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

Achondroplasia: Update on diagnosis, follow-up and treatment

Achondroplasia requieres a multidisciplinary follow-up, with the aim of preventing and managing complications, improving the quality of life and favoring their independence and social inclusion. This review is justified by the multiple publications generated in recent years that have carried out a change in its management. Different guidelines and recommendations have been developed, among which the one made by the American Academy of Pediatrics in 2005 recently updated (2020), the Japanese guide (2020), the first European Consensus (2021) and the International Consensus on the diagnosis, approach multidisciplinary approach and management of individuals with achondroplasia throughout life (2021). However, and despite these recommendations, there is currently a great worldwide variability in the management of people with achondroplasia, with medical, functional and psychosocial consequences in patients and their families. Therefore, it is essential to integrate these recommendations into daily clinical practice, taking into account the particular situation of each health system.(c) 2022 Asociacion Espanola de Pediatria. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/)

Prenatal exposure to fluoride and neuropsychological development in early childhood: 1-to 4 years old children

Background: Cross-sectional and prospective studies have provided evidence of the neurotoxic effect of early exposure to fluoride (F) in pregnancy. It has been negatively associated with cognitive development during childhood, with most research conducted in areas with high F levels in community drinking water (CDW). Method: Data from 316 to 248 mother-child pairs from the Infancia y Medio Ambiente (Childhood and Environment, INMA) birth cohort project with maternal urinary F level adjusted for creatinine (MUFcr) measurements in the first and third trimesters of pregnancy. Children's cognitive domains and intelligence indexes were evaluated using the Bayley Scales (age of 1) and the McCarthy Scales (age of 4). Multiple linear regression analyses were carried out adjusting for a wide range of covariates related to the child, mother, family context and other potential neurotoxicants. Results: No association was found between MUFcr levels and Bayley Mental Development Index score. Nevertheless, regarding the McCarthy scales, it was found that per unit (mg/g) of MUFcr across the whole pregnancy, scores in boys were greater for the verbal, performance, numeric and memory domains (β = 13.86, CI 95%: 3.91, 23.82), (β = 5.86, CI 95%: 0.32, 11.39), (β = 6.22, CI 95%: 0.65, 11.79) and (β = 11.63, CI 95%: 2.62, 20.63) respectively and for General Cognitive Index (β = 15.4, CI 95%: 6.32, 24.48). For girls there was not any cognitive score significantly associated with MUFcr, being the sex-F interactions significant (P interaction <0.05). Including other toxicants levels, quality of family context or deprivation index did not substantially change the results. Conclusions: In boys, positive associations were observed between MUFcr and scores in cognitive domains at the age of 4. These findings are inconsistent with those from some previous studies and indicate the need for other population-based studies to confirm or overturn these results at low levels of F in CDW

Maternal pre-pregnancy overweight and obesity, and child neuropsychological development: two Southern European birth cohort studies

Background Maternal pre-pregnancy obesity may be associated with impaired infant neuropsychological development; however, there are few studies and it is unclear if reported associations are due to intrauterine mechanisms. Methods We assessed whether maternal pre-pregnancy overweight and obesity were associated with cognitive and psychomotor development scores (mean 100 +/- 15) of children aged 11-22 months in two birth cohorts: Environment and Childhood (INMA, Spain; n = 1967) and Mother-Child (RHEA, Greece: n = 412). Paternal body mass index (BMI) was used as a negative control exposure. Results The percentage of overweight and obese mothers was 18% and 8%, respectively, in INMA and 20% and 11% in RHEA, respectively. Maternal pre-pregnancy obesity was associated with reduced infant cognitive development scores in both INMA (score reduction: -2.72; 95% CI: -5.35, -0.10) and RHEA (score reduction: -3.71; 95% CI: -8.45, 1.02), after adjusting for socioeconomic variables and paternal BMI. There was evidence in both cohorts of a dose-response relationship with continuous maternal BMI. Paternal overweight/obesity was not associated with infant cognitive development. Associations with psychomotor scores were not consistent between cohorts, and were stronger for paternal than maternal BMI in RHEA. Conclusions This study in two birth cohorts with moderately high obesity prevalence suggests that maternal pre-pregnancy obesity is associated with reduced child cognitive development at early ages. This association appears more likely to be due to maternal than shared family and social mechanisms, but further research is needed to disentangle a direct intrauterine effect from other maternal confounding factors

Sugar-containing beverages consumption and obesity in children aged 4-5 years in Spain: the INMA study

The consumption of sugar-containing beverages (SCB) has been associated with obesity although the evidence in preschool children is scarce. Cross-sectional analyses were performed to assess the association between obesity and SCB consumption (packaged juices and sugar-sweetened soft drinks) in 1823 children at the age of 4-5 years from the INfancia y Medio Ambiente (INMA) Project. One drink was defined as a glass of 175 mL, and the consumption of SCB was categorized in 1 drink/day. We used multiple logistic regression to estimate odds ratios (OR). The average SCB consumption was 79.1 mL/day, mainly from packaged juices (80.9%). The SCB consumption was lower in non-obese children than in children with obesity, 76.6 vs 118.4 mL/day (p = 0.02). After adjusting for covariates, children who consumed >1 drink/day showed elevated odds of obesity, OR = 3.23 (95% confidence interval (CI): 1.48-6.98) compared to children who consumed <1 SCB drink a week. Each additional SCB drink per day was associated with higher odds of obesity, OR = 1.55 (1.14-2.09). Higher consumption of packaged juices, but not sugar-sweetened soft drinks, was significantly associated with higher odds of obesity, OR = 1.55 (1.09-2.15) and OR = 1.59 (0.76-3.39), respectively. A higher SCB consumption is associated with obesity in preschool children, mainly due to the consumption of packaged juices

Sugar-containing beverages consumption and obesity in children aged 4-5 years in Spain: the INMA study

The consumption of sugar-containing beverages (SCB) has been associated with obesity although the evidence in preschool children is scarce. Cross-sectional analyses were performed to assess the association between obesity and SCB consumption (packaged juices and sugar-sweetened soft drinks) in 1823 children at the age of 4-5 years from the INfancia y Medio Ambiente (INMA) Project. One drink was defined as a glass of 175 mL, and the consumption of SCB was categorized in 1 drink/day. We used multiple logistic regression to estimate odds ratios (OR). The average SCB consumption was 79.1 mL/day, mainly from packaged juices (80.9%). The SCB consumption was lower in non-obese children than in children with obesity, 76.6 vs 118.4 mL/day (p = 0.02). After adjusting for covariates, children who consumed >1 drink/day showed elevated odds of obesity, OR = 3.23 (95% confidence interval (CI): 1.48-6.98) compared to children who consumed <1 SCB drink a week. Each additional SCB drink per day was associated with higher odds of obesity, OR = 1.55 (1.14-2.09). Higher consumption of packaged juices, but not sugar-sweetened soft drinks, was significantly associated with higher odds of obesity, OR = 1.55 (1.09-2.15) and OR = 1.59 (0.76-3.39), respectively. A higher SCB consumption is associated with obesity in preschool children, mainly due to the consumption of packaged juices