The role of confounding in the association between pregnancy complications and subsequent preterm birth: a cohort study

Abstract

Objective To estimate the degree of confounding necessary to explain the associations between complications in a first pregnancy and the subsequent risk of preterm birth.Design Population-based cohort study.Setting Western Australia.Population Women (n = 125 473) who gave birth to their first and second singleton children between 1998 and 2015.Main outcome measures Relative risk (RR) of a subsequent preterm birth (<37 weeks of gestation) with complications of preeclampsia, placental abruption, small-for-gestational age and perinatal death (stillbirth and neonatal death within 28 days of birth). We derived e-values to determine the minimum strength of association for an unmeasured confounding factor to explain away an observed association.Results Complications in a first pregnancy were associated with an increased risk of a subsequent preterm birth. Relative risks were significantly higher when the complication was recurrent, with the exception of first-term perinatal death. The association with subsequent preterm birth was strongest when pre-eclampsia was recurrent. The risk of subsequent preterm birth with preeclampsia was 11.87 (95% CI 9.52-14.79) times higher after a first term birth with pre-eclampsia, and 64.04 (95% CI 53.58-76.55) times higher after a preterm first birth with pre-eclampsia, than an uncomplicated term birth. The e-values were 23.22 and 127.58, respectively.Conclusions The strong associations between recurrent preeclampsia, placental abruption and small-for-gestational age with preterm birth supports the hypothesis of shared underlying causes that persist from pregnancy to pregnancy. High e-values suggest that recurrent confounding is unlikely, as any such unmeasured confounding factor would have to be uncharacteristically large.

Calcium, Potassium, Sodium, and Magnesium Concentrations in the Placenta, Umbilical Cord, and Fetal Membrane from Women with Multiple Pregnancies

“…Na concentration in the umbilical cord showed a positive linear correlation with the duration of the pregnancy. A low level of Na (hyponatremia) is the most common electrolyte abnormality that may pose a risk to pregnancy [ 60 ] and contribute to pre-eclampsia, which can result in a shorter pregnancy [ 61 , 62 , 63 ]. Hsu et al [ 64 ] showed that hyponatremia in pre-eclampsia can lead to maternal respiratory and circulatory arrest.…”

Maternal hypertensive traits and adverse outcome in pregnancy: a Mendelian randomization study

“…High baseline PP at 12 to 19 weeks’ gestation has been demonstrated to be a risk factor for early spontaneous preterm birth in normotensive nulliparous women, and rises in SBP and DBP between baseline and mid-third trimester values associated with an increased risk of early and late spontaneous preterm births in a dose--response manner [ 31 ] especially in women with obesity [ 32 ]. A plausible mechanism for this finding is that raised hypertensive indices increase preeclampsia risk: term preeclampsia in a first pregnancy is a major risk factor for subsequent preterm birth with or without recurrent preeclampsia [ 33 ]. Overall, elevated SBP and PP should alert clinicians to the possibility of pregnancies at a higher risk of preterm delivery and trigger appropriate peripartum care.…”

The effect of prenatal cannabis exposure on offspring preterm birth: a cumulative meta‐analysis

“…The association between preterm birth and prenatal cannabis use may also be due to a range of risk factors such as hypertensive disorders of pregnancy and gestational diabetes [61,62]. Evidence from an epidemiological study has suggested that the risk of preterm birth due to gestational diabetes may be higher if pregnant women develop diabetes prior to the 24th week of gestation [62].…”