Center Groningen, the Netherlands. Singletons born after controlled ovarian hyperstimulation (COH)-IVF (n = 66) and modified natural cycle-IVF (n = 56), singletons born to subfertile couples who conceived naturally (subfertile-naturally conceived, n = 87), and a reference group of 101 2-year-old singletons born to fertile couples. None. Bayley Scales of Infant Development and Achenbach Child Behavior Checklist. Mental and psychomotor development and behavioral outcome in COH-IVF, modified natural cycle-IVF, and subfertile-natural cycle groups was not different. Developmental outcome and behavior of the subfertile groups were largely similar to those of the fertile reference group. Nevertheless, the subfertile groups scored higher on the scale of anxious-depressed behavior than the reference group. This present relatively small study found no differences in cognitive and psychomotor development and behavior at 2 years in children born after COH-IVF or modified natural cycle-IVF or naturally conceived children of subfertile parents. Replication of the study is needed before firm conclusions can be drawn. Furthermore, long-term follow-up is needed to confirm these findings in older childre

Ovarian hyperstimulation and the in vitro fertilization procedure do not influence early neuromotor development; a history of subfertility does

Objective: To evaluate specific effects of ovarian hyperstimulation, the in vitro procedure, and a history of subfertility on neuromotor development at 3 months of age. Design: Prospective, cohort study. Setting: University Medical Center Groningen, The Netherlands. Patient(s): Singletons conceived after controlled ovarian hyperstimulation-IVF/intracytoplasmic sperm injection (COH-IVF: n = 68) or modified natural cycle-IVF/intracytoplasmic sperm injection (MNC-IVF; n = 57), and naturally conceived singletons of subfertile couples (NC; n = 90). Data from a reference population were available (n = 450). Intervention(S): None. Main Outcome Measure(s): Quality of general movements (GMs), classified as normal-optimal, normal-suboptimal, mildly abnormal, or definitely abnormal. Definitely abnormal GMs indicate brain dysfunction, mildly abnormal GMs normal but non-optimal brain function. Result(s): Mildly abnormal and definitely abnormal GMs were observed equally frequently in COH-IVF, MNC-IVF, and NC singletons. The three subfertile groups showed a reduction in GM quality, in particular more mildly abnormal GMs, in comparison with the reference population. Conclusion(s): Singletons born after IVF (with or without ovarian hyperstimulation) are not at increased risk for abnormal GMs compared with naturally conceived peers of subfertile parents. Mildly abnormal GMs occur more often in infants of subfertile parents than in the general population, suggesting that factors associated with subfertility rather than those related to IVF procedures may be associated with less-optimal early neurodevelopmental outcome. These results need confirmation through replication and follow-up at older ages. (Fertil Steril(R) 2010;93:544-53. (C)2010 by American Society for Reproductive Medicine.

Construct validity of the Infant Motor Profile:relation with prenatal, perinatal, and neonatal risk factors

AIM The Infant Motor Profile (IMP) is a qualitative assessment of motor behaviour of infants aged 3 to 18 months. The aim of this study was to investigate construct validity of the IMP through the relation of IMP scores with prenatal, perinatal, and neonatal variables, including the presence of brain pathology indicated by neonatal ultrasound imaging of the brain. METHOD A longitudinal prospective study was performed in a group of 30 term infants (12 females, 18 males; median gestational age 40.1wks, range 37.6-42wks) and 59 preterm infants (25 females, 34 males; median gestational age 29.7wks, range 25-34.7wks). IMP assessments were performed at (corrected) ages of 4, 6, 10, 12, and 18 months. Socio-economic and perinatal data were collected, which, in the case of preterm infants, included information on periventricular leukomalacia and intraventricular haemorrhage based on neonatal cranial ultrasound. Data were analysed by fitting mixed-effects models. RESULTS Gestational age, socio-economic status, and 5-minute Apgar scores were significant determinants of IMP scores in the total group of infants (p INTERPRETATION The findings support the construct validity of the IMP: IMP scores are clearly associated with relevant determinants of neuromotor function

Is ovarian hyperstimulation associated with higher blood pressure in 4-year-old IVF offspring? Part I: multivariable regression analysis Citation for published version (APA): Is ovarian hyperstimulation associated with higher blood pressure in 4-year-old

study question: Does ovarian hyperstimulation, the in vitro procedure, or a combination of these two negatively influence blood pressure (BP) and anthropometrics of 4-year-old children born following IVF? summary answer: Higher systolic blood pressure (SBP) percentiles were found in 4-year-old children born following conventional IVF with ovarian hyperstimulation compared with children born following IVF without ovarian hyperstimulation. what is known already: Increasing evidence suggests that IVF, which has an increased incidence of preterm birth and low birthweight, is associated with higher BP and altered body fat distribution in offspring but the underlying mechanisms are largely unknown. study design, size, duration: We performed a prospective, assessor-blinded follow-up study in which 194 children were assessed. The attrition rate up until the 4-year-old assessment was 10%. participants/materials, setting, methods: We measured BP and anthropometrics of 4-year-old singletons born following conventional IVF with controlled ovarian hyperstimulation (COH-IVF, n ¼ 63), or born following modified natural cycle IV (MNC-IVF, n ¼ 52), or born to subfertile couples who conceived naturally (Sub-NC, n ¼ 79). Both IVF and ICSI were performed. Primary outcome measures were the SBP percentiles and diastolic BP (DBP) percentiles. Anthropometric measures included triceps and subscapular skinfold thickness. Several multivariable regression analyses were applied in order to correct for subsets of confounders. The value &apos;B&apos; is the unstandardized regression coefficient. main results and the role of chance: SBP percentiles were significantly lower in the MNC-IVF group (mean 59, SD 24) than in the COH-IVF (mean 68, SD 22) and Sub-NC groups (mean 70, SD 16). The difference in SBP between COH-IVF and MNC-IVF remained significant after correction for current, early life and parental characteristics (B: 14.09; 95% confidence interval (CI): 5.39 -22.79), whereas the difference between MNC-IVF and Sub-NC did not. DBP percentiles did not differ between groups. After correction for early life factors, subscapular skinfold thickness was thicker in the COH-IVF group than in the Sub-NC group (B: 0.28; 95% CI: 0.03 -0.53). limitations, reasons for caution: Larger study groups are necessary to draw firm conclusions. An effect of gender or ICSI could not be properly investigated as stratifying would further reduce the sample size. We corrected for the known differences between MNC-IVF and COH-IVF but it is possible that the groups differ in additional, more subtle parental characteristics. In addition, we measured BP on 1 day only, had no control group of children born to fertile couples (precluding investigating effects of the underlying subfertility) and included singletons only. As COH-IVF is associated with multiple births we may have underestimated cardiometabolic problems after COH-IVF. Finally, multivariable regression analysis does not provide clear insight in the causal mechanisms and we have performed further explorative analyses. wider implications of the findings: Our findings are in line with other studies describing adverse effects of IVF on cardiometabolic outcome but this is the first study suggesting that ovarian hyperstimulation, as used in IVF treatments, could be a causative mechanism. Perhaps ovarian hyperstimulation negatively influences cardiometabolic outcome via changes in the early environment of the oocyte and/or embryo that result in epigenetic modifications of key metabolic systems that are involved in BP regulation. Future research needs to assess further the role of ovarian hyperstimulation in poorer cardiometabolic outcome and investigate the underlying mechanisms. The findings emphasize the importance of cardiometabolic monitoring of the growing number of children born following IVF

Subfertility factors rather than assisted conception factors affect cognitive and behavioural development of 4-year-old singletons

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 children aged 4 years born to subfertile couples. Subfertility, especially severe subfertility, however, was associated with worse cognition and behaviour. (C) 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved