Renato Natale

Neonatal morbidity associated with late preterm and early term birth: the roles of gestational age and biological determinants of preterm birth

BACKGROUND The aim of this study was to elucidate the role of gestational age in determining the risk of neonatal morbidity among infants born late preterm (34-36 weeks) and early term (37-38 weeks) compared with those born full term (39-41 weeks) by examining the contribution of gestational age within the context of biological determinants of preterm birth. METHODS This was a retrospective cohort study. The sample included singleton live births with no major congenital anomalies, delivered at 34-41 weeks of gestation to London-Middlesex (Canada) mothers in 2002-11. Data from a city-wide perinatal database were linked with discharge abstract data. Multivariable models used modified Poisson regression to directly estimate adjusted relative risks (aRRs). The roles of gestational age and biological determinants of preterm birth were further examined using mediation and moderation analyses. RESULTS Compared with infants born full term, infants born late preterm and early term were at increased risk for neonatal intensive care unit triage/admission [late preterm aRR=6.14, 95% confidence interval (CI) 5.63, 6.71; early term aRR=1.54, 95% CI 1.41, 1.68] and neonatal respiratory morbidity (late preterm aRR=6.16, 95% CI 5.39, 7.03; early term aRR=1.46, 95% CI 1.29, 1.65). The effect of gestational age was partially explained by biological determinants of preterm birth acting through gestational age. Moreover, placental ischaemia and other hypoxia exacerbated the effect of gestational age on poor outcomes. CONCLUSIONS Poor outcomes among infants born late preterm and early term are not only due to physiological immaturity but also to biological determinants of preterm birth acting through and with gestational age to produce poor outcomes.

Human fetal breathing activity during electively induced labor at term

Human fetal breathing movements were measured during the first stage of electively induced labor in 20 healthy term pregnancies. Fetuses made breathing movements 25.6% of the time during a 1 hour control period and breathing decreased significantly to 8.3% during latent-phase labor and further decreased to 0.8% during active labor (P less than 0.001). Patterns of increased fetal breathing activity accompanied by increased gross fetal body movements and increased fetal heart rate variability for periods of 20 to 60 minutes out of every 1.0 to 1.5 hours were observed, and the intermittent patterns of increased body movement and heart rate variability continued throughout the first stage of labor despite the decrease in fetal breathing activity during latent- and active-phase labor. It will be important to account for rest activity patterns when interpreting variability of heart rate during labor. The absence of fetal breathing activity during electively induced labor at term is not a clinical indicator of fetal ill health.

Outcomes of Elective Labour Induction and Elective Caesarean Section in Low-risk Pregnancies Between 37 and 41 Weeks’ Gestation

OBJECTIVE To compare maternal and neonatal outcomes after elective induction of labour and elective Caesarean section with outcomes after spontaneous labour in women with low-risk, full-term pregnancies. METHODS We extracted birth data from 1996 to 2005 from an obstetrical database. Singleton pregnancies with vertex presentation, anatomically normal, appropriately grown fetuses, and no medical or surgical complications were included. Outcomes after elective induction of labour and elective Caesarean section were compared with the outcomes after spontaneous labour, using chi-square and Student t tests and logistic regression. RESULTS A total of 9686 women met the study criteria(3475 nulliparous, 6211 multiparous). The incidence of unplanned Caesarean section was higher in nulliparous women undergoing elective induction than in those with spontaneous labour (P < 0.001). Postpartum complications were more common in nulliparous and multiparous women undergoing elective induction (P < 0.001 and P < 0.01, respectively) and multiparous women undergoing elective Caesarean section, (P < 0.001). Rates of triage in NICU were higher in nulliparous women undergoing elective Caesarean section (P < 0.01), and requirements for neonatal free-flow oxygen administration were higher in nulliparous and multiparous women undergoing elective Caesarean section (P < 0.01 for each). Unplanned Caesarean section was 2.7 times more likely in nulliparous women undergoing elective induction of labour (95% CI 1.74 to 4.28, P < 0.001) and was more common among nulliparous and multiparous women undergoing induction of labour and requiring cervical ripening (P < 0. 001 and P < 0.05, respectively). CONCLUSION Elective induction leads to more unplanned Caesarean sections in nulliparous women and to increased postpartum complications for both nulliparous and multiparous women. Elective Caesarean section has increased maternal and neonatal risks.

Management of premature rupture of membranes at term: Randomized trial

OBJECTIVE We hypothesize that expectant management in the presence of premature rupture of membranes at term would result in a lower cesarean birth rate with no increase in maternal, fetal, or neonatal infection. STUDY DESIGN Term patients who consented to the study were randomly allocated either to expectant management for 48 hours or to induction of labor 8 hours after premature rupture of membranes. Premature rupture of membranes was confirmed by sterile speculum examination of the vagina. Patients randomized to expectant management were transferred to antenatal care and were not examined vaginally until they went into labor. Patients randomized to induction of labor had induction with oxytocin 8 hours after premature rupture of membranes. RESULTS Two hundred sixty-two patients were randomized to the expectant management and induction of labor groups. The cesarean birth rate and the clinical diagnosis of postpartum endometritis was not significantly different in the two groups. Pathologic diagnosis of chorioamnionitis and funisitis, however, was significantly greater in the expectant management group (p < 0.05). Eight of the 15 babies with funisitis were admitted to the neonatal intensive care unit for therapy (two in the induction of labor group and six in the expectant management group, p < 0.05). CONCLUSION Expectant management did not reduce the incidence of cesarean birth and increased the pathologic diagnosis of funisitis and newborn requirements for neonatal intensive care.

The role of carbon dioxide in the generation of human fetal breathing movements

To determine the role of carbon dioxide in the generation of fetal respiratory movements, the effect of induced maternal hypocapnia and hypercapnia on fetal breathing movements, gross body movements, and fetal heart rate was studied in 12 healthy pregnant women near term. Patients were studied for a 1-hour control period breathing room air followed by four randomized 15-minute study periods with patients breathing either room air, a prepared gas mixture with 2% or 4% carbon dioxide, or undergoing controlled hyperventilation as determined by monitoring end-tidal PCO2. The percentage of time fetal breathing movements correlated significantly with maternal end-tidal PCO2 (r = 0.62, p less than 0.01), increasing with maternal breathing of 2% and 4% carbon dioxide and decreasing with maternal hyperventilation. Fetal gross body movements, fetal heart rate, and fetal heart rate variability showed no significant changes. It is concluded that as in adults, the carbon dioxide level in fetuses is an important stimulus for the generation of respiratory movements, acting independent of a change in behavioral state. It is hypothesized that tonic carbon dioxide level input is an important determinant of fetal respiratory center drive, but little or no phasic carbon dioxide input exists because of continuous placental excretion, thus resulting in the episodic occurrence of breathing movements with changes in the fetal behavioral state.

Biological determinants of spontaneous late preterm and early term birth: a retrospective cohort study.

Our aim was to examine the association between biological determinants of preterm birth (infection and inflammation, placental ischaemia and other hypoxia, diabetes mellitus, other) and spontaneous late preterm (34–36 weeks) and early term (37–38 weeks) birth.

Obstetric conditions and the placental weight ratio

INTRODUCTION To elucidate how obstetric conditions are associated with atypical placental weight ratios (PWR)s in infants born: (a) ≥37 weeks gestation; (b) at ≥33 but <37 weeks gestation; and (c) <33 weeks gestation. METHODS The study included all in-hospital singleton births in London, Ontario between June 1, 2006 and March 31, 2011. PWR was assessed as <10th or >90th percentile by gestational age-specific local population standards. Multivariable analysis was carried out using multinomial logistic regression with blockwise variable entry in order of temporality. RESULTS Baseline factors and maternal obstetric conditions associated with PWR <10th percentile were: increasing maternal height, overweight and obese body mass indexes (BMI), large for gestational age infants, smoking, and gestational diabetes. Obstetric factors associated with PWR >90th percentile were: underweight, overweight and obese BMIs, smoking, preeclampsia, placenta previa, and placental abruption. In particular, indicators of hypoxia and altered placental function were generally associated with elevated PWR at all gestations. DISCUSSION An association between obstetric conditions associated with fetal hypoxia and PWR ≥90th percentile was illustrated. CONCLUSIONS The multivariable findings suggest that the PWR is similarly increased regardless of the etiology of the hypoxia.

Population-Based Placental Weight Ratio Distributions

The placental weight ratio (PWR) is a health indicator that reflects the balance between fetal and placental growth. The PWR is defined as the placental weight divided by the birth weight, and it changes across gestation. Its ranges are not well established. We aimed to establish PWR distributions by gestational age and to investigate whether the PWR distributions vary by fetal growth adequacy, small, average, and large for gestational age (SGA, AGA, and LGA). The data came from a hospital based retrospective cohort, using all births at two London, Ontario hospitals in the past 10 years. All women who delivered a live singleton infant between 22 and 42 weeks of gestation were included (n = 41441). Nonparametric quantile regression was used to fit the curves. The results demonstrate decreasing PWR and dispersion, with increasing gestational age. A higher proportion of SGA infants have extreme PWRs than AGA and LGA, especially at lower gestational ages. On average, SGA infants had higher PWRs than AGA and LGA infants. The overall curves offer population standards for use in research studies. The curves stratified by fetal growth adequacy are the first of their kind, and they demonstrate that PWR differs for SGA and LGA infants.

Mild Prematurity, Proximal Social Processes, and Development

OBJECTIVE: To elucidate the role of gestational age in determining the risk of poor developmental outcomes among children born late preterm (34–36 weeks) and early term (37–38 weeks) versus full term (39–41 weeks) by examining the contribution of gestational age to these outcomes in the context of proximal social processes. METHODS: This was an analysis of the Canadian National Longitudinal Survey of Children and Youth. Developmental outcomes were examined at 2 to 3 (N = 15 099) and 4 to 5 years (N = 12 302). The sample included singletons, delivered at 34 to 41 weeks, whose respondents were their biological mothers. Multivariable modified Poisson regression was used to directly estimate adjusted relative risks (aRRs). We assessed the role of parenting by using moderation analyses. RESULTS: In unadjusted analyses, children born late preterm appeared to have greater risk for developmental delay (relative risk = 1.26; 95% confidence interval [CI], 1.01 to 1.56) versus full term. In adjusted analyses, results were nonsignificant at 2 to 3 years (late preterm aRR = 1.13; 95% CI, 0.90 to 1.42; early term aRR = 1.11; 95% CI, 0.96 to 1.27) and 4 to 5 years (late preterm aRR = 1.06; 95% CI, 0.79 to 1.43; early term aRR = 1.03; 95% CI, 0.85 to 1.25). Parenting did not modify the effect of gestational age but was a strong predictor of poor developmental outcomes. CONCLUSIONS: Our findings show that, closer to full term, social factors (not gestational age) may be the most important influences on development.

DIURNAL CHANGES IN MATERNAL PLASMA OESTRONE AND OESTRADIOL AT 30 TO 31, 34 TO 35 AND 38 TO 39 WEEKS GESTATIONAL AGE

Diurnal changes in the concentrations of oestrone (E1) and oestradiol (E2) in maternal peripheral plasma have been measured in samples of blood taken at one hour intervals from women at 30 to 31, 34 to 35 and 38 to 39 weeks of pregnancy. There was a significant effect of time of sampling on the plasma concentration of E1 at all stages of gestation, and circadian changes in the levels of E1 were apparent at 34 to 35 and 38 to 39 weeks. Peak values were measured around 0830 to 0930 hours, and troughs occurred between 0130 and 0530 hours. Significant effects of time of sampling on the plasma concentration of E2 were found at 34 to 35 and 38 to 39 weeks of pregnancy; night‐time concentrations were lower than the peak values at 0730 to 0830 hours. The relation of these changes to the circadian rhythms in the concentrations of cortisol and oestriol in maternal plasma are discussed.