Maternity care increasingly focuses on evaluating psychosocial vulnerability during pregnancy. Re... more Maternity care increasingly focuses on evaluating psychosocial vulnerability during pregnancy. Research and nationwide (public health) programs, both in the USA and Europe, led to the development of new protocols and screening instruments for care providers to systematically screen for psychosocial vulnerability in pregnant women. However, standardised screening for vulnerability is complex since it requires discussion of sensitive issues. Women may fear stigmatisation and may have limited trust in their care providers or the health system. Our study contributes to the growing field of client-facing risk work by exploring care providers' interpretations and evaluation of psychosocial vulnerability in pregnant women. Drawing on semi-structured interviews with Dutch maternity care providers, we explore how they conceptualise risk and vulnerability and identify 'vulnerable pregnant women' in their practices. We find that care providers conceptualise 'vulnerability' as primarily based on risk, which contributes to an imbalanced focus on individual mothers, rather than on both parents and the social context. Our findings highlight care providers' concerns around 'care avoidance', seen as a risk factor affecting 'vulnerability' during pregnancy and as a possible consequence of risk screening. The care providers we interviewed employ "in between-strategies" based on intuition, emotion, and trust to skillfully attend to the risk that comes with risk work, in terms of its potential impact on relationships of trust and open communication. We conclude that 'vulnerability' should be understood as a multi-layered, situated and relational concept rather than simply as an epidemiological category. Since a trusting relationship between pregnant women and care providers is crucial for the evaluation of vulnerability, we reflect critically on the risk of standardised perinatal psychosocial risk evaluations. Policy should recognise providers' "in between-strategies" to embed epidemiological understandings of risk in the context of everyday risk work.
Background Unplanned or unintended pregnancies form a major public health concern because they ar... more Background Unplanned or unintended pregnancies form a major public health concern because they are associated with unfavorable birth outcomes as well as social adversity, stress and depression among parents-to-be. Several risk factors for unplanned pregnancies in women have previously been identified, but studies usually take a unidimensional approach by focusing on only one or few factors, disregarding the possibility that predictors might cluster. Furthermore, data on predictors in men are largely overlooked. The purpose of this study is to determine predictors of unplanned versus planned pregnancy, to determine predictors of ambivalent feelings regarding pregnancy, and to investigate how characteristics of men and women with an unplanned pregnancy cluster together. Methods This study was embedded in Generation R, a multiethnic population-based prospective cohort from fetal life onwards. Pregnancy intention was reported by 7702 women and 5367 partners. Information on demographic, ...
PurposeThe purpose of this study is to describe the implementation and outcomes of an Eye Movemen... more PurposeThe purpose of this study is to describe the implementation and outcomes of an Eye Movement and Desensitization Reprocessing (EMDR) treatment-program for women with posttraumatic stress disorder (PTSD) after childbirth.MethodsA prospective cohort-study with pre- and post-measurements was carried out in the setting of an academic hospital in the Netherland. Included were women who gave birth to a living child at least 4 weeks ago, with a diagnosis of PTSD, or severe symptoms of PTSD combined with another psychiatric diagnosis. All received up to 8 sessions of EMDR-therapy. The posttraumatic stress disorder Checklist for DSM-5 was administered before and after treatment. Trauma history was assessed before treatment with the Life Events Checklist for the DSM-5, the Childhood Trauma Questionnaire and the Childbirth Perception Scale. Descriptive statistics were used.ResultsForty-four women were referred, 26 met the inclusion criteria. After treatment, none of the women met the cri...
International Journal of Environmental Research and Public Health
The COVID-19 pandemic has a major impact on society, particularly affecting its vulnerable member... more The COVID-19 pandemic has a major impact on society, particularly affecting its vulnerable members, including pregnant women and their unborn children. Pregnant mothers reported fear of infection, fear of vertical transmission, fear of poor birth and child outcomes, social isolation, uncertainty about their partner’s presence during medical appointments and delivery, increased domestic abuse, and other collateral damage, including vaccine hesitancy. Accordingly, pregnant women’s known vulnerability for mental health problems has become a concern during the COVID-19 pandemic, also because of the known effects of prenatal stress for the unborn child. The current narrative review provides a historical overview of transgenerational effects of exposure to disasters during pregnancy, and the role of maternal prenatal stress. We place these effects into the perspective of the COVID-19 pandemic. Hereby, we aim to draw attention to the psychological impact of the COVID-19 pandemic on women o...
Pregnancy and the puerperium do not protect against acute psychiatric illness. During puerperium,... more Pregnancy and the puerperium do not protect against acute psychiatric illness. During puerperium, the chance of acute psychiatric illness, such as a psychotic episode or relapse of bipolar disorder, is greatly increased. Suicide is a leading cause of maternal death. Both psychiatric disease and ongoing drug addiction impact not only the pregnant woman's somatic and mental health but also impact short-term and long-term health of the child. Indeed, prompt recognition and expeditious treatment of acute psychiatric illness during pregnancy and the puerperium optimize health outcomes for two patients. Pregnancy and puerperium represent a stage of life of great physiologic adaptations, as well as emotional and social changes. This conjunction of changes in somatic, emotional health and social health may mitigate the occurrence, clinical presentation, and clinical course of acute psychiatric illness and call for a multidisciplinary approach, taking into account both the medical and social domains. This chapter describes acute psychiatric illnesses during pregnancy and the puerperium and illicit substance abuse, from a clinical perspective, while also describing general principles of diagnosis and clinical management during this stage of life, which is an important window of opportunity for both the pregnant woman and the child.
Supplemental material, Supplementary_Material for Lithium exposure during pregnancy increases fet... more Supplemental material, Supplementary_Material for Lithium exposure during pregnancy increases fetal growth by Eline MP Poels, Karin Sterrenburg, André I Wierdsma, Richard Wesseloo, Annemerle Beerthuizen, Laura van Dijke, Condon Lau, Witte JG Hoogendijk, Hanan El Marroun, Inge L van Kamp, Hilmar H Bijma and Veerle Bergink in Journal of Psychopharmacology
ObjectivesApproximately 11%–13% of pregnant women suffer from depression. Bright light therapy (B... more ObjectivesApproximately 11%–13% of pregnant women suffer from depression. Bright light therapy (BLT) is a promising treatment, combining direct availability, sufficient efficacy, low costs and high safety for both mother and child. Here, we examined the effects of BLT on depression during pregnancy.DesignRandomised, double-blind controlled trial.SettingPrimary and secondary care in The Netherlands, from November 2016 to March 2019.Participants67 pregnant women (12–32 weeks gestational age) with a DSM-5 diagnosis of depressive disorder (Diagnostic and Statistical Manual of Mental Disorders).InterventionsParticipants were randomly allocated to treatment with either BLT (9000 lux, 5000 K) or dim red light therapy (DRLT, 100 lux, 2700 K), which is considered placebo. For 6 weeks, both groups were treated daily at home for 30 min on awakening. Follow-up took place weekly during the intervention, after 6 weeks of therapy, 3 and 10 weeks after treatment and 2 months postpartum.Primary and ...
Background Alcohol consumption during pregnancy is associated with major birth defects and develo... more Background Alcohol consumption during pregnancy is associated with major birth defects and developmental disabilities. Questionnaires concerning alcohol consumption during pregnancy underestimate alcohol use while the use of a reliable and objective biomarker for alcohol consumption enables more accurate screening. Phosphatidylethanol can detect low levels of alcohol consumption in the previous two weeks. In this study we aimed to biochemically assess the prevalence of alcohol consumption during early pregnancy using phosphatidylethanol in blood and compare this with self-reported alcohol consumption. Methods To evaluate biochemically assessed prevalence of alcohol consumption during early pregnancy using phosphatidylethanol levels, we conducted a prospective, cross-sectional, single center study in the largest tertiary hospital of the Netherlands. All adult pregnant women who were under the care of the obstetric department of the Erasmus MC and who underwent routine blood testing a...
OBJECTIVES Lithium is an effective treatment for bipolar disorder, also during pregnancy to preve... more OBJECTIVES Lithium is an effective treatment for bipolar disorder, also during pregnancy to prevent the recurrence of episodes in the perinatal period. Little is known about the neuropsychological development of lithium-exposed offspring. The current study was designed to investigate neuropsychological functioning in lithium-exposed children with the aim to provide further knowledge on the long-term effects of lithium use during pregnancy. METHODS Participants were offspring of women with a diagnosis of bipolar spectrum disorder, aged 6 to 14 years. In total 99 children participated in the study, 56 were exposed to lithium in utero and 43 were not exposed to lithium. Neuropsychological tests were administered, including the Snijders-Oomen Nonverbal Intelligence Test and the NEPSY-II-NL assessment. Linear and Negative Binomial regression models were used to investigate the association between prenatal lithium exposure and neuropsychological functioning. In secondary analyses, the association between lithium blood level during pregnancy and neuropsychological functioning was assessed. Additionally, norm scores and percentiles for task outcomes were calculated. RESULTS Lithium use during pregnancy was associated with the total number of mistakes made on the Auditory Attention task, but not statistically significant after full adjustment for potential confounding factors. No association between prenatal lithium exposure and IQ was found. Also, no relationship between lithium blood level during pregnancy and neuropsychological functioning was found after adjustment for potential confounders. Task outcomes in both groups were comparable to the general population. CONCLUSION In this study we found no evidence for significantly altered neuropsychological functioning of lithium-exposed children at the age of 6 to 14 years, when compared to non-lithium-exposed controls.
Background: There is a need for non-invasive prenatal markers of the brain to assess fetuses at r... more Background: There is a need for non-invasive prenatal markers of the brain to assess fetuses at risk for poor postnatal neurodevelopmental outcome. Periconceptional maternal conditions and pregnancy complications impact prenatal brain development. Aims: To investigate associations between growth trajectories of fetal brain structures and neurodevelopmental outcome in children in the early life course. Study design: Periconceptional prospective observational cohort. Subjects: Singleton pregnancies were included in the Rotterdam periconception cohort. Two-and three-dimensional ultrasound scans at 22, 26 and 32 weeks gestational age were analysed. Outcome measures: Head circumference (HC), cerebellum, corpus callosum (CC), Sylvian fissure, insula and parieto-occipital fissure (POF) were measured. Neurodevelopment was evaluated using the Age-and-Stagesquestionnaire-3 (ASQ-3) and the Child-Behaviour-Checklist (CBCL) at 2 years of age. Linear mixed models, used to estimate the prenatal brain growth trajectories, and linear regression models, used to evaluate the associations between prenatal brain structures and neurodevelopmental outcomes, were applied in the total study population, and in subgroups: fetal growth restriction (FGR), preterm birth (PTB), fetal congenital heart disease (CHD), and uncomplicated controls. Results: Consent for participation was received from parents on behalf of their child 138/203 (68%). ASQ-3 was completed in 128/203 children (63%) and CBCL in 93/203 children (46%). Significant smaller subject-specific growth trajectories (growth rate of CC, HC, left insula, left POF and right POF and the baseline size of CC, HC, left POF and right POF) were found in the FGR subgroup, compared to the other subgroups (all p-values < 0.05). In the total group (n = 138), the growth rate of the left insula was associated with poorer ASQ-3 score (β = −869.51; p < 0.05). Healthy controls (n = 106) showed a comparable association (β = −1209.87; p < 0.01). FGR (n = 10) showed a larger baseline size of the right Sylvian fissure in association with poorer CBCL-score (β = 4.13; p < 0.01). In CHD (n = 12) the baseline size of the left Sylvian fissure and its growth rate were associated with respectively poorer and better CBCL-scores (β = 3.11; p < 0.01); (β = −171.99; p < 0.01). In PTB (n = 10) no associations were found. Conclusions: This explorative study suggests associations between ultrasound measurements of fetal brain growth and neurodevelopmental outcome at 2 years of age. In future, this non-invasive technique may improve early identification of fetuses at risk for neurodevelopmental outcome and follow-up postnatal clinical care.
Background: Lithium is an effective treatment in pregnancy and postpartum for the prevention of r... more Background: Lithium is an effective treatment in pregnancy and postpartum for the prevention of relapse in bipolar disorder, but there is a lack of knowledge about the potential adverse impact on fetal development. Aims: To investigate the impact of lithium exposure on early fetal growth. Methods: In this retrospective observational cohort study, we included all singleton pregnancies of women using lithium and referred for advanced fetal ultrasound scanning between 1994 and 2018 to the University Medical Centers in Leiden and Rotterdam, the Netherlands ( n=119). The Generation R study, a population-based cohort, served as a non-exposed control population from the same geographic region ( n=8184). Fetal head circumference, abdominal circumference, femur length, and transcerebellar diameter were measured by ultrasound at 18–22 weeks of gestation. Results: Lithium use during pregnancy was associated with an average increase in head circumference of 1.77 mm (95% confidence interval: 0.5...
Background: Maternal use of benzodiazepines during pregnancy is common and has increased over the... more Background: Maternal use of benzodiazepines during pregnancy is common and has increased over the last decades. In this systematic review and meta-analysis, we studied the literature to estimate the worldwide use of benzodiazepines before, during and after pregnancy, which could help to estimate benzodiazepine exposure and to prioritize and guide future investigations. Methods: We systematically searched Embase, Medline Ovid, Web of Science and Cochrane Central up until July 2019 for studies reporting on benzodiazepine use before (12 months), during and after pregnancy (12 months). Random effects meta-analysis was conducted to calculate pooled prevalence estimates, as well as stratified according to substantive variables. Results: We identified 32 studies reporting on 28 countries, together reporting on 7,343,571 pregnancies. The worldwide prevalence of benzodiazepine use/prescriptions during pregnancy was 1.9% (95%CI 1.6%-2.2%; I 2 97.48%). Highest prevalence was found in the third trimester (3.1%; 95%CI 1.8%-4.5%; I 2 99.83%). Lorazepam was the most frequently used/prescribed benzodiazepine (1.5%; 95%CI 0.5%-2.5%; I 2 99.87%). Highest prevalence was found in Eastern Europe (14.0%; 95%CI 12.1%-15.9%; I 2 0.00%). Limitations: All analyses revealed considerable heterogeneity. Conclusions: Our meta-analysis confirmed that benzodiazepine use before, during and after pregnancy is prevalent. The relatively common use of benzodiazepines with possible risks for both mother and (unborn) child is worrying and calls for prescription guidelines for women, starting in the preconception period. Given the substantial proportion of children exposed to benzodiazepines in utero, future research should continue to study the short-and long-term safety of maternal benzodiazepine use during pregnancy and to explore non-pharmacological alternative treatments. with estimations of 27-93% of pregnant women filling at least one prescription drug during pregnancy (e.g. anti-infectives, antihypertensive agents and psychotropic drugs), with a wide range between countries (Daw et al., 2011). In addition, the use of these medications during pregnancy has increased in the past decades (
Background: While antidepressant use during pregnancy is increasingly common, there is concern ab... more Background: While antidepressant use during pregnancy is increasingly common, there is concern about the possible effects of in-utero antidepressant exposure on the child. Our objective was to examine whether there is a dose-effect of maternal serotonin reuptake inhibitors (SRI) during pregnancy on birth outcomes. Methods: Women between 12 and 16 weeks of gestation, who were using an SRI, were eligible for participation in this nationwide prospective observational cohort study. Recruitment took place between April 2015 and February 2018 (n = 145). SRI exposure and psychopathology symptoms were assessed throughout pregnancy. Exposure was defined as SRI standardized dose at 36 weeks of gestation and mean SRI standardized dose over total pregnancy. Multivariable linear and logistic regression were used to examine the associations with birth weight, gestational age at birth, and being small for gestational age. Results: Maternal SRI dose at 36 weeks of gestation was significantly associated with birth weight (adjusted ß =-180.7, 95%CI-301.1;-60.2, p-value < 0.01) as was mean SRI standardized dose during total pregnancy (adjusted ß =-187.3, 95%CI-322.0;-52.6, p-value < 0.01). No significant associations between maternal SRI dose and gestational age or being small for gestational age were observed. Limitations: Although prospective, we cannot make full causal inferences given that we did not randomize women to different dosages. Conclusion: These findings suggest that careful dosing of SRI use during pregnancy may prevent a negative impact on birth weight and indicate the need for further investigation of causality. 1. Introduction Antidepressants (ADs) are the first-choice drug treatment for mood and anxiety disorders. The use of ADs during pregnancy has been growing steadily (Molenaar et al., 2019), with prevalence rates ranging between 2 and 13% (Molenaar et al., 2020). As ADs cross the placenta, there is substantial concern about the possible effects of in utero AD exposure on the unborn child (Ewing et al., 2015). Several studies showed associations between in utero AD exposure and unfavorable neonatal outcomes, such as preterm birth, low birth weight, low Apgar score, Persistent Pulmonary Hypertension of the Neonate, and cardiac abnormalities (
Maternity care increasingly focuses on evaluating psychosocial vulnerability during pregnancy. Re... more Maternity care increasingly focuses on evaluating psychosocial vulnerability during pregnancy. Research and nationwide (public health) programs, both in the USA and Europe, led to the development of new protocols and screening instruments for care providers to systematically screen for psychosocial vulnerability in pregnant women. However, standardised screening for vulnerability is complex since it requires discussion of sensitive issues. Women may fear stigmatisation and may have limited trust in their care providers or the health system. Our study contributes to the growing field of client-facing risk work by exploring care providers&#39; interpretations and evaluation of psychosocial vulnerability in pregnant women. Drawing on semi-structured interviews with Dutch maternity care providers, we explore how they conceptualise risk and vulnerability and identify &#39;vulnerable pregnant women&#39; in their practices. We find that care providers conceptualise &#39;vulnerability&#39; as primarily based on risk, which contributes to an imbalanced focus on individual mothers, rather than on both parents and the social context. Our findings highlight care providers&#39; concerns around &#39;care avoidance&#39;, seen as a risk factor affecting &#39;vulnerability&#39; during pregnancy and as a possible consequence of risk screening. The care providers we interviewed employ &quot;in between-strategies&quot; based on intuition, emotion, and trust to skillfully attend to the risk that comes with risk work, in terms of its potential impact on relationships of trust and open communication. We conclude that &#39;vulnerability&#39; should be understood as a multi-layered, situated and relational concept rather than simply as an epidemiological category. Since a trusting relationship between pregnant women and care providers is crucial for the evaluation of vulnerability, we reflect critically on the risk of standardised perinatal psychosocial risk evaluations. Policy should recognise providers&#39; &quot;in between-strategies&quot; to embed epidemiological understandings of risk in the context of everyday risk work.
Background Unplanned or unintended pregnancies form a major public health concern because they ar... more Background Unplanned or unintended pregnancies form a major public health concern because they are associated with unfavorable birth outcomes as well as social adversity, stress and depression among parents-to-be. Several risk factors for unplanned pregnancies in women have previously been identified, but studies usually take a unidimensional approach by focusing on only one or few factors, disregarding the possibility that predictors might cluster. Furthermore, data on predictors in men are largely overlooked. The purpose of this study is to determine predictors of unplanned versus planned pregnancy, to determine predictors of ambivalent feelings regarding pregnancy, and to investigate how characteristics of men and women with an unplanned pregnancy cluster together. Methods This study was embedded in Generation R, a multiethnic population-based prospective cohort from fetal life onwards. Pregnancy intention was reported by 7702 women and 5367 partners. Information on demographic, ...
PurposeThe purpose of this study is to describe the implementation and outcomes of an Eye Movemen... more PurposeThe purpose of this study is to describe the implementation and outcomes of an Eye Movement and Desensitization Reprocessing (EMDR) treatment-program for women with posttraumatic stress disorder (PTSD) after childbirth.MethodsA prospective cohort-study with pre- and post-measurements was carried out in the setting of an academic hospital in the Netherland. Included were women who gave birth to a living child at least 4 weeks ago, with a diagnosis of PTSD, or severe symptoms of PTSD combined with another psychiatric diagnosis. All received up to 8 sessions of EMDR-therapy. The posttraumatic stress disorder Checklist for DSM-5 was administered before and after treatment. Trauma history was assessed before treatment with the Life Events Checklist for the DSM-5, the Childhood Trauma Questionnaire and the Childbirth Perception Scale. Descriptive statistics were used.ResultsForty-four women were referred, 26 met the inclusion criteria. After treatment, none of the women met the cri...
International Journal of Environmental Research and Public Health
The COVID-19 pandemic has a major impact on society, particularly affecting its vulnerable member... more The COVID-19 pandemic has a major impact on society, particularly affecting its vulnerable members, including pregnant women and their unborn children. Pregnant mothers reported fear of infection, fear of vertical transmission, fear of poor birth and child outcomes, social isolation, uncertainty about their partner’s presence during medical appointments and delivery, increased domestic abuse, and other collateral damage, including vaccine hesitancy. Accordingly, pregnant women’s known vulnerability for mental health problems has become a concern during the COVID-19 pandemic, also because of the known effects of prenatal stress for the unborn child. The current narrative review provides a historical overview of transgenerational effects of exposure to disasters during pregnancy, and the role of maternal prenatal stress. We place these effects into the perspective of the COVID-19 pandemic. Hereby, we aim to draw attention to the psychological impact of the COVID-19 pandemic on women o...
Pregnancy and the puerperium do not protect against acute psychiatric illness. During puerperium,... more Pregnancy and the puerperium do not protect against acute psychiatric illness. During puerperium, the chance of acute psychiatric illness, such as a psychotic episode or relapse of bipolar disorder, is greatly increased. Suicide is a leading cause of maternal death. Both psychiatric disease and ongoing drug addiction impact not only the pregnant woman's somatic and mental health but also impact short-term and long-term health of the child. Indeed, prompt recognition and expeditious treatment of acute psychiatric illness during pregnancy and the puerperium optimize health outcomes for two patients. Pregnancy and puerperium represent a stage of life of great physiologic adaptations, as well as emotional and social changes. This conjunction of changes in somatic, emotional health and social health may mitigate the occurrence, clinical presentation, and clinical course of acute psychiatric illness and call for a multidisciplinary approach, taking into account both the medical and social domains. This chapter describes acute psychiatric illnesses during pregnancy and the puerperium and illicit substance abuse, from a clinical perspective, while also describing general principles of diagnosis and clinical management during this stage of life, which is an important window of opportunity for both the pregnant woman and the child.
Supplemental material, Supplementary_Material for Lithium exposure during pregnancy increases fet... more Supplemental material, Supplementary_Material for Lithium exposure during pregnancy increases fetal growth by Eline MP Poels, Karin Sterrenburg, André I Wierdsma, Richard Wesseloo, Annemerle Beerthuizen, Laura van Dijke, Condon Lau, Witte JG Hoogendijk, Hanan El Marroun, Inge L van Kamp, Hilmar H Bijma and Veerle Bergink in Journal of Psychopharmacology
ObjectivesApproximately 11%–13% of pregnant women suffer from depression. Bright light therapy (B... more ObjectivesApproximately 11%–13% of pregnant women suffer from depression. Bright light therapy (BLT) is a promising treatment, combining direct availability, sufficient efficacy, low costs and high safety for both mother and child. Here, we examined the effects of BLT on depression during pregnancy.DesignRandomised, double-blind controlled trial.SettingPrimary and secondary care in The Netherlands, from November 2016 to March 2019.Participants67 pregnant women (12–32 weeks gestational age) with a DSM-5 diagnosis of depressive disorder (Diagnostic and Statistical Manual of Mental Disorders).InterventionsParticipants were randomly allocated to treatment with either BLT (9000 lux, 5000 K) or dim red light therapy (DRLT, 100 lux, 2700 K), which is considered placebo. For 6 weeks, both groups were treated daily at home for 30 min on awakening. Follow-up took place weekly during the intervention, after 6 weeks of therapy, 3 and 10 weeks after treatment and 2 months postpartum.Primary and ...
Background Alcohol consumption during pregnancy is associated with major birth defects and develo... more Background Alcohol consumption during pregnancy is associated with major birth defects and developmental disabilities. Questionnaires concerning alcohol consumption during pregnancy underestimate alcohol use while the use of a reliable and objective biomarker for alcohol consumption enables more accurate screening. Phosphatidylethanol can detect low levels of alcohol consumption in the previous two weeks. In this study we aimed to biochemically assess the prevalence of alcohol consumption during early pregnancy using phosphatidylethanol in blood and compare this with self-reported alcohol consumption. Methods To evaluate biochemically assessed prevalence of alcohol consumption during early pregnancy using phosphatidylethanol levels, we conducted a prospective, cross-sectional, single center study in the largest tertiary hospital of the Netherlands. All adult pregnant women who were under the care of the obstetric department of the Erasmus MC and who underwent routine blood testing a...
OBJECTIVES Lithium is an effective treatment for bipolar disorder, also during pregnancy to preve... more OBJECTIVES Lithium is an effective treatment for bipolar disorder, also during pregnancy to prevent the recurrence of episodes in the perinatal period. Little is known about the neuropsychological development of lithium-exposed offspring. The current study was designed to investigate neuropsychological functioning in lithium-exposed children with the aim to provide further knowledge on the long-term effects of lithium use during pregnancy. METHODS Participants were offspring of women with a diagnosis of bipolar spectrum disorder, aged 6 to 14 years. In total 99 children participated in the study, 56 were exposed to lithium in utero and 43 were not exposed to lithium. Neuropsychological tests were administered, including the Snijders-Oomen Nonverbal Intelligence Test and the NEPSY-II-NL assessment. Linear and Negative Binomial regression models were used to investigate the association between prenatal lithium exposure and neuropsychological functioning. In secondary analyses, the association between lithium blood level during pregnancy and neuropsychological functioning was assessed. Additionally, norm scores and percentiles for task outcomes were calculated. RESULTS Lithium use during pregnancy was associated with the total number of mistakes made on the Auditory Attention task, but not statistically significant after full adjustment for potential confounding factors. No association between prenatal lithium exposure and IQ was found. Also, no relationship between lithium blood level during pregnancy and neuropsychological functioning was found after adjustment for potential confounders. Task outcomes in both groups were comparable to the general population. CONCLUSION In this study we found no evidence for significantly altered neuropsychological functioning of lithium-exposed children at the age of 6 to 14 years, when compared to non-lithium-exposed controls.
Background: There is a need for non-invasive prenatal markers of the brain to assess fetuses at r... more Background: There is a need for non-invasive prenatal markers of the brain to assess fetuses at risk for poor postnatal neurodevelopmental outcome. Periconceptional maternal conditions and pregnancy complications impact prenatal brain development. Aims: To investigate associations between growth trajectories of fetal brain structures and neurodevelopmental outcome in children in the early life course. Study design: Periconceptional prospective observational cohort. Subjects: Singleton pregnancies were included in the Rotterdam periconception cohort. Two-and three-dimensional ultrasound scans at 22, 26 and 32 weeks gestational age were analysed. Outcome measures: Head circumference (HC), cerebellum, corpus callosum (CC), Sylvian fissure, insula and parieto-occipital fissure (POF) were measured. Neurodevelopment was evaluated using the Age-and-Stagesquestionnaire-3 (ASQ-3) and the Child-Behaviour-Checklist (CBCL) at 2 years of age. Linear mixed models, used to estimate the prenatal brain growth trajectories, and linear regression models, used to evaluate the associations between prenatal brain structures and neurodevelopmental outcomes, were applied in the total study population, and in subgroups: fetal growth restriction (FGR), preterm birth (PTB), fetal congenital heart disease (CHD), and uncomplicated controls. Results: Consent for participation was received from parents on behalf of their child 138/203 (68%). ASQ-3 was completed in 128/203 children (63%) and CBCL in 93/203 children (46%). Significant smaller subject-specific growth trajectories (growth rate of CC, HC, left insula, left POF and right POF and the baseline size of CC, HC, left POF and right POF) were found in the FGR subgroup, compared to the other subgroups (all p-values < 0.05). In the total group (n = 138), the growth rate of the left insula was associated with poorer ASQ-3 score (β = −869.51; p < 0.05). Healthy controls (n = 106) showed a comparable association (β = −1209.87; p < 0.01). FGR (n = 10) showed a larger baseline size of the right Sylvian fissure in association with poorer CBCL-score (β = 4.13; p < 0.01). In CHD (n = 12) the baseline size of the left Sylvian fissure and its growth rate were associated with respectively poorer and better CBCL-scores (β = 3.11; p < 0.01); (β = −171.99; p < 0.01). In PTB (n = 10) no associations were found. Conclusions: This explorative study suggests associations between ultrasound measurements of fetal brain growth and neurodevelopmental outcome at 2 years of age. In future, this non-invasive technique may improve early identification of fetuses at risk for neurodevelopmental outcome and follow-up postnatal clinical care.
Background: Lithium is an effective treatment in pregnancy and postpartum for the prevention of r... more Background: Lithium is an effective treatment in pregnancy and postpartum for the prevention of relapse in bipolar disorder, but there is a lack of knowledge about the potential adverse impact on fetal development. Aims: To investigate the impact of lithium exposure on early fetal growth. Methods: In this retrospective observational cohort study, we included all singleton pregnancies of women using lithium and referred for advanced fetal ultrasound scanning between 1994 and 2018 to the University Medical Centers in Leiden and Rotterdam, the Netherlands ( n=119). The Generation R study, a population-based cohort, served as a non-exposed control population from the same geographic region ( n=8184). Fetal head circumference, abdominal circumference, femur length, and transcerebellar diameter were measured by ultrasound at 18–22 weeks of gestation. Results: Lithium use during pregnancy was associated with an average increase in head circumference of 1.77 mm (95% confidence interval: 0.5...
Background: Maternal use of benzodiazepines during pregnancy is common and has increased over the... more Background: Maternal use of benzodiazepines during pregnancy is common and has increased over the last decades. In this systematic review and meta-analysis, we studied the literature to estimate the worldwide use of benzodiazepines before, during and after pregnancy, which could help to estimate benzodiazepine exposure and to prioritize and guide future investigations. Methods: We systematically searched Embase, Medline Ovid, Web of Science and Cochrane Central up until July 2019 for studies reporting on benzodiazepine use before (12 months), during and after pregnancy (12 months). Random effects meta-analysis was conducted to calculate pooled prevalence estimates, as well as stratified according to substantive variables. Results: We identified 32 studies reporting on 28 countries, together reporting on 7,343,571 pregnancies. The worldwide prevalence of benzodiazepine use/prescriptions during pregnancy was 1.9% (95%CI 1.6%-2.2%; I 2 97.48%). Highest prevalence was found in the third trimester (3.1%; 95%CI 1.8%-4.5%; I 2 99.83%). Lorazepam was the most frequently used/prescribed benzodiazepine (1.5%; 95%CI 0.5%-2.5%; I 2 99.87%). Highest prevalence was found in Eastern Europe (14.0%; 95%CI 12.1%-15.9%; I 2 0.00%). Limitations: All analyses revealed considerable heterogeneity. Conclusions: Our meta-analysis confirmed that benzodiazepine use before, during and after pregnancy is prevalent. The relatively common use of benzodiazepines with possible risks for both mother and (unborn) child is worrying and calls for prescription guidelines for women, starting in the preconception period. Given the substantial proportion of children exposed to benzodiazepines in utero, future research should continue to study the short-and long-term safety of maternal benzodiazepine use during pregnancy and to explore non-pharmacological alternative treatments. with estimations of 27-93% of pregnant women filling at least one prescription drug during pregnancy (e.g. anti-infectives, antihypertensive agents and psychotropic drugs), with a wide range between countries (Daw et al., 2011). In addition, the use of these medications during pregnancy has increased in the past decades (
Background: While antidepressant use during pregnancy is increasingly common, there is concern ab... more Background: While antidepressant use during pregnancy is increasingly common, there is concern about the possible effects of in-utero antidepressant exposure on the child. Our objective was to examine whether there is a dose-effect of maternal serotonin reuptake inhibitors (SRI) during pregnancy on birth outcomes. Methods: Women between 12 and 16 weeks of gestation, who were using an SRI, were eligible for participation in this nationwide prospective observational cohort study. Recruitment took place between April 2015 and February 2018 (n = 145). SRI exposure and psychopathology symptoms were assessed throughout pregnancy. Exposure was defined as SRI standardized dose at 36 weeks of gestation and mean SRI standardized dose over total pregnancy. Multivariable linear and logistic regression were used to examine the associations with birth weight, gestational age at birth, and being small for gestational age. Results: Maternal SRI dose at 36 weeks of gestation was significantly associated with birth weight (adjusted ß =-180.7, 95%CI-301.1;-60.2, p-value < 0.01) as was mean SRI standardized dose during total pregnancy (adjusted ß =-187.3, 95%CI-322.0;-52.6, p-value < 0.01). No significant associations between maternal SRI dose and gestational age or being small for gestational age were observed. Limitations: Although prospective, we cannot make full causal inferences given that we did not randomize women to different dosages. Conclusion: These findings suggest that careful dosing of SRI use during pregnancy may prevent a negative impact on birth weight and indicate the need for further investigation of causality. 1. Introduction Antidepressants (ADs) are the first-choice drug treatment for mood and anxiety disorders. The use of ADs during pregnancy has been growing steadily (Molenaar et al., 2019), with prevalence rates ranging between 2 and 13% (Molenaar et al., 2020). As ADs cross the placenta, there is substantial concern about the possible effects of in utero AD exposure on the unborn child (Ewing et al., 2015). Several studies showed associations between in utero AD exposure and unfavorable neonatal outcomes, such as preterm birth, low birth weight, low Apgar score, Persistent Pulmonary Hypertension of the Neonate, and cardiac abnormalities (
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