Fetal fraction of cell-free DNA in noninvasive prenatal testing and adverse pregnancy outcomes: a nationwide retrospective cohort study of 56,110 pregnant women.

BACKGROUND: Noninvasive prenatal testing by cell-free DNA analysis is offered to pregnant women worldwide to screen for fetal aneuploidies. In noninvasive prenatal testing, the fetal fraction of cell-free DNA in the maternal circulation is measured as a quality control parameter. Given that fetal cell-free DNA originates from the placenta, the fetal fraction might also reflect placental health and maternal pregnancy adaptation. OBJECTIVE: This study aimed to assess the association between the fetal fraction and adverse pregnancy outcomes. STUDY DESIGN: We performed a retrospective cohort study of women with singleton pregnancies opting for noninvasive prenatal testing between June 2018 and June 2019 within the Dutch nationwide implementation study (Trial by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing [TRIDENT]-2). Multivariable logistic regression analysis was used to assess associations between fetal fraction and adverse pregnancy outcomes. Fetal fraction was assessed as a continuous variable and as <10th percentile, corresponding to a fetal fraction <2.5%. RESULTS: The cohort comprised 56,110 pregnancies. In the analysis of fetal fraction as a continuous variable, a decrease in fetal fraction was associated with increased risk of hypertensive disorders of pregnancy (adjusted odds ratio, 2.27 [95% confidence interval, 1.89-2.78]), small for gestational age neonates <10th percentile (adjusted odds ratio, 1.37 [1.28-1.45]) and <2.3rd percentile (adjusted odds ratio, 2.63 [1.96-3.57]), and spontaneous preterm birth from 24 to 37 weeks of gestation (adjusted odds ratio, 1.02 [1.01-1.03]). No association was found for fetal congenital anomalies (adjusted odds ratio, 1.02 [1.00-1.04]), stillbirth (adjusted odds ratio, 1.02 [0.96-1.08]), or neonatal death (adjusted odds ratio, 1.02 [0.96-1.08]). Similar associations were found for adverse pregnancy outcomes when fetal fraction was <10th percentile. CONCLUSION: In early pregnancy, a low fetal fraction is associated with increased risk of adverse pregnancy outcomes. These findings can be used to expand the potential of noninvasive prenatal testing in the future, enabling the prediction of pregnancy complications and facilitating tailored pregnancy management through intensified monitoring or preventive measures.

Commentary: Promoting positive mental health during pregnancy-reflections on Lähdepuro et al. (2023).

Lähdepuro et al. performed a sound large-scale prospective pregnancy cohort study showing an association between positive maternal prenatal mental health and a reduced risk of developing clinically diagnosed childhood mental and behavioral disorders. Beneficial effects were also observed among the offspring of mothers experiencing mental health problems before and during pregnancy. The pathbreaking findings of Lähdepuro et al. set the stage for future research to shed more light on the so far almost unknown (neuro)biological mechanisms underlying the link between positive maternal prenatal mental health and child outcomes. More knowledge is needed about prenatal psychological and social factors enacting the potential of positive mental health as a resilience source buffering against maternal prenatal mental health problems and by this protecting subsequent child development. This also calls for further development, optimization, and evaluation of positive mental health-enhancing interventions during pregnancy, especially for future mothers having mental health problems.

Experiences of peripartum depressive symptoms among Chinese middle-class migrant women in the Netherlands: a qualitative study of migrant motherhood.

BACKGROUND: A low educational level and poor economic status have repeatedly been identified as the main risk factors of peripartum depression among migrant women in existing studies. However, there is limited knowledge about a group of highly educated and middle-class migrant women, and how this group of migrant women deals with those risks and which protective factors facilitate a successful transition into motherhood in the host country. This study aims to shed light on the multifaceted psychosocial challenges during the peripartum period for Chinese migrant women in their relationships with intimate partners, mothers, and mothers-in-law. METHODS: In this qualitative study, semi-structured in-depth interviews were conducted digitally with 46 pregnant and postpartum middle-class Chinese migrant women with peripartum depressive symptoms in the Netherlands. The interview data were analyzed using content analysis. RESULTS: The multifaceted psychosocial challenges for women with peripartum depressive symptoms were classified into three key categories: the ambivalence towards different mothering values, perceived inadequate and mismatching social support and adverse childhood experiences. CONCLUSION: Well-educated middle-class Chinese migrant women with peripartum depressive symptoms faced challenges in the transition into motherhood due to the unmet self-expectations regarding the pursuit of a good quality of life and a happy motherhood. The nurturing intimate relationships and adequate social support in the host country have mitigated recollections of their adverse childhood experiences. Future prevention programs and postpartum care should consider the contextual specificity based on the childhood history. International mental health research should pay more attention to the growing and potentially vulnerable group of well-educated middle-class migrant women.

Associations of severe adverse perinatal outcomes among continuous birth weight percentiles on different birth weight charts: a secondary analysis of a cluster randomized trial.

OBJECTIVE: To identify neonatal risk for severe adverse perinatal outcomes across birth weight centiles in two Dutch and one international birth weight chart. BACKGROUND: Growth restricted newborns have not reached their intrinsic growth potential in utero and are at risk of perinatal morbidity and mortality. There is no golden standard for the confirmation of the diagnosis of fetal growth restriction after birth. Estimated fetal weight and birth weight below the 10th percentile are generally used as proxy for growth restriction. The choice of birth weight chart influences the specific cut-off by which birth weight is defined as abnormal, thereby triggering clinical management. Ideally, this cut-off should discriminate appropriately between newborns at low and at high risk of severe adverse perinatal outcomes and consequently correctly inform clinical management. METHODS: This is a secondary analysis of the IUGR Risk Selection (IRIS) study. Newborns (n = 12 953) of women with a low-risk status at the start of pregnancy and that received primary antenatal care in the Netherlands were included. We examined the distribution of severe adverse perinatal outcomes across birth weight centiles for three birth weight charts (Visser, Hoftiezer and INTERGROWTH) by categorizing birth weight centile groups and comparing the prognostic performance for severe adverse perinatal outcomes. Severe adverse perinatal outcomes were defined as a composite of one or more of the following: perinatal death, Apgar score < 4 at 5 min, impaired consciousness, asphyxia, seizures, assisted ventilation, septicemia, meningitis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis. RESULTS: We found the highest rates of severe adverse perinatal outcomes among the smallest newborns (< 3rd percentile) (6.2% for the Visser reference curve, 8.6% for the Hoftiezer chart and 12.0% for the INTERGROWTH chart). Discriminative abilities of the three birth weight charts across the entire range of birth weight centiles were poor with areas under the curve ranging from 0.57 to 0.61. Sensitivity rates of the various cut-offs were also low. CONCLUSIONS: The clinical utility of all three charts in identifying high risk of severe adverse perinatal outcomes is poor. There is no single cut-off that discriminates clearly between newborns at low or high risk. TRIAL REGISTRATION: Netherlands Trial Register NTR4367 . Registration date March 20th, 2014.

Psychosocial and peripartum determinants of postpartum depression: Findings from a prospective population-based cohort. The ABCD study.

BACKGROUND: Postpartum depression is prevalent and concerns a serious health problem for women and their families. The current large-scale birth cohort study investigated: (1) the associations of various potential determinants of postpartum depression using a multidimensional approach, and (2) the individual contribution of obstetric and perinatal determinants and pregnancy-specific anxiety to the risk of postpartum depression. METHODS: This study was based on a large-scale birth cohort study in Amsterdam, the Netherlands (ABCD-study). In 5109 women depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (cut-off ≥16 indicating high risk of postpartum depression). Determinants were assessed using self-report or perinatal registries. RESULTS: In the final multivariable model, other-Western and non-Western ethnic background, increased antepartum depressive symptoms, increased antepartum anxiety, increased pregnancy-specific anxiety, being unemployed, poor sleep quality, unwanted pregnancy, abuse, multiparity, and congenital abnormality were all independently related to an increased risk of postpartum depression. The strongest risk factors for postpartum depression were antepartum depressive symptoms (adjusted odds ratio (AOR) = 3.86, 95% confidence interval (CI) 3.02-4.92), having a baby with a congenital abnormality (AOR = 2.33, 95% CI 1.46-3.73), and abuse (AOR = 1.95, 95% CI 1.02-3.73). The final model accounted for 24.5% of the variance. LIMITATIONS: Our dataset did not provide information on social support or maternal and family history of depression. Next to these determinants, future research should include biological factors. CONCLUSIONS: The determinants identified provide opportunities for the development of multidimensional early screening and early intervention strategies for women with an increased risk of postpartum depression.

Effectiveness of a guided ACT-based self-help resilience training for depressive symptoms during pregnancy: Study protocol of a randomized controlled trial embedded in a prospective cohort.

BACKGROUND: During pregnancy, about 10 to 20% of women experience depressive symptoms. Subclinical depression increases the risk of peripartum depression, maternal neuro-endocrine dysregulations, and adverse birth and infant outcomes. Current treatments often comprise face-to-face psychological or pharmacological treatments that may be too intensive for women with subclinical depression leading to drop-out and moderate effectiveness. Therefore, easily accessible, resilience enhancing and less stigmatizing interventions are needed to prevent the development of clinical depression. This paper describes the protocol of a prospective cohort study with an embedded randomized controlled trial (RCT) that aims to improve mental resilience in a sample of pregnant women through a self-help program based on the principles of Acceptance and Commitment Therapy (ACT). Maternal and offspring correlates of the trajectories of peripartum depressive symptoms will also be studied. METHODS: Pregnant women (≥ 18 years) receiving care in Dutch midwifery practices will participate in a prospective cohort study (n ~ 3500). Between 12 and 18 weeks of pregnancy, all women will be screened for depression with the Edinburgh Postnatal Depression Scale (EPDS). Women with an EPDS score ≥ 11 will be evaluated with a structured clinical interview. Participants with subclinical depression (n = 290) will be randomized to a 9-week guided self-help ACT-training or to care as usual (CAU). Primary outcomes (depressive symptoms and resilience) and secondary outcomes (e.g. anxiety and PTSD, bonding, infant development) will be collected via online questionnaires at four prospective assessments around 20 weeks and 30 weeks gestation and at 6 weeks and 4 months postpartum. Maternal hair cortisol concentrations will be assessed in a subsample of women with a range of depressive symptoms (n = 300). The intervention's feasibility will be assessed through qualitative interviews in a subsample of participants (n = 20). DISCUSSION: This is the first study to assess the effectiveness of an easy to administer intervention strategy to prevent adverse mental health effects through enhancing resilience in pregnant women with antepartum depressive symptomatology. This longitudinal study will provide insights into trajectories of peripartum depressive symptoms in relation to resilience, maternal cortisol, psychological outcomes, and infant developmental milestones. TRIAL REGISTRATION: Netherlands Trial Register (NTR), NL7499 . Registered 5 February 2019.

Children prenatally exposed to maternal anxiety devote more attentional resources to neutral pictures.

Maternal anxiety during pregnancy can negatively affect fetal neurodevelopment, predisposing the offspring to a higher risk of behavioral and emotional problems later in life. The current study investigates the association between maternal anxiety during pregnancy and child affective picture processing using event-related brain potentials (ERPs). Mothers reported anxiety during the second trimester using the anxiety subscale of the Symptom Checklist (SCL-90). At age 4 years, child affective picture processing (N = 86) was measured by recording ERPs during viewing of neutral, pleasant, and unpleasant pictures selected from the International Affective Pictures System. The late positive potential (LPP)-an ERP component reflecting individual differences in affective processing-was used as child outcome. The expected positive association between maternal anxiety and LPP amplitude for unpleasant pictures was not found. Nevertheless, we found a positive association between maternal anxiety during pregnancy and LPP amplitudes for neutral pictures in the middle and late time window at anterior locations (all p < .05). These associations remained significant after adjusting for maternal postnatal anxiety and gestational age at birth and after FDR correction for multiple comparisons. Our study provides neurophysiological evidence that children prenatally exposed to higher maternal anxiety devote more attentional resources to neutral pictures, but not to unpleasant pictures. Possibly, these children show enhanced vigilance for threat when viewing neutral pictures. Although useful in dangerous environments, this enhanced vigilance may predispose children prenatally exposed to higher maternal anxiety to developing behavioral and/or emotional problems later in life. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=kEzYi6IS2HA.

Effectiveness and cost-effectiveness of routine third trimester ultrasound screening for intrauterine growth restriction: study protocol of a nationwide stepped wedge cluster-randomized trial in The Netherlands (The IRIS Study).

BACKGROUND: Intrauterine growth retardation (IUGR) is a major risk factor for perinatal mortality and morbidity. Thus, there is a compelling need to introduce sensitive measures to detect IUGR fetuses. Routine third trimester ultrasonography is increasingly used to detect IUGR. However, we lack evidence for its clinical effectiveness and cost-effectiveness and information on ethical considerations of additional third trimester ultrasonography. This nationwide stepped wedge cluster-randomized trial examines the (cost-)effectiveness of routine third trimester ultrasonography in reducing severe adverse perinatal outcome through subsequent protocolized management. METHODS: For this trial, 15,000 women with a singleton pregnancy receiving care in 60 participating primary care midwifery practices will be included at 22 weeks of gestation. In the intervention (n = 7,500) and control group (n = 7,500) fetal growth will be monitored by serial fundal height assessments. All practices will start offering the control condition (ultrasonography based on medical indication). Every three months, 20 practices will be randomized to the intervention condition, i.e. apart from ultrasonography if indicated, two routine ultrasound examinations will be performed (at 28-30 weeks and 34-36 weeks). If IUGR is suspected, both groups will receive subsequent clinical management as described in the IRIS study protocol that will be developed before the start of the trial. The primary dichotomous clinical composite outcome is 'severe adverse perinatal outcome' up to 7 days after birth, including: perinatal death; Apgar score <4 at 5 minutes after birth; impaired consciousness; need for assisted ventilation for more than 24 h; asphyxia; septicemia; meningitis; bronchopulmonary dysplasia; intraventricular hemorrhage; cystic periventricular leukomalacia; neonatal seizures or necrotizing enterocolitis. For the economic evaluation, costs will be measured from a societal perspective. Quality of life will be measured using the EQ-5D-5 L to enable calculation of QALYs. Cost-effectiveness and cost-utility analyses will be performed. In a qualitative sub-study (using diary notes from 32 women for 9 months, at least 10 individual interviews and 2 focus group studies) we will explore ethical considerations of additional ultrasonography and how to deal with them. DISCUSSION: The results of this trial will assist healthcare providers and policymakers in making an evidence-based decision about whether or not introducing routine third trimester ultrasonography. TRIAL REGISTRATION: NTR4367 , 21 March 2014.

Early lexical development and risk of verbal and nonverbal cognitive delay at school age.

AIM: To characterise the relationship between preschool lexical delay and language comprehension and nonverbal intelligence at school age. METHODS: The mothers of 2724 children completed the MacArthur Communicative Development Inventory when their child reached 1.5 years and the Language Development Survey and the Parent Report of Children's Ability at 2.5 years. When the children were 6 years old, we assessed vocabulary comprehension and nonverbal intelligence using Dutch batteries for language and nonverbal intelligence. RESULTS: Demographic factors explained 9.9% of the variance in vocabulary comprehension and 8.7% of the variance in nonverbal intelligence at 6 years. Male gender, low maternal education and non-Western ethnic background predicted vocabulary comprehension delay at 6 years. Lexical development at 1.5 and 2.5 years explained only 3.8% of the variance in language comprehension at the age of six. Late onset expressive vocabulary delay increased the risk of language comprehension and nonverbal intelligence delay at 6 years (OR=2.31, 95% CI: 1.62-3.29 and OR=1.74, 95% CI: 1.17-2.58, respectively). CONCLUSION: Sociodemographic factors are important predictors of delays in language and nonverbal abilities as children enter school. In contrast, early expressive lexical delays, in particular before the age of two, have limited predictive power for language delays at the age of six.

The Association Between Unintended Pregnancy and Perinatal Outcomes in Low-Risk Pregnancies: A Retrospective Registry Study in the Netherlands.

INTRODUCTION: People with unintended pregnancies might be at increased risk of adverse perinatal outcomes due to structural factors, distress, or delayed prenatal care. Existing studies addressing this association yielded inconsistent findings. Using contemporary data from a large Dutch midwifery care registry, we investigated the association between unintended pregnancy ending in birth and neonatal outcomes, parental morbidity, and obstetric interventions. We extend previous research by exploring whether delayed initiation of prenatal care mediates these associations. METHOD: This study used data (N = 9803) from a Dutch nationally representative registry of people with low-risk pregnancies receiving primary midwife-led care in the Netherlands between 2012 and 2020. Using logistic (mediation) regression analyses adjusted for potential confounders we investigated associations between unintended pregnancy and neonatal outcomes (low Apgar score, small for gestational age, and prematurity), parental morbidity (hypertension and gestational diabetes mellitus), and obstetric interventions (induction of labor, pain medication, assisted vaginal birth, and cesarean birth) and whether delayed initiation of prenatal care mediated these associations. RESULTS: Unintended pregnancies were associated with increased odds of low Apgar scores (odds ratio [OR], 1.68; 95% CI, 1.09 -2.59), preterm birth (OR, 1.27; 95% CI, 1.02-1.58), small for gestational age (OR, 1.19; 95% CI, 1.00-1.41), and induction of labor (OR, 1.14; 95% CI, 1.01-1.28). Conversely, unintended pregnancy was associated with a decreased odds of cesarean birth (OR, 0.83; 95% CI, 0.71-0.97). The timing of prenatal care initiation did not mediate any of these associations. DISCUSSION: Our findings suggest that people in primary midwifery-led care with unintended pregnancies ending in birth are at increased risk for adverse perinatal health outcomes and that structural factors might underlie this link. Health care professionals and policy makers should attend to their own biases and offer nonjudgmental, tailored preventive preconception care and antenatal care strategies for people with higher vulnerabilities.

Correlates of physical activity in 2-year-old toddlers: the generation R study.

OBJECTIVE: To describe and identify correlates of objectively measured physical activity and sedentary behavior in 2-year-old toddlers. STUDY DESIGN: A total of 347 children participating in a birth cohort study wore a unaxial ActiGraph accelerometer during 1 weekday and 1 weekend day. Information on potential correlates was assessed by parent-reported questionnaires, delivery reports, and regular visits to child health centers. Univariate and multivariable linear regression analyses were conducted to examine the associations between potential correlates and the following physical activity outcomes: percentage of time spent in sedentary behavior, percentage of time spent in moderate-to-vigorous physical activity, and mean counts per minute. RESULTS: A high percentage of monitored time was spent in sedentary behavior; 85.6% on weekdays and 84.5% on weekend days. Four correlates were significantly associated with at least 1 physical activity outcome in the multivariable regression models: child's sex, child's age, number of siblings, and season of measurement. The associations of gross motor development with moderate-to-vigorous physical activity and mean counts per minute approached significance. Associations of socioeconomic variables and child's body mass index z-score with physical activity outcomes were not significant. CONCLUSION: Two-year-old toddlers spend most of their time in sedentary behavior. No modifiable correlates were identified. Further research on physical activity and associated health benefits among very young children is warranted.

Maternal hypothyroxinemia and effects on cognitive functioning in childhood: how and why?

Exposure to maternal hypothyroxinemia during pregnancy, which is characterized by low free T4 but normal thyroid-stimulating hormone (TSH) levels, can negatively affect the foetus. This review provides an overview of present findings concerning the association between maternal hypothyroxinemia during pregnancy and childhood cognitive functioning. Possible causes of maternal hypothyroxinemia and potential mechanisms underlying this association are also discussed. Clinical and epidemiological studies suggest that maternal hypothyroxinemia in the first half of pregnancy but not later in pregnancy impairs cognitive development in infancy and childhood. Animal models confirm that the first half of pregnancy may constitute a sensitive period in which maternal hypothyroxinemia alters neurogenesis and causes neuronal migration errors in the developing foetal brain. However, observational studies in humans cannot demonstrate causality of the association between hypothyroxinemia and neurodevelopment. In the only completed randomized trial of antenatal thyroid screening and subsequent levothyroxine treatment of mild maternal subclinical thyroid dysfunction, including hypothyroxinemia, the interventions did not affect offspring intelligence quotient (IQ). More randomized trials are needed investigating whether screening for hypothyroxinemia and its treatment earlier in the first trimester of pregnancy can improve child cognitive functioning or prevent neurodevelopmental changes. Long-term observational studies should identify molecular, neuroanatomical and neurophysiological factors involved in the association between maternal hypothyroxinemia and offspring cognitive functioning. Information on such mechanisms can be used for the development of innovative prevention and intervention studies that address maternal hypothyroxinemia and its potential consequences.

Understanding the relationship between maternity care providers and middle-class Chinese migrant women in the Netherlands: A qualitative study.

OBJECTIVE: This study aims to provide insights into the formation and the quality of the maternity care provider-woman relationship between midwives, maternity care assistants and middle-class Chinese migrant women in the Netherlands. DESIGN: online in-depth interviews addressing interpersonal trust, women's autonomy in shared decision making and culturally sensitive care PARTICIPANTS: 46 middle-class Chinese migrant women, 13 midwives and 12 maternity care assistants in the Netherlands FINDINGS: Midwives and maternity care assistants reported challenges interpreting the needs of middle-class Chinese migrant women in care practices while Chinese migrant women experienced receiving insufficient emotional support. Midwives and maternity care assistant tended to attribute women's different preferences for care to culture which reinforced difficulties of addressing women's needs. Middle-class Chinese migrant women experienced a lack of responsive care, feelings of being overlooked, being uncomfortable to express different opinions and challenges in developing autonomy in the shared decision-making process. CONCLUSIONS: A trusting relationship, effective communication with maternity care providers, and a culturally sensitive and safe environment could be beneficial for middle-class migrant mothers. Chinese migrant women held ambivalent attitudes towards both traditional Chinese health beliefs and Dutch maternity care values. Each individual woman adopted the practice of the "doing the month" tradition to a different extent. This indicated the need for maternity care providers to recognize women's various needs for more responsive and individualized care, especially for first-time migrant mothers to negotiate their ways through the new healthcare system. IMPLICATIONS FOR PRACTICE: We suggest a more proactive role for maternity care providers addressing the individual's subjectivity and preferences. Our findings are relevant and applicable for maternity care professionals conducting shared decision making with middle-class and highly educated migrant women living in Western contexts.

What are antenatal maternity care needs of women who conceived through fertility treatment?: a mixed methods systematic review.

BACKGROUND: Existing research indicates that pregnant women who conceived through fertility treatment might experience more stress and anxiety compared to women who conceived spontaneously. Therefore, these women might have additional antenatal care needs. METHODS: A search for both quantitative and qualitative studies was performed in PubMed, PsycINFO, CINAHL and MEDLINE through May 2021, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. 21 articles met the inclusion criteria. After methodological quality appraisal using the Mixed Methods Appraising Tool, 15 studies were included in the review. RESULTS: Analysis of the studies identified behavioral, relational/social, emotional, and cognitive needs and women's preference about maternity care. Women who conceived through fertility treatment reported lower social and physical functioning scores and elevated levels of anxiety and depression compared to women who conceived spontaneously. They reported difficulties adjusting to pregnancy and experienced a care gap between discharge from the fertility clinic and going to local maternity care services for their first consultation, and a care gap postpartum. CONCLUSIONS: Women who conceived through fertility treatment have additional antenatal care needs. We recommend to offer these women more frequent check-ins, and to pay attention to the impact of their infertility and treatment on their pregnancy.

Correlates of posttraumatic stress disorder in forensic psychiatric outpatients in the Netherlands.

Using a sample of 154 Dutch forensic psychiatric outpatients aged 18-62 years, this study investigated whether risk factors of posttraumatic stress disorder (PTSD), mainly identified in nonforensic research, forensic psychiatric factors, and potential comorbid mental disorders were associated with PTSD. Data on demographics, victimization during childhood or adolescence, and forensic psychiatric factors were derived from electronic medical records. Mental disorders were assessed using structured psychiatric interviews and consensus diagnoses were established during weekly case consultations. The PTSD rate was 75% in the sample. Whereas the PTSD group was significantly more likely to be older, female, not Dutch, and to have a history of victimization, previously perpetrated family violence, and lower psychosocial and occupational functioning than the non-PTSD group, the latter group had significantly higher rates of psychiatric history, attention-deficit/hyperactivity disorder (ADHD), antisocial personality disorder, drug abuse, and previous repeated nonfamily violence perpetration. Effect sizes ranged from Nagelkerke R(2) = .04 for psychosocial and occupational functioning to Nagelkerke R(2) = .70 for ADHD. This study demonstrated differences between those with and without PTSD in demographic, victim, forensic, and psychological characteristics. Future studies should examine the complexity between early victimization, delinquency patterns, and psychopathology regarding the prediction of PTSD among forensic psychiatric outpatients.

Associations Between Maternal Lipid Blood Levels at the 13th Week of Pregnancy and Offspring's Adiposity at Age 11-12 Years.

CONTEXT: There is increasing evidence that intrauterine lipid metabolism influences the adiposity of the newborn and the first years thereafter. It remains unclear if these effects persist when these children grow older. OBJECTIVE: This study examined the associations between maternal lipid blood levels during the 13th week of pregnancy and an offspring's adiposity, measured at age 11-12, and if these associations were moderated by the child's sex. METHODS: Data were obtained from a community-based birth cohort, the Amsterdam Born Children and their Development (ABCD) study. At a median of 13 weeks' gestation, nonfasting blood samples of triglycerides (TGs), total cholesterol (TC), free fatty acids (FFAs), and apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) were measured. An offspring's body mass index (BMI), subcutaneous fat (SCF), waist-to-height-ratio (WHtR), and fat percentage (fat%) were measured at age 11-12. Mothers with at-term born children were included (n = 1853). Multivariable linear regression analyses were performed to assess the associations between maternal lipids and each offspring's adiposity outcome separately. Sex differences were additionally evaluated. RESULTS: TGs, TC, ApoB/ApoA1, and FFAs were significantly positively associated with BMI, WHtR, and fat% (adjusted for gestational age at blood sampling, child's age, sex, and sexual maturation). After additional adjustments for potential confounders and covariates, only TGs remained significantly associated with WHtR (0.45, 95% CI -0.007; 0.91). There were no associations between maternal lipids and SCF and no clear sex-specific results were found. CONCLUSION: Overall, our results do not strongly support that maternal lipid profile during the 13th week of pregnancy has programming effects on adiposity in preadolescence.

Resilience-enhancing interventions for antepartum depressive symptoms: systematic review.

BACKGROUND: Antepartum depressive symptoms (ADS) are highly prevalent and may affect the mother and child. Cognitive-behavioural therapy and interpersonal therapy are effective psychological interventions for depression. However, low adherence and high attrition rates in studies of prevention and treatment of antepartum depression suggest that these approaches might not be entirely suitable for women with mild/moderate ADS. Considering the protective association between resilience and ADS, women with ADS might benefit more from interventions focusing on promotion of mental well-being and resilience. AIMS: We aimed to provide an overview of studies evaluating the effectiveness of antepartum resilience-enhancing interventions targeting the improvement of ante- and postpartum depressive symptoms. We also investigated whether these interventions improve resilience and resilience factors in the peripartum period. METHOD: We conducted a systematic review, using PRISMA guidelines. Studies were eligible for inclusion when they utilised a randomised controlled trial or quasi-experimental design, studied pregnant women with ADS, and implemented psychological interventions that (a) aimed to reduce maternal ADS and/or prevent peripartum major depression, and (b) addressed one or more psychological resilience factors. RESULTS: Five of the six included cognitive-behavioural therapy interventions and all four mindfulness-based interventions were effective in reducing peripartum depressive symptoms and/or the incidence of depression. However, the methodological quality of most of the included studies was low to moderate. Only three studies assessed change in resilience factors. CONCLUSIONS: Resilience-enhancing interventions might be beneficial for mental well-being of pregnant women with ADS, although more rigorously designed intervention studies are needed.

Mediating role of C-reactive protein in associations between pre-pregnancy BMI and adverse maternal and neonatal outcomes: the ABCD-study cohort.

OBJECTIVES: Increased body mass index (BMI) is associated with several adverse pregnancy outcomes, though the underlying mechanism of this association has not been fully elucidated. A mediating role of low-grade systemic inflammation in these associations is suspected but has been understudied. Our objective was to examine the effect of pre-pregnancy BMI (pBMI) on maternal and neonatal pregnancy outcomes and to explore potential mediation of these effects by C-reactive protein (CRP), a first trimester peripheral marker of inflammation. METHODS: Data from the prospective community-based ABCD-study cohort (n = 3547) was used to assess associations between self-reported continuous and categorized pBMI and outcome measures gestational hypertension (GH) and preeclampsia (PE), preterm birth (PTB) and small for gestational age (SGA) based on national perinatal registration linkage data. High-sensitivity CRP concentrations determined in serum were used to explore potential mediation of these associations by inflammation. RESULTS: Multivariable logistic regression analyses, adjusted for confounders, showed that pBMI was significantly related to gestational hypertensive disorders (odds ratio (OR) per standard deviation (SD) 1.66, 95% confidence interval (CI) 1.51-1.83) and PTB (OR 1.20, 95% CI 1.05-1.37). Dose-response relationships between categorical pBMI and gestational hypertensive disorders (overweight OR 2.37, 95% CI 1.85-3.03 and obese OR 4.45, 95% CI 2.93-6.72) and PTB (obese OR 2.12, 95% CI 1.16-3.87) were found as well. SGA was only significantly more prevalent in the underweight BMI category (OR 2.06, 95% CI 1.33-3.19). Mediation analyses revealed small but significant indirect effects of pBMI on overall PTB (0.037, bootstrapped 95% CI 0.005-0.065) and spontaneous PTB (0.038, bootstrapped 95% CI 0.002-0.069) through higher CRP. CRP was not a significant mediator of associations between BMI and gestational hypertensive disorders although larger mediation was found for GH than for PE. CONCLUSION: Our findings provide additional evidence that high(er) pBMI increases the risk of adverse maternal and neonatal outcomes and that systemic inflammation mediates some of these risks. Further research in large cohorts including (morbidly) obese women is warranted to identify pathways that may be incorporated in future interventions to reduce the risk of adverse pregnancy outcomes due to maternal obesity.

Cost-Effectiveness of Routine Third Trimester Ultrasound Screening for Fetal Growth Restriction Compared to Care as Usual in Low-Risk Pregnancies: A Pragmatic Nationwide Stepped-Wedge Cluster-Randomized Trial in The Netherlands (the IRIS Study).

Routine third trimester ultrasonography is increasingly used to screen for fetal growth restriction. However, evidence regarding its cost-effectiveness is lacking. We aimed to evaluate the cost-effectiveness of routine third trimester ultrasonography to reduce adverse perinatal outcomes compared to usual care (selective ultrasonography). An economic evaluation alongside a stepped-wedge cluster-randomized trial was conducted. Via 60 midwifery practices 12,974 Dutch women aged ≥16 years with low-risk pregnancies were enrolled at 22.8 (SD = 2.4) weeks' gestation. All practices provided usual care. At 3, 7, and 10 months a third of the practices were randomized to the intervention strategy providing routine ultrasonography at 28-30 and 34-36 weeks' gestation and usual care. The primary clinical outcome was a dichotomous composite measure of 12 severe adverse perinatal outcomes (SAPO) up to one week postpartum. Information on perinatal care and societal costs was derived from Netherlands Perinatal Registry, hospital records and a survey. Cost-effectiveness analyses revealed no significant differences in SAPO and healthcare and societal costs between the intervention strategy (n = 7026) and usual care (n = 5948). Cost-effectiveness acceptability curves showed that the probability of cost-effectiveness was never higher than 0.6 for all possible ceiling ratios. Adding routine third trimester ultrasonography to usual care is not cost-effective in reducing SAPO.

Maternal thyroid function during pregnancy and behavioral problems in the offspring: the generation R study.

Maternal thyroid function during pregnancy is implicated in the neurodevelopment of the offspring, yet little is known about the effect of maternal thyroid parameters on the behavior of children. We investigated the association of maternal thyroid function during the first half of pregnancy with parent-reported problem behavior of the offspring up to age of 3 y. In the Generation R study, a population-based cohort of 3736 children and their mothers, data on maternal thyroid function and child's behavior were examined. The degree of internalizing and externalizing problems in the children were assessed with the Child Behavior Checklist at ages 1½ and 3 y. Higher levels of maternal TSH during pregnancy predicted a higher externalizing scores in children at 1½ and 3 y (B = 0.22 per SD of TSH; 95% CI: 0.04, 0.40; B = 0.10 per SD for internalizing scores; 95% CI: -0.01, 0.21). Maternal free thyroxine (T4) and total T4 were not associated with internalizing or externalizing scores of children. The linear relationship with more externalizing scores was across the range of TSH; this implies that subtle impairments of maternal thyroid function may affect the child. The results suggest that thyroid function is crucial for fetal brain development, which determines problem behavior later in life.