Growth reference charts for children with hypochondroplasia.

Hypochondroplasia (HCH) is a rare skeletal dysplasia causing mild short stature. There is a paucity of growth reference charts for this population. Anthropometric data were collected to generate height, weight, and head circumference (HC) growth reference charts for children with a diagnosis of HCH. Mixed longitudinal anthropometric data and genetic analysis results were collected from 14 European specialized skeletal dysplasia centers. Growth charts were generated using Generalized Additive Models for Location, Scale, and Shape. Measurements for height (983), weight (896), and HC (389) were collected from 188 (79 female) children with a diagnosis of HCH aged 0-18 years. Of the 84 children who underwent genetic testing, a pathogenic variant in FGFR3 was identified in 92% (77). The data were used to generate growth references for height, weight, and HC, plotted as charts with seven centiles from 2nd to 98th, for ages 0-4 and 0-16 years. HCH-specific growth charts are important in the clinical care of these children. They help to identify if other comorbidities are present that affect growth and development and serve as an important benchmark for any prospective interventional research studies and trials.

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.

Use of focus point for plane acquisition to improve reproducibility in fetal biometry.

OBJECTIVE: To assess the reproducibility of ultrasound measurements of fetal biometry using a 'focus point' to assist the acquisition of the relevant plane. METHODS: This was a study of 80 women with a singleton non-anomalous pregnancy who attended University College London Hospital, London, UK, between 18 and 37 weeks' gestation. Planes to measure head circumference (HC), abdominal circumference (AC) and femur length (FL) were obtained four times by two different sonographers with different levels of experience, who were blinded to one another; the first set of images was obtained with reference to a standard image, and the second set of images was obtained using the focus point technique. The focus point was defined as a unique fetal anatomical landmark in each plane (cavum septi pellucidi for HC, two-thirds of the umbilical vein for AC and one of the two extremities of the diaphysis for FL). Once identified, the focus point was maintained in view while the sonographer rotated the probe along three axes (x, y, z) to acquire the relevant plane. Sonographers were either in training or had > 3000 scans worth of experience. Intra- and interobserver reproducibility were assessed using Bland-Altman plots, and absolute values and percentages for mean difference and 95% limits of agreement (LoA) were reported. RESULTS: Overall reproducibility was good, with all 95% LoA < 8%. Reproducibility was improved by use of the focus point compared with the standard technique for both intraobserver comparison (95% LoA, < 4% vs < 6%) and interobserver comparison (95% LoA, < 7% vs < 8%). These findings were independent of sonographer seniority and plane acquired. CONCLUSIONS: Reproducibility of fetal biometry assessment is improved with use of the focus point for plane acquisition, regardless of sonographer experience. We propose that this method should be implemented in clinical practice and training programs in fetal biometry. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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 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.

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.

Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero.

INTRODUCTION: Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre-pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population. MATERIAL AND METHODS: Individual data from three randomized controlled triasl were pooled. The randomized controlled trials investigated the effects of metformin in pregnant women with PCOS. In all, 397 and 403 were randomized to the metformin and placebo groups, respectively. A Scandinavian growth reference was used to calculate sex and gestational age adjusted z-scores. Linear regression models were used to estimate the effect of metformin on offspring z-scores of head circumference, birth length, birthweight, placental weight, body mass index, ponderal index and birthweight:placental weight ratio. S-testosterone, s-androstenedione, and s-sex-hormone binding globulin from four timepoints in pregnancy were analyzed. RESULTS: Compared with the PCOS-placebo group, newborns in the PCOS-metformin group had larger head circumference (head circumference z-score: mean difference = 0.25, 95% CI = 0.11- 0.40). This effect of metformin on head circumference z-score was particularly observed among offspring of overweight/obese mothers and mothers with hyperandrogenic PCOS-phenotype. We observed no difference in other anthropometric measures between the metformin and placebo groups or any clear interaction between maternal androgen levels and metformin. Newborns in the PCOS-placebo group were shorter than in the reference population (birth length z-score: mean = -0.04, 95% CI = -0.05 to -0.03), but head circumference and birthweight were similar. CONCLUSIONS: Larger head circumference was observed at birth in metformin-exposed offspring of mothers with PCOS. PCOS-offspring were also shorter, with a similar birthweight to the reference population, indirectly indicating higher weight-to-height ratio at birth.

The impact of late pregnancy dating on the detection of fetal growth restriction at term.

INTRODUCTION: The inaccuracy of late pregnancy dating is often discussed, and the impact on diagnosis of fetal growth restriction is a concern. However, the magnitude and direction of this effect has not previously been demonstrated. In this study, we aimed to investigate the effect of late pregnancy dating by head circumference on the detection of late onset growth restriction, compared to first trimester crown-rump length dating. MATERIAL AND METHODS: This was a cohort study of 14 013 pregnancies receiving obstetric care at a tertiary center over a three-year period. Universal scans were performed at 12 weeks, including crown-rump length; at 20 weeks including fetal biometry; and at 36 weeks, where biometry, umbilical artery doppler and cerebroplacental ratio were used to determine the incidence of fetal growth restriction according to the Delphi consensus. For the entire cohort, the gestational age was first calculated using T1 dating; and was then recalculated using head circumference at 20 weeks (T2 dating); and at 36 weeks (T3 dating). The incidence of fetal growth restriction following T2 and T3 dating was compared to T1 dating using four-by-four sensitivity tables. RESULTS: When the cohort was redated from T1 to T2, the median gestation at delivery changed from 40 + 0 to 40 + 2 weeks (p < 0.001). When the cohort was redated from T1 to T3, the median gestation at delivery changed from 40 + 0 to 40 + 3 weeks (p < 0.001). T2 dating resulted in fetal growth restriction sensitivity of 80.2% with positive predictive value of 78.8% compared to T1 dating. T3 dating resulted in sensitivity of 8.6% and positive predictive value of 27.7%, respectively. The sensitivity of abnormal CPR remained high despite T2 and T3 redating; 98.0% and 89.4%, respectively. CONCLUSIONS: Although dating at 11-14 weeks is recommended, late pregnancy dating is sometimes inevitable, and this can prolong the estimated due date by an average of two to three days. One in five pregnancies which would be classified as growth restricted if the pregnancy was dated in the first trimester, will be reclassified as nongrowth restricted following dating at 20 weeks, whereas nine out of 10 pregnancies will be reclassified as non-growth restricted with 36-week dating.

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.

The head circumference to chest circumference ratio provided an easy way to detect foetal growth restriction in term infants.

AIM: The head circumference to chest circumference (HC/CC) ratio has been used to identify low birth weight infants in developed countries. This study was conducted to examine whether the ratio could distinguish asymmetrical foetal growth restriction (FGR). METHODS: This retrospective observational study was conducted with 1955 infants (50.5% male) born at term between 2016 and 2020 at Tokyo Metropolitan Toshima Hospital, Japan. RESULTS: We found that 120 (6.1%) had FGR. Their mean birth weight was 3052.1 ± 367.3 g, and their mean gestational age was 39.1 ± 1.1 weeks. Logistic regression analysis showed that the association between the HC/CC ratio and FGR had a regression coefficient of -20.6 (p < 0.000). The linear regression analysis showed that the association between the HC/CC ratio and the birth weight z-score had a regression coefficient of -8.59 (p < 0.000). The coefficient of correlation was -0.33 (p < 0.001). The receiver operating characteristic curve for detecting FGR showed that the area under the curve was 0.75 and the cut-off value was 0.93, with sensitivity of 75.8% and specificity of 60.8%. CONCLUSION: Our study established the associations between HC/CC ratio and FGR and birth weight z-scores and confirmed that the ratio provided an easy way to detect FGR in term-born infants.

Ratios of head circumference to ventricular size vary over time and predict eventual need for CSF diversion in intraventricular hemorrhage of prematurity.

PURPOSE: Intraventricular hemorrhage (IVH) of prematurity can lead to hydrocephalus, sometimes necessitating permanent cerebrospinal fluid (CSF) diversion. We sought to characterize the relationship between head circumference (HC) and ventricular size in IVH over time to evaluate the clinical utility of serial HC measurements as a metric in determining the need for CSF diversion. METHODS: We included preterm infants with IVH born between January 2000 and May 2020. Three measures of ventricular size were obtained: ventricular index (VI), Evan's ratio (ER), and frontal occipital head ratio (FOHR). The Pearson correlations (r) between the initial (at birth) paired measurements of HC and ventricular size were reported. Multivariable longitudinal regression models were fit to examine the HC:ventricle size ratio, adjusting for the age of the infant, IVH grade (I/II vs. III/IV), need for CSF diversion, and sex. RESULTS: A total of 639 patients with an average gestational age of 27.5 weeks were included. IVH grade I/II and grade III/IV patients had a positive correlation between initial HC and VI (r = 0.47, p < 0.001 and r = 0.48, p < 0.001, respectively). In our longitudinal models, patients with a low-grade IVH (I/II) had an HC:VI ratio 0.52 higher than those with a high-grade IVH (p-value < 0.001). Patients with low-grade IVH had an HC:ER ratio 12.94 higher than those with high-grade IVH (p-value < 0.001). Patients with low-grade IVH had a HC:FOHR ratio 12.91 higher than those with high-grade IVH (p-value < 0.001). Infants who did not require CSF diversion had an HC:VI ratio 0.47 higher than those who eventually did (p < 0.001). Infants without CSF diversion had an HC:ER ratio 16.53 higher than those who received CSF diversion (p < 0.001). Infants without CSF diversion had an HC:FOHR ratio 15.45 higher than those who received CSF diversion (95% CI (11.34, 19.56), p < 0.001). CONCLUSIONS: There is a significant difference in the ratio of HC:VI, HC:ER, and HC:FOHR size between patients with high-grade IVH and low-grade IVH. Likewise, there is a significant difference in HC:VI, HC:ER, and HC:FOHR between those who did and did not have CSF diversion. The routine assessments of both head circumference and ventricle size by ultrasound are important clinical tools in infants with IVH of prematurity.

Neonatal head circumference to maternal mid-transverse pelvic distance ratio as a key anatomical predictor for dystocia: Retrospective case-control study.

OBJECTIVE: This study aimed to examine maternal and neonatal factors in cesarean deliveries due to dystocia, including cephalopelvic disproportion, latent-phase prolongation, and fetal malposition or malpresentation. Additionally, we sought to compare the differences between the dystocia subgroups. METHOD AND MATERIALS: This retrospective case-control study included women who delivered between January 2010 and June 2021 after 37 weeks of pregnancy and underwent abdominal-pelvic CT scans within 5 years before and after delivery. Neonatal factors were extracted from medical charts immediately after delivery. RESULTS: Among the 292 women studied, those with cesarean deliveries for dystocia were older (mean ± SD, 34.2 ± 4.27 vs. 32.2 ± 3.8, p-value = 0.002), had higher pre-pregnancy BMI (22.7 ± 3.67 vs. 21.4 ± 3.48, p-value = 0.012) and term-BMI (27.4 ± 3.72 vs. 25.9 ± 3.66, p-value = 0.010), shorter interspinous distance (ISD, the distance between ischial spine) (10.8 ± 0.76 vs. 11.2 ± 0.85 cm, p-value = 0.003), and longer head circumference (HC) (35 ± 1.47 vs. 34.4 ± 1.36 cm, p-value = 0.003) compared to those who had vaginal deliveries. Univariate logistic regression for dystocia revealed associations between HC/maternal height and HC/ISD ratios (OR, 2.02 [95% confidence interval, CI, 1.4 ~ 2.92], 12.13 [3.2 ~ 46.04], respectively). Multivariate logistic analysis indicated that maternal age, ISD, and HC were significant factors for dystocia (OR, 1.11 [95% CI, 1.01 ~ 1.21], 0.49 [0.26 ~ 0.91], 1.53 [1.07 ~ 2.19], respectively). The subgroup with latent-phase prolongation exhibited the lowest birthweight/term-BMI ratio (124 ± 18.8 vs. 113 ± 10.3 vs. 134 ± 19.1, p-value = 0.013). CONCLUSION: The HC/ISD ratio emerged as a crucial predictor of dystocia, suggesting that reducing term-BMI could potentially mitigate latent-phase prolongation. Further research assessing the maternal mid-pelvis during pregnancy and labor is warranted, along with efforts to reduce BMI during pregnancy.

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.

Comparison of the ratio of second trimester fetal biometric measurements to fetal nasal bone length in fetuses with normal karyotype and trisomy 21.

AIM: In this study, we compared the ratio of second trimester fetal biometric measurements to nasal bone length (NBL) in fetuses with normal karyotype and trisomy 21 to determine their diagnostic prognostic value. MATERIALS AND METHODS: The study included 148 pregnant women who obtained second-trimester ultrasonographic fetal anatomy and had amniocentesis (AS) for fetal karyotyping. The fetal karyotype results divided the groups into normal and trisomy 21 fetuses. Age, obstetric history, first and/or second trimester screening test risk ratios, fetal biometric measurements, and NBL mm, median (MoM) multiples, and percentile values were recorded and compared between groups. RESULTS: BPD/NBL ratios above 9.26 predict trisomy 21 in fetuses with 77.6% sensitivity and 86.1% specificity (p = 0.001). HC/NBL ratios above 34.50 predict trisomy 21 in fetuses with 77.8% sensitivity and 88.8% specificity (p = 0.001). FL/NBL ratios above 6.02 predict trisomy 21 in fetuses with 69.6% sensitivity and 72.2% specificity (p = 0.001). HL/NB ratios above 6.56 predict trisomy 21 in fetuses with 95.5% sensitivity and 47.2% specificity (p = 0.001). The NBL MoM value demonstrated a high diagnostic accuracy for normal-karyotype fetuses (p = 0.021). CONCLUSION: We found that BPD/NBL, HC/NBL, FL/NBL, and HL/NBL ratios differed between fetuses with a normal karyotype and those with trisomy 21, specifically the HC/NBL ratio, which predicted trisomy 21 with good diagnostic accuracy. In identifying normal-karyotype fetuses, the NBL MoM was highly accurate.

Prenatal exposure to polycyclic aromatic hydrocarbons and growth parameters.

BACKGROUND AND OBJECTIVES: It has long been known that airborne polycyclic aromatic hydrocarbons (PAHs) can negatively affect pregnancy and birth outcomes, such as birth weight, fetal development, and placental growth factors. However, similar studies yield divergent results. Our goal was to estimate the amount of monohydroxylated PAH (OH-PAH) metabolites in the urine of pregnant women/mothers and their newborns in relation to birth outcomes, such as placenta weight, Apgar 5', and the growth parameters of children up to the age of two. METHODS: Two cohorts of children born in 2013 and 2014 during the summer and winter seasons in the Czech Republic in the cities Karviná (N = 144) and Ceské Budejovice (N = 198), which differ significantly in the level of air pollution, were studied. PAH exposure was assessed by the concentration of benzo[a]pyrene (B[a]P) in the air and the concentration of 11 OH-PAH metabolites in the urine of newborns and mothers. Growth parameters and birth outcomes were obtained from medical questionnaires after birth and from pediatric questionnaires during the following 24 months of the child's life. RESULTS: Concentrations of B[a]P were significantly higher in Karviná (p < 0.001). OH-PAH metabolites were significantly higher in the mothers' as well as in the newborns' urine in Karviná and during the winter season. Neonatal length was shorter in newborns in Karviná (p < 0.001), but this difference evened out during the next 3 to 24 months. Compared to Ceské Budejovice, newborns in Karviná showed significantly lower weight gain between birth and three months after delivery. The OH-PAH metabolites in mothers' or newborns' urine did not affect birth weight. The presence of seven OH-PAH (top 25% of values of concentrations higher than the median) metabolites in the newborns' urine is associated with decreased length of newborn. Nine OH-PAH metabolites decreased placenta weight, which was the most significant, while seven OH-PAH metabolites decreased Apgar 5'. CONCLUSION: We have shown a possible connection between higher concentration of OH-PAH metabolites in newborns' urine and decreased length, head circumference, placenta weight, and Apgar 5', but not birth weight.

Association of Postnatal Growth Changes and Neurodevelopmental Outcomes in Preterm Neonates of <29 Weeks' Gestation.

OBJECTIVE: To examine associations between weight and head circumference (HC) changes and neurodevelopment in preterm infants. STUDY DESIGN: This retrospective cohort study of Canadian Neonatal Network and Canadian Neonatal Follow-Up Network sites included preterm infants born 2010-2018. Logistic regression and model diagnostics evaluated relationships between changes in z score and velocity of weight and HC from birth to discharge from a tertiary neonatal intensive care unit, discharge to 18-24 months corrected age (CA), and birth to 18-24 months CA and significant cognitive/motor impairment at 18-24 months CA classified using a Bayley Scales of Infant and Toddler Development-Third Edition cognitive or motor composite score <70. RESULTS: In total, 4530 infants (53.0% male) with a mean (SD) gestational age of 26.3 (1.4) weeks and birth weight of 920 (227) g were included. Weight and HC changes were associated with lower odds of significant cognitive/motor impairment including an OR of 0.87 (95% CI: 0.83, 0.91; P < .001) for a 1-g/d increase in weight from discharge to 18-24 months CA and 0.81 (95% CI: 0.75, 0.88; P < .001) for a 1-unit increase in HC z score from birth to 18-24 months CA. Associations were not statistically significant in morbidity-free neonates. Weight and HC gains poorly discriminated between infants with and without significant cognitive/motor impairment (areas under the receiver operating characteristic curve of <0.64). No growth measure had a clinically useful balance of sensitivity and specificity. CONCLUSIONS: Weight and HC changes were associated with significant cognitive/motor impairment but had poor discriminatory capability. Neonatal morbidities may make a larger contribution than postnatal growth to neurodevelopment.

Birth size after embryo cryopreservation: larger by all measures?

STUDY QUESTION: Are the changes in birthweight after frozen and fresh embryo transfer associated with corresponding changes in other measures of foetal growth and placental efficiency? SUMMARY ANSWER: Although placental efficiency was reduced for both frozen and fresh embryo transfer, children born after frozen embryo transfer (frozen-ET) had symmetrically increased size at birth, whereas children born after fresh embryo transfer (fresh-ET) were asymmetrically smaller at birth, compared to naturally conceived children. WHAT IS KNOWN ALREADY: In pregnancies following frozen-ET, the risk of being born large, as measured by birthweight, is higher than after natural and fresh-ET conceptions. It is not known whether this is a result of symmetrically increased growth and increased placental efficiency. STUDY DESIGN, SIZE, DURATION: A Norwegian nationwide registry-based cohort study of 3093 singletons born after frozen-ET, 15 510 singletons born after fresh-ET and 1 125 366 singletons born after natural conception from 1988 to 2015 was performed. We identified 6334 sibships with at least two different conception methods. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from the Medical Birth Registry of Norway and the Norwegian National Education Database. Main outcome measures were birth length, birthweight, head circumference, ponderal index (birthweight relative to birth length in kg/m3), placental weight, birthweight:placental weight ratio, gestational age, and birthweight z-score. We estimated mean differences between children born after frozen-ET and fresh-ET compared to natural conception, at the population level and within sibships. Adjustments were made for birth year, maternal age, parity, and education. MAIN RESULTS AND THE ROLE OF CHANCE: Estimates at the population level and within sibships were consistent for all outcomes, for both fresh and frozen-ET compared to natural conception. Within sibships, children born after frozen-ET had longer mean length (Δ = 0.42 cm, 95% CI 0.29 to 0.55) and head circumference (Δ = 0.32 cm, 95% CI 0.23 to 0.41) at birth, but a similar ponderal index (Δ = 0.11 kg/m3, 95% CI -0.04 to 0.26), compared to naturally conceived. Children born after fresh-ET had a shorter length (Δ = -0.22 cm, 95% CI -0.29 to -0.15) and head circumference (Δ = -0.15 cm, 95% CI -0.19 to -0.10), and lower ponderal index (Δ = -0.15 kg/m3, 95% CI -0.23 to -0.07) at birth compared to natural conception within sibships. Furthermore, mean placental weight was larger after both frozen-ET (Δ = 37 g, 95% CI 28 to 45) and fresh-ET (Δ = 7 g, 95% CI 2 to 13) compared to natural conception within sibships, whereas mean birthweight:placental weight ratio was reduced for both frozen-ET (Δ = -0.11, 95% CI -0.17 to -0.05) and fresh-ET (Δ = -0.13, 95% CI -0.16 to -0.09). A range of sensitivity analyses all gave similar conclusions as the main models, including restriction to full siblings, restriction to single embryo transfer, and adjustment for maternal BMI, height, and smoking. LIMITATIONS, REASONS FOR CAUTION: Additional adjustment for maternal BMI, height, and smoking was possible only for a small sample of the study population (15%). Data on causes and duration of infertility, as well as treatment details, were limited. WIDER IMPLICATIONS OF THE FINDINGS: The increased birthweight observed in singletons after frozen-ET is associated with a symmetrically increased birth size and large placentas, also after controlling for maternal factors through sibship analyses. Identifying the responsible treatment factors and the long-term health outcomes are particularly important considering the increase in elective freezing of all embryos. STUDY FUNDING/COMPETING INTEREST(S): This work was partly supported by the Central Norway Regional Health Authorities (project number 46045000), the Norwegian University of Science and Technology (project number 81850092) and the Research Council of Norway through its Centres of Excellence funding scheme (project number 262700). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Maternal Iron Status Is Dynamic Throughout Pregnancy and Might Predict Birth Outcomes in a Sex Dependent Manner: Results from the Alberta Pregnancy Outcomes and Nutrition (APrON) Cohort Study.

BACKGROUND: Developmental responses to nutrient deprivation may differ by fetal sex. Despite this, relationships between maternal prenatal iron biomarkers and birth outcomes when stratifying by offspring sex are poorly described, especially in healthy cohorts. OBJECTIVES: This study aimed to determine associations between maternal iron biomarkers and birth weights (BWs) and birth head circumferences (BHCs) among female and male newborns to assess whether the potential predictive ability of iron biomarkers on birth outcomes differs by offspring sex. METHODS: The Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study recruited 2189 pregnant individuals from Calgary and Edmonton, Canada. Maternal blood was drawn at each trimester and 3 mo postpartum. Maternal serum ferritin (SF) concentrations were measured using chemiluminescent immunoassays and erythropoietin (EPO), hepcidin, and soluble transferrin receptor (sTfR) using enzyme-linked immunosorbent assays. Ratios of sTfR:SF and hepcidin:EPO were calculated and birth outcomes accessed through delivery records. Directed acyclic graphs informed multivariate regression models. RESULTS: The risk of maternal iron deficiency increased throughout pregnancy because ∼61% showed depleted iron stores (SF < 15 µg/L) by the third trimester. Maternal hepcidin, SF, sTfR, and sTfR:SF concentrations changed across time (P < 0.01), and participants carrying female fetuses consistently (across 6 biomarkers) showed a lower iron status during the third trimester compared with those with male fetuses (P < 0.05). Higher maternal SF and hepcidin:EPO during the third trimester was associated with lower BWs in males (P = 0.006 for SF; P = 0.03 for hepcidin:EPO) and females (P = 0.02 for SF; P = 0.02 for hepcidin:EPO). There were additional inverse associations between BWs and third trimester maternal hepcidin (P = 0.03) and hemoglobin (P = 0.004) and between BHCs and maternal SF (second trimester; P < 0.05) and Hb (third trimester P = 0.02) but only in males. CONCLUSIONS: Relationships between maternal iron biomarkers and BWs and BHCs may depend on the timing of pregnancy and offpsring sex. There was a high risk of third trimester iron storage depletion among generally healthy pregnant individuals.

Nonlinear Catch-Up Growth in Height, Weight, and Head Circumference from Birth to Adolescence: A Longitudinal Twin Study.

Owing to high rates of prenatal complications, twins are, on average, substantially smaller than population norms on physical measurements including height, weight, and head circumference at birth. By early childhood, twins are physically average. This study is the first to explore the process of catch-up growth by fitting asymptotic growth models to age-standardized height, weight, and head circumference measurements in a community sample of twins (n = 1281, 52.3% female) followed at up to 17 time points from birth to 15 years. Catch-up growth was rapid over the first year and plateaued around the population mean by early childhood. Shared environmental factors accounted for the majority of individual differences in initial physical size (57.7-65.5%), whereas additive genetic factors accounted for the majority of individual differences in the upper asymptotes of height, weight, and head circumference (73.4-92.6%). Both additive genetic and shared environmental factors were associated with variance in how quickly twins caught up. Gestational age and family SES emerged as important environmental correlates of physical catch-up growth.

Sex-specific differences in head circumference of term singletons after assisted reproductive technology: a multicentre study in Japan.

RESEARCH QUESTION: Does fertility treatment, specifically assisted reproductive technology (ART), affect head circumference in term singletons? DESIGN: A total of 32,651 women who delivered at term at 12 maternity hospitals in Japan between 2010 and 2018 were included in the analysis; of these, 1941 (5.9%) and 2984 (9.1%) women conceived through ART and non-ART fertility treatments (timed intercourse, ovulation induction or artificial insemination), respectively. The study evaluated the adjusted odds ratios of head circumference ≥90th percentile stratified by infant sex and type of ART procedure after adjusting for covariates, with natural conception as the reference group. RESULTS: ART significantly increased the risk of head circumference ≥90th percentile (adjusted odds ratio 1.56 [95% confidence interval 1.25-1.96]), whereas non-ART fertility treatment did not increase the risk (1.14 [0.92-1.42]). This increased risk of head circumference ≥90th percentile was observed exclusively in male neonates (1.73 [1.33-2.26]) and not in female neonates (1.18 [0.76-1.85]) in the ART group. Frozen embryo transfer (FET), FET in a hormone replacement cycle (HRC-FET) and blastocyst-stage embryo transfer were significantly associated with head circumference ≥90th percentile (1.60 [1.26-2.02], 1.70 [1.30-2.22] and 1.72 [1.33-2.24], respectively). CONCLUSIONS: The use of ART, particularly FET, HRC-FET or blastocyst-stage embryo transfer, was linked with a heightened risk of head circumference ≥90th percentile compared with non-ART fertility treatment or natural conception. The increased risk was observed only in male neonates.

Exposure to ultra-processed foods during pregnancy and ultrasound fetal growth parameters.

Periconceptional maternal ultra-processed food (UPF) consumption impairs embryonic growth. Impacts of exposure to UPF on distinct components of fetal growth in late pregnancy are unknown. We investigated the influence of frequency of UPF consumption during pregnancy on fetal head circumference (HC), abdominal circumference (AC) and femur length (FL). This study included 417 live-born singleton pregnancies prospectively followed-up since the antenatal period in the MINA-Brazil Study, with an available ultrasound scan at >24 gestational weeks. Frequency of food groups consumption in the previous month was categorised as no/monthly, weekly or daily. Ultrasound scans were conducted at 27·8 (sd: 1·7) gestational weeks. HC, AC and FL z-scores were calculated for gestational age using the INTERGROWTH-21st Project standards. Simultaneous-quantile regression models were fitted at the 10th, 50th and 90th percentiles of the distribution of each ultrasound parameter according to UPF consumption, with adjustment for potential confounders. Participants were aged on average 24·7 (sd: 6·5) years, 44·8 % were primiparous, and 26·9 % and 24·9 %, respectively, had weekly and daily UPF consumption. Compared with no/monthly intake, daily UPF consumption impaired HC across its distribution, with significant effect sizes varying from -0·24 to -0·40 z-score. Weekly UPF consumption decreased HC at the 90th percentile by -0·39 z-score (95 % CI: -0·78, -0·01) and FL at the 50th percentile by -0·32 z-score (95 % CI: -0·60, -0·04). No association was noted with AC. Frequency of UPF consumption was negatively associated with skeletal components of fetal growth in late pregnancy. Infant body composition may benefit from healthy food practices since pregnancy.