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. This study aimed to assess the association between the fetal fraction and adverse pregnancy outcomes. 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%. 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. 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.

Objectives: Maternal anxiety during pregnancy is a risk factor for child behavioral/emotional problems. Knowledge about explanatory factors mediating this link is scarce. Maternal anxiety during pregnancy may be an indicator of adverse postnatal environmental conditions, including maternal anxiety and poor parenting, possibly affecting child behavior. This study investigated whether maternal anxiety and mindful parenting in early childhood mediate the association between maternal anxiety during pregnancy and child behavioral/emotional problems. Methods: This study was based on a sample of 118 mother-child dyads who participated in a cohort study that followed participants from pregnancy until 4 years after birth. At 21 weeks’ gestation and when the child was 4 years old, mothers completed questionnaires to assess state anxiety (State-Trait Anxiety Inventory) and general anxiety (Symptom Checklist-90 anxiety subscale). At age 4 years, mothers reported mindful parenting (Interpersonal Mindfulness in Parenting Scale) and child behavioral/emotional problems (Child Behavior Checklist). Results: Maternal state anxiety during pregnancy was positively associated with child internalizing problems and negatively with mindful parenting. Maternal general anxiety during pregnancy was related with more child internalizing and externalizing problems but not with mindful parenting. The association between maternal state anxiety during pregnancy and child internalizing problems was sequentially mediated via concurrent maternal general anxiety and mindful parenting. Conclusions: These findings suggest that maternal anxiety during pregnancy continues into early childhood and, because of this, it subsequently affects child internalizing behavior via poor mindful parenting. Replication studies are needed before developing interventions for tackling maternal anxiety during pregnancy and promoting mindful parenting.

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 10^thpercentile 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 (< 3^rdpercentile) (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 RegisterNTR4367.Registration date March 20^th, 2014.

Maternal prenatal distress (i.e., anxiety and depressive symptoms) increases the risk for childhood behavioral and emotional problems. So far, the potential role of maternal bonding in this association still needs further study. Maternal prenatal distress can affect the development of maternal bonding from pregnancy onwards. Maternal prenatal and postnatal bonding in turn have been shown to predict child behavioral functioning. We aimed to investigate whether maternal prenatal and postnatal bonding mediate the association between maternal prenatal distress and toddlers’ internalizing and externalizing problems. Data from a Dutch prospective longitudinal sample (N = 666) were used to conduct single and multiple mediation models. Mothers reported prenatal anxiety (State Anxiety Inventory) and prenatal depressive symptoms (Edinburgh Postnatal Depression Scale) at 24 weeks’ gestation and maternal prenatal bonding (Maternal Antenatal Attachment Scale) at 32 weeks’ gestation. At 6 weeks and 6 months postpartum mothers completed questionnaires to assess maternal postnatal bonding (Maternal Postnatal Attachment Scale). Mothers reported child internalizing and externalizing problems (Child Behavior Checklist) at 28 months postpartum. Maternal prenatal and postnatal bonding mediated the link between maternal prenatal anxiety and child externalizing problems but not internalizing problems. Only maternal bonding 6 months postpartum mediated the link between maternal prenatal depressive symptoms and child internalizing problems but not externalizing problems. Our study showed that maternal postnatal bonding more consistently mediated links between measures of maternal prenatal distress and child behavioral and emotional problems than maternal prenatal bonding. Interventions reducing maternal prenatal distress and promoting maternal bonding should be developed.

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.

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.