Psychomotor development, emotional regulation, and executive functions in 2-years-old children after a threatened preterm labour: a prospective study

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The aim of this study was to assess TPL impact on children’s psychomotor and socioemotional development at 2 years of age. Methods A cohort of mother-infants was recruited at the time of TPL diagnoses and followed up until 30 months of children’s corrected age. Participants were classified in three groups regarding gestational age at delivery: Full-term TPL ( n = 35), Late Preterm TPL ( n = 67), Very Preterm TPL ( n = 41). A Control group ( n = 62) of mothers without TPL and their infants born at term completed the sample. Children’s assessment was performed using the Ages & Stages Questionnaires for psychomotor development, the Early Childhood Behavior Questionnaire–Very Short Form for temperament, and the Behavior Rating Inventory of Executive Function-Preschool Version for executive functions. Then, MANCOVA were conducted to detect differences between groups. Results TPL children, regardless of delivery time, showed worse emotional regulation ( ps < .03) and more inhibition problems ( ps < .02) than control ones. In addition, Very preterm TPL children exhibited lower psychomotor development ( ps ≤ .040), more difficulties in working memory ( ps ≤ .002) and planification/organization ( ps ≤ .003) domains. Conclusion TPL per se may represent a risk factor for children’s neurodevelopmental disturbances, specifically in emotional and regulation competences, even in the absence of prematurity. threatened preterm labour prematurity neurodevelopment temperament cognitive impairment Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Prematurity represents one of the main causes of perinatal morbimortality and long-term sequels in neurodevelopment 1–5 . Thus, lower cognitive, motor and socioemotional competences 6–11 , as well as higher risk of autism spectrum disorder (ASD) 2,3 and attention deficit and hyperactivity disorder (ADHD) 5,12,13 have been reported in preterm individuals. In the last decades, rise of preterm birth incidence and survival rates 14–18 has led scientific community to increase efforts on investigating those potential effects on neurodevelopment and their underlying mechanisms. Although traditionally studies focused on psychomotor impairments detected at school ages 1,4 , more recent research indicate that preterm babies may show some emotional difficulties since the first months of life 6–8 . Moreover, latest studies reveal that late-preterm infants without neurological abnormalities also present alterations in neurodevelopment 19–22 , suggesting the influence of other factors apart from brain immaturity linked to preterm birth. In addition, it is known that maternal stress during pregnancy can have an impact on offspring’s neurodevelopment 23–27 , and a threatened preterm labour (TPL) episode itself represents a stressful event for women 28 . Therefore, the deleterious effect associated to prematurity may already start at prenatal stages, with the occurrence and management of TPL. A TPL episode is characterized by the onset of uterine dynamic before completing normal gestation and constitutes one of the main reasons for obstetrics admission. Despite the final delivery outcome (more than 50% do not progress to active labour and preterm delivery), it can affect fetal neurodevelopment via hypothalamic-pituitary-adrenal (HPA) axis programming in response to prenatal stress 29 . As for TPL management, corticosteroids use for fetal lung maturation is associated with a decrease in neonatal morbimortality 30,31 , but some authors reported that multiple corticosteroids courses may increase risk of neurobehavioral disorders 32,33 . Therefore, distinct factors occurring in a TPL episode could be involved in neurodevelopmental alterations later observed in infants, regardless of prematurity. Then, it is important to study TPL infants who finally were born at term since this population experience risk factors inherent to TPL, but no other conditions associated to prematurity. Previous studies examining TPL and infant neurodevelopment have observed higher incidence of intrauterine growth restriction and small for gestational age neonates 34–37 , as well as delayed psychomotor development at 6 and 24 months 35,38 . Furthermore, some recent research suggest the presence of early emotional disturbances 38 , autistic symptomatology 39 and ADHD manifestations 40 in children born after a TPL even when delivery was at term. However, literature regarding TPL is still scarce and does not include other neurodevelopmental dimensions such as executive functions, which could also be affected. Concerning early emotional manifestations, growing research in the last years focus on identifying subtle alterations already present in early infancy as potential predictors of future neuropsychiatric disorders 41–43 , including ASD 2,44,45 and ADHD 5 . In particular, preterm infants show certain characteristic temperamental traits, coined by some authors as “preterm behavioural phenotype”, not always related to a clinical diagnosis 8 but deserving further consideration. Several studies have reported an increased risk of emotional dysregulation and behavioural problems in preterm children at preschool and school ages 22,46 whereas other works failed to detect significant differences compared to full term pairs 47,48 . These discrepancies may be explained due to methodological issues such as sample heterogeneity, time of assessment of type of instrument. Less literature exists regarding TPL population when prematurity condition is controlled. Critically, in one study of our team, TPL infants showed higher negative affect, lower surgency/ extraversion and worse emotional regulation at 6 months age compared to those born at term without TPL 38 . Nevertheless, it is necessary to conduct long-term follow-up studies to gain more knowledge on the course and clinical impact of these early emotional alterations observed in high-risk perinatal population and disentangle the potential effect of TPL per se . With regards to executive functions (EF), there are no published studies specifically assessing EF in TPL population. Executive functions refer to those mental processes needed for appropriately direct and regulate behaviour, which is: inhibition, cognitive flexibility, working memory, emotional control, and planification/organization. Infants start to develop these competences during the first year but the process gradually continues along childhood with the an exponential growth between 3–5 years-old age 49 . Among them, inhibition has been considered as the main component, since it is the first to be acquired and the basis that provides time to put in action the rest while preventing impulses and inappropriate behaviour 50 . EF impairments are associated with poorer academic, social and emotional functioning 49,51 . Moreover, assessment of executive functions domains is related to ADHD risk or symptomatology and EF difficulties have been proposed as early manifestations already present before ADHD diagnosis 49,50,52 . Numerous studies indicate that preterm children show lower performance in EF both measured by parental questionnaires or direct tests 10,11,53,54 . Given the mentioned findings in terms of psychomotor delay, emotional dysregulation and ADHD symptoms in infants born after a TPL 35,38,40 , it would be interesting to broaden the study directly assessing executive functions in these children. According to previous literature supporting the potential impact of TPL on fetal and infant neurodevelopment 19–21,24–27,35,38–40 , the aim of this follow-up study was to evaluate psychomotor development, executive functions, and temperament in 30 months-old children born after a TPL, with a multidimensional approach. We did it by including three groups of TPL children based on delivery time (at term, late preterm, very preterm) as well as a control group of full-term children whose mother did not suffer from a TPL. We hypothesized that TPL infants, regardless of delivery time group, would show certain degree of psychomotor delay and difficulties in emotion regulation compared to controls 35,38 . In addition, we expected that TPL infants would exhibit more EF impairments, even when delivered at term. Finally, very preterm children would show greater difficulties than late preterm and full term TPL infants, due to its immaturity. Methods Study design and participants This was a prospective cohort study of mother-infant dyads recruited after a TPL, at the Department of Obstetrics and Gynecology at the University and Polytechnic Hospital La Fe, Valencia (Spain). The follow-up covered from TPL diagnosis until 30 months (corrected age for preterm infants). To ensure that all women received the same protocol treatment, pregnant women were recruited between 23- and 34- week gestation. After the delivery, the cohort was classified into 3 groups based on gestational age at birth: TPL Full-term (≥ 37 weeks), Late Preterm (32–37 weeks), and Very Preterm (< 32 weeks). A control group of pregnant women without TPL of other complications and who delivered at term completed the sample, with their offspring respectively. The Ethics Committee at the Health Research Institute La Fe approved the study protocol (ref. 2015/0086) and written informed consent was obtained from all the participants. Diagnosis of TPL was defined by regular and painful uterine contractions registered by cardiotocography and cervical changes measured by cervical ultrasound (cervical length < 25mm), with intact membranes 30 . All eligible TPL patients received a single corticosteroid course (2x12mg/24h) and similar tocolytic treatment, which consisted of: a) atosiban (initial bolus of 6.75mg/min followed by 300 µg/min -1 loading infusion and 100µg/min -1 as maintenance dose until 48h), or b) nifedipine (initial 20mg, followed by 10mg every 20 min until 40mg for 1h) (Conde-Agudelo et al., 2011 ). Tocolytic therapy with atosiban or nifedipine extended by at least 24h. Exclusion criteria for mothers were previous history of medical disorders (e.g., diabetes mellitus, lupus), severe obstetric complications (cervical dilatation > 4cm, abruptio placenta, obstructed labour, preeclampsia, clinical infection), mental disorder, drug abuse, risk of social exclusion according to Europe 2020 strategy (Savova et al., 2020) or significant language barriers. Newborns with congenital malformations, chromosomopathy, and postnatal severe disease were also excluded. Additionally, the control group had to be exempt from a TPL episode. A final sample of 143 infants in the TPL group (35 Full-term, 67 Late Preterm, 41 Very Preterm) and 62 infants in the control group whose mothers had accepted to participate were accessible when we contacted them for the 30 months post birth assessment. See Fig. 1 for recruitment flow diagram. Outcome variables Women’s sociodemographic and obstetric information was recorded in the hospital database at study recruitment. Data concerning pregnancy follow-up and perinatal variables were registered prospectively. Children’s neurodevelopment and early psychopathology were assessed at corrected age of 30 months. Children were evaluated in a quiet room at the hospital in the presence of at least one parent, in the morning. Two trained clinical psychologist/psychiatrist who were blind to obstetric and perinatal variables applied the questionnaires. Parents’ reports were validated by means of direct clinical observation of their infant’s abilities. Psychomotor development was assessed using the Ages & Stages Questionnaires-Third edition (ASQ-3) 55 , a well-recognized and validated set of scales which grade psychomotor developmental progress in children from 1 month to 5.5 years of age. The questionnaire for 30-month (28 months 16 days through 31 months 15 days) was administered in this study. It consists of 30 items, gathered in five domains: a) Communication: child’s verbal skills, including both comprehensive and expressive language; b) Gross Motor: motor abilities needed to run, jump, use stairs; c) Fine Motor: eye-hand coordination and manipulation of small objects; d) Problem solving: child’s ability to deal with obstacles and difficulties while playing; and e) Personal-social: autonomy, self-awareness, and interaction with other people. Each domain is composed by 6 items graded on a 3-point Likert-scale (0= “not yet”, 5= “sometimes”, 10= “yes”), being the total score from 0 to 60. Internal consistency for the global scale was adequate (Cronbach α = 0.90). Temperament was evaluated through the Early Childhood Behavior Questionnaire–Very Short Form (ECBQ/VSF) 56 , an instrument designed to assess temperament in toddlers between 18 and 36 months old. The ECBQ/VSF contains 36 items rated on a 7-point Likert-scale, according to the frequency of behaviours observed by parents. Results are usually gathered in 3 broad dimensions of temperament: a) Negative Affect: fear, anger-frustration, and social discomfort, reflecting the degree to which an infant is shy and not easily calmed; b) Surgency/Extraversion: positive anticipation, activity level, and sensation seeking, showing the degree to which an infant is happy, active, and enjoys vocalizing and seeking stimulation; and c) Emotional regulation/Effortful control: inhibitory control, attentional focusing, and perceptual sensitivity, indicating the degree to which an infant is not easily distracted, manages planning, and is able to inhibit non-desirable dominant responses. The test showed adequate internal consistency (α = 0.70). Executive functions were examined with the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) 57 , an standardized instrument used to assess EF in children between 2 and 5 years-old. It is composed of 63 items rated on a 3-point Likert-scale (1= “never”, 2= “sometimes”, 3= “frequently”) and classified into 5 subscales: Inhibition (ability to resist impulses and stop/abolish inappropriate behaviours according to the context), Flexibility (ability to change attention focus and find alternatives towards difficult situations), Emotional control (ability to contain an regulation emotion expression), Working Memory (ability to retain information and use it for direct actions), and Planification/Organization (ability to order/arrange and prioritise relevant information, set out goals and execute sequential steps to achieve them). Lower punctuations indicate optimum functioning whereas higher scores may reflect difficulties in each EF area. The internal consistency for the global scale was adequate (Cronbach α = 0.93). Statistical analysis Data were summarized using mean and standard deviation in the case of continuous variables, absolute and relative frequencies in the case of categorical variables. To examine the relationship between TPL and neurodevelopment, 3 Multivariate Analysis of Covariance (MANCOVA) were conducted with Group (TPL Full-term, Late Preterm, Very Preterm, and Control) as independent variable, for psychomotor development (ASQ-3: Communication, Gross Motor, Fine Motor, Problem Solving, Personal-Social), temperament (ECBQ/VSF: Negative affect; Surgency/Extraversion; Emotional regulation) and executive functions (BRIEF-P: Inhibition, Flexibility, Emotional Control, Working Memory, Planification/Organization) as dependent variables. Multiple pregnancy and in vitro fertilization (IVF) were included as covariates in order to control for potential cofounders. Significant group effects were then examined through pair-comparisons. All statistical analyses were performed using SPSS software (version 25.0). Results Table 1 shows main demographic and clinical characteristics of the sample. No significant differences regarding maternal age, educational level, parity, miscarriages, postpartum depression, infant sex, breastfeeding, or nursery attendance were observed between groups. Multiple gestation and IVF were more frequent among women with preterm delivery, as the association is well stated in literature 58 , that women undergoing IVF present increased risk of multiple pregnancy and preterm birth, and therefore included as covariate in the statistical model of this study. Table S2 and S3 illustrate differences between groups on psychomotor development, temperament, and executive functions, after controlling for IVF and multiple pregnancy. Table 1 Demographic and clinical characteristics of the sample. Total Control (n = 62) TPL-T (n = 35) TPL-LP (n = 67) TPL-VP (n = 41) p value Maternal age, M ( SD ) 32.48 (4.93) 31.87 (4.59) 32.94 (5.41) 33.24 (5.01) 31.76 (4.66) 0.293 Educational level N (%). Primary Secondary University 34/186 (18) 66/186 (36) 86/186 (46) 8/54 (15) 17/54 (31) 29/54 (54) 7/29 (24) 9/29 (31) 13/29 (45) 9/64 (14) 27/64 (42) 28/64 (44) 10/39 (26) 13/39 (33) 16/39 (41) 0.554 EPDS M ( SD ) 5.93 (4.19) 4.83 (3.68) 6.81 (4.58) 6.12 (4.59) 5.97 (3.91) 0.226 Parity M ( SD ) 0.43 (0.77) 0.53 (0.62) 0.34 (0.64) 0.46 (0.88) 0.32 (0.91) 0.476 Previous miscarriage N (%) 39 (19.0) 12 (19.4) 7 (20) 13 (19.4) 7 (17.1) 0.667 Multiple gestation N (%) 71 (34.6) 0 (0) 8 (22.9) 41 (61.2) 22 (53.7) < 0.001 IFV N (%) 57 (27.8) 4 (6.6) 12 (34.3%) 19 (28.4%) 22 (53.7%) < 0.001 C-section N (%) 92 (44.9) 14 (22.6) 13 (37.1) 42 (62.7) 23 (56.1) < 0.001 Urgent C-section N (%) 60 (29.3) 5 (8.1) 4 (11.8) 32 (47.8) 19 (46.3) < 0.001 Maternal BMI M ( SD ) 23.60 (4.45) 23.08 (4.24) 21.73 (3.94) 25.16 (4.74) 23.72 (4.14) 0.019 Delivery week M ( SD ) 35.63 (4.36) 39.80 (0.98) 38.50 (1.33) 34.42 (1.47) 28.81 (2.43) < 0.001 Female N (%) 106 (51.7) 36 (58) 19 (54.3) 30 (44.78) 21 (51.23) 0.496 Birth weight (g) M ( SD ) 2399.86 (877.51) 3260.44 (392.67) 2896.67 (429.44) 2061.59 (425.33) 1226.13 (446.59) < 0.001 Birth weight percentile for GA M ( SD ) 40.78 (28.37) 46.32 (27.54) 34.9 (25.49) 33.78 (26.64) 47.63 (31.68) 0.019 Apgar1 M ( SD ) 8.51 (1.76) 9.02 (1.60) 9.33 (0.62) 8.62 (1.34) 7.02 (2.17) < 0.001 Apgar5 M ( SD ) 9.60 (0.91) 9.87 (0.34) 9.93 (0.27) 9.78 (0.66) 8.71 (1.42) < 0.001 Apgar10 M ( SD ) 9.92 (0.36) 10 (0.00) 9.96 (0.19) 9.93 (0.31) 9.69 (0.69) 0.001 Hospitalization N (%) 95 (48.97) 4 (6.6) 3/ 30 48/ 62 40 (100) < 0.001 Oxygen N (%) 49 (25.4) 2 (3.3) 0 (0) 16/62 (25.8) 31 (77.5%) < 0.001 Breastfeeding N (%) 129 (67.2) 50 (82) 14 /28 40 /62 25 (62.5) 0.087 Nursery N (%) 156/179 (87) 47/54 (87) 27/28 (96) 54/61 (89) 28/36 (78) 0.166 Note. TPL: Threatened preterm labour. T: full-term. LP: Late preterm. VP: Very preterm. EPDS: Edinburgh Postpartum Depression Scale. IFV: in vitro fecundation. BMI: body mass index. M: mean. SD: standard deviations. GA: Gestational age. *Significant p value < .05 indicated in bold in the table. Psychomotor development MANCOVA revealed statistically significant differences between groups on all the combined psychomotor ASQ-3 subscales ( F (15,541) = 3.23, p < .001, Wilks’ Λ = .789, ɳ 2 = .076), that is, Communication ( p = < .001, η 2 = 099), Gross Motor ( p = < .001, η 2 = .111), Fine Motor ( p = .03, η 2 = .044), Problem Solving ( p = .002, η 2 = .069) and Personal-social ( p = < .001, η 2 = .091). When pair-groups comparisons were examined, VP-TPL infants showed lower psychomotor development scores than the rest (control, LP-TPL, FT-TPL) in all the domains except for Fine Motor ( p > .06). No significant differences were detected comparing other groups of TPL infants (LP-TPL, FT-TPL) to control ones. Figure 2 graphically depicts these results. Temperament After controlling by potential confounders, MANCOVA found statistically significant differences in Emotional Regulation factor/domain ( F (3,200) = 4.71, p = .003, Wilks’ Λ = .906, ɳ 2 = .066) but not for Negative Affect neither Surgency/Extraversion dimensions ( ps > .05). Pair-groups comparisons indicated that TPL infants (VP-TPL, LP-TPL, FT-TPL) presented lower emotional regulation skills than controls, regardless of the delivery time group ( ps < .03, Δs ≥ .57). No significant differences were observed between TPL groups. See Fig. 3 for graphical representation. Executive functions MANCOVA revealed statistically significant differences between groups in Inhibition ( F (3,200) = 7.31, p < .001, Wilks’ Λ = .771, ɳ 2 =.099), Working Memory ( F (3,200) = 11.14, p < .001, ɳ 2 =.143), and Planification/Organization ( F (3,200) = 5.63, p = .001, ɳ 2 =.078). When comparing for pair-groups, all TPL children (VP-TPL, LP-TPL, FT-TPL) showed more Inhibition problems than controls, regardless of the delivery group ( ps < .02, Δs ≥ .65). No detectable differences between the distinct groups of TPL children were found in inhibition domain. As for Working Memory, Very-Preterm TPL infants obtained higher scores (indicating more difficulties) than the other groups ( ps ≤ .002, Δs ≥ .73). Also, VP-TPL infants showed increased difficulties in Planification/Organization skills when compared to controls and Full-Term TPL infants ( ps ≤ .003, Δs ≥ .68), but with respect to Late-Preterm TPL ( p = .173). Figure 4 illustrates these findings. Discussion Main findings and interpretation The aim of this study was to assess psychomotor, cognitive and emotional development in children born after a TPL, given the potential impact of TPL on neurodevelopment and previous findings in the same cohort at earlier ages 38 . In the present work, TPL children as a whole group -even when birth was at term- showed worse emotional regulation skills and more inhibition problems than children whose mothers did not suffer from a TPL. Very preterm infants exhibited lower psychomotor development as well as greater difficulties in working memory and planification/organization skills. Concerning psychomotor development, children born after a TPL presented lower scores in communication and personal-social domains compared to control group. These findings are in line with data reported at 6 months assessment 38 . However, at 30 months only very preterm children reached statistically significant differences. Since we employed the same measurement instrument (ASQ) -selecting the correspondent age scale- and sample size was similar, other factors such as children development course may explain this discrepancy. Thus, it is possible that some deficits observed during the first months of life could later be modulated/corrected as the child grows up and therefore not persistent. Paules et al. (2016) evaluated psychomotor development in TPL children at 2 years and found that both late preterm and at term children obtained lower developmental scores -compared to controls- in most areas except expressive language. These differences could be attributed in part to distinct instruments of assessment, as they used the Merrill-Palmer-Revised Developmental Scale. As for very preterm TPL children, we observed that they also exhibited lower gross motor and problem solving skills when compared to controls (statistically significant) and other TPL groups. These results are in concordance with literature that supports the existence of global impairment in cognitive and motor skills of preterm children, more serious as lower gestational age and birthweight 59,60 . With respect to early emotional manifestations and temperament, TPL children, regardless of delivery time, registered lower emotional regulation scores, which may indicate a reduced ability to properly regulate emotions expression and behaviour. This finding agrees with previous results reported at 6 months assessment 38 . However, initial differences observed in terms of higher negative affect and lower surgency/extraversion were not present at 30 months assessment. The loss of differences between TPL and control pairs could be due to influence of external factors (i.e., familiar environment) which may modulate and mitigate those initial traits of difficult temperament. Another possible explanation could be that the ECBQ/VSF test lacks sufficient power/precision to discriminate subtle differences at 2-years-old. There are no other published studies examining temperament in children born after a TPL, including preterm and at term, to compare results. Therefore, it is necessary to conduct further research on temperamental outcomes and emotional regulation in TPL population. Regarding executive functions, TPL infants as a whole group showed higher scores in inhibition, that may reflect greater difficulties to control impulses and suppress inappropriate responses according to the context. As for other domains, only very preterm children exhibited differences in working memory and planification/organization skills. These results are in line with previous work that assessed executive functions in preterm children and found that preterm children exhibited poorer global performance, detecting a correlation with gestational age (the lower gestational age, the greater EF impairment) 11,51,54 . A recent metanalysis on late-preterm children (34–36 gestational weeks) reported lower performance in EF, verbal memory, processing speed and attention tasks 53 . Moreover, the authors suggested that some alterations seemed transitory whereas others would persist in future stages; therefore, the need to extend follow-up studies. Some research works support the association between EF impairments and higher risk of emotional and behavioural problems 51 . In our study, inhibition was the only component with significant differences for all TPL children, regardless of delivery date. To note, given the age of participants, in a period of dynamic development, it is conceivable that other components of EF could not be appropriate differentiated between groups yet 52 . In addition, most studies about EF in preterm individuals conducted evaluation by means of direct tasks (e.g., Go-no go, Stroop test), either a as single measure or combined with parental questionnaires, usually administered at scholar ages. Nevertheless, assessing children younger than 3 years entails additional difficulties due to lack of specific instruments and particularly dynamic developmental process 52 . For this reason, we decided to employ BRIEF-P, a well-validated parent reported questionnaire with proved representativity for executive functions in children 52 . TPL as a prenatal adverse event may alter fetal neurodevelopment both by its stressful effect per se and fetal exposure to tocolytic and corticosteroid treatment. On the one hand, it is well known that adverse life events and/or perceived maternal stress can impact on offspring development 23–27 . In this sense, maternal stress can induce changes in fetal HPA 29,61,62 and consequently program physiologic system of stress response with potential long-term deleterious effects. Cortex development and cortico-thalamic connections occurred fundamentally during third trimester 63 , so any adverse event at this critical period could hamper normal formation of neuronal networks involved in cognitive, motor and socioemotional development. On the other hand, concern exists about the potential effect of antenatal corticosteroids (ACS) on fetal neurodevelopment via HPA axis modification. Although some metanalysis did not find significant association between ACS and children development or behaviour problems 31,64,65 , there are still few studies on the field. Regarding tocolytic agents and children’s outcomes, literature is scarce 66,67 . Finally, a TPL episode may also involve inflammatory and placental dysfunction processes that could compromise/endanger oxygen and nutrient supply to the fetus, with consequent sequels for development 68,69 . Strengths and limitations This is one of the few studies examining the impact of TPL, as stressful prenatal event, on offspring’s neurodevelopment. One of the main strengths is the combined use of multiple assessment measures, broadly considering cognitive, motor and emotional competences. The inclusion of children born at term after a TPL helps discriminating the potential effect of TPL per se regardless of other risk factors connected to prematurity. Another strength is its prospective design and its accurate selection of the sample, with well-defined inclusion and exclusion criteria. The 30 months assessment complements previous assessment by exploring the course of initial alterations detected at 6 months and allow us to detect new difficulties in early stages. However, some limitations should be considered. First, evaluation was carried out through parental questionnaires with clinical observation at hospital, so the utilization of direct tasks and/or home observation would be more representative of children behaviour repertoire. Second, familiar and social factors not analysed in this study may also influenced the outcomes. A more extended follow-up would be useful to better characterize these alterations and their clinical course in future stages. Finally, since exclusion criteria were restricted, results are not generalizable to other populations such as comorbidity during pregnancy or social risk groups. By this method, we attempted to isolate TPL impact and separate it from other stressful conditions acting as potential cofounding factors. Conclusion TPL may represent a risk factor for children’s neurodevelopment, with potential long-term effects, even in absence of prematurity. Findings suggest that these alterations occur especially in areas of emotional regulation and inhibition control, which bears relation to future neuropsychiatric disorders. Further studies are necessary to discern underlying mechanisms and clinical course of this early disturbances. We highlight the importance to conduct preventing and intervention programs with these mothers and infants in order to detect early manifestations and improve their prognosis. Declarations Conflicts of interests: Authors declare no potential conflicts of interest to disclose. Authors have no financial relationships relevant to this article to disclose. Funding: This work was supported by the Health Institute Carlos III (ISCIII; Spanish Ministry of Economy and Innovation) and co-funded by the European Union [grant numbers: LC (CM20/00143), FG (FI19/00202), JB (CM21/00049), and AGB (CP21/00085, PI18/01352, PI21/00549)]. 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Proceedings of the National Academy of Sciences of the United States of America , 112 (20), 6485–6490. https://doi.org/10.1073/pnas.1422638112 van Winden T, Klumper J, Kleinrouweler CE, Tichelaar MA, Naaktgeboren CA, Nijman TA, van Baar AL, van Wassenaer-Leemhuis AG, Roseboom TJ, Van’t Hooft J, Roos C, Mol BW & Pajkrt E, O.M. (2020). Effects of tocolysis with nifedipine or atosiban on child outcome: follow-up of the APOSTEL III trial. BJOG: An International Journal of Obstetrics and Gynaecology . https://doi.org/10.1111/1471-0528.16186 Zentner, M. & Bates, J.E. (2008). Child Temperament: An Integrative Review of Concepts , Research Programs, and Measures. International Journal of Developmental Science , 2 (1), 7–37. Zwaigenbaum, L., Bryson, S., Rogers, T., Roberts, W., Brian, J. & Szatmari, P. (2005). Behavioral manifestations of autism in the first year of life. Int J Dev Neurosci 23 , 143–152. Additional Declarations No competing interests reported. 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16:12:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":855397,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3286668/v1/b283a43c-8833-4a57-9a07-731e392ddc8d.pdf"},{"id":42153141,"identity":"7f78efc8-ece3-4f59-b6cf-fcc07e64b73a","added_by":"auto","created_at":"2023-08-25 17:42:29","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":24152,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-3286668/v1/d3ae9f538d812a1f1cb549b7.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Psychomotor development, emotional regulation, and executive functions in 2-years-old children after a threatened preterm labour: a prospective study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrematurity represents one of the main causes of perinatal morbimortality and long-term sequels in neurodevelopment \u003csup\u003e1\u0026ndash;5\u003c/sup\u003e. Thus, lower cognitive, motor and socioemotional competences \u003csup\u003e6\u0026ndash;11\u003c/sup\u003e, as well as higher risk of autism spectrum disorder (ASD) \u003csup\u003e2,3\u003c/sup\u003e and attention deficit and hyperactivity disorder (ADHD) \u003csup\u003e5,12,13\u003c/sup\u003e have been reported in preterm individuals. In the last decades, rise of preterm birth incidence and survival rates \u003csup\u003e14\u0026ndash;18\u003c/sup\u003e has led scientific community to increase efforts on investigating those potential effects on neurodevelopment and their underlying mechanisms. Although traditionally studies focused on psychomotor impairments detected at school ages \u003csup\u003e1,4\u003c/sup\u003e, more recent research indicate that preterm babies may show some emotional difficulties since the first months of life \u003csup\u003e6\u0026ndash;8\u003c/sup\u003e. Moreover, latest studies reveal that late-preterm infants without neurological abnormalities also present alterations in neurodevelopment \u003csup\u003e19\u0026ndash;22\u003c/sup\u003e, suggesting the influence of other factors apart from brain immaturity linked to preterm birth. In addition, it is known that maternal stress during pregnancy can have an impact on offspring\u0026rsquo;s neurodevelopment \u003csup\u003e23\u0026ndash;27\u003c/sup\u003e, and a threatened preterm labour (TPL) episode itself represents a stressful event for women \u003csup\u003e28\u003c/sup\u003e. Therefore, the deleterious effect associated to prematurity may already start at prenatal stages, with the occurrence and management of TPL.\u003c/p\u003e \u003cp\u003eA TPL episode is characterized by the onset of uterine dynamic before completing normal gestation and constitutes one of the main reasons for obstetrics admission. Despite the final delivery outcome (more than 50% do not progress to active labour and preterm delivery), it can affect fetal neurodevelopment via hypothalamic-pituitary-adrenal (HPA) axis programming in response to prenatal stress \u003csup\u003e29\u003c/sup\u003e. As for TPL management, corticosteroids use for fetal lung maturation is associated with a decrease in neonatal morbimortality \u003csup\u003e30,31\u003c/sup\u003e, but some authors reported that multiple corticosteroids courses may increase risk of neurobehavioral disorders \u003csup\u003e32,33\u003c/sup\u003e. Therefore, distinct factors occurring in a TPL episode could be involved in neurodevelopmental alterations later observed in infants, regardless of prematurity. Then, it is important to study TPL infants who finally were born at term since this population experience risk factors inherent to TPL, but no other conditions associated to prematurity.\u003c/p\u003e \u003cp\u003ePrevious studies examining TPL and infant neurodevelopment have observed higher incidence of intrauterine growth restriction and small for gestational age neonates \u003csup\u003e34\u0026ndash;37\u003c/sup\u003e, as well as delayed psychomotor development at 6 and 24 months \u003csup\u003e35,38\u003c/sup\u003e. Furthermore, some recent research suggest the presence of early emotional disturbances \u003csup\u003e38\u003c/sup\u003e, autistic symptomatology\u003csup\u003e39\u003c/sup\u003e and ADHD manifestations\u003csup\u003e40\u003c/sup\u003e in children born after a TPL even when delivery was at term. However, literature regarding TPL is still scarce and does not include other neurodevelopmental dimensions such as executive functions, which could also be affected.\u003c/p\u003e \u003cp\u003eConcerning early emotional manifestations, growing research in the last years focus on identifying subtle alterations already present in early infancy as potential predictors of future neuropsychiatric disorders \u003csup\u003e41\u0026ndash;43\u003c/sup\u003e, including ASD \u003csup\u003e2,44,45\u003c/sup\u003e and ADHD \u003csup\u003e5\u003c/sup\u003e. In particular, preterm infants show certain characteristic temperamental traits, coined by some authors as \u0026ldquo;preterm behavioural phenotype\u0026rdquo;, not always related to a clinical diagnosis \u003csup\u003e8\u003c/sup\u003e but deserving further consideration. Several studies have reported an increased risk of emotional dysregulation and behavioural problems in preterm children at preschool and school ages \u003csup\u003e22,46\u003c/sup\u003e whereas other works failed to detect significant differences compared to full term pairs \u003csup\u003e47,48\u003c/sup\u003e. These discrepancies may be explained due to methodological issues such as sample heterogeneity, time of assessment of type of instrument. Less literature exists regarding TPL population when prematurity condition is controlled. Critically, in one study of our team, TPL infants showed higher negative affect, lower surgency/ extraversion and worse emotional regulation at 6 months age compared to those born at term without TPL \u003csup\u003e38\u003c/sup\u003e. Nevertheless, it is necessary to conduct long-term follow-up studies to gain more knowledge on the course and clinical impact of these early emotional alterations observed in high-risk perinatal population and disentangle the potential effect of TPL \u003cem\u003eper se\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eWith regards to executive functions (EF), there are no published studies specifically assessing EF in TPL population. Executive functions refer to those mental processes needed for appropriately direct and regulate behaviour, which is: inhibition, cognitive flexibility, working memory, emotional control, and planification/organization. Infants start to develop these competences during the first year but the process gradually continues along childhood with the an exponential growth between 3\u0026ndash;5 years-old age \u003csup\u003e49\u003c/sup\u003e. Among them, inhibition has been considered as the main component, since it is the first to be acquired and the basis that provides time to put in action the rest while preventing impulses and inappropriate behaviour \u003csup\u003e50\u003c/sup\u003e. EF impairments are associated with poorer academic, social and emotional functioning \u003csup\u003e49,51\u003c/sup\u003e. Moreover, assessment of executive functions domains is related to ADHD risk or symptomatology and EF difficulties have been proposed as early manifestations already present before ADHD diagnosis \u003csup\u003e49,50,52\u003c/sup\u003e. Numerous studies indicate that preterm children show lower performance in EF both measured by parental questionnaires or direct tests \u003csup\u003e10,11,53,54\u003c/sup\u003e. Given the mentioned findings in terms of psychomotor delay, emotional dysregulation and ADHD symptoms in infants born after a TPL \u003csup\u003e35,38,40\u003c/sup\u003e, it would be interesting to broaden the study directly assessing executive functions in these children.\u003c/p\u003e \u003cp\u003eAccording to previous literature supporting the potential impact of TPL on fetal and infant neurodevelopment \u003csup\u003e19\u0026ndash;21,24\u0026ndash;27,35,38\u0026ndash;40\u003c/sup\u003e, the aim of this follow-up study was to evaluate psychomotor development, executive functions, and temperament in 30 months-old children born after a TPL, with a multidimensional approach. We did it by including three groups of TPL children based on delivery time (at term, late preterm, very preterm) as well as a control group of full-term children whose mother did not suffer from a TPL. We hypothesized that TPL infants, regardless of delivery time group, would show certain degree of psychomotor delay and difficulties in emotion regulation compared to controls \u003csup\u003e35,38\u003c/sup\u003e. In addition, we expected that TPL infants would exhibit more EF impairments, even when delivered at term. Finally, very preterm children would show greater difficulties than late preterm and full term TPL infants, due to its immaturity.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThis was a prospective cohort study of mother-infant dyads recruited after a TPL, at the Department of Obstetrics and Gynecology at the University and Polytechnic Hospital La Fe, Valencia (Spain). The follow-up covered from TPL diagnosis until 30 months (corrected age for preterm infants). To ensure that all women received the same protocol treatment, pregnant women were recruited between 23- and 34- week gestation. After the delivery, the cohort was classified into 3 groups based on gestational age at birth: TPL Full-term (\u0026ge;\u0026thinsp;37 weeks), Late Preterm (32\u0026ndash;37 weeks), and Very Preterm (\u0026lt;\u0026thinsp;32 weeks). A control group of pregnant women without TPL of other complications and who delivered at term completed the sample, with their offspring respectively. The Ethics Committee at the Health Research Institute La Fe approved the study protocol (ref. 2015/0086) and written informed consent was obtained from all the participants.\u003c/p\u003e \u003cp\u003eDiagnosis of TPL was defined by regular and painful uterine contractions registered by cardiotocography and cervical changes measured by cervical ultrasound (cervical length\u0026thinsp;\u0026lt;\u0026thinsp;25mm), with intact membranes \u003csup\u003e30\u003c/sup\u003e. All eligible TPL patients received a single corticosteroid course (2x12mg/24h) and similar tocolytic treatment, which consisted of: a) atosiban (initial bolus of 6.75mg/min followed by 300 \u0026micro;g/min\u003csup\u003e-1\u003c/sup\u003e loading infusion and 100\u0026micro;g/min\u003csup\u003e-1\u003c/sup\u003e as maintenance dose until 48h), or b) nifedipine (initial 20mg, followed by 10mg every 20 min until 40mg for 1h) (Conde-Agudelo et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Tocolytic therapy with atosiban or nifedipine extended by at least 24h.\u003c/p\u003e \u003cp\u003eExclusion criteria for mothers were previous history of medical disorders (e.g., diabetes mellitus, lupus), severe obstetric complications (cervical dilatation\u0026thinsp;\u0026gt;\u0026thinsp;4cm, \u003cem\u003eabruptio\u003c/em\u003e placenta, obstructed labour, preeclampsia, clinical infection), mental disorder, drug abuse, risk of social exclusion according to Europe 2020 strategy (Savova et al., 2020) or significant language barriers. Newborns with congenital malformations, chromosomopathy, and postnatal severe disease were also excluded. Additionally, the control group had to be exempt from a TPL episode. A final sample of 143 infants in the TPL group (35 Full-term, 67 Late Preterm, 41 Very Preterm) and 62 infants in the control group whose mothers had accepted to participate were accessible when we contacted them for the 30 months post birth assessment. See Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e for recruitment flow diagram.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eOutcome variables\u003c/h2\u003e \u003cp\u003eWomen\u0026rsquo;s sociodemographic and obstetric information was recorded in the hospital database at study recruitment. Data concerning pregnancy follow-up and perinatal variables were registered prospectively. Children\u0026rsquo;s neurodevelopment and early psychopathology were assessed at corrected age of 30 months. Children were evaluated in a quiet room at the hospital in the presence of at least one parent, in the morning. Two trained clinical psychologist/psychiatrist who were blind to obstetric and perinatal variables applied the questionnaires. Parents\u0026rsquo; reports were validated by means of direct clinical observation of their infant\u0026rsquo;s abilities.\u003c/p\u003e \u003cp\u003ePsychomotor development was assessed using the Ages \u0026amp; Stages Questionnaires-Third edition (ASQ-3) \u003csup\u003e55\u003c/sup\u003e, a well-recognized and validated set of scales which grade psychomotor developmental progress in children from 1 month to 5.5 years of age. The questionnaire for 30-month (28 months 16 days through 31 months 15 days) was administered in this study. It consists of 30 items, gathered in five domains: a) Communication: child\u0026rsquo;s verbal skills, including both comprehensive and expressive language; b) Gross Motor: motor abilities needed to run, jump, use stairs; c) Fine Motor: eye-hand coordination and manipulation of small objects; d) Problem solving: child\u0026rsquo;s ability to deal with obstacles and difficulties while playing; and e) Personal-social: autonomy, self-awareness, and interaction with other people. Each domain is composed by 6 items graded on a 3-point Likert-scale (0= \u0026ldquo;not yet\u0026rdquo;, 5= \u0026ldquo;sometimes\u0026rdquo;, 10= \u0026ldquo;yes\u0026rdquo;), being the total score from 0 to 60. Internal consistency for the global scale was adequate (Cronbach α\u0026thinsp;=\u0026thinsp;0.90).\u003c/p\u003e \u003cp\u003eTemperament was evaluated through the Early Childhood Behavior Questionnaire\u0026ndash;Very Short Form (ECBQ/VSF) \u003csup\u003e56\u003c/sup\u003e, an instrument designed to assess temperament in toddlers between 18 and 36 months old. The ECBQ/VSF contains 36 items rated on a 7-point Likert-scale, according to the frequency of behaviours observed by parents. Results are usually gathered in 3 broad dimensions of temperament: a) Negative Affect: fear, anger-frustration, and social discomfort, reflecting the degree to which an infant is shy and not easily calmed; b) Surgency/Extraversion: positive anticipation, activity level, and sensation seeking, showing the degree to which an infant is happy, active, and enjoys vocalizing and seeking stimulation; and c) Emotional regulation/Effortful control: inhibitory control, attentional focusing, and perceptual sensitivity, indicating the degree to which an infant is not easily distracted, manages planning, and is able to inhibit non-desirable dominant responses. The test showed adequate internal consistency (α\u0026thinsp;=\u0026thinsp;0.70).\u003c/p\u003e \u003cp\u003eExecutive functions were examined with the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) \u003csup\u003e57\u003c/sup\u003e, an standardized instrument used to assess EF in children between 2 and 5 years-old. It is composed of 63 items rated on a 3-point Likert-scale (1= \u0026ldquo;never\u0026rdquo;, 2= \u0026ldquo;sometimes\u0026rdquo;, 3= \u0026ldquo;frequently\u0026rdquo;) and classified into 5 subscales: Inhibition (ability to resist impulses and stop/abolish inappropriate behaviours according to the context), Flexibility (ability to change attention focus and find alternatives towards difficult situations), Emotional control (ability to contain an regulation emotion expression), Working Memory (ability to retain information and use it for direct actions), and Planification/Organization (ability to order/arrange and prioritise relevant information, set out goals and execute sequential steps to achieve them). Lower punctuations indicate optimum functioning whereas higher scores may reflect difficulties in each EF area. The internal consistency for the global scale was adequate (Cronbach α\u0026thinsp;=\u0026thinsp;0.93).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were summarized using mean and standard deviation in the case of continuous variables, absolute and relative frequencies in the case of categorical variables. To examine the relationship between TPL and neurodevelopment, 3 Multivariate Analysis of Covariance (MANCOVA) were conducted with Group (TPL Full-term, Late Preterm, Very Preterm, and Control) as independent variable, for psychomotor development (ASQ-3: Communication, Gross Motor, Fine Motor, Problem Solving, Personal-Social), temperament (ECBQ/VSF: Negative affect; Surgency/Extraversion; Emotional regulation) and executive functions (BRIEF-P: Inhibition, Flexibility, Emotional Control, Working Memory, Planification/Organization) as dependent variables. Multiple pregnancy and \u003cem\u003ein vitro\u003c/em\u003e fertilization (IVF) were included as covariates in order to control for potential cofounders. Significant group effects were then examined through pair-comparisons. All statistical analyses were performed using SPSS software (version 25.0).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows main demographic and clinical characteristics of the sample. No significant differences regarding maternal age, educational level, parity, miscarriages, postpartum depression, infant sex, breastfeeding, or nursery attendance were observed between groups. Multiple gestation and IVF were more frequent among women with preterm delivery, as the association is well stated in literature \u003csup\u003e58\u003c/sup\u003e, that women undergoing IVF present increased risk of multiple pregnancy and preterm birth, and therefore included as covariate in the statistical model of this study. Table S2 and S3 illustrate differences between groups on psychomotor development, temperament, and executive functions, after controlling for IVF and multiple pregnancy.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics of the sample.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTPL-T\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTPL-LP\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;67)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTPL-VP\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age, \u003cem\u003eM\u003c/em\u003e (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.48 (4.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.87 (4.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.94 (5.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33.24 (5.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31.76 (4.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.293\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducational level \u003cem\u003eN\u003c/em\u003e (%).\u003c/p\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003cp\u003eUniversity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34/186 (18)\u003c/p\u003e \u003cp\u003e66/186 (36)\u003c/p\u003e \u003cp\u003e86/186 (46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/54 (15)\u003c/p\u003e \u003cp\u003e17/54 (31)\u003c/p\u003e \u003cp\u003e29/54 (54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7/29 (24)\u003c/p\u003e \u003cp\u003e9/29 (31)\u003c/p\u003e \u003cp\u003e13/29 (45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9/64 (14)\u003c/p\u003e \u003cp\u003e27/64 (42)\u003c/p\u003e \u003cp\u003e28/64 (44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10/39 (26)\u003c/p\u003e \u003cp\u003e13/39 (33)\u003c/p\u003e \u003cp\u003e16/39 (41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.554\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEPDS \u003cem\u003eM\u003c/em\u003e (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.93 (4.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.83 (3.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.81 (4.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.12 (4.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.97 (3.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.226\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity \u003cem\u003eM\u003c/em\u003e (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.43 (0.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.53 (0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.34 (0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.46 (0.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.32 (0.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.476\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious miscarriage \u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (19.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (19.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.667\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple gestation \u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (34.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (22.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41 (61.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22 (53.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIFV \u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (34.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19 (28.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22 (53.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-section \u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (44.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (37.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42 (62.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23 (56.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrgent C-section \u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (29.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32 (47.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19 (46.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal BMI \u003cem\u003eM\u003c/em\u003e (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.60 (4.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.08 (4.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.73 (3.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.16 (4.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.72 (4.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelivery week \u003cem\u003eM\u003c/em\u003e (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.63 (4.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.80 (0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.50 (1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.42 (1.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28.81 (2.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale \u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106 (51.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (54.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 (44.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21 (51.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.496\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight (g) \u003cem\u003eM\u003c/em\u003e (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2399.86 (877.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3260.44\u003c/p\u003e \u003cp\u003e(392.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2896.67\u003c/p\u003e \u003cp\u003e(429.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2061.59 (425.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1226.13 (446.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight percentile for GA \u003cem\u003eM\u003c/em\u003e (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.78 (28.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.32 (27.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.9 (25.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33.78 (26.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.63 (31.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApgar1 \u003cem\u003eM\u003c/em\u003e (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.51 (1.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.02 (1.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.33 (0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.62 (1.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.02 (2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApgar5 \u003cem\u003eM\u003c/em\u003e (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.60 (0.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.87 (0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.93 (0.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.78 (0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.71 (1.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApgar10 \u003cem\u003eM\u003c/em\u003e (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.92 (0.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.96 (0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.93 (0.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.69 (0.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization \u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (48.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3/ 30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48/ 62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxygen \u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16/62 (25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 (77.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreastfeeding \u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129 (67.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 /28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40 /62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNursery \u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e156/179 (87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47/54 (87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27/28 (96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54/61 (89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28/36 (78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.166\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eNote. TPL: Threatened preterm labour. T: full-term. LP: Late preterm. VP: Very preterm. EPDS: Edinburgh Postpartum Depression Scale. IFV: \u003cem\u003ein vitro\u003c/em\u003e fecundation. BMI: body mass index. M: mean. SD: standard deviations. GA: Gestational age.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e*Significant \u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;.05 indicated in bold in the table.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePsychomotor development\u003c/h2\u003e \u003cp\u003eMANCOVA revealed statistically significant differences between groups on all the combined psychomotor ASQ-3 subscales (\u003cem\u003eF\u003c/em\u003e\u003csub\u003e(15,541)\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;3.23, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001, Wilks\u0026rsquo; Λ\u0026thinsp;=\u0026thinsp;.789, \u003cem\u003eɳ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e = .076), that is, Communication (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;.001, \u003cem\u003eη\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;099), Gross Motor (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;.001, \u003cem\u003eη\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;.111), Fine Motor (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.03, \u003cem\u003eη\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;.044), Problem Solving (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.002, \u003cem\u003eη\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;.069) and Personal-social (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;.001, \u003cem\u003eη\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;.091). When pair-groups comparisons were examined, VP-TPL infants showed lower psychomotor development scores than the rest (control, LP-TPL, FT-TPL) in all the domains except for Fine Motor (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;.06). No significant differences were detected comparing other groups of TPL infants (LP-TPL, FT-TPL) to control ones. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e graphically depicts these results.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eTemperament\u003c/h2\u003e \u003cp\u003eAfter controlling by potential confounders, MANCOVA found statistically significant differences in Emotional Regulation factor/domain (\u003cem\u003eF\u003c/em\u003e\u003csub\u003e(3,200)\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;4.71, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.003, Wilks\u0026rsquo; Λ\u0026thinsp;=\u0026thinsp;.906, \u003cem\u003eɳ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e = .066) but not for Negative Affect neither Surgency/Extraversion dimensions (\u003cem\u003eps\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;.05). Pair-groups comparisons indicated that TPL infants (VP-TPL, LP-TPL, FT-TPL) presented lower emotional regulation skills than controls, regardless of the delivery time group (\u003cem\u003eps\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.03, \u003cem\u003eΔs\u003c/em\u003e\u0026thinsp;\u0026ge;\u0026thinsp;.57). No significant differences were observed between TPL groups. See Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e for graphical representation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eExecutive functions\u003c/h2\u003e \u003cp\u003eMANCOVA revealed statistically significant differences between groups in Inhibition (\u003cem\u003eF\u003c/em\u003e\u003csub\u003e(3,200)\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;7.31, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001, Wilks\u0026rsquo; Λ\u0026thinsp;=\u0026thinsp;.771, \u003cem\u003eɳ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e =.099), Working Memory (\u003cem\u003eF\u003c/em\u003e\u003csub\u003e(3,200)\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;11.14, \u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;.001, \u003cem\u003eɳ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e =.143), and Planification/Organization (\u003cem\u003eF\u003c/em\u003e\u003csub\u003e(3,200)\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;5.63, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;.001, \u003cem\u003eɳ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e =.078). When comparing for pair-groups, all TPL children (VP-TPL, LP-TPL, FT-TPL) showed more Inhibition problems than controls, regardless of the delivery group (\u003cem\u003eps\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.02, \u003cem\u003eΔs\u003c/em\u003e\u0026thinsp;\u0026ge;\u0026thinsp;.65). No detectable differences between the distinct groups of TPL children were found in inhibition domain. As for Working Memory, Very-Preterm TPL infants obtained higher scores (indicating more difficulties) than the other groups (\u003cem\u003eps\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;.002, \u003cem\u003eΔs\u003c/em\u003e\u0026thinsp;\u0026ge;\u0026thinsp;.73). Also, VP-TPL infants showed increased difficulties in Planification/Organization skills when compared to controls and Full-Term TPL infants (\u003cem\u003eps\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;.003, \u003cem\u003eΔs\u003c/em\u003e\u0026thinsp;\u0026ge;\u0026thinsp;.68), but with respect to Late-Preterm TPL (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.173). Figure\u0026nbsp;4 illustrates these findings.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMain findings and interpretation\u003c/h2\u003e \u003cp\u003eThe aim of this study was to assess psychomotor, cognitive and emotional development in children born after a TPL, given the potential impact of TPL on neurodevelopment and previous findings in the same cohort at earlier ages \u003csup\u003e38\u003c/sup\u003e. In the present work, TPL children as a whole group -even when birth was at term- showed worse emotional regulation skills and more inhibition problems than children whose mothers did not suffer from a TPL. Very preterm infants exhibited lower psychomotor development as well as greater difficulties in working memory and planification/organization skills.\u003c/p\u003e \u003cp\u003eConcerning psychomotor development, children born after a TPL presented lower scores in communication and personal-social domains compared to control group. These findings are in line with data reported at 6 months assessment \u003csup\u003e38\u003c/sup\u003e. However, at 30 months only very preterm children reached statistically significant differences. Since we employed the same measurement instrument (ASQ) -selecting the correspondent age scale- and sample size was similar, other factors such as children development course may explain this discrepancy. Thus, it is possible that some deficits observed during the first months of life could later be modulated/corrected as the child grows up and therefore not persistent. Paules et al. (2016) evaluated psychomotor development in TPL children at 2 years and found that both late preterm and at term children obtained lower developmental scores -compared to controls- in most areas except expressive language. These differences could be attributed in part to distinct instruments of assessment, as they used the Merrill-Palmer-Revised Developmental Scale. As for very preterm TPL children, we observed that they also exhibited lower gross motor and problem solving skills when compared to controls (statistically significant) and other TPL groups. These results are in concordance with literature that supports the existence of global impairment in cognitive and motor skills of preterm children, more serious as lower gestational age and birthweight \u003csup\u003e59,60\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWith respect to early emotional manifestations and temperament, TPL children, regardless of delivery time, registered lower emotional regulation scores, which may indicate a reduced ability to properly regulate emotions expression and behaviour. This finding agrees with previous results reported at 6 months assessment \u003csup\u003e38\u003c/sup\u003e. However, initial differences observed in terms of higher negative affect and lower surgency/extraversion were not present at 30 months assessment. The loss of differences between TPL and control pairs could be due to influence of external factors (i.e., familiar environment) which may modulate and mitigate those initial traits of difficult temperament. Another possible explanation could be that the ECBQ/VSF test lacks sufficient power/precision to discriminate subtle differences at 2-years-old. There are no other published studies examining temperament in children born after a TPL, including preterm and at term, to compare results. Therefore, it is necessary to conduct further research on temperamental outcomes and emotional regulation in TPL population.\u003c/p\u003e \u003cp\u003eRegarding executive functions, TPL infants as a whole group showed higher scores in inhibition, that may reflect greater difficulties to control impulses and suppress inappropriate responses according to the context. As for other domains, only very preterm children exhibited differences in working memory and planification/organization skills. These results are in line with previous work that assessed executive functions in preterm children and found that preterm children exhibited poorer global performance, detecting a correlation with gestational age (the lower gestational age, the greater EF impairment) \u003csup\u003e11,51,54\u003c/sup\u003e. A recent metanalysis on late-preterm children (34\u0026ndash;36 gestational weeks) reported lower performance in EF, verbal memory, processing speed and attention tasks \u003csup\u003e53\u003c/sup\u003e. Moreover, the authors suggested that some alterations seemed transitory whereas others would persist in future stages; therefore, the need to extend follow-up studies. Some research works support the association between EF impairments and higher risk of emotional and behavioural problems \u003csup\u003e51\u003c/sup\u003e. In our study, inhibition was the only component with significant differences for all TPL children, regardless of delivery date. To note, given the age of participants, in a period of dynamic development, it is conceivable that other components of EF could not be appropriate differentiated between groups yet \u003csup\u003e52\u003c/sup\u003e. In addition, most studies about EF in preterm individuals conducted evaluation by means of direct tasks (e.g., Go-no go, Stroop test), either a as single measure or combined with parental questionnaires, usually administered at scholar ages. Nevertheless, assessing children younger than 3 years entails additional difficulties due to lack of specific instruments and particularly dynamic developmental process \u003csup\u003e52\u003c/sup\u003e. For this reason, we decided to employ BRIEF-P, a well-validated parent reported questionnaire with proved representativity for executive functions in children \u003csup\u003e52\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTPL as a prenatal adverse event may alter fetal neurodevelopment both by its stressful effect \u003cem\u003eper se\u003c/em\u003e and fetal exposure to tocolytic and corticosteroid treatment. On the one hand, it is well known that adverse life events and/or perceived maternal stress can impact on offspring development \u003csup\u003e23\u0026ndash;27\u003c/sup\u003e. In this sense, maternal stress can induce changes in fetal HPA \u003csup\u003e29,61,62\u003c/sup\u003e and consequently program physiologic system of stress response with potential long-term deleterious effects. Cortex development and cortico-thalamic connections occurred fundamentally during third trimester \u003csup\u003e63\u003c/sup\u003e, so any adverse event at this critical period could hamper normal formation of neuronal networks involved in cognitive, motor and socioemotional development. On the other hand, concern exists about the potential effect of antenatal corticosteroids (ACS) on fetal neurodevelopment via HPA axis modification. Although some metanalysis did not find significant association between ACS and children development or behaviour problems \u003csup\u003e31,64,65\u003c/sup\u003e, there are still few studies on the field. Regarding tocolytic agents and children\u0026rsquo;s outcomes, literature is scarce \u003csup\u003e66,67\u003c/sup\u003e. Finally, a TPL episode may also involve inflammatory and placental dysfunction processes that could compromise/endanger oxygen and nutrient supply to the fetus, with consequent sequels for development \u003csup\u003e68,69\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and limitations\u003c/h2\u003e \u003cp\u003eThis is one of the few studies examining the impact of TPL, as stressful prenatal event, on offspring\u0026rsquo;s neurodevelopment. One of the main strengths is the combined use of multiple assessment measures, broadly considering cognitive, motor and emotional competences. The inclusion of children born at term after a TPL helps discriminating the potential effect of TPL \u003cem\u003eper se\u003c/em\u003e regardless of other risk factors connected to prematurity. Another strength is its prospective design and its accurate selection of the sample, with well-defined inclusion and exclusion criteria. The 30 months assessment complements previous assessment by exploring the course of initial alterations detected at 6 months and allow us to detect new difficulties in early stages. However, some limitations should be considered. First, evaluation was carried out through parental questionnaires with clinical observation at hospital, so the utilization of direct tasks and/or home observation would be more representative of children behaviour repertoire. Second, familiar and social factors not analysed in this study may also influenced the outcomes. A more extended follow-up would be useful to better characterize these alterations and their clinical course in future stages. Finally, since exclusion criteria were restricted, results are not generalizable to other populations such as comorbidity during pregnancy or social risk groups. By this method, we attempted to isolate TPL impact and separate it from other stressful conditions acting as potential cofounding factors.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTPL may represent a risk factor for children\u0026rsquo;s neurodevelopment, with potential long-term effects, even in absence of prematurity. Findings suggest that these alterations occur especially in areas of emotional regulation and inhibition control, which bears relation to future neuropsychiatric disorders. Further studies are necessary to discern underlying mechanisms and clinical course of this early disturbances. We highlight the importance to conduct preventing and intervention programs with these mothers and infants in order to detect early manifestations and improve their prognosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflicts of interests:\u0026nbsp;\u003c/strong\u003eAuthors declare no potential conflicts of interest to disclose. Authors have no financial relationships relevant to this article to disclose. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis work was supported by the Health Institute Carlos III (ISCIII; Spanish Ministry of Economy and Innovation) and co-funded by the European Union [grant numbers: LC (CM20/00143), FG (FI19/00202), JB (CM21/00049), and AGB (CP21/00085, PI18/01352, PI21/00549)]. AMG is supported by NUTRISHIELD (grant agreement H2020 #818110) and BA and ML by the Spanish Ministry of Education (FPU18/01997, FPU20/02548). The funding sources have not been implicated in the design or publication of the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAldao, A., Nolen-Hoeksema, S. \u0026amp; Schweizer, S. (2010). Emotion-regulation strategies across psychopathology: A meta-analytic review. \u003cem\u003eClinical Psychology Review\u003c/em\u003e, \u003cem\u003e30\u003c/em\u003e(2), 217\u0026ndash;237. https://doi.org/10.1016/j.cpr.2009.11.004\u003c/li\u003e\n \u003cli\u003eAnand, K. J. S. \u0026amp; Scalzo, F. M. (2000). Can adverse neonatal experiences alter brain development and subsequent behavior? \u003cem\u003eBiology of the Neonate\u003c/em\u003e, \u003cem\u003e77\u003c/em\u003e(2), 69\u0026ndash;82. https://doi.org/10.1159/000014197\u003c/li\u003e\n \u003cli\u003eBastek, J. A., Weber, A. L., Mcshea, M. A., Ryan, M. E. \u0026amp; Elovitz, M. A. (2014). 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(2022).\u0026nbsp;Cognitive and Socioemotional Development at 5 and 9 Years of Age of Children Born with Very Low Birth Weight and Extremely Low Birth Weight in the Czech Republic. \u003cem\u003eMedical Science\u003c/em\u003e, 1\u0026ndash;11. https://doi.org/10.12659/MSM.935784\u003c/li\u003e\n \u003cli\u003eToulmin, H., Beckmann, C.F., O\u0026rsquo;Muircheartaigh, J., Ball, G., Nongena, P., Makropoulos, A., Ederies, A., Counsell, S. J., Kennea, N., Arichi, T., Tusor, N., Rutherford, M.A., Azzopardi, D., Gonzalez-Cinca, N., Hajnal, J.V. \u0026amp; Edwards, A.D. (2015). Specialization and integration of functional thalamocortical connectivity in the human infant. \u003cem\u003eProceedings of the National Academy of Sciences of the United States of America\u003c/em\u003e, \u003cem\u003e112\u003c/em\u003e(20), 6485\u0026ndash;6490. https://doi.org/10.1073/pnas.1422638112\u003c/li\u003e\n \u003cli\u003evan Winden T, Klumper J, Kleinrouweler CE, Tichelaar MA, Naaktgeboren CA, Nijman TA, van Baar AL, van Wassenaer-Leemhuis AG, Roseboom TJ, Van\u0026rsquo;t Hooft J, Roos C, Mol BW \u0026amp; Pajkrt E, O.M. (2020). Effects of tocolysis with nifedipine or atosiban on child outcome: follow-up of the APOSTEL III trial. \u003cem\u003eBJOG: An International Journal of Obstetrics and Gynaecology\u003c/em\u003e. https://doi.org/10.1111/1471-0528.16186\u003c/li\u003e\n \u003cli\u003eZentner, M. \u0026amp; Bates, J.E. (2008). Child Temperament: An Integrative Review of Concepts , Research Programs, and Measures. \u003cem\u003eInternational Journal of Developmental Science\u003c/em\u003e,\u003cem\u003e2\u003c/em\u003e(1), 7\u0026ndash;37.\u003c/li\u003e\n \u003cli\u003eZwaigenbaum, L., Bryson, S., Rogers, T., Roberts, W., Brian, J. \u0026amp; Szatmari, P. (2005). Behavioral manifestations of autism in the first year of life. \u003cem\u003eInt J Dev Neurosci 23\u003c/em\u003e, 143\u0026ndash;152.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-child-and-adolescent-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ecap","sideBox":"Learn more about [European Child \u0026 Adolescent Psychiatry](http://link.springer.com/journal/787)","snPcode":"787","submissionUrl":"https://submission.nature.com/new-submission/787/3","title":"European Child \u0026 Adolescent Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"threatened preterm labour, prematurity, neurodevelopment, temperament, cognitive impairment","lastPublishedDoi":"10.21203/rs.3.rs-3286668/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3286668/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eA threatened preterm labour (TPL) represents an adverse prenatal event with potential long-term consequences on offspring\u0026rsquo; neurodevelopment, regardless of prematurity condition. The aim of this study was to assess TPL impact on children\u0026rsquo;s psychomotor and socioemotional development at 2 years of age.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA cohort of mother-infants was recruited at the time of TPL diagnoses and followed up until 30 months of children\u0026rsquo;s corrected age. Participants were classified in three groups regarding gestational age at delivery: Full-term TPL (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;35), Late Preterm TPL (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;67), Very Preterm TPL (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;41). A Control group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;62) of mothers without TPL and their infants born at term completed the sample. Children\u0026rsquo;s assessment was performed using the Ages \u0026amp; Stages Questionnaires for psychomotor development, the Early Childhood Behavior Questionnaire\u0026ndash;Very Short Form for temperament, and the Behavior Rating Inventory of Executive Function-Preschool Version for executive functions. Then, MANCOVA were conducted to detect differences between groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTPL children, regardless of delivery time, showed worse emotional regulation (\u003cem\u003eps\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.03) and more inhibition problems (\u003cem\u003eps\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.02) than control ones. In addition, Very preterm TPL children exhibited lower psychomotor development (\u003cem\u003eps\u0026thinsp;\u0026le;\u003c/em\u003e\u0026thinsp;.040), more difficulties in working memory (\u003cem\u003eps\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;.002) and planification/organization (\u003cem\u003eps\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;.003) domains.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTPL \u003cem\u003eper se\u003c/em\u003e may represent a risk factor for children\u0026rsquo;s neurodevelopmental disturbances, specifically in emotional and regulation competences, even in the absence of prematurity.\u003c/p\u003e","manuscriptTitle":"Psychomotor development, emotional regulation, and executive functions in 2-years-old children after a threatened preterm labour: a prospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-08-25 17:42:24","doi":"10.21203/rs.3.rs-3286668/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-22T19:26:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-22T19:17:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"df017d83-3c1a-438c-b28e-be9b698a2b31","date":"2024-02-19T15:15:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-10-02T21:49:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-08-23T04:26:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-08-23T04:26:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Child \u0026 Adolescent Psychiatry","date":"2023-08-22T16:36:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-child-and-adolescent-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ecap","sideBox":"Learn more about [European Child \u0026 Adolescent Psychiatry](http://link.springer.com/journal/787)","snPcode":"787","submissionUrl":"https://submission.nature.com/new-submission/787/3","title":"European Child \u0026 Adolescent Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"230d912e-a40e-4365-b565-a3d8455c6857","owner":[],"postedDate":"August 25th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-25T16:07:17+00:00","versionOfRecord":{"articleIdentity":"rs-3286668","link":"https://doi.org/10.1007/s00787-024-02612-6","journal":{"identity":"european-child-and-adolescent-psychiatry","isVorOnly":false,"title":"European Child \u0026 Adolescent Psychiatry"},"publishedOn":"2024-11-20 15:57:43","publishedOnDateReadable":"November 20th, 2024"},"versionCreatedAt":"2023-08-25 17:42:24","video":"","vorDoi":"10.1007/s00787-024-02612-6","vorDoiUrl":"https://doi.org/10.1007/s00787-024-02612-6","workflowStages":[]},"version":"v1","identity":"rs-3286668","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3286668","identity":"rs-3286668","version":["v1"]},"buildId":"pf3fE39SIOqb-0xH_OWvX","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}