High first trimester ferritin levels differ according to parity and are independently related to preterm birth: A prospective cohort study.

INTRODUCTION: A considerable amount of neonatal morbidity and mortality worldwide is caused by preterm birth. To date, the underlying etiology of preterm birth has not been fully clarified. Previous studies demonstrate that inflammation is one of the pathological factors that might cause preterm birth, and that there is a difference between primiparous and multiparous women in immune response to pregnancy. The objective of this prospective cohort study was to investigate the role of two inflammatory markers, ferritin and C-reactive protein (CRP) and preterm birth, in first trimester women, stratified for parity. In addition, a possible association between high ferritin and CRP, and a possible association between high ferritin and CRP and preterm birth were assessed. MATERIAL AND METHODS: A total of 2044 healthy, low-risk pregnant women from primary obstetric care in the Netherlands participated in this study. Their ferritin and CRP levels were evaluated at 12 weeks' gestation. Levels above the parity specific 95th percentile were defined as high. The main outcome of this study was to assess the presence of a possible association between parity specific high ferritin and CRP, and preterm birth. The secondary outcomes were the ferritin and CRP levels of women, stratified for parity, and the possible association between high ferritin and CRP levels. Logistic regression analysis was performed with preterm birth as a dependent variable and parity specific high ferritin and CRP as an independent variable, adjusting for age and history of preterm birth. RESULTS: Ferritin levels decreased with increasing parity. Ferritin and CRP levels at 12 weeks' gestation were significantly higher in women with preterm birth. In primiparous women, high ferritin levels (OR: 2.5, CI: 1.14-5.38) and high CRP levels (OR: 5.0, CI: 2.61-9.94) were independently associated with preterm birth. In multiparous women, high ferritin levels (OR: 6.0, CI: 2.28-16.67) were independently associated with preterm birth while high CRP levels were not. CONCLUSIONS: First trimester parity specific ferritin and CRP levels could play a part in predictive models for preterm birth, and further research for their additive role in preterm birth is needed.

Hypothyroxinaemia during gestation is associated with low ferritin and increased levels of inflammatory markers.

Objective: Pregnancy is a state of physiological inflammation facilitating implantation. Early isolated hypothyroxinaemia (IH) and increased inflammation (including obesity) have been associated with severe obstetric complications. The current study evaluated the association between IH, low ferritin and inflammation parameters (interleukin 6 (IL-6), C-reactive protein (CRP), human chorionic gonadotrophin (hCG) and obesity. Moreover, the course of these parameters throughout pregnancy was evaluated in relation to IH. Methods: In the cross-sectional study (A) at 12 weeks, 2759 women participated and 2433 participated in the longitudinal study (B) with assessments at 12, 20 and 28 weeks gestation. At the first trimester, 122 (4.4%) IH women (free thyroxine (FT4) <5th percentile, normal TSH levels) were compared with 2114 (76.6%) reference women (FT4 between tenth and 90th percentiles, normal thyrotrophin (TSH) levels), in study B these figures were 99 (4.1%) and 1847 (75.9%), respectively. Results: Cross-sectionally, compared to reference women, IH was independently associated with low ferritin (<5th percentile, OR: 2.6, 95% CI: 1.4-4.9), high CRP (>95th percentile: OR: 1.9, 95% CI: 1.04-3.7), low hCG ( 30, OR: 1.7, 95% CI: 1.12.9) and higher age (OR: 1.1, 95% CI: 1.04-1.15). Longitudinally, compared to reference women, women with IH at 12 weeks gestation showed persistently and significantly lower ferritin and hCG levels, and persistently higher CRP and IL-6 levels throughout gestation. Conclusion: Gestational IH could be viewed as a condition of increased inflammation, as reported in non-thyroidal illness syndrome. Less favourable inflammation parameters and low iron status during early gestation in IH women seem to persist throughout gestation.

Browsing throughout pregnancy: The longitudinal course of social media use during pregnancy.

BACKGROUND: The number of people using social media has substantially increased over the past years. Previous studies have shown associations between social media overuse and mental health problems during pregnancy. The current study evaluates changes in social media use during pregnancy. METHODS: Pregnant women were recruited at their first antenatal appointment between January 2020 and July 2022 (N = 1135). The time spent on social media, frequency of social media use and problematic social media use, using the Bergen Social Media Addiction Scale (BSMAS), were assessed at 12, 20 and 28 weeks of pregnancy. Pearson r correlations and repeated measures ANOVAs were performed to assess possible changes in social media use over the course of pregnancy. Lastly, we stratified social media use throughout pregnancy for parity. RESULTS: There was a significant change in social media use over time, for the time spent on social media, frequency of social media use and problematic social media use. Mean social media scores were the lowest at 12 weeks of pregnancy and increased significantly at 20 weeks of pregnancy, after which they remained stable at 28 weeks. Compared to multiparous women, primiparous women spent more time on social media at 20 weeks of pregnancy, but not at 12 or 28 weeks. CONCLUSION: Because overuse of social media has been associated with poor mental health, healthcare professionals should be aware of the intensity of social media use throughout pregnancy.

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches.

CONTEXT: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. METHODS: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. RESULTS: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. CONCLUSION: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Paternal bonding in pregnancy and early parenthood: a qualitative study in first-time fathers.

The birth of an infant marks a period of profound change in first-time parents. Parental love and warmth, however, already begin to develop during pregnancy. Also for fathers, the development of bonding to the infant may be a unique process. The current qualitative study aimed to explore views and experiences of first-time fathers on the origins and development of paternal bonding during pregnancy and early childhood. In total, 30 in-depth semi-structured interviews were conducted with expectant fathers (second or third trimester of pregnancy; n = 10) and fathers of infants (0-6 months postpartum; n = 11) and toddlers (2-3 years of age; n = 9). Two major themes were uncovered from the data: feelings of bonding and facilitators of bonding. The first theme was supported with three subthemes: 1) from abstract to concrete, 2) positive emotions, and 3) uncertainties and worries. The second theme, facilitators of bonding, was supported with four subthemes: 1) experiencing the foetus, 2) meeting the child, 3) interaction, and 4) communication. Similar to previous studies, our results suggested that, in most fathers, paternal bonding originates in pregnancy and that it evolves over time. Seeing or feeling the child, both during pregnancy and postpartum, as well as interacting or communicating with the child, appears to facilitate fathers' feelings of bonding. Involving fathers in pregnancy, childbirth, and parenting may be essential for their bonding process.

Maternal-infant bonding and partner support during pregnancy and postpartum: Associations with early child social-emotional development.

The first 1000 days after conception are considered critical for healthy development and well-being throughout life. Fundamental to health practices during pregnancy and positive parenting after birth is the development of maternal-infant bonding. Previous research has demonstrated the importance of having an involved partner during pregnancy and in parenting for optimal maternal-infant bonding. The current study examined maternal-infant bonding and partner support during pregnancy and the postpartum period, and their associations with early child social-emotional development. A total of 227 women completed the Pre- and Postnatal Bonding Scale (PPBS) and Tilburg Pregnancy Distress Scale (TPDS) during pregnancy (32 weeks of gestation) and at 8 months postpartum, assessing maternal-infant bonding and partner support. Additionally, a questionnaire on social-emotional behavior of the Bayley Scales of Infant and Toddler Development was administered to mothers to measure child development at 2 years of age. Path analyses revealed an indirect positive effect of prenatal maternal-infant bonding on child social-emotional development through postnatal maternal-infant bonding, as well as mediating effects of pre- and postnatal maternal-infant bonding on the association between pre- and postnatal partner support and child social-emotional development. Our findings support the notion that an emotional connection from mother to child originates in pregnancy and that experiencing positive feelings towards the fetus promotes positive maternal-infant bonding after birth and social-emotional capacities of the child. Additionally, having a supportive partner during pregnancy and postpartum, might be essential for the development of optimal maternal-infant bonding.

Social media use as a risk factor for depressive symptoms during pregnancy.

BACKGROUND: Accumulating research has shown associations between excessive social media use (SMU) with depressive symptoms. Depression is common during pregnancy, but it is not known whether SMU plays a role in the etiology and clinical course of depressive symptoms during pregnancy. METHODS: The current study is a prospective cohort study with Dutch-speaking pregnant women recruited at the first antenatal appointment (N = 697). Depressive symptoms were measured at each trimester of pregnancy using the Edinburgh Depression Scale. Growth mixture modeling was used to determine classes of women based on longitudinal trajectories of depressive symptoms. SMU was assessed at 12 weeks of pregnancy, specifically, intensity (time and frequency) and problematic SMU (Bergen Social Media Addiction Scale). Multinomial logistic regression analyses were used to examine the associations between SMU and trajectories of depressive symptoms. RESULTS: Three trajectories of depressive symptoms during pregnancy were identified: a low stable (N = 489, 70.2 %), intermediate stable (N = 183, 26.3 %), and high stable (N = 25, 3.6 %) class. SMU Time and Frequency were significantly associated with belonging to the high stable class. Problematic SMU was significantly associated with belonging to the intermediate or high stable class. LIMITATIONS: The study does not allow to draw conclusions about causality. The group sizes of the three trajectories differed considerably. Data were collected during the COVID-19 pandemic which may have influenced the results. SMU was measured by self-report. CONCLUSIONS: These results indicate that both higher intensity of SMU (time and frequency) and problematic SMU may be a risk factor for higher levels of prenatal depressive symptoms during pregnancy.

Online mindfulness-based intervention for women with pregnancy distress: A randomized controlled trial.

BACKGROUND: Pregnancy distress among childbearing women is common and can negatively affect both mother and infant. Mindfulness-based interventions (MBIs) may have a positive effect on pregnancy distress but randomized controlled trials with sufficient power are lacking. The current study examined the effectiveness of an online self-guided MBI in pregnant women with pregnancy distress. METHODS: Pregnant women with elevated pregnancy distress levels at 12 weeks of pregnancy, measured with the Edinburgh Depression Scale (EDS) and Tilburg Pregnancy Distress Scale negative affect (TPDS-NA), were randomized into an intervention group (online MBI, N = 109) or control group (care as usual, N = 110). The primary outcome was the change in pregnancy distress post-intervention and at eight-weeks-follow-up. Secondary outcomes were mindfulness skills (Three Facet Mindfulness Questionnaire-Short Form), rumination (Rumination-Reflection Questionnaire), and self-compassion (Self-Compassion Scale-Short Form) at post-intervention and follow-up in the intervention group. RESULTS: Significant improvements were found in pregnancy distress scores, but no significant differences between intervention and control group appeared. The MBI group showed improvements in mindfulness skills, rumination, and self-compassion. LIMITATIONS: Low adherence to the intervention and assessment of secondary outcome measures in the intervention group only. CONCLUSIONS: An intervention trial with one of the largest samples (N = 219) provided no evidence of a significant effect of an online self-guided MBI in distressed pregnant women. An online MBI may be associated with an improvement in mindfulness skills, rumination, and self-compassion. Future research should address the effectiveness of MBI's with different formats (online and group-based combined) and examine a possible delayed effect. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03917745, registered on 4 March 2019.

The first trimester plasma copper-zinc ratio is independently related to pregnancy-specific psychological distress symptoms throughout pregnancy.

OBJECTIVES: High plasma copper (Cu) and low zinc (Zn) levels have been associated with depression. However, most studies used low sample sizes and a cross-sectional design, and perinatal data are scarce. We investigated the possible association between pregnancy-specific psychological distress and the plasma CuZn ratio using a prospective design. METHODS: Pregnancy-specific distress symptoms were assessed at each trimester by means of the Tilburg Pregnancy Distress Scale, negative affect subscale, in 2036 pregnant women. Cu and Zn were assessed at 12 wk of gestation in plasma samples by inductively coupled plasma mass spectrometry. Growth mixture modeling determined trajectories of women's pregnancy-specific negative affect (P-NA) symptoms, which were entered in a multiple logistic regression analysis as dependent variable and the CuZn ratio as independent variable. RESULTS: Two P-NA symptom classes were found: 1) persistently low (n = 1820) and 2) persistently high (n = 216). A higher CuZn ratio was independently associated with persistently high P-NA symptom scores (odds ratio = 1.52; 95% confidence interval, 1.13-2.04) after adjustment for confounders. A sensitivity analysis was performed excluding all women with high P-NA scores at 12 wk of gestation (>1 SD above the mean P-NA score). In the 1719 remaining women, a higher CuZn ratio significantly predicted the development of increasing P-NA symptom scores after adjustment for confounders (odds ratio = 1.40; 95% confidence interval, 1.04-1.95). CONCLUSIONS: A higher CuZn plasma ratio is an independent determinant of developing pregnancy-specific distress symptoms throughout pregnancy, suggesting that micronutrients could be used as novel biomarkers for psychological distress research of perinatal mood disorders.

Association between high levels of comorbid anxiety and depressive symptoms and decreased likelihood of birth without intervention: A longitudinal prospective cohort study.

OBJECTIVE: To assess the association between trajectories of comorbid anxiety and depressive (CAD) symptoms assessed in each pregnancy trimester and physiological birth. DESIGN: Large longitudinal prospective cohort study with recruitment between January 2013 and September 2014. SETTING: Primary care, in the Netherlands. POPULATION: Dutch-speaking pregnant women with gestational age at birth ≥37 weeks, and without multiple pregnancy, severe psychiatric disorder or chronic disease history. METHODS: Pregnancy-specific anxiety and depressive symptoms were measured prospectively in each trimester of pregnancy using the negative affect subscale of the Tilburg Pregnancy Distress Scale and Edinburgh (Postnatal) Depression Scale. Data on physiological birth were obtained from obstetric records. Multivariate growth mixture modelling was performed in MPLUS to determine longitudinal trajectories of CAD symptoms. Multiple logistic regression analysis was used to examine the association between trajectories and physiological birth. MAIN OUTCOME MEASURES: Trajectories of CAD symptoms and physiological birth. RESULTS: Seven trajectories (classes) of CAD symptoms were identified in 1682 women and subsequently merged into three groups: group 1-persistently low levels of symptoms (reference class 1; 79.0%), group 2-intermittently high levels of symptoms (classes 3, 6 and 7; 11.2%), and group 3-persistently high levels of symptoms (classes 2, 4 and 5; 9.8%). Persistently high levels of CAD symptoms (group 3) were associated with a lower likelihood of physiological birth (odds ratio 0.67, 95% confidence interval 0.47-0.95, P = 0.027) compared with the reference group (persistently low levels of symptoms), after adjusting for confounders. CONCLUSIONS: This study is the first showing evidence that persistently high CAD levels, assessed in each pregnancy trimester, are associated with a lower likelihood of physiological birth.

The Tilburg Pregnancy Distress Scale revised (TPDS-R): Psychometric aspects in a longitudinal cohort study.

Pregnant women may be specifically prone to experience pregnancy-specific distress, which has been associated with adverse maternal, pregnancy and child outcomes. Accurately identifying pregnancy-specific distress is thus crucial. The Tilburg Pregnancy Distress Scale (TPDS) - translated into many different languages - was previously developed to measure pregnancy-specific distress, resulting in a 16-item screening scale with a partner involvement dimension (PI) and a negative affect dimension (NA). A critical evaluation of the psychometric properties of the TPDS-NA items and feedback from pregnant women over the last decade has led to the need to revise the TPDS. Therefore, in the current study, we describe the procedure for revision and evaluate the psychometric properties of the revised TPDS (TPDS-R). More specifically, we describe the revision of the TPDS-R-PI (4 items) and the TPDS-R-NA (10 items: five-item pregnancy and five-item childbirth subcomponent). A sample of 1081 pregnant women participating in the Brabant Study completed the TPDS-R at 12, 20 and 28 weeks of pregnancy. An exploratory factor analysis and confirmatory factor analysis, descriptive statistics and repeated measures ANOVA demonstrated good test-retest reliability, concurrent validity, internal consistency, and construct validity of the TPDS-R. The TPDS-R provides a robust screening tool to accurately identify pregnant women at risk of pregnancy-specific distress.

TSH and FT4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis.

CONTEXT: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. OBJECTIVE: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. METHODS: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. RESULTS: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. CONCLUSION: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.

Psychological distress is independently related to new coronary events at 8 years' follow-up in elderly primary care patients with hypertension.

OBJECTIVE: Occurrence of psychological distress in hypertensive patients could have a negative synergistic effect on future cardiovascular events (CVEs). The aim of this study was to determine the association between anxiety or depressive symptoms in elderly hypertensive primary care patients and the development of new CVEs and all-cause mortality. METHODS: A prospective cohort study was conducted in five Dutch general practices between June 2010 and January 2012. Patients with primary care managed hypertension, aged 60-85 years, were included and completed the GAD-7 and PHQ-9, measuring anxiety and depressive symptoms respectively. The incidence of new CVEs (coronary event, cerebrovascular disease, atrial fibrillation and heart failure) and all-cause mortality at 8 years' follow-up was recorded by data extraction of the digital information systems. RESULTS: Among the 555 included participants (mean age 70 ± 6.6 years; 56% female), 29 (5.2%) had a new coronary event, 42 (7.6%) a cerebrovascular disease, 57 (10.3%) atrial fibrillation, 22 (4%) heart failure and 68 (12.3%) died. Elevated anxiety and depression scores increased the risk of a coronary event independently and significantly by 12% (HR 1.12; 95% CI [1.04-1.22], p = 0.005) and 18% (HR 1.18; 95% CI [1.08-1.28], p < 0.0001), respectively, adjusted for relevant (Framingham) baseline covariates. No associations were found with regard to other CVEs and all-cause mortality. CONCLUSION: In a random sample of elderly primary care hypertension patients there was a significant association between psychological distress and the occurrence of new coronary events after 8 years' follow-up but not with other CVEs and all-cause mortality.

Implementing "Online Communities" for pregnant women in times of COVID-19 for the promotion of maternal well-being and mother-to-infant bonding: a pretest-posttest study.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic elevated the risk for mental health problems in pregnant women, thereby increasing the risk for long-term negative consequences for mother and child well-being. There was an immediate need for easily accessible interventions for pregnant women experiencing elevated levels of pandemic related stress. METHODS: A three-session intervention "Online Communities" (OC) was developed at the beginning of the Dutch lockdown, and implemented by a team of midwives and psychologists specialized in Infant Mental Health. Pretest (N = 34) and posttest (N = 17) measurements of depressive symptoms, worries about COVID-19 and worries in general, and mother-to-infant bonding were administered, as well as a posttest evaluation. RESULTS: At pretest, the OC group was compared to two reference groups of pregnant women from an ongoing pregnancy cohort study: a COVID-19 (N = 209) and pre-COVID-19 reference group (N = 297). OC participants had significantly more depressive symptoms than both reference groups, and less positive feelings of bonding than the COVID-19 but not the pre-COVID-19 reference group. Compared to pretest, significant decreases in depressive symptoms (with significantly less participants scoring above cut-off) and worries about COVID-19 (large effect sizes) and worries in general (moderate to large effect size) were found at posttest for the OC participants. No significant improvement was found in bonding. Participants rated the intervention positively. CONCLUSIONS: The current study provides initial evidence supporting the idea that OC is a promising and readily accessible intervention for pregnant women experiencing stress due to the COVID-19 pandemic, and possibly also applicable to other stressors. TRIAL REGISTRATION: This intervention was registered in the Netherlands Trial Registration (registration number Trial NL8842 , registration date 18/08/2020).

Association of Thyroid Peroxidase Antibodies and Thyroglobulin Antibodies with Thyroid Function in Pregnancy: An Individual Participant Data Meta-Analysis.

Objectives: Thyroid autoimmunity is common in pregnant women and associated with thyroid dysfunction and adverse obstetric outcomes. Most studies focus on thyroid peroxidase antibodies (TPOAbs) assessed by a negative-positive dichotomy and rarely take into account thyroglobulin antibodies (TgAbs). This study aimed at determining the association of TPOAbs and TgAbs, respectively, and interdependently, with maternal thyroid function. Methods: This was a meta-analysis of individual participant cross-sectional data from 20 cohorts in the Consortium on Thyroid and Pregnancy. Women with multiple pregnancy, pregnancy by assisted reproductive technology, history of thyroid disease, or use of thyroid interfering medication were excluded. Associations of (log2) TPOAbs and TgAbs (with/without mutual adjustment) with cohort-specific z-scores of (log2) thyrotropin (TSH), free triiodothyronine (fT3), total triiodothyronine (TT3), free thyroxine (fT4), total thyroxine (TT4), or triiodothyronine:thyroxine (T3:T4) ratio were evaluated in a linear mixed model. Results: In total, 51,138 women participated (51,094 had TPOAb-data and 27,874 had TgAb-data). Isolated TPOAb positivity was present in 4.1% [95% confidence interval, CI: 3.0 to 5.2], isolated TgAb positivity in 4.8% [CI: 2.9 to 6.6], and positivity for both antibodies in 4.7% [CI: 3.1 to 6.3]. Compared with antibody-negative women, TSH was higher in women with isolated TPOAb positivity (z-score increment 0.40, CI: 0.16 to 0.64) and TgAb positivity (0.21, CI: 0.10 to 0.32), but highest in those positive for both antibodies (0.54, CI: 0.36 to 0.71). There was a dose-response effect of higher TPOAb and TgAb concentrations with higher TSH (TSH z-score increment for TPOAbs 0.12, CI: 0.09 to 0.15, TgAbs 0.08, CI: 0.02 to 0.15). When adjusting analyses for the other antibody, only the association of TPOAbs remained statistically significant. A higher TPOAb concentration was associated with lower fT4 (p < 0.001) and higher T3:T4 ratio (0.09, CI: 0.03 to 0.14), however, the association with fT4 was not significant when adjusting for TgAbs (p = 0.16). Conclusions: This individual participant data meta-analysis demonstrated an increase in TSH with isolated TPOAb positivity and TgAb positivity, respectively, which was amplified for individuals positive for both antibodies. There was a dose-dependent association of TPOAbs, but not TgAbs, with TSH when adjusting for the other antibody. This supports current practice of using TPOAbs in initial laboratory testing of pregnant women suspected of autoimmune thyroid disease. However, studies on the differences between TPOAb- and TgAb-positive women are needed to fully understand the spectrum of phenotypes.

The association of unplanned pregnancy with perinatal depression: a longitudinal cohort study.

Perinatal depression is common, affecting approximately 7-13% of women. Studies have shown an association between unplanned pregnancy and perinatal depressive symptoms, but many used a cross-sectional design and limited postnatal follow-up. The current study investigated the association of unplanned pregnancy with perinatal depressive symptoms using a longitudinal cohort study that followed women from the first trimester until 12 months postpartum. Pregnant women (N = 1928) provided demographic and clinical data and information about pregnancy intention at the first trimester. Depressive symptoms were assessed during each trimester of pregnancy and five times postpartum using the Edinburgh Postnatal Depression Scale (EPDS) until 12 months postpartum. Mixed model analyses were used to investigate the association between an unplanned pregnancy and the level of depressive symptoms. Women with an unplanned pregnancy (N = 111, 5.8%) reported persistently higher levels of depressive symptoms during the entire perinatal period compared to women with a planned pregnancy, after adjustment for confounders (p < 0.001). However, the course of depressive symptom scores over time in women with an unplanned pregnancy was similar to that of women with a planned pregnancy. Lower age (p = 0.006), unemployment (p = 0.004), and history of depression (p < 0.001) were significantly associated with higher levels of perinatal depressive symptoms. An unplanned pregnancy may have a long-lasting negative impact on a woman's perinatal mental health. Therefore, women with an unplanned pregnancy may benefit from systematic follow-up during the perinatal period with contingent mental health support.

Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis.

BACKGROUND: Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia. METHODS: In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585. FINDINGS: We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT4 concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3·2%) had subclinical hypothyroidism, 933 (2·3%) had isolated hypothyroxinaemia, 619 (1·6%) had subclinical hyperthyroidism, and 337 (0·8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2·1% vs 3·6%; OR 1·53 [95% CI 1·09-2·15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0·0001). FT4 concentrations were not associated with the outcomes measured. INTERPRETATION: Compared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies. FUNDING: Arkansas Biosciences Institute and Netherlands Organization for Scientific Research.

Toddler motor performance and intelligence at school age in preterm born children: A longitudinal cohort study.

BACKGROUND: Current knowledge regarding differences in verbal intelligence scores (VIQ) and performance intelligence scores (PIQ) in preterm born children is limited. As early motor performance may be essential for developing later visual-perceptual and visual-motor skills, early motor performance may be associated with PIQ. AIMS: To evaluate whether in preterm born children motor performance at two years was associated with PIQ at eight years. METHODS: Single-centre cohort study including 88 children born <30 weeks' gestation between 2007 and 2011, who completed the Bayley Scales of Infant and Toddler Development-III (BSID-III) at two years and the Wechsler Intelligence Scale for Children-III-NL (WISC-III-NL) at eight years. Outcome measurements (mean (SD)) were gross and fine motor performance based on the BSID-III, and PIQ and VIQ based on the WISC-III-NL. Linear regression analysis was performed to evaluate the association between motor performance at two years and PIQ at eight years. RESULTS: At two years, mean BSID-III gross motor scaled score was 9.0 (SD 3.0) and fine motor score was 11.5 (SD 2.3). At eight years, mean PIQ was 94.9 (SD 13.5) and mean VIQ 101.8 (SD 13.7). A one-point increase in fine motor scaled score was associated with 1.7 points (95% CI 0.5-2.8) increase in PIQ. Gross motor scaled score was not associated with PIQ. CONCLUSIONS: Fine motor performance in toddlerhood was related to PIQ at school age, with lower scores indicating a lower PIQ. Early assessment of fine motor performance may be beneficial in identifying children at risk for lower performance intelligence.

Psychological Distress During Pregnancy and the Development of Pregnancy-Induced Hypertension: A Prospective Study.

OBJECTIVE: Pregnancy-induced hypertension (PIH) is associated with serious complications in both the mother and the unborn child. We examined the possible association between trajectories of maternal psychological distress symptoms and PIH separately in primiparous and multiparous women. METHODS: Pregnancy-specific negative affect (P-NA) and depressive symptoms were assessed prospectively at each trimester using the Tilburg Pregnancy Distress Scale pregnancy negative affect subscale (P-NA) and the Edinburgh Depression Scale (EDS). Data on PIH were collected from medical records. Growth mixture modeling analysis was used to identify trajectories of P-NA and EDS. The independent role of P-NA and EDS symptom trajectories on developing PIH was examined using multivariate logistic regression models. RESULTS: One hundred (7.6%) women developed PIH and were compared with 1219 women without hypertension or other complications during pregnancy. Three P-NA trajectories were identified: low stable (reference group; 90%), decreasing (5.2%), and increasing (4.8%). The latter two classes showed persistently and significantly higher P-NA symptoms during pregnancy compared with the reference group. In multiparous women, high P-NA scores (belonging to classes 2 and 3) were related to PIH (odds ratio [OR] = 6.91, 95% confidence interval [CI] = 2.26-21.2), independent of body mass index (OR = 1.17, 95% CI = 1.06-1.27) and previous PIH (OR = 14.82, 95% CI = 6.01-32.7). No associations between P-NA and PIH were found in primiparous women. EDS trajectories were not related to PIH in both primiparous and multiparous women. CONCLUSIONS: In multiparous women, persistently high levels of P-NA symptoms but not depressive symptoms were independently associated with development of PIH.