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Fertility and Sterility Feb 2023To investigate the impact of endometrial receptivity array (ERA) before frozen embryo transfer in patients undergoing in vitro fertilization (IVF). There is a lack of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the impact of endometrial receptivity array (ERA) before frozen embryo transfer in patients undergoing in vitro fertilization (IVF). There is a lack of consensus regarding the use of ERA for increasing the success rate of IVF cycles, mainly in terms of the live birth rate.
DESIGN
PubMed, Web of Science and Embase were searched from inception up to February 15, 2022.
SETTING
Not applicable.
PATIENT(S)
Patients undergoing ERA vs no ERA before frozen embryo transfer.
INTERVENTION(S)
Only comparative studies evaluating pregnancy rates of patients undergoing frozen embryo transfer cycles with or without prior ERA were included. Inter-study heterogeneity was also assessed using Cochrane's Q test and the I statistic. The random-effects model was used to pool the odds ratio (OR) with the corresponding 95% confidence intervals (CIs). Subgroup analyses were performed to investigate the impact of ERA on pregnancy rates according to the number of previous embryo transfer (ET) failures (≤ 2 previous failed ETs vs. > 2 failed ETs, defined as recurrent implantation failure). Separate analyses were performed according to the study design and adjustment for confounders.
MAIN OUTCOME MEASURES(S)
The primary outcomes of the study were live birth rate and/or ongoing pregnancy rate. Implantation rate, biochemical pregnancy rate, clinical pregnancy rate, and miscarriage rate were considered secondary outcomes.
RESULT(S)
Eight studies (representing data on n = 2,784 patients; n = 831 had undergone ERA and n = 1,953 without ERA) were found to be eligible for this meta-analysis. The live birth or ongoing pregnancy rate for the ERA group was not significantly different compared with the non-ERA group (OR, 1.38; 95% CI, 0.79-2.41; I 83.0%), nor was a difference seen in subgroup analyses based on the number of previous failed ETs. The rates of implantation, biochemical pregnancy, clinical pregnancy, and miscarriage were also comparable between the ERA and the non-ERA groups. After separate analyses according to the study design and adjustment for confounding factors, overall pooled estimates remained statistically nonsignificant.
CONCLUSION(S)
The findings of the current meta-analysis did not reveal a significant change in the rate of pregnancy after IVF cycles using ERA, and it is not clear whether ERA can increase the pregnancy rate or not.
SYSTEMATIC REVIEW REGISTRATION
Prospectively registered in PROSPERO (CRD42022310862).
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Embryo Transfer; Fertilization in Vitro; Pregnancy Rate; Embryo Implantation; Live Birth; Retrospective Studies
PubMed: 36414088
DOI: 10.1016/j.fertnstert.2022.11.012 -
Cureus Jan 2021Low back pain (LBP) is a very common pathology among pregnant women and various methods are used to reduce the pain. The aim of this study is to conduct an...
INTRODUCTION
Low back pain (LBP) is a very common pathology among pregnant women and various methods are used to reduce the pain. The aim of this study is to conduct an evidence-based systematic review and meta-analysis regarding the effectiveness of the interventions used to reduce low back pain related to pregnancy. Methods and materials: The PEDro database, PubMed, and Cochrane Library were searched from January 2012 until December 2020 as well as the reference lists from identified articles. Studies of any non-pharmaceutical treatment to decrease low back pain were included but only randomized controlled trials were selected. The articles found were screened using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) question. Details about the type of intervention, sample size, outcome measures, results, and statistical significance were extracted from the selected studies. A meta-analysis for pain intensity was conducted and the I index as well as x test were used to determine the heterogeneity between studies. A random-effects meta-analysis was carried out. The aim was to compare the effectiveness between various methods and the typical care provided on low back pain during pregnancy. Results: From all the articles found in the mentioned databases only 13 studies met the criteria. In these studies, exercise, manipulation, ear acupuncture, Kinesio tape, transcutaneous electrical nerve stimulation (TENS), and neuroemotional technique were the interventions used. In the meta-analysis, six studies with 693 participants were included. The interventions were found to have in total a statistically significant effect on low back pain in comparison with the control group that included the typical care provided to pregnant women (95%CI: 0.08 (0.02,0.31), p<0,01) and they had a high heterogeneity (considerable, Tau² = 2.70; Chi² = 64.11, I² = 91%). Exercise and TENS were determined as more effective than the other types of interventions.
CONCLUSIONS
TENS and progressive muscle relaxation exercises accompanied by music were found to be the most effective interventions. Although exercise decreased LBP it was not found to have a statistically significant result even though it seems to improve the disability and quality of life of pregnant women. Osteopathic manual treatment (OMT), Kinesio tape, and ear acupuncture affected the lumbar pain intensity but the difference compared to typical care or sham treatment was not statistically significant, while yoga did not improve pregnancy-related LBP. Further research is needed to determine the effectiveness of the interventions mentioned.
PubMed: 33728108
DOI: 10.7759/cureus.13011 -
JAMA Aug 2019Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent,... (Meta-Analysis)
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.
Topics: Adult; Autoantibodies; Autoimmune Diseases; Female; Gestational Age; Humans; Hypothyroidism; Infant, Newborn; Iodide Peroxidase; Pregnancy; Pregnancy Complications; Premature Birth; Thyroid Diseases; Thyroid Function Tests; Thyrotropin; Thyroxine
PubMed: 31429897
DOI: 10.1001/jama.2019.10931 -
BJOG : An International Journal of... Jan 2019There is no international consensus on how to manage women with a pregnancy of unknown location (PUL). (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is no international consensus on how to manage women with a pregnancy of unknown location (PUL).
OBJECTIVES
To present a systematic quantitative review summarising the evidence related to management protocols for PUL.
SEARCH STRATEGY
MEDLINE, COCHRANE and DARE databases were searched from 1 January 1984 to 31 January 2017. The primary outcome was accurate risk prediction of women initially diagnosed with a PUL having an ectopic pregnancy (high risk) as opposed to either a failed PUL or intrauterine pregnancy (low risk).
SELECTION CRITERIA
All studies written in the English language, which were not case reports or series that assessed women classified as having a PUL at initial ultrasound.
DATA COLLECTION AND ANALYSIS
Forty-three studies were included. QUADAS-2 criteria were used to assess the risk of bias. We used a novel, linear mixed-effects model and constructed summary receiver operating characteristic curves for the thresholds of interest.
MAIN RESULTS
There was a high risk of differential verification bias in most studies. Meta-analyses of accuracy were performed on (i) single human chorionic gonadotrophin (hCG) cut-off levels, (ii) hCG ratio (hCG at 48 hours/initial hCG), (iii) single progesterone cut-off levels and (iv) the 'M4 model' (a logistic regression model based on the initial hCG and hCG ratio). For predicting an ectopic pregnancy, the areas under the curves (95% CI) for these four management protocols were as follows: (i) 0.42 (0.00-0.99), (ii) 0.69 (0.57-0.78), (iii) 0.69 (0.54-0.81) and (iv) 0.87 (0.83-0.91), respectively.
CONCLUSIONS
The M4 model was the best available method for predicting a final outcome of ectopic pregnancy. Developing and validating risk prediction models may optimise the management of PUL.
TWEETABLE ABSTRACT
Pregnancy of unknown location meta-analysis: M4 model has best test performance to predict ectopic pregnancy.
Topics: Chorionic Gonadotropin; Decision Support Techniques; Female; Humans; Logistic Models; Pregnancy; Pregnancy, Ectopic; Progesterone; ROC Curve; Risk Assessment; Sensitivity and Specificity
PubMed: 30129999
DOI: 10.1111/1471-0528.15442 -
Human Reproduction Update Apr 2020Recurrent pregnancy loss (RPL) occurs in 1-3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recurrent pregnancy loss (RPL) occurs in 1-3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses.
OBJECTIVE AND RATIONALE
The aim of this systematic review was to evaluate the current evidence on the prevalence of abnormal test results for RPL amongst patients with two versus three or more pregnancy losses. We also aimed to contribute to the debate regarding whether the investigations for RPL should take place after two or three or more pregnancy losses.
SEARCH METHODS
Relevant studies were identified by a systematic search in OVID Medline and EMBASE from inception to March 2019. A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale.
OUTCOMES
From a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79-1.27, I2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86-1.25, I2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55-1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06-4.56).
WIDER IMPLICATIONS
A difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present.
Topics: Abortion, Habitual; Antiphospholipid Syndrome; Chromosome Aberrations; Female; Fertilization; Humans; Pregnancy; Risk Factors; Thrombophilia; Thyroid Diseases; Urogenital Abnormalities; Uterus
PubMed: 32103270
DOI: 10.1093/humupd/dmz048 -
International Journal of Environmental... Apr 2022Women commonly suffer from depression during pregnancy. For reducing depression, yoga seems to be more suitable for pregnant women than other physical activities because... (Meta-Analysis)
Meta-Analysis
Women commonly suffer from depression during pregnancy. For reducing depression, yoga seems to be more suitable for pregnant women than other physical activities because of its low exercise intensity. The objective of this study was to assess the efficacy of prenatal yoga on the treatment of depression during pregnancy. Three electronic databases were searched for relevant articles from their inception to May 2021, including PubMed, Cochrane Library, and ScienceDirect. Pre- and post-test outcomes were adopted to estimate standardized mean difference with a 95% confidence interval for assessing the efficacy of yoga. Heterogeneity among articles was detected using I2 value. A total of 13 articles that contained 379 subjects were included for meta-analysis. No significant improvement in depression scores after practicing yoga was observed for women without depression (p = 0.09) but significant improvement was observed for women with depression (p = 0.001). Although significant improvement in anxiety scores after yoga was observed for women without depression (p = 0.02), the results of the sensitivity analysis were not consistent, while significant improvement in anxiety scores after yoga was also observed for women with depression (p < 0.00001). The current evidence has suggested that yoga had significant improvement in depression and anxiety scores in pregnant women with depression. However, the level of evidence of this study was not high. More articles with high levels of evidence should be conducted to confirm our conclusion in the future.
Topics: Anxiety; Anxiety Disorders; Depression; Female; Humans; Pregnancy; Pregnant Women; Yoga
PubMed: 35564762
DOI: 10.3390/ijerph19095368 -
Asia Pacific Journal of Clinical... 2020Despite enduring efforts in Indonesia to eliminate anemia in pregnancy, it remains a major nutritional problem. Its nutritional contributors were reevaluated. (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Despite enduring efforts in Indonesia to eliminate anemia in pregnancy, it remains a major nutritional problem. Its nutritional contributors were reevaluated.
METHODS
A meta-analysis of reports on anemia during pregnancy in Indonesia from January 2001 to December 2019 in the PubMed and ProQuest databases was conducted. Pooled ORs were obtained in fixed- and random-effects models. Funnel plots and Egger's and Begg's tests were used to evaluate publication bias. Review Manager 5.3 and Stata version 14.2 were used for analysis.
RESULTS
A total of 2,474 articles were appraised. Systematic review and meta-analysis were performed on 10 studies including 4,077 participants. Chronic energy deficiency had the highest OR for the risk of anemia (3.81 [95% CI: 2.36-6.14]) followed by greater parity (OR=2.66 [95% CI: 1.20-5.89]), low education level (OR=2.56 [95% CI: 1.04-6.28]), and limited health knowledge (OR=1.70 [95% CI: 1.17-2.49]), whereas older age and inadequate iron supplementation were not apparently associated with maternal anemia (p > 0.05).
CONCLUSION
Future policies and strategic action to reduce nutritional anemia during pregnancy in Indonesia should increase emphasis on local nutritional epidemiology to establish the pathogenesis of anemia and the validity of stand-alone single-nutrient interventions. Attention to chronic energy deficiency as a barrier to preventing anemia in pregnancy may be necessary to enable health workers and women at risk to be better informed in their efforts.
Topics: Age Factors; Anemia; Anemia, Iron-Deficiency; Dietary Supplements; Educational Status; Energy Intake; Female; Health Knowledge, Attitudes, Practice; Health Policy; Humans; Indonesia; Iron; Iron Deficiencies; Malnutrition; Micronutrients; Nutrients; Nutritional Status; Parity; Pregnancy; Pregnancy Complications; Prenatal Care; Risk Factors
PubMed: 33377743
DOI: 10.6133/apjcn.202012_29(S1).02 -
Journal of Diabetes Investigation Jan 2019Pregnant women with gestational diabetes mellitus (GDM) are at a higher risk of adverse pregnancy outcomes. The aim of the present study was to estimate the pooled... (Meta-Analysis)
Meta-Analysis
AIMS/INTRODUCTION
Pregnant women with gestational diabetes mellitus (GDM) are at a higher risk of adverse pregnancy outcomes. The aim of the present study was to estimate the pooled prevalence of GDM in mainland China according to International Association of Diabetes and Pregnancy Study Groups criteria.
MATERIALS AND METHODS
We carried out a systematic review by searching both English and Chinese literature databases. Random effects models were used to summarize the prevalence of GDM in mainland China. Subgroup and sensitivity analyses were carried out to address heterogeneity. Publication bias was evaluated using Egger's test.
RESULTS
A total of 25 papers were included in the meta-analysis, involving 79,064 Chinese participants. The total incidence of GDM in mainland China was 14.8% (95% confidence interval 12.8-16.7%). Subgroup analysis showed that the age, bodyweight and family history of diabetes mellitus could significantly increase the incidence of GDM.
CONCLUSIONS
To the best of our knowledge, this systematic review is the first to estimate the pooled prevalence of GDM among women in mainland China according to International Association of Diabetes and Pregnancy Study Groups criteria. The results of our systematic review suggest a high prevalence of GDM in mainland China, indicating that this country might have the largest number of GDM patients worldwide.
Topics: Asian People; China; Diabetes, Gestational; Female; Humans; Pregnancy; Prevalence; Risk Factors
PubMed: 29683557
DOI: 10.1111/jdi.12854 -
Human Reproduction Update Jun 2022Several interventions and techniques are suggested to improve the outcome of embryo transfer (ET) in assisted conception. However, there remains no consensus on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several interventions and techniques are suggested to improve the outcome of embryo transfer (ET) in assisted conception. However, there remains no consensus on the optimal practice, with high variations among fertility specialists.
OBJECTIVE AND RATIONALE
We conducted a comprehensive systematic review and meta-analyses of randomized controlled trials (RCTs) aiming to identify effective interventions that could be introduced around the time of ET to improve reproductive outcomes.
SEARCH METHODS
We searched the electronic databases (MEDLINE, EMBASE and Cochrane CENTRAL) from inception until March 2021 using a multi-stage search strategy of MeSH terms and keywords, and included all RCTs that evaluated an intervention in the 24-h period before/after ET in women undergoing IVF/ICSI. Our primary outcome was clinical pregnancy rate post-ET confirmed as viable pregnancy on ultrasound scan. We assessed the risk of bias in included trials and extracted data in duplicate. We pooled data using a random-effect meta-analysis and reported using risk ratio (RR) with 95% CI. We explored publication bias and effect modifiers using subgroup analyses.
OUTCOMES
Our search yielded 3685 citations of which we included 188 RCTs (38 interventions, 59 530 participants) with a median sample size of 200 (range 26-1761). The quality of included RCTs was moderate with most showing a low risk of bias for randomization (118/188, 62.8%) and attrition (105/188, 55.8%) but there was a significant risk of publication bias (Egger's test P = 0.001). Performing ET with ultrasound guidance versus clinical touch (n = 24, RR 1.265, 95% CI 1.151-1.391, I2 = 38.53%), hyaluronic acid versus routine care (n = 9, RR 1.457, 95% CI 1.197-1.261, I2 = 46.48%) and the use of a soft versus hard catheter (n = 27, RR 1.122, 95% CI 1.028-1.224, I2 = 57.66%) led to higher clinical pregnancy rates. Other pharmacological add-ons also showed a beneficial effect including granulocyte colony-stimulating factor (G-CSF: n = 4, RR 1.774, 95% CI 1.252-2.512, I2 = 0), Atosiban (n = 7, RR 1.493, 95% CI 1.184-1.882, I2 = 68.27%) and hCG (n = 17, RR 1.232, 95% CI 1.099-1.382, I2 = 57.76%). Bed rest following ET was associated with a reduction in clinical pregnancy (n = 6, RR 0.857, 95% CI 0.741-0.991, I2 = 0.01%). Other commonly used interventions, such as non-steroidal anti-inflammatory drugs, prophylactic antibiotics, acupuncture and cervical mucus removal, did not show a significant benefit on reproductive outcomes. Our effect estimates for other important outcomes, including miscarriage and live birth, were limited by the varied reporting across included RCTs.
WIDER IMPLICATIONS
Using ultrasound guidance, soft catheters and hyaluronic acid at the time of ET appears to increase clinical pregnancy rates. The use of Atosiban, G-CSF and hCG showed a trend towards increased clinical pregnancy rate, but larger trials are required before adopting these interventions in clinical practice. Bed rest post-ET was associated with a reduction in clinical pregnancy and should not be recommended.
Topics: Embryo Transfer; Female; Granulocyte Colony-Stimulating Factor; Humans; Hyaluronic Acid; Live Birth; Pregnancy; Pregnancy Rate
PubMed: 35325124
DOI: 10.1093/humupd/dmac009 -
The Lancet. Diabetes & Endocrinology Jun 2020Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight.
METHODS
In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496.
FINDINGS
We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (p=0·10). Each 1 SD increase in FT concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second.
INTERPRETATION
Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy.
FUNDING
Netherlands Organization for Scientific Research (grant 401.16.020).
Topics: Birth Weight; Female; Gestational Age; Humans; Hypothyroidism; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Pregnancy Complications; Thyroid Function Tests; Thyroid Gland
PubMed: 32445737
DOI: 10.1016/S2213-8587(20)30061-9