Pregnancy and birth complications and long-term maternal mental health outcomes: A systematic review and meta-analysis.

BACKGROUND: Few studies have examined the associations between pregnancy and birth complications and long-term (>12 months) maternal mental health outcomes. OBJECTIVES: To review the published literature on pregnancy and birth complications and long-term maternal mental health outcomes. SEARCH STRATEGY: Systematic search of Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (Embase), PsycInfo®, PubMed® and Web of Science from inception until August 2022. SELECTION CRITERIA: Three reviewers independently reviewed titles, abstracts and full texts. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and appraised study quality. Random-effects meta-analyses were used to calculate pooled estimates. The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines were followed. The protocol was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022359017). MAIN RESULTS: Of the 16 310 articles identified, 33 studies were included (3 973 631 participants). Termination of pregnancy was associated with depression (pooled adjusted odds ratio, aOR 1.49, 95% CI 1.20-1.83) and anxiety disorder (pooled aOR 1.43, 95% CI 1.20-1.71). Miscarriage was associated with depression (pooled aOR 1.97, 95% CI 1.38-2.82) and anxiety disorder (pooled aOR 1.24, 95% CI 1.11-1.39). Sensitivity analyses excluding early pregnancy loss and termination reported similar results. Preterm birth was associated with depression (pooled aOR 1.37, 95% CI 1.32-1.42), anxiety disorder (pooled aOR 0.97, 95% CI 0.41-2.27) and post-traumatic stress disorder (PTSD) (pooled aOR 1.75, 95% CI 0.52-5.89). Caesarean section was not significantly associated with PTSD (pooled aOR 2.51, 95% CI 0.75-8.37). There were few studies on other mental disorders and therefore it was not possible to perform meta-analyses. CONCLUSIONS: Exposure to complications during pregnancy and birth increases the odds of long-term depression, anxiety disorder and PTSD.

Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis.

AIMS: To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age. METHODS AND RESULTS: Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (-0.53 mmHg; 95% CI:-1.59 to 0.53), DBP (-0.24 mmHg; -0.83 to 0.35), or HR (0.02 beat/min; -0.91 to 0.94). Total cholesterol (2.59%; 0.10-5.07), HDL cholesterol (4.16%; 2.52-5.81), LDL cholesterol (4.95%; 0.47-9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant. CONCLUSION: These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease.

Maternal and perinatal outcomes following a diagnosis of Hodgkin lymphoma during or prior to pregnancy: A systematic review.

BACKGROUND: The initial peak incidence of Hodgkin lymphoma (HL) occurs during reproductive years. OBJECTIVES: Synthesise published literature on the relationship between HL and maternal and perinatal outcomes. SEARCH STRATEGY: Systematic search of PubMed/Medline, Cochrane Library, Scopus, Embase and Science Direct from inception to June 2022, supplemented by hand-searching reference lists. SELECTION CRITERIA: Two reviewers independently reviewed titles, abstracts and full-text articles. Published studies containing original data were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and appraised study quality. Outcomes for pregnant women with a previous/current diagnosis of HL were compared separately with women never diagnosed with HL. Where data permitted, meta-analyses of odds ratios and proportions were performed. Certainty of evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. MAIN RESULTS: Of the 5527 studies identified, 33 met the inclusion criteria. In the groups with HL before pregnancy and HL during pregnancy, adjusted odds ratios were not statistically significant for congenital malformation (aOR 1.7, 95% CI 0.9-3.1, and aOR 1.84, 95% CI 0.81-4.15, respectively), preterm birth (PTB) (aOR 0.99, 95% CI 0.65-1.51, and aOR 6.74, 95% CI 0.52-88.03, respectively) and miscarriage (aOR 0.78, 95% CI 0.55-1.10, and aOR 0.38, 95% CI 0.05-2.72, respectively). The aORs for all other outcomes were not statistically significant, except for blood transfusion (aOR 1.38, 95% CI 1.05-1.82) and venous thromboembolism (VTE) (aOR 7.93, 95% CI 2.97-21.22) in the group for HL during pregnancy. The proportion of anaemia was also increased in this group (69%, 95% CI 57%-80% vs 4%, 95% CI 4%-5%, respectively). The GRADE certainty of findings ranged from low to very low. CONCLUSIONS: Rates of most adverse pregnancy outcomes among women with a previous/current HL diagnosis are not increased significantly compared with the general pregnant population. Women with HL diagnosed during pregnancy may have a higher PTB rate and increased likelihood of VTE, anaemia and blood transfusion; however, small study numbers and the low to very low GRADE certainty of findings preclude firm conclusions.

Association between socioeconomic status with pregnancy and neonatal outcomes: An international multicenter cohort.

INTRODUCTION: Previous evidence examining the association between socioeconomic status and pregnancy complications are conflicted and often limited to using area-based measures of socioeconomic status. In this study, we aimed to examine the association between individual-level socioeconomic factors and a wide range of adverse pregnancy and neonatal outcomes using data from the IMPROvED birth cohort conducted in Sweden, the Netherlands and Republic of Ireland. MATERIAL AND METHODS: The study cohort consisted of women who participated in the IMPROvED birth cohort between 2013 and 2017. Data on socioeconomic factors were self-reported and obtained at 15 weeks' gestation, and included level of education, employment status, relationship status, and income. Data on pregnancy and neonatal outcomes included gestational hypertension, pre-eclampsia, gestational diabetes mellitus, emergency cesarean section, preterm birth, post term delivery, small for gestational age and Apgar score at 1 min. These data were obtained within 72 h following delivery and confirmed using medical records. Multivariable logistic regression examined the association between each socioeconomic variable and each outcome separately adjusting for maternal age, maternal body mass index, maternal smoking, maternal alcohol consumption and cohort center. We also examined the effect of exposure to any ≥2 risk factors compared to none. RESULTS: A total of 2879 participants were included. Adjusted results suggested that those with less than third level of education had an increased odds of gestational hypertension (OR: 1.74, 95% CI: 1.23-2.46), while those on a middle level of income had a reduced odds of emergency cesarean section (OR: 0.59, 95% CI: 0.42-0.84). No significant associations were observed between socioeconomic variables and neonatal outcomes. Exposure to any ≥2 socioeconomic risk factors was associated with an increased risk of preterm birth (OR: 1.75, 95% CI: 1.06-2.89). CONCLUSIONS: We did not find strong evidence of associations between individual-level socioeconomic factors and pregnancy and neonatal outcomes in high-income settings overall, with only few significant associations observed among pregnancy outcomes.

Heterogenous Differences in Cellular Senescent Phenotypes in Pre-Eclampsia and IUGR following Quantitative Assessment of Multiple Biomarkers of Senescence.

Premature ageing of the placenta in pregnancy outcomes is associated with the persistent presence of oxidative stress and placental insufficiency reducing its functional capacity. In this study, we investigated cellular senescence phenotypes of pre-eclampsia and IUGR pregnancies by simultaneously measuring several biomarkers of senescence. Maternal plasma and placental samples were collected at term gestation from nulliparous women undergoing pre-labour elective caesarean section with pre-eclampsia without intrauterine growth restriction (PE; n = 5), pre-eclampsia associated with intrauterine growth restriction (n = 8), intrauterine growth restriction (IUGR < 10th centile; n = 6), and age-matched controls (n = 20). Placental absolute telomere length and senescence gene analysis was performed by RTqPCR. The expression of cyclin-dependent kinase inhibitors (p21 and p16) was determined by Western blot. Senescence-associated secretory phenotypes (SASPs) were evaluated in maternal plasma by multiplex ELISA assay. Placental expression of senescence-associated genes showed significant increases in CHEK1, PCNA, PTEN, CDKN2A, and CCNB-1 (p < 0.05) in pre-eclampsia, while TBX-2, PCNA, ATM, and CCNB-1 expression were evident (p < 0.05) and were significantly decreased in IUGR compared with controls. Placental p16 protein expression was significantly decreased in pre-eclampsia only compared with controls (p = 0.028). IL-6 was significantly increased in pre-eclampsia (0.54 pg/mL ± 0.271 vs. 0.3 pg/mL ± 0.102; p = 0.017) while IFN-γ was significantly increased in IUGR (4.6 pg/mL ± 2.2 vs. 2.17 pg/mL ± 0.8; p = 0.002) compared with controls. These results provide evidence of premature senescence in IUGR pregnancies, and while cell cycle checkpoint regulators are activated in pre-eclampsia, the cellular phenotype is one of cell repair and subsequent proliferation rather than progression to senescence. The heterogeneity of these cellular phenotypes highlights the complexity of characterising cellular senescence and may equally be indicative of the differing pathophysiological insults unique to each obstetric complication.

Chronic kidney disease and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVE: Limited evidence exists on the role that the cause of chronic kidney disease plays in determining pregnancy outcomes. The aim of this systematic review and meta-analysis was to examine the association between chronic kidney disease and adverse pregnancy outcomes by the cause and severity of chronic kidney disease where reported. The protocol was registered under the International Prospective Register of Systematic Reviews (CRD42020211925). DATA SOURCES: PubMed, Embase, and Web of Science were searched until May 24, 2021, supplemented with reference list checking. STUDY ELIGIBILITY CRITERIA: Studies that compared the pregnancy outcomes in women with or without chronic kidney disease were included. Two reviewers independently screened titles, abstracts, and full-text articles according to a priori defined inclusion criteria. METHODS: Data extraction and quality appraisal were performed independently by 3 reviewers. The grading of recommendations, assessment, development, and evaluation approach was used to assess the overall certainty of the evidence. Random-effects meta-analyses were used to calculate the pooled estimates using the generic inverse variance method. The primary outcomes included preeclampsia, cesarean delivery, preterm birth (<37 weeks' gestation), and small for gestational age babies. RESULTS: Of 4076 citations, 31 studies were included. Prepregnancy chronic kidney disease was significantly associated with a higher odds of preeclampsia (pooled crude odds ratio, 8.13; [95% confidence interval, 4.41-15], and adjusted odds ratio, 2.58; [1.33-5.01]), cesarean delivery (adjusted odds ratio, 1.65; [1.21-2.25]), preterm birth (adjusted odds ratio, 1.73; [1.31-2.27]), and small for gestational age babies (adjusted odds ratio, 1.93; [1.06-3.52]). The association with stillbirth was not statistically significant (adjusted odds ratio, 1.67; [0.96-2.92]). Subgroup analyses indicated that different causes of chronic kidney disease might confer different risks and that the severity of chronic kidney disease is associated with a risk of adverse pregnancy outcomes, as pregnancies with later stages of chronic kidney disease had higher odds of preeclampsia, preterm birth, and small for gestational age babies than those at earlier stages. The grading of recommendations, assessment, development, and evaluation certainty of the evidence overall was "very low". CONCLUSION: This meta-analysis quantified the associations between prepregnancy chronic kidney disease and adverse pregnancy outcomes, both overall and according to the cause and severity of the disease. These findings might support the clinicians aiming to counsel women having chronic kidney disease by allowing them to tailor their advice according to cause and severity of the chronic kidney disease. We identified the gaps in the literature, and further studies examining the effect of specific kidney diseases and other clinical characteristics (eg, proteinuria, hypertension) on adverse pregnancy outcomes are warranted.

The association between hypertensive disorders of pregnancy and childhood asthma.

BACKGROUND: Asthma is a chronic long-term inflammatory disease of the airways and is a major global health challenge. The primary aim of this study was to investigate the association between hypertensive disorders of pregnancy (HDP) and the risk of asthma at or before the age of seven years using the UK Millennium Cohort Study (MCS). METHODS: Overall, 18,552 families were recruited for wave one of the MCS when the child was 9 months old, and subsequently participated in waves two, three and four when they were three, five and seven years respectively. HDP were self-reported by mothers in wave one. The primary outcome was a parent-reported diagnosis of "ever asthma" at seven years, based on responses to a validated questionnaire. RESULTS: Following adjustment for a range of potential confounding factors, HDP was found to be associated with asthma in the offspring (adjusted odds ratio (AOR 1.35; 95% CI: 1.15-1.59)). A larger effect estimate was observed amongst children exposed to HDP and born preterm (AOR 1.81; 95% CI: 1.25-2.61) or small for gestational age (SGA) (AOR = 1.58; (95% CI: 1.15-2.18)). CONCLUSIONS: In conclusion, children exposed to HDP may be at increased odds of asthma diagnosis by age seven, particularly if they were born preterm or SGA. IMPACT: There is a paucity of data investigating the relationship between hypertensive disorders of pregnancy and childhood asthma, with recent studies showing conflicting results. Our study investigated this relationship using a large cohort with ample information on a wide range of confounding factors. Our study showed that individuals exposed to HDP may be at increased odds of asthma diagnosis by age seven years, particularly if they were also born SGA or preterm.

Fetal and maternal outcomes after maternal biologic use during conception and pregnancy: A systematic review and meta-analysis.

BACKGROUND: Biologic medications, specifically tumour necrosis factor-α (TNF-α) inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in pregnancy. OBJECTIVE: To determine pregnancy outcomes in women with CID exposed to biologics during pregnancy. SEARCH STRATEGY: PubMed and EMBASE databases were searched through January 1998-July 2021. SELECTION CRITERIA: Peer-reviewed, English-language cohort, case-control, cross-sectional studies, and case series that contained original data. DATA COLLECTION AND ANALYSIS: Two authors independently conducted data extraction. A meta-analysis of proportions using a random-effects model was used to pool outcomes. Linear regression analysis was used to compare the mean of proportions of outcomes across exposure groups using the 'treated' group as the reference category. All studies were evaluated using an appropriate quality assessment tool. The GRADE approach was used to assess the overall certainty of evidence. MAIN RESULTS: Thirty-five studies, describing 11 172 pregnancies, were eligible for inclusion. Analysis showed pooled proportions for congenital malformations as follows: treated 0.04 (95% CI 0.03-0.04; I2  = 77) versus disease-matched 0.04 (95% CI 0.03-0.05. I2  = 86; p = 0.238); preterm delivery treated 0.04 (95% CI 0.10-0.14; I2  = 88) versus disease-matched 0.10 (95% CI 0.09-0.12; I2  = 87; p = 0.250); severe neonatal infection: treated 0.05 (95% CI 0.03-0.07; I2  = 88) versus disease-matched 0.05 (95% CI 0.02-0.07; I2  = 94; p = 0.970); low birthweight: treated 0.10 (95% CI 0.07-0.12; I2  = 93) versus disease-matched 0.08 (95% CI 0.07-0.09; I2  = 0; p = 0.241); pooled miscarriage: treated 0.13 (95% CI 0.10-0.15; I2  = 77) versus disease-matched 0.08 (95% CI 0.04-0.11; I2  = 5; p = 0.078); pre-eclampsia; treated 0.01 (95% CI 0.01-0.02; I2  = 0) versus disease-matched 0.01 (95% CI 0.00-0.01; I2  = 0; p = 0.193). No statistical differences in proportions were observed. GRADE certainty of findings was low to very low. CONCLUSION: We demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease-matched controls and CID-free pregnancies using the GRADE approach.

Obstetrical mode of delivery and behavioural outcomes in childhood and adolescence: findings from the Millennium Cohort Study.

PURPOSE: To examine the association between mode of delivery (in particular caesarean section) and behavioural outcomes in offspring at six time-points between age 3 and 17 years. METHODS: Similar to previous work examining the association between mode of delivery and behavioural outcomes in offspring at age 7, we used maternal-reported data from the Millennium Cohort Study. Data on mode of delivery were collected when children were 9 months and categorised as spontaneous vaginal delivery, assisted vaginal delivery, induced vaginal delivery, emergency caesarean section, planned caesarean section and caesarean section after induction of labor. Data on behavioural outcomes were collected at ages 3, 5, 7, 11, 14 and 17 years using the Strengths and Difficulties Questionnaire (SDQ). Crude and adjusted logistic regression examined mode of delivery-behavioural difficulties relationship, using validated SDQ cut-off points (total SDQ ≥ 17, emotional ≥ 5, conduct ≥ 4, hyperactivity ≥ 7, peer problems ≥ 4 and prosocial behaviour ≤ 4). Multilevel models with linear splines examined the association between mode of delivery and repeated measures of SDQ. RESULTS: There were 18,213 singleton mother-child pairs included at baseline, 13,600 at age 3; 13,831 at age 5; 12,687 at age 7; 11,055 at age 11; 10,745 at age 14 and 8839 at age 17. Adjusted logistic regression suggested few associations between mode of delivery and behavioural outcomes at ages 3, 5, 11, 14 and 17 years using validated SDQ cut-off points. After correction for multiple testing, only the protective association between planned caesarean section-Conduct difficulties at age 5 years (OR 0.63, 95% CI 0.46, 0.85) and positive association between caesarean section after induction-Emotional difficulties at age 11 years (OR 1.57, 95% CI 1.19, 2.07) remained statistically significant. Multilevel modelling suggested mean SDQ scores were similar in each mode of delivery group at each time point. CONCLUSIONS: Results of this study indicate that mode of delivery is unlikely to have a major impact on behavioural outcomes.

Puberty timing and markers of cardiovascular structure and function at 25 years: a prospective cohort study.

BACKGROUND: Whether earlier onset of puberty is associated with higher cardiovascular risk in early adulthood is not well understood. Our objective was to examine the association between puberty timing and markers of cardiovascular structure and function at age 25 years. METHODS: We conducted a prospective birth cohort study using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were born between April 1, 1991, and December 31, 1992. Exposure of interest was age at peak height velocity (aPHV), an objective and validated growth-based measure of puberty onset. Outcome measures included cardiovascular structure and function at age 25 years: carotid intima-media thickness (CIMT), left ventricular mass index (LVMI) and relative wall thickness (RWT), pulse wave velocity (PWV) and systolic blood pressure (SBP). Multiple imputation was used to impute missing data on covariates and outcomes. Linear regression was used to examine the association between aPHV and each measure of cardiac structure and function, adjusting for maternal age, gestational age, household social class, maternal education, mother's partner's education, breastfeeding, parity, birthweight, maternal body mass index, maternal marital status, maternal prenatal smoking status and height and fat mass at age 9. All analyses were stratified by sex. RESULTS: A total of 2752-4571 participants were included in the imputed analyses. A 1-year older aPHV was not strongly associated with markers of cardiac structure and function in males and females at 25 years and most results spanned the null value. In adjusted analyses, a 1-year older aPHV was associated with 0.003 mm (95% confidence interval (CI) 0.00001, 0.006) and 0.0008 mm (95% CI - 0.002, 0.003) higher CIMT; 0.02 m/s (95% CI - 0.05, 0.09) and 0.02 m/s (95% CI - 0.04, 0.09) higher PWV; and 0.003 mmHg (95% CI - 0.60, 0.60) and 0.13 mmHg (95% CI - 0.44, 0.70) higher SBP, among males and females, respectively. A 1-year older aPHV was associated with - 0.55 g/m2.7 (95% CI - 0.03, - 1.08) and - 0.89 g/m2.7 (95% CI - 0.45, - 1.34) lower LVMI and - 0.001 (95% CI - 0.006, 0.002) and - 0.002 (95% CI - 0.006, 0.002) lower RWT among males and females. CONCLUSIONS: Earlier puberty is unlikely to have a major impact on pre-clinical cardiovascular risk in early adulthood.

Association between hypertensive disorders of pregnancy and the risk of asthma, eczema and allergies in offspring: A systematic review and meta-analysis.

OBJECTIVE: Conduct a systematic review and meta-analysis examining the association between hypertensive disorders of pregnancy (HDP) and risk of asthma, eczema, food allergies and allergic rhinitis in the offspring. DESIGN: A systematic review and random-effects meta-analyses were used to synthesize the published literature. PRISMA guidelines were followed throughout. Two independent reviewers carried out data extraction and quality assessment of included studies. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess certainty of findings. DATA SOURCES: A systematic search of PubMed, Embase, Web of Science and CINAHL was performed from inception of databases-21 April 2020, supplemented by hand-searching reference lists of included articles. ELIGIBILITY CRITERIA: Two reviewers independently reviewed titles, abstracts and full-text articles. English language, cohort, case-control and cross-sectional published studies examining the association between HDP (primary exposure: pre-eclampsia; secondary exposures: all other HDP) and asthma, eczema, food allergies and allergic rhinitis were included. RESULTS: Of the 2833 studies retrieved, 14 studies met inclusion criteria. Of these, 11 studies reported evidence of association between HDP and atopic disorders. Thirteen studies reported estimates for asthma. Seven of these included adjusted estimates (including 3 645 773 participants) for a pre-eclampsia-asthma relationship resulting in a pooled odds ratio (OR) of 1.14 (95% CI: 1.04, 1.26) (I2  = 62%). However, this OR was reduced to 1.08 (95% CI: (0.78, 1.48) when the large registry-based cohort studies were excluded, and only studies using parent-reported measures to determine a diagnosis of asthma were included. Four studies included adjusted estimates (including 254 998 participants) for other HDP and asthma (pooled OR: 1.02, 95% CI: 0.96, 1.09) (I2  = 0%). Two studies provided adjusted estimates (including 1 699 663 participants) for a pre-eclampsia-eczema relationship (pooled OR: 1.06, 95% CI: 0.98, 1.14) (I2  = 0%). One study including pre-eclampsia-food allergies was identified (OR: 1.28, 95% CI: 1.11, 1.46). Three studies examined a HDP (including pre-eclampsia) and allergic rhinitis relationship, with effect estimates ranging from 1.14 to 2.10. Studies were classified as low or low-moderate risk of bias, while GRADE certainty of findings were low to very low. CONCLUSIONS: While pre-eclampsia was associated with a possible increased risk of asthma in offspring, there was no evidence for a relationship between other HDP and asthma. There is a lack of published literature examining the association between HDP and eczema, food allergy and allergic rhinitis. Further primary research is warranted to gain a better understanding of the association between HDP and the risk of childhood atopic disease. SYSTEMATIC REVIEW REGISTRATION: Review protocol in appendix.

Association between preeclampsia and autism spectrum disorder: a population-based study.

BACKGROUND: The environmental contribution of autism spectrum disorder (ASD) is approximately 17%-50%, highlighting the importance of investigating factors potentially contributing to the likelihood of its development, and of gaining a greater understanding of the pathogenesis surrounding ASD. The objective of this study was to examine the association between preeclampsia and ASD using a population-based cohort study. METHODS: All singleton live births in Sweden from 1982 to 2010 were included, using data from Swedish National Registers. Exposures of interest included: (a) preeclampsia (classified according to ICD-8, ICD-9 and ICD-10) and (b) preeclampsia and small for gestational age (SGA) combined, used as a proxy for preeclampsia with placental dysfunction. ASD status was based on ICD-9 and ICD-10. The cohort consisted of 2,842,230 children, with 54,071 cases of ASD. Follow-up began from the child's first birthday, and data were censored at first diagnosis of ASD, death, migration or end of study period (31st December 2016). We conducted multivariate Cox proportional hazards regression analysis, adjusting for several perinatal and sociodemographic factors, selected a priori. We further controlled for shared genetic and familial confounding using sibling-matched analysis. RESULTS: In the adjusted Cox proportional hazards regression analysis, preeclampsia was associated with a 25% increase in the likelihood of ASD (Hazard Ratio (HR): 1.25, 95% CI:1.19, 1.30) compared with those unexposed to preeclampsia, while in the sibling-matched analysis the HR was 1.17 (95% CI: 1.06, 1.28). The HR for preeclampsia and SGA combined was 1.66 (95% CI: 1.49, 1.85) in the adjusted Cox model and 1.95 (95% CI: 1.53, 2.48) in the sibling-matched analysis. CONCLUSIONS: Exposure to preeclampsia or preeclampsia/SGA (i.e. SGA baby exposed to preeclampsia) was associated with ASD. The stronger association with preeclampsia/SGA than preeclampsia alone suggests that placental pathology may be a mechanism for the increased likelihood of ASD.

The Association Between Preeclampsia and Childhood Development and Behavioural Outcomes.

OBJECTIVES: To examine the associations between preeclampsia and longitudinal child developmental and behavioural outcomes using data from a nationally representative study of children living in Ireland. METHODS: We used maternal-reported data from the Growing Up in Ireland longitudinal study of children. Data on preeclampsia and preeclampsia + small for gestational age (SGA) were collected when children were 9-months old. Data on child development and behavioural outcomes were collected at 9-months using the Ages and Stages Questionnaire (ASQ), and at 3 years, 5 years and 7-8 years using the Strengths and Difficulties Questionnaire (SDQ). Multivariate logistic regression analysis was used to examine the association between preeclampsia exposure and failure of ASQ domains, and abnormal SDQ domains. Linear spline multilevel models were used to examine the association between preeclampsia and preeclampsia + SGA and repeated measures of SDQ. All models controlled for several perinatal and sociodemographic factors. RESULTS: A total of 10,692 children were included in the study at baseline, representing a weighted total of 70,791. Multivariate logistic regression suggested that preeclampsia was not associated with failing any ASQ domain. Preeclampsia was associated with abnormal SDQ cut-off of emotional (≥ 5) and hyperactivity (≥ 7) domains at age 5 years only. In the linear spline model, mean SDQ score was higher at each time point in exposed groups. CONCLUSIONS FOR PRACTICE: While we did not find strong evidence of associations between preeclampsia and child developmental and behavioural outcomes overall, some associations between preeclampsia-exposure and subtle behavioural issues did persist. Further research is needed to replicate these findings, and determine the clinical significance of changes in SDQ scores.

Protective lifestyle behaviours and depression in middle-aged Irish men and women: a secondary analysis.

OBJECTIVE: To examine the association between protective lifestyle behaviours (PLB) and depression in middle-aged Irish adults. DESIGN: Secondary analysis of a cross-sectional study. PLB (non-smoker, moderate alcohol, physical activity, adequate fruit and vegetable intake) were assessed using a general health and lifestyle questionnaire and a validated FFQ. Depression was assessed using the Center for Epidemiologic Studies Depression Scale. A score of 15-21 indicates mild/moderate depression and a score of 22 or more indicates a possibility of major depression. Binary logistic regression was used to examine the association between PLB and depression. SETTING: Livinghealth Clinic, Mitchelstown, North Cork, Republic of Ireland. SUBJECTS: Men and women aged 50-69 years were selected at random from a list of patients registered at the clinic (n 2047, 67 % response rate). RESULTS: Over 8 % of participants engaged in zero or one PLB, 24 % and 39 % had two and three PLB respectively, while 28 % had four PLB. Those who practised three/four PLB were significantly more likely to be female, have a higher level of education and were categorised as having no depressive symptoms. Engaging in zero or one PLB was significantly associated with an increased odds of depression compared with four PLB. Results remained significant after adjusting for several confounders, including age, gender, education and BMI (OR=2·2; 95 % CI 1·2, 4·0; P for trend=0·001). CONCLUSIONS: While causal inference cannot be established in a cross-sectional study, the findings suggest that healthy behaviours may play a vital role in the promotion of positive mental health or, at a minimum, are associated with lower levels of depression.

The association between caesarean section delivery and obesity at age 17 years. Evidence from a longitudinal cohort study in the United Kingdom.

BACKGROUND: Childhood and adolescent obesity are major, preventable public health concerns. Studies to date are inconclusive regarding an association between caesarean section (CS) delivery and offspring obesity, with fewer studies conducted in late adolescence. This study examined the association between CS delivery, with a specific focus on planned CS, and induction of labour and adolescent body mass index (BMI) and body fat percentage (BF%) at age 17 years. METHODS: Data on 8,880 mother-child pairs from the United Kingdom Millennium Cohort Study were analysed. The exposures were mode of delivery (normal vaginal delivery (VD) (reference), assisted VD, planned CS and emergency CS) and mode of delivery by induction of labour status. Crude and adjusted binary logistic regression and linear regression models were fitted examining BMI and BF% at age 17 years respectively, adjusting for several potential confounders. RESULTS: Adolescents born by CS did not have an elevated BMI or BF% compared to those born by normal VD. The fully adjusted results for overweight and obesity in children born by planned CS, compared to VD, were 1.05 (95% CI: 0.86-1.28) and 0.94 (95% CI: 0.72-1.23), respectively. The results were similar for the associations between CS and BF%, and between induction of labour and BMI. CONCLUSION: Overall, this large longitudinal study did not support an association between CS or induction of labour and overweight, obesity or BF%. It is possible that previously reported associations are due to residual or unmeasured confounding and/or underlying indications for CS delivery.

The Association between Threatened Miscarriage and Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder in Offspring by Age 14 Years.

OBJECTIVE: To examine the association between threatened miscarriage, and neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring by age 14 years. METHODS: We used data from the Millennium Cohort Study, a nationally representative longitudinal study of children born in the UK. Data on threatened miscarriage and potential confounders were maternal-reported and collected at 9 months postpartum. Data on ASD and ADHD were based on maternal-reported doctor diagnoses and collected when children were aged 5, 7, 11 and 14 years. A diagnosis of ASD or ADHD was assumed if parents reported ASD or ADHD at age 5, 7, 11 or 14 years. Crude and adjusted logistic regression examined threatened miscarriage and ASD and ADHD relationship, adjusting for several sociodemographic, maternal and lifestyle factors. RESULTS: A total of 18,294 singleton babies were included at baseline, and 1,104 (6.0%) women experienced a threatened miscarriage during their pregnancy. Adjusted results suggested an association between threatened miscarriage and ASD (OR: 1.55, 95% CI 1.15, 2.08), and ADHD (OR: 1.51, 95% CI 1.09, 2.10) by age 14 years. E-values for threatened miscarriage and ASD were 2.47, while the lower limits of the 95% CI were 1.57. E-values for threatened miscarriage and ADHD were 2.39, while the corresponding lower limits of the 95% CI were 1.40. CONCLUSION: Threatened miscarriage was associated with an increased likelihood of ASD and ADHD by the age of 14 years, however, residual confounding cannot be ruled out. Placental pathology may be a potential mechanism for the observed associations.

Maternal hypertensive disorders of pregnancy and depression or anxiety in adolescence: Findings from the Millennium Cohort Study.

BACKGROUND: The short-term effects of hypertensive disorders of pregnancy (HDP) on the health of the fetus are well known; however, their impacts on the risk of mental health in the exposed offspring are not fully understood. Our aim was to examine the association between HDP and depression/anxiety at age 17 years. METHODS: We used data from The Millennium Cohort Study, a nationally representative longitudinal study of children born in the United Kingdom. Data on HDP and potential confounders were collected when children were 9-months. Data on depression and anxiety were collected as one variable when children were aged 17 years using self-reported doctor diagnosis, and reclassified as depression/anxiety (overall), depression/anxiety with treatment, and depression/anxiety without treatment. Crude and adjusted logistic regression models were performed to examine the association between HDP and depression/anxiety, adjusting for several maternal and socio-economic factors. RESULTS: There were 9517 singleton mother-child pairs included in the analyses. Adjusted logistic regression suggested an association between HDP and depression/anxiety (adjusted odds ratio, (aOR):1.30 [95 % CI, 1.02-1.66]) at age 17 years. A similar association was observed for HDP and depression/anxiety with treatment (aOR:1.33 [95 % CI, 1.01-1.73]) and HDP and depression/anxiety without treatment (aOR: 1.30 [95 % CI, 0.80-2.12]), although the latter did not reach statistical significance. LIMITATIONS: Data on severity and classifications of HDP were not available. CONCLUSION: Exposure to HDP may be associated with an increased likelihood of depression or anxiety at age 17 years. Future research should consider severity and different classifications of HDP.

Pregnancy and birth complications associations with long-term adverse maternal mental health outcomes: a systematic review and meta-analysis protocol.

Background: Existing studies have established an association between pregnancy, birth complications, and mental health in the first few weeks postpartum. However, there is no clear understanding of whether pregnancy and birth complications increase the risk of adverse maternal mental outcomes in the longer term. Research on maternal adverse mental health outcomes following pregnancy and birth complications beyond 12 months postpartum is scarce, and findings are inconsistent. Objective: This systematic review and meta-analysis will examine the available evidence on the association between pregnancy and birth complications and long-term adverse maternal mental health outcomes. Methods and analysis: We will include cohort, cross-sectional, and case-control studies in which a diagnosis of pregnancy and/or birth complication (preeclampsia, pregnancy loss, caesarean section, preterm birth, perineal laceration, neonatal intensive care unit admission, major obstetric haemorrhage, and birth injury/trauma) was reported and maternal mental disorders (depression, anxiety disorders, bipolar disorders, psychosis, and schizophrenia) after 12 months postpartum were the outcomes. A systematic search of PubMed, Embase, CINAHL, PsycINFO, and Web of Science will be conducted following a detailed search strategy until August 2022. Three authors will independently review titles and abstracts of all eligible studies, extract data using pre-defined standardised data extraction and assess the quality of each study using the Newcastle-Ottawa Scale. We will use random-effects meta-analysis for each exposure and outcome variable to calculate overall pooled estimates using the generic inverse variance method. This systematic review will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Ethical consideration: The proposed systematic review and meta-analysis is based on published data; ethics approval is not required. The results will be presented at scientific meetings and publish in a peer-reviewed journal. PROSPERO registration: CRD42022359017.