Infertility treatment and offspring blood pressure-a systematic review and meta-analysis

Studies have inconsistently observed that children conceived by IVF or ICSI have higher blood pressure compared to children not conceived by these ARTs. The aim was to perform a systematic review and meta-analysis of blood pressure measures of offspring conceived by ART and those conceived naturally. Resolving the suspicion of ART as a risk factor of higher blood pressure, and therefore of heart disease, has public health and clinical implications. A biomedical librarian searched the Embase, PubMed, and Web of Science databases. Searches were limited to records published in English since 1978. Grey literature was searched. Inclusion criteria were humans born via infertility treatment (vs no treatment) who underwent a blood pressure assessment. Exclusion criteria were non-human participants, non-quantitative studies, absence of a control group, and specialty populations (e.g. cancer patients only). Two reviewers independently screened each record's title and abstract and full text using Covidence, extracted data using Excel, and assessed bias using the National Heart, Lung, and Blood Institute's Quality Assessment Tool for cohort studies. Of 5082 records identified, 79 were included in the systematic review and 36 were included in the meta-analysis of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in ART and non-ART groups. Overall, 34 reports including 40 effect sizes from 25 unique cohorts, compared blood pressure between ART (N = 5229) and non-ART (N = 8509, reference) groups with no covariate adjustment. No standardized mean differences (SMD) in SBP (0.06 per SD of mmHg, 95% CI = -0.05, 0.18) or DBP (0.11, 95% CI = -0.04, 0.25) by treatment were found, but the heterogeneity was considerable (I2=76% for SBP and 87% for DBP). Adjusted analyses were presented in 12 reports, representing 28 effect sizes from 21 unique cohorts (N = 2242 treatment vs N = 37 590 non-treatment). Studies adjusted for varied covariates including maternal (e.g. age, education, body mass index, smoking, pregnancy complications), child (e.g. sex, age, physical activity, BMI, height), and birth characteristics (e.g. birth weight and gestational age). Adjusted results similarly showed no SMD for SBP (-0.03, 95% CI = -0.13, 0.08) or DBP (0.02, 95% CI = -0.12, 0.16), though heterogeneity remained high (I2 = 64% and 86%). Funnel plots indicated a slight publication bias, but the trim and fill approach suggested no missing studies. Removal of five studies which adjusted