Antenatal Fetal Adrenal Measurements at 22 to 30 Weeks' Gestation, Fetal Growth Restriction, and Perinatal Morbidity.

OBJECTIVE: Our objective was to test the association of fetal adrenal size with perinatal morbidity among fetuses with fetal growth restriction (FGR; estimated fetal weight [EFW] < 10th percentile). STUDY DESIGN: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) adrenal study, which measured fetal adrenal gland size at 22 to 30 weeks' gestation. We analyzed the transverse adrenal area (TAA) and fetal zone area (absolute measurements and corrected for fetal size) and the ratio of the fetal zone area to the total transverse area using a composite perinatal outcome of stillbirth, neonatal intensive care unit admission, respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, sepsis, mechanical ventilation, seizure, or death. Among fetuses with FGR, adrenal measurements were compared between those that did and did not experience the composite perinatal outcome. RESULTS: There were 1,709 eligible neonates. Seven percent (n = 120) were diagnosed with FGR at the time of adrenal measurement, and 14.7% (n = 251) experienced perinatal morbidity. EFW-corrected and absolute adrenal measurements were similar among fetuses with and without FGR as well as among those who did and did not experience morbidity. The area under the curve for corrected TAA was 0.52 (95% confidence interval 0.38-0.67). CONCLUSION: In our cohort, adrenal size was not associated with risk of morbidity among fetuses with FGR.

Residential proximity to roadways and placental-associated stillbirth: a case-control study.

We conducted a retrospective case-control study of 1,097 women in Massachusetts and Rhode Island, USA, to examine the association between stillbirth related to placental abruption or placental insufficiency and maternal exposure to traffic-related air pollution. We utilized distance to nearest roadway proximity metrics as a proxy for traffic-related air pollution exposure. No meaningful increase in the overall odds of placental-associated stillbirths was observed (adjusted OR: 1.1, 95% CI: 0.5-2.8). However, mothers living within 50 m of a roadway had a 60% increased odds of experiencing a stillbirth related to placental abruption compared to mothers living greater than 200 m away. This suggestive finding was imprecise due to the small case number in the highest exposure category (95% CI: 0.6-4.0). Future studies of placental abruption with more precise exposure assessments are warranted.

Reduced growth velocity from the mid-trimester is associated with placental insufficiency in fetuses born at a normal birthweight.

BACKGROUND: Fetal growth restriction (FGR) due to placental insufficiency is a major risk factor for stillbirth. While small-for-gestational-age (SGA; weight < 10th centile) is a commonly used proxy for FGR, detection of FGR among appropriate-for-gestational-age (AGA; weight ≥ 10th centile) fetuses remains an unmet need in clinical care. We aimed to determine whether reduced antenatal growth velocity from the time of routine mid-trimester ultrasound is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency among term AGA infants. METHODS: Three hundred and five women had biometry measurements recorded from their routine mid-trimester (20-week) ultrasound, at 28 and 36 weeks' gestation, and delivered an AGA infant. Mid-trimester, 28- and 36-week estimated fetal weight (EFW) and abdominal circumference (AC) centiles were calculated. The EFW and AC growth velocities between 20 and 28 weeks, and 20-36 weeks, were examined as predictors of four clinical indicators of placental insufficiency: (i) low 36-week cerebroplacental ratio (CPR; CPR < 5th centile reflects cerebral redistribution-a fetal adaptation to hypoxia), (ii) neonatal acidosis (umbilical artery pH < 7.15) after the hypoxic challenge of labour, (iii) low neonatal body fat percentage (BF%) reflecting reduced nutritional reserve and (iv) placental weight < 10th centile. RESULTS: Declining 20-36-week fetal growth velocity was associated with all indicators of placental insufficiency. Each one centile reduction in EFW between 20 and 36 weeks increased the odds of cerebral redistribution by 2.5% (odds ratio (OR) = 1.025, P = 0.001), the odds of neonatal acidosis by 2.7% (OR = 1.027, P = 0.002) and the odds of a < 10th centile placenta by 3.0% (OR = 1.030, P < 0.0001). Each one centile reduction in AC between 20 and 36 weeks increased the odds of neonatal acidosis by 3.1% (OR = 1.031, P = 0.0005), the odds of low neonatal BF% by 2.8% (OR = 1.028, P = 0.04) and the odds of placenta < 10th centile by 2.1% (OR = 1.021, P = 0.0004). Falls in EFW or AC of > 30 centiles between 20 and 36 weeks were associated with two-threefold increased relative risks of these indicators of placental insufficiency, while low 20-28-week growth velocities were not. CONCLUSIONS: Reduced growth velocity between 20 and 36 weeks among AGA fetuses is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency. These fetuses potentially represent an important, under-recognised cohort at increased risk of stillbirth. Encouragingly, this novel fetal assessment would require only one additional ultrasound to current routine care, and adds to the potential benefits of routine 36-week ultrasound.

Roles of the underlying cause of delivery and gestational age on long-term child health.

BACKGROUND: Clinical conditions leading to delivery are heterogeneous. However, most studies examining the short- and long-term consequences of birth on child health only consider gestational age at delivery, not the underlying cause. OBJECTIVE: To examine the effect of both gestational age at delivery and underlying cause of delivery on child health outcomes. METHODS: This population-based retrospective cohort study of singleton infants born in Alberta (April 2004-March 2005) used linked administrative and perinatal data to identify birth subtypes by underlying cause (infection/inflammation (I/I), placental dysfunction (PD), both, or neither), gestational age at delivery, and child health outcomes (neonatal morbidity and mortality, paediatric complex chronic conditions, and neurodevelopmental disorders and disabilities). Poisson regression with robust variance was used to assess differences in the (adjusted) risk ratio (RR) of each outcome by gestational age, and by cause of delivery. The roles of gestational age and cause of delivery were examined using mediation analysis methods. RESULTS: A total of 38,192 children were included, with 66.7% experiencing neither I/I nor PD (I/I: 4.0%, PD: 27.5%, both: 1.8%). Infants born preterm had higher risk of all outcomes compared to those born at term and late-term. Infants with exposure to both causes had higher risk of all outcomes (neonatal morbidity, RR 8.96, 95% confidence interval [CI] 7.55, 10.63; paediatric complex chronic conditions, RR 3.94, 95% CI 3.08, 5.05; and neurodevelopmental disorders, RR 1.58, 95% CI 1.37, 1.84). The effect of underlying cause of delivery on child health outcomes was partially explained by gestational age, more in cases involving I/I than in those involving PD alone. CONCLUSIONS: Short- and long-term child health outcomes differ by the underlying cause leading to delivery, as well as the gestational age at delivery. Having a clearer prognosis for infants may promote the use of clinical interventions earlier for children at increased risk.

Association of abnormal placental perfusion with the risk of male hypospadias: a hospital-based retrospective cohort study.

BACKGROUND: The effect and extent of abnormal placental perfusion (APP) on the risk of male hypospadias are poorly understood. We compared the prevalence of male hypospadias in the offspring of women with APP and quantify the extent of the APP effect on the anomaly. METHODS: A hospital-based retrospective analysis of births from 2012 to 2016 was conducted in 2018. Women of singleton pregnancy and male infants born to them were included (N = 21,447). A multivariate analysis was performed to compare the prevalence of male hypospadias in infants exposed to APP with those that were not exposed to APP. RESULTS: Compared with the infants of women without APP, infants of women with APP showed an increased risk of male hypospadias (odds ratio, 2.40; 95% confidence interval, 1.09-5.29). The male hypospadias cumulative risk increased with the severity of APP. Infants exposed to severe APP had a significantly higher risk of male hypospadias than those without APP exposure (9.2 versus 1.7 per 1000 infants, P < 0.001). A path analysis indicated that 28.18-46.61% of the risk of hypospadias may be attributed to the effect of APP. CONCLUSIONS: Male hypospadias risk was associated with APP and increased with APP severity, as measured in the second trimester. APP had an important role in the development of the anomaly.

Postmortem examination protocol and systematic re-evaluation reduce the proportion of unexplained stillbirths.

Background Stillbirth often remains unexplained, mostly due to a lack of any postmortem examination or one that is incomplete and misinterpreted. Methods This retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, Helsinki University Hospital, Finland, and comprised 214 antepartum singleton stillbirths from 2003 to 2015. Maternal and fetal characteristics and the results of the systematic postmortem examination protocol were collected from medical records. Causes of death were divided into 10 specific categories. Re-evaluation of the postmortem examination results followed. Results Based on our systematic protocol, the cause of death was originally defined and reported as such to parents in 133 (62.1%) cases. Re-evaluation of the postmortem examination results revealed the cause of death in an additional 43 (20.1%) cases, with only 23 (10.7%) cases remaining truly unexplained. The most common cause of stillbirth was placental insufficiency in 56 (26.2%) cases. A higher proportion of stillbirths that occurred at ≥39 gestational weeks remained unexplained compared to those that occurred earlier (24.1% vs. 8.6%) (P = 0.02). Conclusion A standardized postmortem examination and a re-evaluation of the results reduced the rate of unexplained stillbirth. Better knowledge of causes of death may have a major impact on the follow-up and outcome of subsequent pregnancies. Also, closer examination and better interpretation of postmortem findings is time-consuming but well worth the effort in order to provide better counseling for the grieving parents.

Achieving orphan designation for placental insufficiency: annual incidence estimations in Europe.

OBJECTIVE: To determine whether a novel therapy for placental insufficiency could achieve orphan drug status by estimating the annual incidence of placental insufficiency, defined as an estimated fetal weight below the 10th centile in the presence of abnormal umbilical artery Doppler velocimetry, per 10 000 European Union (EU) population as part of an application for European Medicines Agency (EMA) orphan designation. DESIGN: Incidence estimation based on literature review and published national and EU statistics. SETTING AND POPULATION: European Union. METHODS: Data were drawn from published literature, including national and international guidelines, international consensus statements, cohort studies and randomised controlled trials, and published national and EU statistics, including birth rates and stillbirth rates. Rare disease databases were also searched. RESULTS: The proportion of affected pregnancies was estimated as 3.17% (95% CI 2.93-3.43%), using a weighted average of the results from two cohort studies. Using birth rates from 2012 and adjusting for a pregnancy loss rate of 1/100 gave an estimated annual incidence of 3.33 per 10 000 EU population (95% CI 3.07-3.60 per 10 000 EU population). This fell below the EMA threshold of 5 per 10 000 EU population. CONCLUSIONS: Maternal vascular endothelial growth factor gene therapy for placental insufficiency was granted EMA orphan status in 2015 after we demonstrated that it is a rare, life-threatening or chronically debilitating and currently untreatable disease. Developers of other potential obstetric therapies should consider applying for orphan designation, which provides financial and regulatory benefits. TWEETABLE ABSTRACT: Placental insufficiency meets the European Medicines Agency requirements for orphan disease designation.

Incidence and Management of Umbilical Artery Flow Abnormalities during Open Fetal Surgery.

INTRODUCTION: Umbilical artery (UA) Doppler ultrasound is used to assess uteroplacental insufficiency. Absent or reversed end diastolic flow (AREDF) in the UA is associated with increased perinatal mortality in fetuses with intrauterine growth restriction. We describe the incidence of UA Doppler abnormalities during open fetal surgery. METHODS: We conducted a retrospective review of patients undergoing open in utero myelomeningocele (MMC) repair between 2008 and 2015. Intermittent UA Dopplers were performed during key portions of all cases. Our primary outcome was the rate of any AREDF. Secondary outcomes included analysis of absent versus reversed end diastolic flow (EDF), vasopressor use, and volatile anesthetic and clinical outcomes. RESULTS: Thirty-four of 47 fetuses developed UA Doppler abnormalities intraoperatively. Nineteen had absent EDF and 15 had reversed EDF. No AREDF was present before induction, and all AREDF resolved by postoperative day 1. Ten of 19 (52.6%) patients who received sevoflurane had reversed EDF, versus 5/28 (17.9%) for desflurane, odds ratio (95% CI) 5.11 (1.36-19.16), p = 0.02. One intraoperative fetal death occurred in the AREDF group. DISCUSSION: AREDF is a common phenomenon during open MMC repair. Anesthetic agent choice may influence this risk. Future studies of UA flow during fetal surgery are needed to further evaluate the impact of intraoperative AREDF on fetal well-being.

Short-term outcome of periviable small-for-gestational-age babies: is our counseling up to date?

OBJECTIVE: There are limited data for counseling on and management of periviable small-for-gestational-age (SGA) fetuses. We therefore aimed to investigate the short-term outcome of periviable SGA fetuses in relation to the likely underlying cause. METHODS: This was a retrospective study of data from three London tertiary fetal medicine centers obtained between 2000 and 2015. We included viable singleton pregnancies with a severely small fetus, defined as those with an abdominal circumference ≤ 3rd percentile, identified between 22 + 0 and 25 + 6 weeks' gestation. Data obtained included fetal biometry, presence of placental anomalies, uterine and fetal Doppler and neonatal outcome. We excluded cases with structural abnormalities, proven or suspected abnormal karyotype or genetic syndromes. Cases were classified according to the suspected underlying cause of the small fetal size into one of the following categories: uteroplacental insufficiency, evidence of placental damage with normal uterine artery Doppler, viral infection, or unclassied. RESULTS: There were 245 cases included in the study. Of these, at diagnosis of SGA, 201 (82%) were categorized as uteroplacental cause, 13 (5%) as suspected placental cause, one (0.4%) as suspected viral cause and 30 (12%) could not be assigned to any of these categories. Overall, 101 (41%) cases survived the neonatal period; 89 (36%) underwent in-utero fetal demise, 22 (9%) died neonatally and 33 (14%) pregnancies were terminated. The diagnosis-to-delivery interval was 8.1 weeks in those that survived and 4.5 weeks in those that died neonatally. CONCLUSIONS: Almost 90% of periviable SGA cases are associated with uteroplacental insufficiency or intraplacental damage. Survival is related to gestational age at delivery, with outcomes better than might be assumed at diagnosis and some pregnancies reaching term. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Number of episodes of reduced fetal movement at term: association with adverse perinatal outcome.

OBJECTIVE: The aims of this study were evaluation of the association of reduced fetal movements (RFM) and small-for-gestational-age (SGA) birth at term and to explore if fetal and maternal outcomes are different with single vs repeated episodes of RFM and normal fetal assessment test results. STUDY DESIGN: This was a retrospective cohort study of all singleton pregnancies referred for RFMs at a tertiary fetal medicine unit from January 2008 through September 2014. Ultrasound and Doppler indices were obtained from a computerized ultrasound database and pregnancy outcome was collected from hospital records. RESULTS: Of the 21,944 women with a singleton pregnancy booked for maternity care during the study period, 1234 women (5.62%) reported RFMs >36+0 weeks. Of these, 1029 women (83.4%) reported a single episode of RFM and 205 (16.6%) had ≥2 presentations for RFM. Women with repeated RFMs had a significantly higher mean uterine artery pulsatility index in the second trimester. The prevalence of SGA baby at birth in women presenting with a single episode as compared to repeated episodes of RFM was 9.8% and 44.2%, respectively (odds ratio, 7.3; 95% confidence interval, 5.1-10.4; P < .05). CONCLUSION: Repeated episodes of RFMs at term are more likely to occur in women with high second-trimester uterine artery Doppler resistance indices and are strongly associated with the birth of SGA infants. Women presenting with repeated episodes of RFM should be treated as being at high risk of placental dysfunction irrespective of the results of prenatal ultrasound and Doppler assessment.

Vasculoplacental complications in pregnant women with HIV infection: a case-control study.

OBJECTIVE: Data from the international literature suggest that there may be an association between maternal human immunodeficiency virus (HIV) infection and vasculoplacental complications during pregnancy. Studies on this subject have reached discordant conclusions. The aim of this study was to assess the incidence of vasculoplacental complications during pregnancy in women with and without HIV infection. STUDY DESIGN: This single-center case-control study compared the incidence of pregnancy-related hypertension, preeclampsia, eclampsia, and vascular intrauterine growth restriction in 280 women with HIV and 560 women not infected with HIV, matched for age, parity, and geographic origin. RESULTS: The incidence rates of pregnancy-related hypertension, preeclampsia, eclampsia, and vascular growth restriction did not differ between the women with and without HIV infection. The overall incidence of vasculoplacental complications did not differ between the 2 groups (7.5% vs 9.8%, respectively; P = .27). The risk of these was not associated with exposure to antiretroviral treatments, viral load, or CD4 T-cell counts at the beginning of pregnancy. CONCLUSION: This study shows no difference in the incidence of vasculoplacental complications between women with and without HIV infection.

Famines in the last 100 years: implications for diabetes.

Overnutrition is a major cause of diabetes. The contrary situation of undernutrition has also been suggested to increase the risk of the disease. Especially undernutrition during prenatal life has been hypothesized to program the structure and physiology of the fetus in such a way that it is more prone to develop diabetes in later life. Famines over the last 100 years have provided historical opportunities to study later-life health consequences of poor nutritional circumstances in early life. The majority of studies based on famine exposure during prenatal life clearly show that diabetes risk is increased. Postnatal famine exposure in childhood, adolescence, or young adulthood also seems to raise risk for diabetes, although prenatal famine effects seem to be more substantial. These study results not only have implications for the consequences of famines still happening but also for pregnancies complicated by factors mimicking poor nutritional situations.

Risk factors and consequences of maternal anaemia and elevated haemoglobin levels during pregnancy: a population-based prospective cohort study.

BACKGROUND: To determine sociodemographic and life style-related risk factors and trimester specific maternal, placental, and fetal consequences of maternal anaemia and elevated haemoglobin levels in pregnancy. METHODS: In a population-based prospective cohort study of 7317 mothers, we measured haemoglobin levels in early pregnancy [gestational age median 14.4 weeks (inter-quartile-range 12.5-17.5)]. Anaemia (haemoglobin ≤11 g/dl) and elevated haemoglobin levels (haemoglobin ≥13.2 g/dl) were defined according to the WHO criteria. Maternal blood pressure, placental function and fetal growth were measured in each trimester. Data on gestational hypertensive disorders and birth outcomes was collected from hospitals. RESULTS: Older maternal age, higher body mass index, primiparity and European descent were associated with higher haemoglobin levels (P < 0.05). Elevated haemoglobin levels were associated with increased systolic and diastolic blood pressure throughout pregnancy (mean differences 5.1 mmHg, 95% confidence interval [CI] 3.8, 6.5 and 4.1 mmHg, 95% CI 3.0, 5.2, respectively) and with a higher risk of third trimester uterine artery notching (RR 1.3, 95% CI 1.0, 1.7). As compared with maternal normal haemoglobin levels, not anaemia, but elevated haemoglobin levels were associated with fetal head circumference, length, and weight growth restriction from third trimester onwards (P < 0.05). Elevated haemoglobin levels were associated with increased risks of gestational hypertensive disorders (RR 1.4, 95% CI 1.1, 1.8) and adverse birth outcomes (RR 1.4, 95% CI 1.1, 1.7). CONCLUSIONS: In a low-risk population, various sociodemographic and life style factors affect haemoglobin levels during pregnancy. Elevated haemoglobin levels are associated with increased risks of maternal, placental, and fetal complications.

[Characterization of fetal deaths and associated factors in a high complexity hospital in a Latin American country]. / Caracterización de las muertes fetales y factores asociados en una institución latinoamericana de IV nivel de atención.

BACKGROUND: Stillbirth remains a problem; therefore requires delving analyzed to assess their causes and strategies that prevent or decrease. OBJECTIVE: To establish the frequency, describe the sociodemographic and medical characteristics, and factors associated with fetal death in a high complexity hospital in Bogotá, Colombia. MATERIALS AND METHODS: A cross-sectional study quantifying stillbirth and associated factors was conducted in the period from January 1, 2010 to December 31, 2013. RESULTS: There were 112 fetal deaths, from a total of 15408 births, for a fetal mortality rate of 7.3 per 1000 live births. The average age of the patients was 27.9 years (SD 7.7), 70.5 % of fetal deaths occurred in mothers aged 20-35 years, in primigravidae (33%), between 20 and 28 weeks gestational age (42.9%), in fetuses with weights between 500 and 1000 gr (47.8%). The most frequent medical history was hypothyroidism (5.4%) and chronic hypertension (4.5%). The most common diseases associated with pregnancy were oligohydramnios (21.4%), hypertensive disorders of pregnancy (17%), intrauterine growth restriction (IUGR) (17%), and polyhydramnios (16.9%). The most frequently altered test for evaluation of fetal wellbeing was the absent or decreased fetal movements (44.6%), autopsy was performed in 45.5% of cases being the main reported causes of death, chorioamnionitis (21.5%) and placental insufficiency (15.6%). CONCLUSION: Stillbirth remains a prevalent problem, our findings suggest the need to develop methods to implement the fetal surveillance in patients with risk factors in order to make timely decisions.

[PREDICTORS OF FORMATION OF NEW FORMS--OF BRONCHOPULMONARY DYSPLASIA AT THE PRENATAL STAGE].

The analysis of history in 116 premature infants, of which 74 children formed a new form of bronchopulmionary dysplasia. The analysis revealed that predictors of the formation of new forms of bronchopulmonary dysplasia are the pregnant woman, accompanied by hypoxia (jeopardy throughout pregnancy, fetoplacental insufficiency, hypotension, pregnancy, anemia) or infectious inflammation (presence of IgG to a pregnant ureaplasma, chorioamnionitis, polyhydramnios).

[Congenital heart diseases in pregnant women--a risk factor for fetal distress].

The condition of fetoplacental system in pregnant women with congenital heart diseases was studied by means of ultrasound, dopplerometry, cardiotocography, by determination of estradiol, progesterone and placental lactogen in the blood of pregnant women and in the umbilical cord and by means of pathomorphologic study of the placenta. It is shown that congenital heart diseases complicated by heart failure in pregnant women--a important risk factor for fetal distress bouth in the preclinical stage of placental insufficiency (violation of the utero-placental blood flow, changes of fetoplacental hormones levels) and in conjunction with clinical signs of fetal suffering (distress and growth retardation).

Factors related to fetal demise in cases with congenital heart defects.

BACKGROUND: Congenital heart defects are the most common congenital anomaly. Despite the increasing survival of these children, there is still an increased incidence of fetal demise, frequently attributed to cardiac failure. Considering that abnormal placental development has been described in congenital heart disease, our hypothesis is that placental insufficiency may contribute to fetal death in congenital heart disease. OBJECTIVE: This study aimed to assess cases with fetal congenital heart disease and intrauterine demise, and analyze factors that are related to the demise. STUDY DESIGN: All congenital heart disease cases diagnosed prenatally during the period January 2002 to January 2021 were selected from the regional prospective congenital heart disease registry, PRECOR. Multiple pregnancies and pregnancies with fetal trisomy 13 or 18, triploidy, and Turner's syndrome were excluded from the analysis, because fetal demise is attributed to the chromosomal abnormality in these cases. Cases were categorized into 4 groups based on the possible cause of fetal death as follows: cardiac failure, additional (genetic) diagnosis, placental insufficiency, and a group in which no cause was found. A separate analysis was performed for isolated congenital heart disease cases. RESULTS: Of the 4806 cases in the PRECOR registry, 112 had fetal demise, of which 43 were excluded from the analysis (13 multiple pregnancies, 30 genetic). Of these, 47.8% were most likely related to cardiac failure, 42.0% to another (genetic) diagnosis, and 10.1% to placental insufficiency. No cases were allocated to the group with an unknown cause. Only 47.8% of the cases had isolated congenital heart disease, and in this group 21.2% was most likely related to placental insufficiency. CONCLUSION: This study shows that in addition to cardiac failure and other (genetic) diagnoses, placental factors play an important role in fetal demise in congenital heart disease, especially in cases of isolated heart defects. Therefore, these findings support the importance of regular ultrasonographic assessment of fetal growth and placental function in fetal congenital heart disease.

Single umbilical artery in twin pregnancies.

OBJECTIVE: Our purpose was to evaluate the antenatal incidence of single umbilical artery (SUA) in twin pregnancies according to chorionicity and to assess its relationship with outcome. METHODS: Consecutive twin pregnancies undergoing ultrasound evaluation at our institutions were included. A targeted sonographic evaluation of the umbilical cord and vessels was performed in all cases. Chorionicity was determined according to standard ultrasound criteria. RESULTS: A total of 174 twin pregnancies, 100 dichorionic (DC) and 74 monochorionic (MC), were included in the study. An SUA was identified in 17 (9.8%) pregnancies, and in 18 (5.2%) fetuses. No difference was found in the incidence of SUA in DC and MC twins. Among affected pregnancies, all but one DC twin pregnancy were discordant for SUA. Structural and/or chromosomal abnormalities were present in 27.8% of fetuses with SUA. The prevalence of small-for-gestational-age fetuses and of discordant birth weight (> 20% discordance) was higher in the SUA group than in the rest of the population, although these differences were not statistically significant. Twin pairs discordant for SUA had significantly higher weight discordance than those with normal umbilical cords. The sonographic cross-sectional area of the SUA did not appear to show the typical adaptive dilatation usually seen in singleton pregnancies with SUA. CONCLUSIONS: The incidence of SUA in twins is higher than in singletons, with no difference between MC and DC twins. Intrapair discordance for SUA in identical twins provides evidence against an exclusively genetic origin of this anomaly. The apparent failure of compensatory dilatation of the umbilical artery in twins with SUA may explain in part the higher risk for fetal growth restriction in these cases.

An immunologic basis for placental insufficiency in fetal growth restriction.

OBJECTIVE: We sought to determine whether chronic villitis, an immunologic disease of the placenta, was related to fetal growth restriction. METHODS: Beginning in October 1999, a protocol was instituted that required placentas of high-risk births be submitted for standardized histological examination. Chronic villitis was diagnosed when a lymphohistiocytic infiltrate involving placental villi was present and was graded according to the extent and location of the infiltrate. Fetal growth restriction was defined as weight less than 3rd, 5th, and 10th percentiles. Placental hypoplasia was defined as weight less than 10th percentile. RESULTS: In the 10,204 placental examinations that were performed, low-grade and high-grade chronic villitis was associated with hypoplastic placentas and fetal growth restriction. Infants with placentas with low-grade and high-grade chronic villitis were more likely to require cesarean delivery for nonreassuring fetal heart rate compared with controls (27% and 25% versus 21%; p < 0.05). Fetal acidemia (umbilical artery pH < 7.0) was associated with high-grade chronic villitis compared with controls (4% versus 2%; p < 0.05). CONCLUSION: Chronic villitis was associated with anatomic and functional placental insufficiency manifested as placental hypoplasia, growth restriction, increased risk of cesarean for nonreassuring fetal heart rate, and fetal acidemia. These findings support an immunologic basis for fetal growth restriction.

Early Childhood Growth Parameters in South African Children with Exposure to Maternal HIV Infection and Placental Insufficiency.

Maternal HIV exposure and intrauterine growth restriction (IUGR) due to placental insufficiency both carry major risks to early child growth. We compared the growth outcomes of children aged 18 months who had abnormal umbilical artery resistance indices (UmA-RI), as a marker of placental insufficiency, with a comparator group of children with normal UmA-RI during pregnancy, as mediated by maternal HIV infection. The cross-sectional study included 271 children, grouped into four subgroups based on HIV exposure and history of normal/abnormal UmA-RI, using available pregnancy and birth information. Standard procedures were followed to collect anthropometric data, and z-scores computed as per World Health Organization growth standards. Lower length-for-age z-scores (LAZ) were observed in children who were HIV-exposed-uninfected (CHEU) (-0.71 ± 1.23; p = 0.004) and who had abnormal UmA-RI findings (-0.68 ± 1.53; p < 0.001). CHEU with abnormal UmA-RI had lower LAZ (-1.3 ± 1.3; p < 0.001) and weight-for-age z-scores (WAZ) (-0.64 ± 0.92; p = 0.014) compared to the control group. The prevalence of stunting was 40.0% in CHEU with abnormal UmA-RI and 16.0% in CHEU with normal UmA-RI (p < 0.001; p = 0.016, respectively). In conclusion, maternal HIV exposure and placental insufficiency are independent risk factors for childhood stunting, with this risk potentiated when these two risk factors overlap.