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BMJ (Clinical Research Ed.) May 2022To investigate the association between gestational diabetes mellitus and adverse outcomes of pregnancy after adjustment for at least minimal confounding factors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the association between gestational diabetes mellitus and adverse outcomes of pregnancy after adjustment for at least minimal confounding factors.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Web of Science, PubMed, Medline, and Cochrane Database of Systematic Reviews, from 1 January 1990 to 1 November 2021.
REVIEW METHODS
Cohort studies and control arms of trials reporting complications of pregnancy in women with gestational diabetes mellitus were eligible for inclusion. Based on the use of insulin, studies were divided into three subgroups: no insulin use (patients never used insulin during the course of the disease), insulin use (different proportions of patients were treated with insulin), and insulin use not reported. Subgroup analyses were performed based on the status of the country (developed or developing), quality of the study, diagnostic criteria, and screening method. Meta-regression models were applied based on the proportion of patients who had received insulin.
RESULTS
156 studies with 7 506 061 pregnancies were included, and 50 (32.1%) showed a low or medium risk of bias. In studies with no insulin use, when adjusted for confounders, women with gestational diabetes mellitus had increased odds of caesarean section (odds ratio 1.16, 95% confidence interval 1.03 to 1.32), preterm delivery (1.51, 1.26 to 1.80), low one minute Apgar score (1.43, 1.01 to 2.03), macrosomia (1.70, 1.23 to 2.36), and infant born large for gestational age (1.57, 1.25 to 1.97). In studies with insulin use, when adjusted for confounders, the odds of having an infant large for gestational age (odds ratio 1.61, 1.09 to 2.37), or with respiratory distress syndrome (1.57, 1.19 to 2.08) or neonatal jaundice (1.28, 1.02 to 1.62), or requiring admission to the neonatal intensive care unit (2.29, 1.59 to 3.31), were higher in women with gestational diabetes mellitus than in those without diabetes. No clear evidence was found for differences in the odds of instrumental delivery, shoulder dystocia, postpartum haemorrhage, stillbirth, neonatal death, low five minute Apgar score, low birth weight, and small for gestational age between women with and without gestational diabetes mellitus after adjusting for confounders. Country status, adjustment for body mass index, and screening methods significantly contributed to heterogeneity between studies for several adverse outcomes of pregnancy.
CONCLUSIONS
When adjusted for confounders, gestational diabetes mellitus was significantly associated with pregnancy complications. The findings contribute to a more comprehensive understanding of the adverse outcomes of pregnancy related to gestational diabetes mellitus. Future primary studies should routinely consider adjusting for a more complete set of prognostic factors.
REVIEW REGISTRATION
PROSPERO CRD42021265837.
Topics: Cesarean Section; Diabetes, Gestational; Female; Fetal Macrosomia; Humans; Infant, Newborn; Insulin; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 35613728
DOI: 10.1136/bmj-2021-067946 -
Annals of Nutrition & Metabolism 2015Fetal macrosomia, defined as a birth weight ≥ 4,000 g, may affect 12% of newborns of normal women and 15-45% of newborns of women with gestational diabetes mellitus... (Review)
Review
BACKGROUND
Fetal macrosomia, defined as a birth weight ≥ 4,000 g, may affect 12% of newborns of normal women and 15-45% of newborns of women with gestational diabetes mellitus (GDM). The increased risk of macrosomia in GDM is mainly due to the increased insulin resistance of the mother. In GDM, a higher amount of blood glucose passes through the placenta into the fetal circulation. As a result, extra glucose in the fetus is stored as body fat causing macrosomia, which is also called 'large for gestational age'. This paper reviews studies that explored the impact of GDM and fetal macrosomia as well as macrosomia-related complications on birth outcomes and offers an evaluation of maternal and fetal health.
SUMMARY
Fetal macrosomia is a common adverse infant outcome of GDM if unrecognized and untreated in time. For the infant, macrosomia increases the risk of shoulder dystocia, clavicle fractures and brachial plexus injury and increases the rate of admissions to the neonatal intensive care unit. For the mother, the risks associated with macrosomia are cesarean delivery, postpartum hemorrhage and vaginal lacerations. Infants of women with GDM are at an increased risk of becoming overweight or obese at a young age (during adolescence) and are more likely to develop type II diabetes later in life. Besides, the findings of several studies that epigenetic alterations of different genes of the fetus of a GDM mother in utero could result in the transgenerational transmission of GDM and type II diabetes are of concern.
Topics: Adipose Tissue; Blood Glucose; Cesarean Section; Diabetes, Gestational; Dystocia; Epigenesis, Genetic; Female; Fetal Macrosomia; Humans; Infant, Newborn; Insulin; Insulin Resistance; Insulin Secretion; Maternal-Fetal Exchange; Metabolic Syndrome; Obesity; Overweight; Pancreas; Pregnancy; Prenatal Exposure Delayed Effects; Shoulder
PubMed: 26045324
DOI: 10.1159/000371628 -
American Journal of Obstetrics and... Dec 2017Prenatal care providers are advised to evaluate maternal weight at each regularly scheduled prenatal visit, monitor progress toward meeting weight gain goals, and... (Review)
Review
Prenatal care providers are advised to evaluate maternal weight at each regularly scheduled prenatal visit, monitor progress toward meeting weight gain goals, and provide individualized counseling if significant deviations from a woman's goals occur. Today, nearly 50% of women exceed their weight gain goals with overweight and obese women having the highest prevalence of excessive weight gain. Risks of inadequate weight gain include low birthweight and failure to initiate breast-feeding whereas the risks of excessive weight gain include cesarean deliveries and postpartum weight retention for the mother and large-for-gestational-age infants, macrosomia, and childhood overweight or obesity for the offspring. Prenatal care providers have many resources and tools to incorporate weight and other health behavior counseling into routine prenatal practices. Because many women are motivated to improve health behaviors, pregnancy is often considered the optimal time to intervene for issues related to eating habits and physical activity to prevent excessive weight gain. Gestational weight gain is a potentially modifiable risk factor for a number of adverse maternal and neonatal outcomes and meta-analyses of randomized controlled trials report that diet or exercise interventions during pregnancy can help reduce excessive weight gain. However, health behavior interventions for gestational weight gain have not significantly improved other maternal and neonatal outcomes and have limited effectiveness in overweight and obese women.
Topics: Breast Feeding; Cesarean Section; Counseling; Diet; Exercise; Female; Fetal Macrosomia; Health Behavior; Humans; Infant, Low Birth Weight; Motivational Interviewing; Obesity; Overweight; Pediatric Obesity; Pregnancy; Pregnancy Complications; Prenatal Care; Risk Factors; Weight Gain
PubMed: 28549978
DOI: 10.1016/j.ajog.2017.05.040 -
Ultrasound in Obstetrics & Gynecology :... Sep 2019To determine accurate estimates of risks of maternal and neonatal complications in pregnancies with fetal macrosomia by performing a systematic review of the literature... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine accurate estimates of risks of maternal and neonatal complications in pregnancies with fetal macrosomia by performing a systematic review of the literature and meta-analysis.
METHODS
A search of MEDLINE, EMBASE, CINAHL and The Cochrane Library was performed to identify relevant studies reporting on maternal and/or neonatal complications in pregnancies with macrosomia having a birth weight (BW) > 4000 g and/or those with birth weight > 4500 g. Prospective and retrospective cohort and population-based studies that provided data regarding both cases and controls were included. Maternal outcomes assessed were emergency Cesarean section (CS), postpartum hemorrhage (PPH) and obstetric anal sphincter injury (OASIS). Neonatal outcomes assessed were shoulder dystocia, obstetric brachial plexus injury (OBPI) and birth fractures. Meta-analysis using a random-effects model was used to estimate weighted pooled estimates of summary statistics (odds ratio (OR) and 95% CI) for each complication, according to birth weight. Heterogeneity between studies was estimated using Cochran's Q, I statistic and funnel plots.
RESULTS
Seventeen studies reporting data on maternal and/or neonatal complications in pregnancy with macrosomia were included. In pregnancies with macrosomia having a BW > 4000 g, there was an increased risk of the maternal complications: emergency CS, PPH and OASIS, which had OR (95% CI) of 1.98 (1.80-2.18), 2.05 (1.90-2.22) and 1.91 (1.56-2.33), respectively. The corresponding values for pregnancies with BW > 4500 g were: 2.55 (2.33-2.78), 3.15 (2.14-4.63) and 2.56 (1.97-3.32). Similarly, in pregnancies with a BW > 4000 g, there was an increased risk of the neonatal complications: shoulder dystocia, OBPI and birth fractures, which had OR (95% CI) of 9.54 (6.76-13.46), 11.03 (7.06-17.23) and 6.43 (3.67-11.28), respectively. The corresponding values for pregnancies with a BW > 4500 g were: 15.64 (11.31-21.64), 19.87 (12.19-32.40) and 8.16 (2.75-24.23).
CONCLUSION
Macrosomia is associated with serious maternal and neonatal adverse outcomes. This study provides accurate estimates of these risks, which can be used for decisions on pregnancy management. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Cesarean Section; Dystocia; Female; Fetal Macrosomia; Humans; Infant, Newborn; Infant, Newborn, Diseases; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications; Retrospective Studies
PubMed: 30938004
DOI: 10.1002/uog.20279 -
Obstetrics and Gynecology Clinics of... Jun 2021Abnormal fetal growth (growth restriction and overgrowth) is associated with perinatal morbidity, mortality, and lifelong risks to health. To describe abnormal growth,... (Review)
Review
Abnormal fetal growth (growth restriction and overgrowth) is associated with perinatal morbidity, mortality, and lifelong risks to health. To describe abnormal growth, "small for gestational age" and "large for gestational age" are commonly used terms. However, both are statistical definitions of fetal size below or above a certain threshold related to a reference population, rather than referring to an abnormal condition. Fetuses can be constitutionally small or large and thus healthy, whereas fetuses with seemingly normal size can be growth restricted or overgrown. Although golden standards to detect abnormal growth are lacking, understanding of both pathologic conditions has improved significantly.
Topics: Female; Fetal Development; Fetal Growth Retardation; Fetal Macrosomia; Fetus; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Placenta; Placental Insufficiency; Pregnancy; Ultrasonography, Doppler; Ultrasonography, Prenatal; Umbilical Arteries
PubMed: 33972065
DOI: 10.1016/j.ogc.2021.02.002 -
Nutrients Jul 2020Leptin is highly expressed in the placenta, mainly by trophoblastic cells, where it has an important autocrine trophic effect. Moreover, increased leptin levels are... (Review)
Review
Leptin is highly expressed in the placenta, mainly by trophoblastic cells, where it has an important autocrine trophic effect. Moreover, increased leptin levels are found in the most frequent pathology of pregnancy: gestational diabetes, where leptin may mediate the increased size of the placenta and the fetus, which becomes macrosomic. In fact, leptin mediates the increased protein synthesis, as observed in trophoblasts from gestational diabetic subjects. In addition, leptin seems to facilitate nutrients transport to the fetus in gestational diabetes by increasing the expression of the glycerol transporter aquaporin-9. The high plasma leptin levels found in gestational diabetes may be potentiated by leptin resistance at a central level, and obesity-associated inflammation plays a role in this leptin resistance. Therefore, the importance of anti-inflammatory nutrients to modify the pathology of pregnancy is clear. In fact, nutritional intervention is the first-line approach for the treatment of gestational diabetes mellitus. However, more nutritional intervention studies with nutraceuticals, such as polyphenols or polyunsaturated fatty acids, or nutritional supplementation with micronutrients or probiotics in pregnant women, are needed in order to achieve a high level of evidence. In this context, the Mediterranean diet has been recently found to reduce the risk of gestational diabetes in a multicenter randomized trial. This review will focus on the impact of maternal obesity on placental inflammation and nutrients transport, considering the mechanisms by which leptin may influence maternal and fetal health in this setting, as well as its role in pregnancy pathologies.
Topics: Anti-Inflammatory Agents; Diabetes, Gestational; Diet, Mediterranean; Female; Fetal Macrosomia; Humans; Leptin; Nutrition Therapy; Nutritional Status; Obesity; Placenta; Pregnancy; Pregnancy Complications; Trophoblasts
PubMed: 32630697
DOI: 10.3390/nu12071970 -
BMJ (Clinical Research Ed.) Sep 2016To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified.
DESIGN
Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials.
DATA SOURCES
Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome.
APPRAISAL AND DATA EXTRACTION
Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools.
RESULTS
25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of fasting and two hour post-load glucose concentrations (after a 75 g OGTT) were 2.15 (95% confidence interval 1.60 to 2.91) and 1.20 (1.13 to 1.28), respectively. Heterogeneity was low between studies in all analyses.
CONCLUSIONS
This review and meta-analysis identified a large number of studies in various countries. There was a graded linear association between fasting and post-load glucose concentration across the whole glucose distribution and most adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. Research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for diagnosis of gestational diabetes on perinatal and longer term outcomes.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42013004608.
Topics: Birth Weight; Diabetes, Gestational; Dystocia; Evidence-Based Medicine; Female; Fetal Macrosomia; Glucose Tolerance Test; Humans; Hyperglycemia; Infant, Newborn; Pregnancy; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 27624087
DOI: 10.1136/bmj.i4694 -
American Journal of Obstetrics and... Feb 2018
Topics: Delivery, Obstetric; Disease Management; Female; Fetal Development; Fetal Growth Retardation; Fetal Macrosomia; Humans; Laser-Doppler Flowmetry; Placenta; Pregnancy; Time Factors; Ultrasonography, Prenatal
PubMed: 29422202
DOI: 10.1016/j.ajog.2018.01.010 -
The New England Journal of Medicine Jun 2005We conducted a randomized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
We conducted a randomized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications.
METHODS
We randomly assigned women between 24 and 34 weeks' gestation who had gestational diabetes to receive dietary advice, blood glucose monitoring, and insulin therapy as needed (the intervention group) or routine care. Primary outcomes included serious perinatal complications (defined as death, shoulder dystocia, bone fracture, and nerve palsy), admission to the neonatal nursery, jaundice requiring phototherapy, induction of labor, cesarean birth, and maternal anxiety, depression, and health status.
RESULTS
The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group (1 percent vs. 4 percent; relative risk adjusted for maternal age, race or ethnic group, and parity, 0.33; 95 percent confidence interval, 0.14 to 0.75; P=0.01). However, more infants of women in the intervention group were admitted to the neonatal nursery (71 percent vs. 61 percent; adjusted relative risk, 1.13; 95 percent confidence interval, 1.03 to 1.23; P=0.01). Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group (39 percent vs. 29 percent; adjusted relative risk, 1.36; 95 percent confidence interval, 1.15 to 1.62; P<0.001), although the rates of cesarean delivery were similar (31 percent and 32 percent, respectively; adjusted relative risk, 0.97; 95 percent confidence interval, 0.81 to 1.16; P=0.73). At three months post partum, data on the women's mood and quality of life, available for 573 women, revealed lower rates of depression and higher scores, consistent with improved health status, in the intervention group.
CONCLUSIONS
Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman's health-related quality of life.
Topics: Adult; Birth Weight; Blood Glucose; Cesarean Section; Depression, Postpartum; Diabetes, Gestational; Dystocia; Female; Fetal Macrosomia; Fractures, Bone; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Infant Mortality; Infant, Newborn; Insulin; Labor, Induced; Paralysis; Pregnancy; Pregnancy Outcome
PubMed: 15951574
DOI: 10.1056/NEJMoa042973 -
The Pan African Medical Journal 2017The delivery of a macrosomic infant is a relatively common situation. It can put mother and fetus at high risk. The main maternal complications are the increase in...
The delivery of a macrosomic infant is a relatively common situation. It can put mother and fetus at high risk. The main maternal complications are the increase in cesarean rates, postpartum hemorrhage and cervicovaginal traumatic lacerations. The main fetal complication is shoulder dystocia increasing the risk of brachial plexus. The objective was to identify risk factors and maternal-fetal complications associated with fetal macrosomia. Comparative retrospective study conducted at Kairouan University Hospital maternity unit in 2010. We compared a group of 820 cases of macrosomic infants to a control group of 800 cases of infants born in the same period of time. During the study period we collected clinical data of 820 macrosomic cases on a total of 7.495 deliveries, corresponding to a total incidence of 10.94%. Several factors predisposing to fetal macrosomia were highlighted: Maternal age> 35 years was present in 28.5% of cases; Maternal obesity was found in 45% of cases; A personal history of macrosomia was noted in 28,8% of cases; Prolonged pregnancies > 41 weeks of amenorrhoea was noted in 35.6% of cases; Multiparity was found in 47% of cases. Maternal complications were essentially postpartum hemorrhage: 71 cases and genital traumas: 24 cases. Perinatal complications were dominated by shoulder dystocia: 27 cases (3.3%). Traumatic postpartum complications were found in 11.6%.
Topics: Adult; Female; Fetal Macrosomia; Hospitals, University; Humans; Male; Maternal Age; Obesity; Pregnancy; Pregnancy Complications; Prognosis; Puerperal Disorders; Retrospective Studies; Risk Factors; Tunisia
PubMed: 29515744
DOI: 10.11604/pamj.2017.28.126.8508