Every Newborn: progress, priorities, and potential beyond survival

Challenges in defining and classifying the preterm birth syndrome

Objective: To determine whether preterm birth in a twin pregnancy increases the risk of subsequent preterm birth (PTB) in a singleton pregnancy and to identify predictors for singleton PTB in women with previous twin PTB.Method: A retrospective cohort study of women with prior twin birth followed by a singleton birth in two tertiary referral centres between 2000 and 2016 was conducted. Rate of PTB in subsequent singleton pregnancy was compared between women who experienced previous preterm versus term twin birth. Analysis was further stratified by gestational age at twin and singleton birth, etiology for PTB and chorionicity in the twin pregnancy.Results: A total of 378 women met the inclusion criteria, of whom 252 (66.7%) experienced PTB in the index twin pregnancy. The overall rate of PTB in the subsequent singleton pregnancy was 11.6% (44/378). Women with prior twin PTB had a higher rate of PTB in the subsequent singleton pregnancy compared with women with prior term twin birth (17.5 versus 6.3%, p = .003, or 3.12, 95%-CI 1.42–6.85), mainly due to a higher rate of late singleton preterm birth (13.1 versus 4.0%, p = .005). Findings of higher odds of PTB in the subsequent singleton pregnancy was limited to women who gave birth before 340/7 weeks in the twin pregnancy and was related to the degree of prematurity (prior twin PTB at 300/7–336/7 weeks: OR 3.09, 95%-CI 1.12–8.51; prior twin PTB at <300/7 weeks: OR 5.8, 95%-CI 2.46–13.68). The association between previous twin PTB and subsequent singleton PTB was limited to women with prior spontaneous twin PTB (OR 3.34, 95%-CI 1.50–7.45).Conclusion: Women with a history of spontaneous PTB in a twin pregnancy are at increased odds of PTB in subsequent singleton pregnancies compared to women with prior term twin birth, and the risk is related to the severity of prematurity in the index twin pregnancy.

The role of maternal age in twin pregnancy outcomes

ObjectiveTo estimate cause-of-death distributions in the early (0–6 days of age) and late (7–27 days of age) neonatal periods, for 194 countries between 2000 and 2013.MethodsFor 65 countries with high-quality vital registration, we used each country’s observed early and late neonatal proportional cause distributions. For the remaining 129 countries, we used multinomial logistic models to estimate these distributions. For countries with low child mortality we used vital registration data as inputs and for countries with high child mortality we used neonatal cause-of-death distribution data from studies in similar settings. We applied cause-specific proportions to neonatal death estimates from the United Nations Inter-agency Group for Child Mortality Estimation, by country and year, to estimate cause-specific risks and numbers of deaths.FindingsOver time, neonatal deaths decreased for most causes. Of the 2.8 million neonatal deaths in 2013, 0.99 million deaths (uncertainty range: 0.70–1.31) were estimated to be caused by preterm birth complications, 0.64 million (uncertainty range: 0.46–0.84) by intrapartum complications and 0.43 million (uncertainty range: 0.22–0.66) by sepsis and other severe infections. Preterm birth (40.8%) and intrapartum complications (27.0%) accounted for most early neonatal deaths while infections caused nearly half of late neonatal deaths. Preterm birth complications were the leading cause of death in all regions of the world.ConclusionThe neonatal cause-of-death distribution differs between the early and late periods and varies with neonatal mortality rate level. To reduce neonatal deaths, effective interventions to address these causes must be incorporated into policy decisions.

Severe neonatal bacterial infections: when numbers matter

Maternal obesity is associated with an increased risk of late pregnancy complications such as stillbirth, gestational diabetes, and cesarean delivery. A low body mass index (BMI), however, has been reported to correlate with an increased risk of preterm delivery, and in some studies a BMI above the “normal” range is associated with decreased rate of spontaneous preterm birth. This study, based on the Scottish Morbidity Record, examined the association between maternal BMI and the risk of preterm delivery in 187,290 women. Preterm delivery was defined as childbirth before 37 weeks’ gestation. With increasing BMI, the risk of spontaneous preterm delivery decreased while the risk of elective preterm delivery increased. Elective preterm delivery was associated with a reduced risk of neonatal death (relative risk [RR], 0.72; 95% confidence interval [CI], 0.55–0.94), and an increased risk of delivering an ELBW infant who survived for 12 months (RR, 1.92; 95% CI, 1.49–2.47). However, the net effect of BMI on these adverse outcomes varied by parity. Nulliparous women with a BMI ≥35 had an increased risk of overall preterm birth (OR, 1.34; 95% CI, 1.15–1.56) and elective preterm birth (OR, 2.13; 95% CI, 1.75–2.58), of which 40% were due to preeclampsia. They were also at increased risk of neonatal death (OR, 2.77; 95% CI, 1.54–4.99) and an ELBW infant still alive at one year (OR, 3.31; 95% CI, 2.13–5.14). In contrast, multiparous women with a BMI ≥35 were not at increased risk of overall preterm birth, neonatal death, or ELBW infant alive at one year. They were at increased risk of elective preterm birth, although to a lesser degree than nulliparas (OR, 1.45; 95% CI, 1.21–1.75) and only 18% of their elective preterm deliveries were due to preeclampsia. These findings show that maternal obesity is associated with an increased risk of preterm delivery. Nulliparous obese women are at highest risk of elective preterm delivery, probably reflecting their increased risk of preeclampsia, as well as increased perinatal mortality and long-term disability in surviving offspring.

Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. Despite early evidence indicating a beneficial effect of antenatal corticosteroids on fetal lung maturation and widespread recommendations to use this treatment in women at risk of preterm delivery, some uncertainty remains about their effectiveness particularly with regard to their use in lower-resource settings, different gestational ages and high-risk obstetric groups such as women with hypertension or multiple pregnancies. This updated review (which supersedes an earlier review Crowley 1996) was first published in 2006 and subsequently updated in 2017.

Screening of pregnant women for preterm birth, based on their obstetric history and sonographic measurement of the cervical length, can identify greater than 50% of those at risk. Administration of progesterone to at-risk women with a singleton pregnancy can significantly reduce rates of preterm birth. However, effects of this agent on the actual perinatal and long-term consequences of prematurity are difficult to assess. Existing randomized controlled trials (RCTs) and systematic reviews have focused mainly on the primary outcome of reduction of preterm birth rates. The aim of this meta-analysis was to systematically review published evidence and pool data on the perinatal outcome in women treated with progesterone for the prevention of preterm birth. MEDLINE and SCOPUS databases were searched for clinical trials in which progesterone was given to prevent preterm birth in pregnant women at risk compared with placebo. Randomized controlled trials that compared progesterone versus placebo in women with singleton or multiple pregnancies at risk for preterm birth based on previous history or short cervix were selected. The CONSORT statement was used to address the reporting quality of the RCTs. The risk of bias in the RCTs was assessed with the “risk-of-bias” tool from the Cochrane Collaboration. The primary outcomes were the rates of neonatal and perinatal mortality. Secondary outcomes were the rates of perinatal complications, including respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) grade 3–4, sepsis, necrotizing enterocolitis (NEC), sepsis, retinopathy, and admission to the neonatal intensive care unit (NICU); a composite adverse outcome was also determined and defined as the presence of any perinatal morbidity or mortality. Of 628 retrieved items, 16 RCTs reporting on the use of progesterone in asymptomatic women to prevent preterm birth were included in the meta-analysis. Pooled data indicated that progesterone administration in these women significantly decreased the risk for composite adverse outcome (RR, 0.576; 95% confidence interval [CI], 0.373–0.891), neonatal death (relative risk, 0.487; 95% CI, 0.290–0.818), RDS (RR, 0.677; 95% CI, 0.490–0.935), and admission to the NICU (RR, 0.410; 95% CI, 0.204–0.823). No significant differences were found in rates of perinatal death, grade 3–4 IVH, NEC, retinopathy, or sepsis. Pooled data from 3 studies that used vaginal progesterone in women with a short cervix showed that progesterone significantly decreased the rate of composite adverse outcome (RR, 0.576; 95% CI, 0.373–0.891) and RDS (RR, 0.464; 95% CI, 0.275–0.786), but results did not reach statistical significance for rates of neonatal death, perinatal death, grade 3–4 IVH, NEC, sepsis, or admission to the NICU. Three studies tested systemic progesterone in women with a singleton pregnancy and a history of preterm birth; pooled results found that progesterone significantly decreased rates of neonatal death (RR, 0.412; 95% CI, 0.201–0.842) and NICU admission (RR, 0.277; 95% CI, 0.160–0.479). In 7 RCTs reporting on women with twin pregnancies, progesterone administration did not significantly affect the rates of neonatal death, grade 3–4 IVH, NEC, retinopathy, sepsis, or NICU admission. Progesterone significantly increased the rates of composite adverse outcome (RR, 1.211; 95% CI, 1.029–1.425), perinatal death (RR, 1.551; 95% CI, 1.014–2.372), and RDS (RR, 1.218; 95% CI, 1.038–1.428). The pooled data from 2 RCTs on women with triplets did not show significant differences in the rates of composite adverse outcome, neonatal death, RDS, grade 3–4 IVH, NEC, or sepsis. Preterm birth is a major cause of perinatal mortality and morbidity with long-term consequences. Results of this meta-analysis indicate that prophylactic progesterone administration in singleton pregnancies at risk can lower the rates of neonatal mortality, RDS, admission to the NICU, and a composite adverse outcome. Data, however, also indicate that use of progesterone in multiple pregnancies may lead to increased rates of perinatal death, RDS, and a composite adverse outcome.

To examine international rates of preterm birth and potential associations with stillbirths and neonatal deaths at late preterm and term gestation. Ecological study. Canada, USA and 26 countries in Europe. All deliveries in 2004. Information on preterm birth (<37, 32-36, 28-31 and 24-27 weeks of gestation) and perinatal deaths was obtained for 28 countries. Data sources included files and publications from Statistics Canada, the EURO-PERISTAT project and the National Center for Health Statistics. Pearson correlation coefficients and random-intercept Poisson regression were used to examine the association between preterm birth rates and gestational age-specific stillbirth and neonatal death rates. Rate ratios with 95% confidence intervals were estimated after adjustment for maternal age, parity and multiple births. Stillbirths and neonatal deaths ≥ 32 and ≥ 37 weeks of gestation. International rates of preterm birth (<37 weeks) ranged between 5.3 and 11.4 per 100 live births. Preterm birth rates at 32-36 weeks were inversely associated with stillbirths at ≥ 32 weeks (adjusted rate ratio 0.94, 95% CI 0.92-0.96) and ≥ 37 weeks (adjusted rate ratio 0.88, 95% CI 0.85-0.91) of gestation and inversely associated with neonatal deaths at ≥ 32 weeks (adjusted rate ratio 0.88, 95% CI 0.85-0.91) and ≥ 37 weeks (adjusted rate ratio 0.82, 95% CI 0.78-0.86) of gestation. Countries with high rates of preterm birth at 32-36 weeks of gestation have lower stillbirth and neonatal death rates at and beyond 32 weeks of gestation. Contemporary rates of preterm birth are indicators of both perinatal health and obstetric care services.

World Prematurity Day: improving survival and quality of life for millions of babies born preterm around the world

ObjectiveThis study aimed to assess the contribution of postnatal services to the risk of neonatal mortality, and the relative contributions of antenatal iron/folic acid supplements and postnatal care in preventing...

The prevalence of cannabis use in pregnancy is rising and is associated with adverse perinatal outcomes. In parallel, combined prenatal use of cannabis and nicotine is also increasing, but little is known about the combined impact of both substances on pregnancy and offspring outcomes compared with each substance alone. To assess the perinatal outcomes associated with combined cannabis and nicotine exposure compared with each substance alone during pregnancy. This retrospective population-based cohort study included linked hospital discharge data (obtained from the California Department of Health Care Access and Information) and vital statistics (obtained from the California Department of Public Health) from January 1, 2012, through December 31, 2019. Pregnant individuals with singleton gestations and gestational ages of 23 to 42 weeks were included. Data were analyzed from October 14, 2023, to March 4, 2024. Cannabis-related diagnosis and prenatal nicotine product use were captured using codes from International Classification of Diseases, Ninth Revision, Clinical Modification, and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification. The main outcomes were infant and neonatal death, infants small for gestational age, and preterm delivery. Results were analyzed by multivariable Poisson regression models. A total of 3 129 259 pregnant individuals were included (mean [SD] maternal age 29.3 [6.0] years), of whom 23 007 (0.7%) had a cannabis-related diagnosis, 56 811 (1.8%) had a nicotine-use diagnosis, and 10 312 (0.3%) had both in pregnancy. Compared with nonusers, those with cannabis or nicotine use diagnoses alone had increased rates of infant (0.7% for both) and neonatal (0.3% for both) death, small for gestational age (14.3% and 13.7%, respectively), and preterm delivery (<37 weeks) (12.2% and 12.0%, respectively). Moreover, risks in those with both cannabis and nicotine use were higher for infant death (1.2%; adjusted risk ratio [ARR], 2.18 [95% CI, 1.82-2.62]), neonatal death (0.6%; ARR, 1.76 [95% CI, 1.36-2.28]), small for gestational age (18.0%; ARR, 1.94 [95% CI, 1.86-2.02]), and preterm delivery (17.5%; ARR, 1.83 [95% CI, 1.75-1.91]). These findings suggest that co-occurring maternal use of cannabis and nicotine products in pregnancy is associated with an increased risk of infant and neonatal death and maternal and neonatal morbidity compared with use of either substance alone. Given the increasing prevalence of combined cannabis and nicotine use in pregnancy, these findings can help guide health care practitioners with preconception and prenatal counseling, especially regarding the benefits of cessation.

This study aimed to ascertain the outcomes associated with a cervical cerclage among individuals with a history of previable prelabor rupture of membranes (PROM). This study was a retrospective cohort study conducted at a single tertiary center between 2011 and 2021. We included individuals with a history of previable (before 24 weeks) PROM and the subsequent viable pregnancy. Women with multifetal gestation, preterm birth (PTB) or cerclage in previous gestation, or abdominal cerclage after trachelectomy were excluded. Primary outcome was PTB rate (delivery <37 weeks). Recurrence of preterm PROM and adverse composite maternal and neonatal outcomes (CMO and CNO) were evaluated as secondary outcomes. CMO included any of the following: suspected chorioamnionitis, endometritis, red blood cell transfusion, uterine rupture, unplanned hysterectomy, or death. CNO included any of the following: previable PTB (<24 weeks of gestation), bronchopulmonary dysplasia, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, mechanical ventilation, seizures, hypoxic ischemic encephalopathy, or death. During the study period, 118 individuals had a history of previable PROM and a documented subsequent pregnancy, out of which 74 (62.7%) met inclusion criteria. Nineteen (25.7%) of eligible individuals underwent a cerclage for prior previable PROM and were compared with controls (n = 55, 74.3%). Women who underwent a cerclage had higher rates of PTB < 37 weeks (63.2 vs. 10.9%, p < 0.001; odds ratio [OR]: 14.00, 95% confidence interval [CI]: 3.97-49.35) and < 34 weeks (21.1 vs. 3.6%, p = 0.03; OR: 7.07, 95% CI: 1.18-42.39) compared with those without cerclage. Furthermore, recurrent preterm PROM and previable PTB rates were higher among patients who underwent cerclage. The survival curve further indicated that individuals with cerclage delivered earlier. CMO and CNO rates were similar in those with and without cerclage. Cerclage placement in individuals with prior previable PROM was associated with higher rates of recurrent preterm PROM and PTB. · The management of individuals in a subsequent pregnancy following previable PROM is a conundrum.. · Cerclage following previable PROM is associated with higher rates of recurrent preterm PROM and PTB.. · Composite maternal and neonatal outcome rates were similar in those with and without cerclage..

Introduction: Maternal pregnancy smoking has adverse perinatal outcomes and the relationship between maternal smoking and neonatal death has not been fully elucidated. We aimed to examine the risk of neonatal death in relation to maternal smoking and to quantify potential mediators of these associations. Methods: We did a population-based cohort study using Period Linked Birth-Infant Death data from 2016 to 2019 in the US National Vital Statistics System. The exposure was maternal smoking status. The main outcome was neonatal death. Association between maternal smoking and neonatal death was estimated through logistic regression. Mediation analysis was performed to assess the extent to which the association between maternal smoking and neonatal death was mediated by neonatal complications. Results: The final sample consisted of 14,717,020 mothers with live singleton births. The overall neonatal mortality rate was 2.2 per 1,000 live births. Maternal pregnancy smoking was associated with an increased risk of neonatal death {adjusted odds ratio (aOR, 1.33 [95% CI, 1.28–1.38]; p < 0.001)}, while smoking cessation during the whole pregnancy showed a comparable risk of neonatal death with nonsmokers (aOR, 1.06 [95% CI, 0.99–1.14]; p = 0.116). Mediation analysis indicated that the association between pregnancy smoking and neonatal death might be mainly mediated by preterm birth and low Apgar score at 5 min. Conclusions: Maternal pregnancy smoking, regardless of pregnancy trimester and intensity, was associated with increased risk of neonatal death. Efforts are needed for policymakers to promote smoking cessation before pregnancy, and professional perinatal care should be provided for those who smoked during pregnancy.

Birth weight discordancy and adverse perinatal outcomes among twin gestations in the United States: The effect of placental abruption