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The association between obstetrical interventions and late preterm birth

Published:February 28, 2014DOI:https://doi.org/10.1016/j.ajog.2014.02.023

      Objective

      There is concern that obstetric interventions (prelabor cesarean section and induced delivery) are drivers of late preterm (LP) birth. Our objective was to evaluate the independent association between obstetric interventions and LP birth and explore associated independent maternal and fetal risk factors for LP birth.

      Study Design

      In this population-based cross-sectional study, the BORN Information System was used to identify all infants born between 34 and 40 completed weeks of gestation between 2005 and 2012 in Ontario, Canada. The association between obstetric interventions (preterm cesarean section and induced delivery) and LP birth (34 to 36 completed weeks' gestation vs 37 to 40 completed weeks' gestation) was assessed using generalized estimating equation regression.

      Results

      Of 917,013 births between 34 and 40 weeks, 49,157 were LP (5.4%). In the adjusted analysis, “any obstetric intervention” (risk ratio [RR], 0.65; 95% confidence interval [CI], 0.57–0.74), induction (RR, 0.71; 95% CI, 0.61–0.82) and prelabor cesarean section (RR, 0.66; 95% CI, 0.59–0.74) were all associated with a lower likelihood of LP vs term birth. Several independent potentially modifiable risk factors for LP birth were identified including previous cesarean section (RR, 1.28; 95% CI, 1.16–1.40), smoking during pregnancy (RR, 1.28; 95% CI, 1.21–1.36) and high material (RR, 1.1; 95% CI, 1.03–1.18) and social (RR, 1.09; 95% CI, 1.02–1.16) deprivation indices.

      Conclusion

      After accounting for differences in maternal and fetal risk, LP births had a 35% lower likelihood of obstetric interventions than term births. Obstetric care providers may be preferentially avoiding induction and prelabor cesarean section between 34 and 37 weeks' gestation.

      Key words

      Preterm birth is the leading cause of infant morbidity and mortality and has been described as the most important perinatal challenge facing industrialized countries.
      • Kramer M.S.
      • Demissie K.
      • Yang H.
      • Platt R.W.
      • Sauve R.
      • Liston R.
      The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System.
      Among preterm infants (<37 weeks' of gestation), “late preterm” (LP) infants (born between 340 and 366 weeks of gestation) account for the largest proportion (74%) and are the fastest growing subgroup.
      • Kramer M.S.
      • Demissie K.
      • Yang H.
      • Platt R.W.
      • Sauve R.
      • Liston R.
      The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System.
      • Davidoff M.J.
      • Dias T.
      • Damus K.
      • et al.
      Changes in the gestational age distribution among U.S. singleton births: impact on rates of late preterm birth, 1992 to 2002.
      Children born LP are at greater risk than term infants (≥37 weeks) for numerous short and long-term adverse outcomes.
      • Tomashek K.M.
      • Shapiro-Mendoza C.K.
      • Davidoff M.J.
      • Petrini J.R.
      Differences in mortality between late-preterm and term singleton infants in the United States, 1995-2002.
      • Loftin R.W.
      • Habli M.
      • Snyder C.C.
      • Cormier C.M.
      • Lewis D.F.
      • Defranco E.A.
      Late preterm birth.
      • Ramachandrappa A.
      • Jain L.
      Health issues of the late preterm infant.
      • Huddy C.L.
      • Johnson A.
      • Hope P.L.
      Educational and behavioural problems in babies of 32-35 weeks gestation.
      • Santos I.S.
      • Matijasevich A.
      • Domingues M.R.
      • Barros A.J.
      • Victora C.G.
      • Barros F.C.
      Late preterm birth is a risk factor for growth faltering in early childhood: a cohort study.
      Two groups of LP birth have been defined by their etiology: spontaneous LP births (ie, premature labor with intact membranes or preterm prelabor rupture of membranes), and LP births because of obstetric intervention (ie, induction of labor or cesarean section).
      • Mohan S.S.
      • Jain L.
      Late preterm birth: preventable prematurity?.
      There is concern that obstetric interventions may be driving the increase in LP birth in recent years and are responsible for a substantial proportion of LP births.
      • Martin J.A.
      • Kirmeyer S.
      • Osterman M.
      • Shepherd R.A.
      Born a bit too early: recent trends in late preterm births.
      • Voelker R.
      US preterm births: “D” is for dismal.
      Understanding the independent contribution of obstetric interventions in the context of maternal and fetal risk factors for LP birth has been challenging largely owing to limitations in population based data on maternal and fetal risk factors for LP birth.
      The objective of this study was to evaluate the magnitude and direction of the association between obstetric interventions (induced delivery and cesarean section) and LP birth (relative to term birth) in the context of known risk factors for preterm birth. We also aimed to explore the magnitude of the associations between maternal and fetal risk factors for LP birth, independent of obstetric interventions, which could be targets for interventions to prevent LP birth.

      Methods

      This was a population-based cohort study of pregnant women in Ontario, Canada, between April 1, 2005, and March 31, 2012.

      Study population

      All women who gave birth in a hospital to a live infant >500 g birthweight with a gestational age between 340/7 and 406/7 weeks in Ontario, Canada, between 2005 and 2012 were eligible for inclusion in this study. Women who gave birth between 410/7 and 416/7 weeks' gestation were excluded to avoid capturing an increased risk of obstetric interventions in the 41st week of gestation.

      Sources of data

      Data were obtained from the BORN Information System (BIS), which is a provincial, internet-based maternal newborn surveillance system managed by the Better Outcomes Registry & Network (BORN Ontario). Maternal, fetal, and obstetric data were extracted for the study time period, April 1, 2004, to March 31, 2012. In a birth number validation exercise between the CIHI Discharge Abstract Database and the BIS, the BORN system captured 82% of hospital births in the 2004-2005 fiscal year and increased yearly until 100% of hospital births from 106 sites were captured by 2010-11. The BIS includes information on maternal demographic characteristics and health behaviors, preexisting maternal health problems, obstetric complications, intrapartum interventions, and birth outcomes. Various quality assurance mechanisms were used to ensure high data quality and consistency including data entry operating manuals, automated system checks, and training sessions for data entry staff.

      Canadian Institute for Health Information. Reducing gaps in health: a focus on socioeconomic status in urban Canada. Ottawa, Ontario: CIHI; 2008. Available at: https://secure.cihi.ca/free_products/Reducing_Gaps_in_Health_Report_EN_081009.pdf. Accessed April 10, 2013.

      A validation study of the BORN birth record system found a high level of agreement with the original patient record for many of the variables used in this study including gestational age, induced delivery and cesarean section, which had 91%, 90%, and 99% agreement with the original patient record respectively.
      • Dunn S.
      • Bottomley J.
      • Ali A.
      • Walker M.
      2008 Niday Perinatal Database quality audit: report of a quality assurance project.
      The variance for percentage agreement across all variables evaluated was 97.2% (interquartile range, 93.0–99.4%).
      • Dunn S.
      • Bottomley J.
      • Ali A.
      • Walker M.
      2008 Niday Perinatal Database quality audit: report of a quality assurance project.

      Exposure variables

      Our primary exposure was ‘any obstetric intervention’ defined as prelabor cesarean section or induced delivery. Our secondary exposures were prelabor cesarean section and induced delivery separately. To avoid overlap between obstetric intervention categories and capture of the event that primarily influenced gestational age at birth, induced deliveries were defined as those with medical or surgical intervention to initiate uterine contractions before the onset of spontaneous labor and included those that subsequently resulted in cesarean section. Prelabor cesarean sections were defined as delivery by cesarean section without prior induction of labor or spontaneous onset of labor. Spontaneous onset of labor was defined as labor that was initiated without intervention, which may have been preceded by spontaneious rupture of membranes.
      We also explored maternal and obstetric factors known or suspected to be associated with preterm birth. These included maternal characteristics such as maternal age at delivery, socioeconomic status, smoking during pregnancy, parity (nulliparous, primiparous, or multiparous), multifetal pregnancy, previous cesarean section, and number of previous preterm births; maternal health problems including preexisting diabetes (insulin and noninsulin dependent), gestational diabetes, chronic hypertension (hypertension that predates the pregnancy or was diagnosed before the 20th week of gestation), gestational hypertension, infection during pregnancy (composite of any periodontal, urinary tract, vaginal, or cervical infections), and obstetrical complications including preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption (premature separation of a normally implanted placenta after the 20th week of gestation and before the fetus is delivered), cord prolapse, chorioamnionitis, breech presentation and small for gestational age (<10 percentile gender specific birthweight for gestational age relative to a Canadian standard reference population for any fetus).
      • Kramer M.S.
      • Platt R.W.
      • Wen S.W.
      • et al.
      A new and improved population-based Canadian reference for birth weight for gestational age.
      Socioeconomic status was measured using material and social deprivation from the Deprivation Index, a national index that has been used in many epidemiologic studies and by the Canadian Institute for Health Information as a proxy for socioeconomic status.

      Canadian Institute for Health Information. Reducing gaps in health: a focus on socioeconomic status in urban Canada. Ottawa, Ontario: CIHI; 2008. Available at: https://secure.cihi.ca/free_products/Reducing_Gaps_in_Health_Report_EN_081009.pdf. Accessed April 10, 2013.

      • Pampalon R.
      • Raymond G.
      A deprivation index for health and welfare planning in Quebec.
      The material deprivation component includes: (1) the proportion of persons aged 15 and over who have no high school diploma; (2) the average income of persons aged 15 and over; and (3) the employment to population ratio for persons aged 15 and over. The social deprivation component includes (1) the proportion of people who live alone; (2) the proportion of people separated, divorced, or widowed; and (3) the proportion of single parent families. A factor score is derived from a principal component analysis of these variables at the dissemination area (DA) level, a small, relatively stable geographic unit with a population of 400 to 700 people of relatively homogenous socioeconomic status. Each DA is divided into quintiles based on the corresponding factor scores. DAs in the highest deprivation quintile (Q5) represent the neighborhoods at the highest social disadvantage. We used automated geographic coding based on the Statistics Canada postal code conversion files (PCCF+ v5h) to link the maternal residential postal code in the BORN dataset to the corresponding quintile of deprivation.

      Outcome variables

      For our primary outcome, gestational age at birth was dichotomized as LP (340/7 to 366/7 weeks' gestation) or term (370/7 to 406/7 weeks' gestation) based on estimated gestational age at the time of delivery as reported on the birth record.
      • Engle W.A.
      A recommendation for the definition of “late preterm” (near-term) and the birth weight-gestational age classification system.
      Gestational age was estimated from the date of last menstrual period or dating ultrasound as indicated on the patient record.

      Statistical methods

      For the primary analysis, multivariable generalized estimating equation (GEE) regression was used to test the association between obstetric interventions and late preterm birth (vs term birth) adjusted for maternal and obstetric factors known or suspected to be associated with preterm birth (see above). We chose to use GEE regression to account for clustering within hospitals, which would allow for a more equitable representation of the relationship between risk factors and LP birth than traditional regression techniques. Variables considered for inclusion contained less than 10% missing data and records with missing information on variables included in the models were excluded in the final computation. All variables specified above were included in the final models regardless of traditional statistical significance as all were believed to be clinically important. Unadjusted and adjusted risk ratio (RR) estimates were computed using a log binomial regression model with hospital site used as the clustering unit for the GEE model to account for clustering of obstetrical interventions within hospitals.
      • Austin P.C.
      • Mamdani M.M.
      • Juurlink D.N.
      • Hux J.E.
      Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health.
      Colinearity between model parameters was assessed using the variance inflation factor with a cutoff value of 2.0. To explore a dose effect, the association between obstetric interventions and gestational age at birth was explored by week of gestation between 34 and 37 weeks relative to term.
      For our secondary analysis, the primary analysis was repeated but using induced delivery and prelabor cesarean section as separate exposures. We also conducted an exploratory analysis to examine the independent association between maternal and obstetrical factors known or suspected to be associated with preterm birth and LP birth (vs term birth) adjusted for obstetric interventions.
      To internally validate our model and minimize the risk of spurious associations from multiple hypothesis testing, for both the primary and secondary analyses, all births were randomly assigned to equally sized derivation and validation cohorts.
      • Austin P.C.
      • Mamdani M.M.
      • Juurlink D.N.
      • Hux J.E.
      Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health.
      The analysis was completed on both cohorts, however, the validation cohort was used to test the associations identified through the derivation cohort. All covariates were included in both derivation and validation models.
      Statistical analyses were performed using SAS statistical software version 9.2 (SAS Institute, Cary NC) with statistical significance evaluated using 2-sided P values at the 5% level. The study protocol was approved by the Research Ethics Boards of the Children's Hospital of Eastern Ontario, the St. Michael's Hospital and the Mount Sinai Hospital in Toronto.

      Results

      From April 2005 through March 2012 there were 925,293 live births in Ontario hospitals, 6.5% of births had incomplete data capture. After excluding births with a birthweight <500 g and those with incomplete data, there were 917,013 live births between 34 to 40 completed weeks of gestation, of which 49,157 (5.4%) were identified as LP. Obstetricians provided care to 79%, family physicians to 27%, midwives to 7% and nurse practitioners to 2% of women (15% of women had multiple care providers). Births occurred in 106 different hospital sites; 23% Level 3, 65% Level 2, and 12% Level 1 centers.
      The derivation and validation cohorts consisted of 458,629 and 458,384 births respectively. Overall, the patient characteristics were similar between the 2 cohorts (Table 1). The most common maternal age range was 25–34 years and most mothers had not had a previous preterm birth. In both cohorts, any obstetric intervention’ occurred in 38% of births, 21% were induced deliveries and 17% were prelabor cesarean sections. Overall, variable colinearity was low (variance inflation factor between 1.00-1.9).
      Table 1Patient characteristics of the derivation and validation cohorts
      Characteristics, n (%)Derivation cohort

      (n = 458,629)
      Validation cohort

      (n = 458,384)
      Term (37-40 wks)

      n = 433,929
      Late preterm (34-36 wks)

      n = 24,700
      Term (37-40 wks)

      n = 433,927
      Late preterm (34-36 wks)

      n = 24,457
      Maternal age, y
       <2015,080 (3.48)952 (3.85)15,292 (3.52)877 (3.59)
       20-2457,999 (13.37)3196 (12.94)57,755 (13.31)3193 (13.06)
       25-34269,006 (62.00)14,696 (59.51)269,456 (62.10)14,415 (58.95)
       35-3975,819 (17.47)4664 (18.87)75,414 (17.38)4704 (19.23)
       >4015,998 (3.69)1189 (4.81)15,980 (3.68)1264 (5.17)
      Previous cesarean section59,703 (13.97)3637 (14.96)59,257 (13.87)3569 (14.80)
      Previous preterm birth
       One22,459 (5.27)2874 (11.88)22,626 (5.31)2684 (11.19)
       Multiple7690 (1.80)882 (3.65)7589 (1.78)872 (3.63)
      Parity
       Nuliparous188,353 (43.80)11,682 (47.82)189,002 (43.94)11,601 (47.95)
       Primiparous153,461 (35.69)7674 (31.41)153,818 (35.76)7659 (31.66)
       Multiparous88,203 (20.51)5073 (20.77)87,302 (20.30)4934 (20.39)
      Multifetal pregnancy5236 (1.21)3082 (12.48)51,45 (1.19)3083 (12.61)
      Smoking during pregnancy45,960 (11.51)3272 (14.56)45,876 (11.50)3294 (14.81)
      Material deprivation index quintiles
       1 (lowest)71,913 (17.14)4037 (16.95)72,043 (17.17)4024 (17.09)
       282,869 (19.75)4574 (19.21)82,514 (19.66)4623 (19.63)
       382,629 (19.70)4650 (19.53)82,129 (19.57)4541 (19.28)
       485,986 (20.49)4865 (20.42)86,618 (20.64)4841 (20.54)
       5 (highest)96,145 (22.92)5685 (23.88)96,400 (22.97)5523 (23.45)
      Social deprivation index quintiles
       1 (lowest)84,090 (20.04)4587 (19.26)83,954 (20.00)4527 (19.22)
       283,439 (19.89)4601 (19.32)83,299 (19.85)4552 (19.33)
       382,408 (19.64)4712 (19.79)82,485 (19.65)4657 (19.77)
       484,642 (20.17)4813 (20.20)84,620 (20.16)4788 (20.31)
       5 (highest)84,963 (20.25)5098 (21.41)85,346 (20.33)5028 (21.35)
      Maternal health problems
       Preexisting diabetes6090 (1.53)878 (3.84)6291 (1.58)833 (3.67)
       Gestational diabetes18,205 (4.55)1621 (6.97)18,165 (4.53)1643 (7.11)
       Chronic hypertension2677 (0.67)432 (1.89)2764 (0.69)417 (1.84)
       Infection during pregnancy3880 (0.97)301 (1.29)3962 (0.99)289 (1.25)
      Obstetric complications
       Infection during pregnancy3880 (0.97)301 (1.29)3962 (0.99)289 (1.25)
       Eclampsia122 (0.03)33 (0.14)140 (0.03)38 (0.16)
       Preeclampsia7736 (1.89)1755 (7.43)7870 (1.92)1761 (7.50)
       Placental previa2157 (0.53)671 (2.85)2206 (0.54)667 (2.85)
       Uterine bleeding2967 (0.73)695 (3.01)3077 (0.76)729 (3.17)
       Placental abruption1952 (0.48)521 (2.21)2043 (0.50)563 (2.41)
       Cord prolapse711 (0.17)65 (0.28)665 (0.16)85 (0.37)
       Chorioamnionitis1516 (0.37)111 (0.48)1595 (0.39)104 (0.45)
       Breech presentation17,431 (4.16)2514 (10.54)17,616 (4.21)2509 (10.60)
       Small for gestational age (10th percentile)38,699 (9.03)2192 (10.15)38,773 (9.05)2195 (10.28)
      Obstetric interventions
       Any obstetric intervention
      Includes both induction and cesarean deliveries
      164,315 (37.87)9269 (37.53)164,913 (38.00)9316 (38.09)
       Induction
      Includes inductions ultimately resulting in a cesarean delivery
      101,660 (23.53)4794 (19.49)102,145 (23.64)4923 (20.21)
       Prelabor cesarean section
      Excludes cesarean sections that were preceded by induction or spontaneous labor.
      62,655 (14.50)4475 (18.20)62,768 (14.53)4393 (18.04)
      Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
      a Includes both induction and cesarean deliveries
      b Includes inductions ultimately resulting in a cesarean delivery
      c Excludes cesarean sections that were preceded by induction or spontaneous labor.
      In the univariable analysis of the derivation cohort, ‘any obstetric intervention’ was not significantly associated with LP birth (RR, 0.96; 95% confidence interval [CI], 0.85–1.09). Prelabor cesarean section was positively associated with LP birth (RR, 1.30; 95% CI, 1.21–1.40) and induction was negatively associated with LP birth (RR, 0.76; 95% CI, 0.65–0.89).
      For our primary analysis, adjustment for maternal and obstetric factors known or suspected to be associated with preterm birth identified that ‘any obstetric intervention’ was associated with a lower likelihood of LP birth relative to term birth in the derivation cohort (RR, 0.65; 95% CI, 0.57–0.74).
      For our secondary analysis, adjusted risk ratio estimates for induction and prelabor cesarean section were also negatively associated with LP birth relative to term birth (RR, 0.71; 95% CI, 0.61–0.82 and RR, 0.66; 95% CI, 0.59–0.74 respectively) (Table 2).
      Table 2Unadjusted and adjusted associations between obstetric interventions and LP gestational age at birth relative to term birth
      VariableDerivation cohortValidation cohort
      uRRaRR
      Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age.
      uRRaRR
      Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age.
      Any obstetric intervention0.96 (0.85–1.09)0.65 (0.57–0.74)0.97 (0.85–1.11)0.65 (0.57–0.73)
      Induction0.76 (0.65–0.89)0.71 (0.61–0.82)0.79 (0.69–0.90)0.71 (0.63–0.81)
      Prelabor cesarean section1.30 (1.21–1.40)0.66 (0.59–0.74)1.28 (1.19–1.39)0.66 (0.59–0.73)
      aRR, adjusted risk ratio; uRR, unadjusted risk ratio.
      Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
      a Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age.
      Exploring the adjusted association between obstetric interventions by week of gestational age at birth in the derivation cohort revealed that ‘any obstetric interventions’, induction and prelabor cesarean section were negatively associated with LP birth through the 36th week of gestation with cesarean section reaching statistical nonsignificance at 37 weeks' gestation (Table 3).
      Table 3Associations between obstetrical interventions by week of gestation relative to term birth in the derivation cohort
      Variable34 wks35 wks36 wks37 wks
      aRR
      Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age
      aRR
      Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age
      aRR
      Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age
      aRR
      Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age
      aRR for the 37th week gestation calculated by considering term gestation to be 380⁄7 to 406⁄7 weeks.
      Any obstetric intervention0.49 (0.39–0.62)0.57 (0.49–0.68)0.65 (0.57–0.74)0.92 (0.83–1.03)
      Induction0.43 (0.32–0.58)0.61 (0.51–0.74)0.74 (0.65–0.85)0.81 (0.75–0.88)
      Prelabor cesarean section0.73 (0.58–0.93)0.63 (0.53–0.76)0.59 (0.51–0.68)0.79 (0.72–0.87)
      aRR, adjusted risk ratio.
      Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
      a Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age
      b aRR for the 37th week gestation calculated by considering term gestation to be 380⁄7 to 406⁄7 weeks.
      For our exploratory analysis, most of the hypothesized risk factors for preterm birth were independently associated with LP gestational age at birth in the derivation cohort (Table 4). The strongest associated risk factor for LP gestational age at birth was multifetal pregnancy (RR, 6.28; 95% CI, 5.85–6.74) followed by placenta previa (RR, 4.35; 95% CI, 3.88–4.89), preeclampsia (RR, 3.32; 95% CI, 3.05–3.60) and previous preterm birth (RR, 2.93; 95% CI, 2.27–3.78). Several potentially modifiable risk factors were also associated with LP gestational age at birth including smoking during pregnancy (RR, 1.28; 95% CI, 1.21–1.36), previous cesarean section (RR, 1.28; 95% CI, 1.16–1.40) and high material (RR, 1.1; 95% CI, 1.03–1.18) and social (RR, 1.09; 95% CI, 1.02–1.16) deprivation indices.
      Table 4Associations between maternal and fetal factors and LP gestational age at birth
      Maternal characteristicsDerivation cohortValidation cohort
      uRRaRR
      Adjusted for induction, smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age.
      uRRaRR
      Adjusted for induction, smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age.
      Maternal age, y
       <201.18 (1.08–1.28)1.06 (0.98–1.16)1.09 (0.99–1.19)1.00 (0.91–1.10)
       20-241.02 (0.97–1.08)1.02 (0.97–1.07)1.06 (1.01–1.10)1.06 (1.01–1.11)
       25-34RefRefRefRef
       35-391.11 (1.05–1.17)1.06 (1.01–1.12)1.14 (1.08–1.20)1.10 (1.05–1.15)
       >401.34 (1.23–1.46)1.15 (1.06–1.25)1.44 (1.33–1.57)1.25 (1.16–1.34)
      Material deprivation index quintiles
       1 (lowest)RefRefRefRef
       21.05 (0.97–1.14)1.08 (1.03–1.13)1.09 (1.03–1.16)1.06 (1.00–1.11)
       31.09 (0.98–1.20)1.08 (1.01–1.16)1.09 (1.02–1.17)1.04 (0.99–1.10)
       41.10 (1.00–1.21)1.05 (0.99–1.12)1.11 (1.04–1.19)1.05 (1.00–1.10)
       5 (highest)1.15 (1.04–1.27)1.10 (1.03–1.18)1.14 (1.07–1.22)1.07 (1.01–1.13)
      Social deprivation index quintiles
       1 (lowest)RefRefRefRef
       21.02 (0.97–1.07)1.02 (0.98–1.07)1.01 (0.96–1.06)1.03 (0.98–1.09)
       31.04 (0.99–1.09)1.05 (1.00–1.10)1.03 (0.97–1.09)1.05 (0.99–1.11)
       41.02 (0.95–1.10)1.05 (0.99–1.11)1.02 (0.96–1.08)1.04 (0.99–1.10)
       5 (highest)1.05 (0.97–1.14)1.09 (1.02–1.16)1.03 (0.96–1.11)1.07 (1.01–1.12)
      Multifetal pregnancy8.70 (7.99–9.46)6.28 (5.85–6.74)8.89 (8.19–9.64)6.18 (5.74–6.64)
      Smoking during pregnancy1.35 (1.26–1.45)1.28 (1.21–1.36)1.41 (1.33–1.49)1.34 (1.28–1.41)
      Previous cesarean section1.06 (1.01–1.12)1.28 (1.16–1.40)1.05 (0.99–1.12)1.28 (1.18–1.39)
      Previous preterm birth
       One2.71 (1.88–3.89)2.93 (2.27–3.78)2.52 (1.78–3.57)2.70 (2.14–3.41)
       Multiple2.58 (1.63–4.10)2.77 (1.85–4.15)2.60 (1.65–4.09)2.78 (1.80–4.32)
      Parity
       NuliparousRefRefRefRef
       Primiparous0.80 (0.76–0.84)0.68 (0.63–0.73)0.81 (0.77–0.85)0.70 (0.66–0.74)
       Multiparous0.94 (0.89–1.00)0.68 (0.62–0.74)0.94 (0.88–1.00)0.68 (0.63–0.74)
      Maternal health problems
       Preexisting diabetes2.55 (2.34–2.79)2.04 (1.81–2.30)2.37 (2.14–2.64)1.92 (1.74–2.12)
       Gestational diabetes1.60 (1.50–1.71)1.32 (1.22–1.43)1.65 (1.52–1.79)1.39 (1.28–1.51)
       Chronic hypertension2.72 (2.43–3.05)1.52 (1.30–1.78)2.56 (2.32–2.83)1.50 (1.33–1.69)
       Infection during pregnancy1.30 (1.07–1.60)1.21 (1.03–1.42)1.21 (0.95–1.55)1.19 (1.00–1.42)
      Obstetric complications
       Eclampsia4.44 (3.33–5.93)2.23 (1.58–3.16)4.46 (2.95–6.73)2.16 (1.52–3.08)
       Preeclampsia3.91 (3.58–4.27)3.32 (3.05–3.60)3.88 (3.58–4.21)3.15 (2.86–3.47)
       Placental previa5.01 (4.53–5.53)4.35 (3.88–4.89)4.93 (4.29–5.66)4.42 (3.86–5.06)
       Uterine bleeding4.01 (3.44–4.68)1.83 (1.59–2.11)4.05 (3.47–4.71)1.85 (1.63–2.10)
       Placental abruption4.34 (3.67–5.14)2.05 (1.68–2.50)4.47 (3.79–5.27)2.33 (2.00–2.72)
       Cord prolapse1.56 (1.07–2.27)0.81 (0.52–1.28)2.22 (1.66–2.97)1.60 (1.21–2.12)
       Chorioamnionitis1.22 (0.88–1.69)1.12 (0.84–1.49)1.04 (0.69–1.57)1.09 (0.81–1.46)
       Breech presentation2.69 (2.54–2.84)2.08 (1.96–2.22)2.68 (2.53–2.84)2.06 (1.93–2.21)
       Small for gestational age (10th percentile)1.14 (1.03–1.26)1.04 (0.95–1.13)1.16 (1.06–1.26)1.05 (0.98–1.13)
      aRR, adjusted risk ratio; LP, late preterm; ref, reference; uRR, unadjusted risk ratio.
      Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
      a Adjusted for induction, smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age.
      Repeating the primary and secondary analyses using the validation cohort led to similar findings (Table 2, Table 3, Table 4).

      Comment

      We have used population based data from the largest province in Canada, to examine the magnitude of the association between obstetrical interventions and LP birth taking into account numerous known or suspected maternal and obstetrical risk factors for preterm birth. We have identified that induction and prelabor cesarean section were associated with a lower likelihood of LP birth relative to term birth for pregnancies with similar maternal and fetal risk. Further, this trend persisted through each LP gestational week up to 37 weeks. We have also identified several potentially modifiable risk factors which were associated with LP birth, independent of obstetrical interventions, including previous cesarean section, smoking during pregnancy and high social and material deprivation.
      There has been concern that the escalation in LP birth over the past 20 years may be related to obstetric interventions and iatrogenic preterm birth.
      • Joseph K.S.
      • D'Alton M.
      Theoretical and empirical justification for current rates of iatrogenic delivery at late preterm gestation.
      In Canada, the overall rate of cesarean delivery increased from 21.9% in 2001/2002 to 27.8% in 2009/2010.

      Public Health Agency of Canada. Perinatal Health Indicators for Canada, 2011. Available at: http://www.phac-aspc.gc.ca/rhs-ssg/phi-isp-2011-eng.php. Accessed April 1, 2014.

      A recent multicountry analysis that aimed to understand the main drivers for the increase in the preterm birth rate over time identified that cesarean section and labor induction together accounted for approximately 20% of the change in LP birth between 1989 and 2004.
      • Chang H.H.
      • Larson J.
      • Blencowe H.
      • et al.
      Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index.
      However, maternal and fetal health problems are also increasing and expedited delivery through obstetric intervention in the setting of maternal or fetal compromise is generally accepted practice to avoid potentially disastrous maternal or neonatal outcomes.
      • Fuchs K.
      • Gyamfi C.
      The influence of obstetric practices on late prematurity.
      Overall rates of stillbirth and perinatal death in the US have decreased in parallel to the increase in LP births prompting some to argue that obstetric intervention may be preventing stillbirth and perinatal death.
      • Ananth C.V.
      • Joseph K.S.
      • Kinzler W.L.
      The influence of obstetric intervention on trends in twin stillbirths: United States, 1989-99.
      • Kramer M.S.
      • Zhang X.
      • Iams J.
      The rise in late preterm obstetric intervention: has it done more good than harm?.
      Our findings add to this literature by suggesting that obstetrical care providers may be preferentially avoiding interventions to bring about LP birth in the setting of equivalent maternal and obstetric risk. We speculate that increased awareness among obstetric care providers about the harms of unnecessary LP birth may be a contributing factor. Another contributing factor may be elective cesarean section and induction which obstetric care providers may be more liberal with in the term than in the late preterm period.
      We have also identified several potentially modifiable factors which were independently associated with LP birth and may be useful targets for interventions to reduce LP birth. Consistent with other studies, previous cesarean section was associated with a 28% increased likelihood of LP birth suggesting that efforts to minimize term and preterm cesarean sections may decrease risk of LP birth in subsequent pregnancies.
      • Di Renzo G.C.
      • Giardina I.
      • Rosati A.
      • Clerici G.
      • Torricelli M.
      • Petraglia F.
      Maternal risk factors for preterm birth: a country-based population analysis.
      • Taylor L.K.
      • Simpson J.M.
      • Roberts C.L.
      • Olive E.C.
      • Henderson-Smart D.J.
      Risk of complications in a second pregnancy following caesarean section in the first pregnancy: a population-based study.
      • Kennare R.
      • Tucker G.
      • Heard A.
      • Chan A.
      Risks of adverse outcomes in the next birth after a first cesarean delivery.
      Smoking during pregnancy was associated with a 30% increased likelihood of LP birth.
      Strengths of our study include the clinical richness of the BORN Information System, which allowed for more thorough adjustment for maternal and obstetric risk factors. The magnitude of the change of the association between obstetric interventions and LP birth before and after adjustment for maternal and obstetric risk factors underscores the influence that such risk factors likely have on care provider decisions around obstetric interventions. Population based data also allowed us to use a validation cohort to verify our findings and minimize risk of spurious findings from multiple hypothesis testing.
      • Picard R.R.
      • Berk K.N.
      Data splitting.
      GEE modeling allowed us to account for clustering of obstetric interventions, which have been documented to vary considerably between hospitals.
      • Kelly S.
      • Sprague A.
      • Fell D.B.
      • et al.
      Examining caesarean section rates in Canada using the robson classification system.
      Our study has several limitations. Although a validation exercise has examined our primary outcome and primary exposure variables, several of the variables used in our analysis have not been validated raising the potential for coding error or misclassification.
      • Dunn S.
      • Bottomley J.
      • Ali A.
      • Walker M.
      2008 Niday Perinatal Database quality audit: report of a quality assurance project.
      Induction and prelabor cesarean section were coded as mutually exclusive categories to capture the obstetric intervention that initiated the birth process. This resulted in a lower than expected frequency of cesarean sections since those that were proceeded by spontaneous labor or induction of labor were not included in the prelabor cesarean variable. It is also possible that our findings may have been influenced by incomplete adjustment. However, when we repeated our primary analysis using only the 32% of pregnancies with no identified risk factor for LP birth, the effect sizes were similar to our primary analysis (data not shown). We also considered that our finding of a negative association between obstetric interventions and LP birth may be reflective of increased risk of obstetrical interventions past 40 weeks gestation and our definition of “term” pregnancy included women up to 40 6/7 weeks' gestation. However, a sensitivity analysis excluding births over 40 weeks' gestation resulted in similar findings to our primary analysis (data not shown).
      Our findings suggest that over the past 7 years, the likelihood of birth associated with obstetric interventions in Ontario was lower in the LP period than the term period once maternal and obstetric risk factors were taken into account. Obstetric care providers may be preferentially not intervening to bring about birth before term in the setting of equivalent maternal and obstetric risk. Although ongoing vigilance to avoid unnecessary late preterm obstetric interventions is warranted, strategies focusing on modifiable risk factors for LP birth may be helpful including minimizing unnecessary prelabor cesarean sections, smoking cessation, and reducing material and social deprivation.

      Acknowledgments

      Support for this study was provided by both the Physician Services Incorporated Foundation and the St. Michael's Hospital AFP Innovation Fund. Funding agencies had no role in the design, collection, analysis or interpretation of results in this study.
      We would also like to acknowledge the following individuals for their technical, administrative, and statistical support of this study:
      Sharmilaa Kandasamy, Research Coordinator II, Employed and Funded by the Department of Paediatrics, St. Michael's Hospital
      Julie DeGroot, Clinical Research Project Manager, Employed and Funded by the Pediatric Outcomes Research Team, Hospital for Sick Children
      Rosane Nisenbaum, Senior Biostatistician, Employed and Funded by the Applied Health Research Centre, St. Michael's Hospital

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