The human yolk sac size reflects involvement in embryonic and fetal growth regulation.

INTRODUCTION: The human yolk sac provides the embryo with stem cells, nutrients, and gas exchange. We hypothesized that more maternal resources, reflected in body size and body composition, would condition a a larger yolk sac, ensuring resources for the growing embryo. Thus, we aimed to determine the relation between maternal size in early pregnancy and yolk sac size. MATERIAL AND METHODS: This subsidiary study was embedded in the multinational World Health Organization fetal growth project that included healthy women with a body mass index of 18-30, reliable information of their regular last menstrual period and singleton pregnancies. Yolk sac diameter, crown-rump length, and maternal height, weight, body mass index, and body composition were assessed before 13 weeks of gestation, and the fetal biometry was repeated during the pregnancy. RESULTS: Of 140 participants, 122 with a successful yolk sac measurement were entered in the present analysis. Maternal weight was negatively associated with the yolk sac diameter (P = 0.007) and so was maternal height (P = 0.011), fat mass (P = 0.037), and lean body mass (P = 0.018), but not body mass index (P = 0.121). Significant effects were predominantly due to the female embryos and could be traced at 24 weeks of gestation. That is, a small yolk sac : crown-rump length ratio in early pregnancy was associated with a high fetal abdominal circumference (P < 0.001) and estimated fetal weight (P = 0.001). CONCLUSIONS: The human yolk sac is involved in the regulation of embryonic growth, but contrary to our hypothesis, the yolk sac has a compensatory capacity, being larger when the mothers are smaller; and the effect can be traced on fetal size at 24 weeks of gestation.

Velamentous or marginal cord insertion and the risk of spontaneous preterm birth, prelabor rupture of the membranes, and anomalous cord length, a population-based study.

INTRODUCTION: Anomalous cord insertion is associated with increased risk of adverse maternal and perinatal outcome. Our aim was to study whether anomalous cord insertion is associated with prelabor rupture of membranes (PROM), preterm PROM (pPROM), long or short umbilical cord, and time trend of spontaneous preterm birth (SPTB) and anomalous cord insertion. MATERIAL AND METHODS: A population-based register study using data from the Medical Birth Register of Norway including all singleton births (gestational age >16 weeks and <45 weeks) during 1999-2013 (n = 860 465) to calculate odds ratios (ORs) for PROM, pPROM, SPTB, and cord length (>95th or <5th centile) according to the cord insertion site by logistic regression with adjustment for possible confounders. We also assessed time trends of SPTB and anomalous cord insertion. RESULTS: Velamentous insertion of the cord was associated with an increased risk of PROM (OR 1.6, 95% CI 1.5-1.7), pPROM (OR 2.7, 95% CI 2.4-3.0), SPTB (OR 2.0, 95% CI 1.9-2.2), and a short cord (OR 1.7, 95% CI 1.5-1.8). Marginal insertion was to a lesser extent associated with these complications. Occurrences of SPTB and anomalous insertion declined. The decline in SPTB persisted after including an interaction term between anomalous insertion and time. CONCLUSIONS: Velamentous and, to a lesser extent, marginal cord insertions were associated with increased risk of PROM, pPROM, SPTB, and short cord. This suggests a common pathogenesis behind altered function of the membranes, cord, and placenta. The decline in SPTB could not be explained by the reduction in the occurrence of anomalous cord insertion.

Use of conditional centiles of middle cerebral artery pulsatility index and cerebroplacental ratio in the prediction of adverse perinatal outcomes.

INTRODUCTION: Centiles of middle cerebral artery pulsatility index and cerebroplacental ratio are useful for predicting adverse perinatal outcomes. A 'conditional centile' is conditioned by a previous measurement reflecting degree of individual change over time. Here we test whether such centiles are independent predictors and whether their combination improves prediction. MATERIAL AND METHODS: This prospective longitudinal study included 220 pregnant women diagnosed with or at risk of having a small-for-gestational-age fetus. Serial Doppler measurements of the umbilical artery and middle cerebral artery pulsatility indexs were used to calculate cerebroplacental ratio. Preterm birth, operative delivery due to fetal distress, admission to neonatal intensive care unit, 5-min Apgar score <7, newborn hypoglycemia, and perinatal mortality were considered adverse outcomes. Possible associations were analyzed by log-binomial regression analysis. RESULTS: Serial Doppler measurements of the middle cerebral artery were available in 207 participants and cerebroplacental ratio in 205. Conditional centiles ≤5 and ≤10 for both middle cerebral artery pulsatility index and cerebroplacental ratio were associated with increased risk for adverse perinatal outcomes. However, only the combination of cerebroplacental ratio centile and conditional centile ≤10 showed a better performance in the prediction of operative delivery due to fetal distress (p = 0.032), admission to neonatal intensive care unit (p = 0.048), and the combined variable "any adverse outcomes" (p = 0.034) compared with the use of centile ≤10 alone. CONCLUSIONS: Conditional centile for middle cerebral artery pulsatility index and cerebroplacental ratio ≤5 and ≤10 are associated with adverse perinatal outcomes. When adding conditional centile to conventional centile for cerebroplacental ratio, the prediction improved compared with the use of conventional centile alone.

Third stage of labor risks in velamentous and marginal cord insertion: a population-based study.

OBJECTIVE: To assess whether anomalous cord insertion is associated with risk of complications in the third stage of labor. DESIGN: A population-based study. SETTING: Norwegian Medical Birth Register. POPULATION: All singleton births (gestational age >16 weeks and <45 weeks) during the period 1999-2011 (n = 738,443 singletons). Deliveries by cesarean were excluded, leaving 628,680 vaginal singleton deliveries for the analyses. METHODS: Calculation of odds ratios for complications in the third stage of labor (postpartum hemorrhage, manual delivery of the placenta, curettage) in velamentous and marginal cord insertion by logistic regression with adjustment for confounders. MAIN OUTCOME MEASURES: Complications in the third stage of labor, postpartum hemorrhage, manual placental removal and curettage. RESULTS: Anomalous cord insertion was associated with an increased risk of complications in the third stage of labor, the risk being higher for velamentous than for marginal insertion. The risks persisted after adjusting for possible confounding factors. Velamentous cord insertion carried a 5.6% risk of a need for manual removal of the placenta, compared with the risk of 1.1% for nonvelamentous insertion (odds ratio = 5.21, 95% confidence interval 4.71-5.76) in vaginal delivery, and we found increased risks of curettage (odds ratio = 3.29, 95% confidence interval 2.87-3.77) and postpartum hemorrhage (odds ratio = 2.06, 95% confidence interval 1.77-2.39). CONCLUSIONS: Marginal and especially velamentous cord insertion is associated with an increased risk of hemorrhage in the third stage of labor, need for manual removal of the placenta and curettage. Anomalous cord insertion can be identified prenatally and so possibly influence obstetric management.

WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component.

BACKGROUND: In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. METHODS: This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week) to be performed by trained ultrasonographers.The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. DISCUSSION: The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards.

Fetal size in the second trimester is associated with the duration of pregnancy, small fetuses having longer pregnancies.

BACKGROUND: Conventionally, the pregnancy duration is accepted to be 280-282 days. Fetuses determined by ultrasound biometry to be small in early pregnancy, have an increased risk of premature birth. We speculate that the higher rate of preterm delivery in such small fetuses represents a pathological outcome not applicable to physiological pregnancies. Here we test the hypothesis that in low-risk pregnancies fetal growth (expressed by fetal size in the second trimester) is itself a determinant for pregnancy duration with the slower growing fetuses having a longer pregnancy. METHODS: We analysed duration of gestation data for 541 women who had a spontaneous delivery having previously been recruited to a cross-sectional study of 650 low-risk pregnancies. All had a regular menses and a known date of their last menstrual period (LMP). Subjects were examined using ultrasound to determine fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) at 10-24 weeks of gestation. Length of the pregnancy was calculated from LMP, and birth weights were noted. The effect of fetal size at 10-24 weeks of gestation on pregnancy duration was assessed also when adjusting for the difference between LMP and ultrasound based fetal age. RESULTS: Small fetuses (z-score -2.5) at second trimester ultrasound scan had lower birth weights (p < 0.0001) and longer duration of pregnancy (p < 0.0001) than large fetuses (z-score +2.5): 289.6 days (95%CI 288.0 to 291.1) vs. 276.1 (95%CI 273.6 to 278.4) for HC, 289.0 days (95%CI 287.4 to 290.6) vs. 276.9 days (95%CI 274.4 to 279.2) for AC and 288.3 vs. 277.9 days (95%CI 275.6 to 280.1) for FL. Controlling for the difference between LMP and ultrasound dating (using HC measurement), the effect of fetal size on pregnancy length was reduced to half but was still present for AC and FL (comparing z-score -2.5 with +2.5, 286.6 vs. 280.2 days, p = 0.004, and 286.0 vs. 280.9, p = 0.008, respectively). CONCLUSION: Fetal size in the second trimester is a determinant of birth weight and pregnancy duration, small fetuses having lower birth weights and longer pregnancies (up to 13 days compared with large fetuses). Our results support a concept of individually assigned pregnancy duration according to growth rates rather than imposing a standard of 280-282 days on all pregnancies.

The shifting trajectory of growth in femur length during gestation.

Bone size is a determinant of bone strength and tracks in its percentile of origin during childhood and adolescence. We hypothesized that the ranking of an individual's femur length (FL) is established in early gestation and tracks thereafter. Fetal FL was measured serially using 2D ultrasound in 625 Norwegian fetuses. Tracking was assessed using Pearson correlation, a generalized estimating equation model, and by calculating the proportion of fetuses whose FL remained within the same quartile. Baseline FL Z-score (weeks 10 to 19) and later measurements correlated, but more weakly as gestation advanced: r = 0.59 (weeks 20 to 26); r = 0.45 (weeks 27 to 33); and r = 0.32 (weeks 34 to 39) (p < 0.001). Tracking within the same quartile throughout gestation occurred in 13% of fetuses. Of the 87% deviating, 21% returned to the quartile of origin, so 34% began and ended in the same quartile, 38% deviated by one quartile, and 28% deviated by two or more quartiles by the end of gestation. A standard deviation higher baseline FL Z-score, placental weight (150 g), maternal height (5 cm), and weight (10 kg), was associated with a 0.25, 0.15, 0.10, and 0.05 SD higher FL Z-score at the end of gestation, respectively (p ranging from <0.001 to 0.02). Tracking within the same percentile throughout the whole of gestation, as suggest by growth charts, is uncommon. Deviation from tracking is more common and is the result of changes in growth velocity within and between fetuses and is partly influenced by maternal, fetal, and placental factors.