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Objective: To evaluate perinatal outcomes in fetuses with severe late-onset fetal growth restriction., Methods: This was a retrospective and observational cohort study in which pregnant women diagnosed with late-onset fetal growth restriction assisted at perinatal maternity birth from 2010 to 2017 were included. The outcomes were intensive care unit (ICU) admission and perinatal complications, such as neonatal death, intraventricular hemorrhage, periventricular leukomalacia, hypoxic-ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, and sepsis., Results: We selected 277 pregnant women, of whom 124 newborns (44.76%) went to the ICU. The chance of a newborn needing ICU decreases by 62, 7, and 9% according to an increase of one gestational week, 1 cm of the abdominal circumference, or 1 cm of the amniotic fluid index, respectively. Oligohydramnios increases the risk of going to the ICU by 2.13 times. The increase in the umbilical artery pulsatility index (PI) Doppler increases the chance of ICU admission by 7.9 times. The normal middle cerebral artery PI Doppler and the normal cerebroplacental ratio reduce the risk of ICU admission., Conclusion: The estimated fetal weight, abdominal circumference, and amniotic fluid index diagnosed severe late-onset fetal growth restriction. With the decrease in middle cerebral artery PI Doppler, there is a greater probability of admission to the ICU, with the most common complications being intraventricular hemorrhage and necrotizing enterocolitis.

Introduction: The mitigation measures to face the health emergency due to the COVID 19 pandemic generated a deep economic, social, and psychological crisis at the community level. This effect is greater in the people, who are the most violated in their rights. In relation to the social crisis and gender perspective, women are particularly affected by the pandemic. Given the disadvantaged situation of women socially, economically, and politically, their self-care is diminished., Objective: To identify whether there is an association between the classic risk factors for prematurity and fetal growth restriction and the increase in these pathologies in the period March-September 2020, in a maternity hospital that assists women from low resources., Materials and Methods: A retrospective study, with a comparative analysis of the periods between 15 March and 30 September 2019 and the same period in 2020. The data were obtained from an electronic clinical database. The prevalence of preterm birth and small-for-gestational age newborn was analyzed. Indicators available in the database that reflect maternal conditions that lead to an unfavorable maternal environment were selected and they were classified into categories., Results: In the period of 2019, 3225 births were registered and in the period of 2020, 3036 births. In the 2019 period, 12.2% of prematurity was evidenced, while in the 2020 period, 14.5% (RR = 1.19, IC 95% = 1.05-1.35, p = .005). In relation to PEG 5.5% in the first period versus 6.9% in the second (RR = 1.26, CI 95% = 1.04-1.53, p = .01). No increases were found in the indicators that are traditionally related to the etiologies proposed to explain the increase in prematurity and small-for-age gestational, there was no evidence of an increase in inflammatory or vascular conditions., Conclusion: The economic, psychological and social crises, in the 1st semester of the health emergency, seriously affected the social determinants of the health of pregnant women who use the Public Maternity of reference in Uruguay. This situation is at the base of the poor perinatal results in the period of the maximum mediated mitigation of the pandemic.

Introduction: In singleton pregnancies, maternal complications, such as preeclampsia and thyroid dysfunction are associated with small for gestational age (SGA). However, data on the association between SGA and maternal complications in twin pregnancies are limited and conflicting. Small sample size and the application of singleton birth weight reference (SBWR) to define SGA in twins may be reasons for the inconsistent conclusions. Purpose of this study was to define SGA in dichorionic diamniotic (DCDA) and monochorionic diamniotic (MCDA) twin pregnancies using both SBWR and twin birth weight reference (TBWR) and to determine whether certain maternal complications are associated with SGA in twin pregnancies., Materials and Methods: This retrospective cohort study included all twins delivered in a single tertiary center between 2013 and 2018. SGA was defined as a twin with birth weight <10th centile for gestational age using either SBWR or TBWR. The association between SGA and maternal complications was analyzed separately for DCDA and MCDA twin pregnancies, expressed as odds ratio (OR) and adjusted odds ratio (aOR) with 95% confidence interval (95%-CI)., Results: A total of 2005 DCDA and 467 MCDA twin pregnancies were enrolled. In DCDA pregnancies, SGA was significantly associated with PE according to TBWR (22.73 vs. 14.56%, aOR 1.823, 95%-CI 1.137-2.922). This association was even more pronounced between SGA and severe PE (9.09 vs. 4.54%, aOR 2.234, 95%-CI 1.115-4.479). In turn, PE was associated with higher risk of SGA defined according to TBWR (8.31 vs. 4.99%, aOR 1.825, 95%-CI 1.139-2.925). No association was detected between SGA and other maternal complications. Using SBWR, no association was found between preeclampsia and SGA. In MCDA pregnancies, according to TBWR, SGA was associated only with severe PE (12.5 vs. 4.06%, aOR 3.470, 95%-CI 1.256-9.587) and lower risk of PROM (aOR 0.067, 95%-CI 0.014-0.322)., Conclusion: PE was associated with SGA in DCDA pregnancies only when TBWR was used, suggesting that DCDA pregnancies complicated with PE should be closely monitored for signs of SGA and vice versa. In MCDA pregnancies, SGA defined according to TBWR was associated with only severe PE (but not with all PE) and lower risk of PROM. More basic experiments are needed to investigate the mechanisms underlying PE and SGA in DCDA and MCDA twin pregnancies respectively.

Purpose: To derive a prescriptive sex-specific fetal growth standard and assess clinical management and outcomes according to sex-specific growth status., Materials and Methods: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a prospective observational study of 10,038 nulliparas from eight U.S. centers who underwent ultrasounds at 14-20 and 22-29 weeks with outcomes ascertained after delivery. From these, we selected a nested cohort of lower risk participants (excluded those with chronic hypertension, pre-gestational diabetes, suspected aneuploidy, and preterm delivery) to derive a sex-specific equation for expected fetal growth using fetal weights by ultrasound and at birth. We compared the male-female discrepancy in the rate of weight <10th (small for gestational age [SGA]) and >90th (large for gestational age [LGA]) percentiles between the sex-specific and sex-neutral (Hadlock) standards. Using the full unselected cohort, we then assessed outcomes and clinical management according to sex-specific SGA and LGA status., Results: Overall, 7280 infants in the lower risk nested cohort were used to derive a sex-specific equation with fetal sex included as an equation intercept. The sex-neutral standard diagnosed SGA more often in female newborns (21% vs. 13%, p  < .001) and LGA more often in male newborns (5% vs. 3%, p  < .001). The sex-specific standard resolved these disparities (SGA: 9% vs. 10%, p  = .23; LGA: 13% vs. 13%, p  = .58). To approximate an unselected population, 1059 participants initially excluded for risk factors for abnormal growth were then included for our secondary objective ( N  = 8339). In this unselected cohort, 39% (95% CI 37.0-42.0%) of the 1498 newborns classified as SGA by the sex-neutral standard were reclassified as appropriate for gestational age (AGA) by the sex-specific standard. These reclassified newborns were more likely to be delivered for growth restriction despite having lower risk of morbidity (females) or comparable risk of morbidity (males) compared to newborns considered AGA by both methods. Of the 6485 newborns considered AGA by the sex-neutral standard, 737 (11.4%, 95% CI 10.6-12.2%) were reclassified as LGA by the sex-specific standard. These reclassified newborns had higher rates of cesarean for arrest of descent, cesarean for arrest of dilation, and shoulder dystocia than newborns considered AGA by both methods. None were reclassified from LGA to AGA by the sex-specific standard., Conclusion: The Hadlock sex-neutral standard generates sex disparities in SGA and LGA at birth. Our sex-specific standard resolves these disparities and has the potential to improve accuracy of growth pathology risk stratification.

Objective: To assess obstetric, perinatal, and placental histologic findings in small-for-gestational-age (SGA) neonates according to different growth charts., Methods: A retrospective cohort of singleton deliveries from 2008 to 2019 were divided into SGA neonates according to the local population-based chart, SGA according to universal standard growth charts (but appropriate for gestational age [AGA] according to local charts) and AGA deliveries according to both charts., Results: A total of 626 local population SGA deliveries, 132 universal SGA and 468 AGA deliveries were compared. The local population SGA group had a significantly higher rate of preterm and cesarean deliveries. An adverse neonatal outcome occurred in 27.2% of the local population SGA group, 9.8% of the universal SGA group and 6.7% of the AGA group (P < 0.001). In the local population SGA group, placental weight was lower, birth weight to placental weight ratio was highest, and the rate of maternal malperfusion lesions was highest-55.4% versus 45.4% in the universal SGA group and 39.1% in the AGA group (P < 0.001). Villitis of unknown etiology was significantly more common and histologic chorioamnionitis was significantly less common in the local population SGA group., Conclusions: Our findings support the use of a local population-based growth chart for the diagnosis of fetal growth restriction., (© 2022 International Federation of Gynecology and Obstetrics.)

Objective: The aim of this study was to determine the association of prenatal marijuana exposure with and without tobacco smoke exposure and small for gestational age (SGA) at birth., Study Design: We conducted a secondary analysis of the prospective Lifestyle and Early Achievement in Families (LEAF) cohort enrolled from 2010 to 2015. We included singleton nonanomalous liveborn pregnancies. We assessed marijuana use inclusive of any pregnancy urine specimen with a Δ9-THC-COOH concentration of more than 15 ng/mL by mass spectrometry, self-report on questionnaire, and/or electronic health record; and self-reported maternal tobacco use. Because of the high co-frequency of marijuana with tobacco exposure in pregnancy and the known association between tobacco and fetal growth restriction, we modeled the exposure as: both marijuana and tobacco (hereafter "co-use"), only marijuana, only tobacco, and neither (reference). Incidence of SGA in each group was compared with the neither group. The primary outcome was SGA less than 10th percentile, and secondarily less than 5th percentile, using parity-specific definitions per 2017 US natality reference data., Results: Among 325 assessed mothers, 46% had neither exposure, 11% had only prenatal marijuana exposure, 20% only tobacco exposure, and 23% co-use exposure. A third (33%) of infants were SGA less than 10th percentile and 20% SGA less than 5th percentile. Marijuana exposure only was associated with an increased risk of SGA less than 10th percentile (43 vs. 26%; adjusted relative risk [aRR]: 1.66; 95% confidence interval [CI]: 1.02-2.69), and SGA less than5th percentile (30 vs. 13%; aRR: 2.26; 95% CI: 1.15-4.47). Tobacco was not associated with SGA less than 10th percentile, but was with SGA less than 5th percentile (26 vs. 13%; aRR: 2.01; 95% CI: 1.13, 3.56). Co-use was not associated with increased SGA risk in multivariate analysis, but was in sensitivity analysis when tobacco use was defined using a cotinine assay rather than self-report (SGA <10th percentile, aRR: 1.97; 95% CI: 1.24-3.15) and (SGA <5th percentile, aRR: 2.03; 95% CI: 1.09-3.78)., Conclusion: Prenatal marijuana exposure in addition to tobacco may increase the risk of SGA. Given the rising prevalence of marijuana use in pregnancy, further research is warranted to understand how in utero marijuana exposure may impact fetal growth and birth weight with and without tobacco exposure., Key Points: · Marijuana and tobacco are commonly used together in pregnancy.. · Prenatal marijuana and tobacco exposure may increase the risk of a small for gestational age infant.. · Further research is warranted to understand how in utero marijuana exposure impacts fetal growth.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To determine the optimal timing of delivery in Dichorionic-diamniotic (DCDA) pregnancies complicated by preeclampsia without severe features., Methods: A decision-analytic model was created to compare outcomes of expectant management vs. delivery from 34 to 37w0d. Outcomes included quality-adjusted life years (QALYs), development of severe preeclampsia, maternal mortality, maternal stroke, small for gestational age (SGA) due to fetal growth restriction (FGR) detected antenatally, stillbirth, cerebral palsy (CP), and neonatal mortality. Probabilities, utilities, and life expectancies were derived from the literature. Univariate analysis was used to evaluate the impact of delivery at various gestational ages. Maternal and neonatal outcomes were calculated for a theoretical cohort of 10,000 DCDA pregnancies with preeclampsia., Results: The optimal gestational age for delivery was 36w0d when the total QALYs (868,112) were highest. Delivery at 34w0d resulted in the fewest cases of severe preeclampsia, maternal mortality, and maternal stroke (0, 4, and 15 cases per 10,000, respectively). The incidence of each of these adverse outcomes increased with gestational age, with the greatest number of adverse outcomes at 37w0d (2452 cases of severe preeclampsia, eight maternal deaths, and 31 cases of maternal stroke per 10,000). Delivery at 34w0d resulted in the fewest cases of severe preeclampsia (0), maternal stroke (15), maternal mortality (4), stillbirth (0), and SGA (1183). However, this strategy was also associated with most cases of neonatal CP (91) and neonatal mortality (87)., Conclusion: DCDA twin pregnancies complicated by preeclampsia without severe features appear to have the best outcomes when delivered at 36w0d. Specifically, when compared to delivery at 37w0d, this strategy reduced maternal and neonatal morbidity and mortality.

Constant exposure to plastics particulates has raised concerns against human health, particularly when it comes to birth outcomes. The present study explores the first appraisal of plastic particles in fresh human placenta and its association with foetal growth in neonates. Specifically, 43 pregnant women from general population were selected and their placentas were analyzed by digital microscopy and Raman microspectroscopy for microplastics (MPs <5 mm). We used regression analysis to estimate associations between MPs count in placenta and neonatal anthropometric measurements. MPs were found in all (13 out of 13) intrauterine growth restriction (IUGR) pregnancies and their average abundance ranged from 2 to 38 particles per placenta, but were less than limit of detection (LOD) in normal pregnancies except three out of 30 subjects. This study is one of very few that detected MPs in human placenta in which particles <10 μm were the most abundant in both IUGR and normal pregnancies, accounting for up to 64%. Fragments clearly prevailed at normal pregnancies and fragments together with fibers predominated at IUGR placentas. Despite four different polymers forming the MPs being identified, the majority of MPs comprised of PE (polyethylene) and PS (polystyrene). Inverse associations between MPs exposure and birth outcomes were observed in terms of birth weight (r = - 0.82, p < 0.001), length (r = - 0.56, p < 0.001), head circumference (r = - 0.50, p = 0.001), and 1-min Apgar score (r = - 0.75, p < 0.001) among those with IUGR, compared to those that were nominated as normal pregnancies. While it seems plastic particles may affect placental-foetal interrelationship, the pattern of associations between their content in placenta and birth outcomes, however, shows evidence of a nonlinear or nonmonotonic dose response possibly through perturbation of gas and nutrients exchange which is worth future investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: Previous research suggests that job loss in a household during pregnancy may perturb fetal growth. However, this work often cannot rule out unmeasured confounding due to selection into job loss. Recent work using data on exogenous job loss (due to a plant closure) finds that a father's unexpected job loss during his spouse's pregnancy increases the risk of a low weight birth. Using a unique set of linked registries in Denmark, we build on this work and examine whether associations between a father's unexpected job loss and low birthweight differ by trimester of in utero exposure. We additionally examine trimester-specific associations of job loss with small-for-gestational-age, a proxy for restricted fetal growth, which may cause low birthweight., Methods: We apply a sibling control design to over 1.4 million live births in Denmark, 1980 to 2017, to examine whether this plausibly exogenous form of job loss corresponds with increased risk of low weight or small-for-gestational-age births, depending on the timing of displacement in the first, second, or third trimester., Results: Results indicate an elevated risk of low birthweight (OR = 1.80, 95% CI: 1.24, 2.62) and small-for-gestational-age (OR = 1.40, 95% CI: 1.02, 1.93) among gestations exposed to job loss in the second trimester of pregnancy. Sensitivity analyses using continuous outcome measures (e.g., birthweight in grams, birthweight for gestational age percentile) and maternal fixed effects analyses produce substantively similar inference., Conclusions: Findings support the notion that unexpected job loss may affect fetal growth and that the second trimester in particular appears sensitive to this external stressor., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Little is known about the association between hypospadias and small fetuses, as well as the pathological implications of fetal growth restriction (FGR). Thus, we aimed to investigate the association between hypospadias and small fetuses using a database of fetal ultrasound and obstetric events., Methods: A cohort of male singleton infants delivered after 22 weeks of gestation at Keio University Hospital between 2013 and 2019 was retrospectively reviewed. FGR was defined according to the Delphi criteria. Logistic regression analysis was performed to identify the significant predictors of hypospadias. Placental pathology was reviewed in cases with hypospadias., Results: Of the 2,040 male infants included in the present study, 23 had hypospadias. The prevalences of a single umbilical artery (SUA), small for gestational age, maternal hypertensive disorders of pregnancy, and a small placenta, were significantly higher in infants with hypospadias. Multiple logistic regression analysis revealed that FGR (odds ratio [OR] = 9.39; 95% confidence interval [CI], 2.50-35.3) and the presence of a SUA (OR = 33.4; 95% CI, 8.00-139.5) were independently and significantly associated with hypospadias. When FGR was stratified by the time of onset, its association with hypospadias was significant regardless of the time of onset. Moreover, placental histological findings suggested that fetal vascular malperfusion might play a role in hypospadias., Discussion: FGR and SUAs are independent prenatal predictors of the development of hypospadias, and fetal vascular malperfusion of the placenta may be involved in the etiology of hypospadias., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To compare in singleton multiparous pregnancies the effect of having a new father for an index pregnancy as compared with multiparas with the same male partner and primiparas., Material and Methods: 21 year data, 2001-2021, Reunion island. We compared 2233 multiparas who had a new partner NewPMP (cases) with 50,364 same partner multiparas samePMP (controls) and 30,741 primiparas. Paired t-test in for parametric, Mann-Whitney U test for non-parametric continuous variables. P-values < 0.05., Results: As compared with primiparas, New paternity multiparas had similar neonatal outcomes: average birthweights 3044 g and 3017 g (vs 3125 g grams SamePMP, p < 0.0001), rates of low birthweights, very low birthweights (< 1500 g), rate of prematurity < 37 weeks, rate of early prematurity < 33 weeks and also "placental " intrauterine growth retardation, IUGR. Both primiparas and NewPMP had significant worse neonatal outcomes as compared with same partner multiparas for all these same items (all p < 0.05)). NewPMP had a much higher risk of preeclampsia than primiparas and samePMP (respectively, OR 1.74 and 2.9, p < 0.001), fetal deaths and perinatal mortality respectively, OR 1.4 and 1.8, p < 0.001. In 4 logistical models (primiparity, primipaternity, preeclampsia and "placental IUGR") new paternity multiparas had similar results compared with primiparas but very different results when compared with same partner multiparas., Conclusions: New paternity multiparas share with primiparas a significantly higher risk of perinatal and maternal morbidities than same partner multiparas. Paternity needs to be specified in all obstetrical files, perinatal databases- Health Registries., Competing Interests: Competing interest statement There are no competing interests for the authors., (Copyright © 2022. Published by Elsevier B.V.)

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.

Background: Fetal Growth restriction (FGR) is the pathological failure of a fetus to reach its biologically determined growth potential. Detection of FGR fetuses is a universally agreed key objective of antenatal care. Antenatal detection of FGR has undeniable benefits, juggling between intensive fetal surveillance and optimized timing of delivery; it reduces adverse perinatal outcomes by up to four-fold. However, FGR is still widely underdiagnosed. We aimed to identify the prevalence of FGR diagnosis in our wards and study the impact of the 2013 published French guidelines on the detection rate of FGR. The secondary objective aimed to highlight the factors of suboptimal screening in the population of non-diagnosed FGR fetuses and emphasize the screening method that led to antenatal diagnosis of FGR., Materials and Methods: We conducted a retrospective study at a single tertiary maternity center in Lyon-France, the Femme Mère Enfant Hospital, including the exhaustive population of FGR born after 24 + 0 weeks of gestation from 1 January 2011 to 31 December 2017. FGR was defined combining the neonatal and antenatal consensus-based definitions for early and late FGR in absence of congenital anomalies, excluding small for gestational age fetuses. For all FGR fetuses, we compared the antenatal detection rate of FGR during 2011-2013 to 2015-2017, since the French guidelines were published in December 2013. When FGR fetuses underwent an antenatal diagnosis of FGR, we retrospectively collected the characteristics that led to the diagnosis. When fetuses were not diagnosed as FGR, we retrospectively reviewed the implementation of the recommended screening method, enabling to evaluate whether screening was optimal or not. Statistical analysis was performed in July 2018, and statistical significance was regarded as a p -value <.05., Results: Over the seven-year period, and among 31,052 newborns, 1020 (3.3%) infants were identified as FGR and met the inclusion criteria. The detection rate of FGR was similar before and after publication of the French Guidelines related to FGR in 2013. Indeed, 50.8% (201/395) FGR were diagnosed between 2011 and 2013 versus 52.6% (245/465) between 2015 and 2017 ( p  = .59). In the population of non-diagnosed FGR infants, screening was suboptimal in 80%. Symphysis-fundal height (SFH) was not measured in 10.7%, with no difference before and after 2014 (7.3 versus 11.8% p  = .11). Ultrasound examination for fetal biometry had not been prescribed in spite of abnormal SFH in 47.7% of undiagnosed FGR infants. Diagnosis has been missed in 11.5% of infants because of misinterpretation of the estimated fetal weight's centile., Conclusion: FGR is widely underdiagnosed. However, the limited performances can partially be explained by the regular misuse of screening method in clinical practice. Despite the systematic third trimester ultrasound screening, the detection rate of FGR was similar to the one reported in the medical literature. The timing of routine third trimester ultrasound in low-risk women may be rethought.

Objective: To explore the appropriate fetal weight of twin pregnancies at different gestational weeks and the association with pregnancy complications and outcomes. Methods: Fetal weight at different gestational weeks and related pregnancy complications and outcomes from 1 225 twin pregnancies, who gave birth at Peking University First Hospital from January 2004 to December 2020, were analyzed in this study, including hypertensive disorders in pregnancy, gestational diabetes mellitus (GDM), fetal growth restriction (FGR), fetal distress, preterm birth and neonatal asphyxia. The appropriate fetal weight of twin pregnancies at different gestational weeks were analysed based on the information from 616 twin pregnancies without complications (except preterm birth), and were expressed as P 10 ~ P 90 . The chi-square test was used to compare the risk of pregnancy complications and adverse outcomes in large for gestational age (LGA), appropriate for gestational age (AGA) and small for gestational age (SGA) twin pregnancies and the difference in incidence of pregnancy complications and adverse outcomes in different years. Results: The appropriate fetal weights of normal twin pregnancies at 28 to 37 weeks and 38-40 weeks of gestation were 910-1 255 g, 996-1 518 g, 1 105-1 785 g, 1 295-1 825 g, 1 336-2 000 g, 1 754-2 321 g, 1 842-2 591 g, 1 913-2 615 g, 2 150-2 847 g, 2 350-3 130 g and 2 450-3 250 g, respectively. The incidences of hypertensive disorders in pregnancy, FGR, fetal distress and neonatal asphyxia related to SGA twin pregnancies were significantly higher than AGA twin pregnancies (all P <0.05). The incidence of GDM in twin pregnant from 2017 to 2020 was higher than that from 2004 to 2009 or from 2010 to 2016, but the incidence of fetal distress and neonatal asphyxia were lower than those from 2010 to 2016, and the differences were statistically significant (all P <0.05). Conclusions: The appropriate weights of twin fetuses at different gestational weeks are different from singleton. The incidence of pregnancy complications and adverse outcomes in AGA fetuses is significantly lower than that in SGA fetuses under the specific weight standard for twin fetuses, which could provide a practical basis for clinical management of twin pregnancy.

Objective: To explore differences among placental anastomoses, territory discordance, and umbilical cord insertion of twin-to-twin transfusion syndrome (TTTS) with and without selective intrauterine growth restriction (sIUGR)., Methods: This study retrospectively analyzed 57 patients with TTTS who received conservative treatment and finally delivered at the Department of Obstetrics and Gynecology of Peking University Third Hospital from April 2014 to April 2019. Nine of the patient's placentas were too broken to finish the perfusion, and 48 were kept for graph analysis after perfusion. Among the 48 placentas, there were 17 in the TTTS with sIUGR group and 31 in the TTTS without sIUGR group. Differences in the placentas were compared between groups., Results: The birth weight discordance ratio in the sIUGR group was significantly higher than that in the non-sIUGR group (0.41 ± 0.20 vs 0.24 ± 0.15, p  = .001). The prevalence of thick artery-artery (AA) anastomoses in the sIUGR group was significantly higher than that in the non-sIUGR group (35.3% vs 6.5%, p  = .017). The placental territory discordance ratio in the sIUGR group was significantly higher than that in the non-sIUGR group (0.40 [0.05, 0.86] vs 0.25 [0.02, 0.67], p  = .024). The prevalence of velamentous cord insertion in the sIUGR group was significantly higher than that in the non sIUGR group (35.3% and 6.5%, p  = .017)., Conclusions: Placental territory discordance and velamentous umbilical cord insertion may be causes of TTTS with sIUGR. Compared with TTTS without sIUGR, TTTS with sIUGR had a higher prevalence of protective AA anastomoses in the placenta.

Objective: Studies evaluating pregnancy outcomes in systemic sclerosis (SSc) are limited. SSc is associated with maternal complications and adverse neonatal outcomes. This study investigated the impact of disease stage (stable vs active) on the maternal and neonatal outcomes of pregnancies of patients followed at an Israeli medical centre., Method: The charts of 354 SSc female patients followed during 2003-2020 were reviewed. Data on clinical and laboratory features, number of pregnancies close to SSc diagnosis, and maternal and neonatal outcomes were analysed. Patients were divided into a stable disease and an active/early disease group., Results: The active/early disease group included 26 patients [19 diffuse SSc (dSSc)], with 38 pregnancies. Median disease duration was 1 year, except for four patients who were first diagnosed during pregnancy. SSc was exacerbated in all patients during pregnancy or shortly after delivery [skin, lung, and heart involvement in dSSc; severe vasculopathy in limited SSc patients]. Six patients had hypertensive disorders of pregnancy; four pregnancies ended with foetal death. Thirty-three children were born, 60% with intrauterine growth retardation (IUGR)/low birthweight (LBW). The stable disease group included 19 patients, including seven with previously active disease, now stabilized (five dSSc), and 32 pregnancies. All pregnancies were planned and monitored closely. Disease remained stable in all patients. Four patients had hypertensive disorders of pregnancy; 12/29 newborns had LBW (41%)., Conclusion: Active maternal disease during pregnancy poses an increased risk of SSc aggravation. The maternal and neonatal outcomes in planned pregnancy during stable disease are favourable. IUGR/LBW is common among neonates, even in stable disease.

Background: Stillbirth, preterm birth, and small for gestational age (SGA) birth have an increased recurrence risk. The occurrence of one of these biologically related outcomes could also increase the risk for another one of these outcomes in a subsequent pregnancy., Objectives: We assessed cross-outcome risks for subsequent stillbirth, preterm birth, and SGA., Methods: We used live birth and fetal death records to identify singleton, sequential birth pairs in California (1997-2017). Stillbirth was defined as delivery at ≥20 weeks of gestation of a foetus that died in utero; preterm birth as live birth at 20-36 weeks; and small for gestational age as sex-specific birthweight <10th percentile for gestational age. Risk ratios (RR) were computed using modified Poisson regression and adjusted for potential confounders. Sensitivity analyses included analysing a cohort restricted to primiparous index births and using inverse-probability censoring weights., Results: Of 3,108,532 birth pairs, 16,668 (0.5%), 260,596 (8.4%) and 331,109 (10.7%) of index births were stillborn, preterm and SGA, respectively. Among individuals with an index stillbirth, the adjusted RRs were 1.90 (95% confidence interval [CI] 1.83, 1.98) for subsequent preterm and 1.35 (95% CI 1.28, 1.41) for subsequent SGA. Among those with index preterm birth, the adjusted RRs were 2.02 (95% CI 1.92, 2.13) for stillbirth and 1.42 (95% CI 1.41, 1.44) for SGA. Among those with index SGA, the adjusted RRs were 1.54 (95% CI 1.46, 1.63) for stillbirth and 1.45 (95% CI 1.44, 1.47) for preterm birth. Similar results were reported for sensitivity analyses., Conclusions: Individuals experiencing stillbirth, preterm birth, or SGA in one pregnancy had an increased risk of one of these biologically related outcomes in a subsequent pregnancy. These findings could encourage enhanced surveillance for individuals who experience stillbirth, preterm birth, or SGA and desire a subsequent pregnancy., (© 2022 John Wiley & Sons Ltd.)

Background: The incidence of extrauterine growth retardation (EUGR) varies considerably in different countries due to the distinct definitions and inclusion criteria of individual studies. Most studies included small for gestational age (SGA) very preterm infants (VPIs), resulting in a higher incidence of EUGR. Experts have suggested the accurate definition of "EUGR" in SGA infants is not "true EUGR". The postnatal growth curve of multiple premature births also differs from that of singletons. As far as we know, there is no study about relationship between singleton-non-SGA preterm infants and EUGR., Objectives: To analyze the factors influencing EUGR among VPIs who were singleton-non-SGA in China., Methods: A prospective-multicenter study was conducted in 28 hospitals distributed through China from September 2019 to December 2020. The clinical data on singleton-non-SGA among VPIs were divided into EUGR group (n = 692) and non-EUGR group (n = 912)., Results: Compared to non-EUGR group, the mean gestational age (GA), mean birth weight (BW) and percentage of BW in Fenton curve in EUGR group were lower (P < 0.001 for all). The incidence of EUGR among distinct GA groups (classifications of GA < 28weeks, 28-28 +6 weeks, 29-29 +6 weeks, 30-30 +6 weeks and 31-31 +6 weeks) and distinct BW groups (classifications of BW<1000 g, 1000-1249 g, 1250-1499 g, 1500-1999g and 2000-2500 g) were statistically significant (P = 0.004 and P <.001). Logistic regression analysis indicated that later addition of human milk fortifier (HMF), later attainment of HMF sufficient fortification, later return to BW, more accumulative days of fasting, longer duration of parenteral nutrition, total duration of oxygen support and moderate/severe bronchopulmonary dysplasia (BPD) were risk factors for the development of EUGR in singleton-non-SGA VPIs (P < 0.001, P = 0.002, P < 0.001, P = 0.002, P = 0.017, P = 0.003 and P = 0.002, respectively). The use of full-course antenatal steroids, greater BW as a percentile of the Fenton curve, breastfeeding initiation and faster average velocity of weight growth effectively protected against EUGR (P = 0.008, P < 0.001, P < 0.001 and P < 0.001, respectively)., Conclusions: The overall incidence of EUGR was 43.1% among singleton-non-SGA VPIs in China. Raising the full-course antenatal steroids usage, reducing the incidence of moderate and severe BPD, attaching importance to the management of enteral nutrition in VPIs and increasing the weight growth velocity can reduce the incidence of EUGR., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to assess the rate of adverse obstetrical and neonatal outcomes in pregnancies diagnosed with confined placental mosaicism relative to that of unaffected controls., Data Sources: Web-based databases were searched using relevant key words, and articles published from 1980 to February 2022 were retrieved., Study Eligibility Criteria: Observational studies in English language including ≥10 cases of singleton pregnancies with diagnosis of confined placental mosaicism were included. The diagnosis was established after detection of any chromosomal abnormality at chorionic villus sampling for any indication, followed by normal karyotype from amniotic fluid or neonatal leukocyte culture., Methods: Two authors independently screened the references for eligibility, data extraction, and assessment of methodological quality using the Newcastle-Ottawa scale. All available obstetrical and neonatal outcomes were recorded. Random-effect meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals of available outcomes in pregnancies with and without confined placental mosaicism. Statistical heterogeneity was evaluated with I 2 statistics (International Prospective Register of Systematic Reviews registration number: CRD42021260319)., Results: Of the 80 articles reviewed, 8 retrospective matched-cohort studies (708 cases of confined placental mosaicism and 11,599 unaffected controls) compared cases with and without confined placental mosaicism and were included in the meta-analysis. The risk of delivering small-for-gestational-age neonates was significantly increased in confined placental mosaicism pregnancies according to crude analysis (odds ratio, 2.45; 95% confidence interval, 1.23-4.89; I 2 =72%) and to sensitivity analysis of high-quality studies (odds ratio, 3.65; 95% confidence interval, 2.43-5.57; I 2 =0%). Similarly, confined placental mosaicism resulted in an increased risk of birthweight below the third centile (odds ratio, 5.33; 95% confidence interval, 1.19-24.19; I 2 = 83%). Subgroup analysis revealed that the risk of delivering small-for-gestational-age neonates was 3-fold higher for confined placental mosaicism excluding trisomy 16, and 11-fold higher for cases including trisomy 16 only vs unaffected controls, respectively. No difference was found in the risk of low birthweight and preterm birth (at <37 weeks' gestation). Other outcomes were insufficiently reported, therefore they were not analyzed., Conclusion: Pregnant women prenatally diagnosed with confined placental mosaicism have an increased risk of impaired fetal growth, suggesting the need for intensified antenatal surveillance., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Sex impacts birthweight, with male babies heavier on average. Birthweight charts are thus sex specific, but ultrasound fetal weights are often reported by sex neutral standards. We aimed to identify what proportion of infants would be re-classified as SGA if sex-specific charts were used, and if this had a measurable impact on perinatal outcomes., Methods: Retrospective cohort study including all infants born in Victoria, Australia, from 2005-2015 (529,261 cases). We applied GROW centiles, either adjusted or not adjusted for fetal sex. We compared overall SGA populations, and the populations of males considered small by sex-specific charts only (SGAsex-only), and females considered small by sex-neutral charts only (SGAunadjust-only)., Results: Of those <10th centile by sex-neutral charts, 39.6% were male and 60.5% female, but using sex-specific charts, 50.3% were male and 49.7% female. 19.2% of SGA females were reclassified as average for gestational age (AGA) using sex-specific charts. These female newborns were not at increased risk of stillbirth, combined perinatal mortality, NICU admissions, low Apgars or emergency CS compared with an AGA infant, but were at greater risk of being iatrogenically delivered on suspicion of growth restriction. 25.0% male infants were reclassified as SGA by sex-specific charts. These male newborns, compared to the AGAall infant, were at greater risk of stillbirth (RR 1.94, 95%CI 1.30-2.90), combined perinatal mortality (RR 1.80, 95%CI 1.26-2.57), NICU admissions (RR 1.38, 95%CI 1.12-1.71), Apgars <7 at 5 minutes (RR 1.40, 95%CI 1.25-1.56) and emergency CS (RR 1.12, 95%CI 1.06-1.18)., Conclusions: Use of growth centiles not adjusted for fetal sex disproportionately classifies female infants as SGA, increasing their risk of unnecessary intervention, and fails to identify a cohort of male infants at increased risk of adverse outcomes, including stillbirth. Sex-specific charts may help inform decisions and improve outcomes., Competing Interests: The authors have declared that no competing interests exist.

Objectives: We conducted a systematic review and meta-analysis to quantitatively summarize the present data on the association of prenatally identified lateral placenta in singleton pregnancies with small for gestational age (SGA) neonates, preeclampsia and other perinatal outcomes., Methods: From inception to November 2021, we searched PubMed/Medline, Scopus and The Cochrane Library for papers comparing the risk of SGA and preeclampsia, as well as other perinatal outcomes in singleton pregnancies with a prenatally identified lateral placenta to those with non-lateral placentas. The revised Newcastle-Ottawa Scale was used to evaluate the quality of eligible papers. The I 2  test was employed to evaluate the heterogeneity of outcomes among the studies. To investigate the possibility of publication bias, funnel plots were constructed. Prospero RN: CRD42021251590., Results: The search yielded 5,420 articles, of which 16 were chosen, comprising of 15 cohort studies and one case control study with a total of 4,947 cases of lateral and 96,035 of non-lateral placenta (controls) reported. SGA neonates were more likely to be delivered in cases with a lateral placenta (OR: 1.74; 95% CI: 1.54-1.96; p<0.00001; I 2 =47%). Likewise, placental laterality was linked to a higher risk of fetal growth restriction (OR: 2.18; 95% CI: 1.54-3.06; p<0.00001; I2=0%), hypertensive disorders of pregnancy (OR: 2.39; 95% CI: 1.65-3.51; p=0.0001; I 2 =80%), preeclampsia (OR: 2.92; 95% CI: 1.92-4.44; p<0.0001; I 2 =82%) and preterm delivery (OR: 1.65; 95% CI: 1.46-1.87; p<0.00001; I 2 =0%)., Conclusions: The prenatal diagnosis of a lateral placenta appears to be associated with a higher incidence of preeclampsia, fetal growth restriction, preterm delivery and SGA. This may prove useful in screening for these conditions at the second trimester anomaly scan., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Introduction: Villitis of unknown etiology (VUE) is associated with fetal growth restriction (FGR) and adverse short-term neonatal outcomes. No investigation to date has found which VUE features are driving the association with FGR diagnosis., Methods: A retrospective cohort study of placenta pathology specimens (2013-2017) was conducted. Independent variables of interest were: VUE distribution (focal vs diffuse), location (basal vs non-basal), and grade (high vs low). The primary outcome was FGR, and secondary outcomes were neonatal intensive care unit (NICU) admission, NICU length of stay, Apgar scores <7 at 1, 5, and 10-min, and recurrence rate of villitis in subsequent pregnancies. Association between VUE characteristics and our primary outcome were investigated using logistic regression. Secondary outcomes were explored with regression analyses and recurrence rate of VUE for members of the cohort with a recorded subsequent pregnancy was calculated., Results: One hundred and twenty seven placentas were included. Adjusted models showed no difference in the odds of FGR between high-grade versus low-grade VUE [aOR 1.25 95% CI (0.50, 3.26), p = 0.6], focal/multi-focal vs diffuse cases [aOR 1.03 95% CI (0.28, 4.34), p = >0.9], and basal vs non-basal VUE [aOR 0.06 95% CI (0.00, 1.10), p = 0.058]. After adjusting for prematurity <37 weeks, there were lower odds of NICU admission in basal vs non-basal cases [aOR 0.25, 95% CI (0.06, 0.90), p = 0.048). There was no difference in the odds of neonates presenting with Apgar <7 for the distinct VUE histopathology features. Three cases had recurrent VUE, resulting in a 6.8% [95% CI (3.02%, 10.61%)] recurrence rate. All recurrent cases were high-grade and identified with basal localization., Discussion: There are no statistical associations between distinct VUE features and FGR diagnosis, however location of villitis may be associated with worse neonatal outcomes. Villitis of any type (severity, degree, location) could potentially drive insufficient placental function and poor fetal growth., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Report survival rates, neonatal mortality and morbidity and long-term outcomes of monochorionic (MC) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) or TTTS plus selective fetal growth restriction (sFGR) treated by endoscopic laser surgery., Methods: Retrospective cohort study including 149 MC twin pregnancies complicated by TTTS or TTTS plus sFGR.Medical records were reviewed for survival rates, neonatal mortality, neonatal morbidity and long-term outcomes at 2 and 6 years of age., Results: Survival of both babies was higher in the TTTS group than in the TTTS plus sFGR group (72.9%vs.54.8%); survival of at least one baby was similar in the two groups (90.7% and 88.1%). The incidence of severe neurological disability was not significantly different between TTTS and TTTS plus fetal growth restriction group at both stages, 1.9% versus 2.3% (p-value = 1) and 3.4%vs6.1% (p-value = 0.31). Multivariable analysis demonstrated that intact neurological outcome at 2 years of age was related with gestational age (GA) at birth and z score birthweight (Z BW), and at 6 years of age with GA at birth, Z BW and TTTS stage4. sFGR or abnormal brain findings at neonatal ultrasound were not related with impaired neurological outcome at two or 6 years of age., Conclusions: In pregnancies with TTTS and TTTS plus sFGR survival of at least one baby and long-term neurological outcome are comparable between both groups., (© 2022 John Wiley & Sons Ltd.)

Tobacco smoking is an important public health issue recognized by the world health organization as one of the most serious, preventable risk factors for developing a series of pregnancy pathologies. Maternal smoking is positively associated with intrauterine growth restriction (IUGR) and gestational diabetes (GDM), but negatively associated with preeclampsia (PE). In this review, we examine epidemiological, clinical and laboratory studies of smoking effects on immunoregulation during pregnancy, trophoblast function, and placental vasculature development and metabolism. We aim to identify effects of tobacco smoke components on specific placental compartments or cells, which may contribute to the understanding of the influences of maternal smoking on placenta function in normal and pathological pregnancies. Data corroborates that in any trimester, smoking is unsafe for pregnancy and that its detrimental effects outweigh questionable benefits. The effects of maternal smoking on the maternal immune regulation throughout pregnancy and the impact of different tobacco products on fetal growth have not yet been fully understood. Smoking cessation rather than treatment with replacement therapies is recommended for future mothers because also single components of tobacco and its smoke may have detrimental effects on placental function., (Copyright © 2021. Published by Elsevier Ltd.)

Background: There are multiple etiologies for being born small for gestational age (SGA). However, extended familial data in idiopathic cases have been scarcely reported., Objective: Our aim was to explore the familial history of SGA newborns and describe the proportion and distribution of SGA in their parents and parental siblings., Methods: This was a retrospective study performed at an obstetrics clinic holding a detailed reliable electronic database. Between 2008 and 2017, data of 14,003 patients and 20,617 pregnancies were recorded. Parents of SGA infants were identified and extended familial history was obtained by questionnaires, including birth weights (BWs) and gestational age at birth of the parents and parents' siblings. SGA was defined as a BW below the 10th percentile. Proportions of maternal, paternal, and parental siblings' SGA were calculated. Chi-square test was performed to assess the relationship between SGA family member's gender and SGA infants' gender, and between the relative's gender and their family relationship to the infant., Results: About 2100 women had a history of a previous infant born SGA, however, after exclusion the final cohort comprised 926 women with a previous SGA infant. In 473 cases there was at least one other family member of the infant born SGA: father, mother, aunt, or uncle of the infant, representing a prevalence of 51% (473/926) of familial SGA. Out of familial SGA cases, maternal SGA was found in 55% (260/473), and paternal SGA was found in 28.1% (133/473). 27.6% had more than one SGA relative. Eighteen infants had both an SGA father and an SGA mother (3.8%). A history of an SGA aunt or uncle was found in 44% (209/473) of familial SGA cases, which was 22.5% (209/926) of the entire cohort. Parental sibling SGA occurred almost twice in mother's siblings as compared to father's siblings. Chi-square test revealed no association between the SGA relative's gender and their family relationship to the infant. There was no association between the SGA infant's gender and the SGA relative's gender., Conclusions: A family history of SGA is common in SGA infants, and occurs most often in mothers. This study found 22% SGA in parental siblings, in maternal siblings more than paternal siblings, supporting the possibility of a genetic component in SGA trait transmission. In clinical practice, when counseling parents with a growth-restricted fetus from an unknown etiology, extended familial birthweight history should be obtained and taken into account, which may be helpful in reducing parental anxiety.

Background: Postnatal growth restriction (PGR) is common in very preterm infants (VPIs) and is associated with adverse short and long-term developmental outcomes. Postnatal growth status for VPIs in middle- or low-income countries remains unclear., Aims: To evaluate PGR in VPIs and identify maternal and neonatal factors, clinical practice, and major neonatal morbidities associated with PGR in China., Study Design: Prospective cohort study., Subjects: We included 6085 infants born at <32 weeks gestation who were admitted at 57 hospitals in the Chinese Neonatal Network in 2019., Outcome Measures: Birth and discharge weights were converted to age-specific Z-scores. PGR was defined as a decrease in weight z-score from birth to discharge >2., Results: The overall incidence of PGR was 19.9 %. The mean (standard deviation [SD]) weight Z-score was 0.12 (0.78) at birth and decreased to -1.36 (0.98) at discharge. About 4.0 % of VPIs were small for gestational age (SGA) at birth and 25.5 % of SGA infants had PGR. The incidence of PGR increased with decreasing gestational age except in the SGA subgroup. Each 1-unit increase in birthweight Z-score was associated with a 1.49-fold increased risk for PGR. Late initiation of enteral feeds and late achievement of full enteral feeds were positively associated with PGR. The common morbidities that influenced PGR were necrotizing enterocolitis ≥ stage II, patent ductus arteriosus requiring medical or surgical treatment, sepsis, bronchopulmonary dysplasia, and respiratory distress syndrome requiring surfactants., Conclusion: Nearly one fifth of VPIs were PGR, and one fourth of SGA had PGR, which warranted further study to investigate underlying causes by which to improve postnatal growth in very preterm infants in future., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose and confirm that there is no prior presentation of study data as an abstract or poster., (Copyright © 2022. Published by Elsevier B.V.)

Pathological low birth weight due to fetal growth restriction (FGR) is an important predictor of adverse obstetric and neonatal outcomes. It is more common amongst native lowlanders when gestating in the hypoxic environment of high altitude, whilst populations who have resided at high altitude for many generations are relatively protected. Genetic study of pregnant populations at high altitude permits exploration of the role of hypoxia in FGR pathogenesis, and perhaps of FGR pathogenesis more broadly. We studied the umbilical cord blood DNA of 316 neonates born to pregnant women managed at the Sonam Norboo Memorial Hospital, Ladakh (altitude 3540m) between February 2017 and January 2019. Principal component, admixture and genome wide association studies (GWAS) were applied to dense single nucleotide polymorphism (SNP) genetic data, to explore ancestry and genetic predictors of low birth weight. Our findings support Tibetan ancestry in the Ladakhi population, with subsequent admixture with neighboring Indo-Aryan populations. Fetal growth protection was evident in Ladakhi neonates. Although no variants achieved genome wide significance, we observed nominal association of seven variants across genes (ZBTB38, ZFP36L2, HMGA2, CDKAL1, PLCG1) previously associated with birthweight., Competing Interests: The authors have declared that no competing interests exist.

Combustible cigarette smoking impacts fetal growth during pregnancy. However, the risk associated with heated tobacco products (HTPs) remains unclear. This nationwide cross-sectional study investigated whether HTP use during pregnancy is associated with small for gestational age (SGA) outcomes among 5647 post-delivery women with singleton pregnancies, which were divided into four groups: lifetime never-smokers, former smokers before pregnancy, and current smokers for each of the tobacco products during pregnancy (sole HTP and sole combustion smokers). Information on the prevalence of SGA, defined as birth weight and height below the 10th percentile, was retrieved from the Maternal and Child Health Handbooks of post-delivery women. Using logistic regression, the association between sole HTP smokers during pregnancy and SGA, adjusted for covariates, with lifetime never-smokers as reference, was investigated. The prevalence was: current sole HTP smokers during pregnancy, 1.8% (102/5647); and SGA, 2.9% (164/5647). Sole HTP smokers during pregnancy had a higher prevalence of SGA (5.9% [6/102] vs. 2.7% [111/4144]) with an adjusted odds ratio (OR) of 2.50 (95% confidence interval [CI], 1.03-6.05) than lifetime never-smokers. Among sole combustion smokers, the adjusted OR for SGA was 1.95 (95% CI, 0.81-4.67). In Japan, HTP smoking during pregnancy may be associated with an increased risk for SGA., Competing Interests: The authors declare no conflict of interest.

Objective: This study aimed to describe neurodevelopment in fetal growth restriction children at the age of six. Secondly, we tried to demonstrate influencing factors that can improve or exacerbate this development, as well as predictive factors that might select a population at risk to assist with early childhood support., Method: It was a study of 70 children affected with FGR. FGR was based on these definitions: birth weight below the 3rd percentile or birth weight below the 10th percentile with an abnormal hemodynamic Doppler study. Neurodevelopment was assessed at 6 years old by means of Batelle Development Inventory. A global development quotient under a 100 score was considered a neurodevelopment delay. All variables regarding pregnancy care, delivery episode, postpartum, neonatal care, sociodemographic issues, and the need for support in the first years were studied., Results: The mean gestational age at diagnosis was 33.14 weeks (standard deviation (SD = 4.31), with 32.9% of early-onset diagnoses. The mean gestational age at delivery was 35.61 (SD = 3.21), and the cesarean rate was 64.3%. The average age of the children at the moment of the evaluation was 76.20-month-old (SD = 3.70). The mean global development quotient was 97.28 (SD = 13.97). We were able to record a 57.1% of global development delay. In the cases of cognition, only 17.1% of the children registered a delay. Motor and communication skills were the most frequently affected. We discovered that socioeconomic status was positively related to the global development quotient, as well as both gestational age at delivery and middle cerebral artery pulsatility index was positively related to the global development quotient., Conclusions: We found a higher neurodevelopment delay rate (57.1%). We could relate a higher gestational age at delivery and a higher MCA percentile with better global neurodevelopment quotients.

Background: The COVID-19 pandemic has been associated with a worsening of perinatal outcomes in many regions around the world. Melbourne, Australia, had one of the longest and most stringent lockdowns worldwide in 2020 while recording only rare instances of COVID-19 infection in pregnant women., Objective: This study aimed to compare the stillbirth and preterm birth rates in women who were exposed or unexposed to lockdown restrictions during pregnancy., Study Design: This was a retrospective, multicenter cohort study of perinatal outcomes in Melbourne before and during the COVID-19 lockdown. The lockdown period was defined as the period from March 23, 2020 to March 14, 2021. Routinely-collected maternity data on singleton pregnancies ≥24 weeks gestation without congenital anomalies were obtained from all the 12 public hospitals in Melbourne. We defined the lockdown-exposed cohort as those women for whom weeks 20 to 40 of gestation occurred during the lockdown and the unexposed control group as women from the corresponding calendar periods 12 and 24 months before. The main outcome measures were stillbirth, preterm birth, fetal growth restriction (birthweight < third centile), and iatrogenic preterm birth for fetal compromise. We performed multivariable logistic regression analysis to compare the odds of stillbirth, preterm birth, fetal growth restriction, and iatrogenic preterm birth for fetal compromise, adjusting for multiple covariates., Results: There were 24,817 births in the exposed group and 50,017 births in the control group. There was a significantly higher risk of preterm stillbirth in the exposed group than the control group (0.26% vs 0.18%; adjusted odds ratio, 1.49; 95% confidence interval, 1.08-2.05; P=.015). There was also a significant reduction in the preterm birth of live infants <37 weeks (5.68% vs 6.07%; adjusted odds ratio, 0.93; 95% confidence interval, 0.87-0.99; P=.02), which was largely mediated by a significant reduction in iatrogenic preterm birth (3.01% vs 3.27%; adjusted odds ratio, 0.91; 95% confidence interval, 0.83-0.99; P=.03), including iatrogenic preterm birth for fetal compromise (1.25% vs 1.51%; adjusted odds ratio, 0.82; 95% confidence interval, 0.71-0.93; P=.003). There were also significant reductions in special care nursery admissions during lockdown (11.53% vs 12.51%; adjusted odds ratio, 0.90; 95% confidence interval, 0.86-0.95; P<.0001). There was a trend to fewer spontaneous preterm births <37 weeks in the exposed group of a similar magnitude to that reported in other countries (2.69% vs 2.82%; adjusted odds ratio, 0.95; 95% confidence interval, 0.87-1.05; P=.32)., Conclusion: Lockdown restrictions in Melbourne, Australia were associated with a significant reduction in iatrogenic preterm birth for fetal compromise and a significant increase in preterm stillbirths. This raises concerns that pandemic conditions in 2020 may have led to a failure to identify and appropriately care for pregnant women at an increased risk of antepartum stillbirth. Further research is required to understand the relationship between these 2 findings and to inform our ongoing responses to the pandemic., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Accumulating evidence suggests that vitamin D deficiency increases the risk of adverse perinatal outcomes. However, the dose-response relationship between maternal vitamin D status and adverse birth outcomes remains unclear. Focusing on prospective observational studies, we aimed to explore the dose-response relationship of vitamin D status with the risk of low birth weight (LBW), macrosomia (MA), preterm birth (PTB), small for gestational age (SGA), and intrauterine growth restriction (IUGR)., Methods: Databases including PubMed, Embase, Scopus, and Web of Science were used up to 19 January 2021 to search for observational studies that fulfilled criteria as follows: cohort studies, case-cohort studies, or nested case-control studies. Random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs) in the observational studies., Results: A total of 72 publications were included in this systematic review and 71 in the meta-analysis. Maternal 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with the risk of LBW (RR: 0.65; 95% CI 0.48-0.86), PTB (RR: 0.67; 95% CI 0.57-0.79), and SGA (RR: 0.61; 95% CI 0.49-0.76) in the highest versus lowest meta-analysis, but not associated with MA and IUGR. Linear dose-response analysis showed that each 25 nmol/L increase in 25(OH)D was associated with a 6% and 10% reduction in the risk of PTB (RR: 0.94; 95% CI 0.90-0.98) and SGA (RR: 0.90; 95% CI 0.84-0.97), respectively., Conclusion: Our study suggests that a sufficient vitamin D status during pregnancy is protective against the risk of LBW, PTB, and SGA., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: This study aimed to investigate and compare the prenatal and neonatal outcomes of monochorionic twin pregnancies complicated with fetal growth restriction (sFGR) with or without twin-to-twin transfusion syndrome (TTTS) after cord occlusion by radiofrequency ablation (RFA)., Methods: This prospective cross-sectional study was conducted in women with monochorionic twin pregnancies of 16 to 26 weeks of gestational age (GA) in an academic hospital from 2016 to 2020. Demographic and obstetrical characteristics such as cervical length, GA of RFA and delivery, amnioreduction, cesarean section (C/S) rate, and maximum vertical pocket as well as prenatal, neonatal, and maternal outcomes were evaluated and compared between groups using Statistical Package for the Social Sciences (SPSS). Mann-Whitney U test or independent t test was used for quantitative data and Chi square test was applied for comparing qualitative variables. The significance level of tests was 0.05., Results: Totally 213 (106 sFGR and 107 TTTS+sFGR) cases were enrolled. The mean of maternal age (P=0.787), body mass index (P=0.932), gestational age at RFA (P=0.265), as well as gestational age of delivery (P=0.482), and C/S rate (P=0.124) were not significant between the two groups, but a significant difference (P<0.001) in cervical length was observed between the two groups. No significant differences were found in newborn and fetal outcomes such as fetal demise (P=0.827), PPROM (P=0.233), abortion (P=0.088), and admission to intensive care unit (P=0.822) between the groups., Conclusion: Although worse fetal and neonatal outcomes were expected in the TTTS+sFGR group after RFA, no significant difference was observed between groups., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

Prior international studies have shown mixed results regarding the association of hepatitis B and hepatitis C with adverse pregnancy outcomes. We performed an updated evaluation of the prevalence of associated adverse pregnancy outcomes and evaluated trends over time of diagnosis of chronic hepatitis B (HBV) and chronic hepatitis C (HCV) in pregnant women in a national database. All pregnant women with HBV and HCV were identified from the National Inpatient Sample database 2012 to 2018. Multivariate logistic regression analyses were performed to compare pregnancy-related complications, including rates of preeclampsia/eclampsia, gestational diabetes, intrauterine growth restriction, antepartum/intrapartum hemorrhage, preterm labor, and Cesarean section. We evaluated all-cause in-hospital mortality, length of stay, and total cost of hospitalizations. A total of 28.7 million pregnancy-related hospitalizations that met our eligibility criteria were identified, including 51,200 with HBV and 131,695 with HCV. In comparison with the uninfected controls, the HBV group was significantly more likely to develop gestational diabetes (12.94% vs. 6.94%, p < 0.001). The HCV group was more likely to have preterm labor (9.63% vs. 6.27%, p < 0.001), intrauterine growth restriction (6.04% vs. 2.89%, p < 0.001), longer length of stay (3.4 days vs. 2.7 days, p < 0.001), and higher hospitalization cost (15,052 dollars vs. 14,258 dollars, p < 0.001). These findings should inform counseling of women who are found to have HBV or HCV during pregnancy regarding the risk of adverse pregnancy outcomes and support the need for an interdisciplinary approach to optimize maternal and neonatal outcomes., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Small-for-gestational-age neonates (birthweight of <10th percentile for gestational age) are significantly more likely to have multiple adverse outcomes than appropriate-for-gestational-age neonates (birthweight of 10th-90th percentile). Most small-for-gestational-age neonates are undetected during pregnancy (ie, not diagnosed as fetal growth restriction), but the sequela of being undetected remains uncertain., Objective: The primary objective of this study was to compare the composite neonatal adverse outcomes among singleton pregnancies that were at least 37 weeks and delivered small-for-gestational-age neonates, which were diagnosed as either fetal growth restriction during pregnancy (detected small for gestational age) or not (undetected small for gestational age)., Study Design: This was a secondary analysis of a retrospective cohort, the Consortium for Safe Labor. Singleton births at 37.0 to 41.6 weeks of gestation without congenital anomalies born small for gestational age were included in the analysis. The primary outcome was the rate of composite neonatal adverse outcome, defined as any of the following: Apgar score of <5 at 5 minutes, cardiopulmonary resuscitation at birth, respiratory distress syndrome, continuous positive airway pressure, mechanical ventilation, neonatal seizures, hypoxic-ischemic encephalopathy or diagnosis of asphyxia, intraventricular hemorrhage, necrotizing enterocolitis, neonatal sepsis, or fetal or neonatal death. The secondary outcome was the rate of composite maternal adverse outcome, which included any of the following: postpartum hemorrhage, peripartum infection, thromboembolism, hysterectomy, uterine rupture, eclampsia, intensive care unit admission, or maternal death. Small for gestational age with a prenatal diagnosis of fetal growth restriction (detected small for gestational age) was compared with small for gestational age without a prenatal diagnosis of fetal growth restriction (undetected small for gestational age). Multivariate logistic regression models were used to compare groups. A P value of <.05 was considered statistically significant. Gestational age-specific risks of composite neonatal adverse outcome and perinatal death were computed for each week of gestation among ongoing pregnancies., Results: Of the 228,438 deliveries in the Consortium for Safe Labor, 18,607 (8.1%) met the inclusion criteria. Among these deliveries, 17,689 (95.0%) were undetected small for gestational age, and 918 (5.0%) were detected small for gestational age. The overall rate of composite neonatal adverse outcome was 3.0%. Moreover, the rate of composite neonatal adverse outcome was similar between undetected small for gestational age and detected small for gestational age (3.0% vs 3.9%, respectively; adjusted odds ratio, 1.33; 95% confidence interval, 0.88-2.00). Some components of the composite-respiratory distress syndrome, mechanical ventilation, and necrotizing enterocolitis-were significantly higher among undetected small for gestational age than among detected small for gestational age. The overall rate of composite maternal adverse outcome was 6.2%. The rate of composite maternal adverse outcome between undetected small for gestational age and detected small for gestational age (6.2% vs 5.1%, respectively; adjusted odds ratio, 0.84; 95% confidence interval, 0.60-1.18) was similar. In gestational age-specific comparisons of composite neonatal adverse outcome, no difference was found between the undetected small-for-gestational-age group and the detected small-for-gestational-age group except for in pregnancies >41 weeks. In pregnancies at 41.0 to 41.6 weeks, the rate of composite neonatal adverse outcome was significantly greater in detected small for gestational age than in undetected small for gestational age (10.0% vs 2.5%, respectively; P=.035)., Conclusion: Antenatal detection of small for gestational age was not associated with improved composite neonatal adverse outcomes, although some components of morbidity improved with detection. Maternal outcomes did not differ between detected small for gestational age and undetected small for gestational age., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We investigated the relationships between syndromic manifestations of defective placentation and the incidence of intellectual disability (ID) in offspring by conducting a population-based cohort study of 1,581,200 nonmalformed, live singleton infants born in Sweden between 1998 and 2014. Exposures were: 1) placental abruption, 2) preterm preeclampsia (<34 weeks of gestation), 3) preeclampsia combined with infant being small for gestational age (SGA) at birth, and 4) spontaneous preterm birth. The outcome was an ID diagnosis after 3 years of age. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for each syndrome using Cox regression and robust variances. There were 9,451 children with ID (5.5 per 10,000 child-years). ID incidence rates increased with placental abruption (HR = 2.8, 95% CI: 2.3, 3.5), preterm preeclampsia (HR = 3.7, 95% CI: 2.9, 4.7), preeclampsia combined with SGA (HR = 3.3, 95% CI: 2.6, 4.1), and spontaneous preterm birth (for 32-36 and 22-31 weeks, respectively, HR = 1.6 (95% CI: 1.4, 1.8) and 5.2 (95% CI: 4.3, 6.2)). The same pattern of results was evident in sibling-controlled analyses among 1,043,158 full siblings. The strength of associations increased with ID severity. Preterm birth only partly explained the associations of placental abruption, preeclampsia, or SGA with ID. We conclude that defective placentation is related to increased incidence of ID in the offspring., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Many growth charts provide single centile cutoffs for each week of gestation, yet fetuses gain weight throughout the week. We aimed to assess whether using a single centile per week distorts the proportion of infants classified as small and their risk of stillbirth across the week., Design: Retrospective cohort study., Setting: Victoria, Australia., Population: Singleton, non-anomalous infants born from 2005-2015 (529,261)., Methods: We applied growth charts to identify small-for-gestational-age (SGA) fetuses on week-based charts (single centile per gestational week) and day-based charts (centile per gestational day)., Main Outcome Measures: Proportions <10th centile by each chart, and stillbirth risk amongst SGA infants., Results: Using week-based charts, 12.1% of infants born on the first day of a gestational week were SGA, but only 7.8% on the final day; ie. an infant born at the end of the week was 44% less likely to be classed as SGA (p<0.0001). The relative risk of stillbirth amongst SGA infants born on the final day of the week compared with the first was 1.47 (95%CI 1.09-2.00, p = 0.01). Using day charts, SGA proportions were similar and stillbirth risk equal between the beginning and end of the week (9.5% vs 9.9%)., Conclusions: Growth standards using a single cutoff for a gestational week overestimate the proportion of infants that are small at the beginning of the week and underestimate the proportion at the end. This distorts the risk of stillbirth amongst SGA infants based on when in the week an infant is born. Day-based charts should be used., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: Women with epilepsy treated with antiseizure medication (ASM) have increased risk of pregnancy complications including preterm birth, fetal growth restriction, and preeclampsia. We aimed to investigate whether folic acid supplementation is associated with these pregnancy complications in women with epilepsy using ASM., Methods: Singleton pregnancies in the prospective Norwegian Mother and Child Cohort Study (MoBa) (1999-2008) were included. Information on maternal epilepsy, ASM, folic acid supplementation, and pregnancy outcomes was obtained from the MoBa questionnaires and the Norwegian Medical Birth Registry. The main exposure, periconceptional folic acid supplementation, was defined as intake between 4 weeks before pregnancy and 12 weeks into pregnancy, retrospectively collected by recall of the mothers in weeks 17-19. The primary outcomes were preterm birth (gestational age <37 weeks at birth), small for gestational age (SGA), and preeclampsia., Results: The study included 100,105 pregnancies: 99,431 without maternal epilepsy, 316 with maternal epilepsy and ASM exposure in pregnancy, and 358 with untreated maternal epilepsy. Among ASM-treated women with epilepsy, the risk of preterm birth was higher in those who did not use periconceptional folic acid (n = 64) compared with those who did (n = 245, the reference) (adjusted odds ratio [aOR] 3.3, 95% CI 1.2-9.2), while the risk of preterm birth among the reference was similar to the risk among women without epilepsy using folic acid periconceptionally (aOR 0.9, 95% CI 0.5-1.6). ASM-treated women with epilepsy starting folic acid after the first trimester had a higher risk compared with women without epilepsy with similar timing of folic acid (aOR 2.6, 95% CI 1.1-6.5), and even higher if not using folic acid (aOR 9.4, 95% CI 2.6-34.8). Folic acid was not associated with risk of preterm birth among women with epilepsy without ASM or among women without epilepsy. Folic acid was not associated with risk of preeclampsia or SGA among women with epilepsy., Discussion: In women with epilepsy using ASM, periconceptional folic acid was associated with a lower risk of preterm birth. This finding supports the recommendation that ASM-treated women with epilepsy of childbearing potential should use folic acid supplementation on a regular basis., Classification of Evidence: This study provides Class III evidence that for women with epilepsy using ASM, periconceptional folic acid supplementation decreases the risk of preterm birth., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Substantial evidence show that intrauterine growth restriction (IUGR) is linked to both short-term and long-term health consequences. Recent studies have shown that the intrauterine environment harbors a diverse community of microbes. However, the relationship between intrauterine microbiome and IUGR has been rarely studied. In our investigation of 35 neonates with IUGR and 187 neonates without IUGR, we found that the intrauterine microbiome was largely composed of nonpathogenic commensal microbiota from the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes phyla. Carriage of genera Afipia [odds ratio (OR) 0.24; 95% confidence interval (CI) 0.10-0.60], Hydrogenophaga (OR 0.10; 95% CI 0.01-0.76), and Perlucidibaca (OR 0.25; 95% CI 0.10-0.61) were significantly associated with decreased risk of IUGR, while one log10-unit increasing of relative abundance the genera Catenibacterium (OR 2.56; 95% CI 1.09-6.01) and Senegalimassilia (OR 1.78; 95% CI 1.00-3.16), and carriage of Holdemanella (OR 4.07; 95% CI 1.54-10.76), Parvimonas (OR 3.33; 95% CI 1.16-9.57), Sandaracinus (OR 3.27; 95% CI 1.21-8.84), and Streptococcus (OR 3.52; 95% CI 1.13-10.95) were associated with increased risk of IUGR. The present study firstly demonstrated that carriage of Afipia, Hydrogenophaga, and Perlucidibaca in the intrauterine environment is associated with a decreased risk of IUGR, while carriage of Holdemanella, Parvimonas, Sandaracinus, and Streptococcus, and increased relative abundance of Catenibacterium and Senegalimassilia are associated with an increased risk of IUGR. The study provides evidence that the intrauterine microbiome may play a role in the etiology of IUGR.

Background: Small-for-gestational-age neonates (SGA) are at increased risk of neonatal morbidity. Nulliparity represents a risk factor for SGA; birthweight charts may perform differently for the detection of SGA among nulliparas. This study aimed at describing the prevalence of SGA in nulliparas according to different birthweight charts and evaluating the diagnostic performance of these charts to maternal and perinatal outcomes., Methods: This is a secondary analysis of a Brazilian cohort of nulliparas named Preterm SAMBA study. Birthweight centiles were calculated using the Intergrowth-21st, WHO-Fetal Growth Charts, Birth in Brazil population chart and GROW-customised chart. The risks of outcomes among SGA neonates and their mothers in comparison to neonates with birthweights between the 40 th -60 th centiles were calculated, according to each chart. ROC curves were used to detect neonatal morbidity in neonates with birth weights below different cutoff centiles for each chart., Results: A sample of 997 nulliparas was assessed. The rate of SGA infants varied between 7.0-11.6%. All charts showed a significantly lower risk of caesarean sections in women delivering SGA neonates compared to those delivering adequate-for-gestational-age neonates (OR 0.55-0.64, p < .05). The charts had poor performance (AUC 0.492 - 0.522) for the detection of neonatal morbidity related to SGA born at term., Conclusion: The populational and customised birthweight charts detected different prevalence of small-for-gestational-age neonates and showed similar and poor performance to identify related neonatal adverse outcomes in this population., (© 2022. The Author(s).)

Phthalates (PAEs) are common endocrine disrupting chemicals (EDCs) that disrupt fetal development. The present study aimed to evaluate the effects of single and coexposure to phthalates in early pregnancy on fetal growth restriction (FGR) by a nested case-control study based on the Guangxi Zhuang Birth Cohort (GZBC). Maternal serum concentrations of seven phthalates in 97 neonates with FGR and 291 matched controls were detected through gas chromatography-mass spectrometry (GC-MS). The associations between phthalates and FGR were analyzed using multiple logistic regression, weight quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. We found that exposures to butyl-benzyl phthalate (BBP, OR adj  = 1.849, 95% CI: 1.080-3.177, P adj  = 0.025, P trend  = 0.046), di (2-ethyl-hexyl) phthalate (DEHP, OR adj  = 3.893, 95% CI: 1.305-11.910, P adj  = 0.015, P trend  = 0.098) and dimethyl phthalate (DMP, OR adj  = 1.722, 95% CI: 1.089-2.725, P adj  = 0.020, P trend  = 0.002) were significantly positively associated with the risk of FGR, while mono-butyl phthalate (MBP) showed a significant negative association with FGR (OR high  = 0.192, 95% CI: 0.036-0.795, P adj  = 0.033, P trend  = 0.035) only among girls. The WQS model identified that BBP, di(2-ethyl)phthalate (DEP), DMP, DEHP, di-n-butyl phthalate (DBP), and MBP were highly weighted in the association with FGR. The BKMR model supported the positive association between joint exposure to phthalates and the risk of FGR and identified no significant interaction between the seven phthalates. Overall, maternal exposure to BBP, DEHP, and DMP may cause adverse effects on FGR, especially with combined effects., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Fetal growth restriction (FGR) is the primary cause of infant morbidity and mortality. Although nutritional intervention is generally used to cure FGR, its effects on early- and late-onset FGR have not been reported. This study aimed to resolve this issue in a real-world setting., Study Design: We collected the data of pregnant women whose fetuses were diagnosed with FGR and subsequently born at Nanshan Women and Children's Care Hospital in Shenzhen, China. We conducted a MANOVA and series of Cox regression analyses to evaluate the effects of a prenatal nutritional intervention on early and late FGR after adjusting for potential confounders., Results: Our results demonstrated that the average birth weights in the four sub-intervention groups were 50.36-160.05 g higher than those in the nonintervention group. These differences were insignificant with respect to early-onset FGR. In late-onset FGR, however, the interventions led to birth weight increases of 164.95-244.45 g greater than those in the nonintervention group, and these differences were significant. During early-onset FGR, four different nutritional interventions reduced the incidence of small-for-gestational age by 8.00-13.76% relative to the incidence in the nonintervention group, while in late-onset FGR, the incidence decreased by 11.37-17.39%., Conclusions: Our results based on a real-world setting reaffirmed that a prenatal nutritional intervention could improve the birth outcomes in cases of FGR and further suggested a better effectiveness on late-onset FGR.

Objective: To characterize abnormal growth processes and their associated cardiovascular abnormalities in SGA fetuses using Individualized Growth Assessment (IGA)., Methods: This longitudinal investigation utilized a SGA cohort [EFW and BW <10th percentile] derived from the PORTO study. Fetuses categorized by their Fetal Growth Pathology Score [FGPS1] patterns [Pattern 2 { n  = 12}, Pattern 3 { n  = 11}, Pattern 5 { n  = 13}] were evaluated. Growth pathology was measured using the -FGPS1 and the individual composite Prenatal Growth Assessment Score {-icPGAS]. Paired cardiovascular assessments utilized measurements of the Pulsatility Index [umbilical artery {UA}, middle cerebral artery {MCA}, ductus venosus {DV}] and the myocardial performance index [MPI; heart]. Outcome variables were birth age [preterm or, term] and birth weight [small or normal (IGA criteria)]., Results: Pattern 2 was usually characterized by a single, growth abnormality (67% of cases) of variable magnitude that occurred within two weeks of delivery {median onset age: 37.6 weeks}. The incidence of UA abnormalities was low (25%) while those of MCA and DV/MPI were high {60%, 42%}. Most neonates were of normal size (67%) and delivered at term (67%).Pattern 3 had an initial progressive growth restriction phase, followed by constant but abnormally low growth. Growth pathology had an early onset (median age: 31.6 weeks), was moderate but persistently abnormal. The incidences of cardiovascular abnormalities were moderate [30-50%]. Most neonates were abnormally small (80%) but delivered at term (90%).Pattern 5 had an initial progressive phase with an early onset [onset age {median}: 31.6 weeks]. However, this process was arrested and returned toward normal. Growth pathology magnitudes were minor as were the incidences of cardiovascular abnormalities. Neonatal size was usually normal and all fetuses delivered at term., Conclusions: Characteristics of SGA Growth Restricted, Patterns 2, 3 and 5 are clearly different from those found in SGA Normal or SGA Growth Restricted Pattern 1 groups. They also differed from one another, indicating that growth restriction can manifest itself in several different ways. Pattern 2 is similar to "late" growth restriction reported previously. Patterns 3 and 5 are novel and have been designated as "adaptive" and "recovering" types of growth restriction.

Background: Chronic hypertension (CH) adversely impacts pregnancy. It remains unclear whether antihypertensive treatment alters these risks. We examined the role of antihypertensive treatment in the association between CH and adverse pregnancy outcomes., Methods: Electronic health records from the UK Caliber and Clinical Practice Research Datalink were used to define a cohort of women delivering between 1997 and 2016. Primary outcomes were preeclampsia, preterm birth (PTB), and fetal growth restriction (FGR). We used multivariable logistic regression to compare outcomes in women with CH to women without CH and propensity score matching to compare antihypertensive agents., Results: The study cohort consisted of 1 304 679 women and 1 894 184 births. 14 595 (0.77%) had CH, and 6786 (0.36%) were prescribed antihypertensive medications in pregnancy. Overall, women with CH (versus no CH), had higher odds of preeclampsia (adjusted odds ratio [aOR], 5.74 [95% CI, 5.44-6.07]); PTB (aOR, 2.53 [2.39-2.67]); and FGR (aOR, 2.51 [2.31-2.72]). Women with CH prescribed treatment (versus untreated women) had higher odds of preeclampsia (aOR, 1.17 [1.05-1.30]), PTB (1.25 [1.12-1.39]), and FGR (1.80 [1.51-2.14]). Women prescribed methyldopa (versus β-blockers) had higher odds of preeclampsia (aOR, 1.43 [1.19-1.73]); PTB (1.59 [1.30-1.93]), but lower odds of FGR (aOR, 0.66 [0.48-0.90]). Odds of adverse outcomes were similar in relation to calcium channel blockers (versus β-blockers) except for PTB (aOR, 1.94 [1.15-3.27]). Among women prescribed treatment, lower average blood pressure (<135/85 mm Hg) was associated with better pregnancy outcomes., Conclusions: Treatment with antihypertensive agents and control of hypertension ameliorates some effects but higher risks of adverse outcomes persist. β-Blockers versus methyldopa may be associated with better pregnancy outcomes except for FGR. Powered trials are needed to inform optimal treatment of CH during pregnancy.

Background and Aims: The incidence of inflammatory bowel disease (IBD) among women is highest during their reproductive years and current estimates suggest that the rate of conception is low in female IBD patients. The aim of our study was to assess the burden of adverse maternal and perinatal outcomes among female IBD patients., Methods: Using the national inpatient sample database from 2016 to 2018, we recruited all female patients above the age of 15 years admitted with a primary diagnosis of pregnancy and a secondary diagnosis of IBD. We adjusted our results for hospital and patient level variables including age, race, socioeconomic status, hypertension, diabetes mellitus, obesity, smoking, hyperlipidemia, alcohol use, and malnutrition. Multivariable regression analysis was used for analysis., Results: Pregnant women with IBD had greater odds of gestational diabetes (adjusted odds ratio [AOR] 1.55, 95% confidence interval [CI] 1.04-2.3, p 0.02), hypertensive complications (AOR 1.35, 95% CI 1.06-1.72, p 0.01), and pre-term delivery (AOR, 1.41 95% CI 1.13-1.76, p 0.003). Pregnancies with co-existent IBD were associated with fetal growth restriction (AOR 1.27, 95% CI 1-1.63, p 0.04) and fetal death (AOR 3.21, 95% CI 1.72-6.00, p < 0.01). Odds of experiencing postpartum hemorrhage or large for gestational age infant were comparable to general population. Crohn's disease was independently associated with increased odds of worse maternal and fetal outcome. IBD patients had increased mean length of stay by 0.14 days and increased mean hospital charges of $2741., Conclusions: Women with IBD had greater likelihood of poor maternal and fetal outcomes and increased hospital resource utilization., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The effect of severe maternal infectious morbidity on fetal growth during the second half of pregnancy is under debate. Preliminary evidence suggests that such association may be plausible. The objectives of this study were to determine: 1) The association between severe maternal infectious morbidity and adverse pregnancy outcome; and 2) The effect of maternal infection during pregnancy on fetal growth., Study Design: This retrospective population - based cohort study included 4771 women who gave birth at our medical center during the study period. Parturients were allocated into two groups: 1) patients with severe maternal infection during the second half of pregnancy (n = 368); and 2) control group comprised of normal pregnant women who were matched to the study group by maternal age, gravidity and parity (n = 4403)., Results: The severe maternal infection group included women with pneumonia (n = 198), pyelonephritis (n = 131), and viral pneumonitis (n = 39). In comparison to the normal patients group: 1) having had pneumonia during the second half of pregnancy was associated with increased rates of fetal growth restriction, placental abruption, fetal demise (P < 0.001, for all comparisons) and preeclampsia (P = 0.041); 2) Pyelonephritis during the second half of gestation was associated with higher rates of fetal growth restriction (P < 0.001), placental abruption (P = 0.006) and labor induction (P = 0.039). As a group, women with severe maternal infection had higher rates of small for gestational age neonates compared to normal parturients (P < 0.001). Among women with infections, only those who had pyelonephritis (P = 0.032) or pneumonia (P = 0.008), had a higher rate of small for gestational age neonates than those in the control group. After adjustment to confounding factors, maternal infection (OR = 1.42, 95% CI 1.085-1.85) and previous delivery of a small for gestational age neonate (OR = 2.54, 95% CI 2.02-3.19), were independent risk factors for the delivery of a small for gestational age neonate., Conclusion: Severe maternal infectious morbidity during the second half of pregnancy is an independent risk factor for the delivery of a small for gestational age neonate and is associated with adverse pregnancy outcomes. Both, pneumonia and pyelonephritis, during the second half of gestation affect fetal growth and are related to higher rates of small for gestational age neonates., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Nutritional deficiency soon after birth is a risk factor of chronic lung disease (bronchopulmonary dysplasia, BPD). Afflicted infants are further prone to inadequate growth during hospitalization (extrauterine growth restriction, EUGR). This multi-center retrospective study investigated risk factors of EUGR, specifically in very preterm infants with BPD., Method: Data of infants with BPD who were born less than 32 weeks gestation (n = 1010) were collected from 7 regions of China. All infants were non-small for gestational age at birth. Infants were characterized as EUGR or non-EUGR at 36 weeks gestation or discharge, or stratified by gestational age or birthweight. Logistic regression analysis was applied., Results: In 65.5% of the population, the BPD was mild. Infants with severe BPD (8.3%) had the highest rate of EUGR (72.6%, P < 0.001). Groups stratified by gestational age did not differ in rates of EUGR, but the birthweight of the EUGR group was significantly lower than that of the non-EUGR (P < 0.001). Birthweights of < 1000, 1000-1499, and ≥ 1500 g showed EUGR rates of 65.9%, 43.4%, and 23.8%, respectively (P < 0.001). Overall, the independent risk factors of EUGR were: moderate-to-severe BPD, gestational hypertension, cesarean section, cumulative fasting time, time required to achieve 110 kcal/kg/d, and hemodynamically significant patent ductus arteriosus (hsPDA)., Conclusion: In very preterm infants with BPD, the lower the birthweight or the more severe the BPD, the greater the risk of EUGR. In those with hsPDA, or moderate-to-severe BPD, it is especially important to prevent EUGR through perinatal management, enteral nutrition, and nutritional strategies., (© 2022. The Author(s).)

Introduction: Background: small-for-gestational-age (SGA) newborns present a higher morbidity and mortality rate when compared to infants born appropriate for gestational age (AGA), as well as insufficient growth, with height far from their target and in some cases a low final height (< -2 SDs). Objective: the aim of this study was to determine when catch-up growth (CUG) in height occurs in these children, and which factors are associated with lack of CUG. Material and methods: this is a retrospective study of SGAs born between 2011 and 2015 in a secondary hospital. Anthropometric measurements were taken consecutively until CUG was reached, and fetal, placental, parental, newborn, and postnatal variables were studied. Results: a total of 358 SGAs were included from a total of 5,585 live newborns. At 6 and 48 months of life, 93.6 % and 96.4 % of SGAs achieved CUG, respectively. By subgroups, symmetric SGAs performed worse than asymmetric SGAs with CUG in 84 % and 92 % at 6 and 48 months of life, respectively. The same occurred in the subgroup of preterm SGAs with respect to term SGAs, with worse CUGs of 88.2 % and 91.2 % at 6 and 48 months of life, respectively. Prematurity, symmetrical SGA, intrauterine growth retardation (IUGR), preeclampsia, previous child SGA, perinatal morbidity, and comorbidity during follow-up were associated with absence of CUG. Conclusions: the majority of SGAs had CUG in the first months of life. The worst outcomes were for preterm and symmetric SGAs.

Objectives: India has a high rate of stillbirths, and many deaths are due to fetal growth restriction and potentially preventable. Screening and identification of the small for gestational age (SGA) fetus during the antenatal period has been shown to reduce stillbirths. We set out to evaluate the impact of implementing the Growth Assessment Protocol (GAP), a programme designed for screening for SGA., Methods: Observational study comparing two-time epochs; before (years 2011-2014) and after (years 2015-2018) introduction of GAP. The programme includes identification of risk factors, risk categorization, serial fundal height measurement, customised fetal growth charts and appropriate referral protocols. Fetal growth charts and birth centiles were generated based on the hospital database of normal outcome pregnancies, customised to women's ethnicity, parity, height, and weight. The protocol was introduced following training of obstetric and midwifery care providers. We evaluated SGA detection rates, stillbirth rates (from 28 weeks) and neonatal morbidity at term., Results: There were 26,199 and 31,498 births, with 115 and 108 stillbirths in the pre and post-GAP implementation periods, respectively. SGA detection rates increased from 51.1 to 67.1%, representing a 31% improvement (p<0.001). Overall stillbirth rates declined from 4.4 to 3.4 per 1000 births (RR 0.78 CI 95% 0.60-1.02) and at term from 1.5 to 0.6 (RR 0.37 CI 95% 0.20-0.66). Neonatal intensive care admission and neonatal encephalopathy in term neonates also decreased significantly., Conclusions: Introduction of the GAP programme in an Indian tertiary maternity service was associated with improved antenatal detection of SGA and reduced stillbirth rates and neonatal morbidity., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)