Lower Birth Weight Percentile Research Articles

Validity of a Delphi consensus definition of growth restriction in the newborn for identifying neonatal morbidity

BackgroundSmall-for-gestational age (SGA) is defined as a birthweight below a birthweight-percentile threshold, usually the 10th percentile, with the 3rd or 5th percentile used to identify severe SGA. SGA is used as a proxy for growth restriction in the newborn, but SGA newborns can be physiologically small and healthy. This definition also excludes growth restricted newborns who have weights above the 10th percentile. To address these limits, a Delphi study developed a new consensus definition of growth restriction in the newborn based on neonatal anthropometric and clinical parameters, but it has not been evaluated. ObjectivesTo assess the prevalence of growth restriction in the newborn according to the Delphi consensus definition and to investigate associated morbidity risks compared to definitions of SGA using birthweight-percentile thresholds. Study designData come from the 2016 and 2021 French National Perinatal Surveys which include all births ≥22 weeks and/or with birthweights ≥500 grams in all maternity units in France over a one-week period. Data are collected from medical records and interviews with mothers after the delivery. The study population included 23,897 liveborn singleton births. The Delphi consensus definition of growth restriction was birthweight <3rd percentile or at least 3 of the following criteria: birthweight, head circumference or length <10th percentile, antenatal diagnosis of growth restriction or maternal hypertension. A composite of neonatal morbidity at birth, defined as five-minute Apgar score <7, cord arterial pH <7.10, resuscitation and/or neonatal admission, was compared using the Delphi definition and usual birthweight-percentile thresholds for defining SGA using the following birthweight percentile groups: <3rd, 3rd-4th and 5th-9th percentiles. Relative risks were adjusted (aRR) for maternal characteristics (age, parity, body mass index, smoking, educational level, pre-existing hypertension and diabetes, and study year) and then for the consensus definition and birthweight percentile groups. Multiple imputation by chained equations was used to impute missing data. Analyses were carried out in the overall sample and among term and preterm newborns separately. Results4.9% (95% confidence intervals (CI): 4.6-5.2) of newborns were identified with growth restriction, of whom 29.7% experienced morbidity, yielding a aRR of 2.5 (95% CI: 2.2-2.7) compared to newborns without growth restriction. Compared to birthweight ≥10th percentile, morbidity risks were higher for low birthweight percentiles (<3rd aRR=3.3 (95%CI: 3.0-3.7), 3rd-4th RR=1.4 (95%CI:1.1-1.7), 5th-9th RR=1.4, (95%CI:1.2-1.6)). In adjusted models including the definition of growth restriction and birthweight percentile groups and excluding birthweights <3rd percentile, which are included in both definitions, morbidity risks remained higher for birthweights at the 3rd-4th percentile (aRR=1.4, 95% CI: 1.1-1.7) and 5th-9th percentile (aRR= 1.4, 95%CI: 1.2-1.6), but not for the Delphi definition of growth restriction (aRR= 0.9, 95%CI: 0.7-1.2). Similar patterns were found for term and preterm newborns. ConclusionThe Delphi consensus definition of growth restriction did not identify more newborns with morbidity than definitions of SGA based on birthweight percentiles. These findings illustrate the importance of evaluating the results of Delphi consensus studies before their adoption in clinical practice.

Dose-response effect of prenatal alcohol exposure on perinatal outcomes.

A better understanding of the effects of lower levels of prenatal alcohol exposure (PAE), as a common exposure, is needed. The goal of this study was to examine the effects of mild-moderate PAE and episodic binge drinking on perinatal outcomes. The data were obtained from three prospective cohorts with a combined sample of 281 participants: 125 with PAE and 156 without PAE. Alcohol-related measures included the Alcohol Use Disorders Identification Test, timeline follow-back questionnaires (covering the periconceptional period, mid-gestation, and late gestation), and biomarkers. Absolute alcohol per day (AAD) and per drinking day (AADD), number of binge episodes, and maximum number of drinks in a 24-h period were estimated. Perinatal outcomes included gestational age and anthropometric measures. Data were analyzed using correlation and multivariable regression analysis. Among women with PAE, average alcohol consumption across the periconceptional period and pregnancy was 0.37 oz ± 0.74 AA/day (~5 drinks/week). After adjusting for tobacco co-exposure and sociodemographic characteristics, significant associations between all alcohol measures and gestational age at delivery were observed, including cumulative measures of AAD (β = -0.58; 95% CI: -0.98; -0.17) and AADD (β = -0.58; 95% CI: -0.90; -0.26) during pregnancy and the periconceptional period. A significant association between the maximum number of drinks in a 24-h period and birth length percentile (β = -0.70; 95% CI: -1.36; -0.04) was observed in the final model. PAE was associated with lower birth weight percentile in univariate analyses only. Results of this study demonstrate a negative association between mild-moderate PAE and episodic binge drinking with gestational age at delivery and birth length percentile after controlling for other factors. Robust negative effects of PAE, including in the periconceptional period before pregnancy recognition, on duration of gestation highlight the need for primary prevention efforts aimed at PAE in persons of reproductive age.

Infant Mortality Categorized by Birth Weight Percentiles for Deliveries Between 22 and 28 Weeks of Gestation.

Our objective was to describe infant mortality within 1 year of life according to gestational age and birth weight percentile in infants delivered between 22 and 28 weeks of gestation. This study was a retrospective cohort study based on publicly available U.S. birth certificate data linked to infant death data between 2014 and 2020. Maternal-neonate pairs of singleton live births between 220/7 and 286/7 weeks' gestation (vaginal or cesarean) were evaluated. We excluded infants with major fetal anomalies, chromosomal disorders, and birth weight outliers. Our primary outcome was infant mortality within 1 year of life. Individuals were categorized into eight sex-specific birth weight percentiles categories: less than the 3rd, 3rd-less than the 10th, 10th-less than the 25th, 25th-to less than the 50th, 50th-less than the 75th, 75th-to less than the 90th, 90th-less than the 97th, and 97th or higher. Of 27,014,444 individuals with live births from January 2014 to December 2020, 151,677 individuals who gave birth at 22 to 28 weeks of gestation were included in the study population. The mortality rate ranged from 4.2% for the 50th-less than the 75th percentiles at 28 weeks to 80.3% for the 3rd-less than the 10th percentile at 22 weeks. Using the 50th-less than the 75th birth weight percentile at each gestational age as a reference group, birth weight less than the 50th percentile was associated with increased mortality at all gestational ages in a dose-dependent manner. From 22 to 25 weeks of gestation, higher birth weight percentiles were associated with lower mortality, while the 97th or higher birth weight percentile was associated with increased mortality compared with the 50th-less than the 75th birth weight percentile at 26 to 28 weeks of gestation. The lower birth weight percentiles were associated with higher mortality across all gestational ages, but the association between higher birth weight percentiles and infant mortality exhibited an opposite pattern at 22 to 25 weeks as compared to later gestational age. · Birth weight ≥97th percentile was associated with increased infant mortality at 26 to 28 weeks.. · Higher birth weight percentiles were associated with a lower risk of mortality at 22 to 25 weeks.. · Lower birth weight percentiles were associated with a higher risk of mortality at 22 to 28 weeks..

Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight

Children conceived through assisted reproductive technologies (ART) have an elevated risk of lower birthweight, yet the underlying cause remains unclear. Our study explores mitochondrial DNA (mtDNA) variants as contributors to birthweight differences by impacting mitochondrial function during prenatal development. We deep-sequenced the mtDNA of 451 ART and spontaneously conceived (SC) individuals, 157 mother-child pairs and 113 individual oocytes from either natural menstrual cycles or after ovarian stimulation (OS) and find that ART individuals carried a different mtDNA genotype than SC individuals, with more de novo non-synonymous variants. These variants, along with rRNA variants, correlate with lower birthweight percentiles, independent of conception mode. Their higher occurrence in ART individuals stems from de novo mutagenesis associated with maternal aging and OS-induced oocyte cohort size. Future research will establish the long-term health consequences of these changes and how these findings will impact the clinical practice and patient counselling in the future.

Diurnal cortisol throughout pregnancy and its association with maternal depressive symptoms and birth outcomes

BackgroundDepression during pregnancy is a common complication that can negatively affect fetal health and birth outcomes. Cortisol is believed to be a key mediator of this association. Although pregnancy entails a natural increase in cortisol levels, preclinical depression could alter its circadian rhythm, producing excessively high overall diurnal cortisol levels that might be harmful for the fetus and future offspring development. ObjectivesUsing a prospective longitudinal design, we aimed to study (i) trimestral cortisol circadian rhythm and its overall levels throughout pregnancy in healthy women, (ii) the extent to which maternal depressive symptoms influence both cortisol rhythmicity and overall levels, and (iii) the possible adverse consequences of elevated maternal cortisol on the offspring’s weight and gestational age at birth. Study design112 healthy pregnant women from the general Spanish population were recruited before their first pregnancy. To assess cortisol circadian rhythm, participants provided four saliva samples at each trimester of pregnancy (at awakening, 30 min after awakening, before lunch and before going to bed). Overall cortisol levels were calculated with AUCg approximation. Depressive symptoms were evaluated in each trimester and defined according to EPDS cut-off values (1st trimester, EPDS ≥ 11; 2nd and 3rd trimesters, EPDS ≥ 10). At birth, the risk for low weight, prematurity and weight birth percentile was retrieved for 100 infants. Mixed models and simple effects were employed to study changes of maternal cortisol circadian rhythm and overall levels throughout pregnancy and the possible influence of maternal depressive symptoms. Finally, logistic regressions were performed to assess the associations between maternal overall cortisol levels in each trimester of pregnancy and birth anthropometrics. ResultsAlthough overall diurnal cortisol levels increase throughout pregnancy, cortisol circadian rhythm is preserved in all trimesters [1st (F(3110)= 92.565, p < .001), 2nd (F(3,85)= 46.828, p < .001) and 3rd (F(3,90)= 65.555, p < .001)]. However, women with depressive symptoms showed a flattened cortisol circadian pattern only during the second trimester, characterized by a blunted awakening peak and reduced evening decline (F(3,85)= 4.136, p = .009), but not during the first (F(3,11)= 1.676, p = .176) or the third (F(3,90)= 1.089, p = .358) trimesters. Additionally, they did not show a cortisol increase from second to third trimester (p = .636). Finally, higher maternal cortisol levels in second and third trimesters seemed to be associated with increased risk of prematurity (adjusted OR −0.371, 95% CI 0.490–0.972, p = .034) and low birth weight percentile (adjusted OR −0.612, 95% CI 0.348–0.846, p = .007) respectively. ConclusionMaternal cortisol levels increased throughout pregnancy, although cortisol circadian rhythm was preserved in all trimesters of pregnancy. However, prenatal depressive symptoms were associated with flattened maternal cortisol circadian rhythm in mid-pregnancy. Therefore, it seems that women with depressive symptoms tended to increase less gradually their cortisol levels from mid to late pregnancy. Finally, higher maternal cortisol levels in mid and late-pregnancy seem to be associated with poorer birth anthropometrics Early detection of depressive symptoms in general population could help to prevent putative obstetrical and birth adverse outcomes.

Infant Outcomes Categorized by Birth Weight Percentile for Deliveries Between 28 and 41 Weeks of Gestation.

To examine the association between birth weight percentile and severe infant outcomes according to gestational age category. We conducted a population-based retrospective cohort study using publicly available U.S. birth certificate data linked to infant death data from 2017 to 2019. Maternal-neonate pairs of singleton live births between 28 0/7 and 41 6/7 weeks of gestation (vaginal or cesarean delivery) were evaluated. We excluded infants with major fetal anomalies, chromosomal disorders, missing data, and birth weight outliers. The primary outcome was infant mortality within 1 year of life. Neonates were divided into eight sex-specific birth weight percentile categories: less than the 3rd, 3rd-less than the 10th, 10th-less than the 25th, 25th-to less than the 49th, 50th-less than the 75th, 75th-to less than the 90th, 90th-less than the 97th, and 97th or higher. There were 10,459,388 births between 28 and 41 weeks of gestation: 69,793 (0.7%) at 28-31 weeks, 88,673 (0.8%) at 32-33 weeks, 635,904 (6.1%) at 34-36 weeks, 2,763,110 (26.4%) at 37-38 weeks, 6,269,894 (59.9%) at 39-40 weeks, and 632,014 (6.0%) at 41 weeks. Infant mortality during the first year of life significantly increased at higher and lower birth weight percentiles at 28-36 weeks of gestation, with the lowest risk observed at the 50th-less than the 75th percentile. The highest mortality rates were 13.6% at less than the 3rd percentile and 8.4% at the 97th percentile or higher at 28-31 weeks of gestation; the second-highest mortality rates were 7.7% at less than the 3rd percentile and 3.1% at the 97th percentile or higher at 32-33 weeks of gestation. At 34-36 weeks of gestation, the highest and second-highest mortality rates were 3.4% at less than the 3rd percentile and 1.4% at the 3rd-10th percentile. At 37-41 weeks of gestation, infant mortality was associated with lower birth weight percentile, but higher birth weight percentiles were not significantly associated with increased mortality. We found different patterns in the association between birth weight percentile and infant mortality depending on gestational age category.

Association of Birth Weight Centiles and Gestational Age With Cognitive Performance at Age 5 Years

Birth weight percentiles (BWPs) are often dichotomized at the 10th percentile and show statistically significant association with later cognitive performance, for both preterm and term-born children. However, research testing nonlinear associations between BWPs and cognitive performance is scarce. To investigate culturally invariant, nonlinear associations of BWPs and gestational age with later cognitive performance. In this cohort study, participants with valid neonatal and cognitive data were combined from 4 observational cohorts, including the Millennium Cohort Study, the National Longitudinal Survey of Youth 1979 Child and Young Adult cohort, Growing Up in Ireland, and the Longitudinal Study of Australian Children, with children born between 2000 and 2002, 1980 and 2010, 2007 and 2008, and 2003 and 2004, respectively. Neonatal data were parent reported before age 1 year. At approximately 5 years of age, multiple cognitive tests were performed. Follow-up at 5 years of age was the predominant focus. Data were analyzed July 17, 2023. The parent-reported neonatal data were used to calculate BWPs according to the Fenton growth chart. Scores for IQ were created from multiple measures of cognition, which were z standardized separately within each cohort. Of 30 643 participants (50.8% male), 7.5% were born preterm (before 37 weeks gestation) and 92.5% were term born (between 37 and 42 weeks gestation). In the pooled data using multivariate adaptive regression splines, IQ linearly increased by 4.2 points as BWPs increased from the first to the 69th percentile before completely plateauing. For gestational age, IQ linearly increased by 1.3 points per week up until 32 weeks, with the association reducing to 0.3 points per week after 32 weeks. The association of BWP with IQ was not moderated by gestational age. For term-born infants, the estimated IQ score was only clinically meaningfully lower than average when birth weight was below the third percentile. Consistent results were found when instead using multivariable regression where gestational age and BWPs were categorized into groups. In this cohort study, lower BWPs and gestational age were independently associated with lower IQ. For term-born infants, a cutoff of the third percentile would be more appropriate than the traditionally used 10th percentile when the aim is estimating meaningful cognitive differences.

Adverse outcomes of nonnuchal umbilical cord entanglement.

To evaluate perinatal effects of umbilical cord entanglement (UCE) of different body parts. The database of a tertiary medical center was retrospectively searched for women who gave birth to a liveborn singleton newborn in 2014-2018. Those diagnosed postpartum with UCE were matched 1:10 with women who were not and compared for adverse obstetric and neonatal outcomes, overall and by site of entanglement. A total of 14 299 women were evaluated, of whom 1243 were diagnosed with UCE: 78.7% neck, 26% trunk, 6.7% limb. UCE was associated with lower birth weight percentile and higher rate of small for gestational age, but findings were significant only for neck and trunk UCE. On multivariate regression analysis adjusted for maternal age, parity, gestational age at birth, and history of cesarean delivery, UCE was an independent risk factor for nonreassuring fetal heart rate, labor induction, operative vaginal delivery, cesarean delivery, and meconium-stained amniotic fluid, but not for lower absolute birth weight/birth weight percentile, small for gestational age, low 1-min Apgar score, or neonatal asphyxia. While fetuses with UCE might be more compromised during labor, they apparently recover shortly after birth. The impact on perinatal outcomes was similar for UCE of the neck and trunk and lower for UCE of the limb.

A lower birth weight percentile is associated with central corneal thickness thinning: Results from the Gutenberg Prematurity Eye Study (GPES).

Prematurity, prenatal growth restriction, and retinopathy of prematurity (ROP) are associated with altered ocular geometry, such as a steeper corneal shape in childhood, but it is unclear whether perinatal history affects corneal thickness development, so this study investigated whether corneal thickness in adulthood is affected by perinatal history. The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. The corneal thickness was measured by Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany), and the relationship between perinatal parameters respective birth weight percentile and corneal thickness at different locations was assessed using uni- and multivariable linear regression models. Covariates included age, sex, mean corneal radius, white-to-white distance, gestational age, birth weight percentile, ROP occurrence, and treatment. The main outcome measures were corneal thickness at the apex, the pupil center, and the corneal periphery. The corneal thickness was measured in 390 participants (754 eyes, mean age 29.7+/-8.7 years, 224 females). In multivariable analyses, a lower birth weight percentile was associated with a lower corneal thickness at the apex (B=0.20, p=0.003) and the pupil (B=0.19, p=0.007). These effects diminished towards the corneal periphery and were not observed beyond the 4-mm diameter circle around the thinnest corneal position. Neither gestational age, ROP occurrence, or ROP treatment affected the corneal thickness. A lower birth weight percentile in subjects born preterm as a proxy for restricted fetal growth is associated with corneal thickness thinning in adults aged 18 to 52 years, indicating that corneal thickness development, particularly in the corneal center, may originate in the fetal stage.

Corneal Aberrations and Thickness in Adults Born Small, Appropriate, or Large for Gestational Age at Term.

Background/Aims: This study investigated whether there are changes in corneal surface regularity and corneal thickness in adults born small, appropriate, or large for gestational age at term. Methods: This retrospective cohort study involved prospective Scheimpflug imaging of the cornea (Pentacam®) to compare the corneal thickness and aberrations between adults classified as small for gestational age (SGA), normal birth weight (BW), and large for gestational age (LGA). Multivariable linear regression was applied to analyze associations with gestational age, BW percentile, placental insufficiency, preeclampsia, and breastfeeding. Results: In total, 448 eyes of 261 individuals born full term (aged 29.9 ± 9.5 years, 140 females) were examined, including 29 severe SGA (BW < 3rd percentile), 32 moderate SGA (BW between 3rd and <10th percentile), 132 normal BW (BW between 10th and 90th percentile), 35 moderate LGA (BW between >90th and 97th percentile), and 33 severe LGA (BW > 97th percentile). There were no differences between groups in the corneal aberrations of the total cornea as well as of the corneal front surface, except for higher-order aberrations in the front of the cornea (p = 0.032). There was an association between the increased total root mean square of higher-order aberrations and lower birth weight percentile (p = 0.004), with increased higher-order aberrations correlating with lower visual acuity and spherical equivalent. Conclusion: Restricted prenatal growth is associated with increased higher-order aberrations in adulthood.

Emergent prelabor cesarean delivery in solid organ transplant recipients: associated risk factors and outcomes

BackgroundPregnancies after solid organ transplant are at a higher risk of antepartum admission and pregnancy complications including cesarean delivery. Emergent prelabor cesarean delivery is associated with increased maternal and neonatal morbidity in other high-risk populations, but its incidence and impact in transplant recipients is not well-understood. ObjectiveThis study aimed to characterize the risk factors and outcomes of emergency prelabor cesarean delivery in kidney and liver transplant recipients. Study DesignThis was a retrospective cohort study of all kidney and liver transplant recipients at >20 weeks gestation enrolled in the Transplant Pregnancy Registry International between 1976 and 2019. Participants admitted antepartum who required emergency prelabor cesarean delivery were compared with those admitted antepartum who underwent nonemergent birth. The primary outcomes were severe maternal morbidity and neonatal composite morbidity. Multivariable logistic regression was conducted for neonatal composite morbidity. ResultsOf 1979 births, 181 pregnancies (188 neonates) with antepartum admission were included. 51 pregnancies (53 neonates, 28%) were delivered by emergent prelabor cesarean delivery compared with 130 pregnancies (135 neonates, 72%) admitted antepartum who subsequently did not require emergent delivery. The most common indication for emergent delivery was nonreassuring fetal heart tracing (44 pregnancies /51 emergent deliveries = 86%). Pregnant people who underwent emergent prelabor cesarean delivery were less likely to deliver at a transplant center (37.3% vs 41.5%; P=.04) and had increased rates of chronic hypertension (33.3% vs 16.2%; P=.02). There was no significant difference in severe maternal morbidity (3.9% vs 4.6%; P=.84), though there was an increase in surgical site infection in the emergent prelabor cesarean delivery cohort (3.9% vs 0%; P=.02). Among those with emergent prelabor cesarean delivery, there was a significant increase in neonatal composite morbidity (43.4% vs 19.3%; P<.001) with earlier gestational age at delivery (33.4 vs 34.7 weeks; P=.02), lower birthweight (1899 g vs 2321 g; P<.001), lower birthweight percentile (30.3% vs 40.6%; P=.03), increased neonatal intensive care unit admission (52.8% vs 35.6%; P=.03), and increased neonatal mortality (11.3% vs 1.5%; P=.002). After adjusting for year of conception, race, hypertensive disorders, and fetal malformations, there was a persistent increased risk of neonatal morbidity (adjusted odds ratio, 3.01; 95% confidence interval, 1.50–6.08; P=.002) associated with emergent prelabor cesarean delivery after transplant. ConclusionAlmost one-third of kidney and liver transplant recipients admitted antepartum had an emergency prelabor cesarean delivery, and 63% of this cohort delivered outside of a transplant center. Pregnancies after transplantation should involve multidisciplinary transplant-obstetrics collaboration to ensure optimal antepartum disease management, especially for preexisting hypertension, to prevent and mitigate obstetrical and neonatal morbidity in the setting of emergent cesarean delivery.

Impact of chemotherapy during pregnancy on fetal growth

Background Chemotherapy crosses the placenta, however, it remains unclear to what extent it affects fetal growth. The current literature suggests up to 21% of the offspring of women receiving chemotherapy are small for gestational age (SGA, birth weight <10th percentile). Limiting research to birth weights only might misjudge fetal growth restriction (FGR) in this high-risk population with multiple risk factors for impaired fetal growth. Moreover, the role of the duration of chemotherapy and gestational age at initiation of chemotherapy in fetal growth is yet poorly understood. Objective This retrospective cohort study evaluates fetal growth and neonatal birthweights in pregnant women receiving chemotherapy. Study design All pregnant patients, registered by the International Network of Cancer, Infertility and Pregnancy (INCIP), treated with chemotherapy with at least two ultrasounds reporting on fetal growth, were eligible for this study. Duration and gestational age at initiation of chemotherapy were our major determinants, followed by cancer type and stage, maternal characteristics (parity, BMI, ethnicity hypertension, and diabetes) and individual cytotoxic agents (anthracycline, taxanes, and platinum). Fetal growth outcomes were described using the following mutually exclusive groups (1) FGR, based on a Delphi consensus (2016); (2) “low risk SGA” (birth weight below the 10th percentile), but an estimated growth above the 10th percentile; (3) “fetal growth disturbance”, which did not meet all FGR criteria; (4) “non-FGR”. Obstetric and oncological characteristics were compared between the growth impaired groups and non-FGR group. We calculated estimated fetal weight (EFW) according to Hadlock’s formula (1991) and birth weight percentile according to Nicolaides (2018). We used univariable and multivariable regression, and linear mixed effect models to investigate the effect of duration and gestational age at initiation of chemotherapy on birth weight, and fetal growth, respectively. Results We included 201 patients, diagnosed with cancer between March 2000 and March 2020. Most patients were diagnosed with breast cancer (n = 132, 66%). Regimens included anthracyclines (n = 121, 60%), (anthracyclines and) taxanes (n = 45, 22%) and platinum (n = 35, 17%). Fetal growth abnormalities were detected in 75 pregnancies: 43 (21%) FGR, 10 (5%) low risk SGA and 22 (8.5%) fetal growth disturbance. Chemotherapy prior to 20 weeks of gestation (47% vs. 25%, p = .04) and poor maternal gestational weight gain (median percentile 15 (range 0–97) vs. 8 (0–84), p = .03) were more frequent in the FGR group compared to the non-FGR group, whereas no difference was seen for specific chemotherapy or cancer types. Univariable regression identified gestational weight gain, hypertension, systemic disease, parity, neonatal sex and maternal BMI as confounders for birth weight percentiles. Multivariable regression revealed that each additional week of chemotherapy was associated with lower birth weight percentiles (–1.06; 95%CI −2.01; −0.04; p = .04), and that later initiation of chemotherapy was associated with an increase in birth weight percentile (1.10 per week; 95%CI 0.26; 1.95; p = .01). Each additional week of chemotherapy was associated with lower EFW and abdominal circumference (AC) percentiles (–1.77; 95%CI −2.21; −1.34, p < .001; −1.64; 95%CI −1.96; –1.32, p < .001, respectively). Conclusions This study demonstrates that FGR is common after chemotherapy in pregnancy, and that the duration of chemotherapy has a negative impact. Sonographic follow-up of fetal growth and well-being is recommended.

The role of preterm birth, retinopathy of prematurity and perinatal factors on corneal aberrations in adulthood: Results from the Gutenberg prematurity eye study.

Prematurity and retinopathy of prematurity (ROP) are associated with altered corneal shape and reduced visual acuity in childhood, but their long-term effects on corneal shape in later life are still unclear. This study evaluated whether prematurity and related perinatal factors are associated with corneal aberrations in adulthood. The Gutenberg Prematurity Eye Study (GPES) is a cohort study using Scheimpflug imaging of the cornea. Associations were assessed between corneal Zernike aberrations and gestational age (GA), birth weight (BW), BW percentile, ROP occurrence, ROP treatment and other perinatal factors using univariate and multivariable linear regression analyses. This study involved 444 eyes of 256 individuals born preterm (aged 28.1±8.4 years, 146 females) and 231 eyes of 132 individuals born full-term (aged 29.8±8.9 years, 77 females). Multivariable analyses revealed an association between corneal higher-order aberrations and lower birth weight percentile (B=-0.001, p< 0.001) as well as ROP treatment (B=0.120, p= 0.03). Corneal lower-order aberrations were also associated with lower birth weight percentile (B=-0.004; p= 0.001) and ROP treatment (B=0.838, p= 0.01) but not with ROP occurrence. Increased corneal aberrations were correlated with lower visual acuity and the spherical equivalent refractive error. Perinatal factors, particularly low birth weight percentile and ROP treatment lead to a more irregular corneal shape in adulthood, thereby reducing optical image quality and potentially contributing to reduced visual acuity and altered refractive error.

Peripapillary Retinal Nerve Fiber Layer Thickness in Adults Born Extremely, Very, and Moderately Preterm With and Without Retinopathy of Prematurity: Results From the Gutenberg Prematurity Eye Study (GPES)

This study investigated whether prematurity and associated factors or prenatal growth restriction have long-term effects on the peripapillary retinal nerve fiber layer (pRNFL) in adulthood. Retrospective cohort study. The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. Selected individuals born term and preterm (age 18-52 years) were examined with spectral-domain optical coherence tomography (SD-OCT) in adulthood, and perinatal medical charts were reviewed. The pRNFL thickness was measured using SD-OCT. Univariate and multivariable linear regression analyses were conducted to investigate associations between pRNFL and gestational age (GA; categorical), birth weight percentile (categorical), retinopathy of prematurity (ROP) occurrence, and treatment and other perinatal parameters with adjustment for age, sex, and spherical equivalent. In total, 766 eyes of 406 preterm and full-term individuals were included (mean age 28.4 ± 8.6 years, 228 females). After adjustment for age, sex, and spherical equivalent, global pRNFL thinning was associated with moderate (GA=33-36 wk, β=-4.68, P < .001), very (GA=29-32 wk, β=-5.72, P < .001), and extreme (GA ≤ 28 wk, β=-8.69, P < .001) prematurity but not with low birth weight percentile (<25th percentile, P=.9) and ROP occurrence (P=.9) in multivariable analysis. ROP treatment was associated with increased pRNFL in the temporal sector (P=.002). Maternal smoking during pregnancy showed an association with pRNFL thinning (P=.07). Our data indicate that the more preterm individuals are born the more pRNFL thinning occurs, whereas prenatal growth restriction and postnatal occurrence of ROP show less effects on pRNFL thickness. Furthermore, individuals with severe ROP with treatment but not lower ROP stages without treatment showed an increased temporal pRNFL thickness.

Foveal and Peripapillary Choroidal Thickness in Adults Born Extremely, Very, and Moderately Preterm With and Without ROP-Results From the Gutenberg Prematurity Eye Study.

PurposeThe present study investigated the long-lasting effect of prematurity, prenatal growth restriction, and associated factors on foveal and peripapillary choroidal thickness in adulthood.MethodsThe Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. Foveal and peripapillary choroidal thicknesses were measured at different sectors using spectral-domain optical coherence tomography. Multivariable linear regression analyses were performed to determine associations among gestational age, birth weight percentile, retinopathy of prematurity (ROP) occurrence and treatment, and other perinatal factors, such as maternal smoking and others with foveal and global peripapillary choroidal thickness.ResultsA total of 735 eyes of 408 study participants were included (age = 28.4 ± 8.6 years, 229 women). Multivariable regression analyses revealed that foveal choroidal thinning was associated with maternal smoking during pregnancy (B = −38.1, 95% confidence interval [CI] = −65.5 to −10.7, P = 0.006), whereas other perinatal factors revealed no association. Global peripapillary choroidal thinning showed a trend to a lower birth weight percentile (B = 0.22, 95% CI = −0.01 to 0.45, P = 0.057). No correlation was observed between foveal and peripapillary choroidal thicknesses with visual acuity.ConclusionsThis study indicates that maternal cigarette smoking during pregnancy has adverse long-lasting effects on choroidal development in the fovea and low birth weight percentile as a surrogate marker for adverse perinatal growth might be linked with peripapillary choroidal thinning whereas prematurity showed no long-term effects.Translational RelevanceAltered choroidal layer development caused by perinatal influence factors might be a risk factor for reduced visual function and predispose affected individuals to eye diseases in later life.

Ocular geometry in adults born extremely, very and moderately preterm with and without retinopathy of prematurity: results from the Gutenberg Prematurity Eye Study

Background/aimsTo evaluate whether anterior segment anatomy and axial length are associated with prematurity and perinatal factors in adults.MethodsThe Gutenberg Prematurity Eye Study examined adults born preterm and term aged 18–52...

A longitudinal study of exposure to fine particulate matter during pregnancy, small-for-gestational age births, and birthweight percentile for gestational age in a statewide birth cohort

BackgroundPrevious studies observed associations between prenatal exposure to fine particulate matter (≤ 2.5 μm; PM2.5) and small-for-gestational-age (SGA) birth and lower birthweight percentile for gestational age. Few, if any, studies examine prenatal air pollution exposure and these pregnancy outcomes in neonates born to the same women. Here, we assess whether prenatal exposure to ambient fine particulate matter (PM2.5) is associated with small-for-gestational-age (SGA) birth or birthweight percentile for gestational age in a longitudinal setting.MethodsDetailed birth record data were used to identify women who had singleton live births at least twice in North Carolina during 2002–2006 (n = 53,414 women, n = 109,929 births). Prenatal PM2.5 exposures were calculated using daily concentration estimates obtained from the US EPA Fused Air Quality Surface using Downscaling data archive. Associations between PM2.5 exposure and birthweight percentile and odds of SGA birth were calculated using linear and generalized mixed models, comparing successive pregnancies to the same woman. Odds ratios and associations were also estimated in models that did not account for siblings born to the same mother.ResultsAmong NHW women, pregnancy-long PM2.5 exposure was associated with SGA (OR: 1.11 [1.06, 1.18]) and lower birthweight percentile (− 0.46 [− 0.74, − 0.17]). Trimester-specific PM2.5 was also associated with SGA and lower birthweight percentile. Among NHB women, statistically significant within-woman associations between PM2.5, SGA, and birthweight percentile were not observed. However, in models that did not account for births to the same mother, statistically significant associations were observed between some PM2.5 exposure windows and higher odds of SGA and lower birthweight percentile among NHB women.ConclusionsFindings suggest that a woman is at greater risk of delivering an SGA or low birthweight percentile neonate when she has been exposed to higher PM2.5 levels. The within-woman comparison implemented here better controls for factors that may differ between women and potentially confound the relationship between PM2.5 exposure and pregnancy outcomes.This adds to the evidence that PM2.5 exposure may be causally related to SGA and birthweight percentile, even at concentrations close to or below National Ambient Air Quality Standards.

O-184 Maternally inherited differences in mitochondrial DNA genotype between ART and spontaneously conceived individuals associate with low birthweight

Abstract Study question Can mitochondrial DNA (mtDNA) variants explain the differences in birthweight between ART and spontaneously conceived (SC) individuals and how do they originate? Summary answer Children born after ART carry more frequently a different mtDNA variant composition, both maternally inherited and de novo, which are predictive of their birthweight percentile. What is known already Children born after ART show an increased risk of lower birthweight and of developing a mild abnormal cardio-metabolic profile later in life. Variation in the mtDNA associates with overall health in the general population, including cardio-metabolic fitness, and can result in changes in mitochondrial function. We hypothesized that mitochondrial DNA variants could explain the differences in birthweight between ART and SC individuals and that these differences may result from maternal transmission and/or from the ovarian stimulation (OS) used in ART. Study design, size, duration We deep-sequenced the mtDNA of 472 individuals of who 283 ART and 189 SC, 182 mother-child pairs and 113 single oocytes from both natural menstrual cycles and OS cycles. The mtDNA was compared between groups and Fisher linear discriminant analysis was used as predictive model for the birthweight percentile. Participants/materials, setting, methods Mitochondrial DNA was enriched by long-range PCR and subsequently sequenced on an Illumina platform. mtDNA server and MuTect were used for variant calling for variants with a load higher than 1.5%, versus the reference NC_012920.1. An orthogonally rotated factor analysis was used to reduce the dimensionality of the studied dependent variables in the complex data of the heteroplasmic variants. Main results and the role of chance ART individuals carried more frequently haplogroup U4 (p = 0.004) and component analysis indicated that they carry a different mtDNA heteroplasmic variant composition than SC individuals (p = 0.01), driven by non-synonymous protein-coding and rRNA-coding variants. These differences were also predictive of the risk of a lower birthweight percentile, especially for the SC children, together with the absence of haplogroup T, the presence of homoplasmic tRNA-variants, pregnancy-induced hypertension and the embryo culture medium used. The differences in heteroplasmic variation observed in the ART children resulted from both maternal transmission (p = 0.03) and de novo mutagenesis (p = 0.02). Mothers of ART children showed a similar mtDNA genotype as their children and differed in the same variant composition when compared to the mothers of SC children (p = 0.03). Furthermore, the comparison of oocytes from the same donors retrieved in natural menstrual cycles and after one OS cycle showed that OS does not increase de novo mutagenesis. Additionally, clinical parameters such as the total dosage of FSH units, the number of oocytes retrieved, and maternal age did not show any correlation with the differences observed in ART individuals. Limitations, reasons for caution This study is observational with no functional tests being performed. Wider implications of the findings We demonstrate an association between a lower birthweight percentile and a mtDNA variant composition which is more frequently carried by ART children. These non-disease associated mtDNA variants could cause a suboptimal mitochondrial function affecting the birthweight. Long-term health consequences of these differences remain to be further elucidated. Trial registration number Not applicable

Endometrial thickness in the prediction of neonatal adverse outcomes in frozen cycles for singleton pregnancies

Research questionDoes endometrial thickness (EMT) predict adverse neonatal outcomes in singleton pregnancies after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) frozen embryo transfer (FET)? DesignThis retrospective study involved 13,383 women undergoing IVF/ICSI FET cycles between January 2010 and December 2018 in Women's Hospital of Zhejiang University. The primary outcome was preterm delivery (PTD). The secondary outcomes were small for gestational age (SGA), large for gestational age (LGA) and low birthweight (LBW). ResultsA total of 13,383 FET cycles resulting in 5220 singleton live births and 8163 failed cycles were included. Multiple spline regression visualization showed an increasing risk of PTD and LBW for a thin EMT. By comparing multiple cut-off points using area under the curve, a cut-off point of 8 mm was identified, which was used to categorize EMT. A reference point of EMT greater than 8 mm was used; after adjusting for covariates, individuals with EMT less than 8 mm had an adjusted odds ratio of 1.75 (95% CI 1.30 to 2.34) for PTD, 1.57 (95% CI 1.09 to 2.26) for LBW, 0.97 (95% CI 0.63 to 1.50) for SGA and 1.04 (95% CI 0.79 to 1.37) for LGA. Additional analyses showed similar increasing risk with a thin endometrium for both PTD with and without caesarean section, and PTD with low and normal birthweight percentiles. ConclusionA clinical cut-off point of 8 mm has been identified, below which risk of PTD and LBW increases in women undergoing IVF/ICSI.

Association of term isolated microcephaly with mode of delivery and perinatal outcome - a retrospective case-control analysis

BackgroundWe aimed to evaluate the association of isolated fetal microcephaly measured by ultrasound prior to delivery at term with mode of delivery and perinatal outcome.MethodsA single-center retrospective study was conducted in 2012–2016. Fetal microcephaly was defined as head circumference > 2 standard deviations of the mean for gestational age and sex. We compared the obstetric, delivery, and outcome parameters of women in whom ultrasound performed up to 10 days prior to term delivery showed isolated fetal microcephaly (study group) or normal head circumference (reference group). Exclusion criteria were intrauterine fetal death, birthweight below the 10th percentile, and antepartum cesarean delivery for any indication.ResultsOf 3677 women included in the study, 26 (0.7%) had a late ultrasound finding of isolated fetal microcephaly. Baseline characteristics were similar in the two groups except for estimated fetal weight based on abdominal circumference and biparietal diameter, which was lower in the microcephaly group (3209.8 ± 557.6 vs. 2685.8 ± 420.8 g, p < .001). There was no significant between-group difference in rate of vaginal operative deliveries (11.7% vs 14.8%, respectively, p = 0.372). The study group had no intrapartum cesarean deliveries compared to 6.3% of the reference group (NS). Compared to controls, neonates in the study group were smaller (3323.2 ± 432.2 vs. 2957.0 ± 330.4 g, p < .001), with lower birthweight percentile (60.5 ± 26.5 vs. 33.6 ± 21.5%, p < .001) and were more often males (48.2 vs. 90.0%, p < .001). No significant differences were noted in perinatal outcomes between the groups, including admission to neonatal intensive care unit, intraventricular hemorrhage, 5-min Apgar score < 7, asphyxia, seizures, and sepsis.ConclusionsIsolated microcephaly in term fetuses is not advantageous for a vaginal delivery, nor does it does not pose a greater than normal risk of adverse perinatal outcome.