The trajectory of head circumference and neurodevelopment in very preterm newborns during the first two years of life: a cohort study

Abstract Objective To evaluate the growth trajectory of head circumference and neurodevelopment, and to correlate head circumference with cognitive, language, and motor outcomes during the first two years. Method Prospective cohort study in a tertiary hospital including 95 newborns under 32 weeks or 1500 g. Neonates who developed major neonatal morbidities were excluded. The head circumference was measured at birth, at discharge, and at term-equivalent age, 1, 3, 5, 12, 18, and 24 months of corrected age, and the Bayley Scales (Bayley-III) were applied at 12, 18 and 24 months of corrected age to assess cognitive, language and, motor domains. Scores below 85 were classified as mild/moderate deficits and scores below 70 as severe deficits. The association between head circumference Z score and Bayley scores was assessed using Pearson's correlation. The study considered a significance level of 0.05. Results There was a decrease of -0.18 in the head circumference Z score between birth and discharge and the catch-up occurred between discharge and 1 month (an increase of 0.81 in the Z score). There was a positive correlation between head circumference and Bayley scores at 18 months. There was also a positive correlation between head circumference at discharge and at 5 months with the three domains of the Bayley. Conclusion Serial measurements of head circumference provide knowledge of the trajectory of growth, with early catch-up between discharge and 1 month, as well as its association with neurodevelopment. Head circumference is therefore a valuable clinical marker for neurodevelopment, especially in very preterm newborns.

A Longitudinal Study of Head Circumference Trajectories in Autism and Autistic Traits.

Increased head circumference is an established finding in autism spectrum disorder (ASD); however, it is unclear when this increase occurs, if it persists and whether it manifests across the whole ASD spectrum. Head circumference is a strong predictor of brain size and can therefore provide key insights into brain development in ASD. We used data from the Avon Longitudinal Study of Parents and Children to compare head circumference trajectories from birth to 15 years in children with an ASD diagnosis (N = 78, controls = 6,404) or elevated autistic traits as measured using the Social Communication Disorder Checklist (N = 639, controls = 6,230). Exploratory analyses were conducted in those with ASD and co-morbid cognitive learning needs (CLN). Children with an ASD diagnosis had larger head circumference from birth across childhood and adolescence compared to controls in univariable (B = 0.69, 95% confidence interval [CI]: 0.28-1.09, p = 0.001) and multivariable models (B = 0.38, 95% CI: 0.003-0.75, p = 0.048). Differences were more marked in those with co-morbid CLN. Children with elevated autistic traits had significantly smaller head circumference compared to controls. There was weak evidence of group differences when height was included as a covariate. Head circumference trajectories in ASD deviate from control children and persist until adolescence. Autistic traits were associated with smaller head circumference, suggesting distinct growth trajectories between clinical cases from those with non-clinical traits.

Childhood growth of singletons conceived following intracytoplasmic sperm injection - irrelevance of gonadotropin stimulation.

Background: In conventional, gonadotropin stimulated, in vitro fertilization or intracytoplasmic sperm injection (c-IVF/ICSI) growth and development of multiple follicles is induced by gonadotropins, combined with gonadotropin-releasing hormone agonist or antagonist. In recent studies, singletons conceived after c-IVF/ICSI cycles had lower birth weight not only than spontaneously conceived children but also children born after unstimulated natural IVF/ICSI cycles (NC-IVF/ICSI). Lower birth weight is associated with a catch-up growth within the first years of life. Following the Barker hypothesis accelerated growth has been associated with a higher risk of cardiovascular diseases later in life. The aim of the study is to assess, if children conceived with NC-IVF/ICSI have a higher birthweight and therefore do not show a catch-up growth within the first two years. Therefore, we assume that children born after NC-IVF/ICSI have a better long-term cardiometabolic risk profile. Whether the weight- and height gain is comparable to spontaneously conceived children is unknown, since to our knowledge we are the first study to investigate the longitudinal growth of children born after unstimulated natural cycle ICSI (NC-ICSI). Material and methods: We conducted a single-center, prospective cohort study (2010-2017) including children (n = 139) born after NC-ICSI or c-ICSI treatment. Growth parameters up to 24 months were collected. Standard deviation scores based on growth references were calculated. Results: The study included 98 children in the NC-ICSI and 41 children in the c-ICSI group. The median birth weight in NC-ICSI children was 3.4 kg [0.1 standard deviation score (SDS)] compared to 3.3 kg (-0.3 SDS) in c-ICSI children (p = 0.61). Median length at birth was 50 cm in both groups (NC-ICSI (-0.5 SDS), c-ICSI children (-0.8 SDS), p = 0.48). At age 24 months, median weight in NC-ICSI children was 12.2 kg (0.3 SDS) versus 12.2 kg (0.2 SDS) in c-ICSI children (p = 0.82) and median length 87.5 cm (0.1 SDS) versus 88.0 cm (0.4 SDS) (p = 0.43). Conclusion: We found no difference in growth between children conceived after stimulated and unstimulated ICSI. Growth parameters of both treatment groups did not differ from Swiss national growth references (N = 8500). One of the main limitations of our study was the small sample size (N = 139) of complete data sets over time and the high drop-out rate of 49% (68/139). Nevertheless, with the increasing number of children born after IVF/ICSI every year it is of immense importance to search for possibilities to reduce their long-term cardiometabolic risk and we want our data to contribute to this discussion.

Prenatal alcohol exposure and associations with physical size, dysmorphology and neurodevelopment: a systematic review and meta-analysis.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a significant public health concern, yet there is no internationally agreed set of diagnostic criteria or summary of underlying evidence to inform diagnostic decision-making. This systematic review assesses associations of prenatal alcohol exposure (PAE) and outcomes of diagnostic assessments, providing an evidence base for the improvement of FASD diagnostic criteria. METHODS: Six databases were searched (inception-February 2023). Case-controls or cohort studies examining associations between participants with/without PAE or a FASD diagnosis and the domains of physical size, dysmorphology, functional neurodevelopment and/or brain structure/neurology were included. Excluded studies were non-empirical, sample size < 10, PAE determined via biological markers only, or no suitable comparison group. Summary data were extracted and associations between outcomes and standardised levels of PAE or FASD diagnosis determined using random-effects meta-analyses. Certainty of the evidence was assessed using GRADE. RESULTS: Of the 306 included studies, 106 reported physical size, 43 dysmorphology, 195 functional neurodevelopment and 110 structural/neurological outcomes, with 292 different outcomes examined. There was a dose-response relationship between PAE and head circumference, as well as measures of physical size, particularly at birth. There was also an association between higher PAE levels and characteristic sentinel facial dysmorphology, as well as many of the current functional neurodevelopmental outcomes considered during diagnosis. However, data were often lacking across the full range of exposures. There was a lack of evidence from studies examining PAE to support inclusion of non-sentinel dysmorphic features, social cognition, speech-sound impairments, neurological conditions, seizures, sensory processing or structural brain abnormalities (via clinical MRI) in diagnostic criteria. GRADE ratings ranged from very low to moderate certainty of evidence. CONCLUSIONS: This comprehensive review provides guidance on which components are most useful to consider in the diagnostic criteria for FASD. It also highlights numerous gaps in the available evidence. Future well-designed pregnancy cohort studies should specifically focus on dose-response relationships between PAE and dysmorphology, neurodevelopment and brain structure/neurological outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42021230522.

Predicting newborn birth outcomes with prenatal maternal health features and correlates in the United States: a machine learning approach using archival data.

BACKGROUND: Newborns are shaped by prenatal maternal experiences. These include a pregnant person's physical health, prior pregnancy experiences, emotion regulation, and socially determined health markers. We used a series of machine learning models to predict markers of fetal growth and development-specifically, newborn birthweight and head circumference (HC). METHODS: We used a pre-registered archival data analytic approach. These data consisted of maternal and newborn characteristics of 594 maternal-infant dyads in the western U.S. Participants also completed a measure of emotion dysregulation. In total, there were 22 predictors of newborn HC and birthweight. We used regularized regression for predictor selection and linear prediction, followed by nonlinear models if linear models were overfit. RESULTS: HC was predicted best with a linear model (ridge regression). Newborn sex (male), number of living children, and maternal BMI predicted a larger HC, whereas maternal preeclampsia, number of prior preterm births, and race/ethnicity (Latina) predicted a smaller HC. Birthweight was predicted best with a nonlinear model (support vector machine). Occupational prestige (a marker similar to socioeconomic status) predicted higher birthweight, maternal race/ethnicity (non-White and non-Latina) predicted lower birthweight, and the number of living children, prior preterm births, and difficulty with emotional clarity had nonlinear effects. CONCLUSIONS: HC and birthweight were predicted by a variety of variables associated with prenatal stressful experiences, spanning medical, psychological, and social markers of health and stress. These findings may highlight the importance of viewing prenatal maternal health across multiple dimensions. Findings also suggest that assessing difficulties with emotional clarity during standard obstetric care (in the U.S.) may help identify risk for adverse newborn outcomes.

Assessing the Evidence for Nonobstetric Risk Factors for Deformational Plagiocephaly: Systematic Review and Meta-Analysis.

BACKGROUND: Plagiocephaly is defined as an asymmetrical distortion of the skull, resulting in an oblique trapezoid or parallelogram head shape. Deformational plagiocephaly (DP) is caused by forces acting on one side of the back of the head, distorting normal skull symmetry. OBJECTIVE: The aims of this systematic review and meta-analysis were to critically assess the evidence for nonobstetric risk factors for DP and to make evidence-based recommendations for reducing the prevalence of DP. METHODS: The selection criterion was studies reporting risk factors for DP. Case reviews, case series, expert opinions, and systematic reviews were excluded. PubMed and Web of Science were searched from August 21, 2010, to August 21, 2022. Publication bias was assessed using funnel plots. Meta-analyses were presented using forest plots. RESULTS: A total of 19 studies (cohort studies: n=13, 68%; case-control studies: n=5, 26%; and cross-sectional studies: n=1, 5%) with a total of 14,808 participants were included. Of the 43 investigated potential nonobstetric factors, 16 (37%) were associated with DP. Of these 16 factors, 12 (75%) had odds ratios (ORs) with 95% CIs not crossing 1: insufficient vitamin D intake (OR 7.15, 95% CI 3.77-13.54), head position preference (OR 4.75, 95% CI 3.36-6.73), bottle-only feeding (OR 4.65, 95% CI 2.70-8.00), reduced tummy time (OR 3.51, 95% CI 1.71-7.21), sleeping position (OR 3.12, 95% CI 2.21-4.39), fewer motor milestones reached by the age of 6 months (OR 2.56, 95% CI 1.66-3.96), obesity (OR 2.45, 95% CI 1.02-5.90), maternal education level (OR 1.66, 95% CI 1.17-2.37), male sex (OR 1.51, 95% CI 1.07-2.12), formula feeding (OR 1.51, 95% CI 1.00-2.27), head circumference (OR 1.22, 95% CI 1.06-1.40), and mechanical ventilation (OR 1.10, 95% CI 1.00-1.14). No evidence of publication bias was detected. CONCLUSIONS: This study provides a comprehensive assessment of the nonobstetric factors associated with DP and presents 11 evidence-based recommendations for reducing its prevalence. The primary limitation is that only publication bias was assessed. TRIAL REGISTRATION: PROSPERO CRD42020204979; https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42020204979.

Inpatient Growth in Infants Requiring Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome.

Aim: To assess inpatient growth parameter trajectories and to identify the type of opioid exposure and treatment characteristics influencing growth parameters of infants admitted to the newborn intensive care unit (NICU) for pharmacological treatment of neonatal opioid withdrawal syndrome (NOWS). Methods: Charts of term infants with NOWS admitted to NICU from 2012 to 2019, who received pharmacologic treatment, were reviewed. Intake (volume: mL/kg/day; calorie: kcal/kg/day) and growth parameter trajectories (weight, head circumference, and length) were analyzed based on the type of prenatal opioid exposure (short-acting opioids (SAOs), long-acting opioids (LAOs), and polysubstance), pharmacologic treatment, and sex. Growth measurement patterns over time were compared between groups using longitudinal mixed-effects models. Results: One hundred nineteen infants were included in the study with median birth weight Z-score of -0.19 at birth and decreased to a median of -0.72 at discharge. Exposure to SAO was associated with an increase in Z-scores nearing discharge across all growth parameters (Z-score for weight p = 0.03). Polysubstance exposure was associated with a decrease in Z-scores for length and head circumference throughout hospitalization. Infants with adjunct clonidine treatment had an increase in Z-score for weight trends. Male infants had a decrease in Z-scores for weight (male -0.96, female -0.59, interaction p = 0.06) and length (male -1.17, female -0.57, interaction p = 0.003) at Day 28. Despite the difference in growth trajectories, intake in terms of amount (mL/kg/day) and calorie intake (kcal/kg/day) was similar based on prenatal exposure, treatment, and sex. Conclusion: Infants with NOWS requiring pharmacologic treatment have a decrease in Z-scores for weight, length, and head circumference at birth and at hospital discharge. Infants with prenatal polysubstance exposure were at particular risk for poorer inpatient growth relative to infants exposed to SAO and LAO, indicated by lower Z-scores for length and occipital frontal circumference (OFC).

Observed-to-expected lung-area-to-head-circumference ratio on ultrasound examination vs total fetal lung volume on magnetic resonance imaging in prediction of survival in fetuses with left-sided diaphragmatic hernia.

OBJECTIVE: To assess and compare the value of antenatally determined observed-to-expected (O/E) lung-area-to-head-circumference ratio (LHR) on ultrasound examination vs O/E total fetal lung volume (TFLV) on magnetic resonance imaging (MRI) examination to predict postnatal survival of fetuses with isolated, expectantly managed left-sided congenital diaphragmatic hernia (CDH). METHODS: This was a multicenter retrospective study including all consecutive fetuses with isolated CDH that were managed expectantly in Mannheim, Germany, and in five other European centers, that underwent at least one ultrasound examination for measurement of O/E-LHR and one MRI scan for measurement of O/E-TFLV during pregnancy. All MRI data were centralized, and lung volumes were measured by two experienced operators blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect on survival at hospital discharge of various perinatal variables, including the center of management. In left-sided CDH with intrathoracic herniation of the liver, receiver-operating-characteristics (ROC) curves were constructed separately for cases from Mannheim and the other five European centers and were used to compare O/E-TFLV and O/E-LHR in the prediction of postnatal survival. RESULTS: From Mannheim, 309 patients were included with a median gestational age (GA) at ultrasound examination of 29.6 (range, 19.7-39.1) weeks and median GA at MRI examination of 31.1 (range, 18.0-39.9) weeks. From the other five European centers, 116 patients were included with a median GA at ultrasound examination of 26.7 (range, 20.6-37.6) weeks and median GA at MRI examination of 27.7 (range, 21.3-37.9) weeks. Regression analysis demonstrated that the survival rates at discharge were lower in left-sided CDH (odds ratio (OR), 0.349 (95% CI, 0.133-0.918), P = 0.033) and those with intrathoracic liver (OR, 0.297 (95% CI, 0.141-0.628), P = 0.001), and higher with increasing O/E-TFLV (OR, 1.123 (95% CI, 1.079-1.170), P < 0.001), advanced GA at birth (OR, 1.294 (95% CI, 1.055-1.588), P = 0.013) and when birth occurred in Mannheim (OR, 7.560 (95% CI, 3.368-16.967), P < 0.001). Given the difference in survival rate between Mannheim and the five other European centers, ROC curve comparisons between the two imaging modalities were presented separately. For cases of left-sided CDH with intrathoracic herniation of the liver, pairwise comparison showed no significant difference between the area under the ROC curves for the prediction of postnatal survival between O/E-TFLV and O/E-LHR in Mannheim (mean difference = 0.025, P = 0.610, standard error = 0.050), whereas there was a significant difference in the other European centers studied (mean difference = 0.056, P = 0.033, standard error = 0.056). CONCLUSIONS: In fetuses with left-sided CDH and intrathoracic herniation of the liver, the predictive value for postnatal survival of O/E-TFLV on MRI examination and O/E-LHR on ultrasound examination was similar in one center (Mannheim), but O/E-TFLV had better predictive value compared to O/E-LHR in the five other European centers. Hence, in these five European centers, MRI should be included in the diagnostic process for left-sided CDH. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Head circumference growth in children with Autism Spectrum Disorder: trend and clinical correlates in the first five years of life.

Background: Macrocephaly is described in almost 15% of children with Autism Spectrum Disorder (ASD). Relationships between head growth trajectories and clinical findings in ASD children show a high degree of variability, highlighting the complex heterogeneity of the disorder. Objectives: The aim of this study was to measure differences of the early growth trajectory of head circumference (HC) in children with ASD and macrocephaly compared to ASD normocephalic children, examining clinical correlates in the two groups of patients. Methods: HC data were collected from birth to 5 years of age in a sample of children with a confirmed diagnosis of ASD. Participants were classified into two groups: ASD macrocephaly (ASD-M, Z-scores ≥1.88 in at least two consecutive HC measurements), and ASD non-macrocephaly (ASD-N). Based on the distribution of HC measurements (Z-scores), five age groups were identified for the longitudinal study. Developmental and behavioral characteristics of the ASD-M children compared to the ASD-N group were compared by using standardized scores. Results: 20,8% of the children sample met criteria for macrocephaly. HC values became indicative of macrocephaly in the ASD-M group at the age range from 1 to 6 months, and persisted thereafter throughout the first five years of age. ASD-M children showed significantly higher developmental quotients of Griffiths III B and D subscales compared to ASD-N group. No significant differences in the severity of ASD symptoms assessed by ADOS-2 were observed between ASD-M and ASD-N groups. Conclusion: In this study HC size from birth to 5 years links to accelerated HC growth rate as early as the first 6 months of age in children with ASD and macrocephaly, preceding the onset and diagnosis of ASD. We found that in early childhood, children with ASD-M may exhibit some advantages in language and social communication and emotional skills without differences in autism severity, when compared with age-matched normocephalic ASD children. Longitudinal analyses are required to catch-up prospectively possible relationships between head size as proxy measure of brain development and neuro-developmental and behavioral features in children with ASD.

Quantitative Approach to Quality Review of Prenatal Ultrasound Examinations: Fetal Biometry.

Background/Objectives: To evaluate the quality of an ultrasound practice, both large-scale and focused audits are recommended by professional organizations, but such audits can be time-consuming, inefficient, and expensive. Our objective was to develop a time-efficient, quantitative, objective, large-scale method to evaluate fetal biometry measurements for an entire practice, combined with a process for focused image review for personnel whose measurements are outliers. Methods: Ultrasound exam data for a full year are exported from commercial ultrasound reporting software to a statistical package. Fetal biometry measurements are converted to z-scores to standardize across gestational ages. For a large-scale audit, sonographer mean z-scores are compared using analysis of variance (ANOVA) with Scheffe multiple comparisons test. A focused image review is performed on a random sample of exams for sonographers whose mean z-scores differ significantly from the practice mean. A similar large-scale audit is performed, comparing physician mean z-scores. Results: Using fetal abdominal circumference measurements as an example, significant differences between sonographer mean z-scores are readily identified by the ANOVA and Scheffe test. A method is described for the blinded image audit of sonographers with outlier mean z-scores. Examples are also given for the identification and interpretation of several types of systematic errors that are unlikely to be detectable by image review, including z-scores with large or small standard deviations and physicians with outlier mean z-scores. Conclusions: The large-scale quantitative analysis provides an overview of the biometry measurements of all the sonographers and physicians in a practice, so that image audits can be focused on those whose measurements are outliers. The analysis takes little time to perform after initial development and avoids the time, complexity, and expense of auditing providers whose measurements fall within the expected range. We encourage commercial software developers to include tools in their ultrasound reporting software to facilitate such quantitative reviews.

Evaluating the Concept of Brain Sparing in a High Income Setting, Using Historical Records of Maternal Influenza or Syphilis Infection.

INTRODUCTION: In the context of adverse in utero environments, the fetal brain might be preserved at the expense of other tissues. This trade-off, brain sparing, has not been studied in the context of maternal infection. We investigated cases of maternal syphilis in the early 20th century and influenza during the 1918-1920 pandemic, in the Swiss city of Lausanne, a relatively high-income setting. We tested the brain sparing hypothesis, that head circumference is protected at the expense of birth weight. METHODS: A total of 8530 individual birth records from 1911 to 1922 from the University Maternity Hospital of Lausanne were used. We fitted generalized linear and additive linear models to explain how neonatal size varies under disease exposure. RESULTS: Influenza reduced head circumference and birth weight among livebirths similarly, by -0.11 and -0.14 standard deviation (SD) units respectively. Conversely, for syphilis-exposed infants, head circumference was affected more than birth weight (-0.61 SD vs. -0.46 SD). Stillborn infants exposed to syphilis experienced a much greater reduction in head circumference (-1.92 SD) than liveborn infants. After adjustment for gestational age, these findings persisted in the case of influenza, but the effects of syphilis were reduced. Furthermore, half of syphilis-exposed infants were born before term, suggesting that lower infant size was partly mediated by shorter gestation. Nevertheless, head circumference among stillbirths exposed to syphilis was still substantially reduced, even after adjustment for gestational age (-1.26 SD). CONCLUSION: Our findings do not support the brain sparing hypothesis. Moreover, the substantial reduction in head circumference among syphilis-exposed fetuses might help explain why a quarter of them were stillborn.

Segmentation and Estimation of Fetal Biometric Parameters using an Attention Gate Double U-Net with Guided Decoder Architecture.

The fetus's health is evaluated with the biometric parameters obtained from the low-resolution ultrasound images. The accuracy of biometric parameters in existing protocols typically depends on conventional image processing approaches and hence, is prone to error. This study introduces the Attention Gate Double U-Net with Guided Decoder (ADU-GD) model specifically crafted for fetal biometric parameter prediction. The attention network and guided decoder are specifically designed to dynamically merge local features with their global dependencies, enhancing the precision of parameter estimation. The ADU-GD displays superior performance with Mean Absolute Error of 0.99 mm and segmentation accuracy of 99.1 % when benchmarked against the well-established models. The proposed model consistently achieved a high Dice index score of about 99.1 ± 0.8, with a minimal Hausdorff distance of about 1.01 ± 1.07 and a low Average Symmetric Surface Distance of about 0.25 ± 0.21, demonstrating the model's excellence. In a comprehensive evaluation, ADU-GD emerged as a frontrunner, outperforming existing deep-learning models such as Double U-Net, DeepLabv3, FCN-32s, PSPNet, SegNet, Trans U-Net, Swin U-Net, Mask-R2CNN, and RDHCformer models in terms of Mean Absolute Error for crucial fetal dimensions, including Head Circumference, Abdomen Circumference, Femur Length, and BiParietal Diameter. It achieved superior accuracy with MAE values of 2.2 mm, 2.6 mm, 0.6 mm, and 1.2 mm, respectively.

Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring.

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period. GDM leaves fingerprints on the infant's gut microbiome, which are confounded by delivery mode. Further, Clostridium species positively correlate with a larger head circumference at month 12 in male offspring but not females. The gut microbiome of GDM mothers with male fetuses displays depleted gut-brain modules, including acetate synthesis I and degradation and glutamate synthesis II. The gut microbiome of female infants of GDM mothers has higher histamine degradation and dopamine degradation. Together, our integrative analysis indicates that GDM affects maternal and infant gut composition, which is associated with sexually dimorphic infant head growth.

Interaction of maternal smoking and gestational diabetes mellitus on newborn head circumference and birthweight.

INTRODUCTION: Maternal smoking during pregnancy and gestational diabetes mellitus (GDM) have opposite effects on fetal growth during pregnancy. The aim of the study was to evaluate the interaction of smoking during pregnancy and gestational diabetes mellitus on head circumference and birthweight of newborns. MATERIAL AND METHODS: The study included all primiparous women with singleton pregnancies (n = 290 602) without previously diagnosed diabetes or hypertension in Finland between 2006 and 2018. The information on gestational diabetes mellitus, newborn birthweight and head circumference, and maternal smoking and backgrounds was derived from the Finnish Medical Birth Register. Linear regression models were used in the analyses. RESULTS: In total 8.0% of parturients quit smoking during the first trimester and 9.9% continued smoking thereafter. The prevalence of GDM was 8.9% (n = 25 948). Newborns of women who continued smoking had a smaller head circumference (b = -0.24, SE = 0.01, p < 0.0001) and birthweight (b = -0.28, SE = 0.01, p < 0.0001) compared to newborns of women who did not smoke. Head circumference and birthweight were greater in newborns of women with GDM (b = 0.09, SE = 0.01, p < 0.0001 and b = 0.16, SE = 0.01, p < 0.0001, respectively) compared to newborns of women without GDM. In the interaction analyses, head circumference (b = -0.13, SE = 0.01, p < 0.0001) was smaller and birthweight (b = -0.13, SE = 0.02, p < 0.0001) was lower in newborns of women with GDM who continued smoking compared to newborns of women without GDM who did not smoke. CONCLUSIONS: Although smoking and GDM have opposite effects on fetal growth, the negative effects of exposure to smoking are also seen in newborns of women with GDM. Compared to smoking after the first trimester of pregnancy, cessation of smoking during the first trimester was associated with greater head circumference and birthweight in newborns.

Determination of the Accuracy of Transcerebellar Diameter in Estimating Gestational Age in the Second and Third Trimesters of Pregnancy.

Background Every antenatal woman and her treating doctor aim for a healthy newborn. In obstetrics, accurately determining the gestational age (GA) is a critical aspect of managing pregnancy and evaluating fetal growth and development. The transcerebellar diameter (TCD) is the greatest transverse measurement of the fetal cerebellum. The growth of the cerebellum is minimally affected by fluctuations in growth, making the TCD the most reliable measurement for predicting GA. The purpose of the present research is to determine the accuracy of TCD in estimating GA in the second and third trimesters of pregnancy. Materials and methods The study included 500 antenatal women at 18-40 weeks of gestation. We also measured TCD in addition to routine ultrasound parameters like biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). We used IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States) for statistical analysis. The collected data was subjected to statistical tests, including Pearson's correlation coefficient and coefficient of determination. We conducted a regression analysis and used correlation coefficients to compare each ultrasound-measured parameter with the GA. Results The current research demonstrates a significant linear relationship between the TCD and GA (r = 0.9865; p = 0.0001), a strong association between BPD and GA (r = 0.9541; p = 0.0001), between HC and GA (r = 0.9613; p = 0.0001), between AC and GA (r = 0.9489; p = 0.0001), and between FL and GA (r = 0.9697; p = 0.0001). TCD showed the best correlation with GA among all the biometric parameters. TCD showed a correct assessment of GA by the last menstrual period (LMP) in 479 (95.8%) antenatal women. Conclusion The current research concludes that the TCD can be utilized as an independent measure to determine GA in the second and third trimesters of pregnancy, particularly in cases where the LMP is unknown, no dating scan has been performed in the first trimester, initial assessment taking place in the third trimester and in fetuses with variations in head shape such as dolichocephaly and brachycephaly.

Maternal thyroid function and offspring birth anthropometrics in women with polycystic ovary syndrome.

Objectives: Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within the normal range may influence fetal growth. Our aim was to investigate whether maternal thyroid function is associated with newborn anthropometrics in PCOS and explore the potential modifying effect of metformin. Methods: Post-hoc analyses of two RCTs in which pregnant women with PCOS were randomized to metformin or placebo, from first trimester to delivery. Maternal serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at gestational weeks (gw) 5-12, 19, 32 and 36 in 309 singleton pregnancies. The mean z-scores of birthweight, birth length, and head circumference were estimated in the offspring. Associations of maternal thyroid parameters with offspring anthropometrics and the outcomes large for gestational age (LGA) and small for gestational age (SGA) were studied using linear and logistic regression models, with adjustment for body mass index (BMI) when relevant. Results: Maternal fT4 at baseline was negatively associated with birth length (b= -0.09, p=0.048). Furthermore, ΔfT4 during pregnancy correlated positively to z-score of both birth weight and length (b=0.10, p=0.017 and b=0.10, p=0.047 respectively), independently of treatment group. TSH at baseline and gw19 was inversely associated with LGA (OR 0.47, p=0.012 and OR 0.58, p=0.042), while ΔTSH was positively associated with LGA (OR 1.99, p=0.023). There were inverse associations between TSH at baseline and SGA (OR 0.32, p=0.005) and between ΔfT4 and SGA (OR 0.59, p=0.005) in the metformin group only. There were no associations between maternal thyroid function and head circumference of the newborns. Conclusion: In women with PCOS, a higher maternal fT4 in early pregnancy and a greater decrease in fT4 during pregnancy was associated with a lower offspring birthweight and shorter birth length. Higher TSH by mid-gestation and smaller increase in TSH during pregnancy was associated with less risk of LGA. Subclinical variations in maternal thyroid function might play a role for birth anthropometrics of PCOS offspring.

Neonatal Physical Growth Predicts Electroencephalography Power in Rural South African Children.

Anthropometric measures at birth, indexing prenatal growth, are associated with later cognitive development. Children in low- and middle-income countries (LMIC) are at elevated risk for impaired prenatal and early postnatal growth and enduring cognitive deficits. However, the associations of neonatal physical growth with neural activity are not well-characterized in LMIC contexts, given the dearth of early childhood neuroimaging research in these settings. The current study examined birth length, weight, and head circumference as predictors of EEG relative power over the first three years of life in rural Limpopo Province, South Africa, controlling for postnatal growth and socioeconomic status (SES). A larger head circumference at birth predicted lower relative gamma power, lower right hemisphere relative beta power, and higher relative alpha and theta power. A greater birth length also predicted lower relative gamma power. There were interactions with timepoints such that the associations of birth head circumference and length with EEG power were most pronounced at the 7-month assessment and were attenuated at the 17- and 36-month assessments. The results identify birth head circumference and length as specific predictors of infant neural activity within an under-resourced context.

The Association of Infant Birth Sizes and Anemia under Five Years Old: A Population-Based Prospective Cohort Study in China.

Infant birth sizes are vital clinical parameters to predict poor growth and micronutrient deficiency in early life. However, their effects on childhood anemia remain unclear. We aimed to explore the associations between birth weight, crown-heel length, and head circumference with anemia in early childhood, as well as potential modification factors. This population-based prospective cohort study included 204,556 participants with singleton live births delivered at gestational ages of 28-42 weeks. A logistic regression model was used to estimate the associations of the measures of infant birth size and their Z-score with anemia under five years old. There were 26,802 (13.10%) children under five years old who were diagnosed has having anemia. Compared with children who did not have anemia, children who had anemia had a lower birth weight and smaller head circumference and a longer crown-heel length (all p-values < 0.05). After adjusting for confounders, not only birth weight (ß coefficient, -0.008; 95% CI, -0.011--0.004; p < 0.001) and head circumference (ß coefficient, -0.004; 95% CI, -0.007--0.001; p = 0.009), but also the related Z-scores were negatively associated with childhood anemia, while the trends for crown-heel length were the opposite. We further found significant interactions of folic acid use and maternal occupation with infant birth sizes. In conclusion, infants having abnormal sizes at birth are significantly associated with the risk for childhood anemia, which can be modified by folic acid use during pregnancy and maternal occupation.

Maternal rest improves growth in small-for-gestational-age fetuses (<10th percentile).

BACKGROUND: Optimal management of fetuses diagnosed as small for gestational age based on an estimated fetal weight of <10th percentile represents a major clinical problem. The standard approach is to increase fetal surveillance with serial biometry and antepartum testing to assess fetal well-being and timing of delivery. Observational studies have indicated that maternal rest in the left lateral position improves maternal cardiac output and uterine blood flow. However, maternal bed rest has not been recommended based on the results of a randomized clinical trial that showed that maternal rest does not improve fetal growth in small-for-gestational-age fetuses. This study was conducted to revisit this question. OBJECTIVE: This study aimed to determine whether maternal bed rest was associated with an increase in the fetal biometric parameters that reflect growth after the diagnosis of a small-for-gestational-age fetus. STUDY DESIGN: A retrospective study was conducted on fetuses who were diagnosed as small for gestational age because of an estimated fetal weight of <10th percentile for gestational age. The mothers were asked to rest in the left lateral recumbent position. Fetal biometry was performed 2 weeks after the diagnosis. All fetuses before entry into the study had a previous ultrasound that demonstrated an estimated fetal weight of >10th percentile. To assess the response to bed rest, the change in fetal biometric parameters (estimated fetal weight, head circumference, abdominal circumference, and femur length) after the recommendation of bed rest was computed for 2 periods: (1) before the diagnosis of a weight of <10th percentile vs at the time of diagnosis of a weight of <10th percentile and (2) at the time of diagnosis of a weight of <10th percentile vs 2 weeks after maternal bed rest. For repeated measures, proportions were compared using the McNemar test, and percentile values were compared using the Bonferroni Multiple Comparison Test. A P value of <.05 was considered significant. To describe changes in the estimated fetal weight without bed rest, 2 control groups in which the mothers were not placed on bed rest after the diagnosis of a small-for-gestational-age fetus were included. RESULTS: A total of 265 fetuses were observed before and after maternal bed rest. The following were observed in this study: (1) after 2 weeks of maternal rest, 199 of 265 fetuses (75%) had a fetal weight of >10th percentile; (2) the median fetal weight percentile increased from 6.8 (interquartile range, 4.4-8.4) to 18.0 (interquartile range, 9.5-29.5) after 2 weeks of bed rest; (3) similar trends were noted for the head circumference, abdominal circumference, and femur length. In the groups of patients who were not asked to be on bed rest, a reassignment to a weight of >10th percentile at a follow-up examination only occurred in 7 of 37 patients (19%) in the Texas-Michigan group and 13 of 111 patients (12%) in the Colorado group compared with the bed rest group (199/265 [75%]) (P<.001). CONCLUSION: Patients who were prescribed 2 weeks of bed rest after the diagnosis of a fetal weight of <10th percentile had an increase in weight of >10th percentile in 199 of 265 fetuses (75%). This increase in fetal weight was significantly higher than that in the 2 control groups in which bed rest was not prescribed. This observation suggests that bed rest improves fetal growth in a subset of patients.

Duration of labor in consecutive deliveries: a retrospective data analysis.

PURPOSE: Labor is shorter in multiparous women. However, there are no individualized data on differences in duration of labor for consecutive deliveries in the same parturient. METHODS: We conducted a retrospective data analysis from 2004 to 2021 at the University Hospital of Zurich and included all women with 2 or more vaginal deliveries of a singleton child in cephalic position, between 22 and 42 weeks of gestation. Descriptive statistics were performed with SPSS version 25.0 (IBM, SPSS Inc., USA). The primary endpoint was the ratio between durations of labor stages in consecutive deliveries of the same parturient. RESULTS: A total of 3344 women with 7066 births (2601 first [P0], 2987 s [P1], 1176 third [P2], and 302 fourth [P3]) were included. The ratio of duration of the active first stage of labor between P1 and P0 was 0.49 (95% CI 0.47-0.51, p < 0.001) meaning that the active first stage of labor was 51% shorter. The second stage of labor with a ratio of 0.26 (95% CI 0.24-0.27, p < 0.001) was 74% shorter in P1 compared to P0. Higher birthweight of the first child led to an even greater decrease in duration of the second stage of labor in P1 compared to P0 (p = 0.003). Neuraxial anesthesia was an independent risk factor for a longer duration of labor, irrespective of parity (p < 0.001). Birthweight and HC of the neonates did not significantly differ between the children born by the same women. However, higher birthweight in of the first child significantly augmented the rate of second stage of labor between P0 and P1 (p = 0.003). DISCUSSION: Up to the third delivery, duration of labor decreased with each consecutive delivery of the same parturient. An individualized assessment of the expected duration of labor in multiparous women should be encouraged.