OBJECTIVE: The objective of this meta-analysis was to evaluate obstetric outcomes in gestational diabetes mellitus (GDM) patients treated with flexible management based on intrauterine ultrasound fetal growth (FMIUFG) or strict maternal glycemic adjustment (SMGA).
METHODS: We performed a comprehensive systematic review of electronic databases for randomized clinical trials (RCTs) comparing obstetrics outcomes of singleton GDM patients managed according to FMIUFG or SMGA. The review protocol was registered in PROSPERO (CRD497888). Searches were conducted in PubMed, Embase, Cochrane, and LILACS. Primary outcomes were gestational age at delivery and birth weight. Random-effect model meta-analyses were used to minimize the effects of uncertainty associated with inter-study variability. Results are reported as standardized mean differences (SMDs) or as odds ratios (ORs) and their 95% confidence interval (CI). Heterogeneity between studies was estimated using the I2 statistic. The Cochrane Risk of Bias Scale was used to assess the quality of studies. There were five RCTs with low to moderate risk of bias, including 450 patients managed according to the FMIUFSG and 381 according to the SMGA.
RESULTS: The macrosomia (birthweight >4000 g) rate was lower in pregnancies managed according to FMIUFG than SMGA adjustments (OR: 0.34; 95%CI: 0.16, 0.71). There were no significant differences in hypertensive disorder, cesarean section, neonatal intensive care unit admission, and large newborn for gestational age rates.
CONCLUSIONS: The macrosomia rate was lower in women managed with the FMIUFG. There were no significant differences in other obstetric and neonate outcomes.

BACKGROUND: Long-term (visit-to-visit) blood pressure variability (BPV) and heart rate variability (HRV) outside pregnancy are associated with adverse cardiovascular outcomes. Given the limitations of relying solely on blood pressure level to identify pregnancies at risk, long-term (visit-to-visit) BPV or HRV may provide additional diagnostic/prognostic counsel. To address this, we conducted a systematic review to examine the association between long-term BPV and HRV in pregnancy and adverse maternal and perinatal outcomes.
RESULTS: Databases were searched from inception to May 2023 for studies including pregnant women, with sufficient blood pressure or heart rate measurements to calculate any chosen measure of BPV or HRV. Studies were excluded that reported short-term, not long-term, variability. Adjusted odds ratios were extracted. Eight studies (138 949 pregnancies) reporting BPV met our inclusion criteria; no study reported HRV and its association with pregnancy outcomes. BPV appeared to be higher in women with hypertension and preeclampsia specifically, compared with unselected pregnancy cohorts. Greater BPV was associated with significantly more adverse pregnancy outcomes, particularly maternal (gestational hypertension [odds ratio range, 1.40-2.15], severe hypertension [1.40-2.20]), and fetal growth (small-for-gestational-age infants [1.12-1.32] or low birth weight [1.18-1.39]). These associations were independent of mean blood pressure level. In women with hypertension, there were stronger associations with maternal outcomes but no consistent pattern for perinatal outcomes.
CONCLUSIONS: Future work should aim to confirm whether BPV could be useful for risk stratification prospectively in pregnancy, and should determine the optimal management path for those women identified at increased risk of adverse outcomes.

BACKGROUND: Multiple systematic reviews on prenatal ambient temperature and adverse birth outcomes exist, but the overall epidemiological evidence and the appropriate metric for thermal stress remain unclear. An umbrella review was performed to summarise and appraise the evidence with recommendations.
METHODS: Systematic reviews and meta-analyses on the associations between ambient temperature and adverse birth outcomes (preterm birth, stillbirth, birth weight, low birth weight, and small for gestational age) up to December 20, 2023, were synthesised according to a published protocol. Databases PubMed, CINAHL, Scopus, MEDLINE/Ovid, EMBASE/Ovid, Web of Science Core Collection, systematic reviews repositories, electronic grey literature, and references were searched. Risk of bias was assessed using Joanna Briggs Institute\'s critical appraisal tool.
RESULTS: Eleven systematic reviews, including two meta-analyses, were included. This comprised 90 distinct observational studies that employed multiple temperature assessment metrics with a very high overlap of primary studies. Primary studies were mostly from the United States while both Africa and South Asia contributed only three studies. A majority (7 out of 11) of the systematic reviews were rated as moderate risk of bias. All systematic reviews indicated that maternal exposures to both extremely high and low temperatures, particularly during late gestation are associated with increased risks of preterm birth, stillbirth, and reduced fetal growth. However, due to great differences in the exposure assessments, high heterogeneity, imprecision, and methodological limitations of the included systematic reviews, the overall epidemiological evidence was classified as probable evidence of causation. No study assessed biothermal metrics for thermal stress.
CONCLUSIONS: Despite the notable methodological differences, prenatal exposure to extreme ambient temperatures, particularly during late pregnancy, was associated with adverse birth outcomes. Adhering to the appropriate systematic review guidelines for environmental health research, incorporating biothermal metrics into exposure assessment, evidence from broader geodemographic settings, and interventions are recommended in future studies.

Δ9-tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, has been implicated in affecting fetal neurodevelopment by readily crossing the placenta. However, little is known regarding the long-term effects of intrauterine cannabis exposure. This systematic review and meta-analysis synthesized prospective and cross-sectional human studies to measure the effects of intrauterine cannabis exposure on birth, behavioral, psychological and cognitive outcomes in infancy until early childhood.
Reporting according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, cross-sectional and prospective studies published from database inception until June 2023, investigating developmental outcomes of infants, toddlers and young children with intrauterine cannabis exposure were considered. All articles were obtained from PubMed or PsycINFO databases.
The literature search resulted in 932 studies, in which 57 articles met eligibility criteria. The meta-analysis revealed that intrauterine cannabis exposure increases the risk of preterm delivery [odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.05-2.71, P = 0.03], low birth weight (OR = 2.60, CI = 1.71-3.94, P < 0.001) and requirement for neonatal intensive care unit (NICU) admission (OR = 2.51, CI = 1.46-4.31; P < 0.001). Our qualitative synthesis suggests that intrauterine cannabis exposure may be associated with poorer attention and externalizing problems in infancy and early childhood. We found no evidence for impairments in other cognitive domains or internalizing behaviors.
Prenatal cannabis use appears to be associated with lower birth weight, preterm birth and neonatal intensive care unit admission in newborns, but there is little evidence that prenatal cannabis exposure adversely impacts behavioral or cognitive outcomes in early childhood, with the exception of attention and externalizing problems.

Sleep disordered breathing is extremely common in pregnancy and is a risk factor for maternal complications. Animal models demonstrate that intermittent hypoxia causes abnormal fetal growth. However, there are conflicting data on the association between maternal sleep disordered breathing and offspring growth in humans. We investigated this association by conducting a systematic review and meta-analysis. Sixty-three manuscripts, and total study population of 67, 671, 110 pregnant women were included. Thirty-one studies used subjective methods to define sleep disordered breathing, 24 applied objective methods and eight used international codes. Using a random effects model, habitual snoring, defined by subjective methods, and obstructive sleep apnea, diagnosed by objective methods, were associated with an increased risk for large for gestational age (OR 1.46; 95%CI 1.02-2.09 and OR 2.19; 95%CI 1.63-2.95, respectively), while obstructive sleep apnea, identified by international codes, was associated with an increased risk for small for gestational age newborns (OR 1.28; 95%CI 1.02-1.60). Our results support that maternal sleep disordered breathing is associated with offspring growth, with differences related to the type of disorder and diagnostic methods used. Future studies should investigate underlying mechanisms and whether treatment of sleep disordered breathing ameliorates the neonatal growth.

Pregnancy is increasingly considered a period of vulnerability for extreme heat exposure. Multiple lines of evidence support that heat stress is associated with placental insufficiency, poor fetal growth and decreased birth weight. In this narrative review, we first summarize evidence linking ambient temperature or experimentally-induced heat stress with fetal and placental growth outcomes in humans, ruminants and murine species. We then synthesize the literature on putative underlying biological pathways with a focus on the placenta. Reviewed mechanisms include: reduced uterine-placental blood flow, impaired supply of metabolic substrates to the fetus, activation of the maternal stress-response system, and disruption of other endocrine and immune system endpoints. Taken together, this body of evidence supports that exposure to extreme ambient heat likely has adverse consequences for placental development and function. However, research investigating placenta-mediated pathophysiological mechanisms in humans remains extremely limited.

BACKGROUND: The autonomic nervous system (ANS) is known as a critical regulatory system for pregnancy-induced adaptations. If it fails to function, life-threatening pregnancy complications could occur. Hence, understanding and monitoring the underlying mechanism of action for these complications are necessary.
OBJECTIVE: We aimed to systematically review the literature concerned with the associations between heart rate variability (HRV), as an ANS biomarker, and pregnancy complications.
METHODS: We performed a comprehensive search in the PubMed, Medline Completion, CINAHL Completion, Web of Science Core Collection Classic, Cochrane Library, and SCOPUS databases in February 2022 with no time span limitation. We included studies concerned with the association between any pregnancy complications and HRV, with or without a control group. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was used for the review of the studies, and Covidence software was used for the study selection process. For data synthesis, we used the guideline by Popay et al.
RESULTS: Finally, 12 studies with 6656 participants were included. Despite the methodological divergency that hindered a comprehensive comparison, our findings suggest that ANS is linked with some common pregnancy complications including fetal growth. However, existing studies do not support an association between ANS and gestational diabetes mellitus. Studies that linked pulmonary and central nervous system disorders with ANS function did not provide enough evidence to draw conclusions.
CONCLUSIONS: This review highlights the importance of understanding and monitoring the underlying mechanism of ANS in pregnancy-induced adaptations and the need for further research with robust methodology in this area.

This study aimed to compare 2 aspirin dosage regimens for the prevention of preterm preeclampsia (PE): 75 to 81 mg vs 150 to 162 mg taken daily starting in the first trimester of pregnancy.
A systematic search was performed using PubMed, Embase, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials from January 1985 to April 2023.
The inclusion criteria were randomized controlled trials that compared the effect of 2 aspirin dosage regimens during pregnancy for the prevention of PE initiated in the first trimester of pregnancy. The intervention was an aspirin dosage between 150 and 162 mg daily, and the control was an aspirin dosage between 75 and 81 mg daily.
Of note, 2 reviewers independently screened all citations, selected studies, and evaluated the risk of bias. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and applied the Cochrane risk of bias tool. The corresponding authors of the included studies were contacted to validate each of the collected results. The primary outcome was the risk of preterm preeclampsia, and the secondary outcomes included term preeclampsia, any preeclampsia regardless of gestational age, and severe preeclampsia. Relative risks with their 95% confidence interval were calculated for each study and pooled for global analysis.
Of note, 4 randomized controlled trials were retrieved involving 552 participants. Moreover, 2 randomized controlled trials were at unclear risk of bias, 1 trial at low risk of bias and 1 trial at high risk of bias, which did not have the information for the primary outcome. The pooled analysis demonstrated that an aspirin dosage of 150 to 162 mg was associated with a significant reduction of preterm preeclampsia, compared with an aspirin dosage of 75 to 81 mg (3 studies; 472 participants; relative risk, 0.34; 95% confidence interval, 0.15-0.79; P=.01; I2=0%). There was no significant effect on the risk of term preeclampsia (3 studies; 472 participants; relative risk, 0.57; 95% confidence interval, 0.12-2.64; P=.48; I2=64%) and all preeclampsia (4 studies; 552 participants; relative risk, 0.42; 95% confidence interval, 0.17-1.05; P=.06; I2=58%), but there was a reduction of severe preeclampsia (3 studies; 472 participantst; RR, 0.23; 95% CI, 0.09-0.62; P=.003; I2=0%).
When initiated in the first trimester of pregnancy, an aspirin dosage of 150 to 162 mg daily was associated with a lower risk of preterm PE than an aspirin dosage of 75 to 81 mg daily. However, the lack of large, high-quality studies limited the clinical scope of the current results taken alone.

Adequate reference ranges of size of the corpus callosum (CC) are necessary to improve characterization of CC abnormalities and parental counseling. The objective of this study was to evaluate the methodology used in studies developing references charts for CC biometry.
We conducted a systematic review of studies on fetal CC biometry using a set of predefined quality criteria of study design, statistical analysis and reporting methods. We included observational studies whose primary aim was to create ultrasound or magnetic resonance imaging charts for CC size in a normal population of fetuses. Studies were scored against a predefined set of independently agreed methodological criteria, and an overall quality score was given for each study.
Twelve studies met the inclusion criteria. Quality scores ranged between 17.4% and 95.7%. The greatest potential for bias was noted for the following items: sample selection and sample-size calculation, as only 17% of the studies were population-based and had consecutive or random recruitment of patients and with a justification of the sample size; number of measurements obtained for CC biometry, as only 17% of the studies performed more than one measurement per fetus and per scan; and description of characteristics of the study population, as only 8% of the studies clearly reported a minimum dataset of demographic characteristics.
Our review demonstrates substantial heterogeneity in methods and final biometric values of the fetal CC across the evaluated studies. The use of uniform methodology of the highest quality is essential in order to define a \'short\' CC and provide appropriate parental counseling. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ensuring nutritional adequacy during pregnancy is one of the necessary factors to achieve favorable pregnancy outcomes. In order to clarify the current optimal diet for achieving favorable pregnancy outcomes among East Asian women, we conducted a systemic literature review. English and Japanese articles were searched using PubMed and Igaku Chuo Zasshi. A total of 167 papers were retrieved, and six papers were finally selected for review. Five studies were conducted prospectively, and one was a case-control study. No significant associations were observed between dietary intakes and infant birthweight, but low intakes of fat and vitamin E were associated with preterm birth risk. Maternal diet with various food groups including vegetables was associated with higher birthweight and lower risk of preterm birth. A balanced diet with a combination of diverse food groups may be effective in achieving favorable pregnancy outcomes.