Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Maternal and fetal genetic contribution to gestational weight gain.

BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Effects of prolonged breastfeeding and colostrum fatty acids on allergic manifestations and infections in infancy.

BACKGROUND: In developed countries World Health Organization recommendation of 6 months' exclusive breastfeeding is under debate. OBJECTIVE: We assessed the impact of predominant breastfeeding (PBF) duration and colostrum long-chain polyunsaturated fatty acids (LC-PUFAs) profile on the risk of allergic manifestations (wheezing and atopic eczema) and infections [low respiratory tract infections (LRTIs) and gastroenteritis] in infancy. METHODS: Information on child feeding practices was obtained from 580 infants of a pregnancy cohort. Presence of infant's health outcomes was documented through questionnaires at 6 and 14 months of age. The LC-PUFAs were measured in colostrum. Adjusted odds ratios (adjOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models. RESULTS: In comparison with never breastfeeding, PBF for 4-6 months was associated with lower risk of wheezing (adjOR = 0.53; 95% CI, 0.32, 0.89), LRTIs (adjOR = 0.51; 95% CI, 0.31, 0.83) and atopic eczema (adjOR = 0.58; 95% CI, 0.32, 1.04) between months 7 and 14 of life. Results of a risk period-specific analysis (restricted to infants at risk for outcome onset after 6 months of age), showed no indication for reverse causation (results were not very different compared with an overall analysis). Predominantly breastfeeding for 4-6 months was associated with lower risk of gastroenteritis during the first 6 months of life (adjOR = 0.34; 95% CI, 0.18, 0.64). Among breastfed infants higher doses of arachidonic acid (AA), docosahexaenoic acid, and total n-3 in were associated with a decreased risk of gastroenteritis, but no association was found for allergic manifestations or LRTI. CONCLUSIONS AND CLINICAL RELEVANCE: Promotion of PBF for 4-6 months could reduce the burden of allergic manifestations and infections in infancy. Beneficial effects of breastfeeding on gastroenteritis were explained in part by exposure to higher doses of n-3 and AA received from colostrum. No significant effects from fatty acid dose were found on risk of allergic manifestations or LRTIs.

Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort.

BACKGROUND: Mental health has been reported to be associated with allergy, but only a few cohort studies have assessed if neurodevelopment predicts atopy. OBJECTIVE: To investigate if neurobehavioral status of healthy 4-year-old children was associated with specific immunoglobulin E (IgE) at the same age and skin prick test results 2 years later. METHODS: A population-based birth cohort enrolled 482 children, 422 of them (87%) provided neurobehavioral data, 341 (71%) had specific IgE measured at the age of 4 years; and 395 (82%) had skin prick tests completed at the age of 6 years. Atopy was defined as IgE levels higher than 0.35 kU/l to any of the three tested allergens at the age of 4 or as a positive skin prick test to any of the six tested allergens at the age of 6. McCarthy Scales of Child Abilities and California Preschool Social Competence Scale were the psychometric instruments used. RESULTS: Twelve percent of children at the age of 4 and 17% at the age of 6 were atopic. Neurobehavioral scores were negatively associated with 6-year-old atopy after adjustment for socio-demographic and allergic factors, A relative risk of 3.06 (95% CI: 1.30-7.24) was associated with the lowest tertile (scorings < or =90 points) of the general cognitive scale. Similar results were found for verbal abilities, executive functions, and social competence. Asthma, wheezing, rhinitis, and eczema at the age of 6, but not at the age of 4, were associated with neurodevelopment at the age of 4. CONCLUSIONS: Neuropsychologic functioning and later atopy are negatively associated in preschool age children.

Maternal psychological distress during pregnancy and childhood health outcomes: a narrative review.

Maternal psychological distress is common in pregnancy and may influence the risk of adverse outcomes in children. Psychological distress may cause a suboptimal intrauterine environment leading to growth and developmental adaptations of the fetus and child. In this narrative review, we examined the influence of maternal psychological distress during pregnancy on fetal outcomes and child cardiometabolic, respiratory, atopic and neurodevelopment-related health outcomes. We discussed these findings from an epidemiological and life course perspective and provided recommendations for future studies. The literature in the field of maternal psychological distress and child health outcomes is extensive and shows that exposure to stress during pregnancy is associated with multiple adverse child health outcomes. Because maternal psychological distress is an important and potential modifiable factor during pregnancy, it should be a target for prevention strategies in order to optimize fetal and child health. Future studies should use innovative designs and strategies in order to address the issue of causality.

Mediterranean dietary pattern in pregnant women and offspring risk of overweight and abdominal obesity in early childhood: the INMA birth cohort study.

BACKGROUND: Animal models have suggested that maternal diet quality may reduce offspring obesity risk regardless of maternal body weight; however, evidence from human studies is scarce. OBJECTIVE: The aim of this study was to evaluate associations between adherence to the Mediterranean diet (MD) during pregnancy and childhood overweight and abdominal obesity risk at 4 years of age. METHODS: We analysed 1827 mother-child pairs from the Spanish 'Infancia y Medio Ambiente' cohort study, recruited between 2003 and 2008. Diet was assessed during pregnancy using a food frequency questionnaire and MD adherence by the relative Mediterranean diet score (rMED). Overweight (including obesity) was defined as an age-specific and sex-specific body mass index ≥85th percentile (World Health Organization referent), and abdominal obesity as a waist circumference (WC) >90th percentile. Multivariate adjusted linear and logistic regression models were used to evaluate associations between pregnancy rMED and offspring overweight and abdominal obesity. RESULT: There was no association between rMED and body mass index z-score, whereas there was a significant association between higher adherence to MD and lower WC (ß of high vs. low rMED: -0.62 cm; 95% confidence interval: -1.10, -0.14 cm, P for trend = 0.009). CONCLUSION: Pregnancy adherence to the MD was not associated with childhood overweight risk, but it was associated with lower WC, a marker of abdominal obesity.

Modelling indoor electromagnetic fields (EMF) from mobile phone base stations for epidemiological studies.

Radio frequency electromagnetic fields (RF-EMF) from mobile phone base stations can be reliably modelled for outdoor locations, using 3D radio wave propagation models that consider antenna characteristics and building geometry. For exposure assessment in epidemiological studies, however, it is especially important to determine indoor exposure levels as people spend most of their time indoors. We assessed the accuracy of indoor RF-EMF model predictions, and whether information on building characteristics could increase model accuracy. We performed 15-minute spot measurements in 263 rooms in 101 primary schools and 30 private homes in Amsterdam, the Netherlands. At each measurement location, we collected information on building characteristics that can affect indoor exposure to RF-EMF, namely glazing and wall and window frame materials. Next, we modelled RF-EMF at the measurement locations with the 3D radio wave propagation model NISMap. We compared model predictions with measured values to evaluate model performance, and explored if building characteristics modified the association between modelled and measured RF-EMF using a mixed effect model. We found a Spearman correlation of 0.73 between modelled and measured total downlink RF-EMF from base stations. The average modelled and measured RF-EMF were 0.053 and 0.041mW/m(2), respectively, and the precision (standard deviation of the differences between predicted and measured values) was 0.184mW/m(2). Incorporating information on building characteristics did not improve model predictions. Although there is exposure misclassification, we conclude that it is feasible to reliably rank indoor RF-EMF from mobile phone base stations for epidemiological studies.

Sociodemographic, reproductive and dietary predictors of organochlorine compounds levels in pregnant women in Spain.

Organochlorine pesticides and polychlorinated biphenyls (PCBs) are consistently found in human tissues. Serum levels of organochlorine compounds (OC) in pregnant women in particular have raised concern about possible harm to humans in the early phases of physical and behavioural development. The objective of the present study was to evaluate the association between concentration of OCs in serum of two cohorts of pregnant women from Gipuzkoa and Sabadell in Spain and socioeconomic, reproductive and dietary variables. Concentration of polychlorinated biphenyls (PCBs: 28, 52, 101, 118, 138, 153 and 180), hexachlorobenzene (HCB), beta and gamma-hexachlorocyclohexane (ß-HCH and γ-HCH), heptachlor epoxide, dichlorodiphenyl dichloroethylene (p,p'-DDE) and dichlorodiphenyl trichloroethane (p,p'-DDT) were measured in the serum of 1259 pregnant women. Associations between OCs and potential predictor variables were assessed using linear regression models adjusted for potential confounders. The compounds most commonly found in the serum were p,p'-DDE (99% of the samples) and PCB-153 (95% of the samples). Geometric means of serum concentrations (ng g⁻¹ lipid) of organochlorine pesticides were 110.0, 19.1, and 33.5 for p,p'-DDE, ß-HCH, and HCB respectively, while the geometric means of PCBs were 21.8, 38.9 and 26.9 for PCB 138, 153, and 180 respectively. The levels of all OCs increased with age. BMI was positively associated with the concentration of organochlorine pesticides but inversely related to PCB concentrations. The serum levels of OCs fell only after a cumulative period of breastfeeding of over a year. Levels of PCBs were related to fish intake, but in general dietary factors did not improve the explained variability of the concentrations of OCs. Overall, the levels of OCs found in the study are at the lower end of the range reported in Spain and other countries.

Iodine intake in a population of pregnant women: INMA mother and child cohort study, Spain.

BACKGROUND: Monitoring iodine status during pregnancy is essential to prevent iodine-related disorders. The objectives of this study are to estimate iodine intake and excretion, to assess their association and to evaluate the compliance of the recommendations in a multicentre cohort of pregnant women. METHODS: Cross-sectional data on maternal iodine nutritional status, compiled between weeks 8 and 22 of gestation in three Spanish areas (Valencia, Gipuzkoa and Sabadell), were analysed. Information on iodine intake from diet, salt and supplements was estimated through questionnaires. Spot urine samples were analysed for urinary iodine concentration (UIC). Tobit regression analysis was used to assess the association between iodine intake and UIC. RESULTS: 1522 women were included in the study. Median UIC was 134 (IQR 80-218) µg/l in Valencia, 168 (IQR 108-272) µg/l in Gipuzkoa and 94 (IQR 57-151) µg/l in Sabadell. 48.9% of Valencian women consumed iodine supplements, 93.3% in Gipuzkoa and 11.0% in Sabadell. Prevalence of iodised salt consumption was 50.5% in the whole sample. UIC was associated with intake of supplements, iodised salt, dietary iodine and water. UIC levels were lower than expected according to the estimated iodine intake. CONCLUSION: Median UIC reflected iodine deficiency according to WHO reference levels, except in Gipuzkoa where supplements are widely consumed. It is necessary to strengthen iodised salt consumption since it is already far from the objective proposed of coverage of 90% of households. More data would be valuable to assess the correspondence between iodine intake and excretion during pregnancy.

Iodine levels and thyroid hormones in healthy pregnant women and birth weight of their offspring.

INTRODUCTION: The fetus is most vulnerable to severe iodine deficiency and hypothyroidism during pregnancy. The effects of mild iodine deficiency and subclinical hypothyroidism are poorly known. The present study assesses the association between thyroid hormones (TH)s and urinary iodine concentration (UIC) in healthy pregnant women and the birth weight of their children. METHODS: About 657 pregnant women were recruited in Sabadell and followed until delivery. The association between THs during the first trimester, UIC during the first and third trimesters, and birth weight was studied in 557, 251, and 528 mother-newborn pairs respectively, using linear and logistic regression models adjusted for potential confounders. Only 239 women had all the data available (thyroid function and UIC at the first and third trimesters). Six percent of newborns were classified as small for gestational age (SGA). RESULTS: The median UIC was 95 and 104 microg/l during the first and third trimesters respectively. Women with the third trimester UICs between 100 and 149 microg/l had lower risk of having an SGA newborn than women with UICs below 50 microg/l (adjusted OR (95%CI): 0.15 (0.03-0.76). There was no significant reduction in SGA among mothers with higher UICs. Lower free thyroxine and higher TSH levels during the first trimester were not associated with birth weight or SGA. Nevertheless, the analyses were repeated including only those women with all the data available, and high TSH levels became statistically significantly associated with lower birth weight and higher risk of SGA. CONCLUSIONS: The present study suggests that iodine status during pregnancy may be related to prenatal growth in healthy women.