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Acta Obstetricia Et Gynecologica... Mar 2021Risk factors for pelvic floor disorders are often related to pregnancy and delivery. Consistent evidence is needed to develop prevention strategies targeting risk... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Risk factors for pelvic floor disorders are often related to pregnancy and delivery. Consistent evidence is needed to develop prevention strategies targeting risk factors. The objective of this study is to identify which pregnancy- and/or obstetric-related risk factors can predict urinary incontinence, fecal incontinence, or pelvic organ prolapse later in life by means of a systematic review and meta-analysis.
MATERIAL AND METHODS
Systematic review Prospero number: CRD42019131758. Literature searches of PubMed, EMBASE, CINAHL, and Cochrane Library were conducted according to PRISMA guidelines (April 2020). Prospective cohort studies describing more than two pregnancy- and/or obstetric-related risk factors on urinary incontinence, fecal incontinence (including flatal incontinence), or pelvic organ prolapse were eligible. Risk of bias was assessed (using Quality In Prognosis Studies [QUIPS]). Studies with high risk of bias were excluded. Data were extracted and checked for accuracy with the CHARMS checklist. Sub-groups were used to distinguish between a short- and long-term follow-up period: <18 months (shortterm) and >18 months (long-term) postpartum. Odds ratios were calculated from reported prevalence rates. Log odds ratios were calculated using SPSS v.24. Variables were pooled using RevMan5.
RESULTS
Data were extracted from nineteen studies for urinary incontinence, nine for fecal incontinence, and two for pelvic organ prolapse. Multivariate analysis was not possible because of the heterogeneity of the population and outcome measures. Pooled univariate risk factors for urinary incontinence were: urinary incontinence during pregnancy, instrumental vaginal delivery, episiotomy, tears, and constipation. Pooled univariate risk factors for fecal incontinence were: fecal incontinence during pregnancy, maternal age over 35 years, prenatal body mass index over 30 kg/m , instrumental vaginal delivery, a spontaneous vaginal delivery, oxytocin augmentation, and when the weight of the newborn was more than 4000 g. Both studies for pelvic organ prolapse had a short-term follow-up period and cesarean section was the only risk factor that could be pooled.
CONCLUSIONS
Pregnancy- and obstetric-related risk factors predicting pelvic floor disorders postpartum are multifactorial and differ between pelvic floor disorders. The strongest risk factor for incontinence later in life was incontinence during pregnancy. Better quality research with long-term follow up is needed on this topic.
Topics: Adult; Fecal Incontinence; Female; Humans; Obstetric Labor Complications; Pelvic Organ Prolapse; Pregnancy; Pregnancy Complications; Risk Factors; Urinary Incontinence
PubMed: 33064839
DOI: 10.1111/aogs.14027 -
Annals of the New York Academy of... Aug 2019Maternal anemia is a well-recognized global health problem; however, there remain questions on specific hemoglobin (Hb) thresholds that predict health risk or protection... (Meta-Analysis)
Meta-Analysis
Maternal anemia is a well-recognized global health problem; however, there remain questions on specific hemoglobin (Hb) thresholds that predict health risk or protection for mother and child. We conducted a systematic review and meta-analysis to examine the associations of maternal Hb concentrations with a range of maternal and infant health outcomes, accounting for the timing of measurement (preconception, and first, second, and third trimesters), etiology of anemia, and cutoff category. The systematic review included 272 studies and the meta-analysis included 95 studies. Low maternal Hb (<110 g/L) was associated with poor birth outcomes (low birth weight, preterm birth, small-for-gestational-age (SGA), stillbirth, and perinatal and neonatal mortality) and adverse maternal outcomes (postpartum hemorrhage, preeclampsia, and blood transfusion). High maternal Hb (>130 g/L) was associated with increased odds of SGA, stillbirth, preeclampsia, and gestational diabetes. Relationships varied by the timing of measurement and cutoff category (stronger associations with lower cutoffs); limited data were available on anemia etiology. There were insufficient data for other maternal outcomes and long-term child health outcomes. Current data are insufficient for determining if revisions to current Hb cutoffs are required. Pooled high-quality individual-level data analyses, as well as prospective cohort studies, would be valuable to inform the reevaluation of Hb cutoffs.
Topics: Child Health; Female; Hemoglobins; Humans; Infant, Small for Gestational Age; Maternal Health; Obstetric Labor Complications; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth
PubMed: 30994929
DOI: 10.1111/nyas.14093 -
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 -
The Cochrane Database of Systematic... Feb 2023Gestational diabetes with onset or first recognition during pregnancy is an increasing problem worldwide. Myo-inositol, an isomer of inositol, is a naturally occurring... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gestational diabetes with onset or first recognition during pregnancy is an increasing problem worldwide. Myo-inositol, an isomer of inositol, is a naturally occurring sugar commonly found in cereals, corn, legumes and meat. Myo-inositol is one of the intracellular mediators of the insulin signal and correlates with insulin sensitivity in type 2 diabetes. The potential beneficial effect of improving insulin sensitivity suggests that myo-inositol may be useful for women in preventing gestational diabetes. This is an update of a review first published in 2015.
OBJECTIVES
To assess if antenatal dietary supplementation with myo-inositol is safe and effective, for the mother and fetus, in preventing gestational diabetes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO ICTRP (17 March 2022) and the reference lists of retrieved studies.
SELECTION CRITERIA
We included published and unpublished randomised controlled trials (RCTs) including cluster-RCTs and conference abstracts, assessing the effects of myo-inositol for the prevention of gestational diabetes in pregnant women. We included studies that compared any dose of myo-inositol, alone or in a combination preparation, with no treatment, placebo or another intervention. Quasi-randomised and cross-over trials were not eligible. We excluded women with pre-existing type 1 or type 2 diabetes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, assessed risk of bias and extracted the data. We checked the data for accuracy. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included seven RCTs (one conducted in Ireland, six conducted in Italy) reporting on 1319 women who were 10 weeks to 24 weeks pregnant at the start of the studies. The studies had relatively small sample sizes and the overall risk of bias was low. For the primary maternal outcomes, meta-analysis showed that myo-inositol may reduce the incidence of gestational diabetes (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.31 to 0.90; 6 studies, 1140 women) and hypertensive disorders of pregnancy (RR 0.34, 95% CI 0.19 to 0.61; 5 studies, 1052 women). However, the certainty of the evidence was low to very low. For the primary neonatal outcomes, only one study measured the risk of a large-for-gestational-age infant and found myo-inositol was associated with both appreciable benefit and harm (RR 1.40, 95% CI 0.65 to 3.02; 1 study, 234 infants; low-certainty evidence). None of the included studies reported on the other primary neonatal outcomes (perinatal mortality, mortality or morbidity composite). For the secondary maternal outcomes, we are unclear about the effect of myo-inositol on weight gain during pregnancy (mean difference (MD) -0.25 kilogram (kg), 95% CI -1.26 to 0.75 kg; 4 studies, 831 women) and perineal trauma (RR 4.0, 95% CI 0.45 to 35.25; 1 study, 234 women) because the evidence was assessed as being very low-certainty. Further, myo-inositol may result in little to no difference in caesarean section (RR 0.91, 95% CI 0.77 to 1.07; 4 studies, 829 women; low-certainty evidence). None of the included studies reported on the other secondary maternal outcomes (postnatal depression and the development of subsequent type 2 diabetes mellitus). For the secondary neonatal outcomes, meta-analysis showed no neonatal hypoglycaemia (RR 3.07, 95% CI 0.90 to 10.52; 4 studies; 671 infants; very low-certainty evidence). However, myo-inositol may be associated with a reduction in the incidence of preterm birth (RR 0.35, 95% CI 0.17 to 0.70; 4 studies; 829 infants). There were insufficient data for a number of maternal and neonatal secondary outcomes, and no data were reported for any of the long-term childhood or adulthood outcomes, or for health service utilisation outcomes.
AUTHORS' CONCLUSIONS
Evidence from seven studies shows that antenatal dietary supplementation with myo-inositol during pregnancy may reduce the incidence of gestational diabetes, hypertensive disorders of pregnancy and preterm birth. Limited data suggest that supplementation with myo-inositol may not reduce the risk of a large-for-gestational-age infant. The current evidence is based on small studies that were not powered to detect differences in outcomes such as perinatal mortality and serious infant morbidity. Six of the included studies were conducted in Italy and one in Ireland, which raises concerns about the lack of generalisability to other settings. There is evidence of inconsistency among doses of myo-inositol, the timing of administration and study population. As a result, we downgraded the certainty of the evidence for many outcomes to low or very low certainty. Further studies for this promising antenatal intervention for preventing gestational diabetes are encouraged and should include pregnant women of different ethnicities and varying risk factors. Myo-inositol at different doses, frequency and timing of administration, should be compared with placebo, diet and exercise, and pharmacological interventions. Long-term follow-up should be considered and outcomes should include potential harms, including adverse effects.
Topics: Adult; Female; Humans; Pregnancy; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dietary Supplements; Hypertension, Pregnancy-Induced; Inositol; Insulin Resistance; Perinatal Death; Premature Birth
PubMed: 36790138
DOI: 10.1002/14651858.CD011507.pub3 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2020Maternal vitamin D deficiency has been associated with an increased risk for preeclampsia. Despite this, the current evidence regarding the efficacy of vitamin D... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal vitamin D deficiency has been associated with an increased risk for preeclampsia. Despite this, the current evidence regarding the efficacy of vitamin D supplementation in preventing preeclampsia is controversial. To assess the impact of vitamin D supplementation on the risk of preeclampsia, we performed a systematic review of the literature and a meta-analysis of the available randomized clinical trials (RCTs).
METHODS
The primary outcome was preeclampsia. Subgroup analyses were carried out considering the timing of the supplementation, type of intervention and the study design. Meta-regression analysis, including the amount of vitamin D and maternal age, were planned to explore heterogeneity (PROSPERO database registration number: CRD42019119207).
RESULTS
Data were pooled from 27 RCTs comprising 59 arms, which included overall 4777 participants, of whom 2487 were in the vitamin D-treated arm and 2290 in the control arm. Vitamin D administration in pregnancy was associated with a reduced risk of preeclampsia (odd ratio [OR] 0.37, 95% confidence interval [CI]: 0.26, 0.52; I = 0%). If the vitamin D supplementation was started up to 20 weeks' gestation, the odds was a little lower (OR 0.35, 95% CI: 0.24, 0.50, p < 0.001). The effect was largely independent of the supplementation cessation (until delivery or not), type of intervention (vitamin D alone or in association with calcium), and study design. Increasing dose of vitamin D was associated with reduced incidence of preeclampsia (slope of log OR: -1.1, 95% CI: -1.73, -0.46; p < 0.001).
CONCLUSIONS
Results suggest that vitamin D supplementation may be useful in preventing preeclampsia. These data are especially useful for health-care providers who engage in the management of pregnant women at risk for preeclampsia. Our findings are a call for action to definitively address vitamin D supplementation as a possible intervention strategy in preventing preeclampsia in pregnancy.
Topics: Adolescent; Adult; Avitaminosis; Dietary Supplements; Female; Humans; Incidence; Middle Aged; Pre-Eclampsia; Pregnancy; Protective Factors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Vitamin D; Young Adult
PubMed: 31526611
DOI: 10.1016/j.clnu.2019.08.015 -
Frontiers in Endocrinology 2021Gestational Diabetes Mellitus (GDM) is defined as the type of hyperglycemia diagnosed for the first-time during pregnancy, presenting with intermediate glucose levels... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gestational Diabetes Mellitus (GDM) is defined as the type of hyperglycemia diagnosed for the first-time during pregnancy, presenting with intermediate glucose levels between normal levels for pregnancy and glucose levels diagnostic of diabetes in the non-pregnant state. We aimed to systematically review and meta-analyze studies of prevalence of GDM in European countries at regional and sub-regional levels, according to age, trimester, body weight, and GDM diagnostic criteria.
METHODS
Systematic search was conducted in five databases to retrieve studies from 2014 to 2019 reporting the prevalence of GDM in Europe. Two authors have independently screened titles and abstracts and full text according to eligibility using Covidence software. A random-effects model was used to quantify weighted GDM prevalence estimates. The National Heart, Lung, and Blood Institute criteria was used to assess the risk of bias.
RESULTS
From the searched databases, 133 research reports were deemed eligible and included in the meta-analysis. The research reports yielded 254 GDM-prevalence studies that tested 15,572,847 pregnant women between 2014 and 2019. The 133 research reports were from 24 countries in Northern Europe (44.4%), Southern Europe (27.1%), Western Europe (24.1%), and Eastern Europe (4.5%). The overall weighted GDM prevalence in the 24 European countries was estimated at 10.9% (95% CI: 10.0-11.8, : 100%). The weighted GDM prevalence was highest in the Eastern Europe (31.5%, 95% CI: 19.8-44.6, : 98.9%), followed by in Southern Europe (12.3%, 95% CI: 10.9-13.9, : 99.6%), Western Europe (10.7%, 95% CI: 9.5-12.0, : 99.9%), and Northern Europe (8.9%, 95% CI: 7.9-10.0, : 100). GDM prevalence was 2.14-fold increased in pregnant women with maternal age ≥30 years ( 15-29 years old), 1.47-fold if the diagnosis was made in the third trimester ( second trimester), and 6.79- fold in obese and 2.29-fold in overweight women ( normal weight).
CONCLUSIONS
In Europe, GDM is significant in pregnant women, around 11%, with the highest prevalence in pregnant women of Eastern European countries (31.5%). Findings have implications to guide vigilant public health awareness campaigns about the risk factors associated with developing GDM.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42020161857.
Topics: Adolescent; Adult; Cross-Sectional Studies; Diabetes, Gestational; Europe; Female; Humans; Pregnancy; Prevalence; Risk Factors; Young Adult
PubMed: 34956073
DOI: 10.3389/fendo.2021.691033 -
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 -
BMC Pregnancy and Childbirth Apr 2023Growing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Growing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on specific Hb thresholds to define anemia and high Hb as well as how cutoffs may vary by anemia etiology and timing of assessment.
METHODS
We conducted an updated systematic review (using PubMed and Cochrane Review) on low (< 110 g/L) and high (≥ 130 g/L) maternal Hb concentrations and associations with a range of maternal and infant health outcomes. We examined associations by timing of Hb assessment (preconception; first, second, and third trimesters, as well as at any time point in pregnancy), varying cutoffs used for defining low and high hemoglobin concentrations and performed stratified analyses by iron-deficiency anemia. We conducted meta-analyses to obtain odds ratios (OR) and 95% confidence intervals.
RESULTS
The updated systematic review included 148 studies. Low maternal Hb at any time point in pregnancy was associated with: low birthweight, LBW (OR (95% CI) 1.28 (1.22-1.35)), very low birthweight, VLBW (2.15 (1.47-3.13)), preterm birth, PTB (1.35 (1.29-1.42)), small-for-gestational age, SGA (1.11 (1.02-1.19)), stillbirth 1.43 (1.24-1.65)), perinatal mortality (1.75 (1.28-2.39)), neonatal mortality (1.25 (1.16-1.34), postpartum hemorrhage (1.69 (1.45-1.97)), transfusion (3.68 (2.58-5.26)), pre-eclampsia (1.57 (1.23-2.01)), and prenatal depression (1.44 (1.24-1.68)). For maternal mortality, the OR was higher for Hb < 90 (4.83 (2.17-10.74)) than for Hb < 100 (2.87 (1.08-7.67)). High maternal Hb was associated with: VLBW (1.35 (1.16-1.57)), PTB (1.12 (1.00-1.25)), SGA (1.17 (1.09-1.25)), stillbirth (1.32 (1.09-1.60)), maternal mortality (2.01 (1.12-3.61)), gestational diabetes (1.71 (1.19-2.46)), and pre-eclampsia (1.34 (1.16-1.56)). Stronger associations were noted earlier in pregnancy for low Hb and adverse birth outcomes while the role of timing of high Hb was inconsistent. Lower Hb cutoffs were associated with greater odds of poor outcomes; for high Hb, data were too limited to identify patterns. Information on anemia etiology was limited; relationships did not vary by iron-deficiency anemia.
CONCLUSION
Both low and high maternal Hb concentrations during pregnancy are strong predictors of adverse maternal and infant health outcomes. Additional research is needed to establish healthy reference ranges and design effective interventions to optimize maternal Hb during pregnancy.
Topics: Pregnancy; Female; Child; Infant, Newborn; Humans; Pregnancy Outcome; Stillbirth; Premature Birth; Anemia, Iron-Deficiency; Pre-Eclampsia; Infant Health; Anemia; Hemoglobins
PubMed: 37076797
DOI: 10.1186/s12884-023-05489-6 -
American Journal of Obstetrics and... Sep 2022Hyperemesis gravidarum is characterized by severe nausea and vomiting in pregnancy, frequently resulting in severe maternal nutritional deficiency. Maternal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Hyperemesis gravidarum is characterized by severe nausea and vomiting in pregnancy, frequently resulting in severe maternal nutritional deficiency. Maternal undernutrition is associated with adverse offspring health outcomes. Whether hyperemesis gravidarum permanently affects offspring health remains unclear. This review aimed to evaluate the effects of maternal hyperemesis gravidarum on offspring health.
DATA SOURCES
MEDLINE and Embase were searched from inception to September 6, 2021.
STUDY ELIGIBILITY CRITERIA
Studies reporting on health at any age beyond the perinatal period of children born to mothers with hyperemesis gravidarum were included.
METHODS
Two reviewers independently selected studies and extracted data. The Newcastle-Ottawa Quality Assessment Scale was used to assess risk of bias. We conducted a narrative synthesis and meta-analysis where possible. In meta-analyses with high heterogeneity (I>75%), we did not provide a pooled odds ratio.
RESULTS
Nineteen studies were included in this systematic review (n=1,814,785 offspring). Meta-analysis (n=619, 2 studies: 1 among adolescents and 1 among adults) showed that hyperemesis gravidarum was associated with anxiety disorder (odds ratio, 1.74; 95% confidence interval, 1.04-2.91; I, 0%) and sleep problems in offspring (odds ratio, 2.94; 95% confidence interval, 1.25-6.93; I, 0%). Hyperemesis gravidarum was associated with testicular cancer in male offspring aged up to 40 years on meta-analysis (5 studies, n=20,930 offspring), although heterogeneity was observed on the basis of a wide 95% prediction interval (odds ratio, 1.60; 95% confidence interval, 1.07-2.39; I, 0%; 95% prediction interval, 0.83-3.08). All 6 studies reporting on attention deficit (hyperactivity) disorder and autism spectrum disorder reported an increase among children of mothers with hyperemesis gravidarum in comparison with children of unaffected mothers. Meta-analysis showed high heterogeneity, precluding us from reporting a pooled odds ratio. Most studies reporting on cognitive and motor problems found an increase among hyperemesis gravidarum-exposed children. One study investigated brain structure and found smaller cortical volumes and areas among children from hyperemesis gravidarum-affected pregnancies than among those from unaffected pregnancies. Studies evaluating anthropometry and cardiometabolic disease risk of hyperemesis gravidarum-exposed children had inconsistent findings.
CONCLUSION
Our systematic review showed that maternal hyperemesis gravidarum is associated with small increases in adverse health outcomes among children, including neurodevelopmental disorders, mental health disorders, and possibly testicular cancer, although evidence is based on few studies of low quality.
Topics: Adolescent; Adult; Aged; Autism Spectrum Disorder; Child; Female; Humans; Hyperemesis Gravidarum; Male; Neoplasms, Germ Cell and Embryonal; Outcome Assessment, Health Care; Pregnancy; Testicular Neoplasms
PubMed: 35367190
DOI: 10.1016/j.ajog.2022.03.052 -
Human Reproduction Update Sep 2020Although spontaneous miscarriage is the most common complication of human pregnancy, potential contributing factors are not fully understood. Advanced maternal age has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although spontaneous miscarriage is the most common complication of human pregnancy, potential contributing factors are not fully understood. Advanced maternal age has long been recognised as a major risk factor for miscarriage, being strongly related with fetal chromosomal abnormalities. The relation between paternal age and the risk of miscarriage is less evident, yet it is biologically plausible that an increasing number of genetic and epigenetic sperm abnormalities in older males may contribute to miscarriage. Previous meta-analyses showed associations between advanced paternal age and a broad spectrum of perinatal and paediatric outcomes. This is the first systematic review and meta-analysis on paternal age and spontaneous miscarriage.
OBJECTIVE AND RATIONALE
The aim of this systematic review and meta-analysis is to evaluate the effect of paternal age on the risk of spontaneous miscarriage.
SEARCH METHODS
PubMed, Embase and Cochrane databases were searched to identify relevant studies up to August 2019. The following free text and MeSH terms were used: paternal age, father's age, male age, husband's age, spontaneous abortion, spontaneous miscarriage, abortion, miscarriage, pregnancy loss, fetal loss and fetal death. PRISMA guidelines for systematic reviews and meta-analysis were followed. Original research articles in English language addressing the relation between paternal age and spontaneous miscarriage were included. Exclusion criteria were studies that solely focused on pregnancy outcomes following artificial reproductive technology (ART) and studies that did not adjust their effect estimates for at least maternal age. Risk of bias was qualitatively described for three domains: bias due to confounding, information bias and selection bias.
OUTCOMES
The search resulted in 975 original articles. Ten studies met the inclusion criteria and were included in the qualitative synthesis. Nine of these studies were included in the quantitative synthesis (meta-analysis). Advanced paternal age was found to be associated with an increased risk of miscarriage. Pooled risk estimates for miscarriage for age categories 30-34, 35-39, 40-44 and ≥45 years of age were 1.04 (95% CI 0.90, 1.21), 1.15 (0.92, 1.43), 1.23 (1.06, 1.43) and 1.43 (1.13, 1.81) respectively (reference category 25-29 years). A second meta-analysis was performed for the subgroup of studies investigating first trimester miscarriage. This showed similar pooled risk estimates for the first three age categories and a slightly higher pooled risk estimate for age category ≥45 years (1.74; 95% CI 1.26, 2.41).
WIDER IMPLICATIONS
Over the last decades, childbearing at later ages has become more common. It is known that frequencies of adverse reproductive outcomes, including spontaneous miscarriage, are higher in women with advanced age. We show that advanced paternal age is also associated with an increased risk of spontaneous miscarriage. Although the paternal age effect is less pronounced than that observed with advanced maternal age and residual confounding by maternal age cannot be excluded, it may have implications for preconception counselling of couples comprising an older aged male.
Topics: Abortion, Spontaneous; Adult; Aged; Fathers; Female; Humans; Male; Maternal Age; Middle Aged; Paternal Age; Pregnancy; Pregnancy Outcome; Prenatal Care; Risk Factors; Young Adult
PubMed: 32358607
DOI: 10.1093/humupd/dmaa010