Impact of perinatal asphyxia on parental mental health and bonding with the infant: a questionnaire survey of Swiss parents

Objective To compare current mental health symptoms and infant bonding in parents whose infants survived perinatal asphyxia in the last 2 years with control parents and to investigate which sociodemographic, obstetric and neonatal variables correlated with parental mental health and infant bonding in the asphyxia group. Design Cross-sectional questionnaire survey of parents whose children were registered in the Swiss national Asphyxia and Cooling register and of control parents (Post-traumatic Diagnostic Scale, Hospital Anxiety and Depression Scale, Mother-to-Infant Bonding Scale). Results The response rate for the asphyxia group was 46.5%. Compared with controls, mothers and fathers in the asphyxia group had a higher frequency of post-traumatic stress disorder (PTSD) symptoms (p<0.001). More mothers (n=28, 56%) had a symptom diagnosis of either full or partial PTSD than controls (n=54, 39%) (p=0.032). Similarly, more fathers (n=31, 51%) had a symptom diagnosis of either partial or full PTSD than controls (n=19, 33%) (p=0.034). Mothers reported poorer bonding with the infant (p=0.043) than controls. Having a trauma in the past was linked to more psychological distress in mothers (r=0.31 (95% CI 0.04 to 0.54)) and fathers (r=0.35 (95% CI 0.05 to 0.59)). For mothers, previous pregnancy was linked to poorer bonding (r=0.41 (95% CI 0.13 to 0.63)). In fathers, therapeutic hypothermia of the infant was related to less frequent PTSD symptoms (r=−0.37 (95% CI −0.61 to −0.06)) and past psychological difficulties (r=0.37 (95% CI 0.07 to 0.60)) to more psychological distress. A lower Apgar score was linked to poorer bonding (r=−0.38 (95% CI −0.64 to −0.05)). Conclusions Parents of infants hospitalised for perinatal asphyxia are more at risk of developing PTSD than control parents

Performance of the German version of the PARCA-R questionnaire as a developmental screening tool in two-year-old very preterm infants.

To validate and test a German version of the revised Parent Report of Children's Abilities questionnaire (PARCA-R). Multicentre cross-sectional study. Parents of infants born <32 gestational weeks, completed the PARCA-R within three weeks before the follow-up assessment of their child at age two years. Infants were assessed using the Mental Development Index (MDI) of the Bayley Scales of Infant Development 2nd edition (BSID-II). Pearson correlation between the Parent Report Composite (PRC) of the PARCA-R and MDI was tested. The optimal PRC cut-off for predicting moderate-to-severe mental delay, defined as MDI<70, was identified through the receiver operating characteristic (ROC) curve. PARCA-R and BSID-II data were collected from 154 consecutive infants [51% girls, mean (SD) gestational age 29.0 (2.0) weeks, birth weight 1174 (345) grams] at 23.2 (1.6) months of corrected age. The PRC score [70.5 (31.1)] correlated with the MDI [92.2 (17.3); R = 0.54; p < 0.0001]. The optimal PRC cut-off for identifying mental delay was 44 with 0.81 (0.54-0.96) sensitivity (95%-CI), 0.81 (0.74-0.87) specificity, area under the ROC curve of 0.840 (0.729-0.952). The German version of the PARCA-R had good validity with the BSID-II and PCR scores < 44 proved optimal discriminatory power for the identification of mental delay at two years of corrected age

Association of growth with neurodevelopment in extremely low gestational age infants: a population-based analysis.

To assess the association between postnatal growth and neurodevelopment at the age of 2 years in extremely low gestational age newborns (ELGAN, < 28 weeks' gestation). Retrospective population-based cohort study including all live born ELGAN in 2006-2012 in Switzerland. Growth parameters (weight, length, head circumference, body mass index) were assessed at birth, at hospital discharge home, and 2-year follow-up (FU2). Unadjusted and adjusted regression models assessed associations between growth (birth to hospital discharge and birth to FU2) and neurodevelopment at FU2. A total of 1244 infants (mean GA 26.5 ± 1.0 weeks, birth weight 853 ± 189 g) survived to hospital discharge and were included in the analyses. FU2 was documented for 1049 (84.3%) infants. The mean (± SD) mental and a psychomotor development index at 2FU were 88.9 (± 18.0) and 86.9 (± 17.7), respectively. Moderate or severe neurodevelopmental impairment was documented in 23.2% of patients. Changes of z-scores between birth and discharge and between birth and FU2 for weight were - 1.06 (± 0.85) and - 0.140 (± 1.15), for length - 1.36 (± 1.34), and - 0.40 (± 1.33), for head circumference - 0.61 (± 1.04) and - 0.76 (± 1.32) as well as for BMI 0.22 (± 3.36) and - 0.006 (± 1.45). Unadjusted and adjusted analyses showed that none of the four growth parameters was significantly associated with any of the three outcome parameters of neurodevelopment. This was consistent for both time intervals. CONCLUSION In the present population-based cohort of ELGAN, neither growth between birth and hospital discharge nor between birth and FU2 were significantly associated with neurodevelopment at age of 2 years. WHAT IS KNOWN • Studies assessing the association between growth and neurodevelopment in extremely low gestational age newborns (28 weeks' gestation) show conflicting results. WHAT IS NEW • Neither growth between birth and hospital discharge nor between birth and corrected age of 2 years were significantly associated with neurodevelopment at age of 2 years. • The role of postnatal growth as a predictor of neurodevelopmental outcome during infancy might be smaller than previously assumed

Association of growth with neurodevelopment in extremely low gestational age infants: a population-based analysis

To assess the association between postnatal growth and neurodevelopment at the age of 2 years in extremely low gestational age newborns (ELGAN, < 28 weeks' gestation). Retrospective population-based cohort study including all live born ELGAN in 2006-2012 in Switzerland. Growth parameters (weight, length, head circumference, body mass index) were assessed at birth, at hospital discharge home, and 2-year follow-up (FU2). Unadjusted and adjusted regression models assessed associations between growth (birth to hospital discharge and birth to FU2) and neurodevelopment at FU2. A total of 1244 infants (mean GA 26.5 ± 1.0 weeks, birth weight 853 ± 189 g) survived to hospital discharge and were included in the analyses. FU2 was documented for 1049 (84.3%) infants. The mean (± SD) mental and a psychomotor development index at 2FU were 88.9 (± 18.0) and 86.9 (± 17.7), respectively. Moderate or severe neurodevelopmental impairment was documented in 23.2% of patients. Changes of z-scores between birth and discharge and between birth and FU2 for weight were - 1.06 (± 0.85) and - 0.140 (± 1.15), for length - 1.36 (± 1.34), and - 0.40 (± 1.33), for head circumference - 0.61 (± 1.04) and - 0.76 (± 1.32) as well as for BMI 0.22 (± 3.36) and - 0.006 (± 1.45). Unadjusted and adjusted analyses showed that none of the four growth parameters was significantly associated with any of the three outcome parameters of neurodevelopment. This was consistent for both time intervals. CONCLUSION In the present population-based cohort of ELGAN, neither growth between birth and hospital discharge nor between birth and FU2 were significantly associated with neurodevelopment at age of 2 years. WHAT IS KNOWN • Studies assessing the association between growth and neurodevelopment in extremely low gestational age newborns (28 weeks' gestation) show conflicting results. WHAT IS NEW • Neither growth between birth and hospital discharge nor between birth and corrected age of 2 years were significantly associated with neurodevelopment at age of 2 years. • The role of postnatal growth as a predictor of neurodevelopmental outcome during infancy might be smaller than previously assumed

Nutrient Intake in the First Two Weeks of Life and Brain Growth in Preterm Neonates.

BACKGROUND: Optimizing early nutritional intake in preterm neonates may promote brain health and neurodevelopment through enhanced brain maturation. Our objectives were (1) to determine the association of energy and macronutrient intake in the first 2 weeks of life with regional and total brain growth and white matter (WM) maturation, assessed by 3 serial MRI scans in preterm neonates; (2) to examine how critical illness modifies this association; and (3) to investigate the relationship with neurodevelopmental outcomes. METHODS: Forty-nine preterm neonates (21 boys, median [interquartile range] gestational age: 27.6 [2.3] weeks) were scanned serially at the following median postmenstrual weeks: 29.4, 31.7, and 41. The total brain, basal nuclei, and cerebellum were semiautomatically segmented. Fractional anisotropy was extracted from diffusion tensor imaging data. Nutritional intake from day of life 1 to 14 was monitored and clinical factors were collected. RESULTS: Greater energy and lipid intake predicted increased total brain and basal nuclei volumes over the course of neonatal care to term-equivalent age. Similarly, energy and lipid intake were significantly associated with fractional anisotropy values in selected WM tracts. The association of ventilation duration with smaller brain volumes was attenuated by higher energy intake. Brain growth predicted psychomotor outcome at 18 months\u27 corrected age. CONCLUSIONS: In preterm neonates, greater energy and enteral feeding during the first 2 weeks of life predicted more robust brain growth and accelerated WM maturation. The long-lasting effect of early nutrition on neurodevelopment may be mediated by enhanced brain growth. Optimizing nutrition in preterm neonates may represent a potential avenue to mitigate the adverse brain health consequences of critical illness

Association between perinatal interventional activity and 2-year outcome of Swiss extremely preterm born infants: a population-based cohort study.

To investigate if centre-specific levels of perinatal interventional activity were associated with neonatal and neurodevelopmental outcome at 2 years of age in two separately analysed cohorts of infants: cohort A born at 22-25 and cohort B born at 26-27 gestational weeks, respectively. Geographically defined, retrospective cohort study. All nine level III perinatal centres (neonatal intensive care units and affiliated obstetrical services) in Switzerland. All live-born infants in Switzerland in 2006-2013 below 28 gestational weeks, excluding infants with major congenital malformation. Outcomes at 2 years corrected for prematurity were mortality, survival with any major neonatal morbidity and with severe-to-moderate neurodevelopmental impairment (NDI). Cohort A associated birth in a centre with high perinatal activity with low mortality adjusted OR (aOR 0.22; 95% CI 0.16 to 0.32), while no association was observed with survival with major morbidity (aOR 0.74; 95% CI 0.46 to 1.19) and with NDI (aOR 0.97; 95% CI 0.46 to 2.02). Median age at death (8 vs 4 days) and length of stay (100 vs 73 days) were higher in high than in low activity centres. The results for cohort B mirrored those for cohort A. Centres with high perinatal activity in Switzerland have a significantly lower risk for mortality while having comparable outcomes among survivors. This confirms the results of other studies but in a geographically defined area applying a more restrictive approach to initiation of perinatal intensive care than previous studies. The study adds that infants up to 28 weeks benefited from a higher perinatal activity and why further research is required to better estimate the added burden on children who ultimately do not survive

Infant exposure to Fluvoxamine through placenta and human milk: a case series - A contribution from the ConcePTION project [case report].

INTRODUCTION Fluvoxamine is widely used to treat depression during pregnancy and lactation. However, limited data are available on its transfer to the fetus or in human milk. This case series provides additional information on the infant exposure to fluvoxamine during pregnancy and lactation. CASE PRESENTATION Two women, aged 38 and 34 years, diagnosed with depression were treated with 50 mg fluvoxamine during pregnancy and lactation. At delivery a paired maternal and cord blood sample was collected for each woman. The first mother exclusively breastfed her child for 4 months and gave one foremilk and one hindmilk sample at 2 days and 4 weeks post-partum, whereas the second mother did not breastfeed. RESULTS The cord to plasma concentration ratios were 0.62 and 0.48, respectively. At 2 weeks post-partum, relative infant doses (RID) were 0.47 and 0.57% based on fluvoxamine concentrations in foremilk and hindmilk, respectively. At 4 weeks post-partum, the RIDs were 0.35 and 0.90%, respectively. The child from the first mother was born healthy and showed a normal development at the 6th, 18th and 36th month follow-ups. One of the twins from the second woman was hospitalized for hypoglycemia that was attributed to gestational diabetes and low birth weight. The second one was born healthy. CONCLUSION These results suggest a minimal exposure to fluvoxamine during lactation which is in accordance with previously published data. Larger clinical and pharmacokinetic studies assessing the long-term safety of this drug during lactation and the variability of its exposure through breastmilk are warranted

Emotional and effortful control abilities in 42-month-old very preterm and full-term children

Background: Very preterm (VP) infants are at greater risk for cognitive difficulties that may persist during schoolage, adolescence and adulthood. Behavioral assessments report either effortful control (part of executive functions) or emotional reactivity/regulation impairments. Aims: The aim of this study is to examine whether emotional recognition, reactivity, and regulation, as well as effortful control abilities are impaired in very preterm children at 42 months of age, compared with their full-term peers, and to what extent emotional and effortful control difficulties are linked. Study design: Children born very preterm (VP; b 29 weeks gestational age, n = 41) and full-term (FT) agedmatched children (n = 47) participated in a series of specific neuropsychological tests assessing their level of emotional understanding, reactivity and regulation, as well as their attentional and effortful control abilities. Results: VP children exhibited higher scores of frustration and fear, and were less accurate in naming facial expressions of emotions than their aged-matched peers. However, VP children and FT children equally performed when asked to choose emotional facial expression in social context, and when we assessed their selective attention skills. VP performed significantly lower than full terms on two tasks of inhibition when correcting for verbal skills. Moreover, significant correlations between cognitive capacities (effortful control) and emotional abilities were evidenced. Conclusions: Compared to their FT peers, 42 month-olds who were born very preterm are at higher risk of exhibiting specific emotional and effortful control difficulties. The results suggest that these difficulties are linked. Ongoing behavioral and emotional impairments starting at an early age in preterms highlight the need for early interventions based on a better understanding of the relationship between emotional and cognitive difficulties

A population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project.

AIMS Sertraline is frequently prescribed for mental health conditions in both pregnant and breastfeeding women. According to the limited available data, only small amounts of sertraline are transferred into human milk, yet with a large amount of unexplained interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model to describe the pharmacokinetics of sertraline during the perinatal period and explain interindividual variability. METHODS Pregnant women treated with sertraline were enrolled in the multicenter prospective cohort SSRI-Breast Milk study. A popPK model for sertraline maternal plasma and breast milk concentrations was developed and allowed estimating the milk-to-plasma ratio (MPR). An additional fetal compartment allowed cord blood concentrations to be described. Several covariates were tested for significance. Ultimately, model-based simulations allowed infant drug exposure through placenta and breast milk under various conditions to be predicted. RESULTS Thirty-eight women treated with sertraline were included in the study and provided 89 maternal plasma, 29 cord blood and 107 breast milk samples. Sertraline clearance was reduced by 42% in CYP2C19 poor metabolizers compared to other phenotypes. Doubling milk fat content increased the MPR by 95%. Simulations suggested a median daily infant dosage of 6.9 μg kg-1 after a 50 mg maternal daily dose, representing 0.95% of the weight-adjusted maternal dose. Median cord blood concentrations could range from 3.29 to 33.23 ng mL-1 after maternal daily doses between 25 and 150 mg. CONCLUSIONS Infant exposure to sertraline, influenced by CYP2C19 phenotype and breast milk fat content, remains low, providing reassurance regarding the use of sertraline during pregnancy and breastfeeding

Neuroimaging in infants with congenital cytomegalovirus infection and its correlation with outcome: emphasis on white matter abnormalities

Objective: To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs). Methods: Multicentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at ≤3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at ≥6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability. Results: Neuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89±0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia. Conclusions: Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis